Search

Background Subendocardial late gadolinium enhancement (LGE) detected with cardiac MRI in myocarditis represents a diagnostic dilemma, since it may resemble myocardial ischemia. Purpose To explore and compare the histopathologic characteristics and clinical features and outcomes in patients with myocarditis with and without subendocardial involvement at cardiac MRI. Materials and Methods This retrospective study evaluated 39 patients with myocarditis pathologically proven by means of either endomyocardial biopsy or explant pathologic findings between 2015 and 2020. Patients were divided into two groups according to cardiac MRI phenotype: 18 with subendocardial involvement (mean age ± standard deviation, 40 years ± 17; 10 women) and 21 with no subendocardial involvement (mean age, 35 years ± 11; six women). The median follow-up period was 784 days (interquartile range [IQR], 90-1123 days). The Student t test, Mann-Whitney U test, and univariable Cox regression were used for statistical analyses. Results In the 18 patients with subendocardial involvement, 12 (67%) had lymphocytic myocarditis and six (33%) had giant cell myocarditis. Patients with subendocardial involvement compared with those without subendocardial involvement had lower left ventricular ejection fraction (mean ± standard deviation, 27% ± 11 vs 41% ± 19; P = .004), larger LGE extent (median, 13% [IQR, 10%-22%] vs 5% [IQR, 2%-17%]; P < .001), higher rates of cardiac death or transplant (eight of 18 patients [44%] vs one of 21 patients [4.8%]; P = .006), higher probability of giant cell myocarditis (six of 18 [33%] vs one of 21 [4.8%]; P = .02), and more major adverse cardiovascular events (MACE) (15 of 18 [83%] vs seven of 21 [33%]; P = .002). In a subgroup of patients with comparable LGE extent (median, 15% vs 16%; P = .40) and left ventricular ejection fraction (median, 27% vs 31%; P = .26), the prognostic difference in terms of MACE remained (15 of 17 patients [88%] vs five of 10 [50%]; P = .02). Conclusion Subendocardial involvement detected with cardiac MRI in myocarditis indicated more severe clinical features, including a higher frequency of severe lymphocytic myocarditis or giant cell myocarditis and worse prognosis. © RSNA, 2021 See also the editorial by de Roos in this issue.

Chansu has demonstrated adverse side effects in clinical settings, which is associated with its toxicity and limits its clinical applications. But there are methodological limitations of drug safety evaluation. In this study, ultra-high performance liquid chromatography, lipidomic profiling, and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets. Compared with the EtOAc extraction, Chansu water fraction comprised of indolealkylamines which caused obvious acute inflammatory irritation in rats, including acute pain (spontaneous raising foot reaction), and inflammation (paw edema). At the molecular level, lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways. However, anti-inflammatory mediators from the CYP 450, ALA, and DHA pathways were markedly decreased following exposure to the Chansu water fraction. Moreover, four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target, 5-HT2AR. These results suggest that Chansu-induced inflammatory irritation is related to the distinct dysregulation of inflammatory lipids, and peripheral 5-HT2AR is a potential target for irritation therapy. The strategy used in this study can be a crucial technology in the safety evaluation of Natural medicinal substances.

Purpose This article analyzes the image heterogeneity of clear cell renal cell carcinoma (ccRCC) based on positron emission tomography (PET) and positron emission tomography-computed tomography (PET/CT) texture parameters, and provides a new objective quantitative parameter for predicting pathological Fuhrman nuclear grading before surgery. Methods A retrospective analysis was performed on preoperative PET/CT images of 49 patients whose surgical pathology was ccRCC, 27 of whom were low grade (Fuhrman I/II) and 22 of whom were high grade (Fuhrman III/IV). Radiological parameters and standard uptake value (SUV) indicators on PET and computed tomography (CT) images were extracted by using the LIFEx software package. The discriminative ability of each texture parameter was evaluated through receiver operating curve (ROC). Binary logistic regression analysis was used to screen the texture parameters with distinguishing and diagnostic capabilities and whose area under curve (AUC) > 0.5. DeLong's test was used to compare the AUCs of PET texture parameter model and PET/CT texture parameter model with traditional maximum standardized uptake value (SUVmax) model and the ratio of tumor SUVmax to liver SUVmean (SUL)model. In addition, the models with the larger AUCs among the SUV models and texture models were prospectively internally verified. Results In the ROC curve analysis, the AUCs of SUVmax model, SUL model, PET texture parameter model, and PET/CT texture parameter model were 0.803, 0.819, 0.873, and 0.926, respectively. The prediction ability of PET texture parameter model or PET/CT texture parameter model was significantly better than SUVmax model (P = 0.017, P = 0.02), but it was not better than SUL model (P = 0.269, P = 0.053). In the prospective validation cohort, both the SUL model and the PET/CT texture parameter model had good predictive ability, and the AUCs of them were 0.727 and 0.792, respectively. Conclusion PET and PET/CT texture parameter models can improve the prediction ability of ccRCC Fuhrman nuclear grade; SUL model may be the more accurate and easiest way to predict ccRCC Fuhrman nuclear grade. Graphic abstract

BACKGROUND: Preoperative anxiety in children is harmful. Despite this, there is a scarcity of studies examining the incidence of preoperative anxiety and its related effects in China. This study investigated preoperative anxiety in children aged 2 to 7 in the pediatric surgery department of a tertiary hospital in China. The factors influencing preoperative anxiety in these children were identified. METHODS: The researchers used the Chinese version of the modified Yale Preoperative Anxiety Scale (CmYPAS) and the Short Form of CmYPAS (CmYPAS-SF) to assess the preoperative anxiety state of children aged 2 to 7 who underwent elective surgery in the pediatric department of a tertiary hospital in China from July 1, 2020 to September 30, 2020 were enrolled in this study. The generalized estimating equation model was used to analyze the factors influencing preoperative anxiety in children. RESULTS: The preoperative anxiety rate of 220 children in the tertiary hospital was 67.6%. Multivariate analysis revealed that children who attended elementary school had a lower risk of preoperative anxiety compared to children who did not attend school [odd ratio (OR) =0.39, 95% confidence interval (CI), 0.19 to 0.79, P=0.010]. Children whose caregivers felt very worried experienced an increased risk of preoperative anxiety compared to children whose caregivers were not worried about the surgery at all (OR =3.40, 95% CI, 1.35 to 8.56, P=0.009). Children who were very resistant, cried violently, twisted their bodies during puncturing the needle were 5.8 times more likely to experience preoperative anxiety compared to children who were very cooperative. The risk of preoperative anxiety in children who cooperated with a staff member was about 1.5 times higher than that of children who were very cooperative. CONCLUSIONS: The incidence of preoperative anxiety in children aged 2 to 7 in the tertiary hospital in China was similar to the children in other countries. The caregivers’ degree of concern priored to the operation and the degree of cooperation from the children during puncturing the indwelling needle were the main factors influencing the occurrence of preoperative anxiety.

