[STATE-OF-THE-ART OF GLOBAL START-UP INVESTMENT FOR ALLERGY AND IMMUNOLOGY 2022].

BACKGROUND: In 2022, the "New Capitalism Grand Design and Implementation Plan" was adopted in Japan, emphasizing the promotion and environmental development of startups. Given this context, an investigation into the startup and investment landscape in the allergy sector, both domestically and internationally, becomes imperative. METHODS: We analyzed 156 allergy-related startups from Japan, the US, and Europe from 2010 to 2021. Data on corporate information and investment trends were extracted from databases and VC websites. RESULTS: The total investment reached approximately 7.2 billion USD, with a ratio of 20:6:1 for the US, Europe, and Japan, respectively. The US showed a decline post its peak from 2016-2018, while Europe and Japan experienced growth. Notably, the US primarily invested in biopharmaceuticals for atopic dermatitis and food allergies, Europe in asthma-related apps, and Japan in healthcare apps and cross-border startups. DISCUSSION AND CONCLUSION: While Japan's investment environment in the allergy sector remains in its nascent stages and has room for development, the US and Europe are evidently ahead. Considering the rise of startups and funding limitations in Japan, external funding from regions like the US becomes a potential avenue. These findings are anticipated to contribute to the strategic activation of startups in allergy research and development.

Human ocular thelaziasis with genetic analysis in Niigata Prefecture, Japan: A case report on an emerging zoonosis.

Purpose: We report the clinical findings and molecular identification of ocular Thelazia callipaeda from Niigata Prefecture in the Hokuriku area of Japan during winter. Observations: A 77-year-old male visited an ophthalmology clinic in Niigata Prefecture in January 2022 after a 2-week-duration of a conjunctival injection in the left eye and foreign body sensation. Slit-lamp microscopy revealed 11 active nematodes in the left conjunctival sac. Morphological characteristics included longer female body length than male, buccal cavity lacking teeth and lips, and serrated striations along the body surface. The specimens were determined to be T. callipaeda. Genetic analysis of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene revealed an h9 haplotype. Conclusions and Importance: T. callipaeda infection, especially the h9 haplotype, commonly occurs in western Japan owing to its higher incidence in warmer climates, suggesting the origin of the case. Here, we report a human case of Thelaziasis diagnosed in a cold region of Japan (the Hokuriku area) during winter. This human case of T. callipaeda infection from a cold, previously unassociated region, raises concerns about the potential geographical widening of its distribution, and further investigation may be warranted to prevent its spread.

Optimal cutoff value of the dry eye-related quality-of-life score for diagnosing dry eye disease.

This retrospective study aimed to determine the optimal cutoff values of the Dry Eye-Related Quality-of-Life Score (DEQS) questionnaire for diagnosing dry eye disease (DED) and classifying DED severities. Participants completed the DEQS questionnaire, the Japanese version of the Ocular Surface Disease Index (J-OSDI) questionnaire, and DED examinations. DED was diagnosed according to the 2016 Asia Dry Eye Society diagnostic criteria based on DED symptoms (J-OSDI ≥ 13 points) and tear film breakup time ≤ 5 s. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the DEQS summary score for detecting DED and grading its severity. Among 427 patients, 296 (69.3%) and 131 (30.7%) were diagnosed with DED and non-DED, respectively. ROC analysis determined an optimal cutoff value of 15.0 points for DED diagnosis, with 83.5% sensitivity, 87.0% specificity, and an area under the curve of 0.915. The positive and negative predictive values for DEQS ≥ 15.0 points were 93.6% and 69.9%, respectively. DEQS cutoff values of 15.0, 20.0, and 26.8 points could be accepted for severity classification of DED subjective symptoms in clinical use and represent mild, moderate, and severe DED, respectively. Conclusively, the optimal cutoff values of DEQS enable DED detection and subjective symptom severity classification.

Using the AllerSearch Smartphone App to Assess the Association Between Dry Eye and Hay Fever: mHealth-Based Cross-Sectional Study.

