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Background Pepper from Capsicum species is a well-established spice with a rich history of culinary use. Some observations have linked its consumption to gastrointestinal discomfort and alterations in stool patterns while it is considered beneficial in some cultures. However, there is lack of information on the direct effect of pepper consumption on human gut microbiota, we conducted dietary intervention studies to assess the impact of pepper on gut bacteriome composition in humans. Methods Ten healthy volunteers were recruited, and each person received 200 ml of 0.14 g/ml fresh Habanero Pepper (Capsicum chinense) daily over a 4-day period after which they abstained from pepper consumption for the subsequent 4 days before resumption of their normal diet. Stool samples were collected at baseline, after pepper consumption, after 4 days without pepper and after 4- and 6-days resumption of normal diet. We sequenced the V3-V4 region of the 16S rRNA gene and analyzed microbial diversity and composition using the QIIME2 pipeline and relevant R packages. Results Consumption of pepper over a 4-day period led to a higher abundance of Verrucomicrobia, a phylum rarely found in significant proportions at other time points. There was a gradual depletion of Shigella and Staphylococcus spp. from baseline untill the end of the study. Other taxa showed timepoint specific associations, emphasizing the potential impact of short-term dietary interventions on the relative abundance of these genera. Conclusions Our study adds nuance to the understanding of diet-microbiota interactions, highlighting the intricate relationship between pepper consumption and gut bacteriome composition. Further exploration of these dynamics holds promise for personalized dietary recommendations and targeted interventions to support gut microbial health.

Background: Pepper from Capsicum species is a well-established spice with a rich history of culinary use. Some observations have linked its consumption to gastrointestinal discomfort and alterations in stool patterns while it is considered beneficial in some cultures. However, there is lack of information on the direct effect of pepper consumption on human gut microbiota, we conducted dietary intervention studies to assess the impact of pepper on gut bacteriome composition in humans. Methods: Ten healthy volunteers were recruited, and each person received 200 ml of 0.14 g/ml fresh Habanero Pepper (Capsicum chinense) daily over a 4-day period after which they abstained from pepper consumption for the subsequent 4 days before resumption of their normal diet. Stool samples were collected at baseline, after pepper consumption, after 4 days without pepper and after 4- and 6-days resumption of normal diet. We sequenced the V3-V4 region of the 16S rRNA gene and analyzed microbial diversity and composition using the QIIME2 pipeline and relevant R packages. Results: Consumption of pepper over a 4-day period led to a higher abundance of Verrucomicrobia, a phylum rarely found in significant proportions at other time points. There was a gradual depletion of Shigella and Staphylococcus spp. from baseline untill the end of the study. Other taxa showed timepoint specific associations, emphasizing the potential impact of short-term dietary interventions on the relative abundance of these genera. Conclusions: Our study adds nuance to the understanding of diet-microbiota interactions, highlighting the intricate relationship between pepper consumption and gut bacteriome composition. Further exploration of these dynamics holds promise for personalized dietary recommendations and targeted interventions to support gut microbial health. [ABSTRACT FROM AUTHOR]

Growth of cerium-doped gadolinium pyrosilicate (Ce:[Gd.sub.2][Si.sub.2] [O.sub.7]) single crystals, which show 2.5 times greater light output for gamma-rays and five times greater light output for alpha-particles than GSO single crystals, is accomplished using the floating zone growth method (FZ method). Although growth of [Gd.sub.2][Si.sub.2] [O.sub.7] (GPS) single crystal is considered to be difficult because it melts incongruently according to the phase diagram of [Gd.sub.2] [O.sub.3]-Si[O.sub.2] system, we attempted crystal growth of Ce:GPS because of the possibility that heavy Ce doping would change the phase diagram. Transparent single crystals were obtained, although some cracks were observed in the crystals. The crystal structure was triclinic with P/1 space group and density of 5.5 g/[cm.sup.3]. Two peaks, which were observed using photoluminescence spectrometry at 372 nm and 394 nm, were attributed to 5d-4f transition in [Ce.sup.3+]ion. Decay times of Ce:GPS scintillation were 46 ns for gamma-ray excitation and 39 ns for alpha-particle excitation. We consider that fabrication of crack free crystals will improve the energy resolution. Index Terms--Crystal growth, gadolinium compounds, [Gd.sub.2][Si.sub.2] [O.sub.7], neutron detectors, radiation detectors, scintillators.

