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cFLIP, a master anti-apoptotic regulator, targets the FADD-induced DED complexes of procaspase-8 in death receptor and ripoptosome signaling pathways. Several tumor cells maintain relatively high levels of cFLIP in achieving their immortality. However, understanding the three-dimensional regulatory mechanism initiated or mediated by elevated levels of cFLIP has been limited by the absence of the atomic coordinates for cFLIP-induced DED complexes. Here we report the crystal plus cryo-EM structures to uncover an unconventional mechanism where cFLIP and procaspase-8 autonomously form a binary tandem DED complex, independent of FADD. This complex gains the ability to recruit FADD, thereby allosterically modulating cFLIP assembly and partially activating caspase-8 for RIPK1 cleavage. Our structure-guided mutagenesis experiments provide critical insights into these regulatory mechanisms, elucidating the resistance to apoptosis and necroptosis in achieving immortality. Finally, this research offers a unified model for the intricate bidirectional hierarchy-based processes using multiprotein helical assembly to govern cell fate decisions., (© 2024. The Author(s).)

Objective: To report the efficacy and safety of a drug-coated balloon (Ranger, Boston Scientific) in patients with dysfunctional autogenous arteriovenous fistula., Methods: In this investigator-initiated, prospective observational cohort study, 25 participants with dysfunctional arteriovenous fistula were enrolled from January 2018 to June 2019. The drug-coated balloon was applied after successful vessel preparation by high-pressure balloon angioplasty. The primary endpoint was the target lesion primary patency rate at 6 months. The secondary outcome included anatomical and clinical success rate, postoperative major adverse events within 30 days, and the target lesion primary patency rate at 12 months. Statistical analysis of the data was performed. The χ test or Fisher's exact test was used for analyzing categorical variables, and continuous variables were analyzed using Student's t -test. Also, Kaplan-Meier analysis was used to evaluate the target lesion primary patency days with the log-rank test., Results: At 6 months, the target lesion primary patency rate was 68% in the drug-coated balloon treatment group. The anatomical and clinical success rates were 100%. One patient had thrombosed access 10 days after the index procedure, and two died of cardiovascular events 4 months after the operation. Subgroup analysis showed that the early recurrent stenosis group had non-inferior mean drug-coated balloon primary patency days (less than 90 days after prior percutaneous angioplasty, n  = 10) compared with the late recurrence group (prior PTA patency days more than 90 days, n  = 10), 179.3 ± 102.9 versus 257.1 ± 71 days ( p  = 0.153). DCB angioplasty had significant improvement in primary patency days for early recurrent stenosis (67.7 ± 19.3 vs 179.3 ± 102.9, p  < 0.001)., Conclusions: The results demonstrated the appliance of Ranger DCB in stenotic AVFs is a safe and effective treatment modality, especially for early recurrent AVF stenosis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In recent years, with the increasing demand for high-quality images in various fields, more and more attention has been focused on noise removal techniques for image processing. The effective elimination of unwanted noise plays a crucial role in improving image quality. To meet this challenge, many noise removal methods have been proposed, among which the diffusion model has become one of the focuses of many researchers. In order to make the restored image closer to the real image and retain more features of the image, this paper proposes a DIR-SDE method with reference to the diffusion models of IR-SDE and IDM, which improve the feature retention of the image in the de-raining process, and then improve the realism of the image for the image de-raining task. In this study, IR-SDE was used as the base structure of the diffusion model, IR-SDE was improved, and DINO-ViT was combined to enhance the image features. During the diffusion process, the image features were extracted using DINO-ViT, and these features were fused with the original images to enhance the learning effect of the model. The model was also trained and validated with the Rain100H dataset. Compared with the IR-SDE method, it improved 0.003 in the SSIM, 0.003 in the LPIPS, and 1.23 in the FID. The experimental results show that the diffusion model proposed in this study can effectively improve the image restoration performance.

Fas-associated protein with death domain (FADD), procaspase-8, and cellular FLICE-inhibitory proteins (cFLIP) assemble through death-effector domains (DEDs), directing death receptor signaling towards cell survival or apoptosis. Understanding their three-dimensional regulatory mechanism has been limited by the absence of atomic coordinates for their ternary DED complex. By employing X-ray crystallography and cryogenic electron microscopy (cryo-EM), we present the atomic coordinates of human FADD-procaspase-8-cFLIP complexes, revealing structural insights into these critical interactions. These structures illustrate how FADD and cFLIP orchestrate the assembly of caspase-8-containing complexes and offer mechanistic explanations for their role in promoting or inhibiting apoptotic and necroptotic signaling. A helical procaspase-8-cFLIP hetero-double layer in the complex appears to promote limited caspase-8 activation for cell survival. Our structure-guided mutagenesis supports the role of the triple-FADD complex in caspase-8 activation and in regulating receptor-interacting protein kinase 1 (RIPK1). These results propose a unified mechanism for DED assembly and procaspase-8 activation in the regulation of apoptotic and necroptotic signaling across various cellular pathways involved in development, innate immunity, and disease., (© 2024. The Author(s).)

Introduction: Early detection and treatment of sepsis improves chances of survival; however, sepsis is often difficult to diagnose initially. This is especially true in the prehospital setting, where resources are scarce, yet time is of great significance. Early warning scores (EWS) based on vital signs were originally developed to guide medical practitioners in determining the degree of illness of a patient in the in-patient setting. These EWS were adapted for use in the prehospital setting to predict critical illness and sepsis. We performed a scoping review to evaluate the existing evidence for use of validated EWS to identify prehospital sepsis., Methods: We performed a systematic search using the CINAHL, Embase, Ovid-MEDLINE, and PubMed databases on September 1, 2022. Articles that examined the use of EWS to identify prehospital sepsis were included and assessed., Results: Twenty-three studies were included in this review: one validation study, two prospective studies, two systematic reviews, and 18 retrospective studies. Study characteristics, classification statistics, and primary conclusions of each article were extracted and tabulated. Classification statistics varied markedly for prehospital sepsis identification across all included EWS: sensitivities ranged from 0.02-1.00, specificities from 0.07-1.00, and PPV and NPV from 0.19-0.98 and 0.32-1.00, respectively., Conclusions: All studies demonstrated inconsistency for the identification of prehospital sepsis. The variety of available EWS and study design heterogeneity suggest it is unlikely that new research can identify a single gold standard score. Based on our findings in this scoping review, we recommend future efforts focus on combining standardized prehospital care with clinical judgment to provide timely interventions for unstable patients where infection is considered a likely etiology, in addition to improving sepsis education for prehospital clinicians. At most, EWS can be used as an adjunct to these efforts, but they should not be relied on alone for prehospital sepsis identification.