Rectal cancer patients can conceivably obtain relief from neoadjuvant concurrent chemoradiotherapy (CCRT) for downstaging before resection, but the stratification of risk and clinical outcomes remains challenging. Therefore, identifying effective predictive biomarkers offers clinicians the opportunity to individually tailor early interventions, which would help optimize therapy. Using a public rectal cancer transcriptome dataset (GSE35452), we focused on cytoskeletal protein binding (GO: 0008092)-related genes and identified FERM domain containing 3 (FRMD3) as the most significant differentially expressed gene associated with CCRT resistance. We gathered 172 tumor samples from rectal cancer patients treated with neoadjuvant CCRT accompanied by curative resection and estimated the expression level of FRMD3 using immunohistochemistry. The results revealed that high FRMD3 immunoexpression was remarkably associated with advanced pre-CCRT and post-CCRT tumor status (p = 0.004 and p

Aims This study aims to demonstrate the characteristics of late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance (CMR) imaging in patients with giant cell myocarditis (GCM). Methods and results Six patients histologically diagnosed with GCM were retrospectively recruited in this study. All of them underwent CMR during hospitalization. The distribution and extent of LGE were assessed on both ventricles, and the AHA‐17 segment model was used for left ventricular (LV) analysis. Nine case reports with CMR in GCM were reviewed and summarized to investigate the features of LGE further. LGE was detected on both ventricular walls in all subjects. For a detailed analysis of LGE in the LV, the extent ranged from 21.6% to 56%. Among 70 segments (68.6%) involved by LGE, the subendocardial LGE was the most common pattern (46/102, including 24 segments located in the right‐sided septum), followed by the subepicardial pattern (23/102). The right‐sided septum, the subepicardial anterior wall, and the subendocardial right ventricular (RV) wall were observed in all subjects. To summarize the results of the present study with these case reports, the three most common patterns of LGE are the right‐sided septum (73%), the subepicardial anterior wall (60%), and the subendocardial RV wall (53%). Conclusions Extensive LGE seems to be common in GCM, affecting both LV and RV walls. Apart from subepicardial LGE, subendocardial LGE, which was used to be implicated in ischaemic disease, was frequently presented in GCM. The right‐sided subendocardial septum, the subepicardial anterior wall, and the subendocardial RV wall might be the vulnerable areas of LGE in GCM.

Objective: Current antiplatelet medications increase the risk of bleeding, which leads to a clear clinical need in developing novel mechanism-based antiplatelet drugs. TYMP (Thymidine phosphorylase), a cytoplasm protein that is highly expressed in platelets, facilitates multiple agonist-induced platelet activation, and enhances thrombosis. Tipiracil hydrochloride (TPI), a selective TYMP inhibitor, has been approved by the Food and Drug Administration for clinical use. We tested the hypothesis that TPI is a safe antithrombotic medication. Approach and Results: By coexpression of TYMP and Lyn, GST (glutathione S-transferase) tagged Lyn-SH3 domain or Lyn-SH2 domain, we showed the direct evidence that TYMP binds to Lyn through both SH3 and SH2 domains, and TPI diminished the binding. TYMP deficiency significantly inhibits thrombosis in vivo in both sexes. Pretreatment of platelets with TPI rapidly inhibited collagen- and ADP-induced platelet aggregation. Under either normal or hyperlipidemic conditions, treating wild-type mice with TPI via intraperitoneal injection, intravenous injection, or gavage feeding dramatically inhibited thrombosis without inducing significant bleeding. Even at high doses, TPI has a lower bleeding side effect compared with aspirin and clopidogrel. Intravenous delivery of TPI alone or combined with tissue plasminogen activator dramatically inhibited thrombosis. Dual administration of a very low dose of aspirin and TPI, which had no antithrombotic effects when used alone, significantly inhibited thrombosis without disturbing hemostasis. Conclusions: This study demonstrated that inhibition of TYMP, a cytoplasmic protein, attenuated multiple signaling pathways that mediate platelet activation, aggregation, and thrombosis. TPI can be used as a novel antithrombotic medication without the increase in risk of bleeding.

This study explores whether online claims for investor protection (informal systems) of a province have an effect on the capital structures of the companies located in this province, thereby expanding our knowledge of the effects of informal systems on investor protection. Results in this study imply that online claims for investor protection on the Internet as an informal system play the role of an alternative mechanism and produce a positive effect on real investor protection, which should garner the attention of both regulators and investors.

In this paper, we investigate whether the academic experience of senior corporate leaders, often referred to as ‘top management’, impacts the quality of corporate internal control. Data collected from Shanghai and Shenzhen A-share listed firms in China demonstrate that senior leaders having academic experience can improve corporate internal control quality significantly. This study also finds that this impact varies with a firm’s agency costs and risk. In firms with higher agency cost (state-owned or larger firms) or higher risk, academic top managers play a more significant role in improving corporate internal control quality. The results are attributed to higher ethical standards, risk aversion and risk management abilities of senior executives given the perspectives awarded them during their academic experience. Further analysis shows that the differing roles of senior executives within such teams are quite distinct in how they improve internal control quality. Our findings contribute to the current internal control literature and have policy implications for evaluation of corporate internal control. It may also help enhance the processes in recruiting and selecting senior executives.

We report a case of a 21-year-old man with a cardiac pheochromocytoma involving the right atrium and extending to the right ventricular inflow tract, which was diagnosed by somatostatin receptor scintigraphy. For the preoperative evaluation, we chose multiple methods of imaging to accurately describe the anatomic extent and location of the tumor and its surrounding tissues, which showed that no major coronary artery ran through the tumor. The tumor was resected with disease-free margins effectively and safely with the use of cardiopulmonary bypass and with cardiac arrest. The patient remained asymptomatic at the 3-month follow-up.

An operational cost minimisation model is established for a smart energy hub (S.E. Hub) consisting of a combined heat and power (CHP) unit, a heating, ventilation and air-conditioning (HVAC) system, and thermal and electricity storage units. The optimal operation of CHP is combined with the load management of HVAC under a time-of-use (TOU) tariff. The heat and power split ratio of CHP is dynamically determined during the operation. The scheduling of HVAC load and the charging/discharging of energy storage systems are also determined through the optimisation model. The energy management system can therefore shift the load demand and manage energy supply simultaneously. System operation requirements and environment factors including the outdoor air-temperature variation, seasonal variation, and battery degradation are considered. Comprehensive case studies are carried out to examine the effectiveness of the proposed strategy, from which insights are obtained for different energy management strategies and possible upgrade of S.E. Hub. Simulation results reveal that dynamic control of the CHP heat and power split ratio is an effective way to save the total operational cost, and a clear cost saving is shown through the proposed optimal operation strategy.

A smart car park with electrical vehicles (EVs) has the potential to participate in a commercial building’s energy storage and power supply activities, via bidirectional power flow techniques. In this paper, the management of energy usage of a shopping mall with smart car park is investigated. An optimal control model is built up to determine EVs’ charging/discharging status under real-time price, the on/off switching of the heating, ventilation and air conditioning (HVAC) unit in the shopping mall, so that the overall energy cost can be minimised under normal and emergency operations. Key factors such as EV battery degradation, constraints on battery states and the emergency power supply requirements are included in the model. Simulation studies demonstrate that a proper-sized smart car park can be used as an extra power supply to the shopping mall under emergency power shut down. This can help to reduce reliance on traditional power supply under emergency requirements.

