Ensemble detection of hand joint ankylosis and subluxation in radiographic images using deep neural networks.

The modified total Sharp score (mTSS) is often used as an evaluation index for joint destruction caused by rheumatoid arthritis. In this study, special findings (ankylosis, subluxation, and dislocation) are detected to estimate the efficacy of mTSS by using deep neural networks (DNNs). The proposed method detects and classifies finger joint regions using an ensemble mechanism. This integrates multiple DNN detection models, specifically single shot multibox detectors, using different training data for each special finding. For the learning phase, we prepared a total of 260 hand X-ray images, in which proximal interphalangeal (PIP) and metacarpophalangeal (MP) joints were annotated with mTSS by skilled rheumatologists and radiologists. We evaluated our model using five-fold cross-validation. The proposed model produced a higher detection accuracy, recall, precision, specificity, F-value, and intersection over union than individual detection models for both ankylosis and subluxation detection, with a detection rate above 99.8% for the MP and PIP joint regions. Our future research will aim at the development of an automatic diagnosis system that uses the proposed mTSS model to estimate the erosion and joint space narrowing score.

Successful treatment of PR3-ANCA-positive interstitial pneumonia with a moderate dose of glucocorticoid and rituximab.

Antineutrophil cytoplasmic antibody (ANCA)-positive interstitial pneumonia (IP) is reported as IP that is ANCA-positive and does not involve organ damage associated with vasculitis other than the lungs. While the combination of glucocorticoid and rituximab is effective in ANCA-associated vasculitis, the treatment strategy for ANCA-positive IP has not been established. Here, we report the first case of successful treatment of proteinase 3 (PR3)-ANCA-positive IP with a moderate dose of glucocorticoid and rituximab. The patient was an 80-year-old male who presented with subacute dry cough and dyspnoea. Blood tests revealed elevated levels of C-reactive protein, Krebs von den Lungen 6 (KL-6), and PR3-ANCA. Chest computed tomography (CT) showed interstitial shadows and infiltrates around honeycomb cysts. 18F-fluorodeoxyglucose (FDG) positron emission tomography CT revealed an uptake of FDG in the IP area. After starting treatment with a moderate dose of prednisolone and rituximab, the patient's clinical symptoms disappeared, C-reactive protein and KL-6 turned to be normal, and infiltrates around the cysts of honeycomb lungs disappeared. Prednisolone was gradually decreased to 2 mg, and no relapse or adverse events were observed during the course of treatment. Our case suggests that early treatment with a moderate dose of glucocorticoid and rituximab is effective for PR3-ANCA-positive IP.

Atypical Cogan's Syndrome with Large-vessel Vasculitis Successfully Treated with Tocilizumab.

A 61-year-old man presented with weight loss, bilateral ocular redness, blurred vision, and sensorineural hearing loss. Fluorodeoxyglucose-position emission tomography/computed tomography demonstrated an uptake in the ascending and descending aorta, abdominal aorta and femoral arteries. Atypical Cogan's syndrome complicated with large-vessel vasculitis (LVV) was diagnosed. He was treated with high-dose prednisolone and subcutaneous tocilizumab (162 mg/week), resulting in successful improvements in his ocular and vascular involvements. Although there is currently no established treatment strategy for LVV associated with Cogan's syndrome, our case and literature review suggest that tocilizumab is a viable treatment option for this rare but life-threatening complication.

Allergic disorders and their risk factors in primary Sjögren's syndrome.

Objective: This study aimed to evaluate the prevalence of allergic disorders in patients with primary Sjögren's syndrome (pSS), compare it with that of patients with rheumatoid arthritis (RA), and examine the risk factors in patients with pSS. Methods: We retrospectively examined the records of patients diagnosed with pSS and RA who regularly visited our department between 2010 and 2020. Allergic disorders included drug allergy, food allergy, allergic contact dermatitis (ACD), allergic rhinitis (AR)/allergic conjunctivitis (AC), and asthma. Results: Patients with pSS (292 patients) had a higher prevalence of food allergy, drug allergy, and AR/AC than those with RA (413 patients). The multivariate analysis revealed that patients with pSS who had drug allergy had a higher prevalence of food allergy, higher eosinophil levels, and higher positivity rates of anti-SS-related antigen A (SSA) antibodies than those without drug allergy; those with food allergy had a higher rate of ACD than those without food allergy and vice versa; those with AR/AC had a higher rate of ACD and asthma and higher eosinophil levels than those without AR/AC; those with asthma had a higher rate of AR/AC than those without asthma. Conclusions: Patients with pSS had a higher prevalence of allergic disorders than those with RA. Among patients with pSS, the risk factors for drug allergy were food allergy, higher eosinophil levels, and positivity for anti-SSA antibodies, the risk factor for food allergy was ACD and vice versa, the risk factors for AR/AC were ACD, asthma, and high eosinophil levels, and the risk factor for asthma was AR/AC.

Detecting hand joint ankylosis and subluxation in radiographic images using deep learning: A step in the development of an automatic radiographic scoring system for joint destruction.

We propose a wrist joint subluxation/ankylosis classification model for an automatic radiographic scoring system for X-ray images. In managing rheumatoid arthritis, the evaluation of joint destruction is important. The modified total Sharp score (mTSS), which is conventionally used to evaluate joint destruction of the hands and feet, should ideally be automated because the required time depends on the skill of the evaluator, and there is variability between evaluators. Since joint subluxation and ankylosis are given a large score in mTSS, we aimed to estimate subluxation and ankylosis using a deep neural network as a first step in developing an automatic radiographic scoring system for joint destruction. We randomly extracted 216 hand X-ray images from an electronic medical record system for the learning experiments. These images were acquired from patients who visited the rheumatology department of Keio University Hospital in 2015. Using our newly developed annotation tool, well-trained rheumatologists and radiologists labeled the mTSS to the wrist, metacarpal phalangeal joints, and proximal interphalangeal joints included in the images. We identified 21 X-ray images containing one or more subluxation joints and 42 X-ray images with ankylosis. To predict subluxation/ankylosis, we conducted five-fold cross-validation with deep neural network models: AlexNet, ResNet, DenseNet, and Vision Transformer. The best performance on wrist subluxation/ankylosis classification was as follows: accuracy, precision, recall, F1 value, and AUC were 0.97±0.01/0.89±0.04, 0.92±0.12/0.77±0.15, 0.77±0.16/0.71±0.13, 0.82±0.11/0.72±0.09, and 0.92±0.08/0.85±0.07, respectively. The classification model based on a deep neural network was trained with a relatively small dataset; however, it showed good accuracy. In conclusion, we provided data collection and model training schemes for mTSS prediction and showed an important contribution to building an automated scoring system.

Successful treatment with tofacitinib for relapse of rapidly progressive interstitial lung disease in anti-melanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody is associated with clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD). Recently, several studies have reported that tofacitinib (TOF), a Janus kinase inhibitor, might be effective for cases of new or refractory RP-ILD in anti-MDA5 antibody-positive CADM; however, it is unknown whether TOF can also be effective for relapsed cases. We herein report a relapsed case of RP-ILD in anti-MDA5 antibody-positive CADM, which was successfully treated by combination therapy with TOF (5 mg twice daily). Our case suggests that TOF may also be a potential treatment option for relapsed cases of this disease.

Aseptic meningitis as an initial manifestation of primary Sjögren's syndrome.

Aseptic meningitis is a rare life-threatening complication of primary Sjögren's syndrome (pSS), and its characteristics and prognosis remain unknown. We present our case of aseptic meningitis associated with pSS and reviewed the published literature to elucidate their characteristics and prognosis. An 84-year-old man was admitted to our hospital for fever and disturbance of consciousness. Acute aseptic meningitis was diagnosed based on the results for cerebrospinal fluid and head imaging tests. As an aetiological investigation for his aseptic meningitis, serum anti-Sjögren's-syndrome-related antigen A and anti-Sjögren's-syndrome-related antigen B antibodies were found to be positive, and the biopsy specimen of his labial salivary gland revealed lymphocytic sialadenitis, confirming a diagnosis of pSS. Treatment with moderate-dose glucocorticoid completely improved his aseptic meningitis. Relapse of the disease was not observed during his clinical course over 12 months. Our present case and literature review suggest that aseptic meningitis can be an initial manifestation of pSS and be treatable by immunosuppressive therapy. Thus, early recognition and treatment initiation are critical to prevent the irreversible damage of central nervous system in pSS-associated aseptic meningitis. In aseptic meningitis of unknown origin, pSS should be included in differential diagnoses, and testing for serum anti-Sjögren's-syndrome-related antigen A and anti-Sjögren's-syndrome-related antigen A antibodies may be useful as an initial screening.

