94 research outputs found

    Extradural granulocytic sarcoma causing acute paraparesis

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    A case of 9 years old female presenting with rapidly progressive paraparesis during remission phase of acute myeloblastic leukemia is reported. Radiological imaging revealed an extradural mass in the upper dorsal spine producing significant cord compression. The patient showed a dramatic neurological recovery after spinal cord decompression and subsequently treated with appropriate chemotherapy and local radiotherapy

    Model-based approaches for the detection of biologically active genomic regions from next generation sequencing data

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    Next Generation Sequencing (NGS) technologies are quickly gaining popularity in biomedical research. A popular application of NGS is to detect potential gene regulatory elements that are captured or enriched by certain experimental procedures, for example, Chromatin Immunoprecipitation (ChIP-seq), DNase hypersensitive site mapping (DNase-seq), and Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE-seq), among others. While ChIP-seq can be use to identify protein-DNA interaction sites, both DNase-seq and FAIRE-seq can be used to identify open chromatin regions, which are more likely to contain elements involved in gene expression regulation. We collectively refer to these types of sequencing data as DAE-seq, where DAE stands for DNA After Enrichment. DAE-seq data can provide important insight into gene regulation, which is crucial to understanding the molecular mechanism of phenotypic outcomes, such as complex diseases. Here we address several practical issues facing biomedical researchers in the analysis of DAE-seq data through the development of several new and relevant statistical methods. We first introduce a three-component mixture regression model to discover ``enriched regions, i.e., the genomic regions with more DAE-seq signal than expected in relation to background regions. We demonstrate its practical utility and accuracy in detecting regions of active regulatory elements across a wide range of commonly used DAE-seq datasets and experimental conditions. We then develop a novel Autoregressive Hidden Markov Model (AR-HMM) to account for often-ignored spatial dependence in DAE-seq data, and demonstrate that accounting for such dependence leads to increased performance in identifying biologically active genomic regions in both simulated and real datasets. We also introduce an efficient and novel variable selection procedure in the context of Hidden Markov Models when the means of the emission distributions of each state are modelled with covariates. We study the asymptotic properties of the proposed variable selection procedure and apply this approach to simulated and real DAE-seq data. Lastly, we introduce a new method for the joint analysis of total and allele-specific read counts from DAE-seq data and RNA-seq data. In all, we develop several statistical procedures for the analysis of DAE-seq data that are highly relevant to biomedical researchers and have broader applicability to other problems in statistics.Doctor of Philosoph

    Cerebellopontine angle medulloblastoma

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    Post-traumatic Back Pain Revealed as Tuberculous Spondylitis -A Case Report-

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    Tuberculous spondylitis is a very rare disease, but it can result in bone destruction, kyphotic deformity, spinal instability, and neurologic complications unless early diagnosis and proper management are done. Because the most common symptom of tuberculous spondylitis is back pain, it can often be misdiagnosed. Atypical tuberculous spondylitis can be presented as a metastatic cancer or a primary vertebral tumor. We must make a differential diagnosis through adequate biopsy. A 30-year-old man visited our clinic due to back and chest pain after a recent traffic accident. About 1 year ago, he had successfully recovered from tuberculous pleurisy after taking anti-tuberculosis medication. We performed epidural and intercostal blocks but the pain was not relieved. For the further evaluation, several imaging and laboratory tests were done. Finally, we confirmed tuberculous spondylitis diagnosis with the biopsy results

    Microalgae-based biofuels, resource recovery and wastewater treatment: a pathway towards sustainable biorefinery

