Miracle-dz/UniFAR-FTUs huggingface dataset:
Does variation in neurodegenerative disease susceptibility and phenotype reflect cerebral differences at the network level?

Abstract Alzheimer's disease (AD) is 10-fold more frequent than Parkinson's disease (PD), which in turn is 10-fold more frequent than amyotrophic lateral sclerosis (ALS). The differences between these neurodegenerative diseases have been ascribed to a selective vulnerability of specific neuronal sub-types that then determine each disorder. However, there are non-neuronal cells that are ubiquitously and possibly primarily involved in all of them, and they share regulatory mechanisms through similar interneurons and, typically inhibitory, neurotransmitters. There is recognized clinical and neuropathological overlap between AD, PD and ALS, the best example being Guamanian Lytico-Bodig, but increasingly recognized in larger populations, e.g. carriers of C9orf72 hexanucleotide expansions. From early embryogenesis to adulthood, genetic and experience-dependent functional neural networks develop primarily in relation to the neocortex. From an evolutionary standpoint, cognition, memory, executive function, linguistics and fine motor function are most prominent in humans. It is concluded that neural networks, rather than specific neuronal sub-types defined regionally or by individual transmitters, underlie the marked differences between neurodegenerative disorders in terms of susceptibility and clinical features. This requires the continued development of strategies to study brain function in health and disease as the ‘system’, greater than the sum of its parts.
Deregulation of Rho GTPases in cancer

ABSTRACT In vitro and in vivo studies and evidence from human tumors have long implicated Rho GTPase signaling in the formation and dissemination of a range of cancers. Recently next generation sequencing has identified direct mutations of Rho GTPases in human cancers. Moreover, the effects of ablating genes encoding Rho GTPases and their regulators in mouse models, or through pharmacological inhibition, strongly suggests that targeting Rho GTPase signaling could constitute an effective treatment. In this review we will explore the various ways in which Rho signaling can be deregulated in human cancers.
Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways

The biochemistry of cancer cells diverges significantly from normal cells as a result of a comprehensive reprogramming of metabolic pathways. A major factor influencing cancer metabolism is hypoxia, which is mediated by HIF1α and HIF2α. HIF1α represents one of the principal regulators of metabolism and energetic balance in cancer cells through its regulation of glycolysis, glycogen synthesis, Krebs cycle and the pentose phosphate shunt. However, less is known about the role of HIF1α in modulating lipid metabolism. Lipids serve cancer cells to provide molecules acting as oncogenic signals, energetic reserve, precursors for new membrane synthesis and to balance redox biological reactions. To study the role of HIF1α in these processes, we used HCT116 colorectal cancer cells expressing endogenous HIF1α and cells in which the hif1α gene was deleted to characterize HIF1α-dependent and independent effects on hypoxia regulated lipid metabolites. Untargeted metabolomics integrated with proteomics revealed that hypoxia induced many changes in lipids metabolites. Enzymatic steps in fatty acid synthesis and the Kennedy pathway were modified in a HIF1α-dependent fashion. Palmitate, stearate, PLD3 and PAFC16 were regulated in a HIF-independent manner. Our results demonstrate the impact of hypoxia on lipid metabolites, of which a distinct subset is regulated by HIF1α.
Protruding atherosclerotic aortic plaques and dyslipidaemia: correlation to subtypes of ischaemic stroke.

