Miracle-dz/UniFAR-FTUs huggingface dataset:
Increases in bone mineral density in response to oral dehydroepiandrosterone replacement in older adults appear to be mediated by serum estrogens.

CONTEXT The mechanisms by which dehydroepiandrosterone (DHEA) replacement increases bone mineral density (BMD) in older adults are not known. OBJECTIVE The aims were to determine the effects of DHEA therapy on changes in sex hormones and IGF-I and their associations with changes in BMD. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blinded, placebo-controlled trial was conducted at an academic research institution. Participants were 58 women and 61 men, aged 60-88 yr, with low serum DHEA sulfate (DHEAS) levels. INTERVENTION The intervention was oral DHEA 50 mg/d or placebo for 12 months. MAIN OUTCOME MEASURES BMD and serum DHEAS, testosterone, estradiol (E(2)), estrone (E(1)), SHBG, IGF-I, and IGF binding protein 3 were measured before and after intervention. Free testosterone and estrogen (FEI) indices were calculated. RESULTS The average changes in hip and spine BMD (DHEA vs. placebo) ranged from 1.1 to 1.6%. Compared with placebo, DHEA replacement increased serum DHEAS, testosterone, free testosterone index, E(1), E(2), FEI, and IGF-I (all P < 0.001) and decreased SHBG (P = 0.02) in women and, in men, increased DHEAS, E(1), FEI (all P < 0.001), and E(2) (P = 0.02) and decreased SHBG (P = 0.037). The changes in total and regional hip BMD were associated with 12-month E(2) (all P <or= 0.001) and FEI (all P <or= 0.013). The effects of DHEA treatment were eliminated by adjustment for 12-month E(2). CONCLUSIONS The significant increases in hip BMD in older adults undergoing DHEA replacement were mediated primarily by increases in serum E(2) rather than direct effects of DHEAS.
Validation of a food frequency questionnaire for assessing dietary intake in a study of coronary heart disease risk factors in children.

A food frequency questionnaire (FFQ) was designed and validated for use in an epidemiological survey measuring coronary heart disease risk factors in British children. The questionnaire asked about the frequency of children's consumption of 35 food items over the previous month and was completed by parents/guardians. Food items represented a range of food groups from which children may eat, with emphasis on foods with a high fat and fibre content. The questionnaire was validated against 14 daily recalls of consumption, using the same food list as the FFQ. The sample consisted of 272 children, aged 5-11 years, The response rate for the FFQ was 92% and for the recall, 82% in the first week and 66% in the second week. The level of agreement between the FFQ and the recall was measured by calculating (McGinnis JM & Nestle M, 1989, Am. J. Clin. Nutr. 49, 23-28) the median difference between results from the two methods and (Willett WC (ed.), 1990, Nutritional epidemiology, ch. 15; Oxford University Press) the percentage of children classified by FFQ to within +/- 1 day per week of the recall. Median differences between individual items on the questionnaire and the recall were < or = 0.5 days for 91% of items and equal to 1 day for the remainder. The percentage agreement to within +/- 1 day per week between frequencies reported in the two methods ranged from 99.8% for lamb to 46.8% for low-fibre cereal. Better agreement was found for food items representative of fat intake than those of fibre intake. (ABSTRACT TRUNCATED AT 250 WORDS)
A low-power time-interleaved 128-point FFT for IEEE 802.15.3c standard

This paper proposed a 128-point FFT for low data rate Audio Visual PHY (AVPHY) mode of IEEE 802.15. 3c standard. The architecture process a continuous flow of 2 samples in parallel, leading to a throughput of 317.25 MSamples/s with a symbol duration 492 ns. The FFT computed in seven stages that uses radix-2 butterflies and complex rotations. The radix-2 butterflies and complex rotations are time-interleaved by factor of 2. This technique increases the area slightly for the radix-2 butterflies and complex rotators than the conventional radix-2 butterfly and complex rotator. However, this technique reduces the operating frequency of the radix-2 butterflies and complex rotators, which results the reduction of the power consumption of the whole FFT. Besides, the proposed architecture meets requirements of the throughput and latency. Experimental results reveal that besides its requirements, the design is efficient in area and power consumption, improving the results of previous approaches. Specifically, the proposed design consumes 2.87 mW and its area is 0.57 mm2, while the wordlength is 16 bits.
Comparison Between High-Holding-Voltage SCR and Stacked Low-Voltage Devices for ESD Protection in High-Voltage Applications

