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Yao An Shen,1,* Ing Luen Shyu,2,* Maggie Lu,3 Chun Lin He,4 Yen Mei Hsu,2 Hsiang Fa Liang,3 Chih Peng Liu,3 Ren Shyan Liu,5,6 Biing Jiun Shen,7 Yau Huei Wei,1 Chi Mu Chuang2,4 1Institute of Biochemistry and Molecular Biology, School of Life Sciences, 2Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, 3Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, 4Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, 5Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 6National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, Taiwan; 7Division of Psychology, Nanyang Technological University, Singapore *These authors contributed equally to the work Abstract: The current enhanced permeability and retention (EPR)-based approved nanomedicines have had little impact in terms of prolongation of overall survival in patients with cancer. For example, the two Phase III trials comparing Doxil®, the first nanomedicine approved by the US Food and Drug Administration, with free doxorubicin did not find an actual translation of the EPR effect into a statistically significant increase in overall survival but did show less cardiotoxicity. In the current work, we used a two-factor factorial experimental design with intraperitoneal versus intravenous delivery and nanomedicine versus free drug as factors to test our hypothesis that regional (intraperitoneal) delivery of nanomedicine may better increase survival when compared with systemic delivery. In this study, we demonstrate that bypassing, rather than exploiting, the EPR effect via intraperitoneal delivery of nanomedicine harboring a sustained-release function demonstrates dual pharmacokinetic advantages, producing more efficient tumor control and suppressing the expression of stemness markers, epithelial-mesenchymal transition, angiogenesis signals, and multidrug resistance in the tumor microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic system) are also better controlled by intraperitoneal delivery of nanomedicine than by standard systemic delivery of the corresponding free drug. Moreover, the intraperitoneal delivery of nanomedicine has the potential to replace hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the best approach for developing a nanomedicine. Because intraperitoneal chemotherapy is a type of regional chemotherapy, the pharmaceutical industry might consider the regional delivery of nanomedicine as a valid alternative pathway to develop their nanomedicine(s) with the goal of better tumor control in the future. Keywords: enhanced permeability and retention effect, liposome, paclitaxel, ovarian cancer

Shen YA, Shyu IL, Lu M, et al. Int J Nanomedicine. 2015; 10:2485–2502.The authors advise that Figure 2B on page 2490 contains the incorrect image for the EP group. The correct Figure 2B image is shown below.Read the original article

Panax Notoginseng Burk (PN) has been reported to improve blood circulation, as well as learning and memory functions. The purpose of the present study was to investigate the effect of PN on learning and memory functions in chronic cerebral infarct rats. A cerebral infarct animal model was established by blocking the blood flow of both common carotid arteries and right middle cerebral artery for 90 min followed by reperfusion for 4 weeks. PN (0.5 g/kg) was administered orally 3 days per week for 4 weeks, whereas the control group provided bait and water only. The learning and memory functions were estimated by measuring how successful rats were able to negotiate an 8-arm radial maze test; the test was performed after operation once a week for 4 weeks. Finally, the rats were sacrificed and their brains were removed. The brains were sectioned and analyzed for ED1, glial fibrillary acid protein (GFAP), nuclear factor-kappaB, and brain derivative neurotrophin factor (BDNF) and beta-secretase by immunostaining. Cerebral infarct rats given PN were able to successfully navigate the 8-arm radial maze test four weeks after cerebral infarction. PN also increased ED1, BDNF and beta-secretase immunoreactive cells, but did not increase GFAP and NF-kappaB immunoreactive cells. PN attenuated the reduction in learning and memory functions induced by cerebral infarction in cerebral ischemia-reperfusion injured rats; it also increased the amount of activated microglia and BDNF. These data suggest that the effect of PN, at least in part, is closely related to the increase in BDNF that was generated by activated microglia. The effect that PN has on astrocytes, NF-kappaB and beta-secreatase immunoreactive cells requires further study. [ABSTRACT FROM AUTHOR]

Abstract: In a previous report, we showed that voltage-gated K+ (Kv) Kv1 and Kv2 channels are involved in cAMP-induced neuritogenesis of mouse neuronal N2A cells. In this report, we examined the effects of tannic acid (TA) on Kv channels and neuritogenesis in N2A cells. TA (15 μM) mildly enhanced Kv currents at -30 to -20 mV but strongly inhibited Kv currents at higher voltages, causing a preferential activation of currents at low voltages. When enhancement and suppression of Kv currents (at -20 and +70 mV, respectively) by different concentrations of TA were analyzed, TA at 4 μM produced strong enhancement at -20 mV with relatively mild suppression at + 70 mV. TA (4 μM) also promoted neuritogenesis; such promotion was suppressed by a Kv channel blocker tetraethylammonium ion, or a combination of hongotoxin-1 (blocker of Kv1.1), UK 78282 (blocker of Kv1.4) and guangxitoxin 1E (blocker of Kv2.1). Our results demonstrate, for the first time, TA at low concentrations could modulate Kv channels and thereby promote neuritogenesis., (Copyright © 2025 Journal of Physiological Investigation.)

Objectives: Mitochondrial Ca 2+ uniporter (MCU) provides a Ca 2+ influx pathway from the cytosol into the mitochondrial matrix and a moderate mitochondrial Ca 2+ rise stimulates ATP production and cell growth. MCU is highly expressed in various cancer cells including breast cancer cells, thereby increasing the capacity of mitochondrial Ca 2+ uptake, ATP production, and cancer cell proliferation. The objective of this study was to examine MCU inhibition as an anti-cancer mechanism., Methods: The effects of MCU-i4, a newly developed MCU inhibitor, on cell viability, apoptosis, cytosolic Ca 2+ , mitochondrial Ca 2+ and potential, glycolytic rate, generation of ATP, and reactive oxygen species, were examined in breast cancer BT474 cells., Results: MCU-i4 caused apoptotic cell death, and it decreased and increased, respectively, mitochondrial and cytosolic Ca 2+ concentration. Inhibition of MCU by MCU-i4 revealed that cytosolic Ca 2+ elevation resulted from endoplasmic reticulum (ER) Ca 2+ release via inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors (RYR). Unexpectedly, MCU-i4 enhanced glycolysis and ATP production; it also triggered a large production of reactive oxygen species (ROS) and mitochondrial membrane potential collapse., Conclusion: Cytotoxic mechanisms of MCU-i4 in cancer cells involved enhanced glycolysis and heightened formation of ATP and ROS. It is conventionally believed that cancer cell death could be caused by inhibition of glycolysis. Our observations suggest cancer cell death could also be induced by increased glycolytic metabolism., Competing Interests: The authors declare no conflicts of interest to report regarding the present study., (© 2025 The Authors.)

Catheter ablation for tachyarrhythmia via superior approach has been used in patients without possible inferior vena cava access such as in cases of venous occlusion or complex anomaly. Difficulty in catheter manipulation, instability, number of required vascular access, and radiation exposure of operator had been described in the procedure. Application of three-dimensional (3-D) mapping system in catheter ablation via superior approach could navigate the guiding catheter and provide more precise ablation. We reported four cases receiving catheter ablation due to atrioventricular nodal reentry tachycardia, atrial fibrillation, and right ventricular arrhythmia via superior approach facilitated by 3-D mapping system with fewer vascular access and catheters., (© 2024 The Author(s). Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

In recent years, third-generation solar cells have experienced a remarkable growth in efficiency, making them a highly promising alternative energy solution. Currently, high-efficiency solar cells often use top electrodes fabricated by thermal evaporation, which rely on high-cost and high energy-consumption vacuum equipment, raising significant concerns for mass production. This study develops a method for fabricating silver electrodes using the screen-printing process, aiming to achieve solar cell production through an all-solution coating process. By selecting appropriate blocking-layer materials and optimizing the process, we have achieved device efficiencies for organic photovoltaics (OPVs) with screen-printed silver electrodes comparable to those with silver electrodes fabricated by thermal evaporation. Furthermore, we developed a method to cure the silver ink using near-infrared (NIR) annealing, significantly reducing the curing time from 30 min with hot air annealing to just 5 s. Additionally, by employing sheet-to-sheet (S2S) slot-die coating, we scaled up the device area and completed module development, successfully verifying stability in ambient air. We have also extended the application of screen-printed silver electrodes to perovskite solar cells (PSCs).

