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73; 95% CI, 3.10 to 19.33, P = 6.14E-05) when comparing age and gender and ethnicity-matched controls tested on the same platform. selleck kinase inhibitor The overall uptake rate for index testing was 59.2% and was significantly higher with 1-on-1 consultations and group consultations compared to telehealth consultations (88.9% vs 82.9% vs 61.8%, P less then .001). CONCLUSION In a prospective clinic-based cohort of patients with PDAC referred for testing irrespective of family history, germline PV were detected in 14.1%. PV in ATM accounted for half of all PVs and were significantly associated with PDAC. These findings support recent guidelines and will guide future service planning in this population. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.The father's involvement in childrearing can positively influence health outcomes not only for the man himself but also for his partner and their children. However, the experience of first-time fatherhood is limited in Chinese communities. The aim of this study is to explore men's experience of first-time fatherhood and coping in Hong Kong. An exploratory qualitative design was used. A purposive sample of 44 first-time Chinese fathers who had participated in a couple-based cognitive-behavioral intervention for postnatal depression were recruited for telephone interviews at 1-3 months postpartum. Data were collected by a semistructured interview guide and analyzed using thematic analysis. The process involved in men's transition to first-time fatherhood reveals four major themes changes in daily life, new paternal roles and responsibilities, availability of resources to enhance adaptation, and coping strategies. The findings have implications for health care professionals and policy-makers in the provision of comprehensive perinatal care and family-friendly policies to aid men's transition to first-time fatherhood in Chinese communities. © 2020 John Wiley & Sons Australia, Ltd.6-Methylpurine (MeP) is a cytotoxic adenine analog that does not exhibit selectivity when administered systemically and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli purine nucleoside phosphorylase (PNP). 9-(6-Deoxy-β-D-allofuranosyl)-6-methylpurine [methyl(allo)-MePR, 18] and 9-(6-deoxy-α-L-talofuranosyl)-6-methylpurine [methyl(talo)-MePR, 21] were synthesized as potential prodrugs for MeP in the E. coli PNP/prodrug cancer gene therapy approach. The detailed syntheses of [methyl(allo)-MePR] and [methyl(talo)-MePR] are described. The glycosyl donors, 1,2-di-O-acetyl-3,5-di-O-benzyl-α-D-allofuranose (12) and 1-O-acetyl-3-O-benzyl-2,5-di-O-benzoyl-α-L-talofuranose (16) were prepared from 1,25,6-di-O-isopropylidene-α-D-glucofuranose (4) in nine and eleven steps, respectively. Vorbrüggen coupling of the latter glycosyl donors with 6-methylpurine (3), followed by deprotection of the sugar hydroxyl groups, gave the title compounds in good overall yields. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1 Preparation of 6-methylpurine Basic Protocol 2 Preparation of the D-allofuranose derivative (12) Basic Protocol 3 Preparation of 6-deoxy-α-L-talofuranoside Basic Protocol 4 Preparation of methyl(allo)-MePR (18) Basic Protocol 5 Preparation of methyl(talo)-MePR (21).Translation of transplanted alginate-encapsulated pancreatic islets to treat type 1 diabetes has been hindered by inconsistent long-term efficacy. This loss of graft function can be partially attributed to islet dysfunction associated with the destruction of extracellular matrix (ECM) interactions during the islet isolation process as well as immunosuppression-associated side effects. This study aims at recapitulating islet-ECM interactions by the direct functionalization of alginate with the ECM-derived peptides RGD, LRE, YIGSR, PDGEA, and PDSGR. Peptide functionalization is controlled in a concentration-dependent manner and its presentation is found to be homogeneous across the microcapsule environment. Preweaned porcine islets are encapsulated in peptide-functionalized alginate microcapsules, and those encapsulated in RGD-functionalized alginate displays enhanced viability and glucose-stimulated insulin release. Effects are RGD-specific and not observed with its scrambled control RDG nor with LRE, YIGSR, PDGEA, and PDSGR. This study supports the sustained presentation of ECM-derived peptides in helping to maintain health of encapsulated pancreatic islets and may aid in prolonging longevity of encapsulated islet grafts. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The genomes of DNA viruses encode deceptively complex transcriptomes evolved to maximize coding potential within the confines of a relatively small genome. Defining the full range of viral RNAs produced during an infection is key to understanding the viral replication cycle and its interactions with the host cell. Traditional short-read (Illumina) sequencing approaches are problematic in this setting due to the difficulty of assigning short reads to individual RNAs in regions of transcript overlap and to the biases introduced by the required recoding and amplification steps. Additionally, different methodologies may be required to analyze the 5' and 3' ends of RNAs, which increases both cost and effort. The advent of long-read nanopore sequencing simplifies this approach by providing a single assay that captures and sequences full length RNAs, either in cDNA or native RNA form. The latter is particularly appealing as it reduces known recoding biases whilst allowing more advanced analyses such as estimation of poly(A) tail length and the detection of RNA modifications including N6 -methyladenosine. Using herpes simplex virus (HSV)-infected primary fibroblasts as a template, we provide a step-by-step guide to the production of direct RNA sequencing libraries suitable for sequencing using Oxford Nanopore Technologies platforms and provide a simple computational approach to deriving a high-quality annotation of the HSV transcriptome from the resulting sequencing data. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1 Productive infection of primary fibroblasts with herpes simplex virus Support Protocol Cell passage and plating of primary fibroblasts Basic Protocol 2 Preparation and sequencing of dRNA-seq libraries from virus-infected cells Basic Protocol 3 Processing, alignment, and analysis of dRNA-seq datasets.