Implementation of Do Not Attempt Resuscitate Orders in a Japanese Nursing Home

Objective: To investigate whether do not attempt resuscitation (DNAR) orders can be implemented in a standard nursing home in Japan, where routine DNAR orders are not yet common in many facilities including hospitals. Method: Ninety-eight residents in a 100-bed nursing home were evaluated. All of the eligible residents and/or their family members were asked whether they wanted to receive resuscitation, including mechanical ventilation. Result: The residents were 54 to 101 years of age (mean 83.3), with 27 males and 71 females. After administering the questionnaire, 92 (94%) patients did not want resuscitation and mechanical ventilation. Conclusion: In a nursing home, it was possible to obtain advance directives by which most residents/families rejected resuscitation and mechanical ventilation. This could avoid unnecessary and undesirable resuscitation procedures

Prediction of pharmacological activities from chemical structures with graph convolutional neural networks

化合物の薬理作用を予測する技術を開発 --薬理作用ビッグデータを用いて--. 京都大学プレスリリース. 2021-01-13.Many therapeutic drugs are compounds that can be represented by simple chemical structures, which contain important determinants of affinity at the site of action. Recently, graph convolutional neural network (GCN) models have exhibited excellent results in classifying the activity of such compounds. For models that make quantitative predictions of activity, more complex information has been utilized, such as the three-dimensional structures of compounds and the amino acid sequences of their respective target proteins. As another approach, we hypothesized that if sufficient experimental data were available and there were enough nodes in hidden layers, a simple compound representation would quantitatively predict activity with satisfactory accuracy. In this study, we report that GCN models constructed solely from the two-dimensional structural information of compounds demonstrated a high degree of activity predictability against 127 diverse targets from the ChEMBL database. Using the information entropy as a metric, we also show that the structural diversity had less effect on the prediction performance. Finally, we report that virtual screening using the constructed model identified a new serotonin transporter inhibitor with activity comparable to that of a marketed drug in vitro and exhibited antidepressant effects in behavioural studies

Living donor liver transplantation using sensitized lymphocytotoxic crossmatch positive graft

We describe a successful living donor liver transplantation (LDLT) using a lymphocytotoxic crossmatch highly positive graft. A 41-year-old woman with alcoholic liver cirrhosis was referred as a potential candidate for LDLT, and her husband was willing to donate his partial liver. As the T-lymphocytotoxic crossmatch titer was over 10,000×, the patient was first infused with rituximab for preoperative desensitization, and then five rounds of plasmapheresis were performed. After the third plasmapheresis, the lymphocytotoxic crossmatch test was negative. A left liver graft including the caudate lobe was implanted, and anti-CD25 antibody (basiliximab) was administered on postoperative days 1 and 4. The postoperative course was uneventful except for an episode of mild acute cellular rejection on postoperative day 27. Although the impact of a lymphocytotoxic crossmatch-positive liver graft on acute cellular rejection and graft survival in LDLT remains controversial, perioperative desensitization may provide benefits when using a highly sensitized liver graft

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology