Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of Fetal Hemoglobin in Sickle Cell Anemia Using an Ensemble of Genetic Risk Prediction Models

Background—Fetal hemoglobin (HbF) is the major modifier of the clinical course of sickle cell anemia. Its levels are highly heritable, and its interpersonal variability is modulated in part by 3 quantitative trait loci that affect HbF gene expression. Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) in these quantitative trait loci that are highly associated with HbF but explain only 10% to 12% of the variance of HbF. Combining SNPs into a genetic risk score can help to explain a larger amount of the variability of HbF level, but the challenge of this approach is to select the optimal number of SNPs to be included in the genetic risk score. Methods and Results—We developed a collection of 14 models with genetic risk score composed of different numbers of SNPs and used the ensemble of these models to predict HbF in patients with sickle cell anemia. The models were trained in 841 patients with sickle cell anemia and were tested in 3 independent cohorts. The ensemble of 14 models explained 23.4% of the variability in HbF in the discovery cohort, whereas the correlation between predicted and observed HbF in the 3 independent cohorts ranged between 0.28 and 0.44. The models included SNPs in BCL11A, the HBS1L-MYB intergenic region, and the site of the HBB gene cluster, quantitative trait loci previously associated with HbF. Conclusions—An ensemble of 14 genetic risk models can predict HbF levels with accuracy between 0.28 and 0.44, and the approach may also prove useful in other applications.
The need for national deep decarbonization pathways for effective climate policy

Constraining global average temperatures to 2 °C above pre-industrial levels will probably require global energy system emissions to be halved by 2050 and complete decarbonization by 2100. In the nationally orientated climate policy framework codified under the Paris Agreement, each nation must decide the scale and method of their emissions reduction contribution while remaining consistent with the global carbon budget. This policy process will require engagement amongst a wide range of stakeholders who have very different visions for the physical implementation of deep decarbonization. The Deep Decarbonization Pathways Project (DDPP) has developed a methodology, building on the energy, climate and economics literature, to structure these debates based on the following principles: country-scale analysis to capture specific physical, economic and political circumstances to maximize policy relevance, a long-term perspective to harmonize short-term decisions with the long-term objective and detailed sectoral analysis with transparent representation of emissions drivers through a common accounting framework or ‘dashboard’. These principles are operationalized in the creation of deep decarbonization pathways (DDPs), which involve technically detailed, sector-by-sector maps of each country’s decarbonization transition, backcasting feasible pathways from 2050 end points. This article shows how the sixteen DDPP country teams, covering 74% of global energy system emissions, used this method to collectively restrain emissions to a level consistent with the 2 °C target while maintaining development aspirations and reflecting national circumstances, mainly through efficiency, decarbonization of energy carriers (e.g. electricity, hydrogen, biofuels and synthetic gas) and switching to these carriers. The cross-cutting analysis of country scenarios reveals important enabling conditions for the transformation, pertaining to technology research and development, investment, trade and global and national policies. Policy relevance In the nation-focused global climate policy framework codified in the Paris Agreement, the purpose of the DDPP and DDPs is to provide a common method by which global and national governments, business, civil society and researchers in each country can communicate, compare and debate differing concrete visions for deep decarbonization in order to underpin the necessary societal and political consensus to design and implement short-term policy packages that are consistent with long-term global decarbonization.
Herramientas de Análisis Técnico para Carteras de Inversiones Bursátiles: Aplicación al Mercado Bursátil Chileno Technical Analysis Tools for Portfolios: Application to the Chilean Stock Exchange Market

