Serum levels of vault RNA significantly varied in patients with haematological malignancies.

Among extracellular non­coding RNAs, serum levels of microRNAs have been extensively investigated in cancers. In contrast, the serum levels of vault RNAs (vtRNAs) in relation to various disease conditions remain poorly understood. The present study evaluated the clinical significance of serum vtRNA1­1 levels in patients with blood diseases. The stability and sub­localisation of serum vtRNA1­1 was assessed and a reverse transcription­quantitative PCR method using spiked RNA to quantify serum vtRNA1­1 was developed. Serum vtRNA1­1 levels were assessed in 102 individuals with blood diseases. Serum vtRNA1­1 was demonstrated to be stable for three weeks at 4˚C and was not confined to the exosome fractions. Spiking RNA was used to correct for the inconsistency in RNA extraction. The serum vtRNA1­1 levels ranged between 7.28 and 8.76 log10 cps/ml (median 8.05) in control individuals (n=46). Serum vtRNA1­1 levels correlated with leukocyte counts and increased to a maximum of 10.01 log10 cps/ml in patients with bulky leukaemia and lymphoma and decreased to 6.52 log10 cps/ml during intensive chemotherapy. The serum vtRNA1­1 levels varied significantly in patients with haematological malignancies. Serum vtRNA1­1 may originate from haematological cells and are a potential biomarker of normal and malignant haematological activities.

Urban modeling of shrinking cities through Bayesian network analysis using economic, social, and educational indicators: Case of Japanese cities.

Shrinking cities due to low birthrates and aging populations represent a significant urban planning issue. The research question of this study is: which economic, social, and educational factors affect population decline in Japanese shrinking cities? By modeling shrinking cities using the case of Japanese cities, this study aims to clarify the indicators that affect the population change rate. The study employed Bayesian network analysis, a machine learning technique, using a dataset of economic, social, and educational indicators. In conclusion, this study demonstrates that social and educational indicators affect the population decline rate. Surprisingly, the impact of educational indicators is more substantial than that of economic indicators such as the financial strength index. Considering the limitations in fiscal expenditures, increasing investment in education might help solve the problem of shrinking cities because of low birthrates and aging populations. The results provide essential insights and can function as a planning support system.

Relationship between Health Status and Daily Activities Based on Housing Type among Suburban Residents during COVID-19 Self-Isolation.

COVID-19 significantly impacted residents' health status and daily activities in suburban residential areas. This study elucidated the relationship between health scores, daily activities, and housing types. The method was a questionnaire survey of 378 residents of suburban residential estates in Teraikedai, Kongo District, Japan, during the COVID-19 self-isolation period. Since the survey cohort was New Town, the suburban residential area identified by the Ministry of Land, Infrastructure, Transport and Tourism was targeted. The questions included participant demographics, the Basic Survey on Japanese Social Life, and the SF-12v2. The Tukey-Kramer HSD test and stepwise decreasing logistic regression were used for the statistical analysis of the responses. The COVID-19 self-isolation led to lower physical and mental health scores than usual, and the health scores of residents living in detached houses were better than those of residents in apartments, both those over the age of 65 and those under the age of 65. There was also a correlation between residents' daily activities and their health scores. For those aged under 65 years, the health scores of residents living in detached houses were significantly better than those living in apartments, indicating that daily activities such as sports and recreational hobbies may contribute to health scores.

Time series cross-correlation between home range and number of infected people during the COVID-19 pandemic in a suburban city.

Control of human mobility is one of the most effective measures to prevent the spread of coronavirus disease 2019 (COVID-19). However, the imposition of emergency restrictions had significant negative impacts on citizens' daily lives. As vaccination progresses, we need to consider more effective measures to control the spread of the infection. The research question of this study is as follows: Does the control of home range correlate with a reduction in the number of infected people during the COVID-19 pandemic? This study aims to clarify the correlation between home range and the number of people infected with SARS-CoV-2 during the COVID-19 pandemic in Ibaraki City. Home ranges are analyzed by the Minimum Convex Polygon method using mobile phone GPS location history data. We analyzed the time series cross-correlation between home range lengths and the number of infected people. Results reveal a slight positive correlation between home range and the number of infected people after one week during the COVID-19 pandemic. Regarding home range length, the cross-correlation coefficient is 0.4030 even at a lag level of six weeks, which has the most significant coefficient. Thus, a decrease in the home range is a weak factor correlated with a reduction in the number of infected people. This study makes a significant contribution to the literature by evaluating key public health challenges from the perspective of controliing the spread of the COVID-19 infectuion. Its findings has implications for policy makers, practitioners, and urban scientists seeking to promote urban sustainability.