Background: Depression is a common mental disorder that significantly contributes to the global burden of disease. Studies have consistently reported that migrant workers experience higher levels of depressive symptoms, especially women., Aims: This study aimed to examine the mediation role of sexual self-efficacy on the relationship between psychological wellbeing, and depressive symptoms among young female migrant workers in Vietnam's industrial zones., Methods: A cross-sectional study was conducted among 1061 female migrant workers aged 18 to 29 from January to November 2020 in Hanoi, Vietnam. Anonymous interview questionnaires were used to collect data on demographic characteristics, psychosocial wellbeing (PWB), sexual self-efficacy, and depressive symptoms. Mediation analysis was conducted to explore the mediation effect of sexual self-efficacy on the relationship between PWB and depressive symptoms., Results: Nearly 8% of the female migrant workers reported experiencing depressive symptoms. The final mediation model showed that the effect of overall psychological wellbeing on depressive symptoms was partially mediated by sexual self-efficacy. Specifically, 4.1% of the effect of overall PWB on depressive symptoms was mediated through sexual self-efficacy. In the PWB subdimension analyses, sexual self-efficacy mediated 14.3% of the effect of personal growth, 8.8% of the effect of purpose in life, 8.0% of the effect of autonomy, and 7.8% of the effect of environmental mastery on depressive symptoms, respectively., Conclusion: The study findings demonstrate that sexual self-efficacy plays an important role in the relationship between psychosocial wellbeing and depressive symptoms among female migrant workers in industrial zones in Vietnam. Improving psychosocial wellbeing and promoting sexual health including sexual self-efficacy should be prioritized when addressing depressive symptoms and mental health concerns among industrial zone female migrant workers in Vietnam, which may also be applicable in other low- and middle-income countries with similar socio-cultural settings.

Introduction: Balloon angioplasty maturation (BAM) is a salvage method for autologous arteriovenous fistula (AVF) maturation failure. AVF creation using small-diameter veins is considered to have poor outcomes. Therefore, this study aimed to explore the long-term patency of small-diameter veins (≤3 mm) using BAM., Methods: BAM was performed if the fistula failed to mature and function adequately to provide prescribed dialysis., Findings: Out of 61 AVFs, 22 AVFs successfully matured without further intervention (AVF group) and 39 AVFs failed to mature. Except for 1 patient who required peritoneal dialysis, the remaining 38 patients received salvage BAM, and 36 of those successful matured (BAM group). Kaplan-Meier analysis revealed no significant differences between the AVF and BAM groups in terms of primary functional patency (p = 0.503) and assisted functional patency (p = 0.499). Compared with the AVF group, the BAM group had similar assisted primary functional patency (1-year: 94.7% vs. 93.1%; 3-year: 88.0% vs. 93.1%; 5-year: 79.2% vs. 88.3%). In addition, there were no significant difference between groups in the duration of primary functional patency and assisted primary functional patency (p > 0.05). Multivariate analyses showed that vein diameter and number of BAM procedures were independent predictors of primary functional patency in the AVF group and BAM group, respectively. Patient with 1 mm increase in vein size had 0.13-fold probability of having decreased duration of patency (HR = 0.13, 95% CI: 0.02-0.99, p = 0.049), while patients who received two times of BAM procedures were 2.885 as likely to have decreased duration of primary functional patency (HR = 2.885, 95% CI: 1.09-7.63, p = 0.033) than patients who received one BAM procedure., Discussion: BAM is a relatively effective salvage management option with an acceptable long-term patency rate, even for small cephalic veins., (© 2023 International Society for Hemodialysis.)

Objective: Balloon-assisted maturation (BAM) by an endovascular method plays an important role in treating an immature arteriovenous fistula. However, the results between radiocephalic fistula and brachiocephalic fistula were rarely reported. This retrospective study aimed to investigate the effectiveness and outcome of BAM in different sites of autogenous arteriovenous fistulas., Methods: This single-center retrospective study included patients who underwent BAM procedures from January 2015 to December 2016. Of 148 patients, 117 and 31 patients had a radiocephalic fistula (RC) and a brachiocephalic fistula (BC), respectively. The primary outcome was BAM success. Data regarding fistula lesions, balloon types and size, frequency of procedures, and maturation time were collected for BAMs. The secondary outcome was the patency of a fistula in the follow-up period., Results: No difference was observed in procedure of BAM frequency between the RC and BC groups. The total success rate was 77.7%, without significant difference between the RC and BC groups (81.20% vs 64.50%; P = .055). Within the procedures, the culprit lesion of juxta-anastomosis segment (73.5% vs 25.5%; P < .001) and arterial inlet (21.2% vs 7.8%; P = .04) were more common in the RC group, whereas the venous outlet was more common in the BC group (88.2% vs 57.7%; P < .001). Both groups had an equivalent patency rate after the BAM within the follow-up period (P = .272)., Conclusions: BAM was an effective procedure for immature fistulas, without significant difference between RCs and BCs. Through the procedure, the culprit lesions causing non-maturation were found to be different between the two groups. The patency rate between the two groups after surgery seems to be equivalent within the follow-up period., (Copyright © 2022. Published by Elsevier Inc.)

Background & Aims: Primary hyperparathyroidism(PHPT) has been evolving into a milder asymptomatic disease. No study has assessed the association between famine exposure and such a shift. We aim to explore the effects of China's Great Famine exposure on the changing pattern of PHPT phenotypes., Methods: 750 PHPT patients diagnosed from 2000 to 2019 were studied. The clinical presentations were compared between them in recent 10 years (2010-2019) and previous 10 years (2000-2009). Participants were then categorized into fetal, childhood, adolescent, adult exposure, and unexposed groups. Logistic regression was used to estimate the odds ratios (ORs) and confidence intervals (CIs) of famine exposure as factors contributing to the changes in the clinical presentations of PHPT., Results: Serum levels of PTH, albumin-corrected Ca, tumor size, eGFR, BMDs (all P<0.001), and clinical symptoms became milder in recent 10 years. Famine exposure (72.6% vs 58.4%, P<0.001), especially the adult exposure (18.8% vs 4.1%, P<0.001)was significant less in recent 10 years. The ORs (95%CIs) of having upper 3 rd tertile PTH were 2.79(1.34,5.8), 2.07(1.04,4.11), 3.10(1.15,8.38) and 8.85(2.56,30.56) for patients with fetal, childhood, adolescent and adult famine exposure, respectively. The ORs (95%CIs) of upper 3 rd tertile albumin-corrected Ca and upper 3 rd tertile of tumor size was 4.78(1.39, 16.38) and 4.07(1.12,14.84) for participants with adult famine exposure, respectively. All these associations were independent of age, sex, disease duration and other confounders., Conclusions: The clinical manifestations of PHPT in China continue to be milder. Exposure to famine is associated with PHPT. Less famine exposure might be responsible for the mile form of PHPT in recent years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yuan, Yang, Zhu, He, Zhao, Zhou, Su, Zhao, Sun, Tao and Liu.)

Objective: May-Thurner syndrome (MTS) is an anatomic stenotic variation associated with deep vein thrombosis (DVT) of the left leg. The classical DVT treatment strategy is medical treatment without thrombus removal. This study was performed to assess the clinical outcomes of the combination of AngioJet™ rheolytic thrombectomy and stenting for treatment of MTS-related DVT., Methods: We conducted a retrospective cohort study of patients treated for MTS-related DVT from January 2017 to June 2020 at a single institution., Results: Fourteen patients (nine women) underwent AngioJet™ rheolytic thrombectomy for MTS-related DVT during the study period. The median DVT onset time was 8 days (interquartile range (IQR), 3-21 days). The median procedure time was 130 minutes (IQR, 91-189 minutes), and the median hospital stay was 7 days (IQR, 5-26 days). One patient had a residual thrombus and occluded iliac stent and underwent adjuvant catheter-directed thrombolysis for revascularization. The primary patency rate for the iliac stent was 92.9% at 12 months., Conclusion: Concomitant AngioJet™ rheolytic thrombectomy and stenting of MTS-induced lesions may be beneficial for patients with MTS-related DVT.

