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Microfossils are a powerful tool in earth sciences, and they have been widely used for the determination of geological age and in paleoenvironmental studies. However, the identification of fossil species requires considerable time and labor by experts with extensive knowledge and experience. In this study, we successfully automated the acquisition of microfossil data using an artificial intelligence system that employs a computer-controlled microscope and deep learning methods. The system was used to calculate changes in the relative abundance (%) of Cycladophora davisiana , a siliceous microfossil species (Radiolaria) that is widely used as a stratigraphic tool in studies on Pleistocene sediments in the Southern Ocean. The estimates obtained using this system were consistent with the results obtained by a human expert (< ± 3.2%). In terms of efficiency, the developed system was capable of performing the classification tasks approximately three times faster than a human expert performing the same task.

Critical rainfall events are used in landslide early warning systems to predict the occurrence and severity of landslides. In the present study, historical critical rainfall events triggering landslides in Japan were analyzed. We mainly considered the amount of exceeding/nonexceeding rainfall (referred to as critical rainfall here) within an existing 1-km grid covering Japan where landslides occurred. Furthermore, this study could inform the LEWS operational performance. For this purpose, we used historical landslide records retrieved from a Japanese inventory, radar-based rainfall data (1-km grid resolution), and critical rainfall data collected over the past 17 years. Nearly equal numbers of rainfall events were identified with rainfall below and exceeding the critical rainfall level. The probability that a series of rainfall events could cause a landslide was approximately 1.15% when the critical rainfall level was exceeded and 0.09% when the critical rainfall level was not exceeded, with a difference of approximately 10 times. It was also found that even if critical rainfall was not exceeded, in the case of debris flows and slope failures, rainfall exceeding the critical rainfall level occurred one or two days before. In the case of landslides, there occurred rainfall exceeding the critical rainfall level one or two weeks before, and if critical rainfall was exceeded during a subsequent rainfall event, a landslide could occur. In addition, operational evaluation of the Japanese LEWS revealed a recall value of 0.486 in regard to the occurrence prediction accuracy, which was related to the fact that almost half of the rainfall events exhibited rainfall not exceeding the reference rainfall level. The nonoccurrence prediction accuracy reached 0.935, which was greatly influenced by true negative data of nonexceeding rainfall events, accounting for most of the data.

The migration and positioning of osteoclast precursor monocytes are controlled by the blood-enriched lipid mediator sphingosine-1-phosphate (S1P) and have recently been shown to be critical points of control in osteoclastogenesis and bone homeostasis. Here, we show that calcitriol, which is the hormonally active form of vitamin D, and its therapeutically used analog, eldecalcitol, inhibit bone resorption by modulating this mechanism. Vitamin D analogs have been used clinically for treating osteoporosis, although the mode of its pharmacologic action remains to be fully elucidated. In this study, we found that active vitamin D reduced the expression of S1PR2, a chemorepulsive receptor for blood S1P, on circulating osteoclast precursor monocytes both in vitro and in vivo. Calcitriol- or eldecalcitol-treated monocytoid RAW264.7 cells, which display osteoclast precursor-like properties, migrated readily to S1P. Concordantly, the mobility of circulating CX ₃CR1 ⁺ osteoclast precursor monocytes was significantly increased on systemic administration of active vitamin D. These results show a mechanism for active vitamin D in controlling the migratory behavior of circulating osteoclast precursors, and this action should be conducive to limiting osteoclastic bone resorption in vivo.

Soil Water Index (SWI) represents the conceptual water stored in the soil and is calculated using a three-layer tank model with hourly precipitation. In Japan, landslide disasters are likely to occur when SWI in an event exceeds the maximum value of the past 10 years; however, snowmelt-driven landslide disasters have not been considered yet. Using the tank model that simultaneously calculates SWI and runoff, we implemented the snowfall-accumulation-snowmelt processes into the original SWI and applied the modified SWI to meteorological data in Tomsk, Russia, in spring 2010 when severe flood and landslide disasters had occurred. We conducted a sensitivity analysis of hourly precipitation in snowy region in Japan considering that meteorological data in Russia are available every 3 h. When we input the average of the three-hourly accumulated precipitation to calculate SWI, the result was almost identical to that of the observed hourly precipitation being given. We then estimated the hourly temperature by linearly interpolating the data every 3 h, and set the threshold of liquid/solid precipitation. The degree-hour method was employed to calculate the snowmelt. The modified SWI predicted the occurrence of snowmelt-driven landslide disasters in Japan when the calculated SWI exceeded the maximum value in the snowmelt season (March–May) for the past 10 years. When applied to meteorological data in Tomsk, the modified SWI and calculated runoff captured the timing of snowmelt-driven flood and landslide disasters in spring 2010. We demonstrated that by focusing on the maximum value of SWI in the snowmelt season for the past 10 years, we can predict snowmelt-driven landslide disasters.

