Deregulated JNK signaling enhances apoptosis during hyperthermia.

Purpose: c-Jun N-terminal kinases (JNKs) comprise a subfamily of mitogen-activated protein kinases (MAPKs). The JNK group is known to be activated by a variety of stimuli. However, the molecular mechanism underlying heat-induced JNK activation is largely unknown.

Cryo-EM structures of RAD51 assembled on nucleosomes containing a DSB site.

RAD51 is the central eukaryotic recombinase required for meiotic recombination and mitotic repair of double-strand DNA breaks (DSBs). However, the mechanism by which RAD51 functions at DSB sites in chromatin has remained elusive. Here we report the cryo-electron microscopy structures of human RAD51-nucleosome complexes, in which RAD51 forms ring and filament conformations.

Effectiveness of a web-based learning program for promoting local healthcare planning competencies.

Objective: To determine the effectiveness of a web-based educational program regarding local healthcare planning by public health nurses (PHNs) in Japan.

Design: A single-blind randomized controlled trial.

Sample: Full-time PHNs working for local governments across Japan.

Meiotic chromosome organization and its role in recombination and cancer.

Chromosomes adopt specific conformations to regulate various cellular processes. A well-documented chromosome configuration is the highly compacted chromosome structure during metaphase. More regional chromatin conformations have also been reported, including topologically associated domains encompassing mega-bases of DNA and local chromatin loops formed by kilo-bases of DNA.

Association between public health nurses' involvement in local healthcare planning and the corresponding off-the-job training.

Objective: This study investigated the association between receiving off-the-job training and the involvement of public health nurses in local healthcare planning.

Design: A nationwide, cross-sectional study design.

Methods: We sent self-report questionnaires to 2,185 public health nurses with experience in developing local healthcare plans in Japan since 2013 and collected information related to three main categories: demographic data, involvement in local healthcare planning and strategies for healthcare planning.

Infection control measures promoted by the public health center for "housing for the elderly" facilities during norovirus cluster outbreaks.

"Housing for the elderly" is a type of facility where a few healthcare staff and care workers provide long-term care to residents. This study aimed to explore the infection control measures promoted by the public health centers (PHC) when a cluster of norovirus cases occurred in this type of facility. This study involved a prefectural office in Japan and collected the records of PHC surveys/instructions of norovirus cluster cases that occurred in "housing for the elderly" facilities between 2017 and 2019.

[Public health nurses' activities during normal times and factors associated with their promotion of residents' mutual support during disasters].

Objective　To clarify the actual state of activities conducted by public health nurses (PHNs) during normal times and assess factors related to the implementation of such activities for the promotion of residents' mutual support during disasters, across different municipalities in Japan.Methods　We conducted a nationwide cross-sectional self-report questionnaire survey of PHNs in 1,463 municipalities. The questionnaires included descriptions of municipalities, activities related to disaster prevention and the rationale for them, and the details of activities that were being conducted to promote residents' mutual support in times of disaster.

Feasibility of an educational program for public health nurses to promote local healthcare planning: protocol for a pilot randomized controlled trial.

Background: Promoting of local healthcare planning is crucial for assisting public health nurses in improving community health inequities. However, there is no effective educational program for developing relevant skills and knowledge among these nurses. Therefore, this study aims to assess the feasibility of a newly developed web-based self-learning program to promote the involvement of public health nurses in the local healthcare planning process.

[Factors associated with community collaboration in the implementation phase of the local health-care, medical, and welfare plan].

Objective　The aim of this study was to elucidate the status of health-care, medical, and welfare planning (hereafter, "planning")-in which public health nurses (PHNs) had participated-and the factors associated with community collaboration in the implementation phase. Additionally, suggestions regarding health activities that would contribute to improving the entire community's health level were obtained.Methods　The Plan-Do-Check-Act (PDCA) cycle was the conceptual framework for this study, and the focus was the implementation phase of the plan (i.

Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia.

Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing.

Implications of the germline variants of DNA damage response genes detected by cancer precision medicine for radiological risk communication and cancer therapy decisions.

Large-scale cancer-associated gene testing is now being rapidly incorporated into clinical settings, and is leading to incidental identification of the germline variants present in cancer patients. Because many cancer susceptibility genes are related to DNA damage response and repair, the variants may reflect not only the susceptibility to cancer but also the genetically defined radiation sensitivity of the patients and their relatives. When the presence of a certain germline variant increases the risk for developing radiation toxicity or radiation-induced secondary cancers, it will greatly influence the clinical decision-making.

Self-reported competences of public health nurses for developing needs-oriented local healthcare plans: A nationwide cross-sectional survey.

Aim: To identify self-reported competencies of public health nurses for reflecting community healthcare needs in local healthcare plans.

Design: We conducted a nationwide cross-sectional survey in Japan from October 7-November 30, 2019.

