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We are interested in the amplification of very low voltages produced by solar cells during sunset or weak sunshine. The study uses a device consisting of a Duffing oscillator, which amplifies and automatically regulates a low-voltage input, an inverter that reverses the negative voltage of one of the outputs of the oscillator, and a summing device to add the voltages of the two oscillator outputs. Experimental and theoretical investigations are conducted, and it is observed from the results that the output voltage can reach to 7.03V for an input voltage of 0.43V, i.e. a gain of 24.3dB. Furthermore, we observe from the amplification factor, and the behavior of the cyclic ratio that the whole system nonlinearly amplifies the input voltage with a large factor for weak inputs. We finally compare the results produced by the proposed system and those produced by a conventional boost converter at very low voltages. It then results that the Duffing oscillator provides large amplification factors for low voltages.

Abstract Background Low-income is one of the well-established determinants of people’s health and health-related behavior, including susceptibility to the coronavirus disease 2019 (COVID-19) infection. Two social welfare services are available in Japan to support financial and medical care among low-income patients: Public Assistance (PA), which provide both minimum income and medical costs; and Free/Low-Cost Medical Care (FLCMC), wherein only medical costs were covered. In this study, changes in Health-Related Quality of Life (HRQOL) scores of low-income patients on PA and FLCMC, before and after COVID-19 pandemic, were described and compared against those that are not utilizing the said services (comparison group) to evaluate the contribution of social welfare services in protecting the HRQOL of the beneficiaries during the pandemic. Methods We used repeated cross-sectional data of adult beneficiaries of FLCMC and PA, as well as those without social welfare services, who regularly visit the Kamigyo clinic in Kyoto, Japan. We collected the data from 2018 and 2021 using a questionnaire on patients’ socioeconomic attributes and the Japanese version of Medical Outcomes Study 12-Item Short Form Health Survey (SF-12). The Japanese version of SF-12 can calculate the three components scores: physical health component summary (PCS), the mental health component summary (MCS), and the role-social component summary (RCS), which can be transformed to a 0–100 range scale with a mean of 50 and standard deviation of 10. Results Data of 200 and 174 beneficiaries in 2018 and 2021, respectively, were analyzed. Low-income patients on social welfare services had lower PCS, and RCS than the comparison group in both years. Multiple linear regression analyses with cluster-adjusted standard error estimator showed that the decline in MCS was significantly higher among FLCMC beneficiaries than in those without welfare services (Beta: -4.71, 95% Confidence Interval [CI]: –5.79 to -3.63, p

Background: The Free/Low-Cost Medical Care Program (FLCMC) can subsidize the payment (exempt/lower) in designated institutions in Japan. Given that poverty is a multidimensional concept including social isolation, the FLCMC applicants may need social support over and above financial aid to improve their quality of life. However, there was no data to discuss what services should be provided and to whom. Hence, we aimed to describe the changes in health-related quality of life scores among users of the FLCMC, with respect to their socioeconomic backgrounds. Methods: This cohort study included patients who newly used FLCMC from July 2018 to April 2019. We used patients’ social work records, obtained at baseline, and self-report questionnaires on the Medical Outcomes Study 8 Items Short Form Health Survey (SF-8), measured both at baseline and 6 months after the application. We used the change in physical and mental health component summary scores (PCS-8 and MCS-8, respectively) as outcome variables. Results: Multiple linear regression analyses, adjusting for age, sex, healthcare institute, and baseline PCS-8 and MCS-8, showed that lower income was associated with an increase in PCS-8 (coef. −0.09; 95% CI, −0.15 to, −0.03) and MCS-8 (coef. −0.04; 95% CI, −0.11, to 0.03). Living alone (versus living with someone) was potentially associated with a decrease in both PCS-8 (coef. −1.58; 95% CI, −7.26 to 4.09) and MCS-8 (coef. −3.62; 95% CI, −9.19 to 1.95). Conclusion: Among patients using FLCMC, those who live alone may need additional support. Further study testing the generalizability of the findings is required.

