Miracle-dz/UniFAR-FTUs huggingface dataset:
Cortical connections to single digit representations in area 3b of somatosensory cortex in squirrel monkeys and prosimian galagos

The ventral posterior nucleus of thalamus sends highly segregated inputs into each digit representation in area 3b of primary somatosensory cortex. However, the spatial organization of the connections that link digit representations of areas 3b with other somatosensory areas is less understood. Here we examined the cortical inputs to individual digit representations of area 3b in four squirrel monkeys and one prosimian galago. Retrograde tracers were injected into neurophysiologically defined representations of individual digits of area 3b. Cortical tissues were cut parallel to the surface in some cases and showed that feedback projections to individual digits overlapped extensively in the hand representations of areas 3b, 1, and parietal ventral (PV) and second somatosensory (S2) areas. Other regions with overlapping populations of labeled cells included area 3a and primary motor cortex (M1). The results were confirmed in other cases in which the cortical tissues were cut in the coronal plane. The same cases also showed that cells were primarily labeled in the infragranular and supragranular layers. Thus, feedback projections to individual digit representations in area 3b mainly originate from multiple digits and other portions of hand representations of areas 3b, 1, PV, and S2. This organization is in stark contrast to the segregated thalamocortical inputs, which originate in single digit representations and terminate in the matching digit representation in the cortex. The organization of feedback connections could provide a substrate for the integration of information across the representations of adjacent digits in area 3b. J. Comp. Neurol. 521:3768–3790, 2013. © 2013 Wiley Periodicals, Inc.
Diabetes and endometrial cancer: An Italian case‐control study

We considered the association between diabetes and risk of endometrial cancer using data from a large case‐control study conducted in Italy. Cases were 752 women with incident, histologically confirmed endometrial cancer <75 years of age (median age 60 years, range 28–74) admitted to a network of hospitals in Milan. Controls were 2,606 patients (median age 54 years, range 25–74) aged <75 years, admitted for acute non‐neoplastic, non‐gynecological, non‐hormone‐related conditions to the same network of hospitals where cases had been identified. A total of 132 (17.6%) cases and 116 controls (4.5%) reported a history of diabetes. The corresponding multivariate odds ratio (OR) was 2.9 [95% confidence interval (CI) 2.2–3.9]. No association emerged with diabetes diagnosed under age 40 (likely to be insulin‐dependent diabetes), whereas the OR of endometrial cancer was 3.1 (95% CI 2.3–4.2) for diabetes diagnosed at age ≥40 years. The OR of endometrial cancer in women with history of diabetes was 3.0 for women with a body mass index (BMI) (QI) kg/m2 <25, 3.6 for those with a BMI of 25–29, and 3.3 for those with a BMI ≥30. No consistent interaction or modifying effect was observed for any other covariate. Our results confirm that non‐insulin‐dependent diabetes is associated with the risk of endometrial cancer. The association may be mediated through elevated oestrogen levels in diabetic women, hyperinsulinemia or insulin‐like growth factor‐I (IGF‐I). Int. J. Cancer 81:539–542, 1999. © 1999 Wiley‐Liss, Inc.
Comparison of the adjuvanticity of two different delivery systems on the induction of humoral and cellular responses to synthetic peptides

The aim of this work was to test, evaluate, and compare the immunogenicity of the S3 malarial short synthetic model peptide in Balb/c mice when it was delivered with different adjuvants. Specifically, it studied the adjuvanticity of two different particulate delivery systems, human compatible Montanide® ISA 720 w/o emulsion and poly-lactide-co-glycolide acid microparticles, in terms of the enhancement and sub-set type of the immune response elicited following immunization. Aditionally, conventional aluminum hydroxide gel adjuvant was included as a reference. Aluminum adjuvant failed to improve the lack of immunogenicity of this antigenic peptide on its own. On the other hand, Montanide and microparticles given subcutaneously resulted in effective adjuvants and revealed mixed Th1/Th2 immune responses, with moderate antibody and lymphoproliferative responses, and higher IFN-γ secretion for Montanide. Hence, microparticles administered intradermally (not possible with Montanide) elicited superior and potent antibody levels, including higher cytophilic isotype (IgG2a), and the greatest limphoproliferation and IFN-γ levels. The results here presented support the capability and suitability of microparticle delivery systems to reach the adequate adjuvanticity necessary for future malaria vaccine development.
Neuroticism's prospective association with mental disorders halves after adjustment for baseline symptoms and psychiatric history, but the adjusted association hardly decays with time: a meta-analysis on 59 longitudinal/prospective studies with 443 313 participants

