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Abstract This paper proposes novel methods for extracting a single Speech signal of Interest (SOI) from a multichannel observed signal in underdetermined situations, i.e., when the observed signal contains more speech signals than microphones. It focuses on extracting the SOI using prior knowledge of the SOI’s Direction of Arrival (DOA). Conventional beamformers (BFs) and Blind Source Separation (BSS) with spatial regularization struggle to suppress interference speech signals in such situations. Although Switching Minimum Power Distortionless Response BF (Sw-MPDR) can handle underdetermined situations using a switching mechanism, its estimation accuracy significantly decreases when it relies on a steering vector determined by the SOI’s DOA. Spatially-Regularized Independent Vector Extraction (SRIVE) can robustly enhance the SOI based solely on its DOA using spatial regularization, but its performance degrades in underdetermined situations. This paper extends these conventional methods to overcome their limitations. First, we introduce a time-varying Gaussian (TVG) source model to Sw-MPDR to effectively enhance the SOI based solely on the DOA. Second, we introduce the switching mechanism to SRIVE to improve its speech enhancement performance in underdetermined situations. These two proposed methods are called Switching weighted MPDR (Sw-wMPDR) and Switching SRIVE (Sw-SRIVE). We experimentally demonstrate that both surpass conventional methods in enhancing the SOI using the DOA in underdetermined situations.

ObjectiveTo determine the optimal montage and vocalization conditions for high-gamma language mapping using stereoelectroencephalography.MethodsWe studied 12 epilepsy patients who underwent invasive monitoring with depth electrodes and measurement of auditory-naming related high-gamma modulations. We determined the effects of electrode montage and vocalization conditions of the response on the high-gamma (60–140 Hz) amplitudes.ResultsCompared to common average reference montage, bipolar and Laplacian montages effectively reduced the degree of auditory naming-related signal deflections in the white matter during the stimulus and response phases (mixed model estimate: −21.2 to −85.4%; p

Abstract The severity of chest X-ray (CXR) findings is a prognostic factor in patients with coronavirus disease 2019 (COVID-19). We investigated the clinical and genetic characteristics and prognosis of patients with worsening CXR findings during early hospitalization. We retrospectively included 1656 consecutive Japanese patients with COVID-19 recruited through the Japan COVID-19 Task Force. Rapid deterioration of CXR findings was defined as increased pulmonary infiltrates in ≥ 50% of the lung fields within 48 h of admission. Rapid deterioration of CXR findings was an independent risk factor for death, most severe illness, tracheal intubation, and intensive care unit admission. The presence of consolidation on CXR, comorbid cardiovascular and chronic obstructive pulmonary diseases, high body temperature, and increased serum aspartate aminotransferase, potassium, and C-reactive protein levels were independent risk factors for rapid deterioration of CXR findings. Risk variant at the ABO locus (rs529565-C) was associated with rapid deterioration of CXR findings in all patients. This study revealed the clinical features, genetic features, and risk factors associated with rapid deterioration of CXR findings, a poor prognostic factor in patients with COVID-19.

Abstract A 73‐year‐old woman with lung adenocarcinoma (cT4N3M1a: Stage IVA) was treated with atezolizumab as the eighth line of therapy. Four weeks after the fourth dose of atezolizumab, the prothrombin time (PT) and activated thromboplastin time (APTT) were prolonged. Coagulation factor V (FV) activity was decreased, and FV inhibitors were observed. There was no history of PT or APTT prolongation or bleeding before the use of atezolizumab. Atezolizumab‐induced coagulation FV inhibitor was diagnosed. After 2 weeks, the PT and APTT spontaneously normalized. FV activity improved and the FV inhibitors disappeared after 6 and 9 weeks, respectively.

