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Background The antiviral resistance of cytomegalovirus (CMV) infections is associated with mutations in the CMV UL54 and UL97 gene regions and is a serious problem in immunocompromised patients. However, the molecular epidemiology of UL54 and UL97 in Taiwan is unclear. Methods We conducted a retrospective study of patients with CMV infections between January and December 2016 in two tertiary hospitals, one regional hospital in Taiwan. CMV DNAemia was confirmed by elevated CMV DNA titers. Then the regions of the UL54 and UL97 mutations were amplified by PCR and sequenced. Results Of 729 patients with CMV syndrome, 112 CMV DNAemia patients were enrolled. Twelve novel variants in UL54 (P342S, S384F, K434R, S673F, T754M, R778H, C814S, M827I, G878E, S880L, E888K, and S976N) and one novel variant in UL97 (M615T) were discovered. UL97 antiviral resistance mutations (L595S, M460I, and M460V) were found in four patients (3.6%). In the drug resistance strains, the mutation events occurred after 83–150 days of therapy, and drug resistance was also observed in these patients. The following high frequency variants were observed: D605E in UL97 and A885T, N898D, V355A, N685S, and A688V in UL54. Conclusion The results demonstrate that the positive rate of CMV DNAemia was 15.3% (112/729) among the patients with clinical CMV infection symptoms. The proportion of antiviral resistance CMV strains within CMV DNAemia patients was 3.6%. With the information of polymorphism incidence in the UL54 and UL97 patients from our study, determination of the genetic profile of UL54 and UL97 among immunocompromised populations with refractory CMV infection is recommended.

Enterococcus faecium is a clinically important pathogen that can cause significant morbidity and death. In this study, we aimed to develop a machine learning (ML) algorithm-based rapid susceptibility method to distinguish vancomycin-resistant E. faecium (VREfm) and vancomycin-susceptible E. faecium (VSEfm) strains. A predictive model was developed and validated to distinguish VREfm and VSEfm strains by analyzing the matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (MS) spectra of unique E. faecium isolates from different specimen types. The algorithm used 5,717 mass spectra, including 2,795 VREfm and 2,922 VSEfm mass spectra, and was externally validated with 2,280 mass spectra of isolates (1,222 VREfm and 1,058 VSEfm strains). A random forest-based algorithm demonstrated overall good classification performances for the isolates from the specimens, with mean accuracy, sensitivity, and specificity of 0.78, 0.79, and 0.77, respectively, with 10-fold cross-validation, timewise validation, and external validation. Furthermore, the algorithm provided rapid results, which would allow susceptibility prediction prior to the availability of phenotypic susceptibility results. In conclusion, an ML algorithm designed using mass spectra obtained from the routine workflow may be able to rapidly differentiate VREfm strains from VSEfm strains; however, susceptibility results must be confirmed by routine methods, given the demonstrated performance of the assay. IMPORTANCE A modified binning method was incorporated to cluster MS shifting ions into a set of representative peaks based on a large-scale MS data set of clinical VREfm and VSEfm isolates, including 2,795 VREfm and 2,922 VSEfm isolates. Predictions with the algorithm were significantly more accurate than empirical antibiotic use, the accuracy of which was 0.50, based on the local epidemiology. The algorithm improved the accuracy of antibiotic administration, compared to empirical antibiotic prescription. An ML algorithm designed using MALDI-TOF MS spectra obtained from the routine workflow accurately differentiated VREfm strains from VSEfm strains, especially in blood and sterile body fluid samples, and can be applied to facilitate the rapid and accurate clinical testing of pathogens.

Oral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficiently expands CTC from patients to test Antrodia Cinnamomea mycelium-derived bioactive compounds. Three ACM-derived bioactive compounds were evaluated for tumor chemosensitization characteristics. Significant and consistent cytotoxic/5-FU sensitizing effects of GKB202 were found on 8 different patient-derived tumors. Acute toxicity profile and hepatic metabolism of GKB202 in rats suggest GKB202 is rapidly cleared by liver and is well tolerated up to the dose of 20 mg/kg. This comprehensive study provides new evidence that liquid fermentation of Antrodia cinnamomea mycelium (ACM) contains bioactive compounds that lead to effective control of CTC, especially when combined with 5-FU. Together, these data suggest ACM-derived GKB202 may be considered for further clinical investigation in the context of 5-FU-based combination therapy.

Cabrol shunt and several of its modifications have been used as adjunctive procedures to control inaccessible bleeding occurring after aortic root surgeries. Nevertheless, the hemostatic effect of the shunt is suboptimal when the reconstructive procedure extends to the aortic arch and coronary arteries. We propose a "Mantle-style" modified Cabrol shunt to facilitate hemostasis of the exsanguination from the neo-root after aortic root replacement with concomitant arch and coronary reconstruction.

Background A bloodstream infection in patients undergoing cardiovascular operations is crucial because it can result in significantly worse outcomes. However, microbiological patterns have rarely been investigated in these patients. Methods We retrospectively reviewed the data of 1,041 adult patients who underwent cardiovascular operations using cardiopulmonary bypass from January 2013 to December 2017 at the National Cheng Kung University Hospital, Tainan, Taiwan. The microbiological pattern and associated variables were analyzed in patients with early postoperative primary bloodstream infection. Results Primary bloodstream infection developed in 28 patients (2.7%) within 7 days after cardiovascular operations using cardiopulmonary bypass. In patients with early primary bloodstream infection, 36 microorganisms were isolated, and a gram-negative bacillus was identified to be the predominant pathogen (28 of 36 [77.8%]). The most common microorganisms comprised the Enterobacter (n = 8) and Acinetobacter (n = 7) species, and 16 of the 28 gram-negative bacilli belonged to the Enterobacteriaceae family. Compared with those without postoperative bloodstream infection, patients with Enterobacteriaceae family–related early postoperative bloodstream infections had a significantly longer cardiopulmonary bypass time and also worse early and late survival rates. Conclusions Most patients with early primary bloodstream infection after cardiovascular operations using cardiopulmonary bypass were infected with gram-negative bacilli, and the Enterobacteriaceae family was the most common microorganism observed. Endogenous bacterial translocation after prolonged cardiopulmonary bypass is a possible mechanism of Enterobacteriaceae family–related early primary bloodstream infection in these patients. Prophylactic use of an antibiotic regimen with broader gram-negative bacteria coverage in cardiovascular surgical patients with prolonged cardiopulmonary bypass should be considered.

