Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatitis C virus infection: opportunities for an earlier detection in primary care

Background/aim In the era of direct-acting antiviral medications, which can cure the hepatitis C virus (HCV) infection, the actual epidemiology of this condition in the general population is still unclear. We therefore aimed to estimate the prevalence rate of HCV and assess the determinants for incident cases of HCV in primary care in Italy. Methods We identified outpatients aged at least 15 years registered in the Italian Health Search IMS Health Longitudinal Patient Database from 1 January 2002 to 30 June 2013. The annual trend of HCV prevalence was estimated. The candidate determinants for the risk of incident HCV infection included geographical area of residence, sex, age, infections by the HIV, hepatitis B virus (HBV), or other forms of hepatitis, and abuse of illicit substances or drugs. Results The eligible cohort included 826 300 patients (53.5% women, mean age 48.1±19.1 years). The prevalence rate of HCV increased over the 11-year study period, ranging from 0.24 to 0.50%, with a small increase in men versus women. Patients aged more than 24 years had a higher risk than those aged 14–24 years, with up to a five-fold increase among patients aged 65–74 years. Being resident of Southern/Islands Italy, concurrent diagnosis HBV or HIV, and drug or illicit substance abuse were significant determinants for HCV infection. Conclusion Our study shows that the prevalence of HCV in Italy has doubled over the last decade. Patients with certain demographics and clinical characteristics are more prone to be infected by HCV. In this scenario, general practitioners may play a crucial role in screening, early identification, and therapy of high-risk patients.
Rescripting a Troubled Past: John Brown's Family and the Harpers Ferry Conspiracy

The John Brown family was unique among famous nineteenth-century American families: it owed its public reputation largely to a single dramatic civil disturbance the Harpers Ferry crisis. That desperate effort to free the slaves cost the lives of John's sons Watson and Oliver and nearly that of their half brother, Owen, who escaped Virginia's justice. John Brown's raid, his trial, and his execution on December 2, 1859, gave his wife and children a notoriety reborn with each new tale of the Old Man's fanaticism and daring. ' But the Browns remained in the public eye only as witnesses to his deeds, defenders of his cause, and bearers of his legacy. None ofJohn Brown's eight-surviving children or his score of grandchildren gained public attention in his or her own right. Unlike such celebrated American families as the Adamses, Byrds, Harrimans, Roosevelts, and Winthrops, the Browns could boast neither wealth nor learning nor conspicuous careers, apart from the brief tenure ofJohn himself as a guerrilla leader. And whereas the histories of other wellknown families begin with the success stories of the founders, the Browns' fame was rooted in spectacular failure. In a profound sense, the family was born anew in the heroic gesture that ended with the hanging of its founder. It is not the family's modest achievements, but its rebirtha remarkable mutation of consciousnessthat commends Brown's heirs to our attention. That transformation emerged gradually in their long struggle to come to terms with the troubled legacy of Harpers Ferry. It set new emotional and social parameters for their lives. To be sure, children of the famous must often learn to live with burdensome family traditions. But John Brown's sons were adults when their father suddenly became a martyr to the antislavery cause. All of them, and one of Brown's daughters, had played some part in his "war against slavery. " The need to justify their own roles
In vitro fertilisation of mouse oocytes reconstructed by transfer of metaphase II chromosomes results in live births

The interaction between nucleus and cytoplasm can be explored through nuclear transfer. We describe here another tool to investigate this interaction: MII meiotic apparatus transfer (MAT) between mouse oocytes. In this study, the MII oocyte meiotic apparatus or spindle from C57BL/6 mice, a black strain, was transferred into an enucleated metaphase oocyte from Kunming mouse, a white strain. The results showed that the enucleation rate by treating oocytes with 3% sucrose was 100%, but the electrofusion efficiency was very low, with only 17.6% of reconstructed karyoplast-recipient cytoplasm pairs fused. When the fused oocytes were exposed to spermatozoa from C57BL/6 mice, 9 of 11 (82%) were fertilised. Eight reconstructed embryos at 1- to 4-cell stages were transferred into the oviducts of two synchronously pregnant Kunming strain fosters and one delivered two normal C57BL/6 offspring. This study indicates that MII meiotic apparatus or spindle sustains normal structure and function after micromanipulation and electrofusion. MAT provides a model for further research on the application of this technique to assisted human reproduction.
Role of DNA sequence in chromatin remodeling and the formation of nucleosome-free regions

