Miracle-dz/UniFAR-FTUs huggingface dataset:
The tumor metabolome.

The tumor metabolome is characterized by high glycolytic and glutaminolytic capacities, high phosphometabolite levels and a high channelling of glucose carbons to synthetic processes. This allows tumor cells to proliferate under strong variations in oxygen and glucose supply (http://www.metabolic-database.com). One key regulator of the tumor metabolome is the glycolytic isoenzyme pyruvate kinase type M2 (M2-PK) that is generally over-expressed in all tumor cells. M2-PK can occur in a highly active tetrameric form and in a nearly inactive dimeric form. In tumor cells the dimeric form of M2-PK always predominates and has therefore been termed tumor M2-PK. The dimerization of M2-PK is caused by direct interaction of M2-PK with certain oncoproteins. When M2-PK is in its dimeric state energy is produced by glutaminolysis. The metabolic Achilles' heel of the tumor metabolome is its sensitivity to a reduction of NAD levels caused by activation of poly(ADP-ribose) polymerase after DNA damage.
Subcellular Localization of Survivin Determines Its Function in Cardiomyocytes

Rationale:Reducing cardiomyocyte death and enhancing their proliferation after myocardial infarction is perhaps the single largest challenge for cardiac tissue regeneration. Survivin (SVV) is the smallest member of the inhibitor of apoptosis (IAP) family but plays two important roles; inhibiting caspase-9 activation in the intrinsic apoptosis pathway, and regulating microtubule dynamics and chromosome segregation during cell division. Genetic depletion of cardiac SVV leads to incomplete cardiomyocyte division and abnormal heart development. However, the function of SVV in adult hearts after myocardial infarction remains unclear. Methods: A homozygous inducible cardiomyocyte-specific SVV knockout transgenic mouse model was established through crossbreeding SVVflox/flox and αMHC-MCM transgenic mice. Adult mice received consecutive intraperitoneal injection of tamoxifen to induce genetic removal of SVV in cardiomyocytes. A SVV overexpressing model was established via local delivery of SVV in wild-type mouse hearts. Results: We found that 30.82% of cardiomyocytes in the peri-infarct region of SVV knockout mice were apoptotic, significantly higher than the 22.18% in control mice. In addition, ejection fraction was 29.00±0.40% in knockout mice compared to 38.04±0.50% in control mice 21 days after myocardial infarction. On the contrary, locally overexpressing SVV in the heart improved cardiac functions. Unexpectedly, we found that altering the subcellular localization of SVV overexpression produced different outcomes. Overexpression of SVV in the cytoplasm decreased cardiomyocyte apoptosis, whereas overexpression of SVV in the nucleus enhanced cardiac regeneration. The ejection fraction of mice overexpressing SVV was 36.58±0.91%, significantly higher than 28.18±1.70% in the GFP control group. Apoptotic cardiomyocytes were only 4.63% in mouse overexpressing cytosolic SVV, compared to 9.31% in the GFP group, and activation of caspase-3 was also reduced. Moreover, mice overexpressing NLS-SVV exhibited a better ejection fraction (36.19±1.02%,) than GFP controls (26.69±0.75%). NLS-SVV enhanced H3P-positive cardiomyocytes in the border zone to 0.28%, compared to only 0.08% in GFP group, through interacting with Aurora B. Conclusions:We demonstrate the importance of SVV subcellular localization in regulating post-MI cardiac repair and regeneration. We hope that this will open new translational approaches through targeted delivery of SVV.
Cotation des niveaux de confinement en vue d'une évaluation semi-quantitative des risques d'exposition aux agents chimiques

La determination des niveaux de confinement s'inscrit dans le cadre d'une methodologie globale d'evaluation semi-quantitative des expositions aux agents chimiques qui se decline en quatre etapes: 1) definition de groupes d'exposition; 2) determination du danger toxicologique des substances manipulees par la methode des Classes de Danger et definition d'un OHB (Occupational Hazard Band); 3) determination de l'exposition potentielle comme etant la resultante du niveau de confinement, de la duree d'exposition et de la dilution de la substance chimique dans le procede ; 4) evaluation du niveau de risque d'exposition et mise en place eventuelle d'actions correctrices de reduction des expositions.
A Phase II Study of 5‐Fluorouracil and Leucovorin in Advanced Carcinoma of the Esophagus

