Lambertsenruiz3249

DNA sequencing technologies provide unprecedented opportunities to analyze within-host evolution of microorganism populations. Often, within-host populations are analyzed via pooled sequencing of the population, which contains multiple individuals or "haplotypes." However, current next-generation sequencing instruments, in conjunction with single-molecule barcoded linked-reads, cannot distinguish long haplotypes directly. Computational reconstruction of haplotypes from pooled sequencing has been attempted in virology, bacterial genomics, metagenomics, and human genetics, using algorithms based on either cross-host genetic sharing or within-host genomic reads. Here, we describe PoolHapX, a flexible computational approach that integrates information from both genetic sharing and genomic sequencing. We demonstrated that PoolHapX outperforms state-of-the-art tools tailored to specific organismal systems, and is robust to within-host evolution. Importantly, together with barcoded linked-reads, PoolHapX can infer whole-chromosome-scale haplotypes from 50 pools each containing 12 different haplotypes. By analyzing real data, we uncovered dynamic variations in the evolutionary processes of within-patient HIV populations previously unobserved in single position-based analysis.

NRF2 and its effectors NAD(P)Hquinoneoxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) are of interest in kidney disease. We therefore reviewed studies about their status in patients with chronic kidney disease (CKD).

We undertook systematic searches of PubMed and EMBASE databases. Alterations of NRF2, NQO1 and HO-1 in CKD, their responses to interventions and their relation to clinically relevant parameters were reported.

We identified 1373 articles, of which 32 studies met the inclusion criteria. NRF2 levels were decreased in the majority of analyses of CKD patients. Half of the analyses showed a similar or increased NQO1 level vs. control, whereas NQO1 was decreased in half of the analyses. Most of the studies reported either an increased or similar HO-1 level in CKD patients compared to controls. For patients with CKD stages 1-4, studies reported positive correlations to markers of kidney disease severity. Also, positive associations of NQO1/HO-1 levels to inflammation and comorbidities were repornical studies of high quality. Research on gene expression together with protein analyses is indispensable to understand NRF2 system alterations in CKD.

Atacicept reduced SLE disease activity in the Phase IIb ADDRESS II study, particularly in patients with high disease activity (HDA; SLEDAI-2K ≥10) at screening. We assessed long-term safety and efficacy of atacicept in the long-term extension (LTE) of ADDRESS II.

In the 24-week, randomised, double-blind, placebo-controlled ADDRESS II study, patients received weekly atacicept (75 or 150 mg) or placebo. Atacicept was continued at the same dose in atacicept-treated patients in the LTE; placebo-treated patients switched to atacicept 150 mg. Long-term safety was the primary end point. Secondary endpoints included SLE responder index (SRI)-4 and SRI-6 response rates and flares.

253 patients entered the ADDRESS II LTE; 88 received atacicept 150 mg, 82 atacicept 75 mg and 83 placebo/atacicept 150 mg. Median active treatment duration in the LTE was 83.8 weeks. Frequencies of treatment-emergent adverse events (TEAEs) were similar across groups (90.4-93.2%). 12.5%, 14.6% and 21.7% of patients in the atacicept 150 mg, atacicept 75 mg and placebo/atacicept 150 mg groups reported serious TEAEs during the treatment period. The proportions of patients with TEAEs leading to discontinuation were 5.7%, 4.9% and 10.8%, respectively. SRI-4 and SRI-6 response rates were maintained with atacicept in the modified intent-to-treat and HDA populations and those on continuous 150 mg had a reduced risk of first severe flare and longer time to first severe flare vs those who initially received placebo.

Long-term treatment with atacicept 150 mg in SLE patients had an acceptable safety profile, with durable efficacy.

NCT02070978.

NCT02070978.To understand the effect of fluctuating temperature on the population characteristics of Tetranychus pacificus, we determined their life tables under constant temperatures between 10 and 35°C and fluctuating temperatures (12 h per day at each of 5°C above and 5°C below the corresponding constant temperature). Tetranychus pacificus eggs did not hatch when held at a constant temperature of 10°C, whereas 77.6% of the T. pacificus eggs reached an adult life stage at fluctuating temperature 10°C ± 5°C. Female preadult development was faster under fluctuating temperatures 12.5, 15, and 20°C than under constant temperatures, whereas it was not significantly different at temperatures ≥ 22.5°C. The lower developmental thresholds (T0) for female preadult development were 10.24 and 5.73°C for the constant and fluctuating temperatures, respectively, while the thermal summations (K) were 215.10 and 265.64 degree days, respectively. The net reproductive rates (R0) at constant temperatures 15 and 35°C were significantly higher than those at the corresponding fluctuating temperatures. However, for 20, 25, and 30°C, the R0 values were not significantly different between constant and fluctuating temperatures. The intrinsic rate of increase (r) and finite rate of increase (λ) at fluctuating temperatures 10, 20, and 30°C were higher compared to the corresponding constant temperature. However, the values of r and λ at constant 25 and 35°C were higher than those at fluctuating temperature. The differential responses of life history between constant and fluctuating temperatures help to understand the population dynamics of T. pacificus under natural conditions.We review some of the current insights derived from the analyses of new large-scale, genome-wide autosomal variation data studies incorporating Ethiopians. Consistent with their substantial degree of cultural and linguistic diversity, genetic diversity among Ethiopians is higher than that seen across much larger geographic regions worldwide. This genetic variation is associated in part with ethnic identity, geography and linguistic classification. Numerous and varied admixture events have been inferred in Ethiopian groups, for example, involving sources related to present-day groups in West Eurasia and North Africa, with inferred dates spanning a few hundred to more than 4500 years ago. These disparate inferred ancestry patterns are correlated in part with groups' broad linguistic classifications, though with some notable exceptions. While deciphering these complex genetic signals remains challenging with available data, these studies and other projects focused on resolving competing hypotheses on the origins of specific ethnolinguistic groups demonstrate how genetic analyses can complement findings from anthropological and linguistic studies on Ethiopians.

