Miracle-dz/UniFAR-FTUs huggingface dataset:
Virulence and Antimicrobial Resistance in Campylobacter spp. from a Peruvian Pediatric Cohort

The presence of virulence factors (VFs) and mechanisms of quinolones and macrolide resistance was analyzed in Campylobacter spp. from a pediatric cohort study in Lima. In 149 isolates (39 Campylobacter jejuni and 24 Campylobacter coli from diarrheic cases; 57 C. jejuni and 29 C. coli from controls), the presence of the cdtABC and cadF genes and iam marker was established. Nalidixic acid, ciprofloxacin, erythromycin, and azithromycin susceptibilities were established in 115 isolates and tetracycline-susceptibility was established in 100 isolates. The presence of mutations in the gyrA, parC, and 23S rRNA genes was determined. The cadF gene and all genes from the cdtABC operon were significantly more frequent among C. jejuni (P < 0.0001); the iam marker was more frequent in C. coli (P < 0.0001). No differences were observed in VFs between cases and controls. Almost all isolates were tetracycline-resistant; nalidixic acid and ciprofloxacin resistance reached levels of 90.4% and 88.7%, respectively. Resistance to macrolides was 13% (C. jejuni 4.3%; C. coli 26.1%). Resistance to ciprofloxacin was related to GyrA Thr86 substitutions, while 13 of 15 macrolide-resistant isolates possessed a 23S rRNA mutation (A2075G). Differences in the presence of VFs and alarming levels of resistance to tested antimicrobial agents were observed among C. jejuni and C. coli.
Composite Functional Gradient Learning of Generative Adversarial Models

Generative adversarial networks (GAN) have become popular for generating data that mimic observations by learning a suitable variable transformation from a random variable. However, empirically, GAN is known to suffer from instability. Also, the theory provided based on the minimax optimization formulation of GAN cannot explain the widely-used practical procedure that uses the so-called logd trick. This paper provides a different theoretical foundation for generative adversarial methods which does not rely on the minimax formulation. We show that with a strong discriminator, it is possible to learn a good variable transformation via functional gradient learning, which updates the functional definition of a generator model, instead of updating only the model parameters as in GAN. The theory guarantees that the learned generator improves the KL-divergence between the probability distributions of real data and generated data after each functional gradient step, until the KL-divergence converges to zero. This new point of view leads to enhanced stable procedures for training generative models that can utilize arbitrary learning algorithms. It also gives a new theoretical insight into the original GAN procedure both with and without the logd trick. Empirical results are shown on image generation to illustrate the effectiveness of our new method.
Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction.

