Search

Background: Bone marrow metastasis (BMM) of gastric cancer (GC), which is the most common cause of disseminated intravascular coagulation (DIC) among solid tumors, has a poor prognosis. Studies on prognostic improvement beyond one year in patients with GC with BMM are limited. This is the first report of a patient who survived over three years after 30 months of S-1 plus oxaliplatin (SOX) therapy for GC with BMM., Case Report: The patient was a 72-year-old woman who presented with anemia and high levels of alkaline phosphatase (ALP) and carbohydrate antigen 19-9 (CA19-9). Detailed examination led to the diagnosis with BMM of GC uncomplicated by DIC and the SOX regimen was initiated in November 2018. After six cycles, she was switched to S-1 monotherapy, and both ALP and CA19-9 levels reached normal by November 2019. However, computed tomography in April 2021 showed multiple bone metastases. Therefore, she was switched to paclitaxel-based therapy. In November 2021, the patient was further switched to nivolumab monotherapy, but she succumbed due to DIC in March 2022., Conclusion: GCs with BMM are prone to DIC, and the SOX regimen, which includes S-1 with efficacy against micrometastases, may constitute a safe and effective treatment modality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Suto, Inui and Okamura.)

Subcommittee on Survey of Nuclear Medicine Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5 years since 1982 to survey contemporary nuclear medicine practice and its changes over the years. The subcommittee sent questionnaires, including the number and category of examinations as well as the kind of the radiopharmaceuticals during the 30 days of June 2022 to all nuclear medicine institutes in Japan. The total numbers of them for the year 2022 were estimated depends on the 1-month data. A total of 1095 institutes responded to the survey, including 364 positron emission tomography (PET) centers. The recovery rate was 90.6%. The number of gamma cameras installed was 1299 in total, with 2.5% decrease in 5 years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 83.8% and 35.5%, respectively. The number of single-photon tracer studies in 2022 was 1.11 million which means increase in 2.7% in 5 years. Bone scintigraphy was a leading examination (31.0%), followed by myocardial scintigraphy (27.1%) and cerebral perfusion study (23.8%) in order. The percentage of SPECT studies showed an increase from 63.5% in previous survey to 66.8% in this survey. PET centers have also increased from 389 to 412, as compared with the previous one. One hundred and twenty-two PET centers have installed one or two in-house cyclotrons. Increasing trends of the PET studies were observed from 1992 to 2017, the trend changed and PET studies showed 1.5% decrease in 5 years. 18 F-FDG accounted for 98.6% (610,497 examinations). PET examinations using 11 C-methionine, 13 N-NH 3 and 11 C-PIB have decreased, with 1624, 2146 and 525 examinations, respectively in 2022. The total number of nuclear medicine examination was eventually increased by 1.0%. Therapies for pheochromocytoma or paraganglioma (PPGL) with 131 I-MIBG and for neuroendocrine tumor with 177 Lu-DOTA-TATE were newly started, however, a total number of targeted radionuclide therapy was decreased by 17.7% because 131 I-radioiodine and 223 Ra targeted therapies were decreased and supply of some radioisotopes was discontinued. 131 I-radioiodine targeted therapy showed a decrease in 5 years (- 15.9%), including 4099 patients for thyroid cancer. The number of out-patient thyroid bed ablation therapy with 1110 MBq of 131 I was also decreased to 1015 per year. The number of admission rooms specialized for radionuclide targeted therapy increased from 157 to 160. The number of 223 Ra targeted therapies for castration-resistant metastatic prostate cancer (mCRPC) was 1041 patients. This survey was performed during COVID-19 pandemic, however, total number of nuclear medicine examinations was almost same as previous survey (+ 1.0%). Radionuclide therapies with 131 I-MIBG and 177 Lu-DOTA-TATE were newly started, and new radionuclide therapy will be available in future, therefore, the development of radionuclide therapy will be continued. We are convinced that this survey report is useful in understanding the current status of the nuclear medicine practice in Japan, and in devising the new strategy to strengthen a role of nuclear medicine., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

The imbalance in the phosphorylation and the dephosphorylation of proteins leads to various diseases. Therefore, in vivo, the functions of protein kinases and protein phosphatases are strictly regulated. Mg 2+ /Mn 2+ -dependent protein phosphatase PPM1M has been implicated in immunity and cancer; however, the regulation mechanism remains unknown. In this study, we show that PPM1M is regulated in different ways by multiple phosphorylation. PPM1M has four Ser/Thr-Pro motifs (Ser27, Ser43, Ser60, and Thr254) that are recognized by proline-directed kinases, and Ser60 was found to be phosphorylated by cyclin-dependent kinase 5 (CDK5) in the cell. The phospho-mimetic mutation of Ser27 and Ser43 in the N-terminal domain suppresses the nuclear localization of PPM1M and promotes its accumulation in the cytoplasm. The phospho-mimetic mutation of Ser60 decreases PPM1M activity; conversely, the phospho-mimetic mutation of Thr254 increases PPM1M activity. These results suggest that the subcellular localization and phosphatase activity of PPM1M are regulated by protein kinases, including CDK5, via phosphorylation at multiple sites. Thus, PPM1M is differentially regulated by proline-directed kinases, including CDK5., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We report the complete organellar genome sequences of an ultrasmall green alga, Medakamo hakoo strain M-hakoo 311, which has the smallest known nuclear genome in freshwater green algae. Medakamo hakoo has 90.8-kb chloroplast and 36.5-kb mitochondrial genomes containing 80 and 33 putative protein-coding genes, respectively. The mitochondrial genome is the smallest in the Trebouxiophyceae algae studied so far. The GC content of the nuclear genome is 73%, but those of chloroplast and mitochondrial genomes are 41% and 35%, respectively. Codon usages in the organellar genomes have a different tendency from that in the nuclear genome. The organellar genomes have unique characteristics, such as the biased encoding of mitochondrial genes on a single strand and the absence of operon structures in chloroplast ribosomal genes. Medakamo hakoo will be helpful for understanding the evolution of the organellar genome and the regulation of gene expression in chloroplasts and mitochondria.