AIMS To evaluate whether thoracic aortic plaques together with dyslipidaemia are related to ischaemic stroke, and if so, to which of the subtypes of stroke. METHODS AND RESULTS We performed transoesophageal echocardiography in 50 patients with acute ischaemic stroke and in 401 controls. The aorta was divided into two segments: (1) the proximal, proximal to the left subclavian artery, and (2) the distal aorta. Protruding plaques (Intima > or =4 mm in thickness) in the proximal aorta were detected in 14 of the 50 patients (28%) with stroke, and in 53 of the 401 controls (13%) (P<0.01). Plaque score in the proximal aorta (2.1 +/- 1.8 vs 0.9 +/- 0.7; P<0.05), low-density lipoprotein cholesterol level (3.60 +/- 0.85 vs 2.87 +/- 0.72 mmol/l; P<0.05), and apolipoprotein B/A-I ratio (0.98 +/-0.17 vs 0.73 +/- 0.16; P<0.005) were higher in patients with athero-thrombotic than in cardioembolic stroke. The score in the proximal aorta correlated with low-density lipoprotein cholesterol level (r=0.44, P<0.005) and apolipoprotein B/A-I ratio (r=0.40, P<0.01). CONCLUSION Severe plaques in the proximal aorta together with dyslipidaemia are seen more frequently in patients with atherothrombotic stroke. Lipid analysis may contribute to the prediction and the treatment of the patients who are at high risk for atherothrombotic stroke.
RELATIONSHIP BETWEEN RADIATION DOSE AND IMAGE QUALITY IN DIGITAL BREAST TOMOSYNTHESIS

This phantom-based study aimed to examine radiation dose from digital breast tomosynthesis (DBT) and digital mammography (DM) and to assess the potential for dose reductions for each modality. Images were acquired at 10-60 mm thicknesses and four dose levels and mean glandular dose was determined using a solid-state dosemeter. Eleven readers assessed image quality and compared simulated lesions with those on a reference image, and the data produced was analysed with the Friedman and Wilcoxon signed-rank tests. For a phantom thickness of 50 mm (typical breast thickness), DBT dose was 13 % higher than DM, but this differential is highly dependent on thickness. Visibility of masses was equal to a reference image (produced at 100 % dose) when dose was reduced by 75 and 50 % for DBT and DM. For microcalcifications, visibility was comparable with the reference image for both modalities at 50 % dose. This study highlighted the potential for reducing dose with DBT.
Unbiased selection of bone marrow derived cells as carriers for cancer gene therapy

There is currently great interest in development of cell‐based carriers for delivery of viral vectors to metastatic tumors. To date, several cell carriers have been tested based largely upon their predicted tumor‐localizing properties. However, cell types may exist which can be mobilized from the circulation by a tumor which have not yet been identified. Here we use an unbiased screen of bone marrow (BM) cells to identify cells which localize to tumors and which might serve as effective candidate cell carriers without any prior prediction or selection.
Clinical utility of dronabinol in the treatment of weight loss associated with HIV and AIDS

Since the beginning of the HIV/AIDS epidemic, weight loss has been a common complaint for patients. The use of various definitions defining HIV wasting syndrome has made it difficult to determine its actual prevalence. Despite the use of highly active antiretroviral therapy, it is estimated that the prevalence of HIV wasting syndrome is between 14% and 38%. HIV wasting syndrome may stem from conditions affecting chewing, swallowing, or gastrointestinal motility, neurologic disease affecting food intake or the perception of hunger or ability to eat, psychiatric illness, food insecurity generated from psychosocial or economic concerns, or anorexia due to medications, malabsorption, infections, or tumors. Treatment of HIV wasting syndrome may be managed with appetite stimulants (megestrol acetate or dronabinol), anabolic agents (testosterone, testosterone analogs, or recombinant human growth hormone), or, rarely, cytokine production modulators (thalidomide). The goal of this review is to provide an in-depth evaluation based on existing clinical trials on the clinical utility of dronabinol in the treatment of weight loss associated with HIV/AIDS. Although total body weight gain varies with dronabinol use (–2.0 to 3.2 kg), dronabinol is a well-tolerated option to promote appetite stimulation. Further studies are needed with standardized definitions of HIV-associated weight loss and clinical outcomes, robust sample sizes, safety and efficacy data on chronic use of dronabinol beyond 52 weeks, and associated virologic and immunologic outcomes.
The Efficiency of Aggressive Hydration With Lactated Ringer Solution for the Prevention of Post-ERCP Pancreatitis: A Systematic Review and Meta-analysis