The modified silicon-controlled rectifier (SCR) fabricated in a 0.25-<inline-formula> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> high-voltage (HV) bipolar-CMOS-DMOS (BCD) technology has been proposed to seek for both effective electrostatic discharge (ESD) protection and latchup immunity. Experimental results show that one of the proposed SCRs has a high holding voltage of up to ~30 V in the 100-ns transmission line pulsing measurement results. However, through the experimental verification by using the transient latchup test, the holding voltage of such proposed device decreases to ~20 V. It is due to the increased bipolar junction transistor current gains of the SCR path induced by the Joule-heating effect in the long-term measurement. For 20-V circuit applications, the ESD robustness of the proposed SCR with a holding voltage of ~20 V is lower than that of stacked low-voltage p-type MOS in the previous studies. Developing special modification of such HV devices is inefficient to achieve both effective ESD protection and latchup-free design in this 0.25-<inline-formula> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> HV BCD technology.
Earlier Positivity of Central-Venous- versus Peripheral-Blood Cultures Is Highly Predictive of Catheter-Related Sepsis

ABSTRACT To diagnose catheter-related sepsis without removing the catheter, we evaluated the differential positivity times of cultures of blood drawn simultaneously from central venous catheter and peripheral sites. In a 450-bed cancer reference center, simultaneous central- and peripheral-blood cultures were prospectively performed for patients with suspicion of catheter-related sepsis over an 18-month period. Data for 64 patients for whom the same microorganisms were found when central- and peripheral-blood samples were cultured were retrospectively reviewed by two independent physicians blinded to the differential positivity time values in order to establish or refute the diagnosis of catheter-related sepsis. The diagnosis was established in 28 cases, refuted in 14, and indeterminate in the remaining 22. The differential positivity time was significantly greater for patients with catheter-related sepsis (P < 10−4). A cutoff limit of +120 min had 100% specificity and 96.4% sensitivity for the diagnosis of catheter-related sepsis. These results strongly suggest that measurement of the differential positivity time might be a reliable tool facilitating the diagnosis of catheter-related sepsis in patients with an indwelling catheter.
An overview of testicular germ cell tumors.

CONTEXT More than 90% of testicular neoplasms originate from germ cells. Testicular germ cell tumors (GCTs) are a heterogeneous group of neoplasms with diverse histopathology and clinical behavior. OBJECTIVE To help the readers distinguish various subtypes of GCTs, to highlight the clinical manifestations and pathologic features of these tumors, and to review several newly developed immunohistochemical markers for GCTs. DATA SOURCES Review of the pertinent literature and our experience. CONCLUSIONS The etiology of GCTs is largely unknown. Cytogenetic studies suggest a different pathogenesis for each group of infantile/prepubertal GCTs, postpubertal GCTs, and spermatocytic seminoma. Unclassified intratubular germ cell neoplasia is the precursor of all GCTs, excluding spermatocytic seminoma and infantile/prepubertal GCTs. Seminoma, the most common GCT in adults, does not occur before 5 years of age. Spermatocytic seminoma, a tumor of elderly men, typically has an indolent clinical behavior, but rarely it undergoes sarcomatous transformation associated with an aggressive behavior. Embryonal carcinoma is the most common component in mixed GCTs. Eighty percent or more of embryonal carcinoma component and vascular invasion are recognized predictors of occult metastasis for clinical stage I mixed GCTs. Most patients with prepubertal yolk sac tumor, the most common pediatric GCT, have stage I disease at presentation. Most choriocarcinomas present with metastatic symptoms because of the propensity for rapid hematogenous dissemination. Teratomas in children regardless of maturity and dermoid cysts in adults are benign; in contrast, teratomas in adults have a malignant behavior. With appropriate therapy, the majority of testicular GCTs are curable.
Characterization of a Novel Dye-Decolorizing Peroxidase (DyP)-Type Enzyme from Irpex lacteus and Its Application in Enzymatic Hydrolysis of Wheat Straw