BACKGROUND: Dry eye (DE) and hay fever (HF) show synergistic exacerbation of each other's pathology through inflammatory pathways. OBJECTIVE: This study aimed to investigate the association between DE and HF comorbidity and the related risk factors. METHODS: A cross-sectional observational study was conducted using crowdsourced multidimensional data from individuals who downloaded the AllerSearch smartphone app in Japan between February 2018 and May 2020. AllerSearch collected the demographics, medical history, lifestyle and residential information, HF status, DE symptoms, and HF-related quality of life. HF symptoms were evaluated using the nasal symptom score (0-15 points) and nonnasal symptom score (0-12 points). HF was defined by the participants' responses to the questionnaire as HF, non-HF, or unknown. Symptomatic DE was defined as an Ocular Surface Disease Index total score (0-100 points), with a threshold score of 13 points. HF-related quality of life was assessed using the Japanese Allergic Conjunctival Disease Standard Quality of Life Questionnaire (0-68 points). We conducted a multivariable linear regression analysis to examine the association between the severity of DE and HF symptoms. We subsequently conducted a multivariable logistic regression analysis to identify the factors associated with symptomatic DE (vs nonsymptomatic DE) among individuals with HF. Dimension reduction via Uniform Manifold Approximation and Projection stratified the comorbid DE and HF symptoms. The symptom profiles in each cluster were identified using hierarchical heat maps. RESULTS: This study included 11,284 participants, classified into experiencing HF (9041 participants), non-HF (720 participants), and unknown (1523 participants) groups. The prevalence of symptomatic DE among individuals with HF was 49.99% (4429/9041). Severe DE symptoms were significantly associated with severe HF symptoms: coefficient 1.33 (95% CI 1.10-1.57; P<.001) for mild DE, coefficient 2.16 (95% CI 1.84-2.48; P<.001) for moderate DE, and coefficient 3.80 (95% CI 3.50-4.11; P<.001) for severe DE. The risk factors for comorbid symptomatic DE among individuals with HF were identified as female sex; lower BMI; medicated hypertension; history of hematologic, collagen, heart, liver, respiratory, or atopic disease; tomato allergy; current and previous mental illness; pet ownership; living room and bedrooms furnished with materials other than hardwood, carpet, tatami, and vinyl; discontinuation of contact lens use during the HF season; current contact lens use; smoking habits; and sleep duration of <6 hours per day. Uniform Manifold Approximation and Projection stratified the heterogeneous comorbid DE and HF symptoms into 14 clusters. In the hierarchical heat map, cluster 9 was comorbid with the most severe HF and DE symptoms, and cluster 1 showed severe HF symptoms with minimal DE-related symptoms. CONCLUSIONS: This crowdsourced study suggested a significant association between severe DE and HF symptoms. Detecting DE among individuals with HF could allow effective prevention and interventions through concurrent treatment for ocular surface management along with HF treatment.

Smartphone App-Based and Paper-Based Patient-Reported Outcomes Using a Disease-Specific Questionnaire for Dry Eye Disease: Randomized Crossover Equivalence Study.

BACKGROUND: Using traditional patient-reported outcomes (PROs), such as paper-based questionnaires, is cumbersome in the era of web-based medical consultation and telemedicine. Electronic PROs may reduce the burden on patients if implemented widely. Considering promising reports of DryEyeRhythm, our in-house mHealth smartphone app for investigating dry eye disease (DED) and the electronic and paper-based Ocular Surface Disease Index (OSDI) should be evaluated and compared to determine their equivalency. OBJECTIVE: The purpose of this study is to assess the equivalence between smartphone app-based and paper-based questionnaires for DED. METHODS: This prospective, nonblinded, randomized crossover study enrolled 34 participants between April 2022 and June 2022 at a university hospital in Japan. The participants were allocated randomly into 2 groups in a 1:1 ratio. The paper-app group initially responded to the paper-based Japanese version of the OSDI (J-OSDI), followed by the app-based J-OSDI. The app-paper group responded to similar questionnaires but in reverse order. We performed an equivalence test based on minimal clinically important differences to assess the equivalence of the J-OSDI total scores between the 2 platforms (paper-based vs app-based). A 95% CI of the mean difference between the J-OSDI total scores within the ±7.0 range between the 2 platforms indicated equivalence. The internal consistency and agreement of the app-based J-OSDI were assessed with Cronbach α coefficients and intraclass correlation coefficient values. RESULTS: A total of 33 participants were included in this study. The total scores for the app- and paper-based J-OSDI indicated satisfactory equivalence per our study definition (mean difference 1.8, 95% CI -1.4 to 5.0). Moreover, the app-based J-OSDI total score demonstrated good internal consistency and agreement (Cronbach α=.958; intraclass correlation=0.919; 95% CI 0.842 to 0.959) and was significantly correlated with its paper-based counterpart (Pearson correlation=0.932, P<.001). CONCLUSIONS: This study demonstrated the equivalence of PROs between the app- and paper-based J-OSDI. Implementing the app-based J-OSDI in various scenarios, including telehealth, may have implications for the early diagnosis of DED and longitudinal monitoring of PROs.

