Miracle-dz/UniFAR-FTUs huggingface dataset:
Muscular effects of vitamin D in young athletes and non-athletes and in the elderly

Muscles are major targets of vitamin D. Exposure of skeletal muscles to vitamin D induces the expression of multiple myogenic transcription factors enhancing muscle cell proliferation and differentiation. At the same time vitamin D suppresses the expression of myostatin, a negative regulator of muscle mass. Moreover, vitamin D increases the number of type II or fast twitch muscle cells and in particular that of type IIA cells, while its deficiency causes type IIA cell atrophy. Furthermore, vitamin D supplementation in young males with low vitamin D levels increases the percentage of type IIA fibers in muscles, causing an increase in muscular high power output. Vitamin D levels are strongly associated with exercise performance in athletes and physically active individuals. In the elderly and in adults below the age of 65, several studies have established a close association between vitamin D levels and neuromuscular coordination. The aim of this review is to appraise our current understanding of the significance of vitamin D on muscular performance in both older and frail individuals as well as in younger adults, athletes or non-athletes with regard to both ordinary everyday musculoskeletal tasks and peak athletic performance.
Fingolimod effect on gray matter, thalamus, and white matter in patients with multiple sclerosis

Objective To study the effect of fingolimod on deep gray matter (dGM), thalamus, cortical GM (cGM), white matter (WM), and ventricular volume (VV) in patients with relapsing-remitting multiple sclerosis (RRMS). Methods Data were pooled from 2 phase III studies. A total of 2,064 of 2,355 (88%) contributed to the analysis: fingolimod 0.5 mg n = 783, fingolimod 1.25 mg n = 799, or placebo n = 773. Percentage change from baseline in dGM and thalamic volumes was evaluated with FMRIB’s Integrated Registration & Segmentation Tool; WM, cGM, and VV were evaluated with structural image evaluation using normalization of atrophy cross-sectional version (SIENAX) at months 12 and 24. Results At baseline, compound brain volume (brain volume in the z block [BVz] = cGM + dGM + WM) correlated with SIENAX-normalized brain volume (r = 0.938, p < 0.001); percentage change from baseline in BVz over 2 years correlated with structural image evaluation using normalization of atrophy percentage brain volume change (r = 0.713, p < 0.001). For placebo, volume reductions were most pronounced in cGM, and relative changes from baseline were strongest in dGM. Over 24 months, there were significant reductions with fingolimod vs placebo for dGM (0.5 mg −14.5%, p = 0.017; 1.25 mg −26.6%, p < 0.01) and thalamus (0.5 mg −26.1%, p = 0.006; 1.25 mg −49.7%, p < 0.001). Reduction of cGM volume loss was not significant. Significantly less WM loss and VV enlargement were seen with fingolimod vs placebo (all p < 0.001). A high T2 lesion volume at baseline predicted on-study cGM, dGM, and thalamic volume loss (p < 0.0001) but not WM loss. Patients taking placebo with high dGM (hazard ratio [HR] 0.54, p = 0.0323) or thalamic (HR 0.58, p = 0.0663) volume at baseline were less likely to show future disability worsening. Conclusions Fingolimod significantly reduced dGM volume loss (including thalamus) vs placebo in patients with RRMS. Reducing dGM and thalamic volume loss might improve long-term outcome.
Minibeam radiotherapy with small animal irradiators; in vitro and in vivo feasibility studies

