Automated Generation of Radiologic Descriptions on Brain Volume Changes From T1-Weighted MR Images: Initial Assessment of Feasibility

Purpose: To examine the feasibility and potential difficulties of automatically generating radiologic reports (RRs) to articulate the clinically important features of brain magnetic resonance (MR) images.Materials and Methods: We focused on examining brain atrophy by using magnetization-prepared rapid gradient-echo (MPRAGE) images. The technology was based on multi-atlas whole-brain segmentation that identified 283 structures, from which larger superstructures were created to represent the anatomic units most frequently used in RRs. Through two layers of data-reduction filters, based on anatomic and clinical knowledge, raw images (~10 MB) were converted to a few kilobytes of human-readable sentences. The tool was applied to images from 92 patients with memory problems, and the results were compared to RRs independently produced by three experienced radiologists. The mechanisms of disagreement were investigated to understand where machine–human interface succeeded or failed.Results: The automatically generated sentences had low sensitivity (mean: 24.5%) and precision (mean: 24.9%) values; these were significantly lower than the inter-rater sensitivity (mean: 32.7%) and precision (mean: 32.2%) of the radiologists. The causes of disagreement were divided into six error categories: mismatch of anatomic definitions (7.2 ± 9.3%), data-reduction errors (11.4 ± 3.9%), translator errors (3.1 ± 3.1%), difference in the spatial extent of used anatomic terms (8.3 ± 6.7%), segmentation quality (9.8 ± 2.0%), and threshold for sentence-triggering (60.2 ± 16.3%).Conclusion: These error mechanisms raise interesting questions about the potential of automated report generation and the quality of image reading by humans. The most significant discrepancy between the human and automatically generated RRs was caused by the sentence-triggering threshold (the degree of abnormality), which was fixed to z-score >2.0 for the automated generation, while the thresholds by radiologists varied among different anatomical structures

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Pulmonary Artery and Central Venous Pressures as Prognostic Indicators of Post Lung Transplant Outcome

Thesis (Master's)--University of Washington, 2014Background The relationship between elevated mean pulmonary arterial pressure (mPAP) and central venous pressure (CVP) on poor prognosis in patients undergoing lung transplants has been widely debated. We hypothesized that not only the isolated values of mPAP and CVP, but also the combination of discordant values in these variables may represent an unfavorable condition in lung transplantation. Methods We retrospectively reviewed 80 consecutive patients undergoing lung transplantation between 2008 and 2010. We investigated the relationship between of increased mPAP, CVP, and the discordance of the two variables (discordance group; DG vs. concordance group; CG) on the lowest PO2/FiO2 (P/F) ratio in the first 24 hours after admission to the ICU. We also assessed the impact of these indicators on ventilation time, ICU and hospital length of stay (LOS). Results Of the subjects in this study, 70 patients had bilateral lung transplantation, 40 were male, and the mean age was 51.2 (±14.5). All were intubated at ICU admission. For 1 mmHg increase in mPAP and CVP, the P/F ratio was 5.1 (95% CI 1.06, 9.12) and 8.48 (95% CI 2.89, 14.07) lower respectively. One mmHg increase in mPAP was also associated with hypoxia (defined as P/F ratio 27hrs) (OR 1.13; 95%CI 1.02-1.25) and ICU LOS (>5 days) (OR1.19; 95% CI 1.06-1.33). One mmHg increase in CVP was also associated with prolonged ICU LOS (OR1.19; 95% CI 1.04-1.37). DG was associated with prolonged ICU LOS compared to CG (OR 6.95; 95% CI 1.37-35.23). Conclusion Post-operative mPAP, CVP as well as the interaction of the two have prognostic values in patients undergoing lung transplantation

Clinical Outcome Comparison of Patients Requiring Extracorporeal Membrane Oxygenation With or Without COVID-19 Infection.

In severe COVID-19-related respiratory failure, extracorporeal membrane oxygenation (ECMO) is a useful modality that is used to provide effective oxygenation and ventilation to the patient. This descriptive study aimed to investigate and compare the outcomes between COVID-19-infected patients and patients who were not infected and required ECMO support. A retrospective study was undertaken on a cohort of 82 adult patients ([Formula: see text]18-year-old) who required venoarterial (VA-ECMO) and venovenous (VV-ECMO) ECMO between January 2019 and December 2022 in a single academic center. Patients who were cannulated for COVID-19-related respiratory failure (C-group) were compared to patients who were cannulated for non-COVID etiologies (non-group). Patients were excluded if data were missing regarding cannulation, decannulation, presenting diagnosis, and survival status. Categorical data were reported as counts and percentages, and continuous data were reported as means with 95% confidence intervals. Out of the 82 included ECMO patients, 33 (40.2%) were cannulated for COVID-related reasons, and 49 (59.8%) were cannulated for reasons other than COVID-19 infection. Compared to the non-group, the C-group had a higher in-hospital (75.8% vs. 55.1%) and overall mortality rate (78.8% vs. 61.2%). The C-group also had an average hospital length of stay (LOS) of 46.6 ± 13.2 days and an average intensive care unit (ICU) LOS of 44.1 ± 13.3 days. The non-group had an average hospital LOS of 24.8 ± 6.6 days and an average ICU LOS of 20.8 ± 5.9 days. Subgroup analysis of patients only treated with VV-ECMO yielded a greater in-hospital mortality rate for the C-group compared to the non-group (75.0% vs. 42.1%). COVID-19-infected patients may experience different morbidity and mortality rates as well as clinical presentations compared to non-COVID-infected patients when requiring ECMO support

Fine-tuning of highly bright benzo[c,d]indole-oxazolopyridine cyanine dye for nucleolar RNA imaging in living cells

Here we report on fine-tuning of highly bright fluorogenic cyanine dye, benzo[c,d]indole-oxazolo[5,4-c]pyridine (BIOP: λem = 570 nm, Φfree = 0.00038, Φbound = 0.52), recently developed by our group for nucleolar RNA imaging in living cells. We tuned an emission maximum to the longer wavelength by replacing oxazolopyridine unit with its isomer. The resulting probe with oxazolo[4,5-b]pyridine, named BIOP [4,5-b], exhibited a significant off-on signaling ability for RNA (λem = 580 nm, Φfree = 0.002, Φbound = 0.46) that almost compared with BIOP. BIOP [4,5-b] was applicable to live-cell imaging, where wash-free protocol was available. Importantly, the slight change in spectral features would be expected to minimize the false signal from BIOP [4,5-b] in co-staining experiments with typical green-emissive dyes. In addition, thanks to the unique spectral shape that is typical of cyanine dyes, we demonstrate that yellow-emissive BIOP [4,5-b] also did work as a pseudo red-emissive dye (λem > 600 nm) for live-cell RNA imaging, for which we just switch filter set to typical one for real red-emissive dyes (Ex 560/40 nm; Em 645/75 nm)