Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunophenotypic characterization of lymphomas from the mediastinum of young ferrets.

OBJECTIVE To determine the phenotype of naturally developing lymphomas in young ferrets. ANIMALS 10 ferrets with lymphoma. PROCEDURE Neoplastic tissues were graded histologically according to the National Cancer Institute's Working Formulation for non-Hodgkin's lymphoma and phenotype was determined by means of immunohistochemical staining. A polyclonal anti-human CD3 and a monoclonal anti-human CD79 antibody were used to classify the lymphomas in situ as T-cell or B-cell origin. Specificity of antibodies was determined by evaluating lymphoid tissue from normal ferrets in situ, which was confirmed by western blot analyses. RESULTS All 10 ferrets had clinically aggressive tumors, irrespective of the phenotype. Nine ferrets had T-cell lymphoma that extensively involved the mediastinum. Remnants of thymic tissue, indicative of thymic origin, were identified in lymphoma of these 9 ferrets. One ferret had a B-cell multicentric lymphoma without involvement of the mediastinum. CONCLUSIONS The majority of lymphomas in these young ferrets involved the mediastinum and were of T-cell phenotype. Impact for Human Medicine-There are many similarities between the lymphoma syndrome of ferrets and the condition documented for cats and children with lymphoma of the mediastinal area. CLINICAL RELEVANCE Differential diagnoses for young ferrets with clinical signs of lethargy or respiratory distress should include T-cell lymphoma of the mediastinum.
Sirolimus and Everolimus Pathway: Reviewing Candidate Genes Influencing Their Intracellular Effects

Sirolimus (SRL) and everolimus (EVR) are mammalian targets of rapamycin inhibitors (mTOR-I) largely employed in renal transplantation and oncology as immunosuppressive/antiproliferative agents. SRL was the first mTOR-I produced by the bacterium Streptomyces hygroscopicus and approved for several medical purposes. EVR, derived from SRL, contains a 2-hydroxy-ethyl chain in the 40th position that makes the drug more hydrophilic than SRL and increases oral bioavailability. Their main mechanism of action is the inhibition of the mTOR complex 1 and the regulation of factors involved in a several crucial cellular functions including: protein synthesis, regulation of angiogenesis, lipid biosynthesis, mitochondrial biogenesis and function, cell cycle, and autophagy. Most of the proteins/enzymes belonging to the aforementioned biological processes are encoded by numerous and tightly regulated genes. However, at the moment, the polygenic influence on SRL/EVR cellular effects is still not completely defined, and its comprehension represents a key challenge for researchers. Therefore, to obtain a complete picture of the cellular network connected to SRL/EVR, we decided to review major evidences available in the literature regarding the genetic influence on mTOR-I biology/pharmacology and to build, for the first time, a useful and specific “SRL/EVR genes-focused pathway”, possibly employable as a starting point for future in-depth research projects.
Preventing Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in High-Risk Patients: Protocol of a Randomized Placebo-Controlled Trial of Prednisone (PredART Trial)

Background Early antiretroviral therapy (ART) initiation in patients diagnosed with HIV-associated tuberculosis (TB) reduces mortality among those with the lowest CD4 counts. At the same time, both early ART and a low CD4 count heighten the risk of paradoxical TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). TB is common in patients starting ART in sub-Saharan Africa. Safe interventions that reduce the incidence or severity of TB-IRIS are needed. Prednisone has been shown to reduce symptoms and markers of inflammation when used to treat TB-IRIS. Objective To determine whether prophylactic prednisone in patients at high risk for paradoxical TB-IRIS initiating ART reduces the incidence of TB-IRIS. Methods We are conducting a randomized, double-blind, placebo-controlled trial of prophylactic prednisone (40 mg/day for 2 weeks, followed by 20 mg/day for 2 weeks) initiated at the same time as ART in patients at high risk for TB-IRIS (starting ART within 30 days of TB treatment and CD4 count ≤100/μL). The primary endpoint is development of TB-IRIS, defined using an international consensus case definition. Secondary endpoints include time to TB-IRIS event, severity of TB-IRIS, quality of life, mortality, hospitalization, other infections and malignancies, and adverse events including corticosteroid adverse effects. Results Enrollment for the trial began in August 2013. All 240 participants have been enrolled, and safety follow-up will be completed in March 2017. Conclusion No preventive strategies for TB-IRIS currently exist. If results of this trial demonstrate the efficacy and safety of prednisone, this will provide clinicians with an evidence-based preventive strategy in patients at high risk for paradoxical TB-IRIS when initiating ART.
Charge transport in mesoscopic conducting polymer wires

