Bartlettmunoz4429

Evaluate the efficacy of guselkumab for the treatment of active psoriatic arthritis (PsA) utilizing composite indices.

Data were pooled from the Phase 3 DISCOVER-1 (N = 381) and DISCOVER-2 (N = 739) studies. In both studies, patients were randomized 111 to subcutaneous guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, then Q8W; or placebo Q4W with crossover to guselkumab 100 mg Q4W at week 24. Composite indices used to assess efficacy through week 52 included Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), minimal disease activity (MDA), and very low disease activity (VLDA). Through week 24, treatment failure rules were applied. Through week 52, non-responder imputation was used for missing data.

Greater proportions of guselkumab- than placebo-treated patients achieved DAPSA low disease activity (LDA) and remission, PASDAS LDA and VLDA, MDA, and VLDA at week 24 vs placebo (all unadjusted p< 0.05). At week 52, in the guselkumab Q4W and Q8W groups, respectively, response rates were as follows DAPSA LDA, 54.2% and 52.5%; DAPSA remission, 18.2% and 17.6%; PASDAS LDA, 45.3% and 41.9%; PASDAS VLDA, 16.9% and 19.5%; MDA, 35.9% and 30.7%; and VLDA, 13.1% and 14.4%. In the placebo-crossover-to-guselkumab group, response rates for all composite indices increased after patients switched to guselkumab, from week 24 through week 52.

Treatment with guselkumab provided robust and sustained benefits across multiple PsA domains through 1 year, indicating that guselkumab is an effective therapy for the diverse manifestations of PsA.

NCT03162796; NCT03158285.

NCT03162796; NCT03158285.

Assess the proportion of myeloid derived suppressor cells (MDSC), their expression of arginase-1 and PD-L1, and their relationship with the clinical phenotype of patients with idiopathic inflammatory myopathies (IIM).

We recruited 37 IIM adult patients and 10 healthy donors in Mexico City. We evaluated their clinical features, the proportion of MDSC and their expression of PD-L1 and arginase-1 by flow cytometry. Polymorphonuclear (PMN)-MDSC were defined as CD33int, CD11b+ and CD66b+ whilst monocytic (M)-MDSC were CD33+, CD11b+, HLA-DR- and CD14+. Serum cytokines were analyzed with a multiplex assay. We compared the quantitative variables with the Kruskal-Wallis and Mann-Whitney U tests and assessed correlations with Spearman Rho.

Most patients had dermatomyositis (N = 30, 81.0%). IIM patients had a peripheral expansion of PMN-MDSC, and M-MDSC with an enhanced expression of arginase-1 and PD-L1. Patients with active disease had a decreased percentage (1.75% (0.31-5.50 vs 10.71 (3.16-15.58), p= 0.011) of M-MDSC, higher absolute number of PD-L1+ M-MDSC (23.21 cells/mm3 (11.16-148.9) vs 5.95 (4.66-102.7), p= 0.046) with increased expression of PD-L1 (3136 arbitrary units (2258-4992) vs 1961 (1885-2335), p= 0.038). PD-L1 expression in PMN-MDSC correlated with the visual analogue scale (VAS) of pulmonary disease activity (R = 0.34, p= 0.040), and damage (R = 0.36, p= 0.031), serum IL-5 (R = 0.55, p= 0.003), IL-6 (R = 0.46, p= 0.003), IL-8 (R = 0.53, p= 0.018), IL-10 (R = 0.48, p= 0.005) and GM-CSF (R = 0.48, p= 0.012). M-MDSC negatively correlated with the skeletal MITAX (R=-0.34, p= 0.038) and positively with IL-6 (R = 0.40, p= 0.045).

MDSC expressing arginase-1 and PD-L1 are expanded in IIM and correlate with disease activity, damage accrual and serum cytokines.

MDSC expressing arginase-1 and PD-L1 are expanded in IIM and correlate with disease activity, damage accrual and serum cytokines.Microarray-based techniques are an important testing method in etiological studies of intellectual disability and autism spectrum disorder. Interstitial deletion in the p11-p12 region of chromosome 10 is rare, having been reported in just 12 cases to date. Intellectual disability associated with the WAC gene in this region is referred to as DeSanto-Shinawi syndrome . Although all individuals with p11-p12 region of chromosome 10 deletion share a common phenotype involving intellectual disability and dysmorphic features, individuals with DeSanto-Shinawi syndrome usually do not experience the cardiac and neurologic abnormalities or cryptorchidism associated with a 10p11-p12 deletion. With this case report, we aim to expand the phenotypic spectrum of 10p11-p12 deletion. Our patient was a 9-year-old boy with intellectual disability, autism symptoms, dysmorphic features, and behavioral abnormalities. He had no cardiac problems or neurologic symptoms such as hypotonia, feeding difficulties, or seizures. However, he presented cryptorchidism in addition to symptoms that are consistent with DeSanto-Shinawi syndrome. Array comparative genomic hybridization of genomic DNA isolated from a peripheral blood sample revealed a heterozygous deletion in 10p11.23-p12.1, which contains the WAC gene. We discuss our case in the context of a literature review of candidate genes. It is still difficult to establish genotype-phenotype correlations for neurologic, cardiac, and visual symptoms, and cryptorchidism, in individuals with a 10p11-p12 deletion. As more individuals are diagnosed with deletion in this chromosomal region, the associated phenotypes will become clearer.

