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There is a clinical need to develop lipid nanoparticles (LNPs) to deliver congenital therapies to the fetus during pregnancy. The aim of these therapies is to restore normal fetal development and prevent irreversible conditions after birth. As a first step, LNPs need to be optimized for transplacental transport, safety on the placental barrier and fetal organs and transfection efficiency. We developed and characterized a library of LNPs of varying compositions and used machine learning (ML) models to delineate the determinants of LNP size and zeta potential. Utilizing different in vitro placental models with the help of a Random Forest algorithm, we could identify the top features driving percentage LNP transport and kinetics at 24 h, out of a total of 18 input features represented by 41 LNP formulations and 48 different transport experiments. We further evaluated the LNPs for safety, placental cell uptake, transfection efficiency in placental trophoblasts and fetal lung fibroblasts. To ensure the integrity of the LNPs following transplacental transport, we screened LNPs for transport and transfection using a high-throughput integrated transport-transfection in vitro model. Finally, we assessed toxicity of the LNPs in a tracheal occlusion fetal lung explant model. LNPs showed little to no toxicity to fetal and placental cells. Immunoglobin G (IgG) orientation on the surface of LNPs, PEGylated lipids, and ionizable lipids had significant effects on placental transport. The Random Forest algorithm identified the top features driving LNPs placental transport percentage and kinetics. Zeta potential emerged in the top driving features. Building on the ML model results, we developed new LNP formulations to further optimize the transport leading to 622 % increase in transport at 24 h versus control LNP formulation. To induce preferential siRNA transfection of fetal lung, we further optimized cationic lipid percentage and the lipid-to-siRNA ratio. Studying LNPs in an integrated placental and fetal lung fibroblasts model showed a strong correlation between zeta potential and fetal lung transfection. Finally, we assessed the toxicity of LNPs in a tracheal occlusion lung explant model. The optimized formulations appeared to be safe on ex vivo fetal lungs as indicated by insignificant changes in apoptosis (Caspase-3) and proliferation (Ki67) markers. In conclusion, we have optimized an LNP formulation that is safe, with high transplacental transport and preferential transfection in fetal lung cells. Our research findings represent an important step toward establishing the safety and effectiveness of LNPs for gene delivery to the fetal organs., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Although various walking training robots have been developed and their effectiveness has been recognised, operating these robots requires the implementation of safety measures to avoid the risk of falling. This study aimed to confirm whether arm swing rhythm training in the sitting position using an arm swing rhythm-assisted robot, WMR, improved subsequent walking. Healthy older adults (N = 20) performed arm swing rhythm training in a sitting position for 1 min × three times while being presented with tactile stimulation synchronised with the arm swing rhythm from a robot. An increase in walking performance was observed with increases in stride length and speed. In addition, the stabilisation of the gait pattern was observed, with a decrease in the proportion of the double-foot support phase and an increase in the proportion of the swing phase in one gait cycle. These results suggest that arm swing rhythm training in a sitting position using WMR improves gait in older adults. This will lead to the realisation of safe and low-cost robot-based walking training in sitting position., (© 2024. The Author(s).)

Previous studies have reported that bodily self-consciousness could be altered so that one's body was perceived in extra-personal space. However, whether this could be induced without tactile stimuli has not been investigated. We investigated whether out-of-body illusion could be induced via synchronized audio-visual stimuli, in which auditory stimuli were used instead of tactile stimuli. We conducted an experiment in which a sounding bell was moved in front of the participant, and synchronously, a non-sounding bell was moved in front of a camera that captured the image and projected on a head-mounted device. We expected the participants to experience that the sound came from the non-sounding bell in the video and they were in the camera's position. Results from the questionnaires conducted after the experiment revealed that items related to out-of-body illusion were significantly enhanced in the synchronized conditions. Furthermore, participants reported a similarly strong out-of-body illusion for both the synchronized audio-visual and tactile-visual stimuli. This study demonstrated that out-of-body illusion could also be induced by synchronized audio-visual stimuli, which was a novel finding., (© 2024. The Author(s).)

