Personalized Federated Learning for Institutional Prediction Model using Electronic Health Records: A Covariate Adjustment Approach.

Federated learning (FL) has attracted attention as a technology that allows multiple medical institutions to collaborate on AI without disclosing each other's patient data. However, FL has the challenge of being unable to robustly learn when the data of participating clients is non-independently and non-identically distributed (Non-IID). Personalized Federated Learning (PFL), which constructs a personalized model for each client, has been proposed as a solution to this problem. However, conventional PFL methods do not ensure the interpretability of personalization, specifically, the identification of which data samples are contributed to each personalized learning, which is important for AI in medical applications. In this study, we propose a novel PFL framework, Federated Adjustment of Covariate (FedCov), which acquires a propensity score model representing the covariate shift among clients through prior FL, then learns a final model by weighting the contribution of each training sample to PFL based on the estimated propensity score. This approach enables both the learning of personalized models through covariate adjustment and the visualization of the contribution of each client to PFL. FedCov was evaluated in the prediction of in-hospital mortality across 50 hospitals in the eICU Collaborative Research Database, achieving an ROC-AUC of 0.750. This result outperformed the AUCs in the 0.720-0.735 range achieved by conventional FL methods and was closest to the AUC of 0.754 achieved by centralized learning.Clinical Relevance- This study demonstrates the feasibility of providing sophisticated and personalized AI-driven clinical decision support to any medical institution through personalized federated learning.

Clinical efficacy of assessment of swallowing ability for pneumonia and other assessment tools for occurrence and mortality from pneumonia among older inpatients in a long-term care hospital.

BACKGROUND: Aspiration pneumonia is an important condition in elderly patients and detecting dysphagia early can help clinicians identify patients with a high risk of aspiration pneumonia. We previously reported the usefulness of the Assessment of Swallowing Ability for Pneumonia (ASAP) in predicting the occurrence of and mortality from pneumonia in patients in acute care hospitals; however, there are very few reports on the utility of this screening test for patients in stable condition. METHODS: Elderly patients in stable condition (n = 133) without pneumonia were prospectively enrolled. Associations between ASAP, Functional Independence Measure (FIM), Controlling Nutrition Status (CONUT), and Charlson Co-morbidity Index (CCI) scores and occurrence of/mortality from pneumonia during hospitalization were evaluated. RESULTS: The occurrence of pneumonia was observed in 27 (20.3%) patients, and 18 (13.5%) died during hospitalization. Multivariate analysis showed that low ASAP score and low FIM motor were independent predictors for the occurrence of pneumonia, and low ASAP score was an independent predictor for mortality from pneumonia. Areas under the curve for ASAP, FIM motor, FIM cognition, and CONUT scores were 0.895 (95% confidence interval [CI], 0.829-0.960), 0.913 (95% CI, 0.860-0.968), 0.841 (95% CI, 0.761-0.921), and 0.753 (95% CI, 0.649-0.858), respectively, for occurrence, and 0.881 (95% CI, 0.807-0.955), 0.904 (95% CI, 0.860-0.949), 0.829 (95% CI, 0.727-0.931), 0.746 (95% CI, 0.617-0.874), respectively, for mortality. CONCLUSION: The ASAP and FIM motor are useful for predicting the occurrence of and mortality from pneumonia in elderly inpatients in long-term care hospitals.

Pathology of Critical Limb Ischemia; Comparison of Plaque Characteristics Between Anterior and Posterior Tibial Arteries.

