Modeling and predicting individual variation in COVID-19 vaccine-elicited antibody response in the general population.

As we learned during the COVID-19 pandemic, vaccines are one of the most important tools in infectious disease control. To date, an unprecedentedly large volume of high-quality data on COVID-19 vaccinations have been accumulated. For preparedness in future pandemics beyond COVID-19, these valuable datasets should be analyzed to best shape an effective vaccination strategy. We are collecting longitudinal data from a community-based cohort in Fukushima, Japan, that consists of 2,407 individuals who underwent serum sampling two or three times after a two-dose vaccination with either BNT162b2 or mRNA-1273. Using the individually reconstructed time courses of the vaccine-elicited antibody response based on mathematical modeling, we first identified basic demographic and health information that contributed to the main features of the antibody dynamics, i.e., the peak, the duration, and the area under the curve. We showed that these three features of antibody dynamics were partially explained by underlying medical conditions, adverse reactions to vaccinations, and medications, consistent with the findings of previous studies. We then applied to these factors a recently proposed computational method to optimally fit an "antibody score", which resulted in an integer-based score that can be used as a basis for identifying individuals with higher or lower antibody titers from basic demographic and health information. The score can be easily calculated by individuals themselves or by medical practitioners. Although the sensitivity of this score is currently not very high, in the future, as more data become available, it has the potential to identify vulnerable populations and encourage them to get booster vaccinations. Our mathematical model can be extended to any kind of vaccination and therefore can form a basis for policy decisions regarding the distribution of booster vaccines to strengthen immunity in future pandemics.

Exercise Stress Echocardiography-Based Phenotyping of Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome requiring improved phenotypic classification. Previous studies have identified subphenotypes of HFpEF, but the lack of exercise assessment is a major limitation. This study sought to identify distinct pathophysiologic clusters of HFpEF based on clinical characteristics, and resting and exercise assessments. METHODS: A total of 265 patients with HFpEF underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. Cluster analysis was performed by the K-prototype method with 21 variables (10 clinical and resting echocardiographic variables and 11 exercise echocardiographic parameters). Pathophysiological features, exercise tolerance, and prognosis were compared among phenogroups. RESULTS: Three distinct phenogroups were identified: Phenogroup 1 (n=112, 42%) was characterized by preserved biventricular systolic reserve and cardiac output augmentation. Phenogroup 2 (n=58, 22%) was characterized by a high prevalence of atrial fibrillation, increased pulmonary arterial and right atrial pressures, depressed RV systolic functional reserve, and impaired right ventricular-pulmonary artery coupling during exercise. Phenogroup 3 (n=95, 36%) was characterized by the smallest body mass index, ventricular and vascular stiffening, impaired LV diastolic reserve, and worse exercise capacity. Phenogroups 2 and 3 had higher rates of composite outcomes of all-cause mortality or HF events than phenogroup 1 (log-rank p=0.02). CONCLUSION: Exercise echocardiography-based cluster analysis identified three distinct phenogroups of HFpEF, with unique exercise pathophysiological features, exercise capacity, and clinical outcomes.

Accelerometer-based gait characteristics and their discrimination of gait independence in inpatients with subacute stroke.