Giant cell arteritis successfully treated with subcutaneous tocilizumab monotherapy.

Glucocorticoid remains the mainstay for treatment of large vessel vasculitis (LVV) including giant cell arteritis (GCA); however, the disease affects the elderly for whom the adverse effects of glucocorticoid are problematic. Recently, some reports have suggested that intravenous tocilizumab (TCZ) monotherapy is effective for this disease. To date, it remains unknown whether subcutaneous TCZ monotherapy is also effective. Here, we present a first case of GCA successfully treated with subcutaneous TCZ monotherapy. A 75-year-old woman presented with shoulder and hip pain. She was diagnosed with polymyalgia rheumatica (PMR) and treated with low-dose prednisolone (15 mg daily); however, she discontinued glucocorticoid therapy at her discretion due to the psychiatric adverse effect (cognitive dysfunction). Seven months later, her shoulder and hip pain relapsed. Furthermore, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) revealed uptake in the descending thoracic aorta, indicating a complication of LVV. She refused to take glucocorticoid for fear of psychiatric adverse effects and chose subcutaneous TCZ monotherapy (162 mg weekly) for treating this life-threatening urgent condition. Nine months later, her shoulder and hip pain resolved and FDG-PET/CT demonstrated no uptake in the descending thoracic aorta, indicating a successful treatment with subcutaneous TCZ monotherapy for the disease. No adverse events and disease relapse were found during observation period. Our case and the literature review suggest that not only intravenous injection but also subcutaneous injection of TCZ monotherapy can serve as an alternative treatment for patients with GCA who have comorbidities or refuse to take glucocorticoid.

Serum cytokines and bone metabolic markers in patients with rheumatoid arthritis treated with biological disease modifying anti-rheumatic drugs.

INTRODUCTION: /objectives Several biological disease-modifying anti-rheumatic drugs (bDMARDs) have been widely used for the management of rheumatoid arthritis (RA). These drugs target different molecules important for the pathophysiology of RA; however, only a few studies have compared the effects of these biological drugs on cytokines and bone metabolic markers. The main aim of this study is to clarify the effects of bDMARDs with different modes of action on the cytokine and bone metabolic marker levels in patients with RA. METHODS: Patients with RA who were initiated on infliximab, tocilizumab, or abatacept as the first bDMARD were prospectively enrolled in this study. Serum cytokine and bone metabolic marker levels were measured longitudinally, and changes in their levels were compared. RESULTS: A total of 174 patients were enrolled in this study, with 55, 70, and 49 patients in the infliximab, tocilizumab, and abatacept groups, respectively. At six months, despite the similar clinical effectiveness of the three drugs, changes in the cytokine and bone metabolic marker levels were distinct; interferon-γ and tumor necrosis factor-α levels were significantly increased with infliximab, interleukin-6 levels were increased with tocilizumab, and interleukin-1ß and interleukin-8 levels were increased with abatacept treatment. Bone-specific alkaline phosphatase and osteocalcin levels increased more significantly with tocilizumab than with infliximab, while osteopontin and osteonectin levels decreased with infliximab treatment. CONCLUSIONS: bDMARDs with different modes of action exert different effects on the cytokine and bone metabolic marker levels in patients with RA.

Risk factors associated with cytomegalovirus reactivation in patients receiving immunosuppressive therapy for rheumatic diseases: a retrospective study.

Immunosuppressive treatment is a common cause of cytomegalovirus (CMV) reactivation. However, there is no consensus regarding the risk factors for CMV reactivation in rheumatic diseases. Therefore, this study aimed to elucidate the risk factors associated with CMV reactivation. We retrospectively collected the data of 472 patients with rheumatic diseases whose CMV pp65 antigen (C7-HRP) titer was measured. We divided the patients into those with and those without C7-HRP. We retrospectively collected data on age, sex, primary condition and organ involvement, and blood test results. We also investigated the use of immunosuppressants and the maximum and cumulative doses of prednisolone (PSL). We performed univariate and multivariate analyses to identify risk factors for CMV reactivation. Multivariate analysis showed that higher age (71.2 vs. 64.4 years, p = 0.0022), hypoalbuminemia (2.9 vs. 3.4 g/dL, p = 0.0104), higher creatinine level (1.2 vs. 0.9 mg/dL, p = 0.0026), cyclosporine use (8.2 vs. 3.6%, p = 0.0101), and higher maximum (552.4 vs. 243.3 mg, p < 0.0001) and cumulative (2785.9 vs. 1330.5 mg, p < 0.0001) doses of PSL were associated with CMV reactivation. Older age, hypoalbuminemia, higher creatinine level, cyclosporine use, and higher maximum and cumulative doses of PSL were significant risk factors for CMV reactivation in rheumatic diseases.