A tumor microenvironment-based classification of gastric cancer for more effective diagnosis and treatment.

With approximately one million diagnosed cases and over 700,000 deaths recorded annually, gastric cancer (GC) is the third most common cause of cancer-related deaths worldwide. GC is a heterogeneous tumor. Thus, optimal management requires biomarkers of prognosis, treatment selection, and treatment response. The Cancer Genome Atlas program sub-classified GC into molecular subtypes, providing a framework for treatment personalization using traditional chemotherapies or biologics. Here, we report a comprehensive study of GC vascular and immune tumor microenvironment (TME)-based on stage and molecular subtypes of the disease and their correlation with outcomes. Using tissues and blood circulating biomarkers and a molecular classification, we identified cancer cell and tumor archetypes, which show that the TME evolves with the disease stage and is a major determinant of prognosis. Moreover, our TME-based subtyping strategy allowed the identification of archetype-specific prognostic biomarkers such as CDH1-mutant GC and circulating IL-6 that provided information beyond and independent of TMN staging, MSI status, and consensus molecular subtyping. The results show that integrating molecular subtyping with TME-specific biomarkers could contribute to improved patient prognostication and may provide a basis for treatment stratification, including for contemporary anti-angiogenesis and immunotherapy approaches.

Clinical utility of maximum blink interval measured by smartphone application DryEyeRhythm to support dry eye disease diagnosis.

The coronavirus disease (COVID-19) pandemic has emphasized the paucity of non-contact and non-invasive methods for the objective evaluation of dry eye disease (DED). However, robust evidence to support the implementation of mHealth- and app-based biometrics for clinical use is lacking. This study aimed to evaluate the reliability and validity of app-based maximum blink interval (MBI) measurements using DryEyeRhythm and equivalent traditional techniques in providing an accessible and convenient diagnosis. In this single-center, prospective, cross-sectional, observational study, 83 participants, including 57 with DED, had measurements recorded including slit-lamp-based, app-based, and visually confirmed MBI. Internal consistency and reliability were assessed using Cronbach's alpha and intraclass correlation coefficients. Discriminant and concurrent validity were assessed by comparing the MBIs from the DED and non-DED groups and Pearson's tests for each platform pair. Bland-Altman analysis was performed to assess the agreement between platforms. App-based MBI showed good Cronbach's alpha coefficient, intraclass correlation coefficient, and Pearson correlation coefficient values, compared with visually confirmed MBI. The DED group had significantly shorter app-based MBIs, compared with the non-DED group. Bland-Altman analysis revealed minimal biases between the app-based and visually confirmed MBIs. Our findings indicate that DryEyeRhythm is a reliable and valid tool that can be used for non-invasive and non-contact collection of MBI measurements, which can assist in accessible DED detection and management.

Evaluation of a Medical Interview-Assistance System Using Artificial Intelligence for Resident Physicians Interviewing Simulated Patients: A Crossover, Randomized, Controlled Trial.

Medical interviews are expected to undergo a major transformation through the use of artificial intelligence. However, artificial intelligence-based systems that support medical interviews are not yet widespread in Japan, and their usefulness is unclear. A randomized, controlled trial to determine the usefulness of a commercial medical interview support system using a question flow chart-type application based on a Bayesian model was conducted. Ten resident physicians were allocated to two groups with or without information from an artificial intelligence-based support system. The rate of correct diagnoses, amount of time to complete the interviews, and number of questions they asked were compared between the two groups. Two trials were conducted on different dates, with a total of 20 resident physicians participating. Data for 192 differential diagnoses were obtained. There was a significant difference in the rate of correct diagnosis between the two groups for two cases and for overall cases (0.561 vs. 0.393; p = 0.02). There was a significant difference in the time required between the two groups for overall cases (370 s (352-387) vs. 390 s (373-406), p = 0.04). Artificial intelligence-assisted medical interviews helped resident physicians make more accurate diagnoses and reduced consultation time. The widespread use of artificial intelligence systems in clinical settings could contribute to improving the quality of medical care.

