Miracle-dz/UniFAR-FTUs huggingface dataset:
Survival analysis approach to risk factors associated with hyperlipemia in donkeys.

OBJECTIVE To investigate the effect of gender, body condition, and age as risk factors for the development of hyperlipemia in a population of donkeys. DESIGN Retrospective survival analysis. ANIMALS 130 donkeys with hyperlipemia from a source population of 4,126 donkeys. PROCEDURE A Kaplan-Meier product limit survival method was used to evaluate the effect of gender and body condition on the probability of diagnosis of clinical hyperlipemia. Cox's proportional hazard model was used to evaluate the risk of being diagnosed with hyperlipemia controlling for gender, body condition, and age at entry into the population. RESULTS Female donkeys and donkeys of obese body condition were more at risk for developing hyperlipemia than males or those of moderate or poor body condition, respectively. None of the females in the study was pregnant. Donkeys were more likely to become hyperlipemic soon after entering the source population. Investigation of the effect of age at entry into the population indicated that older animals were at higher risk than younger animals and, controlling for age, the hazard ratios associated with being female and being overweight were 2 and 1.5, respectively. CLINICAL IMPLICATIONS Although pregnancy and lactation are widely acknowledged as risk factors for hyperlipemia, in this population, females and obese donkeys were at highest risk, regardless of pregnancy status. Risk was greatest around the time donkeys first entered the source population. Control of body condition, reduction of stress, and close monitoring of high-risk donkeys might reduce incidences of, or allow more timely intervention for, this potentially fatal condition.
Does Body Weight Influence the Response to Intravenous Tissue Plasminogen Activator in Stroke Patients?

Background: The recommended dose of IV tissue plasminogen activator (t-PA) for ischemic stroke patients weighing >100 kg (ISPW >100 kg) is fixed at 90 mg. Elevated levels of plasminogen activator inhibitor-1 (PAI-1) and impaired fibrinolysis have been reported in heavy patients, suggesting that ISPW >100 kg may require higher doses of t-PA. We hypothesized that ISPW >100 kg are less likely to benefit from IV t-PA compared to patients who weigh ≤100 kg and receive a weight-based dose. Methods: We queried the National Institute of Neurological Disorders and Stroke t-PA study database, and performed multivariate logistic regression analyses to analyze the effects of weight (>100 vs. ≤100 kg) and t-PA dose on functional outcomes at 3 months. Results: Six percent of the t-PA and 10% of the placebo cohorts had an actual body weight >100 kg. Weight >100 kg emerged as a predictor of worse outcome (OR = 5.76; p = 0.017) and neurological deterioration (OR = 3.4; p = 0.07) after t-PA. This negative impact of body weight on outcome was not seen among placebo-treated patients. We also found a trend for an association between lower doses of t-PA and unfavorable 3-month outcomes in t-PA-treated patients (OR = 1.9; p = 0.05). Conclusions: ISPW >100 kg seem to derive less benefit from IV t-PA than their lighter counterparts. This may be partly attributed to the use of fixed non-weight-adjusted dosing in heavier patients. The mechanism(s) underlying this observation and its potential therapeutic implications require further investigations.
[Local treatment of chronic arthritis with radionuclides].

Radiosynoviorthesis plays an important role in local treatment of rheumatoid arthritis. Depending on the size of the joint, radionuclides are used at different depths of penetration. Data from the literature and our own results with 396 treated joints indicate that in 2/3 of cases good therapeutic effects are achieved, e.g. the effect on the local inflammatory process is comparable with surgical synovectomy. This is in agreement with the results of our longterm follow-up of 141 joints after radiosynoviorthesis. As with surgical synovectomy, early synoviorthesis was most successful; however, longterm observations revealed a slight increase in local recurrences. These and primary non-responder cases show a good response to secondary injection of radionuclides. The effect of intraarticular injection of isotopes is possibly due to irradiative action on the inflamed cells, with subsequent fibrosis of the synovium. Side effects of radiosynoviorthesis are rare and generally avoidable. Since late complications cannot be excluded, careful consideration should be given to the indication for radiosynoviorthesis. Radiosynoviorthesis represents an alternative treatment to surgical synovectomy in patients over 40 years of age.
Robust Computer Algebra, Theorem Proving, and Oracle AI