Thirty-five patients with advanced epidermoid carcinoma of the esophagus were treated with 5-fluorouracil (5-FU) 425 mg/m2 and leucovorin 20 mg/m2, day 1–5 every 28 days. Six patients had a partial response (95% confidence limit, 7–35%) with a median response duration of 32 weeks. The median survival time of the patients on study was 14 weeks. The toxicity was acceptable, with only two patients experiencing severe hematologic toxicity and one patient experiencing severe nausea and vomiting. The addition of leucovorin at this dose level in this population of patients with advanced disease does not appear to enhance the activity of 5-FU for patients with squamous cell cancer of the esophagus. Since only a small percentage of patients experienced significant toxicity, a higher response rate could be achieved in patients treated with the maximally tolerated dose.
Levels of Soluble CD163 and Severity of Malaria in Children in Ghana

ABSTRACT CD163 is an acute-phase-regulated monocyte/macrophage membrane receptor expressed late in inflammation. It is involved in the haptoglobin-mediated removal of free hemoglobin from plasma, has been identified as a naturally soluble plasma glycoprotein with potential anti-inflammatory properties, and is possibly linked to an individual's haptoglobin phenotype. High levels of soluble CD163 (sCD163) in a malaria episode may therefore downregulate inflammation and curb disease severity. In order to verify this, the relationships between sCD163 levels, malaria severity, and selected inflammatory mediators (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and IL-10) were assessed by enzyme-linked immunosorbent assay using plasma samples obtained from pediatric malaria patients with uncomplicated malaria (UM [n = 38]), cerebral malaria (CM [n = 52]), and severe malarial anemia (SA [n = 55]) during two consecutive malaria transmission seasons (2002 and 2003). Median sCD163 levels were higher in UM (11.9 μg/ml) patients than in SA (7.7 μg/ml; P = 0.010) and CM (8.0 μg/ml; P = 0.031) patients. Levels of sCD163 were also higher in all patient groups than in a group of 81 age-matched healthy controls. The higher sCD163/TNF-α ratio in UM patients, coupled with the fact that sCD163 levels correlated with TNF-α levels in UM patients but not in CM and SA patients, suggests inflammatory dysregulation in the complicated cases. The study showed that sCD163 levels are elevated during acute malaria. High sCD163 levels in UM patients may be due to the induction of higher-level anti-inflammatory responses, enabling them to avoid disease complications. It is also possible that UM patients simply lost their CD163 receptors from macrophages in inflammatory sites while complicated-malaria patients still had their receptors attached to activated macrophages, reflecting ongoing and higher-level inflammation associated with complicated malaria.
The Role of the Public Health Sector in Promoting Physical Activity: National, State, and Local Applications.

BACKGROUND Regular physical activity has been demonstrated to protect against coronary heart disease, Type 2 diabetes mellitus, selected cancers, hypertension, obesity, and other chronic conditions. Therefore, the public health significance of promoting physical activity and preventing inactivity has become a well-established agenda for public health agencies at all levels. METHODS A secondary search of the literature, focusing on existing evidence reviews, was conducted to identify effective or promising public health physical activity interventions. Further examination of published evidence-based programs also was carried out to supplement the known evidence base. Intervention strategies were selected using criteria prescribed by each of the systematic reviews to yield categories of intervention effectiveness. KEY RECOMMENDATIONS The selected physical activity interventions conformed to the domains identified by The Guide to Community Preventive Services. Recommended evidenced-based strategies from within the domain of informational approaches include 2 exemplary community-wide campaigns; mass media campaigns, represented by VERB; and an emerging practice of delivery of short physical activity messages at key community sites. Exemplary representative behavioral/social interventions include social support through organized walking clubs/partners within communities. Exemplary environmental/policy approaches include creating/enhancing access to places for physical activity with informational outreach activities and the emerging strategy of community-wide policies and planning.
Risk of malignancy and death in neurofibromatosis.