Association of work environment with stress and depression among Japanese workers.

BACKGROUND: There is a lack of studies that investigated the effect of a wide range of work environmental factors on stress and depression in Japan. OBJECTIVES: To examine the association of work environment factors with stress and depression among workers in Japan. METHODS: We conducted questionnaire surveys of workers that mainly engage in desk work in Japan. Stress was assessed through the Perceived Stress Scale (PSS), depression through the Patient Health Questionnaire-9 (PHQ-9), and work environment through physical and psychological workplace environment questionnaires. Workers were divided into low and high stress groups based on PSS score (median split), and divided into non-depressed and depressed groups based on their PHQ-9 score (< 5, and ≥5); these groups were then compared with their working environment. In addition, a multiple regression analysis was performed. RESULTS: Responses were obtained from 210 subjects. Multiple regression analysis showed that "Ability to work at one's own pace" and "Ability to apply personal viewpoint to work," etc., had effect on stress, while "Workplace harassment" and "Support from colleagues," etc., had effect on depression. CONCLUSIONS: The results suggest that stress and depression in Japanese workers are related to factors such as job demands, control of work, workplace harassment, and psychological safety.

Dermatomyositis Which Was Double Positive for Anti-MDA5 and Anti-ARS Antibodies That Was Successfully Treated by Intensive Immunosuppressive Therapy.

Myositis-specific autoantibody is associated with the clinical phenotype and prognosis of dermatomyositis. Anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl-tRNA synthetase (ARS) antibodies are generally mutually exclusive. We herein present an extremely rare case of dermatomyositis which showed double positivity for anti-MDA5 and anti-ARS antibodies. There have been very few reported cases of double positive anti-MDA5, anti-ARS antibodies. In such cases, the clinical characteristics of each autoantibody can coexist. Thus, we should pay attention to the rapidly progressing features of anti-MDA5 as well as the chronic relapsing features of anti-ARS for the better management of this rare condition.

Immune-mediated necrotizing myopathy which showed deposition of C5b-9 in the necrotic muscle fibers and was successfully treated with intensive combined therapy with high-dose glucocorticoids, tacrolimus, and intravenous immunoglobulins.

Currently, no standard treatment strategy has been established for immune-mediated necrotizing myopathy (IMNM). Here we present a case of IMNM which was successfully treated with intensive combined therapy with high-dose glucocorticoids, tacrolimus, and intravenous immunoglobulins. Her muscle weakness was rapidly progressive and severe so that she became bedridden one week after admission. She was complicated with dysphagia and had serum myogenic enzymes elevation, ventricular diastolic dysfunction, and interstitial lung disease. Serum anti-SRP antibody was positive and her muscle biopsy revealed many necrotic fibers with minimal inflammation. Further histological analysis demonstrated infiltration of phagocytic macrophages with deposition of membrane attack complex (C5b-9) in the necrotic muscle fibers, suggesting activation of complement pathway and macrophages as a pathomechanism of this disease. She was diagnosed as IMNM and was immediately initiated a combination therapy described above, which led to dramatic clinical improvements. Recent studies suggest that intravenous immunoglobulins and tacrolimus can inhibit the activation of complement pathway and macrophages. Our present case suggests that early initiation of intensive combined therapy including intravenous immunoglobulins and tacrolimus might be effective for preventing irreversible muscle damages by disrupting a pathogenic activation of complement and macrophages in IMNM.

Acute encephalitis in primary Sjögren's syndrome: A case report and literature review.