Abstract Background Although cases of respiratory bacterial infections associated with coronavirus disease 2019 (COVID-19) have often been reported, their impact on the clinical course remains unclear. Herein, we evaluated and analyzed the complication rates of bacterial infections, causative organisms, patient backgrounds, and clinical outcome in Japanese patients with COVID-19. Methods We performed a retrospective cohort study that included inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021) and obtained demographic, epidemiological, and microbiological results and the clinical course and analyzed the cases of COVID-19 complicated by respiratory bacterial infections. Results Of the 1,863 patients with COVID-19 included in the analysis, 140 (7.5%) had respiratory bacterial infections. Community-acquired co-infection at COVID-19 diagnosis was uncommon (55/1,863, 3.0%) and was mainly caused by Staphylococcus aureus, Klebsiella pneumoniae and Streptococcus pneumoniae. Hospital-acquired bacterial secondary infections, mostly caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were diagnosed in 86 patients (4.6%). Severity-associated comorbidities were frequently observed in hospital-acquired secondary infection cases, including hypertension, diabetes, and chronic kidney disease. The study results suggest that the neutrophil–lymphocyte ratio (> 5.28) may be useful in diagnosing complications of respiratory bacterial infections. COVID-19 patients with community-acquired or hospital-acquired secondary infections had significantly increased mortality. Conclusions Respiratory bacterial co-infections and secondary infections are uncommon in patients with COVID-19 but may worsen outcomes. Assessment of bacterial complications is important in hospitalized patients with COVID-19, and the study findings are meaningful for the appropriate use of antimicrobial agents and management strategies.

Objectives: Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for severe COVID-19. However, limited literature exists on the effect of COPD and smoking on COVID-19 outcomes. This study examined the impact of smoking exposure in pack-years (PY) and COPD on COVID-19 outcomes among smokers in Japan. Methods: The study included 1266 smokers enrolled by the Japan COVID-19 task force between February 2020 and December 2021. PY and COPD status was self-reported by patients. Patients were classified into the non-COPD (n = 1151) and COPD (n = 115) groups; the non-COPD group was further classified into 30 PY (n = 361). The study outcome was the need for invasive mechanical ventilation (IMV). Results: The incidence of IMV increased with increasing PY and was highest in the COPD group (30 PY = 15.2%, COPD = 26.1%; P 30 PY and COPD groups through univariate (odds ratio [OR]: >30 PY = 2.11, COPD = 4.14) and multivariate (OR: >30 PY = 2.38; COPD = 7.94) analyses. Increasing PY number was also associated with increased IMV requirement in patients aged

ObjectiveVagus nerve stimulation (VNS) is a palliative surgery for drug-resistant epilepsy. The two objectives of this study were to (1) determine the seizure type most responsive to VNS and (2) investigate the preventive effect on status epilepticus (SE) recurrence.MethodsWe retrospectively reviewed 136 patients with drug-resistant epilepsy who underwent VNS implantation. We examined seizure outcomes at 6, 12, and 24 months following implantation of VNS as well as at the last visit to the Juntendo Epilepsy Center. Univariate analysis and multivariate logistic regression models were used to estimate the prognostic factors.Results125 patients were followed up for at least 1 year after VNS implantation. The percentage of patients with at least a 50% reduction in seizure frequency compared with prior to VNS implantation increased over time at 6, 12, and 24 months after VNS implantation: 28, 41, and 52%, respectively. Regarding overall seizure outcomes, 70 (56%) patients responded to VNS. Of the 40 patients with a history of SE prior to VNS implantation, 27 (67%) showed no recurrence of SE. The duration of epilepsy, history of SE prior to VNS implantation and seizure type were correlated with seizure outcomes after VNS implantation in univariate analysis (p = 0.05, p

Abstract Background We aimed to elucidate differences in the characteristics of patients with coronavirus disease 2019 (COVID-19) requiring hospitalization in Japan, by COVID-19 waves, from conventional strains to the Delta variant. Methods We used secondary data from a database and performed a retrospective cohort study that included 3261 patients aged ≥ 18 years enrolled from 78 hospitals that participated in the Japan COVID-19 Task Force between February 2020 and September 2021. Results Patients hospitalized during the second (mean age, 53.2 years [standard deviation {SD}, ± 18.9]) and fifth (mean age, 50.7 years [SD ± 13.9]) COVID-19 waves had a lower mean age than those hospitalized during the other COVID-19 waves. Patients hospitalized during the first COVID-19 wave had a longer hospital stay (mean, 30.3 days [SD ± 21.5], p