AT-rich DNA is concentrated in the nucleosome-free regions (NFRs) associated with transcription start sites of most genes. Lorch et al. find that the AT-rich sequences present in many NFRs have little effect on the stability of nucleosomes. These sequences instead facilitate the removal of nucleosomes by the RSC chromatin remodeling complex. RSC activity is stimulated by AT-rich sequences in nucleosomes and inhibited by competition with AT-rich DNA.
The calcium channel blocker used with cyclosporin has an effect on gingival overgrowth.

BACKGROUND/AIMS To investigate whether the choice of calcium channel blocker, used in conjunction with cyclosporin A, affected the prevalence of gingival overgrowth. METHOD A cohort of 135 renal transplant recipients who had been medicated with cyclosporin A in combination with either nifedipine (89) or amlodipine (46) since transplant, took part in the study. The inclusion criteria were that eligible subjects had been in receipt of a kidney transplant for at least 12 months, had at least 10 teeth and had not received specialist periodontal treatment. The age, gender, current drug regimen and dosage were recorded for each participant and alginate impressions taken of both arches. The presence and severity of gingival overgrowth were scored from plaster models. RESULTS A higher proportion (72%) of the amlodipine group were categorised as having gingival overgrowth compared with only 53% of the nifedipine group, chi square=4.5, p<0.05. Logistic regression analysis was used to explore the relationship between the presence or absence of gingival overgrowth (dependent variable) and age, gender, time since transplant, dose of cyclosporin A, centre in which the patient was treated, and the calcium channel blocker used (independent variables). Independent predictors of gingival overgrowth in this multivariate analysis were whether the individual was treated with amlodipine or nifedipine (p=0.01) and whether the individual was young or old (p=0.01). Within the multivariate analysis, the odds ratio for amlodipine to be associated with gingival overgrowth compared with nifedipine was 3.0 (confidence interval 1.3-6.9). CONCLUSIONS The prevalence of gingival overgrowth in renal transplant recipients maintained on cyclosporin A and nifedipine is lower than those treated with cyclosporin A and amlodipine.
Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus1

Vaccination with replication-competent vaccinia protects against heterologous orthopoxvirus challenge. CD4 T cells have essential roles helping functionally important Ab and CD8 antiviral responses, and contribute to the durability of vaccinia-specific memory. Little is known about the specificity, diversity, or dominance hierarchy of orthopoxvirus-specific CD4 T cell responses. We interrogated vaccinia-reactive CD4 in vitro T cell lines with vaccinia protein fragments expressed from an unbiased genomic library, and also with a panel of membrane proteins. CD4 T cells from three primary vaccinees reacted with 44 separate antigenic regions in 35 vaccinia proteins, recognizing 8 to 20 proteins per person. The integrated responses to the Ags that we defined accounted for 49 to 81% of the CD4 reactivity to whole vaccinia Ag. Individual dominant Ags drove up to 30% of the total response. The gene F11L-encoded protein was immunodominant in two of three subjects and is fragmented in a replication-incompetent vaccine candidate. The presence of protein in virions was strongly associated with CD4 antigenicity. These findings are consistent with models in which exogenous Ag drives CD4 immunodominance, and provides tools to investigate the relationship between Ab and CD4 T cell specificity for complex pathogens.
Effects of hemodilution, blood loss, and consumption on hemostatic factor levels during cardiopulmonary bypass.

