Miracle-dz/UniFAR-FTUs huggingface dataset:
Arterial norepinephrine concentration is inversely and independently associated with insulin clearance in obese individuals with metabolic syndrome.

CONTEXT Impaired insulin clearance contributes to the hyperinsulinemia of obesity, yet relatively little is known concerning the pathophysiological determinants of insulin clearance in obese populations. OBJECTIVE To examine the cross-sectional relationship between insulin clearance and resting sympathetic nervous system activity in a cohort of obese subjects with metabolic syndrome. PARTICIPANTS AND METHODS Unmedicated, nonsmoking subjects (31 male, 27 female; aged 56 ± 1 year; body mass index 33.7 ± 0.6 kg/m(2)) underwent euglycemic hyperinsulinemic clamp to determine insulin sensitivity (M) and insulin clearance, assessment of norepinephrine kinetics, peripheral arterial tonometry, Doppler echocardiography, and oral glucose tolerance test. RESULTS Univariate correlation analyses showed inverse associations between insulin clearance and arterial norepinephrine concentration (r = -0.44, P = .0006), calculated norepinephrine spillover rate (r = -0.33, P = .01), augmentation index (AI, r = -0.37, P = .005), and positive associations with M (r = 0.30, P = .02), Matsuda insulin sensitivity index (r = 0.27, P = .04), and cardiac output (r = 0.27, P = .04). Insulin clearance and sensitivity did not differ between genders, however females had higher AI compared to males (35 ± 3% versus 14 ± 2%, P < .001). In age and gender adjusted stepwise regression analyses, arterial norepinephrine concentration alone explained 19% of the variance in insulin clearance. When all significant variables were entered into the regression model, arterial norepinephrine, AI, gender, and M were independent predictors of insulin clearance, together explaining 41% of the variance. CONCLUSIONS Arterial norepinephrine concentration is inversely and independently associated with whole-body insulin clearance rate in obese individuals with metabolic syndrome. Prospective studies are needed to determine the direction of causality and the chronology of interactions between insulin clearance and sympathetic neural activity.
Bispecific antibodies for cancer therapy

With 23 approvals in the US and other countries and 4 approvals outside US, antibodies are now widely recognized as therapeutic molecules. The therapeutic and commercial successes met by rituximab, trastuzumab, cetuximab and other mAbs have inspired antibody engineers to improve the efficacy of these molecules. Consequently, a new wave of antibodies with engineered Fc leading to much higher effector functions such as antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity is being evaluated in the clinic, and several approvals are expected soon. In addition, research on a different class of antibody therapeutics, bispecific antibodies, has recently led to outstanding clinical results, and the first approval of the bispecific antibody catumaxomab, a T cell retargeting agent that was approved in the European Union in April 2009. This review describes the most recent advances and clinical study results in the field of bispecific antibodies, a new class of molecules that might outshine conventional mAbs as cancer immunotherapeutics in a near future.
An Empirical Investigation of the Effects of Brain Drain on Developing Countries since 21st Century: A Case of Afghanistan

The purpose of this study is to find out the factors behind the flood of Afghan migrants the world witnessed during the past couple of years. After the withdrawal of some portion of US and NATO forces in 2014, people of Afghanistan suffered mainly from continued security concerns which ultimately stimulated migration of young minds at large but this is not the only factor we analyzed during the process. The push factors such as cost of weddings in some parts of Afghanistan is a profound problem and it was observed from the investigation of the sample population as a stimulus for youth to go abroad to work and save money for getting married. We investigated the unemployment factor on brain drain from Afghanistan on a large scale. This factor clearly proved to be the major driver of migration based on the results obtained in this empirical study. Furthermore, each year thousands of students leave Afghanistan to study in different parts of the world on scholarship. We investigated the role of educational scholarships on motivating youth to leave Afghanistan and their probability to return back to their homeland. It was demonstrated through the analysis of sample data that mostly those students who travel abroad for study purposes do not return back to Afghanistan, thereby creating a vacuum in terms of productive young minds. In addition, Social pressure is a common influence on people’s behavior within the different communities in Afghanistan. We analyzed the relationship between people adopting the path of migration with social pressures from society. The analysis of the data showed a positive relationship of the societal pressures on the youth leaving country. The nature of research for my study is based on quantitative methodology. This research targeted mainly the Afghan population living overseas because these are the people who are most affected one way or the other by some internal factors that’s why they migrated. We have also included citizen’s views that live within Afghanistan in order to understand prospects of migration from the participants. However, a convenience sampling method was used in this study as specific people were targeted that we believe would take part in the survey. Social Media such as Facebook and Vkontakte was used to deliver the questionnaires to the respondents. The Statistical Package for Social Sciences (SPSS) statistical models such as Chi square test, binomial probability test, and a one sample test were used to test the hypotheses statements. A pairwise test was used to rank the factors in terms of major influence on migration.
Imprinting and the Epigenetic Asymmetry Between Parental Genomes