Background: As shown in studies, aggressive hydration during the perioperative period of endoscopic retrograde cholangiopancreatography (ERCP) effectively prevents post-ERCP pancreatitis (PEP). We conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of aggressive hydration with lactated Ringer solution at preventing PEP. Materials and Methods: We searched all relevant research from PubMed, the Cochrane Library, Embase, the Web of Science, ClinicalTrial.gov, and Scopus database for randomized controlled trials (RCTs) published before March 2017. Reference lists from reviews or relevant articles were screened for RCTs. The primary outcomes were the incidence of PEP and the incidence of moderate to severe pancreatitis. The secondary outcomes were the incidence of hyperamylasemia and pain and the length of hospital stay. The meta-analysis was conducted using the Cochrane Program Review Manager. Results: Three RCTs were included in our study. On the basis of the results of the meta-analysis, the aggressive hydration group had a lower incidence of pancreatitis after ERCP [odds ratio (OR)=0.29; 95% confidence interval (CI), 0.16-0.53]; a lower incidence of moderate to severe PEP (OR=0.16; 95% CI, 0.03-0.96); lower incidence of hyperamylasemia (OR=0.38; 95% CI, 0.25-0.59); lower risk of pain (OR=0.17; 95% CI, 0.08-0.38); and a shorter duration of hospital stay (standardized mean difference=−0.41; 95% CI, −0.69 to −0.14). Conclusions: Aggressive hydration with lactated Ringer solution can reduce the overall incidence of PEP, moderate to severe pancreatitis and hyperamylasemia, shorten the length of hospitalization and reduce pain.
Complexity of generic biochemical circuits: topology versus strength of interactions

The historical focus on network topology as a determinant of biological function is still largely maintained today, illustrated by the rise of structure-only approaches to network analysis. However, biochemical circuits and genetic regulatory networks are defined both by their topology and by a multitude of continuously adjustable parameters, such as the strength of interactions between nodes, also recognized as important. Here we present a class of simple perceptron-based Boolean models within which comparing the relative importance of topology versus interaction strengths becomes a quantitatively well-posed problem. We quantify the intuition that for generic networks, optimization of interaction strengths is a crucial ingredient of achieving high complexity, defined here as the number of fixed points the network can accommodate. We propose a new methodology for characterizing the relative role of parameter optimization for topologies of a given class.
The Analytical Hierarchy Process Approach for Prioritizing Features in the Selection of Web Service

A selection of an appropriate Web service can be viewed as a multi-criteria decision-making problem involving selection of multi-attribute candidate service from a set of available services. This selection should not be based on intuition but need thorough understanding of the decision problem and the process to prioritize the features and, hence services. This study proposes analytical hierarchy process (AHP) approach for prioritizing Web service features, thus aiding the decision making process in a quantitative way. The AHP method is a way of solving the decision problem by pairwise comparison of elements with consistency in results. An illustrative problem for prioritizing Web service features is also detailed here so as to substantiate our proposal.
Premature mortality after suicide attempt in relation to living arrangements. A register-based study in Finland in 1988–2007

Background: Several studies have shown that individuals with a history of suicide attempt form a high-risk mortality group. Completed suicide is the main cause of death among them, but excess mortality for other causes of death is much less studied. Furthermore, little is known whether living with others modifies the excess risk of mortality among suicide attempters. Methods: We evaluated an 11% sample from the population registration data of Finns aged 15 years and older in the period 1988–2007 with an 80% oversample of death records and a linkage with information on causes of hospitalisation. We estimate standardised mortality rates and Poisson regression models separately for the general population and those treated in hospital for suicide attempt. Results: Compared with the general population, all-cause mortality risk was ∼10-fold among women and well over 10-fold among men during the first 3 months following suicide attempt. The risk for suicide was even greater, but in addition to external causes of death, mortality from smoking- and alcohol-related diseases was elevated. Instead, the proportion of alcohol-associated suicides was smaller among the suicide attempters. Among suicide attempters, the association between living arrangements and mortality was much weaker than in the general population. Conclusion: Premature mortality is extremely high after suicide attempt, especially in the first year. Our results do not support the idea that the resources provided by living with others ameliorate the effects of suicide attempt on subsequent mortality. Suicide prevention should focus on designing adequate aftercare following the attempt, especially for those with alcohol problems.
Epley and beyond: an update on treating positional vertigo