The efficacy of dual antiplatelet therapy (DAPT) for patients with peripheral artery disease (PAD) after lower-limb intervention remains controversial. Currently, the prescription of DAPT after an intervention is not fully recommended in guidelines due to limited evidence. This study compares and analyzes the prognosis for symptomatic PAD patients receiving DAPT versus monotherapy after lower-limb revascularization. Up to November 2021, PubMed/MEDLINE, Embase, and Cochrane databases were searched to identify studies reporting the efficacy, duration, and bleeding complications when either DAPT or monotherapy were used to treat PAD patients after revascularization. Three randomized controlled trials and seven nonrandomized controlled trials were included in our study. In total, 74,651 patients made up these ten studies. DAPT in PAD patients after intervention was associated with lower rates of all-cause mortality (HR = 0.86; 95% CI, 0.79−0.94; p < 0.01), major adverse limb events (HR = 0.60; 95% CI, 0.47−0.78; p < 0.01), and major amputation (HR = 0.78; 95% CI, 0.64−0.96) when follow-up was for more than 1-year. DAPT was not associated with major bleeding events when compared with monotherapy (OR = 1.22; 95% CI, 0.69−2.18; p = 0.50) but was associated with a higher rate of minor bleeding as a complication (OR = 2.54; 95% CI, 1.59−4.08; p < 0.01). More prospective randomized studies are needed to provide further solid evidence regarding the important issue of prescribing DAPT.

Background: To compare the tunnel transposition and elevation transposition methods used for superficialization of the basilic vein in terms of complication and patency rates., Methods: This retrospective study included patients who underwent 2-stage basilic vein transposition between August 2016 and December 2019. Patients were categorized into brachial-basilic fistula tunnel transposition (n = 32) and elevation transposition (n = 21) groups using medical records. Primary patency was defined as a conduit that remains patent without any re-intervention to maintain patency. Primary assisted patency was defined as a conduit that has undergone intervention to maintain patency but has never been thrombosed., Results: The distribution of baseline characteristics was similar between the 2 groups. Coronary artery disease was the only variable that was significantly different between the tunnel transposition and elevation transposition groups (31.1% vs. 4.8%, P = 0.035). The tunnel transposition group had a greater amount of blood loss (P < 0.001) and a longer period of hospitalization (P = 0.002) than the elevation transposition group. The rates of suture repair to stop bleeding from the conduit was significantly different between the tunnel transposition and elevation transposition groups (31.8% vs. 4.8%, P = 0.035), whereas those of other complications were not significantly different. The elevation transposition group had a significantly higher primary patency rate than the tunneled transposition group (P = 0.033); however, primary assisted patency was achieved in all patients (100%) in both groups., Conclusion: Elevation transposition might be a more reliable method than tunnel transposition for superficialization of a basilic venous fistula., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: Recent studies have proposed associations between systemic sclerosis (SSc) and atherosclerosis and between SSc and cardiovascular disease. However, in Asia, no large-scale studies have focused on the association between peripheral arterial disease (PAD) and SSc., Setting: A nationwide observation retrospective cohort study., Participants: The National Health Insurance Research Database was used for selecting patients diagnosed with SSc from 2000 to 2011. Patients diagnosed with PAD before the index date were excluded., Primary and Secondary Outcome Measures: The SSc cohort comprised 1106 patients with SSc, and the non-SSc cohort comprised 4424 matched controls. The Cox proportional hazards regression model was used for analysing the adjusted risk of PAD between the case and control patients., Results: The SSc cohort exhibited a significantly higher risk (HR=2.15, 95% CI=1.47 to 3.14) of PAD than did the non-SSc cohort. Patients with heart failure exhibited the highest risk of PAD (adjusted HR=2.10, 95% CI=1.20 to 3.70). Moreover, even without any comorbidities, the SSc cohort exhibited a significantly higher risk (adjusted HR=4.17 fold, 95% CI=1.98 to 8.77) of PAD than did the non-SSc cohort., Conclusion: SSc is associated with a significantly high risk of PAD. Further studies are required to reduce the PAD risk among patients with SSc., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the short-term outcome of totally percutaneous endovascular aortic repair (pEVAR) of ruptured abdominal aortic aneurysms (AAAs) compared with femoral cut-down endovascular aortic repair (cEVAR)., Materials and Methods: The medical records of patients with ruptured AAAs that underwent EVAR between March 2010 and April 2017 were retrospectively reviewed. Demographic information, preoperative vital signs, preoperative laboratory data, method of anesthesia, procedure duration, aneurysm morphology, brand of device used, length of hospital stay, access complications, and short-term outcomes were recorded. Univariate as well as multivariate logistic regression was used to identify predictors of 30-day mortality., Results: Among 77 patients with ruptured AAAs, 17 (22.1%) received cEVAR and 60 (77.9%) received pEVAR. Significant differences in the procedure time (P = 0.004), method of anesthesia (P = 0.040), and 30-day mortality (P = 0.037) were detected between the cEVAR and pEVAR groups. Local anesthesia plus intravenous general anesthesia (odds ratio = 0.141, P = 0.018) was an independent factor associated with 30-day mortality and local anesthesia was better than general anesthesia for 24-hr mortality (P = 0.001) and 30-day mortality (P = 0.003)., Conclusion: In patients with ruptured AAAs, pEVAR procedures took less time than cEVAR procedures, but the length of hospital stay did not differ significantly. The 30-day mortality rate was lower with pEVAR than with cEVAR. Local anesthesia may be the key factor in EVAR to improved technical and clinical success., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the safety of outpatient percutaneous endovascular abdominal aortic repair (PEVAR) versus inpatient PEVAR without or with adjunct procedures., Materials and Methods: Between January 2012 and June 2019, a cohort of 359 patients comprising 168 (46.8%) outpatients and 191 (53.2%) inpatients who had undergone PEVAR were enrolled. All the patients were asymptomatic but had indications for endovascular aortic repair, ie, fit for intravenous anesthesia and anatomically feasible with standard devices. Patient sex, age, comorbidities, smoking status, type of anesthesia, adjunct procedures, type of graft device, operative times, mortality, complications, and readmissions were analyzed., Results: Median follow-up period was 16.5 months (interquartile range, 9-31 months). Except for a higher percentage of tobacco use (42.6% vs 28.8%; P = .04), dyslipidemia (39.7% vs 19.2%; P < .01), and use of local anesthesia (99.4% vs 82.2%; P < .01) in the outpatients, there was no significant difference in the type of graft and adjunct procedures used. No outpatient mortality occurred. There was no difference in the number, severity, and onset of complications (all P > .05). Outpatient unexpected same-day admission, 30-day readmission, and emergency department visit rates were 4.8%, 2.4% (P = .13), and 10% (P < .01), respectively. Operative times for outpatient PEVAR without adjunct procedures were shorter (P < .01)., Conclusions: Outpatient PEVAR can be performed with a safety profile similar to that of inpatient PEVAR. The unexpected same-day admission, 30-day readmission, and emergency department visit rates were low. The outpatient PEVARs without adjunct procedures took less time., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Surgical resection could be an eradication treatment for patients with infected hemodialysis arteriovenous grafts (AVGs). This study aimed to investigate the outcomes of 3 surgical methods, including total resection, subtotal resection, and revision., Methods: The patients who underwent surgical excision of infected AVGs performed at a single center from August 2012 to March 2019 were retrospectively analyzed. The following 3 surgical methods were used in our study: revision, subtotal resection, and total resection. Patients' demographics, medical history, perioperative details, reconstruction time, and follow-up data were collected. The outcomes including perioperative complications (within 30 days), mortality, reinfection rate of AVGs, with new access reconstruction or not, and the outcomes between reconstruction and nonreconstruction in the follow-up period were evaluated., Results: Forty-one patients had infected AVGs in our study. Patients' mean age was 62 years, and 65.9% of the patients were female. The mean duration from the time of diagnosis to the operation was 14.4 days. Signs and symptoms at presentation included fever (51.2 %), swelling (43.9%), pain (58.5%), erythematous change (92.7%), and more severe features, such as altered consciousness (14.6%) and hypotension (12.2%). The pathological changes in the infected grafts included bleeding (29.3%), pus formation (73.2%), pseudoaneurysm (26.8%), and graft exposure (17.1%). Wound and graft cultures revealed an infectious etiology with fungi (7.3%), Pseudomonas aeruginosa (12.2%), Enterococcus spp. (2.4%), and Staphylococcus spp. (58.5%), with methicillin-resistant Staphylococcus aureus accounting for only 7.3%. Total resection, subtotal resection, and revision surgery were performed in 17.1%, 63.4%, and 19.5% of patients, respectively. Seven patients with complications required reoperation (17.1%), and adhesion ileus and hospital-acquired pneumonia occurred in only 2.4% and 7.3% of patients, respectively. During follow-up, most patients (82.9%) had reconstruction of the peripheral hemodialysis access with mean time of 64.3 (range: 21-92) days; mean time of use of new access was 90.5 days; and mean time of removal of catheter was about 106.3 days. Mortality rates in patients without and with reconstructed AV access during follow-up were 50% and 18%, respectively (P < 0.004). Eight cases (19.5%) had recurrence of AV access infections during follow-up; of these, 2 had revision surgery and 6 had subtotal resection. However, no patient with total resection had recurrent infections., Conclusions: The total resection group had no recurrent infection compared to the subtotal and revision groups. In addition, patients with reconstruction of peripheral hemodialysis access had a low mortality rate during the follow-up period., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To demonstrate post-treatment computed tomography (CT) findings and outcomes of endovascular aortic repair (EVAR) for mycotic aortic aneurysm (MAA)., Materials and Methods: Clinical data of patients with MAA who underwent EVAR from June 2010 to December 2017 were retrospectively reviewed. A total of 22 patients were included (19 men and 3 women). The periaortic features of the MAA regression after EVAR were graded and evaluated by follow-up CT., Results: The median follow-up was 36.5 months (range, 0.5-97 months.). The cumulative survival rate at 1 month, 6 months, 1 year, and 5 years was 95.5%, 86.4%, 81.6%, and 73.4%, respectively. The early and late infection-related complication (IRC) rate was 18.2% and 13.6%, respectively. One patient died within 1 month from severe acidosis and shock. Of the other patients, the median time to stable response of the MAA was 6 months (range, 3-36 months). Fourteen patients (66.7%) showed early response of the MAA, while 7 patients (33.3%) showed delayed response. A significant association was observed between delayed response and late IRCs (P = .026)., Conclusions: The post-EVAR periaortic features on follow-up CT aid in monitoring the treatment response of the MAA. Early response of the MAA was associated with a low rate of late IRCs and might aid in adjusting the antibiotic duration after the patient has achieved complete or nearly complete regression of the MAA., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: Up to 40% of patients with pheochromocytomas or paragangliomas (PPGLs) carry a germline mutation. This study aimed to build a nomogram using clinical information to predict the probability of germline mutation in PPGLs., Methods: The data were collected from 563 patients who were diagnosed with PPGLs between 2002 and 2015. Clinical and pathologic features were assessed with a multivariable logistic regression analysis to predict the presence of germline mutations. A nomogram to predict the probability of germline mutation was constructed with R software. Discrimination and calibration were employed to evaluate the performance of the nomogram., Results: By multivariate analysis, age at manifestation, bilateral, or multifocal tumors and family history were identified as independent predictors of the presence of any germline mutation. The nomogram was then developed using these three variables. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0. 841 (95% confidence interval [CI], 0.809-0.871). The calibration plot indicated that the nomogram-predicted probabilities compared very well with the actual probabilities (Hosmer-Lemeshow test: P = 0.888)., Conclusion: The nomogram is a valuable predictive tool for the presence of germline mutations in patients with PPGLs.