Methods: We sent 2,185 self-reported questionnaires to public health nurses in Japan who had developed a local healthcare plan since 2013.

Synaptonemal complex proteins modulate the level of genome integrity in cancers.

The synaptonemal complex (SC) is a proteinaceous structure that is transiently formed during meiosis to promote homologous recombination between maternal and paternal chromosomes. As this structure is required only for meiotic recombination, the proteins constituting the complex are almost undetectable in normal somatic cells, but they can be expressed under the conditions in which the transcriptional machinery is deregulated. Accumulating evidence indicates that they are epigenetically expressed in cancers of various origin.

High-throughput functional evaluation of BRCA2 variants of unknown significance.

Numerous nontruncating missense variants of the BRCA2 gene have been identified, but there is a lack of convincing evidence, such as familial data, demonstrating their clinical relevance and they thus remain unactionable. To assess the pathogenicity of variants of unknown significance (VUSs) within BRCA2, here we develop a method, the MANO-B method, for high-throughput functional evaluation utilizing BRCA2-deficient cells and poly (ADP-ribose) polymerase (PARP) inhibitors. The estimated sensitivity and specificity of this assay compared to those of the International Agency for Research on Cancer classification system is 95% and 95% (95% confidence intervals: 77-100% and 82-99%), respectively.

[A Case of Breast Cancer Complicated with Castleman's Disease].

The patient was a 57-year-old woman with Castleman's disease. The follow-up CT scans obtained during the treatment of Castleman's disease, detected a 15mm nodule in the right breast AC area, and the patient was diagnosed with breast cancer. Lymphadenopathy was noted on both sides of the axilla; however, it was considered to be due to Catsleman's disease.

Impact of web-based learning for health program planning competency, knowledge and skills among mid-level public health nurses: A randomized controlled trial.

Objectives: To evaluate the impact of web-based learning modules for health program planning competency, recognition, knowledge and skills among mid-level public health nurses (PHNs).

Design: Parallel-group randomized controlled trial.

Sample: During 2018, 244 Japanese PHNs were eligible as participants with 5-20 years experiences as a PHN were randomly allocated to the intervention (n = 121) or control group (n = 123).

Effectiveness of an educational program for mid-level Japanese public health nurses to improve program planning competencies: A preliminary randomized control trial.

Objective: To evaluate the effectiveness of an education program for mid-level Japanese public health nurses (PHNs) to improve their competencies in program planning, which will fulfill community health needs.

Design: Randomized control trial.

Sample: During 2017, 103 PHNs with 5-20 years of PHN work experience in Japan were enrolled and randomly allocated to the intervention (n = 51) or control group (n = 52).

Somatic role of SYCE2: an insulator that dissociates HP1α from H3K9me3 and potentiates DNA repair.

The synaptonemal complex is a proteinaceous structure essential for meiotic recombination, and its components have been assumed to play a role exclusively in the germ line. However, SYCE2, a component constituting the synaptonemal complex, is expressed at varying levels in somatic cells. Considering its potent protein-binding activities, it may be possible that SYCE2 plays a somatic role by affecting nuclear functions.

Prognostic factors of Erdheim-Chester disease: a nationwide survey in Japan.

Erdheim-Chester disease is a rare histiocytosis with insufficient clinical data. To clarify the clinical features and prognostic factors of Erdheim-Chester disease, we conducted a nationwide survey to collect the detailed data of 44 patients with Erdheim-Chester disease in Japan. The median age of onset of the participants was 51 (range: 23-76) years, and the median number of involved organs per patient was 4 (range: 1-11).

Educational program for middle-level public health nurses to develop new health services regarding community health needs: protocol for a randomized controlled trial.

Background: Developing health services is a key strategy for improving the community health provided by public health nurses. However, an effective educational program for improving their skills in planning such services has not been developed. To describe our program and its evaluation protocol for the education of middle-level public health nurses to improve their skills in developing new health services to fulfil community health needs in Japan.

SYCP3 regulates strand invasion activities of RAD51 and DMC1.

The synaptonemal complex is a higher-ordered proteinaceous architecture formed between homologous chromosomes. SYCP3 is a major component of the lateral/axial elements in the synaptonemal complex and is essential for meiotic recombination. Previous genetic studies showed that SYCP3 functions in meiotic homologous recombination biased to interhomologous chromosomes, by regulating the strand invasion activities of the RAD51 and DMC1 recombinases.

PI3K/mTOR pathway inhibition overcomes radioresistance via suppression of the HIF1-α/VEGF pathway in endometrial cancer.

Radiation therapy is a key therapeutic strategy for endometrial carcinomas. However, biomarkers that predict radiosensitivity and drugs to enhance this sensitivity have not yet been established. We aimed to investigate the roles of TP53 and MAPK/PI3K pathways in endometrial carcinomas and to identify appropriate radiosensitizing therapeutics.