Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of inflammatory cytokines in peripheral nerve injury☆

Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro- and anti-inflammatory cytokines that upregulate and downregulate, respectively, the production of inflammatory mediators. While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages, anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines, thus determining the end of the process. In this review, we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration. In particular, we focus on interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor-β, interleukin-10 and transforming growth factor-β.
A longitudinal study on quality of life after gynecologic cancer treatment.

OBJECTIVE The objective was to describe the pattern of quality of life (QOL) over time and to assess the impact of age, symptoms, disease parameters, and treatment on the overall QOL. METHODS A longitudinal study on patients with newly diagnosed gynecologic cancer using individual patients as their own control was performed. The 33-item EORTC QLQ-C30(+3) was used as the QOL measure. Patients were assessed before treatment, after completion of treatment, and at 6, 12, and 24 months. Spearman's correlation analyses were performed. A mixed effect model was fitted to the data. Bonferroni pairwise comparisons were used to analyze the different variables. RESULTS One hundred forty-four women completed the study. Overall QOL improved after the completion of treatment but remained the same throughout the 2 years after treatment. The individual patient's QOL before treatment was insignificant while the impact of treatment on the individual patient was significant in determining QOL after treatment. There was a strong correlation for all time points in most factors, indicating that the global health status, functional scales, and symptom scales exhibit a dependent change over time. Relief in symptoms was associated with improvements in functional scales. The scores on overall QOL were lower for younger patients and for patients treated with chemotherapy than for patients treated with surgery. CONCLUSIONS Strategies for supportive care need to focus on symptom management. Psychosocial interventions, to be effective, should include all patients and should aim to reduce the impact of treatment on the individual patient.
Bibliometric Indicators: Why Do We Need More Than One?

This paper provides an overview of the main features of several bibliometric indicators which were proposed in the last few decades. Their pros and cons are highlighted and compared with the features of the well-known impact factor (IF) to show how alternative metrics are specifically designed to address the flaws that the IF was shown to have, especially in the last few years. We also report the results of recent studies in the bibliometric literature showing how the scientific impact of journals as evaluated by bibliometrics is a very complicated matter and it is completely unrealistic to try to capture it by any single indicator, such as the IF or any other. As such, we conclude that the adoption of more metrics, with complementary features, to assess journal quality would be very beneficial as it would both offer a more comprehensive and balanced view of each journal in the space of scholarly publications, as well as eliminate the pressure on individuals and their incentive to do metric manipulation which is an unintended result of the current (mis)use of the IF as the gold standard for publication quality.
Ecology and evolution of pathogens in natural populations of Lepidoptera

Pathogens are ubiquitous in insect populations and yet few studies examine their dynamics and impacts on host populations. We discuss four lepidopteran systems and explore their contributions to disease ecology and evolution. More specifically, we elucidate the role of pathogens in insect population dynamics. For three species, western tent caterpillars, African armyworm and introduced populations of gypsy moth, infection by nucleopolyhedrovirus (NPV) clearly regulates host populations or reduces their outbreaks. Transmission of NPV is largely horizontal although low levels of vertical transmission occur, and high levels of covert infection in some cases suggest that the virus can persist in a nonsymptomatic form. The prevalence of a mostly vertically transmitted protozoan parasite, Ophryocystis elektroscirrha, in monarch butterflies is intimately related to their migratory behaviour that culls highly infected individuals. Virulence and transmission are positively related among genotypes of this parasite. These systems clearly demonstrate that the interactions between insects and pathogens are highly context dependent. Not only is the outcome a consequence of changes in density and genetic diversity: environmental factors, particularly diet, can have strong impacts on virulence, transmission and host resistance or tolerance. What maintains the high level of host and pathogen diversity in these systems, however, remains a question.
Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis

African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.
Ieee Transactions on Pattern Analysis and Machine Intelligence 1 Motion Detail Preserving Optical Flow Estimation

