Miracle-dz/UniFAR-FTUs huggingface dataset:
Observations concerning the binding of thyroid hormones in sera of normal subjects of varying ages.

In man, from childhood through senescence, there occur alterations in several metabolic functions that are regulated in part by the thyroid hormones. Thus, aging is associated with a decrease in basal oxygen consumption per unit surface area and an increase in total serum cholesterol and beta-lipoprotein cholesterol (1-5). Several indexes of thyroid function per se indicate greater thyroid activity in children and adolescents than in young adults and, conversely, less thyroid activity in the elderly. The extensive literature on this subject has been considered in recent publications (6, 7). It has been suggested, therefore, that there exist in childhood and senescence states of physiologic hyperand hypothyroidism, respectively (4, 6, 8). It is not clear, however, whether this is truly the case. In this regard it may be significant that, in contrast to the situation in clinically recognizable thyroid disease, the serum protein-bound iodine (PBI) varies little, if at all, throughout the life-span of man (6, 9, 10). Recent studies related to these questions have indicated that the fractional rate of turnover of thyroxine (T4) in peripheral tissues decreases significantly from childhood through senescence (6, 8, 10-12). Since variations in the binding of thyroid hormones to extracellular proteins greatly influence the kinetics of hormonal metabolism (1315), the present studies were undertaken to determine whether the changes in the metabolism of T4 that accompany aging can be ascribed to
Characterization of pinhole SPECT acquisition geometry

A method is presented to estimate the acquisition geometry of a pinhole single photon emission computed tomography (SPECT) camera with a circular detector orbit. This information is needed for the reconstruction of tomographic images. The calibration uses the point source projection locations of a tomographic acquisition of three point sources located at known distances from each other. It is shown that this simple phantom provides the necessary and sufficient information for the proposed calibration method. The knowledge of two of the distances between the point sources proves to be essential. The geometry is estimated by fitting analytically calculated projections to the measured ones, using a simple least squares Powell algorithm. Some mild a priori knowledge is used to constrain the solutions of the fit. Several of the geometrical parameters are however highly correlated. The effect of these correlations on the reconstructed images is evaluated in simulation studies and related to the estimation accuracy. The highly correlated detector tilt and electrical shift are shown to be the critical parameters for accurate image reconstruction. The performance of the algorithm is finally demonstrated by phantom measurements. The method is based on a single SPECT scan of a simple calibration phantom, executed immediately after the actual SPECT acquisition. The method is also applicable to cone-beam SPECT and X-ray CT.
Radiation and Dissipation of Internal Waves Generated by Geostrophic Motions Impinging on Small-Scale Topography: Application to the Southern Ocean

Abstract Recent estimates from observations and inverse models indicate that turbulent mixing associated with internal wave breaking is enhanced above rough topography in the Southern Ocean. In most regions of the ocean, abyssal mixing has been primarily associated with radiation and breaking of internal tides. In this study, it is shown that abyssal mixing in the Southern Ocean can be sustained by internal waves generated by geostrophic motions that dominate abyssal flows in this region. Theory and fully nonlinear numerical simulations are used to estimate the internal wave radiation and dissipation from lowered acoustic Doppler current profiler (LADCP), CTD, and topography data from two regions in the Southern Ocean: Drake Passage and the southeast Pacific. The results show that radiation and dissipation of internal waves generated by geostrophic motions reproduce the magnitude and distribution of dissipation previously inferred from finescale measurements in the region, suggesting that it is one of the.
Nilotinib counteracts thioacetamide‐induced hepatic oxidative stress and attenuates liver fibrosis progression