Abstract Background Respiratory symptoms are associated with coronavirus disease 2019 (COVID-19) outcomes. However, the impacts of upper and lower respiratory symptoms on COVID-19 outcomes in the same population have not been compared. The objective of this study was to characterize upper and lower respiratory symptoms and compare their impacts on outcomes of hospitalized COVID-19 patients. Methods This was a multicenter, retrospective cohort study; the database from the Japan COVID-19 Task Force was used. A total of 3314 COVID-19 patients were included in the study, and the data on respiratory symptoms were collected. The participants were classified according to their respiratory symptoms (Group 1: no respiratory symptoms, Group 2: only upper respiratory symptoms, Group 3: only lower respiratory symptoms, and Group 4: both upper and lower respiratory symptoms). The impacts of upper and lower respiratory symptoms on the clinical outcomes were compared. The primary outcome was the percentage of patients with poor clinical outcomes, including the need for oxygen supplementation via high-flow oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation or death. Results Of the 3314 COVID-19 patients, 605, 1331, 1229, and 1149 were classified as Group 1, Group 2, Group 3, and Group 4, respectively. In univariate analysis, patients in Group 2 had the best clinical outcomes among all groups (odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.11–0.39), while patients in Group 3 had the worst outcomes (OR: 3.27, 95% CI: 2.43–4.40). Group 3 patients had the highest incidence of pneumonia, other complications due to secondary infections, and thrombosis during the clinical course. Conclusions Upper and lower respiratory tract symptoms had vastly different impacts on the clinical outcomes of COVID-19.

A 53-year-old woman was brought to the emergency room with headache and progressive deterioration of consciousness. Radiological examinations revealed acute subdural hematoma extending along the cerebellar tentorium to the falx cerebri, and a mass lesion with hemorrhage in the left cerebellum, with acute hydrocephalus. Emergency tumor and hematoma removal with decompressive craniectomy of the occiput was performed. Histopathological diagnosis was microcystic meningioma. Postoperatively, the patient recovered to clear consciousness with sequelae of left cerebellar ataxia, cerebellar dysarthria, and vertigo. This case of tentorial microcystic meningioma associated with acute subdural hematoma in the posterior cranial fossa is extremely rare, with only reported 4 similar cases.

Abstract Background The clinical course of coronavirus disease (COVID-19) is diverse, and the usefulness of phenotyping in predicting the severity or prognosis of the disease has been demonstrated overseas. This study aimed to investigate clinically meaningful phenotypes in Japanese COVID-19 patients using cluster analysis. Methods From April 2020 to May 2021, data from inpatients aged ≥ 18 years diagnosed with COVID-19 and who agreed to participate in the study were collected. A total of 1322 Japanese patients were included. Hierarchical cluster analysis was performed using variables reported to be associated with COVID-19 severity or prognosis, namely, age, sex, obesity, smoking history, hypertension, diabetes mellitus, malignancy, chronic obstructive pulmonary disease, hyperuricemia, cardiovascular disease, chronic liver disease, and chronic kidney disease. Results Participants were divided into four clusters: Cluster 1, young healthy (n = 266, 20.1%); Cluster 2, middle-aged (n = 245, 18.5%); Cluster 3, middle-aged obese (n = 435, 32.9%); and Cluster 4, elderly (n = 376, 28.4%). In Clusters 3 and 4, sore throat, dysosmia, and dysgeusia tended to be less frequent, while shortness of breath was more frequent. Serum lactate dehydrogenase, ferritin, KL-6, d-dimer, and C-reactive protein levels tended to be higher in Clusters 3 and 4. Although Cluster 3 had a similar age as Cluster 2, it tended to have poorer outcomes. Both Clusters 3 and 4 tended to exhibit higher rates of oxygen supplementation, intensive care unit admission, and mechanical ventilation, but the mortality rate tended to be lower in Cluster 3. Conclusions We have successfully performed the first phenotyping of COVID-19 patients in Japan, which is clinically useful in predicting important outcomes, despite the simplicity of the cluster analysis method that does not use complex variables.