The present study aimed to explore whether water and ethanol extracts of Armillaria mellea mycelia produce sedative and hypnotic effects in rats. Male Sprague–Dawley rats were surgically implanted with two electroencephalogram electrodes on the skull and an electromyogram electrode on neck muscle to evaluate the alterations in rapid eye movement (REM) and non-REM (NREM) sleep after oral administration of the water and ethanol extracts. Following post-surgical recovery, thirty-six rats were randomly divided into four treatment groups and two control groups. They were treated orally with vehicle, 75 and 150 mg/kg doses of water and ethanolic extracts 15 min prior to the onset of dark (active) period. Electroencephalography results showed that the low dose of A. mellea mycelia water extract increased REM sleep time while the high dose enhanced both REM and NREM sleep times during the subsequent light (rest) period. On the other hand, although the low dose of A. mellea mycelia ethanolic extract did not alter both NREM sleep and REM sleep during the dark and light periods, the high dose increased both REM and NREM sleep during the light periods in naive rats. The HPLC-DAD analyses of both extracts allowed the identification of GABA and seven sesquiterpenoids. Based on these findings, the present study showed for the first time that water and ethanolic extracts of A. mellea mycelia, containing a source of biologically active compounds, could increase both NREM sleep and REM sleep during the rest period and may be useful for the treatment of insomnia.

Background: Information technology (IT) is an industry related to the production of computers, information processing, and telecommunications. Such industries heavily rely on the knowledge and solutions provided by IT specialists. Previous reports found that the subjective stress scores were higher in IT specialists who developed diabetes, hypertension, and depression. Specific probiotics, known as psychobiotics, may alleviate stress and mood symptoms. This study aimed to examine whether an 8-week intervention of a novel psychobiotic, Lactobacillus plantarum PS128TM (PS128TM), improved self-perceived stress and mood symptoms among high-stress IT specialists.Methods: This open-label, single-arm, baseline-controlled study included IT specialists from a large IT company in Northern Taiwan. Participants with a Perceived Stress Scale (PSS) 10-item version score of 27 or higher were included. Participants were asked to take two capsules containing PS128TM powder, equivalent to 20 billion colony-forming units, daily. Self-report measures, such as the Job Stress Scale, Visual Analog Scale of Stress, the Insomnia Severity Index, the State and Trait Anxiety Index, the Questionnaire for Emotional Trait and State, the Patient Health Questionnaire, the Quality of Life Enjoyment and Satisfaction Questionnaire, and Gastrointestinal Severity Index were compared at baseline and at the end of the trial period. The primary outcome was a 20% reduction in the PSS score at endpoint. Objective measures included salivary levels of stress biomarkers, including cortisol, α-amylase, immunoglobulin A, lactoferrin, and lysozymes, as well as results of the Test of Attentional Performance.Results: Of the 90 eligible IT specialists, 36 met the inclusion criteria. After the 8-week trial period, significant improvements in self-perceived stress, overall job stress, job burden, cortisol level, general or psychological health, anxiety, depression, sleep disturbances, quality of life, and both positive and negative emotions were found.Conclusion: Our results suggest that PS128TM has the distinct advantage of providing stress relief and can improve mental health for people with a high-stress job. Future placebo-controlled studies are warranted to explore the effect and underlying mechanisms of action of PS128TM.Clinical Trial Registration:https://clinicaltrials.gov/ (identifier: NCT04452253-sub-project 2).

This paper focuses on the use of an attention-based encoder-decoder model for the task of breathing sound segmentation and detection. This study aims to accurately segment the inspiration and expiration of patients with pulmonary diseases using the proposed model. Spectrograms of the lung sound signals and labels for every time segment were used to train the model. The model would first encode the spectrogram and then detect inspiratory or expiratory sounds using the encoded image on an attention-based decoder. Physicians would be able to make a more precise diagnosis based on the more interpretable outputs with the assistance of the attention mechanism.The respiratory sounds used for training and testing were recorded from 22 participants using digital stethoscopes or anti-noising microphone sets. Experimental results showed a high 92.006% accuracy when applied 0.5 second time segments and ResNet101 as encoder. Consistent performance of the proposed method can be observed from ten-fold cross-validation experiments.

