Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of frontal cortex lesions on action sequence learning in the rat

To understand the role of frontal cortex in motor sequence learning we compared the effects of motor (M1), premotor (M2) and midline frontal (MFr) cortical lesions on rats making nose‐pokes guided by luminance cues. Organizational demands were manipulated by varying the number (1 vs. 5) and predictability (random vs. repeated) of nose‐pokes in a response. Learning was studied by comparing sessions with random or repeated cues. All cortical lesions increased reaction time (RT) during response initiation. These effects were larger for nose‐pokes initiating sequential responses but spared RT for nose‐pokes completing them. Repetition learning had significant effects on the speed and accuracy of single nose‐poke responses that were unaffected by any of the cortical lesions. Repetition learning had more complex effects on sequential responding. RTs increased for nose‐pokes initiating sequences over several sessions of continuous repetition and then decreased or leveled off. RTs decreased incrementally across all repetition sessions for subsequent nose‐pokes in repeated sequences, following a time‐course consistent with habit learning. Lesions involving M2 and MFr cortex exacerbated the increase in RT during initiation without affecting the incremental decrease in RT for nose‐pokes completing repeated sequences. These results were confirmed by analyses of interference effects when training shifted from repeated (learned) to random (novel) sequences or to a new repeated sequence. These results implicate dorsomedial frontal cortex in organizational aspects of sensory‐guided responding and motor sequence learning reflected in RT during response initiation.
Myofibrillar Myopathies: A Clinical and Myopathological Guide

Myofibrillar myopathies (MFMs) are histopathologically characterized by desmin‐positive protein aggregates and myofibrillar degeneration. Because of the marked phenotypic and pathomorphological variability, establishing the diagnosis of MFM can be a challenging task. While MFMs are partly caused by mutations in genes encoding for extramyofibrillar proteins (desmin, αB‐crystallin, plectin) or myofibrillar proteins (myotilin, Z‐band alternatively spliced PDZ‐containing protein, filamin C, Bcl‐2‐associated athanogene‐3, four‐and‐a‐half LIM domain 1), a large number of these diseases are caused by still unresolved gene defects. Although recent years have brought new insight into the pathogenesis of MFMs, the precise molecular pathways and sequential steps that lead from an individual gene defect to progressive muscle damage are still unclear. This review focuses on the clinical and myopathological aspects of genetically defined MFMs, and shall provide a diagnostic guide for this numerically significant group of protein aggregate myopathies.
The evolution of sexual and parthenogenetic Warramaba: a window onto Plio–Pleistocene diversification processes in an arid biome

Environmental changes over the Plio‐Pleistocene have been key drivers of speciation patterns and genetic diversification in high‐latitude and mesic environments, yet comparatively little is known about the evolutionary history of species in arid environments. We applied phylogenetic and phylogeographic analyses to understand the evolutionary history of Warramaba grasshoppers from the Australian arid zone, a group including sexual and parthenogenetic lineages. Sequence data (mitochondrial COI) showed that the four major sexual lineages within Warramaba most likely diverged in the Pliocene, around 2–7 million years ago. All sexual lineages exhibited considerable phylogenetic structure. Detailed analyses of the hybrid parthenogenetic species W. virgo and its sexual progenitors showed a pattern of high phylogenetic diversity and phylogeographic structure in northern lineages, and low diversity and evidence for recent expansion in southern lineages. Northern sexual lineages persisted in localized refugia over the Pleistocene, with sustained barriers promoting divergence over this period. Southern parts of the present range became periodically unsuitable during the Pleistocene, and it is into this region that parthenogenetic lineages have expanded. Our results strongly parallel those for sexual and parthenogenetic lineages of the gecko Heteronotia from the same region, indicating a highly general effect of Plio‐Pleistocene environmental change on diversification processes in arid Australia.
UvA-DARE ( Digital Academic Repository ) Surgical patient safety : analysis and interventions

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First interim analysis of the GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) non‐interventional study

