Miracle-dz/UniFAR-FTUs huggingface dataset:
Nephrotic Syndrome and AA Amyloidosis Revealing Adult-Onset Cryopyrin-Associated Periodic Syndrome

Cryopyrin-associated periodic syndrome (CAPS) is due to gain-of-function mutations in the cryopyrin gene, which determines an overactive inflammatory response. AA amyloidosis is a complication of this syndrome. A 53-year-old man was referred to us because of lower limb edema. Past history: at the age of 20, he complained of arthralgia/arthritis and bilateral hypoacusis. At the age of 35, he presented posterior uveitis, several episodes of conjunctivitis, and progressive loss of visual acuity. Laboratory tests disclosed nephrotic syndrome, and renal biopsy showed AA amyloidosis. He was given anakinra with improvement of arthritis. A genetic study revealed the p.D303N mutation in the cryopyrin gene, and he was diagnosed as having AA amyloidosis due to CAPS. Twenty-one months after starting anakinra, the arthritis has disappeared, although nephrotic-range proteinuria persisted. It is important to be aware of cryopyrin-associated periodic syndrome because it can cause irreversible complications, and there is effective therapy.
Quantitative immunohistochemical analysis of duodenal ghrelin cells after sleeve gastrectomy in Wistar rats.

PURPOSE Sleeve gastrectomy (SG) removes substantial part of the gastric mucosa, which produces ghrelin. This reduction is expected to force other organs, such as the duodenum, to compensate by increasing the number of ghrelin-producing cells. The purpose of this study was to evaluate whether this response occurs. METHODS Twelve adult male, Wistar rats underwent SG and were reoperated 30 or 60 days after the initial surgery. During the second surgery, a segment of the duodenum was resected to count ghrelin cells using immunohistochemistry. In six animals, SG was not performed, and the duodenal segment served as a control for ghrelin cell counts. The ghrelin cell index (GCI), which is the number of ghrelin cells divided by the number of villi in each segment, was measured and used in statistical analysis by one-way analysis of variance (ANOVA). RESULTS There were increases in the absolute numbers of cells 30 and 60 days after SG, but statistical analysis by ANOVA showed no significant difference between the groups. CONCLUSION A compensatory increase in the number of duodenal immunopositive ghrelin cells did not occur as a response to sleeve gastrectomy.
Tolerability of up to 200 days of prophylaxis with valganciclovir oral solution and/or film‐coated tablets in pediatric kidney transplant recipients at risk of cytomegalovirus disease

This multicenter, open‐label study evaluated the tolerability of extended prophylaxis with valganciclovir in pediatric kidney transplant recipients at risk of CMV disease. Fifty‐six patients aged 4 months to 16 years received once‐daily valganciclovir oral solution and/or tablets, dosed by BSA and renal function, for up to 200 days. The most common AEs on treatment were upper respiratory tract infection (33.9%), urinary tract infection (33.9%), diarrhea (32.1%), leukopenia (25.0%), neutropenia (23.2%), and headache (21.4%). There were fewer AEs during days 101‐228 vs days 1‐100. Twenty‐seven patients (48.2%) had treatment‐related AEs during valganciclovir treatment, most commonly leukopenia (21.4%), neutropenia (19.6%), anemia (7.1%), and tremor (5.4%). Treatment‐related serious AEs were reported for nine patients (16.1%) and six withdrew due to AEs. Viremia was centrally confirmed in 10 patients; there was no confirmed CMV disease. One patient tested positive for a resistance mutation (UL97 L595F). Biopsy‐proven acute rejection occurred in six patients (10.7%), but no graft loss or deaths occurred. In conclusion, up to 200 days of valganciclovir prophylaxis in pediatric kidney allograft recipients showed a safety profile consistent with that established in adult transplant patients.
The Human Glucocorticoid Receptor as an RNA-Binding Protein: Global Analysis of Glucocorticoid Receptor-Associated Transcripts and Identification of a Target RNA Motif