Genomic imprinting confers a developmental asymmetry on the parental genomes, through epigenetic modifications in the germ line and embryo. These heritable modifications regulate the monoallelic activity of parental alleles resulting in their functional differences during development. Specific cis-acting regulatory elements associated with imprinted genes carry modifications involving chromatin structural changes and DNA methylation. Some of these modifications are initiated in the germ line. Comparative genomic analysis at imprinted domains is emerging as a powerful tool for the identification of conserved elements amenable to more detailed functional analysis, and for providing insight into the emergence of imprinting during the evolution of mammalian species. Genomic imprinting therefore provides a model system for the analysis of the epigenetic control of genome function.
Epididymal SPAM1 Is a Marker for Sperm Maturation in the Mouse1

Abstract Sperm adhesion molecule 1 (SPAM1), is a glycosyl phoshatidylinositol-linked sperm membrane protein that is dually expressed in testis and epididymis. Epididymal SPAM1 is secreted in all three regions of the epididymis in all mammalian species studied, including humans. It shares the same molecular mass and neutral hyaluronidase activity as the testicular and sperm isoforms that are responsible for the penetration of the cumulus during fertilization. Using wild-type (W/T) sperm and those from mice homozygous for either a null (Spam1−/−) or mutant Spam1 allele, which results in decreased mRNA and protein, we demonstrate that sperm binding of epididymal SPAM1 occurs in vitro after exposure to W/T sperm-free epididymal luminal fluid (ELF). Binding or adsorption that occurred after incubation at room temperature or 32°C was detected immunocytochemically and confirmed quantitatively using flow cytometry. The localization of SPAM1 on the plasma membrane of Spam1-null sperm mimicked that seen in the W/T. The remarkable increase in binding on W/T caudal sperm indicates that they are not fully saturated with SPAM1 during storage, and suggests that uptake of epididymal SPAM1 in vivo augments testicular SPAM1. Spam1-null sperm exposed to W/T ELF for 45–60 min during in vitro capacitation to allow epididymal SPAM1 binding showed a highly significant (P < 0.001) increase in cumulus penetration after 6–7 h compared to those incubated in ELF from null males. Similarly, the number of cumulus-free oocytes was also highly significantly greater (P < 0.001) than that for sperm capacitated in W/T SPAM1-antibody-inhibited ELF. Because epididymal SPAM1 uptake significantly increases cumulus penetration, we conclude that it is a marker of sperm maturation.
Coverage and utilization of the health insurance among migrant workers in Shanghai, China.