Aging and pre-existing cognitive impairment are considered to be independent risk factors for sepsis-associated encephalopathy. This study aimed to investigate the manner in which aging and pre-existing cognitive dysfunction modified neuroinflammation, synaptic plasticity, and basal synaptic transmission during the acute phase of sepsis using Senescence-Accelerated Mice Prone 8 (SAMP8) and Senescence-Accelerated Resistant Mice 1 (SAMR1). We used 6-month-old SAMP8 and SAMR1. Sepsis was induced using cecal ligation and puncture (CLP). The animal's hippocampi and blood were collected for subsequent investigations 24 h after surgery. Long-term potentiation (LTP) was impaired in the Shaffer-collateral (SC)-CA1 pathway of the hippocampus in SAMP8 without surgery compared to the age-matched SAMR1, which was reflective of cognitive dysfunction in SAMP8. CLP impaired the SC-CA1 LTP in SAMR1 compared to the sham-operated controls, but not in SAMP8. Moreover, CLP decreased the input-output curve and increased the paired-pulse ratio in SAMP8, suggesting the reduced probability of basal synaptic transmission due to sepsis. Immunohistochemical analysis revealed that CLP elevated IL-1β levels, especially in the hippocampi of SAMP8 with microglial activation. peripheral IL-1 receptor antagonist (IL-1ra) administration in the septic SAMP8 revealed that the neuroinflammation was not correlated with the peripheral elevation of IL-1β. IL-1ra administration to the hippocampus ameliorated LTP impairment in SAMR1 and the reduction in basal transmission in SAMP8 after sepsis. The mechanism of the modulation of synaptic transmission and synaptic plasticity by the acute stage of sepsis differed between SAMR1 and SAMP8. These changes were related to centrally derived IL-1 receptor-mediated signaling and were accompanied by microglial activation, especially in SAMP8.

Poly (ADP-ribose) polymerase (PARP) inhibitors have improved the prognosis of homologous recombination deficient (HRD) ovarian cancer (OC), while effective therapeutic strategies for HR-proficient (HRP) OC still need to be established. This study investigates senescence-mediated inflammation as a novel mechanism of action for PARP inhibitors in HRP cancers. Transcriptome analyses were performed in olaparib-treated HeLa cells as a HRP model. Interferon regulatory factor-Lucia luciferase (IRF-Luc) reporter activity was assessed. The effects of PARP inhibitors on senescence-like phenotypes were assessed in seven HRP cancer cell lines, based on morphological changes, senescence-associated β-galactosidase (SA-β-GAL) activity, cellular granularity, and senescence-associated secretory phenotype (SASP)-related gene expression. Peripheral blood mononuclear cell (PBMC) migration assays were also performed with the conditioned medium in treatment with the PARP inhibitor. Transcriptome analyses revealed numbers of inflammatory cytokine- and chemokine-related pathways were significantly upregulated in olaparib-treated HeLa cells, which were confirmed by IRF-Luc reporter assays. The PARP inhibitors induced senescent phenotypes in HRP cancer cell lines: flattened and enlarged morphology, increased SA-β-GAL activity, elevated cellular granularity, and upregulated expressions of SASP-related genes (e.g., IL1B , IL6 , and CXCL10 ). Furthermore, in vitro migration assays revealed that PARP inhibitor-treated HRP cancer cells attracted PBMCs more abundantly , suggesting the potential for recruiting immune cells to HRP cancer cells through senescence-mediated immunological activation. Our findings suggest that PARP inhibitors recruit immune cells to HRP cancer cells, potentially activating immune responses in the tumor microenvironment, providing new insights into the clinical benefits of PARP inhibitors in immunotherapy for patients with HRP OC.

IntroductionOlder people aged over 75 are more prone to falls because physical functions become deteriorated along with aging, and also fracture risk is strongly correlated with age. We evaluated the effects of anti-osteoporosis agents, eldecalcitol (ELD) and alendronate (ALN) on physical functions by assessing dynamic and static postural balance in aged patients with osteoporosis.Materials and methodsA randomized, open-label, controlled clinical trial has been conducted with 124 female patients aged 65 or over with osteoporosis. Patients were randomly assigned to receive either 0.75 μg of ELD once-a-day or 35 mg of ALN once-a-week for 24 weeks. The primary endpoint was the change in a postural balance index, adjusted composite equilibrium score (CES) of sensory organization test (SOT). The SOT equilibrium scores, leg muscle strength, and other physical functions were also evaluated.ResultsThe Adjusted CES increased from baseline by 6.10% in the ELD group and 6.28% in the ALN group. There was no statistically significant difference between the two groups. The static postural balance at fixed platform were maintained in the ELD group, but declined in the ALN group. The dynamic postural balance at swaying platform and knee extension power increased from baseline in both groups.ConclusionsThese results suggest that ELD and ALN treatments may each be beneficial to improve postural balance control in older patients with osteoporosis via different mechanisms of action.