Posttranscriptional regulation is emerging as a key factor in glucocorticoid (GC)-mediated gene regulation. We investigated the role of the human GC receptor (GR) as an RNA-binding protein and its effect on mRNA turnover in human airway epithelial cells. Cell treatment with the potent GC budesonide accelerated the decay of CCL2 mRNA (t1/2 = 8 ± 1 min versus 62 ± 17 min in DMSO-treated cells) and CCL7 mRNA (t1/2 = 15 ± 4 min versus 114 ± 37 min), but not that of CCL5 mRNA (t1/2=231 ± 8 min versus 266 ± 5 min) in the BEAS-2B cell line. This effect was inhibited by preincubation with an anti-GR Ab, indicating that GR itself plays a role in the turnover of these transcripts. Coimmunoprecipitation and biotin pulldown experiments showed that GR associates with CCL2 and CCL7 mRNAs, but not CCL5 mRNA. These methods confirmed CCL2 mRNA targeting by GR in human primary airway epithelial cells. Association of the GR was localized to the 5′ untranslated region of CCL2 mRNA and further mapped to nt 44–60. The collection of transcripts associated with GR, identified by immunoprecipitation of GR-mRNA complexes followed by microarray analysis, revealed 479 transcripts that associated with GR. Computational analysis of the primary sequence and secondary structures of these transcripts yielded a GC-rich motif, which was shown to bind to GR in vitro. This motif was used to predict binding of GR to an additional 7889 transcripts. These results indicate that cytoplasmic GR interacts with a subset of mRNA through specific sequences and can regulate turnover rates, suggesting a novel posttranscriptional role for GR as an RNA-binding protein.
[Effects of daily physical exercise at school on cardiovascular risk--results of a 2-year cluster-randomized study].

BACKGROUND AND OBJECTIVE It was the aim of this study to measure the effects over two years of daily sport activity during the school-day on their physical fitness (primary endpoint), motor coordination and blood pressure (secondary endpoints). METHODS A total of 232 children from eleven different 6 (th) grade classes were enrolled after informed parental consent. Their mean age was 11.1 ± 0.6 years. Six classes were randomly assigned for intervention (n=141), five as control (n=91). Those of the intervention cohort undertook, for five days weekly during the school year one hour of regulated sport exercise, including 15 min of endurance training. The pupils of the control group undertook customary sport activity (two hours a week). Anthropometric data were recorded and maximal oxygen uptake measured in each pupil, as well as blood pressure and motor coordination at the beginning and at the end of each of the two years of the study. The data were analyzed using the cluster randomization method. RESULTS Maximal oxygen uptake (VO (2)max) had improved among the intervention group after two years, compared with the controls (3.12 m/kg/min, 95% confindence interval [CI] 0.06-6.19), while improvement in motor coordination just failed to reach statistical significance (3.06, 95% CI -0.17-6.29). There was no significant difference in systolic and diastolic blood pressure, but a downward trend in the prevalence of overweight and obesity from 12.1% to 7.8% in the intervention group. CONCLUSION The results indicate that daily physical exercise during school hours should be given greater importance. But it will require a long-term trial to determine whether promotion of increased physical activity at school influences the prevalence of cardiovascular risk factors when the pupils reach adulthood.
Inhibition of matrix metalloproteinase on hepatic transforming growth factor beta1 and caspase-3 activation in hemorrhage.

OBJECTIVES Hemorrhage initiates an inflammatory response that induces the systemic release of cytokines and sequestration of polymorphonuclear neutrophils. Sequestered polymorphonuclear neutrophils release proteases, including matrix metalloproteinases (MMPs) that degrade elements of the extracellular matrix, contributing to the morbidity and mortality seen from hemorrhage. Activation of MMPs may be associated with changes in transforming growth factor beta1 (TGF-beta1) and caspase-3 signaling pathways. In this study, the authors examined hemorrhage-induced changes in the expression of rat hepatic MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-l), TGF-beta1, and caspase-3 activities in the presence and absence of the MMP inhibitor hydroxamate. METHODS Hemorrhagic shock was induced in fasted, anesthetized, and cannulated rats by rapid phlebotomy to a mean arterial pressure level of 40 mm Hg, maintained for 90 minutes by withdrawal and infusion of blood, followed by a resuscitation period of lactated Ringer's infusion. Rats received either hydroxamate (25 mg/kg) or vehicle by gavage before hemorrhage. Twenty-four hours after resuscitation, plasma and liver samples were collected. Liver MMP-9, TGF-beta1, and caspase-3 levels were quantified by Western immunoblotting. Plasma glutamic oxaloacetic transaminase (GOT) and plasma glutamic pyruvic transaminase (GPT) were determined enzymatically. RESULTS Plasma GOT, plasma GPT, and liver MMP-9, TGF-beta1, and caspase-3 levels were all significantly elevated at 24 hours postresuscitation when compared with the control values. Hepatic TIMP-1, an in vivo inhibitor of MMP-9, was unaltered at 24 hours. Hydroxamate treatment reduced GOT, GPT, MMP-9, TGF-beta1, and caspase-3 levels at 24 hours. The mortality of hemorrhaged untreated rats was 29% after 24 hours, and pretreatment with hydroxamate reduced mortality to 0%. CONCLUSIONS These results indicate the beneficial effects of MMP inhibitor in preventing an increase in GOT, GPT, MMP-9, TGF-beta1, and caspase-3 activity with the potential for improvement of hepatic injury due to hemorrhage.
PLASMA BIOCHEMISTRY AND HEMATOLOGIC VALUES FOR WILD-CAUGHT FLYING FOXES (PTEROPUS GIGANTEUS) IN INDIA