Background/objective: With increased life expectancy, the incidence of colorectal cancer in oldest-old patients has been rising. Advanced age is a risk factor for adverse outcomes after surgery. This study aimed to evaluate the short- and long-term outcomes of curative resection for colorectal cancer in nonagenarians. Methods: Patients who had undergone curative resection for colorectal cancer (CRC) at Stage I to III from January 2010 to December 2019 were included. Cases of emergent surgery were excluded. The clinical characteristics were documented retrospectively, and factors affecting the long-term outcome were analyzed using multivariate analysis. Results: Fifty patients met the selection criteria. Most of them were women (58.0%), and the median age was 92 years. Among these patients, 29 (58.0%) had a poor performance status (ASA-PS≥3). Laparoscopic surgery was performed in 42.0% of the patients, and 50% of the patients had postoperative complications classified as Clavien–Dindo grade 2 or severer, including 3 patients (6.0%) with grade 3 disease. No postoperative mortality occurred. The 30-day, 180-day, 1-year, 3-year and 5-year survival rates were 100%, 80.4%, 71.0%, 46.3%, and 33.8%, respectively. Multivariate analysis showed that a preoperative poor performance status (ASA-PS≥3) (HR: 3.067; 95% CI: 1.220–7.709; p = 0.017) was an independent prognostic factor for OS. Conclusion: Curative elective resections for CRC in nonagenarians were performed safely without postoperative mortality. The preoperative performance status was significantly associated with OS after curative elective resection of colorectal cancer in nonagenarians. Our results suggest that excellent long-term outcomes can be achieved in a selected group with a good performance status.

Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. To understand the molecular mechanism of MuV infection, a functional analysis of the involved host factors is required. However, little is known about the host factors involved in MuV infection, especially those involved in the late stage of infection. Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein.

BackgroundAn accurate evaluation of the nutritional status of malnourished hospitalized patients at a higher risk of complications, such as frailty or disability, is crucial. Visual methods of estimating food intake are popular for evaluating the nutritional status in clinical environments. However, from the perspective of accurate measurement, such methods are unreliable. ObjectiveThe accuracy of estimating leftover liquid food in hospitals using an artificial intelligence (AI)–based model was compared to that of visual estimation. MethodsThe accuracy of the AI-based model (AI estimation) was compared to that of the visual estimation method for thin rice gruel as staple food and fermented milk and peach juice as side dishes. A total of 576 images of liquid food (432 images of thin rice gruel, 72 of fermented milk, and 72 of peach juice) were used. The mean absolute error, root mean squared error, and coefficient of determination (R2) were used as metrics for determining the accuracy of the evaluation process. Welch t test and the confusion matrix were used to examine the difference of mean absolute error between AI and visual estimation. ResultsThe mean absolute errors obtained through the AI estimation approach were 0.63 for fermented milk, 0.25 for peach juice, and 0.85 for the total. These were significantly smaller than those obtained using the visual estimation approach, which were 1.40 (P

Many efforts have been dedicated to the discovery of antiviral drug candidates against the mumps virus (MuV); however, no specific drug has yet been approved. The development of efficient screening methods is a key factor for the discovery of antiviral candidates. In this study, we evaluated a screening method using an Aequorea coerulescens green fluorescent protein-expressing MuV infectious molecular clone. The application of this system to screen for active compounds against MuV replication revealed that CD437, a retinoid acid receptor agonist, has anti-MuV activity. The point of antiviral action was a late step(s) in the MuV life cycle. The replication of other paramyxoviruses was also inhibited by CD437. The induction of retinoic acid-inducible gene (RIG)-I expression is a reported mechanism for the antiviral activity of retinoids, but our results indicated that CD437 did not stimulate RIG-I expression. Indeed, we observed antiviral activity despite the absence of RIG-I, suggesting that CD437 antiviral activity does not require RIG-I induction.

