Miracle-dz/UniFAR-FTUs huggingface dataset:
Follistatin Expression in Human Invasive Breast Tumors: Pathologic and Clinical Associations

Follistatin is a potent native activin antagonist that is expressed in the normal mammary gland and in different breast proliferative diseases. Despite experimental evidence that follistatin can modulate the breast cancer cell cycle, the clinical significance of follistatin expression in these tumors is unknown. The aim of this study was to correlate the intensity of follistatin expression in invasive breast cancer with some of its clinical and pathologic features, such as the disease stage and the hormonal receptor status. Paraffin blocks of tumor samples that had been fixed in buffered formalin were obtained from 154 women subjected to surgery for breast cancer between 2008 and 2012. Sections from all paraffin blocks were cut and processed together by immunohistochemistry using a commercial monoclonal antibody to human follistatin. The intensity of follistatin staining was unrelated to the menopausal status, the disease stage, the grade, progesterone receptor expression, and local or systemic recurrence. However, follistatin immunoreactivity was significantly stronger in estrogen receptor (ER)-negative tumors than in ER-positive tumors. These findings suggest that follistatin expression in invasive breast cancer is unrelated to the disease severity and the risk of recurrence, but is more intense in ER-negative tumors.
Distribution and Diurnal Variations of the Mu Opioid Receptor Expression in the Arcuate Nucleus of the Male Rat

Using an in situ hybridization method with radioactively labeled riboprobes, the distribution of µ-opioid-receptor-expressing cells was investigated in the arcuate nucleus (ARC) of the male rat. We simultaneously tested the hypothesis that expression of µ-opioid receptor mRNA displayed diurnal variations in neurons of the ARC, and an image analysis system was used to measure cellular levels of µ-opioid receptor expression. Rats were sacrificed in groups of 5 at 06.00, 12.00 and 20.00 h. In the ARC, µ-opioid receptor mRNA was expressed in scattered neurons located in ventromedial, ventrodorsal and ventrolateral portions. The level of expression was very low in sections taken from animals sacrificed at 06.00 and 12.00 h. The level of µ-opioid receptor mRNA expression was significantly (p < 0.001) increased in neurons of animals killed at 20.00 h in comparison with the other hours of the day, i.e. 06.00 and 12.00 h. However, the number and general distribution of µ-receptor-expressing neurons did not vary across these time points (p > 0.05). In conclusion, this study presents evidence for the presence of low levels of µ-opioid-receptor-expressing cells in the ARC. We observed that the receptor synthesis increases in the evening. These results suggest that the µ-opioid receptor may play a significant role in modulating the processing of neuropeptides located in this nucleus. The daily rhythm in µ-receptor expression is brought together with the diurnal fluctuation in pro-opiomelanocortin mRNA and the circadian variation in β-endorphin concentrations in the ARC.
HIV infection and the risk of acute myocardial infarction.

IMPORTANCE Whether people infected with human immunodeficiency virus (HIV) are at an increased risk of acute myocardial infarction (AMI) compared with uninfected people is not clear. Without demographically and behaviorally similar uninfected comparators and without uniformly measured clinical data on risk factors and fatal and nonfatal AMI events, any potential association between HIV status and AMI may be confounded. OBJECTIVE To investigate whether HIV is associated with an increased risk of AMI after adjustment for all standard Framingham risk factors among a large cohort of HIV-positive and demographically and behaviorally similar (ie, similar prevalence of smoking, alcohol, and cocaine use) uninfected veterans in care. DESIGN AND SETTING Participants in the Veterans Aging Cohort Study Virtual Cohort from April 1, 2003, through December 31, 2009. PARTICIPANTS After eliminating those with baseline cardiovascular disease, we analyzed data on HIV status, age, sex, race/ethnicity, hypertension, diabetes mellitus, dyslipidemia, smoking, hepatitis C infection, body mass index, renal disease, anemia, substance use, CD4 cell count, HIV-1 RNA, antiretroviral therapy, and incidence of AMI. MAIN OUTCOME MEASURE Acute myocardial infarction. RESULTS We analyzed data on 82 459 participants. During a median follow-up of 5.9 years, there were 871 AMI events. Across 3 decades of age, the mean (95% CI) AMI events per 1000 person-years was consistently and significantly higher for HIV-positive compared with uninfected veterans: for those aged 40 to 49 years, 2.0 (1.6-2.4) vs 1.5 (1.3-1.7); for those aged 50 to 59 years, 3.9 (3.3-4.5) vs 2.2 (1.9-2.5); and for those aged 60 to 69 years, 5.0 (3.8-6.7) vs 3.3 (2.6-4.2) (P < .05 for all). After adjusting for Framingham risk factors, comorbidities, and substance use, HIV-positive veterans had an increased risk of incident AMI compared with uninfected veterans (hazard ratio, 1.48; 95% CI, 1.27-1.72). An excess risk remained among those achieving an HIV-1 RNA level less than 500 copies/mL compared with uninfected veterans in time-updated analyses (hazard ratio, 1.39; 95% CI, 1.17-1.66). CONCLUSIONS AND RELEVANCE Infection with HIV is associated with a 50% increased risk of AMI beyond that explained by recognized risk factors.
Prevention and Management of Platelet Transfusion Refractoriness