AIMS: Though the number of patients with peripheral arterial disease (PAD) and critical limb ischemia (CLI) is increasing, few histopathological studies of PAD, particularly that involving below-the-knee arteries, has been reported. We analyzed the pathology of anterior tibial artery (ATA) and posterior tibial artery (PTA) specimens obtained from patients who underwent lower extremity amputation due to CLIMethods: Dissected ATAs and PTAs were subjected to ex-vivo soft X-ray radiography, followed by pathological examination using 860 histological sections. This protocol was approved by the Ethics Review Board of Nihon University Itabashi Hospital (RK-190910-01) and Kyorin University Hospital (R02-179). RESULTS: The calcified area distribution was significantly larger in PTAs than in ATAs on soft X-ray radiographic images (ATAs, 48.3% ±19.2 versus PTAs, 61.6% ±23.9; p＜0.001). Eccentric plaque with necrotic core and macrophage infiltration were more prominent in ATAs than in PTAs (eccentric plaque: ATAs, 63.7% versus PTAs, 49.1%; p＜0.0001, macrophage: ATAs, 0.29% [0.095 - 1.1%] versus PTAs, 0.12% [0.029 - 0.36%]; p＜0.001), histopathologically. Thromboembolic lesions were more frequently identified in PTAs than in ATAs (ATAs, 11.1% versus PTAs 15.8%; p＜0.05). Moreover, post-balloon injury pathology differed between ATAs and PTAs. CONCLUSIONS: Histological features differed strikingly between ATAs and PTAs obtained from CLI patients. Clarifying the pathological features of CLI would contribute to establishing therapeutic strategies for PAD, particularly disease involving below-the knee-arteries.

Adherence to CPAP in summer to autumn predicts self-reported common cold symptoms in patients with obstructive sleep apnea in winter: A prospective observational study.

OBJECTIVE: We conducted a prospective observational study to determine the relationship between adherence to continuous positive airway pressure (CPAP) and susceptibility to the common cold in moderate-to-severe obstructive sleep apnea (OSA) patients. METHODS: We prospectively investigated the number of days with common cold symptoms from November 2019 to February 2020. The rate of CPAP use for 4 h/night in the preceding four months (July to October 2019) was used as a measure of CPAP adherence. Multiple generalized linear models were used to evaluate the association to days of common cold symptoms after controlling for demographic variables, habitual short sleep duration, and insomnia severity. RESULTS: We included 123 outpatients (median age 63 years) with moderate-to-severe OSA treated with CPAP. In the multivariate generalized linear model, better CPAP adherence was independently significantly associated with days with fewer common cold symptoms (ß = -0.248, P = 0.031); meanwhile, the severity of insomnia and habitual short sleep duration was not significantly associated with it. Subgroup analyses revealed that the association between CPAP adherence and days with common cold symptoms was also significant in young to middle-aged (<65 years) participants (ß = -0.407, P = 0.005). In contrast, the association was negligible in older (≥65 years) participants. CONCLUSIONS: CPAP adherence may be protective against viral infections in patients with moderate-to-severe OSA. This effect appears to be more pronounced in young to middle-aged patients with OSA.

Adverse effects of thyroid-hormone-disrupting chemicals 6-propyl-2-thiouracil and tetrabromobisphenol A on Japanese medaka (Oryzias latipes).

Thyroid-hormone-disrupting chemicals are increasingly attracting attention because of their potential harmful effects on animal health, including on fishes. Here, we investigated the effects of exposure to the thyroid-hormone-disrupting chemicals 6-propyl-2-thiouracil (PTU) and tetrabromobisphenol A (TBBPA) on swim bladder inflation, eye development, growth, swimming performance, and the expression of thyroid-related genes in Japanese medaka (Oryzias latipes). PTU exposure resulted in reductions in eye size, growth, and swim bladder inflation, and these effects led to poorer swimming performance. These phenotypic effects were accompanied by increased expression of the thyroid-stimulating hormone subunit beta (tshß) paralog tshß-like, but there were no significant changes in expression for tshß, deiodinase 1 (dio1), deiodinase 2 (dio2), and thyroid hormone receptor alpha (trα) and beta (trß). For PTU exposure, we identified the key event (swim bladder inflation reduction) and an adverse outcome (swimming performance reduction). No significant effects from TBBPA exposure were seen on swim bladder inflation, eye development, growth, or swimming performance. However, expression of tshß-like and tshß (significantly enhanced) and trα and trß (significantly reduced) were affected by TBBPA exposure albeit not in dose-dependent manners. There were no effects of TBBPA on the expression of dio1 and dio2. We thus show that the two thyroid-hormone-disrupting chemicals PTU and TBBPA differ in their effect profiles with comparable effects on the studied phenotypes and thyroid-related gene expression to those reported in zebrafish.

Long-term outcomes regarding arterial stiffness and carotid artery atherosclerosis in female patients with rapid eye movement obstructive sleep apnea.