Irpex lacteus is a white rot basidiomycete proposed for a wide spectrum of biotechnological applications which presents an interesting, but still scarcely known, enzymatic oxidative system. Among these enzymes, the production, purification, and identification of a new dye-decolorizing peroxidase (DyP)-type enzyme, as well as its physico-chemical, spectroscopic, and catalytic properties, are described in the current work. According to its N-terminal sequence and peptide mass fingerprinting analyses, I. lacteus DyP showed high homology (>95%) with the hypothetical (not isolated or characterized) protein cpop21 from an unidentified species of the family Polyporaceae. The enzyme had a low optimal pH, was very stable to acid pH and temperature, and showed improved activity and stability at high H2O2 concentrations compared to other peroxidases. Other attractive features of I. lacteus DyP were its high catalytic efficiency oxidizing the recalcitrant anthraquinone and azo dyes assayed (kcat/Km of 1.6 ï¿½ 106 s-1 M-1) and its ability to oxidize nonphenolic aromatic compounds like veratryl alcohol. In addition, the effect of this DyP during the enzymatic hydrolysis of wheat straw was checked. The results suggest that I. lacteus DyP displayed a synergistic action with cellulases during the hydrolysis of wheat straw, increasing significantly the fermentable glucose recoveries from this substrate. These data show a promising biotechnological potential for this enzyme.
Adjuvant Drug-Assisted Bone Healing: Advances and Challenges in Drug Delivery Approaches

Bone defects of critical size after compound fractures, infections, or tumor resections are a challenge in treatment. Particularly, this applies to bone defects in patients with impaired bone healing due to frequently occurring metabolic diseases (above all diabetes mellitus and osteoporosis), chronic inflammation, and cancer. Adjuvant therapeutic agents such as recombinant growth factors, lipid mediators, antibiotics, antiphlogistics, and proangiogenics as well as other promising anti-resorptive and anabolic molecules contribute to improving bone healing in these disorders, especially when they are released in a targeted and controlled manner during crucial bone healing phases. In this regard, the development of smart biocompatible and biostable polymers such as implant coatings, scaffolds, or particle-based materials for drug release is crucial. Innovative chemical, physico- and biochemical approaches for controlled tailor-made degradation or the stimulus-responsive release of substances from these materials, and more, are advantageous. In this review, we discuss current developments, progress, but also pitfalls and setbacks of such approaches in supporting or controlling bone healing. The focus is on the critical evaluation of recent preclinical studies investigating different carrier systems, dual- or co-delivery systems as well as triggered- or targeted delivery systems for release of a panoply of drugs.
T2 hypointensity in the deep gray matter of patients with benign multiple sclerosis

Background Gray matter (GM) magnetic resonance imaging (MRI) T2 hypointensity, a putative marker of iron deposition, commonly occurs in multiple sclerosis (MS). However, GM T2 hypointensity in benign MS (BMS) has not yet been characterized. Objective To determine the presence of deep GM T2 hypointensity in BMS, compare it to secondary progressive (SP) MS and assess its association with clinical and diffusion tensor (DT) MRI measures. Methods Thirty-five cognitively unimpaired BMS, 26 SPMS patients, and 25 healthy controls were analyzed for normalized T2-intensity in the basal ganglia and thalamus, global T2 hyperintense lesion volume, global atrophy, and white matter and GM DT metrics. Results BMS and SPMS patients showed deep GM T2 hypointensity compared with controls. T2 hypointensity was similar in both MS subgroups and moderately correlated (r = −0.45 to 0.42) with DT MRI metrics. GM T2 hypointensity in BMS showed a weak to moderate correlation (r = −0.44 to −0.35) with disability. Conclusions GM in BMS is not spared from structural change including iron deposition. However, while T2 hypointensity is related to global tissue disruption reflected in DT MRI, the expression of benign versus non-benign MS is likely related to other factors.
FALKON: An Optimal Large Scale Kernel Method