Organic-inorganic nanocomposites have the potential to be used in photovoltaic materials due to their eco-friendliness, suitable band gaps, and high stability. In this work, we integrated gold and Fe 3 O 4 magnetic nanoparticles with poly-m-amino benzene sulfonic (m-ABS) to synthesize Fe 3 O 4 @Au@poly-(m-aminobenzenesulfonic acid) (Fe 3 O 4 @Au@m-ABS) magneto-plasmonic nanoparticles (MPNPs) to enhance the performance of the organic photovoltaic (OPV). These MPNPs exhibit broad UV-Vis absorption and a low band gap of 2.878 eV, enhancing their suitability for photovoltaic applications. The MPNPs were introduced into the ZnO electron transporting layer (ETL) and active layer to investigate the influence of MPNPs on the power conversion efficiency (PCE) of the OPVs. When 0.1 vol% MPNPs were incorporated in the ETL, the OPVs achieved a PCE of 14.24% and a fill factor (FF) of 69.10%. On the other hand, when 0.1 vol% MPNPs were incorporated in the active layer, the OPVs showed a PCE of 14.11% and an FF of 68.83%. However, the OPVs without MPNPs only possessed a PCE of 13.15% and an FF of 63.69%. The incorporation of MPNPs increased the PCE by 8.3% in the OPV device. These findings suggest that Fe 3 O 4 @Au@m-ABS MPNPs are promising nanocomposite materials for enhancing the performance of OPVs.

Importance: Catheter ablation for persistent atrial fibrillation (AF) has shown limited success., Objective: To determine whether AF drivers could be accurately identified by periodicity and similarity (PRISM) mapping ablation results for persistent AF when added to pulmonary vein isolation (PVI)., Design, Setting, and Participants: This prospective randomized clinical trial was performed between June 1, 2019, and December 31, 2020, and included patients with persistent AF enrolled in 3 centers across Asia. Data were analyzed on October 1, 2022., Intervention: Patients were assigned to the PRISM-guided approach (group 1) or the conventional approach (group 2) at a 1:1 ratio., Main Outcomes and Measures: The primary outcome was freedom from AF or other atrial arrhythmia for longer than 30 seconds at 6 and 12 months., Results: A total of 170 patients (mean [SD] age, 62.0 [12.3] years; 136 men [80.0%]) were enrolled (85 patients in group 1 and 85 patients in group 2). More group 1 patients achieved freedom from AF at 12 months compared with group 2 patients (60 [70.6%] vs 40 [47.1%]). Multivariate analysis indicated that the PRISM-guided approach was associated with freedom from the recurrence of atrial arrhythmia (hazard ratio, 0.53 [95% CI, 0.33-0.85])., Conclusions and Relevance: The waveform similarity and recurrence pattern derived from high-density mapping might provide an improved guiding approach for ablation of persistent AF. Compared with the conventional procedure, this novel specific substrate ablation strategy reduced the frequency of recurrent AF and increased the likelihood of maintenance of sinus rhythm., Trial Registration: ClinicalTrials.gov Identifier: NCT05333952.

Chemotherapy, radiotherapy, targeted therapy, and immunotherapy are established cancer treatment modalities that are widely used due to their demonstrated efficacy against tumors and favorable safety profiles or tolerability. Nevertheless, treatment resistance continues to be one of the most pressing unsolved conundrums in cancer treatment. Hypoxia-inducible factors (HIFs) are a family of transcription factors that regulate cellular responses to hypoxia by activating genes involved in various adaptations, including erythropoiesis, glucose metabolism, angiogenesis, cell proliferation, and apoptosis. Despite this critical function, overexpression of HIFs has been observed in numerous cancers, leading to resistance to therapy and disease progression. In recent years, much effort has been poured into developing innovative cancer treatments that target the HIF pathway. Combining HIF inhibitors with current cancer therapies to increase anti-tumor activity and diminish treatment resistance is one strategy for combating therapeutic resistance. This review focuses on how HIF inhibitors could be applied in conjunction with current cancer treatments, including those now being evaluated in clinical trials, to usher in a new era of cancer therapy., (© 2023. The Author(s).)

Background: Ovarian cancer has the highest mortality among gynecological cancers due to late diagnosis and lack of effective targeted therapy. Although the study of interplay between cancer cells with their microenvironment is emerging, how ovarian cancer triggers signaling that coordinates with immune cells to promote metastasis is still elusive., Methods: Microarray and bioinformatics analysis of low and highly invasive ovarian cancer cell lines were used to reveal periostin (POSTN), a matrix protein with multifunctions in cancer, with elevated expression in the highly invasive cells. Anchorage independent assay, Western blot, RNA interference, confocal analysis and neutralizing antibody treatment were performed to analyze the effects of POSTN on tumor promotion and to explore the underlying mechanism. Chemotaxis, flow cytometry and cytokine array analyses were undertaken to analyze the involvement of POSTN in cancer-associated fibroblast (CAF) and macrophage modulation. Correlations between POSTN expression levels and clinical characteristics were analyzed using the Oncomine, commercial ovarian cancer cDNA and China Medical University Hospital patient cohort. In vivo effect of POSTN on metastasis was studied using a mouse xenograft model., Results: Expression of POSTN was found to be elevated in highly invasive ovarian cancer cells. We observed that POSTN was co-localized with integrin β3 and integrin β5, which was important for POSTN-mediated activation of ERK and NF-κB. Ectopic expression of POSTN enhanced whereas knockdown of POSTN decreased cancer cell migration and invasion in vitro, as well as tumor growth and metastasis in vivo. POSTN enhanced integrin/ERK/NF-κB signaling through an autocrine effect on cancer cells to produce macrophage attracting and mobilizing cytokines including MIP-1β, MCP-1, TNFα and RANTES resulting in increased chemotaxis of THP-1 monocytes and their polarization to M2 macrophages in vitro. In agreement, tumors derived from POSTN-overexpressing SKOV3 harbored more tumor-associated macrophages than the control tumors. POSTN induced TGF-β2 expression from ovarian cancer cells to promote activation of adipose-derived stromal cells to become CAF-like cells expressing alpha smooth muscle actin and fibroblast activation protein alpha. Consistently, increased CAFs were observed in POSTN overexpressing SKOV3 cells-derived metastatic tumors. In clinical relevance, we found that expression of POSTN was positively correlated with advanced-stage diseases and poor overall survival of patients., Conclusions: Our study revealed a POSTN-integrin-NF-κB-mediated signaling and its involvement in enhancing M2 macrophages and CAFs, which could potentially participate in promoting tumor growth. Our results suggest that POSTN could be a useful prognosis marker and potential therapeutic target., (© 2022. The Author(s).)

Objectives: Recent research has demonstrated the commonality of several biological markers between Kawasaki disease (KD) and juvenile idiopathic arthritis (JIA), including interleukin-1β and -6. Therefore, in this cohort study, we assessed whether KD increases the risk of JIA., Methods: This study enrolled 7009 patients with and 56 072 individuals without KD in the period 2010-2018 from Taiwan's National Health Insurance Research Database. On the basis of sex, age, and comorbidities, we executed propensity score matching at the ratio 1:8. The adjusted hazard ratio (aHR) for JIA was determined through multiple Cox regression. Stratified analysis and sensitivity tests were also employed., Results: When adjusting for age, sex, and comorbidities, the JIA risk was noted to be 2.02-fold greater in children with KD than it was in those without (aHR: 2.02, 95% confidence interval: 1.12-3.67, p = 0.0205). The sensitivity test and subgroup analysis obtained consistent findings in the different sex and comorbidity subgroups., Conclusion: Children's risk of JIA is higher if they have KD. Pediatricians should consider the possibility of JIA in this population. More investigations are necessary to identify the pathological mechanisms that link JIA and KD., 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 Liao, Fu, Chuang, Liao, Wei and Fu.)