Benign paroxysmal positional vertigo (BPPV) is the commonest cause of dizziness. It is characterised by brief episodes of vertigo and imbalance with nystagmus. The direction of nystagmus allows the identification of the culprit semicircular canal. As it is readily treatable—and often curable—BPPV should not be missed. Although recurrent episodes of vertigo triggered by movement suggest BPPV, the diagnosis can only be confirmed with the Dix-Hallpike manoeuvre. Here we review the diagnostic manoeuvres required to diagnose BPPV, and the various repositioning manoeuvres for treating different types of BPPV.
Is electrical coupling involved in the generation of posterior hypothalamic theta rhythm?

Data obtained in in vitro experiments and urethane anaesthetized animals have revealed that the mechanisms responsible for the generation of hippocampal cholinergic theta rhythm are specifically affected by the administration of broad spectrum gap junctions (GJs) blocker – carbenoxolone (CBX). The aim of this study was to examine the effect of GJs modulation on the production of posterior hypothalamic theta. Specifically, we were interested in evaluating whether CBX could attenuate the theta rhythm recorded from the supramammillary nucleus and posterior hypothalamic nuclei, in both in vitro and in vivo preparations. The data we obtained from in vitro and in vivo preparations demonstrated that the administration of CBX did not suppress cholinergically induced theta in posterior hypothalamic area (PHa) slices nor the theta rhythm observed in the PHa of urethane anaesthetized rats. Moreover, the application of trimethylamine, while very effective in the enhancement of hippocampal theta rhythm, did not produce any changes in theta oscillations observed in either in vitro or in vivo posterior hypothalamic area preparations. These data show that electrical coupling via GJs is not involved in theta rhythm generation in the PHa. Surprisingly, we observed a significant enhancement of theta activity in response to the carbenoxolone administration in both in vitro and in vivo PHa preparations. The theta rhythm enhancement detected in those experiments was attenuated by the application of spironolactone (mineralocorticoid receptors antagonist). We suggest that the observed excitatory effects of CBX on posterior hypothalamic oscillatory activity in the theta band could be mediated by mineralocorticoid receptors.
Cis-eQTL-based trans-ethnic meta-analysis reveals novel genes associated with breast cancer risk

Breast cancer is the most common solid organ malignancy and the most frequent cause of cancer death among women worldwide. Previous research has yielded insights into its genetic etiology, but there remains a gap in the understanding of genetic factors that contribute to risk, and particularly in the biological mechanisms by which genetic variation modulates risk. The National Cancer Institute’s “Up for a Challenge” (U4C) competition provided an opportunity to further elucidate the genetic basis of the disease. Our group leveraged the seven datasets made available by the U4C organizers and data from the publicly available UK Biobank cohort to examine associations between imputed gene expression and breast cancer risk. In particular, we used reference datasets describing the breast tissue and whole blood transcriptomes to impute expression levels in breast cancer cases and controls. In trans-ethnic meta-analyses of U4C and UK Biobank data, we found significant associations between breast cancer risk and the expression of RCCD1 (joint p-value: 3.6x10-06) and DHODH (p-value: 7.1x10-06) in breast tissue, as well as a suggestive association for ANKLE1 (p-value: 9.3x10-05). Expression of RCCD1 in whole blood was also suggestively associated with disease risk (p-value: 1.2x10-05), as were expression of ACAP1 (p-value: 1.9x10-05) and LRRC25 (p-value: 5.2x10-05). While genome-wide association studies (GWAS) have implicated RCCD1 and ANKLE1 in breast cancer risk, they have not identified the remaining three genes. Among the genetic variants that contributed to the predicted expression of the five genes, we found 23 nominally (p-value < 0.05) associated with breast cancer risk, among which 15 are not in high linkage disequilibrium with risk variants previously identified by GWAS. In summary, we used a transcriptome-based approach to investigate the genetic underpinnings of breast carcinogenesis. This approach provided an avenue for deciphering the functional relevance of genes and genetic variants involved in breast cancer.
Relative contribution of early life and adult socioeconomic factors to adult morbidity in the Whitehall II study

