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BACKGROUND: CA125 level normalization at different chemotherapy cycles has been reported to be a prognosticator in advanced epithelial ovarian cancer. OBJECTIVE: In the present study, we investigated whether the time (in days) to CA125 normalization or nadir during treatment could be used as markers to predict survival. METHODS: Patients with FIGO stage III–IV epithelial ovarian cancer treated with cytoreductive surgery followed by adjuvant chemotherapy between 2008 and 2016 were enrolled in this retrospective study. Clinicopathological characteristics, changes in CA125 level during treatment, and survival outcomes were analyzed. Time-dependent receiver operating characteristic curve analysis was used to determine the optimal cut-off values of the time to normalization and time to nadir of CA125 levels to predict survival. Univariate and multivariate Cox regression analysis were used to examine the impact of each variable on survival. RESULTS: A total of 106 patients were included in the analysis. The optimal cut-off values for the time to normalization and nadir for predicting survival were 60 and 194 days, respectively. In Kaplan-Meier survival analysis, CA125 level normalization ⩽ 60 days and CA125 ⩽ 35 u/mL after the third cycle, and CA125 level ⩽ 10 u/mL after the sixth cycle of chemotherapy were associated with significantly better 5-year progression-free survival (PFS) and overall survival (OS). In multivariate analysis, only CA125 level normalization > 60 days was significantly associated with poor survival outcomes (PFS, HR 2.62 [95% CI: 1.54, 4.45], p= 0.004; OS, HR 2.40 [95% CI: 1.19, 4.81], p= 0.014). CONCLUSIONS: Normalization of CA125 level within 60 days after cytoreductive surgery followed by adjuvant chemotherapy in patients with advanced ovarian epithelial cancer could be used as a marker to predict survival.

Anticytokine autoantibodies are an emerging disease etiology, through the disturbance of physiological functions of cognate cytokines. Anti-interferon (IFN)-γ autoantibodies (AIGAs) were first identified in patients with severe mycobacterial infections, and were considered to be an autoimmune phenocopy of inborn genetic errors of the IL-12/IFN-γ axis. More than 600 reported cases, most originating from Southeast Asia, have been diagnosed over the last decade. Specific HLA class II molecules are associated with these autoantibodies, which provide a genetic basis for the high prevalence of this immunodeficiency syndrome in certain ethnic groups. Salmonellosis and herpes zoster reactivation are observed in more than half the patients with AIGAs. Moreover, AIGAs have been shown to underlie severe Taralomyce marneffei infection in HIV-negative patients. AIGAs may, thus, be considered a new form of late-onset immunodeficiency conferring a predisposition not only to severe mycobacterial, but also to some bacterial and fungal infections.

Screening for mismatch repair (MMR) deficiency in unselected patients with endometrial carcinoma (EC) and the clinicopathologic descriptions of ECs with MMR deficiency have been well demonstrated in Western populations, but studies on Asian populations are relatively scarce. In this study, we described the clinicopathologic features of ECs according to MMR status in unselected Taiwanese patients. We also conducted subgroup analysis of MMR-deficient (dMMR) cases according to the presence or absence of MLH1. Patients diagnosed with ECs between January 2017 and February 2020 at our institution were included. Immunohistochemistry analysis of MLH1, PMS2, MSH2, and MSH6 proteins on endometrial primary tumors and clinicopathologic variables were assessed retrospectively. A total of 231 EC patients were enrolled, of whom 50 (21.6%) had dMMR tumors. Of these 50 cases, 39 had tumors that lacked MLH1 expression and 11 were positive for MLH1. The overall dMMR group was significantly related to older age, parity, and high histologic grade compared with the MMR-proficient (pMMR) group. ECs with MLH1 deficiency were obviously associated with several poor pathologic features, including high histologic grade, lymph node metastasis, and lymphovascular space invasion. Moreover, we first reported that parity and the late age at menopause are strongly correlated with MLH1-related dMMR EC group compared with pMMR group. In conclusion, triaging EC patients into pMMR, MLH1-related dMMR and non-MLH1-related dMMR groups by immunohistochemistry analysis may help clinicians to predict disease behavior and guide further management. The strong association between parity and MLH1-related dMMR ECs warrants further investigation on the underlying mechanism.

Hao Lin,1 Wen-Hsin Chen,1 Chen-Hsuan Wu,1,2 Yu-Che Ou,3 Yu-Jen Chen,3 Ying-Yi Chen,1 Yu-Han Lin,4 Hung-Chun Fu1– 3 1Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Graduate Institute of Clinical Medical Sciences, Chang Gung University, Lin-Kou, Taiwan; 3Department of Obstetrics and Gynecology, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi, Taiwan; 4Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: Hung-Chun FuDepartment of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta Pei Road, Niao Sung District, Kaohsiung City, Taiwan, Republic of ChinaTel +886 7 731712Fax +886 7 7322915Email allen133@adm.cgmh.org.twAim: To investigate whether the time interval between primary debulking surgery (PDS) and initiating adjuvant chemotherapy affects survival in patients with epithelial ovarian cancer (EOC).Methods: We retrospectively reviewed FIGO stage IIB to IV EOC patients who received PDS followed by adjuvant chemotherapy in our hospital between January 2008 and December 2016. The optimal cut-off time interval to chemotherapy related to survival was determined using the Contal and O’Quigley method and Cox hazard models. Cox regression analysis was used to identify the independent effect of time interval on survival.Results: A total of 152 patients were identified and divided into three groups based on the time interval between PDS and initiating adjuvant chemotherapy: early (< 23 days), intermediate (23– 43 days) and late (> 43 days). The intermediate group had a significantly better median progression-free survival (PFS, 35.5 months) compared to the early (20 months) and late (22.6 months) groups. After adjustments for confounding factors, time interval was still an independent variable affecting PFS. The intermediate group was associated with a better PFS compared with the early and late groups (hazard ratio 0.27, 95% CI 0.10– 0.83, p=0.002). There was no statistical significance in overall survival (OS) in univariate or multivariate analysis, although there was a trend towards better OS in the intermediate group.Conclusion: Our results provide evidence that the time interval from PDS to chemotherapy influences PFS in patients with advanced EOC. The optimal time to initiate chemotherapy was between 23 and 43 days, within 3– 6 weeks post-operatively. Initiating chemotherapy early (< 23 days) did not appear to benefit PFS.Keywords: time interval, chemotherapy, ovarian cancer