Objectives: This study aimed to identify the relationship between abnormal serum uric acid levels or a history of hyperuricemia and COVID-19 severity in the Japanese population. Methods: We included 1523 patients enrolled in the Japan COVID-19 Task Force cohort between February 2020 and May 2021. We compared the clinical characteristics, including co-morbidities, laboratory findings, and outcomes, particularly invasive mechanical ventilation (IMV), among patients with and without abnormal uric acid levels or a history of hyperuricemia. Results: Patients with high serum uric acid levels were older and had higher body weight and body mass index than those without. In addition, the multiple logistic regression analysis revealed a significant association between high serum uric acid levels or a history of hyperuricemia and an increased risk of IMV (odds ratio [OR] = 1.77; P = 0.03/OR = 1.56; P = 0.04). Moreover, patients with low uric acid levels on admission were also associated significantly with the requirement of IMV (OR = 5.09; P

Abstract Background Obesity is reported to be a risk factor for severe disease in patients with coronavirus disease 2019 (COVID-19). However, there are no specific reports on the risk of severe disease according to body mass index (BMI) in Japan. Thus, this study aimed to investigate the effect of obesity stratified by BMI on the severity of COVID-19 in the general Japanese population. Methods From February 2020 to May 2021, 1 837 patients aged ≥18 years were enrolled in the Japan COVID-19 Task Force. Patients with known BMI and disease severity were analyzed. Severity was defined as critical if the patient was treated in the intensive care unit, required invasive mechanical ventilation, or died. Results Class 1 obesity (25.0 ≤ BMI

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Background and design: The coronavirus disease (COVID-19) pandemic is having a devastating effect worldwide. Host genome differences between populations may influence the severity of COVID-19.The Japan COVID-19 Task Force is conducting host genome analysis of hospitalized patients with COVID-19 from more than 70 institutions nationwide in Japan. This report describes the clinical characteristics of patients enrolled to date. Results: The median (interquartile range) age of the 1674 patients included in the analysis was 59 (45–71) years, and more than half of the patients (66.2%) were male. Less than half of the patients (41.2%) had severe disease. The case fatality rate was 3.2%. Conclusions: Since this is a hospital-based study, the number of severe cases was relatively high, but the case fatality rate was relatively low, when compared to that of other countries. In the future, we will continue to enroll patients and conduct genome analyses of patients with COVID-19.

BackgroundThe spread of COVID-19 has affected stroke rehabilitation. Given that inpatient visits are restricted in most institutions, alternative ways of providing information to family members are imperative. Informing families about patients’ rehabilitation progress via the web may help involve families in the rehabilitation process, enhance patients’ motivation to continue rehabilitation, and contribute overall to patients’ improvement in activities of daily living (ADL). ObjectiveWe aimed to investigate the feasibility of the Internet-Based Rehabilitation Information Sharing (IRIS) intervention for families of patients with stroke at a rehabilitation hospital and examine the effect of IRIS on patients’ ADL improvement. MethodsIn this case-control study, participants were inpatients at a rehabilitation hospital between March 2020 and April 2021. The intervention group (information and communication technology [ICT] group) included patients and families who requested IRIS, which consisted of a progress report on patients’ rehabilitation using text, photos, and videos. Those who did not receive internet-based information were included in the non-ICT group. The control group, matched with the ICT group based on a 1:1 propensity score, was selected from the non-ICT group. The covariates for calculating the propensity score were patients’ age, sex, and motor and cognitive scores on the Functional Independence Measure at admission. The main outcome was the degree of ADL improvement during hospitalization. Multiple regression analysis (forced entry method) was performed to confirm the impact of ICT use on ADL improvement. The independent variables were the presence of intervention, length of hospital stay, and number of days from onset to hospitalization. ResultsIn total, 16 groups of patients and families participated in the IRIS. The mean age of patients was 78.6 (SD 7.2) and 78.6 (SD 8.2) years in the ICT and control groups, respectively. The median total Functional Independence Measure difference was 28.5 (IQR 20.3-53.0) and 11.0 (IQR 2.8-30.0) in the ICT and control groups, respectively, and the ICT group showed significant improvement in ADL function (P=.02). In the multiple regression analysis of the ICT and control groups, the unstandardized regression coefficient was 11.97 (95% CI 0.09-23.84) for ICT use. These results indicate that ICT use was independently and significantly associated with improvement in ADL. ConclusionsThis study examined the effect of IRIS on family members to improve ADL in patients with stroke who are hospitalized. The results showed that IRIS promotes the improvement of patients’ ADL regardless of age, sex, motor and cognitive functions at admission, and the length of hospital stay.