Aims: Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON), a global, non‐interventional, surveillance study, aims to evaluate the safety of sorafenib in all patients with unresectable hepatocellular carcinoma (uHCC) under real‐life practice conditions, particularly Child‐Pugh B patients, who were not well represented in clinical trials.
Fc Receptor-Mediated Immunity Against Bordetella pertussis1

The relevance of specific Abs for the induction of cellular effector functions against Bordetella pertussis was studied. IgG-opsonized B. pertussis was efficiently phagocytosed by human polymorphonuclear leukocytes (PMN). This process was mediated by the PMN IgG receptors, FcγRIIa (CD32) and FcγRIIIb (CD16), working synergistically. Furthermore, these FcγR triggered efficient PMN respiratory burst activity and mediated transfer of B. pertussis to lysosomal compartments, ultimately resulting in reduced bacterial viability. Bacteria opsonized with IgA triggered similar PMN activation via FcαR (CD89). Simultaneous engagement of FcαRI and FcγR by B. pertussis resulted in increased phagocytosis rates, compared with responses induced by either isotype alone. These data provide new insights into host immune mechanisms against B. pertussis and document a crucial role for Ig-FcR interactions in immunity to this human pathogen.
Simulations of the Temperature Dependence of the Charge Transfer Inefficiency in a High-Speed CCD

Results of detailed simulations of the charge transfer inefficiency of a prototype serial readout CCD chip are reported. The effect of radiation damage on the chip operating in a particle detector at high frequency at a future accelerator is studied, specifically the creation of two electron trap levels, 0.17 eV and 0.44 eV below the bottom of the conduction band. Good agreement is found between simulations using the ISE-TCAD DESSIS program and an analytical model for the former level but not for the latter. Optimum operation is predicted to be at about 250 K where the effects of the traps is minimal; this being approximately independent of readout frequency in the range 7-50 MHz. This work has been carried out within the Linear Collider Flavour Identification (LCFI) collaboration in the context of the International Linear Collider (ILC) project.
Altered microRNA expression profile in human pituitary GH adenomas: down-regulation of miRNA targeting HMGA1, HMGA2, and E2F1.

CONTEXT MicroRNA (miRNA) are an important class of regulators of gene expression. Altered miRNA expression has been constantly found in human neoplasias and plays an important role in the process of carcinogenesis. OBJECTIVE The aim of this study was to identify specific miRNA whose expression is altered in GH-secreting pituitary adenomas. DESIGN Using a miRNACHIP microarray, we have analyzed the miRNA expression profile of human GH adenomas vs. normal pituitary gland. RESULTS We report the identification of a set of miRNA, including miR-34b, miR-326, miR-432, miR-548c-3p, miR-570, and miR-603, drastically and constantly down-regulated in GH adenomas. We demonstrate that these miRNA target genes such as high-mobility group A1 (HMGA1), HMGA2, and E2F1, whose overexpression and/or activation plays a critical role in pituitary tumorigenesis. We also show that the enforced expression of the down-regulated miRNA has a negative role on the growth regulation of pituitary adenoma cells. Finally, an inverse correlation is found between the expression of these miRNA and HMGA1 and HMGA2 protein levels in GH adenomas. CONCLUSION Our study identifies a specific subset of miRNA, whose down-regulation might contribute to pituitary tumorigenesis.
Concordance of breast imaging reporting and data system assessments and management recommendations in screening mammography.