Objectives We investigated hippocampal-sparing lesionectomy (HSL) outcomes in temporal lobe epilepsy (TLE) and the significance of high-frequency oscillations (HFOs) detected by hippocampography in HSL. Methods We retrospectively reviewed data from patients who underwent HSL for lesional TLE. Patients were included when MRI confirmed (i) a lesion limited to the temporal lobe with normal hippocampi preoperatively and (ii) hippocampal integrity postoperatively. Factors possibly related to outcomes were collected. Intraoperative hippocampography was reviewed, and spikes, ripples, and fast ripples were marked. Seizure outcomes were tracked ≥ 2 years. Postoperative neuropsychological tests were performed and analyzed. Results We included 67 patients (35 males/32 females, median age at surgery 28 years, 57 seizure-free). Complete resection was significantly associated with being seizure-free without aura, an outcome achieved by 32 (69.6%) patients with complete resection vs 1 (12.5%) with incomplete resection (p = 0.004). Spikes/ripples/fast ripples appeared frequently in the hippocampus, occurring in 86.4%/82.4%/75.0% of cases before resection and 76.7%/78.1%/63.0% after resection. The presence and rate were unconnected to seizure outcome. Postoperative neuropsychological outcomes in intelligence and visual memory improved overall. Conclusions HSL in lesional TLE can produce satisfactory seizure and cognitive outcomes. Intraoperative hippocampography-guided resection of apparently normal hippocampi should be performed cautiously and might not be necessary. Significance This study provided evidence in decision making for patients with lesional TLE with a radiologically normal hippocampus.

AIMS To examine the level of decision difficulties of long-term-care facility (LTCF) nurses when transferring residents to the emergency department (ED) and associated influencing factors. DESIGN A cross-sectional nationwide study. METHODS The LTCFs were selected through random stratified sampling across the whole Taiwan during February 2018 to January 2019. LTCF nurses who met the selection criteria were invited to participate with two or three nurses selected from each LTCF. The Patient Transfer Decision Difficulty Scale (PTDDS) was used to measure the level of difficulty in making decisions related to the transfer of residents to the ED. Data were collected by mailing the questionnaires and asking the nurses to return the completed form in 2 weeks. Data were analysed using simple linear regression and multiple regression with stepwise methods. RESULTS In total, 618 valid questionnaires with an 85.32% response rate from 319 LTCFs were used for the data analysis. Decision difficulties that LTCF nurses experienced were moderate, the nursing personnel-bed ratio, LTCF professional training and basic life support training were predictive factors of the level of difficulty experience (scores of PTDDS) for the LTCF nurse (F = 6.81, p

BACKGROUND Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate. AIM To investigate whether RL can improve the prognosis of patients with T1b GBC. METHODS We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not. RESULTS Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50). CONCLUSION T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC.

Summary Electrochemical synthesis of high-value chemicals using renewable electricity could lead to sustainability advantages over conventional chemical manufacturing. The tight coupling between paired anodic and cathodic reactions in conventional electrochemical processes, however, constrains the products and their efficiencies. Here, we demonstrate a strategy to achieve modular electrochemical synthesis (ModES) of different chemicals by decoupling and pairing the oxidative and reductive half-reactions with a heterogeneous redox reservoir (RR). Specifically, sodium nickel hexacyanoferrate (NaNiHCF) can serve as a robust and reversible RR that enables the modular production of several strong oxidants, hydrogen peroxide (H2O2) and sodium persulfate (Na2S2O8) or active chlorine, in separate RR-coupled electrochemical processes. The system’s excellent performance and operational stability is demonstrated by continuous operation over 100 cycles (∼36 h) to produce H2O2 and Na2S2O8 with a high voltage efficiency. The concept presented here highlights the prospects for using RRs to enable efficient, modular, and on-demand electrochemical synthesis of valuable chemicals.

Integrating experiential and institutional perspectives on ecotourism programs is currently a hot topic in the management of sustainable marine tourism. We establish a preference model of ecotouris...

OBJECTIVES To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis. RESULTS In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to

The origin and fate of renal myofibroblasts is not clear after acute kidney injury (AKI). Here, we demonstrate that myofibroblasts were activated from quiescent pericytes (qPericytes) and the cell numbers increased after ischemia/reperfusion injury–induced AKI (IRI-AKI). Myofibroblasts underwent apoptosis during renal recovery but one-fifth of them survived in the recovered kidneys on day 28 after IRI-AKI and their cell numbers increased again after day 56. Microarray data showed the distinctive gene expression patterns of qPericytes, activated pericytes (aPericytes, myofibroblasts), and inactivated pericytes (iPericytes) isolated from kidneys before, on day 7, and on day 28 after IRI-AKI. Hypermethylation of the Acta2 repressor Ybx2 during IRI-AKI resulted in epigenetic modification of iPericytes to promote the transition to chronic kidney disease (CKD) and aggravated fibrogenesis induced by a second AKI induced by adenine. Mechanistically, transforming growth factor-β1 decreased the binding of YBX2 to the promoter of Acta2 and induced Ybx2 hypermethylation, thereby increasing α-smooth muscle actin expression in aPericytes. Demethylation by 5-azacytidine recovered the microvascular stabilizing function of aPericytes, reversed the profibrotic property of iPericytes, prevented AKI-CKD transition, and attenuated fibrogenesis induced by a second adenine-AKI. In conclusion, intervention to erase hypermethylation of pericytes after AKI provides a strategy to stop the transition to CKD.

Converting sunlight into a storable form of energy by spontaneous water splitting is of great interest but the difficulty in simultaneous management of optical, electrical, and catalytic properties has limited the efficiency of photoelectrochemical (PEC) devices. Herein, we implemented a decoupling scheme of light harvesting and electrocatalysis by employing a back-buried junction (BBJ) PEC cell design, which enables >95% front side light-harvesting, whereas the electrochemical reaction in conjunction with carrier separation/transport/collection occurs on the back side of the PEC cell. The resultant silicon BBJ-PEC half-cell produces a current density of 40.51 mA cm−2 for hydrogen evolution by minimizing optical, electrical, and catalytic losses (as low as 6.11, 1.76, and 1.67 mA cm−2, respectively). Monolithic fabrication also enables three BBJ-PEC cells to be connected in series as a single module, enabling unassisted solar water-splitting with a solar-to-hydrogen conversion efficiency of 15.62% and a hydrogen generation rate of 240 μg cm−2 h−1., The simultaneous management of optical, electrical, and catalytic properties is challenging for photoelectrochemical devices. Here, authors design Si back-buried junction photoelectrodes that can be series connected for unassisted water-splitting with a high solar-to-hydrogen efficiency of 15.62%.

