Variations in echolocation click characteristics of finless porpoise in response to day/night and absence/presence of vessel noise.

Small odontocetes produce echolocation clicks to feed and navigate, making it an essential function for their survival. Recently, the effect of vessel noise on small odontocetes behavior has attracted attention owing to increase in vessel activities; however, the effects of the surrounding environmental factor, vessel noise, and day/night on echolocation click characteristics have not been well studied. Here, we examined the effects of vessel noise and day/night on variations in echolocation clicks and click trains parameters. Passive acoustic monitoring of on-axis echolocation clicks produced by free-ranging finless porpoises (Neophocaena asiaeorientalis sunameri) was performed at two sites in Japan, Seto Inland Sea and Mikawa Bay, in June-September 2021 and March-August 2022, using A-tag and SoundTrap 300HF. Generalized Linear Model was used to elucidate the effect of vessel noise, day/night, and surrounding environmental factors (water temperature, synthetic flow velocity, and noise level) on echolocation click and click train parameters. Echolocation click and click train parameters were strongly affected by day/night, whereas the absence/presence vessel noise did not exhibit statistically significant influence. Particularly, -3 dB bandwidth was wider, click duration was shorter, and inter-click intervals in a train were shorter at night, which may facilitate information processing at night, thereby compensating for the lack of visual information. The interaction between day/night and the absence/presence of vessel noise affected the source level of finless porpoises, with higher levels observed in the absence of vessel noise during the daytime compared to other conditions at the site with low vessel traffic. Overall, these results suggest that echolocation clicks by finless porpoise were likely to fluctuate to adapt with surrounding complex environmental conditions, especially day/night.

A Mobile Medication Support App and Its Impact on People Living With HIV: 12-Week User Experience and Medication Compliance Pilot Study.

BACKGROUND: The continuity of care between hospital visits conducted through mobile apps creates new opportunities for people living with HIV in situations where face-to-face interventions are difficult. OBJECTIVE: This study investigated the user experience of a mobile medication support app and its impact on improving antiretroviral therapy compliance and facilitating teleconsultations between people living with HIV and medical staff. METHODS: Two clinics in Japan were invited to participate in a 12-week trial of the medication support app between July 27, 2018, and March 31, 2021. Medication compliance was assessed based on responses to scheduled medication reminders; users, including people living with HIV and medical staff, were asked to complete an in-app satisfaction survey to rate their level of satisfaction with the app and its specific features on a 5-point Likert scale. RESULTS: A total of 10 people living with HIV and 11 medical staff were included in this study. During the trial, the medication compliance rate was 90%, and the mean response rates to symptom and medication alerts were 73% and 76%, respectively. Overall, people living with HIV and medical staff were satisfied with the medication support app (agreement rate: mean 81% and 65%, respectively). Over 80% of medical staff and people living with HIV were satisfied with the ability to record medications taken (9/11 and 8/10 medical staff and people living with HIV, respectively), record symptoms of concern (10/11 and 8/10),and inquire about drug combinations (8/10, 10/10). And further, 90% of people living with HIV were satisfied with the function for communication with medical staff (9/10). CONCLUSIONS: Our preliminary results demonstrate the feasibility of the medication support app in improving medication compliance and enhancing communication between people living with HIV and medical staff.

Auditory change-related cortical response is associated with hypervigilance to pain in healthy volunteers.

BACKGROUND: Patients with chronic pain exhibit hypervigilance (heightened responsiveness to stimuli) to innocuous auditory stimuli as well as noxious stimuli. "Generalized hypervigilance" suggests that individuals who show heightened responsiveness to one sensory system also show hypervigilance to other modalities. However, research exploring the existence of generalized hypervigilance in healthy subjects is limited. METHODS: We investigated whether hypervigilance to pain is associated with auditory stimuli in healthy subjects using the pain vigilance and awareness questionnaire (PVAQ) and auditory change-related cortical responses (ACRs). ACRs are thought to reflect a change detection system, based on preceding sensory memory. We recorded ACRs under conditions that varied in terms of the accumulation of sensory memory as follows: short-ACR, with short preceding continuous stimuli and long-ACR, with long preceding continuous stimuli. In addition, the attention to pain (PVAQ-AP) and attention to changes in pain (PVAQ-ACP) subscales were evaluated. RESULTS: Amplitudes of long-ACR showed significant positive correlations with PVAQ-ACP, whereas those of short-ACR did not show any significant correlations. CONCLUSIONS: Generalized hypervigilance may be observed even in healthy subjects. ACR may be a useful index to evaluate the hypervigilance state in the human brain.

