The effect of anastrozole on bone mineral density during the first 5 years of adjuvant treatment in postmenopausal women with early breast cancer

PURPOSE: The administration of aromatase inhibitors is associated with bone loss in postmenopausal women. We assessed changes in bone mineral density (BMD) from baseline to 60 months of treatment in patients receiving anastrozole as initial adjuvant therapy. METHODS: Postmenopausal women with hormone receptor-positive breast cancer receiving anastrozole as adjuvant therapy at our center since 2004 were enrolled in this study. BMD was assessed by dual-energy X-ray absorptiometry at baseline and after 6, 12, 24, 36, 48 and 60 months. Oral bisphosphonate (Bis) treatment was initiated when patients were diagnosed with osteoporosis having a T-score of −2.5 or lower. RESULTS: Fifty-five patients were enrolled in the study between 2004 and 2011, and the mean follow-up period was 53.6 months. Thirty-five patients were administered Bis (risedronate in 27 patients, alendronate in 8 patients). After 6 months of hormone therapy, BMD decreased by 0.5% from baseline at the lumbar spine (LS) and BMD decreased by 1.5% at the femoral neck (FN). However, BMD increased by 1.9% at the LS and BMD decreased by 1.5% at the FN for 60 months of treatment. In patients treated with upfront Bis (n = 19), 5.4% BMD increase from baseline was noted at the LS whereas in those without Bis (n = 21) BMD decreased by 4.3% from baseline within 24 months (P < 0.0001). Fractures were observed in 4 patients (7.3%), and 1 patient (1.8%) had a fragility fracture. CONCLUSIONS: Upfront treatment of Bis with anastrozole significantly increased BMD at the LS and an optimal use of Bis would not increase bone fractures. TRIAL REGISTRATION: UMIN000001757

Direction of collaborative problem solving-based STEM learning by learning analytics approach.

The purpose of this study was to explore the factors that might affect learning performance and collaborative problem solving (CPS) awareness in science, technology, engineering, and mathematics (STEM) education. We collected and analyzed data on important factors in STEM education, including learning strategy and learning behaviors, and examined their interrelationships with learning performance and CPS awareness, respectively. Multiple data sources, including learning tests, questionnaire feedback, and learning logs, were collected and examined following a learning analytics approach. Significant positive correlations were found for the learning behavior of using markers with learning performance and CPS awareness in group discussion, while significant negative correlations were found for some factors of STEM learning strategy and learning behaviors in pre-learning with some factors of CPS awareness. The results imply the importance of an efficient approach to using learning strategies and functional tools in STEM education

Cognitive clustering in schizophrenia patients, their first-degree relatives and healthy subjects is associated with anterior cingulate cortex volume

Cognitive impairments are a core feature in schizophrenia patients (SCZ) and are also observed in first-degree relatives (FR) of SCZ. However, substantial variability in the impairments exists within and among SCZ, FR and healthy controls (HC). A cluster-analytic approach can group individuals based on profiles of traits and create more homogeneous groupings than predefined categories. Here, we investigated differences in the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery (six subscales) among SCZ, unaffected FR and HC. To identify three homogeneous and meaningful cognitive groups regardless of categorical diagnoses (SCZ, FR and HC), cognitive clustering was performed, and differences in the BACS subscales among the cognitive cluster groups were investigated. Finally, the effects of diagnosis and cognition on brain volumes were examined. As expected, there were significant differences in the five BACS subscales among the diagnostic groups. The cluster-analytic approach generated three meaningful subgroups: (i) neuropsychologically normal, (ii) intermediate impaired and (iii) widespread impaired. The cognitive subgroups were mainly affected by the clinical diagnosis, and significant differences in all BACS subscales among clusters were found. The effects of the diagnosis and cognitive clusters on brain volumes overlapped in the frontal, temporal and limbic regions. Frontal and temporal volumes were mainly affected by the diagnosis, whereas the anterior cingulate cortex (ACC) volumes were affected by the additive effects of diagnosis and cognition. Our findings demonstrate a cognitive continuum among SCZ, FR and HC and support the concept of cognitive impairment and the related ACC volumes as intermediate phenotypes in SCZ

Protocol for a randomized study of the efficacy of ibandronic acid plus eldecalcitol in patients with gastric cancer after gastrectomy: A comparative study of different routes of administration of ibandronic acid [version 2; peer review: 2 approved]

Background: Patients who undergo gastrectomy for gastric cancer are susceptible to osteoporosis. To prevent a decrease in bone mineral density, an appropriate prophylaxis is considered important to adjust the post-gastrectomy condition. In this study, we will compare two different routes of administration of ibandronic acid (oral or intravenous) plus eldecalcitol as a potentially more suitable treatment for patients at a high risk of fragile fracture. Protocol: This study protocol describes a randomized, active-controlled, non-blind, single-center, phase II trial. For patients in the investigational arm (Group A), sodium ibandronate hydrate will be administered intravenously once a month with daily oral intake of eldecalcitol; for those in the control arm (Group B), sodium ibandronate hydrate will be administered orally once a month with daily oral intake of eldecalcitol. We will recruit patients aged 45–85 years who have undergone gastrectomy for gastric cancer and are at a risk of fragility fractures. The study will include patients with existing vertebral fractures and/or femoral proximal fractures, or with lumbar and/or proximal femur bone mineral density of less than 80% of the young adult mean. The primary outcome of this study will be the change in lumbar bone mineral density. We will also evaluate the changes in femur bone mineral density, bone metabolism markers, health-related quality of life as evaluated using the EuroQol 5 Dimension (EQ-5D), and digestive symptoms as evaluated using the Gastrointestinal Symptom Rating Scale after 52 weeks of treatment. Conclusions: We believe that appropriate treatments that are adjusted to the condition of patients after gastrectomy are important for the prevention of bone mineral loss. Registration: This study was accepted by the Japan Registry of Clinical Trials (jRCT1041200059, November 6, 2021)

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

Impact drag force exerted on a projectile penetrating into a hierarchical granular bed

Context. The impact of a solid object onto a small-body surface can be modeled by the solid impact onto a hierarchically structured granular target. Aims. We develop an impact drag force model for the hierarchically structured granular target based on the experiment. Methods. We performed a set of granular impact experiments in which the mechanical strength and porosity of target grains were systematically varied. Tiny glass beads (5 μm in diameter) were agglomerated to form porous grains of 2–4 mm in diameter. Then, the grains were sintered to control their strength. A polyethylene sphere (12.7 mm in diameter) was dropped onto a hierarchical granular target consisting of these porous grains. Motion of the penetrating sphere was captured by a high-speed camera and analyzed. Results. We find that the impact drag force produced by the hierarchically structured granular target can be modeled by the sum of inertial drag and depth-proportional drag. The depth-proportional drag in a hierarchical granular impact is much greater than that of the usual granular target consisting of rigid grains. The ratio between the grain strength and the impact dynamic pressure is a key dimensionless parameter for characterizing this extraordinary large depth-proportional drag. Conclusions. Grain fracturing plays an important role in the impact dynamics when the impact dynamic pressure is sufficiently larger than the grain strength. This implies that the effect of grain fracturing should be considered also for the impact on a small body. It may be that the effective strength of the surface grains can be estimated based on kinematic observations of the intrusion or touchdown of a planetary explorator