ObjectiveAlthough mass eradication ofHelicobacter pylorihas been proposed as a means to eliminate gastric cancer, its long-term effects remain unclear.DesignMass eradication ofH. pyloriinfection was launched in 2004 and continued until 2018 for a high-risk Taiwanese population aged 30 years or older dwelling on Matsu Islands with prevalentH. pyloriinfection. Test positives for the13C-urea breath test underwent eradication therapy. We evaluated the effectiveness of the mass eradication in reducing two main outcomes, incidence and mortality rates of gastric cancer, until the end of 2016 and 2018, respectively.ResultsAfter six rounds of mass screening and eradication, the coverage rate reached 85.5% (6512/7616). The referral rate for treatment was 93.5% (4286/4584). The prevalence rates ofH. pylorifell from 64.2% to 15.0% with reinfection rates of less than 1% per person-year. The presence and severity of atrophic gastritis and intestinal metaplasia also decreased with time. Compared with the historical control period from 1995 to 2003, the effectiveness in reducing gastric cancer incidence and mortality during the chemoprevention period was 53% (95% CI 30% to 69%, pH. pylori.ConclusionPopulation-based eradication ofH. pylorihas significantly reduced gastric cancer incidence with no increase in the likelihood of adverse consequences. A significant reduction in mortality is likely to be achieved with a longer follow-up period.Trial registration numberNCT00155389

Background and aim The reliable method to stratify the gastric cancer risk after Helicobacter pylori eradication remains an elusive goal. Methods Mass eradication of H. pylori began in 2004 in a high-risk population. After eradication, a screening program involving first-stage serological tests (pepsinogen-I, pepsinogen-II, H. pylori immunoglobin G, and gastrin-17) and second-stage endoscopic examination was launched in 2015-2018. Index lesions included gastric cancer or extensive premalignant lesions. We evaluated the performance of the serological tests to "rule in" and "rule out" the risk based on positive and negative likelihood ratios, respectively. The methylation levels of microRNA-124a-3 in the stomach were measured to indicate genetic damage. Results Among 6512 invited subjects, 3895 (59.6%) participated. Both gastrin-17 and pepsinogen tests were normal in 3560 (91.4%) subjects; 206 (5.3%) gastrin-17 and 129 (3.3%) pepsinogen tests were abnormal. Years after eradication, the severity of gastritis had fallen greatly, and extensive premalignant lesions or gastric cancer frequently occurred in newly non-atrophic-appearing mucosa. Pepsinogen testing could moderately predict atrophic gastritis (positive likelihood ratio: 4.11 [95% confidence interval: 2.92-5.77]; negative likelihood ratio: 0.14 [0.10-0.19]). Gastrin-17 was not useful (0.66 and 1.20, respectively). However, pepsinogen testing poorly predicted the index lesions (2.04 [1.21-3.42] and 0.57 [0.34-0.95]). DNA methylation levels in the post-eradication mucosa were more discriminative for predicting index lesions (3.89 [2.32-6.54] and 0.25 [0.15-0.42]). Conclusions After eradication, pepsinogen false-negative results become more frequent because histology is improved but genetic damage may persist. Direct testing for genetic damage offers better discrimination.

The fast penetration of electrification in rural areas calls for the development of competitive decentralized approaches. A promising solution is represented by low-cost and compact integrated solar flow batteries; however, obtaining high energy conversion performance and long device lifetime simultaneously in these systems has been challenging. Here, we use high-efficiency perovskite/silicon tandem solar cells and redox flow batteries based on robust BTMAP-Vi/NMe-TEMPO redox couples to realize a high-performance and stable solar flow battery device. Numerical analysis methods enable the rational design of both components, achieving an optimal voltage match. These efforts led to a solar-to-output electricity efficiency of 20.1% for solar flow batteries, as well as improved device lifetime, solar power conversion utilization ratio and capacity utilization rate. The conceptual design strategy presented here also suggests general future optimization approaches for integrated solar energy conversion and storage systems. Voltage matching and rational design of redox couples enable high solar-to-output electricity efficiency and extended operational lifetime in a redox flow battery integrated with a perovskite/silicon tandem solar cell.

Purpose To determine the intensity of corneal pigmented arc in orthokeratology (ortho-k)-treated children and its correlation with wide epithelial thickness map (ETM) obtained through anterior segment optical coherent tomography (AS-OCT). Methods This retrospective case series reviews medical records of children who received ortho-k treatment for myopia control. Intensity of ortho-k-associated pigmented arc after wearing ortho-k lens more than 12 months and its correlation with each sector/zone of wide ETM obtained by AS-OCT was explored. Pigmented arcs were further divided into apparent and unapparent groups, and the clinical differences between groups were determined. Results This study included 57 eyes of 29 children (mean age, 11.4 years, range 9–15); after initiating ortho-k treatment, the incidence of the corneal pigmented arc was 91.2% with mean lens wear duration of 26.1 months. Intensity of pigmented arc was significantly correlated with lens wear duration, target power, baseline degree of myopia, C zone and sectors I2, I3 and IT3 on wide ETM. Comparison between apparent and unapparent groups showed the same significant results except for C zone. After adjusting for lens wear duration and target power, sector I2 has the highest association with pigmented arc severity. Conclusion Children treated with ortho-k are likely to develop ortho-k-associated pigmented arcs. The new wide ETM of AS-OCT can provide important information regarding the intensity of pigmented arc in these children. This can support customized pigmented arc-free ortho-k treatment for children in the future.

In 2017 and 2018, Food and Drug Administration has approved YESCARTA (axicabtagene ciloleucel) and KYMRIAH (tisagenlecleucel), two chimeric antigen receptor (CAR)-engineered T-cell products, for B-cell malignancies. It also marked a watershed moment in the development of immunotherapies for cancer. Despite the successes in adults, it remains clinically applicable only in B-cell acute lymphoblastic leukemia in pediatrics. Notably, multiple clinical trials and recent case reports about childhood central nervous system (CNS) tumors, the leading cause of deaths in children, have emerged and granted promising results. With the growing consideration of the biological responses in the interaction of human immunity, the major technical obstacles such as on-target off-tumor toxicity in widespread solid tumors, antigenic heterogeneity, adaptive resistance, difficult T-cell (CD4/CD8) trafficking, and immunosuppressive environments in CNS are gradually approached and ameliorated. The new spotlights of this review are focusing on current development, and emerging treatments for pediatric CNS tumors integrating molecular research with the mainstream of CAR-T therapeutic strategies to sketch a main axis and pathway forward in the improvement of novel gene-modified-based cellular platform.