This paper presents an analysis of off board bidirectional Plug in Electric Vehicle (PEV) Charger. Since, normally, the control command for such chargers are given in terms of desired real and reactive power, a model of the system is formulated directly in terms of these variables. A detailed steady state analysis of the system is presented for the entire possible range of operation and for a given battery state of charge (SOC) rather than selecting points of operation a priori. This result shows the various possibilities of the system and informs further structural studies of the system and the design of controllers to meet the desired control objectives. [ABSTRACT FROM AUTHOR]

Objective: Various studies worldwide have found that sound levels in hospitals significantly exceed the World Health Organization (WHO) guidelines, and that this noise is associated with audible signals from various medical devices. The pulse oximeter is now widely used in health care; however the health effects associated with the noise from this equipment remain largely unclarified. Here, we analyzed the sounds of variable-pitch pulse oximeters, and discussed the possible associated risk of sleep disturbance, annoyance, and hearing loss.Methods: The Nellcor N 595 and Masimo SET Radical pulse oximeters were measured for equivalent continuous A-weighted sound pressure levels (L(Aeq)), loudness levels, and loudness. Pulse beep pitches were also identified using Fast Fourier Transform (FFT) analysis and compared with musical pitches as controls.Results: Almost all alarm sounds and pulse beeps from the instruments tested exceeded 30 dBA, a level that may induce sleep disturbance and annoyance. Several alarm sounds emitted by the pulse oximeters exceeded 70 dBA, which is known to induce hearing loss. The loudness of the alarm sound of each pulse oximeter did not change in proportion to the sound volume level. The pitch of each pulse beep did not correspond to musical pitch levels.Conclusions: The results indicate that sounds from pulse oximeters pose a potential risk of not only sleep disturbance and annoyance but also hearing loss, and that these sounds are unnatural for human auditory perception. [ABSTRACT FROM AUTHOR]

Polymyxin B haemoperfusion is commonly used to adsorb endotoxins in septic shock caused by Gram-negative bacterial infections. Polymyxin B haemoperfusion has been reported to improve hypotension in Gram-positive bacterial infections; however, its efficacy and mechanism in treating such cases are unclear. We hypothesised that polymyxin B haemoperfusion would be equally effective in improving haemodynamics during Gram-positive bacterial infections as in Gram-negative bacterial infections. We conducted a retrospective study that included patients with septic shock admitted to the intensive care unit. The patients were divided into two groups according to bacterial culture results: Gram-negative rod (GNR) and Gram-positive coccus (GPC). We calculated the vasoactive inotropic score (VIS) before (0 h) and 2, 6, 12 and 24 h after polymyxin B haemoperfusion therapy. Data were analysed using two-way analysis of variance and post hoc tests for the associations between infection type and treatment time. Overall, 157 patients with septic shock were enrolled in the study: 81 and 76 patients were treated or not treated with extracorporeal haemoperfusion therapy, respectively. Although there was no significant difference in the VIS in polymyxin B haemoperfusion between patients with GNR and GPC infections, there was a significant decrease in the VIS over time, even when GPC was the causative organism. In addition, the degree of reduction in the VIS was significantly different in both the GNR and GPC groups compared with that in the non-extracorporeally treated group. Thus, polymyxin B haemoperfusion for septic shock caused by GNR reduced the VIS and could be effective even in cases of GPC infection., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: This study investigated the implementation of the ABCDEF bundle and the factors associated with its implementation according to national income levels., Methods: This study is cross-sectional research. We conducted a secondary analysis of an international 1-day point-prevalence study that investigated the implementation of the ABCDEF bundle in critically ill patients. All patients admitted to the ICU were eligible. This study was conducted across 135 ICUs in 54 countries, including data from 664 patients. Outcomes were categorized according to the income level of the country (high-income, middle-income, and low-income countries) in which each ICU was located. A multilevel generalized linear model was developed to identify the factors associated with ABCDEF bundle implementation for each income level., Results: We identified 664 patients in 79 high-income countries, 278 in 26 middle-income countries, and 287 in 30 low-income countries ICUs. Implementation rates of the ABCDEF bundle were low for all income levels but varied. Few individuals completed the entire bundle on the survey date. Common factors associated with the implementation among all income levels were a multidisciplinary team approach for Element A (pain) and mechanical ventilation use for Element C (sedation), which were also associated with lower Element E (mobility). The existence of a protocol was frequently identified as a promoting factor associated with ABCDEF bundle implementation. The associated factors varied by income level; for example, dedicated intensivists were only identified in high-income countries, but not in middle-income countries or low-income countries., Conclusions: The overall low ABCDEF bundle implementation rates necessitate action. As factors associated with its implementation vary according to national income level, tailored strategies are essential for improving ICU care quality., Trial Registration: NA., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2025.)