Platelet transfusion refractoriness is a major complication of long–term platelet supportive care. Refractoriness may lead to fatal bleeding complications in thrombocytopenic patients. Major factors involved are factors related to the clinical condition of the patient as well as HLA alloimmunisation. Non–alloimmune factors may occur in up to 80% of the patients. However, platelet transfusion outcome is impaired in only 50% of the patients having these conditions. HLA alloimmunisation has been convincingly reduced by the use of leucocyte–depleted transfusions. UV–B irradiation of platelet transfusions may be alternatively used to reduce HLA alloimmunisation. Despite these measures, patients with a history of pregnancy or non–leucocyte–depleted transfusions form HLA antibodies in a high proportion (up to 50%). HPA antibodies play a minor but relatively important role in patients with HLA antibodies. ABO antibodies may play a role in refractoriness, which can be abolished by transfusion of ABO–identical platelets. Screening for the presence of HLA and/or HPA antibodies is indicated in case of transfusion failure after ABO–identical or HLA–matched platelets. If no alloantibodies are detected, further analysis to define a role of drug– related or autoantibodies is required. In case of HLA and/or HPA alloimmunisation associated with refractoriness, matched platelet transfusions are indicated. In case of non–alloimmune factors associated with increased platelet consumption, increasing the transfusion frequency can be considered. Additional investigations are still necessary to define risk factors for secondary HLA alloimmunisation and refractoriness due to non–immune factors to further decrease the incidence of refractoriness.
10 years EU regulation of pediatric medicines – impact on cardiovascular drug formulations

ABSTRACT Introduction: Child-appropriate drug formulations are mandatory for an efficient and safe drug therapy in children. Since the implementation of supportive legislations development of novel drug formulations has significantly been enforced despite the fact that children are a heterogeneous group of patients with varying needs according to age, maturation and disease. Areas covered: In this review, recent advances and current strategies are evaluated how to overcome the specific hurdles in pediatric drug development. For cardiovascular diseases as an example, EMA’s decisions on pediatric investigation plans (PIPs) have been evaluated. New developments with innovative platform technologies such as mini-tablets and orodispersible preparations have been identified indicating a clear shift from liquid preparations to small-sized solid (multiparticulate) or orodispersible dosage forms. Reasons for this shift of paradigm are discussed. Expert opinion: Innovative platform technologies for solid drug dosage forms such as mini-tablets, orodispersible tablets or film preparations will continue to conquer the pharmaceutical market. Still, there are some major issues to be resolved, e.g. how to ensure quality of the new dosage forms and dose accuracy in flexible dosing, but the governmental incentives will continue to accelerate development of pediatric medicines and will bridge the still existing gaps in the near future.
Organ Pathology following Mild Hypothermia Used as Neural Rescue Therapy in Newborn Piglets

