Miracle-dz/UniFAR-FTUs huggingface dataset:
Derivation and validation of a composite index of severity in chronic obstructive pulmonary disease: the DOSE Index.

RATIONALE Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a multicomponent disease with systemic consequences and effects on quality of life. Single measures such as lung function provide a limited reflection of how the disease affects patients. Composite measures have the potential to account for many of the facets of COPD. OBJECTIVES To derive and validate a multicomponent assessment tool of COPD severity that is applicable to all patients and health care settings. METHODS The index was derived using data from 375 patients with COPD in primary care. Regression analysis led to a model explaining 48% of the variance in health status as measured by the Clinical COPD Questionnaire with four components: dyspnea (D), airflow obstruction (O), smoking status (S), and exacerbation frequency (E). The DOSE Index was validated in cross-sectional and longitudinal samples in various health care settings in Holland, Japan, and the United Kingdom. MEASUREMENTS AND MAIN RESULTS The DOSE Index correlated with health status in all data sets. A high DOSE Index score (> or = 4) was associated with a greater risk of hospital admission (odds ratio, 8.3 [4.1-17]) or respiratory failure (odds ratio, 7.8 [3.4-18.3]). The index predicted exacerbations in the subsequent year (P < or = 0.014). CONCLUSIONS The DOSE Index is a simple, valid tool for assessing the severity of COPD. The index is related to a range of clinically important outcomes such as health care consumption and predicts future events.
Comparison of magnetic resonance imaging and video capsule enteroscopy in diagnosing small-bowel pathology: Localization-dependent diagnostic yield

Abstract Objective. New technology has considerably advanced the diagnosis of small-bowel pathology. However, its significance in clinical algorithms has not yet been fully assessed. The aim of the present analysis was to compare the diagnostic utility and yield of video-capsule enteroscopy (VCE) to that of magnetic resonance imaging (MRI) in patients with suspected or established Crohn's disease (Group I), obscure gastrointestinal blood loss (Group II), or suspected tumors (Group III). Material and methods. Forty-six out of 182 patients who underwent both modalities were included: 21 in Group I, 20 in Group II, and five in Group III. Pathology was assessed in three predetermined sections of the small bowel (upper, middle, and lower). The McNemar and Wilcoxon tests were used for statistical analysis. Results. In Group I, lesions were found by VCE in nine of the 21 patients and by MRI in six. In five patients, both modalities showed pathology. In Group II, pathological changes were detected in 11 of the 20 patients by VCE and in eight patients by MRI. In five cases, pathology was found with both modalities. In Group III, neither modality showed small-bowel pathology. For the patient groups combined, diagnostic yield was 43% with VCE and 30% with MRI. The diagnostic yield of VCE was superior to that of MRI in the upper small bowel in both Groups I and II. Conclusion. VCE is superior to MRI for the detection of lesions related to Crohn's disease or obscure gastrointestinal bleeding in the upper small bowel.
Smooth endoplasmic reticulum dilation and degeneration in Purkinje neuron dendrites of aging ethanol-fed female rats

The effects of chronic ethanol consumption on the extensive Purkinje neuron (PN) dendritic arbor of male rats include dilation of the smooth endoplasmic reticulum (SER) and dendritic regression. The purpose of the present study was to examine the molecular layer of female rats for the presence of ethanol-related SER dilation and evidence of degeneration within the PN dendritic arbor. Twenty-one 12-month-old Fischer 344 female rats (n=7/treatment group) received a liquid ethanol, liquid control, or rat chow diet for a period of 40 weeks. Ethanol-fed rats received 35% of their dietary calories as ethanol. Pair-fed rats received a liquid control diet that was isocaloric to the ethanol diet. Chow-fed rats received standard laboratory rat chow ad libitum. At the end of treatment, tissues from the anterior and posterior lobes of the cerebellar vermis were viewed and photographed with the electron microscope. The diameters of SER profiles were measured and the density of degenerating bodies within the PN dendritic arbor was quantitated. In the posterior lobe, ethanol-related SER dilation was apparent. In the anterior lobe, the density of degenerating bodies within PN dendritic shafts was significantly increased but SER dilation in PN dendritic shafts was absent. These results confirm that SER dilation and dendritic degeneration in PN dendrites may precede and contribute to ethanol-related regression in female rats. In addition, comparison of these results with data obtained in male rats from a previous study suggests that PN dendrites in females may be more sensitive to the effects of ethanol.
Testing the Governance-Productivity Nexus for Emerging Asian Countries

