Miracle-dz/UniFAR-FTUs huggingface dataset:
A long-acting neutralizing monoclonal ACTH antibody blocks corticosterone and adrenal gene responses in neonatal rats.

The control of steroidogenesis in the neonatal adrenal gland is of great clinical interest. We have previously demonstrated that the postnatal day (PD) 2 rat exhibits a large plasma corticosterone response to hypoxia in the absence of an increase in plasma ACTH measured by RIA, whereas the corticosterone response to exogenous ACTH is intact. By PD8, the corticosterone response to hypoxia is clearly ACTH-dependent. We hypothesized that this apparently ACTH-independent response to hypoxia in the newborn rat is due to an increase in a bioactive, non-immunoassayable form of ACTH. To evaluate this phenomenon, we pretreated neonatal rats with a novel, specific, neutralizing anti-ACTH antibody (ALD1611) (20 mg/kg or 1 mg/kg ip) on the morning of PD1, PD7, and PD14. 24 hours later, we measured hypoxia- or ACTH-stimulated plasma ACTH and corticosterone. For long-term effects, ALD1611 was given on PD1 and pups studied on PD8 and PD15. Pretreatment with ALD1611 significantly decreased baseline corticosterone and completely blocked the corticosterone response to hypoxia and exogenous ACTH stimulation at all ages. The effect of 1 mg/kg ALD1611 on PD1 had dissipated by PD15. The decrease in corticosterone in ALD1611 treated pups was associated with decreases in baseline and hypoxia- and ACTH-stimulated adrenal Ldlr, Mrap, and Star mRNA expression at all ages. The adrenal response to hypoxia in the newborn rat is ACTH-dependent suggesting the release of non-immunoassayable, biologically active forms of ACTH. ALD1611 is useful as a tool to attenuate stress-induced, ACTH-dependent adrenal steroidogenesis in vivo.
Combined administration of serogroup B meningococcal vaccine and conjugated serogroup C meningococcal vaccine is safe and immunogenic in college students

SUMMARY This study evaluated the first use of a combination of the lyophilized components of the conjugated group C vaccine Menjugate™ reconstituted with the liquid group B outer membrane vesicle (OMV) vaccine MeNZB™. At 6-week intervals, healthy residential students received three doses of MeNZB alone or concomitantly with one dose of Menjugate (MeNZB+MenC). Short-lasting injection-site reactions of mild or moderate intensity were frequent in both groups. There were no vaccine-related serious adverse events. After three doses, the percentage of subjects with serum bactericidal assay (SBA) titres ⩾1:8 against the serogroup B strain NZ98/254 was 82% for MeNZB+MenC and 78% for MeNZB. All subjects in the MeNZB+MenC group achieved SBA titres ⩾1:8 against serogroup strain C11 and 67% in the MeNZB group. All SBA and ELISA responses of the combined vaccine were at least as good as for MeNZB alone. After vaccination, the pharyngeal carriage rate of any meningococcus in the vaccinated group had declined from 40% to 21%.
Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures

In bone, sclerostin is mainly osteocyte‐derived and plays an important local role in adaptive responses to mechanical loading. Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two‐sample Mendelian randomization (MR). A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta‐analysis of serum sclerostin in 10,584 European‐descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank. Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10−49) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10−11). B4GALNT3 is an N‐acetyl‐galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin‐type O‐linked glycosylation. Using these two single‐nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = –0.12, 95% confidence interval [CI] –0.20 to –0.05) and eBMD (β = –0.12, 95% CI –0.14 to –0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21). Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%). Our findings suggest that higher sclerostin levels are causally related to lower BMD and greater fracture risk. Hence, strategies for reducing circulating sclerostin, for example by targeting glycosylation enzymes as suggested by our GWAS results, may prove valuable in treating osteoporosis. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.
Effects of Inducible Nitric Oxide Synthase Inhibition on the Rat Tail Vascular Bed Reactivity Three Days After Myocardium Infarction

