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7× and 43.9 × (>12× on average), respectively, with its CPU implementation, and by up to 413× and 689 × (>400× on average), respectively, with FPGA and GPU acceleration. For long sequences, the CPU implementation of SneakySnake accelerates Parasail and KSW2 (sequence aligner of minimap2) by up to 979 × (276.9× on average) and 91.7 × (31.7× on average), respectively. As SneakySnake does not replace sequence alignment, users can still obtain all capabilities (e.g., configurable scoring functions) of the aligner of their choice, unlike existing acceleration efforts that sacrifice some aligner capabilities. https//github.com/CMU-SAFARI/SneakySnake. Supplementary data is available at Bioinformatics online.Supplementary data is available at Bioinformatics online.Aging in mammals is characterized by failure of the homeostatic mechanisms that regulate energy balance. Several mechanisms have been proposed such as the presence of a low-grade chronic inflammation in different tissues, as well as leptin and insulin resistance, but the primary alteration is not fully elucidated. The gut microbiota has recently emerged as a key player in a variety of metabolic and neurological disorders. A main concept in this context is the gut-brain axis that refers to alterations in the gut that mediate effects in the central nervous system, including those related with the control of energy balance. Using 16S rRNA analysis, we demonstrate that aged male Wistar rats have increased presence of mucin-degrading and lipopolysaccharide (LPS)-producing bacteria. In addition, old animals exhibit a lower number of neutral mucin secreting goblet cells, and a decrease of tight junctions and adeherens junctions marker proteins, zonula occludens protein-1(ZO-1) and β-catenin, respectively. These data are compatible with a thinner mucus layer and a weaker gut barrier in older animals that likely facilitate LPS leakage. Our data also show that cholecystokinin (CCK) satiating effect is impaired in aged rats, one of the expected effects of increased LPS leakage. In contrast, no overt signs of gut or systemic inflammation are observed. Changes in microbiota in old male Wistar rats present features of situations of increased adiposity, but different from those of obese animals. They could partly explain the increased adiposity and fat deposition in liver and heart observed here. Risk of reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed risk and incidence rate of documented SARS-CoV-2 reinfection in a cohort of laboratory-confirmed cases in Qatar. All SARS-CoV-2 laboratory-confirmed cases with at least one PCR positive swab that is ≥45 days after a first-positive swab were individually investigated for evidence of reinfection, and classified as showing strong, good, some, or weak/no evidence for reinfection. https://www.selleckchem.com/products/bay1251152.html Viral genome sequencing of the paired first-positive and reinfection viral specimens was conducted to confirm reinfection. Risk and incidence rate of reinfection were estimated. Out of 133,266 laboratory-confirmed SARS-CoV-2 cases, 243 persons (0.18%) had at least one subsequent positive swab ≥45 days after the first-positive swab. Of these, 54 cases (22.2%) had strong or good evidence for reinfection. Median time between first and reinfection swab was 64.5 days (range 45-129). Twenty-three of the 54 cases (42.6%) were diagnosed at a health facility suggesting presence of symptoms, while 31 (57.4%) were identified incidentally through random testing campaigns/surveys or contact tracing. Only one person was hospitalized at time of reinfection, but was discharged the next day. No deaths were recorded. Viral genome sequencing confirmed four reinfections out of 12 cases with available genetic evidence. Reinfection risk was estimated at 0.02% (95% CI 0.01-0.02%) and reinfection incidence rate at 0.36 (95% CI 0.28-0.47) per 10,000 person-weeks. SARS-CoV-2 reinfection can occur but is a rare phenomenon suggestive of protective immunity against reinfection that lasts for at least a few months post primary infection.SARS-CoV-2 reinfection can occur but is a rare phenomenon suggestive of protective immunity against reinfection that lasts for at least a few months post primary infection. To evaluate the long-term effects on airway in patients with mini-screw-assisted rapid palatal expansion (MARPE), rapid palatal expansion (RPE), and controls with three-dimensional cone-beam computed tomography (CBCT) analysis. A total of 180 CBCTs of 60 patients were analyzed at different time points, such as pretreatment, postexpansion, and posttreatment. Patients were divided into three groups mini-screw assisted rapid palatal expansion (MARPE), rapid palatal expansion (RPE), and controls. The nasal cavity, nasopharyngeal, oropharyngeal, and laryngopharyngeal airway volume and area were measured. Changes in total airway volume, total airway area, minimal cross-sectional area, maxillary intermolar width, external maxillary width, and palatal width were also evaluated. Both MARPE and RPE caused a statistically significant increase in the airway after expansion as compared with the control group, but there was no statistically significant difference in the change in airway between MARPE, RPE, and the co did not correlate with the increase in pharyngeal airway volume. We sought to assess the relationship between retinal nonperfusion area (NPA) on ultra-widefield fluorescein angiography (UWFA) and renal function in type 2 diabetes mellitus (DM) patients with diabetic retinopathy (DR) and nephropathy. UWFA was performed in 248 eyes (124 patients) with DR, comprising 94 eyes from patients with chronic kidney disease (CKD) caused by diabetes and 154 eyes without CKD (non-CKD). Serum creatinine level (Cr), estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio (UACR), and urine protein/creatinine ratio (UPCR) were collected. On