Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease.

BACKGROUND The statin treatment of dyslipidemia is associated with a reduced risk of development of Alzheimer disease (AD). The effect may be mediated by a reduction in cholesterol biosynthesis in the brain, by lowering levels of apolipoprotein E (apo E)-containing lipoproteins, or by pleitropic effects such as reduction in beta-amyloid production. In the brain, cholesterol from damaged or dying neurons is converted to 24S-hydroxycholesterol by cholesterol 24-hydroxylase (CYP46). The oxysterol is subsequently transferred across the blood-brain barrier, transported to the liver by low-density lipoproteins (LDLs), and excreted as bile acids. Most of plasma 24S-hydroxycholesterol is derived from brain cholesterol; consequently, plasma levels of the oxysterol reflect brain cholesterol catabolism. OBJECTIVE To examine the effect of 3 statins and a nonstatin hypolipidemic agent on plasma levels of 24S-hydroxycholesterol and apo E in patients with AD. STUDY DESIGN The study had a sequential parallel design. It was open-labeled and involved lipoprotein and 24S-hydroxycholesterol evaluations at baseline and at 6 weeks of treatment with 40 mg of lovastatin, simvastatin, or pravastatin sodium per day, or 1 g of extended-release niacin per day. Blood samples were drawn after a 12-hour fast for measurement of plasma sterols, oxysterols, lipoprotein cholesterol, and levels of apo E, plasma transaminases, and glucose. Measurements were made at baseline and during treatment. RESULTS Statin treatment reduced levels of plasma lathosterol by 49.5%, 24S-hydroxycholesterol by 21.4%, LDL cholesterol by 34.9%, and total cholesterol by 25%. The ratios of lathosterol-campesterol and 24S-hydroxycholesterol-LDL cholesterol were reduced significantly, but the ratio of 24S-hydroxycholesterol-total cholesterol was unchanged. Extended-release niacin also significantly reduced levels of 24S-hydroxycholesterol by 10% and LDL cholesterol by 18.1%. None of the agents lowered plasma concentration of apo E. CONCLUSIONS Statins lowered levels of plasma 24S-hydroxycholesterol without affecting levels of apo E. The LDL lowering was more pronounced than 24S-hydroxycholesterol reductions. The effect of statins on LDL partially explains the reduction of plasma oxysterol level.
Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation

Despite the fact that most cancer cells display high glycolytic activity, cancer cells selectively express the less active M2 isoform of pyruvate kinase (PKM2). Here we demonstrate that PKM2 expression makes a critical regulatory contribution to the serine synthetic pathway. In the absence of serine, an allosteric activator of PKM2, glycolytic efflux to lactate is significantly reduced in PKM2-expressing cells. This inhibition of PKM2 results in the accumulation of glycolytic intermediates that feed into serine synthesis. As a consequence, PKM2-expressing cells can maintain mammalian target of rapamycin complex 1 activity and proliferate in serine-depleted medium, but PKM1-expressing cells cannot. Cellular detection of serine depletion depends on general control nonderepressible 2 kinase-activating transcription factor 4 (GCN2-ATF4) pathway activation and results in increased expression of enzymes required for serine synthesis from the accumulating glycolytic precursors. These findings suggest that tumor cells use serine-dependent regulation of PKM2 and GCN2 to modulate the flux of glycolytic intermediates in support of cell proliferation.
Sodium content in processed foods in Argentina: compliance with the national law.

