Lidam1087
The new coronavirus, which began to be called SARS-CoV-2, is a single-stranded RNA beta coronavirus, initially identified in Wuhan (Hubei province, China) and currently spreading across six continents causing a considerable harm to patients, with no specific tools until now to provide prognostic outcomes. Thus, the aim of this study is to evaluate possible findings on chest CT of patients with signs and symptoms of respiratory syndromes and positive epidemiological factors for COVID-19 infection and to correlate them with the course of the disease. In this sense, it is also expected to develop specific machine learning algorithm for this purpose, through pulmonary segmentation, which can predict possible prognostic factors, through more accurate results. Our alternative hypothesis is that the machine learning model based on clinical, radiological and epidemiological data will be able to predict the severity prognosis of patients infected with COVID-19. We will perform a multicenter retrospective longitudinal cy; 6) Death. We will use the AUC and F1-score of these algorithms as the main metrics, and we hope to identify algorithms capable of generalizing their results for each specified primary and secondary outcome.The piRNA pathway is a highly conserved mechanism to repress transposon activation in the germline in Drosophila and mammals. This pathway starts from transcribing piRNA clusters to generate long piRNA precursors. The majority of piRNA clusters lack conventional promoters, and utilize heterochromatin- and HP1D/Rhino-dependent noncanonical mechanisms for transcription. However, information regarding the transcriptional regulation of piRNA clusters is limited. Here, we report that the Drosophila acetyltransferase Enok, which can activate transcription by acetylating H3K23, is critical for piRNA production from 54% of piRNA clusters including 42AB, the major piRNA source. Surprisingly, we found that Enok not only promotes rhino expression by acetylating H3K23, but also directly enhances transcription of piRNA clusters by facilitating Rhino recruitment. Taken together, our study provides novel insights into the regulation of noncanonical transcription at piRNA clusters and transposon silencing.RNA structures are dynamic. As a consequence, mutational effects can be hard to rationalize with reference to a single static native structure. We reasoned that deep mutational scanning experiments, which couple molecular function to fitness, should capture mutational effects across multiple conformational states simultaneously. Here, we provide a proof-of-principle that this is indeed the case, using the self-splicing group I intron from Tetrahymena thermophila as a model system. We comprehensively mutagenized two 4-bp segments of the intron. These segments first come together to form the P1 extension (P1ex) helix at the 5' splice site. Following cleavage at the 5' splice site, the two halves of the helix dissociate to allow formation of an alternative helix (P10) at the 3' splice site. Using an in vivo reporter system that couples splicing activity to fitness in E. coli, we demonstrate that fitness is driven jointly by constraints on P1ex and P10 formation. We further show that patterns of epistasis can be used to infer the presence of intramolecular pleiotropy. Using a machine learning approach that allows quantification of mutational effects in a genotype-specific manner, we demonstrate that the fitness landscape can be deconvoluted to implicate P1ex or P10 as the effective genetic background in which molecular fitness is compromised or enhanced. Our results highlight deep mutational scanning as a tool to study alternative conformational states, with the capacity to provide critical insights into the structure, evolution and evolvability of RNAs as dynamic ensembles. Our findings also suggest that, in the future, deep mutational scanning approaches might help reverse-engineer multiple alternative or successive conformations from a single fitness landscape.Many viral infections can be prevented by immunizing with live, attenuated vaccines. Early methods of attenuation were hit-and-miss, now much improved by genetic engineering. However, even current methods operate on the principle of genetic harm, reducing the virus's ability to grow. Reduced viral growth has the undesired side-effect of reducing the host immune response below that of infection with wild-type. Might some methods of attenuation instead lead to an increased immune response? We use mathematical models of the dynamics of virus with innate and adaptive immunity to explore the tradeoff between attenuation of virus pathology and immunity. We find that modification of some virus immune-evasion pathways can indeed reduce pathology yet enhance immunity. Thus, attenuated vaccines can, in principle, be directed to be safe yet create better immunity than is elicited by the wild-type virus.Lyme disease, which is caused by infection with Borrelia burgdorferi and related species, can lead to inflammatory pathologies affecting the joints, heart, and nervous systems including the central nervous system (CNS). Inbred laboratory mice have been used to define the kinetics of B. burgdorferi infection and host immune responses in joints and heart, however similar studies are lacking in the CNS of these animals. A tractable animal model for investigating host-Borrelia interactions in the CNS is key to understanding the mechanisms of CNS pathogenesis. Therefore, we characterized the kinetics of B. burgdorferi colonization and associated immune responses in the CNS of mice during early and subacute infection. Using fluorescence-immunohistochemistry, intravital microscopy, bacterial culture, and quantitative PCR, we found B. burgdorferi routinely colonized the dura mater of C3H mice, with peak spirochete burden at day 7 post-infection. Dura mater colonization was observed for several Lyme disease agents inctial mechanisms of CNS pathology associated with this important pathogen.Ethanol is a widely used drug, excessive consumption of which could lead to medical conditions with diverse symptoms. Ethanol abuse causes dysfunction of memory, attention, speech and locomotion across species. Dopamine signaling plays an essential role in ethanol dependent behaviors in animals ranging from C. elegans to humans. We devised an ethanol dependent assay in which mutants in the dopamine autoreceptor, dop-2, displayed a unique sedative locomotory behavior causing the animals to move in circles while dragging the posterior half of their body. Here, we identify the posterior dopaminergic sensory neuron as being essential to modulate this behavior. We further demonstrate that in dop-2 mutants, ethanol exposure increases dopamine secretion and functions in a DVA interneuron dependent manner. DVA releases the neuropeptide NLP-12 that is known to function through cholinergic motor neurons and affect movement. Thus, DOP-2 modulates dopamine levels at the synapse and regulates alcohol induced movement through NLP-12.