Nasopharyngeal carcinoma (NPC), characterized by the infiltration of lymphocytes, is a malignancy derived from the epithelium of the nasopharynx. Despite its sensitivity to radiation and chemotherapy, NPC has a high propensity for recurrence and metastasis. Although lymph node levels have been indicated as an independent prognostic factor for NPC, there has been no precise prognostic biomarker to predict clinical outcomes for NPC before advanced disease. In the present study, we surveyed differentially expressed genes in NPC via the next-generation sequencing (NGS)-based Oncomine database and identified the spindlin family member 4 (SPIN4) gene as the most relevant to advanced nodal status. We collected 124 tumor samples from NPC patients receiving biopsy, and the expression level of SPIN4 was evaluated by immunohistochemistry. The results showed that tumors with high SPIN4 expression were significantly correlated with advanced nodal status (p &lt, 0.001) and advanced AJCC stages (p &lt, 0.001). High SPIN4 expression in tumor samples was an unfavorable prognostic factor for all three endpoints at the univariate level: disease-specific survival (DSS), distal metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) (all p &lt, 0.05). High SPIN4 expression remained independently prognostic of worse DMeFS (p = 0.049) at the multivariate level. Using bioinformatics analysis, we further found that high SPIN4 level may link tight junctions to cancer cell survival. Collectively, these results imply that high SPIN4 expression is linked to an aggressive clinical course, including advanced nodal status and poor survival in NPC patients, emphasizing the promising prognostic utility of SPIN4 expression.

Background Cognitive decline leading to dementia, accompanied by the accumulation of amyloid-beta (Aβ) in neuritic plaques together with the appearance of neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein (tau), are previously noted hallmarks of Alzheimer's disease (AD). We previously discovered hypervascularity in brain specimens from AD patients and consistent with this observation, we demonstrated that overexpression of Aβ drives cerebrovascular neoangiogenesis leading to hypervascularity and coincident tight-junction disruption and blood-brain barrier (BBB) leakiness in animal models of AD. We subsequently demonstrated that amyloid plaque burden and cerebrovascular pathogenesis subside when pro-angiogenic Aβ levels are reduced. Based on these data, we propose a paradigm of AD etiology where, as a compensatory response to impaired cerebral blood flow (CBF), Aβ triggers pathogenic cerebrovascular neoangiogenesis that underlies the conventional hallmarks of AD. Consequently, here we present evidence that repurposing anti-cancer drugs to modulate cerebrovascular neoangiogenesis, rather than directly targeting the amyloid cascade, may provide an effective treatment for AD and related vascular diseases of the brain. Methods We explored whether the anti-cancer drug, Axitinib, a small molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR) can inhibit aberrant cerebrovascular neoangiogenic changes, reduce Aβ deposits and reverse cognitive decline in an animal model of AD. One month post-treatment with Axitinib, we employed a battery of tests to assess cognition and memory in aged Tg2576 AD mice and used molecular analysis to demonstrate reduction of amyloid plaques, BBB leakage, hypervascularity and associated disease pathology. Findings Targeting the pro-angiogenic pathway in AD using the cancer drug, Axitinib, dramatically reduced cerebrovascular neoangiogenesis, restored BBB integrity, resolved tight-junction pathogenesis, diminishes Aβ depositions in plaques and effectively restores memory and cognitive performance in a preclinical mouse model of AD. Interpretation Modulation of neoangiogenesis, in an analogous approach to those used to treat aberrant vascularization in cancer and also in the wet form of age-related macular degeneration (AMD), provides an alternative therapeutic strategy for intervention in AD that warrants clinical investigation. Funding None

BackgroundThe mitochondrial pyruvate dehydrogenase complex (PDC) link glycolysis to the tricarboxylic acid cycle by decarboxylating pyruvate to acetyl coenzyme A irreversibly. Cancer cells are characterized by a shift in cellular metabolism from mitochondrial respiration to glycolysis. PDC activity inhibition mediated by phosphorylation via pyruvate dehydrogenase kinase (PDK) has been linked to cancer. However, the clinical significance of PDKs in urothelial cancer prognosis is not clear. We investigated the role and prognostic value of PDK3 expression in patients with upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC).Patients and MethodsWe retrospectively analyzed clinical data and pathological features. Formalin-fixed urothelial carcinoma (UC) tissues were collected and embedded in paraffin. The correlation of PDK3 expression with clinical characteristics, pathological findings and patient outcomes, including metastasis-free survival (MFS) and disease-specific survival (DSS) were analyzed by Pearson’s chi-square test, Kaplan–Meier analysis, and the multivariate Cox proportional hazards model.ResultsData from 295 patients with UBUC and 340 patients with UTUC were evaluated. High PDK3 expression significantly correlated with several pathologic variables such as high T stage, lymph node metastases, high tumor grade, vascular invasion, and high mitotic rate (all P < 0.001). High PDK3 expression was associated with poor disease-specific survival (DSS) (P < 0.0001) and metastatic free survival (MFS) (P < 0.0001) in a Kaplan–Meier analysis. Additionally, multivariate analysis demonstrated increased PDK3 expression is a significant predictive risk factor for DSS [hazard ratio (HR) in UBUC, 2.79, P = 0.009; in UTUC, 2.561, P = 0.03] and MFS (HR in UBUC, 1.907, P = 0.024; in UTUC, 1.793, P = 0.044). The gene co-expression analysis showed abundant PDK3 co-upregulated genes were involved in the processes of DNA replication and repair through the Gene Ontology classification system.ConclusionHigh PDK3 expression has been linked to negative pathologic characteristics and poor oncological outcomes, suggesting that it could be used as a predictive biomarker for UC. PDK3 mRNA levels and its co-upregulated genes were strongly associated with DNA replication and repair. These results suggest that PDK3 may play a key role in tumor proliferation and development.

Background: Patients with rectal cancer can prospectively be favored for neoadjuvant concurrent chemoradiotherapy (CCRT) to downstage before a radical proctectomy, but the risk stratification and clinical outcomes remain disappointing. Methods: From a published rectal cancer transcriptome dataset (GSE35452), we highlighted extracellular matrix (ECM)-linked genes and identified the serine protease inhibitor Kazal-type 4 (SPINK4) gene as the most relevant among the top 10 differentially expressed genes associated with CCRT resistance. We accumulated the cases of 172 rectal cancer patients who received neoadjuvant CCRT followed by surgery and collected tumor specimens for the evaluation of the expression of SPINK4 using immunohistochemistry. Results: The results revealed that high SPINK4 immunoexpression was significantly related to advanced pre-CCRT and post-CCRT tumor status (both p &lt, 0.001), post-CCRT lymph node metastasis (p = 0.001), more vascular and perineurial invasion (p = 0.015 and p = 0.023), and a lower degree of tumor regression (p = 0.001). In univariate analyses, high SPINK4 immunoexpression was remarkably correlated with worse disease-specific survival (DSS) (p &lt, 0.0001), local recurrence-free survival (LRFS) (p = 0.0017), and metastasis-free survival (MeFS) (p &lt, 0.0001). Furthermore, in multivariate analyses, high SPINK4 immunoexpression remained independently prognostic of inferior DSS and MeFS (p = 0.004 and p = 0.002). Conclusion: These results imply that high SPINK4 expression is associated with advanced clinicopathological features and a poor therapeutic response among rectal cancer patients undergoing CCRT, thus validating the prospective prognostic value of SPINK4 for those patients.