Aims: Lung type 2 alveolar cells, by secreting surfactant to lower surface tension, contribute to enhance lung compliance. Stretching, as a result of lung expansion, triggers type 1 alveolar cell to release ATP, which in turn stimulates Ca 2+ -dependent surfactant secretion by neighboring type 2 cells. In this report, we studied ATP-triggered Ca 2+ signaling in human alveolar type 2 A549 cells., Main Methods: Ca 2+ signaling was examined using microfluorimetric measurement with fura-2 as fluorescent dye., Key Findings: Ca 2+ oscillations triggered by ATP relied on inositol 1,4,5-trisphosphate-induced Ca 2+ release and store-operated Ca 2+ entry. Pathological conditions such as influenza virus infection and diabetes reportedly inhibit sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase (SERCA). We found that a very mild inhibition of SERCA by cyclopiazonic acid (CPA) sufficed to decrease Ca 2+ oscillation frequency and the percentage of cells exhibiting Ca 2+ oscillations. Ochratoxin A (OTA), an activator of SERCA, could prevent the suppressive effects by CPA. Inhibition of SERCA by hydrogen peroxide also suppressed Ca 2+ oscillations. Interestingly, hydrogen peroxide-induced inhibition was prevented by OTA but aggravated by CDN1163, an allosteric activator of SERCA. CDN1163 also had an untoward effect of releasing intracellular Ca 2+ ., Significance: Different modes of activation of SERCA may determine the outcome of rescue of Ca 2+ oscillations in case of SERCA inhibition in alveolar type 2 cells., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Although women with ovarian cancer experience depression and poor sleep quality, little is known about how various factors, particularly self-efficacy, might be associated with these conditions., Objectives: The aim of this study was to examine the prevalence of and changes in depression and sleep quality and the factors associated with these conditions in a cohort of women with ovarian cancer before, during, and after chemotherapy., Methods: A prospective repeated-measures design was adopted in this study. Participants were women with ovarian cancer who were expected to receive 4 to 6 cycles of chemotherapy and were recruited at a medical center in Taiwan. The participants were asked to complete a questionnaire that included the Symptom Distress Scale, Center for Epidemiologic Studies Depression Scale, General Self-efficacy Scale, and Pittsburgh Sleep Quality Index. The data were collected before, during, and after the course of chemotherapy., Results: Overall, 24.6% to 36.9% of women were at risk for depression; 75.4% to 80.0% of women had poor sleep quality. There were no significant changes in depressive symptoms and sleep quality throughout the course of chemotherapy. More severe depressive symptoms were associated with higher levels of symptom distress and lower self-efficacy. Poorer sleep quality was associated with higher levels of symptom distress., Conclusions: Among participants, more depressive symptoms and poorer sleep quality were associated with higher levels of symptom distress or lower self-efficacy., Implications for Practice: Healthcare providers should continuously assess depression and sleep quality in women with ovarian cancer. These symptoms may be improved by strengthening self-efficacy and relieving symptom distress., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Propofol, a general anesthetic administered intravenously, may cause pain at the injection site. The pain is in part due to irritation of vascular endothelial cells. We here investigated the effects of propofol on Ca2+ transport and pain mediator release in human umbilical vein endothelial cells (EA.hy926). Propofol mobilized Ca2+ from cyclopiazonic acid (CPA)-dischargeable pool but did not cause Ca2+ release from the lysosomal Ca2+ stores. Propofol-elicited Ca2+ release was suppressed by 100 μM ryanodine, suggesting the participation of ryanodine receptor channels. Propofol did not affect ATP-triggered Ca2+ release but abolished the Ca2+ influx triggered by ATP; in addition, propofol also suppressed store-operated Ca2+ entry elicited by CPA. Ca2+ clearance during CPA-induced Ca2+ discharge was unaffected by a low Na+ (50 mM) extracellular solution, but strongly suppressed by 5 mM La3+ (an inhibitor of plasmalemmal Ca2+ pump), suggesting Ca2+ extrusion was predominantly through the plasmalemmal Ca2+ pump. Propofol mimicked the effect of La3+ in suppressing Ca2+ clearance. Propofol also stimulated release of pain mediators, namely, reactive oxygen species and bradykinin. Our data suggest propofol elicited Ca2+ release and repressed Ca2+ clearance, causing a sustained cytosolic [Ca2+]i elevation. The latter may cause reactive oxygen species and bradykinin release, resulting in pain., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Bacterial vaginosis (BV) is prevalent among women of reproductive age and has a high rate of recurrence, which can be largely attributed to ineffective BV biofilm eradication by current first-line antibiotics. In this study, we report that the Nile tilapia piscidin 4 (TP4) exhibits broad-spectrum antimicrobial and antibiofilm activity against BV-associated bacteria, but not beneficial lactobacilli. In addition, BV-associated Gardnerella vaginalis remains susceptible to TP4 even after continual exposure to the peptide for up to 22 passages. Gardnerella vaginalis and Streptococcus anginosus are both biofilm-forming BV-associated bacteria, and we found that combining TP4 peptide and disodium EDTA with the biofilm-disrupting agent, chitosan, can eradicate biofilms formed by single or mixed G. vaginalis and S. anginosus . In addition, long-term storage of TP4 peptide in chitosan did not diminish its bactericidal activity toward G. vaginalis . Preformulation studies were performed using High performance liquid chromatography (HPLC) and Circular Dichroism (CD). The long-term stability of TP4 peptide was assessed under various conditions, such as different temperatures and ionic strengths, and in the presence of H 2 O 2 and lactic acid. When exposed to sodium dodecyl sulfate (SDS), TP4 maintained its secondary structure at various temperatures, salt and disodium EDTA concentrations. Furthermore, the TP4 microbicide formulation significantly reduced the colonization density of BV-associated bacteria in mice infected with single or mixed bacteria ( G. vaginalis and S. anginosus ). The TP4 microbicide formulation showed biocompatibility with beneficial human vaginal lactobacilli and female reproductive tissues in C57BL/6 mice. These results suggest that the TP4 microbicide formulation could be a promising topical microbicide agent for BV treatment., 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 Lin, Chen, Chuang and Chen.)

