Miracle-dz/UniFAR-FTUs huggingface dataset:
Iron‐chelating effect of silymarin in patients with β‐thalassemia major: A crossover randomised control trial

This study aimed to determine the potential iron‐chelating effects of silymarin in patients with β‐thalassemia major receiving standard iron‐chelation therapy. We evaluated whether addition of silymarin to standard iron‐chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo‐controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2‐week washout period, patients were crossed over to the other groups. Silymarin efficacy was assessed by measuring serum iron level, ferritin level, total iron‐binding capacity and liver and cardiac function on magnetic resonance imaging. Silymarin treatment resulted in a negative change in the serum iron and ferritin levels and a positive change in the total iron‐binding capacity levels (treatment effect, p < .001, p = .06, and p = .05, respectively). Silymarin treatment led to positive changes in cardiac and liver function in both treatment sequences of study; however, this was not statistically significant. There was a negative change in liver iron concentration in both treatment sequences (treatment effect, p = .02). In conclusion, combined iron‐chelation and silymarin therapy was effective for improving the iron‐burden status in patients with β‐thalassemia major.
The Effect of Sex on Heart Rate Variability at High Altitude

There is evidence suggesting that high altitude (HA) exposure leads to a fall in heart rate variability (HRV) that is linked to the development of acute mountain sickness (AMS). The effects of sex on changes in HRV at HA and its relationship to AMS are unknown. Methods HRV (5-min single-lead ECG) was measured in 63 healthy adults (41 men and 22 women) 18–56 yr of age at sea level (SL) and during a HA trek at 3619, 4600, and 5140 m, respectively. The main effects of altitude (SL, 3619 m, 4600 m, and 5140 m) and sex (men vs women) and their potential interaction were assessed using a factorial repeated-measures ANOVA. Logistic regression analyses were performed to assess the ability of HRV to predict AMS. Results Men and women were of similar age (31.2 ± 9.3 vs 31.7 ± 7.5 yr), ethnicity, and body and mass index. There was main effect for altitude on heart rate, SD of normal-to-normal (NN) intervals (SDNN), root mean square of successive differences (RMSSD), number of pairs of successive NN differing by >50 ms (NN50), NN50/total number of NN, very low-frequency power, low-frequency (LF) power, high-frequency (HF) power, and total power (TP). The most consistent effect on post hoc analysis was reduction in these HRV measures between 3619 and 5140 m at HA. Heart rate was significantly lower and SDNN, RMSSD, LF power, HF power, and TP were higher in men compared with women at HA. There was no interaction between sex and altitude for any of the HRV indices measured. HRV was not predictive of AMS development. Conclusions Increasing HA leads to a reduction in HRV. Significant differences between men and women emerge at HA. HRV was not predictive of AMS.
Evidence of epigenetic admixture in the Colombian population

&NA; DNA methylation (DNAm) measured in lymphoblastoid cell lines has been repeatedly demonstrated to differ between various human populations. Due to the role that DNAm plays in controlling gene expression, these differences could significantly contribute to ethnic phenotypic differences. However, because previous studies have compared distinct ethnic groups where genetic and environmental context are confounded, their relative contribution to phenotypic differences between ethnicities remains unclear. Using DNAm assayed in whole blood and colorectal tissue of 132 admixed individuals from Colombia, we identified sites where differential DNAm levels were associated with the local ancestral genetic context. Our results are consistent with population specific DNAm being primarily driven by between population genetic differences in cis, with little environmental contribution, and with consistent effects across tissues. The findings offer new insights into a possible mechanism driving phenotypic differences among different ethnic groups, and could help explain ethnic differences in colorectal cancer incidence.
Evaluation and Enumeration Problems for Regular Path Queries

Regular path queries (RPQs) are a central component of graph databases. We investigate decision- and enumeration problems concerning the evaluation of RPQs under several semantics that have recently been considered: arbitrary paths, shortest paths, and simple paths. Whereas arbitrary and shortest paths can be enumerated in polynomial delay, the situation is much more intricate for simple paths. For instance, already the question if a given graph contains a simple path of a certain length has cases with highly non-trivial solutions and cases that are long-standing open problems. We study RPQ evaluation for simple paths from a parameterized complexity perspective and define a class of simple transitive expressions that is prominent in practice and for which we can prove a dichotomy for the evaluation problem. We observe that, even though simple path semantics is intractable for RPQs in general, it is feasible for the vast majority of RPQs that are used in practice. At the heart of our study on simple paths is a result of independent interest: the two disjoint paths problem in directed graphs is W[1]-hard if parameterized by the length of one of the two paths.
The ethics of reporting all the results of clinical trials