This paper presents panel data estimates of the relationship between governance, aggregate labor productivity (ALP) growth and total factor productivity (TFP) growth for 12 Asian economies between 1996 and 2013. Our results show that government effectiveness has a positive and significant effect on ALP in both levels and first differences. Regulatory quality has a positive impact on ALP only in first difference. Although both government effectiveness and regulatory quality have a positive effect on TFP growth in first difference, only political stability is significant and positive in the levels specification. Other findings indicate that physical capital and human capital have a positive effect on ALP growth. We also find evidence of positive spillover effects with respect to human capital. The positive association between governance, economic growth and productivity provide a better understanding of the role of governance in enhancing economic performance. Our findings have policy implications for ways to achieve good governance to enhance economic growth and productivity.
Dopamine receptor D4 (DRD4) gene in Han Chinese children with attention‐deficit/hyperactivity disorder (ADHD): Increased prevalence of the 2‐repeat allele

There is an increased prevalence of the 7‐repeat (7R) allele of the dopamine receptor D4 (DRD4) gene in attention‐deficit/hyperactivity disorder (ADHD). However, the population prevalence of the 7R allele varies considerably across ethnicity and is very low in Asians. To test whether this 7R allele/ADHD association still held in a Chinese clinical sample, 32 Han Chinese children with a confirmed ADHD diagnosis and normal IQ who were methylphenidate‐responders were genotyped. None of them had a DRD4 7R allele. Instead, we observed a significantly increased prevalence of the 2‐repeat (2R) allele in this clinical sample (33%) compared to ethnically‐matched controls (20%) (χ2(1d.f.) = 5.90, P = 0.015). This approximately 1.65‐fold increase of the 2R allele in our probands is close to the observed increase of the 7R allele in European‐ancestry ADHD children. Recent genetic studies have indicated that the 2R allele in Asians is likely derived from the 7R allele. Further, available biochemical data indicate that both the 2R and 7R protein have blunted responses to dopamine compared to the 4R protein. Based on these results, we propose that the observed increased prevalence of the 2R allele in our Han Chinese ADHD probands is still consistent with the 7R allele hypothesis of ADHD in European‐ancestry children. Recent studies have suggested that any variant from the conserved ancestral 4R allele might potentially alter biochemistry/phenotype. We hypothesize that an increased frequency of any non‐4R allele may define the association of the DRD4 gene with ADHD that holds across ethnicity. The present findings, however, obtained with a small ADHD sample size, should be replicated. © 2004 Wiley‐Liss, Inc.
Dealing with Ambiguities by Underspecification: Construction, Representation and Deduction

In this paper we develop a theory of language meaning that represents scope ambiguities by underspecified structures. The set of possible meanings of a sentence, or text is determined by a set of meta-level constraints that restricts the class of semantic representations appropriately. Thus the way ambiguities are represented does not correspond to any of the usual concepts of formalizing ambiguities by means of disjunctions. A sound and complete proof theory is provided that relates these structures directly, without considering cases.
Permeability of the murine blood-brain barrier to some octapeptide analogs of somatostatin.

