Meredith Riber (italylaura3)

A key advantage of pyfastx over other tools is that it offers an efficient way to randomly extract subsequences directly from gzip compressed FASTA/Q files without needing to uncompress beforehand. Pyfastx can easily be installed from PyPI (https//pypi.org/project/pyfastx) and the source code is freely available at https//github.com/lmdu/pyfastx. Intracellular tenofovir diphosphate (TFV-DP) concentration measured in dried blood spots (DBS) is used to monitor cumulative adherence to pre-exposure prophylaxis (PrEP). We evaluated TFV-DP in DBS following daily oral PrEP (emtricitabine 200mg/tenofovir diphosphate 300mg) among pregnant and postpartum adolescent girls and young women (AGYW). Directly observed PrEP was administered for 12 weeks in a pregnancy group (14-24 weeks gestation, n=20) and a postpartum group (6-12 weeks postpartum, n=20) of AGYW aged 16-24 years in sub-Saharan Africa. Weekly DBS TFV-DP was measured by validated liquid chromatography-tandem mass spectrometry assay. Week 12 TFV-DP distributions were compared between groups with the Wilcoxon test. Population pharmacokinetic models were fit to estimate steady-state concentrations and create benchmarks for adherence categories. Baseline correlates of TFV-DP were evaluated. Participant median age was 20 years (IQR19,22). Of 3360 doses, 3352 (>99%) were directly observed. TFV-DP median half-life was ten days (IQR7, 12) in pregnancy and 17 days (IQR14, 21) postpartum, with steady-state achieved by five and eight weeks, respectively. Observed median steady-state TFV-DP was 965fmol/punch (IQR691, 1166) in pregnancy vs 1406fmol/punch (IQR1053, 1859) postpartum (p=0.006). Modelled median steady-state TFV-DP was 881fmol/punch (IQR 667,1105) in pregnancy vs 1438fmol/punch (IQR 1178,1919) postpartum. In pooled analysis, baseline creatinine clearance was associated with observed TFV-DP concentrations. TFV-DP in African AGYW was approximately one-third lower in pregnancy than postpartum. Population-specific benchmarks provided by this study can be used to guide PrEP adherence support in pregnant/postpartum African women. TFV-DP in African AGYW was approximately one-third lower in pregnancy than postpartum. Population-specific benchmarks provided by this study can be used to guide PrEP adherence support in pregnant/postpartum African women.Single-domain antibody fragments known as VHH have emerged in the pharmaceutical industry as useful biotherapeutics. These molecules, which are naturally produced by camelids, share the characteristics of high affinity and specificity with traditional human immunoglobulins, while consisting of only a single heavy chain. Currently, the most common method for generating VHH is via animal immunization, which can be costly and time-consuming. Here we describe the development of a synthetic VHH library for in vitro selection of single domain binders. We combine structure-based design and next-generation sequencing analysis to build a library with characteristics that closely mimic the natural repertoire. To validate the performance of our synthetic library, we isolated VHH against three model antigens (soluble mouse PD-1 ectodomain, amyloid-β peptide, and MrgX1 GPCR) of different sizes and characteristics. We were able to isolate diverse binders targeting different epitopes with high affinity (as high as 5 nM) against all three targets. We then show that anti-mPD-1 binders have functional activity in a receptor blocking assay. The pathogenesis of IgG4-related disease (IgG4-RD) remains unclear. Metabolomic profiling of IgG4-RD patients offers an opportunity to identify novel pathophysiological targets and biomarkers. This study aims to identify potential plasma biomarkers associated with IgG4-RD. Thirty newly diagnosed IgG4-RD patients, age-matched healthy controls and post-treated IgG4-RD patients were enrolled. Patients' clinical data, laboratory parameters and plasma were col