CONTEXT The clinical benefit of glucose-insulin-potassium (GIK) infusion in patients with ST-segment elevation myocardial infarction (STEMI) is unclear. While some smaller trials suggest benefit, in the CREATE-ECLA trial, GIK infusion had no effect on 30-day mortality in 20,201 patients. OBJECTIVES To determine the association between GIK infusion therapy and 30-day and 6-month outcomes in patients with STEMI. DESIGN, SETTING, AND PARTICIPANTS Primary analysis of the OASIS-6 GIK randomized controlled trial of 2748 patients with acute STEMI; prespecified analyses of the combined trial data from the OASIS-6 GIK and CREATE-ECLA GIK trial populations of 22,943 patients with acute STEMI; subgroup analysis on the timing of initiation of GIK infusion therapy and outcomes; and post hoc analyses exploring whether GIK infusion may cause early harm by increasing glucose and potassium levels and net fluid gain. INTERVENTION High-dose GIK solution consisting of 25% glucose, 50 U/L of regular insulin, and 80 mEq/L of potassium infused at 1.5 mL/kg per hour for 24 hours. MAIN OUTCOME MEASURES Mortality rates at 30 days and 6 months in the OASIS-6 GIK trial and rates of death, heart failure, and the composite of death or heart failure at 3 and 30 days in the combined OASIS-6 GIK and CREATE-ECLA GIK trial populations. RESULTS At 6 months, 148 (10.8%) GIK infusion patients and 143 (10.4%) control patients died in the OASIS-6 trial (hazard ratio [HR], 1.04; 95% CI, 0.83-1.31; P = .72); 153 (11.1%) GIK patients and 185 (13.5%) control patients had heart failure (HR, 0.83; 95% CI, 0.67-1.02; P = .08); and 240 (17.5%) GIK patients and 264 (19.2%) control patients had a composite of death or heart failure (HR, 0.91; 95% CI, 0.76-1.08; P = .27). In the prespecified analyses of the combined trial data, there were 712 deaths (6.2%) in the GIK group and 632 deaths (5.5%) in the control group at 3 days (HR, 1.13; 95% CI, 1.02-1.26; P = .03). This difference disappeared by 30 days, with 1108 deaths (9.7%) in the GIK group and 1068 (9.3%) in the control group (HR, 1.04; 95% CI, 0.96-1.13; P = .33). GIK therapy increased levels of glucose, potassium, and net fluid gain postinfusion, all 3 of which predicted death after adjusting for multiple confounders. Adjusting for glucose, potassium, and net fluid gain eliminated the apparent increase in mortality at 3 days observed with GIK infusion, suggesting a direct association with these factors. Administration of GIK infusion within 4 hours of symptom onset yielded no benefit compared with later initiation. CONCLUSIONS Infusion of GIK provided no benefit and may cause early harm following STEMI. Avoidance of infusion-related hyperglycemia, hyperkalemia, and net fluid gain may be advisable in future studies of metabolic modulation in patients with STEMI. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00064428.
Rifaximin versus chlortetracycline in the short‐term treatment of small intestinal bacterial overgrowth

Bacterial overgrowth of the small intestine is a condition characterized by nutrient malabsorption due to an excessive number of bacteria in the lumen of the small intestine. Current treatment is based on empirical courses of broad spectrum antibiotics; few controlled data, with respect to the duration and choice of antibiotic drug, exist at present. The recent availability of rifaximin, a non‐absorbable rifamycin derivative, highly effective against anaerobic bacteria, prompted us to carry out a randomized, double‐blind controlled trial in order to compare its efficacy and tolerability to those of tetracycline, currently considered the first‐choice drug.
The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD)

Objective To replicate and refine the reported association of ankylosing spondylitis (AS) with two non-synonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1. Methods Firstly, 730 independent UK patients with AS were genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879 previously typed historic disease controls. Secondly, the two data sets were combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and rs6979, were analysed in 1604 cases and 1020 controls. Results The association of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to 1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002, OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72), respectively, were identified. Conclusions The region on chromosome 16 that has been replicated in the present work is interesting as the highly plausible candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death domain (TRADD), is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS.
Mismatch negativity and P3a amplitude in young adolescents with first-episode psychosis: a comparison with ADHD

Background Deficient mismatch negativity (MMN) has been proposed as a candidate biomarker in schizophrenia and may therefore be potentially useful in early identification and intervention in early onset psychosis. In this study we explored whether deficits in the automatic orienting and reorienting responses, measured as MMN and P3a amplitude, are present in young adolescents with first-episode psychosis (FEP) and whether findings are specific to psychosis compared to young adolescents with attention deficit hyperactivity disorder (ADHD). Method MMN and P3a amplitude were assessed in young adolescents (age 12–17 years) with either FEP (N = 27) or ADHD (N = 28) and age- and gender-matched healthy controls (N = 43). The MMN paradigm consisted of a four-tone auditory oddball task with deviant stimuli based on frequency, duration and their combination. Results Significantly less MMN was found in patients with psychosis compared to healthy controls in response to frequency and duration deviants. MMN amplitudes in the group of patients with ADHD were not significantly different from patients with psychosis or healthy controls. No significant group differences were found on P3a amplitude. Conclusion Young adolescents with FEP showed impaired MMN compared to healthy controls while intermediate and overlapping levels of MMN were observed in adolescents with ADHD. The findings suggest that young FEP patients already exhibit pre-attentive deficits that are characteristic of schizophrenia albeit expressed on a continuum shared with other neuropsychiatric disorders.
Comparison of the diversity of the vaginal microbiota in HIV-infected and HIV-uninfected women with or without bacterial vaginosis.