Key Points Question Can a machine learning model provide survival risk stratification for patients with advanced oral cancer who have comprehensive clinicopathologic and genetic data? Findings In this 15-year cohort study of 334 patients, a risk stratification model using comprehensive clinicopathologic and genetic data accurately differentiated the high-risk group from the low-risk group in postoperative cancer-specific and locoregional recurrence–free survival for patients with advanced oral cancer. Meaning The proposed model demonstrated good discrimination in stratifying patients with different risks of survival by using comprehensive clinicopathologic and genetic data, which can provide additional personalized information for postoperative management of patients with advanced oral squamous cancer., Importance A tool for precisely stratifying postoperative patients with advanced oral cancer is crucial for the treatment plan, such as intensifying or deintensifying the regimen to improve their quality of life and prognosis. Objective To develop and validate a machine learning–based algorithm that can provide survival risk stratification for patients with advanced oral cancer who have comprehensive clinicopathologic and genetic data. Design, Setting, and Participants In this prognostic cohort study, the elastic net penalized Cox proportional hazards regression–based risk stratification model was developed and validated using single-center data collected between January 1, 1996, and December 31, 2011. In total, comprehensive clinicopathologic and genetic data (including clinical, pathologic, and 44 cancer-related gene variant profiles) of 334 patients with stage III or IV oral squamous cell carcinoma were used to develop and validate the algorithm in this 15-year cohort study. Data analysis was conducted between February 1, 2018, and May 6, 2020. Main Outcomes and Measures The main outcomes were cancer-specific survival, distant metastasis–free survival, and locoregional recurrence–free survival. Model performance was compared in terms of the Akaike information criterion and the Harrell concordance index (C index). Results Complete data were available for 334 patients (315 men; median age at onset, 48 years [interquartile range, 42-56 years]). The predictive models using comprehensive clinicopathologic and genetic data outperformed those using clinicopathologic data alone. In the groups of postoperative patients receiving adjuvant concurrent chemoradiotherapy, the models demonstrated higher classification performance than those using clinicopathologic data alone in cancer-specific survival (mean [SD] C index, 0.689 [0.050] vs 0.673 [0.051]; P = .02) and locoregional recurrence–free survival (mean [SD] C index, 0.693 [0.039] vs 0.678 [0.035]; P = .004). The classification performance in distant metastasis–free survival was not different (mean [SD] C index, 0.702 [0.056] vs 0.688 [0.048]; P = .09). Conclusions and Relevance A risk stratification model using comprehensive clinicopathologic and genetic data accurately differentiated the high-risk group from the low-risk group in cancer-specific survival and locoregional recurrence–free survival for postoperative patients with advanced oral cancer. This algorithm could be used through an online calculator to provide additional personalized information for postoperative management of patients with advanced oral squamous cell carcinoma., This cohort study developed and validated a machine learning–based algorithm that can provide survival risk stratification for patients with advanced oral cancer who have comprehensive clinicopathologic and genetic data.

Enterococcus faecium is one of the leading pathogens in the world. In this study, we proposed a strategy to rapidly and accurately distinguish vancomycin-resistant Enterococcus faecium (VREfm) and vancomycin-susceptible E. faecium (VSEfm) to help doctors correctly determine the use of vancomycin by a machine learning (ML)-based algorithm. A predictive model was developed and validated to distinguish VREfm and VSEfm by analyzing MALDI-TOF MS spectra of unique E. faecium isolates from different specimen types. Firstly, 5717 mass spectra, including 2795 VREfm and 2922 VSEfm, were used to develop the algorithm. And 2280 mass spectra of isolates, namely 1222 VREfm and 1058 VSEfm, were used to externally validate the algorithm. The random forest-based algorithm demonstrated good classification performances for overall specimens, whose mean AUROC in 5-fold cross validation, time-wise validation, and external validation was all greater than 0.84. For the detection of VREfm in blood, sterile body fluid, urinary tract, and wound, the AUROC in external validation was also greater than 0.84. The predictions with algorithms were significantly more accurate than empirical antibiotic use. The accuracy of antibiotics administration could be improved by 30%. And the algorithm could provide rapid antibiotic susceptibility results at least 24 hours ahead of routine laboratory tests. The turn-around-time of antibiotic susceptibility could be reduced by 50%. In conclusion, a ML algorithm using MALDI-TOF MS spectra obtained in routine workflow accurately differentiated VREfm from VSEfm, especially in blood and sterile body fluid, which can be applied to facilitate the clinical testing process due to its accuracy, generalizability, and rapidness.

Background Coronary artery bypass grafting (CABG) is frequently performed in patients with end-stage renal disease (ESRD) together with severe coronary artery disease, after which, patients with ESRD have higher surgical risk and poorer long-term outcomes. We report our experience in patients with ESRD who survived in CABG and identify predictors of long-term outcomes. Methods We retrospectively investigated 93 consecutive patients with ESRD who survived to discharge after isolated CABG between January 2005 and December 2016 at our institution. Long-term outcomes, including all-cause mortality after discharge, readmission due to major adverse cardiac events, and reintervention, were evaluated. Predictors affecting long-term outcomes were also analyzed. Results The rates of freedom from all-cause mortality after discharge in 1, 3, 5, and 10 years were 92.1, 81.3, 71.9, and 34.9%, respectively. The rates of freedom from readmission due to major adverse cardiac events in 1, 3, 5, and 10 years were 90.7, 79.1, 69.9, and 55.6%, respectively. The rates of freedom from reintervention in 1, 3, 5, and 10 years were 95.3, 86.5, 79.0, and 66.6%, respectively. Postoperative β-blocker and statin use significantly improved overall long-term survival (β-blocker, p = 0.013; statin, p = 0.009). After case–control matching, patients who received statins showed better long-term survival than those without statins. The comparison of long-term survival between patients with and without β-blockers showed no significant difference after matching. Conclusions After CABG, dialysis patients who survived to discharge had acceptable long-term overall survival. Post-CABG statin use in dialysis patients is a predictor of better long-term survival.

Background: Although thoracic endovascular aneurysm repair (TEVAR) has been widely used as the first choice of emergency surgical procedure for ruptured descending thoracic aortic aneurysms (rDTAAs), the risk factors of adverse outcome have less been investigated. Purpose: To investigate the outcomes of patients undergoing TEVAR for rDTAA and to identified risk factors of worse prognoses. Materials and Methods: The surgical outcome of TEVAR for rDTAA in National Cheng Kung University Hospital was retrospectively analyzed. From February 2008 to December 2016, 27 patients were included, after excluding patients with traumatic aortic injury, infected aneurysm, esophageal malignancy-related aortoesophageal fistula or those in association with aortic dissection. Results: There were 5 (18.5%) 30-day mortalities, including 3 (11.1%) intraoperative deaths. Seven additional patients died during follow-up and the estimated survival rate at 1 year and 3 years was 61.3 ± 9.7% and 50.5 ± 10.6%, respectively. Among these patients with late mortality, five patients presented with hematemesis or hemoptysis preoperatively. Aortoesophageal fistula was confirmed in three patients by esophagogastroduodenoscopy presenting with hematemesis. These patients underwent subsequent open debridement along with esophagectomy after TEVAR and remained alive during follow-up. On the other hand, those with possible occult aortic fistulations that were not detected by endoscopic examinations and not surgically managed had worse late outcomes (P = 0.058). Conclusions: For patients with rDTAA having hematemesis or hemoptysis as part of the initial presentations, careful survey for possible aorta-related fistulation is important. Although definite diagnosis of fistulation might be difficult, surgical exploration for hematoma evacuation, adequate debridement, and repair of intraoperative identified fistulation should be advocated.