In an attempt to reconcile transport in aniline oligomers with that observed in bulk polyaniline, we constructed meso-scale (60 nm) molecular junctions bridged by polyanion-stabilized polyaniline (PANI) strands. Junctions were characterized by their conductance versus electrochemical potential (G–E) and current versus voltage (I–V) characteristics, In contrast to bulk polyaniline, sharp peaks were seen in the G–E data, and these gave rise to negative differential resistance in the I–V curves, behavior much like that observed in aniline oligomers. The width of the conductance peaks increased with the amount of polymer deposited in the junction. In contrast to oligomers, the peaks in the meso-scale devices displayed a large hysteresis. The absolute conductance of the junctions is far too high to be consistent with transport along isolated chains, suggesting that a fundamental charge carrying unit is something morphologically more complex than a single polymer molecule.
Field-Caught Permethrin-Resistant Anopheles gambiae Overexpress CYP6P3, a P450 That Metabolises Pyrethroids

Insects exposed to pesticides undergo strong natural selection and have developed various adaptive mechanisms to survive. Resistance to pyrethroid insecticides in the malaria vector Anopheles gambiae is receiving increasing attention because it threatens the sustainability of malaria vector control programs in sub-Saharan Africa. An understanding of the molecular mechanisms conferring pyrethroid resistance gives insight into the processes of evolution of adaptive traits and facilitates the development of simple monitoring tools and novel strategies to restore the efficacy of insecticides. For this purpose, it is essential to understand which mechanisms are important in wild mosquitoes. Here, our aim was to identify enzymes that may be important in metabolic resistance to pyrethroids by measuring gene expression for over 250 genes potentially involved in metabolic resistance in phenotyped individuals from a highly resistant, wild A. gambiae population from Ghana. A cytochrome P450, CYP6P3, was significantly overexpressed in the survivors, and we show that the translated enzyme metabolises both alpha-cyano and non–alpha-cyano pyrethroids. This is the first study to demonstrate the capacity of a P450 identified in wild A. gambiae to metabolise insecticides. The findings add to the understanding of the genetic basis of insecticide resistance in wild mosquito populations.
External evaluation of topic models

Topic models can learn topics that are highly interpretable, semantically-coherent and can be used similarly to subject headings. But sometimes learned topics are lists of words that do not convey much useful information. We propose models that score the usefulness of topics, including a model that computes a score based on pointwise mutual information (PMI) of pairs of words in a topic. Our PMI score, computed using word-pair co-occurrence statistics from external data sources, has relatively good agreement with human scoring. We also show that the ability to identify less useful topics can improve the results of a topic-based document similarity metric.
A Transgenic Platform for Testing Drugs Intended for Reversal of Cardiac Remodeling Identifies a Novel 11βHSD1 Inhibitor Rescuing Hypertrophy Independently of Re-Vascularization