Background: Right ventricular outflow tract obstruction relief is one of the major procedures during the total correction of tetralogy of Fallot (TOF). Pulmonary insufficiency (PI) is usually inevitable after a transannular incision with a patch repair is performed. Therefore, some surgeons advocate to place a monocusp valve within the transannular patch (TAP) in order to decrease the severity of the PI. However, the monocusp valve seemed not be very effective in some patients who underwent the complete TOF repair., Methods: Patients who had the classic form of TOF between January 2009 and January 2017 and underwent the corrective surgery with a TAP by the same cardiovascular surgeon were identified for further analysis. Clinical information including demographics at operation, perioperative data, and postoperative outcome were collected retrospectively and compared between the group with and without a monocusp valve., Results: A total of 24 TOF cases were included in the final analysis, and 16 (66.7%) patients received a monocusp valve placement. The patients' characteristics before and during the surgery were similar between the two groups. The median duration of chest tube drainage after the total correction in the monocusp group was longer than those without the valve (p = 0.04). There was no difference in the immediate postoperative data, including the inflammation/infection status, the duration of mechanical ventilation, and the length of ICU and hospital stay., Conclusion: Implantation of a monocusp valve during the total TOF correction using a TAP did not bring benefit to improve the immediate postoperative outcomes, especially the duration of the pleural drainage. Further study with a prospective design and a larger number of cases is needed., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Background: Cisplatin-based chemotherapy (CBC) is highly efficacious for advanced cervical cancer; its efficacy can be enhanced by combining with 15 mg/kg (standard dose) bevacizumab (BEV). However, this standard dose is associated with various adverse events (AEs). Therefore, in this retrospective study, we analyzed the survival outcomes and AEs in patients with advanced or recurrent cervical cancer treated with CBC in combination with BEV 7.5 mg/kg., Methods: Registered patient data were retrieved between October 2014 and September 2019, and 64 patients with advanced or recurrent cervical cancer treated with CBC + BEV (n = 21) or CBC alone (n = 43) were analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoints were the frequency and severity of AEs. The Cox proportional-hazards model was applied to explore prognostic factors associated with PFS and OS., Results: The 1-, 2-, and 3-year PFS rates (95% CI) were 36.24% (22.0-50.5), 20.7% (9.8-34.2), and 17.7% (7.7-31.1) for the CBC group; and 71.4% (47.1-86.0), 51.0% (27.9-70.1), and 51.0% (27.9-70.1) for the CBC + BEV group, respectively. The 1-, 2-, and 3-year OS rates were 62.6% (46.4-75.18), 32.4% (18.8-46.9), and 23.2% (11.2-37.6) for the CBC group; and 85.7% (61.9-95.1), 66.6% (42.5-82.5), and 55.5% (27.1-76.7) for the CBC + BEV group, respectively. The CBC + BEV group presented higher PFS and OS rates, p = 0.003 and p = 0.005, respectively. Proteinuria (6 vs 9, p = 0.025) and hypertension (0 vs 10, p < 0.001) were less common, but anemia was more common in the CBC group (35 vs 11, p = 0.021)., Conclusion: Overall, CBC + BEV significantly improved the PFS and OS compared with CBC alone. CBC + BEV also prevents severe AEs and hence is an efficacious and safe therapeutic option., Competing Interests: Conflicts of interest: Dr. Peng-Hui Wang and Dr. Yi-Jen Chen, editorial board members at Journal of the Chinese Medical Association, have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

PBX1 is a transcription factor involved in diverse cellular functions including organ development, stem cell renewal, and tumorigenesis. PBX1 is localized at chr1q23.3, a frequently amplified chromosomal region, and it is overexpressed in many human malignancies. Cancer cells with elevated PBX1 signaling are particularly vulnerable to PBX1 withdrawal. We designed a series of small molecule compounds capable of docking to the interface between PBX1 and its cognate DNA target sequence. Among them, T417 is found to be a lead compound. In cell-based assays, T417 significantly suppressed self-renewal and proliferation of cancer cells expressing high levels of PBX1. T417 also re-sensitized platinum-resistant ovarian tumors to carboplatin. T417 did not affect healthy tissues likely due to their lower PBX1 expression levels. Therefore, targeting PBX-DNA interface can be a promising strategy for treating human tumors reliant on PBX1 for survival., Competing Interests: T.-L.W. is the founder of Ovata, Incov. T.-L.W. and I.-M.S. have a patent related to this work., (© 2021 The Authors.)

Background: Atrial fibrillation (AF) prevalence increases with age. Aging affects the substrate properties of the left atrium (LA) and the outcomes of catheter ablation for treating AF. We investigated the AF trigger distribution and catheter ablation outcomes in patients of different ages with AF., Methods: 1585 patients with AF (1181 paroxysmal and 404 non- paroxysmal AF) who had undergone catheter ablation were enrolled. The patients were divided into young (20-40 year-old, n = 175), middle-aged (41-64 year-old, n = 1134), and old (≥ 65 year-old, n = 276) groups. Electrophysiological characteristics and AF trigger sites were recorded., Result: The incidence of AF with only non-pulmonary vein (non-PV) foci was higher in the young group than in the other groups (8.6% vs. 3.6% vs. 3.3%, p < 0.01). Non-PV foci were more commonly located in the superior vena cava (SVC) in the young group than in the other groups (13.1% vs. 7.8% vs. 6.5%, p = 0.03). The left atrium (LA) mean voltage was higher and the incidence of very late recurrence after AF ablation was lower in the young group than in the other groups. However, the final AF recurrence rate after multiple procedures and complication rates were similar among all the groups at a mean follow-up of 5.6 years., Conclusion: The young patients with AF had a higher incidence of only non-PV foci, mostly located in SVC, than the middle-aged and old patients. Our study highlights the importance of identifying the non-PV foci in catheter ablation of young patients with AF., (© 2021 Wiley Periodicals LLC.)

Thermal and dielectric properties of rigid-rod bifunctional epoxy resin 4,4-bis(2,3-epoxypropoxy) biphenyl epoxy (BP) and commercial epoxy resin diglycidyl ether of bisphenol A (DGEBA) were studied using differential scanning calorimeter (DSC), thermogravimetric analyzer (TGA), dynamic mechanical analyzer (DMA), thermal mechanical analyzer (TMA) and dielectric analyzer (DEA). These two epoxies were cured with cyanate ester hardener 2,2'-bis(4-cyanatophenyl) propane (AroCy B10). The BP/B10 system consisting of a rigid-rod structure exhibited better thermal properties than the DGEBA/B10 system with a flexible structure. Anisotropic BP/B10 (2:1) had the highest 5% weight loss temperature, the highest amount of residue and a smaller thermal expansion coefficient than the commercial DGEBA/B10 system. The BP/B10 system, which cured at the LC phase temperature, had higher Tg than the commercial DGEBA/B10 system, as found from dynamic mechanical analysis. The BP/B10 system also demonstrated better dielectric properties than the commercial DGEBA/B10 system when enough curing agent was provided.

Background: Transmural lesion creation is essential for effective atrial fibrillation (AF) ablation. Lesion characteristics between conventional energy and high-power short-duration (HPSD) setting in contact force-guided (CF) ablation for AF remained unclear., Methods: Eighty consecutive AF patients who received CF with conventional energy setting (power control: 25-30 W, force-time integral = 400 g s, n = 40) or with HPSD (power control: 40-50 W, 10 s, n = 40) ablation were analyzed. Of them, 15 patients in each conventional and HPSD group were matched by age and gender respectively for ablation lesions analysis. Type A and B lesions were defined as a lesion with and without significant voltage reduction after ablation, respectively. The anatomical distribution of these lesions and ablation outcomes among the 2 groups were analyzed., Results: 1615 and 1724 ablation lesions were analyzed in the conventional and HPSD groups, respectively. HPSD group had a higher proportion of type A lesion compared to conventional group (P < 0.01). In the conventional group, most type A lesions were at the right pulmonary vein (RPV) posterior wall (50.2%) whereas in the HPSD group, most type A lesions were at the RPV anterior wall (44.0%) (P = 0.04). The procedure time and ablation time were significantly shorter in the HPSD group than that in the conventional group (91.0 ± 12.1 vs. 124 ± 14.2 min, P = 0.03; 30.7 ± 19.2 vs. 57.8 ± 21 min, P = 0.02, respectively). At a mean follow-up period of 11 ± 1.4 months, there were 13 and 7 patients with recurrence in conventional and HPSD group respectively (P = 0.03)., Conclusion: Optimal ablation lesion characteristics and distribution after conventional and HPSD ablation differed significantly. HPSD ablation had shorter ablation time and lower recurrence rate than did conventional ablation., (© 2021. The Author(s).)

