A new early warning method for mild cognitive impairment due to Alzheimer's disease based on dynamic evaluation of the "spatial executive process".

Objective: Mild cognitive impairment (MCI) due to Alzheimer's disease (AD), as an early stage of AD, is an important point for early warning of AD. Neuropathological studies have shown that AD pathology in pre-dementia patients involves the hippocampus and caudate nucleus, which are responsible for controlling cognitive mechanisms such as the spatial executive process (SEP). The aim of this study is to design a new method for early warning of MCI due to AD by dynamically evaluating SEP. Methods: We designed fingertip interaction handwriting digital evaluation paradigms and analyzed the dynamic trajectory of fingertip interaction and image data during "clock drawing" and "repetitive writing" tasks. Extracted fingertip interaction digital biomarkers were used to assess participants' SEP disorders, ultimately enabling intelligent diagnosis of MCI due to AD. A cross-sectional study demonstrated the predictive performance of this new method. Results: We enrolled 30 normal cognitive (NC) elderly and 30 MCI due to AD patients, and clinical research results showed that there may be neurobehavioral differences between the two groups in digital biomarkers captured during SEP. The early warning performance for MCI due to AD of this new method (areas under the curve (AUC) = 0.880) is better than that of the Minimum Mental State Examination (MMSE) neuropsychological scale (AUC = 0.856) assessed by physicians. Conclusion: Patients with MCI due to AD may have SEP disorders, and this new method based on dynamic evaluation of SEP will provide a novel human-computer interaction and intelligent early warning method for home and community screening of MCI due to AD.

Process of developing a cervical cancer education program for female university students in a Health and Physical Education teacher training course: an action research.

BACKGROUND: The purpose of this study was to develop a cervical cancer education program for students and evaluate the process for female students of an HPE teacher education university who were training to become Japanese Health and Physical Education teachers. METHODS: This study used Action Research (AR) methodology. In developing program, we analyzed the description of the teaching material development process, the lectures, and the students' report contents, which was the main activity in the program development. Thirty five third- and fourth-year students majoring in health promotion at a Health and Physical Education teacher education university, which trains Health and Physical Education teachers in Tokyo, Japan, participated in this study. RESULTS: After a review of the prototype version of the cervical cancer education material, six out of nine reviewers determined that it can be published. In the revised cervical cancer education materials, messages from students, university lecturers, and gynecologists have been added as a column in the section on 'how to prevent cervical cancer. Analysis of the contents of the texts (16,792 characters in total) of 35 student reports resulted in the generation of 51 codes, 3 categories, and 15 subcategories. CONCLUSIONS: This study reflects the intentions of female university students to contribute their knowledge to the development of educational materials on cervical cancer, which, alongside the lectures, have deepened the knowledge and awareness of cervical cancer. Based on this, the teaching material development process, lectures by experts, and students' mindset after learning about cervical cancer is reported in this study. There is a need for more educational programs on cervical cancer that are implemented through the education of female university students.

A New Smart 2-Min Mobile Alerting Method for Mild Cognitive Impairment Due to Alzheimer's Disease in the Community.

The early identification of mild cognitive impairment (MCI) due to Alzheimer's disease (AD), in an early stage of AD can expand the AD warning window. We propose a new capability index evaluating the spatial execution process (SEP), which can dynamically evaluate the execution process in the space navigation task. The hypothesis is proposed that there are neurobehavioral differences between normal cognitive (NC) elderly and AD patients with MCI reflected in digital biomarkers captured during SEP. According to this, we designed a new smart 2-min mobile alerting method for MCI due to AD, for community screening. Two digital biomarkers, total mission execution distance (METRtotal) and execution distance above the transverse obstacle (EDabove), were selected by step-up regression analysis. For the participants with more than 9 years of education, the alerting efficiency of the combination of the two digital biomarkers for MCI due to AD could reach 0.83. This method has the advantages of fast speed, high alerting efficiency, low cost and high intelligence and thus has a high application value for community screening in developing countries. It also provides a new intelligent alerting approach based on the human-computer interaction (HCI) paradigm for MCI due to AD in community screening.

Effect of Physical Activity/Exercise on Cardiorespiratory Fitness in Children and Adolescents with Type 1 Diabetes: A Scoping Review.