—A common problem of optical flow estimation in the multi-scale variational framework is that fine motion structures cannot always be correctly estimated, especially for regions with significant and abrupt displacement variation. A novel extended coarse-to-fine (EC2F) refinement framework is introduced in this paper to address this issue, which reduces the reliance of flow estimates on their initial values propagated from the coarse level and enables recovering many motion details in each scale. The contribution of this paper also includes adaptation of the objective function to handle outliers and development of a new optimization procedure. The effectiveness of our algorithm is demonstrated using the Middlebury optical flow benchmark and by experiments on challenging examples that involve large-displacement motion.
Urinary Tract Stones and Osteoporosis: Findings From the Women's Health Initiative

Kidney and bladder stones (urinary tract stones) and osteoporosis are prevalent, serious conditions for postmenopausal women. Men with kidney stones are at increased risk of osteoporosis; however, the relationship of urinary tract stones to osteoporosis in postmenopausal women has not been established. The purpose of this study was to determine whether urinary tract stones are an independent risk factor for changes in bone mineral density (BMD) and incident fractures in women in the Women's Health Initiative (WHI). Data were obtained from 150,689 women in the Observational Study and Clinical Trials of the WHI with information on urinary tract stones status: 9856 of these women reported urinary tract stones at baseline and/or incident urinary tract stones during follow‐up. Cox regression models were used to determine the association of urinary tract stones with incident fractures and linear mixed models were used to investigate the relationship of urinary tract stones with changes in BMD that occurred during WHI. Follow‐up was over an average of 8 years. Models were adjusted for demographic and clinical factors, medication use, and dietary histories. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (HR 1.10; 95% CI, 1.04 to 1.17). However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in BMD at any skeletal site or to incident fractures. In conclusion, urinary tract stones in postmenopausal women are not an independent risk factor for osteoporosis. © 2015 American Society for Bone and Mineral Research.
Formation and characterization of polyethylene blends for autoclave-based expanded-bead foams

Blends of linear-low-density polyethylene (LLDPE), low-density polyethylene (LDPE), and high- density polyethylene (HDPE) were foamed and characterized in this research. The goal was to generate clear dual peaks from the expanded polyethylene (EPE) foam beads made from these blends in autoclave processing. Three blends were prepared in a twin-screw mixing extruder at two rotational speeds of 5 and 50 rpm: Blend1 (LLDPE with 20 wt% HDPE), Blend 2 (LLDPE with 20 wt% LDPE), and Blend 3 (LLDPE with 10 wt% HDPE and 10 wt% LDPE). The differential scanning calorimetric (DSC) measurement was taken at two cooling rates: 5 and 50°C/min. Although no dual peaks were present, the results showed that blending with HDPE has a more noticeable effect on the DSC curve of LLDPE than blending with LDPE. Also, the rotational speed and cooling rate affected the shape of the DSC curves and the percentage area below the onset point. The DSC characterization of the batch foamed blends revealed multiple peaks at certain temperatures, which may be mainly due to the annealing effect during the gas saturation process. POLYM. ENG. SCI., 2010. © 2009 Society of Plastics Engineers
Doppler Evaluation of Umbilical and Uterine- Arcuate Arteries in the Postdates Pregnancy

To assess the correlation between Doppler velocimetry and perinatal outcome in the postdates pregnancy, 75 women who were at least 41 weeks' gestation were evaluated twice weekly until delivery. Evaluation included Doppler velocimetry of the umbilical and uterine-arcuate arteries, as well as nonstress testing and amniotic fluid volume estimation. The mean umbilical artery systolic-diastolic ratio (S/D) was significantly higher in the pregnancies with subsequent abnormal perinatal outcomes than in those with normal outcomes (2.42 versus 2.19; P=.03). Using a receiver operating characteristic curve, an abnormal umbilical artery S/D was defined as 2.40 or greater. Using this value, sensitivity was 57.1% and specificity was 77.8%. Our study suggests that an umbilical artery S/D of 2.40, rather than the more traditionally accepted cutoff of 3.0, may be a useful threshold to identify those postdates pregnancies at high risk for abnormal perinatal outcome. (Obstet Gynecol 78: 363, 1991)
Grand Challenges in Migration Biology