In the present work the principal statistic technical analysis tools of financial theory are studied, including: mean, mobile, momentum, stochastic, R of Williams and RSI. The main objective is to determine which tools are of greater efficiency in the Chilean Stock Exchange Market. To carry out this investigation the daily closing prices of the stocks from companies that compose the IPSA index were obtained between January 3th 2000 and December 30th 2004. The study included 22 companies, , considering the permanency of the stock during the period in study as a criterion. Subsequently the statistic technical analysis tools were applied to the indicated period, and then a comparison was performed between them and a selection of the tools that turned out to be more profitable in the local market was carried out. The results show that the R of Williams indicator delivers greater returns than the other indicators. The previous results differ from similar studies applied to stocks belonging to the Dow Jones Industry and Nasdaq indexes of the American Stock Exchange. The foregoing would indicate that the techniques that have better performance in developed capital markets, not necessarily deliver the same results in smaller markets and vice versa.
Virus immunocapture provides evidence of CD8 lymphocyte-derived HIV-1 in vivo

Objectives:To demonstrate that HIV-1 immunocapture with an antibody against CD8 specifically captures virions derived from infected CD8 T cells, and to determine the proportion of HIV-1 derived from CD8 lymphocytes in plasma samples from HIV-infected individuals. Methods:A virus capture method was developed to enable the detection of HIV-1 virions based upon the presence of certain cell-specific host-derived proteins (CD8, CD3, CD36) within the viral envelope. HIV-1 virions were captured using antibodies against these proteins and levels of bound virus were determined by quantitative reverse transcriptase–polymerase chain reaction. Highly pure CD8 and CD3+CD8− T-cell cultures were used as in-vitro models to determine the specificity of the virus capture technique. Results:The in-vitro model demonstrates that incorporation of the CD8 molecule into released virions is specific to infection of CD8 T cells. Levels of HIV-1 immunocaptured from plasma of infected individuals using the anti-CD8 antibody indicate that up to 15% (range 10–33) of the plasma viral load is derived from CD8 lymphocytes. Conclusion:This study demonstrates for the first time that HIV-1-infected CD8 T cells can contribute substantially to levels of circulating virus during the course of infection. Levels of CD8-derived virus did not correlate with the level of infection of circulating CD8 T cells, but do show a significantly good fit to plasma viral loads based on a power model. The extensive infection of CD8 T cells implied by these results may contribute towards immune dysfunction and disease progression to AIDS.
The immunogenicity of biosimilar infliximab: can we extrapolate the data across indications?

Biopharmaceuticals or ‘biologics’ have revolutionized the treatment of many diseases. However, some patients generate an immune response to such drugs, potentially limiting clinical efficacy and safety. Infliximab (Remicade®) is a monoclonal antibody used to treat several immune-mediated inflammatory disorders. A biosimilar of infliximab, CT-P13 (Remsima®, Inflectra®), has recently been approved in Europe for all indications in which infliximab is approved. Approval of CT-P13 was based in part on extrapolation of clinical trial data from two indications (rheumatoid arthritis and ankylosing spondylitis) to all other indications, including inflammatory bowel disease. This review discusses the validity of extrapolating immunogenicity data across indications – a process adopted by the EMA as part of their biosimilar approval process – with a focus on CT-P13.
On calibration of correction law for EMF measurement errors due to the proximity of the human body

We present in this paper the calibration of a correction law to overcome the electric field (e-field) measurement errors due to the presence of the dosimeter in the vicinity of the human body. The Correction law proposes to use only two measuring points close to the body. These measurements are made at regularly goshawks separate points of the body, either in the chest, abdomen or waist. The goal is to propose a useful distributed worn-body dosimeter who can apply a correction law to these separate values compared to the maximum value known beforehand. This correction law is currently derived to simulation for GSM, DCS and UMTS downlink Bands and shortly performed by measurements. Assessing the real EMF exposure value in real-time is the key question for sanitary authorities as well as for industry (Manufacturer and Operator).
Mesenchymal stem cell-secreted soluble signaling molecules potentiate tumor growth