Background This meta-analysis seeks to quantify the prospective association between neuroticism and the common mental disorders (CMDs, including anxiety, depression, and substance abuse) as well as thought disorders (psychosis/schizophrenia) and non-specific mental distress. Data on the degree of confounding of the prospective association of neuroticism by baseline symptoms and psychiatric history, and the rate of decay of neuroticism's effect over time, can inform theories about the structure of psychopathology and role of neuroticism, in particular the vulnerability theory. Method This meta-analysis included 59 longitudinal/prospective studies with 443 313 participants. Results The results showed large unadjusted prospective associations between neuroticism and symptoms/diagnosis of anxiety, depression, and non-specific mental distress (d = 0.50–0.70). Adjustment for baseline symptoms and psychiatric history reduced the associations by half (d = 0.10–0.40). Unadjusted prospective associations for substance abuse and thought disorders/symptoms were considerably weaker (d = 0.03–0.20), but were not attenuated by adjustment for baseline problems. Unadjusted prospective associations were four times larger over short (<4 year) than long (⩾4 years) follow-up intervals, suggesting a substantial decay of the association with increasing time intervals. Adjusted effects, however, were only slightly larger over short v. long time intervals. This indicates that confounding by baseline symptoms and psychiatric history masks the long-term stability of the neuroticism vulnerability effect. Conclusion High neuroticism indexes a risk constellation that exists prior to the development and onset of any CMD. The adjusted prospective neuroticism effect remains robust and hardly decays with time. Our results underscore the need to focus on the mechanisms underlying this prospective association.
An antigen fragment encompassing the AD2 domains of glycoprotein B from two different strains is sufficient for differentiation of primary vs. recurrent human cytomegalovirus infection by ELISA

Primary human cytomegalovirus (HCMV) infection during pregnancy is a frequent cause of fatal damage in populations with low prevalence of HCMV. Differentiation of primary vs. recurrent HCMV infection is an important issue in prenatal counseling. Antibodies specific for viral glycoproteins become detectable only with considerable delay with relation to HCMV infection or IgG seroconversion. Thus, lack of glycoprotein specific (gp‐specific) antibodies can serve as a convenient indicator to identify those pregnant women that bear an elevated risk for HCMV transplacental transmission and fetal sequelae. In the opposite case, presence of gp‐specific antibodies virtually excludes HCMV primary infection several weeks before sampling. However, no standardized screening assay for HCMV gp‐specific antibodies had been available thus far. For this reason, an ELISA based on procaryotically expressed fragments of HCMV glycoprotein B (gB; gpUL55) was developed. Small fragments of gB from two different laboratory strains, encompassing the antigenic domain 2 (AD2) sufficed for sensitive and specific detection of gp‐specific antibodies. The gB‐ELISA titers correlated with titers of virus neutralizing antibodies in serum samples from primary or recurrent HCMV infections. Seroconversion kinetics of the gB‐ELISA in samples from patients with primary HCMV infection closely paralleled the delay in seroconversion of gp‐specific antibodies as determined by neutralization assay. Thus this assay provides a diagnostic tool that is easy to perform and can significantly add to available methods for the timely identification of primary HCMV infection during pregnancy. In addition, the gB‐ELISA may be helpful in other clinical settings for the differentiation of primary HCMV infection from diseases caused by other pathogens. J. Med. Virol. 65:719–729, 2001. © 2001 Wiley‐Liss, Inc.
[Ocular surface squamous neoplasia: analysis of 34 cases].