The acute phase of myocardial infarction promotes an inflammatory response that stimulates inducible nitric oxide synthase (iNOS). We investigated the iNOS role on the rat tail vascular bed reactivity 3 days after myocardial infarction. Vasodilator and vasoconstrictor responses were determined in isolated caudal vascular beds from Wistar rats 3 days after coronary artery ligation (CAL) and sham-operated animals (SHAM). Rats were treated with the iNOS inhibitor S-methylisothiourea sulfate (SMT), 5 mg−1 Kg−1 day, i.p. or placebo. Concentration of plasma nitrite/nitrate (NOx) and the expression of iNOS mRNA in tail arteries were evaluated. The CAL group showed increased maximal vasoconstrictor response to phenylephrine (SHAM= 241 ± 8; CAL= 288 ± 13 mm Hg, P < 0.05) and SMT treatment normalized this effect (CAL-SMT = 253 ± 7 mm Hg, P < 0.05). The sensitivity to acetylcholine was reduced in the CAL group, but SMT treatment did not alter this response. The plasma NOx and iNOS mRNA expression in tail arteries were increased in CAL rats. SMT treatment reduced the plasma NOx in the CAL group and the arterial expression of iNOS mRNA in SHAM and CAL group. In conclusion, iNOS inhibition prevented the increased phenylephrine reactivity in rat caudal vascular beds 3 days after myocardial infarction.
Screening of Crude Drugs Used in Japanese Kampo Formulas for Autophagy-Mediated Cell Survival of the Human Hepatocellular Carcinoma Cell Line

Background: Autophagy is a catabolic process through which dysfunctional proteins and organelles are degraded, and that is associated with the proliferation of cancer cells. The aim of this study was to screen approximately 130 kinds of crude drugs used in Japanese Kampo formulas to identify crude drugs that would regulate the proliferation through autophagy of human hepatocellular carcinoma HepG2 cells. Methods: Extracts of each crude drug were prepared using methanol. Protein levels were determined using Western blotting. Cell viability was measured by MTT assay. Results: Among the 130 crude extracts, 24 of them increased LC3-II expression. Among these, Goboshi (burdock fruit), Soboku (sappan wood), Mokko (saussurea root), Rengyo (forsythia fruit), and Hikai (dioscorea) notably suppressed the proliferation of HepG2 cells and increased p62 expression levels, which suggested that these five extracts downregulate the autophagic activity resulting in the accumulation of p62. On the other hand, Hishinomi (water chestnut), Biwayo (loquat leaf), and Binroji (areca) induced cell growth and decreased or were uninvolved with p62 expression levels, which implied that these three extracts might induce autophagy modulators for cell growth. Conclusions: The results suggest that the compounds contained in the crude drugs selected for this study could control cell viability by regulating autophagic activity in HepG2 cells. The isolation and identification of the active compounds in these drugs might lead to the development of agents for autophagy research and cancer chemoprevention.
Do supplements of Acacia mearnsii and grapeseed extracts alone or in combination alleviate metabolic nitrogen load and manure nitrogen emissions of lambs fed a high crude protein diet?

ABSTRACT Diets excessive in crude protein (CP) are unfavourable in terms of metabolic and environmental load. Dietary phenols, often binding to dietary proteins, may alleviate these problems. In an experiment with 60 lambs (3.2 ± 1.6 months of age; 29.7 ± 5.1 kg body weight), kept in pairs, five diets were tested. A diet with 157 g CP/kg dry matter (DM) served as negative control. Four diets with on average 229 (225–233) g CP/kg DM remained either non-supplemented or were supplemented with 13 g/kg DM of Acacia mearnsii extract, grapeseed extract, or a combination of both (26 g extract/kg DM). The analysed concentrations of total extractable phenols were 7.1, 8.1, 14.3, 16.6 and 25.4 g/kg DM for low (CP‒) and high CP (CP+), and high CP with acacia (CP+A), grapeseed (CP+G) and acacia plus grapeseed (CP+AG), respectively. Diets were fed for 10 weeks, and for 6 d faeces and urine were collected and subsequently stored as complete manure for 8 weeks. In blood plasma, phenol concentrations and activities of enzymes indicating liver and kidney stress were analysed. The CP+ diet increased apparent digestibility of N and its removal with the urine, with the expected increase in gaseous N emissions from the manure (13.5 vs 6.5 g/lamb per day during 8 weeks) compared to CP‒. However, no clear signs of metabolic stress were detected. Supplementing the extracts did not impair intake, growth performance and digestibility. Only the supplementation with both extracts decreased urinary N proportion of manure N, and the concomitant weak decline in gaseous emission from the manure was not significant. At least part of the phenols of both extracts seem to be bioavailable as their supplementation elevated blood plasma phenol concentrations by 15% to 40% compared to CP+. A combination of both extracts did not result in a further increase. Further studies have to identify the minimally effective dosage for reducing N emissions, which, at the same time, does not cause adverse side effects in performance.
MICROPLASMIN (OCRIPLASMIN) IN PEDIATRIC VITREORETINAL SURGERY: Update and Review