BACKGROUND: Gait analysis using inertial measurement devices can identify multifaceted gait disorders after a stroke. Although the usefulness of gait assessment using inertial measurement devices has been reported, its accuracy in discriminating gait independence in patients hospitalized for subacute stroke has not yet been validated. RESEARCH QUESTION: Can trunk acceleration indices discriminate between dependent and independent walking in patients with subacute stroke? METHODS: Thirty-five patients with subacute stroke (mean ± standard deviation, 75.5 ± 9.8 years, 19 males), who were able to understand instructions, had a premorbid modified Rankin scale <3, and were able to walk 16 m straight ahead under supervision were included. The stride regularity, harmonic ratio, and normalized root mean square of trunk accelerations were measured in three directions (mediolateral, vertical, and anterioposterior) during comfortable walking. The Functional Ambulation Categories were used as the dependent variable to classify the patients into two groups (dependent and independent walking groups), and each trunk acceleration index was used as the independent variable to calculate the area under the curve using receiver operating characteristic curves. RESULTS: Twelve patients were in the dependent group and 23 were in the independent group. The normalized root mean square in both the mediolateral and vertical directions were excellent discriminators of walking independence, with an area under the curve greater than 0.8. The cutoff values (sensitivity/specificity) were 2.20 m2/s2 (0.783/0.833) and 2.82 m2/s2 (0.739/0.833), respectively. SIGNIFICANCE: The magnitude of vertical and lateral acceleration during gait in patients with subacute stroke, has excellent accuracy in discriminating between dependent and independent gaits. The results of this study will be useful for inexperienced clinicians working with stroke patients presenting with gait disturbances to accurately determine gait independence based on objective data.

Diminished neutralizing activity against the XBB1.5 strain in 55.9% of individuals post 6 months COVID-19 mRNA booster vaccination: insights from a pseudovirus assay on 1,353 participants in the Fukushima vaccination community survey, Japan.

This study investigates the neutralizing activity against the XBB1.5 variant and the ancestral strain in a population post-bivalent vaccination using a pseudo virus assay validated with authentic virus assay. While bivalent booster vaccination and past infections enhanced neutralization against the XBB 1.5 strain, individuals with comorbidities showed reduced responses. The study suggests the need for continuous vaccine updates to address emerging SARS-CoV-2 variants and highlights the importance of monitoring real-world immune responses.

Antibody Profiling of Microbial Antigens in the Blood of COVID-19 mRNA Vaccine Recipients Using Microbial Protein Microarrays.

Although studies have demonstrated that infections with various viruses, bacteria, and parasites can modulate the immune system, no study has investigated changes in antibodies against microbial antigens after the COVID-19 mRNA vaccination. IgG antibodies against microbial antigens in the blood of vaccinees were comprehensively analyzed using microbial protein microarrays that carried approximately 5000 microbe-derived proteins. Changes in antibodies against microbial antigens were scrutinized in healthy participants enrolled in the Fukushima Vaccination Community Survey conducted in Fukushima Prefecture, Japan, after their second and third COVID-19 mRNA vaccinations. Antibody profiling of six groups stratified by antibody titer and the remaining neutralizing antibodies was also performed to study the dynamics of neutralizing antibodies against SARS-CoV-2 and the changes in antibodies against microbial antigens. The results showed that changes in antibodies against microbial antigens other than SARS-CoV-2 antigens were extremely limited after COVID-19 vaccination. In addition, antibodies against a staphylococcal complement inhibitor have been identified as microbial antigens that are associated with increased levels of neutralizing antibodies against SARS-CoV-2. These antibodies may be a predictor of the maintenance of neutralizing antibodies following the administration of a COVID-19 mRNA vaccine.

Characteristics of Vulnerable Foreigners in Need of Emergency Care Support in Japan: A Case Study of Thai Nationals from 2004 to 2020.

In Japan, a considerable number of foreigners encounter challenges in accessing appropriate healthcare services due to the lack of insurance coverage. However, the absence of a public database on these individuals makes it difficult to assess their health problems and healthcare access status. This study aims to investigate the characteristics of vulnerable Thai patients in Japan and to shed light on the specific challenges they face within Japan's healthcare system. A retrospective analysis was conducted using records of patients who required emergency healthcare support from the Royal Thai Embassy in Tokyo between 2004 and 2020. Descriptive statistical analyses were performed to examine the general characteristics, insurance status, and diseases of the patients. Additionally, patients were classified as either prolonged residents or brief residents based on their duration of stay in Japan until hospital admission (1 year or more or less than 1 year). A total of 74 patients were identified, with the majority (91.9%) lacking insurance coverage. Notably, there was an increase in the number of brief residents, including tourists, during the 2010s. Prolonged residents were more likely to experience chronic diseases, whereas brief residents were more prone to sustaining injuries. The patient records from the Thai Embassy consistently highlight the urgent requirement for emergency healthcare support within this population. However, the existing policies in Japan fall short in adequately addressing the healthcare access needs of this vulnerable population. Therefore, it is crucial to provide additional support and interventions to enhance their healthcare access.