In previous studies, we and others have shown that bone marrow mesenchymal stem cells (MSCs) are recruited to sites of growing tumors and promote tumor growth in mouse xenograft models, suggesting that interactions between MSCs and tumor cells may play an important role in this process. However, the exact mechanism remains unclear. In the present study, we investigated whether the physical presence or the continuous presence of MSCs is required for enhanced tumor growth, and we found that pretreatment of tumor cells SGC-7901 with a single dose of human MSC-conditioned medium (hMSC-CM) in vitro is sufficient to potentiate tumor growth comparable to the effect of MSC co-injection in vivo in mouse xenograft models. We further showed that significant tumor modifying activity is present in post-ultracentrifigation soluble fraction. Biochemical analysis suggests that hMSC-CM induces the expression of VEGF of tumor cells as well as the activation of RhoA-GTPase and ERK1/2. Furthermore, hMSC-CM-enhanced tumor growth is sustainable in serial transplantation, suggesting that MSC-secreted factors have profound effects on “reprogramming” of tumor growth. Our data provide new insights into the way in which MSCs modify tumor growth and offer a new and exciting opportunity to develop effective therapeutics for intercepting tumor progression.
Reflecting on Parental Concerns in the Treatment of Pediatric Brain Tumors: Observations From A General Pediatrician

This issue of Narrative Inquiry in Bioethics explores the concerns and point of view of parents who have had to confront the devastating diagnosis of a pediatric brain tumor. This commentary, written by a general pediatrician, is a synthesis of several narrative themes which touch on a range of topics from relapse to long-term sequelae and other issues that effect a growing population of pediatric brain tumor patients. It offers a glimpse into the problems that need to be addressed by health professionals, educators and support teams who provide short and long term care to these patients and their families.
Stereotactic Radiation Therapy Augments Antigen-Specific PD-1–Mediated Antitumor Immune Responses via Cross-Presentation of Tumor Antigen

Sharabi and colleagues show in two mouse tumor models that radiotherapy combined with PD-1 blockade or Treg depletion improves local tumor control by increasing antigen-experienced and effector-memory T cells, antigen-MHC complexes, and T-cell infiltration into tumors via antigen cross-presentation in the tumor-draining lymph node. The immune-modulating effects of radiotherapy (XRT) have gained considerable interest recently, and there have been multiple reports of synergy between XRT and immunotherapy. However, additional preclinical studies are needed to demonstrate the antigen-specific nature of radiation-induced immune responses and elucidate potential mechanisms of synergy with immunotherapy. Here, we demonstrate the ability of stereotactic XRT to induce endogenous antigen-specific immune responses when it is combined with anti–PD-1 checkpoint blockade immunotherapy. Using the small animal radiation research platform (SARRP), image-guided stereotactic XRT delivered to B16-OVA melanoma or 4T1-HA breast carcinoma tumors resulted in the development of antigen-specific T cell– and B cell–mediated immune responses. These immune-stimulating effects of XRT were significantly increased when XRT was combined with either anti–PD-1 therapy or regulatory T cell (Treg) depletion, resulting in improved local tumor control. Phenotypic analyses of antigen-specific CD8 T cells revealed that XRT increased the percentage of antigen-experienced T cells and effector memory T cells. Mechanistically, we found that XRT upregulates tumor-associated antigen–MHC complexes, enhances antigen cross-presentation in the draining lymph node, and increases T-cell infiltration into tumors. These findings demonstrate the ability of XRT to prime an endogenous antigen-specific immune response and provide an additional mechanistic rationale for combining radiation with PD-1 blockade in the clinic. Cancer Immunol Res; 3(4); 345–55. ©2014 AACR.
Epizootics in Industrial Livestock Production: Preventable Gaps in Biosecurity and Biocontainment