Post-stroke gait disorders involve altered lower limb kinematics. Recently, the endpoint of the lower limb has been used as a control variable to understand gait kinematics better. In a cross-sectional study of sixty-seven post-stroke patients, the limb extension angle and effective limb length during gait were used as input variables with a mixed Gaussian model-based probabilistic clustering approach to identify five distinct clusters. Each cluster had unique characteristics related to motor paralysis, spasticity, balance ability, and gait strategy. Cluster 1 exhibited high limb extension angle and length values, indicating increased spasticity. Cluster 2 had moderate extension angles and high limb lengths, indicating increased spasticity and reduced balance ability. Cluster 3 had low limb extension angles and high limb length, indicating reduced balance ability, more severe motor paralysis, and increased spasticity. Cluster 4 demonstrated high extension angles and short limb lengths, with a gait strategy that prioritized stride length in the component of gait speed. Cluster 5 had moderate extension angles and short limb lengths, with a gait strategy that prioritized cadence in the component of gait speed. These findings provide valuable insights into post-stroke gait impairment and can guide the development of personalized and effective rehabilitation strategies., (© 2024. The Author(s).)

Objective High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective treatment option for relapsed and refractory aggressive malignant lymphoma. However, patients frequently experience treatment-induced gastrointestinal symptoms. Synbiotics, including live microorganisms and nondigestible food ingredients, reportedly ameliorate chemotherapy-induced mucosal damage. In this study, we assessed the efficacy and safety of synbiotics in patients undergoing auto-HSCT. Methods This randomized, double-blinded study included patients with malignant lymphoma eligible for auto-HSCT. The patients were randomly assigned to either a synbiotic group receiving Bifidobacterium longum (BB536) and guar gum or a placebo group receiving a placebo containing dextrin. The supplements were administered twice daily from the start of conditioning chemotherapy up to 28 days after auto-HSCT. The primary endpoint was the duration of total parenteral nutrition (TPN). Results In total, 12 patients were included and randomized. The median duration of TPN was 15 (range, 12-33) days in the synbiotic group and 17.5 (range, 0-32) days in the placebo group. The median duration of grade ≥3 diarrhea was shorter in the synbiotic group than in then placebo group (2.5 vs. 6.5 days), as was the duration of hospital stay (31.5 vs. 43 days). The oral intake and quality of life regarding diarrhea and anorexia improved in the synbiotic group after engraftment. Synbiotic infections, including bacteremia, were not observed. Conclusion Synbiotics may reduce gastrointestinal toxicity, thereby reducing nutritional problems and improving the quality of life of patients undergoing auto-HSCT, without severe adverse events.

Coherent Ising machine (CIM) is a network of optical parametric oscillators that can solve large-scale combinatorial optimisation problems by finding the ground state of an Ising Hamiltonian. As a practical application of CIM, Aonishi et al., proposed a quantum-classical hybrid system to solve optimisation problems of [Formula: see text]-regularisation-based compressed sensing. In the hybrid system, the CIM was an open-loop system without an amplitude control feedback loop. In this case, the hybrid system is enhanced by using a closed-loop CIM to achieve chaotic behaviour around the target amplitude, which would enable escaping from local minima in the energy landscape. Both artificial and magnetic resonance image data were used for the testing of our proposed closed-loop system. Compared with the open-loop system, the results of this study demonstrate an improved degree of accuracy and a wider range of effectiveness., (© 2023. Springer Nature Limited.)