The aim of this study was to evaluate and compare the effects of imatinib and nilotinib to that of silymarin on established liver fibrosis and oxidative stress in a thioacetamide (TAA) rat model. Male Wistar rats received intraperitoneal (i.p.) injections of TAA (150 mg/kg, twice weekly) for 12 weeks. Daily treatments with imatinib (10 mg/kg), nilotinib (10 mg/kg), and silymarin (100 mg/kg) were administered orally during the last 4 weeks of TAA‐administration. At the end of the study, hepatic damage was evaluated by analysis of liver function tests in serum. Hepatic histopathology and collagen content were employed to quantify liver fibrosis. Hepatic oxidative stress was assessed by measuring malondialdehyde (MDA), 4‐hydroxynonenal (4‐HNE), total nitrate/nitrite (NOx), and reduced glutathione (GSH) contents, as well as myeloperoxidase (MPO) and superoxide dismutase (SOD) activities. Nilotinib, silymarin and, to a lesser extent, imatinib treatments ameliorated TAA‐induced hepatic oxidative stress and damage as indicated by hepatic MDA, 4‐HNE, NOx, GSH, MPO and SOD levels, as well as liver function tests. Hepatic histopathology results revealed that nilotinib, imatinib, and silymarin treatments decreased the mean score of fibrosis in TAA‐treated rats by 24, 14, and 3%, respectively. However, nilotinib and silymarin, but not imatinib, treatments decreased hepatic collagen content in TAA‐treated rats by 17 and 36%, respectively. In conclusion, we demonstrated for the first time that nilotinib not only protected against hepatic oxidative stress, but also slowed down liver fibrosis progression. Thus, we provide the first evidence that nilotinib might be a promising anti‐fibrotic drug.
Fiscal Capacity , Tax Composition and the ( in ) Stability of Government Revenues in the Interwar Period

Large changes in government revenues can have disruptive effects on the action of states and increase uncertainty in the economy. In the interwar period, and during the Great Depression years in particular, many countries experienced such events. This paper investigates how the composition of taxes and countries’ fiscal capacity interacted with economic conditions to determine the evolution of government financing. The results highlight an important role for fiscal capacity in reducing its cyclical volatility. The evidence also indicates that this mitigating effect worked mainly by providing an easier access to borrowing, whereas there is no conclusive evidence for a dampening in the volatility of tax revenues. These findings have significant bearing on the debate regarding policy responses to the Great Depression, indicating that governments were constrained in their actions by past investments aimed at building up fiscal systems. They also lend support to the hypothesis that institutionally-based borrowing constraints can play an important role in fiscal policy procyclicality. This paper also contributes to recent research highlighting the importance of fiscal development by demonstrating the impact of fiscal capacity on cyclical variables. By presenting a novel dataset on the composition of tax revenues at the central and local level, the paper also contributes to a better understanding of the fiscal history of a period, which, in many countries, marked the beginning of far-reaching changes in the role of governments in the economy and in the structure of taxation. JEL: N10, N40, E32, E62, H11, H72
Dietary Metabolites and Chronic Kidney Disease

Dietary contents and their metabolites are closely related to chronic kidney disease (CKD) progression. Advanced glycated end products (AGEs) are a type of uremic toxin produced by glycation. AGE accumulation is not only the result of elevated glucose levels or reduced renal clearance capacity, but it also promotes CKD progression. Indoxyl sulfate, another uremic toxin derived from amino acid metabolism, accumulates as CKD progresses and induces tubulointerstitial fibrosis and glomerular sclerosis. Specific types of amino acids (d-serine) or fatty acids (palmitate) are reported to be closely associated with CKD progression. Promising therapeutic targets associated with nutrition include uremic toxin absorbents and inhibitors of AGEs or the receptor for AGEs (RAGE). Probiotics and prebiotics maintain gut flora balance and also prevent CKD progression by enhancing gut barriers and reducing uremic toxin formation. Nrf2 signaling not only ameliorates oxidative stress but also reduces elevated AGE levels. Bardoxolone methyl, an Nrf2 activator and NF-κB suppressor, has been tested as a therapeutic agent, but the phase 3 clinical trial was terminated owing to the high rate of cardiovascular events. However, a phase 2 trial has been initiated in Japan, and the preliminary analysis reveals promising results without an increase in cardiovascular events.
NEONATAL VITAMIN D STATUS AND RISK OF SCHIZOPHRENIA: A POPULATION-BASED CASE-CONTROL STUDY

