Miracle-dz/UniFAR-FTUs huggingface dataset:
Update on the role of lenalidomide in patients with multiple myeloma

Lenalidomide is a derivative of thalidomide and belongs to the class of drugs known as the immunomodulatory drugs (IMiDs). The IMiDs have played a large role in improving the survival outcomes of patients with multiple myeloma. In particular, lenalidomide is currently standard of care in the newly diagnosed setting, in the maintenance setting post-autologous stem cell transplant, as well as in the relapsed/refractory setting. While the combination of lenalidomide and various proteasome inhibitors has proven particularly effective, there are emerging data demonstrating the effectiveness of lenalidomide in combination with other important classes of drugs including the monoclonal antibodies. Recent studies have provided insight into the molecular target of lenalidomide and the other IMiDs, although there is still much to be learned regarding the mechanisms by which lenalidomide affects the myeloma cell and the immune system. Here we review the molecular mechanisms of action, side effects, and the results of the clinical trials which have led to the widespread incorporation of lenalidomide into the myeloma therapeutic armamentarium.
Notes on the stability criterion for linear discrete systems

It is known that linear time-invariant discrete systems can be described by constant coefficient linear difference equations. One of the problems in the analysis of such systems is the test for stability. These tests involve both graphical procedures such as Nyquist locus, Bode diagrams and the root-locus, and analytical methods such as Schur-Cohn1 or Routh-Hurwitz criteria. Because of the high-order determinants to be evaluated using the present form of the Schur-Cohn criterion, many authors have used the bilinear transformation which maps the inside of the unit circle in the z = eTs plane into the left half of the w plane and then applied the Routh-Hurwitz criterion. This transformation involves algebraic manipulation which for higher-order systems becomes complicated.
I, Sex Robot: the health implications of the sex robot industry

The sex technology industry is already estimated to be worth US$30 billion.1 While sex toys are well-established, sex robots (’sexbots'), anthropomorphic devices created for sexual gratification, are no longer science fiction. Four companies sell adult sexbots priced between US$5000 and US$15 000. They must be distinguished from ’paedobots' – childlike robotic models at present only produced by one company.2 The market appears to be men, and so far only ‘female’ adult sexbots have been created, although one company reports aiming to sell ‘male’ devices later in 2018.3 Sex robots are realistic mannequins with variable ages, appearances and textures, and customisable oral, vaginal and anal openings. The medical profession needs to be prepared for inevitable questions about the impact of sex robots on health. Apart from free-market profits, the majority of arguments in their favour use ‘harm limitation’ somewhat defensively to convince others that this is one way to protect the vulnerable. Opponents reject the hypothesis that they reduce sexual crimes, and instead raise concerns about the potential for harm by further promoting the pervasive idea that living women too are sex objects that should be constantly available - ‘misogynistic objectification’ - and intensifying existing physical and sexual violence against women and children. What characterises all discussions of this issue is the paucity of an evidence base. This might falsely reassure clinicians not to concern themselves with changing their current clinical practice. However, an absence of evidence does not excuse the medical profession from discussing and debating the issues, as there will inevitably be consequences for physical, mental and social well-being. We aim to provide a succinct summary of the arguments for and against the sex robot industry and to assess the potential health implications that may affect both patients and clinicians. To find information about the health consequences of …
Analysis of Different Approaches for Clinical Cochlear Coverage Evaluation After Cochlear Implantation.