In the context of superintelligent AI systems, the term “oracle” has two meanings. One refers to modular systems queried for domain-specific tasks. Another usage, referring to a class of systems which may be useful for addressing the value alignment and AI control problems, is a superintelligent AI system that only answers questions. The aim of this manuscript is to survey contemporary research problems related to oracles which align with long-term research goals of AI safety. We examine existing question answering systems and argue that their high degree of architectural heterogeneity makes them poor candidates for rigorous analysis as oracles. On the other hand, we identify computer algebra systems (CASs) as being primitive examples of domain-specific oracles for mathematics and argue that efforts to integrate computer algebra systems with theorem provers, systems which have largely been developed independent of one another, provide a concrete set of problems related to the notion of provable safety that has emerged in the AI safety community. We review approaches to interfacing CASs with theorem provers, describe well-defined architectural deficiencies that have been identified with CASs, and suggest possible lines of research and practical software projects for scientists interested in AI safety.
Extensive cortical spongiform changes with cerebellar small amyloid plaques: The clinicopathological case of MV2K+C subtype in Creutzfeldt‐Jakob disease

We report a clinical case report of the MV2K+C subtype of sporadic Creutzfeldt‐Jakob disease (sCJD). The patient was a 72‐year‐old woman who exhibited progressive dementia over the course of 22 months. Diffusion‐weighted MRI during this period showed abnormal hyperintensity in the cerebral cortex in the early stage. The clinical course was similar to that of previously reported patients with the MV2K or MV2K+C subtype of sCJD. However, histopathological examination revealed unique features: severe extensive spongiform changes with perivacuolar deposits in the cerebrum and basal ganglia, plaque‐like PrP deposits in the cerebrum, and only mild changes in the cerebellum with small amyloid plaques (∼20 μm in diameter), smaller than those in the MV2K subtype or variant CJD (40–50 μm in diameter). Molecular analysis showed a methionine/valine heterozygosity at codon 129 and no pathogenic mutation in the PrP gene (PRNP). Western blot analysis of the protease‐resistant PrP (PrPSc) in the right temporal pole revealed the type 2 pattern, which is characterized by a single unglycosylated band, in contrast to the doublet described for the typical MV2 subtype of sCJD. The other intermediate band might exist in the cerebellum with kuru plaques. Therefore, small amyloid plaques in the cerebellum can be crucial for MV2K+C subtype.
Differential Expression of Estrogen Receptors in Two Hippocampal Regions During the Estrous Cycle of the Rat

In the hippocampus, estrogens increase dendritic arborization, long‐term potentiation, neuroprotection, and participate in many functions related with learning, memory, and affective behaviors. The presence of both estrogen receptors alpha (ERα) and beta (ERβ) isoforms has been described in the hippocampus where they play different physiological roles. The aim of this study was to investigate, by using both techniques immunohistochemistry and Western Blot, the expression pattern of ERα and ERβ in the hippocampus of the rat along the estrous cycle. Western blot analysis was used to confirm the specificity of the antibodies used against ERα and ERβ and its relative content in the hippocampus. Results from immunohistochemical studies indicate that ERβ expression increased more than the ERα in CA1 and CA3 regions during all phases of the estrous cycle. ERβ immunoreactivity was mainly located in the nucleus and predominantly expressed in CA1 during estrous and metestrus, and in CA3 during diestrus. ERα was more abundant during estrous in comparison to other phases of the cycle in CA1 region, while it was more abundant during metestrus in CA3. Interestingly, the immunolocalization of ERα subtype was both cytoplasmic and nuclear. The overall results indicate that there is a differential expression, cellular localization, and distribution of both ER subtypes in CA1 and CA3 regions, suggesting different roles for these two receptors in the hippocampus along the estrous cycle. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
Transcriptional and Electrophysiological Maturation of Neocortical Fast-Spiking GABAergic Interneurons