Background: Stroke patients have difficulty walking in outdoor environments, including uneven surfaces, reducing their opportunities for social participation. Changes in stroke patients' gait while walking on even surfaces have been reported; however, gait alterations on uneven surfaces remain unclear., Research Question: To what extent do biomechanical parameters and muscle activity during even and uneven surface walking differ between stroke patients and healthy people?, Methods: Twenty stroke patients and 20 age-matched healthy people walked on a 6 m even and uneven surfaces. Data on gait speed, root mean square (RMS) of trunk acceleration as a measure of gait stability, maximum joint angle, average muscle activity, and muscle activity time were quantified using accelerometers attached to the trunk, video camera images, and electromyography of lower extremities. A two-factor mixed-model analysis of variance was used to test the effects of group, surface, and group × surface interactions., Results: Gait speed decreased (p < 0.001) on the uneven surface in stroke patients and healthy people. RMS showed an interaction (p < 0.001), and the post-hoc test revealed an increase in stroke patients in the mediolateral direction during the swing phase on the uneven surface. The hip extension angle during the stance phase showed an interaction (p = 0.023), and the post-hoc test revealed a decrease in stroke patients on the uneven surface. The soleus muscle activity time showed an interaction during the swing phase (p = 0.041), and the post-hoc test revealed an increase in stroke patients compared to healthy people only on the uneven surface., Significance: While walking on an uneven surface, stroke patients showed decreased gait stability, decreased hip extension angle during stance phase, and increased ankle plantar flexor activity time during swing phase. These changes may result from impaired motor control and compensatory strategies used by stroke patients on uneven surfaces., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: As less autopsies are performed, the need for postmortem computed tomography (PMCT) as an alternative is increasing. It is important to know how postmortem changes over time are reflected on CT, in order to improve the diagnostic capability of PMCT and replace forensic pathology evaluations such as time of death estimation., Methods: In this study, we examined temporal changes on postmortem chest CT images of a rat model. After acquiring antemortem images under isoflurane inhalation anesthesia, the rats were euthanized with a rapid intravenous injection of anesthetics. From immediately after death to 48 hours postmortem, chest images were acquired using small-animal CT. The 3D images were then evaluated on a workstation to measure the antemortem and postmortem air content in the lungs, trachea, and bronchi over time., Results: The air content in the lungs decreased, but the air content of the trachea and bronchi temporarily increased 1-12 hours postmortem, then decreased at 48 hours postmortem. Therefore, the measurement of trachea and bronchi volumes on PMCT could be an objective way to estimate the time of death., Conclusions: While the air content of the lungs decreased, the volume of the trachea and bronchi temporarily increased after death, indicating the potential to use such measurements to estimate time of death., Competing Interests: None.

Background/aim: Bone marrow metastasis (BMM) of gastric cancer (GC) is complicated by disseminated intravascular coagulation syndrome (DIC), which is more prominent in poorly differentiated carcinoma. This is one of the first case reports of a slowly progressing BMM of GC after approximately 1 year of follow-up without treatment., Case Report: A 72-year-old woman underwent total gastrectomy and splenectomy for GC in February 2012. The pathological diagnosis was that of a moderately differentiated adenocarcinoma. Five years later in December 2017, she developed anemia; however, its cause remained unknown. Due to worsening of the anemia, the patient visited the Kakogawa Central City Hospital in October 2018. Bone marrow biopsy revealed an infiltration of caudal type homeobox 2-positive cancer cells, and our diagnosis was BMM of GC. There was no DIC. The incidence of BMM is high in well- or moderately differentiated breast cancer but rarely causes DIC., Conclusion: As with breast cancer, in moderately differentiated cancer cells, BMM of GC may progress slowly after the appearance of symptoms without causing DIC., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Ultrasmall algae have attracted the attention of biologists investigating the basic mechanisms underlying living systems. Their potential as effective organisms for producing useful substances is also of interest in bioindustry. Although genomic information is indispensable for elucidating metabolism and promoting molecular breeding, many ultrasmall algae remain genetically uncharacterized. Here, we present the nuclear genome sequence of an ultrasmall green alga of freshwater habitats, Medakamo hakoo. Evolutionary analyses suggest that this species belongs to a new genus within the class Trebouxiophyceae. Sequencing analyses revealed that its genome, comprising 15.8 Mbp and 7629 genes, is among the smallest known genomes in the Viridiplantae. Its genome has relatively few genes associated with genetic information processing, basal transcription factors, and RNA transport. Comparative analyses revealed that 1263 orthogroups were shared among 15 ultrasmall algae from distinct phylogenetic lineages. The shared gene sets will enable identification of genes essential for algal metabolism and cellular functions., (© 2023. The Author(s).)

During de novo plant organ regeneration, auxin induction mediates the formation of a pluripotent cell mass called callus, which regenerates shoots upon cytokinin induction. However, molecular mechanisms underlying transdifferentiation remain unknown. Here, we showed that the loss of HDA19 , a histone deacetylase (HDAC) family gene, suppresses shoot regeneration. Treatment with an HDAC inhibitor revealed that the activity of this gene is essential for shoot regeneration. Further, we identified target genes whose expression was regulated through HDA19-mediated histone deacetylation during shoot induction and found that ENHANCER OF SHOOT REGENERATION 1 and CUP-SHAPED COTYLEDON 2 play important roles in shoot apical meristem formation. Histones at the loci of these genes were hyperacetylated and markedly upregulated in hda19 . Transient ESR1 or CUC2 overexpression impaired shoot regeneration, as observed in hda19 . Therefore, HDA19 mediates direct histone deacetylation of CUC2 and ESR1 loci to prevent their overexpression at the early stages of shoot regeneration., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

Abstract: Approximately 50% of autosomal dominant polycystic kidney disease (ADPKD) patients have gross hematuria, but few cases of bladder cancer complications are known. We report a case of a 49-year-old female ADPKD patient with bladder cancer, who was presented to our hospital 4 months after the onset of gross hematuria. A computed tomography (CT) scan showed a bladder mass, enlarged pelvic and left inguinal lymph nodes, multiple liver cysts, and a polycystic kidney. Based on family history, CT scan results, and lymph node biopsy, we diagnosed the patient with uroplakin III-negative bladder cancer with squamous metaplasia and ADPKD. The patient was treated with systemic chemotherapy but died 2 months after the definitive diagnosis. The delayed diagnosis was disastrous, and malignancy should be considered in the differential diagnosis when symptoms suggestive of malignancy such as hematuria appear. Particularly, uroplakin III-negative advanced bladder cancer has a poor prognosis and requires early diagnosis and treatment., (Copyright © 2022 Copyright: © 2022 Journal of Cancer Research and Therapeutics.)