Abstract Although bats of the genus Pteropus are important ecologically as pollinators and natural hosts for zoonotic pathogens, little is known about their basic physiology. Hematology and plasma biochemistries were determined from wild-caught flying foxes (Pteropus giganteus) in northern India (n = 41). Mean lymphocyte differential count was higher for juveniles than adults. Mean platelet count was lower than previously reported. No hemoparasites were observed. No differences were observed between plasma biochemistry values of male and female bats, juveniles and adults, or lactating and nonlactating females. Variation in aspartate aminotransferase (AST) was seen based on body condition score. Blood urea nitrogen and cholesterol concentrations were lower in P. giganteus than other mammalian groups, but were consistent with those reported from other Pteropus species. Alanine aminotransferase and AST concentrations were higher than those reported for Pteropus vampyrus, a closely related species. This study provides basic physiologic information that can be used in future health and disease studies of Indian flying foxes.
Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVE To assess the efficacy and safety of milnacipran at a dosage of 100 mg/day (50 mg twice daily) for monotherapy treatment of fibromyalgia. METHODS A double-blind, placebo-controlled trial was performed to assess 1,025 patients with fibromyalgia who were randomized to receive milnacipran 100 mg/day (n = 516) or placebo (n = 509). Patients underwent 4-6 weeks of flexible dose escalation followed by 12 weeks of stable-dose treatment. Two composite responder definitions were used as primary end points to classify the response to treatment. The 2-measure composite response required achievement of ≥30% improvement from baseline in the pain score and a rating of "very much improved" or "much improved" on the Patient's Global Impression of Change (PGIC) scale. The 3-measure composite response required satisfaction of these same 2 improvement criteria for pain and global status as well as improvement in physical function on the Short Form 36 (SF-36) physical component summary (PCS) score. RESULTS After 12 weeks of stable-dose treatment, a significantly greater proportion of milnacipran-treated patients compared with placebo-treated patients showed clinically meaningful improvements, as evidenced by the proportion of patients meeting the 2-measure composite responder criteria (P < 0.001 in the baseline observation carried forward [BOCF] analysis) and 3-measure composite responder criteria (P < 0.001 in the BOCF). Milnacipran-treated patients also demonstrated significantly greater improvements from baseline on multiple secondary outcomes, including 24-hour and weekly recall pain score, PGIC score, SF-36 PCS and mental component summary scores, average pain severity score on the Brief Pain Inventory, Fibromyalgia Impact Questionnaire total score (all P < 0.001 versus placebo), and Multidimensional Fatigue Inventory total score (P = 0.036 versus placebo). Milnacipran was well tolerated by most patients, with nausea being the most commonly reported adverse event (placebo-adjusted rate of 15.8%). CONCLUSION Milnacipran administered at a dosage of 100 mg/day improved pain, global status, fatigue, and physical and mental function in patients with fibromyalgia.
Mental contamination and mental correction: unwanted influences on judgments and evaluations.