Fast-spiking (FS) interneurons are important elements of neocortical circuitry that constitute the primary source of synaptic inhibition in adult cortex and impart temporal organization on ongoing cortical activity. The highly specialized intrinsic membrane and firing properties that allow cortical FS interneurons to perform these functions are attributable to equally specialized gene expression, which is ultimately coordinated by cell-type-specific transcriptional regulation. Although embryonic transcriptional events govern the initial steps of cell-type specification in most cortical interneurons, including FS cells, the electrophysiological properties that distinguish adult cortical cell types emerge relatively late in postnatal development, and the transcriptional events that drive this maturational process are not known. To address this, we used mouse whole-genome microarrays and whole-cell patch clamp to characterize the transcriptional and electrophysiological maturation of cortical FS interneurons between postnatal day 7 (P7) and P40. We found that the intrinsic and synaptic physiology of FS cells undergoes profound regulation over the first 4 postnatal weeks and that these changes are correlated with primarily monotonic but bidirectional transcriptional regulation of thousands of genes belonging to multiple functional classes. Using our microarray screen as a guide, we discovered that upregulation of two-pore K+ leak channels between P10 and P25 contributes to one of the major differences between the intrinsic membrane properties of immature and adult FS cells and found a number of other candidate genes that likely confer cell-type specificity on mature FS cells.
Relaxin Counteracts Asthma-Like Reaction Induced by Inhaled Antigen in Sensitized Guinea Pigs.

In previous studies, the peptide hormone relaxin (RLX) was found to inhibit mast cell secretion and platelet activation. It has been established that the release of mediators from these cells plays a central pathogenic role in allergic asthma. This prompted us to ascertain whether RLX may counteract the respiratory and histopathological abnormalities of the asthma-like reaction to inhaled antigen in sensitized guinea pigs. Guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received RLX (30 microg/kg BW, twice daily for 4 days) before antigen challenge. Other animals received inactivated RLX in place of authentic RLX. Respiratory abnormalities, such as cough and dyspnea, were analyzed as were light and electron microscopic features of lung specimens. RLX was shown to reduce the severity of respiratory abnormalities, as well as histological alterations, mast cell degranulation, and leukocyte infiltration in sensitized guinea pigs exposed to ovalbumin aerosol. RLX was also found to promote dilation of alveolar blood capillaries and to reduce the thickness of the air-blood barrier. This study provides evidence for an antiasthmatic property of RLX and raises the possibility of new therapeutic strategies for allergic asthma in humans.
Is the cognitive function of older patients affected by antihypertensive treatment? Results from 54 months of the Medical Research Council's treatment trial of hypertension in older adults

Abstract Objective: To establish whether initiation of treatment with diuretic or β blocker is associated over 54 months with change in cognitive function. Design: A cognitive substudy, nested within a randomised, placebo controlled, single blind trial. Setting: 226 general practices from the Medical Research Council's general practice research framework. Subjects: A subset of 2584 subjects sequentially recruited from among the 4396 participants aged 65-74 in the trial of treatment of hypertension in older adults. The 4396 subjects were randomised to receive diuretic, β blocker, or placebo. Subjects had mean systolic pressures of 160-209 mm Hg and mean diastolic pressures <115 mm Hg during an eight week run in. Outcome measures: The rate of change in paired associate learning test (PALT) and trail making test part A (TMT) scores (administered at entry and at 1, 9, 21, and 54 months) over time. Results: There was no difference in the mean learning test coefficients (rate of change of score over time) between the three treatments: diuretic -0.31 (95% confidence interval -0.23 to -0.39), β blocker -0.33 (-0.25 to -0.41), placebo -0.30, (-0.24 to -0.36). There was also no difference in the mean trail making coefficients (rate of change in time taken to complete over time) between the three groups: diuretic -2.73 (95% confidence interval -3.57 to -1.88), β blocker -2.08 (-3.29 to -0.87), placebo -3.01, (-3.69 to -2.32). A less conservative protocol analysis confirmed this negative finding. Conclusion: Treating moderate hypertension in older people is unlikely to influence, for better or for worse, subsequent cognitive function. Key messages Key messages Studies have shown that treating hypertension in older adults reduces cardiovascular mortality and morbidity Treating moderate hypertension with either diuretic or β blocker does not seem to influence cognitive function Concerns about damaging cognition should not deter doctors from treating hypertension in older patients Age should no longer be a factor in the decision to initiate antihypertensive treatment
Prolonged low‐dose dopamine infusion induces a transient improvement in renal function in hemodynamically stable, critically ill patients: A single‐blind, prospective, controlled study