CONTEXT Clues from the epidemiology of schizophrenia suggest that low levels of developmental vitamin D may be associated with increased risk of schizophrenia. OBJECTIVE To directly examine the association between neonatal vitamin D status and risk of schizophrenia. DESIGN Individually matched case-control study drawn from a population-based cohort. SETTING Danish national health registers and neonatal biobank. PARTICIPANTS A total of 424 individuals with schizophrenia and 424 controls matched for sex and date of birth. MAIN OUTCOME MEASURES The concentration of 25 hydroxyvitamin D(3) (25[OH]D3) was assessed from neonatal dried blood samples using a highly sensitive liquid chromatography tandem mass spectroscopy method. Relative risks were calculated for the matched pairs when examined for quintiles of 25(OH)D3. RESULTS Compared with neonates in the fourth quintile (with 25[OH]D3 concentrations between 40.5 and 50.9 nmol/L), those in each of the lower 3 quintiles had a significantly increased risk of schizophrenia (2-fold elevated risk). Unexpectedly, those in the highest quintile also had a significantly increased risk of schizophrenia. Based on this analysis, the population-attributable fraction associated with neonatal vitamin D status was 44%. The relationship was not explained by a wide range of potential confounding or interacting variables. CONCLUSIONS Both low and high concentrations of neonatal vitamin D are associated with increased risk of schizophrenia, and it is feasible that this exposure could contribute to a sizeable proportion of cases in Denmark. In light of the substantial public health implications of this finding, there is an urgent need to further explore the effect of vitamin D status on brain development and later mental health.
Some aspects of the developmental biology of neoplasia.

The major goal of the new hybrid science of developmental biology is an understanding in molecular terms of the processes involved in the development of a fertilized ovum to a mature in dividual organism. In the initial session of this symposium sev eral aspects of this topic were discussed, utilizing the unicellular organism as a model and applying knowledge gained therein to an understanding of the development of multicellular organismal systems. A key term utilized by the developmental biologist is that of "differentiation. " However, when one at
Training-induced alterations of carbohydrate metabolism in women: women respond differently from men.

We examined the hypothesis that glucose flux was directly related to relative exercise intensity both before and after a 12-wk cycle ergometer training program [5 days/wk, 1-h duration, 75% peak O2 consumption (VO2 peak)] in healthy female subjects (n = 17; age 23.8 +/- 2.0 yr). Two pretraining trials (45 and 65% of VO2 peak) and two posttraining trials [same absolute workload (65% of old VO2 peak) and same relative workload (65% of new VO2 peak)] were performed on nine subjects by using a primed-continuous infusion of [1-13C]- and [6,6-2H]glucose. Eight additional subjects were studied by using [6, 6-2H]glucose. Subjects were studied postabsorption for 90 min of rest and 1 h of cycling exercise. After training, subjects increased VO2 peak by 25.2 +/- 2.4%. Pretraining, the intensity effect on glucose kinetics was evident between 45 and 65% of VO2 peak with rates of appearance (Ra: 4.52 +/- 0.25 vs. 5.53 +/- 0.33 mg . kg-1 . min-1), disappearance (Rd: 4.46 +/- 0.25 vs. 5.54 +/- 0.33 mg . kg-1 . min-1), and oxidation (Rox: 2.45 +/- 0.16 vs. 4.35 +/- 0.26 mg . kg-1 . min-1) of glucose being significantly greater (P </= 0.05) in the 65% than in the 45% trial. Training reduced Ra (4.7 +/- 0.30 mg . kg-1 . min-1), Rd (4.69 +/- 0.20 mg . kg-1 . min-1), and Rox (3.54 +/- 0.50 mg . kg-1 . min-1) at the same absolute workload (P </= 0. 05). When subjects were tested at the same relative workload, Ra, Rd, and Rox were not significantly different after training. However, at both workloads after training, there was a significant decrease in total carbohydrate oxidation as determined by the respiratory exchange ratio. These results show the following in young women: 1) glucose use is directly related to exercise intensity; 2) training decreases glucose flux for a given power output; 3) when expressed as relative exercise intensity, training does not affect the magnitude of blood glucose flux during exercise; but 4) training does reduce total carbohydrate oxidation.
Plasma Kallikrein Mediates Retinal Vascular Dysfunction and Induces Retinal Thickening in Diabetic Rats