Minimal detectable change in inertial measurement unit-based trunk acceleration indices during gait in inpatients with subacute stroke.

Gait analysis using inertial measurement units (IMU) provides a multifaceted assessment of gait characteristics, but minimal detectable changes (MDC), the true change beyond measurement error, during gait in patients hospitalized with subacute stroke has not been clarified. This study aimed to determine the MDC in IMU-based trunk acceleration indices during gait in patients hospitalized with subacute stroke. Nineteen patients with subacute stroke (mean ± SD, 75.4 ± 10.9 years; 13 males) who could understand instructions, had a pre-morbid modified Rankin Scale < 3 and could walk straight for 16 m under supervision were included. As trunk acceleration indices, Stride regularity, harmonic ratio (HR), and normalized root mean square (RMS) during gait were calculated on three axes: mediolateral (ML), vertical (VT), and anterior-posterior (AP). MDC was calculated from two measurements taken on the same day according to the following formula: MDC = standard error of measurement × 1.96 × 2. The MDCs for each trunk acceleration index were, in order of ML, VT, and AP: 0.175, 0.179, and 0.149 for stride regularity; 0.666, 0.741, and 0.864 for HR; 4.511, 2.288, and 2.680 for normalized RMS. This finding helps determine the effectiveness of rehabilitation interventions in the gait assessment of patients with stroke.

Five doses of the mRNA vaccination potentially suppress ancestral-strain stimulated SARS-CoV2-specific cellular immunity: a cohort study from the Fukushima vaccination community survey, Japan.

The bivalent mRNA vaccine is recommended to address coronavirus disease variants, with additional doses suggested for high-risk groups. However, the effectiveness, optimal frequency, and number of doses remain uncertain. In this study, we examined the long-term cellular and humoral immune responses following the fifth administration of the mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis. To our knowledge, this is the first study to monitor long-term data on humoral and cellular immunity dynamics in high-risk populations after five doses of mRNA vaccination, including the bivalent mRNA vaccine. Whereas most patients maintained humoral immunity throughout the observation period, we observed reduced cellular immune reactivity as measured by the ancestral-strain-stimulated ELISpot assay in a subset of patients. Half of the individuals (50%; 14/28) maintained cellular immunity three months after the fifth dose, despite acquiring humoral immunity. The absence of a relationship between positive controls and T-Spot reactivity suggests that these immune alterations were specific to SARS-CoV-2. In multivariable analysis, participants aged ≥70 years showed a marginally significant lower likelihood of having reactive results. Notably, among the 14 individuals who received heterologous vaccines, 13 successfully acquired cellular immunity, supporting the effectiveness of this administration strategy. These findings provide valuable insights for future vaccination strategies in vulnerable populations. However, further research is needed to evaluate the involvement of immune tolerance and exhaustion through repeated vaccination to optimize immunization strategies.

Varying Cellular Immune Response against SARS-CoV-2 after the Booster Vaccination: A Cohort Study from Fukushima Vaccination Community Survey, Japan.

Booster vaccination reduces the incidence of severe cases and mortality related to COVID-19, with cellular immunity playing an important role. However, little is known about the proportion of the population that has achieved cellular immunity after booster vaccination. Thus, we conducted a Fukushima cohort database and assessed humoral and cellular immunity in 2526 residents and healthcare workers in Fukushima Prefecture in Japan through continuous blood collection every 3 months from September 2021. We identified the proportion of people with induced cellular immunity after booster vaccination using the T-SPOT.COVID test, and analyzed their background characteristics. Among 1089 participants, 64.3% (700/1089) had reactive cellular immunity after booster vaccination. Multivariable analysis revealed the following independent predictors of reactive cellular immunity: age < 40 years (adjusted odds ratio: 1.81; 95% confidence interval: 1.19-2.75; p-value: 0.005) and adverse reactions after vaccination (1.92, 1.19-3.09, 0.007). Notably, despite IgG(S) and neutralizing antibody titers of ≥500 AU/mL, 33.9% (349/1031) and 33.5% (341/1017) of participants, respectively, did not have reactive cellular immunity. In summary, this is the first study to evaluate cellular immunity at the population level after booster vaccination using the T-SPOT.COVID test, albeit with several limitations. Future studies will need to evaluate previously infected subjects and their T-cell subsets.

