Miracle-dz/UniFAR-FTUs huggingface dataset:
Size at birth as a predictor of mortality in adulthood: a follow-up of 350 000 person-years.

BACKGROUND Small body size at birth, as a marker of an adverse intrauterine environment, has recently emerged as an important risk factor for death from cardiovascular disease. Our aim was to study the relationship between small size at birth and all-cause and non-cardiovascular mortality, which has been poorly documented. METHODS We studied 13 830 individuals born between 1924 and 1944 in Helsinki, Finland, at term as singletons. Dates and primary causes of death between 1971 and 1998 were obtained from the Finnish National Death Register. RESULTS 1668 men and 671 women died during the follow-up at the mean age of 56.0 (range 26.7-74.9) years. Lower birthweight was associated with increased all-cause mortality in females (Odds ratio (OR) for 1 kg decrease in birthweight 1.25, 95% CI 1.05-1.49; P = 0.01) but not in males (OR 1.08; 0.96-1.19; P = 0.2; P for sex-birthweight interaction = 0.09). Similarly, short length at birth was a predictor of all-cause mortality in females (OR for 1 cm decrease 1.10; 1.05-1.15; P < 0.0001) but not in males (OR 1.01; 0.98-1.02; P = 0.4; P for sex-length at birth interaction = 0.002). Low birthweight and short length at birth predicted premature death in adulthood (<55 years) in both sexes. In males, death from cardiovascular disease (n = 654) was associated with lower birthweight (OR for 1 kg decrease 1.33; 1.12-1.59; P = 0.001), and length (OR 1.05; 1.00-1.10; P = 0.03), and in females death from cardiovascular disease (n = 179) was associated with short length at birth (OR 1.11; 1.02-1.20; P = 0.02). In females death from non-cardiovascular diseases was predicted by low birthweight (OR 1.25; 1.01-1.54; P = 0.04) and short length at birth (OR 1.09; 1.03-1.15; P = 0.003) (n = 475), but not in males (n = 975; P for interaction = 0.02 and 0.004, respectively). Cancer-related death was associated with higher birthweight (OR for 1 kg decrease 0.76; 0.61-0.95; P = 0.02) and ponderal index (OR for 1 kg/m(3) increase 0.95; 0.91-0.99; P = 0.01) in males (n = 361) but not in females (n = 269). CONCLUSIONS Small size at birth is associated with increased all-cause mortality at all ages among adult women but only with premature death in adult men. Among women death from both cardiovascular and non-cardiovascular causes is associated with small body size at birth. Among men an association between small birthsize and later cardiovascular disease is counterbalanced by an association between large body size at birth and later cancer.
An application of constraint solving for home health care

Although sometimes it is necessary, no one likes to stay in a hospital, and patients who need to stay in bed but do not require constant medical surveillance prefer their own bed at home. At the same time, a patient in a hospital has a high cost for the community, that is not acceptable if the patient needs service only a few minutes a day. For these reasons, the current trend in Europe and North-America is to send nurses to visit patients at their home: this choice reduces costs for the community and gives better quality of life to patients. The challenge is to deliver the service in a cost effective manner without a detriment of the service quality. These social and health management issues have interesting implications from the mathematical viewpoint, introducing a challenging combinatorial optimization problem. The problem consists in assigning patients' services to traveling nurses and defining the nurse itineraries so that the following optimization aspects are considered: the nurse workloads (including service as well as travel time) are balanced, patients are preferentially served by a single nurse or just a few ones, and the overall travel time is minimized. These objectives are somehow conflicting and a reasonable trade off must be found. The complexity of the problem calls for suitable optimization-based algorithmic support to decisions, in particular in the perspective of an increasing diffusion of the service.This problem is known in the literature as the Home Health Care (HHC) problem. In this paper, we address the HHC problem in the municipality of Ferrara, a mid-sized city in the North of Italy. The problem is currently solved by hand, starting from a partitioning of patients based on predefined zones. We describe a Constraint Programming model that solves the HHC problem, and show significant improvements with respect to the current manual solution.
RAGE: therapeutic target and biomarker of the inflammatory response—the evidence mounts