Analogs of somatostatin are being investigated clinically for the treatment of various malignancies, including brain tumors. We studied the ability of three therapeutically promising radioactively labeled somatostatin octapeptide analogs, RC-160, RC-121, and RC-161, to cross the blood-brain barrier (BBB) after peripheral or central injection. After i.v. injection, intact RC-160 was recovered from the blood and the brain. The entry rates were different from each compound but were generally low. By contrast, entry across the intact BBB increased 220 times when RC-160 was given in a serum-free perfusate. This suggests that some serum-related factor, probably the previously described protein binding or an aggregation-promoting factor, is the main determinant in limiting the blood-to-brain passage of somatostatin analogs. Entry into the brain was not inhibited by the addition of unlabeled analog to the perfusate, showing that passage was probably by diffusion across the membranes that comprise the BBB rather than by saturable transport. By contrast, a saturable system was found to transport peptide out of the central nervous system (CNS). The clearance from the CNS of RC-160 and RC-121, but not RC-161, was faster than could be accounted for by reabsorption of cerebrospinal fluid. Transport of radioactively labeled RC-160 out of the CNS was inhibited by unlabeled RC-160 or somatostatin but was not affected by some other peptide known to cross the BBB by their own transport systems. More than 80% of the radioactivity recovered from the blood after intracerebroventricular injection of RC-160 was eluted by HPLC at the position of the labeled analog, showing that the peptide had crossed the BBB in intact form. Our results indicate the presence of a saturable transport system in one direction across the BBB for some superactive analogs of somatostatin.
Fathers’ Involvement with Their Nonresident Children and Material Hardship

Children in single-parent families, particularly children born to unmarried parents, are at high risk for experiencing material hardship. Previous research based on cross-sectional data suggests that father involvement, especially visitation, diminishes hardship. This article uses longitudinal data to examine the associations between nonresident fathers’ involvement with their children and material hardship in the children’s households. Results suggest that fathers’ formal and informal child support payments and contact with their children independently reduce the number of hardships in the mothers’ households; however, only the impact of fathers’ contact with children is robust in models that include lagged dependent variables or individual fixed effects. Furthermore, cross-lagged models suggest that material hardship decreases future father involvement, but future hardship is not diminished by father involvement (except in-kind contributions). These results point to the complexity of these associations and to the need for future research to focus on heterogeneity of effects within the population.
Diastolic function abnormalities in rheumatoid arthritis. Evaluation by echo Doppler transmitral flow and pulmonary venous flow: relation with duration of disease

OBJECTIVE The aim of this study was to evaluate left ventricular filling in patients with rheumatoid arthritis (RA), analysing transmitral flow and pulmonary venous flow, with special regard to age and disease duration. METHODS 32 patients affected by RA according to ARA criteria were selected, without evidence of cardiac disease, and compared with matched control subjects. All patients and the control group were submitted to M-mode, two dimensional, Doppler and colour Doppler (continuous and pulsed wave) echocardiography. The following diastolic parameters were evaluated: transmitralic flow (E/A ratio), pulmonary venous flow (S/D ratio), a-Pw, IVRT and DT. RESULTS In RA patients left ventricular filling abnormalities were found characterised by a reduced E/A ratio (mean (SD) 1.16 (0.31) vcontrols 1.37 (0.32); p =0.02) and an increased S/D ratio (1.43 (0.40)v controls 1.22 (0.29); p = 0.017). In the group of patients a relation was found between E/A ratio and disease duration (r= 0.40, p =0.01 Spearman rank correlation). CONCLUSIONS At present, it is concluded that RA patients, in absence of clinical evidence of heart disease, show diastolic dysfunction characterised by impaired E/A and S/D ratio. The relation between transmitral flow alteration and disease duration suggests a sub-clinical myocardial involvement.
The influence of Gaussian strain on sublattice selectivity of impurities in graphene

Among the different strategies used to induce the opening of a band gap in graphene, one common practice is through chemical doping. While a gap may be opened in this way, disorder-induced scattering is an unwanted side-effect that impacts the electron mobility in the conductive regime of the system. However, this undesirable side effect is known to be minimised if dopants interact asymmetrically with the two sublattices of graphene. In this work we propose that mechanical strain can be used to introduce such a sublattice asymmetry in the doping process of graphene. We argue that a localised out-of-plane deformation applied to a graphene sheet can make one of the graphene sublattices more energetically favourable for impurity adsorption than the other and that this can be controlled by varying the strain parameters. Two complementary modelling schemes are used to describe the electronic structure of the flat and deformed graphene sheets: a tight-binding model and density functional theory. Our results indicate a novel way to select the doping process of graphene through strain engineering.
Automatic generation of hardware design properties from simulation traces