We define mental contamination as the process whereby a person has an unwanted response because of mental processing that is unconscious or uncontrollable. This type of bias is distinguishable from the failure to know or apply normative rules of inference and can be further divided into the unwanted consequences of automatic processing and source confusion, which is the confusion of 2 or more causes of a response. Mental contamination is difficult to avoid because it results from both fundamental properties of human cognition (e.g., a lack of awareness of mental processes) and faulty lay beliefs about the mind (e.g., incorrect theories about mental biases). People's lay beliefs determine the steps they take (or fail to take) to correct their judgments and thus are an important but neglected source of biased responses. Strategies for avoiding contamination, such as controlling one's exposure to biasing information, are discussed.
The taqI DRD2 A1 allele is associated with alcohol-dependence although its effect size is small.

BACKGROUND Numerous studies of the relationship between the TaqIA DRD2 A1 allele and alcohol-dependence have been performed and many of these have shown an association whereas others have not (Noble, 2003). This has consequently generated some controversy as to whether such an association actually exists (Noble, 2003). In the two recent meta-analyses by Noble (2003) and Young et al. (2004) some very important methodological issues have been discussed, which need to be addressed in forthcoming studies. Thus, the sample size is of great importance. In case-control studies it has been estimated that to detect the role of genes with small effect size of approximately 2, which is in the range of the DRD2 A1 allele-alcoholism relationship, case-control sets of 300-400 subjects are necessary (Noble, 2003). METHODS In the present study, we have consequently recruited a large number of subjects, 375 alcohol-dependent individuals, who were treated as inpatients for alcohol withdrawal symptoms and out of these 357 could be evaluated. As controls, 578 individuals screened and 254 individuals unscreened for alcohol consumption were used. Thus, the total number of subjects was 1217. RESULTS In the present study, in which the TaqI A1/A2 DRD2 polymorphism was in Hardy-Weinberg equilibrium in the patient group and the two control groups, we found that the TaqI DRD2 A1/A2 genotype frequency differed significantly between the alcohol-dependent group and both the total and screened control groups. Furthermore, the TaqI DRD2 A1 allele frequency was significantly overrepresented in the alcohol-dependent subjects as compared with both the total and screened control groups. The odds ratio for alcohol-dependency being associated with the A1 allele was 1.34. CONCLUSIONS Consequently, the findings in this study lend further support to the notion of an association between the DRD2 A1 allele and alcohol-dependence, although the effect size of the DRD2 A1 allele is small.
Regulation of a yeast HSP70 gene by a cAMP responsive transcriptional control element.

HSP70 genes exhibit complex regulation in response to stress and a variety of cellular and developmental events. The SSA3 HSP70 gene of Saccharomyces cerevisiae is activated at the transcriptional level under conditions of nutrient limitation. Analysis of deletions revealed that cis‐acting DNA sequences present immediately upstream and downstream of the previously identified heat shock elements (UASHS) mediate this regulation. A 35 bp region of SSA3, distinct from UASHS, contains sequences capable of activating a heterologous promoter following the diauxic shift and in the stationary phase of the yeast life cycle; this region has been designated an upstream activating sequence, UASPDS. Expression driven by UASPDS is regulated by the RAS/cAMP pathway. Reduced cAMP dependent protein kinase activity results in UASPDS dependent activation of the SSA3 promoter while constitutive cAMP dependent protein kinase activity prevents UASPDS mediated transcription, even under growth conditions that would normally result in full activation. Although the heat shock element alone exhibits no UAS activity under conditions in which UASPDS promotes transcription, UASHS interacts positively with UASPDS to mediate high levels of SSA3 transcription in response to nutrient limitation and lowered intracellular cAMP concentration. This interaction is independent of the precise spacing and relative orientation of the two elements.
On the recovery of hemicellulose before kraft pulping

To assess the feasibility of implementing hemicellulose recovery stages in kraft mills, Eucalyptus globulus wood samples were subjected to aqueous treatments with hot, compressed water (autohydrolysis processing) to achieve partial dissolution of xylan. Autohydrolyzed solids were subjected to kraft pulping under selected conditions to yield a pulp of low kappanumber, and to an optimized TCF bleaching sequence made up of three stages (alkaline oxygen delignification, chelating, and pressurized hydrogen peroxide), with minimized additions of pulping and bleaching chemicals. The final product had a relatively low kappa number (1.4), 641 mL/g ISO intrinsic viscosity, and 86.4% brightness.
In vitro antibiotic removal and bacterial recovery from blood with an antibiotic removal device