PURPOSE To examine how frequently Breast Imaging Reporting and Data System (BI-RADS) mammographic screening assessments were associated with expected clinical management recommendations. MATERIALS AND METHODS Seven Breast Cancer Surveillance Consortium mammography registries recorded screening assessments and recommendations in 1997 to identify the proportion of women in each BI-RADS category. The first screening assessment for a woman without cancer or a prior mammogram within 9 months was associated with its independently recorded recommendation. RESULTS Among 292,795 women, screening assessments included 269,022 (91.9%) with a "negative" or "benign finding," and 267,103 (99.3%) of these women were recommended for normal interval follow-up. Among 11,861 (4.1%) women with screening assessments of "probably benign finding," 4,782 (40.3%) were recommended for short interval follow-up as expected on the basis of the BI-RADS, but a high proportion (36.9%) were recommended for additional imaging. Among 1,625 (0.6%) women with "suspicious abnormality," most were recommended for biopsy (48.7%) or clinical examination and/or surgical consult (9.0%), but many were recommended for additional imaging (38.7%). Among 243 (0.1%) women with screening assessments "highly suggestive of malignancy," a majority were recommended for biopsy (73.3%) or clinical examination and/or surgical consult (18.1%) consistent with BI-RADS, but some were recommended for additional imaging (6.6%). CONCLUSION BI-RADS assessments and management recommendations are consistent for negative and benign assessments, but inconsistencies were found in assessments and recommendations for mammographic abnormalities.
The Epidemiology of Perinatal Mortality in Multiple Births

The epidemiology of perinatal mortality in multiple pregnancies was investigated from data on 16,831 multiple births from New York City's computerized vital records for 1978-1984. Twins had a sixfold higher rate of neonatal death and a threefold higher rate of fetal death during labor than had singleton infants. Much of this excess mortality can be explained by the lower birthweight distribution in twins: between 1,001 and 2,500 grams twins had birthweight-specific death rates equivalent to or substantially less than singletons. However, in infants of normal birthweights, twins had more than three times the mortality risk of singletons. For twins in vertex presentation between 1,001 and 3,000 grams, cesarean section did not appreciably reduce neonatal mortality risk. For twins in vertex presentation who weighted more than 3,000 grams the neonatal mortality rate was more than four times higher in vaginal deliveries than in cesarean sections (exact p = 0.034). Efforts to prevent intrapartum and neonatal mortality in multiple births should aim at reducing the incidence of low birthweight twins. More research is needed on the etiology of perinatal problems in normal birthweight twins (greater than or equal to 2,501 grams), especially on the effects of different modes of delivery.
State Bankruptcy Law and Entrepreneurship: Evidence from a Border Analysis

This paper examines how differences in state bankruptcy laws, specifically the amount of the homestead exemption, affect business location decisions. We expand upon the literature by narrowing the geographic scope and focus on the amount of entrepreneurial activity within a few miles of the state boundary. By including only these border areas, we are more effectively able to control for unobserved local attributes, which are important determinants of business location decisions. Findings indicate that an increase in a state's homestead exemption attracts new businesses to that locality. In addition, we do not find that a more generous homestead exemption has a negative impact on existing businesses. Our results suggest that bankruptcy law is an important policy tool that state governments can use to attract new businesses, without experiencing an adverse effect on existing enterprises.
Distinguishing fibrovascular septa from vasculogenic mimicry patterns.

CONTEXT Molecular analyses indicate that periodic acid-Schiff (PAS)-positive (laminin-rich) patterns in melanomas are generated by invasive tumor cells by vasculogenic mimicry. Some observers, however, consider these patterns to be fibrovascular septa, generated by a stromal host response. OBJECTIVE To delineate differences between vasculogenic mimicry patterns and fibrovascular septa in primary uveal melanomas. DESIGN Frequency distributions, associations with outcome, and thicknesses of trichrome-positive and PAS-positive looping patterns were determined in 234 primary uveal melanomas. Sequential sections of 13 additional primary uveal melanomas that contained PAS-positive/trichrome-negative looping patterns were stained for type I and type IV collagens, laminin, and fibronectin. Real-time quantitative polymerase chain reaction was performed on RNA from cultured uveal melanoma cells for the expression of COL1A1, COL4A2, and fibronectin. RESULTS Trichrome-positive loops were encountered less frequently than PAS-positive loops (10% vs 56%, respectively). Death from metastatic melanoma was strongly associated with PAS-positive (P < .001) but not with trichrome-positive (P = .57) loops. Trichrome-positive loops were significantly thicker than PAS-positive loops (P < .001). The PAS-positive patterns stained positive for laminin, type I and type IV collagens, and fibronectin. Type I collagen was detected within melanoma cells and focally within some PAS-positive patterns. Real-time quantitative polymerase chain reaction revealed 3-fold, 25-fold, and 97-fold increases, respectively, in expression of COL4A2, fibronectin, and COL1A1 by invasive pattern-forming primary melanoma cells compared with poorly invasive non-pattern-forming cells. CONCLUSIONS Fibrovascular septa are rare and prognostically insignificant in uveal melanomas, whereas vasculogenic mimicry patterns are associated with increased mortality. Type I collagen, seen focally in some vasculogenic mimicry patterns, may be synthesized by tumor cells, independent of a host stromal response.
Consumer Attitudes towards Vegetable Attributes: Potential Buyers of Pesticide-Free Vegetables in Accra and Kumasi, Ghana