While technological advances in animal husbandry have facilitated increases in global meat production, the high density and geographic concentration of food animal production facilities pose risks of infectious disease transmission. The scale of the 2014–2015 highly pathogenic avian influenza H5N2 outbreak in the United States demonstrates the challenges in achieving pathogen control within and around industrial animal facilities using existing technologies. We discuss gaps in current practice in two specific systems within these facilities – ventilation and waste management – which are under‐recognized as important drivers of microbial porosity. The development of innovative ventilation systems to reduce influx and efflux of pathogens is critically needed, and cross‐sectoral partnerships should be incentivized to do so. Adapting current human biosolid treatment technologies for farm applications, reducing animal stocking density and shifting waste management responsibility from farmer to corporation would reduce risk from current manure management systems. While innovative approaches to functionally altering the industrial food animal production system remain important priorities to promote sustainability, our intention here is to identify gaps within the current system that allow for pathogen emergence and transmission and address specific areas in which technological, administrative or policy changes are necessary to mitigate these risks.
Carbon dioxide as a short-term restraint anaesthetic in rats with subclinical respiratory disease

The use of carbon dioxide (CO2) with, and without, oxygen (O2) as a short-term restraint anaesthetic for Wistar rats in which subclinical respiratory disease was endemic, was assessed in 3 separate experiments. In the first, rats were placed in a CO2 atmosphere generated from solid CO2 chips in a 701 plastic bin, and removed at time intervals ranging from 0 to 120 s after disappearance of the pedal reflex. Eight of 25 rats died, including 2 which were removed immediately the pedal reflex disappeared; it was concluded that CO2 without O2 was not a suitable short-term anaesthetic for rats. In a second study, rats were anaesthetized in atmospheres of 50 : 50 and 80 : 20 (CO2 : O2) provided from commercially available cylinders, in 2 different environments-a 3·41 glass jar and a 171 plastic bin. Rats became excited in the plastic bin but not the glass jar. Rats in the glass jar displayed visible depression and cessation of whiskers movement significantly more quickly in the 80 : 20 (CO2 : O2) than in the 50 : 50 mixture (4·2±0·98 s, n = 6, and 66·0±4·9 s, n = 6 vs 13·8±2·77 s, n = 5 and 1520±20·8 s, n = 5, respectively). Rats in the 171 plastic bin lost their pedal reflexes in a mean 41·5±4·55 s (n = 11) in the 50 : 50 mixture and in a mean 30·9±6·38 s (n = 11) in the 80 : 20 (CO2 : O2) group. Those left in the 50 : 50 mixture for 60 sand 180 s after disappearance of their pedal reflexes, recovered these reflexes in 20·2±0·44 s and 21·5±7·23 s respectively after removal from the gas. Respiration and heart beat ceased in one rat remaining in the 50 : 50 mixture after 13 min 10 s. No untoward effects occurred in rats left in the 50 : 50 mixture for 180 s after disappearance of the pedal reflex, but 2 died when left for an equivalent period in the 80 : 20 mixture. In the third study, examples of the practical use of a 50 : 50 mixture as a short term restraint anaesthetic are described. It was concluded that this mixture was a cheap, safe, and effective means of short-term restraint for rats with subclinical respiratory disease, when the minimal time of exposure to the gases was employed.
Exploring the Influence of Variability on Single-Electron Transistors Into SET-Based Circuits

We analyze the performance of hybrid single-electron transistor (SET)–FET circuits when different variability sources are considered, e.g., SET’s quantum dot location and FET device dimension variations. For the FET device, FinFET and vertical nanowire configurations have been studied. The hybrid SET–FET circuits with both SET and FET in vertical topology depict the best circuit performance and the highest integration level. The variability impact on different SET-based circuits has been analyzed, including negative differential resistance and logic inverters.
Paternal and maternal genetic and environmental contributions to cerebrospinal fluid monoamine metabolites in rhesus monkeys (Macaca mulatta).