Purpose: To discuss the potential role of microplasmin (ocriplasmin) as a surgical adjunct to vitrectomy in pediatric vitreoretinopathies. Methods: Literature review of the laboratory and clinical evidence to date for the use of both autologous plasmin enzyme as an adjunct to vitrectomy and more recently recombinant microplasmin (ocriplasmin) as monotherapy for focal vitreomacular traction in adults. Results: Autologous plasmin enzyme is currently being used as a surgical adjunct to vitrectomy, with supporting Levels 2 and 3 published evidence in a range of pediatric vitreoretinopathies including Stage 5 retinopathy of prematurity and congenital X-linked retinoschisis. The availability of autologous plasmin enzyme is limited. In recent Phase 3 clinical trials, intravitreal ocriplasmin versus sham injection resulted in resolution of focal vitreomacular traction in 27% versus 10% (P < 0.001, n = 652). Conclusion: Ocriplasmin may potentially be used as a surgical adjunct to vitrectomy in place of autologous plasmin enzyme. A Phase 2, randomized, placebo-controlled surgical trial is under way to assess this.
IRF5 promoter methylation as a new potential marker of rheumatoid arthritis.

INTRODUCTION The interferon regulatory factor 5 (IRF5) gene is implicated in the Toll-like receptor signaling pathway and has pro-inflammatory and chemotactic effects, but its role in the pathogenesis of rheumatoid arthritis (RA) remains unclear. Since the pathobiology of RA shares some similarities with other autoimmune diseases, we tested the hypothesis that RA may be associated with IRF5-related pathways, as has been reported for systemic lupus erythematosus and Sjogren's Syndrome. OBJECTIVES The aim of the study was to investigate how the presence of methylation in the IRF5 promoter is associated with the morbidity and severity of RA and with levels of inflammatory markers. PATIENTS AND METHODS A total of 146 unrelated subjects, 122 patients with RA and 24 healthy controls, were enrolled in the study. All RA patients were genotyped with regard to the following polymorphisms in the IRF5 gene: rs10488631, T>C and rs4728142 G>A. The methylation study included 52 RA patients and 24 healthy controls. Quantitative real-time methylation-specific polymerase chain reaction was used to evaluate methylation status. RESULTS We found differences between RA patients and healthy controls in the methylation pattern of the promoter region. The methylation level was 43.6% lower in RA patients than in the controls (0.79 [0.6-1.13] vs. 1.4 [1.16-1.66], p=0.0001). Variant rs4728142 G>A was more frequently observed in seronegative RA patients. Conclusions: The methylation profile of the IRF5 promoter may be used as a new potential marker of RA which is independent of current criteria of disease activity.
Synchronous integrator based on digital control system for silicon micromachined gyroscope

For the decoupled dual-mass silicon Micromachined gyroscope developed by Southeast University, drive mode and sense mode are analyzed. In order to improve the precision of silicon Micromachined gyroscope, the demodulation algorithm based on synchronous integrator circuit for gyroscope digital control system is proposed. Combining with Automatic Gain Control (AGC) and Phase-Locked Loop (PLL) technology, the closed-loop control of drive mode and high precision output of sense mode of silicon Micromachined gyroscope have been implemented. In order to verify the effect of the synchronous integrator circuit applied in gyroscope control system, the Print Circuit Board (PCB) based on Field Programmable Gate-Array (FPGA) digital circuit is manufactured and the corresponding experiment is carried out. The results of test show that the synchronous integrator demodulation algorithm of digital control system for silicon Micromachined gyroscope has achieved good performance. The bias stability of tested gyroscope is 0.2o/hr and the angle random walk is measured to be 0.14o/√hr. The results demonstrate that the proposed synchronous integrator demodulation scheme is effective.
On the road to unraveling the molecular functions of ether lipids

