Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole chromosome gain does not in itself confer cancer-like chromosomal instability

Significance Aneuploidy, denoting cells with an abnormal number of chromosomes, is a common phenomenon in cancer. Another common finding in cancer cells is chromosomal instability, a condition in which cells change their chromosomal content at a high rate. It is clear that chromosomal instability can lead to aneuploidy, but whether the opposite is true has been much debated in the field of cancer biology. The concept that aneuploidy automatically triggers chromosomal instability has been propagated in the scientific literature in recent years. Here, we show that aneuploidy does not, on its own, lead to chromosomal instability, even when cells acquire chromosome alterations typical of cancer. This has important implications for understanding the role of aneuploidy in cancer development. Constitutional aneuploidy is typically caused by a single-event meiotic or early mitotic error. In contrast, somatic aneuploidy, found mainly in neoplastic tissue, is attributed to continuous chromosomal instability. More debated as a cause of aneuploidy is aneuploidy itself; that is, whether aneuploidy per se causes chromosomal instability, for example, in patients with inborn aneuploidy. We have addressed this issue by quantifying the level of somatic mosaicism, a proxy marker of chromosomal instability, in patients with constitutional aneuploidy by precise background-filtered dual-color FISH. In contrast to previous studies that used less precise methods, we find that constitutional trisomy, even for large chromosomes that are often trisomic in cancer, does not confer a significantly elevated rate of somatic chromosomal mosaicism in individual cases. Constitutional triploidy was associated with an increased level of somatic mosaicism, but this consisted mostly of reversion from trisomy to disomy and did not correspond to a proportionally elevated level of chromosome mis-segregation in triploids, indicating that the observed mosaicism resulted from a specific accumulation of cells with a hypotriploid chromosome number. In no case did the rate of somatic mosaicism in constitutional aneuploidy exceed that of “chromosomally stable” cancer cells. Our findings show that even though constitutional aneuploidy was in some cases associated with low-level somatic mosaicism, it was insufficient to generate the cancer-like levels expected if aneuploidy single-handedly triggered cancer-like chromosomal instability.
Indicators of early research productivity among primary care fellows

AbstractOBJECTIVE: Little is known about the impact of fellowship training in primary care on subsequent research productivity. Our goal was to identify characteristics of research fellows and their training associated with subsequent publications and research funding. DESIGN: Mail survey in 1998. SETTING AND PARTICIPANTS: 1988–1997 graduates of 25 National Research Service Award primary care research fellowships in the United States. OUTCOME MEASURES: 1) Publishing 1 or more papers per year since the beginning of fellowship, or 2) serving as principal investigator (PI) on a federal or non-federal grant. RESULTS: One hundred forty-six of two hundred fifteen program graduates (68%) completed the survey. The median age was 38 years, and 51% were male. Thirty-two percent had published 1 or more papers per year, and 44% were PIs. Male gender (odds ratio [OR], 3.6; 95% confidence interval [95% CI], 1.4 to 9.2), self-reported allocation of 40% or more of fellowship time to research (OR, 4.4; 95% CI, 1.8 to 11.2), and having an influential mentor during fellowship (OR, 5.0; 95% CI, 1.5 to 17.2) were independently associated with publishing 1 or more papers per year. Fellows with funding as a PI were also more likely to have an influential mentor (OR, 3.0; 95% CI, 1.3 to 7.2). CONCLUSION: Primary care fellows who had influential mentors were more productive in research early after fellowship. Awareness of the indicators of early research success can inform the policies of agencies that fund research training and the curricula of training programs themselves.
Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial.