HYPOTHESIS Methods for cochlear coverage determination vary in their accuracy and are hence not equally reliable. BACKGROUND The audiological outcome after cochlear implantation is known to depend on several factors. One factor shown to positively correlate with speech perception is the insertion angle. This parameter is one of the ways to describe the fraction of the cochlea spiral exposed to electric stimulation after implantation, also known as cochlear coverage, which itself is dependent on the length and type of electrode array as well as the size and shape of the implanted cochlea. While the assessment of cochlear coverage as the insertion angle is quick and uncomplicated, the accuracy of representing the relative fraction of the cochlea exposed to electric stimulation by this single measurement value remains unknown. METHODS Both the cochlea spiral and implanted electrode array of N = 10 cochlear implant patients were traced within clinical imaging data and processed to derive the respective cochlear coverage values. These values were compared to ones derived with alternative measures like the insertion angle as well as other methods to yield the accuracy and reliability of these approaches. RESULTS The insertion angle as well as two novel approaches were found to be superior to all other analyzed assessment options and well suited for clinical cochlear coverage evaluations. CONCLUSION Insertion angle measurements are well suited for cochlear coverage determination, especially regarding retrospective analyses. Prospective studies independent of anatomical irregularities should be performed with the newly proposed approaches.
Inhibitory Effect of PgAFP and Protective Cultures on Aspergillus parasiticus Growth and Aflatoxins Production on Dry-Fermented Sausage and Cheese

Aflatoxigenic molds can grow and produce aflatoxins on dry-fermented meat and cheese. The small, basic, cysteine-rich antifungal protein PgAFP displays a time-limited inhibitory ability against unwanted molds by increasing reactive oxygen species (ROS), which can lead to increased aflatoxin production. However, calcium abolishes the inhibitory effect of PgAFP on certain Aspergillus spp. To maximize the antifungal effect, this protein may be combined with protective cultures. Yeasts and lactic acid bacteria may counteract the impact of calcium on PgAFP fungal inhibition. The objective of this work was to study the effect of PgAFP and different combined treatments with Debaryomyces hansenii and/or Pediococcus acidilactici against growth of and aflatoxin production by an aflatoxigenic strain of Aspergillus parasiticus in both culture media and dry-fermented foods with low or high calcium levels. Aflatoxins production was increased by PgAFP but dramatically reduced by P. acidilactici in low calcium culture medium, whereas in the Ca-enriched culture medium, all treatments tested led to low aflatoxins levels. To study whether PgAFP and the protective microorganisms interfere with ROS and aflatoxin production, the relative expression of genes foxA, which is involved in peroxisomal β-oxidation, and aflP, which is required for aflatoxin biosynthesis, were evaluated. The aflatoxin overproduction induced by PgAFP seems not to be linked to peroxisomal β-oxidation. The combination of PgAFP and D. hansenii provided a successful inhibitory effect on A. parasiticus growth as well as on aflatoxin production on sliced dry-fermented sausage and cheese ripened up to 15 days, whereas P. acidilactici did not further enhance the protective effect of the two former agents. Therefore, the combined treatment of PgAFP and D. hansenii seems to provide a promising protective mean against aflatoxin-producing A. parasiticus on dry-fermented foods.
Synthesis Techniques for Gain-Bandwidth Optimization in Passive Transducers

This paper is concerned with an approximating technique for realizing the design of broad-band equalizers and matching networks which approach optimum gain bandwidth performance. Given an arbitrary load impedance, it is possible, by methods of Bode, Fano, LaRosa and Carlin, to derive the limiting constraints for optimum flat power or voltage transfer over a prescribed band. The synthesis of equalizer networks to approximate this optimum response is a difficult matter, particularly when the load has some degree of complexity. This is because methods proposed up till now prescribe an approximating transfer function which includes the load characteristics, and the problem of adjusting the parameters of such an approximating function is quite formidable. The technique proposed here bypasses this problem by producing from the idealized gain-bandwidth constraints a set of functions which specifies the equalizer alone. All load dependence is removed from the specifications as an initial step in the synthesis. The final transducer is then synthesized from the approximating functions which are obtained. Examples of one-port and two-port equalizer network designs utilizing this technique will be given.
Depression, violence and cortisol awakening response: a 3-year longitudinal study in adolescents