BACKGROUND To study genetic and environmental contributions to cerebrospinal fluid (CSF) monoamine concentrations, 55 young rhesus monkeys (Macaca mulatta) were reared apart from their 10 fathers to perform a paternal half-sibling analysis. METHODS To study maternal genetic contributions, 23 infants were reared with their mothers, 23 infants were removed from their mothers at birth and fostered to unrelated lactating female monkeys, and 24 infants were removed from their mothers at birth and reared with age-matched peers. When the monkeys reached age 6 months, CSF samples were obtained via cisternal puncture prior to and during a series of social separations. RESULTS When the results were statistically pooled according to the biological father, comparisons using analysis of variance indicated that both CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) concentrations showed significant heritable (h2) effects (h2 > 0.5) for both sons and daughters, whereas 3-methoxy-4-hydroxyphenylglycol (MHPG) showed a nearly significant paternal genetic effect only for sons (h2 > 0.5). In addition, there were substantial maternal genetic influences on the young monkeys' CSF MHPG and 5-HIAA (h2 > 0.5) levels. Structural equation analyses indicated a maternal genetic contribution without a maternal environmental contribution to CSF 5-HIAA concentration; on the other hand, there was both a maternal genetic and environmental contribution to MHPG. CONCLUSIONS These findings suggest that a significant portion of the variance in the turnover of the monoamine neurotransmitters is determined by genetic mechanisms.
Cultivating Collaborative Data Practices as a Schoolwide Improvement Strategy: A Phase-Based Model of School Leadership Supports

Emphasis on improving student learning has brought increased attention to the execution of schoolwide instructional reforms in general and the use of data by teacher teams in particular as an expected element of a school's instructional reform strategy. With this in mind, the purpose of this article is to focus important attention on the work of school leaders as key developers of collaborative data practices by teacher teams—an area that has received insufficient scholarly attention. Informed by various scholars who have examined organizational change processes and the leadership that underlies organizational changes and drawing from empirical and theoretical data use literature, this article advances a phase-based model of school leadership supports for those tasked with the introduction and cultivation of collaborative data practices in their schools. In so doing, this article provides a testable model for researchers who seek to better understand the work of school leaders in collaborative data contexts. This model should also prove instructive for practicing school leaders as well as those who prepare and develop school leaders.
Potential Benefits of Slow Titration of Paroxetine Treatment in an Elderly Population: Eight-Week Results From a Naturalistic Setting

Background Late-life depression, often in association with anxiety, affects approximately 15% of individuals older than 65 years. Selective serotonin reuptake inhibitors are the first-line treatment but could be responsible of an early exacerbation of anxiety, possibly reduced by a very gradual titration of drugs. The main aim of this study is to compare gradual and rapid (standard) titration of paroxetine in an elderly population. Methods In a naturalistic setting, 50 elderly (≥60 years old) outpatients with unipolar mood disorder or anxiety disorder were naturalistically assigned to abrupt initiation of 10 mg of paroxetine or to a gradual increase with 2.5 mg on alternate days up to 10 mg in 7 days. Then dosage could be maintained at 10 mg or increased according to clinical response. Primary outcome was efficacy as assessed by the Hamilton Depression Rating Scale (HAM-D) 21, HAM-D symptom subscales (core, psychic anxiety, somatic anxiety cluster), and Hamilton Anxiety Rating Scale changes. Secondary outcome was evaluation of overall dropouts at eighth week and evaluation of most common adverse effects through the global judgment of the Dosage Record and Treatment Emergent Symptom Scale. All data were recorded weekly for the first 8 weeks of treatment (with 1 more evaluation after 3 days from the baseline). Results Samples were comparable at baseline, with patients in gradual titration showing a higher level of psychic anxiety. During the first 3 days of treatment, a significant worsening in psychic anxiety was observed in patients treated abruptly with 10 mg of paroxetine (difference in HAM-D psychic anxiety subscale from baseline: 110.61% vs 89.38% with rapid and slow titration, respectively; t test P = 0.03). Overall, a significantly greater improvement in depressive and anxious symptoms favored gradual titration (HAM-D core cluster and HAM-D psychic anxiety cluster, respectively, P = 0.014 and P < 0.001, also when controlling for confounders). At the eighth week, significant higher dropouts in patients administered with abrupt dosage was observed (12.00% vs 40.91%, P = 0.02, respectively for slow and rapid titration). Conclusions Our results suggest that a gradual titration of paroxetine could avoid the initial treatment anxiety worsening and dropout at the beginning of the treatment.