Background: To investigate the hematological features of infants with bronchopulmonary dysplasia (BPD) and their relationships with clinical severity. Methods: This prospective observational study enrolled 73 BPD patients from a total of 331 infants with a birth weight of

Abstract Intracellular tumor-associated antigens are targeted by antibodies known as T-cell receptor mimic antibodies (TCRm-Abs), which recognize T-cell epitopes with better stabilities and higher affinities than T-cell receptors. However, TCRm-Abs have been proven difficult to produce using conventional techniques. Here, we developed TCRm-Abs that recognize the survivin-2B-derived nonamer peptide, AYACNTSTL (SV2B80-88), presented on HLA-A*24 (SV2B80-88/HLA-A*24) from immunized mice by using a fluorescence-activated cell sorting-based antigen-specific plasma cells isolation method combined with a high-throughput single-cell-based immunoglobulin-gene-cloning technology. This approach yielded a remarkable efficiency in generating candidate antibody clones that recognize SV2B80-88/HLA-A*24. The screening of the antibody clones for their affinity and ability to bind key amino-acid residues within the target peptide revealed that one clone, #21-3, specifically recognized SV2B80-88/HLA-A*24 on T2 cells. The specificity of #21-3 was further established through survivin-2B-positive tumor cell lines that exogenously or endogenously express HLA-A*24. A bispecific T-cell engager comprised of #21-3 and anti-CD3 showed specific cytotoxicity towards cells bearing SV2B80-88/HLA-A*24 by recruiting and activating T-cells in vitro. The efficient development of TCRm-Ab overcomes the limitations that hamper antibody-based immunotherapeutic approaches and enables the targeting of intracellular tumor-associated antigens.

Abstract Introduction Patients with stroke often experience pneumonia during the acute stage after stroke onset. Oral care may be effective in reducing the risk of stroke‐associated pneumonia (SAP). We aimed to determine the changes in oral care, as well as the incidence of SAP, in patients with intracerebral hemorrhage, following implementation of a learning health system in our hospital. Methods We retrospectively analyzed the data of 1716 patients with intracerebral hemorrhage who were hospitalized at a single stroke center in Japan between January 2012 and December 2018. Data were stratified on the basis of three periods of evolving oral care: period A, during which conventional, empirically driven oral care was provided (n = 725); period B, during which standardized oral care was introduced, with SAP prophylaxis based on known risk factors (n = 469); and period C, during which oral care was risk‐appropriate based on learning health system data (n = 522). Logistic regression analysis was performed to evaluate associations between each of the three treatment approaches and the risk of SAP. Results Among the included patients, the mean age was 71.3 ± 13.6 years; 52.6% of patients were men. During the course of each period, the frequency of oral care within 24 hours of admission increased (P

Primary infection of human herpesvirus 6B (HHV-6B) occurs in infants after the decline of maternal immunity and causes exanthema subitum accompanied by a high fever, and it occasionally develops into encephalitis resulting in neurological sequelae. There is no effective prophylaxis for HHV-6B, and its development is urgently needed. The glycoprotein complex gH/gL/gQ1/gQ2 (called 'tetramer of HHV-6B') on the virion surface is a viral ligand for its cellular receptor human CD134, and their interaction is thus essential for virus entry into the cells. Herein we examined the potency of the tetramer as a vaccine candidate against HHV-6B. We designed a soluble form of the tetramer by replacing the transmembrane domain of gH with a cleavable tag, and the tetramer was expressed by a mammalian cell expression system. The expressed recombinant tetramer is capable of binding to hCD134. The tetramer was purified to homogeneity and then administered to mice with aluminum hydrogel adjuvant and/or CpG oligodeoxynucleotide adjuvant. After several immunizations, humoral and cellular immunity for HHV-6B was induced in the mice. These results suggest that the tetramer together with an adjuvant could be a promising candidate HHV-6B vaccine.