Abstract Background Despite evidence of links between depression and violent outcomes, potential moderators of this association remain unknown. The current study tested whether a biological marker, cortisol, moderated this association in a longitudinal sample of adolescents. Methods Participants were 358 Dutch adolescents (205 boys) with a mean age of 15 years at the first measurement. Depressive symptoms, the cortisol awakening response (CAR) and violent outcomes were measured annually across 3 years. The CAR was assessed by two measures: waking cortisol activity (CAR area under the curve ground) and waking cortisol reactivity (CAR area under the curve increase). Within-individual regression models were adopted to test the interaction effects between depressive symptoms and CAR on violent outcomes, which accounted for all time-invariant factors such as genetic factors and early environments. We additionally adjusted for time-varying factors including alcohol drinking, substance use and stressful life events. Results In this community sample, 24% of adolescents perpetrated violent behaviours over 3 years. We found that CAR moderated the effects of depressive symptoms on adolescent violent outcomes (βs ranged from −0.12 to −0.28). In particular, when the CAR was low, depressive symptoms were positively associated with violent outcomes in within-individual models, whereas the associations were reversed when the CAR was high. Conclusions Our findings suggest that the CAR should be investigated further as a potential biological marker for violence in adolescents with high levels of depressive symptoms.
Detection of Dengue Virus among Children with Suspected Malaria, Accra, Ghana

We report new molecular evidence of locally acquired dengue virus infections in Ghana. We detected dengue viral RNA among children with suspected malaria by using a multipathogen real-time PCR. Subsequent sequence analysis revealed a close relationship with dengue virus serotype 2, which was implicated in a 2016 outbreak in Burkina Faso.
Ferramentas de trechos de código: uma revisão da literatura

Este artigo apresenta uma revisao da literatura acerca das ferramentas que auxiliam a localizacao de trechos de codigo para reutilizacao. Vinte ferramentas foram pesquisadas e suas caracteristicas sao apresentadas a partir de uma visao arquitetural. Diferentes estrategias utilizadas pelas ferramentas foram identificadas e sao apresentadas as vantagens e desvantagens de cada uma. Por fim, o trabalho sugere alguns trabalhos futuros para suprir algumas deficiencias identificadas na area.
Linear estimation in the presence of errors in assumed plant dynamics

This paper is concerned with certain practical aspects of linear estimation theory. Several questions, which arise during most applications of the theory, are partially answered by considering the following problem: Obtain the linear minimum variance estimate of the systemx_{n+1} = (\Phi_{n+1.n} + \delta\Phi_{n+1.n})x_{n} + w_{n}y_{n} = M_{n}x_{n}when the assumed model is given byx_{n+1} = \Phi_{n+1.n}x_{n} + w_{n}y_{n} = M_{n}x_{n}
Pharmacological reactivation of inactive X-linked Mecp2 in cerebral cortical neurons of living mice

Significance Rett syndrome (RTT) is a devastating neurodevelopmental disorder with no cure. RTT typically affects females and is caused by mutations in one of the two copies of the X-linked gene MECP2. Due to X chromosome inactivation, the random silencing of one X chromosome, females with RTT have a mixture of cells that express either normal or mutant MECP2. Importantly, cells expressing mutant MECP2 retain a normal copy of MECP2 on the inactive X chromosome (Xi), the reactivation of which represents a potential therapeutic approach for RTT. Here we use small-molecule inhibitors to reactivate the Xi-linked Mecp2 gene in brain neurons of living mice. Our results further establish the feasibility of Xi-linked MECP2 reactivation-based therapeutics for treatment of RTT. Rett syndrome (RTT) is a genetic disorder resulting from a loss-of-function mutation in one copy of the X-linked gene methyl-CpG–binding protein 2 (MECP2). Typical RTT patients are females and, due to random X chromosome inactivation (XCI), ∼50% of cells express mutant MECP2 and the other ∼50% express wild-type MECP2. Cells expressing mutant MECP2 retain a wild-type copy of MECP2 on the inactive X chromosome (Xi), the reactivation of which represents a potential therapeutic approach for RTT. Previous studies have demonstrated reactivation of Xi-linked MECP2 in cultured cells by biological or pharmacological inhibition of factors that promote XCI (called “XCI factors” or “XCIFs”). Whether XCIF inhibitors in living animals can reactivate Xi-linked MECP2 in cerebral cortical neurons, the cell type most therapeutically relevant to RTT, remains to be determined. Here, we show that pharmacological inhibitors targeting XCIFs in the PI3K/AKT and bone morphogenetic protein signaling pathways reactivate Xi-linked MECP2 in cultured mouse fibroblasts and human induced pluripotent stem cell-derived postmitotic RTT neurons. Notably, reactivation of Xi-linked MECP2 corrects characteristic defects of human RTT neurons including reduced soma size and branch points. Most importantly, we show that intracerebroventricular injection of the XCIF inhibitors reactivates Xi-linked Mecp2 in cerebral cortical neurons of adult living mice. In support of these pharmacological results, we also demonstrate genetic reactivation of Xi-linked Mecp2 in cerebral cortical neurons of living mice bearing a homozygous XCIF deletion. Collectively, our results further establish the feasibility of pharmacological reactivation of Xi-linked MECP2 as a therapeutic approach for RTT.
An Automatic TV Tracking Theodolite for Range Instrumentation