Recently, phosphorus-based compounds have emerged as potential candidates for thermoelectric materials. One of the key challenges facing this field is to achieve ZT > 1, which is the benchmark for thermoelectric device applications. In this study, it is demonstrated that the thermoelectric performance of environmentally friendly Ag 6 Ge 10 P 12 is enhanced by co-doping Cu and Ga. The mechanical properties, coefficient of linear thermal expansion, work function, and compatibility factor are comprehensively clarified to provide guidelines for reliable device applications. The peak and average dimensionless figures of merit of Ag 5.85 Cu 0.15 Ge 9.875 Ga 0.125 P 12 reach 1.04 at 723 K and 0.63 at 300-723 K, respectively, which are the highest values for phosphorus-based thermoelectric materials. The Young's modulus, Vickers microhardness, fracture toughness, and compressive strength of Ag 5.85 Cu 0.15 Ge 9.875 Ga 0.125 P 12 are 132 GPa, 589, 1.23 MPa m 1/2 , and 219 MPa, respectively, which are superior to those of typical state-of-the-art thermoelectric materials. The remarkable thermoelectric and mechanical performance of Ag 5.85 Cu 0.15 Ge 9.875 Ga 0.125 P 12 mean that it is a promising candidate for medium-temperature thermoelectric conversion. Ti, V, Rh, and Pt are suitable for electrodes without exfoliation under thermal expansion and with ohmic contacts to Ag 5.85 Cu 0.15 Ge 9.875 Ga 0.125 P 12 in terms of the coefficient of linear thermal expansion and work function. Considering that the compatibility factor of Ag 5.85 Cu 0.15 Ge 9.875 Ga 0.125 P 12 is approximately 2.8, half-Heusler, skutterudite, and magnesium silicide-stannide compounds are suitable n-type thermoelectric counterpart materials in thermoelectric devices. These insights will lead to the development of phosphorus-based thermoelectric materials toward practical thermoelectric device applications.

High-sensitivity acceleration sensors have been independently developed by our research group to detect vibrations that are > 10 dB smaller than those detected by conventional commercial sensors. This study is the first to measure high-frequency micro-vibrations in muscle fibers, termed micro-mechanomyogram (MMG) in patients with Parkinson's disease (PwPD) using a high-sensitivity acceleration sensor. We specifically measured the extensor pollicis brevis muscle at the base of the thumb in PwPD and healthy controls (HC) and detected not only low-frequency MMG (< 15 Hz) but also micro-MMG (≥ 15 Hz), which was preciously undetectable using commercial acceleration sensors. Analysis revealed remarkable differences in the frequency characteristics of micro-MMG between PwPD and HC. Specifically, during muscle power output, the low-frequency MMG energy was greater in PwPD than in HC, while the micro-MMG energy was smaller in PwPD compared to HC. These results suggest that micro-MMG detected by the high-sensitivity acceleration sensor provides crucial information for distinguishing between PwPD and HC. Moreover, a deep learning model trained on both low-frequency MMG and micro-MMG achieved a high accuracy (92.19%) in classifying PwPD and HC, demonstrating the potential for a diagnostic system for PwPD using micro-MMG., (© 2024. The Author(s).)

Gait guidance systems that synchronize the gait rhythm with an avatar in a mixed reality (MR) environment are attracting attention owing to their rehabilitation applications. More effective gait guidance can be achieved by changing body sensations for the sense of embodiment (SoE), which refers to the feeling of owning, controlling, and being inside a body in MR. This study investigated full-body synchronous motion between a human and a virtual avatar to enhance the SoE in walking with actual position changes in the real world. The full-body motion and gait rhythm were measured using body-worn inertial measurement units and a visual avatar was provided through a transparent head-mounted display. The results showed that the SoE of the participants was enhanced under higher synchronization conditions. In addition, questionnaire results showed that the SoE in the synchronous condition was significantly higher than that in the asynchronous condition, and the SoE in the self-avatar condition was significantly higher than that in the other-avatar condition. This indicates that a higher synchronization level with the appearance of an avatar leads to a stronger SoE in the human perception mechanism, which is important for potential application in medical or other fields., (© 2024. The Author(s).)

Introduction: The use of anti-epileptic drugs (AEDs) in degenerative dementia (DD) remains uncertain. We aimed to evaluate the association of early AED administration with subsequent DD occurrence., Methods: Using a large nationwide database, we enrolled patients newly diagnosed with epilepsy from 2014 to 2019 ( n = 104,225), and using propensity score matching, we divided them into treatment (those prescribed AEDs in 2014) and control groups. The primary outcome was subsequent DD occurrence in 2019., Results: Overall, 4489 pairs of patients (2156 women) were matched. The odds ratio (treatment/control) for DD occurrence was 0.533 (95% confidence interval: 0.459-0.617). The DD proportions significantly differed between the treatment (340/4489 = 0.076) and control (577/4489 = 0.129) groups., Discussion: Among patients newly diagnosed with epilepsy, compared to non-use, early AED use was associated with a lower occurrence of subsequent DD. Further investigations into and optimization of early intervention for epilepsy in DD are warranted., Highlights: Anti-epileptic drug (AED) use before epilepsy diagnosis was linked with a lower subsequent degenerative dementia (DD) occurrence.Identifying the epileptic phenotype was crucial for justifying early AED use in DD.AED use with an epilepsy diagnosis did not pose an additional risk of DD.The potential contribution of combination drug therapy to the strategy was noted., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information., (© 2024 The Author(s). Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

In photon-collapsed cone convolution (pCCC) algorithm of the Monaco treatment planning system (TPS), the central-axis energy spectrum is assumed constant throughout the entire irradiation area. To consider lateral variations, an off-axis softening factor is applied to attenuation coefficients during the total energy released per unit mass calculation. We evaluated this method through comparison studies of percentage depth doses (PDDs) and off-axis ratios (OARs) calculated by Monaco and measured for a 6 MV photon beam at various off-axis angles and depths. Significant differences were observed, with relative differences exceeding ± 1%. Therefore, this method may not accurately represent lateral variations of energy spectra. We propose directly implementing energy spectra on both central-axis and off-axis to improve dose calculation accuracy for large field. To this end, we introduce reconstruction of PDDs from monoenergetic depth doses (MDDs) along off-axis angles, thereby estimating energy spectra as functions of radial distance. This method derives energy spectra quickly without significantly increasing the beam modeling time. MDDs were computed through Monte Carlo simulations (DOSRZnrc). The variances between reconstructed and measured PDDs were minimized using the generalized-reduced-gradient method to optimize energy spectra. Reconstructed PDDs along off-axis angles of 0°, 1.15°, 2.29°, 3.43°, 4.57°, 5.71°, 6.84°, 7.97°, 9.09°, 10.2° to estimate energy spectra at radial distances of 0-18 cm in 2 cm increments and OARs calculated using estimated energy spectra at 5, 10, and 20 cm depths, well agreed with measurement (relative differences within ± 0.5%). In conclusion, our proposed method accurately estimates lateral energy spectrum variation, thereby improving dose calculation accuracy of pCCC algorithm., (© 2024. The Author(s).)

We previously reported a reduced humoral immune response to the COVID-19 vaccines. Subsequently, we observed a lower susceptibility to COVID-19 in individuals carrying the ALDH2 rs671 variant through a web-based retrospective survey. Based on these findings, we hypothesized that rs671 variant was beneficial for cellular immunity against COVID-19. Using the IFN-γ enzyme-linked immunospot (ELISPOT) assay, we assessed cellular immunity before and after COVID-19 vaccination in two subcohorts of a previously reported cohort. Subcohort 1 (26 participants) had six repeated observations at baseline after one to three doses, whereas subcohort 2 (19 participants) had two observations before and after the third dose. ELISPOT counts at six months after the second dose increased from baseline in carriers of the rs671 variant but not in non-carriers. A positive effect of rs671 on ELISPOT counts was estimated using a mixed model (183 observations from 45 participants), including the random effect of subcohort, repeated measures, and fixed effects of vaccine type, age, sex, height, lifestyle, steroid use, and allergic disease. There was no association between ELISPOT counts and specific IgG levels, suggesting a limitation in estimating protective potential by humoral response. Our sequential observational studies suggest a beneficial effect of the rs671 variant in SARS-CoV-2 infection via enhanced cellular immune response, providing a potential basis for optimizing preventive measures and drug development.

Objective: Although it has been suggested that a decline in oral function is one of the potential risk factors affecting mild cognitive impairment (MCI), evidence is insufficient to draw clear conclusions. This Japanese cross-sectional study examined the association between tongue pressure (TP) and MCI in middle-aged and older adults aged 36-84 years., Methods: Study participants were 1019 (368 men and 651 women). TP was evaluated using a TP measurement device. The maximum value of three measurements was used for analysis. MCI was defined as being present if a participant had a Japanese version of the Montreal Cognitive Assessment score of <26. Adjustment was made for age, smoking status, alcohol consumption, leisure-time physical activity, body mass index, hypertension, dyslipidemia, diabetes mellitus, history of depression, number of teeth, employment, education, and household income., Results: The prevalence of MCI was 45.3%. Among women, compared with the lowest tertile of TP, the second and highest tertiles were significantly associated with a lower prevalence of MCI with a clear dose-response relationship; the adjusted odds ratio (95% confidence intervals) in the second and highest tertiles of TP were 0.54 (0.36-0.83) and 0.55 (0.36-0.84), respectively (p for trend = 0.005). In contrast, no statistically significant association was observed between TP and the prevalence of MCI among men., Conclusions: Our findings suggest that higher TP might be inversely associated with the prevalence of MCI in middle-aged and older Japanese women., (© 2024 John Wiley & Sons Ltd.)

