Mutational signatures reveal mutual exclusivity of homologous recombination and mismatch repair deficiencies in colorectal and stomach tumors.

Decomposing somatic mutation spectra into mutational signatures and their corresponding etiologies provides a powerful approach for investigating the mechanism of DNA damage and repair. Assessing microsatellite (in)stability (MSI/MSS) status and interpreting their clinical relevance in different malignancies offers significant diagnostic and prognostic value. However, little is known about microsatellite (in)stability and its interactions with other DNA repair mechanisms such as homologous recombination (HR) in different cancer types.

Imprecision in vaccine adverse event reporting and a methodological analysis of reporting systems to improve pharmacovigilance and public health.

Introduction: This study documents imprecision in Japanese reports of adverse events following immunization (AEFI). In doing so, it presents methods to analyze this imprecision.

Methods: These methods include use of unique Japanese data on the validity of certain AEFIs.

Imprecision in adverse event reports following immunization against HPV in Japan and COVID-19 in the USA, UK, and Japan-and the effects of vaccine hesitancy and government policy.

Introduction: Erroneous reports of adverse events following immunization (AEFIs) likely exacerbated the 2013 collapse of Japan's HPV immunization program. A similar phenomenon characterized the first months of COVID-19 immunization programs in the USA, UK, and Japan with high rates of reported anaphylaxis. These reports illustrate the susceptibility of supposedly objective medical judgments to public anxiety.

Mutational signatures reveal ternary relationships between homologous recombination repair, APOBEC, and mismatch repair in gynecological cancers.

Background: Revealing the impacts of endogenous and exogenous mutagenesis processes is essential for understanding the etiology of somatic genomic alterations and designing precise prognostication and treatment strategies for cancer. DNA repair deficiency is one of the main sources of endogenous mutagenesis and is increasingly recognized as a target for cancer therapeutics. The role and prevalence of mechanisms that underly different forms of DNA repair deficiencies and their interactions remain to be elucidated in gynecological malignancies.

RNA sequencing identifies clonal structure of T-cell repertoires in patients with adult T-cell leukemia/lymphoma.

The diversity of T-cell receptor (TCR) repertoires, as generated by somatic DNA rearrangements, is central to immune system function. High-throughput sequencing technologies now allow examination of antigen receptor repertoires at single-nucleotide and, more recently, single-cell resolution. The TCR repertoire can be altered in the context of infections, malignancies or immunological disorders.

Mutational Intratumor Heterogeneity is a Complex and Early Event in the Development of Adult T-cell Leukemia/Lymphoma.

The clonal architecture of tumors plays a vital role in their pathogenesis and invasiveness; however, it is not yet clear how this clonality contributes to different malignancies. In this study we sought to address mutational intratumor heterogeneity (ITH) in adult T-cell leukemia/lymphoma (ATL). ATL is a malignancy with an incompletely understood molecular pathogenesis caused by infection with human T-cell leukemia virus type-1 (HTLV-1).

Industry-university collaborations in Canada, Japan, the UK and USA--with emphasis on publication freedom and managing the intellectual property lock-up problem.

As industry-university collaborations are promoted to commercialize university research and foster economic growth, it is important to understand how companies benefit from these collaborations, and to ensure that resulting academic discoveries are developed for the benefit of all stakeholders: companies, universities and public. Lock up of inventions, and censoring of academic publications, should be avoided if feasible. This case-study analysis of interviews with 90 companies in Canada, Japan, the UK and USA assesses the scope of this challenge and suggests possible resolutions.

The importance of new companies for drug discovery: origins of a decade of new drugs.

Understanding the factors that promote drug innovation is important both for improvements in health care and for the future of organizations engaged in drug discovery research and development. By identifying the inventors of 252 new drugs approved by the US Food and Drug Administration from 1998 to 2007 and their places of work, and also classifying these drugs according to innovativeness, this study investigates the contribution of different types of organizations and regions to drug innovation during this period. The data indicate that drugs initially discovered in biotechnology companies or universities accounted for approximately half of the scientifically innovative drugs approved, as well as half of those that responded to unmet medical needs, although their contribution to the total number of new drugs was proportionately lower.