Kernel methods provide a principled way to perform non linear, nonparametric learning. They rely on solid functional analytic foundations and enjoy optimal statistical properties. However, at least in their basic form, they have limited applicability in large scale scenarios because of stringent computational requirements in terms of time and especially memory. In this paper, we take a substantial step in scaling up kernel methods, proposing FALKON, a novel algorithm that allows to efficiently process millions of points. FALKON is derived combining several algorithmic principles, namely stochastic subsampling, iterative solvers and preconditioning. Our theoretical analysis shows that optimal statistical accuracy is achieved requiring essentially $O(n)$ memory and $O(n\sqrt{n})$ time. An extensive experimental analysis on large scale datasets shows that, even with a single machine, FALKON outperforms previous state of the art solutions, which exploit parallel/distributed architectures.
Attention deficit/hyperactivity and comorbid symptoms in preschoolers: Differences between subgroups in neuropsychological basic deficits

Background: There is wide agreement on the heterogeneity of attention deficit/hyperactivity disorder (ADHD). Subgroups with specific comorbid problems, neuropsychological deficits, and developmental trajectories that start in preschool years have been assumed. We analyze whether corresponding subgroups at risk for ADHD development can be identified in a preschool sample and whether these subgroups show the assumed neuropsychological deficits. Methods: The study sample consisted in 141 preschool children (3–6 years; 68 boys), including 41 children at risk for ADHD development (because of high ADHD symptoms or first-degree relatives with an ADHD diagnosis). Parent- and teacher-reported symptoms of ADHD, ODD/CD, and anxiety/depression were assessed. Cluster analyses were conducted on the continuous symptom scores. Inhibitory control and delay aversion were measured by six neuropsychological tasks. Results: Cluster analyses resulted in four groups. Two of these groups showed high ADHD symptoms — one showing multiple comorbid symptoms, one showing hardly any further symptoms. The other two groups were characterized by no problems and by some sensorimotor deficits. A priori contrasts revealed that the “high comorbidity” cluster showed the worst inhibitory control performance while the “pure ADHD symptoms” cluster showed the highest delay aversion. Conclusion: The ADHD-symptom clusters matched types that have been proposed in recent models. This description might help to identify different ADHD-related pathways in future longitudinal research.
Sequential roles of Hedgehog and Wnt signaling in osteoblast development

Signals that govern development of the osteoblast lineage are not well understood. Indian hedgehog (Ihh), a member of the hedgehog (Hh) family of proteins, is essential for osteogenesis in the endochondral skeleton during embryogenesis. The canonical pathway of Wnt signaling has been implicated by studies of Lrp5, a co-receptor for Wnt proteins, in postnatal bone mass homeostasis. In the present study we demonstrate that β-catenin, a central player in the canonical Wnt pathway, is indispensable for osteoblast differentiation in the mouse embryo. Moreover, we present evidence that Wnt signaling functions downstream of Ihh in development of the osteoblast lineage. Finally Wnt7b is identified as a potential endogenous ligand regulating osteogenesis. These data support a model that integrates Hh and Wnt signaling in the regulation of osteoblast development.
Gamma‐variate plasma clearance versus urinary plasma clearance of 51Cr‐EDTA in patients with cirrhosis with and without fluid retention

In patients with fluid retention, the plasma clearance of 51Cr‐EDTA (Clexp obtained by multiexponential fit) may overestimate the glomerular filtration rate (GFR). The present study was undertaken to compare a gamma‐variate plasma clearance (Clgv) with the urinary plasma clearance of 51Cr‐EDTA (Clu) in patients with cirrhosis with and without fluid retention. A total of 81 patients with cirrhosis (22 without fluid retention, 59 with ascites) received a quantitative intravenous injection of 51Cr‐EDTA followed by plasma and quantitative urinary samples for 5 h. Clgv was determined from the injected dose relative to the plasma concentration‐time area, obtained by a gamma‐variate iterative fit. Clexp and Clu were determined by standard technique. In patients without fluid retention, Clgv, Clexp and Clu were closely similar. The difference between Clgv and Clu (Clgv – Clu = ΔCl) was mean −0·6 ml min−1 1·73 m−2. In patients with ascites, ΔCl was significantly higher (11·8 ml min−1 1·73 m−2, P<0·0001), but this value was lower than Clexp – Clu (17·5 mL min−1 1·73 m−2, P<0·01). ΔCl increased with lower values of GFR (P<0·001). In conclusion, in patients with fluid retention and ascites Clgv and Clexp overestimates GFR substantially, but the overestimation is smaller with Clgv. Although Clu may underestimate GFR slightly, patients with ascites should collect urine quantitatively to obtain a reliable measurement of GFR.
Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions.