Background Fatigue presents an important challenge for patients discharged from intensive care units (ICUs). Despite its importance, data on the prevalence and clinical impact of post-ICU fatigue remain limited. In particular, the proportion of patients in clinical settings in Japan who find fatigue distressing, as well as the associations between fatigue, risk factors, and self-rated health, have not been fully explored using validated fatigue measures. Therefore, this study aimed to assess the prevalence of fatigue, identify its associated risk factors, and examine the relationship between fatigue and self-rated health status six months after ICU discharge in Japan. Methods This single-center, ambidirectional cohort study administered a survey to patients aged ≥18 years, six months after ICU discharge, to assess fatigue and self-rated health. Retrospective data were also collected from patients' medical records during hospitalization. Fatigue prevalence was the primary endpoint, measured using the cutoff value of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Logistic regression analysis was performed to identify risk factors for fatigue. Locally weighted scatterplot smoothing (LOWESS) plots were generated with FACIT-F scale scores, and the association between fatigue and EuroQol 5 Dimensions 5-Level Visual Analog Scale (EQ-VAS) was analyzed. Results Questionnaires were sent to 87 patients, of whom 81 (93.1%) responded. Eight patients (9.9%) with missing FACIT-F scores were excluded, leaving 73 patients for analysis. The median (interquartile range) age of eligible patients was 74 (63-81) years, and 33 patients (45%) were male. Forty-six patients (63%) reported fatigue. Multivariate analysis identified a higher body mass index (BMI) at ICU admission as an independent risk factor for fatigue (odds ratio (OR) = 1.195; 95% confidence interval (CI) 1.018-1.447; p < 0.05). EQ-VAS scores were significantly lower in the fatigue group (OR 72.5, 95% CI 60-83.8 vs. OR 90, 95% CI 80-90; p < 0.01). Conclusion This study found that many patients in Japanese ICUs experience fatigue, even when disease severity is low. Additionally, BMI at ICU admission was identified as an independent risk factor for fatigue six months after ICU discharge. Regular follow-up on fatigue after ICU discharge is essential for improving long-term outcomes., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Ethics Review Board of the Graduate School of Nursing at Sapporo City University issued approval No. 10. This study was approved by the Ethics Review Board of the Graduate School of Nursing at Sapporo City University (10 2023-10-13, Central IRB) and the Hospital Director of Sapporo Medical University Hospital (352-125 2023-10-23). Study period: October 23, 2023, to March 31, 2024. 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 © 2025, Niiyama et al.)