Ether lipids are glycerolipids further classified into alkyl‐ether and alkenyl‐ether (also termed plasmalogens) lipids. The two ether lipid subclasses share the first steps of their synthesis. However, alkyl‐ether and alkenyl‐ether lipids differ in their structure and physico‐chemical properties (featuring different head groups) and, thus, probably in their functions. Ether lipids have intermittent distribution across the evolutionary tree and defects in their synthesis have been shown to perturb cellular homeostasis and lead to disease in humans. Here, we review their structure, their interactions with other lipids, and their potential roles in cellular functions, such as membrane homeostasis and membrane trafficking. Moreover, we discuss still unclear aspects of these lipids such as their subcellular distribution, and the need to unravel their molecular functions as well as how novel tools to study lipid biology will help clarify these aspects.
[Prematurity and methods of its screening].

OBJECTIVE Premature delivery is an essential problem in the modern obstetrics. Revealing and marking the high-risk group of pregnant women in time could be used as one of the methods of its prevention. DESIGN Retrospective epidemiological study of the aggregated data of pregnant patients. SETTING OBGYN Clinic of the 1st and 3rd Faculty of Medicine, Prague, FNB, FNKV. METHOD A routine database of pregnant patients was generated. In our study was included the group of 2368 patients who underwent the screening and fulfilled the condition of completion the data in the period from the 15th to the 20th week of pregnancy, during and after the birth. Database is a component of a lager database generated in the last 15 years. The group of premature delivery patients was marked as those who delivered before the beginning of the 10th month of pregnancy. MS-AFP (maternal serum AFP) screening values of pregnants were measured and transformed to the multiples of medians (MOM), corresponding to the particular week of pregnancy for enabling the comparison during the whole period of screening. Statistical investigation was performed using data analysis advanced methods. RESULTS A significant statistical correlation between higher values of MS-AFP, during the period from the 15th to the 20th week of pregnancy, and premature deliveries were found. The cut-off value of 1.8 MOM MS-AFP was included to determine the higher risk group of patients. Women with equal or higher values of AFP were 3.8 times more likely to have premature delivery than those with lower AFP values (95% CI: 2.2;6.3). Sensitivity of 25% and specificity of 92% were proven. CONCLUSION According to our opinion, MS-AFP could not only be used for the hereditary diseases screening, but as well for performing the premature delivery screening at the beginning of the 2nd trimester. Cut-off value of 1.8 MOM for marking the higher risk group was used for marking the high-risk group. Thus the extension of the classical screening technique of hereditary diseases could yield also in other areas of the obstetrical care.
Effects of layer thickness on Power Conversion Efficiency in Perovskite solar cell: A numerical simulation approach

For the past 15 years, traditional solar cells particulary silicon has extended its performance only 1.1 % but within 5 years into the field, the performance of Perovskite solar has enhanced drastically up by 24%. Perovskite based solar cell technologies have been a very appealing area of research in recent years. Natural organic-inorganic perovskite substances are in an expanded evolution in power conversion efficiency. Inorganic substances have been examined on the laboratory stage however their power conversion performance remains constrained due to parameters like layer thickness, irradiance, temperature etc.,. This work is based on GPVDM software program to have a look at the impact of a few parameters on energy conversion efficiency in a perovskite-based heterojunction solar cells. The changes have been made by considering layers of perovskite without defects. The outcomes show that the efficiency of the power conversion can be stepped forward by means of adjusting the layer thickness. Simulation results help us to discover that the electron trap plays a vital role where Power conversion efficiency is also limited by hole and electron trap density.
CME Information: Hodgkin Lymphoma: 2016 update on diagnosis, risk-stratification, and management