The most common type of diabetes among children and adolescents is type 1 diabetes mellitus (T1DM), which is associated with an increased risk of cardiovascular disease (CVD). Additionally, lower levels of cardiorespiratory fitness (CRF) are linked to an increased risk of CVD. Regular exercise is associated with a decreased risk of CVD and improved CRF. We conducted this scoping review to assess the effects of exercise on CRF in youth with T1DM. Three electronic databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) were used to search for the relevant literature. In this analysis, the PICOS method was used to select studies and was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines scoping review guidelines for the evaluation of the effects of physical activity and cardiac function; the criteria may include the type and intensity of physical activity, the duration of the intervention, peak oxygen consumption (VO2), peak minute ventilation (VE), and peak heart rate of cardiorespiratory fitness. Screening resulted in 434 records. Of these, nine articles were included in our study. These nine studies were experimental (noncontrolled trials or randomized controlled trials) (n = 7) and observational (cross-sectional) (n = 2), and could be used to evaluate the effectiveness of physical activity interventions on cardiac function. The effects of exercise on CRF in youth with T1DM vary according to the type, frequency, and intensity of the exercise. According to our review, the duration of exercise included in the studies did not meet the recommendations of the guidelines for youth with T1DM. Additionally, half of the studies revealed that exercise could optimize the lipid profile in youth with T1DM. Hence, this research is to provide an overview of the effects of physical activity and exercise on CRF, cardiovascular fitness, lipid profile, and blood pressure in youth with T1DM, as well as identified potential limitations of the existing studies. Nevertheless, the limited number of clinical studies employing exercise interventions for children and adolescents with T1DM emphasize the need for more studies in this area, and more specific modes of exercise should be developed in the future.

Effectiveness, Policy, and User Acceptance of COVID-19 Contact-Tracing Apps in the Post-COVID-19 Pandemic Era: Experience and Comparative Study.

BACKGROUND: In the post-COVID-19 pandemic era, many countries have launched apps to trace contacts of COVID-19 infections. Each contact-tracing app (CTA) faces a variety of issues owing to different national policies or technologies for tracing contacts. OBJECTIVE: In this study, we aimed to investigate all the CTAs used to trace contacts in various countries worldwide, including the technology used by each CTA, the availability of knowledge about the CTA from official websites, the interoperability of CTAs in various countries, and the infection detection rates and policies of the specific country that launched the CTA, and to summarize the current problems of the apps based on the information collected. METHODS: We investigated CTAs launched in all countries through Google, Google Scholar, and PubMed. We experimented with all apps that could be installed and compiled information about apps that could not be installed or used by consulting official websites and previous literature. We compared the information collected by us on CTAs with relevant previous literature to understand and analyze the data. RESULTS: After screening 166 COVID-19 apps developed in 197 countries worldwide, we selected 98 (59%) apps from 95 (48.2%) countries, of which 63 (66.3%) apps were usable. The methods of contact tracing are divided into 3 main categories: Bluetooth, geolocation, and QR codes. At the technical level, CTAs face 3 major problems. First, the distance and time for Bluetooth- and geolocation-based CTAs to record contact are generally set to 2 meters and 15 minutes; however, this distance should be lengthened, and the time should be shortened for more infectious variants. Second, Bluetooth- or geolocation-based CTAs also face the problem of lack of accuracy. For example, individuals in 2 adjacent vehicles during traffic jams may be at a distance of ≤2 meters to make the CTA trace contact, but the 2 users may actually be separated by car doors, which could prevent transmission and infection. In addition, we investigated infection detection rates in 33 countries, 16 (48.5%) of which had significantly low infection detection rates, wherein CTAs could have lacked effectiveness in reducing virus propagation. Regarding policy, CTAs in most countries can only be used in their own countries and lack interoperability among other countries. In addition, 7 countries have already discontinued CTAs, but we believe that it was too early to discontinue them. Regarding user acceptance, 28.6% (28/98) of CTAs had no official source of information that could reduce user acceptance. CONCLUSIONS: We surveyed all CTAs worldwide, identified their technological policy and acceptance issues, and provided solutions for each of the issues we identified. This study aimed to provide useful guidance and suggestions for updating the existing CTAs and the subsequent development of new CTAs.

Association between social capital and depression among older adults of different genders: Evidence from Hangzhou, China.