The factors affecting the design of a gated Automatic TV Tracking System are discussed, and a system mechanization to achieve the design objectives is outlined. Only the composite video of a closed-circuit TV system is required as an input. A study of the dynamic performance of typical targets indicates that the unpredictable target motion in a frame period of 1/30 sec must be an extremely small fraction of the field of view required for initial target acquisition. This permits the use of a small tracking gate in the larger acquisition field, since the target coordinates of the previous frame may be used to position the gate. This small gate permits a signal-to-noise enhancement and effectively rejects extraneous targets outside the tracking gate. The tracking is effected by subdividing the tracking area into equal early and late video gates in each coordinate. The differential video between these gates is applied to an electronic integrator in such a manner that the integrator output voltage, which is also the reference for the generation of the early-to-late gate transition, changes to place this gate transition on the target. The integrator voltages are, therefore, a measure of the target coordinates in the TV field. The operation of an experimental system fabricated to determine the feasibility of applying this technique to a range-instrumentation system has produced tracking accuracies of better than 0.05 milliradian in an acquisition field of 10×10 milliradians. Current developments and additional applications of the technique are discussed briefly.
Electroluminescence and Related Topics

Light may be generated by the direct action of an electric field on various solid materials by a number of different mechanisms (electroluminescence). Electric fields may also influence luminescence phenomena excited by various types of radiation (electrophotoluminescence). The varied phenomena which have been observed, and their dependence on the operating parameters, are reviewed and theoretical explanations are given where possible. Possible practical applications of electroluminescence and electro-photolutminescence are also discussed.
Association Between Preconception Care and Birth Outcomes

Purpose: To evaluate the association between preconception care and the risk of adverse birth outcomes. Design: A quasi-experimental study comparing 2 groups: (1) integrated maternal health care (MHC) program (with preconception care) and (2) standard MHC program (without preconception care). Setting: Maternal health-care clinics in Alvand and Qazvin cities in Qazvin Province, Iran. Participants: A total of 152 and 247 Iranian women aged 16 to 35 years were enrolled in the integrated MHC and standard MHC program, respectively. Measures: The birth outcomes measured included low birth weight, preterm birth, maternal and neonatal complications, and mode of delivery (normal vaginal delivery and cesarean delivery). Analysis: Multiple logistic regression was performed to determine the impact of preconception care and risk of adverse birth outcomes with adjusted odds ratios (ORs) as effect sizes. Results: One hundred forty-seven women in integrated MHC and 218 women in standard MHC completed this study. Preconception care was associated with reduced risk of preterm birth (OR = 0.298; 95% confidence interval [CI] = 0.120-0.743; P = .009), low birth weight (OR = 0.406; 95% CI = 0.169-0.971; P = .043), maternal complication (OR = 0.399; 95% CI = 0.241-0.663; P < .001), and neonatal complications (OR = 0.460; 95% CI = 0.275-0.771; P = .003). Conclusion: The findings of the present study revealed advantages of preconception care with reduced adverse birth outcomes.
Activation of the KEAP1-NRF2-ARE signaling pathway reduces oxidative stress in Hep2 cells