STUDY OBJECTIVE To determine the relative contribution of adult compared with early life socioeconomic status as predictors of morbidity attributable to coronary heart disease (CHD), chronic bronchitis and depression in the Whitehall II study of British civil servants. DESIGN Prospective observational study with mean 5.3 years (range 3.7–7.6) follow up. SETTING 20 civil service departments originally located in London. PARTICIPANTS 6895 male and 3413 female office-based civil servants aged 35–55 years at baseline. OUTCOME MEASURES New cases at follow up of CHD, chronic bronchitis and depression defined using validated questionnaires. MAIN RESULTS Employment grade was inversely associated with CHD, chronic bronchitis and depression in men (odds ratio per unit decrease in grade 1.30, 1.44 and 1.20 respectively). Employment grade was strongly related to father's social class. Chronic bronchitis, in women, and depression, in men, were more common among those with fathers of higher social class. When mutual adjustment was made for father's social class, grade at entry to the civil service and current grade, the strongest effects on adult morbidity were found for current grade. Among participants in whom neither parent had died ⩽70 years of age the inverse association with adult SES was maintained. CONCLUSIONS Adult socioeconomic status was a more important predictor of morbidity attributable to coronary disease, chronic bronchitis and depression than measures of social status earlier in life. In this population, the importance of social circumstances early in life may be in the way they influence employment and social position and thus exposures in adult life.
An Efficient Intermode Decision Algorithm Based on Motion Homogeneity for H.264/AVC

The latest video coding standard H.264/AVC significantly outperforms previous standards in terms of coding efficiency. H.264/AVC adopts variable block sizes ranging from 4 times 4 to 16 times 16 in inter frame coding, and achieves significant gain in coding efficiency compared to coding a macroblock (MB) using regular block size. However, this new feature causes extremely high computation complexity when rate-distortion optimization (RDO) is performed using the scheme of full mode decision. This paper presents an efficient intermode decision algorithm based on motion homogeneity evaluated on a normalized motion vector (MV) field, which is generated using MVs from motion estimation on the block size of 4 times 4. Three directional motion homogeneity measures derived from the normalized MV field are exploited to determine a subset of candidate intermodes for each MB, and unnecessary RDO calculations on other intermodes can be skipped. Experimental results demonstrate that our algorithm can reduce the entire encoding time about 40% on average, without any noticeable loss of coding efficiency.
Surface Wettability Modification of Cyclic Olefin Polymer by Direct Femtosecond Laser Irradiation

The effect of laser irradiation on surface wettability of cyclic olefin polymer (COP) was investigated. Under different laser parameters, a superhydrophilic or a superhydrophobic COP surface with a water contact angle (WCA) of almost 0° or 163°, respectively, could be achieved by direct femtosecond laser irradiation. The laser power deposition rate (PDR) was found to be a key factor on the wettability of the laser-treated COP surface. The surface roughness and surface chemistry of the laser-irradiated samples were characterized by surface profilometer and X-ray photoelectron spectroscopy, respectively; they were found to be responsible for the changes of the laser-induced surface wettability. The mechanisms involved in the laser surface wettability modification process were discussed.