Korean Patients with Superwarfarin Intoxication and Their Outcome

This observational study aimed at evaluating recent superwarfarin intoxication of Korean patients. Ten patients were diagnosed as or highly suspicious for superwarfarin intoxication. Case report forms described by attending hematologists of the patients were collected and analyzed. Bleeding symptoms were varied among the patients. Patients uniformly showed prolonged prothrombin time (PT) and activated thromboplastin time (aPTT) with decreased activity of vitamin K dependent coagulation factors. Positive serum brodifacoum test results in 4 of 5 requested patients contributed to confirmatory diagnosis. Psychiatric interview revealed an attempted ingestion in one patient. High dose vitamin K1 therapy promptly corrected prolonged PT and aPTT, but hasty discontinuation caused repeated bleeding diathesis in 6 patients. Route of intoxication was unknown or not definite among 8 of 10 patients. Three patients had a possibility of environmental exposure considering their occupations: there might be intoxication by transdermal absorption or inhalation. Therefore, high dose and prolonged use of vitamin K1 therapy is necessary for effective detoxification. Further detailed investigation on environmental exposure and efforts to improve availability of the blood level test in clinic are requested

Primary Cardiac Lymphoma Presenting With Atrioventricular Block

Primary cardiac lymphomas (PCL) are extremely rare. Clinical manifestations may be variable and are attributed to location. Here, we report on a case of PCL presenting with atrioventricular (AV) block. A 55 year-old male had experienced chest discomfort with unexplained dyspnea and night sweating. His initial electrocardiogram (ECG) revealed a first degree AV block. Along with worsening chest discomfort and dyspnea, his ECG changed to show second degree AV block (Mobitz type I). Computed tomography (CT) scan showed a cardiac mass (about 7 cm) and biopsy was performed. Pathologic finding confirmed diffuse large B-cell lymphoma. The patient was treated with multi-drug combination chemotherapy (R-CHOP: Rituximab, cyclophoshamide, anthracycline, vincristine, and prednisone). After treatment, ECG changed to show normal sinus rhythm with complete remission on follow-up CT scan

Вихретоковый анизотропный термоэлектрический первичный преобразователь лучистого потока

Представлена оригинальная конструкция первичного преобразователя лучистого потока, который может служить основой для создания приемника неселективного излучения с повышенной чувствительностью

The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Real-World Outcomes of Ruxolitinib in Patients With Myelofibrosis Focusing on Red Blood Cell Transfusion: A Multicenter Study From the MPN Working Party of the Korean Society of Hematology

© 2022Introduction/Background: Ruxolitinib is an established treatment for myelofibrosis (MF) that has demonstrated clinical benefit by reducing spleen size and debilitating MF-related symptoms. However, despite the efficacy of ruxolitinib, anemia remains a major adverse event that causes dose modification or discontinuation in real-world practice. Additionally, dependence on red blood cell (RBC) transfusion (TF) is common during treatment; therefore, we explored the outcome of ruxolitinib therapy with a primary focus on RBC TF. Patients/Methods: We retrospectively reviewed the medical records of 123 MF patients treated with ruxolitinib between January 2012 and April 2020 at eight academic centers in Korea. Results: At ruxolitinib initiation, 38 patients (30.9%) underwent ≥ 2 units of RBC TF over 8 weeks. The most common reason for permanent discontinuation was intolerant anemia (10/63, 15.9%). The most common reasons for temporary interruption were nonhematologic toxicity (26/55, 21.1%), anemia (23/55, 18.7%) and thrombocytopenia (13/55, 10.6%). Among the 123 patients in the study, 57 (46.3%), 42 (34.1%), and 40 patients (32.5%) who were receiving or stopped ruxolitinib therapy had a status of RBC TF dependence, long-term RBC TF dependence, or severe RBC TF dependence, respectively. The presence of ≥ 2 units of RBC transfusion over 8 weeks at ruxolitinib initiation was an independent risk factor for persistent RBC TF dependence. Conclusion: The requirement for RBC TF is commonly encountered during treatment of MF with ruxolitinib, particularly among those with pre-existing ≥ 2 units of RBC TF over 8 weeks. For those patients, overcoming the barrier of maintenance TF is demanding.N