Objective: To summarize the characteristics of patients with pituitary stalk thickening, analyze the association between pituitary stalk width and hypopituitarism, and develop a diagnostic model to differentiate neoplastic and inflammatory origins. Methods: A total of 325 patients with pituitary stalk thickening in a tertiary teaching hospital between January 2012 and February 2018 were enrolled. Basic characteristics and hormonal status were evaluated. Indicators to predict etiology in patients with histologic diagnoses were analyzed. Results: Of the 325 patients, 62.5% were female. Deficiency in gonadotropin was most common, followed by corticotropin, growth hormone, and thyrotropin. The increase in pituitary stalk width was associated with a risk of central diabetes insipidus (odds ratio [OR], 3.57; P <.001) and with a combination of central diabetes insipidus and anterior pituitary deficiency (OR, 2.28; P = .029). The cut-off pituitary stalk width of 4.75 mm had a sensitivity of 69.2% and a specificity of 71.4% for the presence of central diabetes insipidus together with anterior pituitary deficiency. Six indicators (central diabetes insipidus, pattern of pituitary stalk thickening, pituitary stalk width, neutrophilic granulocyte percentage, serum sodium level, and gender) were used to develop a model having an accuracy of 95.7% to differentiate neoplastic from inflammatory causes. Conclusion: Pituitary stalk width could indicate the presence of anterior pituitary dysfunction, especially in central diabetes insipidus patients. With the use of a diagnostic model, the neoplastic and inflammatory causes of pituitary stalk thickening could be preliminarily differentiated. Abbreviations: APD = anterior pituitary dysfunction; AUC = area under the curve; CDI = central diabetes insipidus; GH = growth hormone; MRI = magnetic resonance imaging; OR = odd ratio; PHBS = posterior hypophyseal bright spots; PST = pituitary stalk thickening; PSW = pituitary stalk width.