Minibeam radiation therapy (MBRT) delivers an ultrahigh dose of x-ray (⩾100 Gy) in 200–1000 µm beams (peaks), separated by wider non-irradiated regions (valleys) usually as a single temporal fraction. Preclinical studies performed at synchrotron facilities revealed that MBRT is able to ablate tumors while maintaining normal tissue integrity. The main purpose of the present study was to develop an efficient and accessible method to perform MBRT using a conventional x-ray irradiator. We then tested this new method both in vitro and in vivo. Using commercially available lead ribbon and polyethylene sheets, we constructed a collimator that converted the cone beam of an industrial irradiator to 44 identical beams (collimator size ≈ 4 × 10 cm). The dosimetry characteristics of the generated beams were evaluated using two different radiochromic films (beam FWHM = 246 ± 32 µm; center-to-center = 926 ± 23 µm; peak-to-valley dose ratio = 24.35 ± 2.10; collimator relative output factor = 0.84 ± 0.04). Clonogenic assays demonstrated the ability of our method to induce radiobiological cell death in two radioresistant murine tumor cell lines (TRP = glioblastoma; B16-F10 = melanoma). A radiobiological equivalent dose (RBE) was calculated by evaluating the acute skin response to graded doses of MBRT and conventional radiotherapy (CRT). Normal mouse skin demonstrated resistance to doses up to 150 Gy on peak. MBRT significantly extended the survival of mice with flank melanoma tumors compared to CRT when RBE were applied (overall p < 0.001). Loss of spatial resolution deep in the tissue has been a major concern. The beams generated using our collimator maintained their resolution in vivo (mouse brain tissue) and up to 10 cm deep in the radiochromic film. In conclusion, the initial dosimetric, in vitro and in vivo evaluations confirmed the utility of this affordable and easy-to-replicate minibeam collimator for future preclinical studies.
Cooked Chickpea Consumption Inhibits Colon Carcinogenesis in Mice Induced with Azoxymethane and Dextran Sulfate Sodium

ABSTRACT Scope: The objective of the study was to evaluate the effect of daily consumption of cooked chickpea (2% and 10%) in ICR male mice in which colon cancer was induced with azoxymethane and dextran sulfate sodium. Methods and Results: The effect of consumption of 2% or 10% cooked chickpeas on carcinogenesis-induced colon azoxymethane (AOM)/dextran sulfate sodium (DSS) in ICR mice was determined. Protein oxidation and lipids were determined by colorimetric methods and oxidation of DNA through the identification of adducts 8-hydroxy-2′-desoxiguanosine and proliferation markers (proliferating cell nuclear antigen [PCNA], Ki-67, and β-catenin), and inflammation (cyclooxygenase [COX]-2 and inducible nitric oxide synthase [iNOS]) were identified by immunohistochemistry reactions. The results showed the protective effect of daily consumption of rich cooked chickpeas in the carcinogenesis process, decreasing lipid, protein, and DNA oxidation and decreasing the expression of inflammatory enzymes (COX-2 and iNOS) as well as β-catenin, one of the most important oncogenic proteins in colon cancer. Animals that were fed with the 10% chickpea diet showed an inhibition in cellular proliferation (Ki-67 and PCNA expression). Conclusions: The addition of cooked chickpea seed (2% and 10%) to the daily diet is proposed as a chemopreventive agent against colon cancer.
Serum inflammatory biomarkers and clinical outcomes of COPD exacerbation caused by different pathogens

Background and objective COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment. Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation. We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens. Methods COPD patients with exacerbation were recruited from a hospital emergency department during 2014–2015. Serum procalcitonin (PCT) and C-reactive protein (CRP) were measured. Dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score was calculated for predicting mortality. Multiplex polymerase chain reaction was carried out for respiratory viral assay from nasopharyngeal swabs, and sputum bacterial culture was also performed. Hospital mortality, invasive mechanical ventilation requirement, and length of hospital stay (LOS) were evaluated, and their associations with clinical characteristics, DECAF score, and serum biomarkers were examined. Results A total of 62 COPD patients were enrolled. These patients were classified as Global Initiative for Obstructive Lung Disease (GOLD) stage 2, 3, and 4 in 12.9%, 6.4%, and 80.7% of cases, respectively. Isolated bacterial exacerbation was recovered in 30.6% of exacerbation episodes: Klebsiella pneumoniae was the most commonly identified bacteria. Viral pathogens and coinfections were noted in 9.6% and 16.1% of exacerbated patients, respectively. Influenza was the most commonly detected viral pathogen. Serum biomarkers and DECAF score for viruses, bacteria, coinfection, and noninfectious causes of exacerbations were similar. Neither DECAF score nor serum biomarkers were able to differentiate patients with and without mortality or requiring mechanical ventilation. Increased serum PCT was noted in patients with LOS ≥7 days when compared with those with LOS <7 days (0.38 ng/mL vs 0.1 ng/mL; P=0.035). Conclusion Increased serum PCT is associated with longer LOS in COPD exacerbation. However, CRP and DECAF score play limited roles in predicting clinical outcome and lack an association with causes of exacerbation.
Effectiveness of pulmonary rehabilitation in COPD patients receiving long‐term oxygen therapy