Background/Aims: In response to traumatic brain injury (TBI), activated microglia exhibit changes in their morphology from the resting ramified phenotype toward the activated hypertrophic or amoeboid phenotype. Here, we provide the first description of the mechanism underlying the neuroprotective effects of γ-secretase inhibitors on TBI outcomes in rats. Methods: The neuroprotective effects of γ-secretase inhibitors such as LY411575 or CHF5074 on TBI-induced neurotoxicity were analysed using a neurological motor function evaluation, cerebral contusion assay, immunohistochemical staining for microglia phenotypes, lung injury score and Evans Blue dye extravasation assay of brain and lung oedema. Results: Hypertrophic or amoeboid microglia accumulated in the injured cortex, the blood-brain-barrier was disrupted and neurological deficits and acute lung injury were observed 4 days after TBI in adult rats. However, a subcutaneous injection of LY411575 (5 mg/kg) or CHF5074 (30 mg/kg) immediately after TBI and once daily for 3 consecutive days post-TBI significantly attenutaed the accumulation of hypertrophic microglia in the injured brain, neurological injury, and neurogenic acute lung injury. Conclusion: Gamma-secretase inhibitors attenuated neurotrauma and neurogenic acute lung injury in rats by reducing the accumulation of hypertrophic microglia in the vicinity of the lesion.

Few studies have investigated the use of postoperative extracorporeal membrane oxygenation (ECMO) in acute type A aortic dissection (aTAAD). We identified aTAAD surgical patients at risk of ECMO implantation postoperatively and analyzed the prognosis of these patients.We retrospectively reviewed 162 consecutive aTAAD patients undergoing operations from January 2008 to December 2015. Patient data were analyzed for risk factors leading to an ECMO requirement. Short-term and long-term outcomes in patients who did and did not require ECMO were compared.Postoperative ECMO was required in 20 patients (12.3%), and in-hospital mortality was higher in the ECMO group (65.0% vs 8.5%, p0.001). Factors predicting postoperative ECMO were preoperative hemodynamic instability (p = 0.049), aortic cross-clamp time (p = 0.036), and postoperative peak creatinine kinase-MB (p = 0.002). ECMO survivors presented at a younger age (p = 0.036) and had a less postoperative blood transfusion (p = 0.034) than ECMO nonsurvivors. The postdischarge survival rate was equivalent in patients with or without ECMO support.Although postoperative ECMO is an important predictor of in-hospital death, this pilot study showed that aTAAD patients supported with postoperative ECMO who survive to hospital discharge have a long-term survival comparable to patients who did not receive ECMO.

2,4,5-Trimethoxybenzaldehyde (2,4,5-TMBA), a natural inhibitor of cyclooxygenase II activity, is a bitter principle present in plants. In our previous study, 2,4,5-TMBA suppresses differentiation of preadipocytes and enhances lipolysis in mature adipocytes. This study aimed to investigate the absolute bioavailability, tissue distribution, and excretion of 2,4,5-TMBA in Sprague-Dawley rats. After oral administration (po) and intravenous administration (iv) of 100 and 10 mg/kg 2,4,5-TMBA, respectively, the absolute bioavailability was estimated as 62.77% by calculating [(AUC po × Dose iv )/(AUC iv × Dose po )] × 100% (AUC: area under curve). Half hour after oral administration, 2,4,5-TMBA reached the highest concentration of 211.661 μg/g in stomach. In one hour, 2,4,5-TMBA reached the highest concentrations in heart, liver, kidney, small intestine, and large intestine. Total amount of unconverted 2,4,5-TMBA eliminated in feces and urine in 24 h is only 0.03% of oral dosage administrated. The data presented provides useful information for the future application of 2,4,5-TMBA as nutraceutical.

// Cheng-Lung Hsu 1 , Jai-Shin Liu 2 , Ting-Wei Lin 3 , Ying-Hsu Chang 4 , Yung-Chia Kuo 1 , An-Chi Lin 1 , Huei-Ju Ting 5 , See-Tong Pang 4 , Li-Yu Lee 6 , Wen-Lung Ma 7 , Chun-Cheng Lin 3 and Wen-Guey Wu 2 1 Division of Hematology-Oncology, Departments of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan 2 Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan 3 Department of Chemistry, National Tsing-Hua University, Hsinchu 300, Taiwan 4 Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan 5 Department of Biological Science and Technology, National University of Tainan, Tainan 700, Taiwan 6 Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan 7 Sex Hormone Research Center, China Medical University Hospital, Taichung 104, Taiwan Correspondence to: Cheng-Lung Hsu, email: hsu2221@adm.cgmh.org.tw Wen-Guey Wu, email: wgwu@life.nthu.edu.tw Chun-Cheng Lin, email: cclin66@mx.nthu.edu.tw Keywords: FxxLF, RIPK1, androgen receptor, prostate cancer, oxadiazole Received: November 04, 2016 Accepted: April 27, 2017 Published: May 13, 2017 ABSTRACT Using bicalutamide-androgen receptor (AR) DNA binding domain-ligand binding domain as bait, we observed enrichment of FxxFY motif-containing peptides. Protein database searches revealed the presence of receptor-interacting protein kinase 1 (RIPK1) harboring one FxxFY motif. RIPK1 interacted directly with AR and suppressed AR transactivation in a dose-dependent manner. Domain mapping experiments showed that the FxxFY motif in RIPK1 is critical for interactions with AR and the death domain of RIPK1 plays a crucial role in its inhibitory effect on transactivation. In terms of tissue expression, RIPK1 levels were markedly higher in benign prostate hyperplasia and non-cancerous tissue regions relative to the tumor area. With the aid of computer modeling for screening of chemicals targeting activation function 2 (AF-2) of AR, we identified oxadiazole derivatives as good candidates and subsequently generated a small library of these compounds. A number of candidates could effectively suppress AR transactivation and AR-related functions in vitro and in vivo with tolerable toxicity via inhibiting AR-peptide, AR-coregulator and AR N-C interactions. Combination of these chemicals with antiandrogen had an additive suppressive effect on AR transcriptional activity. Our collective findings may pave the way in creating new strategies for the development and design of anti-AR drugs.