Obesity is a risk factor for gallbladder cancer (GBC) development and correlates with shorter overall survival. Leptin, derived from adipocytes, has been suggested to contribute to the growth of cancer cells. However, the detailed mechanism of leptin in GBC drug resistance remains uninvestigated. In this study, it is clinically relevant that GBC patients with a higher BMI (BMI ≥ 24 kg/m2) (n=30) were associated with increased GBC risks, including survival. Moreover, obese NOD/SCID mice exhibited a higher circulating concentration of leptin, which is associated with GBC growth and attenuated gemcitabine efficacy. We further revealed that leptin can inhibit gemcitabine-induced GBC cell death through myeloid cell leukemia 1 (MCL1) activation. The transcription factor CCAAT/enhancer-binding protein delta (CEBPD) is responsive to activated signal transducers and activators of transcription 3 (pSTAT3) and contributes to MCL1 transcriptional activation upon leptin treatment. In addition, MCL1 mediates leptin-induced mitochondrial fusion and is associated with GBC cell survival. This study suggests the involvement of the pSTAT3/CEBPD/MCL1 axis in leptin-induced mitochondrial fusion and survival. It provides a new therapeutic target to improve the efficacy of gemcitabine in GBC patients.

Background: Sepsis, a serious condition caused by infection, can ultimately progress to life-threatening septic shock and multiple organ failure. Hitherto, no reliable markers could be used for the early diagnosis and sepsis is still a challenge for clinicians. We investigated the potential role of thymidine phosphorylase (TYMP) in infection and delved its value in diagnosing sepsis and disseminated intravascular coagulation (DIC). Methods: This prospective study enrolled infection patients consecutively admitted to Beijing Friendship Hospital from November 2019 to January 2021. Non-infection volunteers were used as control (NIC). Blood sample were obtained on day 1, 2, 4, and 7 after admission. TYMP serum levels and its correlation with DIC scores, Sequential Organ Failure Assessment (SOFA) scores, and other laboratory parameters were analyzed using the non-parametric Mann-Whitney U test and the Spearman's Rank-Order Correlation analyses. Results: Eighty-three infectious patients were enrolled. Forty-two patients were diagnosed as sepsis (SP) and 41 were non-septic infection (NSP). NIC group included 20 individuals without any infection. Serum TYMP levels were significantly higher in both SP and NSP groups when compared with the NIC group. TYMP serum levels was further higher in the SP than in the NSP group. The increase of TYMP was positively correlated with DIC scores. TYMP was higher in patients with DIC than those patients without DIC. A positive correlation presented between serum TYMP and plasma D-dimer levels. No positive correlations were found between TYMP and inflammatory markers. TYMP was higher in patients with SOFA score > 1 than those with SOFA score zero. The increase of TYMP is also positively correlated with SOFA score and death risk coefficient, and negatively correlated with oxygen index. By conducting receiver operating characteristic curve analyses, we found TYMP has a specific and sensitive predictive value for diagnosing sepsis and a modest value for DIC. Conclusions: This study is the first time to determine the role of TYMP in infectious disease. TYMP is significantly increased in infectious patients and is further higher in patients with sepsis or DIC. TYMP is positively correlated with acuity markers and has a diagnostic and prognostic value for sepsis and DIC.

Obesity is a major independent risk factor for the development of type II diabetes (T2DM), nonalcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Consequently, controlling obesity constitutes a key strategy for reducing the prevalence of these diseases. The majority of drugs developed for treating obesity over the past 20 years have been withdrawn due to the increased risk of cardiovascular and psychiatric complications. Therefore, developing novel mechanism-mediated therapeutics for controlling obesity and its consequent complications is a top priority and urgently needed. Our studies indicate that thymidine phosphorylase (TYMP) could be a promising target. The traditional role of TYMP is to catalyze the reversible conversion of thymidine to thymine and 2-deoxy-D-ribose-1 phosphate and maintain the homeostatic nuclear pool of these molecules. TYMP expression is increased in several diseased conditions, including obesity, T2DM, and NAFLD. However, whether TYMP plays a role in the development of these diseases is unknown. We found that Tymp-deficient (Tymp-/-) male mice exhibited significantly limited body weight gain as well as liver and perigonadal fat weight when fed either a western diet (TD.88137) or a prodiabetic high-fat diet (D12492) compared with the wild-type mice. Male Tymp-/- mice showed better glucose tolerance. TYMP-deficiency reduced expression of enzymes that confer glycolysis and de novo lipogenesis in the liver. TYMP-deficiency enhanced the sensitivity of primary hepatocytes to insulin as evidenced by the increase of AKT activation. Inhibition of TYMP with tipiracil, a selective, potent, and the FDA approved TYMP inhibitor, dramatically reduced western diet and high-fat diet-induced body weight gain. We conclude that TYMP plays a pivotal role in liver glucose and lipid metabolism, which promotes the development of obesity and T2DM. Targeting TYMP with tipiracil could be a new therapy for obesity. Disclosure H. Yue: None. A. M. Belcher: None. A. Bicak: None. W. Li: None.

Background:Infants with cyanotic congenital heart disease demonstrate wide fluctuations in hemoglobin (Hb), oxygen saturation, and cardiac output following palliation. Methemoglobin (Met-Hb), the product of Hb oxidation, may represent a compensatory mechanism during hypoxia and may be utilized as a biomarker.Methods:Arterial and venous Met-Hb levels were obtained from infants requiring palliation. The primary outcome was to describe the relationship between Met-Hb and other indices of tissue oxygenation (venous saturation, estimated arteriovenous oxygen difference [Est AV-Diff], and lactate). Secondary outcomes were to determine the impact of elevated Met-Hb levels ≥1.0% and the effect of red blood cell (RBC) transfusion on Met-Hb levels.Results:Fifty infants and 465 Met-Hb values were studied. Venous Met-Hb levels were significantly higher than arterial levels (venous: 0.84% ± 0.36% vs arterial: 0.45% ± 0.18%; P < .001). Venous Met-Hb demonstrated a significant inverse relationship with venous oxygen saturation ( R = −0.6; P < .001) and Hb ( R = −0.3, P < .001) and a direct relationship with the Est AV-Diff ( R = 0.3, P < .001). A total of 129 (29.6%) venous Met-Hb values were elevated (≥1.0%) and were associated with significantly lower Hb and venous saturation levels and higher Est AV-Diff and lactate levels. Methemoglobin levels decreased significantly following 65 RBC transfusions (0.94 ± 0.40 vs 0.77 ± 0.34; P < .001). Linear mixed models demonstrated that higher venous Met-Hb levels were associated with lower measures of tissue oxygenation and not related to any preoperative clinical differences.Conclusion:Methemoglobin may be a clinically useful marker of tissue oxygenation in infants following surgical palliation.

Hypoxia-inducible factor-2α (HIF2α) plays an important role in the development of tumors. However, the clinicopathologic and prognostic significance of HIF2α in cancer patients remains controversial. Therefore, we performed a meta-analysis to investigate the relationship between the HIF2α status and clinical outcome in human cancer. Studies were screened online using electronic databases. The pooled risk ratios or hazard ratios (HR) with their 95% confidence intervals (CI) were calculated from available publications. Subgroup analysis, sensitivity analysis, heterogeneity, and publication bias were also conducted. A total of 854 studies with 4,345 patients were obtained in this meta-analysis. The results indicated that the increased expression of HIF2α could predict unfavorable overall survival of cancer patients on both univariate analysis (HR, 1.64; 95% CI, 1.41–1.92, P < 0.001) and multivariate analysis (HR, 2.21; 95% CI, 1.70–2.87, P < 0.001). Moreover, HIF2α overexpression was associated closely with tumor differentiation, tumor–node–metastasis stage, and lymph metastasis. In addition, there was no obvious evidence for significant publication bias in this meta-analysis. Our study indicated that HIF2α might be an indicator of poor prognosis and clinicopathologic features of tumors and could serve as a novel biomarker in human cancer.