Objective: To evaluate the length of the effects of long‐term (48 hrs), low‐dose dopamine infusion on both renal function and systemic hemodynamic variables in stable nonoliguric critically ill patients. Design: Prospective, single‐blind, controlled clinical study. Setting: University hospital, 19‐bed multidisciplinary intensive care unit. Patients: Eight hemodynamically stable, critically ill patients with a mild nonoliguric renal impairment (creatinine clearance between 30 and 80 mL/min). Interventions: Each patient consecutively received 4 hrs of placebo, followed by a 3 μg/kg/min dopamine infusion during 48 hrs, then a new 4‐hr placebo period. We measured cardiac output and other hemodynamic variables by using a pulmonary artery catheter. The bladder was emptied to determine urine volume and to collect urine samples. Measurements were performed at six times: after the initial control of 4 hrs of placebo (C1); after 4 hrs (H4), 8 hrs (H8), 24 hrs (H24), and 48 hrs (H48) of dopamine infusion; and after the second control of 4 hrs of placebo (C2). Measurements and Main Results: We saw no significant change in systemic hemodynamic variables with dopamine at all times of infusion. Diuresis, creatinine clearance, and the fractional excretion of sodium (FeNa) at C1 and C2 were not different. Urine flow, creatinine clearance, and FeNa increased significantly 4 hrs after starting dopamine (for all these changes, p < .01 vs. C1 and C2). The maximum changes were obtained at H8, with an increase of 50% for diuresis, 37% for creatinine clearance, and 85% for FeNa (for all these changes, p < .01 vs. C1 and C2). But these effects waned progressively from H24, and both creatinine clearance and FeNa at H48 did not differ from control values. Conclusions: In stable critically ill patients, preventive low‐dose dopamine increased creatinine clearance, diuresis, and the fractional excretion of sodium without concomitant hemodynamic change. These effects reached a maximum during 8 hrs of dopamine infusion. But despite a slight persistent increase in diuresis, improvement in creatinine clearance and FeNa disappeared after 48 hrs. According to these data, it is likely that tolerance develops to dopamine‐receptor agonists in critically ill patients at risk of developing acute renal failure.
Characterization of a novel and functional human prolactin receptor isoform (deltaS1PRLr) containing only one extracellular fibronectin-like domain.

Prolactin (PRL)-dependent signaling occurs as the result of ligand-induced homodimerization of the PRL receptor (PRLr). To date, short, intermediate, and long human PRLr isoforms have been characterized. To investigate the expression of other possible human PRLr isoforms, RT-PCR was performed on mRNA isolated from the breast carcinoma cell line T47D. A 1.5-kb PCR fragment was isolated, subcloned, and sequenced. The PCR product exhibited a nucleotide sequence 100% homologous to the human long isoform except bp 71-373 were deleted, which code for the S1 motif of the extracellular domain. Therefore, this isoform was designated the deltaS1 PRLr. Northern analysis revealed variable deltaS1 PRLr mRNA expression in a variety of tissues. Transfection of Chinese hamster ovary cells with deltaS1 cDNA showed the isoform is expressed at the protein level on the cell surface with a molecular mass of approximately 70 kDa. Kinetic studies indicated the deltaS1 isoform bound ligand at a lower affinity than wild-type receptor. The deltaS1 PRLr was also shown to activate the proximal signaling molecule Jak2 upon addition of ligand to transfected cells, and, unlike the long PRLr, high concentrations of ligand did not function as a self-antagonist to signaling during intervals of PRL serum elevation, i.e. stress and pregnancy. Given its apparent widespread expression, this PRLr isoform may contribute to PRL action. Furthermore, the functionality of this receptor raises interesting questions regarding the minimal extracellular domain necessary for ligand-induced receptor signaling.
Novel CYP4V2 mutations associated with Bietti crystalline corneoretinal dystrophy in Chinese patients.