Purpose: Exercise motivation (EM) is related to individual capabilities and social support. However, in support facilities for people with disabilities, it is susceptible to a lack of social support. In this study, we classified EM into Autonomous Motivation (AM) and controlled motivation (CM) and then examined the influence of social support., Method: Thirty-three residents from a support facility for people with disabilities in Japan participated in this study. We conducted a hierarchical multiple regression analysis in which age, gender and time since admission were entered in Step 1, mobility and self-efficacy as individual capabilities in Step 2, and family support, facility support and peer support as social support in Step 3., Result: A significant increase in variance from Step 2 to Step 3 was found for both AM (Δ R 2  = 0.504, Δ F  = 12.18, p  < .001) and CM (Δ R 2  = 0.269, Δ F  = 3.491, p  = .031). The results also showed that AM was higher among those with high family and facility support, and CM was higher among those with low family and high peer support., Conclusions: Social support was a more significant predictor of EM among participants than individual capabilities.KEY MESSAGESAmong residents of support facilities for people with disabilities, assessing not only individual capabilities but also social support status can lead to better understandings of exercise motivation (EM).To enhance facility residents' autonomous motivation (AM), it is necessary to intervene after evaluating family and facility support.When family support is not readily available among facility residents, efforts should be made to encourage residents to interact with each other to increase peer support.

Renin is the rate-limiting enzyme in the renin-angiotensin-aldosterone system (RAAS) which regulates blood pressure and renal function and hence is an attractive target for the treatment of hypertension and cardiovascular/renal diseases. However, the development of direct renin inhibitors (DRIs) with favorable oral bioavailability has been a longstanding challenge for many years. This problem was thought to be because most of the reported DRIs were peptide-like structures or nonpeptide-like structures with a molecular weight (MW) of > 600. Therefore, we tried to find nonpeptidomimetic DRIs with a MW of < 500 and discovered the promising 2-carbamoyl morpholine derivative 4 . In our efforts to improve the pharmacokinetic profile of 4 without a significant increase in the MW, we discovered compound 18 (SPH3127), which demonstrated higher bioavailability and a more potent antihypertensive effect in preclinical models than aliskiren and has completed a phase II clinical trial for essential hypertension.

This study aimed to investigate the effect of cognitive reserve (CR) on the rate of cognitive decline and cerebral glucose metabolism in amnestic mild cognitive impairment (MCI) using the Study on Diagnosis of Early Alzheimer's Disease-Japan (SEAD-J) dataset. The patients in SEAD-J underwent cognitive tests and fluorodeoxyglucose-positron emission tomography (FDG-PET). MCI to be studied was classified as amnestic MCI due to Alzheimer's disease (AD) with neurodegeneration. A total of 57 patients were visually interpreted as having an AD pattern (P1 pattern, Silverman's classification). The 57 individuals showing the P1 pattern were divided into a high-education group (years of school education ≥13, N = 18) and a low-education group (years of school education ≤12, N = 39). Voxel-based statistical parametric mapping revealed more severe hypometabolism in the high-education group than in the low-education group. Glucose metabolism in the hippocampus and temporoparietal area was inversely associated with the years of school education in the high- and low-education groups ( N = 57). General linear mixed model analyses demonstrated that cognitive decline was more rapid in the high-education group during 3-year follow-up. These results suggest that the cerebral glucose metabolism is lower and cognitive function declines faster in patients with high CR of amnestic MCI due to AD defined by FDG-PET., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kato, Nishita, Otsuka, Inui, Nakamura, Kimura, Ito and SEAD-J Study Group.)

The renin-angiotensin-aldosterone system (RAAS) plays a key role in the regulation of blood pressure. Renin, the first and rate-limiting enzyme of the RAAS, is an attractive target for the treatment of hypertension and cardiovascular/renal diseases. Therefore, various direct renin inhibitors (DRIs) have been researched over recent decades; however, most exhibited poor pharmacokinetics and oral bioavailability due to the peptidomimetic or nonpeptidomimetic structures with a molecular weight (MW) of >600, and only aliskiren is approved. This study introduces a novel class of DRIs comprised of a 2-carbamoyl morpholine scaffold. These compounds have a nonpeptidomimetic structure and a MW of <500. The representative compound 26 was highly potent despite not occupying S1'-S2' sites or the opened flap region used by other DRIs and exerted a significant antihypertensive efficacy via oral administration on double transgenic mice carrying both the human angiotensinogen and the human renin genes., Competing Interests: The authors declare the following competing financial interest(s): D.I., H.S., N.A., Y.T., Y.T., T.T., H.A., T.K., K.T., A.K., M.N., Y.I., H.Y. and T.I. were employed by Mitsubishi Tanabe Pharma Corporation at the time this work was done; J.X., J.S., Y.K. and G.X. were employed by Shanghai Pharmaceuticals Holding Co., Ltd. at the time this work was done., (© 2022 American Chemical Society.)