Correction: Suzuki et al. Cross-Country Student Perceptions about Online Medical Education during the COVID-19 Pandemic. Int. J. Environ. Res. Public Health 2022, 19, 2840.

In the published publication, there was an error regarding the affiliation for "Tomoya Suzuki" [...].

Predictive discriminative accuracy of walking abilities at discharge for community ambulation levels at 6 months post-discharge among inpatients with subacute stroke.

[Purpose] This study aimed to compare the predictive accuracy of walking ability at discharge among subacute stroke inpatients at 6 months post-discharge in terms of community ambulation level and establish optimal cut-off values. [Participants and Methods] This prospective observational study included 78 patients who completed follow-up assessments. Patients were classified into three groups based on the Modified Functional Walking Category (household/most limited community walkers, least limited community walkers, and unlimited community walkers) obtained by telephone survey at 6 months post-discharge. Predictive accuracy and cut-off values for discriminating among groups were calculated from 6-minute walking distance and comfortable walking speed measured at the time of discharge using receiver operating characteristic curves. [Results] Between household/most limited and least limited community walkers, 6-minute walking distance and comfortable walking speed offered similar predictive accuracy (area under the curve, 0.6-0.7), with cut-off values of 195 m and 0.56 m/s, respectively. Between least limited and unlimited community walkers, the areas under the curve were 0.896 for 6-minute walking distance and 0.844 for comfortable walking speed, with cut-off values of 299 m and 0.94 m/s, respectively. [Conclusion] Walking endurance and walking speed among inpatients with subacute stroke provided superior predictive accuracy for unlimited community walkers at 6 months post-discharge.

Antibody and T-Cell Responses against SARS-CoV-2 after Booster Vaccination in Patients on Dialysis: A Prospective Observational Study.

Intensive vaccination is recommended for populations more vulnerable to COVID-19 infection, although data regarding the built of immunity after vaccination for dialysis patients are lacking. This prospective, observational cohort study of maintenance hemodialysis patients examined IgG antibody levels against the SARS-CoV-2 spike (S1) protein, neutralizing activity, and interferon gamma levels after the third dose of the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. Humoral immunity was repeatedly measured for up to two months. The study includes 58 patients on hemodialysis. Median neutralizing antibodies reached a maximum at 56 and 9 days after booster vaccination with BNT162b2 and mRNA-1273, respectively. The median IgG antibody titer reached a maximum of 3104.38 and 7209.13 AU/mL after 16 days of booster dose, and cellular immunity was positive in 61.9% and 100% of patients with BNT162b2 and mRNA-1273 vaccination, respectively. By repeating the measurements over a period of two months, we clarified the chronological aspects of the acquisition of humoral immunity in dialysis patients after a booster COVID-19 vaccination; most dialysis patients acquired not only humoral immunity, but also cellular immunity against SARS-CoV-2. Future research should investigate the continued long-term dynamics of antibody titers and cellular immunity after the third or further vaccinations, evaluating the need for additional vaccinations for hemodialysis patients.

Relationship between gait regularity and harmony, and gait speed at discharge in inpatients with subacute stroke.

