Patients diagnosed with chromosome microdeletions or duplications, known as copy number variants (CNVs), present a unique opportunity to investigate the relationship between patient genotype and cell phenotype. CNVs have high genetic penetrance and give a good correlation between gene locus and patient clinical phenotype. This is especially effective for the study of patients with neurodevelopmental disorders (NDD), including those falling within the autism spectrum disorders (ASD). A key question is whether this correlation between genetics and clinical presentation at the level of the patient can be translated to the cell phenotypes arising from the neurodevelopment of patient induced pluripotent stem cells (iPSCs).Here, we examine how iPSCs derived from ASD patients with an associated CNV inform our understanding of the genetic and biological mechanisms underlying the aetiology of ASD.  https://www.selleckchem.com/products/Decitabine.html  We consider selection of genetically characterised patient iPSCs; use of appropriate control lines; aspects of human neurocellular biology that can capture in vitro the patient clinical phenotype; and current limitations of patient iPSC-based studies. Finally, we consider how future research may be enhanced to maximise the utility of CNV patients for research of pathological mechanisms or therapeutic targets.Background As pharmacogenomics data becomes increasingly integral to clinical treatment decisions, appropriate data storage and sharing protocols need to be adopted. One promising option for secure, high-integrity storage and sharing is Ethereum smart contracts. Ethereum is a blockchain platform, and smart contracts are immutable pieces of code running on virtual machines in this platform that can be invoked by a user or another contract (in the blockchain network). The 2019 iDASH (Integrating Data for Analysis, Anonymization, and Sharing) competition for Secure Genome Analysis challenged participants to develop time- and space-efficient Ethereum smart contracts for gene-drug relationship data. Methods Here we design a specific smart contract to store and query gene-drug interactions in Ethereum using an index-based, multi-mapping approach. Our contract stores each pharmacogenomics observation, a gene-variant-drug triplet with outcome, in a mapping searchable by a unique identifier, allowing for time and spacpharmacogenomics data can be stored and queried efficiently using Ethereum blockchain. Our solutions could potentially be used to store a range of clinical data and extended to other fields requiring high-integrity data storage and efficient access.Background Approximately 30% of appendectomies are for complicated acute appendicitis (CAA). With laparoscopy, the main post-operative complication is deep abscesses (12% of cases of CAA, versus 4% for open surgery). A recent cohort study compared short and long courses of postoperative antibiotic therapy in patients with CAA. There was no significant intergroup difference in the post-operative complication rate (12% of organ/space surgical site infection (SSI)). Moreover, antibiotic therapy is increasingly less indicated for other situations (non-complicated appendicitis, post-operative course of cholecystitis, perianal abscess), calling into question whether post-operative antibiotic therapy is required after laparoscopic appendectomy for CAA. Methods/design This study is a prospective, multicenter, parallel-group, randomized (11), double-blinded, placebo-controlled, phase III non-inferiority study with blind evaluation of the primary efficacy criterion. The primary objective is to evaluate the impact of th24 h for 3 days). In the event of allergy to ceftriaxone, it will be replaced by levofloxacin (500 mg/24 h in one intravenous injection, for 3 days). The expected organ space SSI rate is 12% in the population of patients with CAA operated on by laparoscopy. With a non-inferiority margin of 5%, a two-sided alpha risk of 5%, a beta risk of 20%, and a loss-to-follow-up rate of 10%, the calculated sample size is 1476 included patients, i.e., 738 per group. Due to three interim analyses at 10%, 25%, and 50% of the planned sample size, the total sample size increases to 1494 patients (747 per arm). Trial registration Ethical authorization by the Comité de Protection des Personnes and the Agence Nationale de Sécurité du Médicament ID-RCB 2017-00334-59. Registered on ClinicalTrials.gov (NCT03688295) on 28 September 2018.Background DNA methylation is a highly studied epigenetic signature that is associated with regulation of gene expression, whereby genes with high levels of promoter methylation are generally repressed. Genomic imprinting occurs when one of the parental alleles is methylated, i.e., when there is inherited allele-specific methylation (ASM). A special case of imprinting occurs during X chromosome inactivation in females, where one of the two X chromosomes is silenced, to achieve dosage compensation between the sexes. Another more widespread form of ASM is sequence dependent (SD-ASM), where ASM is linked to a nearby heterozygous single nucleotide polymorphism (SNP). Results We developed a method to screen for genomic regions that exhibit loss or gain of ASM in samples from two conditions (treatments, diseases, etc.). The method relies on the availability of bisulfite sequencing data from multiple samples of the two conditions. We leverage other established computational methods to screen for these regions withinent and disease.Background The rapid growth in off-leash dog parks provides opportunity for canine socialization activities but carries risk of exposure to intestinal parasites. This study assessed the prevalence of these infections in dogs visiting off-leash dog parks. Methods Fresh defecations were collected from dogs visiting parks in 30 metropolitan areas across the USA. Samples were analyzed by coproantigen immunoassay (CAI) (Fecal Dx® and Giardia Test, IDEXX Laboratories, Inc.) and zinc sulfate centrifugal flotation (CF). Owners responded to a questionnaire on their dog's signalment and use of heartworm/intestinal parasite control medications (HWCM). Results Samples were examined from 3006 dogs, 87.9% aged at least 12 months, visiting 288 parks. At least one intestinal parasite was detected in 622 (20.7%) samples, nematodes in 263 (8.8%), with hookworms, whipworms and ascarids in 7.1, 1.9 and 0.6% of samples, respectively. A sample positive for one or more intestinal parasites was found in 245 (85.1%) parks, with nematodes found in 143 (49.