Background/aim: Pulmonary arterial intimal sarcoma (PAIS) is a rare malignant soft tissue tumor that is difficult to differentiate from pulmonary thromboembolism (PTE). Therefore, pre-operative diagnosis is often difficult. However, recent advances in fluorodeoxyglucose positron emission tomography (FDG-PET) have enabled the use of standardized uptake values (SUVs) for the differential diagnosis of PAIS from PTE, and the frequency of diagnosis of PAIS has increased. Here, we report a case of PAIS that was difficult to differentiate from PTE despite using FDG-PET., Case Report: A 40-year-old woman presented with gradually worsening exertional dyspnea. Contrast-enhanced computed tomography (CT) revealed lesions with poor enhancement in the right lateral basal pulmonary artery. FDG-PET/CT did not reveal any tumor or thrombosis in other areas. Cytological evaluation using a right ventricular catheter did not lead to a definitive diagnosis. Because the patient did not respond to anticoagulation, we performed pulmonary artery endarterectomy. Pathological examination of the pulmonary artery tumor revealed a mucinous tumor with an edematous stroma and spindle-shaped tumor-cell proliferation, which confirmed the diagnosis of PAIS. However, FDG/PET demonstrated a low SUV of 3.4., Conclusion: Some PAISs with low cellular densities and high mucous tissue proportions have SUVs similar to those in PTE. In patients with low FDG uptake, if PAIS is suspected based on other objective findings, additional exploration using highly invasive tests or surgical procedures specific to PAIS is warranted., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: Although previous studies have investigated age and gender effects on striatal subregional dopamine transporter (DaT) binding, these studies were mostly based on a conventional regions of interest-based analysis. Here, we investigated age and gender effects on striatal DaT binding at the voxel level, using a multicenter database of [( 123 )I] N-omega-fluoropropyl-2beta-carbomethoxy-3beta-{4-iodophenyl}nortropane ([( 123 )I] FP-CIT)-single photon emission computed tomography (SPECT) scans in 256 healthy Japanese adults., Methods: We used the Southampton method to calculate the specific binding ratios (SBRs) of each subject's striatum and then converted the [ 123 I] FP-CIT SPECT images to quantitative SBRs images. To investigate the effects of age and gender effects on striatal DaT binding, we performed a voxel-based analysis using statistical parametric mapping. Gender differences were also compared between young to middle-aged subjects and elderly subjects (age threshold: 60 years)., Results: When all subjects were explored as a group, DaT binding throughout the striatum decreased with advancing age. Among all subjects, the females showed higher DaT binding in the bilateral caudate compared to the males. In the young to middle-aged subjects, the females showed higher DaT binding throughout the striatum (with a slight caudate predominance) versus the males. In the elderly, there were no gender differences in striatal DaT binding., Conclusion: Our findings of striatal subregional age- and gender-related differences may provide useful information to construct a more detailed DaT database in healthy Japanese subjects., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

BACKGROUND. Whole-body MRI and FDG PET/MRI have shown encouraging results for staging of thoracic malignancy but are poorly studied for staging of small cell lung cancer (SCLC). OBJECTIVE. The purpose of our study was to compare the performance of conventional staging tests, FDG PET/CT, whole-body MRI, and FDG PET/MRI for staging of SCLC. METHODS. This prospective study included 98 patients (64 men, 34 women; median age, 74 years) with SCLC who underwent conventional staging tests (brain MRI; neck, chest, and abdominopelvic CT; and bone scintigraphy), FDG PET/CT, and whole-body MRI within 2 weeks before treatment; coregistered FDG PET/MRI was generated. Two nuclear medicine physicians independently reviewed conventional tests and FDG PET/CT examinations in separate sessions, and two chest radiologists independently reviewed whole-body MRI and FDG PET/MRI examinations in separate sessions. Readers assessed T, N, and M categories; TNM stage; and Veterans Administration Lung Cancer Study Group (VALSG) stage. Reader pairs subsequently reached consensus. Stages determined clinically during tumor board sessions served as the reference standard. RESULTS. Accuracy for T category was higher ( p < .05) for whole-body MRI (94.9%) and FDG PET/MRI (94.9%) than for FDG PET/CT (85.7%). Accuracy for N category was higher ( p < .05) for whole-body MRI (84.7%), FDG PET/MRI (83.7%), and FDG PET/CT (81.6%) than for conventional staging tests (75.5%). Accuracy for M category was higher ( p < .05) for whole-body MRI (94.9%), FDG PET/MRI (94.9%), and FDG PET/CT (94.9%) than for conventional staging tests (84.7%). Accuracy for TNM stage was higher ( p < .05) for whole-body MRI (88.8%) and FDG PET/MRI (86.7%) than for FDG PET/CT (77.6%) and conventional staging tests (72.4%). Accuracy for VALSG stage was higher ( p < .05) for whole-body MRI (95.9%), FDG PET/MRI (95.9%), and FDG PET/CT (98.0%) than for conventional staging tests (82.7%). Interobserver agreement, expressed as kappa coefficients, ranged from 0.81 to 0.94 across imaging tests and staging endpoints. CONCLUSION. FDG PET/CT, whole-body MRI, and coregistered FDG PET/MRI outperformed conventional tests for various staging endpoints in patients with SCLC. Whole-body MRI and FDG PET/MRI outperformed FDG PET/CT for T category and thus TNM stage, indicating the utility of MRI for assessing extent of local invasion in SCLC. CLINICAL IMPACT. Incorporation of either MRI approach may improve initial staging evaluation in SCLC.