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    Intense utilization of natural fuel resources is threatening the global environment and societal sustainability. It triggers up the need for finding environmental-friendly and sustainable sources of energy. In this perspective, microalgae have emerged as a potential alternative. Microalgae are featured with distinct ability to provide ecological services and respond to the sustainability challenges simultaneously. Microalgae can fix atmospheric CO2, valorize waste resources and can produce a wide variety of bio-products. The promising features of microalgae pitch the idea of establishing a sustainable bio-refinery to draw multifaceted benefits and reinforce the objectives of resource efficient bio-economy. Unfortunately, in the last few years, preferential studies have been carried out to assess the potential of microalgae-based integrated bio-refinery. This review critically discussed the recent developments, opportunities, and barriers in the microalgae bio-industry and wastewater treatment. Particularly, microalgae potentials for biofuels and resources recovery are addressed towards sustainable biorefinery. Moreover, techno-economic and commercial viability of microalgae-led bio-refinery is reviewed to drive this technology towards practicality

    Re-examination of siRNA specificity questions role of PICH and Tao1 in the spindle checkpoint and identifies Mad2 as a sensitive target for small RNAs

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    The DNA-dependent adenosine triphosphatase (ATPase) Plk1-interacting checkpoint helicase (PICH) has recently been implicated in spindle checkpoint (SAC) signaling (Baumann et al., Cell 128(1):101–114, 2007). Depletion of PICH by siRNA abolished the SAC and resulted in an apparently selective loss of Mad2 from kinetochores, suggesting a role for PICH in the regulation of the Mad1–Mad2 interaction. An apparent rescue of SAC functionality by overexpression of PICH in PICH-depleted cells initially seemed to confirm a role for PICH in the SAC. However, we have subsequently discovered that all PICH-directed siRNA oligonucleotides that abolish the SAC also reduce Mad2 mRNA and protein expression. This reduction is functionally significant, as PICH siRNA does not abolish SAC activity in a cell line that harbors a bacterial artificial chromosome driving the expression of murine Mad2. Moreover, we identified several siRNA duplexes that effectively deplete PICH but do not significantly affect SAC functionality or Mad2 abundance or localization. Finally, we discovered that the ability of overexpressed PICH to restore SAC activity in PICH-depleted cells depends on sequestration of the mitotic kinase Plk1 rather than ATPase activity of PICH, pointing to an underlying mechanism of “bypass suppression.” In support of this view, depletion or inhibition of Plk1 also rescued SAC activity in cells harboring low levels of Mad2. This observation suggests that a reduction of Plk1 activity partially compensates for reduced Mad2 levels and argues that Plk1 normally reduces the strength of SAC signaling. Collectively, our results question the role of PICH in the SAC and instead identify Mad2 as a sensitive off target for small RNA duplexes. In support of the latter conclusion, our evidence suggests that an off-target effect on Mad2 may also contribute to explain the apparent role of the Tao1 kinase in SAC signaling (Draviam et al., Nat Cell Biol 9(5):556–564, 2007)

    Mass transfer analysis of CO2 capture by PVDF membrane contactor and ionic liquid

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    Post-combustion processes based on ionic liquids (ILs) and membrane contactors are attractive alternatives to traditional systems. Here, a gas stream composed of 15% CO2 and 85% N2 flowed through the lumen side of a hollow-fiber membrane contactor containing poly(vinylidene fluoride)-IL (PVDF-IL) fibers. The IL 1-ethyl-3-methylimidazolium acetate [emim][Ac] served as an absorbent due to its high chemical absorption and CO2 solubility. The overall mass transfer coefficient (Koverall), activation energy (Ea), and resistances of the hollow-fiber membrane were quantified. The Koverall value was one order of magnitude higher than those reported in previous works with conventional solvents, and the Ea was lower than formerly stated values for other solvents. A theoretical simulation was conducted to estimate the operational parameters required for 90% CO2 capture and to quantify intensification effects related to CO2 absorption in a packed column.This research was funded by the Spanish Ministry of Economy and Competitiveness (Projects CTQ2013-48280-C3-1-R and CTQ2016-76231-C2-1-R). The authors thank Dr. J. C. Remigy (Laboratoire de Genie Chimique, UPS, Toulouse, France) for the preparation of 1AQ2-PVDF fibers

    Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

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    Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030
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