Objective: To compare the efficacy of traditional Chinese medicine (TCM) based on Zheng differentiation with angiotensin receptor blocker/angiotensin-converting enzyme inhibitor (ARB/ACEI) in treating diabetic kidney disease (DKD) from the aspects of decreasing urinary microalbumin, declining 24-h urinary protein, reducing endpoint events, and renal function protection. Methods: The Chinese Biomedical Literature Database (CBM), the Chinese Academy of Sciences database (CNKI), the VIP Chinese journal database, Wanfang DATA, Medline database, Cochrane library, excerpt medical database (Embase), and Web of science were used for literature searching. The reviewer manager 5.3 software was utilized to analyze the data. Results: Twenty-four studies including 1956 participants were involved in this review. Results showed that TCM had a better effect (mean difference [MD], −23.20, 95% confidence interval [CI], −30.60 to −15.79, P < 0.00001) than ARB/ACEI on lowering urinary albumin excretion rate (UAER) and urine albumin-to-creatinine ratio (MD −4.56 mg/mmol, 95% CI, −5.76 to −3.36, P < 0.00001). Moreover, the advantage of decreasing UAER was greater as the follow-up period become longer (P = 0.04). TCM also had a better effect in 24-h urinal protein, decreasing 0.36 g/24 h (95% CI, −0.45 to −0.27, P < 0.00001) more than the control in shorter follow-up period (ranged from 12 to 24 weeks) subgroup but only 0.08 g/24 h (95% CI, −0.13 to −0.03, P = 0.0006) in the longer follow-up period (>24 weeks) subgroup. TCM worked as well as ACEI/ARB in reducing endpoint events (relative risk, 0.67, 95% CI, 0.20–2.224, P = 0.51) and decreasing urinary albumin concentration (UAC) (MD, −16.50, 95% CI, −46.28–13.28, P = 0.28). As for protecting renal function, TCM had an equal effect to AECI/ARB in improving creatinine clearance ratio (MD, −3.30, 95% CI, −6.66–0.03, P = 0.05) or estimated glomerular filtration rate (MD, 1.00, 95% CI, −0.59–2.58, P = 0.22). However, TCM had a better effect in releasing the glomerular hyperfiltration state (MD, −9.64, 95% CI, −14.45 to −4.84, P < 0.0001). Conclusions: TCM based on Zheng differentiation can work as well as ACEI/ARB in treating DKD and even better in decreasing urinary microalbumin and releasing glomerular hyperfiltration. It is a good alternative treatment of DKD.

Despite the activation of autophagy may enable residual cancer cells to survive and allow tumor relapse, excessive activation of autophagy may eventually lead to cell death. However, the details of the association of autophagy with primary resistance in hepatocellular carcinoma (HCC) remain less clear. In this study, cohort analysis revealed that HCC patients receiving sorafenib with HBV had higher mortality risk. We found that high epidermal growth factor receptor (EGFR) expression and activity may be linked to HBV-induced sorafenib resistance. We further found that the resistance of EGFR-overexpressed liver cancer cells to sorafenib is associated with low activity of AMP-activated protein kinase (AMPK) and CCAAT/enhancer binding protein delta (CEBPD) as well as insufficient autophagic activation. In response to metformin, the AMPK/cAMP-response element binding protein (CREB) pathway contributes to CEBPD activation, which promotes autophagic cell death. Moreover, treatment with metformin can increase sorafenib sensitivity through AMPK activation in EGFR-overexpressed liver cancer cells. This study suggests that AMPK/CEBPD-activated autophagy could be a potent strategy for improving the efficacy of sorafenib in HCC patients.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), is a human respiratory disease. Hitherto, there is no effective treatment has been established. Patients with cardiovascular or diabetes comorbidities are a high-risk cohort. COVID-19 is accompanied by excessive systemic thrombotic events, but the mechanism is not yet known. Recent studies have indicated that thymidine phosphorylase (TYMP) plays an important role in platelet activation, thrombosis, and TYMP expression is increased in diabetic patients. By using data provided by the MGH (Massachusetts General Hospital) Emergency Department COVID-19 Cohort with Olink Proteomics, here we show that plasma TYMP level is correlated with the COVID-19 associated thrombotic event, inflammation, and organ damage, as evidenced by the positive correlations with plasma D-dimer, CRP (C reactive protein), and LDH (lactate dehydrogenase), as well as Interferons (IFN). Plasma TYMP is also positively correlated with COVID-19 patients who had respiratory symptoms. TYMP thus could be an acuity marker for COVID-19 diagnosis. Targeting TYMP with tipiracil, a selective TYMP inhibitor, which has been approved by the Food and Drug Administration for clinical use, could be a novel effective medicine for COVID-19.

The growing availability of eye-gaze tracking technology has allowed for its employment in a wide variety of applications, one of which is the objective diagnosis and monitoring of neuropsychiatric disorders from features of attentional bias extracted from visual scanning patterns. Current techniques in this field are largely comprised of non-generalizable methodologies that rely on domain expertise and study-specific assumptions. In this paper, we present a general, data-driven, end-to-end framework that extracts relevant features of attentional bias from visual scanning behaviour and uses these features to classify between subject groups with standard machine learning techniques. The general framework uses visual scanning data from free-viewing tasks. In these tasks, subjects look at sets of slides with several thematic images while their visual scanning patterns (sets of ordered fixations) are monitored by an eye-tracking system. Subjects' fixations are encoded into relative visual attention maps (RVAMs), and two data-driven methods are proposed to segment regions of interests (ROIs) from RVAMs: 1) using group average RVAMs, and 2) using differences of group average RVAMs. Relative fixation times within the segmented ROIs are then used as input features for a vanilla multilayered perceptron to classify between patient groups. The methods were evaluated on data from two studies: an anorexia nervosa (AN)/healthy controls study (AN study) with 37 subjects, and a bipolar disorder (BD)/major depressive disorder (MDD) study (BD-MDD study) with 73 subjects. Using leave-one-subject-out cross validation, the general methods achieved an area under the receiver operating curve (AUROC) score of 0.935 for the AN study and 0.888 for the BD-MDD study, the latter of which exceeds the performance of the state-of-the-art analysis model designed specifically for the BD-MDD study, which had an AUROC of 0.879. The results validate the proposed framework's efficacy as a generalizable, standard baseline for analyzing visual scanning data.

The aim of this study was to build a prediction model for epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma. A retrospective analysis was performed on 88 patients with lung adenocarcinoma. All patients underwent an 18F-FDG PET/CT scan and genetic testing of EGFR before the treatment. In the training set, the radiomics features and clinical factors were screened out, and model1 based on CT radiomics features, model2 based on PET radiomics features, model3 based on clinical factors, and model4 based on radiomics features combined with clinical factors were established, respectively. The performance of the prediction model was assessed by area under the receiver operating characteristic (ROC) curve (AUC). The DeLong test was used to compare the performance of the models to screen out the optimal model, and then built the nomogram of the optimal model. The effect and clinical utility of the nomogram was verified in the validation cohort. In our analysis, model4 was superior to the other prediction models in identifying EGFR mutations. The AUC was 0.864 (95% CI: 0.777-0.950), with a sensitivity of 0.714 and a specificity of 0.784. The nomogram of model4 was established. In the validation cohort, the concordance index (C-index) value of the calibration curve of the nomogram model was 0.841 (95% CI: 0.677-1.005), and the nomogram had a good clinical utility. We demonstrated that the model based on 18F-FDG PET/CT radiomics features combined with clinical factors could predict EGFR mutations in lung adenocarcinoma, which was expected to be an important supplement to molecular diagnosis.