Gamma-linolenic acid (GLA), a natural fatty acid obtained from oils of various vegetables and seeds, has been demonstrated as an anticancer agent. In this work, we investigated the anticancer effects of GLA on breast cancer BT-474 cells. GLA at 30 μM, a concentration reportedly within the range of circulating concentrations in clinical studies, caused apoptotic cell death. GLA caused an elevation in mitochondrial Ca 2+ level and a decrease in mitochondrial membrane potential. GLA treatment depleted cyclopiazonic acid (CPA)-sensitive Ca 2+ store and triggered substantial Ca 2+ influx. Intracellular Ca 2+ release triggered by GLA was suppressed by 3 μM xestospongin C (XeC, IP 3 receptor-channel blocker) and 100 μM ryanodine (ryanodine receptor-channel blocker), suggesting that the Ca 2+ release was via IP 3 receptor-channel and ryanodine receptor-channel. Increased expressions of p-eIF2α and CHOP were observed in GLA-treated cells, suggesting GLA-treated cells had increased expressions of p-eIF2α and CHOP, which suggest endoplasmic reticulum (ER) stress. In addition, GLA elicited increased production of reactive oxygen species. Taken together, our results suggest a basal level of GLA induced apoptotic cell death by causing Ca 2+ overload, mitochondrial dysfunction, Ca 2+ store depletion, ER stress, and oxidative stress. This is the first report to show that GLA caused Ca 2+ store depletion and ER stress. GLA-induced Ca 2+ store depletion resulted from opening of IP 3 receptor-channel and ryanodine receptor-channel., Competing Interests: None

The purpose of the study is to explore changes in resilience and physical and psychological distress and their related factors over time in women with endometrial cancer. This study adopted a repeated measures design using purposive sampling and was conducted in a hospital in Taiwan. Data were collected before surgery, 2 weeks after surgery, and 3 months after surgery. The measured variables consisted of demographic and disease characteristics, social support, resilience, and physical and psychological distress. A total of 48 women participated in the study, of whom 42 (mean age = 54.2 years old) completed all of the questionnaires. The results showed that resilience and physical distress in women with endometrial cancer was not statistically significantly changed over time. Rather, their psychological distress was significantly alleviated 2 weeks and 3 months after surgery as compared to before surgery. Women with less social support showed a lower level of resilience. In addition, those with a lower level of resilience experienced greater psychological distress. Compared with those who received only surgical treatment, women who had undergone surgery combined with chemotherapy and radiotherapy had more physical distress. Clinical medical staff should conduct continuing assessments of the resilience, physical distress, and psychological distress of women with endometrial cancer. Interventions related to resilience-enhancing and self-care should be implemented to avoid worsening or to improve women's resilience and distress.

In this work, we propose adopting step-type quantum wells to improve the external quantum efficiency for GaN-based yellow micro light-emitting diodes. The step-type quantum well is separated into two parts with slightly different InN compositions. The proposed quantum well structure can partially reduce the polarization mismatch between quantum barriers and quantum wells, which increases the overlap for electron and hole wave functions without affecting the emission wavelength. Another advantage is that the slightly decreased InN composition in the quantum well helps to decrease the valence band barrier height for holes. For this reason, the hole injection capability is improved. More importantly, we also find that step-type quantum wells can make holes spread less to the mesa edges, thus suppressing the surface nonradiative recombination and decreasing the leakage current.

Amplification and overexpression of the MYC oncogene in tumor cells, including ovarian cancer cells, correlates with poor responses to chemotherapy. As MYC is not directly targetable, we have analyzed molecular pathways downstream of MYC to identify potential therapeutic targets. Here we report that ovarian cancer cells overexpressing glutaminase (GLS), a target of MYC and a key enzyme in glutaminolysis, are intrinsically resistant to platinum-based chemotherapy and are enriched with intracellular antioxidant glutathione. Deprivation of glutamine by glutamine-withdrawal, GLS knockdown, or exposure to the GLS inhibitor CB-839 resulted in robust induction of reactive oxygen species in high GLS-expressing but not in low GLS-expressing ovarian cancer cells. Treatment with CB-839 rendered GLS high cells vulnerable to the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, and prolonged survival in tumor-bearing mice. These findings suggest consideration of applying a combined therapy of GLS inhibitor and PARP inhibitor to treat chemoresistant ovarian cancers, especially those with high GLS expression. SIGNIFICANCE: Targeting glutaminase disturbs redox homeostasis and nucleotide synthesis and causes replication stress in cancer cells, representing an exploitable vulnerability for the development of effective therapeutics. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/20/4514/F1.large.jpg., (©2020 American Association for Cancer Research.)

Background: Precise segmentation of the left atrium (LA) in computed tomography (CT) images constitutes a crucial preparatory step for catheter ablation in atrial fibrillation (AF). We aim to apply deep convolutional neural networks (DCNNs) to automate the LA detection/segmentation procedure and create three-dimensional (3D) geometries., Methods: Five hundred eighteen patients who underwent procedures for circumferential isolation of four pulmonary veins were enrolled. Cardiac CT images (from 97 patients) were used to construct the LA detection and segmentation models. These images were reviewed by the cardiologists such that images containing the LA were identified/segmented as the ground truth for model training. Two DCNNs which incorporated transfer learning with the architectures of ResNet50/U-Net were trained for image-based LA classification/segmentation. The LA geometry created by the deep learning model was correlated to the outcomes of AF ablation., Results: The LA detection model achieved an overall 99.0% prediction accuracy, as well as a sensitivity of 99.3% and a specificity of 98.7%. Moreover, the LA segmentation model achieved an intersection over union of 91.42%. The estimated mean LA volume of all the 518 patients studied herein with the deep learning model was 123.3 ± 40.4 ml. The greatest area under the curve with a LA volume of 139 ml yielded a positive predictive value of 85.5% without detectable AF episodes over a period of one year following ablation., Conclusions: The deep learning provides an efficient and accurate way for automatic contouring and LA volume calculation based on the construction of the 3D LA geometry., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The application of new imaging software for the reconstruction of left atrium (LA) geometry during atrial fibrillation (AF) ablation has not been well investigated., Methods: A total of 27 patients undergoing AF ablation using a CARTO Segmentation Module system were studied (phase I). High-density LA mapping using PentaRay was merged with computed tomography-based geometry from the auto-segmentation module. The spatial distortion between the two LA geometries was analyzed and compared using Registration Match View. The associated contact force on the two LA shells was prospectively validated in 16 AF patients (phase II)., Results: Of the five LA regions, the roof area had the highest quality score between the two LA shells (1.7 ± 0.6). In addition, among the pulmonary veins (PVs), higher quality scores were observed in bilateral PV carinas (both 1.8 ± 0.1, p < 0.05) than in the anterior or posterior PV regions. Furthermore, surrounding the PV ostium, the on-surface points had a significantly higher contact force when targeting the high-density fast anatomical mapping shell than for the auto-segmentation module (right superior pulmonary vein, 20.7 ± 5.8 g vs 12.5 ± 4.4 g; right inferior pulmonary vein, 19.3 ± 6.8 g vs 11.8 ± 4.8 g; left superior pulmonary vein, 22.5 ± 7.3 g vs 11.2 ± 4.5 g; left inferior pulmonary vein, 15.7 ± 6.9 g vs 9.7 ± 4.4 g, p < 0.05 for each group)., Conclusion: The CARTO Segmentation Module and Registration Match View provide better anatomic accuracy and less regional distortion of the LA geometry, and this can prevent excessive contact and potential procedural complications.

Aim: Continuous real-time echocardiographic monitoring is essential for guidance during ASD closure. However, transthoracic echocardiography (TTE) can only be implemented intermittently during fluoroscopy. We evaluate a novel approach to provide real-time imaging during the entire procedure., Finding: We developed a custom-made TTE monitoring apparatus using artificial hand (AH-TTE) that enables real-time TTE images during atrial septal defect (ASD) closure. Thirty-two patients underwent successful device implantation using AH-TTE monitoring without complications. The median duration for real-time AH-TTE monitoring was 22 min and the median fluoroscopy time was 7.2 min. One case of pericardial effusion and one of transient bradycardia event due to air embolism was detected. All patients had uneventful recoveries., Conclusions: Our simple and novel monitoring technique with AH-TTE provides TEE-like monitoring and may be a new alternative method for ASD closure. It gives real-time stable TTE images and minimizes radiation exposure for the interventional team during fluoroscopy.