It has been demonstrated that long‐term oxygen therapy increased exercise capacity, improved the quality of life, reduced hospitalization and increased life expectancy in chronic hypoxemic COPD patients. The present study aims to evaluate the effectiveness of pulmonary rehabilitation (PR) in COPD patients receiving long‐term oxygen therapy (LTOT) compared to COPD patients not receiving LTOT.
Effects of lysolecithin supplementation in low-energy diets on growth performance, nutrient digestibility, viscosity and intestinal morphology of broilers

ABSTRACT 1. The study aimed to investigate the effect of lysolecithin supplementation in low-energy diets on growth, nutrient digestibility and intestinal mucosa characteristics of broilers. 2. A total of 800 one-d-old Ross 308 broiler chickens were assigned to 4 dietary treatments consisting of 10 replicates of 20 broilers each. Broilers were fed with 4 different diets: (i) HE: positive control group broilers received a diet with unaltered energy; (ii) LE: negative control group broilers received a diet with lower energy of about 0.27 MJ/kg; (iii) LElys500: broilers received a diet similar to LE supplemented with 500 g/tn lysolecithin product (Lysoforte Booster DryTM); and (iv) LElys300: broilers received a diet similar to LE supplemented with 300 g/tn lysolecithin product. The experimental period was 42 d. 3. Body weight gain in treatments HE was higher than LE during the overall experimental period, while LElys500 and LElys300 had intermediate values. Feed conversion ratio was lower in HE and LElys500 than LE group, while the LElys300 had intermediate values. Fat digestibility was improved in both LElys 500 and LElys300 compared to the HE group. Apparent metabolisable energy (AMEn) was higher in HE, LElys500 and LElys300 than LE. Ileum viscosity at 42 d was also affected, being higher in LE group compared to HE. At 28 d mucosal thickness was lower both in LElys500 and LElys300 compared to HE and LE, while no difference occurred between treatment proliferation patterns of duodenal epithelial cells. 4. These findings indicated that lysolecithin supplementation at 500 g/tn of feed in low-energy diets maintained broiler performance. Supplementation of reformulated low-energy diets induced an increase in digesta viscosity. Lysolecithin supplementation resulted in variable alterations in the duodenum mucosal morphology.
Lung Toxicity of Condensed Aerosol from E-CIG Liquids: Influence of the Flavor and the In Vitro Model Used

The diffusion of e-cigarette (e-CIG) opens a great scientific and regulatory debate about its safety. The huge number of commercialized devices, e-liquids with almost infinite chemical formulations and the growing market demand for a rapid and efficient toxicity screen system that is able to test all of these references and related aerosols. A consensus on the best protocols for the e-CIG safety assessment is still far to be achieved, since the huge number of variables characterizing these products (e.g., flavoring type and concentration, nicotine concentration, type of the device, including the battery and the atomizer). This suggests that more experimental evidences are needed to support the regulatory frameworks. The present study aims to contribute in this field by testing the effects of condensed aerosols (CAs) from three main e-liquid categories (tobacco, mint, and cinnamon as food-related flavor), with (18 mg/mL) or without nicotine. Two in vitro models, represented by a monoculture of human epithelial alveolar cells and a three-dimensional (3D) co-culture of alveolar and lung microvascular endothelial cells were used. Cell viability, pro-inflammatory cytokines release and alveolar-blood barrier (ABB) integrity were investigated as inhalation toxicity endpoints. Results showed that nicotine itself had almost no influence on the modulation of the toxicity response, while flavor composition did have. The cell viability was significantly decreased in monoculture and ABB after exposure to the mints and cinnamon CAs. The barrier integrity was significantly affected in the ABB after exposure to cytotoxic CAs. With the exception of the significant IL-8 release in the monoculture after Cinnamon exposure, no increase of inflammatory cytokines (IL-8 and MCP-1) release was observed. These findings point out that multiple assays with different in vitro models are able to discriminate the acute inhalation toxicity of CAs from liquids with different flavors, providing the companies and regulatory bodies with useful tools for the preliminary screening of marketable products.
Ghrelin and growth hormone serum levels during the clonidine test in children with short stature and variable growth hormone status