Competition within the energy generation industry provides an incentive for developers to build offshore wind farms with a low levelised cost of energy. Therefore, there is a need for design optimisation to reduce costs and increase energy capture. A sequential approach to optimise turbine placement and cable layout is presented, using a heuristic k-opt algorithm and mixed-integer linear programming respectively. Energy storage is considered as a means to further improve the cable selection process. A case study is carried out on the Lillgrund offshore wind farm and the resulting layout improves energy capture by 6%. Cable costs are increased but the electrical losses are reduced such that there is an overall saving over the project lifetime of 20%. Energy storage as a means to peak shave the power seen by a cable in order to reduce electrical losses or de-rate a cable section was found to be impractically large and not profitable. Future work will consider secondary revenue streams to remedy this.

The human beta coronavirus SARS-CoV-2, causative virus of COVID-19, has infected more than 15 million people globally and continues to spread. Widespread, population level testing to detect active and past infections is critical to curb the COVID-19 pandemic. Antibody (serological) testing is the only option for detecting past infections outside the narrow window accessible to nucleic acid-based tests. However, currently available serological assays commonly lack scalability. Here, we describe the development of a rapid homogenous serological assay for the detection of antibodies to SARS-CoV-2 in patient plasma. We show that the fluorescence-based assay accurately detects seroconversion in COVID-19 patients from less than 1μL of plasma. Using a cohort of samples from COVID-19 infected or healthy individuals, we demonstrate detection with 100% sensitivity and specificity. This assay addresses an important need for a robust, low barrier to implementation, and scalable serological assay with complementary strengths to currently available serological platforms.

For the design of a bio-inspired, fish-like robot with caudal fin, a Fluid Structure Interaction (FSI) analysis has been conducted to investigate the influence of material properties and undulation kinematics on hydrodynamic performance and efficiency. This supports the design process with focus on practical prototype build up.

In this paper, automatic classification of Atrial Fibrillation (AF) based on single lead ECG signal was proposed using three different classification algorithm AdaBoost, K-Nearest Neighbors (KNN) and Support Vector Machine (SVM). SMOTE technique was applied as data oversampling techniques. Many features were extracted and Minimum Redundancy Maximum Relevance (MRMR) algorithm was used to select relevant features. 5834 records were selected from the Physionet Challenge 2017 dataset for this experiment. Classification using oversampling technique yields best results for all classifiers involved. AdaBoost on oversampling data yields the best accuracy of 98.8%.

“Blue Growth” and “Blue Economy” is defined by the World Bank as: “the sustainable use of ocean resources for economic growth, improved livelihoods and jobs, while preserving the health of ocean ecosystem”. Multi-purpose platforms (MPPs) can be defined as offshore platforms serving the needs of multiple offshore industries (energy and aquaculture), aim at exploiting the synergies and managing the tensions arising when closely co-locating systems from these industries. Despite a number of previous projects aimed at assessing, from a multidisciplinary point of view, the feasibility of multipurpose platforms, it is here shown that the state-of-the-art has focused mainly on single-purpose devices, and adopting a single discipline (either economic, or social, or technological, or environmental) approach. Therefore, the aim of the present study is to provide a multidisciplinary state of the art review on, whenever possible, multi-purpose platforms, complementing it with single-purpose and/or single discipline literature reviews when not possible. Synoptic tables are provided, giving an overview of the multi-purpose platform concepts investigated, the numerical approaches adopted, and a comprehensive snapshot classifying the references discussed by industry (offshore renewables, aquaculture, both) and by aspect (technological, environmental, socio-economic). The majority of the multi-purpose platform concepts proposed are integrating only multiple offshore renewable energy devices (e.g. hybrid wind-wave), with only few integrating also aquaculture systems. MPPs have significant potential in economizing CAPEX and operational costs for the offshore energy and aquaculture industry by means of concerted spatial planning and sharing of infrastructure.

RationaleMost of the current anti-platelet drugs inhibit platelet function permanently and have systemic side effects, including thrombocytopenia and hemorrhage. We previously found that thymidine phosphorylase (TYMP), a platelet cytoplasmic protein, facilitates multiple agonist induced platelet activation and enhances thrombosis. A specific TYMP inhibitor, namely, tipiracil hydrochloride (TPI), has been approved by the U.S. Food and Drug Administration for clinical use as an auxiliary drug making it possible to be repositioned as an anti-platelet medicine.ObjectiveWe aimed to test the hypothesis that TPI is a novel and safe anti-platelet drug by examining its role in platelet activation and thrombosis using both in vitro and in vivo studies.Methods and ResultsBy co-expression of TYMP and Lyn or Lyn-SH3 domain tagged with glutathione S-transferase, we showed the direct evidence that TYMP binds to the SH3 domain in its partners. TYMP haplodeficiency is sufficient to inhibit thrombosis in vivo regardless of gender. TPI treatment rapidly inhibited collagen- and ADP-induced platelet aggregation, which copied the phenotype of TYMP deficient platelets. Under both normal and hyperlipidemic conditions, treating wild type (WT) mice with TPI via intraperitoneal injection, intravenous injection, or gavage feeding dramatically inhibited thrombosis without inducing significant bleeding. Even administered above the effective dose, TPI has a lower bleeding side effect compared to aspirin and clopidogrel. Most importantly, intravenously delivery of TPI alone or combined with tissue plasminogen activator dramatically inhibited the growth of developing thrombi. Dual administration of very low dose of aspirin and TPI also dramatically inhibited thrombosis without disturbing hemostasis.ConclusionThis pharmacological study demonstrated that TYMP participates in multiple signaling pathways in platelet and plays a mechanistic role in regulating platelet activation and thrombosis. TPI, a specific TYMP inhibitor, would be a novel safe anti-platelet and anti-thrombosis medicine.

Background Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an extremely rare monogenic autosomal disease associated with the HtrA serine protease 1 (HTRA 1) gene mutation. Recently, a few genetically confirmed CARASIL cases with novel HTRA1 mutations have been reported in countries other than Japan. Case Description Here, we report a case of a patient presenting with worsening right hemiplegia and hemiparesthesia. Physical examination revealed that the patient had typical clinical features of CARASIL including thinning hair, cognitive impairment, emotional changes, lumbago, and gait disorder. Brain magnetic resonance imaging showed abnormal diffuse symmetric changes in white matter and hypertensive diffusion-weighted imaging signals in the left centrum ovale and right splenium of the corpus callosum, and susceptibility-weighted imaging showed multiple cerebral microbleeds. Lumbar magnetic resonance imaging showed herniated disks with degenerative changes. A genetic test showed a novel homozygous nucleotide variation of c.847G>T in the HTRA1 gene, thereby resulting in p.Gly283Ter. Thus the patient met the diagnostic criteria for CARASIL. We provide a literature review of genetically confirmed CARASIL cases reported to date. Conclusions CARASIL is a rare autosomal recessive disease with an HTRA1 mutation. Familiarity with the early clinical and imaging features of CARASIL combined with a genetic test is key for its early diagnosis.