Background Human leukocyte antigen‐identical sibling donor (ISD)‐hematopoietic stem cell transplantation (SCT) is a potentially curative treatment for high‐risk pediatric acute myeloid leukemia (AML). A haploidentical donor (HID) is readily available to almost all children. Previous studies have demonstrated that patients with HID‐SCT had similar outcomes compared to ISD‐SCT for pediatric and adult AML. However, the role of HID‐SCT in high‐risk pediatric AML is unclear. Methods To compare the overall survival of high‐risk AML children who underwent either HID‐SCT or ISD‐SCT, we analyzed 179 cases of high‐risk AML patients under 18 years of age treated with either ISD‐SCT (n = 23) or HID‐SCT (n = 156). Granulocyte colony‐stimulating factor plus anti‐thymocyte globulin‐based regimens were used for HID‐SCT. We also analyzed the subgroup data of AML patients at first complete remission (CR1) before SCT with known cytogenetic risk. Results The numbers of adverse cytogenetic risk recipients were 8 (34.8%) and 13 (18.8%) in the ISD‐SCT group and the HID‐SCT group, and the number of patients with disease status beyond CR1 were 6 (26.1%) and 14 (20.3%) in the two groups. The cumulative rates of grades II‐IV acute graft‐versus‐host disease (GVHD) were 13.0% in the ISD‐SCT group and 34.8% in the HID‐SCT group (P = 0.062), with a three‐year cumulative rates of chronic GVHD at 14.1% and 34.9%, respectively (P = 0.091). The relapse rate in the ISD‐SCT group was significantly higher than that in the HID‐SCT group (39.1% vs. 16.4%, P = 0.027); with non‐relapse mortality at 0.0% and 10.6% (P = 0.113), respectively. The three‐year overall survival rates were 73.0% for the ISD‐SCT group and 74.6% for the HID‐SCT group (P = 0.689). In subgroup analysis, the three‐year relapse rate in the ISD‐SCT group was higher than that in the HID‐SCT group (50.0% vs. 9.2%, P = 0.001) and the three‐year DFS in the ISD‐SCT group (50.0%) was lower than that in the HID‐SCT group (81.2%) (P = 0.021). Conclusions Unmanipulated HID‐SCT achieved DFS and OS outcomes comparable to those of ISD‐SCT for high‐risk pediatric AML patients with potentially higher rate but manageable GVHD.

High-refractive-index (high-n) polymers with a high optical transparency and low birefringence (Δn) have been desired in progressive optoelectronic devices. However, the trade-off between high-n and low-Δn remains a challenge at present. Here, the development of a novel array of high-n, high-sulfur-containing, highly transparent, colorless poly(phenylene sulfide) (PPS) polymers bearing triazine units in the main chains is reported. Six new triazine monomers T1–T6 with various pendant groups via different linkers (−O– and −NH−) could be prepared for developing PPSs with high-n and low Δn values. These PPSs (P1–P6) were obtained by the polycondensation of T1–T6 with commercial aromatic dithiol, 4,4′-thiobisbenzenethiol, respectively, which showed very high-n values (nav: 1.6902–1.7169 at 633 nm), high optical transparency (T % > 90% @ 400 nm), and low birefringence (Δn = 0.0015–0.0042). All the PPSs displayed high n∞ values (1.6340–1.6654), providing valuable information for the development of high-n triazine-based PPS materials for application not only in the visible region but also in the near-infrared region.

Surgical treatments for skull base meningiomas are challenging. We found that most of these lesions (75%), despite locating at the anterior, middle or posterior fossa, could be dealt with a combo skill—the pretemporal trans-cavernous trans-Meckel’s trans-tentorial trans-petrosal approach (PCMTP), which adopted the same curvilinear skin incision as for the classic pterional approach. Our aim of this study is to validate the application of this technique in treating skull base meningiomas. Patients underwent surgical intervention at our institute during 2010–2018 were retrospectively reviewed. We statistically analyzed the clinical, radiological, and pathological outcomes. In total, 109 patients operated with at least part of the PCMTP combo technique were included. The median follow-up time was 26.6 months. Tumor locations were categorized into: Zone I—sphenoid ridge, olfactory groove, and juxtasellar meningiomas which could be dealt with pterional approach. Zone II—clinoidal and cavernous sinus meningiomas which could be dealt with pretemporal trans-cavernous approach. Zone III—Meckel’s and Incisura meningiomas which could be dealt with trans-Meckel’s trans tentorial approach. Zone IV—petroclival menigiomas which could be dealt with trans-petrosal approach. When an extensive tumor occupied the anterior, middle, and posterior fossa, the whole combination of the PCMTP technique was applied. The mortality rate is 3.7% (4 patients). Three patients (2.8%) suffered from postoperative deterioration and required occasional assistance. The location of tumor was associated with different Simpson grade removal (p = 0.0015) and resection rate (p

Objective: To evaluate differences in hysteroscopic findings between benign endometrial polyps and endometrial cancer. Materials and methods: From January 2012 to December 2016, we extracted 179 cases with endometrial polyps from 3066 women who underwent hysteroscopy followed by dilatation and curettage or transcervical resection, with 154 and 25 cases of benign and malignant endometrial polyps, respectively. Clinical characteristics, histopathological and hysteroscopic findings of the women were evaluated retrospectively. Results: The hysteroscopic findings of malignant polyps were hyper-vascular (72%, 18/25), ulcerative (64%, 16/25) and polyps with irregular surfaces (24%, 6/25). In contrast, pedunculate small growths with smooth surfaces were usually seen in the benign endometrial polyps (38.3%, 59/154). Hyper-vascular (OR: 142.6, 95% CI: 25.98–783.4) and polyps with irregular surfaces (OR: 12.02, 95% CI: 1.765–81.83) in hysteroscopic findings were significant strong predictors of endometrial polyps with endometrial cancer. Hysteroscopic findings of ulcerative changes were most strongly associated with a diagnosis of malignant polyps, with sensitivity, specificity, negative (NPV) and positive (PPV) predictive values of 64.0%, 100%, 94.5%, and 100%, respectively. Conclusion: Women with hysteroscopic findings of endometrial polyps with hyper-vascular, ulcerative, and polyps with irregular surfaces had a high likelihood of endometrial cancer. A target biopsy of the polyps with these specific appearances should be performed to exclude malignant lesions. Keywords: Differential diagnoses, Endometrial cancer, Hysteroscopy, Polyps

Sequestering CO2 in the form of carbon-based liquid fuels would provide both a convenient and sustainable form of energy for practical use as well as mitigate the effects of global warming and climate change. Ocean wave energy is an abundant and relatively stable source of renewable energy, which would be highly desirable for the conversion of CO2 to conveniently stored and transported liquid fuels. In this work, we demonstrate a wave-energy-driven electrochemical CO2 reduction system, consisting of triboelectric nanogenerators, a supercapacitor and a CO2 reduction reactor, that converts ocean wave energy to chemical energy in the form of formic acid, a liquid fuel. We optimize the energy storage component of the system and operation voltage of the electrochemical cell to achieve efficient energy storage and maximize the production of formic acid. Under simulated waves, the system can produce 2.798 μmol of formic acid per day via the wave energy harvested from a water surface area of 0.04 m2. Moreover, we have performed field tests in the Red Sea to demonstrate the practicality of such an electrochemical CO2 reduction system. Finally, we present design guidelines for achieving a cost-effective, efficient, and large-scale wave-energy-driven CO2 reduction system for liquid fuel production.