Background: This study aimed to evaluate the usefulness of the Cancer and Aging Research Group (CARG) predictive tool in older Japanese patients with cancer. Methods: Patients aged 65 years or older with solid tumors treated with new anticancer regimens in Kakogawa Central City Hospital between April 2016 and March 2019 were included. Grade 3 or higher risks of developing chemotherapy-related adverse events (CRAEs) were calculated using the tool (low-, intermediate-, or high-risk scores). The association between grade 3−5 CRAE incidence during the first course of each regimen and the calculated risk or the patient characteristics was evaluated. The difference in the incidences of CRAEs between the groups was evaluated by Fisher’s exact test. Results: This study examined 76 patients (mean age: 71 (65−82) years). The incidence of grade 3−5 CRAE was 38%, 55%, and 76% in patients classified as low, medium, and high CARG risk scores (p = 0.035), and the incidence of severe non-hematological toxicities was 4%, 31%, and 52% (p < 0.01), respectively. Eastern Cooperative Oncology Group performance status and age were not associated with chemotherapy toxicity. Conclusions: The CARG predictive tool was valid, suggesting its usefulness in optimizing chemotherapy outcomes in older patients with cancer.

To test the usefulness of the Cancer and Aging Research Group (CARG) predictive tool, it was used to assess elderly cancer patients with prior anticancer therapy. Among patients with solid malignancies aged ≥ 65 years receiving second-line chemotherapy who were admitted to the Department of Medical Oncology/Hematology at Kakogawa Central City Hospital between April 2016 and September 2019, the risk ≥ grade 3 of developing chemotherapy-related adverse events (CRAEs) (low, intermediate, or high) was calculated using the tool. Correlations between grades 3 and 5 CRAE incidence rates in the first course of each regimen and CARG risk score, age, and Eastern Cooperative Oncology Group performance status (ECOG PS) were assessed. Included patients (n = 62) had a mean age of 71 years (range, 65−82 years). Severe CRAE incidence in patients with low, medium, or high CARG risk was 27%, 54%, and 71%, respectively (p = 0.026). The incidence of severe non-hematological toxicities was 5%, 35%, and 64%, respectively (p < 0.01). There was no association between age or ECOG PS and chemotherapy toxicity. The results suggest the validity of the CARG predictive tool in elderly cancer patients with prior anticancer therapy. Particularly, the tool showed potential for predicting non-hematological toxicity.

Recent epidemiological studies have supported the correlation between Helicobacter pylori infection and the development of Alzheimer's disease. HpHpn, a histidine-rich H. pylori protein, forms amyloid-like oligomers; it may be a pathogenic factor for Alzheimer's disease progression. HpHpn may also be transported from the gastric epithelium to the brain. However, HpHpn is secreted from H. pylori on the outer surface of gastric epithelia; therefore, the hypothesized movement of HpHpn across the gastric epithelium to the blood remains controversial. Here, we found the HpHpn showed acidic pH-dependent cellular uptake and subsequent secretion in human gastric epithelial-like carcinoma cells. Furthermore, HpHpn exhibited in vitro permeability across the blood-brain barrier. Although further in vivo experiments are required, our findings suggest that in vitro transcytosis of HpHpn in gastric epithelial cells and the blood-brain barrier may provide new insights into the correlation between H. pylori infections and Alzheimer's disease progression., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Competing Interests: The authors declare no conflicts of interest.

Objective: This study proposes an automated classification of benign and malignant in highly integrated regions in bone single-photon emission computed tomography/computed tomography (SPECT/CT) using a three-dimensional deep convolutional neural network (3D-DCNN)., Methods: We examined 100 regions of 35 patients with bone SPECT/CT classified as benign and malignant by other examinations and follow-ups. First, SPECT and CT images were extracted at the same coordinates in a cube, with a long side two times the diameter of a high concentration in SPECT images. Next, we inputted the extracted image to DCNN and obtained the probability of benignity and malignancy. Integrating the output from DCNN of each SPECT and CT image provided the overall result. To validate the efficacy of the proposed method, the malignancy of all images was assessed using the leave-one-out cross-validation method; besides, the overall classification accuracy was evaluated. Furthermore, we compared the analysis results of SPECT/CT, SPECT alone, CT alone, and whole-body planar scintigraphy in the highly integrated region of the same site., Results: The extracted volume of interest was 50 benign and malignant regions, respectively. The overall classification accuracy of SPECT alone and CT alone was 73% and 68%, respectively, while that of the whole-body planar analysis at the same site was 74%. When SPECT/CT images were used, the overall classification accuracy was the highest (80%), while the classification accuracy of malignant and benign was 82 and 78%, respectively., Conclusions: This study suggests that DCNN could be used for the direct classification of benign and malignant regions without extracting the features of SPECT/CT accumulation patterns., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We analytically and numerically show that the Hillery-Zubairy's entanglement criterion is satisfied both below and above the threshold of coupled non-degenerate optical parametric oscillators (NOPOs) with strong nonlinear gain saturation and dissipative linear coupling. We investigated two cases: for large pump mode dissipation, below-threshold entanglement is possible only when the parametric interaction has an enough detuning among the signal, idler, and pump photon modes. On the other hand, for a large dissipative coupling, below-threshold entanglement is possible even when there is no detuning in the parametric interaction. In both cases, a non-Gaussian state entanglement criterion is satisfied even at the threshold. Recent progress in nano-photonic devices might make it possible to experimentally demonstrate this phase transition in a coherent XY machine with quantum correlations.