[Purpose] Accelerometry indices are a promising and simple method to quantify gait stability. However, the long-term relationship between gait stability and walking ability in patients with stroke has not been fully investigated. The purpose of this study was to longitudinally examine the relationship between gait regularity and harmony at admission and gait speed at discharge in inpatients with subacute mild stroke. [Participants and Methods] Sixteen patients with subacute stroke (median age, 69.5 years [1st-3rd interquartile range, 58.0-73.8 years]; 13 males) were enrolled in the study. A Spearman's rank correlation coefficient was calculated for step regularity, stride regularity, the harmonic ratio at admission, and the walking speed at discharge. We also calculated the partial rank order correlation, controlling for balance ability. [Results] The vertical step regularity, harmonic ratio, and anterior-posterior harmonic ratio were all positively correlated with the walking speed at discharge. Positive correlations with vertical step regularity and harmonic ratio were found in partial rank order correlations when controlled for balance ability. [Conclusion] Vertical step regularity and gait harmony had predictive validity for discharge gait speed in patients with subacute stroke.

Short-term effects of pedaling exercise combined with integrated volitional control electrical stimulation in an older patient hospitalized for subacute stroke: ABA single-case design.

[Purpose] The purpose of this study was to examine effects on gait indices produced by a short-term intervention of pedaling combined with integrated volitional control electric stimulation in an older patient with stroke. [Participant and Methods] This study was a single-case ABA (A-control, B-treatment) design. Each phase lasted four consecutive days (12 days total). Ten minutes of pedaling were performed daily. In Phase B, pedaling was combined with integrated volitional control electric stimulator on the rectus femoris of the affected side. The primary outcomes were the coefficient of variation, a measure of stride time homogeneity during gait; and the root mean square, a measure of trunk sway in the triaxial direction (mediolateral, vertical, anteroposterior) during gait. Assessments were measured before the intervention (day 0) and after the end of each phase (days 4, 8, and 12). [Results] Changes from the previous coefficient of variation were +1.13%, -3.95%, and +0.82% in Phases A, B, and A', respectively, with the greatest improvement occurring after Phase B. The root mean square improved the most with -5.13 for mediolateral after Phase B, -3.33 for vertical, and -6.99 for anteroposterior after Phase A. [Conclusion] A short-term intervention consisting of pedaling combined with integrated volitional control electric stimulation may contribute to the improvement of gait abnormalities.

Loss of participation among evacuees aged 20-37 years in the disaster cohort study after the Great East Japan Earthquake.

The present study aimed to clarify the characteristics of young evacuees who had missed the Comprehensive Health Check of the Fukushima Health Management Survey (FHMS) after the Great East Japan Earthquake in 2011. The FHMS has been conducted as a prospective cohort study to evaluate the health status of evacuees annually after the great earthquake in 2011. This study focused on the annual participation rate in the Comprehensive Health Check of evacuees aged between 20 and 37 years in 2011 who evacuated due to the Fukushima Daiichi Nuclear Power Plant accident. The characteristics of subjects who did not participate after the second survey year were identified with a multivariate logistic regression model. The participation rate was estimated at 26.6% (9720 among 36,502 residents) and 15.6% (5691 residents) in 2011 and 2012, respectively. The logistic regression model revealed the following characteristics at baseline as independent predictors of non-participation after the second year of the survey: age ≤ 24 years (adjusted odds ratio 2.11, 95% CI 1.84-2.42), 25-29 years of age (1.28, 1.13-1.45), men (1.52, 1.38-1.69), evacuation outside the municipality but within Fukushima prefecture (1.54, 1.40-1.70), evacuation outside the Fukushima prefecture (1.40, 1.21-1.63), anemia (1.23, 1.06-1.43), smoking habit (1.34, 1.21-1.48), and drinking habit (1.20, 1.09-1.32). A medical history of heart disease showed opposite odds ratios, which indicate the association with continuous participation (0.43, 0.26-0.72, respectively). We observed deteriorated participation in the prospective study of the Comprehensive Health Check of the FHMS among evacuees of a younger age group, men, those evacuated outside their municipalities, and those with history of anemia, smoking and drinking habits. Hence, the cohort study may have missed certain population groups with worse health behaviors. Thus, it is necessary to consider various measures to increase the participation rate in the disaster cohort study to understand the long-term health effects of disasters on younger residents in evacuation zones.