OBJECTIVES The purpose of this study was to determine quantitatively the effects of consumption, hemodilution, and blood loss on coagulation and fibrinolytic factor levels during cardiopulmonary bypass. DESIGN A combination of measured levels of prothrombin, antithrombin, fibrinogen, plasminogen, and antiplasmin along with their activation markers F1.2, thrombin-antithrombin complex, fibrinopeptide A, plasmin-antiplasmin complex, and D-dimer were used with a computer model of each patient's vascular and hemostatic systems to estimate the cardiopulmonary bypass-associated loss of each factor because of hemodilution, blood loss, and consumption. SETTING University hospital. PARTICIPANTS Nine patients undergoing coronary artery bypass graft surgery. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS At baseline, it was estimated that on average 2%, 3%, and 25%, respectively, of the baseline liver secretion of plasminogen, prothrombin,and fibrinogen were consumed by activation of these proteins. During cardiopulmonary bypass, thrombin and plasmin generation were increased, whereas fibrin generation was decreased because of heparin. Compared with baseline, hemodilution during cardiopulmonary bypass resulted in an average 35% +/- 7% decrease in the concentration of coagulation and fibrinolytic proteins, whereas blood loss was responsible for an average 6% +/- 5% decrease in these proteins. Blood loss varied substantially among patients, resulting in <1% to 14% decreases in hemostatic protein levels. On average, consumption because of activation resulted in less than a 1% drop in the concentration of coagulation and fibrinolytic factors during cardiopulmonary bypass. CONCLUSIONS Hemodilution is the primary cause of the drop in coagulation and fibrinolytic proteins during routine cardiopulmonary bypass, followed by blood loss, whereas consumption accounts for less than a 1% drop in most patients.
Increases in the evolutionary potential of upper thermal limits under warmer temperatures in two rainforest Drosophila species

Tropical and subtropical species represent the majority of biodiversity. These species are predicted to lack the capacity to evolve higher thermal limits in response to selection imposed by climatic change. However, these assessments have relied on indirect estimates of adaptive capacity, using conditions that do not reflect environmental changes projected under climate change. Using a paternal half‐sib full‐sib breeding design, we estimated the additive genetic variance and narrow‐sense heritability for adult upper thermal limits in two rainforest‐restricted species of Drosophila reared under two thermal regimes, reflecting increases in seasonal temperature projected for the Wet Tropics of Australia and under standard laboratory conditions (constant 25°C). Estimates of additive genetic variation and narrow‐sense heritability for adult heat tolerance were significantly different from zero in both species under projected summer, but not winter or constant, thermal regimes. In contrast, significant broad‐sense genetic variation was apparent in all thermal regimes for egg‐to‐adult viability. Environment‐dependent changes in the expression of genetic variation for adult upper thermal limits suggest that predicting adaptive responses to climate change will be difficult. Estimating adaptive capacity under conditions that do not reflect future environmental conditions may provide limited insight into evolutionary responses to climate change.
Applying shannon entropy to select alternative plants as food for livestock: A case study in Ecuador

The semiarid areas of Manabí province in Ecuador are notably decertified due to overgrazing for animal production. In this study, a selection of the best alternative plants as food for livestock using the entropy-weight method, which is based on Shannon entropy theory, is developed. The entropy-weight method was applied to calculate the criteria weights; and then, the studied plants were ranked according to results of a pondered sum. The selection criteria were plant size (C1), dry material (C2), crude protein (C3), and crude fiber (C4). The possible plants were previously identified by their capacity to adapt to semiarid areas. The results shown that the best five plants were Anthyllis vulneraria, Imperta cylindrical, Cynodon plectostachyus, Bothriochloa pertusa, and Paspalidium desertorum, in that order. In the future, these selected plants could be cultivated experimentally; and then, according to the results, they could be considered as an alternative to resolve the food problem for livestock, or to recuperate the decertified areas in Manabí, Ecuador.
Role of oxidative DNA damage in cancer initiation and promotion.