Acute encephalitis is an extremely rare condition in primary Sjogren's syndrome (pSS), and its characteristics and prognosis remain unclear. Here, we report the case of pSS presented with acute encephalitis. She was admitted to our hospital for acute disturbance of consciousness. Acute encephalitis was diagnosed based on the results of the cerebrospinal fluid test (the increase of leucocyte counts, proteins, and interleukin-6 levels), magnetic resonance imaging, and single-photon emission computed tomography with 99mTc. The infectious aetiologies and underlying malignancies were excluded. Serum anti-Sjogren's syndrome-related antigen A autoantibody was positive with extremely high titre. The biopsy specimen of her labial salivary gland revealed a focal lymphocytic sialadenitis with a score of grade 4 in the Greenspan grade. She also developed diffuse alveolar haemorrhage during the clinical course. She was diagnosed with pSS complicated with acute encephalitis followed by diffuse alveolar haemorrhage and successfully treated with pulse steroids, high dose of prednisolone and intravenous cyclophosphamide. Our present case and literature review suggest that acute encephalitis associated with pSS can be treatable with the immunosuppressive therapy, and thus early recognition and treatment initiation are important for this life-threatening condition. Thus, pSS should be included in the differential diagnosis of unexplained encephalitis. Notably, our case characteristically showed diffuse alveolar haemorrhage, adding new insights into the pathogenesis of acute encephalitis associated with pSS that capillaritis might be the underlying cause of this condition.

Dropped head in systemic sclerosis: a case based review.

Dropped head syndrome is a rare disease entity characterized by severe weakness of the cervical para-spinal muscles, resulting in a chin-on-chest deformity. Systemic sclerosis is one of the causes of dropped head syndrome, but its characteristics and prognosis remain unclear due to the extreme rarity of this condition. We present a case of dropped head which occurred in systemic sclerosis. He presented with severe dropped head and relatively mild weakness of the proximal limb muscles. Serum level of creatine kinase was elevated, myopathic change was observed in electromyography, and gadolinium enhancement was found in magnetic resonance imaging of his posterior neck muscles. Anti-topoisomerase I antibody was positive, while other autoantibodies such as anti-PM/Scl and anti-Ku antibodies were negative. Since his dropped head acutely progressed, high dose of glucocorticoid therapy was initiated, which successfully improved dropped head, serum level of creatine kinase, and gadolinium enhancement in magnetic resonance imaging. Our present case and literature review suggest that dropped head occurring in systemic sclerosis can be treatable with immunosuppressive therapy. It is important to recognize this rare but treatable involvement of systemic sclerosis because early diagnosis and treatment initiation are crucial to prevent the irreversible organ damage and the significant decrease of daily activities.

Subjective well-being and month-long LF/HF ratio among deskworkers.

The importance of workers' well-being has been recognized in recent years. The assessment of well-being has been subjective, and few studies have sought potential biomarkers of well-being to date. This study examined the relationship between well-being and the LF/HF ratio, an index of heart rate variability that reflects sympathetic and parasympathetic nerve activity. Pulse waves were measured using photoplethysmography through a web camera attached to the computer used by each participant. The participants were asked to measure their pulse waves while working for 4 weeks, and well-being was assessed using self-reported measures such as the Satisfaction With Life Scale (SWLS), the Positive and Negative Affect Schedule (PANAS), and the Flourishing Scale (FS). Each of the well-being scores were split into two groups according to the median value, and the LF/HF ratio during work, as well as the number of times an LF/HF ratio threshold was either exceeded or subceeded, were compared between the high and low SWLS, positive emotion, negative emotion, and FS groups. Furthermore, to examine the effects of the LF/HF ratio and demographic characteristics on well-being, a multiple regression analysis was conducted. Data were obtained from 169 participants. The results showed that the low FS group had a higher mean LF/HF ratio during work than the high FS group. No significant differences were seen between the high and low SWLS groups, the high and low positive emotion groups, or the high and low negative emotion groups. The multiple regression analysis showed that the mean LF/HF ratio during work affected the FS and SWLS scores, and the number of times the mean LF/HF ratio exceeded +3 SD had an effect on the positive emotion. No effect of the LF/HF ratio on negative emotions was shown. The LF/HF ratio might be applicable as an objective measure of well-being.

[ALLERGIC DISEASES IN ADULT-ONSET STILL'S DISEASE AND RHEUMATOID ARTHRITIS].