Objectives: The usefulness of serial procalcitonin (PCT) measurements for predicting the prognosis and treatment efficacy for hospitalised community-acquired pneumonia (CAP) patients was investigated. Methods: This prospective, multicentre, cohort study enrolled consecutive CAP patients who were hospitalised at 10 hospitals in western Japan from September 2013 to September 2016. PCT and C-reactive protein (CRP) were measured on admission (PCT D1 and CRP D1), within 48–72 h after admission (PCT D3 and CRP D3), and within 144–192 h after admission. CURB-65 and the Pneumonia Severity Index (PSI) were assessed on admission. The primary outcome was 30-day mortality; secondary outcomes were early and late treatment failure rates. Results: A total of 710 patients were included. The 30-day mortality rate was 3.1%. On multivariate analysis, only PCT D3/D1 ratio >1 [odds ratio (95% confidence interval): 4.33 (1.46–12.82),P = 0.008] and PSI [odds ratio (95% confidence interval): 2.32 (1.07–5.03), P = 0.03] were significant prognostic factors. Regarding treatment efficacy, PCT D3/D1 >1 was a significant predictor of early treatment failure on multivariate analysis. PCT D3/D1 with the PSI significantly improved the prognostic accuracy over that of the PSI alone. Conclusions: PCT should be measured consecutively, not only on admission, to predict the prognosis and treatment efficacy in CAP. Keywords: Biomarker, C-reactive protein, Pneumonia, Procalcitonin, Prognosis

Abstract Introduction Dual‐task (DT) exercise can act as a substitute, which can help improve both physical and cognitive functions. Thus, this study investigated the effects of a game‐like cognitive DT exercise called “Synapsology” (SYNAP) among the oldest residents of a nursing home. Methods Participants (aged 85–97 years) were assigned to the intervention group (n = 12) and the control group (n = 12). The intervention group underwent 60‐minute sessions, twice a week for 24 weeks. Results A comparison of the Mini‐Mental State Examination scores and six physical function tests, before and after the intervention, shows that the SYNAP had a positive impact on the cognitive and physical functions among the intervention group. Discussion These findings suggest that SYNAP may help maintain or improve cognitive and physical functions among older adults compared to no interventions. Therefore, SYNAP would act as a beneficial tool amidst a “superaging” society like Japan.

The mechanism of epileptic spasms (ES) in Aicardi syndrome (AS) remains obscure. We compared intraoperative high-frequency oscillations (HFOs) and phase-amplitude coupling (PAC) before and after subtotal hemispherotomy in a 3-month-old girl with drug-resistant ES secondary to AS. Fetal ultrasonography showing corpus callosum agenesis, bilateral ventricular dilatation, and a large choroid plexus cyst confirmed AS diagnosis. Her ES started when she was 1 month old and had ten series of clustered ES per day despite phenobarbital and vitamin B6 treatment. After subtotal hemispherotomy, her ES dramatically improved. We analyzed two intraoperative electrocorticography modalities: (1), occurrence rate (OR) of HFOs; (2), PAC of HFOs and slow wave bands in the frontal, central, and parietal areas. We hypothesized that HFOs and PAC could be the biomarkers for efficacy of subtotal hemispherotomy in AS with ES. PAC in all three areas and OR of HFOs in the frontal and parietal areas significantly decreased, while OR of HFOs in the central area remained unchanged after subtotal hemispherotomy. We have demonstrated the usefulness of evaluating intraoperative HFOs and PAC to assess subtotal hemispherotomy effectiveness in AS patients with ES. Disconnecting the thalamocortical and subcortical pathways in the epileptic network plays a role in controlling ES generation.