IntroductionThis real-world study evaluated whether long-term use of eldecalcitol (ELD) increases the risk of adverse events (AEs), namely, hypercalcemia, acute kidney injury (AKI), and urolithiasis, and analyzed the ELD-induced risk of rare AEs such as osteonecrosis of the jaw (ONJ) and atypical femoral fracture (AFF).Materials and methodsPatient records were retrieved from Medical Data Vision (MDV) and Japan Medical Data Center (JMDC) databases. The ELD-treated osteoporosis patient cohort (ELD cohort) was analyzed to determine the incidence rate of the aforementioned AEs. The patient cohort that was prescribed active vitamin D3 other than ELD (AVD cohort) was analyzed as the reference.ResultsIncidence rates of hypercalcemia, AKI, and urolithiasis in the ELD cohort were 0.942, 0.517, 2.465 events per 100 person-years, respectively, in the MDV dataset, and 0.687, 0.155, 3.785, respectively, in the JMDC dataset. The incidence rates of these AEs in the ELD cohort remained relatively constant throughout ELD treatment. A small number of patients experienced ONJ or AFF during ELD or AVD treatment. The number of ONJ and AFF cases in the both cohorts decreased over time. The two cohorts showed no difference in the concomitant use of anti-bone resorptive agents such as bisphosphonates and denosumab.ConclusionThe risk of hypercalcemia and AKI associated with ELD use observed in this retrospective analysis is similar to that reported previously in the Japanese post-marketing surveillance of ELD. Furthermore, ELD, similar to AVD, may not increase the risk of ONJ and AFF.

INTRODUCTION: Primary gastric carcinosarcoma is extremely rare. Herein, we report a case of primary gastric carcinosarcoma with small intestinal intraluminal metastasis.CASE PRESENTATION: The patient was a 77-year-old man who was referred to our hospital for further examination of occult fecal blood. At this time, the patient reported lightheadedness, and severe anemia was confirmed, with a hemoglobin level of 6.5 g/dL. Upper gastrointestinal endoscopy revealed a mass with bleeding spots in the middle 3rd of the stomach, which was thought to be the cause of the anemia. The patient’s overall condition was poor; therefore, we decided to limit the surgery to local resection of the primary lesion as palliative treatment, with the main goal of controlling bleeding. The final pathological diagnosis was gastric carcinosarcoma. Postoperatively, the progression of anemia stopped, the patient was able to eat without any problems, and he was discharged home. However, 9 days later, the patient visited the emergency department complaining of abdominal pain. He was diagnosed with intestinal obstruction and underwent surgery. During surgery, a hard mass was palpable in the small intestine, and the lesion was resected. The pathological findings of the small intestinal mass were identical to those of the gastric tumor, and the patient was diagnosed with small intestinal intraluminal metastasis of the gastric carcinosarcoma. Eight months after surgery, pulmonary metastasis was detected by a CT scan. Chemotherapy with capecitabine and irinotecan was initiated, and tumor reduction was achieved.CONCLUSIONS: Primary gastric carcinosarcoma may present with intraluminal metastasis of the small intestine, and clinicians should make a note of this when treating such patients.

Background Myocardial infarction (MI) complicated by cardiogenic shock during non-cardiac surgery is a rare but fatal complication. The management of intraoperative MI is challenging. Case presentation A 77-year-old hypertensive man with good functional capacity was scheduled for hepatectomy. After the start of liver resection, the electrocardiogram monitor showed ST depression, and the patient developed refractory cardiogenic shock. Transesophageal echocardiography revealed severe hypokinesis of the anteroseptal wall. The surgery was suspended, and an intra-aortic balloon pump was placed following immediate abdominal closure. Coronary angiography revealed severe stenosis of the left main coronary trunk, and percutaneous coronary intervention (PCI) was performed. Myocardial wall motion improved, and blood pressure stabilized. Two days after PCI, hepatectomy, which had been suspended, was successfully completed. Conclusions Once intraoperative MI has occurred, early diagnosis and multidisciplinary approaches are important to manage the difficult clinical situation.