OBJECTIVE AND METHODS Neurofibromatoses are cancer-prone hamartomatoses that involve a variety of tissue and cell types. As part of a population-based clinical and genetic study of neurofibromatosis in northern Finland, all surgical and autopsy specimens of neurofibromatosis patients were retrieved and histologic slides were reviewed. RESULTS Specimens were available for 69 of the 197 neurofibromatosis type 1 patients identified. Six malignant peripheral nerve sheath tumors and nine other malignant tumors were detected. In this study, the risk for neurofibromatosis-related malignancy was 8%. Nine neurofibromatosis type 1 patients died, at a mean age of 37 years. The cause of death was related to neurofibromatosis in eight. CONCLUSIONS The risk of developing malignant tumors and early death is increased in patients with neurofibromatosis, the most common malignancy being malignant peripheral nerve sheath tumors. These risks need to be recognized, and the families should be advised to seek genetic counseling and proper follow-up.
Methods for Image Enhancement: A Review

Image Enhancement is one of challenging areas of image processing. Loss of information takes place as image clarity is affected by lighting, or equipment used to capture the image. Enhancement operations include improving the quality, removing noise & blurring and to bring out the hidden details without addition of unreal visual appearances. Different techniques are applied on different images as one technique does not work for all the applications. This paper gives a survey on methods used for enhancement of images.
Progressive Breakdown Characteristics of High-K/Metal Gate Stacks

Breakdown characteristics of Hf-based high-k dielectrics in a wide thickness range were investigated to identify the "weak link" in the gate stack and its leading breakdown mechanisms under inversion stress. A strong correlation among the growth rates of the stress leakage current, SILC, and interface trap density suggests that breakdown is triggered by trap generation in the interfacial SiO2 layer. Stress-time evolution of the differential resistance and its slope obtained from SILC data allows progressive breakdown in high-k/metal gate stacks to be identified
Diversification Rates and the Evolution of Species Range Size Frequency Distribution

The geographic range sizes frequency distribution (RFD) within clades is typically right-skewed with untransformed data, and bell-shaped or slightly left-skewed under the log-transformation. This means that most species within clades occupy diminutive ranges, whereas just a few species are truly widespread. A number of ecological and evolutionary explanations have been proposed to account for this pattern. Among the latter, much attention has been given to the issue of how extinction and speciation probabilities influence RFD. Numerous accounts now convincingly demonstrate that extinction rate decreases with range size, both in living and extinct taxa. The relationship between range size and speciation rate, though, is much less obvious, with either small or large ranged species being proposed to originate more daughter taxa. Herein, we used a large fossil database including twenty-one animal clades and more than 80,000 fossil occurrences distributed over more than 400 million years of marine metazoans (exclusive of vertebrates) evolution, to test the relationship between extinction rate, speciation rate, and range size. As expected, we found that extinction rate almost linearly decreases with range size. In contrast, speciation rate peaks at the large (but not the largest) end of the range size spectrum. This is consistent with the peripheral isolation mode of allopatric speciation being the main mechanism of species origination. The huge variation in phylogeny, fossilization potential, time of fossilization, and the overarching effect of mass extinctions suggest caution must be posed at generalizing our results, as individual clades may deviate significantly from the general pattern.
A fast method for tracing multi-valued characteristics in nonlinear circuits

The paper offers a method for tracing multivalued, input-output and parametric characteristics in nonlinear resistive circuits. The main idea of the method is creating of a family of some single-valued characteristics, called the test characteristics. Each of them gives certain points of the traced multi-valued characteristic. Since the time of finding the family of test characteristics is considerably shorter than the time consumed by the known methods, leading to the multi-valued characteristic, the approach is efficient. As a result larger-sized circuits can be considered. Comparison with the results provided by DC Sweep analysis of SPICE shows that there are many circuits, where the proposed method gives correct characteristics, whereas the SPICE simulator loses some branches or exhibits their apparent hysterestic nature. Two numerical examples illustrate the proposed approach.
EBEM: An Event-driven Bandwidth Estimation Method for Mobile Ad Hoc Network

Quality of Service (QoS) support has been well studied as a hotspot in mobile ad hoc network. However, since interference range is much larger than transmission range, estimating available bandwidth at each node remains a challenge. To address this problem, a novel Event-driven Bandwidth Estimation Method (EBEM) is proposed in this paper. By incorporating a comprehensive intra-flow interference predicting approach and an event-driven inter-flow collision detecting strategy, EBEM could estimate nodal available bandwidth substantially, preventing the network from being overloaded. Results from simulation verify that EBEM not only surpasses typical AODV protocol in both end-to-end delay and packet delivery rate, but it also outperforms latest QAR method in both total throughput and packet delivery rate. As such, EBEM can be applied to various QoS routing protocols to estimate nodal available bandwidth.
Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage.