BACKGROUND Despite the body of evidence that documents the unfavorable effects of excessive sodium consumption on blood pressure and cardiovascular health, public health efforts to decrease sodium consumption have been limited to a few countries. Argentina is the first country in Latin America to regulate sodium content of processed foods by means of a national law. The objective of this cross-sectional quantitative study is to provide a baseline comparison against the reduction targets set by the national law before its entry into force. METHODS Data were collected in February 2014 in a leading supermarket chain located in Buenos Aires. Nutrient data from package labels were analysed for 1,320 products within 14 food groups during the study period. To compare sodium concentration levels with the established maximum levels we matched the collected food groups with the food groups included in the law resulting in a total of 292 products. Data analysis was conducted using SPSS version 20 software. RESULTS Food groups with the highest median sodium content were sauces and spreads (866.7 mg/100 g), meat and meat products (750 mg/100 g) and snack foods (644 mg/100 g). Categories with the highest sodium content were appetizers (1,415 mg/100 g), sausages (1,050 mg/100 g) and ready-made meals (940.7 mg/100 g). We also found large variability within products from the same food categories. Products included in the national law correspond to 22.1% (n=292) of the surveyed foods. From the 18 food groups, 15 showed median sodium values below the established targets. Products exceeding the established maximum levels correspond to 15.1% (n=44) of the products included in the analysis. CONCLUSIONS This study is the first analysis of food labels to determine sodium concentrations of processed foods in Argentina and to provide a baseline against the national law standards. Upon the completion of this analysis, maximum levels have been achieved by most of the food groups included in the law. Thus, the introduction of further reductions for the existing maximum levels and the establishment of sodium targets for all relevant product categories not included in the law should be considered as the next steps in the process.
The relation between intracranial pressure and outcome in non‐accidental head injury

The aim of this retrospective study was to ascertain whether physiological derangement and potential secondary brain insult from raised intracranial pressure (ICP) or reduced cerebral perfusion pressure (CPP) in non‐accidental head injury (NAHI) influences outcome. Any child who had a diagnosis of NAHI and had ICP monitoring or measurements during the acute illness was entered in the study. Seventeen children with an average age 5.1 months (range 1 to 20 months) were identified. Details of the acute encephalopathy, lowest mean arterial blood pressure (MAP), mean of maximum ICP measured, lowest CPP, and neurodevelopmental outcome at follow up were obtained from the hospital case notes. Seshia's (1994) outcome classification scale was used. The lowest CPP was very significantly related to outcome (P=0.0047, τ=–0.544). Mean of maximum ICP did not correlate with outcome. The lowest MAP was significantly related to outcome (P=0.039). It was concluded that the degree of secondary brain insult from reduced CPP influences outcome. Developmental Medicine & Child Neurology 1999, 41: 220–225
Guidelines for realistic grounding of mechanism design in demand response

Paradigm-shifting changes in the electric power industry, such as high renewable energy penetration and advancements in infrastructure technologies, have prompted more focus on demand response (DR). This paper highlights four impediments associated with a realistic implementation of mechanism design for aggregator-coordinated DR, focusing in particular on the Vickrey-Clarke-Groves (VCG) mechanism, and describes the necessary assumptions for a realistic grounding to the implementation of mechanism design in DR. Additionally, we propose a two-stage distributed mechanism in which the agents share the computational burden with the aggregator and faithfully implement their intended computations.
Naturally Competent Acinetobacter baumannii Clinical Isolate as a Convenient Model for Genetic Studies

ABSTRACT Acinetobacter baumannii A118 was isolated from a patient's blood culture. It is susceptible to several antibiotics, is naturally competent, and supports replication and stable maintenance of four plasmid replicons. A. baumannii A118 took up a fluorophore-labeled oligonucleotide analog. These characteristics make this isolate a convenient model for genetic studies.
Tablet use in schools: a critical review of the evidence for learning outcomes

The increased popularity of tablets in general has led to uptake in education. We critically review the literature reporting use of tablets by primary and secondary school children across the curriculum, with a particular emphasis on learning outcomes. The systematic review methodology was used, and our literature search resulted in 33 relevant studies meeting the inclusion criteria. A total of 23 met the minimum quality criteria and were examined in detail 16 reporting positive learning outcomes, 5 no difference and 2 negative learning outcomes. Explanations underlying these observations were analysed, and factors contributing to successful uses of tablets are discussed. While we hypothesize how tablets can viably support children in completing a variety of learning tasks across a range of contexts and academic subjects, the fragmented nature of the current knowledge base, and the scarcity of rigorous studies, makes it difficult to draw firm conclusions. The generalizability of evidence is limited, and detailed explanations as to how, or why, using tablets within certain activities can improve learning remain elusive. We recommend that future research moves beyond exploration towards systematic and in-depth investigations building on the existing findings documented here.
Role of D1 and E Cyclins in Cell Cycle Progression of Human Fibroblasts Adhering to Cementum Attachment Protein