The current prebirth cohort study investigated the association between maternal intake of specific types of fatty acids during pregnancy and adolescent depressive symptoms based on the Center for Epidemiologic Studies Depression Scale. Subjects were 873 mother-child pairs. Dietary intake during the preceding month was assessed using a self-administered diet history questionnaire. The risk of depressive symptoms was 23.3% among the 873 adolescents at 13 years of age. Higher maternal saturated fatty acid intake during pregnancy was independently associated with a reduced risk of depressive symptoms in adolescents. Maternal intake of total fat, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol during pregnancy was not significantly related to depressive symptoms in adolescents. Higher maternal intake of saturated fatty acids during pregnancy may be inversely associated with adolescent depressive symptoms.

Background : Now that the spread of COVID-19 has been controlled, it is important to investigate changes in young people's perceptions of the vaccine and their behavior toward infection. The objectives of this study were as follows: (1) to investigate the association between Omicron strain vaccination rates among college students, their perceptions of the vaccine, and past adverse reactions to the vaccine; (2) to compare 2021 (when COVID-19 was spreading) and 2023 (when COVID-19 was strained) to identify changes in attitudes toward vaccination and motivations for vaccination and changes in infection prevention behavior. Methods : This cross-sectional survey was conducted via e-mail from 5 January to 30 January 2023. All students at Hiroshima University were sent an e-mail, which provided them access to the survey form and requested their cooperation. The questionnaire consisted of 33 items related to attributes, vaccination status, adverse reactions after vaccination, motivation for vaccination, perception of the vaccine, presence of coronavirus infection, sequelae, and infection prevention measures. Results : A total of 1083 students responded to the survey. Over 50% of the students were vaccinated with the Omicron booster. Regarding trust in vaccines, the majority of both male and female respondents said they had some trust in vaccines, although this was less than that observed in the 2021 survey. As for infection control measures, only 2% of males and 0.3% of females answered that they did not take any infection control measures. The most common response was "wear a mask", as in the 2021 survey, with 476 men (96.6%) and 575 women (99.5%). Conclusions : The survey showed a high Omicron-responsive vaccination rate of more than 50%. In addition, more than 99% of the students were found to be taking measures to prevent infection, such as wearing masks.

Tightening of environmental regulations against long-chain perfluoroalkyl acids (PFAAs) since the 2000s may have led to significant increases in the occurrence of short-chain PFAAs in the environment. Understanding the impact of the regulations on composition of durable water repellents (DWRs) is imperative to guide implementation of pragmatic actions during their use and end-of-life treatment. Substantial decreases in the frequencies of detection and concentrations of long-chain PFAAs and long-chain PFAA-precursors, and substantial increases in those of short-chain PFAAs and short-chain PFAA-precursors, have been observed in the impurities and hydrolysis products of side-chain fluorinated polymers (SCFPs). Comparison of profiles among the DWRs containing fluorinated ingredients in 2011 indicated that DWRs containing C 8 F 17 - and C 10 F 21 -SCFPs were the dominant products and accounted for 90 % of the samples, whereas DWRs containing C 4 F 9 - and C 6 F 13 -SCFPs were the dominant products and accounted for 70 % of the samples collected in 2021. Tightening of the regulations have caused decreasing applications of long-chain SCFPs and increasing use of short-chain SCFPs in DWRs containing fluorinated ingredients. The ingredients of one DWR were changed from PFAS-free alternatives to short-chain SCFPs, whereas those of another DWR were changed from short-chain SCFPs to PFAS-free alternatives. The presence of unexplained extractable organic fluorine has been observed in DWRs containing fluorinated ingredients, which may be difficult to be hydrolyzed and form known compounds. A historical series of DWRs available from before and after the tightening of regulations and a multifaceted analytical technique consisting of combustion ion chromatographic and mass spectrometric approaches combined with two extraction techniques involving ultrasonic treatment and alkaline hydrolysis revealed the impact of tightening regulations on composition of DWRs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Inflammation triggers various types of diseases that need to be addressed. Macrophages play important roles in the inflammatory responses. As atherosclerosis progresses, macrophages transform into foam cells. Extracellular acidification is observed at and around bacterial infection and atherosclerotic sites. However, the effects of acidification on the inflammatory response of macrophages and the progression of atherosclerosis have not been fully understood. This study investigates the impact of extracellular acidification on lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-α) expression and macropinocytotic activity in RAW264.7 cells. TNF-α expression is measured by real-time polymerase chain reaction (relative value to glyceraldehyde-3-phosphate dehydrogenase expression). Macropinocytotic activity is measured by neutral red uptake (absorbance at 540 nm). Results show that TNF-α expression increased with decreasing extracellular pH in both un-foamed and foamed cells. Macropinocytotic activity was upregulated at pH 6.8 in un-foamed cells, but downregulated in foamed cells stimulated at low pH. Proton-sensing G protein-coupled receptors (GPCRs) were involved in the expression of TNF-α and in the macropinocytotic activity of foamed cells. In conclusion, this study reveals that extracellular acidification differently affect various inflammatory responses such as LPS-induced TNF-α expression and macropinocytotic activity of RAW264.7 cells and different proton-sensing GPCRs are involved in the different inflammatory responses.