BACKGROUND According to the regulations of the Chinese and Shanghai governments, migrant workers employed in Shanghai should all be entitled to Shanghai Migrant Worker Hospitalization Insurance (SMWHI) without premium and the vast majority should also have the New Rural Cooperative Medical System (NRCMS). This study aimed to examine the status of the coverage and utilization of health insurance among migrant workers employed in Shanghai. METHODS Quantitative and qualitative research methods were employed in the study. A survey of 1020 migrant workers employed in Shanghai was conducted in 2010 with a structured questionnaire. Focus group discussions were held with respondents who were unable to maintain health insurance coverage through NRCMS or SMWHI. In-depth interviews were held with village heads and employers of the migrant workers, migrant workers who were hospitalized within the last year, and various individuals employed by the insurance agencies. RESULTS The study found that 72.9% and 36.5% of migrant workers were covered by NRCMS or SMWHI, respectively, while 16.7% of them had no health insurance. The coverage by NRCMS among migrant workers correlated significantly with education level and workplace, while the coverage by SMWHI correlated significantly with the length of employment in Shanghai and workplace. The qualitative results confirmed that migrant workers were the main group who were not covered by NRCMS, and the coverage by SMWHI was completely dependent upon the employers of the migrant worker. The results also showed that health insurance utilization among migrant workers was strongly limited by hospital location. CONCLUSIONS We observed that the status of health insurance among migrant workers was not accordant with theory, and that Chinese health insurance policy should be further reformed in order to realize full coverage and equal utilization of health insurance among migrant workers in China.
Exonuclease mutations in DNA polymerase epsilon reveal replication strand specific mutation patterns and human origins of replication

Tumors with somatic mutations in the proofreading exonuclease domain of DNA polymerase epsilon (POLE-exo*) exhibit a novel mutator phenotype, with markedly elevated TCT→TAT and TCG→TTG mutations and overall mutation frequencies often exceeding 100 mutations/Mb. Here, we identify POLE-exo* tumors in numerous cancers and classify them into two groups, A and B, according to their mutational properties. Group A mutants are found only in POLE, whereas Group B mutants are found in POLE and POLD1 and appear to be nonfunctional. In Group A, cell-free polymerase assays confirm that mutations in the exonuclease domain result in high mutation frequencies with a preference for C→A mutation. We describe the patterns of amino acid substitutions caused by POLE-exo* and compare them to other tumor types. The nucleotide preference of POLE-exo* leads to increased frequencies of recurrent nonsense mutations in key tumor suppressors such as TP53, ATM, and PIK3R1. We further demonstrate that strand-specific mutation patterns arise from some of these POLE-exo* mutants during genome duplication. This is the first direct proof of leading strand-specific replication by human POLE, which has only been demonstrated in yeast so far. Taken together, the extremely high mutation frequency and strand specificity of mutations provide a unique identifier of eukaryotic origins of replication.
Editorial Focus: PPAR (cid:1) differentially regulates energy substrate handling in brown vs. white adipose : focus on “The PPAR (cid:1) agonist rosiglitazone enhances rat brown adipose tissue lipogenesis from glucose without altering glucose uptake”

PEROXISOME PROLIFERATOR - ACTIVATED receptor (cid:1) (PPAR (cid:1) ) is a nuclear receptor and ligand-activated transcription factor that is highly expressed in brown adipose tissue (BAT) and is neces-sary for its development (1, 6, 7). BAT is well recognized for its functions in metabolic rate control in rodents (2), and recent work has also identiﬁed signiﬁcant amounts of BAT in adult humans (9). BAT exhibits relatively high rates of lipid and glucose uptake, and generates signiﬁcant heat in response to sympathetic activation and other stimuli through lipid oxida-tion and activation of uncoupling protein-1. In adipocytes, fatty acids are stored as triacylglycerol (TAG). Given the high metabolic activity of this tissue, the regulation of intracellular synthesis and storage of TAG is of great importance for normal BAT function.
Legislative Coalition Size and Antigovernment Protests in Latin America

This work examines whether the size, as well as the composition, of legislative coalitions is an additional factor that affects the incidence of protests against national governments in Latin America. Based on aggregate data for 18 democracies from 1980 to 2014, the analysis reveals that the relationship between the size of legislative coalitions in the lower house of national assemblies and the odds of antigovernment protests is U-shaped. Specifically, the odds of antigovernment protests occurring decrease until the president has a coalition comprising 50–55 percent of the national assembly; once this threshold is passed, the odds of protests taking place increase as the coalition grows. This result holds after controlling for the party composition of the governing coalition and other factors previously linked to the occurrence of antigovernment protests. The evidence thus indicates that both minority and supermajority scenarios can be socially destabilizing for Latin American democracies.
Análisis de las competencias genéricas de la Universidad de Almería en el Grado en Derecho en relación al mercado laboral