OBJECTIVE: Rapid eye movement (REM) obstructive sleep apnea (OSA) is associated with the risk of cardiovascular events. Arterial stiffness and carotid artery intima-media thickness (IMT) predict these events, but few relevant studies have been conducted. We compared long-term changes in arterial stiffness and IMT between patients with REM OSA and non-REM (NREM) OSA receiving continuous positive airway pressure (CPAP) or oral appliance (OA) therapy. METHODS: Newly diagnosed female patients with OSA received CPAP (n = 6) or OA (n = 7). Pulse wave velocity (PWV) and carotid artery ultrasound were performed before and 60 months after treatment. RESULTS: There were no differences in baseline characteristics (mean age: 56.0 vs. 61.3 years; mean body mass index: 22.6 vs. 21.7 kg/m2) between the REM OSA and non-REM OSA groups. The median apnea-hypopnea index was lower in the REM OSA group than in the non-REM OSA group. Increased PWV (12.92 ± 1.64 to 14.56 ± 2.73 m/s) and deteriorated glucose metabolism were observed in the REM OSA group after treatment. PWV, IMT, and cardiovascular risk factors were unaffected in the non-REM OSA group. CONCLUSION: Arterial stiffness and glucose metabolism are deteriorated in patients with REM OSA compared with these parameters in patients with non-REM OSA after CPAP or OA treatment.

Restriction of SARS-CoV-2 replication in the human placenta.

Although SARS-CoV-2 can infect human placental tissue, vertical transmission is rare. Therefore, the placenta may function as a barrier to inhibit viral transmission to the foetus, though the mechanisms remain unclear. In this study, we confirmed the presence of the SARS-CoV-2 genome in human placental tissue by in situ hybridization with antisense probes targeting the spike protein; tissue staining was much lower when using sense probes for the spike protein. To the best of our knowledge, this is the first evidence directly indicating inefficient viral replication in the SARS-CoV-2-infected placenta. Additional studies are required to reveal the detailed mechanisms.

Introduction of Induction Heating is too late for older residents with difficulty in handling fire.

Handling errors with household flammables, for example pan burning, may result in serious accidents, which may be caused by decreased attention or executive function. Objective: The manuals by several cities simply suggest the use of induction heating (IH) cookers. However, it requires complicated operation of buttons. Furthermore, no previous studies have examined the difficulty of IH operation in older adults. Methods: We examined 166 residents aged 75+ years in Wakuya, consisting 66 Clinical Dementia Rating (CDR) 0 (healthy), 79 CDR 0.5 (very mild dementia), and 21 CDR 1+ (dementia) participants. Based on fire accident, they were classified into "high-risk," "low-risk," and "safety" groups. They were asked to actually use an IH as an examination. The participants who passed all procedures were classified as "good users," and the remaining who failed were classified as "poor users." Their overall cognitive and executive functions were assessed using the Mini-Mental State Examination (MMSE) and Trail Making Test A and Digit Symbol (DS), respectively. Results: The proportions of "good users" in the CDR 0, CDR 0.5, and CDR 1+ groups were 7 (10.6%), 6 (7.3%), and 0 (0%), respectively. For the CDR 0 and CDR 0.5 group, the good users had higher scores on the MMSE and DS than do the poor users. Conclusions: The introduction of IH is too late for "high-risk group." Since the IH cooker requires complicated operation of buttons, they may be difficult for older residents to handle. Executive function may be examined for early detection of handling errors with household flammables.