The minimal clinically important difference of app-based electronic patient-reported outcomes for hay fever.

BACKGROUND: Hay fever is a common allergic disease, with an estimated worldwide prevalence of 14.4% and a variety of symptoms. This study assessed the minimal clinically important difference (MCID) of nasal symptom score (NSS), non-nasal symptom score (NNSS), and total symptoms score (TSS) for app-based hay-fever monitoring. METHODS: MCIDs were calculated based on the data from a previous large-scale, crowdsourced, cross-sectional study using AllerSearch, an in-house smartphone application. MCIDs were determined with anchor-based and distribution-based methods. The face scale score of the Japanese Allergic Conjunctival Disease Standard Quality of Life Questionnaire Domain III and the daily stress level due to hay fever were used as anchors for determining MCIDs. The MCID estimates were summarized as MCID ranges. RESULTS: A total of 7590 participants were included in the analysis (mean age: 35.3 years, 57.1% women). The anchor-based method produced a range of MCID values (median, interquartile range) for NSS (2.0, 1.5-2.1), NNSS (1.0, 0.9-1.2), and TSS (2.9, 2.4-3.3). The distribution-based method produced two MCIDs (based on half a standard deviation, based on a standard error of measurement) for NSS (2.0, 1.8), NNSS (1.3, 1.2), and TSS (3.0, 2.3). The final suggested MCID ranges for NSS, NNSS, and TSS were 1.8-2.1, 1.2-1.3, and 2.4-3.3, respectively. CONCLUSIONS: MCID ranges for app-based hay-fever symptom assessment were obtained from the data collected through a smartphone application, AllerSearch. These estimates may be useful for monitoring the subjective symptoms of Japanese patients with hay fever through mobile platforms.

Symptom-based stratification algorithm for heterogeneous symptoms of dry eye disease: a feasibility study.

BACKGROUND/OBJECTIVE: To test the feasibility of a dry eye disease (DED) symptom stratification algorithm previously established for the general population among patients visiting ophthalmologists. SUBJECT/METHODS: This retrospective cross-sectional study was conducted between December 2015 and October 2021 at a university hospital in Japan; participants who underwent a comprehensive DED examination and completed the Japanese version of the Ocular Surface Disease Index (J-OSDI) were included. Patients diagnosed with DED were stratified into seven clusters using a previously established symptom-based stratification algorithm for DED. Characteristics of the patients in stratified clusters were compared. RESULTS: In total, 426 participants were included (median age [interquartile range]; 63 [48-72] years; 357 (83.8%) women). Among them, 291 (68.3%) participants were diagnosed with DED and successfully stratified into seven clusters. The J-OSDI total score was highest in cluster 1 (61.4 [52.2-75.0]), followed by cluster 5 (44.1 [38.8-47.9]). The tear film breakup time was the shortest in cluster 1 (1.5 [1.1-2.1]), followed by cluster 3 (1.6 [1.0-2.5]). The J-OSDI total scores from the stratified clusters in this study and those from the clusters identified in the previous study showed a significant correlation (r = 0.991, P < 0.001). CONCLUSIONS: The patients with DED who visited ophthalmologists were successfully stratified by the previously established algorithm for the general population, uncovering patterns for their seemingly heterogeneous and variable clinical characteristics of DED. The results have important implications for promoting treatment interventions tailored to individual patients and implementing smartphone-based clinical data collection in the future.

TFOS Lifestyle: Impact of the digital environment on the ocular surface.