Photoinduced Generation of the π-Conjugated Zwitterionic State in the ESIPT Fluorophore of 2,4-Bisimidazolylphenol.

We demonstrate that 2,4-bis(4,5-diphenyl-1H-imidazol-2-yl)phenol (2,4-bImP) undergoes photoinduced conversion into the so-called "π-conjugated zwitterion" after causing an excited-state intramolecular proton transfer (ESIPT) reaction. The powder sample of 2,4-bImP exhibits largely Stokes-shifted fluorescence characteristics to ESIPT fluorophores. On the other hand, its originally colorless solutions become colored when exposed to UV light for several minutes, whose color depends on the type of solvent. In particular, the CHCl3 solution rapidly turns dark green with the absorption maximum around 700 nm, and the colored solution is nearly restored to original by alternating addition of acid and base. To explain such drastic and reversible color changes, we hypothesized that the occurrence of ESIPT (i.e., deprotonation of the phenol and protonation of the imidazolyl group at its 2-position) triggered the charge-separated structure between the negatively charged phenolate and the positively charged imidazoliumyl group at its 4-position, which allowed resonance with the neutral p-quinoid structure. The formation of this π-conjugated zwitterion was strongly supported by the results of 1H and 15N NMR and Raman measurements.

An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids.

Patient-derived tumor organoids (PDOs) represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture models. We have established PDOs from various human tumors to accurately and efficiently recapitulate the tissue architecture and function. Molecular targeted therapies with remarkable efficacy are currently in use against various tumors. Thus, there is a need for in vitro functional-potency assays that can be used to test the efficacy of molecular targeted drugs and model complex interactions between immune cells and tumor cells to evaluate the potential for cancer immunotherapy. This study represents an in vitro evaluation of different classes of molecular targeted drugs, including small-molecule inhibitors, monoclonal antibodies, and an antibody-drug conjugate, using lung PDOs. We evaluated epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2) inhibitors using a suitable high-throughput assay system. Next, the antibody-dependent cellular cytotoxicity (ADCC) activity of an anti-HER2 monoclonal antibody was evaluated to visualize the interactions of immune cells with PDOs during ADCC responses. Moreover, an evaluation system was developed for the immune checkpoint inhibitors, nivolumab and pembrolizumab, using PDOs. Our results demonstrate that the in vitro assay systems using PDOs were suitable for evaluating molecular targeted drugs under conditions that better reflect pathological conditions.

Greater than the Sum of Its Parts: δ can be Constructed from Item Level Data.

"δ", a latent variable constructed from cognitive performance and functional status measures, can accurately diagnose dementia. The minimal assessment needed is unknown. We have constructed a δ homolog, "dTEXAS", from Telephone Executive Assessment Scale (TEXAS) items, and validated it in a convenience sample of Japanese persons (n = 176). dTEXAS scores correlated strongly with both Instrumental Activities of Daily Living (IADL) (r = -0.86, p <  0.001) and Clinical Dementia Rating Scale (CDR) (r = 0.71, p <  0.001). Constructed independently of their diagnoses, dTEXAS scores accurately distinguished dementia versus controls (area under the receiver operating curve [(AUC; ROC) = 0.92], dementia versus mild cognitive impairment (MCI) (AUC = 0.80) and controls versus MCI (AUC = 0.74). These AUCs are higher than those of multiple observed executive measures, as reported recently by Matsuoka et al., 2014. A dTEXAS score of -0.58 best discriminated between dementia versus controls with 90.1% sensitivity and 80.0% specificity.

δ Scores are Exportable Across Cultural and Linguistic Boundaries.