CONTEXT Basic research and observational studies suggest vitamin E or vitamin C may reduce the risk of cardiovascular disease. However, few long-term trials have evaluated men at initially low risk of cardiovascular disease, and no previous trial in men has examined vitamin C alone in the prevention of cardiovascular disease. OBJECTIVE To evaluate whether long-term vitamin E or vitamin C supplementation decreases the risk of major cardiovascular events among men. DESIGN, SETTING, AND PARTICIPANTS The Physicians' Health Study II was a randomized, double-blind, placebo-controlled factorial trial of vitamin E and vitamin C that began in 1997 and continued until its scheduled completion on August 31, 2007. There were 14,641 US male physicians enrolled, who were initially aged 50 years or older, including 754 men (5.1%) with prevalent cardiovascular disease at randomization. INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily. MAIN OUTCOME MEASURES A composite end point of major cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular disease death). RESULTS During a mean follow-up of 8 years, there were 1245 confirmed major cardiovascular events. Compared with placebo, vitamin E had no effect on the incidence of major cardiovascular events (both active and placebo vitamin E groups, 10.9 events per 1000 person-years; hazard ratio [HR], 1.01 [95% confidence interval {CI}, 0.90-1.13]; P = .86), as well as total myocardial infarction (HR, 0.90 [95% CI, 0.75-1.07]; P = .22), total stroke (HR, 1.07 [95% CI, 0.89-1.29]; P = .45), and cardiovascular mortality (HR, 1.07 [95% CI, 0.90-1.28]; P = .43). There also was no significant effect of vitamin C on major cardiovascular events (active and placebo vitamin E groups, 10.8 and 10.9 events per 1000 person-years, respectively; HR, 0.99 [95% CI, 0.89-1.11]; P = .91), as well as total myocardial infarction (HR, 1.04 [95% CI, 0.87-1.24]; P = .65), total stroke (HR, 0.89 [95% CI, 0.74-1.07]; P = .21), and cardiovascular mortality (HR, 1.02 [95% CI, 0.85-1.21]; P = .86). Neither vitamin E (HR, 1.07 [95% CI, 0.97-1.18]; P = .15) nor vitamin C (HR, 1.07 [95% CI, 0.97-1.18]; P = .16) had a significant effect on total mortality but vitamin E was associated with an increased risk of hemorrhagic stroke (HR, 1.74 [95% CI, 1.04-2.91]; P = .04). CONCLUSIONS In this large, long-term trial of male physicians, neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events. These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle-aged and older men. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00270647.
Galanin Fiber Hypertrophy within the Cholinergic Nucleus Basalis during the Progression of Alzheimer’s Disease

Galanin (GAL)-containing fibers enlarge and hyperinnervate remaining cholinergic basal forebrain (CBF) neurons within the anterior nucleus basalis (NB) in late-stage Alzheimer’s disease (AD). Whether GAL hypertrophy occurs in the CBF in the prodromal or early stages of AD remains unknown. The present study used GAL immunohistochemistry and an unbiased semiquantitative scoring method to evaluate GAL innervation in the anterior NB of subjects clinically diagnosed as having no cognitive impairment, mild cognitive impairment or early-stage (mild/moderate) AD. There was no difference in GAL fiber staining within the anterior NB across the three clinical groups examined. Furthermore, GAL fiber innervation was not correlated with the number of NB neurons expressing the nerve growth factor receptors p75NTR or TrkA or with cortical choline acetyltransferase activity in the same cases. Single-cell gene expression analysis demonstrated that cholinergic NB neurons express mRNA for the GAL receptors GALR1, GALR2 and GALR3, yet the levels of these mRNAs were unchanged across the three diagnostic groups. These observations indicate that GAL hypertrophy within the anterior NB subfield is a late-stage AD response, which may play a role in regulating the cholinergic tone of remaining basocortical projection neurons.
Natriuretic Peptide-Guided Therapy in Chronic Heart Failure: A Meta-Analysis of 2,686 Patients in 12 Randomized Trials