In this manuscript, the 10 generic skills of UAL, in the 37 subjects comprising the Degree in Law at the University of Almeria were analysed. The results show that the most frequent skills are: first, “Oral and written communication in the own language”, second, “the Ability to solve problems”, third, “Capacity for critical and self-critical”. On the other hand, the skills that are less present are: “Learning a foreign language”, appearing in only 5% of the subjects, followed by “Social competence and global citizenship”, which appears in 27% of cases. The skills of the use of Information and communication technologies and the ability to learn autonomously are above 70%; that are considered quite appropriate given the great progress our society has undergone in recent years, particularly in this type of skills. As main conclusion, in this study has been detected that the skill to be strengthened is learning a foreign language; because in a globalized world professionals with knowledge of a second language will be the most popular, and can compete for jobs abroad.
Predictive Value of Brachial-Ankle Pulse Wave Velocity for Cardiovascular Events

Background:The aim of this study was to determine the association of pulse wave velocity or left ventricular diastolic function with the development of cardiovascular (CV) events. Methods:Brachial-ankle pulse wave velocity (baPWV) and E/E' were analyzed in 185 patients. The primary end point was CV events including ischemic stroke, coronary arterial disease (CAD), peripheral arterial disease and aortic dissection. Results:There were 30 CV events during a mean follow-up period of 19.8 months. When the baPWV cutoff level was set to 1704 cm/s using the receiver operating characteristic curve, the sensitivity was 70/92% and the specificity 63/62% for differentiating between the group with and without CV events or ischemic stroke. In univariate analysis with the Cox proportional hazard model, higher baPWV was a predictor for CV events and ischemic stroke events. However, high E/E' (>15) was not a predictor for CV, ischemic stroke events or CAD. A higher baPWV was an independent predictor for CV and ischemic stroke risk after adjusting for age, sex, hypertension and diabetes in the Cox proportional hazard analysis. In subgroup analysis, diabetic patients with a baPWV >1704 cm/s had a high CV event and ischemic stroke risk. Conclusions:The results of this study show that higher baPWV was a predictive marker for CV events, especially ischemic stroke. The subgroup analysis suggests that antiplatelet therapy may be needed in diabetic patients with a high baPWV for prevention of ischemic stroke.
Vanilloid receptor VR1 is both presynaptic and postsynaptic in the superficial laminae of the rat dorsal horn

Terminals in the rat spinal cord that express the vanilloid receptor VR1 are from small and medium dorsal root ganglion (DRG) neurons and appear prominent in lamina I and inner lamina II. Because primary afferents from these neurons can be myelinated or unmyelinated and their terminals in these laminae can be of various morphological and functional types, we undertook this study to identify the type(s) of VR1‐positive afferent fibers and terminals. In the DRG, many small and medium‐sized neurons are immunopositive. Under electron microscopy, dorsal root afferents that are immunopositive for VR1 are predominantly unmyelinated. Large numbers of VR1‐positive terminals in lamina I are of the nonglomerular type and may contain dense core vesicles. VR1 immunoreactivity in terminals in lamina I is in good agreement with data on noxious, heat‐sensitive neurons in the dorsal horn. Two types of glomerular afferent terminals in lamina II also are immunopositive for VR1. In both laminae, most VR1‐positive terminals are distinct from substance P‐positive terminals. However, the immunoreactivity in lamina II also is prominent in dendrites that are contacted by primary afferent endings. Because we also observed patchy immunostaining in cell bodies in lamina II, this unexpected result may reflect synthesis of VR1 by neurons in this lamina. However, because dorsal rhizotomy abolishes VR1 staining in both laminae I and II, it is suggested that the expression and intracellular dynamics of VR1 in lamina II neurons are controlled by presynaptic input. J. Comp. Neurol. 436:225–235, 2001. © 2001 Wiley‐Liss, Inc.
Put Your Money Where Your Mouth Is: Real Commitment to Sustainability and Mere Rhetoric