Purpose: To evaluate feasibility and effectiveness using the octopus endograft technique to treat complex aortic aneurysms (CAAs)., Materials and Methods: Endovascular repair of CAAs, including thoracoabdominal aneurysms (TAAAs) and dissections involving major side branches, was performed at a single center from June 2014 to June 2017. Patients included 9 men and 2 women (mean age, 60.5 y; range, 40-89 y) were included. The octopus technique was applied using standard aortic grafts with branch stent grafts to preserve the renovisceral arteries., Results: Aortic pathologies comprised 3 mycotic aneurysms, 2 chronic dissections with acute rupture, 1 progressively enlarging chronic type B dissection, 1 acutely ruptured TAAA, and 4 unruptured TAAAs. Mean procedural and fluoroscopic times were 562 min (range, 324-840 min) and 183 min (range, 73-338 min), respectively. Three patients died within 1 month. Mean duration of follow-up was 26.3 months (range, 8-42 months) for remaining patients. Technical success rate of target vessel stent placement was 89.7% (35/39). Major complication rate was 45.5% (5/11), including 3 deaths, 1 permanent paraplegia, and 1 temporary paraplegia that resolved in 2 months. All 3 mycotic aneurysms with mean duration of follow-up of 29 months (range, 8-42 months) were excluded successfully without endoleak., Conclusions: The octopus technique is feasible for treatment of CAAs requiring urgent management or with difficult anatomy without the use of available custom-made or off-the-shelf branched devices. The procedure carries substantial morbidity and mortality and requires further investigation for its long-term durability., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Hemodialysis graft outflow stenosis is a significant complication occurring in hemodialysis patients with prosthetic grafts for vascular access. Balloon angioplasty remains the first-line endovascular treatment of this complication, although covered stent graft implantation after balloon angioplasty also appears to be an effective and promising treatment. The aim of this study was to evaluate the efficacy and durability of stent graft placement after balloon angioplasty in comparison to balloon angioplasty alone for the treatment of graft outflow stenosis in hemodialysis patients., Methods: We conducted a prospective randomized study of 98 patients with clinically significant dialysis graft outflow stenosis treated in the vascular surgery section of a tertiary medical center. The patients were randomized into two groups; 49 patients were treated with stent graft placement after balloon angioplasty, and 49 patients were treated with balloon angioplasty alone. All patients underwent angiography of the graft site at 3 and 6 months after intervention, and restenosis rates were compared between the two groups. In addition, the duration of postintervention primary patency in the two groups was recorded and analyzed., Results: The postintervention restenosis rate of the stent graft placement group was superior to that seen in the balloon angioplasty alone group (9% vs 69% at 3 months [P < .0001] and 29% vs 72% at 6 months [P < .0001]). The mean postintervention primary patency duration was 380.22 ± 28.54 days for the stent graft placement group and 151.08 ± 16.79 days for the balloon angioplasty alone group (P < .0001)., Conclusions: The use of stent grafts in hemodialysis patients with graft outflow stenosis yielded superior results compared with the results seen in hemodialysis patients treated with balloon angioplasty alone. Patients treated with stent grafts after balloon angioplasty had a lower restenosis rate and a longer duration of postintervention primary patency. The placement of a stent graft after balloon angioplasty appears to be an optimal therapeutic approach for the treatment of hemodialysis patients with graft outflow stenosis., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate outcomes and predictive factors for additional ProGlide device deployment in percutaneous endovascular aortic repair (PEVAR) with the preclose technique., Materials and Methods: Clinical data of patients who underwent PEVAR with the preclose technique from February 2012 to January 2015 were retrospectively reviewed. A total of 268 patients (229 men, 39 women) who underwent PEVAR (thoracic endovascular aortic repair [TEVAR], n = 113; endovascular abdominal aortic repair [EVAR], n = 152; simultaneous TEVAR and EVAR, n = 3) with 418 femoral access sites were enrolled. The mean age of the patients was 69 years ± 14. Univariate and multivariate analyses were performed to identify predictive factors associated with additional ProGlide device deployment., Results: Primary technical success with adequate hemostasis and two ProGlide devices was 87.6%, and 48 femoral arterial access sites (11.5%) required additional ProGlide device deployment. The secondary technical success rate was 99.0%. Four femoral access sites (1.0%) needed surgical repair. Anterior wall calcification near the arteriotomy increased the risk of additional ProGlide device deployment (adjusted odds ratio, 6.19; 95% confidence interval, 2.81-13.64; P < .001), whereas larger sheath size, common femoral artery (CFA) diameter, and depth from the skin to the arteriotomy did not., Conclusions: Additional ProGlide device deployment reduces the rate of surgical repair after primary hemostasis failure in PEVAR. Anterior CFA wall calcification is a significant predictor for additional ProGlide device deployment., (Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.)

Death domain (DD)-fold assemblies play a crucial role in regulating the signaling to cell survival or death. Here we report the crystal structure of the caspase recruitment domain (CARD)-CARD disk of the human apoptosome. The structure surprisingly reveals that three 1:1 Apaf-1:procaspase-9 CARD protomers form a novel helical DD-fold assembly on the heptameric wheel-like platform of the apoptosome. The small-angle X-ray scattering and multi-angle light scattering data also support that three protomers could form an oligomeric complex similar to the crystal structure. Interestingly, the quasi-equivalent environment of CARDs could generate different quaternary CARD assemblies. We also found that the type II interaction is conserved in all DD-fold complexes, whereas the type I interaction is found only in the helical DD-fold assemblies. This study provides crucial insights into the caspase activation mechanism, which is tightly controlled by a sophisticated and highly evolved CARD assembly on the apoptosome, and also enables better understanding of the intricate DD-fold assembly., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Recognition of linear polyubiquitin by specific ubiquitin-binding proteins plays an important role in mediating nuclear factor-κB (NF-κB) signaling. A20 binding proteins, ABINs, recognize linear polyubiquitin and A20 through UBAN and AHD1, respectively, for the inhibition of NF-κB activation. Here we report the crystal structure of the AHD1-UBAN fragment of ABIN2 in complex with linear tri-ubiquitin, which reveals a 2:1 stoichiometry of the complex. Structural analyses together with mutagenesis, pull-down, and isothermal titration calorimetry assays show that the hABIN2:tri-ubiquitin interaction is mainly through the primary ubiquitin-binding site, and also through the secondary ubiquitin-binding site under a high local protein concentration. Surprisingly, three ubiquitin units could form a right-handed helical trimer to bridge two ABIN2 dimers. The residues around the M1-linkage are crucial for ABIN2 to recognize tri-ubiquitin. The tri-ubiquitin bridging two ABIN2 dimers model suggests a possible higher-order signaling complex assembled between M1-linked polyubiquitinated proteins, ubiquitin-binding proteins, and effector signaling proteins in signal transduction., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Inadvertent coverage of origin of internal iliac artery (IIA) during endovascular aneurysm repair may lead to type II endoleak. Except for open surgery, the endovascular solution is limited. We report a case with such complication that was successfully treated with coil embolization using retrograde extrastent approach. This is a new technique that has not been reported before, and as such, had been useful in the treatment of type II endoleak from IIA as an alternative to open ligation of IIA origin.