Eye strain when performing tasks reliant on a digital environment can cause discomfort, affecting productivity and quality of life. Digital eye strain (the preferred terminology) was defined as "the development or exacerbation of recurrent ocular symptoms and/or signs related specifically to digital device screen viewing". Digital eye strain prevalence of up to 97% has been reported, due to no previously agreed definition/diagnostic criteria and limitations of current questionnaires which fail to differentiate such symptoms from those arising from non-digital tasks. Objective signs such as blink rate or critical flicker frequency changes are not 'diagnostic' of digital eye strain nor validated as sensitive. The mechanisms attributed to ocular surface disease exacerbation are mainly reduced blink rate and completeness, partial/uncorrected refractive error and/or underlying binocular vision anomalies, together with the cognitive demand of the task and differences in position, size, brightness and glare compared to an equivalent non-digital task. In general, interventions are not well established; patients experiencing digital eye strain should be provided with a full refractive correction for the appropriate working distances. Improving blinking, optimizing the work environment and encouraging regular breaks may help. Based on current, best evidence, blue-light blocking interventions do not appear to be an effective management strategy. More and larger clinical trials are needed to assess artificial tear effectiveness for relieving digital eye strain, particularly comparing different constituents; a systematic review within the report identified use of secretagogues and warm compress/humidity goggles/ambient humidifiers as promising strategies, along with nutritional supplementation (such as omega-3 fatty acid supplementation and berry extracts).

Dyslipidemia Exacerbates Meibomian Gland Dysfunction: A Systematic Review and Meta-Analysis.

Dry eye is a multifactorial and common age-related ocular surface disease. Dyslipidemia has been reported to be involved in meibomian gland dysfunction (MGD). However, it has not been clearly identified which lipid abnormality is responsible for MGD. In this systematic review and meta-analysis, we discuss how lipid profile changes with aging is responsible for MGD development. METHODS: An article search was performed in PubMed, EMBASE, and Web of Science. Eleven studies involving dyslipidemia in patients with MGD were identified. Five out of eleven studies were further analyzed with meta-analysis. The preferred reporting items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. Study-specific estimates (prevalence of dyslipidemia in MGD patients) were combined using one-group meta-analysis in a random-effects model. RESULTS: Meta-analysis revealed that high total cholesterol (TC) and high triglycerides (TG) were significantly associated with MGD prevalence, with odds ratios of 5.245 (95% confidence interval [CI]: 1.582-17.389; p < 0.001) and 3.264 (95% CI: 1.047-10.181; p < 0.001), respectively, but high low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) were not identified. Systematic review found that the percentage of MGD patients with TC ≥ 200 mg/dL ranged from 20.0-77.6%, TG ≥ 150 mg/dL ranged from 8.3-89.7%, whereas, in the aged-match-adjusted controls, TC range of 200 mg/dL or higher and TG range of 150 mg/dL was 6.1-45.1% and 1.1-47.8%, respectively. The severity of MGD was higher with dyslipidemia. CONCLUSION: Dyslipidemia and higher TC and TG are significant risk factors for MGD.

Diagnostic Ability of a Smartphone App for Dry Eye Disease: Protocol for a Multicenter, Open-Label, Prospective, and Cross-sectional Study.

BACKGROUND: Dry eye disease (DED) is one of the most common ocular surface diseases. Numerous patients with DED remain undiagnosed and inadequately treated, experiencing various subjective symptoms and a decrease in quality of life and work productivity. A mobile health smartphone app, namely, the DEA01, has been developed as a noninvasive, noncontact, and remote screening device, in the context of an ongoing paradigm shift in the health care system, to facilitate a diagnosis of DED. OBJECTIVE: This study aimed to evaluate the capabilities of the DEA01 smartphone app to facilitate a DED diagnosis. METHODS: In this multicenter, open-label, prospective, and cross-sectional study, the test method will involve using the DEA01 smartphone app to collect and evaluate DED symptoms, based on the Japanese version of the Ocular Surface Disease Index (J-OSDI), and to measure the maximum blink interval (MBI). The standard method will then involve a paper-based J-OSDI evaluation of subjective symptoms of DED and tear film breakup time (TFBUT) measurement in an in-person encounter. We will allocate 220 patients to DED and non-DED groups, based on the standard method. The primary outcome will be the sensitivity and specificity of the DED diagnosis according to the test method. Secondary outcomes will be the validity and reliability of the test method. The concordance rate, positive and negative predictive values, and the likelihood ratio between the test and standard methods will be assessed. The area under the curve of the test method will be evaluated using a receiver operating characteristic curve. The internal consistency of the app-based J-OSDI and the correlation between the app-based J-OSDI and paper-based J-OSDI will be assessed. A DED diagnosis cutoff value for the app-based MBI will be determined using a receiver operating characteristic curve. The app-based MBI will be assessed to determine a correlation between a slit lamp-based MBI and TFBUT. Adverse events and DEA01 failure data will be collected. Operability and usability will be assessed using a 5-point Likert scale questionnaire. RESULTS: Patient enrollment will start in February 2023 and end in July 2023. The findings will be analyzed in August 2023, and the results will be reported from March 2024 onward. CONCLUSIONS: This study may have implications in identifying a noninvasive, noncontact route to facilitate a diagnosis of DED. The DEA01 may enable a comprehensive diagnostic evaluation within a telemedicine setting and facilitate early intervention for undiagnosed patients with DED confronting health care access barriers. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs032220524; https://jrct.niph.go.jp/latest-detail/jRCTs032220524. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/45218.