BACKGROUND: A high prevalence of allergic diseases was found in patients with adult-onset Still's disease (AOSD). However, the relative prevalence is unknown compared with other diseases. OBJECTIVES: We sought to compare the prevalence of allergic diseases in the control group of patients with rheumatoid arthritis (RA). METHODS: We retrospectively examined consecutive patients diagnosed with AOSD or RA in our hospital from 2010 to 2020. The patients with AOSD met the preliminary criteria for classification of AOSD. The patients with RA met the EULAR/ACR 2010 criteria. We included patients with RA without other rheumatic diseases. The analysis was performed on six types of allergic reactions: food allergy, drug allergy, allergic contact dermatitis, allergic rhinitis and/or allergic conjunctivitis, and asthma. RESULTS: Twenty-four patients with AOSD and 409 patients with RA were enrolled. The median ages (AOSD, RA) were 46.6, 68.2 years old. Females were 83.3%, 78.0%. Fifty% of AOSD patients and 34.5% of RA patients presented at least one type of allergic diseases (p = 0.12). These included food allergy (4.2%, 6.4%: p = 1.0), drug allergy (37.5%, 16.6%: p = 0.02), allergic rhinitis/allergic conjunctivitis (25.0%, 8.6%: p = 0.02), contact dermatitis (4.2%, 4.4%: p = 1.0), and asthma (4.2%, 5.9%: p = 1.0). CONCLUSION: Patients with AOSD had a higher prevalence of drug allergy, and allergic rhinitis/allergic conjunctivitis than patients with RA.

Steroid-Sparing Effect of Tocilizumab and Methotrexate in Patients with Polymyalgia Rheumatica: A Retrospective Cohort Study.

Polymyalgia rheumatica (PMR) is an inflammatory disorder characterized by pain and stiffness in the shoulders, hips, and proximal limbs; it usually affects elderly patients. The effectiveness of methotrexate and tocilizumab in PMR treatment has not been extensively studied. Thus, we aimed to assess the steroid-sparing effect of tocilizumab and methotrexate in PMR in clinical practice. Consecutive patients with PMR in our hospitals, who were included in our retrospective cohort, were reviewed between 2005 and 2015 and divided into the following groups according to their treatments: prednisolone or none (prednisolone group), methotrexate ± prednisolone (methotrexate group), or tocilizumab ± prednisolone (tocilizumab group). The prednisolone dose at the last follow-up was compared. A total of 227 patients with an average age of 74 years were enrolled. No difference in baseline characteristics was found among the three groups. The prednisolone dose at the last follow-up was lower (0 vs. 3.0 vs. 3.5 mg/day, p < 0.001) and the prednisolone discontinuation rate was higher (80.0% vs. 28.3% vs. 18.8%, p < 0.0001) in the tocilizumab group than in the prednisolone and methotrexate groups. This study suggested that tocilizumab has a steroid-sparing effect in PMR. Tocilizumab can be an option in the management of PMR. Future studies are warranted to confirm our findings.

Unobtrusive Sensing Technology for Quantifying Stress and Well-Being Using Pulse, Speech, Body Motion, and Electrodermal Data in a Workplace Setting: Study Concept and Design.

Introduction: Mental disorders are a leading cause of disability worldwide. Depression has a significant impact in the field of occupational health because it is particularly prevalent during working age. On the other hand, there are a growing number of studies on the relationship between "well-being" and employee productivity. To promote healthy and productive workplaces, this study aims to develop a technique to quantify stress and well-being in a way that does not disturb the workplace. Methods and analysis: This is a single-arm prospective observational study. The target population is adult (>20 years old) workers at companies that often engage in desk work; specifically, a person who sits in front of a computer for at least half their work hours. The following data will be collected: (a) participants' background characteristics; (b) participants' biological data during the 4-week observation period using sensing devices such as a camera built into the computer (pulse wave data extracted from the facial video images), a microphone built into their work computer (voice data), and a wristband-type wearable device (electrodermal activity data, body motion data, and body temperature); (c) stress, well-being, and depression rating scale assessment data. The analysis workflow is as follows: (1) primary analysis, comprised of using software to digitalize participants' vital information; (2) secondary analysis, comprised of examining the relationship between the quantified vital data from (1), stress, well-being, and depression; (3) tertiary analysis, comprised of generating machine learning algorithms to estimate stress, well-being, and degree of depression in relation to each set of vital data as well as multimodal vital data. Discussion: This study will evaluate digital phenotype regarding stress and well-being of white-collar workers over a 4-week period using persistently obtainable biomarkers such as heart rate, acoustic characteristics, body motion, and electrodermal activity. Eventually, this study will lead to the development of a machine learning algorithm to determine people's optimal levels of stress and well-being. Ethics and dissemination: Collected data and study results will be disseminated widely through conference presentations, journal publications, and/or mass media. The summarized results of our overall analysis will be supplied to participants. Registration: UMIN000036814.