MinION, a third-generation sequencer from Oxford Nanopore Technologies, is a portable device that can provide long-nucleotide read data in real-time. It primarily aims to deduce the makeup of nucleotide sequences from the ionic current signals generated when passing DNA/RNA fragments through nanopores charged with a voltage difference. To determine nucleotides from measured signals, a translation process known as basecalling is required. However, compared to NGS basecallers, the calling accuracy of MinION still needs to be improved.

In this work, a simple but powerful neural network architecture called multi-scale recurrent caller (MSRCall) is proposed. MSRCall comprises a multi-scale structure, recurrent layers, a fusion block and a connectionist temporal classification decoder. To better identify both short-and long-range dependencies, the recurrent layer is redesigned to capture various time-scale features with a multi-scale structure. The results show that MSRCall outperforms other basecallers in terms of both read and consensus accuracies.

MSRCall is available at https//github.com/d05943006/MSRCall.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.Pathogenic infections may lead to disruption of homeostasis, thus becoming a serious threat to the human health. Understanding the interactions between bacteria and macrophages is critical for therapeutic development against sepsis or inflammatory bowel disease. Here, we report a technique using droplet biosensors for the detection of nitric oxide (NO) secreted by a single macrophage under inflammatory stimuli. We demonstrated that the limit of detection can be promoted more than two orders of magnitude by our approach, in comparison to the conventional microplate format. The experiments of co-encapsulating single macrophages and different numbers of Escherichia coli (E. coli) enabled fluorescence monitoring of NO secretion by single macrophages over the incubation, and investigation of their interactions inside the isolated droplet for their separate fates. Our approach provides a unique platform to study the bacteria-macrophage interactions at the single cell level.

Hydroxychloroquine (HCQ) and azathioprine (AZA) are used to control disease activity and reduce risk of flare during pregnancy in patients with SLE. The aim of this study was to determine outcomes of children born to mothers with SLE exposed to HCQ or AZA during pregnancy and breast-feeding.

Women attending UK specialist lupus clinics with children ≤17 years old, born after SLE diagnosis, were recruited to this retrospective study. Data were collected using questionnaires and from clinical record review. Factors associated with the outcomes of low birth weight and childhood infection were determined using multivariable mixed effects logistic regression models.

We analysed 284 live births of 199 mothers from 10 UK centres. The first pregnancies of 147/199 (73.9%) mothers was captured in the study. 150/248 (60.4%) and 87 (31.1%) children were exposed to HCQ and AZA respectively. There were no significant differences in the frequency of congenital malformations or intrauterine growth restriction (IUGR) between children exposed or not to HCQ or AZA. Nedisertib AZA use was increased in women with a history of hypertension or renal disease. Although AZA was associated with low birth weight in univariate models, there was no significant association in multivariable models. In adjusted models, exposure to AZA was associated with increased reports of childhood infection requiring hospital management (OR 2.283 [1.003, 5.198], p= 0.049).

There were no significant negative outcomes in children exposed to HCQ in pregnancy. AZA use was associated with increased reporting of childhood infection which warrants further study.

There were no significant negative outcomes in children exposed to HCQ in pregnancy. AZA use was associated with increased reporting of childhood infection which warrants further study.

Fecal microbiota transplantation (FMT) has been investigated as a treatment option for patients with inflammatory bowel disease with controversial results.We sought to perform a systematic review and meta-analysis to evaluate the benefit of FMT in patients with ulcerative colitis.

Double-blind randomized controlled trials (RCTs) including adult patients with active ulcerative colitis who received either FMT or placebo were eligible for inclusion. Outcomes of interest included the rate of combined clinical and endoscopic remission, endoscopic remission or response, clinical remission or response, and specific adverse events. The results were pooled together using Reviewer Manager 5.4 software. Publication bias was assessed using the Egger's test.

Six RCTs involving 324 patients were included. Our findings demonstrate that compared with placebo, FMT has significant benefit in inducing combined clinical and endoscopic remission (odds ratio, 4.11; 95% confidence interval, 2.19-7.72; P < .0001). Subgroup o. Future RCTs are required to standardize study protocols and examine data on maintenance therapy.

In upper-income countries, infants undergo low-risk ventricular septal defect (VSD) repair. Children in low- and middle-income countries frequently present at older ages with elevated pulmonary vascular resistance (PVR) and pulmonary arterial hypertension (PAH). Expensive interventions for pulmonary hypertensive crisis are not available, and children are often denied an operation due to the mortality risk. We report our early and late experiences with these patients who underwent VSD closure by traditional patch (TP) or double patch (DP) techniques.

We extracted data from patients with VSD and PAH who underwent VSD closure operations from 1996 to 2016. Information regarding cardiac catheterizations, operations, time in the intensive care unit and follow-up information was found. We identified 129 children and analysed the differences between the TP (89/129) and the DP (40/129) in unidirectional groups. After 2005, the patients were pretreated with sildenafil 3 months before catheterization.

The TP group was younger (P  < 0.