No commercial support has been accepted related to the development or publication of this activity. CME Editor: Ayalew Tefferi, M.D. has no relevant financial relationships to disclose. Author: Stephen M. Ansell, M.D., Ph.D. discloses research funding for clinical trials from Bristol Myers Squibb, Seattle Genetics, and Celldex. This activity underwent peer review in line with the standards of editorial integrity and publication ethics maintained by American Journal of Hematology. The peer reviewers have no conflicts of interest to disclose. The peer review process for American Journal of Hematology is single blinded. As such, the identities of the reviewers are not disclosed in line with the standard accepted practices of medical journal peer review. Conflicts of interest have been identified and resolved in accordance with Blackwell Futura Media Services’ Policy on Activity Disclosure and Conflict of Interest. The primary resolution method used was peer review and review by a non-conflicted expert.
Metabotropic Glutamate Receptors Regulate APP Processing in Hippocampal Neurons and Cortical Astrocytes Derived from Fetal Rats a

It has previously been shown that stimulation of muscarinic m1 or m3 receptors can, by generating diacylglycerol (DAG) and activating protein kinase C (PKC), accelerate the breakdown of the amyloid precursor protein (APP) to form soluble, non‐amyloidogenic peptides (APPs). This relationship has been demonstrated in human glioma and neuroblastoma cells as well as in transfected human embryonic kidney (HEK) cells and PC12 cells.1,2
Access to Spoken Language and the Acquisition of Orthographic Structure: Evidence from Deaf Readers

Sensitivity to two types of orthographic structure was investigated: linguistically based orthographic regularity and summed single letter positional frequency. Deaf college students were found to make use of positional frequency information no less than hearing college students; however, the extent to which they made use of orthographic regularities in word recognition was related to their speech production skills. In one task, subjects were presented nonword letter strings for short durations, each followed by a masking stimulus and a target letter. They were asked to indicate whether or not the target had been present in the letter string. It was found that the accuracy of deaf subjects with good speech, like that of hearing subjects, was considerably greater for orthographically regular than irregular strings. In contrast, the accuracy of deaf subjects with poor speech was much less related to orthographic regularity. In a second task, in which subjects made judgements about how word-like various letter strings appeared, the judgements of the hearing subjects were more influenced by regularity than those of deaf subjects with poor speech. These results are discussed in terms of how expertise in speech relates to appreciation of orthographic regularity.
Pediatric Adenocarcinoma in Korea: A Multicenter Study

Purpose Adenocarcinoma is an extremely rare malignancy in the pediatric population. Research regarding pediatric adenocarcinoma is very rare in Korea. This study aimed to investigate the clinical features of pediatric adenocarcinomas of various primary organ sites in Korea. Materials and Methods Pediatric patients under 18 years, diagnosed with adenocarcinoma of various sites between January 1995 and December 2016, were included. We retrospectively reviewed patient and tumor characteristics and calculated survival estimates, reported as 5-year survival rate and 95% confidence interval. Results Of 80 patients (median age, 15 years; range, 10 to 17 years), 37 (46.3%) were men, and 24 (30%) had a family history of cancer or underlying disease relevant to malignancy. The cancer locations were the colon and rectum (n=32), ovaries (n=18), stomach (n=15), lung (n=4), small bowel (n=1), and other sites (n=10). Totally, 54.8% patients (42/77) had stage 3 or 4 disease. The median follow-up period was 2.0 years (range, 0 to 20.4). The 5-year overall survival estimate for all patients, and for those with stomach, colorectal, ovarian, and other cancer sites were 57.9%±11.5%, 58.2%±25.7%, 41.5%±18.2%, 87.5%±16.2%, and 64.0%±34.4%, respectively. The 5-year survival rate differed significantly between categories of adenocarcinomas into gastrointestinal (GI) (44.7%) and non-GI adenocarcinomas (78.8%) (p=0.007). The 5-year survival rate also differed significantly according to carcinoembryonic antigen level (69.3% in < 3 ng/mL, 23.8% in > 3 ng/mL; p < 0.001). Conclusion In pediatric patients, adenocarcinomas arise from various organs and are often diagnosed at advanced stages. Large, prospective studies for their accurate clinical characteristics and prognostic factors are needed.