Tailormade bottom-up synthesis of covalent organic frameworks (COFs) from various functional building blocks offer not only tunable topology and pore size but also multidimensional properties. High crystallinity is one of the prerequisites for their structures and associated physicochemical properties. Among different π-conjugated motifs for constructing COFs, pyrene-based tetragonal structures are effective in achieving highly ordered and crystalline states. In the present research, we demonstrated that the substitution of pyrene with 2,7-diazapyrene produces nearly "flat" structures of two-dimensional (2D) COF layers by controlling the torsional angle of linker molecules. Featuring finite pore diameters and excellent thermodynamic stability of ∼500 °C, ordered face-to-face (slipped AA) stacking arrangements were produced. Extended electrical conjugation spanning 2D frames with modest optical bandgaps ( E g ) of ∼2.1 eV shows the planar character of diazapyrene-based COFs. The stacking of the conjugated 2D frames with small E g values is also beneficial for the formation of highly stable conducting pathways in the crystalline state, which was confirmed by the results of the microwave conductivity measurements. Nitrogen centers in diazapyrene units also play a key role as the active sites for proton transfer, and the maximum proton conductivity of σ = 10 -2 S cm -1 was achieved along the cocontinuous nanopore structures surrounded by the active sites. Results show that tetragonal COFs based on diazapyrene can be used as a highly crystalline two-dimensional material with special electrical and proton-conducting capabilities.

Necking and barreling deformation behaviors occurred simultaneously during the bending test of a single-crystal gold micro-cantilever (sample A) with the loading direction parallel to the [1-10] orientation and the neutral plane parallel to the [110] orientation. In contrast, for another single-crystal gold micro-cantilever, sample B, with the loading direction aligned parallel to the [0.37 -0.92 0.05] orientation and the neutral plane parallel to the [0.54 0.28 0.78] orientation, predominant slip band deformation was noted. Sample A exhibited activation of four slip systems, whereas sample B demonstrated activity in only a single-slip system. This difference suggests that the presence of multiple slip systems contributes to the concurrent occurrence of necking and barreling deformations. Furthermore, variations in the thickness of the micro-cantilevers resulted in observable strengthening, indicating that the effect of sample size is intricately linked to the geometry of the cross-section, which we have termed the "sample geometry effect".

Purpose: S-flurbiprofen (SFP) plaster, a non-steroidal anti-inflammatory drug preparation that penetrates effectively into deep tissue, is currently used as a conservative treatment for osteoarthritis. We investigated the analgesic and adverse effects of SFP plaster after total hip arthroplasty (THA)., Methods: A retrospective comparative study identified 100 patients who underwent primary THA in our department. Group A consisted of 50 patients who received the selective cyclooxygenase-2 inhibitor celecoxib for 14 days after surgery, while Group B consisted of 50 patients who received SFP plaster for 14 days after surgery. We noted the numerical rating pain intensity scale (NRS) score, body temperature, and adverse effects of the analgesics., Results: Groups A and B showed no significant difference in NRS scores (p > 0.05). The body temperature was significantly higher in Group B than in Group A on days one, two, three, and five (p < 0.01). In Group A, two patients (4%) showed drug-induced renal dysfunction, and one patient (2%) showed gastrointestinal disturbance. Patients in Group B showed no systemic or local adverse effects., Conclusions: The application of SFP plaster after THA provided an analgesic effect similar to that obtained with oral celecoxib without causing obvious side effects. Applying an SFP plaster may be an effective solution for postoperative analgesia., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of Kawasaki Medical School issued approval 3376. This study was approved by the Ethics Committee of our institution. The need for informed consent was waived by the ethics committee owing to the retrospective nature of the study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Miyake et al.)