A unique glycoprotein is expressed on the virus envelope of human herpesvirus 6B (HHV-6B): the complex gH/gL/gQ1/gQ2 (hereafter referred to as the HHV-6B tetramer). This tetramer recognizes a host receptor expressed on activated T cells: human CD134 (hCD134). This interaction is essential for HHV-6B entry into the susceptible cells and is a determinant for HHV-6B cell tropism. The structural mechanisms underlying this unique interaction were unknown. Herein we solved the interactions between the HHV-6B tetramer and the receptor by using their neutralizing antibodies in molecular and structural analyses. A surface plasmon resonance analysis revealed fast dissociation/association between the tetramer and hCD134, although the affinity was high (KD = 18 nM) and comparable to those for the neutralizing antibodies (anti-gQ1: 17 nM, anti-gH: 2.7 nM). A competition assay demonstrated that the anti-gQ1 antibody competed with hCD134 in the HHV-6B tetramer binding whereas the anti-gH antibody did not, indicating the direct interaction of gQ1 and hCD134. A single-particle analysis by negative-staining electron microscopy revealed the tetramer's elongated shape with a gH/gL part and extra density corresponding to gQ1/gQ2. The anti-gQ1 antibody bound to the tip of the extra density, and anti-gH antibody bound to the putative gH/gL part. These results highlight the interaction of gQ1/gQ2 in the HHV-6B tetramer with hCD134, and they demonstrate common features among viral ligands of the betaherpesvirus subfamily from a macroscopic viewpoint.

Abstract Background According to the linear no-threshold model (LNT), even the smallest amount of radiation is hazardous. Although the LNT is not based on solid data, this hypothesis has been applied to mutagens and carcinogens. As a result, it has been postulated that there are no thresholds for these chemicals. To demonstrate negativity by experiments is practically impossible, because negative data may leave behind the possibility that additional data might make the resolution power high enough to change negativity to positivity. Furthermore, additional data collection may be endless and we may be trapped in agnosticism. When hormesis is established, in which biological responses are higher at low-doses and lower at high-doses than the control, thresholds could be established between the low- and high-doses. Before examination of thresholds in chemical mutagenesis, hormetic responses in cytotoxicity were tested using cultured mammalian cells. Method Human cells (HeLa S3 and TK6) or Chinese hamster cells (CHL/IU) were cultured in 96-well plates and treated with mitomycin C (MMC) or ethyl methanesulfonate (EMS) at various dose levels and optical density was measured after addition of a reagent to detect cellular activity. In hormetic responses, data might fluctuate to and fro; therefore, experimental conditions were examined from various aspects to eliminate confounding factors including cell numbers, detection time, the edge effect of 96-well plates, and measurement time after addition of the reagent for detection. Results The dose response relationship was never linear. Cellular activities after treatment with MMC or EMS were generally higher at lower doses levels and lower at higher doses than the control, showing hormesis and allowing the establishment of thresholds. Dose response curves sometimes showed two or three peaks, probably reflecting different cellular responses. Conclusion Hormetic responses in cytotoxicity tests were observed and thresholds could be established. Based on the results of this investigation, we put forward a tentative protocol to detect chemical hormesis in cytotoxicity tests, i.e., inoculate 2000 cells per well, add various doses of a test chemical 48 h after inoculation, add a detection dye 10 h after treatment, and measure optical density 2 h after addition of the reagent for detection.

Abstract Background Anastomotic leakage after total gastrectomy occurs despite improvements in surgical techniques and patient management. Although many cases of dehiscence can be managed non-operatively, major leakage requires a second surgery and can potentially lead to death. Therefore, accurate and immediate diagnosis and treatment are essential. Case presentation In this report, we describe a 66-year-old Japanese man who was diagnosed with a complete separation of an esophagojejunal anastomosis after laparoscopic total gastrectomy with oral contrast radiography using Gastrografin®. The severe complication was successfully treated by re-anastomosis after two emergency drainage surgeries. After the second surgery, the esophageal end formed a fistula with the jejunum, but balloon dilation failed to open the fistula. Therefore, oral ingestion and conservative treatment were considered unsuitable, and we performed esophagojejunal re-anastomosis 7 months after the first surgery. At a follow-up examination 2 years after re-anastomosis, the patient weighed 47 kg, and his ingestion had recovered to 80% of that before surgery. Conclusions Complete separation of an esophagojejunal anastomosis is a rare but severe complication of total gastrectomy. Therefore, we consider that once separation is diagnosed, aggressive and urgent re-operation and effective drainage are useful. Moreover, it is necessary to take great care to minimize the operative morbidity associated with esophagojejunal anastomosis.