Erros no manuseio de artigos domésticos muito aquecidos, por exemplo, panelas, podem resultar em acidentes graves, que podem ser causados por diminuição da atenção ou de funções executivas. Objetivo: Manuais de várias cidades sugerem simplesmente o uso de fogões de aquecimento por indução (FAI), mas esses aparelhos requerem uma operação complexa, com necessidade de uso de diversos botões. No entanto, nenhum estudo anterior examinou a dificuldade de operação de FAI em adultos mais velhos. Métodos: Foram examinados 166 residentes de Wakuya, Japão, com mais de 75 anos, entre os quais 66 participantes com classificação clínica de demência (CDR) 0 (saudável), 79 CDR 0,5 (demência muito leve) e 21 CDR 1+ (demência). Em função do risco de queimadura, eles foram classificados nos grupos "alto," "baixo risco" e "sem risco". Solicitou-se que realmente utilizassem o FAI como parte do exame. Os participantes que passaram em todos os procedimentos foram classificados como "bons usuários", enquanto os demais foram classificados como "usuários fracos". As funções cognitivas e executivas globais foram avaliadas por meio do Miniexame do Estado Mental (MEEM), do Teste de Trilha A e do Teste Dígito-Símbolo (DS), respectivamente. Resultados: As proporções de "bons usuários" nos grupos CDR 0, CDR 0,5 e CDR 1+ foram 7 (10,6%), 6 (7,3%) e 0 (0%), respectivamente. Para os grupos CDR 0 e CDR 0,5, os "bons usuários" tiveram pontuações mais altas no MEEM e no DS em comparação com os "usuários fracos". Conclusões: A introdução de FAI é muito tardia para o grupo de "alto risco". Uma vez que o FAI requer uma operação complicada com o uso de botões, o seu manuseio pode ser difícil para os residentes mais velhos. A função executiva pode ser examinada para a detecção precoce de erros de manuseio de aparelhos domésticos que podem causar acidentes.

Predictors of Long-Term Survival in Pancreatic Ductal Adenocarcinoma after Pancreatectomy: TP53 and SMAD4 Mutation Scoring in Combination with CA19-9.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is a fatal cancer for which even unfavorable clinicopathological factors occasionally fail to preclude long-term survival. We sought to establish a scoring system that utilizes measurable pre-intervention factors for predicting survival following surgical resection. METHODS: We retrospectively analyzed 34 patients who died from short-term recurrences and 32 long-term survivors among 310 consecutively resected patients with PDA. A logistic regression model was used to define factors related to clinical parameters, molecular profiles of 18 pancreatic cancer-associated genes, and aberrant expression of major tumor suppressors. RESULTS: Carbohydrate antigen 19-9 (CA19-9) had the best ability to classify patients with short-term recurrence and long-term survivors [odds ratio 21.04, 95% confidence interval (CI) 4.612-96.019], followed by SMAD4 and TP53 mutation scoring (odds ratio 41.322, 95% CI 3.156-541.035). Missense TP53 mutations were strongly associated with the nuclear expression of p53, whereas truncating mutations were associated with the absence of nuclear p53. The former subset was associated with a worse prognosis. The combination of aberrant SMAD4 and mutation types of TP53 exhibited a better resolution for distinguishing patients with short-term recurrences from long-term survivors (compared with the assessment of the number of mutated KRAS, CDKN2A, TP53, and SMAD4 genes). Calibration of mutation scores combined with CA19-9 in a logistic regression model setting demonstrated a practical effect in classifying long survivors and patients with early recurrence (c-statistic = 0.876). CONCLUSIONS: Genetic information, i.e., TP53 mutation types and SMAD4 abnormalities, combined with CA19-9, will be a valuable tool for improving surgical strategies for pancreatic cancer.

Posterior pharyngeal wall augmentation using autologous tiered costal cartilage for velopharyngeal insufficiency.

The aim of this study was to retrospectively estimate intervention outcomes and to establish suitable indications for autogenous tiered cartilage augmentation (ATCA) of the posterior pharyngeal wall for velopharyngeal insufficiency (VPI). The sample cohort comprised 17 consecutive patients with VPI (10 boys, 7 girls), excluding syndromic cases. Pre- and postoperative findings were comprehensively evaluated using a combination of speech assessment and lateral pharyngography (LPG). Hypernasality and consonant distortion were scored (normal: 0; mild: 1; moderate: 2; severe: 3). Velopharyngeal gap size at rest (AC) and at maximum closure (BC) were measured on LPG. All patients displayed improvements in velopharyngeal function and speech score, and no patients required re-operation. Pre- and postoperative hypernasality scores were 1.9 ± 0.5 and 0.6 ± 0.5, respectively (P < .001). Pre- and postoperative consonant distortion scores were 1.9 ± 0.6 and 0.6 ± 0.5, respectively (P < .001). Pre- and postoperative AC distances were 8.2 ± 3.4 mm and 5.9 ± 2.6 mm, respectively (P < .001). Pre- and postoperative BC distances were 3.9 ± 2.4 mm and 0.3 ± 0.8 mm, respectively (P < .001). Conclusions: ATCA appears effective for surgical treatment of VPI patients with a gap less than 10 mm.