Rationale Rescuing adverse myocardial remodeling is an unmet clinical goal and, correspondingly, pharmacological means for its intended reversal are urgently needed. Objectives To harness a newly-developed experimental model recapitulating progressive heart failure development for the discovery of new drugs capable of reversing adverse remodeling. Methods and Results A VEGF-based conditional transgenic system was employed in which an induced perfusion deficit and a resultant compromised cardiac function lead to progressive remodeling and eventually heart failure. Ability of candidate drugs administered at sequential remodeling stages to reverse hypertrophy, enlarged LV size and improve cardiac function was monitored. Arguing for clinical relevance of the experimental system, clinically-used drugs operating on the Renin-Angiotensin-Aldosterone-System (RAAS), namely, the ACE inhibitor Enalapril and the direct renin inhibitor Aliskerin fully reversed remodeling. Remodeling reversal by these drugs was not accompanied by neovascularization and reached a point-of-no-return. Similarly, the PPARγ agonist Pioglitazone was proven capable of reversing all aspects of cardiac remodeling without affecting the vasculature. Extending the arsenal of remodeling-reversing drugs to pathways other than RAAS, a specific inhibitor of 11β-hydroxy-steroid dehydrogenase type 1 (11β HSD1), a key enzyme required for generating active glucocorticoids, fully rescued myocardial hypertrophy. This was associated with mitigating the hypertrophy-associated gene signature, including reversing the myosin heavy chain isoform switch but in a pattern distinguishable from that associated with neovascularization-induced reversal. Conclusions A system was developed suitable for identifying novel remodeling-reversing drugs operating in different pathways and for gaining insights into their mechanisms of action, exemplified here by uncoupling their vascular affects.
Novel method to characterize upper-limb movements based on paraconsistent logic and myoelectric signals

This paper presents a novel method that investigates the use of Paraconsistent Artificial Neural Network (PANN) and upper-limb electromyography signals for classification of movements, due to their intrinsic ability to deal with imprecise, inconsistent and paracomplete data. The preliminary study presents promising results in terms of processing time and accuracy. The average classification accuracy for the developed paraconsistent logic method was 76,0±9,1% for 17 distinguish movements and a classification average processing time of 14 ms per movement.
Food Insecurity, Food Based Coping Strategies and Suboptimal Dietary Practices of Adolescents in Jimma Zone Southwest Ethiopia

Despite the high prevalence of adolescent food insecurity in Ethiopia, there is no study which documented its association with suboptimal dietary practices. The objective of this study is to determine the association between adolescent food insecurity and dietary practices. We used data on 2084 adolescents in the age group of 13–17 years involved in the first round survey of the five year longitudinal family study in Southwest Ethiopia. Adolescents were selected using residence stratified random sampling methods. Food insecurity was measured using scales validated in developing countries. Dietary practices were measured using dietary diversity score, food variety score and frequency of consuming animal source food. Multivariable regression models were used to compare dietary behaviors by food security status after controlling for socio-demographic and economic covariates. Food insecure adolescents had low dietary diversity score (P<0.001), low mean food variety score (P<0.001) and low frequency of consuming animal source foods (P<0.001). After adjusting for other variables in a multivariable logistic regression model, adolescent food insecurity (P<0.001) and rural residence (P<0.001) were negatively associated with the likelihood of having a diversified diet (P<0.001) and frequency of consuming animal source foods, while a high household income tertile was positively associated. Similarly, multivariable linear regression model showed that adolescent food insecurity was negatively associated with food variety score, while residence in semi-urban areas (P<0.001), in urban areas (P<0.001) and high household income tertile (P = 0.013) were positively associated. Girls were less likely to have diversified diet (P = 0.001) compared with boys. Our findings suggest that food insecurity has negative consequence on optimal dietary intake of adolescents. Food security interventions should look into ways of targeting adolescents to mitigate these dietary consequences and provide alternative strategies to improve dietary quality of adolescents in Southwest Ethiopia.
Phytoextraction potential of sunflower and white mustard plants in zinc-contaminated soil

Phytoextraction relies on plants with a high capacity to absorb heavy metals and remove them from the soil. The objective of this study was to analyze the potential of sunflower (Helianthus annuus L.) and white mustard (Sinapis alba L.) for phytoextraction of Zn-contaminated soil. Research was based on a strict pot experiment conducted in a greenhouse. Seven treatments were established with increasing Zn concentrations: 0, 25, 50, 100, 200, 400, and 600 mg Zn kg-1 air-dry soil. The first tested plant was fodder sunflower. In the following year, white mustard was sown in the same pots. Plants were harvested at the end of the flowering stage. The toxic effect of Zn on sunflower yields occurred at the contamination level of 200 mg Zn kg-1 soil. In the second year of the experiment, a significant decrease in mustard biomass took place in response to 400 mg Zn kg-1 soil. The contamination level of 600 mg Zn kg-1 soil resulted in complete plant death. Plant growth was not inhibited even at high tissue Zn concentrations of 515 mg Zn kg-1 sunflower DM and 422 mg Zn kg-1 mustard DM. The 2-yr cropping system did not contribute to a significant decrease in soil Zn content. Despite high concentrations of Zn in sunflower and mustard plants, total Zn uptake accounted for only 1% to 8% of the Zn rate introduced into the soil. However, in the long run, the growing of crops could reduce Zn contamination levels in the soil. The relatively high tolerance of sunflower and white mustard for Zn contamination and rapid growth of these species are possible alternatives for phytoextraction and phytostabilization of Zn-contaminated soil.
The Impact of Maternal Age, Pre-Pregnancy Body Mass Index, Weight Gain and Parity on Glucose Challenge Test (GCT)