The RAGE binds multiple ligand families linked to hyperglycemia, aging, inflammation, neurodegeneration, and cancer. Activation of RAGE by its ligands stimulates diverse signaling cascades. The recent observation that the cytoplasmic domain of RAGE interacts with diaphanous or mDia–1 links RAGE signal transduction to cellular migration and activation of the Rho GTPases, cdc42 and rac–1. Pharmacological blockade of RAGE or genetic deletion of RAGE imparts significant protection in murine models of diabetes, inflammatory conditions, Alzheimer’s disease, and tumors. Intriguingly, soluble forms of RAGE, including the splice variant–derived esRAGE, circulate in human plasma. Studies in human subjects suggest that sRAGE levels may be modulated by the diseases impacted by RAGE and its ligands. Thus, in addition to being a potential therapeutic target in chronic disease, monitoring of plasma sRAGE levels may provide a novel biomarker platform for tracking chronic inflammatory diseases, their severity, and response to therapeutic intervention.
Clinical response of large cell neuroendocrine carcinoma of the lung to perioperative adjuvant chemotherapy

Patients with large cell neuroendocrine carcinoma (LCNEC) of the lung are considered to have poor prognosis. However, the benefit of adjuvant chemotherapy for these patients has not been established. In this study, we retrospectively evaluated the efficacy of perioperative chemotherapy for patients with completely resected LCNEC in a single-center setting. From 1999 through 2007, 45 patients with surgically resected LCNEC or mixed LCNEC containing at least one portion of the neuroendocrine differentiation or morphology in non-small cell lung carcinoma were enrolled as participants of this study. Survival rates were calculated by the Kaplan–Meier method. Differences between survival curves were computed with the log-rank test. For multivariate analysis, the Cox's proportional hazards regression model was used to evaluate variables that were significant predictors of survival. Of 1397 patients undergoing surgical resection for primary lung cancer from 1999 to 2007, 45 (3.2%) were classified as LCNEC. Thirty-six (80%) patients were men, and nine (20%) were women. Twenty-four (92%) of 26 patients were present or past smokers. Twenty-three (41%) of 45 patients received perioperative chemotherapy, including seven induction chemotherapies and 16 adjuvant chemotherapies. Survival of patients who underwent perioperative adjuvant chemotherapy was significantly higher than that of those who received surgery alone (P = 0.04). The 5-year survival rate of patients who underwent perioperative adjuvant chemotherapy was 87.5%, whereas that of patients who underwent surgery alone was 58.5%. Even in stage I cases, perioperative adjuvant chemotherapy still favors survival compared with surgery alone. In the Cox proportional hazard multivariate analysis, surgery with or without chemotherapy showed an independent prognostic influence on overall survival (P = 0.0457). Patients who received surgery alone were 9.5 times more likely to die than patients who underwent surgery plus chemotherapy. In conclusion, perioperative chemotherapy will be needed to improve survival in patients with LCNEC. As the population of LCNEC is small, it has been difficult to conduct randomized controlled trials to show the survival benefit of adjuvant chemotherapy. This should be, therefore, evaluated further in prospective multi-institutional phase II trials.
Combined non-invasive assessment of endothelial shear stress and molecular imaging of inflammation for the prediction of inflamed plaque in hyperlipidaemic rabbit aortas

Aims To evaluate the incremental value of low endothelial shear stress (ESS) combined with high-resolution magnetic resonance imaging (MRI)- and computed tomography angiography (CTA)-based imaging for the prediction of inflamed plaque. Methods and results Twelve hereditary hyperlipidaemic rabbits underwent quantitative analysis of plaque in the thoracic aorta with 256-slice CTA and USPIO-enhanced (ultra-small superparamagnetic nanoparticles, P904) 1.5-T MRI at baseline and at 6-month follow-up. Computational fluid dynamics using CTA-based 3D reconstruction of thoracic aortas identified the ESS patterns in the convex and concave curvature subsegments of interest. Subsegments with low baseline ESS exhibited significant increase in wall thickness and plaque inflammation by MRI, in non-calcified plaque burden by CTA, and developed increased plaque size, lipid and inflammatory cell accumulation (high-risk plaque features) at follow-up by histopathology. Multiple regression analysis identified baseline ESS and inflammation by MRI to be independent predictors of plaque progression, while receiver operating curve analysis revealed baseline ESS alone or in combination with inflammation by MRI as the strongest predictor for augmented plaque burden and inflammation (low ESS at baseline: AUC = 0.84, P < 0.001; low ESS and inflammation by molecular MRI at baseline: AUC = 0.89, P < 0.001). Conclusion Low ESS predicts progression of plaque burden and inflammation as assessed by non-invasive USPIO-enhanced MRI. Combined non-invasive assessment of ESS and imaging of inflammation may serve to predict plaque with high-risk features.
Increased attentional blink after focal cerebral lesions