Cementum attachment protein (CAP) is a collagenous protein present in the matrix of tooth cementum that mediates preferential attachment of some mesenchymal cell types, and CAP binding capacity is related to mineralizing tissue‐forming capacity in culture. We have examined if adhesion to surfaces containing CAP as the only attachment protein permits human fibroblasts to escape G1 arrest and synthesize DNA, and if adhesion to CAP modulates the levels of cyclins D1 and E. Human gingival fibroblasts (HGFs) were serum‐starved, trypsinized, and added to plates coated with CAP or bovine serum albumin (BSA). Cells were then exposed to either 10% fetal bovine serum (FBS) or to cementum‐derived growth factor (CGF), an insulin‐like growth factor I (IGF‐I)‐like molecule sequestered in tooth cementum, plus epidermal growth factor (EGF). DNA synthesis was measured as [3H]thymidine uptake, and cyclin D1 and E levels were determined by Western analysis. Cyclin E‐dependent kinase (Cdk) activity was assessed in terms of H1 kinase activity in immunoprecipitates of cyclin E. Cells adhering to CAP synthesized DNA, whereas on BSA they remained unattached and did not synthesize DNA. Protein levels of cyclin D1 were higher in cells adhering to CAP in the absence and presence of growth factors. Cyclin E levels were not affected by adhesion alone, but they increased in the presence of growth factors. Cyclin E‐associated kinase activity was higher in cells adherent on CAP, and it increased further in the presence of growth factors. Our results indicate that adhesion to CAP increases cyclin D1 levels and cyclin E‐associated Cdk activity, and that these increases contribute to cell cycle progression. We previously observed that the signaling reactions induced during adhesion are characteristic of the CAP; together these observations indicate that specific matrix components present in the local environment can contribute to recruitment and differentiation of specific cell types for normal homeostasis and wound healing.
Retrieval of Specific Leaf Area From Landsat-8 Surface Reflectance Data Using Statistical and Physical Models

One of the key traits in the assessment of ecosystem functions is a specific leaf area (SLA). The main aim of this study was to examine the potential of new generation satellite images, such as Landsat-8 imagery, for the retrieval of SLA at regional and global scales. Therefore, both statistical and radiative transfer model (RTM) inversion approaches for estimating SLA from the new Landsat-8 product were evaluated. Field data were collected for 33 sample plots during a field campaign in summer 2013 in the Bavarian Forest National Park, Germany, while Landsat-8 image data concurrent with the time of field campaign were acquired. Estimates of SLA were examined using different Landsat-8 spectral bands, vegetation indices calculated from these bands, and the inversion of a canopy RTM. The RTM inversion was performed utilizing continuous wavelet analysis and a look-up table (LUT) approach. The results were validated using R2 and the root-mean-square error (RMSE) between the estimated and measured SLA. In general, SLA was estimated accurately by both statistical and RTM inversion approaches. The relationships between measured and estimated SLA using the enhanced vegetation index were strong (R2 = 0.77 and RMSE = 4.44%). Furthermore, the predictive model developed from combination of the wavelet features at 654.5 nm (scale 9) and 2200.5 nm (scale 2) correlated strongly with SLA (R2 = 0.79 and RMSE = 7.52%). The inversion of LUT using a spectral subset consisting of bands 5, 6, and 7 of Landsat-8 (R2 = 0.73 and RMSE = 5.33%) yielded a higher accuracy and precision than any other spectral subset. The findings of this study provide insights into the potential of the new generation of multispectral medium-resolution satellite imagery, such as Landsat-8 and Sentinel-2, for accurate retrieval and mapping of SLA using either statistical or RTM inversion methods.
Ewing’s Sarcoma of the Humerus in a Three year-old boy Requiring Radical En-Bloc resection and Total Humeral Expandable Prosthetic Replacement: A Case Report