The M4F project brings together the fusion and fission materials communities working on the prediction of radiation damage production and evolution and their effects on the mechanical behaviour of irradiated ferritic/martensitic (F/M) steels. It is a multidisciplinary project in which several different experimental and computational materials science tools are integrated to understand and model the complex phenomena associated with the formation and evolution of irradiation induced defects and their effects on the macroscopic behaviour of the target materials. In particular the project focuses on two specific aspects: (1) To develop physical understanding and predictive models of the origin and consequences of localised deformation under irradiation in F/M steels; (2) To develop good practices and possibly advance towards the definition of protocols for the use of ion irradiation as a tool to evaluate radiation effects on materials. Nineteen modelling codes across different scales are being used and developed and an experimental validation programme based on the examination of materials irradiated with neutrons and ions is being carried out. The project enters now its 4th year and is close to delivering high-quality results. This paper overviews the work performed so far within the project, highlighting its impact for fission and fusion materials science. Peer Reviewed L. Malerba a,*, M.J. Caturla b, E. Gaganidze c, C. Kaden d, M.J. Konstantinovi´c e, P. Olsson f, C. Robertson g, D. Rodney h, A.M. Ruiz-Moreno i, M. Serrano a, J. Aktaa c, N. Anento j, S. Austin i, A. Bakaev e, J.P. Balbuena b, F. Bergner d, F. Boioli k, M. Boleininger l, G. Bonny e, N. Castin e, J.B. J. Chapman l, P. Chekhonin d, M. Clozel m, B. Devincre k, L. Dupuy g, G. Diego a, S.L. Dudarev l, C.-C. Fu g, R. Gatti k, L. G´el´ebart g, B. G´omez-Ferrer n, D. Gonçalves g, C. Guerrero a, P.M. Gueye n, P. H¨ahner i, S.P. Hannula o, Q. Hayat p, M. Hern´andez-Mayoral a, J. Jagielski m, N. Jennett p, F. Jim´enez a, G. Kapoor d, A. Kraych h, T. Khvan e,q, L. Kurpaska m, A. Kuronen r, N. Kvashin j, O. Libera s, P.-W. Ma l, T. Manninen o, M.-C. Marinica g, S. Merino a, E. Meslin g, F. Mompiou t, F. Mota a, H. Namburi s, C.J. Ortiz a, C. Pareige n, M. Prester u, R.R. Rajakrishnan t, M. Sauzay g, A. Serra j, I. Simonovski i, F. Soisson g, P. Sp¨atig v, D. Tanguy h, D. Terentyev e, M. Trebala o, M. Trochet g, A. Ulbricht d, M.Vallet g, K. Vogel d, T. Yalcinkaya w, J. Zhao r a Centro de Investigaciones Energ´eticas, Medioambientales y Tecnol´ogicas (CIEMAT), Madrid, Spain b Universidad de Alicante, San Vicente del Raspeig, Spain c Karlsruher Institut für Technologie (KIT), Karlsruhe, Germany d Helmholtz-Zentrum Dresden-Rossendorf Ev (HZDR), Rossendorf, Germany e Studiecentrum voor Kernenergie / Centre d’´Etude de l’´Energie Nucl´eaire (SCK CEN), Mol, Belgium f KTH Royal Institute of Technology, Stockholm, Sweden g Universit´e Paris-Saclay, Commissariat `a l’´Energie Atomique et aux ´Energies Alternatives (CEA), Gif-sur-Yvette, France h Institut Lumi`ere Mati`ere (ILM), Centre National de la Recherche Scientifique, Lyon, France i Joint Research Centre (JRC)- European Commission, Petten, the Netherlands j Universitat Polit`ecnica de Catalunya, Barcelona, Spain k Laboratoire d’Etude des Microstructures (LEM), Centre National de la Recherche Scientifique, Chˆatillon, France l United Kingdom Atomic Energy Authority (UKAEA), Culham, UK m Narodowe Centrum Badan Jadrowych (NCBJ), Swierk, Poland n Normandie Univ, UNIROUEN, INSA Rouen, CNRS, Groupe de Physique des Mat´eriaux, 76000 Rouen, France o Aalto University, Espoo, Finland p Coventry University, UK q Universit´e de Li`ege, Belgium r Helsingin Yliopisto, Helsinki, Finland s Centrum Vyzkumu ˇReˇz S.R.O. (CVR), ˇReˇz, Czech Republic t Centre pour l’´Elaboration Elaboration de Mat´eriaux et pour l’´Etude des Structures (CEMES), Centre National de la Recherche Scientifique, Toulouse, France u Institut za Fiziku, Zagreb, Croatia v Paul Scherrer Institut (PSI), Villingen, Switzerland w Middle East Technical University (METU), Ankara, Turkey

BackgroundHeterogeneity exists in sepsis-associated acute kidney injury (SA-AKI). This prospective observational cohort study aimed to perform consensus cluster analysis and investigate the clinical relevance of identified sub-phenotypes of critically ill patients with dialysis-requiring SA-AKI.MethodsAll septic patients with dialysis-requiring SA-AKI, defined by the Sepsis-3 and Kidney Disease: Improving Global Outcomes AKI criteria, admitted to an intensive care unit in Taiwan between 2002 and 2018 were included. We employed unsupervised consensus clustering based on 22 clinical variables upon initialising renal replacement therapy. They were observed until death or 90 days after hospital discharge. The outcomes were mortality and being free of dialysis.ResultsIn total, 1,397 patients were enrolled (mean age of 63.8 ± 16.38 years and 69.7% were men). After a median follow-up period of 31 (interquartile range 8-123) days, all-cause mortality occurred in 911 patients (65.12%). Moreover, 133 (9.51%) survivors were dialysis dependent, where 355 (25.38%) survivors were free of dialysis. Unsupervised consensus clustering identified three sub-phenotypes associated with significantly different risks of mortality and being free of dialysis. This strategy led us to reveal that the pre-dialysis hyperlactatemia of ≥ 3.1 mmol/L was an independent predictor of mortality and being free of dialysis according to the competing risk modeling. Our results were validated in an independent multi-center AKI cohort.ConclusionsBy the data-driven clustering analysis, we identified sub-phenotypes in septic patients with dialysis-requiring SA-AKI and revealed pre-dialysis hyperlactatemia as a novel outcome predictor. This result represents a step towards precision medicine for septic patients.