Background Gestational diabetes mellitus (GDM) complicates 3-7% of all pregnancies and fetomaternal outcomes are strongly related to early diagnosis of GDM. The aim of this study was to determine the impact of risk factors in the prediction of an abnormal glucose challenge test (GCT). Materials and Methods This was a prospective study conducted during 2009-2010 in two prenatal clinics in Rey, Iran. A total of 711 pregnant women who were in their first trimester of pregnancy and met the inclusion criteria were selected. The women were observed once every other week until 24- 28 weeks of gestation. All patients at 24-28 weeks of gestation were screened with 50 g oral glucose GCT. The effects of pre-pregnancy body mass index (BMI), maternal age, and weight gain until the time of GCT, and parity on abnormal GCT were evaluated. All confident intervals were calculated at the 95% level. Data was analyzed using student’s t test and the logistic regression test. Results Maternal age (p<0.001), pre-pregnancy BMI (p<0.00), parity (p=0.05) and weight gain during pregnancy (p=0.05), were significantly higher in women with abnormal GCT compared to women who had normal GCT. Logistic regression analyses confirmed that pre-pregnancy BMI (OR=1.09), maternal age (OR=1.14), and weight gain during pregnancy (OR=1.13) were associated with abnormal GCT. Conclusion Weight gain had a profound impact on the prevalence of abnormal GCT in our population. Therefore, we propose that pregnant women should only gain the recommended amount of weight during pregnancy.
The Double-Stranded RNA Binding Protein 76:NF45 Heterodimer Inhibits Translation Initiation at the Rhinovirus Type 2 Internal Ribosome Entry Site

ABSTRACT Poliovirus (PV) plus-strand RNA genomes initiate translation in a cap-independent manner via an internal ribosome entry site (IRES) in their 5′ untranslated region. Viral translation is codetermined by cellular IRES trans-acting factors, which can influence viral propagation in a cell-type-specific manner. Engineering of a poliovirus recombinant devoid of neuropathogenic properties but highly lytic in malignant glioma cells was accomplished by exchange of the cognate poliovirus IRES with its counterpart from human rhinovirus type 2 (HRV2), generating PV-RIPO. Neuroblast:glioma heterokaryon analyses revealed that loss of neurovirulence is due to trans-dominant repression of PV-RIPO propagation in neuronal cells. The double-stranded RNA binding protein 76 (DRBP76) was previously identified to bind to the HRV2 IRES in neuronal cells and to inhibit PV-RIPO translation and propagation (M. Merrill, E. Dobrikova, and M. Gromeier, J. Virol. 80:3347-3356, 2006). The results of size exclusion chromatography indicate that DRBP76 heterodimerizes with nuclear factor of activated T cells, 45 kDa (NF45), in neuronal but not in glioma cells. The DRBP76:NF45 heterodimer binds to the HRV2 IRES in neuronal but not in glioma cells. Ribosomal profile analyses show that the heterodimer preferentially associates with the translation apparatus in neuronal cells and arrests translation at the HRV2 IRES, preventing PV-RIPO RNA assembly into polysomes. Results of this study suggest that the DRBP76:NF45 heterodimer selectively blocks HRV2 IRES-driven translation initiation in neuron-derived cells.
Imatinib mesylate resistance and mutations: An Indian experience