Objective/background: Pseudoaneurysm formation occurs in 2-10% of hemodialysis arteriovenous grafts (AVGs). Surgical repair often requires pseudoaneurysm resection, interposition graft placement, and insertion of a catheter as a bridge. Endovascular stent graft repair is a controversial alternative therapy. This study was performed to examine the effectiveness and mid-term outcomes of stent graft repair for AVG pseudoaneurysms., Methods: All patients who had undergone stent graft repair for AVG pseudoaneurysms between December 2012 and July 2015 were identified from hospital medical records for retrospective analysis. Outcome measures were technical success, early and late complications, and primary and secondary patency rates., Results: A total of 37 stent graft repairs of AVG pseudoaneurysms were performed in 35 patients (42.9% men; mean age 66.9 years). The mean time from AVG creation to pseudoaneurysm repair was 69 months. The indications of treatment (as per the institutional policy) were large pseudoaneurysm (56.7%), impending rupture (27.1%), and bleeding (16.2%). Mean pseudoaneurysm diameter was 23.0 mm. The most common diameter and length of stent graft used were 7 mm (67.6%) and 50 mm (48.6%), respectively. Technical success was 100%. Only one early complication occurred after stent graft repair, which was due to recurrence of the pseudoaneurysm as a result of a short landing zone. Late complications included infection (17.1%) and thrombosis (37.1%). The 1, 6, and 12 month primary patency rates were 89.2%, 55.5%, and 22.0%, respectively. The 1, 6, and 12 month secondary patency rates were 100%, 88.6%, and 78.6%, respectively. The median follow up was 12.3 months., Conclusions: The study demonstrates that endovascular stent graft repair is an effective and safe alternative therapy for AVG pseudoaneurysms. However, the rate of thrombosis and infection was high and needs to be balanced against open surgery in future studies., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Using a high-throughput optical tracking technique that is based on partially-coherent digital in-line holography, here we report a detailed analysis of the statistical behavior of horse sperms' three-dimensional (3D) swimming dynamics. This dual-color and dual-angle lensfree imaging platform enables us to track individual 3D trajectories of ∼1000 horse sperms at sub-micron level within a sample volume of ∼9μL at a frame rate of 143 frames per second (FPS) and collect thousands of sperm trajectories within a few hours for statistical analysis of their 3D dynamics. Using this high-throughput imaging platform, we recorded >17,000 horse sperm trajectories that can be grouped into six major categories: irregular, linear, planar, helical, ribbon, and hyperactivated, where the hyperactivated swimming patterns can be further divided into four sub-categories, namely hyper-progressive, hyper-planar, hyper-ribbon, and star-spin. The large spatio-temporal statistics that we collected with this 3D tracking platform revealed that irregular, planar, and ribbon trajectories are the dominant 3D swimming patterns observed in horse sperms, which altogether account for >97% of the trajectories that we imaged in plasma-free semen extender medium. Through our experiments we also found out that horse seminal plasma in general increases sperms' straightness in their 3D trajectories, enhancing the relative percentage of linear swimming patterns and suppressing planar swimming patterns, while barely affecting the overall percentage of ribbon patterns., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Schizophrenia is a condition marked by a disrupted brain functional network. In schizophrenia, the brain network is characterized by reduced distributed information processing efficiency; however, the correlation between information processing efficiency and the symptomatology of schizophrenia remains unclear. Few studies have examined path length efficiencies in schizophrenia. In this study, we examined small-world network metrics computed from resting state functional magnetic resonance imaging data collected from 49 patients with schizophrenia and 28 healthy people. We calculated brain network efficiency using graph theoretical analysis of the networks of brain areas, as defined by the Automated Anatomical Labeling parcellation scheme, and investigated efficiency correlations by using the 5-factor model of psychopathology, which considers the various domains of schizophrenic symptoms and might also consider discrete pathogenetic processes. The global efficiency of the resting schizophrenic brains was lower than that of the healthy controls, but local efficiency did not differ between the groups. The severity of psychopathology, negative symptoms, and depression and anxiety symptoms were correlated with global efficiency in schizophrenic brains. The severity of psychopathology was correlated with increased network efficiency from short-range connections, but not networks from long-range connections. Our findings indicate that schizophrenic psychopathology is correlated with brain network information processing efficiency., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Pleural empyema (PE) may evolve into necrosis, fistula in the thorax, and sepsis; thus, it is also associated with high mortality.We investigated and analyzed the risk of aortic aneurysm (AA) in a cohort study of patients with PE.A total of 34,250 patients diagnosed with PE were identified as the PE cohort, and 137,000 patients without PE were selected randomly as the control group and matched by sex, age, and index year of PE diagnosis. Patients ages 20 years and younger with a history of AA were excluded. The risk of AA was analyzed using a Cox proportional hazards regression model.Excess risk of AA development was 1.69-fold higher in PE patients (adjusted hazard ratio [aHR] = 1.69; 95% confidence interval [CI] = 1.39-2.05) compared with non-PE patients. The patients with PE exhibited a greater adjusted risk of AA (aHR = 2.01; CI = 1.44-2.81) even if they did not have any of the 9 comorbidities included in our analysis (diabetes, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, heart failure, cardiac artery disease, stroke, bacterial endocarditis, and rheumatic endocarditis). Compared with the patients without any of the 9 comorbidities or PE, the patients with only PE had a greater risk of developing AA (aHR = 2.00; CI = 1.43-2.79). The PE cohort had a significantly higher cumulative incidence of AA than the non-PE cohort did during 12 years of follow-up.In a large-scale cohort, patients with PE are linked with an increased risk of AA., Competing Interests: The authors have no conflicts of interest to disclose.

The aim of this study was to elucidate the relationship between spinal cord injury (SCI) and the risk of peripheral arterial disease (PAD) in a cohort study with a large representative sample.The National Health Insurance Database was used to select patients who were diagnosed from 2000 to 2010. Patients with a history of PAD were excluded. The SCI group comprised 42,673 patients diagnosed with SCI, and we enrolled 170,389 matched controls (non-SCI group). We used a Cox proportional hazards regression model to analyze the adjusted risk of PAD between the case and control patients.Patients with SCI exhibited a significantly higher risk (hazard ratio [HR] = 1.37; 95% confidence interval [CI] = 1.22-1.53) of PAD than patients without SCI. Patients with diabetes were at the highest risk of developing PAD (adjusted HR = 3.11, 95% CI = 2.80-3.44). Among patients without comorbidity, SCI patients exhibited a significantly higher risk of PAD than non-SCI patients. Furthermore, lumbar, sacral, or coccygeal spine, and multiple spine SCI were significantly associated with an increased risk of PAD (HR = 1.56, 95% CI = 1.33-1.84, HR = 2.11, 95% CI = 1.59-2.79, respectively).SCI is associated with an increased risk of PAD. Future studies should focus on modifying risk factors to reduce PAD risk among patients with SCI.

Vascular cutdown and echo guide puncture methods have its own limitations under certain conditions. There was no available algorithm for choosing entry vessel. A standard algorithm was introduced to help choose the entry vessel location according to our clinical experience and review of the literature. The goal of this study is to analyze the treatment results of the standard algorithm used to choose the entry vessel for intravenous port implantation.During the period between March 2012 and March 2013, 507 patients who received intravenous port implantation due to advanced chemotherapy were included into this study. Choice of entry vessel was according to standard algorithm. All clinical characteristic factors were collected and complication rate and incidence were further analyzed.Compared with our clinical experience in 2006, procedure-related complication rate declined from 1.09% to 0.4%, whereas the late complication rate decreased from 19.97% to 3.55%. No more pneumothorax, hematoma, catheter kinking, fractures, and pocket erosion were identified after using the standard algorithm. In alive oncology patients, 98% implanted port could serve a functional vascular access to fit therapeutic needs.This standard algorithm for choosing the best entry vessel is a simple guideline that is easy to follow. The algorithm has excellent efficiency and can minimize complication rates and incidence.