This paper studies the problem of automatic assertion extraction from simulation traces. Previous approaches to the assertion generation problem have focused on a single aspect of automatic assertion extractions, and have yielded often unfavorable results. We propose a framework that combines searching for known assertion via templates with frequent and sequential patterns mining, while constraining the search by some knowledge about the design. These constraints can be automatically extracted using static analysis methods from the Register Transfer Level (RTL) description of the design, or as a user input to the assertion detector. Our experimental results show that this approach helps in the detection of assertion patterns that are typically common and widely used in today's RTL designs.
Cryptocurrencies Meet Inflation Theory

Using concepts from inflation theory, this study examines the relationship between the returns and volatility of cryptocurrencies. We take Bitcoin, Ethereum, Litecoin and Ripple as the four most popular cryptocurrencies in the market and analyse the relationship between their returns and volatility through the application of GARCH models. The results suggest that Bitcoin and Litecoin behave as a currency subject to inflation showing a causal relationship from returns to volatility [and not the other way around]. In contrast, the results for Ethereum and Ripple show that the causation runs from volatility to returns. Moreover, the volatility of each cryptocurrency is affected by the other three cryptocurrency returns. A panel cointegration analysis shows evidence of a strong cointegration relationship in the cryptocurrency prices.
Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS–NO–nitrite signaling

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by severe intestinal necrosis and for which breast milk represents the most effective protective strategy. Previous studies have revealed a critical role for the lipopolysaccharide receptor toll-like receptor 4 (TLR4) in NEC development through its induction of mucosal injury, yet the reasons for which intestinal ischemia in NEC occurs in the first place remain unknown. We hypothesize that TLR4 signaling within the endothelium plays an essential role in NEC development by regulating perfusion to the small intestine via the vasodilatory molecule endothelial nitric oxide synthase (eNOS). Using a unique mouse system in which we selectively deleted TLR4 from the endothelium, we now show that endothelial TLR4 activation is required for NEC development and that endothelial TLR4 activation impairs intestinal perfusion without effects on other organs and reduces eNOS expression via activation of myeloid differentiation primary response gene 88. NEC severity was significantly increased in eNOS−/− mice and decreased upon administration of the phosphodiesterase inhibitor sildenafil, which augments eNOS function. Strikingly, compared with formula, human and mouse breast milk were enriched in sodium nitrate—a precursor for enteral generation of nitrite and nitric oxide—and repletion of formula with sodium nitrate/nitrite restored intestinal perfusion, reversed the deleterious effects of endothelial TLR4 signaling, and reduced NEC severity. These data identify that endothelial TLR4 critically regulates intestinal perfusion leading to NEC and reveal that the protective properties of breast milk involve enhanced intestinal microcirculatory integrity via augmentation of nitrate–nitrite–NO signaling.
Influence of Glycine spp. on Competitiveness of Bradyrhizobium japonicum and Rhizobium fredii

The displacement of indigenous Bradyrhizobium japonicum in soybean nodules with more effective strains offers the possibility of enhanced N2 fixation in soybean (Glycine max (L.) Merr. ). Our objective was to determine whether the wild soybean (G. soja Sieb. & Zucc.) genotype PI 468397 would cause reduced competitiveness of important indigenous B. japonicum strains USDA 31, 76, and 123 and thereby permit nodulation by Rhizobium fredii, the fast-growing microsymbiont of soybean. In an initial experiment, PI 468397 nodulated and fixed moderate amounts of N2 with USDA 31 and 76 but, despite the formation of nodules, fixed essentially no N2 with USDA 123. In contrast, PI 468397 formed a highly effective symbiosis with R. fredii strain USDA 193. In two subsequent experiments, Williams soybean and PI 468397 were grown in a pasteurized soil mixture or in soybean rhizobium-free soil and inoculated with both USDA 123 and USDA 193. In each experiment, more than 90% of the nodules of Williams contained USDA 123, while only a maximum of 2% were occupied with USDA 193. In contrast, in the two experiments, 16 and 11%, respectively, of the nodules produced on PI 468397 were occupied by USDA 123, while in both experiments 87% contained USDA 193. Thus, in relation to the cultivar Williams, which is commonly grown and used as a parent in soybean breeding programs in the United States, PI 468397 substantially reduced the competitive ability of B. japonicum strain USDA 123 in relation to R. fredii strain USDA 193.
Barbarians at the Imperium Gates: Organizational Culture and Change in EVE Online