Bothrops asper represents the clinically most important snake species in Central America and Northern South America, where it is responsible for an estimated 50-80% of snakebites. Compositional variability among the venom proteomes of B. asper lineages across its wide range mirrors clinical differences in their envenomings. Bothropic antivenoms generated in a number of Latin American countries commonly exhibit a certain degree of paraspecific effectiveness in the neutralization of congeneric venoms. Defining the phylogeographic boundaries of an antivenom's effectivity has implications for optimizing its clinical use. However, the molecular bases and impact of venom compositions on the immune recognition and neutralization of the toxic activities of across geographically disparate populations of B. asper lineages has not been comprehensively studied.
Third-generation antivenomics was applied to quantify the cross-immunorecognizing capacity against the individual components of venoms of three B. TLR agonist asper lineat comparing the preclinical profile of a panel of Latin American homologous and heterologous antivenoms against the venoms of B. asper lineages distributed in SW Colombia. The outcome of this study strongly suggests the suitability of considering the heterologous antivenoms BIOL (Argentina), UCV (Venezuela) and INS-PERU (Perú) as alternatives to homologous Colombian INS-COL and PROBIOL and Costa Rican ICP antivenoms for the treatment of envenomings by B. asper (sensu stricto) in W Colombia and Ecuador, B. ayerbei in Cauca and Nariño (Colombia), and B. rhombeatus in Cauca river valley, SW Colombia.In the present study, we developed a computational method and panel markers to assess microsatellite instability (MSI) using a targeted next-generation sequencing (NGS) platform and compared the performance of our computational method, mSILICO, with that of mSINGS to detect MSI in CRCs. We evaluated 13 CRC cell lines, 84 fresh and 119 formalin-fixed CRC tissues (including 61 MSI-high CRCs and 155 microsatellite-stable CRCs) and tested the classification performance of the two methods on 23, 230, and 3,154 microsatellite markers. For the fresh tissue and cell line samples, mSILICO showed a sensitivity of 100% and a specificity of 100%, regardless of the number of panel markers, whereas for the formalin-fixed tissue samples, mSILICO exhibited a sensitivity of up to 100% and a specificity of up to 100% with three differently sized panels ranging from 23 to 3154. These results were similar to those of mSINGS. With the application of mSILICO, the small panel of 23 markers had a sensitivity of ≥95% and a specificity of 100% in cell lines/fresh tissues and formalin-fixed tissues of CRC. In conclusion, we developed a new computational method and microsatellite marker panels for the determination of MSI that does not require paired normal tissues. A small panel could be integrated into the targeted NGS panel for the concurrent analysis of single nucleotide variations and MSI.
Regional anesthesia offers an alternative to general anesthesia and may be advantageous in low resource environments. There is a paucity of data regarding the practice of regional anesthesia in low- and middle-income countries. Using access data from a free Android app with curated regional anesthesia learning modules, we aimed to estimate global interest in regional anesthesia and potential applications to clinical practice stratified by World Bank income level.
We retrospectively analyzed data collected from the free Android app "Anesthesiologist" from December 2015 to April 2020. The app performs basic anesthetic calculations and provides links to videos on performing 12 different nerve blocks. Users of the app were classified on the basis of whether or not they had accessed the links. Nerve blocks were also classified according to major use (surgical block, postoperative pain adjunct, rescue block).
Practitioners in low- and middle-income countries accessed the app more frequently than in high-income countries as measured by clicks. Users from low- and middle-income countries focused mainly on surgical blocks ankle, axillary, infraclavicular, interscalene, and supraclavicular blocks. In high-income countries, more users viewed postoperative pain blocks adductor canal, popliteal, femoral, and transverse abdominis plane blocks. Utilization of the app was constant over time with a general decline with the start of the COVID-19 pandemic.
The use of an in app survey and analytics can help identify gaps and opportunities for regional anesthesia techniques and practices. This is especially impactful in limited-resource areas, such as lower-income environments and can lead to targeted educational initiatives.
The use of an in app survey and analytics can help identify gaps and opportunities for regional anesthesia techniques and practices. This is especially impactful in limited-resource areas, such as lower-income environments and can lead to targeted educational initiatives.
