Risk-adjusted therapy for pediatric non-T cell ALL improves outcomes for standard risk patients: results of JACLS ALL-02

This study was a second multicenter trial on childhood ALL by the Japan Childhood Leukemia Study Group (JACLS) to improve outcomes in non-T ALL. Between April 2002 and March 2008, 1138 children with non-T ALL were enrolled in the JACLS ALL-02 trial. Patients were stratified into three groups using age, white blood cell count, unfavorable genetic abnormalities, and treatment response: standard risk (SR), high risk (HR), and extremely high risk (ER). Prophylactic cranial radiation therapy (PCRT) was abolished except for CNS leukemia. Four-year event-free survival (4yr-EFS) and 4-year overall survival (4yr-OS) rates for all patients were 85.4% ± 1.1% and 91.2% ± 0.9%, respectively. Risk-adjusted therapy resulted in 4yr-EFS rates of 90.4% ± 1.4% for SR, 84.9% ± 1.6% for HR, and 66.5% ± 4.0% for ER. Based on NCI risk classification, 4yr-EFS rates were 88.2% in NCI-SR and 76.4% in NCI-HR patients, respectively. Compared to previous trial ALL-97, 4yr-EFS of NCI-SR patients was significantly improved (88.2% vs 81.2%, log rank p = 0.0004). The 4-year cumulative incidence of isolated (0.9%) and total (1.5%) CNS relapse were significantly lower than those reported previously. In conclusion, improved EFS in NCI-SR patients and abolish of PCRT was achieved in ALL-02

Enhancing evidence-informed policymaking in medicine and healthcare: stakeholder involvement in the Commons Project for rare diseases in Japan

Kogetsu A., Isono M., Aikyo T., et al. Enhancing evidence-informed policymaking in medicine and healthcare: stakeholder involvement in the Commons Project for rare diseases in Japan. Research Involvement and Engagement 9, 107 (2023); https://doi.org/10.1186/s40900-023-00515-5.Background: Although stakeholder involvement in policymaking is attracting attention in the fields of medicine and healthcare, a practical methodology has not yet been established. Rare-disease policy, specifically research priority setting for the allocation of limited research resources, is an area where evidence generation through stakeholder involvement is expected to be effective. We generated evidence for rare-disease policymaking through stakeholder involvement and explored effective collaboration among stakeholders. Methods: We constructed a space called ‘Evidence-generating Commons’, where patients, family members, researchers, and former policymakers can share their knowledge and experiences and engage in continual deliberations on evidence generation. Ten rare diseases were consequently represented. In the ‘Commons’, 25 consecutive workshops were held predominantly online, from 2019 to 2021. These workshops focused on (1) clarification of difficulties faced by rare-disease patients, (2) development and selection of criteria for priority setting, and (3) priority setting through the application of the criteria. For the first step, an on-site workshop using sticky notes was held. The data were analysed based on KJ method. For the second and third steps, workshops on specific themes were held to build consensus. The workshop agendas and methods were modified based on participants’ feedback. Results: The ‘Commons’ was established with 43 participants, resulting in positive effects such as capacity building, opportunities for interactions, mutual understanding, and empathy among the participants. The difficulties faced by patients with rare diseases were classified into 10 categories. Seven research topics were identified as priority issues to be addressed including ‘impediments to daily life’, ‘financial burden’, ‘anxiety’, and ‘burden of hospital visits’. This was performed by synthesising the results of the application of the two criteria that were particularly important to strengthen future research on rare diseases. We also clarified high-priority research topics by using criteria valued more by patients and family members than by researchers and former policymakers, and criteria with specific perspectives. Conclusion: We generated evidence for policymaking in the field of rare diseases. This study’s insights into stakeholder involvement can enhance evidence-informed policymaking. We engaged in comprehensive discussions with policymakers regarding policy implementation and planned analysis of the participants’ experiences in this project

Tetracyclus Saito-Kato, Hayashi & Tanimura, 2011, sp. nov.