Companies exhibit growing interest in sustainability. A debated issue concerns sustainability communication to stakeholders. In fact, it is difficult to understand whether companies’ commitment towards sustainability is “real”, or it only consists of “empty words” that hide opportunistic strategies. Our paper contributes to this debate proposing a methodological approach which is based on a company’s business model (BM) representation. We argue that the inclusion of adequate sustainability information in a company’s BM representation can testify to a real company’s engagement, as it illustrates how sustainability affects its value creation process. Compared to extant methodological proposals, our approach acts as an “acid test”, which helps users to kill two birds with one stone. In fact, it allows zeroing in on the core of a company’s sustainability rhetoric through the analysis of the information about its BM disclosed in the management commentary. Our approach is consistent with previous contributions that propose a company’s BM as a representation device able to illustrate strategic information that cannot be represented in the traditional corporate reporting. It also offers a possible answer to address the challenges faced by regulators and standard setters involved in the regulation of sustainability disclosure.
Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: A pooled analysis of NCCTG's phase III trials N9741 and N9841.

3571 Background: Symptoms and complications of metastatic colorectal cancer (mCRC) differ by metastatic site(s) and other factors. There is a paucity of data regarding outcomes for patients with peritoneal carcinomatosis (pcCRC) as a manifestation of mCRC derived from prospective studies. We characterized the clinical course of pcCRC pts enrolled in prospective randomized trials of chemotherapy and contrasted that with other forms of mCRC (non-pcCRC). METHODS A total of 2,095 pts enrolled in (N9741 and N9841) were evaluated. Clinical outcomes included overall survival (OS) and progression-free survival (PFS). Stratified log-rank test was used to compare OS and PFS between pcCRC and non-pcCRC pts. The impact of systemic chemotherapy was analyzed separately for 1st (N9741) and 2nd line treatment (N9841). Cox model was used to assess the adjusted associations. RESULTS pcCRC group (n=364) was similar to the non-pcCRC pts in median age (63 vs. 61 years, p=0.23), gender (57% males vs. 61%, p=0.23), performance status (ECOG PS 0-1 94% vs. 96%, p=0.06), but differed in frequency of liver (63% vs. 82%, p<.001) and lung metastases (27% vs. 34%, p=0.01). Median OS (12.7 vs. 17.6 months, hazard ratio (HR) 1.3 [95% CI 1.2-1.5]) and PFS (5.8 vs. 7.2 months, HR 1.2 ([95% CI 1.1-1.3]) were shorter for pcCRC vs. non-pcCRC. The unfavorable prognostic influence of pcCRC remained after adjusting for age, PS, liver metastases and other factors (OS: HR 1.3, p<.001; PFS: HR 1.1, p=0.05). FOLFOX was superior to IFL as a first line treatment among pcCRC (HR for OS 0.62, p=.005) and non-pcCRC pts (HR 0.66, p<0.001; Table). CONCLUSIONS pcCRC is associated with a significantly shorter OS and PFS as compared to other forms of mCRC. Trials for mCRC should consider stratiftification by pcCRC status. [Table: see text].
Money and Debt : Empirical Studies in Northern Europe 1840-2015

This dissertation firstly produces new financial series on money and bankassets which are consistent with current definitions for the UK for the crisisrich period 1840-80 and new monetary aggregates for Ireland from prefamine to independence (1840-1921). By employing the new data, cyclicaland seasonal analysis are conducted to shed light on the business cyclesand financial crises of the period. Secondly, the dissertation explores theevolution of public debt in Ireland (1950-2015) by constructing a consistentlydefined fiscal series, analysing the debt ratio dynamics and reductions of thepast and offering policy lessons for the present. The thesis finally contributesto the post crisis financial regulation debate by testing the use of privatesector debt in macroprudential regulation (as outlined in Basel III) throughconducting a regional analysis (Finland, Ireland, Sweden and the UK)covering the period 1986-2013. (Less)