Background The role of cardiac natriuretic peptides in the management of patients with chronic heart failure (HF) remains uncertain. The purpose of this study was to evaluate whether natriuretic peptide-guided therapy, compared to clinically-guided therapy, improves mortality and hospitalization rate in patients with chronic HF. Methodology/Principal Findings MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched for articles reporting natriuretic peptide-guided therapy in HF until August 2012. All randomized trials reporting clinical end-points (all-cause mortality and/or HF-related hospitalization and/or all-cause hospitalization) were included. Meta-analysis was performed to assess the influence of treatment on outcomes. Sensitivity analysis was performed to test the influence of potential effect modifiers and of each trial included in meta-analysis on results. Twelve trials enrolling 2,686 participants were included. Natriuretic peptide-guided therapy (either B-type natriuretic peptide [BNP]- or N-terminal pro-B-type natriuretic peptide [NT-proBNP]-guided therapy) significantly reduced all-cause mortality (Odds Ratio [OR]:0.738; 95% Confidence Interval [CI]:0.596 to 0.913; p = 0.005) and HF-related hospitalization (OR:0.554; CI:0.399 to 0.769; p = 0.000), but not all-cause hospitalization (OR:0.803; CI:0.629 to 1.024; p = 0.077). When separately assessed, NT-proBNP-guided therapy significantly reduced all-cause mortality (OR:0.717; CI:0.563 to 0.914; p = 0.007) and HF-related hospitalization (OR:0.531; CI:0.347 to 0.811; p = 0.003), but not all-cause hospitalization (OR:0.779; CI:0.414 to 1.465; p = 0.438), whereas BNP-guided therapy did not significantly reduce all-cause mortality (OR:0.814; CI:0.518 to 1.279; p = 0.371), HF-related hospitalization (OR:0.599; CI:0.303 to 1.187; p = 0.142) or all-cause hospitalization (OR:0.726; CI:0.609 to 0.964; p = 0.077). Conclusions/Significance Use of cardiac peptides to guide pharmacologic therapy significantly reduces mortality and HF related hospitalization in patients with chronic HF. In particular, NT-proBNP-guided therapy reduced all-cause mortality and HF-related hospitalization but not all-cause hospitalization, whereas BNP-guided therapy did not significantly reduce both mortality and morbidity.
Enhanced Ras activity promotes spine formation in synRas mice neocortex

The effect of enhanced Ras activity upon dendritic spine formation has been investigated on pyramidal cells in the adult neocortex of synRas mice over-expressing Val12-Ha-Ras specifically in postmitotic neurons. For quantitative analysis, commissural neurons of layers II/III were retrogradely labelled with dextran amine. In synRas mice, spine frequency on several orders of basal dendrites and apical oblique branches was significantly increased. Whereas density on basal dendrites was overall augmented, on apical dendrites, distal regions were most affected. The proportions of different morphological types of spines remained unchanged. It is concluded that Ras might be critically involved in mechanisms that mediate and regulate dendritic spine formation in the adult brain.
Zinc oxide influences intestinal integrity, the expressions of genes associated with inflammation and TLR4-myeloid differentiation factor 88 signaling pathways in weanling pigs

This study explored whether zinc oxide (ZnO) supplementation could alleviate weanling-induced intestinal injury through TLR and NOD-like receptor signaling pathways. Twelve early-weanling piglets were allotted to two dietary treatments (control vs 2200 mg Zn/kg from ZnO) for 1 wk. The results showed that supplemental ZnO improved daily gain and feed intake, decreased post weaning scour scores, increased villus height and villus height:crypt depth ratio at the jejunal mucosa, and decreased diamine oxidase activity and endotoxin concentration in plasma. The intestinal mRNA levels of TLR4 and its downstream signals, including MyD88, IL-1 receptor-associated kinase 1 and TNF-α receptor-associated factor 6, were decreased, and the expressions of intestinal pro-inflammatory cytokines and chemokines were decreased simultaneously in the ZnO-supplemented piglets. Although NF-κB p65 mRNA abundance was not affected by ZnO supplementation, NF-κB p65 protein expression was down-regulated by ZnO. However, ZnO supplementation had no effect on intestinal expressions of NOD1 and NOD2, and their adaptor molecule receptor-interacting serine/threonine-protein kinase 2, as well as protein expressions of caspase-3 and heat shock protein 70. The results indicated that the protective effects of ZnO on intestinal integrity were closely related to decreasing the expressions of genes associated with inflammation through inhibiting the TLR4-MyD88 signaling pathways.
Dependent Random Graphs and Multiparty Pointer Jumping