Tetracyclus radius Saito-Kato, Hayashi & Tanimura, sp. nov. (Figs 1—20). Type: — JAPAN. Deep-sea sediments at the earliest Middle Miocene, 490 cm in depth of the RC12-394 core, recovered from the Yamato Bank, Japan Sea (holotype MPC-04211). Vegetative cells: Valves circular, 10–30 µm in diameter, striae density c. 25–30 in 10 µm at margin on valve face; c. 30 areolae in 10 µm, arranged radially. Valve face flattened, mantle vertical. Valve face with central hyaline area, lacking sternum; valve face and margin with internally developed radial transapical ribs and striae. Some ribs extending towards central area, some part way onto valve face, others present only at mantle. Striae composed of parallel rows of areolae. Single rimoportula, simple slit externally, located within stria, with paired lips, internally. Cingulum composed of more than 5 open copulae, band orientation at 90 o to rimoportula. Each copula with ligula and paired areolae divided by septum; areolae in parallel rows. No evidence of further band differentiation. Initial cells: Hemispherical with thin valve margin, 25–30 µm in diameter. Central area with irregularly arranged areolae and hyaline structures. Marginal area composed of internally developed radial costae and striae. Striae composed of parallel areolae rows, single rimoportula located within stria, structure as in vegetative valve.Published as part of Saito-Kato, Megumi, Hayashi, Tatsuya & Tanimura, Yoshihiro, 2011, Tetracyclus radius (Bacillariophyta) a new fossil species from Miocene freshwater sediments in the Japan Sea, pp. 51-57 in Phytotaxa 24 on page 52, DOI: 10.11646/phytotaxa.24.1.7, http://zenodo.org/record/489408

The turnover of continental planktonic diatoms near the middle/late Miocene boundary and their Cenozoic evolution.

Fossil evidence indicates that modern assemblages of temperate nonmarine planktonic diatoms began near the middle/late Miocene boundary when the genus Actinocyclus, an important constituent of lacustrine planktonic diatom assemblages during the early to middle Miocene, was replaced by genera of the family Stephanodiscaceae. This floral turnover has been confirmed in many regions of the world, except eastern Asia where taxonomic data about early and middle Miocene planktonic diatom assemblages have until recently been scarce. Our analysis of Lower and Middle Miocene lacustrine diatomaceous rocks in Japan confirms that species of nonmarine Actinocyclus were important constituents of lake phytoplankton there as well. The appearance of nonmarine Actinocyclus species near the beginning of the Miocene may have resulted from the introduction of euryhaline species into lacustrine environments during a highstand of sea level at that time. Similarly, it is possible that species of Stephanodiscaceae evolved from marine thalassiosiroid ancestors that invaded high latitude lacustrine environments during multiple Paleogene highstands, resulting in a polyphyletic origin of the family. The turnover from nonmarine Actinocyclus to Stephanodiscaceae genera near the middle/late Miocene boundary may be linked to a contemporaneous increase in silica concentrations in lakes caused by active volcanism, increased weathering of silicate rocks due to orogeny, and the expansion of C4 grasslands. This turnover may also have been influenced by enhanced seasonal environmental changes in the euphotic zone caused by the initiation of monsoon conditions and a worldwide increase in meridional temperature gradients during the late Miocene. Morphological characteristics of Stephanodiscaceae genera, such as strutted processes and small size, suggest their species were better adapted to seasonal environmental changes than nonmarine species of Actinocyclus because of their superiority in floating and drifting capabilities and possibly metabolism, intrinsic growth rate, and reproductivity. As climates deteriorated during the late Miocene, Stephanodiscaceae species may have spread from high latitudes to temperate lakes where they diversified, ultimately displacing Actinocyclus

SEM photographs of <i>Actinocyclus</i> species from early to middle Miocene lacustrine sediments in Japan.

<p>(<b>A</b>) <i>A</i>. sp. 4. (<b>B, C</b>) <i>A</i>. <i>nipponicus</i>. (<b>D</b>) <i>A</i>. <i>bradburyii</i>. In <b>C</b>, a black arrow indicates a pseudonodulus.</p

Localities with nonmarine Miocene species of <i>Actinocyclus</i> in Japan.

<p>Localities with nonmarine Miocene species of <i>Actinocyclus</i> in Japan.</p