Introduction: Accurate identification of slow conducting regions in patients with scar-related atrial tachycardia (AT) is difficult using conventional electrogram annotation for cardiac electroanatomic mapping (EAM). Estimating delays between neighboring mapping sites is a potential option for activation map computation. We describe our initial experience with CARTO 3 Coherent Mapping (Biosense Webster Inc,) in the ablation of complex ATs., Methods: Twenty patients (58 ± 10 y/o, 15 males) with complex ATs were included. We created three-dimensional EAMs using CARTO 3 system with CONFIDENSE and a high-resolution mapping catheter (Biosense Webster Inc). Local activation time and coherent maps were used to aid in the identification of conduction isthmus (CI) and focal origin sites. System-defined slow or nonconducting zones and CI, defined by concealed entrainment (postpacing interval < 20 ms), CV < 0.3 m/s and local fractionated electrograms were evaluated., Results: Twenty-six complex ATs were mapped (mean: 1.3 ± 0.7 maps/pt; 4 focal, 22 isthmus-dependent). Coherent mapping was better in identifying CI/breakout sites where ablation terminated the tachycardia (96.2% vs 69.2%; P = .010) and identified significantly more CI (mean/chamber 2.0 ± 1.1 vs 1.0 ± 0.7; P < .001) with narrower width (19.8 ± 10.5 vs 43.0 ± 23.9 mm; P < .001) than conventional mapping. Ablation at origin and CI sites was successful in 25 (96.2%) with long-term recurrence in 25%., Conclusions: Coherent mapping with conduction velocity vectors derived from adjacent mapping sites significantly improved the identification of CI sites in scar-related ATs with isthmus-dependent re-entry better than conventional mapping. It may be used in conjunction with conventional mapping strategies to facilitate recognition of slow conduction areas and critical sites that are important targets of ablation., (© 2020 The Authors. Journal of Cardiovascular Electrophysiology Published by Wiley Periodicals, Inc.)

Background: Catheter ablation is an effective treatment for atrioventricular nodal reentrant tachycardia (AVNRT). However, the characteristics of extremely late (>3 years) recurrences of AVNRT after a successful initial ablation are not fully elucidated. We aimed to explore the electrophysiological characteristics of extremely late recurrences of AVNRT after a successful ablation., Methods: From 1991 to 2018, 3311 patients (mean age: 48.7 ± 17.4 years; men: 1328 [40.1%]) who underwent catheter ablation for AVNRT were investigated. Baseline characteristics of the patients, recurrence status, and detailed electrophysiological parameters of the index and repeat ablation procedures were obtained for analysis., Results: After a mean follow-up period of 129.5 ± 58.0 months, 65 (2.0%) patients underwent repeat ablation for recurrences of AVNRT, of whom 17 (0.5%) presented with extremely late recurrences. The incidence of transient AV block was significantly higher in patients with extremely late recurrences (5.9%) than in those without recurrences (1.9%) but lower than that in patients with recurrences within <3 years (12.5%, P < .001). In addition, among patients with extremely late recurrences of AVNRT, the atrial-His bundle interval was significantly longer (99.1 ± 23.4 vs. 76.5 ± 13.1 ms, P < .01) and the need for intravenous isoproterenol and/or atropine for the induction of AVNRT (88.2% vs. 47.1%, P = .03) was higher in the repeat ablation procedure than in the index ablation procedure., Conclusion: Recurrences of AVNRT can occur 3 years after a successful initial ablation. The electrophysiological features of the index and repeat ablation procedures differed between patients with extremely late recurrences of AVNRT and those with recurrences within <3 years., Competing Interests: Declaration of competing interest None. Disclosures None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: The administration of androgen deprivation therapy (ADT) to patients with metastatic prostate cancer might be associated with some adverse effects such as anaemia; however, few studies have been performed in East Asian populations. This study aimed to investigate the association between ADT and iron-deficiency anaemia (IDA) among patients with prostate cancer in a population-based nationwide cohort., Design: Cohort study., Setting: Taiwan., Participants: Data for the cohort study were retrieved from the Taiwan National Health Insurance Research Database. Propensity score matching was used to select 7262 patients with prostate cancer who received ADT as the study group and 3631 patients who did not receive ADT as the control group., Primary and Secondary Outcome Measures: This study individually tracked patients over a 3-year study period and identified those who were subsequently diagnosed with IDA following the index date., Results: The incidence rates of IDA in the study and control groups were 1.66 (95% CI CI 1.45 to 1.86) and 1.01 per 100 person-years (95% CI 0.78 to 1.25), respectively. Furthermore, proportional Cox regression revealed an HR of 1.62 (95% CI 1.24 to 2.12) for IDA in the study group after adjusting for patients' age, monthly income, geographic location, residential urbanisation level and incidence of hyperlipidaemia, diabetes, hypertension, coronary heart disease, inflammatory bowel disease, other cancers and gastrointestinal bleeding., Conclusion: Compared with its non-use among patients with prostate cancer, ADT use was associated with a higher risk of IDA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute failure of radiofrequency ablation (RFA) of ventricular arrhythmias (VAs) occur in 10%-20% of patients and is partly attributed to inadequate lesion depth acquired with standard ablation protocols. Half-normal saline (HNS)-irrigation is a promising strategy to improve the success rate of VA ablation., Objective: This study investigated the efficacy of HNS-irrigated ablation after a failed standard plain normal saline solution (PNSS)-irrigated ablation on idiopathic outflow tract ventricular arrhythmia (OT-VA)., Method: This is a prospective observational study of consecutive patients undergoing RFA of idiopathic OT-VA comparing the efficacy of additional HNS-irrigated ablation for failed standard PNSS-irrigated ablation. Acute failure was defined as persistence of spontaneous VA or persistent inducibility of the clinical VA., Results: Out of 160 OT-VA cases (51 ± 15-year-old, 62 males), 31 underwent HNS irrigation after a failed standard PNSS-irrigated ablation. The HNS group had a significantly longer procedure time (60.06 ± 43.83 vs 37.51 ± 33.40 minutes; P = .013) and higher radiation exposure (31.45 ± 20.24 vs 17.22 ± 15.25 minutes; P = .001) than the PNSS group but provided an additional acute success in 21 of 31 (67.7%) patients. Over a follow-up duration of 7.8 ± 4.6 months, 24 recurrences were identified, including 8 (25.8%) in the HNS and 16 (12.4%) in the PNSS group, with lower freedom from recurrence in the HNS group (log rank P = .009). No major complication was observed., Conclusion: HNS-irrigated ablation after failed standard PNSS-irrigated ablation is safe and additionally improves acute ablation success by 67.7% for idiopathic OT-VA but with a higher rate of recurrence on follow-up. Whether the application of HNS as initial irrigant could result in better outcome requires further investigation., (© 2019 Wiley Periodicals, Inc.)

Introduction: We aimed to clarify the effect of vein of Marshall (VOM) ethanol infusion for treating VOM triggers and/or mitral flutter after first-attempt endocardial ablation in patients with nonparoxysmal atrial fibrillation (AF)., Methods and Results: Of the 254 consecutive patients (age, 56 ± 10 years; 221 male) undergoing catheter ablation for drug-refractory nonparoxysmal AF, 32 (12.6%) received VOM ethanol infusion. The patients were stratified into group 1 (pulmonary vein isolation [PVI], substrate modification, VOM ethanol infusion), group 2 (PVI, substrate modification), and group 3 (PVI alone). Propensity-matched analysis (N = 128) of long-term outcomes (3.9 ± 0.5 years) revealed a higher AF recurrence risk in group 2 (hazard ratio [HR], 4.17; 95% confidence interval [95% CI], 1.63-10.69; P = .003) and group 3 (HR, 1.82; 95% CI, 1.09-3.04; P = .021) than in group 1, as well as a higher atrial arrhythmia recurrence risk in group 2 than in group 1 (HR, 2.42; 95% CI, 1.16-5.03; P = .018). A higher procedural termination rate was observed in group 1 than groups 2 and 3 (41.7% vs 17.2% vs 18.8%; P = .042). On multivariate analysis, VOM ethanol injection was an independent predictor of freedom from recurrence of AF (HR, 0.20; 95% CI, 0.08-0.52; P = .001) and atrial arrhythmia (HR, 0.35; 95% CI, 0.17-0.74; P = .005), whereas a left atrial diameter >45 mm and hypertension were independent risk factors for recurrence. Periprocedural complications rates were comparable among the groups., Conclusion: Adjunctive VOM ethanol infusion is effective and safe for treating nonparoxysmal AF in patients with VOM triggers and/or refractory mitral flutter, providing good long-term freedom from AF and atrial arrhythmia., (© 2019 Wiley Periodicals, Inc.)