We initiate a study of a relaxed version of the standard Erdos-Renyi random graph model, where each edge may depend on a few other edges. We call such graphs "dependent random graphs". Our main result in this direction is a thorough understanding of the clique number of dependent random graphs. We also obtain bounds for the chromatic number. Surprisingly, many of the standard properties of random graphs also hold in this relaxed setting. We show that with high probability, a dependent random graph will contain a clique of size ((1-o(1))log(n))/log(1/p), and the chromatic number will be at most (nlog(1/(1-p)))/log(n). We expect these results to be of independent interest. As an application and second main result, we give a new communication protocol for the k-player Multi-Party Pointer Jumping problem (MPJk) in the number-on-the-forehead (NOF) model. Multi-Party Pointer Jumping is one of the canonical NOF communication problems, yet even for three players, its communication complexity is not well understood. Our protocol for MPJ3 costs O((n * log(log(n)))/log(n)) communication, improving on a bound from [BrodyChakrabarti08]. We extend our protocol to the non-Boolean pointer jumping problem, achieving an upper bound which is o(n) for any k >= 4 players. This is the first o(n) protocol and improves on a bound of Damm, Jukna, and Sgall, which has stood for almost twenty years.
Assessment of knowledge level on osteoporosis among a private university students in Malaysia

Osteoporosis is one of the major public health problem with a high prevalence and incidence of morbidity and mortality worldwide. Evidence suggesting that osteoporosis knowledge is a contributor to osteoporosis preventive behavior. Low literacy rates, lack of understanding regarding disease risk, effects and consequences leads to increase the incidence of this combatable disease. So, Osteoporosis can be avoided via educational interventions. The objective of this study was to evaluate osteoporosis knowledge among university students in a private university in Malaysia. Information was collected through a cross sectional survey. The data gathered from seventy three university students using convenience sampling method during the period from August to October, 2016. Respondents had been requested to sign a written informed consent, then self-administered, validated questionnaire consisted of 20 items assessing knowledge regarding osteoporosis was administered. Descriptive statistics was used to analyze the data by Microsoft Excel and Statistical Package for Social Sciences. Out of the seventy three participants, 38 % were males and 61% were female. There were 24 students in foundation and 49 students in bachelor course. The mean age of the respondents were 22.91 ± 1.74 years. Among the participants 53% were Malaysian. Total 79.4% students had poor knowledge and only 6.8% of the respondents had good knowledge on risk, cause, signs and symptoms, prevention, diagnosis and treatment of osteoporosis. Female respondents had poor knowledge (1.60+0.52) than male (1.61+0.49). Bachelor students had poor knowledge (1.29+0.46) than foundation college students (1.92+0.26). The study finding revealed an inadequate knowledge of osteoporosis among university students, so intervention program need to be adopt to increase the knowledge regarding osteoporosis for prevention.
Extraction and Analysis of Respiratory Motion Using Wearable Inertial Sensor System during Trunk Motion

Respiratory activity is an essential vital sign of life that can indicate changes in typical breathing patterns and irregular body functions such as asthma and panic attacks. Many times, there is a need to monitor breathing activity while performing day-to-day functions such as standing, bending, trunk stretching or during yoga exercises. A single IMU (inertial measurement unit) can be used in measuring respiratory motion; however, breathing motion data may be influenced by a body trunk movement that occurs while recording respiratory activity. This research employs a pair of wireless, wearable IMU sensors custom-made by the Department of Electrical Engineering at San Diego State University. After appropriate sensor placement for data collection, this research applies principles of robotics, using the Denavit-Hartenberg convention, to extract relative angular motion between the two sensors. One of the obtained relative joint angles in the “Sagittal” plane predominantly yields respiratory activity. An improvised version of the proposed method and wearable, wireless sensors can be suitable to extract respiratory information while performing sports or exercises, as they do not restrict body motion or the choice of location to gather data.
A Shuttle Car Assignment Problem in the Mining Industry

Shuttle cars form a part of the standard equipment employed by the mining industry in the transportation of coal when using the room-and-piller method for extracting coal from underground seams. These cars are subject to frequent failure, so the problem of assigning shuttle cars to sections of the mine is considered in this paper, with the objective of maximizing expected output. A particularly simple solution is found that could be used readily by any mine foreman.
Joint attention and lexical acquisition style