In China, it is critical to help older adults cope with depression due to the emerging impacts of factors such as increased life expectancy and the "one-child" family planning policy. Meanwhile, differences in retirement age have different effects on health in older adults of different gender. The relationship of gender differences in social capital and depression across the elderly population was unclear. Focusing on this demographic, this study conducted a telephone survey to explore the relationship between social capital and depression. Referring to electronic medical records, we randomly selected 1,042 elderly respondents (426 men, 616 women) from four areas in Hangzhou. We used social capital measurements and the Geriatric Depression Scale (GDS-15) to assess social capital and depression, respectively, then employed a multivariate logistic regression and structural equation modeling to examine the associations between factors, along with a consideration of gender. This study was discovered that differences in both income and morbidity contributed to differences in social capital and depression. In our sample of elderly respondents, we also found gender-based differences in cognitive and structural social capital. Compared to men, women were more likely to attain higher social capital and less likely to develop depression. At the same time, social networking and social engagement had negative impacts on depression in women, which was not the case for men. We found that lower reciprocity (men and women), social work (men), and trust (women) indicated higher risks of depression. Reciprocity and social networks were significantly and negatively correlated with depression among male respondents; in the male model, factors of trust, reciprocity, and social participation had positive effects on reducing the risk of depression, while social networks had a negative effect. For elderly persons, these findings suggest that mental health is affected by differences in social capital caused by policy differences and cultural differences caused by gender differences.

Behavioral Patterns of Supply and Demand Sides of Health Services for the Elderly in Sustainable Digital Transformation: A Mixed Methods Study.

The aging transformation of digital health services faces issues of how to distinguish influencing factors, redesign services, and effectively promote measures and policies. In this study, in-depth interviews were conducted, and grounded theory applied to open coding, main axis coding, and selective coding to form concepts and categories. Trajectory equifinality modeling clarified the evolution logic of digital transformation. Based on the theory of service ecology, a digital health service aging model was constructed from the "macro-medium-micro" stages and includes governance, service, and technology transformation paths. The macro stage relies on organizational elements to promote the institutionalization of management and guide the transformation of governance for value realization, including the construction of three categories: mechanism, indemnification, and decision-making. The meso stage relies on service elements to promote service design and realize service transformation that is suitable for aging design, including the construction of three categories: organization, resources, and processes. The micro stage relies on technical elements to practice experiencing humanization, including the construction of three categories: target, methods, and evaluation. These results deepen the understanding of the main behaviors and roles of macro-organizational, meso-service, and micro-technical elements in digital transformation practice and have positive significance for health administrative agencies to implement action strategies.

Olfactory behavioural and neural responses of planktivorous lacustrine sockeye salmon (Oncorhynchus nerka) to prey odours.

Fish use a variety of sensory systems when foraging. Salmonids are generally considered visual feeders. However, some species feed on zooplanktons under dark conditions, suggesting they also detect prey using nonvisual cues. Under experimental conditions, hatchery-reared rainbow trout (Oncorhynchus mykiss) have been shown to use olfaction when searching for food pellets, but olfactory foraging has not been documented in wild salmonids. In the present study, to examine their behavioural response and neural activity in the olfactory nervous system using c-fos expression as a neural molecular marker, immature wild-caught lacustrine sockeye salmon (Oncorhynchus nerka) in a flow-through aquarium were exposed to zooplanktons (Daphnia spp.) extract including zooplanktons odorant and to dimethyl sulfide. The salmon exposed to zooplanktons odour increased their total swimming distance and time, numbers of turns and ascents, and c-fos expression in the olfactory bulb, suggesting that they can detect zooplanktons extract to locate prey in the laboratory experiments. However, no response was seen in those exposed to dimethyl sulfide. The results of this study suggest that prey odour may serve as a chemosensory cue for wild immature salmonids.

Exploratory Research on Key Technology of Human-Computer Interactive 2.5-Minute Fast Digital Early Warning for Mild Cognitive Impairment.