Background Limited treatment options exist for relapsed advanced lung squamous cell carcinoma (SCC), leading to poor outcomes compared with adenocarcinoma. This study aimed to investigate the efficacy of second-line afatinib versus chemotherapy in patients with advanced lung SCC who progressed after first-line chemotherapy. Methods In this retrospective, multisite cohort study, we recruited patients with initial locally advanced or metastatic lung SCC from four institutes in Taiwan between June 2014 and October 2020. The primary endpoint of this study was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Results The present study enrolled 108 patients: 19 received second-line afatinib, and 89 received second-line chemotherapy. The median ages were 71 and 67 years, respectively. PFS was significantly longer among patients who received afatinib than among those who received chemotherapy (median 4.7 months [95% confidence interval (CI), 0.1–7.5] vs. 2.6 months [95% CI, 0.9–6.7]; hazard ratio (HR) 0.53 [95% CI 0.32–0.88], p = 0.013). Compared with the chemotherapy group, OS was longer in the afatinib group but did not reach significance (median 16.0 months [95% CI, 6.1–22.0] vs. 12.3 months [6.2–33.9]; HR 0.65 [95% CI 0.38–1.11], p = 0.112). Conclusions Afatinib offered a longer PFS and comparable OS to chemotherapy in advanced lung SCC patients in a real-world setting, it may be considered as a 2nd line alternative treatment choice for immunotherapy unfit advanced lung SCC patients.

The aim of the study is to determine the effects of monocular 0.125% atropine daily treatment on the longer axial length (AL) eyes in children with pediatric anisometropia. This was a retrospective cohort study. The charts of children with anisometropia (aged 6–15 years) who had a > 0.2-mm difference in AL between the two eyes were reviewed. Children who received monocular treatment of 0.125% atropine in the eye with longer AL were included for final analysis. The main outcome measure was the difference in AL between the two eyes after treatment. Regression analysis was used to model the changes in AL according to the time of treatment in both eyes. Finally, forty eyes in 20 patients (mean age 10.2 years) were included in the analyses. During the treatment period, AL was controlled in the treated eyes (p = 0.389) but elongated significantly in the untreated eyes (p p

Objective The neuromodulatory effects of focused ultrasound (FUS) have been demonstrated in animal epilepsy models; however, the safety and efficacy of FUS in humans with epilepsy have not been well established. Patients with drug-resistant epilepsy (DRE) undergoing stereo-electroencephalography (SEEG) provide an opportunity to investigate the neuromodulatory effects of FUS in humans. Methods Patients with DRE undergoing SEEG for localization of the seizure onset zone (SOZ) were prospectively enrolled. FUS was delivered to the SOZ using a neuronavigation-guided FUS system (ceiling spatial-peak temporal-average intensity level = 2.8 W/cm2 , duty cycle = 30%, modulating duration = 10 min). Simultaneous SEEG recordings were obtained during sonication and for 3 days after treatment. Seizures, interictal epileptiform discharges, and adverse events after FUS were monitored. Results Six patients met the eligibility criteria and completed FUS treatment. A decrease in seizure frequency was observed in two patients within the 3-day follow-up; however, one patient presented an increase in the frequency of subclinical seizures. Posttreatment magnetic resonance imaging revealed neither lesion nor brain edema. Significant changes in spectral power of SEEG were noted at the targeted electrodes during FUS treatment. One patient reported subjective scalp heating during FUS, and one patient developed transient naming and memory impairment that resolved within 3 weeks after FUS. Significance FUS can be safely delivered to the SOZ of patients with DRE, resulting in significant changes in spectral power of SEEG. A larger sample cohort and pursuing optimal sonication parameters will be required to elucidate the neuromodulatory effects of FUS when used for seizure control.

Introduction: Cerebral palsy (CP) is the leading cause of childhood-onset physical disability. Children with CP often have impaired upper limb (UL) function. Constraint-induced therapy (CIT) is one of the most effective UL interventions for children with unilateral CP. However, concerns about CIT for children have been repeatedly raised due to frustration caused by restraint of the child’s less-affected UL and lack of motivation for the intensive protocol. Virtual reality (VR), which can mitigate the disadvantages of CIT, potentially can be used as an alternative mediator for implementing CIT. Therefore, we developed a VR-based CIT program for children with CP using the Kinect system.Aims: The feasibility of the Kinect-based CIT program was evaluated for children with unilateral CP using a two-phase study design.Materials and Methods: In phase 1, ten children with unilateral CP were recruited. To confirm the achievement of the motor training goals, maximal UL joint angles were evaluated during gameplay. To evaluate children’s perceptions of the game, a questionnaire was used. In phase 2, eight children with unilateral CP were recruited and received an 8 weeks Kinect-based CIT intervention. Performance scores of the game and outcomes of the box and block test (BBT) were recorded weekly.Results: In phase 1, results supported that the design of the program was CIT-specific and was motivational for children with unilateral CP. In phase 2, game performance and the BBT scores began showing stable improvements in the fifth week of intervention.Conclusion: It suggested the Kinect-based CIT program was beneficial to the motor function of the affected UL for children with unilateral CP. According to the results of this feasibility study, larger and controlled effectiveness studies of the Kinect-based CIT program can be conducted to further improve its clinical utility.Clinical Trial Registration: ClinicalTrials.gov, NCT02808195; Comparative effectiveness of a Kinect-based unilateral arm training system vs. CIT for children with CP