Background: Once a person identifies a visual object, the ability to detect a second object is impaired for the next few hundred milliseconds. This attentional blink is reported to increase in subjects with neglect due to acute right hemisphere lesions. Method: To examine neural substrates of the attentional blink, the authors examined the performance of 13 subjects with chronic focal brain lesions visualized by MRI and nine control subjects without neurologic impairments on a rapid serial visual presentation task that used letters as targets. Results: Attentional blink length in the lesion group was more than twice that of controls (p < 0.05). The magnitude of the attentional blink deficit was greatest when the second target appeared 200 ms after the first target, recovering close to baseline by 1,200 ms. Abnormal attentional blink occurred (even in the absence of neglect) with lesions in the occipitotemporal areas (associated with “object” vision) and the prefrontal cortices (thought to mediate visual working memory). Conclusions: Attentional blink length and attentional blink magnitude measure different components of the attentional blink process. Abnormal attentional blink can occur with different chronic focal brain lesions in a network of structures for vision and attention, and it has no special status in hemispatial neglect. Abnormal attentional blink may help explain difficulties on rapid, visually demanding cognitive tasks such as reading and automobile driving and may explain performance deficits in brain damaged patients with nonspatial disorders of visual processing.
Association of NFKB1 and NFKBIA gene polymorphisms with susceptibility of gastric cancer

Xianyou county of Fujian province, located on the southeast coastal of China, has higher gastric cancer mortality. Chronic inflammation plays an important role in the occurrence of gastric cancer, in which the nuclear factor-κB signaling pathway of the inflammatory reaction begins and plays an important role in the amplification process. Studies have found that a single-nucleotide polymorphism of nuclear factor-κB signaling pathway molecules encoding genes is associated with gastric cancer, but the combined effect of the nuclear factor-κB signaling pathway gene has not been explained nor has been cardia and non-cardia gastric cancer risk factors and genetic susceptibility loci. New gastric cancer cases of the Fujian Xianyou Hospital were the research object. They were divided into cardia and non-cardia cancer in order to study a single-nucleotide polymorphism of the nuclear factor-κB signaling pathway important node molecules P50 and I kappa B encoding genes NFKB1 and NFKBIA by desorption ionization time of flight mass spectrometry analysis and by matrix-assisted laser mass spectrometry. The results showed that NFKB1 and NFKBIA single-nucleotide polymorphisms and gastric cancer are related and that the combined effects of polymorphisms in two genes and the NFKBIA gene monomer increased the risk of gastric cancer, and it was found that in different types of gastric cancer (the cardia and non-cardia cancer), susceptible polymorphism sites and combined effects are different.
Depletion of runt-related transcription factor 2 (RUNX2) enhances SAHA sensitivity of p53-mutated pancreatic cancer cells through the regulation of mutant p53 and TAp63

Suberoylanilide hydroxamic acid (SAHA) represents one of the new class of anti-cancer drugs. However, multiple lines of clinical evidence indicate that SAHA might be sometimes ineffective on certain solid tumors including pancreatic cancer. In this study, we have found for the first time that RUNX2/mutant p53/TAp63-regulatory axis has a pivotal role in the determination of SAHA sensitivity of p53-mutated pancreatic cancer MiaPaCa-2 cells. According to our present results, MiaPaCa-2 cells responded poorly to SAHA. Forced depletion of mutant p53 stimulated SAHA-mediated cell death of MiaPaCa-2 cells, which was accomapanied by a further accumulation of γH2AX and cleaved PARP. Under these experimental conditions, pro-oncogenic RUNX2 was strongly down-regulated in mutant p53-depleted MiaPaCa-2 cells. Surprisingly, RUNX2 silencing augmented SAHA-dependent cell death of MiaPaCa-2 cells and caused a significant reduction of mutant p53. Consistent with these observations, overexpression of RUNX2 in MiaPaCa-2 cells restored SAHA-mediated decrease in cell viability and increased the amount of mutant p53. Thus, it is suggestive that there exists a positive auto-regulatory loop between RUNX2 and mutant p53, which might amplify their pro-oncogenic signals. Intriguingly, knockdown of mutant p53 or RUNX2 potentiated SAHA-induced up-regulation of TAp63. Indeed, SAHA-stimulated cell death of MiaPaCa-2 cells was partially attenuated by p63 depletion. Collectively, our present observations strongly suggest that RUNX2/mutant p53/TAp63-regulatory axis is one of the key determinants of SAHA sensitivity of p53-mutated pancreatic cancer cells.
Nucleotide sequence and genomic organization of Aleutian mink disease parvovirus (ADV): sequence comparisons between a nonpathogenic and a pathogenic strain of ADV