Ewing's sarcoma is a malignant bone tumor that affects children typically in their second decade, with a low incidence in patients less than five years of age. Presenting symptoms may be nonspecific and may include pain, swelling, fever, and weight loss. Definitive diagnosis may be difficult and further investigation may be necessary to differentiate Ewing's sarcomas with osteomyelitis. We present a case report of a three year-old boy with Ewing's sarcoma that involved the entire right humerus. Due to his young age, and nonspecific nature of his presentation, the patient was initially misdiagnosed and treated for osteomyelitis. The patient required multi-agent chemotherapy and radical en-bloc resection of the entire right humerus, given the extent of his tumor involvement. A custom expandable modular humeral prosthesis was designed and engineered specifically for this patient. His arm is very functional three years postoperatively, and he is disease free. To our knowledge, this is the youngest report of Ewing's sarcoma that required total humeral resection and prosthetic replacement presented in the literature.
The effects of new steroidal anti-androgen, TZP-4238, and chlormadinone acetate on the pituitary, prostate and adrenal gland of the rat: histopathological and immunocytochemical studies.

The atrophic effects of a synthetic steroidal anti-androgen, TZP-4238, on the pituitary, prostate and adrenal gland of rats were investigated. Male Sprague-Dawley rats were divided into three experimental groups. Group 1 consisted of controls. Groups 2 and 3 received chlormadinone acetate (CMA) 50 mg/kg/day and TZP-4238 10 mg/kg/day p.o. , respectively, for 3 weeks. CMA (Group 2) produced marked atrophy of the prostate. Furthermore, CMA caused marked atrophy of the adrenal gland. Histopathologically, the remarkable atrophy was observed in the adrenal cortical cells of zonae fasciculata and reticularis. The most striking ultrastructural alterations were noted in the mitochondria. In addition, intramitochondrial localization of glutathione-peroxidase (GSH-PO) which effectively reduces the lipid peroxides, was less than that in the controls. In the anterior pituitary gland, CMA induced a reduction in the size of ACTH cells. TZP-4238 (Group 3) produced marked atrophy of the prostate. However, TZP-4238 exerted no effect on the adrenal gland or anterior pituitary ACTH cells. In addition, the present histopathological study showed that TZP-4238 or CMA exerted no effect on the testes or anterior pituitary LH cells. Therefore, it is suggested that TZP-4238 causes atrophy of the prostate without any significant histopathological changes in the adrenal glands or anterior pituitary ACTH cells under the present experimental conditions. We further speculated that TZP-4238 had a more potent anti-prostatic effect than CMA and TZP-4238 had a less inhibitory influence than CMA on the pituitary-adrenal axis.
Association between carotid artery intima-media thickness and cardiovascular risk factors in CKD.

BACKGROUND Common carotid artery intima-media thickness (CCA-IMT) correlates with cardiovascular events in the general population and is an independent predictor of cardiovascular mortality in the hemodialysis population. It has not been evaluated extensively in patients with chronic kidney disease. METHODS CCA-IMT was measured by using high-resolution B-mode ultrasonography, and glomerular filtration rate (GFR) was measured by means of EDTA clearance. Cardiovascular risk factors assessed included homocysteine and lipoprotein(a) levels, as well as smoking, blood pressure, and cholesterol level. RESULTS One hundred fourteen patients were studied; mean measured GFR was 29.6 +/- 18.4 mL/min/1.73 m2 (0.49 +/- 0.31 mL/s). CCA-IMT was significantly elevated (0.59 +/- 0.22 cm) compared with a control group (0.44 +/- 0.08 cm; P = 0.0012). CCA-IMT increases with age (P < 0.0001) and low-density lipoprotein level (P = 0.048) and decreases with high-density lipoprotein level (P = 0.001) and being white (P = 0.014). CONCLUSION This study suggests that arterial changes occur early in the course of renal disease progression and may be related to dyslipidemia in the early stages.
Dermatohistopathology of various types of scleroderma.