OBJECTIVE Plasma kallikrein (PK) has been identified in vitreous fluid obtained from individuals with diabetic retinopathy and has been implicated in contributing to retinal vascular dysfunction. In this report, we examined the effects of PK on retinal vascular functions and thickness in diabetic rats. RESEARCH DESIGN AND METHODS We investigated the effects of a selective PK inhibitor, ASP-440, and C1 inhibitor (C1-INH), the primary physiological inhibitor of PK, on retinal vascular permeability (RVP) and hemodynamics in rats with streptozotocin-induced diabetes. The effect of intravitreal PK injection on retinal thickness was examined by spectral domain optical coherence tomography. RESULTS Systemic continuous administration of ASP-440 for 4 weeks initiated at the time of diabetes onset inhibited RVP by 42% (P = 0.013) and 83% (P < 0.001) at doses of 0.25 and 0.6 mg/kg per day, respectively. Administration of ASP-440 initiated 2 weeks after the onset of diabetes ameliorated both RVP and retinal blood flow abnormalities in diabetic rats measured at 4 weeks’ diabetes duration. Intravitreal injection of C1-INH similarly decreased impaired RVP in rats with 2 weeks’ diabetes duration. Intravitreal injection of PK increased both acute RVP and sustained focal RVP (24 h postinjection) to a greater extent in diabetic rats compared with nondiabetic control rats. Intravitreal injection of PK increased retinal thickness compared with baseline to a greater extent (P = 0.017) in diabetic rats (from 193 ± 10 μm to 223 ± 13 μm) compared with nondiabetic rats (from 182 ± 8 μm to 193 ± 9 μm). CONCLUSIONS These results show that PK contributes to retinal vascular dysfunctions in diabetic rats and that the combination of diabetes and intravitreal injection of PK in rats induces retinal thickening.
Injury Rates in Iranian Taekwondo Athletes; a Prospective Study

Purpose Taekwondo, as the most popular martial art among Iranian sportsmen, might lead to injury for the athletes of this sport during competitions. We decided to report the incidence rate of injuries sustained by the athletes of this sport during national competitions. Methods All competitions of Iran national championship taekwondo league in 2006-2007 with 204 athletes were observed prospectively to detect the occurrence of injuries. The severity of injuries was classified into four groups (mild, moderate, severe, and critical) according to the involvement of medical care team in the contest, ability of the athletes to resume and duration of probable absence of injured athletes from future competitions and training sessions. Athlete-Exposure (A-E) was defined as the number of competitions multiplied by two. On this base, the rate of injury incidence per 1000 A-Es, the rate of injuries per time unit and the rate of injury occurred for each 100 athletes were considered as the major outcomes of this study. Results Of totally 1,338 A-Es, 93 injuries were recorded during the competitions. The rate of injury incidence was found to be 69.5 injuries per 1000 A-Es and the rate of injuries per minute of competitions was 0.023 which corresponded to 23.3 injuries per 1000 minutes of competitions. 45.6 injuries were occurred for each 100 athletes during the course of competitions. The most frequent injuries were mild (68.8%) and critical injuries (24.7%), followed by moderate and severe injuries; 4.3% and 2.1%, respectively. Conclusion The rate of injury we found was lower than that of western countries. In spite of finding the lower limbs as the most frequent place of injuries in other studies, we found the upper limbs as the most predisposed place of injuries which might be due to difference in the method of combat of Iranian athletes with other athletes.
Cytokines and Alcoholic Liver Disease

Chemical messengers called cytokines play an important role during the body’s initial response to infection (i.e., acute inflammation). Cytokines attract and activate components of the immune system, promote blood clotting, and facilitate the release of additional chemical messengers. In addition, cytokines induce the liver to shift its physiological function, emphasizing inflammatory and immune responses at the expense of normal metabolism. Alcohol consumption may cause excessive cytokine production in the liver, leading to inflammatory liver disease. Researchers are seeking ways to moderate the toxic effects of cytokines while sparing their protective functions.
Multimodality Imaging of Endothelial Progenitor Cells with a Novel Multifunctional Probe Featuring Positive Magnetic Resonance Contrast and Near-Infrared Fluorescence