PurposeTo test the reliability and validity of the Chinese version of the Cancer Stigma Scale (CASS).MethodsAfter translation, back-translation and cross-cultural adaptation of the CASS into Chinese (C-CASS), a random online survey of the general population in China was conducted. Reliability was analyzed by internal consistency (Cronbach’s α) and construct validity was analyzed by confirmatory factor analysis. The C-CASS was evaluated in a sample of 382 non-cancer patients through online format.ResultsThe study found that the C-CASS had satisfactory internal reliability (Cronbach’s α of the overall scale and six components was 0.88 and 0.70–0.89, respectively). Confirmatory factor analysis confirmed the six-factor structure (χ2/df = 2.2, GFI = 0.91, CFI = 0.94, RMSEA = 0.056, SRMR = 0.065). Younger individuals and those who had less knowledge of cancer showed more negative attitudes towards cancer.ConclusionThe C-CASS had adequate internal consistency, reliability and indices of model fit, allowing its feasible use to assess levels of cancer stigma in Chinese populations.

Purpose Esophageal carcinoma (EC) is one of the most aggressive type cancers and dysregulation of retinoid X receptor α (RXRα) involves various tumors. However, the relationship of RXRα with the clinicopathological factors of EC, particularly prognostic characteristics, remains unclear. This present study was to evaluate the effect of RXRα expression in the development of EC. Methods The mRNA and protein expression level of RXRα in EC and normal esophageal tissues using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The subcellular localization was detected by immunohistochemistry (IHC) analysis. The clinicopathological parameters were included age, sex, tumor size, differentiation, TNM stages and lymph node metastasis. Kaplan-Meier method and Cox's regression analyses were performed to evaluate the prognosis of 60 patients with EC. Results RXRα was elevated in EC tissues comparing with normal esophageal tissues at both mRNA and protein levels. The overexpression level of RXRα was closely associated to the tumor differentiation, TNM stage and lymph node metastasis of patients with EC. In addition, EC patients with RXRα high expression had significantly lower disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed RXRα expression as an independent predictor for the DFS and OS rate of patients with EC. Conclusions Our results showed that overexpression of RXRα was correlated with unfavorable prognosis, suggesting that RXRα may serve as a potential targeted therapeutic marker in the treatment of EC.

A gain-scheduled feedforward controller, based on pseudo-LIDAR (light detection and ranging) wind speed measurement, is designed to augment the baseline feedback controller for wind turbine′s load reduction in above rated operation. The pseudo-LIDAR measurement data are generated from a commercial software – Bladed using a designed sampling strategy. The nonlinear wind turbine model has been simplified and linearised at a set of equilibrium operating points. The feedforward controller is firstly developed based on a linearised model at an above rated wind speed, and then expanded to the full above rated operational envelope by employing gain scheduling strategy. The combined feedforward and baseline feedback control is simulated on a 5 MW industrial wind turbine model. Simulation studies demonstrate that the proposed control strategy can improve the rotor and tower load reduction performance for large wind turbines.

Blockage is a common problem for microreactors, and the blockage degree directly affects the removing operation. In this work, the blockage degree is first defined as the ratio of the blocking volume over the volume of mixing channel based on computational fluid dynamics (CFD) models of different blockage types. After analyzing the limitation of this standard index, a new blockage index is proposed, in which the blocking volume, the cross-sectional area and the roughness of the blocking body are all taken into account. The relationship between the pressure difference and the new index is obtained through regression of CFD data to determine the blocking degree. Meanwhile, the classification of the removing blockage is also defined. The smaller the blockage index value is, the more difficult it is to remove the blockage. A inlet angle is introduced as a new design factor in choosing removing options.

For locally advanced rectal cancer patients, introducing neoadjuvant concurrent chemoradiotherapy (CCRT) before radical resection allows tumor downstaging and increases the rate of anus retention. Since accurate staging before surgery and sensitivity prediction to CCRT remain challenging, a more precise genetic biomarker is urgently needed to enhance the management of such situations. The epithelial mucous barrier can protect the gut lumen, but aberrant mucin synthesis may defend against drug penetration. In this study, we focused on genes related to maintenance of gastrointestinal epithelium (GO: 0030277) and identified mucin 2 (MUC2) as the most significantly upregulated gene correlated with CCRT resistance through a public rectal cancer transcriptome dataset (GSE35452). We retrieved 172 records of rectal cancer patients undergoing CCRT accompanied by radical resection from our biobank. We also assessed the expression level of MUC2 using immunohistochemistry. The results showed that upregulated MUC2 immunoexpression was considerably correlated with the pre-CCRT and post-CCRT positive nodal status (p = 0.001 and p &lt, 0.001), advanced pre-CCRT and post-CCRT tumor status (p = 0.022 and p &lt, 0.001), vascular invasion (p = 0.015), and no or little response to CCRT (p = 0.006). Upregulated MUC2 immunoexpression was adversely prognostic for all three endpoints, disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) (all p &lt, 0.0001), at the univariate level. Moreover, upregulated MUC2 immunoexpression was an independent prognostic factor for worse DSS (p &lt, 0.001), LRFS (p = 0.008), and MeFS (p = 0.003) at the multivariate level. Collectively, these results imply that upregulated MUC2 expression is characterized by a more advanced clinical course and treatment resistance in rectal cancer patients undergoing CCRT, revealing the potential prognostic utility of MUC2 expression.

The introduction of preoperative concurrent chemoradiotherapy (CCRT) increases the rate of anal preservation and allows tumor downstaging for clinical stage T3/T4 or node-positive rectal cancer patients. However, there is no precise predictive tool to verify the presence of residual tumor apart from surgical resection. The gastrointestinal (GI) tract not only digests nutrients but also coordinates immune responses. As the outermost layer of the GI tract, mucus plays a key role in mediating the interaction between the digestive and immune systems, and aberrant mucus mesh formation may cause chemoresistance by impeding drug delivery. However, the correlations among digestion-related genes, mucin synthesis, and chemoresistance remain poorly understood. In the present study, we evaluated genes related to digestion (GO: 0007586) and identified cathepsin E (CTSE), which is involved in immune regulation, as the most significantly upregulated gene associated with CCRT resistance in rectal cancer in a public transcriptome dataset (GSE35452). We recovered 172 records of rectal cancer patients receiving CCRT followed by surgical resection from our biobank and evaluated the expression level of CTSE using immunohistochemistry. The results revealed that tumors with CTSE overexpression were significantly correlated with pre-CCRT and post-CCRT positive nodal status (both p &lt, 0.001), advanced pre-CCRT and post-CCRT tumor status (p &lt, 0.001 and p = 0.002), perineural invasion (p = 0.023), vascular invasion (p &lt, 0.001), and a lesser degree of tumor regression (p = 0.003). At the univariate level, CTSE overexpression was an adverse prognostic factor for all three endpoints: disease-specific survival (DSS), metastasis-free survival (MeFS) (both p &lt, 0.0001), and local recurrence-free survival (LRFS) (p = 0.0001). At the multivariate level, CTSE overexpression remained an independent prognostic factor for poor DSS, MeFS (both p = 0.005), and LRFS (p = 0.019). Through bioinformatics analysis, we speculated that CTSE overexpression may confer CCRT resistance by forming a defensive mucous barrier. Taken together, these results suggest that CTSE overexpression is related to CCRT resistance and inferior survival in rectal cancer patients, highlighting the potential predictive and prognostic value of CTSE expression.