Background Extracorporeal membrane oxygenation (ECMO) has been used in patients with circulatory collapse or extremely unstable hemodynamics caused by acute massive pulmonary embolism (PE). The effectiveness of simultaneous thrombolytic therapy has been rarely investigated in these patients after being stabilized with ECMO. Methods From January 2008 to December 2018 consecutive patients with acute massive PE requiring ECMO supported in a tertiary medical center were included for retrospective analysis. Results Thirteen patients with PE underwent ECMO implantation and received subsequent thrombolytic therapy as a definite treatment for PE. All patients survived their ECMO courses to a successful decannulation, with a mean ECMO support duration of 6.23 ± 4.69 days. Eleven patients (84.62%) survived to hospital discharge. All survivors were alive during follow-up, although 2 patients (18.2%) had permanent dysfunctional neurologic complications. Major bleeding complications occurred in 4 patients (30.77%), whereas no patient had intracranial hemorrhage. Systemic thrombolysis showed comparable outcomes of catheter-directed thrombolysis in our patients who underwent ECMO. Conclusions Thrombolysis-based therapeutic strategy under ECMO could be a relatively safe and effective definitive treatment for patients with acute massive PE, even for those who were resuscitated. Bleeding complications remain a major concern and should be monitored and managed immediately.

Attention deficit hyperactivity disorder (ADHD), i.e., children’s hyperactivity, is a common neurodevelopmental disorder in childhood. ADHD is mainly characterized by having difficulty in staying focused, behavioral impulsivity and hyperactivity, and is often accompanied by conduct disorders, learning disabilities or learning difficulties. Traditional therapies generally rely on doctors and parents who can observe and assess patients’ behavior through behavioral scales; however, these therapies are time consuming and ineffective in quantifying behavior. Basing on virtual reality technology, this study integrated multiple sensor technologies, such as eye movement sensors and EEG sensors, and developed an assessment and diagnosis system for ADHD. This system constructed a virtual classroom environment and integrated some tasks, such as audio test, Continuous Performance Task (CPT) and Wisconsin Card Sorting Test (WCST), to judge the subject’s sustained attention, abstract reasoning ability and cognitive ability. Distraction elements were also added to the experiment by analyzing the attention shift of the test taker to diagnose ADHD. Physiological data, such as head movements, eyes movements, and EEG, were used to supplement test results to assess the subject’s sustained attention and attention shift.

Erinacine S, so far known to have been produced only in Hericium erinaceus mycelia, has just recently been discovered and is able to reduce amyloid plaque growth and improve neurogenesis in aged brain of rats. However, few investigations have been conducted on the absorption, distribution, and excretion study of Erinacine S. This study aimed to investigate the absolute bioavailability, tissue distribution, and excretion of Erinacine S in H. Erinaceus mycelia in eight-week old Sprague-Dawley rats. After oral administration and intravenous administration of 2.395 g/kg body weight of the H. erinaceus mycelia extract (equivalent to 50 mg/kg body weight Erinacine S) and 5 mg/kg of Erinacine S, respectively, the absolute bioavailability was estimated as 15.13%. In addition, Erinacine S was extensively distributed in organs such as brain, heart, lung, liver, kidney, stomach, small intestine, and large intestine. The maximum concentration of Erinacine S was observed in the stomach, 2 h after the oral administration of H. erinaceus mycelia extract, whereas the maximum amount of Erinacine S found in other tissues were seen after 8 h. Total amount of unconverted Erinacine S eliminated in feces and urine in 24 h was 0.1% of the oral dosage administrated. This study is the first to show that Erinacine S can penetrate the blood&ndash, brain barrier of rats and thus support the development of H. erinaceus mycelia, for the treatment of neurological diseases.

Introduction Evidence indicates that, in animal models, Antrodia cinnamomea (AC) mycelium is in vitro hypotensively active. Convincing evidence of the clinically relevant benefits of AC mycelium in humans, however, is unclear. Hence, this pilot randomised clinical trial was conducted to assess the effects of AC mycelium on blood pressure and other cardiovascular risk factors in patients with mild hypertension. Methods Forty-one patients with systolic blood pressure (SBP) between 130 and 179 mmHg or diastolic blood pressure (DBP) between 85 and 109 mmHg were randomised then treated with either AC mycelium or starch (placebo) for 8 weeks and were followed up for an additional 2 weeks. Results SBP in the patients treated with AC mycelium was significantly lower (144.86 ± 11.34 to 133.10 ± 10.90 mmHg; p Conclusions There were neither adverse events nor abnormal laboratory findings throughout the study period, which suggested that AC mycelium significantly reduced mild hypertension; this might support the hypothesis that it is a safe alternative treatment for mild hypertension. Trial registration Chung Shan Medical University Hospital Internal Review Board approval number: CS11043; ClinicalTrial.gov registration number: NCT02532699.