Introduction or background The terms 'publication bias' and 'reporting bias' describe aspects of a phenomenon by which data from trials are not publicized, and so remain inaccessible. This may generate a false impression about the world; but those facts may have important implications for clinical decisions. Thus, the bias may leave patients worse off than they might be. Sources of data Published journal articles. Areas of agreement There is general agreement that the phenomenon happens, and that to the extent that it happens, it is undesirable for moral rather than simply epistemic reasons. Growing points There is a growing demand across the board for data to be better publicized. Areas timely for developing research There is room for further work on how protocols requiring that data be publicized might be enforced; should it be statutory, or non-statutory? Who should decide what should be made public? There is also room for work on what it is necessary to share, and on whether and how IP law should be reformed.
Ribosomal proteins produced in excess are degraded by the ubiquitin–proteasome system

Overexpression of ribosomal proteins in yeast is prevented by ubiquitination of unassembled ribosomal proteins in the nucleus and/or nucleolus followed by proteasome-dependent degradation. Brief inhibition of proteasome causes strong accumulation of multiple ribosomal proteins in an insoluble fraction, suggesting that this is a general phenomenon.
Inflammatory breast cancer tumor emboli express high levels of anti-apoptotic proteins: use of a quantitative high content and high-throughput 3D IBC spheroid assay to identify targeting strategies

Inflammatory breast cancer (IBC) is one of the most lethal breast cancer variants; with existing therapy, 5-yr survival rate is only 35%. Current barriers to successful treatment of IBC include frequent infiltration and the presence of tumor cell clusters, termed tumor emboli, within the breast parenchyma and lymphatics. Prior studies have identified the role of anti-apoptotic signaling, in particular hyperactivation of NFκB and its target genes, in IBC pathobiology and therapeutic resistance. The objectives of this study were to: (1) determine if IBC tumor emboli express anti-apoptotic proteins and (2) develop a high content, multiparametric assay to assess the morphology of the IBC 3D spheroids and to optimize a high throughput format to screen for compounds that can inhibit the formation of the IBC tumor clusters/embolic structures. Immunohistochemical analysis of IBC patient tumor samples with documented tumor emboli revealed high NFκB (p65) staining along with expression of XIAP, a potent anti-apoptotic protein known to interact with NFκB signaling in enhancing survival of malignant cells. Subsequently, the high content assay developed allowed for simultaneous imaging and morphometric analysis, including count and viability of spheroids derived from SUM149, rSUM149 and SUM190 cells and its application to evaluate XIAP and NFκB inhibitory agents. We demonstrate the efficacy of the off-patent drug disulfiram when chelated with copper, which we had previously reported to inhibit NFκB signaling, was highly effective in disrupting both IBC spheroids and emboli grown in vitro. Taken together, these results identify a high-throughput approach to target tumor spheroid formation for drug discovery. Finally, disulfiram is a safe and approved drug for management of alcohol abuse, warranting its evaluation for repurposing in IBC therapy.
Sexual dysfunction and dissatisfaction in chronic hepatitis C patients.

INTRODUCTION The prevalence of sexual dysfunction (SD) and dissatisfaction with sexual life (DSL) in patients with chronic hepatitis C virus infection (CHC) was jointly investigated via a thorough psychopathological analysis, which included dimensions such as fatigue, impulsiveness, psychiatric comorbidity, health-related quality of life (HRQL) and sociodemographic and clinical characteristics. METHODS Male and female CHC patients from an outpatient referral center were assessed using the Brief Fatigue Inventory, the Barrat Impulsiveness Scale, the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale, the Hamilton Anxiety Scale (HAM-A), and the World Health Organization Quality of Life Scale-Brief Version (WHOQOL-BREF). Structured psychiatric interviews were performed according to the Mini-International Neuropsychiatric Interview. SD was assessed based on specific items in the BDI (item 21) and the HAM-A (item 12). DSL was assessed based on a specific question in the WHOQOL-BREF (item 21). Multivariate analysis was performed according to an ordinal linear regression model in which SD and DSL were considered as outcome variables. RESULTS SD was reported by 60 (57.1%) of the patients according to the results of the BDI and by 54 (51.4%) of the patients according to the results of the HAM-A. SD was associated with older age, female gender, viral genotype 2 or 3, interferon-α use, impulsiveness, depressive symptoms, antidepressant and benzodiazepine use, and lower HRQL. DSL was reported by 34 (32.4%) of the patients and was associated with depressive symptoms, anxiety symptoms, antidepressant use, and lower HRQL. CONCLUSIONS The prevalence of SD and DSL in CHC patients was high and was associated with factors, such as depressive symptoms and antidepressant use. Screening and managing these conditions represent significant steps toward improving medical assistance and the HRQL of CHC patients.
Bottom‐up performance analysis of focal‐plane mixed‐signal hardware for Viola–Jones early vision tasks