OBJECTIVE: The exact role of ghrelin in the control of growth hormone (GH) secretion has not been completely clarified as yet. The aim of the present study was 1) to investigate the effect of a substance promoting GH secretion (clonidine) on ghrelin levels in children with short stature with growth hormone deficiency (GHD) and normal growth hormone (NGH), and 2) to assess possible correlations between GH and ghrelin values during the clonidine test. DESIGN: Eighteen prepubertal children with short stature were included in the study. Using the results of two GH-provocative tests (glucagon and clonidine), the participants were divided into two groups: GHD and NGH. In both groups, ghrelin levels were determined during the clonidine stimulation test. RESULTS: Different responses regarding ghrelin levels during the clonidine stimulation test were observed in the two study groups (GHD and NGH). A decrease in ghrelin levels was observed in the NGH children accompanied by a rise in the circulating GH levels, whereas the GHD children demonstrated a rise in both ghrelin and GH levels. CONCLUSIONS: The data indicate an inverse relationship between circulating ghrelin and GH in NGH children, suggesting the presence of a negative feedback loop between ghrelin and GH. Analogous changes were not observed in GHD children.
A Maximum Entropy Solution of the Covariance Extension Problem for Reciprocal Processes

Stationary reciprocal processes defined on a finite interval of the integer line can be seen as a special class of Markov random fields restricted to one dimension. Nonstationary reciprocal processes have been extensively studied in the past especially by Jamison et al. The specialization of the nonstationary theory to the stationary case, however, does not seem to have been pursued in sufficient depth in the literature. Stationary reciprocal processes (and reciprocal stochastic models) are potentially useful for describing signals which naturally live in a finite region of the time (or space) line. Estimation or identification of these models starting from observed data seems still to be an open problem which can lead to many interesting applications in signal and image processing. In this paper, we discuss a class of reciprocal processes which is the acausal analog of auto-regressive (AR) processes, familiar in control and signal processing. We show that maximum likelihood identification of these processes leads to a covariance extension problem for block-circulant covariance matrices. This generalizes the famous covariance band extension problem for stationary processes on the integer line. As in the usual stationary setting on the integer line, the covariance extension problem turns out to be a basic conceptual and practical step in solving the identification problem. We show that the maximum entropy principle leads to a complete solution of the problem.
The Potential of Collective Intelligence in Emergency Medicine: Pooling Medical Students’ Independent Decisions Improves Diagnostic Performance

Background. Evidence suggests that pooling multiple independent diagnoses can improve diagnostic accuracy in well-defined tasks. We investigated whether this is also the case for diagnostics in emergency medicine, an ill-defined task environment where diagnostic errors are rife. Methods. A computer simulation study was conducted based on empirical data from 2 published experimental studies. In the computer experiments, 285 medical students independently diagnosed 6 simulated patients arriving at the emergency room with dyspnea. Participants’ diagnoses (n = 1,710), confidence ratings, and expertise levels were entered into a computer simulation. Virtual groups of different sizes were randomly created, and 3 collective intelligence rules (follow-the-plurality rule, follow-the-most-confident rule, and follow-the-most-senior rule) were applied to combine the independent decisions into a final diagnosis. For different group sizes, the performance levels (i.e., percentage of correct diagnoses) of the 3 collective intelligence rules were compared with each other and against the average individual accuracy. Results. For all collective intelligence rules, combining independent decisions substantially increased performance relative to average individual performance. For groups of 4 or fewer, the follow-the-most-confident rule outperformed the other rules; for larger groups, the follow-the-plurality rule performed best. For example, combining 5 independent decisions using the follow-the-plurality rule increased diagnostic accuracy by 22 percentage points. These results were robust across case difficulty and expertise level. Limitations of the study include the use of simulated patients diagnosed by medical students. Whether results generalize to clinical practice is currently unknown. Conclusion. Combining independent decisions may substantially improve the quality of diagnoses in emergency medicine and may thus enhance patient safety.
A Nutrigenomic Approach to Non-Alcoholic Fatty Liver Disease