A procedure combining double opposing Z-plasty with buccal flap and skin graft for a cleft palate patient with short palate.

Cleft palate patients with a short palate are sometimes encountered and it is difficult to achieve effective primary palatoplasty and good speech in these cases. Our purpose was to establish an effective palatoplasty for a cleft palate patient with Randall type III short palate. Buccal musculomucosal flap on the nasal side and skin graft on the oral side were performed, along with double opposing Z-plasty. Speech improved postoperation. This procedure brought the nasopharyngeal area closer to the normal anatomical state. In terms of disadvantages, the procedure is rather complicated and depends on the engraftment rate.

Proteomics of serum extracellular vesicles identifies a novel COPD biomarker, fibulin-3 from elastic fibres.

There is an unmet need for novel biomarkers in the diagnosis of multifactorial COPD. We applied next-generation proteomics to serum extracellular vesicles (EVs) to discover novel COPD biomarkers. EVs from 10 patients with COPD and six healthy controls were analysed by tandem mass tag-based non-targeted proteomics, and those from elastase-treated mouse models of emphysema were also analysed by non-targeted proteomics. For validation, EVs from 23 patients with COPD and 20 healthy controls were validated by targeted proteomics. Using non-targeted proteomics, we identified 406 proteins, 34 of which were significantly upregulated in patients with COPD. Of note, the EV protein signature from patients with COPD reflected inflammation and remodelling. We also identified 63 upregulated candidates from 1956 proteins by analysing EVs isolated from mouse models. Combining human and mouse biomarker candidates, we validated 45 proteins by targeted proteomics, selected reaction monitoring. Notably, levels of fibulin-3, tripeptidyl-peptidase 2, fibulin-1, and soluble scavenger receptor cysteine-rich domain-containing protein were significantly higher in patients with COPD. Moreover, six proteins; fibulin-3, tripeptidyl-peptidase 2, UTP-glucose-1-phosphate uridylyl transferase, CD81, CD177, and oncoprotein-induced transcript 3, were correlated with emphysema. Upregulation of fibulin-3 was confirmed by immunoblotting of EVs and immunohistochemistry in lungs. Strikingly, fibulin-3 knockout mice spontaneously developed emphysema with age, as evidenced by alveolar enlargement and elastin destruction. We discovered potential pathogenic biomarkers for COPD using next-generation proteomics of EVs. This is a novel strategy for biomarker discovery and precision medicine.

Otitis Media With Effusion Caused by a Parapharyngeal Tumor Showing Normal Nasopharyngeal Findings.

The objective of this study is to evaluate otitis media with effusion (OME) among patients with parapharyngeal tumor. We have experienced 82 parapharyngeal tumor cases and encountered 14 patients complaining of hearing loss due to OME as the initial symptom. These patients showed normal nasopharyngeal findings and the presence of tumor had been detected long time after the beginning of their hearing symptoms (4 months to 13 years: median 2.5 years). Six patients had undergone ventilation tube insertion on the affected ear, which may lead to delay in diagnosis. Pathological examination was performed in 76 of 82 patients. Among these 76 patients, 13 showed OME. Seven patients had malignant lesions, whereas 6 had benign lesions. Therefore, malignant lesions are prone to occur with OME and its relative risk was 2.26 (95% confidence intervals, 1.16-4.42). This difference was statistically significant (P = .044, Fisher test). Otitis media with effusion is a very common disease and is well-known as a primary symptom of nasopharyngeal carcinoma. Therefore, nasopharyngeal observation is necessary for patients with intractable middle ear effusion. However, present 14 patients with OME showed normal nasopharyngeal findings and finally found after an imaging study. From our data, OME is an important but go-by symptom of parapharyngeal tumors. Imaging studies are potently useful for such patients with intractable OME.

Current state of hypnotic use disorders: Results of a survey using the Japanese version of Benzodiazepine Dependence Self-Report Questionnaire.