This paper deals with the dermatohistopathologic findings in more than 200 cases of different types of scleroderma, including brief comments on pathologic findings in biopsy of specimens of muscle from many patients who had generalized forms of scleroderma. We are not concerned in this review with the systemic manifestations of the disease as it affects various internal organs * ; neither will we endeavor to distinguish morphea, kraurosis, balanitis xerotica obliterans, and lichen sclerosus et atrophicus as they occur on the genitalia. The term "scleroderma of the skin" has been subject to multiple definitions and classifications,‡ and although some group all forms of scleroderma together, we prefer to recognize the following types as having certain characteristics that distinguish one from another. Classification We classify scleroderma as follows: I. Generalized forms of scleroderma (associated with a varying degree of systemic involvement). A. Generalized or diffuse type. This
Histology of familial thyroid tumours linked to a gene mapping to chromosome 19p13.2

This paper describes the pathology of thyroid tumours showing an autosomal mode of inheritance linked to a gene that maps to chromosome 19p13.2. All the affected members from the family (seven males and two females; mean age 23 years) were clinically euthyroid and presented with nodular goitre; tumour recurrence after thyroidectomy was observed in four. In four of the five patients studied, the tumours were multifocal, bilateral well demarcated or encapsulated and composed of follicles, papillae, trabeculae/solid areas (often resembling hyalinizing trabecular adenoma of the thyroid) or an admixture, formed by cells with pale to intense cytoplasmic eosinophilia. A diagnosis of multiple adenomatous goitre was made in the thyroidectomy specimen from two patients, while the other two patients showed, in addition to multiple adenomas, a co‐existent oxyphil papillary carcinoma. The fifth patient had an oxyphil cell carcinoma. All tumours were of follicular cell origin as shown by immunocytochemistry. Less than a third of the benign tumours and all three carcinomas showed a variable number of neoplastic cells diffusely immunostained for mitochondria. Histological findings of a ‘multiple adenomatous goitre’, non‐endemic ‘multinodular goitre’ or multiple neoplasms of follicular cell origin with the morphology of those described here, particularly in young patients, should alert the pathologist and physician to the possibility of an inherited trait, with its implications for family screening. The tumours are usually benign and well demarcated but because of multicentricity and consequently increased risk of recurrence and/or progression to carcinoma, total thyroidectomy should be advocated. Copyright © 1999 John Wiley & Sons, Ltd.
Cancer patients use unconventional medical therapies far more frequently than standard history and physical examination suggest.

BACKGROUND Studies with questionnaires have suggested that many cancer patients utilize unconventional medical therapies (UMT). There are few data evaluating directed questions about the use of UMT. This study was performed to determine if careful directed questioning about UMT reveals a higher rate of utilization compared to standard history and physical examination. MATERIALS AND METHODS A prospective evaluation of 196 consecutive patients presenting for initial consultation at the University of Pennsylvania was performed. Each patient underwent standard history and physical examination, including questions regarding prescription and over-the-counter medications. At the completion of standard questioning, patients were asked an explicit set of directed questions regarding the utilization of UMT. The median age of the patient population was 61 years (range = 28-80 years). Cancer diagnoses included breast (19%), lung (28%), prostate (26%), and other (27%). Females constituted 32% of the patient population. RESULTS Initially, only 13 patients (7%) revealed they were using UMT during a standard history and physical. Evaluation of the remaining 183 patients with directed questioning revealed an additional 66 patients (36%) were utilizing these therapies. Of the 79 patients taking UMT, 84% were identified by directed questioning and 16% by standard history and physical examination (P < 0.0005). Forty-one patients (52%) were using > or = 2 of these therapies (mean = 2.5; range 1-17 therapies). A total of 48 different UMT were used by this patient population. Patients utilizing multivitamin supplementation were significantly more likely to be using an UMT than those who were not (68% vs. 31%; P < 0.0001). Females were more likely to use UMT than males (49% vs. 35%; P = 0.08). CONCLUSIONS The addition of explicitly directed questioning to the standard history and physical examination significantly increases the oncologist's ability to identify cancer patients who utilize UMT. Some of these therapies may interact with conventional cancer treatments and/or cause significant side effects; consequently, it is important for oncologists to detect those patients utilizing these therapies.
A prospective, multicenter cohort study to validate a simple performance status–based survival prediction system for oncologists

Survival prediction systems such as the Palliative Prognostic Index (PPI), which includes the Palliative Performance Scale (PPS), are used to estimate survival for terminally ill patients. Oncologists are, however, less familiar with the PPS in comparison with the Eastern Cooperative Oncology Group (ECOG) performance status (PS). This study was designed to validate a simple survival prediction system for oncologists, the Performance Status–Based Palliative Prognostic Index (PS‐PPI), which is a modified form of the PPI based on the ECOG PS.