Abstract Billions of animals migrate each year. To successfully reach their destination, migrants must have evolved an appropriate genetic program and suitable developmental, morphological, physiological, biomechanical, behavioral, and life-history traits. Moreover, they must interact successfully with biotic and abiotic factors in their environment. Migration therefore provides an excellent model system in which to address several of the “grand challenges” in organismal biology. Previous research on migration, however, has often focused on a single aspect of the phenomenon, largely due to methodological, geographical, or financial constraints. Integrative migration biology asks ‘big questions’ such as how, when, where, and why animals migrate, which can be answered by examining the process from multiple ecological and evolutionary perspectives, incorporating multifaceted knowledge from various other scientific disciplines, and using new technologies and modeling approaches, all within the context of an annual cycle. Adopting an integrative research strategy will provide a better understanding of the interactions between biological levels of organization, of what role migrants play in disease transmission, and of how to conserve migrants and the habitats upon which they depend.
A Testable Prognostic Model of Nicotine Dependence

Individuals’ dependence on nicotine, primarily through cigarette smoking, is a major source of morbidity and mortality worldwide. Many smokers attempt but fail to quit smoking, motivating researchers to identify the origins of this dependence. Because of the known heritability of nicotine-dependence phenotypes, considerable interest has been focused on discovering the genetic factors underpinning the trait. This goal, however, is not easily attained: no single factor is likely to explain any great proportion of dependence because nicotine dependence is thought to be a complex trait (i.e., the result of many interacting factors). Genomewide association studies are powerful tools in the search for the genomic bases of complex traits, and in this context, novel candidate genes have been identified through single nucleotide polymorphism (SNP) association analyses. Beyond association, however, genetic data can be used to generate predictive models of nicotine dependence. As expected in the context of a complex trait, individual SNPs fail to accurately predict nicotine dependence, demanding the use of multivariate models. Standard approaches, such as logistic regression, are unable to consider large numbers of SNPs given existing sample sizes. However, using Bayesian networks, one can overcome these limitations to generate a multivariate predictive model, which has markedly enhanced predictive accuracy on fitted values relative to that of individual SNPs. This approach, combined with the data being generated by genomewide association studies, promises to shed new light on the common, complex trait nicotine dependence.
Inducible Defenses Stay Up Late: Temporal Patterns of Immune Gene Expression in Tenebrio molitor

The course of microbial infection in insects is shaped by a two-stage process of immune defense. Constitutive defenses, such as engulfment and melanization, act immediately and are followed by inducible defenses, archetypically the production of antimicrobial peptides, which eliminate or suppress the remaining microbes. By applying RNAseq across a 7-day time course, we sought to characterize the long-lasting immune response to bacterial challenge in the mealworm beetle Tenebrio molitor, a model for the biochemistry of insect immunity and persistent bacterial infection. By annotating a hybrid de novo assembly of RNAseq data, we were able to identify putative orthologs for the majority of components of the conserved insect immune system. Compared with Tribolium castaneum, the most closely related species with a reference genome sequence and a manually curated immune system annotation, the T. molitor immune gene count was lower, with lineage-specific expansions of genes encoding serine proteases and their countervailing inhibitors accounting for the majority of the deficit. Quantitative mapping of RNAseq reads to the reference assembly showed that expression of genes with predicted functions in cellular immunity, wound healing, melanization, and the production of reactive oxygen species was transiently induced immediately after immune challenge. In contrast, expression of genes encoding antimicrobial peptides or components of the Toll signaling pathway and iron sequestration response remained elevated for at least 7 days. Numerous genes involved in metabolism and nutrient storage were repressed, indicating a possible cost of immune induction. Strikingly, the expression of almost all antibacterial peptides followed the same pattern of long-lasting induction, regardless of their spectra of activity, signaling possible interactive roles in vivo.
Single-Cell Co-expression Analysis Reveals Distinct Functional Modules, Co-regulation Mechanisms and Clinical Outcomes