Oral hygiene care is important for ventilator-associated pneumonia prevention. However, the optimal oral hygiene care approach remains unclear. A network meta-analysis was conducted to compare the efficacy of various oral hygiene care methods for ventilator-associated pneumonia prevention in critically ill patients, and the methods were ranked. A literature search of three representative databases was conducted. We only analyzed parallel randomized controlled trials conducted to analyze the use antiseptics or toothbrushes in oral hygiene care for adult patients undergoing invasive mechanical ventilation in the intensive care unit. The outcome measure was the incidence of ventilator-associated pneumonia. Bias risk was assessed using the Cochrane Risk of Bias 2 tool, and the confidence in the evidence was evaluated using the CINeMA approach. Statistical analyses were performed using R 4.2.0., GeMTC package, and JAGS 4.3.1. The review protocol was registered in PROSPERO (registration number: CRD42022333270). Thirteen randomized controlled trials were included in the qualitative synthesis and twelve randomized controlled trials (2395 participants) were included in the network meta-analysis. Over 50% of the included studies were conducted in medical-surgical intensive care units. Ten treatments were analyzed and 12 pairwise comparisons were conducted in the 12 included studies. Analysis using surface under the cumulative ranking curves revealed that brushing combined with chlorhexidine 0.12% was most likely the optimal intervention for preventing ventilator-associated pneumonia (88.4%), followed by the use of chlorhexidine 0.12% alone (76.1%), and brushing alone (73.2%). Oral hygiene care methods that included brushing had high rankings. In conclusion, brushing combined with chlorhexidine 0.12% may be an effective intervention for preventing ventilator-associated pneumonia in critically ill patients. Furthermore, brushing may be the optimal oral hygiene care method for preventing ventilator-associated pneumonia in the intensive care unit. Further research is needed to verify these findings as the CINeMA confidence rate was low for each comparison., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yamakita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale: To date, family satisfaction with emergency medical technicians (EMTs) has only been reported through narrative statements in subjective evaluations. Although a quantitative assessment of healthcare professional satisfaction is desirable, no specific measures have been devised to assess family satisfaction with the healthcare and care provided by EMTs., Aims and Objectives: This study aimed to develop and validate an EMT care family satisfaction scale to measure patient satisfaction with prehospital emergency care., Methods: The study population comprised 216 family members (N = 216) of patients who used ambulances between November 2020 and May 2021 in a single region in Japan. Questionnaires were distributed to the participants who provided informed consent. An exploratory factor analysis of construct validity was performed to validate the Family Satisfaction Scale. The Cronbach's alpha was used to validate the internal consistency reliability of the scale., Results: The exploratory factor analysis results revealed a four-factor structure: 'explanation and communication,' 'physical treatment,' 'psychological support,' and 'environment in the ambulance.' The Cronbach's range (0.80-0.93) for the total score for each of these four factors and the overall total score confirmed favorable internal reliability of this study., Conclusions: The family satisfaction scale developed in this study was constructed and validated to highlight the role of EMTs and needs of the families in the prehospital care settings. Moreover, this scale can be applied in the evaluation and consideration of interventions to improve family satisfaction with EMTs., (© 2024 John Wiley & Sons Ltd.)

Background This study aims to develop and validate a comprehensive prediction model for ICU readmissions. Readmission following ICU discharge is associated with adverse outcomes such as increased mortality, prolonged hospital stays, and elevated healthcare costs. Consequently, predicting and preventing readmissions is crucial. Previous models for predicting ICU readmissions were primarily based on physiological indices; however, these indices fail to capture the complete nature of treatment or patient conditions beyond physiological measures, thereby limiting the accuracy of these predictions. Methodology A total of 1,400 patients who had an unplanned ICU admission at Sapporo Medical University Hospital from January 2015 to October 2022 were included; a single regression analysis was performed using unplanned ICU readmission as the dependent variable. After performing a single regression analysis, logistic regression analysis using the stepwise method was performed using variables with significant differences, and a predictive nomogram was created using the variables that remained in the final model. To internally validate the predictive nomogram model, nonparametric bootstrapping (1,000 replications) was performed on the original model. Results Of the 1,400 patients who had an unplanned admission to the ICU, 114 (8.1%) were readmitted to the ICU unplanned. Seven main variables (Sequential Organ Failure Assessment score, respiratory rate, Glasgow Coma Scale, sleep disturbance, Continuous Kidney Replacement Therapy, presence of tracheal suctioning, and Oxygen Saturation) were selected to be associated with ICU readmission. The evaluation of the models showed excellent discrimination with an area under the receiver operating characteristic of 0.805 (original model) and 0.796 (bootstrap model). Calibration plots also confirmed good agreement between observed and predicted reentry. Conclusions This new predictive model is more accurate than previous models because it includes physiological indicators as well as other patient conditions and procedures needed and is expected to be used in clinical practice. In particular, the inclusion of new factors, such as sleep disturbance and the need for tracheal suctioning, enabled a more comprehensive patient assessment. The use of this predictive nomogram as a criterion for discharging ICU patients may prevent unplanned ICU readmission., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Institutional Review Board of Sapporo Medical University issued approval 342-157, December 1, 2022. Owing to the observational nature of this study, the information was released on an opt-out basis. 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, Nakano et al.)