AIMS: Benzodiazepine receptor agonists (BZ-RAs) are frequently prescribed to treat insomnia; however, their long-term use is not recommended. To introduce an appropriate pharmaco-therapy, the current state and background factors of BZ-RAs' dependence must be elucidated. In this study, we developed a Japanese version of the Benzodiazepine Dependence Self-Report Questionnaire (Bendep-SRQ-J) and conducted a study of BZ-RAs' use disorder. METHODS: The Bendep-SRQ-J was created with permission from the original developer. Subjects were inpatients and outpatients receiving BZ-RAs between 2012 and 2013. Clinical data collected were Bendep-SRQ-J scores, sleep disorders for which BZ-RAs were prescribed, physical comorbidities, psychotropic drugs, and lifestyle factors. Logistic analysis was performed to extract factors associated with severe symptoms. RESULTS: Of the 707 patients prescribed BZ-RAs, 324 had voluntarily tapered or discontinued their drugs. Logistic analysis showed that the total number of drugs administered in the last 6 months correlated with both worsening of symptoms or conditions. This was more notable among younger patients, and the proportion of patients with severe symptoms or conditions increased with the increasing number of drugs. CONCLUSION: Using the Bendep-SRQ-J, we elucidated the current state of BZ-RA dependence. Nearly half of the patients were non-compliant. The proportion of patients with severe symptoms or disease conditions increased with the increase in the number of drugs administered. These findings highlight the need for clinicians to be aware of the likelihood of benzodiazepine dependence, especially in young patients and patients prescribed multiple hypnotics.

Efficacy of oral myofunctional therapy in middle-aged to elderly patients with obstructive sleep apnoea treated with continuous positive airway pressure.

BACKGROUND: Oral myofunctional therapy (MFT) is an effective treatment for mild-to-moderate obstructive sleep apnoea (OSA) in middle-aged patients. However, few reports have described its use in elderly patients with moderate and severe OSA. Moreover, no studies have examined the relationship between changes in tongue pressure with MFT and the severity of OSA. OBJECTIVE: We conducted an interventional study using MFT to evaluate the effect of MFT on middle-to-senior-aged patients with moderate or severe OSA and compared changes in apnoea-hypopnea index (AHI) and tongue pressure. METHODS: Thirty-two OSA patients (≥45 years) treated with continuous positive airway pressure (CPAP) were included. MFT was performed in parallel with CPAP. Three days after CPAP discontinuation, polysomnographies were performed and tongue pressures were measured before and after MFT. RESULTS: Patients were 69.3 ± 1.5 years old. After 6 months of MFT, AHI decreased significantly from 34.7 to 29.0/h (P = .03), while tongue pressure significantly increased from 35.9 to 45.6 kPa (P < .01). Seven patients (22%), including 6 of the 12 patients with moderate OSA (50%), experienced successful CPAP discontinuation. CONCLUSIONS: MFT can be a useful intervention even among middle-aged to elderly patients with OSA. Increased tongue pressure may have contributed to the AHI improvement. Clinical trials: Trial registration at www.umin.ac.jp UMIN000027547.

Time-saving method for directly amplifying and capturing a minimal amount of pancreatic tumor-derived mutations from fine-needle aspirates using digital PCR.

It is challenging to secure a cytopathologic diagnosis using minute amounts of tumor fluids and tissue fragments. Hence, we developed a rapid, accurate, low-cost method for detecting tumor cell-derived DNA from limited amounts of specimens and samples with a low tumor cellularity, to detect KRAS mutations in pancreatic ductal carcinomas (PDA) using digital PCR (dPCR). The core invention is based on the suspension of tumor samples in pure water, which causes an osmotic burst; the crude suspension could be directly subjected to emulsion PCR in the platform. We examined the feasibility of this process using needle aspirates from surgically resected pancreatic tumor specimens (n = 12). We successfully amplified and detected mutant KRAS in 11 of 12 tumor samples harboring the mutation; the positive mutation frequency was as low as 0.8%. We used residual specimens from fine-needle aspiration/biopsy and needle flush processes (n = 10) for method validation. In 9 of 10 oncogenic KRAS pancreatic tumor samples, the "water-burst" method resulted in a positive mutation call. We describe a dPCR-based, super-sensitive screening protocol for determining KRAS mutation availability using tiny needle aspirates from PDAs processed using simple steps. This method might enable pathologists to secure a more accurate, minimally invasive diagnosis using minute tissue fragments.

A Method to Extract Feature Variables Contributed in Nonlinear Machine Learning Prediction.