UWFA, retinal NPA was measured in an automated manner. link2 The correlation between NPA and renal function was analyzed. The mean NPA value of the total eye was 33.11 ± 45.77-disc diameter (DA) in non-CKD and 100.57 ± 69.52 in CKD (P < 0.001). NPA of posterior pole was 1.21 ± 3.28DA in non-CKD and 7.99 ± 6.75 in CKD group (P < 0.001). The NPA values of both the total eye and posterior pole were significantly correlated with Cr (r = 0.585 and 0.483), eGFR (r = -0.572 and -0.524), UACR (r = 0.541 and 0.482), and UPCR (r = 0.509 and 0.529, respectively) (all P ≤ 0.001). Linear modeling encompassing all clinical factors and relative clinical factors suggested eGFR as the most important predictor for NPAs of the total eye and posterior pole. Larger retinal NPA on UWFA is associated with worse renal function in DM patients. Renal function can be used to predict retinal NPA in type 2 DM patients with nephropathy and DR.Larger retinal NPA on UWFA is associated with worse renal function in DM patients. Renal function can be used to predict retinal NPA in type 2 DM patients with nephropathy and DR. Age-related macular degeneration (AMD) is one of the leading causes of blindness among the elderly, and the exact pathogenesis of the AMD remains unclear. The purpose of this review is to summarize potential metabolic biomarkers and pathways of AMD that might facilitate risk predictions and clinical diagnoses of AMD. We obtained relevant publications of metabolomics studies of human beings by systematically searching the MEDLINE (PubMed) database before June 2020. Studies were included if they performed mass spectrometry-based or nuclear magnetic resonance-based metabolomics approach for humans. In addition, AMD was assessed from fundus photographs based on standardized protocols. The metabolic pathway analysis was performed using MetaboAnalyst 3.0. Thirteen studies were included in this review. Repeatedly identified metabolites including phenylalanine, adenosine, hypoxanthine, tyrosine, creatine, citrate, carnitine, proline, and maltose have the possibility of being biomarkers of AMD. Validation of the biomarker panels was observed in one study. Dysregulation of metabolic pathways involves lipid metabolism, carbohydrate metabolism, nucleotide metabolism, amino acid metabolism, and translation, which might play important roles in the development and progression of AMD. This review summarizes the potential metabolic biomarkers and pathways related to AMD, providing opportunities for the construction of diagnostic or predictive models for AMD and the discovery of new therapeutic targets.This review summarizes the potential metabolic biomarkers and pathways related to AMD, providing opportunities for the construction of diagnostic or predictive models for AMD and the discovery of new therapeutic targets. Tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) activation in Schlemm's canal (SC) endothelium is required for the maintenance of IOP, making the angiopoietin/Tie2 pathway a target for new and potentially disease modifying glaucoma therapies. The goal of the present study was to examine the effects of a Tie2 activator, AKB-9778, on IOP and outflow function. AKB-9778 effects on IOP was evaluated in humans, rabbits, and mice. Localization studies of vascular endothelial protein tyrosine phosphatase (VE-PTP), the target of AKB-9778 and a negative regulator of Tie2, were performed in human and mouse eyes. Mechanistic studies were carried out in mice, monitoring AKB-9778 effects on outflow facility, Tie2 phosphorylation, and filtration area of SC. AKB-9778 lowered IOP in patients treated subcutaneously for diabetic eye disease. In addition to efficacious, dose-dependent IOP lowering in rabbit eyes, topical ocular AKB-9778 increased Tie2 activation in SC endothelium, reduced IOP, and increased outflow facility in mouse eyes. VE-PTP was localized to SC endothelial cells in human and mouse eyes. link3 Mechanistically, AKB-9778 increased the filtration area of SC for aqueous humor efflux in both wild type and in Tie2+/- mice. This is the first report of IOP lowering in humans with a Tie2 activator and functional demonstration of its action in remodeling SC to increase outflow facility and lower IOP in fully developed mice. Based on these studies, a phase II clinical trial is in progress to advance topical ocular AKB-9778 as a first in class, Tie2 activator for treatment for ocular hypertension and glaucoma.This is the first report of IOP lowering in humans with a Tie2 activator and functional demonstration of its action in remodeling SC to increase outflow facility and lower IOP in fully developed mice. Based on these studies, a phase II clinical trial is in progress to advance topical ocular AKB-9778 as a first in class, Tie2 activator for treatment for ocular hypertension and glaucoma. It is currently unclear whether SARS-CoV-2 reinfection will remain a rare event, only occurring in individuals who fail to mount an effective immune response, or whether it will occur more frequently when humoral immunity wanes following primary infection. A case of reinfection was observed in a Belgian nosocomial outbreak involving 3 patients and 2 health care workers. To distinguish reinfection from persistent infection and detect potential transmission clusters, whole genome sequencing was performed on nasopharyngeal swabs of all individuals including the reinfection case's first episode. IgA, IgM, and IgG and neutralizing antibody responses were quantified in serum of all individuals, and viral infectiousness was measured in the swabs of the reinfection case. Reinfection was confirmed in a young, immunocompetent health care worker as viral genomes derived from the first and second episode belonged to different SARS-CoV-2 clades. The symptomatic reinfection occurred after an interval of 185 days, despite the development of an effective humoral immune response following symptomatic primary infection.