Considering the inappropriate use of synthetic pesticides on vegetables in West Africa, the rationale behind this research was to assess the extent to which consumers can function as demanders of risk reduced vegetables and hence act as innovators towards vegetable safety. Using the cases of Kumasi and Accra in Ghana, the study examined possible consumer responses to product certification that communicates freedom from pesticides (e.g., organic certification). Generally, search attributes such as the fresh and healthy appearance of a vegetable were found to be central to consumer choice. While consumers stress the importance of health value, they are mostly unaware of agro-chemical risks related to vegetable consumption.
Temperature and population density: interactional effects of environmental factors on phenotypic plasticity, immune defenses, and disease resistance in an insect pest

Abstract Temperature and crowding are key environmental factors mediating the transmission and epizooty of infectious disease in ectotherm animals. The host physiology may be altered in a temperature‐dependent manner and thus affects the pathogen development and course of diseases within an individual and host population, or the transmission rates (or infectivity) of pathogens shift linearly with the host population density. To our understanding, the knowledge of interactive and synergistic effects of temperature and population density on the host–pathogen system is limited. Here, we tested the interactional effects of these environmental factors on phenotypic plasticity, immune defenses, and disease resistance in the velvetbean caterpillar Anticarsia gemmatalis. Upon egg hatching, caterpillars were reared in thermostat‐controlled chambers in a 2 × 4 factorial design: density (1 or 8 caterpillars/pot) and temperature (20, 24, 28, or 32°C). Of the immune defenses assessed, encapsulation response was directly affected by none of the environmental factors; capsule melanization increased with temperature in both lone‐ and group‐reared caterpillars, although the lone‐reared ones presented the most evident response, and hemocyte numbers decreased with temperature regardless of the population density. Temperature, but not population density, affected considerably the time from inoculation to death of velvetbean caterpillar. Thus, velvetbean caterpillars succumbed to Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) more quickly at higher temperatures than at lower temperatures. As hypothesized, temperature likely affected caterpillars' movement rates, and thus the contact between conspecifics, which in turn affected the phenotypic expression of group‐reared caterpillars. Our results suggest that environmental factors, mainly temperature, strongly affect both the course of disease in velvetbean caterpillar population and its defenses against pathogens. As a soybean pest, velvetbean caterpillar may increase its damage on soybean fields under a scenario of global warming as caterpillars may reach the developmental resistance faster, and thus decrease their susceptibility to biological control by AgMNPV.
Frequency of medication errors in primary care patients with polypharmacy.