Simple Summary Ovarian high-grade serous carcinoma is the deadliest ovarian cancer. Cancer cells develop resistance to anti-cancer regimens leading to poor prognosis. Previous studies showed that the progesterone receptor was associated with better rates of survival of ovarian cancer patients. We aimed to investigate the association between the progesterone receptor and its isoform-B and platinum sensitivity of ovarian high-grade serous carcinoma. We found that strong progesterone receptor-B expression was associated with better platinum sensitivity and better survival in high-grade serous ovarian cancer patients. Our clinical data also showed that a high expression of progesterone receptor-B and optimal debulking were the independent factors associated with better platinum sensitivity. In a cell model, enhancing progesterone receptor-B expression and progesterone treatment increased platinum sensitivity and platinum-related apoptosis of the ovarian cancer cells. These might be potential therapeutic targets of ovarian high-grade serous carcinoma. Abstract Background: Expression of the progesterone receptor (PR) has been reported to influence survival outcomes in patients with ovarian high-grade serous carcinoma (HGSC). In the present study, we attempted to investigate the association among PR and its isoforms’ expression, platinum sensitivity, and survival in ovarian HGSC. Material and methods: This retrospective study reviewed ovarian HGSC patients who received surgery followed by adjuvant chemotherapy. We analyzed total PR and PR isoform-B (PR-B) expression by immunohistochemical staining and quantified using the H-score. Then, we compared platinum sensitivity and survival outcomes between those patients with weak and strong PR-B expression. Cisplatin viability assays were carried out in ovarian HGSC cell lines (OC-3-VGH and OVCAR-3) with different PR-B expression. Results: Among 90 patients, 49 and 41 patients were considered to have platinum-sensitive and platinum-resistant disease, respectively. Pearson’s correlation model showed that the H-score of total PR correlated positively with PR-B (r = 0.813). The PR-B H-score of tumors was significantly higher in the platinum-sensitive group (p = 0.004). Multivariate analysis revealed that the PR-B H-score and optimal debulking status were independent factors predicting platinum sensitivity. When compared with strong PR-B expression, patients with weak PR-B had significantly poorer progression-free (p = 0.021) and cancer-specific survival (p = 0.046). In a cell model, cisplatin-resistant OC-3-VGH cells expressed a lower level of PR-B than wild-type cells. Overexpression of PR-B or progesterone could increase cisplatin sensitivity in both OC-3-VGH and OVCAR-3 cells via the mechanism of promoting cisplatin-related apoptosis. Conclusions: When compared to weak PR-B, ovarian HGSC patients with a strong PR-B expression had a better chance of platinum sensitivity and survival, and this finding was compatible with our experimental results. Progesterone seemed to be a platinum sensitizer, but the value of adding progesterone in the treatment of ovarian HGSC should be further investigated.

BackgroundOvarian clear cell carcinoma (OCCC) is considered to be a relatively platinum-resistant malignancy. In the present study, we investigated the impact of progesterone receptor (PR) expression on platinum sensitivity and survival outcomes in patients with OCCC.MethodsWe retrospectively reviewed 80 patients with OCCC who underwent surgery followed by adjuvant chemotherapy, and analyzed PR expression by immunohistochemical staining. The PR expression was quantified using the H-score. The platinum sensitivity and survival outcomes were compared between those with a weak and strong PR expression. Cisplatin viability experiments were performed in OCCC cell lines (TOV-21G) with different PR expressions.ResultsAmong the 80 patients, 66 and 14 were considered to have platinum-sensitive and platinum-resistant disease, respectively. The mean PR H-score of the platinum-sensitive tumors was significant higher than that of the platinum-resistant tumors (p=0.002). Although there were no significant differences in progression-free and overall survival between the patients with high and low PR expressions, the patients with a high PR expression had a trend towards better survival. In cell models, PR protein was weakly detectable in TOV-21G cells. Through transfection of PR gene, TOV-21G cells were shown to have a strong PR expression by Western blot analysis. After treating the TOV-21G cells with cisplatin, we found that the overexpression of PR enhanced cisplatin cytotoxicity. ConclusionsThe patients in this study with a strong PR expression were associated with better platinum sensitivity and survival, and this was compatible with our experimental findings. The value of PR as a tumor sensitizer to cisplatin in OCCC should be further investigated.

The intermittent nature of solar energy has made it necessary for photovoltaic (PV) systems to rely on external energy storage when deployed off-the-grid. In recent years, solar flow batteries (SFBs) have emerged as a potential alternative, which integrates energy production and storage in an integrated device. Here we performed an environmental assessment by highlighting potential hotspots that might hinder their acceptance, offering less pollutive alternatives. Specifically, we analyzed the environmental impacts of perovskite/silicon tandem based SFB. Our results show that the PV cell is responsible for three fourths of the impact of the device at lab scale, while the stack frame is responsible for the remaining impact. At this scale, the impact of the electrolytes is negligible. We expect the impact of the frame to reduce as the scale increases, while we anticipate an increase for the importance of the electrolytes as more energy is stored. For the future, the impact of the PV cell could be reduced by using a back electrode different than gold, and by substituting the perovskite/silicon tandem configuration with a perovskite/perovskite one.

Detecting multiple ions and solutes in human body is important to medical examinations of patients. In this study, Ti-doped InGaO (IGO) electrolyte–insulator–semiconductor (EIS) biosensors were fabricated for multiple ion and solute sensing capability. To optimize the sensing performance, rapid thermal annealing could enhance up to 70% hydrogen ion sensitivity and more than 50% multiple ion and solute sensitivity compared with the as-deposited sample owing to improvement of material quality. Ti-doped IGO EIS multianalyte biosensors show promise for future portable biosensing applications.

Despite III-V semiconductors demonstrating extraordinary solar-to-hydrogen (STH) conversion efficiencies, high cost and poor stability greatly impede their practical implementation in photoelectrochemical (PEC) water splitting applications. Here, we present a simple and efficient strategy for III-V-based photoelectrodes that functionally and spatially decouples the light harvesting component of the device from the electrolysis part that eliminates parasitic light absorption, reduces the cost, and enhances the stability without any compromise in efficiency. The monolithically integrated PEC cell was fabricated by an epitaxial lift-off and transfer of inversely grown InGaP/GaAs to a robust Ni-substrate and the resultant photoanode exhibits an STH efficiency of ~9% with stability ~150 h. Moreover, with the ability to access both sides of the device, we constructed a fully-integrated, unassisted-wireless “artificial leaf” system with an STH efficiency of ~6%. The excellent efficiency and stability achieved herein are attributed to the light harvesting/catalysis decoupling scheme, which concurrently improves the optical, electrical, and electrocatalytic characteristics., Photoelectrochemical water-splitting devices with III-V semiconductors are efficient for solar-to-hydrogen conversion, but high costs and poor stability limit applications. Here, authors decouple light harvesting from electrolysis to enhance stability without compromising the efficiency.