Schizophrenia is increasingly conceived as a disorder of brain network organization or dysconnectivity syndrome. Functional MRI (fMRI) networks in schizophrenia have been characterized by abnormally random topology. We tested the hypothesis that network randomization is an endophenotype of schizophrenia and therefore evident also in nonpsychotic relatives of patients. Head movement-corrected, resting-state fMRI data were acquired from 25 patients with schizophrenia, 25 first-degree relatives of patients, and 29 healthy volunteers. Graphs were used to model functional connectivity as a set of edges between regional nodes. We estimated the topological efficiency, clustering, degree distribution, resilience, and connection distance (in millimeters) of each functional network. The schizophrenic group demonstrated significant randomization of global network metrics (reduced clustering, greater efficiency), a shift in the degree distribution to a more homogeneous form (fewer hubs), a shift in the distance distribution (proportionally more long-distance edges), and greater resilience to targeted attack on network hubs. The networks of the relatives also demonstrated abnormal randomization and resilience compared with healthy volunteers, but they were typically less topologically abnormal than the patients' networks and did not have abnormal connection distances. We conclude that schizophrenia is associated with replicable and convergent evidence for functional network randomization, and a similar topological profile was evident also in nonpsychotic relatives, suggesting that this is a systems-level endophenotype or marker of familial risk. We speculate that the greater resilience of brain networks may confer some fitness advantages on nonpsychotic relatives that could explain persistence of this endophenotype in the population.

An entry vessel is crucial for intravenous port implantation. A safe alternative entry vessel that can be easily explored is crucial for patients without feasible cephalic vein or for those who need port reimplantation because of disease relapse. In this study, we tried to analyze the safety and feasibility of catheter implantation via the deltoid branch of the thoracoacromial vein.From March 2012 to November 2013, 802 consecutive oncology patients who had received intravenous port implantation via the superior vena cava were enrolled in this study. The functional results and complications of different entry vessels were compared.The majority of patients (93.6%) could be identified as thoracoacromial vessel. The deltoid branch of the thoracoacromial vein is located on the medial aspect of the deltopectoral groove beneath the pectoralis major muscle (85.8%) and in the deep part of the deltopectoral groove (14.2%). Due to the various calibers employed and tortuous routes followed, we utilized 3 different methods for catheter implantation, including vessel cutdown (47.4%), wire assisted (17.9%), and modified puncture method (34.6%). The functional results and complication rate were similar to other entry vessels.The deltoid branch of the thoracoacromial vein is located in the neighborhood of the cephalic vein. The functional results of intravenous port implantation via the deltoid branch of the thoracoacromial vein are similar to other entry vessels. It is a safe alternative entry vessel for intravenous port implantation.

The correlation between hip replacement (Hip-Rep) and peripheral arterial disease (PAD) remains uncertain. Thus, we investigated the relationship between Hip-Rep and risk of developing PAD in a nationwide retrospective cohort study.National Health Insurance data were used to assemble a cohort of patients who were diagnosed from 2000 to 2011. Patients with a history of PAD were excluded. A total of 5284 patients who received a Hip-Rep and 21,124 matched controls were enrolled. We used Cox proportional hazards regression model to analyze the adjusted risk of developing PAD.The risk of developing PAD in the Hip-Rep group was 1.24-fold higher (95% CI = 1.05-1.48) than that in the control group. The adjusted risk of developing PAD increased with patient age; compared with patients aged 50 years or younger, the risk among those ages at least 80 years was 4.87-fold higher. Patients with diabetes exhibited the highest risk of developing PAD (HR = 1.58, 95% CI = 1.34-1.86). Compared with patients who had not received a Hip-Rep or reported any comorbidity, patients who received a Hip-Rep were 2.45-fold more likely to develop PAD (95% CI = 1.54-3.89); the risk increased with the number of comorbidities.Hip-Reps might be independently linked with an increased risk of developing PAD. The impact of Hip-Reps on this risk was greater in women and patients ages 65 years and younger and within the first year of follow-up.

Background: A comprehensive meta-analysis was performed to evaluate the comparative benefits of coronary artery bypass grafting (CABG) versus drug-eluting stents (DES) in patients with diabetes mellitus and severe coronary artery disease (CAD)., Methods: A comprehensive literature search of PubMed, Embase, and ScienceDirect was undertaken. References cited with the papers were also checked to identify relevant articles., Results: In all, four randomized controlled trials, two prospective registries, and 11 retrospective studies were identified for review. Pooled analysis demonstrated that DES was associated with lower all-cause mortality at Day 30. However, there was no significant difference between CABG and DES in mortality at 12 months and at maximum follow-up. Furthermore, DES was associated with lower overall and major adverse cardiac and cerebrovascular events (MACCE)-free survival, as well as a higher incidence of myocardial infarction and repeat revascularization. In contrast, CABG was associated with an increased risk of stroke., Conclusions: For patients with diabetes mellitus and severe CAD, CABG is superior to DES in that it significantly improves overall and MACCE-free survival and reduces the incidence of myocardial infarction and repeat revascularization in the long term, although it is associated with greater perioperative risk and a higher incidence of stroke. Therefore, CABG should remain the gold standard for these patients., (© 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

CARD subfamily is the second largest subfamily in the DD superfamily that plays important roles in regulating various signaling pathways, including but not limited to NF-kB activation signaling, apoptosis signaling and inflammatory signaling. The CARD subfamily contains 33 human CARD-containing proteins, regulating the assembly of many signaling complexes, including apoptosome, inflammsome, nodosome, the CBM complex, PIDDosome, the TRAF2 complex, and the MAVS signalosome, by homotypic CARD-CARD interactions. The mechanism of how CARDs find the right binding partner to form a specific complex remains unclear. This review uses different classification schemes to update the classification of CARD-containing proteins. Combining the classification based on domain structures, functions, associated signaling complexes, and roles would help better understand the structural and function diversity of CARD-containing proteins. This review also summarizes recent structural studies on CARDs. Especially, the CARD-containing complexes can be divided into the homodimeric, heterodimeric, oligomeric, filamentous CARD complexes and the CARD-ubiquitin complex. This review will give an overview of the versatile roles of CARDs in regulating signaling transduction, as well as the therapeutic drugs targeting CARD-containing proteins.

A Lego ® -like swappable fluidic module (SFM) is proposed in this research. We designed and fabricated selected modular fluidic components, including functional and auxiliary types that can be effortlessly swapped and integrated into a variety of modular devices to rapidly assemble a fully-portable, disposable fluidic system. In practice, an integrated SFM uses finger-operated, electricity-free pumps to deliver fluids. Using a swirling mechanism, the vortex mixer can rapidly mix two liquids in a one-shot mixing event. We demonstrate the successful application of this SFM in several microfluidic applications, such as the synthesis of gold nanoparticles (AuNPs) from chloroauric acid (HAuCl 4 ), and nucleic acid amplification from the Hepatitis B virus (HBV) with a capillary convective polymerase chain reaction (ccPCR)., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Venoarterial extracorporeal life support (VA-ECLS) is a lifesaving circulatory support in hemodynamic collapse induced by miscellaneous etiologies. However, survival rates vary among etiologies. To investigate the therapeutic effectiveness of VA-ECLS in hemodynamic collapse induced by fulminant cardiomyopathy (CM), a retrospective chart review of 14 patients was conducted, among the 294 adults receiving VA-ECLS in a single institution from April 2006 to April 2013. All patients received echocardiography, coronary angiography, or computed tomography before or immediately after undergoing VA-ECLS to exclude anatomic cardiac diseases. Myocarditis (n = 12) and peripartum CM (n = 2) were the subcategories of fulminant CM. The median door-to-ECLS duration was 12 hours. Seven patients received cardiopulmonary resuscitation (CPR) before VA-ECLS, and three required ECLS-assisted CPR to regain circulation. Two patients were transplanted as a result of myocardial irreversibility and one survived. Nine of the nontransplant patients survived after a median VA-ECLS of 167 hours. All of the 10 survivors, including the five experiencing dialysis-dependent acute renal failure, had their cardiac and renal function return to normal within 6 months after the episode. The VA-ECLS was a practical therapeutic option in fulminant CM. It could provide expeditious hemodynamic support and preserve organ viability essential to recovery.