Purpose: Fragility hip fractures (FHFs) are associated with a high risk of mortality, but the relative contribution of various factors remains controversial. This study aimed to evaluate predictive factors of mortality at 1 year after discharge in Japan. Methods: A total of 497 patients aged 60 years or older who sustained FHFs during follow-up were included in this study. Expected variables were finally assessed using multivariable Cox proportional hazards models. Results: The 1-year mortality rate was 9.1% (95% confidence interval: 6.8–12.0%, n = 45). Log-rank test revealed that previous fractures ( p = 0.003), Barthel index (BI) at discharge ( p = 0.011), and place-to-discharge ( p = 0.004) were significantly associated with mortality for male patients. Meanwhile, body mass index (BMI; p = 0.023), total Charlson comorbidity index (TCCI; p = 0.005), smoking ( p = 0.007), length of hospital stay (LOS; p = 0.009), and BI ( p = 0.004) were the counterparts for females. By multivariate analyses, previous vertebral fractures (hazard ratio (HR) 3.33; p = 0.044), and BI

RNA contains various chemical modifications, among which N6-methyladenosine (m6A) is the most prevalent modified nucleotide in eukaryotic mRNA. Emerging evidence suggests that m6A plays an important role in regulating a variety of cellular functions by controlling mRNA processing, translation and degradation. Because m6A is not detectable by standard chemical modification-based approaches, immunological methods, such as ELISA, immunoblotting, immunohistochemistry, m6A RNA immunoprecipitation sequencing and m6A individual-nucleotide resolution cross-linking and immunoprecipitation, have been employed to detect m6A in RNA. Although the most important factor determining the success of these methods is the integrity of highly specific antibodies against m6A, the development of m6A-specific monoclonal antibodies has been challenging. We developed anti-m6A monoclonal antibodies using our recently developed single cell-based monoclonal antibody production system. The binding of one selected antibody, #B1-3, to RNA oligoribonucleotide containing a single m6A had an equilibrium dissociation constant of 6.5 nM, and this antibody exhibited negligible binding to oligoribonucleotides containing a single N1-methyladenosine and unmodified adenosine. The binding was competed by the addition of increasing concentrations of N6-methyl-ATP but not N1-methyl-ATP or ATP. Furthermore, this mAb specifically crosslinked m6A-containing oligoribonucleotide by ultraviolet light, resulting in the induction of cDNA truncation at m6A position. These results show the feasibility of using the validated m6A monoclonal antibody for the specific detection of m6A in RNA.

Graphene oxide (GO) shows high proton conductivity (≈10−4 Scm−1), excellent mechanical stability, and electrical insulation property, which makes it an ideal candidate for use as a proton conducting solid state electrolyte. The prospects of using GO as single phase solid electrolyte in an all solid battery is presented herein. A battery with the cell configuration: Zn + ZnSO4•7H2O + graphite (anode) || GO (electrolyte) || MnO2 + graphite (cathode) is fabricated. Cyclic voltammetry confirms its rechargeable nature. The respective discharge capacity and power density of the cell are 360 μAh and 19.5 mW kg−1 at a constant current drain of 3 μA under the experimental conditions employed. GO based proton conductors are cleaner and cheaper than other solid electrolytes. The current study strongly suggests that GO can be used as a practical and beneficial component in solid state battery applications with low energy feedback.