This article looks at organizational culture and identity of different organisations in EVE Online, using a combination of critical historical and ethnographic approaches. We argue that it is helpful to understand major organizations in EVE as analogous to early polities, in terms of the ways in which claims to leadership and power are demonstrated (for example through the writing of history). Yet, as we show, these organizations have strong cultures which demonstrate resilience and a resistance to top-down cultural change, meaning that the successful implementation of such change is governed by rank-and-file members rather than their leadership. We propose that the cultural (rather than political or social) nature of this resilience is centrally important in understanding how organizations in EVE function. This unity of practices and understanding allows EVE’s major organizations to suffer huge losses to their position and prestige, and yet remain viable communities and potentially resurgent powers. This seems to challenge the ‘social network’-type descriptions often used to explain the persistent groups seen in many online games.
Reversal of multi-drug resistance by pSUPER-shRNA-mdr1 in vivo and in vitro.

AIM To explore the possibility of reversing multi-drug resistance (MDR) to HepG2/mdr1 in vitro and in vivo with RNA interference (RNAi). METHODS HepG2/mdr1 was obtained by cloning the whole gene mdr1 into HepG2 cells. shRNA targeting sequence was designed to be homologous to the P-gp encoding MDR1 mRNA consensus sequence. pSUPER-shRNA/mdr1 was constructed using the enzyme-digested technique. HepG2/mdr1 cells were transfected with vectors of pSUPER-shRNA/mdr1 to measure their efficacy by real-time PCR for mdr1 mRNA, flow cytometry (FCM) for P-gp expression, and Rhodamine efflux, MTT method for HepG2/mdr1 function, respectively. In vivo, mice tumors were treated by injecting pSUPER-shRNA/mdr1 in situ and into intra-abdominal cavity. Tumors were collected to create cell suspension and cryosections after chemotherapy with adriamycin and mytomycin. The cell suspension was incubated in RPMI-1640 supplemented with G418 to screen stable cells for appreciating the reversal of MDR. Cryosections were treated with immunohistochemistry technique to show the effectiveness of transfection and the expression of P-gp. RESULTS pSUPER-shRNA/mdr1 was successfully constructed, which was confirmed by sequencing. The MDR phenotype of HepG2/mdr1 was decreased significantly in vitro transfection. HepG2/mdr1 showing its MDR was reversed notably in P-gp expression (11.0% vs 98.2%, P<0.01). Real-time PCR showed that mRNA/mdr1 was lower in test groups than in control groups (18.73+/-1.33 vs 68.03+/-2.21, P<0.001). Compared with HepG2, the sensitivity of HepG2/mdr1 and HepG2/mdr1-dsRNA cells to ADM was decreased by 1.64 times and 15.6 times, respectively. The accumulation of DNR in positive groups was decreased evidently. In vivo, the p-gp expression in positive groups was significantly lower than that in control groups (65.1% vs 94.1%, P<0.05). The tumor suppressing rate in test groups was 57.8%. After chemotherapy, the growth rate in test groups was lower than that in control groups (700.14+/-35.61 vs 1659.70+/-152.54, P<0.05). Similar results were also observed under fluorescence microscope, and confirmed by Image-Pro Plus 4.5 analysis. CONCLUSION pSUPER-shRNA/mdr1 vector system allows simple, stable and durable nonviral knockdown of P-gp by RNAi in malignant cells and animals to restore their sensitivity to adriamycin.