Visualization of intracellular structures and their spatial organization inside cells without any modification is essential to understand the mechanisms underlying the biological functions of cells. Here, we investigated the intracellular structure of cyanobacteria Prochlorococcus in the interphase by X-ray diffraction imaging using X-ray free-electron laser. A number of diffraction patterns from single cells smaller than 1 µm in size were collected with high signal-to-noise ratio with a resolution of up to 30 nm. From diffraction patterns, a set of electron density maps projected along the direction of the incident X-ray were retrieved with high reliability. The most characteristic structure found to be common among the cells was a C-shaped arrangement of 100-nm sized high-density spots, which surrounded a low-density area of 100 nm. Furthermore, a three-dimensional map reconstructed from the projection maps of individual cells was non-uniform, indicating the presence of common structures among cyanobacteria cells in the interphase. By referring to the fluorescent images for distributions of thylakoid membranes, nucleoids, and carboxysomes, we inferred and represented their spatial arrangements in the three-dimensional map. The arrangement allowed us to discuss the relevance of the intracellular organization to the biological functions of cyanobacteria.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic is spreading rapidly all over the world. The Japanese government lifted the state of emergency, announced in April 2020, on May 25, but there are still sporadic clusters. Asymptomatic patients who can transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause some of these clusters. It is thus urgent to investigate the seroprevalence of antibodies against SARS-CoV-2 and their neutralizing activity. We conducted a cross-sectional study of >10,000 samples at hospitals in Hyogo Prefecture, Japan., Methods: Between August 6 and October 1, 2020, we collected samples of residual blood from the patients who visited or were admitted to five hospitals and a foundation in Hyogo. We tested the samples for antibodies against SARS-CoV-2 by electrochemiluminescence immunoassay (ECLIA) and chemiluminescent enzyme immunoassay (CLEIA). Sera that were positive by ECLIA or CLEIA were analyzed by an immunochromatographic (IC) test and neutralizing activity assay., Results: We tested 10,377 samples from patients aged between 0 and 99 years old; 27 cases (0.26%) were positive on the ECLIA, and 51 cases (0.49%) were positive on CLEIA. In the 14 cases that tested positive on both ECLIA and CLEIA, the positive rates on the IC test and for neutralizing activity were high (85% and 92%, respectively). In 50 cases (0.48%) that were positive by either ECLIA or CLEIA, the corresponding rates were low (20% and 6%, respectively). The positive rate of neutralizing antibody was 0.15%., Conclusions: These results indicate that most Hyogo Prefecture residents still do not have antibodies and should avoid the risk of incurring a SARS-CoV-2 infection. Two or more antibody tests should be required for seroepidemiological studies of the antibody for SARS-CoV-2, and a neutralizing activity assay is also essential., Competing Interests: Yasuko Mori received the reagents for 5,000 samples used here from Roche as a collaboration of this research., (Copyright © Japan Medical Association.)