Background: Inhalation studies suggested “protective” roles of exogenous prostaglandin E2, but the clinical relevance of endogenous prostanoids in asthma is poorly known. The objective of this study is to measure sputum levels of prostanoids in asthmatic patients to correlate with clinical indices. Methods: Mild (n = 41) or moderate-to-severe (19) asthmatics and 27 normal controls were examined for pulmonary function (FEV1 and mid-forced expiratory flow), sputum cell differentials, and sputum levels of prostaglandins D2, E2, F2α, and thromboxane B2 measured by sandwich enzyme immunoassay. Results: Each prostanoid level did not differ among the three groups. Sputum number of bronchial epithelial cells was greater in moderate-to-severe asthmatics than in the other two groups, suggesting epithelial desquamation. Levels of prostaglandin F2α, D2, and thromboxane B2 positively correlated with the severity of airflow obstruction in the 60 asthmatic patients, whereas prostaglandin E2 levels were unrelated to pulmonary function. The ratio of combined “contractile” prostanoids (prostaglandin D2/prostaglandin F2α/thromboxane B2) to prostaglandin E2 was 2.5-fold greater in moderate-to-severe asthmatics than in controls (p = 0.001) or in mild asthmatics (p = 0.0002) but did not differ between the latter two groups. In the two asthmatic groups combined, this ratio positively correlated with the sputum number of epithelial cells. The combined “contractile” prostanoids levels positively correlated with prostaglandin E2 levels in controls and in mild asthmatics but not in moderate-to-severe asthmatics. Conclusions: An imbalance in production, breakdown, or both between prostaglandin E2 and other prostanoids possibly due to epithelial damage may be involved in the pathogenesis of moderate-to-severe asthma.

Background: Falls are a serious problem among frail elderly and their prevention is an important health concern. We compared the frequency of falls among institutionalized frail elderly residents following different interventions: low-frequency exercise, vitamin D supplementation, and a combination of both. Methods: Participants (N = 91) were residents in an institution for frail elderly (84.8 ± 8.8 years of age, 69 women). Participants were randomly assigned to one of four conditions: (1) the control group (n = 23) was provided three sessions per week of individualized exercise and usual care, (2) the low-exercise group (n = 22) was provided two sessions of individualized exercise per week, (3) the nutrition group (n = 23) was given oral vitamin D (900 IU/day), and (4) the combined group (n = 23) performed low-level exercise and received vitamin D supplementation. Results: A two-way analysis of variance including interactions between experimental group and time indicated a clear benefit in the groups that received supplementation with vitamin D. A Cox proportional-hazard regression analysis, adjusted for sex and age, showed that compared to the control group, the combined group had a reduced risk of falls (hazard ratio: 0.28, 95% CI: 0.08–0.92, P

Experimental and theoretical studies were conducted on the separation of submicron powder using a revised type of cyclone. The cyclone has a movable inlet guide plate at the inlet section, and 50% cut size is controlled from 0.45 to 0.75 μm by changing the inlet clearance of the guide plate. But the 50% cut size increases again with a very narrow inlet clearance of the guide plate, because the radial velocity of particles decreases and fluid turbulence increases under such condition. The 50% cut size decreases to about 0.4 μm when both the inlet guide plate and the blowdown method are used. The partial separation efficiency with a spiral-inlet cyclone is higher than a cyclone with tangential inlet, and the 50% cut size decreases with a highly polished inside wall surface. † This report was originally printed in KAGAKU KOGAKU RONBUNSHU, 19(3), 476-482 (1993) in Japanese, before being translated into English by KONA Editorial Committee with the permission of the editorial committee of the Soc. Chemical Engineers, Japan.

Fibrates, including bezafibrate (BF), upregulate the expression of ATP binding cassette protein B4 (ABCB4) through gene transcription in mice. To determine the effects of BF on the expression levels of ABCB4 and on the stimulation of biliary phosphatidylcholine (PC) transport in human HepG2 hepatoblastoma cells, mRNA and protein levels as well as subcellular localization were investigated in the cells treated with BF. The canalicular accumulation of a fluorescent PC was assessed by confocal laser scanning microscopy. Treatment with 300 μmol/l BF for 24 h increased levels of ABCB4 mRNA but not protein by up to 151%. BF caused redistribution of ABCB4 into pseudocanaliculi formed between cells. In association with this redistribution, BF accelerated the accumulation of fluorescent PC in bile canaliculi (up to 163% of that in nontreated cells). Suppression of peroxisome proliferator-activated receptor α (PPARα) expression by either a small interfering RNA duplex or morpholino antisense oligonucleotide attenuated the BF-induced redistribution of ABCB4.These findings suggest that BF may enhance the capacity of human hepatocytes to direct PC into bile canaliculi via PPARα-mediated redistribution of ABCB4 to the canalicular membrane. This provides a rationale for the use of BF to improve cholestasis and/or cholangitis that is attributable to hypofunction of ABCB4.