Introduction: This study aimed to evaluate the cost-effectiveness of nirmatrelvir/ritonavir (Nir/Rit) for adult outpatients with COVID-19 from the perspective of a Japanese public healthcare payer., Methods: A cost-effectiveness simulation was conducted comparing Nir/Rit for the outpatient treatment of high-risk COVID-19 patients to best supportive care (BSC) without antiviral or antibody drugs. The analytical model was divided into two phases: the treatment phase, lasting 35 days from the start of COVID-19 treatment, and the post-treatment phase. Patients who survived the treatment phase were assumed to follow a general population survival curve. Expected costs and expected quality-adjusted life years (QALYs) for both BSC and Nir/Rit were calculated for ages 40 to 80 to obtain the incremental cost-effectiveness ratio (ICER). The robustness of the results was evaluated through deterministic and probabilistic sensitivity analysis (PSA)., Results: The ICERs for patients aged 40, 50, 60, 70, and 80 were 18,854,276 Japanese Yen (JPY)/QALY, 8,482,034 JPY/QALY, 4,976,612 JPY/QALY, 2,636,096 JPY/QALY, and 1,597,783 JPY/QALY, respectively. In the deterministic sensitivity analysis, both the mortality risk during the treatment phase and the relative mortality risk with Nir/Rit had a high impact on ICER across all ages. In the PSA, when the willingness-to-pay (WTP) threshold was set at 5 million JPY/QALY, the probability of the ICER being below the WTP threshold was 0%, 0.2%, 45.4%, 99.9%, and 100% at ages 40, 50, 60, 70, and 80, respectively., Conclusion: Nir/Rit is cost-effective for older individuals aged 60 and over but not for younger age groups., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Purpose: This prebirth cohort study examined the relationship between breastfeeding duration and behavioral problems in five-year-old Japanese children., Methods: Study subjects were 1198 mother-child pairs. Data were collected using a self-administered questionnaire. Emotional, conduct, hyperactivity, and peer problems and low prosocial behavior were assessed using the Strengths and Difficulties Questionnaire (SDQ)., Results: Neither exclusive breastfeeding duration nor breastfeeding duration regardless of exclusivity was significantly associated with childhood emotional, conduct, hyperactivity, or peer problems or low prosocial behavior. In children with older siblings only, ≥ 4 months of exclusive breastfeeding was significantly inversely associated with hyperactivity problems (adjusted odds ratio [OR] = 0.57, 95 % confidence interval [CI]: 0.31-0.99). In children without older siblings, ≥ 4 months of exclusive breastfeeding was inversely significantly associated with low prosocial behavior (adjusted OR = 0.54, 95 % CI: 0.30-0.93). No interactions were observed between exclusive breastfeeding duration and the presence of older siblings regarding the two outcomes., Conclusions: No associations were found between breastfeeding duration and any of the outcomes based on the SDQ. Exclusive breastfeeding for ≥ 4 months may be inversely associated with hyperactivity problems in children with older siblings and with low prosocial behavior in children without older siblings., Competing Interests: Declaration of Competing Interest YM and KT were financially supported by Meiji Co. Ltd and Meiji Holdings Co., Ltd. The other authors have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In musical ensembles, people synchronise with each other despite the presence of time delays such as those related to sound transmission. However, the ways in which time delays in synchronisation are overcome remain unclear. This study aimed to investigate the basic characteristics and mechanism of synchronisation with time delays using a dyadic synchronisation-continuation finger-tapping task with time delays ranging from 0 to 240 ms. The results reveal that synchronisation performance improved under time delays of 40-160 ms compared with in the other conditions. This tolerance to the time delay could have been because such a delay allowed both participants in each pair to tap before receiving the stimuli from their partner, as seen in synchronisation with a constant-tempo metronome. In addition, the dependency of the timing control on the partner's previous inter-tap interval decreased at a time delay of 80 ms, relating to the fact that the acceleration and deceleration of the tapping tempo reduced under certain time delays, while the synchronisation performance improved. Uncertainty in the timing of the partner's stimulus could induce greater anticipatory responses, making it possible to tolerate longer time delays in dyadic finger-tapping tasks., (© 2024. The Author(s).)