Human Mobility and Infection from Covid-19 in the Osaka Metropolitan Area

Controlling human mobility is thought to be an effective measure to prevent the spread of the COVID-19 pandemic. This study aims to clarify the human mobility types that impacted the number of COVID-19 cases during the medium-term COVID-19 pandemic in the Osaka metropolitan area. The method used in this study was analysis of the statistical relationship between human mobility changes and the total number of COVID-19 cases after two weeks. In conclusion, the results indicate that it is essential to control the human mobility of groceries/pharmacies to less than 0% and that of parks to more than -20%. The most significant finding for urban sustainability is that urban transit was not found to be a source of infection. Hence governments in cities around the world may be able to encourage communities to return to transit mobility, if they are able to follow the kind of hygiene processes conducted in Osaka.

Work-Related Stress of Work from Home with Housemates Based on Residential Types.

The COVID-19 pandemic has had a significant impact on work environments. Many workers have been requested or instructed to work from home (WFH). This study aimed to clarify the work-related stress of WFH regarding housemates based on residential types during the COVID-19 pandemic. We conducted a web-based questionnaire survey of 500 workers living with housemates in Osaka Prefecture. The WFH environments were analyzed on the basis of high-stress workers (HSWs), which accounted for 17.4% of all subjects, according to three major types of residences in Japan. The main finding is that HSWs with housemates had problems related to noise regardless of the type of residence. This study of workers living with housemates in an urban area contrasts with the findings of preceding study, which found that satisfaction with noise in the environment was higher at home than in the office. HSWs in detached houses and condominium apartments had problems with the levels of noise created by their housemates. The residents living in these types of residences were found to be relatively older, thus potentially having older children who would require a certain level of privacy. WFH workers with insufficient privacy were unable to adapt to WFH environments and suffered from high stress.

Human mobility and infection from Covid-19 in the Osaka metropolitan area.

Controlling human mobility is thought to be an effective measure to prevent the spread of the COVID-19 pandemic. This study aims to clarify the human mobility types that impacted the number of COVID-19 cases during the medium-term COVID-19 pandemic in the Osaka metropolitan area. The method used in this study was analysis of the statistical relationship between human mobility changes and the total number of COVID-19 cases after two weeks. In conclusion, the results indicate that it is essential to control the human mobility of groceries/pharmacies to between -5 and 5% and that of parks to more than -20%. The most significant finding for urban sustainability is that urban transit was not found to be a source of infection. Hence governments in cities around the world may be able to encourage communities to return to transit mobility, if they are able to follow the kind of hygiene processes conducted in Osaka.

Combined Experimental and Theoretical Studies on Planar Chirality of Partially Overlapped C2-Symmetric [3.3](3,9)Dicarbazolophanes.

Partially overlapped dicarbazolophanes exhibit a planar chirality. In this study, C2-symmetrical [3.3](3,9)dicarbazolophane derivatives (CZ1-CZ3) have been optically resolved by preparative chiral high-performance liquid chromatography for the first time. In their circular dichroism (CD) spectra, moderate Cotton effects (CEs) were observed for their 1Lb and 1La transitions (|Δε| = 10-12 and 51-57 M-1 cm-1, respectively), while intense CEs were notified in their 1B transitions (|Δε| = 156-216 M-1 cm-1), absorption dissymmetry (gabs) factors being in orders of 10-2. Circularly polarized luminescence spectrum was also obtained for cyanamide derivative CZ1, with a comparative luminescence dissymmetry (glum) factor of 0.013. A computational investigation was applied to address the factors for such remarkable chiroptical responses in these dicarbazolophanes of planar chirality. Absolute configurations were unambiguously determined by the comparison of experimental and theoretical CD spectra, which was affirmed by the X-ray crystal structural analysis of enantiomerically pure sulfonamide derivative CZ2.