BACKGROUND Chronic diseases affect more than half of the population ≥75 years of age in developed countries. Prescription medication use increases with age. Depending on definition, 25-80% of elderly are exposed to polypharmacy. Polypharmacy increases the risk of hospitalization, interactions and adverse drug reactions. OBJECTIVE To examine the frequency of medication errors in patients with polypharmacy treated in general practice. METHODS The medications of 169 patients with polypharmacy treated in 22 GP surgeries in Austria were analysed. The analysis identified (i) medication errors, including non-evidence-based medications, dosing errors and potentially dangerous interactions in all patients and (ii) potentially inappropriate medications (PIMs) in the subgroup of elderly patients (≥65 years). RESULTS The patients took on average 9.1±3.0 medications per day. The maximum, in one patient, was 20 medications per day. Some 93.5% had at least one non-evidence-based medication. On average, 2.7±1.66 medications per patient were found to be not indicated. At least one dosing error was found in 56.2% of all patients. One potential interaction of the most severe degree (category X interaction) was detected in 1.8% (n = 3) and two such interactions in 0.6% (n = 1). These combinations should have been avoided. Of the 169 patients, 158 were elderly (≥65 years). Of these seniors, 37.3% (n = 59) had at least one PIM according to the PRISCUS list for the elderly. CONCLUSION The frequency of medication errors is high in patients with polypharmacy in primary care. Development of strategies (e.g. external medication review) is required to counteract medication errors.
[Methylation status of PCDH10 and RASSF1A gene promoters in colorectal cancer].

OBJECTIVE To investigate the methylation status of promoters of protocadherin-10 (PCDH10) and Ras-association domain family 1A (RASSF1A) genes in colorectal cancer (CRC), and to study its relationship with development and progress of CRC. METHODS Tumor tissues were collected from 75 CRC patients who received surgical treatment in the Affiliated Hospital of Guizhou Medical University in the period from 2007 to 2010. Methylation-specific polymerase chain reaction (MSP) was applied to detect the methylation status of PCDH10 and RASSF1A gene promoters in CRC and adjacent normal colorectal mucosa. The relationship between methylation of PCDH10 and RASSF1A and clinicopathological features of CRC was analyzed using chi-squared test. RESULTS The rate of PCDH10 methylation in CRC tissue was significantly higher than that in colorectal normal mucosa (58.7%(44/75)vs 22.7%(17/75), P<0.01). There was no significantly correlation between methylation of PCDH10 and patients' age, gender, tumor site, Dukes stage, and lymph node metastasis(all P>0.05). The rate of RASSF1A methylation in CRC tissue was significantly higher than that in colorectal normal mucosa (64.6%(42/65)vs 15.4%(10/65), P<0.01). There was no significantly correlation between methylation of RASSF1A and patients' age, gender, and tumor site (all P>0.05), but the patients in high Dukes stages and with lymph node metastasis had higher RASSF1A methylation rate(92.9%(26/28)vs 43.2%(16/37), 92.9%(26/28)vs 43.2%(16/37), both P<0.05). CONCLUSIONS CRC tissues demonstrate high level of methylation of PCDH10 and RASSF1A genes, which may play a crucial role in the pathogenesis of CRC. The aberrant hypermethylation of RASSF1A gene is observed in more advanced CRC, suggesting that the RASSF1A gene methylation may be related to progression of CRC.
Value of renal biopsy in the prognosis of liver transplantation in familial amyloid polyneuropathy ATTR Val30Met patients

Liver transplantation for familial amyloid polyneuropathy (FAP) patients has been carried out worldwide and the outcomes seem to be promising. To clarify the severity of amyloid deposits on visceral organs, we evaluated the histopathological findings of biopsied renal and sural nerve specimens in 13 FAP patients with ATTR Val30Met by quantitative analysis, and compared them with the outcome of transplantation. Renal dysfunction with proteinuria seemed to correlate with the degree of amyloid deposits in glomeruli, not with that in medullary tissues. The severity of renal amyloid deposition did not consistently parallel that of myelinated nerve fiber loss in sural nerve. Three patients with proteinuria and severe amyloid deposits in glomeruli were considered to be unsuitable for transplantation. Ten patients underwent living donor liver transplantation and three resulted in unfavorable outcomes. These three had heavy amyloid deposits on renal tissues, especially in glomerular areas, but the severity of myelinated nerve fiber loss in their sural nerves was very similar to that in patients who made a good recovery. The prognosis after operation might be closely related to the severity of amyloid deposits in renal glomeruli. Renal biopsy is, therefore, recommended when determining the indications and contraindications for liver transplantation in FAP patients, although this biopsy is not routinely required.