Asymptomatic gastric anisakiasis detected in gastric cancer screening: A case report.

Anisakiasis is a parasitic disease caused by Anisakis simplex and has become an emerging zoonosis as preferences for eating raw or undercooked seafood have become more common. Few case reports of asymptomatic anisakiasis have been published to date. A 79-year-old asymptomatic man underwent esophagogastroduodenoscopy (EGD) for gastric cancer screening. The gastroenterologist diagnosed superficial gastritis without any malignant lesions but found an Anisakis larva while reviewing EGD images. The physician performed a second EGD and removed the larva. The patient reported that he ate the flatfish sashimi for dinner on the day before the first EGD. This case indicates the existence of asymptomatic gastric anisakiasis, indicating that anisakiasis incidence may have previously been underestimated.

Symposium on disaster-related deaths after the Fukushima Daiichi Nuclear Power Plant accident.

Disaster deaths can be classified into direct and indirect deaths. Direct deaths are those caused by the direct physical effects of disasters, such as earthquakes, tsunamis, and radiation exposure. Indirect deaths are those caused by secondary health effects such as emergency evacuation, relocation, evacuation environment, disruption of health care delivery services, and psychosocial effects. In addition, in Japan, the term disaster-related deaths refers to indirect deaths in accordance with the disaster condolence payments system, which provides relief for bereaved families. On 11 March 2011, the Great East Japan Earthquake exposed several issues related to disaster-related deaths in Japan. Therefore, on 1 February 2022, a symposium on disaster-related deaths hosted by this study was held on the website. The symposium discussed the issues and challenges associated with disaster-related deaths for future disaster preparedness. The authors introduced the concept of 'shaking' at the symposium by defining 'shaking' as 'the repeated changes in the social and living environment that worsen health conditions, regardless of the disaster'. It was also pointed out that vulnerable populations are more likely to experience more pronounced health effects. This generalised concept of 'shaking' associated with disaster-related deaths suggests that it is important to anticipate disasters before they occur to take specific preventive measures, targeted at vulnerable populations. This study found that disaster-related deaths in Japan create several problems in terms of future radiation disaster preparedness and medical countermeasures. In the future, there will be a need to examine the relevance of the issues of disaster-related deaths identified as a result of this symposium for future radiation disaster preparedness.

Cross-Country Student Perceptions about Online Medical Education during the COVID-19 Pandemic.

(1) Introduction: Most educational institutions around the world have shifted from traditional face-to-face to online education amid COVID-19. This change may particularly impact medical students, whose education is heavily influenced by clinical learning experiences. Accordingly, we investigated medical students' perceptions about positive and negative aspects of online medical education in Japan and overseas during the COVID-19 pandemic. (2) Methods: In-depth online interviews were conducted among 13 Japanese medical students and five medical students from Slovakia, Norway, and Hungary. Interviews were conducted from 23rd September to 3rd October 2020 using the snowball sampling method. Questions were focused on five main areas: Q1 the type of online education; Q2 advantages and disadvantages of online education; Q3 any changes in the relationship with teachers, friends, and family; Q4 any opinions about further improvements in online education; and Q5 any needs for affiliation with a particular university. Then thematic analysis was conducted. (3) Results: The results of the thematic analysis revealed the following four themes that represent the positive and negative aspects of online medical education; Theme 1: Timesaving and Flexibility; Theme 2: Technical problems and lack of digital skills; Theme 3: Unstandardized teaching skills; Theme 4: Lack of experience beyond medical school lectures. (4) Conclusions: While online education was found useful in terms of saving time and creating a flexible learning environment, many important drawbacks were noted such as internet and computer problems and unstandardized teaching skills, and lack of quality assurance. In addition, experiences outside the classroom such as making relationships with faculty and friends, conducting research and participating in extracurricular activities were missed, which they normally enjoy in college life.