OBJECTIVE To determine whether interleukin-1 (IL-1) or tumor necrosis factor alpha (TNFalpha), or both, plays a role in the excessive degradation that is observed in cultured osteoarthritic (OA) articular cartilage. METHODS Antagonists of IL-1 and TNFalpha, namely, IL-1 receptor antagonist and the PEGylated soluble TNFalpha receptor I, respectively, were added at different concentrations to explant cultures of nonarthritic (5 obtained at autopsy) and OA (15 obtained at arthroplasty) articular cartilage. The cleavage of type II collagen (CII) by collagenase was measured by an immunoassay in cartilage and culture media. Proteoglycan (mainly aggrecan) content and degradation were measured by a colorimetric assay for glycosaminoglycan (GAG) content in cartilage and culture media. Reverse transcriptase-polymerase chain reaction was used to analyze gene expression of matrix metalloproteases (MMPs) 1, 3, and 13, CII, aggrecan, IL-1, and TNFalpha. RESULTS Antagonists of IL-1 and TNFalpha inhibited the increase in CII cleavage by collagenase as well as the increase in GAG release observed in OA cartilage compared with normal cartilage. Inhibition was significant in tissue from some patients but not from others, although significant inhibition was observed when all the results were analyzed together. An increase in the GAG content in cartilage was seen in 4 of 15 cases. However, this increase was not significant when all the data were combined. Preliminary results indicated no effect of these antagonists on nonarthritic cartilage from 3 different donors. Independent analyses of gene expression in cultured cartilage from 9 other OA patients revealed that IL-1 or TNFalpha blockade, either alone and/or in combination, frequently down-regulated MMP-1, MMP-3, and MMP-13 expression. Expression of IL-1 and TNFalpha was inhibited by either antagonist or by the combination in essentially half the cases. The combined blockade up-regulated aggrecan and CII gene expression in approximately half the cases. CONCLUSION These results suggest that the autocrine/paracrine activities of TNFalpha and IL-1 in articular cartilage may play important roles in cartilage matrix degradation in OA patients but not in all patients. Inhibition of either or both of these cytokines may offer a useful therapeutic approach to the management of OA by reducing gene expression of MMPs involved in cartilage matrix degradation and favoring its repair.
Understanding the DSM-5: stasis and change

This paper aims to understand the DSM-5 through situating it within the context of the historical development of the DSM series. When one looks at the sets of diagnostic criteria, the DSM-5 is strikingly similar to the DSM-IV. I argue that at this level the DSM has become ‘locked-in’ and difficult to change. At the same time, at the structural, or conceptual, level there have been radical changes, for example in the definition of ‘mental disorder’, in the role of theory and of values, and in the abandonment of the multiaxial approach to diagnosis. The way that the DSM-5 was constructed means that the overall conceptual framework of the classification only barely constrains the sets of diagnostic criteria it contains.
Hospitalized osteoporotic vertebral fracture increases the risk of stroke: A population‐based cohort study