AIM To analyze the CYP4V2 mutations in five unrelated Chinese patients with Bietti crystalline corneoretinal dystrophy (BCD) and to provide clinical features of these patients. BCD is a rare monogenic autosomal recessively inherited disorder characterized by the presence of crystals in the retina and retinal pigment epithelium atrophy. Mutations in the CYP4V2 gene have been found to be causative for BCD. METHODS Ophthalmic examinations were carried out in the affected individuals. Peripheral blood samples were collected and genomic DNA was extracted. All exons and flanking intronic regions of the CYP4V2 gene were amplified with polymerase chain reaction and screened for mutations by direct DNA sequencing. One hundred control chromosomes were also screened to exclude nonpathogenic polymorphisms. RESULTS Fundus examination revealed the presence of tiny yellowish-sparkling crystals at the posterior pole of the fundus and atrophy of the retinal pigment epithelium in all patients. Choroid neovascularization was noted in one patient. Five different CYP4V2 mutations were identified, including two missense mutations (p.F73L, p.R400H), two splice site mutations (c.802-8_810del17insGC, c.1091-2A>G), and one single base-pair deletion (p.T479TfsX7 or c.1437delC). The two splice site mutations were identified in three of the patients with BCD. Mutation p.T479TfsX7 was a novel mutation not observed in any of 100 ethnically matched control chromosomes. CONCLUSION Mutation c.802-8_810del17insGC and c.1091-2A>G are common mutations in Chinese patients with BCD. Our results expand the allelic heterogeneity of BCD.
Effects of Multicycle-Run Training on Triathlete Performance

Abstract The purpose of this study was to determine the effect of triathlon training using multiple, short cycle-run sequences (multicycle-run training) on cycle-run performance. Twelve competitive triathletes, randomized into two groups, underwent multicycle-run training or normal training for 6 weeks. During this period, baseline training remained the same for both groups, and only the high-intensity component differed. The differentiated exercises were performed at or above 100% maximal aerobic velocity. The improvements in overall cycle-run performance were similar (3.3 ± 1.4 % and 6.1 ± 1.7 % rise in performance in multicycle-run and normal training, respectively). However, the improvement in performance was significantly greater for the multicycle-run training (- 11.2 ± 6.8 s versus −1.2 ± 7.7 s for multicycle-run training and normal training, respectively) during both the cycle-run change and the first 333-m lap, which together are termed the cycle-run transition. We concluded that 6 weeks of multicycle-run training did not induce greater improvement in cycle-run performance than did normal training in competitive triathletes. However, it did induce significant improvement in the cycle-run transition. This finding indicates that multicycle-run training may help competitive triathletes to develop greater skill and better physiological adaptations during this critical transition period of the triathlon race.
Calcium-dependent Protein Interactions in MUC5B Provide Reversible Cross-links in Salivary Mucus*

The macromolecular organization within saliva was investigated by tracer diffusion measurements of fluorescent polystyrene microspheres by fluorescence recovery after photobleaching using a confocal microscope (confocal-FRAP). There was a concentration-dependent reduction in microsphere diffusion; this was much greater in the presence of calcium (10 mm) and was reduced by the addition of EGTA (10 mm). These effects on tracer diffusion showed that native saliva contained a macromolecular organization that was sensitive to free calcium concentrations. This was supported by a major increase in the weight average molecular weight of the high molecular weight mucin fraction in saliva (10–62 × 106) and an increase in intrinsic viscosity of saliva (733 to 1203 ml/g) both caused by calcium. Analysis of the change in tracer diffusion in saliva showed a 20-fold increase in the apparent pore size (from 130 nm in 10 mm CaCl2 to 2600 nm in 10 mm EGTA at physiological concentration). The effect was specific for calcium and was unaffected by up to 2 m NaCl. The calcium binding activity was contained in a high buoyant density fraction of saliva excluded from Sepharose CL-2B. Calcium binding to this fraction gave an approximate Kd of 7 × 10–6 m, and the binding was irreversibly destroyed by treatment with 6 m guanidinium chloride and by mild reduction, suggesting it to be to a protein site. This fraction of saliva was shown to contain MUC5B as the single major protein species by positive ion electrospray ionization-tandem mass spectrometry analysis. The results suggested that oligomeric MUC5B in saliva is assembled into much larger linear or branched assemblies through calcium-mediated protein cross-links.