Abstract The treatment of chronic myeloid leukemia (CML) has been revolutionized by the small molecule selective kinase inhibitor imatinib mesylate. Imanitib was the first BCR-ABL targeted agent approved for the treatment of CML patients and confers significant response in most patients; however, a substantial number of patients are initially refractory to the drug or may develop resistance during the course of treatment. Point mutations in the kinase domain (KD) of BCR-ABL that impact drug binding have been identified as one of the major mechanisms of resistance. We present here an overview of the current practice in monitoring for such mutations, including the methods used, criteria for investigating and guidelines for reporting the mutations. We further present and discuss the experience of our own laboratory in studying the KD mutations in Indian CML patients on imatinib treatment.
A Web-Based Program for Informal Caregivers of Persons With Alzheimer’s Disease: An Iterative User-Centered Design

Background Web-based programs have been developed for informal caregivers of people with Alzheimer’s disease (PWAD). However, these programs can prove difficult to adopt, especially for older people, who are less familiar with the Internet than other populations. Despite the fundamental role of usability testing in promoting caregivers’ correct use and adoption of these programs, to our knowledge, this is the first study describing this process before evaluating a program for caregivers of PWAD in a randomized clinical trial. Objective The objective of the study was to describe the development process of a fully automated Web-based program for caregivers of PWAD, aiming to reduce caregivers’ stress, and based on the user-centered design approach. Methods There were 49 participants (12 health care professionals, 6 caregivers, and 31 healthy older adults) that were involved in a double iterative design allowing for the adaptation of program content and for the enhancement of website usability. This process included three component parts: (1) project team workshops, (2) a proof of concept, and (3) two usability tests. The usability tests were based on a mixed methodology using behavioral analysis, semistructured interviews, and a usability questionnaire. Results The user-centered design approach provided valuable guidelines to adapt the content and design of the program, and to improve website usability. The professionals, caregivers (mainly spouses), and older adults considered that our project met the needs of isolated caregivers. Participants underlined that contact between caregivers would be desirable. During usability observations, the mistakes of users were also due to ergonomics issues from Internet browsers and computer interfaces. Moreover, negative self-stereotyping was evidenced, when comparing interviews and results of behavioral analysis. Conclusions Face-to-face psycho-educational programs may be used as a basis for Web-based programs. Nevertheless, a user-centered design approach involving targeted users (or their representatives) remains crucial for their correct use and adoption. For future user-centered design studies, we recommend to involve end-users from preconception stages, using a mixed research method in usability evaluations, and implementing pilot studies to evaluate acceptability and feasibility of programs.
Intracellular localization and splicing regulation of FUS/TLS are variably affected by amyotrophic lateral sclerosis-linked mutations

TLS (translocated in liposarcoma), also known as FUS (fused in sarcoma), is an RNA/DNA-binding protein that plays regulatory roles in transcription, pre-mRNA splicing and mRNA transport. Mutations in TLS are responsible for familial amyotrophic lateral sclerosis (ALS) type 6. Furthermore, TLS-containing intracellular inclusions are found in polyglutamine diseases, sporadic ALS, non-SOD1 familial ALS and a subset of frontotemporal lobar degeneration, indicating a pathological significance of TLS in a wide variety of neurodegenerative diseases. Here, we identified TLS domains that determine intracellular localization of the murine TLS. Among them, PY-NLS located in the C-terminus is a strong determinant of intracellular localization as well as splicing regulation of an E1A-derived minigene. Disruption of PY-NLS promoted the formation of cytoplasmic granules that were partially overlapped with stress granules and P-bodies. Some of the ALS-linked mutations altered both intracellular localization and splicing regulation of TLS, while most mutations alone did not affect splicing regulation. However, phospho-mimetic substitution of Ser505 (or Ser513 in human) could enhance the effects of ALS mutations, highlighting interplay between post-translational modification and ALS-linked mutations. These results demonstrate that ALS-linked mutations can variably cause loss of nuclear functions of TLS depending on the degree of impairment in nuclear localization.
On designing incentives-compatible peer-to-peer systems

Most existing p2p system are designed to address issues such as scalability, load-balancing and fault-tolerance, but they assume that all participants in the system follow the protocols and observe the system’s fair use policies. However, in a system with open or loosely controlled membership, participants have a self-interest in modifying their software if it allows them to consume the network’s resources without contributing any of their own.