The aim of this study was to assess the possible adverse effects of hypothermia, used as neural rescue therapy in a newborn piglet model. Sixteen newborn piglets were subjected to transient cerebral hypoxia-ischaemia by temporary occlusion of the carotid arteries and reduction of the fractional inspired oxygen to 0.12. On resuscitation 11 piglets were maintained normothermic (38.5–39.0°C) and, in order to assess the cerebroprotective effect of hypothermia, 5 piglets were cooled to 35°C for 12 h before normothermia was resumed. At 48 or 64 h following resuscitation the animals were sacrificed and the heart, left kidney, specimens of distal small bowel, lung and liver were removed and histologically sectioned. No microscopic abnormalities of the heart, bowel or lung were observed in hypothermic or normothermic animals. All kidney specimens were normal except one from the normothermic group. Abnormal liver pathology suggestive of hypoperfusion injury was found in 5 normothermic and 3 hypothermic piglets. There was no significant difference in the proportion of piglets with liver abnormality between the two groups. Mild hypothermia following cerebral hypoxia-ischaemia in the newborn piglet was not associated with an increased incidence of non-cerebral organ damage. The hepatic injury observed may be related to umbilical venous catheterisation and has potential relevance to neonatal intensive care.
Inductive learning of attribute path values in typed-unification grammars

This work is aiming to show that inductive logic programming (ILP) is a suitable tool to learn linguistic phenomena in typed-unification grammars, a class of attribute-value grammars increasingly used in natural language processing (NLP). We present a strategy for generating hypothesis spaces for either generalisation or specialisation of attribute-path values inside type definitions. This strategy is the core of a prototype module, extending the LIGHT system for parsing with typed-unification grammars.
Flavobacterium commune sp. nov., isolated from freshwater and emended description of Flavobacterium seoulense.

A Gram-stain-negative, yellow, facultatively-anaerobic, short, rod-shaped, non-spore-forming bacterium, designated PK15T, was isolated from freshwater. Growth was observed at 4-40 °C (optimum, 30 °C), pH 6-9 (optimum, 8), and in the presence of 0-0.8 % (w/v) NaCl (optimum, 0.4 %). Strain PK15T exhibited both catalase and oxidase activities and was able to reduce nitrate. On the basis of 16S rRNA gene sequence similarities, strain PK15T was shown to belong to the genus Flavobacterium with close similarities to Flavobacterium palustre S44T (97.9 %) and Flavobacterium seoulense EM1321T (97.7 %). Menaquinone-6 (MK-6) was the major respiratory quinone, while the G+C content of the genomic DNA was 35.5 (±0.9) mol%. The major polar lipids were phosphatidylethanolamine, three unidentified aminolipids, one unidentified aminophospholipid and three unidentified polar lipids. The predominant cellular fatty acids (≥10 %) were anteiso-C15 : 0 (17.3 %), a summed feature comprising C16 : 1ω7c and/or C16 : 1ω6c (15.1 %) and iso-C15 : 0 (10.0 %). Chemotaxonomic data supported the affiliation of strain PK15T to the genus Flavobacterium. The results of physiological and biochemical tests allowed genotypic and phenotypic differentiation of strain PK15T from strains of closely related species. It was, therefore, evident that PK15T represents a novel species of the genus Flavobacterium, for which the name Flavobacterium commune sp. nov. is proposed with strain PK15T (=KCTC 52562T=JCM 32115T) as the type strain. Based on the results of the chemotaxonomic characterization in the present study, an emended description of Flavobacterium seoulense is also proposed.
Juvenile Taiep rats have shorter dendritic trees in the dorsal field of the hippocampus without spatial learning disabilities

Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an abnormal accumulation of microtubules in the cytoplasm and the processes on their oligodendrocytes. Demyelination is associated with electrophysiological alterations and the mutant had a progressive astrocytosis. The illness is associated with change in cytokine levels and in the expression of different nitric oxide synthase and concomitantly lipoperoxidation in several areas of the brain. However, until now there has been no detailed anatomical analysis of neurons in this mutant. The aim of this study was to analyze the dendritic morphology in the hippocampus using Golgi‐Cox staining and spatial memory through Morris water maze test in young adult (3 months old) taiep rats and compare them with normal Sprague‐Dawley. Our results showed that taiep rats have altered dendritic tree morphology in pyramidal neurons in the CA1 field of the hippocampus, but not in the CA3 region. These morphological changes did not produce a concomitant deficit in spatial memory acquisition or recall at this early stage of the disease. Our results suggest that impairment of dendritic morphology in the CA1 field of the hippocampus is a landmark of the pathology of this progressive multiple sclerosis model.
Accuracy of FENO for diagnosing asthma: a systematic review