At present there are no studies investigating the effects of the kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) signaling pathway on Hep2 cell line. The present study aimed to investigate this topic through knockdown of the KEAP1 gene. A stable Hep2 cell line specifically silencing the human KEAP1 gene was initially constructed. Hydrogen peroxide (H2O2) was added to the culture medium at various concentrations for various durations to interact with the short hairpin (sh)KEAP1-transfected Hep2 cells. Subsequently, the gene and protein expression levels of KEAP1, NRF2, NAD(P)H quinone oxidoreductase1 (NQO1) and heme oxygenase 1 (HO1) in experimental and control cells were measured by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Furthermore, the viability and apoptotic rate of the shKEAP1-transfected Hep2 cells were detected by a Cell Counting-Kit 8 assay and flow cytometry, respectively. In the shKEAP1 Hep2 cell line, the mRNA and protein expression levels of NRF2, NQO1 and HO1 were markedly higher compared with the scramble control-transfected Hep2 and parent Hep2 cell lines. Immunofluorescence staining indicated that NRF2 was primarily located in the cytoplasm of scHep2 and parent Hep2 cell lines, but was present in the nuclei and cytoplasm of the shKEAP1 Hep2 cell line, where it translocates into the nuclei in response to H2O2. Following knockdown of the KEAP1 gene Hep2 cells, the apoptosis rates were 31.8 and 45.3% in scHep2 cells at 0.1 and 0.25 mmol/l H2O2 respectively and 14.1 and 27.9% in shKEAP1 cells. The present study indicated that the KEAP1-NRF2-ARE signaling pathway may exhibit an antioxidative effect within Hep2 cells and may be used for clinical treatment of cancer.
Precision medicine in food allergy

Purpose of review To familiarize the reader with the concept of precision medicine in food allergy through the most recent insights in the diagnosis, prognosis, and management of the disease. Recent findings With the advent of omics sciences, a new era is commencing. Food protein allergens characterization and quantification together with the immunoglobulin E epitope mapping will contribute to the diagnosis/prognosis of food allergy and will lead to a better safety assessment of foods. The characterization of biomarkers able to identify specific phenotypes and endotypes will improve the diagnostic accuracy. This together with a better understanding of mechanisms of action of the different therapeutic options will allow the accurate selection of the appropriate patient. Summary In the near future, advances in technologies and data interpretation will allow a better understanding of the pathogenesis of food allergy and the development of a personalized treatment tailored on the specific patient’ profile.
Adolescent Connectedness with Parents Promotes Resilience among Homeless Youth

Youth who experience homelessness have worse health and well-being than housed youth. Internal assets, including social competency and positive self-identity, are factors that promote healthy development. This study compared internal assets between homeless and housed youth, and examined whether connectedness with parents moderates the association between homelessness and internal assets. Using data from a large population-based survey of middle- and high-school aged youth, we found that homelessness was associated with lower levels of internal assets. However, having high connectedness with a parent significantly predicted the strength of these assets, suggesting opportunities to promote health equity among homeless youth.
Ocular allergy as a risk factor for dry eye in adults and children

Purpose of review To provide an overview of the pathogenic mechanisms underlying the correlation between ocular allergy and dry eye disease (DED), highlighting how the first condition may be a risk factor for the second one. Recent findings Recent advances in our comprehension of the pathogenesis of ocular allergy and DED allow identifying several pathways of interaction between these two conditions. A growing body of evidence supports the role of ocular allergy as a risk factor for DED. Ocular allergy, particularly the severe forms of keratoconjunctivitis, can impact on different key mechanisms of the DED vicious cycle, including tear film instability, ocular surface inflammation and damage, and neurosensory abnormalities. Summary Ocular allergy and DED are two common, relevant, symptomatic, not mutually exclusive conditions affecting the ocular surface. They share some clinical and biochemical features. To better understand the complex interactions between these two conditions, it's essential to consider the very wide spectrum of clinical conditions included in the term ocular allergy and the still largely unexplored peculiarities of the pediatric ocular surface physio-pathology and DED.