Flow-injection spin-trapping electron paramagnetic resonance (FI-EPR) methods that involve the use of 5,5-dimethyl-pyrroline- N -oxide (DMPO) as a spin-trapping reagent have been developed for the kinetic study of the O 2 •- radical scavenging reactions occurring in the presence of various plant-derived and synthetic phenolic antioxidants (Aox), such as flavonoid, pyrogallol, catechol, hydroquinone, resorcinol, and phenol derivatives in aqueous media (pH 7.4 at 25 °C). The systematically estimated second-order rate constants ( k s ) of these phenolic compounds span a wide range (from 4.5 × 10 to 1.0 × 10 6 M -1 s -1 ). The semilogarithm plots presenting the relationship between k s values and oxidation peak potential ( E p ) values of phenolic Aox are divided into three groups (A1, A2, and B). The k s - E p plots of phenolic Aox bearing two or three OH moieties, such as pyrogallol, catechol, and hydroquinone derivatives, belonged to Groups A1 and A2. These molecules are potent O 2 •- radical scavengers with k s values above 3.8 × 10 4 (M -1 s -1 ). The k s - E p plots of all phenol and resorcinol derivatives, and a few catechol and hydroquinone derivatives containing carboxyl groups adjacent to the OH groups, were categorized into the group poor scavengers ( k s < 1.6 × 10 3 M -1 s -1 ). The k s values of each group correlated negatively with E p values, supporting the hypothesis that the O 2 •- radical scavenging reaction proceeds via one-electron and two-proton processes. The processes were accompanied by the production of hydrogen peroxide at pH 7.4. Furthermore, the correlation between the plots of k s and the OH proton dissociation constant (p K a • ) of the intermediate aroxyl radicals ( k s -p K a • plots) revealed that the second proton transfer process could potentially be the rate-determining step of the O 2 •- radical scavenging reaction of phenolic compounds. The k s - E p plots provide practical information to predict the O 2 •- radical scavenging activity of plant-derived phenolic compounds based on those molecular structures.

Out-of-body experiences are scientifically inducible cognitive phenomena attracting global attention due to their application in the Metaverse and medical care. Despite previous studies suggesting that one's native language influences one's cognition, the out-of-body experiences of humans with different native languages have not been investigated separately. This study replicated an experiment from a 2007 study to investigate whether differences in native language affect the ability to have scientifically induced out-of-body experiences. A total of 19 age-matched native English and Japanese speakers completed the experiment in two blocks. Thereafter, their experiences were evaluated using questionnaires, and their responses were compared. Importantly, no significant differences between the English and Japanese native-speaker conditions were found. The results showed that out-of-body experiences were induced similarly in both groups, suggesting that people can have out-of-body experiences as a response to similar stimuli, regardless of their native language. However, differences in participants' introspective reports suggested that their experiences may differ qualitatively, possibly, due to the different linguistic backgrounds. The elucidation of the mechanisms of science-assisted out-of-body experiences that consider different cultural and cognitive characteristics, such as native language, could lead to the investigation of their applications in the borderless Metaverse and medicine., 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 Uchitomi, Yamamoto, Ueno, Nomura and Miyake.)

CD4 + T cells induced from human iPSCs (iCD4 + T cells) offer a therapeutic opportunity for overcoming immune pathologies arising from hematopoietic stem cell transplantation. However, most iCD4 + T cells are conventional helper T cells, which secrete inflammatory cytokines. We induced high-level expression of FOXP3, a master transcription factor of regulatory T cells, in iCD4 + T cells. Human iPSC-derived, FOXP3-induced CD4 + T (iCD4 + Treg-like) cells did not secrete inflammatory cytokines upon activation. Moreover, they showed demethylation of the Treg-specific demethylation region, suggesting successful conversion to immunosuppressive iCD4 + Treg-like cells. We further assessed these iCD4 + Treg-like cells for CAR-mediated immunosuppressive ability. HLA-A2 CAR-transduced iCD4 + Treg-like cells inhibited CD8 + cytotoxic T cell (CTL) division in a mixed lymphocyte reaction assay with A2 + allogeneic CTLs and suppressed xenogeneic graft-versus-host disease (GVHD) in NSG mice treated with A2 + human PBMCs. In most cases, these cells suppressed the xenogeneic GvHD progression as much as natural CD25 + CD127 - Tregs did., Competing Interests: Declaration of interests S.K. is a director and shareholder at Shinobi Tx and received research funding from Shinobi Tx, Takeda Pharmaceutical, and Astellas. H.K received research funding from Chugai, Kyowa Kirin, Zenyaku Kogyo, Sumitomo Pharma, Eisai, Daiichi Sankyo, Otsuka Pharmaceutical, Perseus Proteomics, CURED, Astellas Pharma, Asahi Kasei, AbbVie, Nippon Shinyaku, JCR Pharmaceuticals, and Takeda Pharmaceutical. S.K. has patent applications related to the research (patent no. WO/2023/182328). T. Sato., T. Shinohara., K.K., A.M., K.N., M.S., and Y.K. are employees of Takeda Pharmaceutical Co. Ltd., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ferrocene (FeCp 2 ) was introduced as a non-magnetic guest molecule to activated carbon fibers (ACFs) as a nanographene-based host having localized spins originating from zigzag edges of graphene. The introduction of the guest molecule was confirmed by FTIR for ACFs-FeCp 2 introduced at 55 (150) °C (FeCp 2 -ACFs-55(150)). The appearance of satellite Fe 2p peaks and the increase in shake-up peak intensity of the C 1s in the XPS spectrum proved the emergence of charge-transfer host-guest interaction in FeCp 2 -ACFs-150, supported by the red-shift of the G-band in the Raman spectrum. The six-times enhancement in the spin concentration in FeCp 2 -ACFs-150 compared with ACFs indicates the spin magnetism of the non-magnetic guest FeCp 2 + molecule induced by a charge-transfer host-guest interaction in the nanographene host. The larger ESR linewidth than that expected from the dipolar interaction estimated by the localized spin concentration suggests the exchange interaction between the nanographene and FeCp 2 spins. The narrowing of the ESR linewidth of FeCp 2 -ACFs-55 upon higher excitation microwave power suggests the inhomogeneity of the environment for FeCp 2 + molecules in the nanographene host. The observed induction of spin magnetism by the interfacial interactions between the nanographene host and the guest molecules will be a promising strategy for developing a new class of molecular magnets., (Copyright © 2024, Suzuki et al.)