Cancer initiating cells (CICs) represent a subpopulation of cancer cells, which are responsible for tumor growth and resistance to chemotherapy. Herein, we first used a cell-based aldehyde dehydrogenase (ALDH) activity assay to identify that YMGKI-2 (also named as Ergone), an active component purified from Antrodia cinnamomea Mycelia extract (ACME), effectively abrogated the ALDH activity and abolished the CICs in head and neck squamous cell carcinoma cells (HNSCCs). Consequently, YMGKI-2 treatment suppressed self-renewal ability and expression of stemness signature genes (Oct-4 and Nanog) of sphere cells with enriched CICs. Moreover, YMGKI-2 treated sphere cells displayed reduction of CICs properties and promotion of cell differentiation, but not significant cytotoxicity. YMGKI-2 treatment also attenuated the tumorigenicity of HNSCC cells in vivo. Mechanistically, treatment of YMGKI-2 resulted in inactivation of STAT3 and Src. Lastly, combinatorial treatments with YMGKI-2 and standard chemotherapeutic drugs (cisplatin or Fluorouracil) restored the chemosensivity on sphere cells and cisplatin-resistant HNSCC cells. Together, we demonstrate that YMGKI-2 treatment effectively induces differentiation and reduces tumorigenicity of CICs. Further, combined treatment of YMGKI-2 and conventional chemotherapy can overcome chemoresistance. These results suggest that YMGKI-2 treatment may be used to improve future clinical responses in head and neck cancer treatment through targeting CICs.

Cerebrovascular events are a common complication among patients with cancer, increasing morbidity and mortality. However, the association between multiple myeloma and cerebrovascular events remains unclear. We therefore investigated multiple myeloma patients' risk factors for stroke to devise a better stroke-prevention strategy. This study includes consecutive patients 20 years and older who were newly diagnosed with symptomatic multiple myeloma at Taipei Veterans General Hospital, a tertiary medical center, between January 1, 2002 and December 31, 2014. The primary outcome was stroke development. Patients with head injuries, brain tumors, brain parenchymal invasions, or antecedent malignancies were excluded. Hazard ratios (HRs) of stroke risk factors for multiple myeloma patients were estimated by Cox proportional regression analysis. Overall, 395 patients with a median age of 70 years were investigated. In the median follow-up period of 18 months, cerebrovascular events occurred in 16 patients, including 10 ischemic strokes and 6 hemorrhagic strokes. The 5-year estimated cumulative incidence rate was 7.45%. In the multivariate analysis, the κ light chain isotype (adjusted HR, 8.37; 95% confidence interval [CI], 1.91-39.8), previous cerebrovascular accidents (adjusted HR, 5.16; 95% CI, 1.48-17.9), and serum creatinine > 2 mg/dL (adjusted HR, 4.21; 95% CI, 1.10-16.0) were identified as independent risk factors for stroke. Subgroup analysis showed that atrial fibrillation (adjusted HR, 8.07) and previous cerebrovascular accident (adjusted HR, 4.89) are significant risk factors for ischemic stroke. Serum creatinine > 2 mg/dL (adjusted HR, 30.6) and previous cerebrovascular accident (adjusted HR, 13.9) are significant for hemorrhagic stroke. Moreover, therapeutic strategies for multiple myeloma were not associated with stroke in our study. This study demonstrates that risk of stroke increases in myeloma patients with a κ light chain isotype, previous cerebrovascular events, and renal impairment. Further prospective clinical studies to clarify the relationship between multiple myeloma and stroke are warranted.

Background Colorectal cancer screening by fecal occult blood testing has been an important public health test and shown to reduce colorectal cancer–related mortality. However, the low participation rate in colorectal cancer screening by the general public remains a problematic public health issue. This fact could be attributed to the complex and unpleasant operation of the screening tool. Objective This study aimed to validate a novel toilet paper–based point-of-care test (ie, JustWipe) as a public health instrument to detect fecal occult blood and provide detailed results from the evaluation of the analytic characteristics in the clinical validation. Methods The mechanism of fecal specimen collection by the toilet-paper device was verified with repeatability and reproducibility tests. We also evaluated the analytical characteristics of the test reagents. For clinical validation, we conducted comparisons between JustWipe and other fecal occult blood tests. The first comparison was between JustWipe and typical fecal occult blood testing in a central laboratory setting with 70 fecal specimens from the hospital. For the second comparison, a total of 58 volunteers were recruited, and JustWipe was compared with the commercially available Hemoccult SENSA in a point-of-care setting. Results Adequate amounts of fecal specimens were collected using the toilet-paper device with small day-to-day and person-to-person variations. The limit of detection of the test reagent was evaluated to be 3.75 µg of hemoglobin per milliliter of reagent. Moreover, the test reagent also showed high repeatability (100%) on different days and high reproducibility (>96%) among different users. The overall agreement between JustWipe and a typical fecal occult blood test in a central laboratory setting was 82.9%. In the setting of point-of-care tests, the overall agreement between JustWipe and Hemoccult SENSA was 89.7%. Moreover, the usability questionnaire showed that the novel test tool had high scores in operation friendliness (87.3/100), ease of reading results (97.4/100), and information usefulness (96.1/100). Conclusions We developed and validated a toilet paper–based fecal occult blood test for use as a point-of-care test for the rapid (in 60 seconds) and easy testing of fecal occult blood. These favorable characteristics render it a promising tool for colorectal cancer screening as a public health instrument.