Aims: Most left atrial tachycardia (LAT) is associated with atrial fibrillation (AF). The clinical and electrophysiological characteristics and outcomes of LAT without AF have not been investigated. This study sought to determine the long-term ablation outcomes and predictors of recurrence of isolated LAT., Methods: This is a single-center study of consecutive patients with isolated LAT. Atrial arrhythmia recurrence was determined from follow-up records of patients who underwent LAT ablation from 2008 to 2017. Clinical and electrophysiologic characteristics associated with atrial arrhythmia recurrence were identified., Results: A total of 50 patients (53 ± 19 years, 46% male) with 59 LAT (1.16 ± 0.47 per patient) were enrolled. Over a mean follow-up of 37 ± 33 months, atrial arrhythmia recurrence occurred in 22 (44%) patients, 11 with atrial tachycardia (AT) only, five with AF only, and six with concurrent AT and AF. The incidence of pulmonary vein (PV) origins increased significantly in the repeat procedure (P = 0.036). Multivariate analysis identified left ventricular ejection fraction (LVEF) as the only predictor of any atrial arrhythmia recurrence and LAT recurrence, while smoking and identified macroreentrant LAT in the index procedure predicted AF recurrence., Conclusion: This study demonstrated a higher rate of atrial arrhythmia recurrence, including AF, among patients with initially isolated LAT. A lower LVEF predicted any atrial arrhythmia and LAT recurrence, whereas smoking and index macroreentrant AT mechanism predicted long-term AF. PV ATs were frequently observed in recurrent patients irrespective of index procedure origin., (© 2019 Wiley Periodicals, Inc.)

Background: Liposomes are drug nano-carriers that are capable of targeting therapeutics to tumor sites because of enhanced permeability retention (EPR). In several preclinical studies with various tumor-bearing mice models, 188 Re-liposome that has been developed by the Institute of Nuclear Energy Research (INER) demonstrates favorable in vivo tumor targeting, biodistribution, pharmacokinetics, and dosimetry. It inhibits the growth of tumors, increased survival, demonstrates good synergistic combination, and was safe to use. This study conducts a phase 0 low-radioactivity clinical trial of nano-targeted radiotherapeutics 188 Re-liposome to evaluate the effectiveness with which it targets tumors and the pharmacokinetics, biodistribution, dosimetry, and its safety in use. Twelve patients with metastatic cancers are studied in this trial. Serial whole-body scans and SPECT/CT are taken at 1, 4, 8, 24, 48, and 72 h after intravenous injection of 111 MBq of 188 Re-liposome. The effectiveness with which tumors are targeted, the pharmacokinetics, biodistribution, dosimetry, and safety are evaluated using the VelocityAI and OLINDA/EXM software. Blood samples are collected at different time points for a pharmacokinetics study and a safety evaluation that involves monitoring changes in liver, renal, and hematological functions., Results: The T ½ z for 188 Re-liposome in blood and plasma are 36.73 ± 14.00 h and 52.02 ± 45.21 h, respectively. The doses of radiation that are absorbed to vital organs such as the liver, spleen, lung, kidney, and bone marrow are 0.92 ± 0.35, 1.38 ± 1.81, 0.58 ± 0.28, 0.32 ± 0.09, and 0.06 ± 0.01 mGy/MBq, respectively, which is far less than the reference maximum tolerance dose after injection of 188 Re-liposome. 188 Re-liposome is absorbed by metastatic tumor lesions and the normal reticuloendothelial (RES) system. Certain patients exhibit a therapeutic response., Conclusion: This phase 0 exploratory IND study shows that nanocarrier 188 Re-liposome achieves favorable tumor accumulation and tumor to normal organ uptake ratios for a subset of cancer patients. The clinical pharmacokinetic, biodistribution, and dosimetry results justify a further dose-escalating phase 1 clinical trial., Trial Registration: Taiwan FDA MA1101G0 (Jan 31, 2012).

Background: Primary spontaneous pneumothorax (PSP) has a high rate of recurrence, and pleurodesis has been shown to decrease the rate of recurrence in adult PSP. For pediatric PSP patients, there are only a few case series available and evidence on the benefits of pleurodesis is insufficient. This study aimed to analyze the outcome of pleurodesis among pediatric PSP patients via a nationwide population-based cohort in Taiwan., Methods: The hospitalization data from the pediatric intensive care sampling file of the National Health Insurance Research Database from January 1 to December 31, 2010, were retrieved and analyzed. Children aged 0-18 years with a discharge diagnosis of PSP (ICD-9: 512, 512.0, and 512.8) were enrolled in the study. Demographic data, management strategies, and clinical outcomes were recorded and analyzed as well., Results: A total of 1005 hospitalization cases were identified and divided into the pleurodesis (409 hospitalizations) and nonpleurodesis (596 hospitalizations) groups. In the univariate analysis, thoracoscopic surgery for PSP decreased the incidence of recurrence (hazard ratio [HR], 0.46; 95% CI, 0.32-0.67) and the need for further surgical intervention (HR, 0.29; 95% CI, 0.18-0.47); however, conventional open surgery did not. A lesser incidence of PSP recurrence (HR, 0.53; 95% CI, 0.37-0.78) and fewer subsequent surgical interventions (HR, 0.32; 95% CI, 0.20-0.52) were found in the pleurodesis group in comparison with the nonpleurodesis group. A multivariate Cox regression analysis revealed that pleurodesis was the only significant factor capable of decreasing the incidence of PSP recurrence (HR, 0.57; 95% CI, 0.38-0.86) and the need for further surgical intervention (HR, 0.40; 95% CI, 0.23-0.69)., Conclusion: Pleurodesis reduces the rate of recurrence and the need for further surgical intervention in pediatric PSP. It may be considered as the method of choice for the management of PSP in children.

Trichomoniasis is caused by infection with the protozoan parasite Trichomonas vaginalis, and prolonged persistence may lead to serious ill effects in patients. Thus, the development of new therapeutic strategies to combat drug-resistant T. vaginalis would be clinically beneficial. Antimicrobial peptides (AMPs) comprise an emerging class of molecules that may serve as effective alternatives to antibiotics. In this report, we demonstrate that the synthetic fish AMP, Epinecidin-1 (Epi-1), acts against T. vaginalis both in vitro and in vivo. Under in vitro conditions, Epi-1 disrupted the membrane of metronidazole-resistant T. vaginalis and completely killed the pathogen. To mimic human infection in vivo, estradiol-stimulated mice with vaginal Lactobacillus acidophilus colonization were infected with T. vaginalis, followed by treatment with Epi-1, Vigill, metronidazole or furazolidone. After seven days, the T. vaginalis content was effectively decreased in Epi-1 treated mice, as measured by acridine orange staining of wet smears and tissue biopsies, as well as qPCR of vaginal discharge DNA. Taken together, our results demonstrate that Epi-1 is a strong candidate for development as an alternative therapeutic for T. vaginalis infection., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Frontline intraperitoneal chemotherapy (IPCT) in the treatment of epithelial ovarian cancer has been well established. However, the role of second-line IPCT is yet to be confirmed. With a view to implementing IPCT to treat recurrent disease, a prerequisite is to perform a cytoreductive procedure to minimize residual tumor size. However, the role of cytoreductive procedure is still in debate due to a higher chance of complications. A matched retrospective cohort study was conducted. From 2008 to 2015, we adopted a relatively simple and safe tumor drilling technique to maximize tumor exposure to second-line IPCT. Patients who received tumor drilling followed by second-line IPCT constituted the cohort group. Concurrently, patients who received standard second-line systemic chemotherapy were selected as the comparison group. After propensity score matching, 85 patients in each group entered into the final analysis. The median progression-free survival was 7.3 months (95% confidence interval [CI], 6.2-7.8) for the cohort group versus 4.1 months (95% CI, 4.0-4.3) for the comparison group (hazard ratio = 0.25 [95% CI, 0.17-0.36]; P < .001, by log-rank test). The median overall survival was 33.6 months (32.1-36.6) for the cohort group versus 25.9 months (20.5-26.9) for the comparison group (hazard ratio = 0.33 [95% CI, 0.23-0.48]; P < .001, by log-rank test). Toxicities in the cohort group were not different from those that were published in reports of IPCT for ovarian cancer. The most commonly observed toxicity was gastrointestinal origin (51.7%), and it may be attributed to the intraperitoneal pharmacokinetic clearance of cisplatin and taxol and we also discussed the mechanism of gastrointestinal toxicity. Tumor drilling followed by second-line IPCT may confer a survival advantage over standard second-line systemic chemotherapy in the treatment of recurrent ovarian cancer.