Families of critically ill patients are predisposed to tremendous burdens when their relatives are admitted to the intensive care unit (ICU). Postintensive care syndrome family (PICS-F) can be described as a devastated life, encompassing psychological, physical, and socioeconomical burdens that begin with the emotional impact experienced by the family when the patient is admitted to the ICU. PICS-F was primarily proposed as a clinically significant psychological impairment, but it needs to be extended beyond the psychological impairment of the family to include physical and socioeconomical impairments in the future. The prevalence of physiological problems including depression, anxiety and post-traumatic syndrome is 20-40%, and that of non-physiological problems including fatigue is 15% at 6 months after the ICU stay. Assessment of PICS-F was frequently conducted at 3- or 6-month points, although the beginning of the evaluation was based on different assessment points among each of the studies. Families of ICU patients need to be given and understand accurate information, such as the patient's diagnosis, planned care, and prognosis. Prevention of PICS-F requires a continuous bundle of multifaceted and/or multidisciplinary interventions including providing a family information leaflet, ICU diary, communication facilitators, supportive grief care, and follow-up, for the patient and families from during the ICU stay to after discharge from the ICU. This is the first comprehensive review of PICS-F to address the concept, risk factors, assessment tools, prevalence, and management to prevent PICS-F to facilitate acute care physicians' understanding of PICS-F., Competing Interests: Nobuyuki Nosaka is working on the research about PICS‐F under funding from SHARP CORPORATION, but he has not received any direct support for the manuscript. Nobuyuki Nosaka is also working on the research about PICS and PICS‐F under funding from LIXIL Corporation, but he has not received any direct support for the manuscript. The remaining authors have disclosed that they do not have any potential conflicts of interest., (© 2024 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Introduction Work-life balance (WLB) is a critical concern for emergency medical technicians (EMTs) because it significantly affects the provision of comprehensive emergency medical services (EMS). This study investigated personal and work-related factors influencing work-to-family negative spillover (WFNS), a key element of WLB, among EMTs. Methods A web-based survey was conducted from July 26 to September 13, 2021, among EMTs in Hokkaido, Japan. The study included 21 facilities that were randomly selected from 42 fire stations. The Japanese version of the Survey Work-Home Interaction-NijmeGen (SWING-J) was used to measure WFNS. Personal background factors, such as age, sex, years of work experience, and education, were surveyed. We also evaluated work environment factors, such as weekly working hours, monthly night shifts, monthly overtime hours, and yearly paid vacation days. Unpaired Student's t-tests, one-way analysis of variance (ANOVA), and multilevel generalized linear model (MGLM) analyses were used to explore the relationships between WFNS and personal and work-related factors. Results A total of 912 respondents were included in our analysis. They were predominantly male (98.2%), with an average EMT work experience of 12.7 years and a mean WFNS score of 1.16 (standard deviation (SD) = 1.67). MGLM analysis, adjusting for covariates, identified years of work experience (β = -0.129, p = 0.001), monthly overtime hours (β = 0.184, p < 0.001), and yearly paid vacation days (β = -0.170, p < 0.001) as independent factors associated with WFNS. Conclusion This study suggested that adjusting WFNS among EMTs could be achieved by reducing overtime hours and fostering an organized approach to paid leave within the work environment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Haruna et al.)

Background: The assessment of post-intensive care syndrome (PICS) is challenging due to the numerous types of instruments. We herein attempted to identify and propose recommendations for instruments to assess PICS in intensive care unit (ICU) survivors., Methods: We conducted a scoping review to identify PICS follow-up studies at and after hospital discharge between 2014 and 2022. Assessment instruments used more than two times were included in the modified Delphi consensus process. A modified Delphi meeting was conducted three times by the PICS committee of the Japanese Society of Intensive Care Medicine, and each score was rated as not important (score: 1-3), important, but not critical (4-6), and critical (7-9). We included instruments with ≥ 70% of respondents rating critical and ≤ 15% of respondents rating not important., Results: In total, 6972 records were identified in this scoping review, and 754 studies were included in the analysis. After data extraction, 107 PICS assessment instruments were identified. The modified Delphi meeting reached 20 PICS assessment instrument recommendations: (1) in the physical domain: the 6-min walk test, MRC score, and grip strength, (2) in cognition: MoCA, MMSE, and SMQ, (3) in mental health: HADS, IES-R, and PHQ-9, (4) in the activities of daily living: the Barthel Index, IADL, and FIM, (5) in quality of life: SF-36, SF-12, EQ-5D-5L, 3L, and VAS (6), in sleep and pain: PSQI and Brief Pain Inventory, respectively, and (7) in the PICS-family domain: SF-36, HADS, and IES-R., Conclusion: Based on a scoping review and the modified Delphi method, 20 PICS assessment instruments are recommended to assess physical, cognitive, mental health, activities of daily living, quality of life, sleep, and pain in ICU survivors and their families., (© 2023. The Author(s).)