Although cerebral hyperperfusion syndrome is rarely encountered, this condition can be serious after procedures that increase cerebral blood flow; most reports are related to carotid revascularization. Sharp cerebral hemodynamic changes, along with impaired cerebrovascular autoregulation, are the main mechanisms contributing to this syndrome. We report a patient who underwent surgical correction for congenital supravalvular aortic stenosis and presented with postoperative hypertension, headache, impairment of consciousness, and cerebral edema 2 days after operation. He recovered well when the blood pressure declined and the brain edema subsided. Cerebral hyperperfusion syndrome was considered, and this uncommon neurologic complication of cardiac operations is discussed.

Clinical introduction A 26-year-old man with an unremarkable medical history sensed a momentary retrosternal ‘pop’ followed by overwhelming dyspnoea, without reporting any prodromal symptoms. At the emergency department, he had a significant tachycardia (170 bpm) and an extreme low diastolic blood pressure ( Supplementary file 3Supplementary file 4 Question What congenital cardiac anomaly did the patient have? Congenital bicuspid aortic valve Doubly committed subarterial ventricular septal defect (VSD) Congenital sinus of Valsalva aneurysm Coronary arteriovenous fistula

Vertebral fractures affect approximately 30% of myeloma patients and lead to a poor impact on survival and life quality. In general, age and body mass index (BMI) are reported to have an important role in vertebral fractures. However, the triangle relationship among age, BMI, and vertebral fractures is still unclear in newly diagnosed multiple myeloma (NDMM) patients. This study recruited consecutive 394 patients with NDMM at Taipei Veterans General Hospital between January 1, 2005 and December 31, 2015. Risk factors for vertebral fractures in NDMM patients were collected and analyzed. The survival curves were demonstrated using Kaplan-Meier estimate. In total, 301 (76.4%) NDMM patients were enrolled in the cohort. In the median follow-up period of 18.0 months, the median survival duration in those with vertebral fractures ≥ 2 was shorter than those with vertebral fracture 75 years and BMI < 18.5 kg/m2 (adjusted RR, 12.22; 95% CI, 3.02-49.40). This is the first study that demonstrated that age had a significant impact on vertebral fractures in NDMM patients with low BMI. Elder patients with low BMI should consider to routinely receive spinal radiographic examinations and regular follow-up.

Laminated sediments in the Taipei Basin which are tentatively assigned to the antepenultimate glacial period were studied to discern the paleoclimatic significance. Analyses of multi proxies including pollen, mineralogy, grain size, and loss on ignition (LOI) were carried out on three 50 cm thick intervals of a 23.7 m thick laminated section of the Hsinchuan Core, western Taipei. The couplets are commonly composed of 2–7 mm light grey layers and 2–3 mm dark grey layers. Major components in the light grey layer are quartz (>70%) associated with clay minerals (illite). Clay minerals increase in the dark grey layer and can dominate. A pollen study indicates that the light grey layers are characterized by more abundant warm elements such as Cyclobalanopsis and Castanopsis , while the dark grey layers have more abundant cool elements including Pinaceae ( Pinus , Picea , Tsuga ), Alnus and significant amounts of Poaceae. Study of the present pollen calendar of the Taipei Basin indicates that Pinus appears during winter–spring and Cyclobalanopsis and Castanopsis appear during early summer. The studied couplets are thus very possibly seasonal deposits of the ancient lake. Spectrum analysis for the thickness variation of the light grey laminae, believed to represent most of the annual precipitation changes in summer–autumn, shows prominent El Nino Southern Oscillation (ENSO) peaks of 3–4 and 6–7 year periods. This may indicate that ENSO events occurred during the middle Pleistocene glaciation.

Head and neck squamous cell carcinoma (HNSCC) is a highly lethal cancer. Previously, we identify head and neck cancer initiating cells (HN-CICs), which are highly tumorigenic and resistant to conventional therapy. Therefore, development of drug candidates that effectively target HN-CICs would benefit future head and neck cancer therapy. In this study, we first successfully screened for an active component, named YMGKI-1, from natural products ofAntrodia cinnamomeaMycelia (ACM), which can target the stemness properties of HNSCC. Treatment of YMGKI-1 significantly downregulated the aldehyde dehydrogenase (ALDH) activity, one of the characteristics of CIC in HNSCC cells. Additionally, the tumorigenic properties of HNSCC cells were attenuated by YMGKI-1 treatmentin vivo. Further, the stemness properties of HN-CICs, which are responsible for the malignancy of HNSCC, were also diminished by YMGKI-1 treatment. Strikingly, YMGKI-1 also effectively suppressed the cell viability of HN-CICs but not normal stem cells. Finally, YMGKI-1 induces the cell death of HN-CICs by dysregulating the exaggerated autophagic signaling pathways. Together, our results indicate that YMGKI-1 successfully lessens stemness properties and tumorigenicity of HN-CICs. These findings provide a new drug candidate from purified components of ACM as an alternative therapy for head and neck cancer in the future.

Modern life is more busy than previous, after a busy day of work, sleep quality at night has become an important part of the next day that can working smoothly. With the development of wearable devices, people must go to the medical center to spend a whole day for sleep diagnosis in the past day, but now they have opportunity achieve a simple sleep quality measurement by using wearable devices.

Supplemental Digital Content is available in the text, The overall survival of patients with multiple myeloma (MM) has been improved greatly over the last 2 decades with the broader use of novel drugs and autologous tandem transplantation. However, more than one tenth of myeloma patients still die shortly after diagnosis. We therefore aim to investigate the risk factors of early mortality (death within 60 days after diagnosis) in patients with MM. We included in this study 451 consecutive patients with MM, newly diagnosed at an Asian tertiary medical center between January 1, 2002 and April 30, 2015. A total of 57 subjects who experienced early mortality were identified. Risk factors for early mortality in myeloma patients were collected and analyzed. Early mortality occurred in 57 (12.6%) of the myeloma patients. In the multivariate analysis, being male (adjusted OR 2.93, 95% CI 1.17–7.31), serum albumin