The multimodal strategy incorporating T1-weighted magnetic resonance imaging (MRI) and near-infrared (NIR) fluorescence imaging can complement their strengths to provide images with high sensitivity and spatial resolution for noninvasively and dynamically monitoring endothelial progenitor cells (EPCs) in potential EPC-dominated therapies. Here we report the development of a protein-based imaging probe, bCD-PLL-Cy5.5 Conjugate 1, in which the bacterial cytosine deaminase (bCD) protein was modified with poly-l-lysine (PLL) that is labeled with imaging reporters, including T1-weighted MRI contrast chelator and NIR fluorophore. Conjugate 1 showed low cytotoxicity in EPCs isolated from the rabbit peripheral blood. The normalized cell viability was maintained above 90% after incubation for 1 to 5 days. Fluorescence microscopy of live cells indicated rapid cellular uptake of Conjugate 1 into EPCs in 15 minutes, and flow cytometry studies demonstrated the time-dependent internalization of Conjugate 1 with maximum uptake 48 hours after the treatment. MRI of phantoms demonstrated significant reduction of the T1 value of the EPC pellet that was pretreated with 2 μM of Conjugate 1 for 24 hours. Our preliminary data suggest that as a multimodal imaging contrast medium, Conjugate 1 offers a promising imaging probe for tracking the delivery and therapeutic response of EPCs in vivo.
Approximate Entropy from Overnight Pulse Oximetry for the Obstructive Sleep Apnea Syndrome

The aim of this preliminary study was to asses whether a time series analysis from overnight pulse oximetry by means of approximate entropy (ApEn) could yield essential information on the diagnosis of obstructive sleep apnea (OSA) syndrome. We analyzed the oxygen saturation (SaO2) signals of 74 patients (44 with a positive diagnosis of OSA and 30 with a negative diagnosis of OSA) by means of ApEn, which quantified the regularity (or complexity) of time series. Results showed that recurrence of apnea events in patients with OSA determined a significant increase in ApEn values with a mean plusmnstandard deviation (SD) of 1.07 plusmn 0.30. A mean plusmn SD ApEn value of 0.47 plusmn 0.25 was estimated in patients without OSA. We obtained an area under the ROC curve of 0.94. The optimum threshold was selected at 0.81, where we achieved a 79.5% sensitivity and 90% specificity. Further analyses are necessary with new and larger data set to test the potential value of our methodology prospectively
Emerging treatments for postmenopausal osteoporosis – focus on denosumab

The pathway of the receptor activator of the nuclear factor κB ligand (RANKL), RANK and osteoprotegerin (OPG) plays a central role in coupling bone formation and resorption during normal bone turnover and in a wide spectrum of diseases characterized by disturbed bone remodeling, increased bone resorption and bone destruction (osteoporosis, Paget’s disease of bone, rheumatoid arthritis [RA], metastatic bone disease). Clinical trials indicate that denosumab, a RANKL-specific recombinant humanized monoclonal antibody, is effective in suppressing bone resorption, resulting in increase in bone mineral density (BMD) in post-menopausal women with low BMD, and has the potential to prevent progression of erosions in RA and of skeletal-related events in metastatic bone disease. The effects on fracture reduction in postmenopausal osteoporosis are awaited from the recently finished FREEDOM study. In clinical trials with denosumab, overall adverse events were similar to placebo or comparators, indicating a favorable safety profile in these diseases, which until now have been available up to 4 years, but data on long-term safety will be needed.
Developmental programming of type 2 diabetes: early nutrition and epigenetic mechanisms

Purpose of reviewThe environment experienced during critical windows of development can ‘programme’ long-term health and risk of metabolic diseases such as type 2 diabetes in the offspring. The purpose of this review is to discuss potential epigenetic mechanisms involved in the developmental programming of type 2 diabetes by early nutrition. Recent findingsMaternal and more recently paternal nutrition have been shown to play key roles in metabolic programming of the offspring. Although the exact mechanisms are still not clear, epigenetic processes have emerged as playing a plausible role. Epigenetic dysregulation is associated with several components that contribute to type 2 diabetes risk, including altered feeding behaviour, insulin secretion and insulin action. It may also contribute to transgenerational risk transmission. SummaryEpigenetic processes may represent a central underlying mechanism of developmental programming of type 2 diabetes. During embryonic and foetal development, extensive epigenetic remodelling takes place not only in somatic but also in primordial germ cells. Therefore, concerns have been raised that epigenetic dysregulation induced by a suboptimal early environment could programme altered phenotypes not only in the first generation but also in the subsequent ones. Characterizing these altered epigenetic marks has great implications for identifying individuals at an increased disease risk as well as potentially leading to novel preventive and treatment strategies.