A DNA sequence of 4,592 nucleotides (nt) was derived for the nonpathogenic ADV-G strain of Aleutian mink disease parvovirus (ADV). The 3'(left) end of the virion strand contained a 117-nt palindrome that could assume a Y-shaped configuration similar to, but less stable than, that of other parvoviruses. The sequence obtained for the 5' end was incomplete and did not contain the 5' (right) hairpin structure but ended just after a 25-nt A + T-rich direct repeat. Features of ADV genomic organization are (i) major left (622 amino acids) and right (702 amino acids) open reading frames (ORFs) in different translational frames of the plus-sense strand, (ii) two short mid-ORFs, (iii) eight potential promoter motifs (TATA boxes), including ones at 3 and 36 map units, and (iv) six potential polyadenylation sites, including three clustered near the termination of the right ORF. Although the overall homology to other parvoviruses is less than 50%, there are short conserved amino acid regions in both major ORFs. However, two regions in the right ORF allegedly conserved among the parvoviruses were not present in ADV. At the DNA level, ADV-G is 97.5% related to the pathogenic ADV-Utah 1. A total of 22 amino acid changes were found in the right ORF; changes were found in both hydrophilic and hydrophobic regions and generally did not affect the theoretical hydropathy. However, there is a short heterogeneous region at 64 to 65 map units in which 8 out of 11 residues have diverged; this hypervariable segment may be analogous to short amino acid regions in other parvoviruses that determine host range and pathogenicity. These findings suggested that this region may harbor some of the determinants responsible for the differences in pathogenicity of ADV-G and ADV-Utah 1.
Chlorpyrifos‐induced changes in the antioxidants and fatty acid compositions of Chroococcus turgidus NTMS12

This study investigated the effect of pesticide chlorpyrifos (CP) on a freshwater cyanobacterium Chroococcus turgidus NTMS12. The changes in chlorophyll‐a, proline, superoxide dismutase (SOD), catalase (CAT) activities and fatty acid composition of the test organism were analysed. Organism was grown at 6, 9 and 12 mg l−1 of CP, and based on the chlorophyll‐a content, 6 mg l−1 of CP was found to be the tolerable concentration. Hence, 6 mg l−1 of CP was taken to evaluate the concentration of proline and activities of SOD and CAT at 48‐h exposure. The changes in the fatty acid profile were analysed after 7 days of exposure. Upon pesticide exposure, increased concentration of proline and activities of SOD and CAT were found. Significant changes in fatty acid profile have also been observed. However, polyunsaturated fatty acid content was decreased in treated cultures when compared with the untreated control. Changes in biochemical activities indicate that cyanobacteria C. turgidus NTMS12 undergo adaptive changes against CP‐induced oxidative stress.
A COMPARATIVE ANALYSIS OF THE ECOLOGICAL SIGNIFICANCE OF MAXIMAL LOCOMOTOR PERFORMANCE IN CARIBBEAN ANOLIS LIZARDS

We examined the sprinting and jumping capabilities of eight West Indian Anolis species during three natural activities (escape from a predator, feeding, and undisturbed activity). We then compared these field data with maximal performance under optimal laboratory conditions to answer three questions: (1) Has maximal (i.e., laboratory) sprinting and jumping performance coevolved with field performance among species? (2) What proportion of their maximum capabilities do anoles sprint and jump in different ecological contexts? (3) Does a relationship exist between maximal sprinting and jumping ability and the proportion of maximal performance used in these contexts? Among species, maximal speed is tightly positively correlated with sprinting performance during both feeding and escape in the field. Sprinting speed during escape closely matches maximal sprinting ability (i.e., about 90% of maximum performance). By contrast, sprinting performance during undisturbed activity is markedly lower (about 32% of maximum) than maximal sprinting performance. Sprinting ability during feeding is intermediate (about 71% of maximum) between field escape and field undisturbed activity. In contrast to sprinting ability, jumping ability is always substantially less than maximum (about 40% of maximum during feeding and undisturbed activity). A negative relationship exists among species between maximal speed and the proportion to which species sprint to their maximal abilities during field escape.
Thiocyanate ions selectively antagonize AMPA‐evoked responses in Xenopus laevis oocytes microinjected with rat brain mRNA