Background: Fetoscopic endoluminal tracheal occlusion (FETO) improves the survival rate in fetuses with severe congenital diaphragmatic hernia (CDH). We hypothesize that prenatal therapies into the trachea during FETO can further improve outcomes. Here, we present an ex vivo microinjection technique with rat lung explants to study prenatal therapy with nanoparticles., Methods: We used microsurgery to isolate lungs from rats on embryonic day 18. We injected chitosan nanoparticles loaded with fluorescein (FITC) into the trachea of the lung explants. We compared the difference in biodistribution of two types of nanoparticles, functionalized IgG-conjugated nanoparticles (IgG-nanoparticles) and bare nanoparticles after 24 h culture with immunofluorescence (IF). We used IF to mark lung epithelial cells with E-cadherin and to investigate an apoptosis (Active-caspase 3) and inflammatory marker (Interleukin, IL-6) and compared its abundance between the two experimental groups and control lung explants., Results: We detected the presence of nanoparticles in the lung explants, and the relative number of nanoparticles to cells was 2.49 fold higher in IgG-nanoparticles than bare nanoparticles (p < 0.001). Active caspase-3 protein abundance was similar in the control, bare nanoparticles (1.20 fold higher), and IgG-nanoparticles (1.34 fold higher) groups (p = 0.34). Similarly, IL-6 protein abundance was not different in the control, bare nanoparticles (1.13 fold higher), and IgG-nanoparticles (1.12 fold higher) groups (p = 0.33)., Conclusions: Functionalized nanoparticles had a higher presence in lung cells and this did not result in more apoptosis or inflammation. Our proof-of-principle study will guide future research with therapies to improve lung development prenatally., Levels of Evidence: N/A TYPE OF STUDY: Animal and laboratory study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The consumption of arsenic and trace-metal-contaminated rice is a human health concern worldwide, particularly in Bangladesh. In this study, the effects of rice varieties and water management practices on the concentrations of arsenic and trace metals in rice grains were investigated to reduce human health risks related to rice consumption. In addition, the performance of risk reduction using the optimum combination of rice variety and water management practices was quantitatively assessed using Monte Carlo simulation, in which non-carcinogenic and carcinogenic risk distributions under the status quo and the optimum combination were compared. The experimental results revealed that Dular and BRRI dhan45 (rice varieties) cultivated under alternate wetting and drying (AWD) and continuous flooding (CF) conditions showed the lowest hazard quotient (HQ) values for copper, cadmium, and arsenic and the lowest target cancer risk (TR) for arsenic. In Dular and BRRI dhan45 (AWD and CF) varieties, the proportion of the population for which HQs exceeded 1.0 (the reference value) tended to decrease (except for arsenic), compared with populations for which the rice varieties and water management practices were not specified. These results suggest that the use of optimum combinations of rice varieties and water management practices could reduce non-carcinogenic and carcinogenic risks associated with arsenic and trace metals uptake via rice grain consumption by the Bangladeshi people., Competing Interests: Declaration of competing interest This study was supported by the Mitsui Bussan Environmental Fund (grant number: R18-2009), Japan. The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)