Objective: Burnout among emergency medical technicians is a serious problem affecting delivery of quality emergency medical services. Although the repetitive nature of the job and lower education level requirements for technicians have been reported as risk factors, little is known about the influence of burden of responsibility, degree of supervisor support, and home environment on burnout among emergency medical technicians. This study aimed to test the hypothesis that burden of responsibility, degree of supervisor support, and home environment increase burnout probability., Methods: A web-based survey was conducted among emergency medical technicians in Hokkaido, Japan from July 26, 2021 to September 13, 2021. A total of 21 facilities were randomly selected from 42 fire stations. Prevalence of burnout was measured using the Maslach Burnout-Human Services Survey Inventory (MBI-HSS). Burden of responsibility was measured using a visual analog scale. Occupational background was also measured. Supervisor support was measured using the Brief Job Stress Questionnaire (BJSQ). Family-work negative spillover was measured using the Japanese version of Survey Work-Home Interaction-NijmeGen (SWING). The cutoff value for burnout syndrome was defined as emotional exhaustion≥27 and/or depersonalization≥10., Results: A total of 700 survey respondents were included, and 27 surveys with missing data were excluded. The suspected burnout frequency was 25.6%. Covariates were adjusted using multilevel logistic regression model analysis. Low supervisor support (odds ratio, 1.421; 95% confidence interval, 1.136-1.406; P<0.001) and high family-work negative spillover (odds ratio, 1.264; 95% confidence interval, 1.285-1.571; P<0.001) were independent factors associated with higher probability of burnout., Conclusion: This study indicated that focusing on improvement of supervisor support for emergency medical technicians and creating supportive home environments may assist in reducing burnout frequency.

Gene therapy has become an important modality for a wide range of therapeutic indications with a rapid increase in the number of therapeutic candidates being developed in this field. Understanding the molecular biology underlying the gene therapy is often critical to develop appropriate safety assessment strategies. We aimed to discuss some of the commonly used gene therapy modalities and common preclinical toxicology testing considerations when developing gene therapies. Non-viral gene delivery methods such as electroporation, microinjection, peptide nanoparticles and lipid nanoparticles are deployed as innovative molecular molecular construct which are included in the design of novel gene therapies and the associated molecular biology mechanisms have become relevant knowledge to non-clinical toxicology. Viral gene delivery methodologies including Adenovirus vectors, Adeno-Associated virus vectors and Lentivirus gene therapy vectors have also advanced considerably across numerous therapeutic areas, raising unique non-clinical toxicology and immunological considerations. General toxicology, biodistribution and tumorigenicity are the pillars of non-clinical safety testing in gene therapies. Evaluating the tumorigenicity potential of a gene editing therapy often leverages molecular pathology while some translational challenges remain. Toxicology study design is entering a new era where science-driven customized approaches and program specific considerations have become the norm.

In this work, we give a characterization of the reservoir computer (RC) by the network structure, especially the probability distribution of random coupling constants. First, based on the path integral method, we clarify the universal behavior of the random network dynamics in the thermodynamic limit, which depends only on the asymptotic behavior of the second cumulant generating functions of the network coupling constants. This result enables us to classify the random networks into several universality classes, according to the distribution function of coupling constants chosen for the networks. Interestingly, it is revealed that such a classification has a close relationship with the distribution of eigenvalues of the random coupling matrix. We also comment on the relation between our theory and some practical choices of random connectivity in the RC. Subsequently, we investigate the relationship between the RC's computational power and the network parameters for several universality classes. We perform several numerical simulations to evaluate the phase diagrams of the steady reservoir states, common-signal-induced synchronization, and the computational power in the chaotic time series inference tasks. As a result, we clarify the close relationship between these quantities, especially a remarkable computational performance near the phase transitions, which is realized even near a nonchaotic transition boundary. These results may provide us with a new perspective on the designing principle for the RC.