To assess the association of severe pulmonary arterial hypertension (PAH) with particulate matter <2.5 μm (PM2.5) and clinical data in patients with systemic autoimmune rheumatic diseases (SARDs).

We used the 2003-2017 nationwide data in Taiwan to identify patients with SARDs, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, dermatomyositis/polymyositis and primary Sjögren's syndrome. We identified 479 cases with severe PAH and selected controls matched (14) for age, sex, and index-year. We used conditional logistic regression analysis to determine factors associated with risks for severe PAH shown as odds ratios (ORs) with 95% confidence intervals (CIs).

We found that severe PAH was highly associated with interstitial lung disease (OR, 8.57; 95% CI, 5.52-13.32), congestive heart failure (OR, 7.62; 95% CI, 5.02-11.55), valvular heart disease (OR, 3.34; 95% CI, 2.03-5.50) and slightly associated with thyroid diseases (OR, 1.88; 95% CI, 1.18-3.00), but not the level of exposure to PM2.5. Increased risk for PAH was found in patients receiving corticosteroid (prednisolone equivalent dosage, mg/day, OR, 1.03; 95% CI, 1.01-1.05), biologics (OR, 2.18; 95% CI, 1.15-4.12) as well as immunosuppressants, including cyclosporin (OR, 2.17; 95% CI, 1.31-3.59), azathioprine (OR, 1.96; 95% CI, 1.48-2.61), cyclophosphamide (OR, 2.01; 95% CI, 1.30-3.11) and mycophenolate mofetil/mycophenolic acid (OR, 2.42; 95% CI, 1.37-4.27), and those with the highest level of insured amount (reference, lowest level; OR, 0.53; 95% CI, 0.34-0.83).

The population-based study identified risks for severe PAH in patients with SARDs, and these findings provide evidence for PAH risk stratification in patients with SARDs.

The population-based study identified risks for severe PAH in patients with SARDs, and these findings provide evidence for PAH risk stratification in patients with SARDs.A 70-year-old female patient treated with methotrexate for diffuse cutaneous systemic sclerosis (SSc) came up with mechanical pain over the left thumb for several months. SSc was diagnosed based on a clinical picture associating puffy fingers, skin sclerosis, wrist arthralgia, pulmonary hypertension, presence of antinuclear factors and antibodies against Topoisomerase-I. Her complaint was attributed to first carpometacarpal joint osteoarthritis and treated with orthesis, which did not provide pain relief after 5 months of regular use. Hand radiograph showed first carpometacarpal arthropathy with joint space narrowing and marked sclerosis of the first proximal metacarpal (A). MRI showed an area of very low signal intensity on T1- and T2-weighted images (B) within the proximal metacarpal, distal trapezium and medial joint recess surrounded by bone marrow edema. Mild peripheral enhancement was present after gadolinium injection. CT-scan (C) showed that the low signal intensity material visible at MRI consisted of calcium. These aspects are suggestive of scleroderma arthropathy rather than common first carpometacarpal osteoarthritis. Though involvement of the first carpometacarpal joint is long time known in SSc [1], it remains exceptional when looking at cross-sectional studies [2]. Carefully analyzing imaging exams is the key point in order not to miss this rare scleroderma feature.

To assess the relationships between female hormonal exposures and risk of rheumatoid arthritis (RA), in a prospective cohort of French women.

E3N is an on-going French prospective cohort that included 98 995 women aged 40-65 years in 1990. Every 2-3 years, women completed mailed questionnaires on their lifestyles, reproductive factors, and health conditions. Cox proportional-hazards regression models were used to determine factors associated with risk of incident RA, with age as the time scale, adjusted for known risk factors of RA, and considering endogenous and exogenous hormonal factors. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. Effect modification by smoking history was investigated.

A total of 698 incident cases of RA were ascertained among 78 452 women. In multivariable-adjusted Cox regression models, risk of RA was increased with early age at first pregnancy (<22 vs ≥27 years; HR = 1.34; 95%CI 1.0-1.7) and menopause (≤45 vs ≥53 years; HR = 1.40; 95%CI 1.0-1.9). For early menopause, the association was of similar magnitude in ever and never smokers, although the association was statistically significant only in ever smokers (HR = 1.