The latent variable "δ", can accurately diagnose dementia. Its generalizability across populations is unknown. We constructed a δ homolog ("dT2J") in data collected by the Texas Alzheimer's Research and Care Consortium (TARCC). From this, we calculated a composite d-score "d". We then tested d's generalizability across random subsets of TARCC participants and to a convenience sample of elderly Japanese persons with normal cognition (NC), mild cognitive impairment (MCI), and dementia (AD) (n = 176). dT2J was indicated by Instrumental Activities of Daily Living and psychometric measures. Embedded in this battery were the Mini-Mental Status Examination (MMSE) and an executive clock-drawing task (CLOX). Only MMSE and CLOX were available in both TARCC and the Japanese cohort. Therefore, a second composite variable, "T2J", was constructed solely from the factor loadings of CLOX and MMSE on d. The diagnostic accuracy of T2J was estimated in the validation sample, the remainder of the TARCC cohort, and in the Japanese sample. The areas under the receiver operating curve (AUC; ROC) for T2J were compared in each sample, and against d in TARCC. The AUCs for T2J were statistically indiscriminable within TARCC, and in Japanese persons. In Japanese persons, AUCs for T2J were 0.97 for the discrimination between AD versus NC, 0.86 for AD versus MCI, and 0.79 for NC versus MCI. The AUCs for T2J in Japanese persons were higher than any individual psychometric measure in that sample. Valid d-score composites can be abstracted from a subset of δ's indicators. Moreover, those composites are exportable across cultural and linguistic boundaries.

Greater than the sum of its parts: δ Improves upon a battery's diagnostic performance.

OBJECTIVE: "δ", a latent variable constructed from batteries that contain both cognitive and functional status measures, can accurately diagnose dementia relative to expert clinicians. The minimal assessment needed is unknown. METHODS: We validated 2 δ homologs in a convenience sample of elderly Japanese persons with normal cognition (NC), mild cognitive impairment (MCI), and dementia (n = 176). The latent δ homolog "d" (for dementia) was constructed from Instrumental Activities of Daily Living (IADL) and Japanese translations of the Executive Clock-Drawing Task (CLOX), Frontal Assessment Battery (FAB), and Executive Interview (EXIT25). The latent delta homolog "d3" was constructed from a restricted set of d's factor loadings. RESULTS: d and d3 were highly intercorrelated (r = .97) and strongly related to both IADL and dementia severity, as rated blindly by the Clinical Dementia Rating Scale (CDR). d was more strongly related to IADL and CDR than any of its indicators. In multivariate regression, d explained more variance in CDR scores than all of its indicators combined. d's areas under the receiver operating characteristic curve (AUC) were 0.95 for the discrimination between Alzheimer's disease (AD) vs. NC, 0.84 for AD vs. MCI and 0.81 for NC vs. MCI. d3's AUC's were statistically indiscriminable. These AUC's are higher than any of d's indicators, as reported recently by Matsuoka et al. (2014), as well as the Mini-Mental State Examination (MMSE), which had been made available by Matsuoka et al. to the CDR raters. CONCLUSIONS: Latent variables can improve upon a battery's diagnostic performance and offer the potential for accurate dementia case-finding after a minimal bedside assessment.

Japanese versions of the executive interview (J-EXIT25) and the executive clock drawing task (J-CLOX) for older people.

BACKGROUND: The aim of the study was to develop the Japanese versions of Executive Interview (J-EXIT25) and Executive Clock Drawing Task (J-CLOX) and to evaluate the aspects of executive function that these two tests will be examining. METHODS: The concurrent validity and reliability of J-EXIT25 and J-CLOX were first examined in all participants (n = 201). Next, the relationship between the two tests was examined using receiver operating characteristic (ROC), correlation, and regression analyses in healthy participants (n = 45) and participants with mild cognitive impairment (n = 36) and dementia (n = 95). RESULTS: Satisfactory concurrent validity and reliability of J-EXIT25 and J-CLOX were shown. ROC analysis indicated that J-EXIT25 and J-CLOX1 were superior to the Frontal Assessment Battery, but inferior to the Mini-Mental State Examination (MMSE), in discriminating between non-dementia and dementia. J-EXIT25, J-CLOX1, and J-CLOX2 scores were significantly correlated with age, scores on the MMSE, Instrumental Activities of Daily Living (IADL) and Physical Self-Maintenance Scale (PSMS), and care level. In stepwise regression analyses of IADL scores, MMSE and J-EXIT25 were significantly independent predictors in men, and MMSE, age, and J-CLOX1 were significantly independent predictors in women. J-EXIT25, MMSE, and J-CLOX1 were significantly independent predictors in stepwise regression analysis of PSMS scores, and J-EXIT25 was the only significantly independent predictor in stepwise regression analysis of care level. CONCLUSIONS: J-EXIT25 and J-CLOX are valid and reliable instruments for assessment of executive function in older people. The present results suggest that these tests have common and distinct psychometric properties in the assessment of executive function.