Recent research has documented systematic individual differences in early lexical development. The current study investigated the relation ship of these differences to differences in the way mothers and children regulate each other's attentional states. Mothers of 6 one-year-olds kept diary records and were videotaped with their children at monthly intervals as well. Language measures from the diary were related to measures of attention manipulation and maintenance derived from a coding of the videotaped interactions. Results showed that when mothers initiated interactions by directing their child's attention, rather than by following into it, their child learned fewer object labels and more personal-social words. Dyads who maintained sustained bouts of joint attentional focus had children with larger vocabularies overall. It was concluded that the way mothers and children regulate each other's attention is an important factor in children's early lexical development.
Rentabilidade dos proprietários rurais em Dourados/MS no arrendamento às usinas sucroenergéticas diante da especificidade locacional

The objective of this study is to investigate the influence of locational specificity in the profitability of agricultural tenancy to produce sugarcane in Dourados / MS. To this end, we used the Transaction Cost Economics with a focus on locational specificity. Data were collected from the landowners of the town in July and August 2011. Data analysis was performed with hypothesis testing by econometric OLS for the preparation of Sample Regression Function. It appears that the locational specificity explains more than 89% of the profitability of these leases, showing inverse relationship between distance and profitability.
Crossroads : environmental priorities for the future

The environmental movement today is at a critical crossroads. Crossroads: Environmental Priorities for the Future is an in-depth assessment of the movement's successes and failures, and also offers prescriptions for the future. It includes contributions from some of the country's top environmental leaders and activists, including Barry Commoner, Stewart Udall, William K. Reilly, Gus Speth, Jay Hair, Lois Gibbs, Michael Frome, Chuck Little, and William Futrell.
The intestine and the kidneys: a bad marriage can be hazardous

The concept that the intestine and chronic kidney disease influence each other, emerged only recently. The problem is multifaceted and bidirectional. On one hand, the composition of the intestinal microbiota impacts uraemic retention solute production, resulting in the generation of essentially protein-bound uraemic toxins with strong biological impact such as vascular damage and progression of kidney failure. On the other hand, the uraemic status affects the composition of intestinal microbiota, the generation of uraemic retention solutes and their precursors and causes disturbances in the protective epithelial barrier of the intestine and the translocation of intestinal microbiota into the body. All these elements together contribute to the disruption of the metabolic equilibrium and homeostasis typical to uraemia. Several measures with putative impact on intestinal status have recently been tested for their influence on the generation or concentration of uraemic toxins. These include dietary measures, prebiotics, probiotics, synbiotics and intestinal sorbents. Unfortunately, the quality and the evidence base of many of these studies are debatable, especially in uraemia, and often results within one study or among studies are contradictory. Nevertheless, intestinal uraemic metabolite generation remains an interesting target to obtain in the future as an alternative or additive to dialysis to decrease uraemic toxin generation. In the present review, we aim to summarize (i) the role of the intestine in uraemia by producing uraemic toxins and by generating pathophysiologically relevant changes, (ii) the role of uraemia in modifying intestinal physiology and (iii) the therapeutic options that could help to modify these effects and the studies that have assessed the impact of these therapies.
Direct Comparison of the Response of Voltammetry and Microdialysis to Electrically Evoked Release of Striatal Dopamine

Abstract: Carbon fiber microelectrodes either were implanted directly into striatal tissue or were mounted into the outlet of microdialysis probes that were implanted into striatal tissue. This allowed voltammetry and microdialysis to be used under identical in vivo experimental conditions to monitor extracellular dopamine levels during electrical stimulation of the medial forebrain bundle both before and after uptake inhibition with nomifensine. The marked differences between the results obtained with each technique cannot be explained on the basis of their inherent analytical attributes (sensitivity, temporal response, etc.). The results demonstrate that the microdialysis recovery factor for endogenous dopamine increases after uptake inhibition, an observation that stands in contradiction to the existing theory and practice of the microdialysis technique. The observations led to the development of a numerical model that rationalizes the observations reported herein and that allows in vivo voltammetry and in vivo microdialysis results to be interpreted within a single theoretical framework.