The antibiotic removal device manufactured by Marion Laboratories (Kansas City., Mo.) is intended for treatment, before culture, of blood specimens from hospital patients being treated with antibiotics. Measurement of 13 antibiotics showed that the antibiotic removal device removed amikacin, ampicillin, carbenicillin, cefazolin, cephalothin, chloramphenicol, gentamicin, nafcillin, tetracycline, tobramycin, and vancomycin and reduced cefoxitin and ticarcillin to extremely low levels. Three combinations of antibiotics were similarly removed or reduced. Five species of anaerobic bacteria, one yeast species, and six species of facultative or aerobic bacteria were used to challenge the possibility that the antibiotic removal device would trap or inhibit microorganisms. All were recovered from the device in the same numbers as were inoculated.
Uncertainty decomposition-based fault-tolerant adaptive control of flexible spacecraft

A fault-tolerant adaptive control scheme is developed for attitude tracking of flexible spacecraft with unknown inertia parameters, external disturbance, and actuator faults. The uncertainties of flexibility and dynamics are parameterized, and the control gain matrix uncertainty is handled using an uncertainty decomposition. The control scheme, with adaptive laws of the overall system uncertain parameter estimates, guarantees the system stability and asymptotic attitude tracking properties. Simulation results illustrate the effectiveness of the proposed control scheme.
An Information Bottleneck Approach for Controlling Conciseness in Rationale Extraction

Decisions of complex language understanding models can be rationalized by limiting their inputs to a relevant subsequence of the original text. A rationale should be as concise as possible without significantly degrading task performance, but this balance can be difficult to achieve in practice. In this paper, we show that it is possible to better manage this trade-off by optimizing a bound on the Information Bottleneck (IB) objective. Our fully unsupervised approach jointly learns an explainer that predicts sparse binary masks over sentences, and an end-task predictor that considers only the extracted rationale. Using IB, we derive a learning objective that allows direct control of mask sparsity levels through a tunable sparse prior. Experiments on ERASER benchmark tasks demonstrate significant gains over norm-minimization techniques for both task performance and agreement with human rationales. Furthermore, we find that in the semi-supervised setting, a modest amount of gold rationales (25% of training examples) closes the gap with a model that uses the full input.
Distribution and hormone regulation of estrogen receptor immunoreactive cells in the hippocampus of male and female rats

Estrogen regulates the synaptic plasticity and physiology of the hippocampus as well as learning behaviors that are mediated by the hippocampus. The density of dendritic spines and synapses, the number of N‐methyl‐D‐aspartate (NMDA) binding sites, the levels of NMDA receptor subunit NR1 protein, muscimol binding to the γ‐amino butyric acid (GABA)A receptor, and levels of glutamic acid decarboxylase message in the CA1 region of the hippocampus are altered with estrogen treatment. In addition, some of these parameters exhibit sex differences in their response to estrogen treatment. To establish that estrogen can have a direct effect on the hippocampus and to determine whether or not sex differences in estrogen responsiveness are due to sex differences in estrogen receptor (ER) levels, we used immunocytochemistry with the AS409 antibody to map the location of ER‐immunoreactive (ER‐ir) cells in the hippocampus of male and female rats. We found that (1) the ERs appear to be in interneurons rather than pyramidal or granule cell neurons, (2) ER‐ir cells are located in greatest concentration in the hilus of the dentate gyrus and the stratum radiatum of the CA1 region, (3) the density of ER‐ir cells exhibits a rostral to caudal gradient in the hilus and the CA1 regions, (4) there are no sex differences in either the number or immunostaining intensity of ER‐ir cells in the hippocampus, (5) the ER levels are down‐regulated by estrogen in both male and female rats, and (6) the mean intensity of staining for the ER‐ir cells in the hippocampus is about 25% of that in the ER‐ir cells of the hypothalamus. From this, we can conclude that estrogen can have a direct effect on hippocampal neurons and that any sex differences in estrogen responsiveness is due to something other than sex differences in ER levels or function in the hippocampus. J. Comp. Neurol. 388:603–612, 1997. © 1997 Wiley‐Liss, Inc.