Quantitative cell motility studies are necessary for understanding biophysical processes, developing models for cell locomotion and for drug discovery. Such studies are typically performed by controlling environmental conditions around a lens-based microscope, requiring costly instruments while still remaining limited in field-of-view. Here we present a compact cell monitoring platform utilizing a wide-field (24 mm(2)) lensless holographic microscope that enables automated single-cell tracking of large populations that is compatible with a standard laboratory incubator. We used this platform to track NIH 3T3 cells on polyacrylamide gels over 20 hrs. We report that, over an order of magnitude of stiffness values, collagen IV surfaces lead to enhanced motility compared to fibronectin, in agreement with biological uses of these structural proteins. The increased throughput associated with lensfree on-chip imaging enables higher statistical significance in observed cell behavior and may facilitate rapid screening of drugs and genes that affect cell motility.

Executive dysfunction is one of the core symptoms of schizophrenia. Functional neuro-imaging studies have suggested an association between deficits in activating the dorsolateral prefrontal cortex (DLPFC) and executive dysfunction, but neuro-integration from the DLPFC to the whole brain remains unclear. Studies investigating the neuro-integration from the DLPFC to the whole brain in unaffected but genetically liable family members are scant. In this study, we report DLPFC neuro-integrative deficits correlated with executive dysfunction and family history of schizophrenia using resting-state functional magnetic resonance imaging (fMRI). Using seed regions in DLPFC, we examined resting-state functional connectivity in 25 patients with schizophrenia, 25 unaffected first-degree relatives (UR), and 25 healthy control (HC) persons. Schizophrenia patients and UR have impaired connectivity from DLPFC to its coordinated regions (ANOVA: F=7.316-10.974, p<0.001). These coordinated brain regions are distributed in the bilateral caudate, left middle/inferior frontal gyrus, left precentral gyrus, and right cerebellum. The individual functional connectivity strength between the left DLPFC and its coordinated regions was correlated with individual executive function performance among whole persons. (Pearson's r=0.244-0.366, p=0.035-0.008) Our findings support that distributed neuro-integrative DLPFC deficits reflect a genetic risk for schizophrenia and that these deficits are present, to a lesser degree, in unaffected first-degree relatives. Our findings also support that neuro-integration might correlate with a patient's executive function performance., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We demonstrate an optoelectronic tweezer (OET) coupled to a lensfree holographic microscope for real-time interactive manipulation of cells and micro-particles over a large field-of-view (FOV). This integrated platform can record the holographic images of cells and particles over the entire active area of a CCD sensor array, perform digital image reconstruction to identify target cells, dynamically track the positions of cells and particles, and project light beams to trigger light-induced dielectrophoretic forces to pattern and sort cells on a chip. OET technology has been previously shown to be capable of performing parallel single cell manipulation over a large area. However, its throughput has been bottlenecked by the number of cells that can be imaged within the limited FOV of a conventional microscope objective lens. Integrating lensfree holographic imaging with OET solves this fundamental FOV barrier, while also creating a compact on-chip cell/particle manipulation platform. Using this unique platform, we have successfully demonstrated real-time interactive manipulation of thousands of single cells and micro-particles over an ultra-large area of e.g., 240 mm(2) (i.e. 17.96 mm × 13.52 mm).

We report the discovery of an entirely new three-dimensional (3D) swimming pattern observed in human and horse sperms. This motion is in the form of 'chiral ribbons', where the planar swing of the sperm head occurs on an osculating plane creating in some cases a helical ribbon and in some others a twisted ribbon. The latter, i.e., the twisted ribbon trajectory, also defines a minimal surface, exhibiting zero mean curvature for all the points on its surface. These chiral ribbon swimming patterns cannot be represented or understood by already known patterns of sperms or other micro-swimmers. The discovery of these unique patterns is enabled by holographic on-chip imaging of >33,700 sperm trajectories at >90-140 frames/sec, which revealed that only ~1.7% of human sperms exhibit chiral ribbons, whereas it increases to ~27.3% for horse sperms. These results might shed more light onto the statistics and biophysics of various micro-swimmers' 3D motion.

The recent revolution in digital technologies and information processing methods present important opportunities to transform the way optical imaging is performed, particularly toward improving the throughput of microscopes while at the same time reducing their relative cost and complexity. Lensfree computational microscopy is rapidly emerging toward this end, and by discarding lenses and other bulky optical components of conventional imaging systems, and relying on digital computation instead, it can achieve both reflection and transmission mode microscopy over a large field-of-view within compact, cost-effective and mechanically robust architectures. Such high throughput and miniaturized imaging devices can provide a complementary toolset for telemedicine applications and point-of-care diagnostics by facilitating complex and critical tasks such as cytometry and microscopic analysis of e.g., blood smears, Papanicolaou (Pap) tests and tissue samples. In this article, the basics of these lensfree microscopy modalities will be reviewed, and their clinically relevant applications will be discussed.

Dynamic tracking of human sperms across a large volume is a challenging task. To provide a high-throughput solution to this important need, here we describe a lensfree on-chip imaging technique that can track the three-dimensional (3D) trajectories of > 1,500 individual human sperms within an observation volume of approximately 8-17 mm(3). This computational imaging platform relies on holographic lensfree shadows of sperms that are simultaneously acquired at two different wavelengths, emanating from two partially-coherent sources that are placed at 45° with respect to each other. This multiangle and multicolor illumination scheme permits us to dynamically track the 3D motion of human sperms across a field-of-view of > 17 mm(2) and depth-of-field of approximately 0.5-1 mm with submicron positioning accuracy. The large statistics provided by this lensfree imaging platform revealed that only approximately 4-5% of the motile human sperms swim along well-defined helices and that this percentage can be significantly suppressed under seminal plasma. Furthermore, among these observed helical human sperms, a significant majority (approximately 90%) preferred right-handed helices over left-handed ones, with a helix radius of approximately 0.5-3 μm, a helical rotation speed of approximately 3-20 rotations/s and a linear speed of approximately 20-100 μm/s. This high-throughput 3D imaging platform could in general be quite valuable for observing the statistical swimming patterns of various other microorganisms, leading to new insights in their 3D motion and the underlying biophysics.

We discuss unique features of lens-free computational imaging tools and report some of their emerging results for wide-field on-chip microscopy, such as the achievement of a numerical aperture (NA) of ∼0.8-0.9 across a field of view (FOV) of more than 20 mm(2) or an NA of ∼0.1 across a FOV of ∼18 cm(2), which corresponds to an image with more than 1.5 gigapixels. We also discuss the current challenges that these computational on-chip microscopes face, shedding light on their future directions and applications.

Sporadic malignant pheochromocytoma, a rare disease with poor prognosis, is always difficult to treat due in part to lack of effective agents. We presented three patients with advanced malignant pheochromocytoma treated by sunitinib, which indicates that sunitinib is an effective agent for this malignancy.