Normal aerobic metabolism produces huge amounts of potentially dangerous oxidants, controlled by a variety of antioxidant systems. An imbalance between the generated and exogenously inflicted oxidants and the oxidant system is termed oxidative stress. Even without oxidative stress, i.e. under normal physiological conditions, the damage to vital cellular micromolecules, such as DNA, is extensive, amounting to hundreds of hits per cell per day. More than one hundred different oxidative modifications in DNA have been described. The hydroxylation of guanine in the 8-position is the most frequent and most mutagenic lesion described. The 8-hydroxylation of guanine leads to lack of base pairing specifically and misreading of the modified base and adjacent residues. The modifications to DNA are so frequent that extensive and specific repair is needed for survival. Indeed, multiple repair enzyme systems to mediate and remove/repair oxidative DNA modification are described. Within DNA, hot-spots of oxidative modification and subsequent mutation have been described, and some specificity appears as compared to other agents that can lead to modification of DNA, i.e. aflatoxin and benzo[a]pyrene. Numerous publications from epidemiology and intervention studies with antioxidants point at oxidative modification as an important factor in cancer development at certain sites. Yet, direct evidence linking oxidative DNA modification to cancer has not been published. With regard to antoxidant prevention of cancer no effective single substance has so far been identified.
Effect of bisphenol A on morphology, apoptosis and proliferation in the resting mammary gland of the adult albino rat

Bisphenol A (BPA) is a synthetic oestrogen that is extensively used in a wide range of daily used plastic products. This makes it one of the environmental chemicals that may have impact on human health. Due to its oestrogenic effect, BPA might affect the mammary gland. This study aimed to investigate the influence of BPA on the histological structure of the mammary gland of the adult female albino rat and its effect on epithelial cell proliferation and apoptosis status, in addition to its possible modulating effect on estrogen receptor expression. Thirty female adult albino rats were divided into control and experimental groups. The rats in the experimental group were gavaged with 5 mg/kg BPA daily for 8 weeks. The mammary glands were dissected and processed for histological and immunohistochemical stains for Ki‐67, activated caspase‐3 and estrogen receptor alpha (ER‐α). BPA induced an increase in the number and size of the acini and ducts in the mammary gland of treated rats with hyperplasia of their lining epithelial cells. The collagen fibre content was significantly increased in the connective tissue stroma separating the ducts. Immunohistochemical results showed a significant increase in Ki‐67 and caspase‐3, but a non‐significant increase in ER‐α expression. Bisphenol A induced structural changes and affected the proliferation rate of mammary glands, so it might be one of the predisposing factors for breast cancer.
A small size circularly polarized patch antenna

A small size circularly polarized (CP) patch antenna by the use of parasitic ellipse-shaped shorting strips is presented in this paper. These parasitic shorting strip elements which provide capacitive and inductive loading effects to the patch can reduce the size of antenna. The total area of reduction is more than 61% in comparison with the conventional half-wave patch antenna. The antenna works at 1.268 GHz. It has impedance bandwidth (VSWR≤2) of 2.1%, axial ratio bandwidth (AR≤3 dB) of 0.4% and peak gain of 0.55 dBic at 1.268 GHz.
The Role of Multiscale Protein Dynamics in Antigen Presentation and T Lymphocyte Recognition

T lymphocytes are stimulated when they recognize short peptides bound to class I proteins of the major histocompatibility complex (MHC) protein, as peptide–MHC complexes. Due to the diversity in T-cell receptor (TCR) molecules together with both the peptides and MHC proteins they bind to, it has been difficult to design vaccines and treatments based on these interactions. Machine learning has made some progress in trying to predict the immunogenicity of peptide sequences in the context of specific MHC class I alleles but, as such approaches cannot integrate temporal information and lack explanatory power, their scope will always be limited. Here, we advocate a mechanistic description of antigen presentation and TCR activation which is explanatory, predictive, and quantitative, drawing on modeling approaches that collectively span several length and time scales, being capable of furnishing reliable biological descriptions that are difficult for experimentalists to provide. It is a form of multiscale systems biology. We propose the use of chemical rate equations to describe the time evolution of the foreign and host proteins to explain how the original proteins end up being presented on the cell surface as peptide fragments, while we invoke molecular dynamics to describe the key binding processes on the molecular level, including those of peptide–MHC complexes with TCRs which lie at the heart of the immune response. On each level, complementary methods based on machine learning are available, and we discuss the relationship between these divergent approaches. The pursuit of predictive mechanistic modeling approaches requires experimentalists to adapt their work so as to acquire, store, and expose data that can be used to verify and validate such models.
Helicobacter pylori hspA‐hspB heat‐shock gene cluster: nucleotide sequence, expression, putative function and immunogenicity