Objective: As the preclinical stage of Alzheimer's disease (AD), Mild Cognitive Impairment (MCI) is characterized by hidden onset, which is difficult to detect early. Traditional neuropsychological scales are main tools used for assessing MCI. However, due to its strong subjectivity and the influence of many factors such as subjects' educational background, language and hearing ability, and time cost, its accuracy as the standard of early screening is low. Therefore, the purpose of this paper is to propose a new key technology of fast digital early warning for MCI based on eye movement objective data analysis. Methodology. Firstly, four exploratory indexes (test durations, correlation degree, lengths of gaze trajectory, and drift rate) of MCI early warning are determined based on the relevant literature research and semistructured expert interview; secondly, the eye movement state is captured based on the eye tracker to realize the data extraction of four exploratory indexes. On this basis, the human-computer interactive 2.5-minute fast digital early warning paradigm for MCI is designed; thirdly, the rationality of the four early warning indexes proposed in this paper and their early warning effectiveness on MCI are verified. Results: Through the small sample test of human-computer interactive 2.5 fast digital early warning paradigm for MCI conducted by 32 elderly people aged 70-90 in a medical institution in Hangzhou, the two indexes of "correlation degree" and "drift rate" with statistical differences are selected. The experiment results show that AUC of this MCI early warning paradigm is 0.824. Conclusion: The key technology of human-computer interactive 2.5 fast digital early warning for MCI proposed in this paper overcomes the limitations of the existing MCI early warning tools, such as low objectification level, high dependence on professional doctors, long test time, requiring high educational level, and so on. The experiment results show that the early warning technology, as a new generation of objective and effective digital early warning tool, can realize 2.5-minute fast and high-precision preliminary screening and early warning for MCI in the elderly.

Correction to: Perceptions of traditional Chinese medicine for chronic disease care and prevention: a cross-sectional study of Chinese hospital-based health care professionals.

Following publication of the original article [1], the author reported that the funding information was missing from the original article.

Perceptions of traditional Chinese medicine for chronic disease care and prevention: a cross-sectional study of Chinese hospital-based health care professionals.

BACKGROUND: In China, demands for disease prevention and health care and the prevalence of chronic non-communicable diseases have increased. TCM and general hospitals are increasingly utilizing TCM strategies for chronic non-communicable disease care and prevention. This study aimed to investigate health care professionals' (HCPs') perceptions of TCM for prevention, their TCM knowledge, and their abilities to provide such services in TCM and general hospitals. METHODS: This cross-sectional study investigated Chinese medicine hospitals and Chinese medicine departments in general hospitals in five Chinese cities. A self-designed questionnaire used to study 400 HCPs focused on basic demographic data, the demand for and effects of TCM for prevention and treatment, and their perceptions of such service implementation. The data analysis included chi-squared tests and descriptive and multi-factor analyses. RESULTS: The 335 HCP respondents comprised 230 (68.7%) females and 105 (31.3%) males, 75.5% of whom overall had knowledge of TCM preventive and health care services. Respondents older than 40 years (28.6%) had greater knowledge of and satisfaction with TCM for preventive and health care services than younger respondents. Moreover, 97.7% of the older respondents were clearly willing to provide TCM preventive services for chronic diseases, 67.8% of whom indicated that their hospitals already provided TCM for prevention and treatment. According to the chi-squared test results, the TCM service characteristics in hospitals, hospital outlooks regarding TCM and TCM development in hospitals were the primary factors affecting the respondents' perceptions of TCM for chronic disease care and prevention. The multivariate analysis showed high satisfaction as significantly associated with older providers and those with lengthier work experience, particularly among those who worked in hospitals that provided typical TCM services and had positive attitudes towards TCM. CONCLUSION: The study HCPs had relatively satisfactory knowledge of and positive attitudes towards TCM for chronic disease care and prevention and would use it in practice. Their perceptions and satisfaction levels correlated closely with the successful application of TCM for preventive care and treatment in hospitals. While the use of TCM for prevention and treatment was well developed in some hospitals, further improvements are warranted.

Analyzing the changes of health condition and social capital of elderly people using wearable devices.