Individual multidisciplinary clinical phenotypes of nasal and ocular symptoms in hay fever: Crowdsourced cross-sectional study using AllerSearch.

BACKGROUND: Multidisciplinary efforts to prospectively collect and analyze symptoms of hay fever are limited. We aimed to identify the characteristics of nasal and ocular symptoms of hay fever, using the AllerSearch smartphone application. METHODS: This mobile health-based prospective observational study using the AllerSearch smartphone application was conducted between February 1, 2018, and May 1, 2020. Individuals who downloaded AllerSearch from Japan and provided comprehensive self-assessments (including 17 items related to quality of life [QoL]-related items) were included. The characteristics and risk factors for allergic rhinitis (AR) and allergic conjunctivitis (AC) were identified using hierarchical heat maps and multivariate logistic regression. RESULTS: Of the 9041 participants with hay fever, 58.8% had AR and AC, 22.2% had AR, and 5.7% had AC. The AR-AC comorbid cohort showed worse symptoms of hay fever and QoL scores than the other cohorts. Factors (odds ratio, 95% confidence interval) associated with AR-AC included a lower age (0.98, 0.97-0.98), female sex (1.31, 1.19-1.45), liver disease (1.58, 1.26-2.35), dry eye disease (1.45, 1.30-1.63), unknown dry eye disease status (1.46, 1.31-1.62), contact lens use discontinuation during the hay fever season (1.69, 1.28-2.23), and bedroom flooring material other than hardwood, carpet, tatami, or vinyl (1.91, 1.16-3.14). CONCLUSIONS: Analysis of medical big data for hay fever performed using a mobile health app helped identify risk factors and characteristics of AC, AR, and AR-AC. Phenotyping of highly variable symptoms of hay fever, such as nasal and ocular symptoms, can facilitate better-quality clinical care.

Amplified Natural Killer Cell Activity and Attenuated Regulatory T-cell Function Are Determinants for Corneal Alloimmunity in Very Young Mice.

BACKGROUND: Corneal transplantation outcomes are generally less favorable in young children compared with adults. The purpose of this study was to determine the immunological mechanisms underlying this difference. METHODS: A murine model of allogeneic corneal transplantation was used in the study, and graft survival was determined by evaluating opacity scores for 8 wk. Syngeneic transplantation in the very young host served as a surgical control. The frequencies of total and activated natural killer (NK) cells in cornea posttransplantation were kinetically evaluated using flow cytometry. The regulatory T cell (Treg) frequency and function in naive animals were assessed by flow cytometry and in vitro suppression assays, respectively. Finally, graft survival and immune responses were determined in NK cell-depleted, or adult naive Treg-transferred, young hosts. RESULTS: Corneal allograft survival in the very young recipients was significantly lower than in adult hosts. The frequencies of total NK cells and their interferon gamma-expressing subset in the cornea were significantly higher in the very young mice posttransplantation. In ungrafted mice, frequencies of Treg in draining lymph nodes as well as their capabilities to suppress NK-cell secretion of interferon gamma were lower in the very young compared with adults. In NK cell-depleted or adult Treg--transferred very young recipients, the allograft survival was significantly improved along with the suppressed NK-cell response. CONCLUSIONS: Our data demonstrate that amplified activity of NK cells, together with lower suppressive function of Treg, contributes to early rejection of corneal allografts in very young graft recipients.