Following the epidemics of obesity due to the consumption of high-calorie diet and sedentary lifestyle, nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in Western countries. NAFLD is epidemiologically associated with metabolic syndrome and insulin resistance, and in susceptible individuals it may progress to cirrhosis and hepatocellular carcinoma. Genetic factors play a key role in NAFLD predisposition by interacting with nutritional and other environmental factors. To date, there is no drug therapy for the treatment of NAFLD, and the main clinical recommendation is lifestyle modification. In the last years, nutrigenomics is promoting an increased understanding of how nutrition affects the switch from health to disease by altering the expression of an individual’s genetic makeup. The present review tries to summarize the most recent data evidencing how the interactions between nutrients and genetic factors can influence NAFLD development. The final goal should be to develop tools to quantify these complex interactions. The definition of a “nutrigenomic risk score” for each individual may represent a novel therapeutic approach for the management of NAFLD patients.
Pacific North American circulation pattern links external forcing and North American hydroclimatic change over the past millennium

Significance We have developed a new reconstruction of changes in the wintertime atmospheric circulation over North America based on data distributed across the region. The record spans almost 1,000 years and shows how variation in ocean temperatures, solar energy, volcanic eruptions, and greenhouse gases has affected circulation over this period. We show that the circulation pattern is strongly correlated with fluctuating drought conditions in the western United States. Climate models do a poor job of simulating the reconstructed record of circulation change, and thus may have difficulty predicting future patterns of drought influenced by changing winter storm tracks across this region. Land and sea surface temperatures, precipitation, and storm tracks in North America and the North Pacific are controlled to a large degree by atmospheric variability associated with the Pacific North American (PNA) pattern. The modern instrumental record indicates a trend toward a positive PNA phase in recent decades, which has led to accelerated warming and snowpack decline in northwestern North America. The brevity of the instrumental record, however, limits our understanding of long-term PNA variability and its directional or cyclic patterns. Here we develop a 937-y-long reconstruction of the winter PNA based on a network of annually resolved tree-ring proxy records across North America. The reconstruction is consistent with previous regional records in suggesting that the recent persistent positive PNA pattern is unprecedented over the past millennium, but documents patterns of decadal-scale variability that contrast with previous reconstructions. Our reconstruction shows that PNA has been strongly and consistently correlated with sea surface temperature variation, solar irradiance, and volcanic forcing over the period of record, and played a significant role in translating these forcings into decadal-to-multidecadal hydroclimate variability over North America. Climate model ensembles show limited power to predict multidecadal variation in PNA over the period of our record, raising questions about their potential to project future hydroclimatic change modulated by this circulation pattern.
Inter‐Rater Reliability of Total Body Score—A Scale for Quantification of Corpse Decomposition

The degree of body decomposition can be quantified using Total Body Score (TBS), a scale frequently used in taphonomic or entomological studies of decomposition. Here, the inter‐rater reliability of the scale is analyzed. The study was made on 120 laymen, which were trained in the use of the scale. Participants scored decomposition of pig carcasses from photographs. It was found that the scale, when used by different people, gives homogeneous results irrespective of the user qualifications (the Krippendorff's alfa for all participants was 0.818). The study also indicated that carcasses in advanced decomposition receive significantly less accurate scores. Moreover, it was found that scores for cadavers in mosaic decomposition (i.e., representing signs of at least two stages of decomposition) are less accurate. These results demonstrate that the scale may be regarded as inter‐rater reliable. Some propositions for refinement of the scale were also discussed.