PURPOSE To evaluate location, treatment and clinical course in cases of ocular surface squamous neoplasia (OSSN). METHODS Thirty-four cases with OSSN [conjunctival intraepithelial neoplasia (CIN) 17 cases; squamous cell carcinoma (SCC) 17 cases] treated in Kyushu University hospital from 2000 to 2011 were retrospectively studied. RESULT Lesions of CIN were observed in the conjunctiva bulbar in sixteen cases (16/17), and in eleven of those, the lesions were seen in the nasal part (nasal : lateral = 11 : 6). The lesions of eight SCC cases (8/17) were observed in the conjunctiva bulbar, of seven cases (7/17) were observed in the conjunctiva palpebral, and of two cases (2/17) in the fornical conjunctiva. Significantly far more cases of SCC in the conjunctiva bulbar were seen in the nasal part compared to the lateral part (nasal : lateral = 7 : 1). Most SCC lesions in the conjunctiva palpebral and fornix were observed in the upper eyelid (upper : lower = 6 : 3). CIN were treated by excision in nine cases (9/17), excision after topical chemotherapy in three cases (3/ 17), and topical chemotherapy in 5 cases (5/17). Nine SCC patients were treated by excision (9/17), four by excision after topical chemotherapy (4/17), and four by radiotherapy (4/17). Three cases of CIN and one case of SCC had recurrence and needed further treatment. CONCLUSION The use of preoperative chemotherapy and radiotherapy for OSSN patients seems useful for a good outcome.
Genetic Profile of an Oka Varicella Vaccine Virus Variant Isolated from an Infant with Zoster

ABSTRACT Varicella virus vaccine strain Oka (V-Oka) has in rare cases caused zoster in vaccinated people. Despite broad usage of V-Oka, little is known about varicella-zoster virus genomic sequence variation of strains in vaccine and isolates from patients with vaccine adverse events. Direct sequencing of 20 regions of V-Oka-GSK was compared to the sequences of the original V-Oka-Biken, GlaxoSmithKline Oka vaccine (V-Oka-GSK), and Oka-parental (P-Oka) strains. We analyzed single nucleotide polymorphisms (SNP) differentiating the Oka parental and Oka vaccine strains identified in open reading frames (ORFs) 6, 9A, 10, 21, 31, 39, 50, 51, 52, 54, 55, and 59 and eight base substitutions within ORF 62. Sixteen of these SNP impose an amino acid change in the corresponding gene product. The genotypic analysis revealed that (i) both V-Oka-GSK and V-Oka-Biken comprise mixtures of strains represented in variable proportion from lot to lot; (ii) V-Oka-GSK/zoster isolated from the zoster patient had six wild-type SNP in ORF 9A, 10, 21, 52, 55, and 62 (mutation 108838); (iii) none of the six revertant SNP would reliably discriminate Oka vaccine from the wild type; and (iv) the genomic variation found in V-Oka/zoster might be associated with changes in the biological behavior of the virus. Further studies will be needed to identify potential virulence factors in variant vaccine strains.
Wired: impacts of increasing power line use by a growing bird population

Power lines are increasingly widespread across many regions of the planet. Although these linear infrastructures are known for their negative impacts on bird populations, through collision and electrocution, some species take advantage of electricity pylons for nesting. In this case, estimation of the net impact of these infrastructures at the population level requires an assessment of trade-offs between positive and negative impacts. We compiled historical information (1958–2014) of the Portuguese white stork Ciconia ciconia population to analyze long-term changes in numbers, distribution range and use of nesting structures. White stork population size increased 660% up to 12000 breeding pairs between 1984 and 2014. In the same period, the proportion of nests on electricity pylons increased from 1% to 25%, likely facilitated by the 60% increase in the length of the very high tension power line grid (holding the majority of the nests) in the stork’s distribution range. No differences in breeding success were registered for storks nesting on electricity pylons versus other structures, but a high risk of mortality by collision and electrocution with power lines was estimated. We discuss the implications of this behavioral change, and of the management responses by power line companies, both for stork populations and for managers.
Closed Testing in Pharmaceutical Research: Historical and Recent Developments