Synthetic and biochemical studies on the effect of persulfidation on disulfide dimer models of amyloid ß42 at position 35 in Alzheimer's etiology.

Protein persulfidation plays a role in redox signaling as an anti-oxidant. Dimers of amyloid ß42 (Aß42), which induces oxidative stress-associated neurotoxicity as a causative agent of Alzheimer's disease (AD), are minimum units of oligomers in AD pathology. Met35 can be susceptible to persulfidation through its substitution to homoCys residue under the condition of oxidative stress. In order to verify whether persulfidation has an effect in AD, herein we report a chemical approach by synthesizing disulfide dimers of Aß42 and their evaluation of biochemical properties. A homoCys-disulfide dimer model at position 35 of Aß42 formed a partial ß-sheet structure, but its neurotoxicity was much weaker than that of the corresponding monomer. In contrast, the congener with an alkyl linker generated ß-sheet-rich 8-16-mer oligomers with potent neurotoxicity. The length of protofibrils generated from the homoCys-disulfide dimer model was shorter than that of its congener with an alkyl linker. Therefore, the current data do not support the involvement of Aß42 persulfidation in Alzheimer's disease.

Longitudinal and Vertical Variations of Dissolved Labile Phosphoric Monoesters and Diesters in the Subtropical North Pacific.

The labile fraction of dissolved organic phosphorus (DOP) - predominantly consisting of phosphoric esters - is an important microbial P source in the subtropical oligotrophic ocean. However, unlike phosphate, knowledge for labile DOP is still limited due to the scarcity of broad and intensive observations. In this study, we examined the concentrations and size-fractionated hydrolysis rates of labile phosphoric monoesters and diesters along a >10,000 km longitudinal transect in the North Pacific (23°N; upper 200-m layer). Depth-integrated monoesters decreased westward with a maximum difference of fivefold. Vertical profiles of monoesters in the eastern and western basins showed decreasing and increasing trends with depth, respectively. The monoester-depleted shallow layer of the western basin was associated with phosphate depletion and monoesterase activity was predominant in the large size fraction (>0.8 µm), suggesting that monoesters are significant P sources particularly for large microbes. In contrast, diester concentrations were generally lower than monoester concentrations and showed no obvious horizontal or vertical variation in the study area. Despite the unclear distribution pattern of diesters, diesterase activity in the particulate fraction (>0.2 µm) increased in the phosphate-depleted shallow layer of the western basin, suggesting that the targeted diesters in the assay were also important microbial P sources. Diesterase activities in the dissolved fraction (<0.2 µm) were not correlated with ambient phosphate concentrations; however, cell-free diesterase likely played a key role in P cycling, as dissolved diesterase activities were substantially higher than those in the particulate fraction. The horizontal and vertical variability of labile monoesters in the subtropical North Pacific were therefore predominantly regulated by P stress in particularly large microbes, whereas the distributions of labile diesters and diesterase activities were generally independent of microbial P stress, indicating a more complex regulation of diesters to that of monoesters.

Treatment patterns, persistence and adherence rates in patients with type 2 diabetes mellitus in Japan: a claims-based cohort study.