BACKGROUND: Although advances in prediction accuracy have been made with new machine learning methods, such as support vector machines and deep neural networks, these methods make nonlinear machine learning models and thus lack the ability to explain the basis of their predictions. Improving their explanatory capabilities would increase the reliability of their predictions. OBJECTIVE: Our objective was to develop a factor analysis technique that enables the presentation of the feature variables used in making predictions, even in nonlinear machine learning models. METHODS: A factor analysis technique was consisted of two techniques: backward analysis technique and factor extraction technique. We developed a factor extraction technique extracted feature variables that was obtained from the posterior probability distribution of a machine learning model which was calculated by backward analysis technique. RESULTS: In evaluation, using gene expression data from prostate tumor patients and healthy subjects, the prediction accuracy of a model of deep neural networks was approximately 5% better than that of a model of support vector machines. Then the rate of concordance between the feature variables extracted in an earlier report using Jensen-Shannon divergence and the ones extracted in this report using backward elimination using Hilbert-Schmidt independence criteria was 40% for the top five variables, 40% for the top 10, and 49% for the top 100. CONCLUSION: The results showed that models can be evaluated from different viewpoints by using different factor extraction techniques. In the future, we hope to use this technique to verify the characteristics of features extracted by factor extraction technique, and to perform clinical studies using the genes, we extracted in this experiment.

Arousal index as a marker of carotid artery atherosclerosis in patients with obstructive sleep apnea syndrome.

PURPOSE: It was shown in a previous cohort study that men with internal carotid artery (ICA) plaque, defined as focal wall thickness of ≥ 1.5 mm, had a threefold higher risk of stroke than those without plaque. We examined the relationship between arousal indices and sleep stages in patients with obstructive sleep apnea syndrome (OSAS) and carotid atherosclerosis. METHODS: Carotid atherosclerosis severity was evaluated using the maximal carotid wall intima-media thickness of the ICA (ICA-maxIMT) and plaque in 83 patients with OSAS. RESULTS: The ICA-maxIMT values were positively correlated with the apnea hypopnea index (AHI) (ρ = 0.294, P = 0.007), arousal index (ρ = 0.289, P = 0.008), oxygen desaturation index (ρ = 0.298, P = 0.006), percentage of visually scored total sleep time spent in nocturnal oxygen saturation < 90% (SpO2 < 90%) (ρ = 0.246, P = 0.025), and the percentage of visually scored total sleep time spent in non-REM sleep stage 1 (ρ = 0.326, P = 0.003) and were negatively correlated with the percentage of visually scored total sleep time spent in non-REM sleep stages 2 and 3. Arousal index, diabetes mellitus, and age were found to be independent predictors of ICA plaque presence (OR 1.052, P = 0.003; OR 8.705, P = 0.026; OR 1.064, P = 0.023, respectively). CONCLUSIONS: Several PSG variables that are indicative of sleep fragmentation, sleep disordered breathing, and poor sleep quality correlated with the occurrence of atherosclerosis, but total arousal index was the only independent predictive factor.

Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging.

Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging, but the mechanism remains unclear. Tetraspanins have emerged as key players in malignancy and inflammatory diseases. Here, we found that CD9/CD81 double knockout (DKO) mice with a COPD-like phenotype progressively developed a syndrome resembling human aging, including cataracts, hair loss, and atrophy of various organs, including thymus, muscle, and testis, resulting in shorter survival than wild-type (WT) mice. Consistent with this, DNA microarray analysis of DKO mouse lungs revealed differential expression of genes involved in cell death, inflammation, and the sirtuin-1 (SIRT1) pathway. Accordingly, expression of SIRT1 was reduced in DKO mouse lungs. Importantly, siRNA knockdown of CD9 and CD81 in lung epithelial cells additively decreased SIRT1 and Foxo3a expression, but reciprocally upregulated the expression of p21 and p53, leading to reduced cell proliferation and elevated apoptosis. Furthermore, deletion of these tetraspanins increased the expression of pro-inflammatory genes and IL-8. Hence, CD9 and CD81 might coordinately prevent senescence and inflammation, partly by maintaining SIRT1 expression. Altogether, CD9/CD81 DKO mice represent a novel model for both COPD and accelerated senescence.