In pharmaceutical research, making multiple statistical inferences is standard practice. Unless adjustments are made for multiple testing, the probability of making erroneous determinations of significance increases with the number of inferences. Closed testing is a flexible and easily explained approach to controlling the overall error rate that has seen wide use in pharmaceutical research, particularly in clinical trials settings. In this article, we first give a general review of the uses of multiple testing in pharmaceutical research, with particular emphasis on the benefits and pitfalls of closed testing procedures. We then provide a more technical examination of a class of closed tests that use additive-combination-based and minimum-based p-value statistics, both of which are commonly used in pharmaceutical research. We show that, while the additive combination tests are generally far superior to minimum p-value tests for composite hypotheses, the reverse is true for multiple comparisons using closure-based testing. The loss of power of additive combination tests is explained in terms worst-case “hurdles” that must be cleared before significance can be determined via closed testing. We prove mathematically that this problem can result in the power of a closure-based minimum p-value test approaching 1, while the power of a closure-based additive combination test approaches 0. Finally, implications of these results to pharmaceutical researchers are given.
Chamber-Dependent Expression of Brain Natriuretic Peptide and Its mRNA in Normal and Diabetic Pig Heart

Brain natriuretic peptide (BNP) is produced in cardiac myocytes, and increased secretion is closely associated with cardiac dysfunction. However, several fundamental aspects of BNP expression in the myocardium have not yet been resolved. In the present study, we report the presence of a precursor BNP mRNA transcript and a mature BNP mRNA transcript in normal porcine hearts. In normal pigs, the amount of precursor BNP mRNA was similar in atrial and ventricular myocardium, whereas the mature BNP transcript was 10- to 50-fold more abundant in atrial than in ventricular myocardium. Quantitation of proBNP in normal porcine hearts by radioimmunoassay disclosed abundant proBNP in the atria, whereas proBNP was undetectable in the ventricles. Laser confocal microscopy revealed proBNP in secretory granules of atrial but not in the ventricular myocardium of normal pigs. Mild streptozotocin-induced diabetes doubled the expression of BNP mRNA in porcine atrial myocardium (P =0.03), but was without effect on BNP mRNA in the ventricular myocardium. The data suggest that BNP mRNA processing and proBNP storage differ between the atrial and ventricular myocardium. The results also imply that diabetes increases cardiac BNP expression in a chamber-dependent manner.
Does migration promote industrial development in Africa

This paper examines the effect of international migration on industrial development in Africa. Econometric estimations are implemented on a panel of 45 African countries over the period 1980-2010 using the generalized method of moment estimators and the migration dataset constructed by BrA¼cker, Capuano and Marfouk in 2013. Our results suggest that on average, emigration affects industrial development in Africa positively and significantly during the period of interest. Both low-skilled and medium-skilled emigrants affect more industrial development. The results also reveal that international financial flows, business networks and scientific networks are the channels through which migration affects industrial development. African countries may benefit more from international migration by developing institutions that facilitate international financial flows, business networks and scientific networks.
The Sensitivity of Microscopy and PCR-Based Detection Methods Affecting Estimates of Prevalence of Blood Parasites in Birds