The association between osteoporosis and cardiovascular diseases has been demonstrated. Higher cardiovascular risk has also been correlated with vertebral fractures. However, the association between osteoporotic vertebral fracture and the possibly higher risk of stroke remains uncertain. This study aimed to evaluate the incidence, risk, and type of stroke in patients with osteoporotic vertebral fracture. Patients with osteoporotic vertebral fracture were identified (n = 380) and 10 age‐ and sex‐matched controls per case (comparison group, n = 3795) were chosen from a nationwide representative cohort of 999,997 people from 1998 to 2005. Both groups were followed‐up for stroke events for 3 years, matched by propensity scores with adjustments for covariates such as comorbidities (ie, hypertension, diabetes, arrhythmia, or coronary heart diseases) and exposure to medications (ie, aspirin, lipid lowering drug, or nitrates), and assessed by Kaplan‐Meier and Cox regression analyses. The incidence rate of stroke in the osteoporotic vertebral fracture group (37.5 per 1000 person‐years; 95% confidence interval [CI], 27.5–51.2) was significantly higher than in the comparison group (14.0 per 1000 person‐years; 95% CI, 12.0–16.4, p < 0.001). Stroke was more likely to occur in the osteoporotic vertebral fracture patients than in the normal controls (crude hazard ratio [HR] 2.68, 95% CI 1.89–3.79, p < 0.001; adjusted HR 2.71, 95% CI 1.90–3.86, p < 0.001). In conclusion, patients with osteoporotic vertebral fracture have a higher risk of stroke (ie, both ischemic and hemorrhagic) and require stroke prevention strategies. © 2013 American Society for Bone and Mineral Research.
Effect of evaporation of solvents from one-step, self-etching adhesives.

PURPOSE To investigate whether and to what extent the bonding capacity of one-step, self-etching adhesives is influenced by the degree to which solvent is evaporated. MATERIALS AND METHODS Seven one-step, self-etching adhesives were tested (Adper Prompt L-Pop, Clearfil S3 Bond, Futurabond NR, G-Bond, Hybrid Bond, iBond, Xeno III). The variation in degree of evaporation was obtained by varying the duration of the air-blowing step. The duration required to immobilize the adhesive layer, as established in a pilot study, was used as control. Two experimental air-blowing durations, shorter (half the control duration) and longer (double the control duration) than the control duration, were chosen. The resin composite Herculite XRV was bonded to flat human dentin surfaces treated with one of the adhesives following manufacturer's instructions, except for the air-blowing duration after application. After being stored in water at 37 degrees C for 1 week, the bonded specimens were broken in shear. Failure modes were evaluated under stereomicroscope. RESULTS Air-blowing duration and brand of adhesive both had an effect on shear bond strength. An interaction was found between adhesive and air-blowing duration. Some adhesives were insensitive to variations in air-drying duration, but in general, air-blowing durations shorter than the control duration produced lower shear bond strengths. Significant effects of adhesive and air-blowing duration were also detected in relation to failure mode. More adhesive failures were observed with shorter air-blowing durations. A significant negative correlation between number of adhesive failures and bond strength was found. CONCLUSION On the basis of this in vitro study, it may be concluded that the one-step, self-etching adhesives evaluated were sensitive to degree of evaporation of the solvents.
State Variation in Increased ADHD Prevalence: Links to NCLB School Accountability and State Medication Laws.

OBJECTIVE The study's objective was to investigate whether attention-deficit hyperactivity disorder (ADHD) diagnoses from 2003 to 2011 were associated with either public school consequential accountability reforms initiated by the No Child Left Behind (NCLB) Act, particularly for low-income children, or with state psychotropic medication laws that prohibit public schools from recommending or requiring medication use. METHODS Logistic regression difference-in-differences models were estimated with repeated U.S. and state-representative cross-sections of responses to the 2003, 2007, and 2011 National Survey of Children's Health. Each wave included approximately 35,000 public school children between ages six and 13. RESULTS From 2003 to 2007, the change in adjusted diagnostic prevalence was 2.8 percentage points higher for children ages six to 13 in households with incomes ≤185% of the federal poverty level residing in states first exposed to consequential accountability through NCLB (from 8.5% to 13.2%), compared with demographically similar children residing in other states (from 10.2% to 12.1%). From 2003 to 2011, the change in adjusted diagnostic prevalence was 2.2 percentage points lower for children ages six to 13 residing in states with a psychotropic medication law (from 8.1% to 7.8%), compared with children residing in other states (from 8.1% to 10.1%). CONCLUSIONS NCLB-initiated consequential accountability reforms were associated with more ADHD diagnoses among low-income children, consistent with increased academic pressures from NCLB for this subgroup. In contrast, psychotropic medication laws were associated with fewer ADHD diagnoses, because they may indirectly reduce diagnoses via restrictions on recommending or requiring medication use. Future research should investigate whether children most affected by these policies are receiving appropriate diagnoses.