All Helicobacter pylori isolates synthesize a 54 kDa immunodominant protein that was reported to be associated with the nickel‐dependent urease of H. pylori. This protein was recently recognized as a homologue of the heat‐shock protein of the GroEL class. The gene encoding the GroEL‐like protein of H. pylori (HspB) was cloned (plLL689) and was shown to belong to a bicistronic operon including the hspA and hspB genes. In Escherichia coli. the constitutive expression of the hspA and hspB genes was initiated from a promoter located within an IS5 insertion element that mapped upstream to the two open reading frames (ORFs). IS5 was absent from the H. pylori genome, and was thus acquired during the cosmid cloning process. hspA and hspB encoded polypeptides of 118 and 545 amino acid residues, corresponding to calculated molecular masses of 13.0 and 58.2 kDa, respectively. Amino acid sequence comparison studies revealed that, although H. pylori HspA and HspB proteins were highly similar to their bacterial homologues, the H. pylori HspA featured a striking motif at the C‐terminus. This unique motif consists of a series of cysteine and histidine residues resembling a nickel‐binding domain, which is not present in any of the other bacterial GroES homologues so far characterized. When the plLL689 recombinant plasmid was introduced together with the H. pylori urease gene cluster (plLL763) into an E. coli host strain, an increase of urease activity was observed. This suggested a close interaction between the HspA and HspB proteins and the urease enzyme, and a possible role for HspA in ihe chelation of nickel ions. The genes encoding each of the HspA and HspB polypeptides were cloned, expressed independently as proteins fused to the maltose‐binding protein (WIBP) and purified in large scale. The MBP‐HspA and MBP‐HspB fusion proteins were shown to retain their antigenic properties. Both HspA and HspB represent antigens that are specifically recognized by the sera from H. pylori‐infected patients. Whereas HspB was known to be immunogenic in humans, this is the first demonstration that HspA per se is also immunogenic as proteins fused to the maltose‐binding protein (WIBP) and purified in large scale. The MBP‐HspA and WlBP‐HspB fusion proteins were shown to retain their antigenic properties. Both HspA and HspB represent antigens that are specifically recognized by the sera from H, py/or/‐infected patients. Whereas HspB was known to be immunogenic in humans, this is the first demonstration that HspA per se is also immunogenic.
Wrist and grasp myocontrol: Online validation in a goal-reaching task

Simultaneous and proportional control of hand and wrist prostheses based upon surface electromyography (myocontrol) is still largely an open issue in the community of assistive robotics. It entails the ability of discriminating the activation levels for each degree of freedom (DOF) of the hand/wrist complex, using as few sensors as possible. Furthermore, one should avoid having the human subject train the underlying machine-learning system with all combinations of activations. To tame this problem we have proposed Linearly Enhanced Training (LET), a procedure through which a training set, composed of single-DOF activations provided by the user, is artificially completed with synthetic multi-DOF activations. In this paper, we validate the LET procedure through an online psychophysical experiment carried out on 16 intact subjects and one trans-radial amputee, in which a specific goal must be reached within a determined amount of time. Each subject tried to reach the goal in either of four different scenarios, while the LET procedure was activated or not, and while an optimisation was used or not. A comparative analysis of the results reveals that the usage of LET does not entail any statistically significant difference in the overall performance, and that the usage of the optimisations significantly improves it. Therefore, one can benefit from the drastic reduction of training time due to LET without suffering from significant reduction in performance. The optimisation showed the strong tendency to reduce the time it took to successfully accomplish a task, on average by 1.195s. A comparison of the intact subjects and the trans-radial amputee showed that half of the performance measures of the amputee lie in the 95% confidence interval determined by the able-bodied group.