BACKGROUND Whether human immunodeficiency virus (HIV) infection is associated with a change in the diversity of genital microbiota in women was investigated. METHODS Amplicon length heterogeneity polymerase chain reaction (LH-PCR) analysis and pyrosequencing of the 16S ribosomal RNA gene were used to analyze the diversity of the microbiota in HIV-positive (HIV(+)) and HIV-negative (HIV(-)) women with or without bacterial vaginosis (BV). RESULTS LH-PCR analysis revealed significantly more microbiota diversity in BV-positive (BV(+)) women than in BV-negative (BV(-)) women, but no significant difference was noted between HIV(+) women and HIV(-) women. Pyrosequencing revealed that Lactobacillus organisms constituted a median of 96% of the bacteria in BV(-) women. BV(+) women had a significantly higher number of taxa found at > or =1% of the total genital microbiota (median, 11 taxa). Common taxa in BV(+) women were Prevotella, Megasphaera, Gardnerella, Coriobacterineae, Lachnospira, and Sneathia. There was a trend (P = .07) toward the presence of a higher number of taxa in HIV(+)BV(+) women than in HIV(-)BV(+) women. Propionibacterineae, Citrobacter, and Anaerococcus were the taxa found only in HIV(+) women (P < .05). CONCLUSIONS The present study demonstrated that both LH-PCR analysis and pyrosequencing differentiated microbiota in BV(+) women from that in BV(-) women and that pyrosequencing indicated a trend toward increased diversity in BV(+)HIV(+) women, suggesting that HIV infection is associated with changes in the diversity of genital microbiota.
ESTABLISHMENT OF AN X-RAY STANDARD CALIBRATION CURVE BY CONVENTIONAL DICENTRIC ANALYSIS AS PREREQUISITE FOR ACCURATE RADIATION DOSE ASSESSMENT

The dicentric assay was established to carry out cytogenetic biodosimetry after suspected radiation overexposure, including a comprehensive documentation system to record the processing of the specimen, all data, results, and stored information. As an essential prerequisite for retrospective radiation dose assessment, a dose-response curve for dicentric induction by in vitro x-ray irradiation of peripheral blood samples was produced. The accelerating potential was 240 kV (maximum photon energy: 240 keV). A total of 8,377 first-division metaphases of four healthy volunteers were analyzed after exposure to doses ranging from 0.2 to 4.0 Gy at a dose rate of 1.0 Gy min−1. The background level of aberrations at 0-dose was determined by the analysis of 14,522 first-division metaphases obtained from unirradiated blood samples of 10 healthy volunteers. The dose-response relationship follows a linear-quadratic equation, Y = c + &agr;D + &bgr;D2, with the coefficients c = 0.0005 ± 0.0002, &agr; = 0.043 ± 0.006, and &bgr; = 0.063 ± 0.004. The technical competence and the quality of the calibration curve were assessed by determination of the dose prediction accuracy in an in vitro experiment simulating whole-body exposures within a range of 0.2 to 2.0 Gy. Dose estimations were derived by scoring up to 500–1,000 metaphase spreads or more (full estimation mode) and by evaluating only 50 metaphase spreads (triage mode) per subject. The triage mode was applied by performing manifold evaluations of the full estimation data in order to test the robustness of the curve for triage purposes and to assess possible variations among the estimated doses referring to a single exposure and preparation.
Plasticity of Cytochrome P450 2B4 as Investigated by Hydrogen-Deuterium Exchange Mass Spectrometry and X-ray Crystallography*