Focal‐plane mixed‐signal arrays have traditionally been designed according to the general claim that moderate accuracy in processing is affordable. The performance of their circuitry has been analyzed in these terms without a comprehensive study of the ultimate consequences of such moderate accuracy. In this paper, for the first time to the best of our knowledge, we do carry out this study. We move expectable performance of mixed‐signal image processing hardware directly into the vision algorithm making use of it. This permits to close a wider design loop, enabling a more aggressive design of this kind of hardware provided that the algorithm, at the highest level—semantic interpretation of the scene—, can afford it. Thus, we present a thorough analysis of the non‐idealities associated with the implementation of a QVGA array tailored for the distinctive characteristics of the Viola–Jones processing framework. The resulting deviation models are then introduced in the processing flow of this framework provided by the OpenCV library. We have found, contrary to what could be expected, that these deviations do not necessarily degrade the performance of the Viola–Jones algorithm. They could be even beneficial for certain high‐level specifications. Additionally, we demonstrate the architectural advantages of our approach: exploitation of focal‐plane distributed memory and ultra‐low‐power operation. Copyright © 2014 John Wiley & Sons, Ltd.
The origins of the Malagasy people, some certainties and a few mysteries

The Malagasy language belongs to the Greater Barito East group of the Austronesian family, the language most closely connected to Malagasy dialects is Maanyan (Kalimantan), but Malay as well other Indonesian and Philippine languages are also related. The African contribution is very high in the Malagasy genetic make-up (about 50%) but negligible in the language. Because of the linguistic link, it is widely accepted that the island was settled by Indonesian sailors after a maritime trek but date and place of landing are still debated. The 50% Indonesian genetic contribution to present Malagasy points in a different direction then Maanyan for the Asian ancestry, therefore, the ethnic composition of the Austronesian settlers is also still debated. In this talk I mainly review the joint research of Filippo Petroni, Dima Volchenkov, S\"oren Wichmann and myself which tries to shed new light on these problems. The key point is the application of a new quantitative methodology which is able to find out the kinship relations among languages (or dialects). New techniques are also introduced in order to extract the maximum information from these relations concerning time and space patterns.
Poison prevention practices and medically attended poisoning in young children: multicentre case–control study

Introduction Childhood poisonings are common, placing a substantial burden on health services. Case–control studies have found inconsistent evidence about modifiable risk factors for poisonings among children aged 0–4 years. This study quantifies associations between poison prevention practices and medically attended poisonings in children aged 0–4 years. Methods Multicentre case–control study conducted at hospitals, minor injury units and family practices from four study centres in England between 2010 and 2013. Participants comprised 567 children presenting with unintentional poisoning occurring at home and 2320 community control participants matched on age, sex, date of event and study centre. Parents/caregivers provided data on safety practices, safety equipment use, home hazards and potential confounders by means of self-completion questionnaires. Data were analysed using conditional logistic regression. Results Compared with community controls, parents of poisoned children were significantly more likely not to store medicines out of reach (adjusted OR (AOR) 1.59; 95% CI 1.21 to 2.09; population attributable fraction (PAF) 15%), not to store medicines safely (locked or out of reach (AOR 1.83; 95% CI 1.38 to 2.42; PAF 16%) and not to have put all medicines (AOR 2.11; 95% CI 1.54 to 2.90; PAF 20%) or household products (AOR 1.79, 95% CI 1.29 to 2.48; PAF 11%) away immediately after use. Conclusions Not storing medicines out of reach or locked away and not putting medicines and household products away immediately after use increased the odds of secondary care attended poisonings in children aged 0–4 years. If associations are causal, implementing these poison prevention practices could each prevent between 11% and 20% of poisonings.
Clinical utility of circulating DNA analysis for rapid detection of actionable mutations to select metastatic colorectal patients for anti-EGFR treatment

Background While tumor-tissue remains the 'gold standard' for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care. Patients and methods Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients). Results are presented according to STARD criteria and were discussed in regard with clinical outcomes of patients. Results Much more mutations were found by ctDNA analysis: 59%, 11.8% and 14.4% of the patients were found KRAS, NRAS and BRAF mutant by ctDNA analysis instead of 44%, 8.8% and 7.2% by tumor-tissue analysis. Median tumor-tissue data turnaround-time was 16 days while 2 days for ctDNA analysis. Discordant samples analysis revealed that use of biopsy, long delay between tumor-tissue and blood collection and resection of the tumor at time of blood draw, tumor site, or type of tissue analyzed seem to affect concordance. Altogether, the clinical data with respect to the anti-epidermal growth factor receptor response (RAS status) and the prognosis (BRAF status) of those discordant patients do not appear contradictory to the mutational status as determined by plasma analysis. Lastly, we present the first distribution profile of the RAS and BRAF hotspot mutations as determined by ctDNA analysis (n = 119), revealing a high proportion of patients with multiple mutations (45% of the population and up to 5 mutations) and only 24% of WT scored patients for both genes. Mutation profile as determined from ctDNA analysis with using various detection thresholds highlights the importance of the test sensitivity. Conclusion Our study showed that ctDNA could replace tumor-tissue analysis, and also clinical utility of ctDNA analysis by considerably reducing data turnaround time.
The role of water, ice nucleators, and inoculation in insect cold survival