We have used a series of human estrogen receptor (ER) mutants to evaluate the cell- and promoter-specific transcriptional activities of the TAF1 and TAF2 transactivation regions within the human ER. We show that the manifestation of TAF1 or TAF2 function depends strongly upon promoter context; on certain promoters, both the TAF1 and TAF2 activators are required for wild-type transcriptional activity, whereas on other promoters, the TAF1 and TAF2 activators function independently. Using these constructs, we show that the antagonist activity of the triphenylethylene-derived antiestrogens, e.g. tamoxifen, arises from their intrinsic inability to activate ER TAF2 function. However, on certain promoters, these antiestrogens efficiently activate gene transcription through ER. Consistent with this observation, the TAF2 function of the ER is not required on all promoters. In these TAF2-independent promoter contexts, TAF2 function may be provided by a separate transcription factor bound to the promoter. These data suggest that 1) TAF1 may be the major transcriptional activator of the ER; and 2) TAF2 functions as a transcriptional facilitator. On promoters where TAF2 function is provided independently of the ER, the TAF1 function of the ER can function independently of TAF2 activity, allowing triphenylethylene-derived antiestrogens to demonstrate partial agonist activity. These observations provide a possible molecular explanation for the tissue-specific partial agonist properties of tamoxifen and related triphenylethylene antiestrogens observed in vivo.
Understanding the Role of Maternal Diet on Kidney Development; an Opportunity to Improve Cardiovascular and Renal Health for Future Generations

The leading causes of mortality and morbidity worldwide are cardiovascular disease (high blood pressure, high cholesterol and renal disease), cancer and diabetes. It is increasingly obvious that the development of these diseases encompasses complex interactions between adult lifestyle and genetic predisposition. Maternal malnutrition can influence the fetal and early life environment and pose a risk factor for the future development of adult diseases, most likely due to impaired organogenesis in the developing offspring. This then predisposes these offspring to cardiovascular disease and renal dysfunction in adulthood. Studies in experimental animals have further illustrated the significant impact maternal diet has on offspring health. Many studies report changes in kidney structure (a reduction in the number of nephrons in the kidney) in offspring of protein-deprived dams. Although the early studies suggested that increased blood pressure was also present in offspring of protein-restricted dams, this is not a universal finding and requires clarification. Importantly, to date, the literature offers little to no understanding of when in development these changes in kidney development occur, nor are the cellular and molecular mechanisms that drive these changes well characterised. Moreover, the mechanisms linking maternal nutrition and a suboptimal renal phenotype in offspring are yet to be discerned—one potential mechanism involves epigenetics. This review will focus on recent information on potential mechanisms by which maternal nutrition (focusing on malnutrition due to protein restriction, micronutrient restriction and excessive fat intake) influences kidney development and thereby function in later life.
Expression of retroviral sequences and oncogenes in rat liver tumors induced by diethylnitrosamine.

The expression of three cellular oncogenes (c-myc, c-Ha-ras, and c-delta-raf), the epidermal growth factor receptor gene, and two endogenous retrovirus-like sequences [rat leukemia virus (RaLV) and 30S] was examined in control rat livers and in 16 liver tumors. The tumors were induced in Sprague-Dawley male and female rats by a single i.p. injection of diethylnitrosamine at 1 or 2 days after birth, followed by dietary exposure to phenobarbital beginning at weaning. Increased expression of c-myc was seen in most of the tumors, but there was no consistent increase or decrease in expression of c-Ha-ras or c-delta-raf. It is of interest that a number of the tumor samples showed a decrease in epidermal growth factor receptor RNA. In all of the tumors, including both hepatocellular adenomas and carcinomas, there was a marked increase in expression of the endogenous RaLV sequence, and over 90% of the tumors displayed increased expression of the 30S endogenous retroviral-like sequence. No or a very low level of expression of the RaLV and 30S sequences was found in the control livers. The extent of expression of the RaLV and 30S sequences in individual tumors did not correlate with the extent of expression of c-myc or c-Ha-ras. Although increased expression of certain endogenous retrovirus-related sequences appears to be a common finding during rat liver carcinogenesis, the significance of this finding remains to be determined.