This paper characterizes the mass transfer and replenishment of glucose and oxygen in tissue engineered cartilage constructs by a numerical approach. Cell population growth modulated by glucose and oxygen is incorporated in the mathematic model. The distribution of synthesized type II collagen and its influence on mediating the chondrocyte growth over scaffold are also investigated. Results from simulation are compared with the experiments in literature to verify the formulation and predictions. It is found that, under static culture, the oftentimes observed phenomenon that the overall cell number densities in thick scaffolds are smaller than in thin scaffolds is mainly due to depletion of glucose rather than oxygen. Cell growth is found to be more sensitive to the change in glucose concentration for thick scaffolds, whereas to be more sensitive to the change in oxygen concentration for thin scaffolds. Results also demonstrate the modulation of chondrocyte growth by type II collagen, presenting the biphasic impact of type II collagen which promotes chondrocyte growth in the initial phase of cultivation, while inhibits cell growth in the long term. The numerical model provides a useful reference for developing cartilaginous constructs in tissue engineering.

Antrodia cinnamomea is a Taiwanese medicinal mushroom with high antioxidant and polysaccharide content. The objective of this study is to investigate developmental toxicity of A. cinnamomea in pregnant Sprague-Dawley rats. Animals were daily gavaged with A. cinnamomea mycelium at dosage levels of 0 (reverse osmosis water), 50, 150, and 500 mg/kg from gestation day (GD) 6 to 15. All dams were sacrificed on GD 20 and were subjected to cesarean section. Fetuses were examined for external, visceral, and skeletal abnormalities. All copulated females survived until the end of the study. No significant differences were recorded in body weight change, food consumption, and maternal gestational parameters. Only two fetal malformations were noted in 970 fetuses from the treatment groups. Some variations, such as enlarged fontanel, split sternebrae, absent sacral, absent caudal vertebral centra, absent thoracic centra, absent 13th-14th ribs, and fused ribs, were found during the skeletal examination, but no treatment-induced abnormalities occurred. No dose dependency was observed in any of the developmental variations. Overall observation of foetal malformations from rats given A. cinnamomea mycelium during pregnancy demonstrates that this material is not teratogenic at doses up to 500 mg/kg. It is concluded that A. cinnamomea BCRC 35398 mycelium has no teratogenic effects in female rats and is safe to be used as a functional food ingredient.

Head and neck cancer (HNC) is one of the most common forms of cancer in Taiwan. In addition, head and neck cancer cells (HNCs) are highly tumorigenic and resistant to conventional therapy. Therefore, development of new therapeutic regimens that are adjuvant to conventional treatments would benefit future head and neck cancer therapy. In this study, we found that the lyophilized particles and ethanolic extracts of Antrodia cinnamomea mycelia inhibited the tumor growth of HNCs by xenograft assay in vivo. Moreover, administration of lyophilized particles or ethanolic extracts to nude mice did not cause significant side effects. Our study revealed that the Antrodia cinnamomea mycelia extract (ACME) efficiently inhibited the tumorigenicity of HNCs without causing organ failure. Furthermore, it showed that ACME may work as a novel drug candidate for alternative treatments for head and neck cancer.

Primary vascular tumour of the heart is rare, especially in neonates and infants. We report a male premature newborn with a right atrial tumour associated with a large amount of pericardial effusion detected by screening foetal echography. Diagnosis of capillary haemangioma was confirmed by histopathological examination after complete surgical resection. Other vascular tumours in the neonates and infants reported in the English literatures are reviewed, and one algorithm for both prenatal and postnatal management is proposed.

Acute intestinal ischemic disorders are potentially life threatening, making early diagnosis and emergency surgery crucial. Although hypercoagulability may induce mesenteric venous thrombosis, its association with mesenteric arterial thromboembolism remains controversial. We present the case of a 52-year-old man with hypercoagulability-induced acute arterial occlusive mesenteric ischemia. The patient suffered from arterial occlusive mesenteric ischemia, recent ischemic stroke, and previous renal infarction. He had no history of atrial fibrillation, atherosclerosis, vascular diseases, autoimmune diseases, malignancy, liver diseases, copper deficiency, or other risk factors for arterial thromboembolism. Segmental resection of the gangrenous bowel with primary end-to-end anastomosis was performed. A pathological examination revealed multiple thrombi within the mesenteric arteries of the infarcted bowel without apparent atherosclerosis of the vessels. The plasma level of factor VIII was high even 64 months postoperatively, which may have contributed to the recurrent and multiple arterial thromboses. A lifelong oral anticoagulation therapy was suggested. From our experience, we recommend that thrombophilia screening be performed in patients with acute intestinal ischemic disorders, particularly in those with a history of recurrent or multiple thromboembolism. Anticoagulant therapy should be prescribed for those with hypercoagulability.

Background Pancreatitis is a serious complication after cardiac surgery and can lead to significant morbidities and mortality. The incidence of pancreatitis is even higher in patients undergoing heart transplantation than in those undergoing other cardiac surgeries. Nevertheless, the clinical presentations of pancreatitis are frequently atypical in these patients. Case presentation We report a heart recipient who was complicated with acute right heart failure initially after orthotopic heart transplantation and developed devastating unanticipated hemorrhagic pancreatitis 1 month after the transplantation. This crypto-symptomatic pancreatitis was not diagnosed until massive internal bleeding and hemorrhagic shock occurred, because the typical presentations of acute pancreatitis were masked by the intra-abdominal manifestations caused by right heart failure and congestive liver dysfunction. The patient underwent a successful transarterial embolization. Conclusions The causes of pancreatitis after heart transplantation include low cardiac output, immunosuppressant use and cytomegalovirus infection. The typical symptoms of pancreatitis might be not apparent in patients after heart transplantation because of their immunosuppressive status. Furthermore, in patients complicated with right heart failure after transplantation, the manifestation of pancreatitis could be even more obscure. The prompt diagnosis is highly depended on the clinician’s astuteness.