Applying Machine Learning to Determine 25(OH)D Threshold Levels Using Data from the AMATERASU Vitamin D Supplementation Trial in Patients with Digestive Tract Cancer

Some controversy remains on thresholds for deficiency or sufficiency of serum 25-hydroxyvitamin D (25(OH)D) levels. Moreover, 25(OH)D levels sufficient for bone health might differ from those required for cancer survival. This study aimed to explore these 25(OH)D threshold levels by applying the machine learning method of multivariable adaptive regression splines (MARS) in post hoc analyses using data from the AMATERASU trial, which randomly assigned Japanese patients with digestive tract cancer to receive vitamin D or placebo supplementation. Using MARS, threshold 25(OH)D levels were estimated as 17 ng/mL for calcium and 29 ng/mL for parathyroid hormone (PTH). Vitamin D supplementation increased calcium levels in patients with baseline 25(OH)D levels ≤17 ng/mL, suggesting deficiency for bone health, but not in those >17 ng/mL. Vitamin D supplementation improved 5-year relapse-free survival (RFS) compared with placebo in patients with intermediate 25(OH)D levels (18–28 ng/mL): vitamin D, 84% vs. placebo, 71%; hazard ratio, 0.49; 95% confidence interval, 0.25–0.96; p = 0.04. In contrast, vitamin D supplementation did not improve 5-year RFS among patients with low (≤17 ng/mL) or with high (≥29 ng/mL) 25(OH)D levels. MARS might be a reliable method with the potential to eliminate guesswork in the estimation of threshold values of biomarkers

Effect of Vitamin D Supplements on Relapse of Digestive Tract Cancer with Tumor Stromal Immune Response: A Secondary Analysis of the AMATERASU Randomized Clinical Trial

The aim was to examine whether vitamin D supplementation (2000 IU/day) reduces the risk of relapse in a subgroup of patients with digestive tract cancer, showing a sufficient immune response in tumor stroma by conducting secondary subgroup analyses of the AMATERASU randomized, double-blind, placebo-controlled trial (UMIN000001977). A total of 372 patients were divided into two subgroups stratified by the median density of immune cells infiltrating in tumor stroma into higher and lower halves. In the higher-half subgroup of CD56+ cells, the relapse ratio was significantly lower in the vitamin D group (7.4%) than in the placebo group (20.5%) (subdistribution hazard ratio (SHR), 0.35; 95% confidence interval (CI), 0.15–0.82), but it was equivalent (25.2% vs. 22.7%) in the lower-half subgroup of CD56+ cells (SHR, 1.21; 95% CI, 0.68–2.19) with a significant interaction (Pinteraction = 0.02). Although there were no significant differences, the risk of relapse was lower in the vitamin D group than in the placebo group in the higher half of CD45RO+ memory T cells (8.9% vs. 19.2%), and of CD8+ cytotoxic T cells (11.3% vs. 22.5%). In patients with digestive tract cancer, vitamin D supplementation was hypothesized to reduce the risk of relapse in the subgroup of patients who already have an adequate infiltration of immune cells in their tumor stroma

Photo images, 3D/CT data and mtDNA of the freshwater mussels (Bivalvia: Unionidae) in the Kyushu and Ryukyu Islands, Japan, with SEM/EDS analysis of the shell

Freshwater mussels (Bivalvia: Unionidae), which are keystone species of freshwater ecosystems, are in global decline. In addition to ecological/genetic studies, morphological examinations are needed to help provide information for the development of additional freshwater mussel studies and eventually conservation efforts for freshwater ecosystems. The microscopic structure, which can be obtained by scanning electron microscopy (SEM) and elemental composition, which can be obtained with energy dispersive X-ray spectrometry (EDS), of mollusc shells are of interest to malacologists. However, information about freshwater mussels is still limited. Kyushu Island is the southernmost island of the four major islands of Japan. Kyushu Island is a hotspot of bitterling fishes in Japan, which simultaneously means that the island is a hotspot of freshwater mussels. The Ryukyu Islands stretch southwest from Kyushu Island to Taiwan; a freshwater mussel of unknown origin was reported from the Ryukyu Islands. Digital archiving for biology and ecology is a continuing challenge for open science. This data paper describes online published photo images, 3D/CT and mtDNA data and SEM/EDS analyses of the shell of freshwater mussels that inhabit the Kyushu and Ryukyu Islands, Japan. Our data will provide basic information regarding freshwater biology and be of public interest as open science. Photo images, 3D/CT data, mtDNA data, SEM images and EDS elemental analysis of freshwater mussels that inhabit the Kyushu and Ryukyu Islands (61 individuals, nine species/subspecies) were published online in a local database (http://ffish.asia/Unionidae3D), GBIF (http://ipt.pensoft.net/resource?r=unionidae3d) and DDBJ/EMBL/Genbank (LC431810–LC431840)

Prognostic significance of osteosarcopenia in older adults with colorectal cancer

Abstract Aim Osteopenia and sarcopenia, features of the aging process, are recognized as major health problems in an aging society. This study investigated the prognostic impact of osteosarcopenia, the coexistence of osteopenia and sarcopenia, in older adults undergoing curative resection for colorectal cancer. Methods We retrospectively reviewed data of older adults aged 65–98 y who had undergone curative resection for colorectal cancer. Osteopenia was evaluated by bone mineral density measurement in the midvertebral core of the 11th thoracic vertebra on preoperative computed tomography images. Sarcopenia was evaluated by measuring the skeletal muscle cross‐sectional area at the third lumbar vertebra level. Osteosarcopenia was defined as the coexistence of osteopenia and sarcopenia. We explored the relationship of preoperative osteosarcopenia with the disease‐free and overall survival after curative resection. Results Among the 325 patients included, those with osteosarcopenia had significantly lower overall survival rates than those with osteopenia or sarcopenia alone (P < 0.01). In the multivariate analysis, male sex (P = 0.045), C‐reactive protein‐to‐albumin ratio (P < 0.01), osteosarcopenia (P < 0.01), pathological T4 stage (P = 0.023), and pathological N1/N2 stage (P < 0.01) were independent predictors of disease‐free survival, while age (P < 0.01), male sex (P = 0.049), C‐reactive protein‐to‐albumin ratio (P < 0.01), osteosarcopenia (P < 0.01), pathological T4 stage (P = 0.036), pathological N1/N2 stage (P < 0.01), and carbohydrate antigen 19–9 (P = 0.041) were independent predictors of overall survival. Conclusion Osteosarcopenia was a strong predictor of poor outcomes in older adults undergoing curative resection for colorectal cancer, suggesting an important role of osteosarcopenia in an aging society

Thioxanthone-containing blue thermally activated delayed fluorescent emitter

Accelerating reverse intersystem crossing (RISC) without sacrificing fast radiative decay is effective in suppressing efficiency roll-off (eRO) in thermally activated delayed fluorescence (TADF)-based organic light-emitting diodes. We here report a TADF emitter, CC-TXO-I, combining a bicarbazole donor (CC) and a sulfur-containing acceptor (TXO). The CC is used to accelerate radiative decay via moderate donor-acceptor torsion angle, and the TXO is expected to provide fast RISC by the heavy-atom effect. We realized very large rate constants of RISC (kRISCs) of ∼10⁷ s⁻¹. Both kRISCs and rate constants of radiative decay of CC-TXO-I increased with increasing doping concentration, resulting in improved eROs