Crystal structures of the xenobiotic metabolizing cytochrome P450 2B4 have demonstrated markedly different conformations in the presence of imidazole inhibitors or in the absence of ligand. However, knowledge of the plasticity of the enzyme in solution has remained scant. Thus, hydrogen-deuterium exchange mass spectrometry (DXMS) was utilized to probe the conformations of ligand-free P450 2B4 and the complex with 4-(4-chlorophenyl)imidazole (4-CPI) or 1-biphenyl-4-methyl-1H-imidazole (1-PBI). The results of DXMS indicate that the binding of 4-CPI slowed the hydrogen-deuterium exchange rate over the B′- and C-helices and portions of the F-G-helix cassette compared with P450 2B4 in the absence of ligands. In contrast, there was little difference between the ligand-free and 1-PBI-bound exchange sets. In addition, DXMS suggests that the ligand-free P450 2B4 is predominantly open in solution. Interestingly, a new high resolution structure of ligand-free P450 2B4 was obtained in a closed conformation very similar to the 4-CPI complex. Molecular dynamics simulations performed with the closed ligand-free structure as the starting point were used to probe the energetically accessible conformations of P450 2B4. The simulations were found to equilibrate to a conformation resembling the 1-PBI-bound P450 2B4 crystal structure. The results indicate that conformational changes observed in available crystal structures of the promiscuous xenobiotic metabolizing cytochrome P450 2B4 are consistent with its solution structural behavior.
Prognostic Impact of Subsequent Acute Coronary Syndrome and Unplanned Revascularization on Long‐Term Mortality After an Index Percutaneous Coronary Intervention: A Report From a Japanese Multicenter Registry

Background Whereas composite end points are often used in clinical trials of percutaneous coronary interventions (PCI), the impact of individual components on subsequent survival is incompletely defined. We evaluated the association of subsequent acute coronary syndromes (ACS) and unplanned coronary revascularization post‐PCI with long‐term survival. Methods and Results From 2009 to 2011, the KiCS‐PCI (Keio interhospital Cardiovascular Studies) consecutively enrolled patients undergoing PCI in 14 Japanese teaching hospitals. We identified patients who experienced ACS or unplanned coronary revascularization following their index PCI and compared subsequent survival during the 2‐year follow‐up period using propensity‐matched cohorts of patients who did and did not experience these events. Cox proportional hazard models were used to assess 2‐year all‐cause mortality. Because unstable angina is less severe than acute myocardial infarction, we also generated a separate propensity‐matched cohort for UA post‐PCI. Among 3348 PCI patients (mean age, 67.5±10.7 years; 79.7% male), 214 (6.4%) experienced a subsequent ACS (168 events [78.5%] were unstable angina), and 198 (5.9%) underwent unplanned revascularization. In the propensity‐matched cohorts, patients with a subsequent ACS admission had an increased risk of mortality as compared with those without (hazard ratio, 4.73; 95% confidence interval=1.35–16.6; P=0.015), whereas those with an unplanned revascularization did not have significantly higher risk (hazard ratio, 2.97; 95% confidence interval=0.57–14.3; P=0.19). Among unstable angina events, no association with mortality was observed (hazard ratio, 1.39; 95% confidence interval=0.48–4.00; P=0.54). Conclusions In the KiCS‐PCI registry, the incidence of a subsequent ACS was associated with higher mortality, but this association was less apparent after unplanned coronary revascularization or unstable angina. The prognostic implications of different outcomes in a composite end point should be considered when interpreting the results of clinical trials in PCI.
Retinal Dysfunction in Carriers of Bardet-Biedl Syndrome

Purpose: To determine whether retinal dysfunction in obligate carriers of the Bardet-Biedl syndrome (BBS) could be observed in local electroretinographic responses obtained with the multifocal electroretinogram (mfERG). Methods: Six obligate carriers of the BBS were examined for the study. Examination of each carrier included an ocular examination and mfERG testing of one eye. For the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal area of approximately 40° in diameter. The amplitudes and implicit times in each location for the mfERG were compared with the corresponding values determined for a group of 34 normally sighted, age-similar control subjects. Results: Mapping of 103 local electroretinographic response amplitudes within a central 40° area with the mfERG showed regions of reduced mfERG amplitudes in three of six carriers. Implicit time measurements in the 6 carriers were all normal except for those locations associated with abnormal amplitude reductions in 3 of the carriers. When present, retinal dysfunction was evident in the presence of a normal-appearing fundus. Conclusions: Multifocal ERG testing can demonstrate areas of retinal dysfunction in carriers of the BBS. This test may therefore be useful for identifying some heterozygous carriers of this disease.
The Reproducibility and Usefulness of the Oral Glucose Tolerance Test in Screening for Diabetes and other Cardiovascular Risk Factors