PURPOSE: Rapid developments in information technology have enabled wearable devices to be applied in the health field. In elderly adults, wearable devices aid in data collection and exerts a positive effect on their social capital. This study evaluated the changes in these two parameters among elderly adults using wearable devices, and analyzed the effect of these devices on their daily lives. METHODS: We selected 18 elderly people using wearable devices, between February and May 2017. The data collected by the wearable devices included the number of steps taken, sleep duration, blood pressure, heart rate, respiratory rate, fatigue, and mood of the wearers. Using a questionnaire and the trajectory equifinality model, we interviewed and surveyed elderly adults in order to understand their health status and social capital. RESULTS: The health of the participants was generally good, and most were able to achieve > 8000 steps per day (p < 0.05). Mild and moderate fatigue symptoms were noted in elderly adults for 90% of the study period (p < 0.05). The number of steps, blood pressure, and heart rate changed significantly within a month. From the commencement of using the wearable devices, a steady increase was noted in the monthly number of steps. Interviews suggested that the elderly adults perceived wearable devices as having the potential to improve health and social capital. CONCLUSIONS: By using wearable devices, the participants had a better understanding of their own health, and were willing to take health-boosting measures. The participants were also more willing to increase their social capital and expand their social network.

Figure Caption Correction: Characteristics of Articles About Human Papillomavirus Vaccination in Japanese Newspapers: Time-Series Analysis Study.

[This corrects the article DOI: .].

Characteristics of Articles About Human Papillomavirus Vaccination in Japanese Newspapers: Time-Series Analysis Study.

BACKGROUND: Media coverage and reports have a major influence on individual vaccination and other health-related activities. People use the media to seek information and knowledge on health-related behaviors. They obtain health-related information from media such as television and newspapers, and they trust such information. While several studies have examined the relation between media coverage and individual health, there is a lack of studies that have analyzed media reports of health information. In particular, we have found no analyses related to cervical cancer (human papillomavirus [HPV]) vaccine. OBJECTIVE: This study aimed to identify mentions of cervical cancer vaccine in Japan's printed news media and to determine their characteristics. METHODS: We used the archival databases of 2 Japanese newspapers, Yomiuri Shimbun (Yomidasu Rekishikan) and Asahi Shimbun (Kikuzo II Visual), for text mining. First, we created a database by extracting articles published between January 1, 2007, and December 31, 2014, that matched the terms "cervical cancer" AND "vaccination" in a keyword search. Then, we tallied the extracted articles based on the month of publication and number of characters in order to conduct a time-series analysis. RESULTS: We extracted a total of 219 articles. Of these, 154 (70.3%) were positive and 51 (23.3%) were negative toward HPV vaccination. Of the 51 negative articles, 4 (7.8%) were published before June 2013, when routine vaccination was temporarily discontinued due to concerns regarding side effects, and 47 (92.2%) were published since then. The negative reports commonly cited side effects, although prior to June 2013, these issues were hardly mentioned. Although foreign media reports mentioned side effects before routine vaccination was temporarily discontinued, fewer articles mentioned side effects than recommendations for vaccination. Furthermore, on June 13, 2013, the World Health Organization's advisory body Global Advisory Committee on Vaccine Safety issued a statement regarding the safety of HPV vaccines, but hardly any articles reported this statement. Rather, several articles were published about the side effects after June 2013. CONCLUSIONS: Since we consider media coverage to be a factor affecting human health behavior, the media should extensively report on the cost of not receiving cervical cancer vaccination, global trends concerning cervical cancer vaccination, and statements released by various agencies on the subject.

Social capital and antenatal depression among Chinese primiparas: A cross-sectional survey.

The aim of this study is to investigate the associations between social capital and antenatal depression among Chinese primiparas. A cross-sectional design was used and a questionnaire survey was conducted with 1471 participants using the intercept method at the provincial hospital in Zhejiang in 2016. Antenatal depression was evaluated using the Edinburgh Postnatal Depression Scale (EPDS) and social capital was assessed by the Chinese version of Social Capital Assessment Questionnaire (C-SCAQ). The prevalence of antenatal depression was assessed among Chinese primiparas in their third trimesters. The antenatal depression prevalence among sub-groups with lower social trust (ST), social reciprocity (SR), social network (SN), and social participation (SP) were significantly higher than those among higher score sub-groups. In the fully adjusted model, primiparas' antenatal depression was significantly associated with ST, SR, SN, and SP. Compared to the structural social capital, the cognitive social capital was a more crucial dimension to the prevalence of antenatal depression. For future community pregnancy health care management programs in China, it might be beneficial to add more social capital related intervention.

Association between low maternal low-density lipoprotein cholesterol levels in the second trimester and delivery of small for gestational age infants at term: a case-control study of the national center for child health and development birth cohort.