1 Responses to kainate (KA), willardiine and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) were recorded from rat brain mRNA‐injected Xenopus laevis oocytes by use of a two‐electrode voltage clamp. 2 Thiocyanate (SCN−; 50 μm − 4 mm) ions reversibly and selectively inhibited the membrane current responses to AMPA in a non‐competitive manner without affecting KA or willardiine‐induced responses. 3 The inhibition of AMPA‐induced responses by SCN− was dependent on the SCN− concentration with an estimated IC50 of 1 mm. The antagonism was not dependent on the AMPA concentration. 4 The response to a high concentration of AMPA (100–200 μm) exhibited a peak inward current which declined to a steady‐state. SCN− inhibited the steady‐state current more than the peak response. The inhibition was unaffected by prior incubation with concanavalin‐A (Con‐A; 10 μm). 5 Responses to KA were antagonized by AMPA in a competitive manner, suggesting that both agonists may activate a common receptor‐channel complex. This interaction between two non‐NMDA agonists was not affected by the SCN−‐induced inhibition of the AMPA response. 6 AMPA‐induced responses recorded from large cultured cerebellar neurones by whole‐cell recording were also inhibited by SCN− in a non‐competitive manner. The AMPA‐induced peak current was less affected than the steady‐state response. 7 We conclude that SCN− can inhibit the response to AMPA in expressed non‐NMDA receptors in Xenopus oocytes and also in native receptors in cultured cerebellar neurones. One possible mechanism of action for SCN− inhibition of responses to AMPA may involve a Con‐A‐insensitive, non‐NMDA receptor‐mediated desensitization.
Factors causing difference in force output among motor units in the rat medial gastrocnemius muscle.

1. The isometric contractile properties and morphological characteristics of the muscle unit portion of motor units were investigated in the medial gastrocnemius (MG) muscle of Fischer 344 rats. Individual motor units were functionally isolated by stimulating single MG axons in finely dissected ventral root filaments. 2. To study the mechanical properties of the motor units in the rat MG muscle, ninety‐six motor units in five animals were classified into three categories (type FF, FR and S units) using two physiological criteria: presence or absence of the 'sag' property and fatigability. The relative distribution of the different motor unit types in the sample was 35.4% for type FF, 47.9% for type FR, and 16.7% for type S units. 3. There was little overlap in the distribution of twitch contraction time between type F (including types FF and FR) and type S units. The mean value was 17.1 ms for type FF, 15.7 ms for type FR, and 28.0 ms for type S units. Type FF units produced the largest tetanic tension (mean +/‐ S.D.; 201 +/‐ 75 mN). Tension output of type S units was the smallest (15 +/‐ 6 mN), and that of type FR units was intermediate (100 +/‐ 45 mN). These values were significantly different. 4. A muscle unit portion of twenty‐three motor units (8 FF, 6 FR, and 9 S units) was depleted of its glycogen through repetitive stimulation after characterization of its mechanical properties. Cross‐sectional areas of units fibres and innervation ratio were directly measured in sections stained for glycogen using a periodic and acid‐Schiff (PAS) reaction. Specific tension of unit fibres was calculated by dividing the maximum tetanic tension of a unit by its total fibre area. 5. The number of unit fibres ranged from 44 to 77 for type S, 116 to 198 for type FR, and 221 to 356 for type FF units, and differences among their means (66, 154 and 271, respectively) were significant. Tetanic tension was correlated with innervation ratio for all of the twenty‐three units, or units within a particular type. 6. Mean fibre area for type S units (1983 microns2) was significantly smaller than that for type FF units (3489 microns2). Fibres belonging to type FR units had an intermediate size (2648 microns2). Correlation between tetanic tension and fibre area was significant for either all units or units within a particular type. 7. Total cross‐sectional area was significantly different among the motor unit types, and was highly correlated to the maximum tetanic tension. (ABSTRACT TRUNCATED AT 400 WORDS)