Background: Alpha-fetoprotein (AFP) is a useful tumor marker for ovarian germ cell tumors, particularly yolk sac tumor (YST). It is valuable for both diagnosis and further follow-up. Epithelial ovarian carcinoma (EOC) rarely secretes AFP, especially for clear cell type and in the postmenopausal women. Based on the limited knowledge about AFP-producing clear cell type EOC, a case and literature review on this topic is extensively reviewed., Case Presentation: We report a 55-year-old postmenopausal woman experienced vaginal spotting for one month, and serum level of AFP was 60,721 ng/ml initially. Histological examination was clear cell type EOC. Tumor cells revealed strong immunoreactivity for glypican-3 (GPC3) and AFP and weak for hepatocyte nuclear factor-1 beta (HNF-1 beta), but negative for CD30, making the diagnosis of AFP-producing clear cell type EOC with fetal gut differentiation in focal areas, FIGO (International Federation of Gynecology and Obstetrics) IIIc. Although the patient underwent an intensive treatment, including optimal debulking surgery and multi-agent chemotherapy, the patient died of disease. To provide a better understanding of clinical and molecular characteristics of the AFP-producing clear cell type EOC, we conducted a systematic literature review., Conclusions: A total of three papers described the AFP-producing clear cell type EOC are available. The overall survival rate of these cases, including the current case is 50%. Although immunohistochemical examination is not always needed in routine for the diagnosis of clear cell type EOC, to distinguish from other tumors, especially germ cell tumors, or to provide the better way to monitor therapeutic response or to evaluate the disease status, immunostaining, including GPC3, HNF-1 beta, CD30, cytokeratin 7 or 20, and AFP is taken into account. Due to rarity, the appropriate chemotherapy regimen and the biological behavior of AFP-producing clear cell type EOC are still unclear.

Background: Long-term cardiovascular risk in patients with intermediate pauses remains unclear. Whether asymptomatic patients with intermediate pauses have increased future cardiovascular events remains unknown. We hypothesize that intermediate pause is associated with increased cardiovascular risk and mortality., Methods and Results: We retrospectively analyzed 5291 patients who have pauses of <3 seconds on 24-hour Holter monitoring. Patients with pauses of 2 to 3 seconds constitute the intermediate pause patients, who are further divided into daytime pause (8:00 am-8:00 pm), nighttime pause (8:00 pm-8:00 am), and daytime plus nighttime pause groups depending on the occurring time of the pauses. The rest of the patients (pause <2 seconds) are the no pause group. The multivariate Cox hazards regression model was used to assess the hazard ratio for mortality (primary outcome) and adverse cardiovascular events (secondary outcome). There were 4859 (91.8%) patients in no pause, 248 (4.7%) in nighttime pause, 103 (1.9%) in daytime pause, and 81 (1.5%) in daytime plus nighttime pause groups. After a follow-up of 8.8±1.7 years' follow-up, 343 (6.5%) patients died. The risk for adverse cardiovascular events, including all-cause hospitalization, cardiovascular-cause hospitalization, pacemaker implantation, new-onset atrial fibrillation/heart failure, and transient ischemic attack, were higher in daytime pause and nighttime pause patients than those in the no pause group. Daytime pause (hazard ratio, 2.35; P =0.008) and daytime plus nighttime pause (hazard ratio, 2.26; P =0.016) patients have a higher mortality rate than that in nighttime pause., Conclusions: Patients with intermediate pause are associated with increased cardiovascular risk. Intermediate pauses occurring at daytime have a higher mortality rate than that at nighttime during long-term follow-up., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Pelvic masses are a common gynecologic problem, and majority of them are diagnosed as ovarian tumors finally. Sometimes, it is hard to distinguish the origin of these pelvic masses. The following case is a solitary neurofibroma arising from the right-side obturator nerve, which was impressed as a right-side ovarian tumor initially. We reported this case, and also performed a PRISMA-driven systematic review to summary the similar cases in the literature. This review includes image, molecular and pathological findings and outcome of neurofibroma., Case Presentation: A 33-year-old woman with a regular menstrual period denied any symptoms or signs. During her physical check-up, image examination revealed a right-side heterogeneous pelvic mass; it was suggestive of a complex of right-side ovarian tumor. A provisional diagnosis of retroperitoneal pelvic mass, probably a benign ovarian tumor, was made. Excision of the right-side pelvic mass was performed. We sent the specimens for frozen pathology, which indicated neurofibroma and lipomatous tumor and that the possibility of liposarcoma cannot be excluded. A segment of the obturator nerve was attached to the tumor and was severed. A right-side obturator nerve tear during tumor excision was observed, and a neurosurgeon was consulted for obturator nerve grafting and repair. The patient complained of mild weakness and paresthesia affecting the right leg, and we consulted a rehabilitation doctor for neuron injury. The patient's recovery was uneventful, and she was discharged eight days after the drain was removed. Further rehabilitation treatment was arranged., Conclusion: A neurofibroma is an uncommon pelvic retroperitoneal tumor, and it can be misdiagnosed as an adnexal mass. To our knowledge, this is a rare case of a solitary neurofibroma arising from the obturator nerve. It usually does not have any neurological deficit. We present this case to demonstrate that pelvic neurofibroma can be mistaken for an adnexal mass. This fact should be borne in mind during the diagnosis process.

The clinical characteristics of clear cell carcinoma (CCC) and endometrioid carcinoma EC) are concomitant with endometriosis (ES), which leads to the postulation of malignant transformation of ES to endometriosis-associated ovarian carcinoma (EAOC). Different deregulated functional areas were proposed accounting for the pathogenesis of EAOC transformation, and there is still a lack of a data-driven analysis with the accumulated experimental data in publicly-available databases to incorporate the deregulated functions involved in the malignant transformation of EOAC. We used the microarray gene expression datasets of ES, CCC and EC downloaded from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database. Then, we investigated the pathogenesis of EAOC by a data-driven, function-based analytic model with the quantified molecular functions defined by 1454 Gene Ontology (GO) term gene sets. This model converts the gene expression profiles to the functionome consisting of 1454 quantified GO functions, and then, the key functions involving the malignant transformation of EOAC can be extracted by a series of filters. Our results demonstrate that the deregulated oxidoreductase activity, metabolism, hormone activity, inflammatory response, innate immune response and cell-cell signaling play the key roles in the malignant transformation of EAOC. These results provide the evidence supporting the specific molecular pathways involved in the malignant transformation of EAOC., Competing Interests: The authors declare no conflict of interest.