Maternal malnutrition during pregnancy can lead to a small for gestational age (SGA) status among infants. In the present study, we compared the lipid levels during the second trimester in women who delivered SGA infants at term with those in women who delivered appropriate for gestational age infants at term, to examine whether abnormalities in maternal lipid levels could be a risk factor for the delivery of an SGA infant. We enrolled pregnant women who gave birth at the National Center for Child Health and Development (NCCHD), their infants, and who volunteered in a Birth cohort study at the NCCHD. We analyzed a total of 843 blood samples obtained from the women during the second trimester. Moreover, we used multi-regression analysis to assess the relationship between low-density lipoprotein cholesterol (LDL-C) levels during the second trimester and the risk of delivering an SGA infant. The adjusted odds ratio (OR) for LDL-C levels was 0.99 (95% CI, 0.98-0.99). These results indicate that a low LDL-C level during the second trimester was associated with an increased risk of delivering an SGA infant at term. The finding would not only help predict future SGA infant birth, but can also help prevent SGA infant birth.

Separation of nucleobases and their derivatives with organic-high ionic strength aqueous phase systems by spiral high-speed counter-current chromatography.

A set of nucleic acid constituents were separated with ultra polar two-phase solvent systems by a spiral multilayer coil mounted on the rotary frame of a type-J coil planet centrifuge. These two-phase systems were composed of 1-butanol/ethanol/50% saturated aqueous ammonium sulfate at various volume ratios. Nucleobases including adenine, cytosine, uracil, and thymine; nucleosides including adenosine, guanosine, cytidine, and uridine; and nucleotides including, AMP, GMP, CMP, UMP, and TMP are partitioned in each group with suitable solvent ratios. Adenine derivatives such as adenosine, AMP, ADP, and ATP were well resolved in the most polar solvent system composed of ethanol/50% saturated aqueous ammonium sulfate at a volume ratio of 1:2. It was found that cytosine and cytidine peaks showed some irregular two peaks probably due to their keto and enol isomers, while the separation of AMP forms two peaks especially when TMP was added in the sample solution, the mechanism of which is now under investigation in our laboratory.

Trends in the incidence of gastric cancer in Japan and their associations with Helicobacter pylori infection and gastric mucosal atrophy.

BACKGROUND: Although age-adjusted mortality from gastric cancer has been decreasing in Japan, the crude incidence of gastric cancer shows a slight increase. METHODS: We have observed trends in the incidence of gastric cancer by sex and 20-year age groups over the past two decades (1976-1996). Source data were obtained from the cancer statistics materials provided by the Research Group for Population-Based Cancer Registration in Japan. Simultaneously, we observed changes in the prevalence of Helicobacter pylori infection and in serological atrophy of the gastric mucosa, and compared the results with those involving changes in the incidence of gastric cancer. RESULTS: A slight decline was observed in all age groups over 40 years old, in both men and women, between 1986 and 1996. However, a marked decline in incidence was observed for those aged 20-39 years. The prevalence of H. pylori infection declined in both sexes between 1989 and 1998. The frequency of serological atrophy of the gastric mucosa significantly declined in all age groups between 1989 and 1996, with young age groups experiencing a more marked decrease. CONCLUSION: The marked decline in gastric cancer incidence observed in the young population will also begin to occur in the elderly population in the future.

Diagnostic accuracy of serological kits for Helicobacter pylori infection with the same assay system but different antigens in a Japanese patient population.

Helicobacter pylori infection is thought to be a causal risk factor for gastric carcinoma. Recently, diagnostic accuracy of serological kits for H. pylori infection that were made in Western countries has been reported to be lower when used among Oriental populations. Diagnostic accuracy of two serological kits [HM-CAP and HM-CAP with antigens extracted from clinically isolated Japanese H. pylori strains (J-HM-CAP)] was investigated in 440 samples from a Japanese patient population by using the (13)C-urea breath test as gold standard. According to the original optimal cut-off value, HM-CAP provided 87.5 % sensitivity and 84.8 % specificity with 86.8 % accuracy and J-HM-CAP provided 95.5 % sensitivity and 81.9 % specificity with 92.3 % accuracy. This study suggests that antigens from HM-CAP are satisfactory for examining a Japanese patient population, but that using local antigens improves accuracy.