Modelling and performance analysis of wind turbine control systems with aeroelastic tailoring blades (ATBs) are investigated. An industrial scale horizontal axis wind turbine (HAWT) model with rigid blades is firstly developed as the baseline model using the blade element momentum (BEM) theory. Designed twist angle variation distributions along blades are then introduced to the baseline model to characterise the ATB nature. The developed ATB wind turbine models are analysed by employing a baseline control system. The performances of the ATB wind turbine systems are compared with that of the baseline turbine using both nonlinear models and linearised models at selected wind speeds. The impacts of ATB design can be clearly observed from the simulation studies. Preliminary results suggest that with ATB design in wind turbines, the blade fatigue loads and the pitching activities can be reduced for large turbines without compromising the energy capture performance.

The intermittency and fluctuations of wind power cause problems in integration of wind energy systems into the grid. To smooth the fluctuations of wind power, a control scheme based on fuzzy empirical mode decomposition (EMD) is proposed with the use of battery energy storage system (BESS). With this idea, the wind power signal is decomposed via EMD and filtered into two parts: the low-frequency part is taken as the target smooth wind power for grid connection, and the high-frequency part is stored by BESS before connecting to the grid to compensate for the fluctuations in the original wind power signal. A fuzzy EMD filter is developed by considering constraints on both the power fluctuation rate and the state of charge (SOC) of the BESS. The performance of the proposed strategy has been examined through case study simulations, which demonstrates improvement in mitigating wind power fluctuations and also in reducing over charging/discharging operations of the integrated BESS.

// Bo Yu 1, 2, * , Qiong Du 1, 2, * , Huan Li 1, 2 , Hong-Yue Liu 1, 2 , Xuan Ye 1, 2 , Bin Zhu 1, 2 , Qing Zhai 1, 2 and Xin-Xiang Li 1, 3 1 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 2 Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, China 3 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China * These authors contributed equally to this work Correspondence to: Qing Zhai, email: zhaiqing63@126.com Xin-Xiang Li, email: lxx1149@163.com Keywords: colorectal carcinoma, exosome, CRNDE-p, miR-217 Received: March 01, 2017 Accepted: July 12, 2017 Published: July 20, 2017 ABSTRACT In this study, we investigated the diagnostic potential of serum exosomal colorectal neoplasia differentially expressed (CRNDE-p) long coding RNA and microRNA-217 in colorectal carcinoma (CRC). We detected high CRNDE-p and low miR-217 levels in exosomes released by multiple CRC cell lines into culture media as well as in sera from CRC xenograft mice and CRC patients. Conversely, we observed lower CRNDE-p and higher miR-217 levels in serum exosomes from post-chemotherapy than from pre-chemotherapy patient samples. The area under curve (AUC) value for the serum exosomal CRNDE-p and miR-217 combination was higher than CRNDE-p or miR-217 alone. Moreover, high CRNDE-p and low miR-217 serum exosomal levels correlated with advanced clinical stages (III/IV), tumor classification (T3/T4), and lymph node or distant metastasis. Thus combined evaluation of serum exosomal CRNDE-p and miR-217 levels show diagnostic and prognostic potential for CRC patients.

// Hsin-Hwa Tsai 1, * , Hong-Yue Lai 2, * , Yueh-Chiu Chen 3, * , Chien-Feng Li 4 , Huei-Sheng Huang 5 , Hsiao-Sheng Liu 6 , Yau-Sheng Tsai 7 , Ju-Ming Wang 1, 8 1 Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan 2 Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan 3 Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan 4 Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan 5 Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan 6 Department of Microbiology and Immunology, National Cheng Kung University, Tainan, Taiwan 7 Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan 8 Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan * The authors contributed equally to this work Correspondence to: Ju-Ming Wang, email: yumingw@mail.ncku.edu.tw Keywords: HCC, autophagy, apoptosis, CEBPD, metformin Received: May 30, 2016 Accepted: January 04, 2017 Published: January 13, 2017 ABSTRACT Metformin, as an AMP-activated protein kinase (AMPK) activator, can activate autophagy. A study showed that metformin decreased the risk of hepatocellular carcinoma (HCC) in diabetic patients. However, the detailed mechanism in the metformin-mediated anticancer effect remains an open question. Transcription factor CCAAT/enhancer-binding protein delta (CEBPD) has been suggested to serve as a tumor suppressor and is responsive to multiple anticancer drugs in HCC. In this study, we found that CEBPD and autophagy are involved in metformin-induced cell apoptosis in Huh7 cells. The underlying mechanisms in this process included a reduction in Src-mediated CEBPD protein degradation and an increase in CEBPD-regulated LC3B and ATG3 gene transcription under metformin treatment. We also found that AMPK is involved in metformin-induced CEBPD expression. Combined treatment with metformin and rapamycin can enhance autophagic cell death through the AMPK-dependent and AMPK-independent pathway, respectively. Taken together, we provide a new insight and therapeutic approach by targeting autophagy in the treatment of HCC.

Objective. To compareT2⁎value of healthy and diseased Achilles tendons (AT) with a recently introduced three-dimensional ultrashort echo time (3D-UTE) sequence and analyze the correlation betweenT2⁎value and clinical scores.Methods. Ten patients with symptomatic Achilles tendon and ten healthy volunteers were investigated with 3D-UTE sequence on a 3T magnetic resonance (MR) scanner.T2⁎values of four regions in Achilles tendons were calculated. The clinical outcomes of patients were evaluated according to the American Orthopaedic Foot and Ankle Society (AOFAS) score and Achilles Tendon Rupture Score (ATRS). An independent samplet-test was used to compare the differences ofT2⁎value and clinical scores between two groups. The Pearson correlation coefficient between clinical scores andT2⁎values was assessed.Results. TheT2⁎values of Achilles tendon were statistically significantly different between patients and volunteers. The Pearson correlation coefficients betweenT2⁎and AOFAS or ATRS scores of patients werer=-0.733andr=-0.634, respectively.Conclusion. The variability ofT2⁎in healthy and pathologic AT can be quantified by UTE-T2⁎.T2⁎may be a promising marker to detect and diagnose AT tendinopathy. UTE-T2⁎could give a precise guidance to clinical outcome.

Tissue reinforcement with acellular dermal matrix (ADM) in implant-based breast reconstruction contributes to the coverage of the implant and avoids its direct exposure to skin incision, yet not without risk of infection. Our integrated technique makes use of the in situ serratus anterior fascia as a support of the implant following mastectomy, which serves the same purpose of ADM in terms of aesthetic outcomes, but minimizes the hazard of infective complications. We retrospectively reviewed all the nipple-sparing mastectomies with direct-to-implant immediate reconstruction in Hong Kong Sanatorium and Hospital from 2012 to 2016. The authors made use of the serratus anterior fascial flap as inferolateral coverage for the subpectoral implant. Consequently, the implant would be completely covered by autologous tissues. Among the 51 women included, primary breast cancers account for 91.8% of our indications for these 61 procedures of integrated mastectomy and implant reconstruction. The remaining five (8.2%) were performed as contralateral prophylactic mastectomy. Almost three quarters of the patients had a bra cup size of B or below. After a mean follow-up of 28.9 months, there was no reported post-operative complication of skin flap or nipple–areolar complex necrosis, or infection or extrusion of the implant. Our series support that the serratus anterior fascial flap could provide autologous coverage in integrated mastectomy and implant breast reconstruction, especially in small- and medium-sized breasts. Appropriate patient selection, as well as meticulous surgical technique, is critical for its success.