Drug-Induced-Liver-Injury (DILI) is a leading cause of termination in drug development programs and removal of drugs from the market, and this is partially due to the inability to identify patients who are at risk 1 . Here, we developed a polygenic risk score (PRS) for DILI by aggregating effects of numerous genome-wide loci identified from previous large-scale genome-wide association studies (GWAS) 2 . The PRS predicted the susceptibility to DILI in patients treated with fasiglifam, amoxicillin-clavulanate or flucloxacillin, and in primary hepatocytes and stem cell-derived organoids from multiple

BACKGROUND Norovirus is one of the genera of the Calicivirus family there are five Known genogroups (GG I through V). 1 It is one of the most common

Dengue is an acute viral disease transmitted by the Aedes aegypti mosquito which is present in most tropical urban areas of the world. There are four antigenically distinct serotypes, designated dengue-1 (DEN-1), dengue-2 (DEN-2), dengue-3 (DEN-3) and dengue-4 virus (DEN-4). In this study, we determined the serotypes of dengue viruses isolated in Guatemala in 1995-1998, and found that DEN-3 viruses appeared in 1995 and became predominant in the following three years. We then sequenced cDNAs from fifteen DEN-3 isolates recovered during 1996-1998. From the nucleic acid sequences and previously determined DEN-3 sequences, a phylogenetic tree was constructed using the neighbor joining method. The tree indicated that all fifteen isolates and other DEN-3 viruses isolated in Sri Lanka, India, Samoa and Mozambique formed subtype III. More than two decades ago, DEN-3 virus was prevalent in the Caribbean, but the isolates obtained at that time belonged to subtype IV. Therefore, we concluded that the 1996-1998 dengue epidemic in Guatemala was caused by DEN-3 strains, imported from a tropical area of Asia or Africa or from a Pacific island.

Adenovirus type 3 (Ad3) isolates, isolated from 45 patients with acute conjunctivitis during the year 1990 in Japan, were studied by DNA restriction enzyme analysis with restriction endonucleases recognizing 6-bp sequences (BamHI, SmaI, HindIII, BglII) and endonucleases recognizing 5-or 4-bp sequences (HinfI and TaqI). All 45 isolates of Ad3 were identified as the genome type Ad3f by six endonucleases. They were further classified into three varieties by HinfI, varieties H 1 (87.5%), H 2 (8.9%), and H 3 (2.2%), and into five varieties by TaqI, varieties T 1 (75.6%), T 2 (13.3%), T 3 (2.2%), T 4 (4.5%), and T 5 (8.9%). The use of HinfI and TaqI was sufficient to distinguish six subgenome types: types Ad3fH 1

Immunization with 2,4-dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH) produced antibodies with combining sites (paratope) which could accomodate not only the 2,4,6-trinitrophenyl (TNP) antigen but also the 4-hydroxy-3-nitrophenyl (NP) and 4-hydroxy-5-iodo-3-nitrophenyl (NIP) antigens, while immunization with NIP-KLH or TNP-KLH produced antibodies with combining sites which could accomodate only the homologous antigens. Utilizing these cross-reacting anti-hapten antibodies mentioned above, an anti-idiotypic antibody was investigated and characterized. Anti-DNP antibodies (Ab₁) cross-reacted with the epitopes TNP, NP or NIP. It was also shown that heterologous anti-anti-DNP antibodies (Ab₂) recognized not only the antibody which was produced by immunization with DNP-KLH, but also the antibodies produced by immunization with NIP-KLH, NP-KLH or TNP-KLH. The guinea pig anti-idiotypic antibody which we obtained using murine anti-DNP antibodies (Ab₁) as antigen is therefore better defined not as an internal image of the antigen but as a mirror image of the paratope of the immunizing Ab₁.