Co-expression analysis has been employed to predict gene function, identify functional modules, and determine tumor subtypes. Previous co-expression analysis was mainly conducted at bulk tissue level. It is unclear whether co-expression analysis at the single-cell level will provide novel insights into transcriptional regulation. Here we developed a computational approach to compare glioblastoma expression profiles at the single-cell level with those obtained from bulk tumors. We found that the co-expressed genes observed in single cells and bulk tumors have little overlap and show distinct characteristics. The co-expressed genes identified in bulk tumors tend to have similar biological functions, and are enriched for intrachromosomal interactions with synchronized promoter activity. In contrast, single-cell co-expressed genes are enriched for known protein-protein interactions, and are regulated through interchromosomal interactions. Moreover, gene members of some protein complexes are co-expressed only at the bulk level, while those of other complexes are co-expressed at both single-cell and bulk levels. Finally, we identified a set of co-expressed genes that can predict the survival of glioblastoma patients. Our study highlights that comparative analyses of single-cell and bulk gene expression profiles enable us to identify functional modules that are regulated at different levels and hold great translational potential.
Pharmacokinetics and Pharmacodynamics of Continuous-Infusion Meropenem in Pediatric Hematopoietic Stem Cell Transplant Patients

ABSTRACT This study explored the pharmacokinetics and the pharmacodynamics of continuous-infusion meropenem in a population of pediatric hematopoietic stem cell transplant (HSCT) patients who underwent therapeutic drug monitoring. The relationship between meropenem clearance (CLM) and estimated creatinine clearance (CLCR) was assessed by nonlinear regression. A Monte Carlo simulation was performed to investigate the predictive performance of five dosing regimens (15 to 90 mg/kg of body weight/day) for the empirical treatment of severe Gram-negative-related infections in relation to four different categories of renal function. The optimal target was defined as a probability of target attainment (PTA) of ≥90% at steady-state concentration-to-MIC ratios (CSS/MIC) of ≥1 and ≥4 for MICs of up to 8 mg/liter. A total of 21 patients with 44 meropenem CSS were included. A good relationship between CLM and estimated CLCR was observed (r2 = 0.733). Simulations showed that at an MIC of 2 mg/liter, the administration of continuous-infusion meropenem at doses of 15, 30, 45, and 60 mg/kg/day may achieve a PTA of ≥90% at a CSS/MIC ratio of ≥4 in the CLCR categories of 40 to <80, 80 to <120, 120 to <200, and 200 to <300 ml/min/1.73 m2, respectively. At an MIC of 8 mg/liter, doses of up to 90 mg/kg/day by continuous infusion may achieve optimal PTA only in the CLCR categories of 40 to <80 and 80 to <120 ml/min/1.73 m2. Continuous-infusion meropenem at dosages up to 90 mg/kg/day might be effective for optimal treatment of severe Gram-negative-related infections in pediatric HSCT patients, even when caused by carbapenem-resistant pathogens with an MIC of up to 8 mg/liter.
Architectural exploration of Forward 4×4 Hadamard Transform applied to H.264/AVC video compression standard

The focus of this work is the improvement of performance of the encoder of the H.264/AVC by exploiting different architectural alternatives for the Forward 4×4 Hadamard Transform. This transform module is present in the critical path for the video compression that uses intra-frame encoding in H.264/AVC standard. Combinational and sequential architectures are proposed for the calculation of the Hadamard transform algorithm. As this transform is composed by a great amount of addition operation, efficient adder compressors are used in order to achieve a higher performance in the proposed architectures. A combination of 4∶2, 8∶2 and 16∶2 adder compressors, are used in the combinational and sequential architectures. The architectures were all described in VHDL and synthesized to TSMC 0. 18µm CMOS standard cell. Synthesis results indicate that the architectures with 16∶2 adder compressor reach the best performance results. While the use of this compressor enables a reduction of 17% of delay value in the combinational architecture, the frequency operation of the sequential architecture can be improved by almost 3 times, with a reduced latency, when using this adder compressor.
Dual Protection Use to Prevent STIs and Unintended Pregnancy

This editorial provides a brief summary of eight research papers concerning dual protection strategies as designed to enhance prevention of both unintended pregnancy and STI/HIV and to better understand factors influencing their use. The papers present findings on dual protection use among adolescents and adults in the United States dual protection use among HIV-positive individuals in Zambia and India biomedical approaches to dual protection the potential impact of multiple risk messaging on condom use among women and biological strategies to enhance the measurement of dual protection.