Over the past century and especially the last few decades a significant progress has been made in our understanding of the mechanisms that underlie the capacity of insects and other ectothermic animals to survive at subzero temperatures. Although we now understand relatively well the complexity of the cold tolerance phenomenon, from the molecular to the ecological level, some aspects remain elusive. This review summarizes current knowledge on the mechanisms of cold tolerance and focuses on the three following issues that remain unsolved in this field: 1) the role of water in preservation of biological structures in organisms that exploit dehydration as a part of their cold survival strategy, 2) the cause of ice nucleation in freeze-intolerant organisms below the temperature range of the activity of ice nucleating proteins and above the temperature of homogeneous nucleation of water, and 3) the capacity of some primarily freeze-intolerant
A microbial signature for Crohn's disease

Objective A decade of microbiome studies has linked IBD to an alteration in the gut microbial community of genetically predisposed subjects. However, existing profiles of gut microbiome dysbiosis in adult IBD patients are inconsistent among published studies, and did not allow the identification of microbial signatures for CD and UC. Here, we aimed to compare the faecal microbiome of CD with patients having UC and with non-IBD subjects in a longitudinal study. Design We analysed a cohort of 2045 non-IBD and IBD faecal samples from four countries (Spain, Belgium, the UK and Germany), applied a 16S rRNA sequencing approach and analysed a total dataset of 115 million sequences. Results In the Spanish cohort, dysbiosis was found significantly greater in patients with CD than with UC, as shown by a more reduced diversity, a less stable microbial community and eight microbial groups were proposed as a specific microbial signature for CD. Tested against the whole cohort, the signature achieved an overall sensitivity of 80% and a specificity of 94%, 94%, 89% and 91% for the detection of CD versus healthy controls, patients with anorexia, IBS and UC, respectively. Conclusions Although UC and CD share many epidemiologic, immunologic, therapeutic and clinical features, our results showed that they are two distinct subtypes of IBD at the microbiome level. For the first time, we are proposing microbiomarkers to discriminate between CD and non-CD independently of geographical regions.
Structural and functional analysis of de‐N‐acetylase PgaB from periodontopathogen Aggregatibacter actinomycetemcomitans

The oral pathogen Aggregatibacter actinomycetemcomitans uses pga gene locus for the production of an exopolysaccharide made up of a linear homopolymer of β-1,6-N-acetyl-d-glucosamine (PGA). An enzyme encoded by the pgaB of the pga operon in A. actinomycetemcomitans is a de-N-acetylase, which is used to alter the PGA. The full length enzyme (AaPgaB) and the N-terminal catalytic domain (residues 25-290, AaPgaBN) from A. actinomycetemcomitans were cloned, expressed and purified. The enzymatic activities of the AaPgaB enzymes were determined using 7-acetoxycoumarin-3-carboxylic acid as the substrate. The AaPgaB enzymes displayed significantly lower de-N-acetylase activity compared with the activity of the deacetylase PdaA from Bacillus subtilis, a member of the CE4 family of enzymes. To delineate the differences in the activity and the active site architecture, the structure of AaPgaBN was determined. The AaPgaBN structure has two metal ions in the active site instead of one found in other CE4 enzymes. Based on the crystal structure comparisons among the various CE4 enzymes, two residues, Q51 and R271, were identified in AaPgaB, which could potentially affect the enzyme activity. Of the two mutants generated, Q51E and R271K, the variant Q51E showed enhanced activity compared with AaPgaB, validating the requirement that an activating aspartate residue in the active site is essential for higher activity. In summary, our study provides the first structural evidence for a di-nuclear metal site at the active site of a member of the CE4 family of enzymes, evidence that AaPgaBN is catalytically active and that mutant Q51E exhibits higher de-N-acetylase activity.
Fast, autonomous flight in GPS‐denied and cluttered environments

One of the most challenging tasks for a flying robot is to autonomously navigate between target locations quickly and reliably while avoiding obstacles in its path, and with little to no a priori knowledge of the operating environment. This challenge is addressed in the present paper. We describe the system design and software architecture of our proposed solution and showcase how all the distinct components can be integrated to enable smooth robot operation. We provide critical insight on hardware and software component selection and development and present results from extensive experimental testing in real‐world warehouse environments. Experimental testing reveals that our proposed solution can deliver fast and robust aerial robot autonomous navigation in cluttered, GPS‐denied environments.