Background Measurement of FENO might substitute bronchial provocation for diagnosing asthma. We aimed to investigate the diagnostic accuracy of FENO measurement compared with established reference standard. Methods Systematic review and diagnostic meta-analysis. Data sources were Medline, Embase and Scopus up to 29 November 2015. Sensitivity and specificity were estimated using a bivariate model. Additionally, summary receiver-operating characteristic curves were estimated. Results 26 studies with 4518 participants (median 113) were included. Risk of bias was considered low for six of seven items in five studies and for five items in seven studies. The overall sensitivity in the meta-analysis was 0.65 (95% CI 0.58 to 0.72), the overall specificity 0.82 (0.76 to 0.86), the diagnostic OR 9.23 (6.55 to 13.01) and the area under the curve 0.80 (0.77 to 0.85). In meta-regression analyses, higher cut-off values were associated with increasing specificity (OR 1.46 per 10 ppb increase in cut-off) while there was no association with sensitivity. Sensitivities varied significantly within the different FENO devices, but not specificities. Neither prevalence, age, use of bronchoprovocation in >90% of participants or as exclusive reference standard test, nor risk of bias were significantly associated with diagnostic accuracy. Conclusions There appears to be a fair accuracy of FENO for making the diagnosis of asthma. The overall specificity was higher than sensitivity, which indicates a higher diagnostic potential for ruling in than for ruling out the diagnosis of asthma.
Integrated dead-time SVPWM algorithm for indirect vector controlled two-level inverter fed induction motor drive

This paper proposes a new integrated dead-time space vector pulse width modulation (IDTSVPWM) technique to control a voltage source inverter (VSI) fed induction motor drive. Several pulse width modulation (PWM) algorithms have been reported in the literature to control a VSI fed induction motor drive. The PWM algorithms for real time implementation either require dead band circuits or special protection circuits to avoid malfunction of the inverter. This increases complexity of the experimental set-up. But with the advent of high speed processors it is possible to achieve integrated dead-time insertion in the range of micro-seconds in SVPWM algorithm itself. Hence a new IDTSVPWM algorithm is developed in MATLAB environment. For experimental validation of the proposed work a prototype is developed using STM32F4 Cortex M4 processor for a 1hp VSI fed induction motor drive.
Effects of Ketoconazole on Digoxin Absorption and Disposition in Rat

Digoxin, a cardiac glycoside, is a substrate of the multidrug transporter P-glycoprotein (Pgp), and in rats has also been identified as a substrate for cytochrome P450 3A (CYP3A). Ketoconazole, an antifungal agent, was shown to inhibit Pgp in a multidrug-resistant cell line, and is known to be a potent inhibitor of CYP3A. Here, we determined the effects of ketoconazole on digoxin absorption and disposition in rats. Digoxin was administered intravenously or orally with or without a concomitant oral dose of ketoconazole. When given intravenously, digoxin AUC increased from 93 ± 22 to 486 ± 26 µg·h/l with ketoconazole administration. Similarly, ketoconazole raised the AUC of orally administered digoxin from 63 ± 17 to 411 ± 50 µg·h/l. Concomitant ketoconazole administration prolonged digoxin elimination, yielding a nonlinear pharmacokinetic profile. Using time-averaged values, digoxin bioavailability increased from 0.68 ± 0.18 to 0.84 ± 0.10, while mean absorption time was reduced from 1.1 ± 0.4 to 0.3 ± 0.1 h. Thus, in rats, ketoconazole increases digoxin plasma concentrations, rate of absorption and bioavailability. Although the effects of ketoconazole on AUC could be explained by inhibition of both CYP3A and Pgp, which cannot be differentiated in this study, the decreased mean absorption time can only be explained by inhibition of Pgp in the intestine.
Improvement of Nutritional Status in Patients Receiving Maintenance Hemodialysis after Correction of Renal Anemia with Recombinant Human Erythropoietin