We examined the reproducibility of oral glucose tolerance tests (OGTT) using the World Health Organization criterion in 212 Chinese subjects (male 149, female 63) who underwent two 75 g OGTTs within a 6-week period. The overall reproducibility was 65.6% (139/212) of which 74 subjects had normal glucose tolerance, 24 had diabetes and 41 had impaired glucose tolerance (IGT) on two occasions. The subjects were divided into three groups [group 1: normal OGTTs on both occasions (n = 74); group 2: one abnormal OGTT (either diabetes or IGT (n = 51); group 3: 2 abnormal OGTTs (n = 87)]. Subjects in group 1 were younger, had lower blood pressure, body mass index (BMI), waist-to-hip ratio (WHR), fasting and 2 h plasma insulin levels, triglyceride, very — low density lipoprotein and apolipoprotein-B concentrations than both groups 2 and 3. Group 2 had similar characteristics as group 3 except for a lower glycated haemoglobin (HbA1c), fasting and 2 h plasma glucose during the two OGTTs. With receiver operating characteristic curve (ROC) analysis, a HbA1c. of 5.3% gave an optimal sensitivity of 70.7% and specificity of 74.3% to predict diabetes as defined by a 2h plasma glucose value ≥ 11.1 mmol/L in the first OGTT. Of the 212 subjects, 73 had HbA1c ≥ 5.3%. The reproducibility of OGTT was 56.2% for these 73 subjects. With ROC analysis, a BMI of 25 kg/m2 gave an optimal sensitivity of 53.7% and specificity of 56.7% to predict diabetes. For the 36 subjects with BMI ≥ 25 kg/m2, the reproducibility of OGTT was 58.3%. Similarly, for the 140 subjects with WHR ≥ 0.9, the reproducibility of OGTT was 57.9%. These findings confirmed the poor reproducibility of OGTT which was not improved even amongst subjects with high HbA1c, BMI or WHR. Furthermore, subjects with one abnormal OGTT, whether reproducible or not, had a higher cardiovascular risk profile compared to subjects who had two normal OGTTs.
A comparison of immunocytochemical markers to identify bipolar cell types in human and monkey retina

As more human retinas affected with genetic or immune-based diseases become available for morphological analysis, it is important to identify immunocytochemical markers for specific subtypes of retinal neurons. In this study, we have focused on bipolar cell markers in central retina. We have done single and double labeling using several antisera previously utilized in macaque monkey or human retinal studies and two new antisera (1) to correlate combinations of antisera labeling with morphological types of bipolar cells in human retina, and (2) to compare human labeling patterns with those in monkey retina. Human bipolar cells showed a wide range of labeling patterns with at least ten different bipolar cell types identified from their anatomy and marker content. Many bipolar cell bodies in the outer part of the inner nuclear layer contained combinations of protein kinase C alpha (PKCα), Islet-1, glycine, and Goα. Bipolar cells labeled with these markers had axons terminating in the inner half of the inner plexiform layer (IPL), consistent with ON bipolar cells. Bipolar cell bodies adjacent to the amacrine cells and with axons in the outer half of the IPL contained combinations of recoverin, glutamate transporter-1, and PKCβ, or CD15 and calbindin. Bipolar cells labeled with these markers were presumed OFF bipolar cells. Calcium-binding protein 5 (CaB5) labeled both putative ON and OFF bipolar cells. Using this cell labeling as a criteria, most cell bodies close to the horizontal cells were ON bipolar cells and almost all bipolar cells adjacent to the amacrine cells were OFF with a band in the middle 2–3 cell bodies thick containing intermixed ON and OFF bipolar cells. Differences were found between human and monkey bipolar cell types labeled by calbindin, CaB5, and CD15. Two new types were identified. One was morphologically similar to the DB3, but labeled for CD15 and CaB5. The other had a calbindin-labeled cell body adjacent to the horizontal cell bodies, but did not contain any accepted ON markers. These results support the use of macaque monkey retina as a model for human, but caution against the assumption that all labeling patterns are identical in the two primates.