OBJECTIVE: To determine real-world trends in antidiabetic drug use, and persistence and adherence, in Japanese patients with type 2 diabetes mellitus (T2DM). DESIGN: Retrospective evaluation of administrative claims data (2011-2015) using the Japan Medical Data Center (JMDC) and Medical Data Vision (MDV) databases. SETTING: Analysis of two administrative claims databases for Japanese patients with T2DM. PARTICIPANTS: Adults (aged ≥18 years) with an International Classification of Diseases, 10th Revision code of T2DM and at least one antidiabetic drug prescription. MAIN OUTCOME MEASURES: Treatment patterns in untreated (UT) or previously treated (PT) patients receiving antidiabetic therapy; persistence with treatment at 12 months; adherence to treatment at 12 months. RESULTS: 40 908 and 90 421 patients were included from the JMDC and MDV databases, respectively. The most frequently prescribed therapy at the index (first prescription) date was dipeptidyl peptidase-4 inhibitor (DPP-4i) in UT patients (JMDC: 44.0%, MDV: 54.8%) and combination therapy in PT patients (74.6%, 81.1%). Most common combinations were DPP-4i plus: biguanide (BG; 11.4%, 10.9%), sulfonylurea (SU; 8.4%, 11.0%) or BG+SU (7.8%, 9.1%). In UT or PT patients from either database whose index prescription was for any antidiabetic drug class(es) other than DPP-4i, the most frequent add-on or switch was to DPP-4i. 12-month persistence with index monotherapy was highest with DPP-4i and BG. Adherence was high (≥80%) for all monotherapy schedules, except insulin and glucagon-like peptide-1 agonist, and for the five most frequent two-drug and three-drug combinations. Persistence was greater in elderly UT patients and in those receiving ≤5 medications, but comparatively worse in UT patients with ≥3 index antidiabetic drug classes. CONCLUSIONS: The findings indicate that DPP-4i is the most commonly used antidiabetic drug class in Japanese patients with T2DM, and persistence and adherence to this antidiabetic drug class are high.

Comparison of persistence and adherence between fixed-dose combinations and two-pill combinations in Japanese patients with type 2 diabetes.

OBJECTIVE: To compare treatment patterns, persistence and adherence between fixed-dose combinations (FDCs) and two-pill combinations (TPCs) of oral antidiabetic drug (OAD) classes in Japanese patients with type 2 diabetes mellitus (T2DM) using administrative claims databases (Japan Medical Data Center [JMDC] and Medical Data Vision [MDV]). METHODS: This was a retrospective, longitudinal cohort analysis conducted between 2011 and 2015, in patients with T2DM receiving OADs as FDC or TPC. Outcomes included prescribing patterns, treatment persistence and adherence. RESULTS: Data from 3474 and 3066 patients receiving FDCs, and 4325 and 5192 patients receiving TPCs from the JMDC and MDV databases, respectively, was extracted. The most common OAD combination received by over half of all patients was dipeptidyl peptidase-4 inhibitor (DPP-4i) + thiazolidinediones (TZDs) (64.1% [JMDC] and 70.5% [MDV]). Overall, 12-month persistence rates were higher in patients receiving FDCs compared with TPCs (70.4 vs. 66.2% [JMDC], 75.6 vs. 55.7% [MDV]). In the JMDC population receiving FDCs or TPCs, persistence rates were highest with DPP-4i schedules (67.5-83.5%). Median time to discontinuation was significantly longer with biguanide + TZD, and DPP-4i + TZD FDC schedules (p < .05) than TPC; adherence rates were ≥80% across all antidiabetic drug classes in both database populations. CONCLUSIONS: Persistence with and adherence to OADs in Japanese patients with T2DM were greater with FDCs than with TPCs, which may suggest increased patient satisfaction due to reduced treatment burden. Further studies are warranted to investigate the impact of adherence and persistence of FDCs of OADs on glycemic control.

A Case of Euthyroid Graves' Ophthalmopathy in a Patient Sero-Negative for TSH Receptor Autoantibody.

We report of a case of Graves' ophthalmopathy presented solely with symptoms of the eyes with normal thyroid function tests and negative immunoreactive TSH receptor autoantibody. 40-year-old male was referred to our hospital due to 2-month history of ocular focusing deficit without any signs or symptoms of hyper- or hypothyroidism. Serum thyroid function tests and 99mTc uptake were both within the normal range. Anti-thyroid autoantibodies were all negative except for the cell-based assay for serum TSH receptor stimulating activity. Since orbital CT scan and MRI gave typical results compatible with Graves' ophthalmopathy, we treated the patients with corticosteroid pulse therapy and orbital radiation therapy, leading to a partial improvement of the symptoms. This case gives insights into the potential pathophysiologic mechanism underlying Graves' ophthalmopathy and casts light upon the difficulties of establishing the diagnosis in a euthyroid case with minimal positive results for anti-thyroid autoantibodies.