Despite a large body of evidence showing the beneficial effects of successful treatment of anemia with recombinant human erythropoietin (EPO) in patients with end-stage renal disease, controversy remains as to whether EPO treatment of anemia can improve the nutritional status in patients on maintenance hemodialysis. This prompted us to conduct a prospective study in 41 hemodialysis patients with basal hemoglobin less than 9 g/dl. The dose of EPO was increased for 12 weeks to achieve the target hemoglobin concentration of 10 g/dl and then titrated in the following 12 weeks to maintain the target value. Nutritional status was assessed at baseline and after 6 months of follow-up, using the global protein-calorie malnutrition (PCM) index proposed by Bilbrey and Cohen. A low global PCM score indicates better nutrition. The results showed that hemoglobin values significantly increased from 8.7 ± 0.8 g/dl at baseline to 10.7 ± 0.5 g/dl in the 6th month (p < 0.001). No significant changes were observed in the normalized protein catabolic rate and Kt/V during the study period. Global PCM scores improved from 30.0 ± 7.5 to 23.6 ± 3.1 (p < 0.001) and paralleled the correction of anemia by EPO treatment. The data were consistent with a major improvement in the nutritional markers of relative body weight, triceps skinfold, midarm circumference, midarm muscle circumference, serum albumin, serum transferrin and total lymphocyte count in the 6th month as compared to baseline. The percentages of mild and moderate-severe PCM at baseline were 32 and 58%, respectively. These percentages were significantly reduced during the 6th month to 20 and 30%, respectively (p = 0.0004). In summary, correction of renal anemia with EPO improves the nutritional status in hemodialysis patients. A postulated mechanism is that EPO may exhibit anabolic effects, with a better utilization of ingested protein.
Effects of SHP465 mixed amphetamine salts in adults with ADHD in a simulated adult workplace environment

ABSTRACT Objectives: Evaluate the efficacy, duration of effect, and safety of 25 mg SHP465 mixed amphetamine salts (MAS) extended-release versus placebo in adults with attention-deficit/hyperactivity disorder (ADHD). Methods: Adults (18–55 years) with ADHD and with ADHD Rating Scale-IV (ADHD-RS-IV) scores ≥24 were randomized to treatment in a double-blind, 2-period, 2-treatment crossover study utilizing the Adult Workplace Environment (AWE), as described by Wigal and Wigal (J Atten Disord 2006;10:92–111). On day 7 of each 7-day treatment period, efficacy was assessed during a 16.5-hour postdose period. The primary endpoint, Permanent Product Measure of Performance (PERMP) total score, was analyzed in the intent-to-treat population using a mixed linear model of analysis of variance. Secondary endpoints, for which the study was not powered, included PERMP problems attempted and answered correctly, ADHD clinician ratings based on counselor observations and inputs during the Time Segment Rating System (Co-ADHD-RS TSRS), and the ADHD self-rating scale (ADHD-SRS). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs. Results: The least squares mean (95% CI) treatment difference (SHP465 MAS–placebo) for PERMP total score significantly favored SHP465 MAS over placebo when averaged across all postdose assessments (19.29 [10.95, 27.63]; P < 0.0001), with significant treatment differences favoring SHP465 MAS over placebo observed at 4–16 hours postdose (all P < 0.01). TEAEs observed with SHP465 MAS (≥5% of participants) included insomnia, decreased appetite, dry mouth, headache, and anorexia. Mean pulse and blood pressure increases with SHP465 MAS exceeded those of placebo. Conclusions: SHP465 MAS (25 mg) was superior to placebo on PERMP total score, with treatment differences observed from 4 to 16 hours postdose; nominal treatment differences on the ADHD-SRS, but not the Co-ADHD-RS TSRS, were also observed. The safety and tolerability profile of SHP465 MAS was similar to previous reports for SHP465 MAS and other long-acting stimulants. Clinical trials registry: clinicaltrials.gov (NCT00202605; https://clinicaltrials.gov/ct2/show/NCT00202605)
Design of a compliant joint actuator for lower-limb exoskeleton robot

For the rigid actuators of conventional exoskeletons are prone to produce motion impact and jitter, so this paper presents a novel design of compliant joint actuator for solve this situation. For the patient with lower limb disability lose the force perception will lead to them can't perceive the movement impact of the exoskeleton, which can reduce the rehabilitation effect or may cause secondary damage to the wearer. The new areas of robotic actuation have been established that requires more versatile structure. The design of new joint actuator adds compliant mechanism in motion transmission part which has a buffer effect to inhibit the external impacts and shocks, and can measure the output torque of the actuator. And in this paper, the detailed design of the exoskeleton structure is proposed based on the concept of compliant actuator. The content of this paper focuses on the mechanism design of the device and makes finite element simulation in ANSYS. Finally, simulation results of the compliant mechanism can describe the design for new actuator which aims at providing a more friendly interaction than existing exoskeleton actuator.