Protein phosphatase PPM1H is known to participate in various biological or pathophysiological mechanisms. However, little is known about the molecular mechanisms of its regulation. In this study, we investigated the protein kinases that directly phosphorylate PPM1H, identifying them as cAMP-dependent protein kinase (PKA) and Ca 2+ /calmodulin-dependent protein kinase I (CaMKI). In vitro and in silico analyses showed that the phosphorylation sites of PPM1H by PKA and CaMKI were Ser-123 and Ser-210, respectively. The phosphorylation state of PPM1H in cells exhibited the kinase activator- and inhibitor-dependent changes. In mouse neuroblastoma Neuro2a cells, phosphorylation of Ser-210 was much higher in the phospho-mimetic mutant (S123D) than in the non-phosphorylatable mutant (S123A) when they were treated with ionomycin. This suggests that a hierarchical phosphorylation, with initial phosphorylation of Ser-123 promoting subsequent phosphorylation of Ser-210, occurs in these neuron-like cells. Moreover, in cell-based assay a PPM1H(S123A/S210A) double mutant barely dephosphorylated Smad1, a transcription factor known as an endogenous substrate of PPM1H. These results suggest that cAMP and Ca 2+ /calmodulin regulate dephosphorylation of Smad1 through the dual phosphorylation of PPM1H at Ser-123 and Ser-210., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Acute myeloid leukemia (AML) with an inv(16)(p13q22) or t(16;16)(p13;q22) chromosomal abnormality represents one of the most common subtypes of de novo cases. These chromosomal rearrangements result in multiple CBFB-MYH11 fusion transcripts, with type-A being the most frequent. We here describe a unique case of de novo AML-M1, with inv(16)(p13q22), leading to an unusual CBFB-MYH11 fusion transcript, and der(7)t(7;11)(q31;q21). The fusion transcript involves a CBFB exon 5 with a breakpoint at nucleotide 754, an insertion of a 13-bp sequence of CBFB intron 5 at the fusion point, and the MYH11 exon 27 with a breakpoint at nucleotide 3464. To our knowledge, this CBFB-MYH11 fusion transcript has never been reported previously. The clinical characteristics of the present case are in line with previous reports suggesting that rare CBFB-MYH11 fusion transcripts lead to aberrant characteristics such as an atypical cytomorphology and additional cytogenetic abnormalities., Competing Interests: Declaration of Competing Interest Dr. Minami reports grants, personal fees and other from Novartis, during the conduct of the study; grants from Asahi-Kasei Pharma, grants from Astellas, other from AstraZeneca, grants, personal fees and other from Bayer, grants and personal fees from Behringer, grants, personal fees and other from Bristol-Myers Squibb, personal fees from Celgene, grants, personal fees and other from Chugai, grants, personal fees and other from DaiichiSankyo, grants and personal fees from DaiNihonSumitomo, grants and personal fees from Eizai, personal fees from Janssen, personal fees from Kowa, grants and personal fees from Kyowa-Kirin, grants and personal fees from Lilly, grants and personal fees from Merck Serono, grants, personal fees and other from MSD, grants from Nihon Shinyaku, grants and personal fees from Nippon Chemiphar, grants and personal fees from Eizai, grants, personal fees and other from Ono Yakuhin, personal fees from Ohtsuka, grants, personal fees and other from Pfizer, grants and personal fees from Sanofi, personal fees from Shire Japan, grants, personal fees and other from Taiho, grants from Taisho-Toyama, grants and personal fees from Takeda, grants from Teijin Pharma, grants from Yakult, personal fees from Genomic Health, grants from CSL Behring, grants from Nihon Kayaku, grants from Shionogi, outside the submitted work; Other Authors: none., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: Evaluating the accuracy of the modified Endoscopic ABC (Endo ABC) classification with an electronic endoscopy with narrow band imaging without magnification in diagnosing Helicobacter pylori (H. pylori)-infected gastritis., Methods: A total of 576 patients were enrolled and they underwent modified Endo ABC. They were stratified into 5 groups (A to E) based on the grades of endoscopic findings. H. pylori-infected gastritis status was determined in the following ways: current H. pylori gastritis was defined as active gastritis and/or chronic atrophic gastritis (CAG) seen on endoscopy and positive H. pylori test, naïve H. pylori gastritis was defined as regular arrangement of collecting venules in the angle of the lesser curvature without CAG and negative H. pylori test, and previous H. pylori gastritis was defined as negative H. pylori tests regardless of the presence of CAG., Results: Endo A has 97% accuracy and 100% positive predictive value in diagnosing naïve H. pylori gastritis. Endo E has 97% accuracy and 100% positive predictive value in diagnosing previous H. pylori gastritis. The accuracy of Endo B and Endo C in diagnosing current H. pylori gastritis was 89 and 82% respectively. Endo D has 87% accuracy in diagnosing previous H. pylori gastritis., Conclusion: This study showed that the modified Endo ABC classification enables to accurately determine the H. pylori-infected gastritis status., (© 2019 S. Karger AG, Basel.)

Objectives: We have established a common normal database (NDB) with applicability in multicenter settings for the statistical analysis of brain perfusion single photon emission computed tomography (SPECT) with triple energy window scatter correction, computed tomography-based attenuation correction (CTAC), and spatial resolution compensation. This study aimed to compare the CTAC normal database (CTAC-NDB) with conventional normal databases for the statistical analysis of 123 I-iodoamphetamine ( 123 I-IMP) brain perfusion SPECT at three institutions and to assess the clinical efficiency of CTAC-NDB., Methods: We recruited 45 patients (26 men and 19 women; mean age, 74.2 ± 3.9 years; Mini-Mental State Examination score, 19.8 ± 6.1) with Alzheimer's disease (AD, n = 26), dementia with Lewy bodies (DLB, n = 9), and mild cognitive impairment (n = 10) from three institutions. Three-dimensional stereotactic surface projection (3D-SSP) technique was used to analyze data obtained from the 123 I-IMP brain perfusion SPECT images compared with both CTAC-NDB and conventional NDB. We visually assessed each 3D-SSP z score map to determine the changes in specific findings, such as AD/DLB pattern. Furthermore, the stereotactic extraction estimation analysis software was used to measure the regional z score severity and extent as a semiquantitative assessment., Results: In the visual assessment, all cases exhibited clearer findings with CTAC-NDB than with conventional NDB in the parietotemporal association cortex as well as in the inferior temporal, frontal, and lateral occipital cortices. Contrarily, the findings from the medial cerebral regions, including the precuneus and the posterior cingulate, became indistinct in 71% of the cases and remained unchanged in 25% of the cases. In the semiquantitative analysis, a similar tendency was observed in the mean z score in the three institutions included in the study., Conclusion: Using the CTAC-NDB, the findings in the vicinity of the cranium became increasingly clear, whereas those in the medial surface of the brain became less defined or remained unchanged. These findings were confirmed via a semiquantitative analysis. Moreover, similar changes in the reduction pattern were observed in the three institutions. Therefore, the new database with CTAC might be applicable in other institutions. Data collected in this study may serve as a CTAC-NDB.