Prevalence and characteristics of dry eye disease in Parkinson's disease: a systematic review and meta-analysis.

We investigated and characterized the prevalence of dry eye disease (DED) in Parkinson's disease (PD). PubMed and EMBASE databases were searched for relevant studies between January 1, 1979 and March 10, 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Study-specific estimates were combined using the DerSimonian-Laird random-effects model. Prevalence of subjective DED symptoms in patients with PD and mean differences in blink rate, corneal thickness, tear film breakup time, and tear secretion volume on Schirmer test I were compared to those in controls. Of 383 studies, 13 (1519 patients with PD) and 12 were included in qualitative and quantitative syntheses, respectively. Meta-analysis revealed a 61.1% prevalence of subjective DED symptoms in PD and that, compared with controls, patients with PD had significantly lower blink rate, thinner corneal thickness, shorter tear film breakup time, and lower tear secretion volumes on Schirmer test I, without and with anesthesia.

Patient and public involvement in mobile health-based research for hay fever: a qualitative study of patient and public involvement implementation process.

BACKGROUND: Smartphones are being increasingly used for research owing to their multifunctionality and flexibility, and crowdsourced research using smartphone applications (apps) is effective in the early detection and management of chronic diseases. We developed the AllerSearch app to gather real-world data on individual subjective symptoms and lifestyle factors related to hay fever. This study established a foundation for interactive research by adopting novel, diverse perspectives accrued through implementing the principles of patient and public involvement (PPI) in the development of our app. METHODS: Patients and members of the public with a history or family history of hay fever were recruited from November 2019 to December 2021 through a dedicated website, social networking services, and web briefing according to the PPI Guidebook 2019 by the Japan Agency for Medical Research and Development. Nine opinion exchange meetings were held from February 2020 to December 2021 to collect opinions and suggestions for updating the app. After each meeting, interactive evaluations from PPI contributors and researchers were collected. The compiled suggestions were then incorporated into the app, establishing an active feedback loop fed by the consistently interactive infrastructure. RESULTS: Four PPI contributors (one man and three women) were recruited, and 93 items were added/changed in the in-app survey questionnaire in accordance with discussions from the exchange meetings. The exchange meetings emphasized an atmosphere and opportunity for participants to speak up, ensuring frequent opportunities for them to contribute to the research. In March 2020, a public website was created to display real-time outcomes of the number of participants and users' hay-fever-preventative behaviors. In August 2020, a new PPI-implemented AllerSearch app was released. CONCLUSIONS: This study marks the first research on clinical smartphone apps for hay fever in Japan that implements PPI throughout its timeline from research and development to the publication of research results. Taking advantage of the distinct perspectives offered by PPI contributors, a step was taken toward actualizing a foundation for an interactive research environment. These results should promote future PPI research and foster the establishment of a social construct that enables PPI efforts in various fields.

Patient and public involvement (PPI) plays an important role in promoting effective execution of health science research, as well as in the establishment of a social agreement and infrastructure for the care of various diseases, including cancer, chronic diseases, and allergic illnesses. Hay fever is one of the most common allergic diseases, affecting more than 30 million people in Japan. It is known for its myriad factors and diverse presentations. Previously, we developed a mobile health (mHealth) smartphone application (app) for hay fever­AllerSearch­released in February 2018. This app is capable of collecting relevant digital phenotypes and user-provided information, which are used in providing tailored, evidence-based suggestions. To our knowledge, no other studies have been conducted on the implementation of PPI in mHealth. Since hay fever presents with a wide variety of symptoms and risk factors, PPI principles appear well-suited for eliciting insights from the patient/public population and for incorporating new, expert perspectives into the research process. In this study, we included PPI contributors in the research plan, app development, and evaluation. Most notably, the survey questionnaire and user interface of the app was tailored based on PPI feedback. The updated AllerSearch app was released during this study period. Since hay fever is a widespread and variable illness, the multifaceted input from patients and public experts enabled by PPI implementation holds promise for improving society-wide healthcare and in empowering a culture toward medical involvement.