Abstract Inferences about the evolution of host-parasitic relationships are often made based on the prevalence of avian malaria, which is usually estimated in a large sample of birds using either microscopic or molecular screening of blood samples. However, different techniques often have variable accuracy; thus, screening methodology can raise issues about statistical bias if method sensitivity varies systematically across parasites or hosts. To examine this possibility, published information was collected on the prevalence of species in 4 genera of avian blood parasites (Plasmodium, Haemoproteus, Leucocytozoon, and Trypanosoma) from various sources that used different tools. The data were tested to determine if the application of different methods provided different estimates for the same hosts. In these comparisons between the main methodologies, the PCR-based molecular methods were generally found to provide higher estimates for Plasmodium spp. prevalence than microscopic tools, while there was no significant tendency for such a trend in species of Haemoproteus and Leucocytozoon. When analyzing intraspecific variance of prevalence within molecular studies, some studies provided consistently higher estimates for Haemoproteus spp. prevalence than others, indicating that differences between studies can affect detected estimates. Within microscopic studies, surveys that examined more microscopic fields were more likely to report higher prevalence for Plasmodium spp. than those relying on fewer microscopic fields. Consequently, studies making comparisons across parasite genera and/or host species from different sources need to consider several types of bias originating from variation in method sensitivity.
Multidrug resistance mechanisms: drug efflux across two membranes

A set of multidrug efflux systems enables Gram‐negative bacteria to survive in a hostile environment. This review focuses on the structural features and the mechanism of major efflux pumps of Gram‐negative bacteria, which expel from the cells a remarkably broad range of antimicrobial compounds and produce the characteristic intrinsic resistance of these bacteria to antibiotics, detergents, dyes and organic solvents. Each efflux pump consists of three components: the inner membrane transporter, the outer membrane channel and the periplasmic lipoprotein. Similar to the multidrug transporters from eukaryotic cells and Gram‐positive bacteria, the inner membrane transporters from Gram‐negative bacteria recognize and expel their substrates often from within the phospholipid bilayer. This efflux occurs without drug accumulation in the periplasm, implying that substrates are pumped out across the two membranes directly into the medium. Recent data suggest that the molecular mechanism of the drug extrusion across a two‐membrane envelope of Gram‐negative bacteria may involve the formation of the membrane adhesion sites between the inner and the outer membranes. The periplasmic components of these pumps are proposed to cause a close membrane apposition as the complexes are assembled for the transport.
Let's be professional about this: ideology and the psychological contracts of registered nurses.

AIMS This study explores whether there is evidence of an ideological component in the psychological contracts of professional employees, as well as evidence of credible supporting commitments by their employer. BACKGROUND Fundamental changes in the employment context have prompted many individuals to seek a closer alignment between themselves and their work, as well as with the organizational and broader societal contexts. For many professional employees identification with their professional ideology is a significant factor in producing such an alignment. METHOD The study uses an exploratory qualitative approach to analyse interview data collected from a sample of registered nurses employed in an Australian public hospital. RESULTS The analysis identifies psychological contract terms best understood by reference to an ideological currency. It also suggests that the organization is perceived as obligated to provide credible support for that professional contribution, and the perceived lack of such support has significant impacts. CONCLUSIONS The findings raise doubts about the utility of the concept of a psychological contract that recognizes only economic and socio-emotional exchanges for understanding the psychological contracts of professional employees.
Evaluating drug resistance in visceral leishmaniasis: the challenges

SUMMARY For decades antimonials were the drugs of choice for the treatment of visceral leishmaniasis (VL), but the recent emergence of resistance has made them redundant as first-line therapy in the endemic VL region in the Indian subcontinent. The application of other drugs has been limited due to adverse effects, perceived high cost, need for parenteral administration and increasing rate of treatment failures. Liposomal amphotericin B (AmB) and miltefosine (MIL) have been positioned as the effective first-line treatments; however, the number of monotherapy MIL-failures has increased after a decade of use. Since no validated molecular resistance markers are yet available, monitoring and surveillance of changes in drug sensitivity and resistance still depends on standard phenotypic in vitro promastigote or amastigote susceptibility assays. Clinical isolates displaying defined MIL- or AmB-resistance are still fairly scarce and fundamental and applied research on resistance mechanisms and dynamics remains largely dependent on laboratory-generated drug resistant strains. This review addresses the various challenges associated with drug susceptibility and -resistance monitoring in VL, with particular emphasis on the choice of strains, susceptibility model selection and standardization of procedures with specific read-out parameters and well-defined threshold criteria. The latter are essential to support surveillance systems and safeguard the limited number of currently available antileishmanial drugs.