Patients with systemic lupus erythematosus (SLE) are at high risk of tuberculosis (TB) because of their immunocompromised status and the use of immunosuppressive drugs. In endemic regions, TB complicates the diagnosis and treatment of SLE, but the risk factors of mortality in these patients have not been investigated. In this study, we reviewed medical records during 2006–2016. Patients who fulfilled the 1997 American College of Rheumatology SLE criteria and presented with definite TB were enrolled. The primary outcome was mortality during TB treatment. There were 5388 SLE patients screened, and 30 patients were enrolled. Seven patients died during follow-up. Compared with the survival group, patients in the mortality group had significantly more central nervous system involvement of TB, higher Systemic Lupus Erythematosus Disease Activity Index-2000 scores and more cyclophosphamide use before TB, and higher prednisolone dose before and during TB treatment. Cox regression showed that prednisolone dose during TB treatment was an independent risk factor for mortality (per 10 mg/day increase, hazard ratio (HR) 1.61, p = .019). For SLE patients, prednisolone dose during TB treatment is an independent risk factor for mortality. Keeping prednisolone dose at less than 25 mg per day during TB treatment might be a reasonable strategy in these patients.

OBJECTIVEIn this study, the authors investigated high-frequency oscillation (HFO) networks during seizures in order to determine how HFOs spread from the focal cerebral cortex and become synchronized across various areas of the brain.METHODSAll data were obtained from stereoelectroencephalography (SEEG) signals in patients with drug-resistant temporal lobe epilepsy (TLE). The authors calculated intercontact cross-coefficients between all pairs of contacts to construct HFO networks in 20 seizures that occurred in 5 patients. They then calculated HFO network topology metrics (i.e., network density and component size) after normalizing seizure duration data by dividing each seizure into 10 intervals of equal length (labeled I1–I10).RESULTSFrom the perspective of the dynamic topologies of cortical and subcortical HFO networks, the authors observed a significant increase in network density during intervals I5–I10. A significant increase was also observed in overall energy during intervals I3–I8. The results of subnetwork analysis revealed that the number of components continuously decreased following the onset of seizures, and those results were statistically significant during intervals I3–I10. Furthermore, the majority of nodes were connected to a single dominant component during the propagation of seizures, and the percentage of nodes within the largest component grew significantly until seizure termination.CONCLUSIONSThe consistent topological changes that the authors observed suggest that TLE is affected by common epileptogenic patterns. Indeed, the findings help to elucidate the epileptogenic network that characterizes TLE, which may be of interest to researchers and physicians working to improve treatment modalities for epilepsy, including resection, cortical stimulation, and neuromodulation treatments that are responsive to network topologies.

Background Selective amygdalohippocampectomy (SAH) is designed to treat patients with mesial temporal lobe epilepsy (MTLE). Objective To determine the volume and impact of temporal lobe infarction after retractorless transsylvian SAH (en bloc resection of the hippocampus) that have not been reported. Methods A retrospective analysis of patients treated with retractorless transsylvian SAH. Infarctions were detected by magnetic resonance imaging (MRI) within the first week after the operation. Neuropsychological testing was performed preoperatively and 6 mo later. Seizure outcome was evaluated 2 yr after epilepsy surgery. Results Between 2010 and 2014, a total of 30 patients were included in this study. Analysis of postoperative MRI showed the following: (1) mean removal volume of the hippocampus-parahippocampus was 5.72 cm3, and (2) mean volumes of temporal and insular infarctions were 1.71 and 0.25 cm3, respectively. Twenty-five patients (83.3%) were free of disabling seizures (Engel class I) at 2 yr of outcome. Neuropsychological testing revealed improvement in Perceptual Organization Index (P = .036) and verbal paired associates II (P = .014) after the operation. Neither infarction volume nor removal volume was related to epilepsy outcome in linear regression model. Conclusion Transsylvian SAH has comparable seizure outcomes but bears inherent risks of vasospasm/vascular injury. Immediate postoperative small infarction volume around resection cavity or along surgical corridor was noticed after retractorless transsylvian SAH, which did not cause neuropsychological deteriorations, in contrast to previous study with the use of self-sustaining rigid retraction system. Further study should be performed to compare procedure-related infarctions and their impacts on neuropsychological outcomes in different selective approaches.

Using a novel ultraviolet (UV) irradiation method, we processed a high-performance thin-film transistor (TFT) at low temperatures. Satisfactory device integrity that was demonstrated by high field-effect mobility values of 92 and 43 cm2/Vs, small subthreshold slopes of 74 and 81 mV/decade, and ON-current/ OFF-current values of $3\times 10^{6}$ and $7\times 10^{5}$ was achieved for the SnO2 TFT at low processing temperatures of 180 °C and 100 °C, respectively. The results of X-ray photoelectron spectroscopy showed that the UV irradiation considerably increased the presence of Sn4+ and reduced the presence of unwanted Sn2+, even at low processing temperatures, improving the quality of SnO2.

Controlling ferroic orders (ferroelectricity, ferromagnetism and ferroelasticity) by optical methods is a significant challenge due to the large mismatch in energy scales between the order parameter coupling strengths and the incident photons. Here, we demonstrate an approach to manipulate multiple ferroic orders in an epitaxial mixed-phase BiFeO3 thin film at ambient temperature via laser illumination. Phase-field simulations indicate that a light-driven flexoelectric effect allows the targeted formation of ordered domains. We also achieved precise sequential laser writing and erasure of different domain patterns, which demonstrates a deterministic optical control of multiferroicity at room temperature. As ferroic orders directly influence susceptibility and conductivity in complex materials, our results not only shed light on the optical control of multiple functionalities, but also suggest possible developments for optoelectronics and related applications.

Depression is increasingly recognized as an inflammatory disease, with inflammatory crosstalk in the brain contributing its pathogenesis. Life stresses may up-regulate inflammatory processes and promote depression. Although cytokines are central to stress-related immune responses, their contribution to stress-induced depression remains unclear. Here, we used unpredictable chronic mild stress (UCMS) to induce depression-like behaviors in mice, as assessed through a suite of behavioral tests. C-X-C motif chemokine ligand 1 (CXCL1)-related molecular networks responsible for depression-like behaviors were assessed through intrahippocampal microinjection of lenti-CXCL1, the antidepressant fluoxetine, the C-X-C motif chemokine receptor 2 (CXCR2) inhibitor SB265610, and the glycogen synthase kinase-3β (GSK3β) inhibitor AR-A014418. Modulation of apoptosis-related pathways and neuronal plasticity were assessed via quantification of cleaved caspase-3, B-cell lymphoma 2-associated X protein, cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) protein expression. CXCL1/CXCL2 expression was correlated with depression-like behaviors in response to chronic stress or antidepressant treatment in the UCMS depression model. Intrahippocampal microinjection of lenti-CXCL1 increased depression-like behaviors, activated GSK3β, increased apoptosis pathways, suppressed CREB activation, and decreased BDNF. Administration of the selective GSK3β inhibitor AR-A014418 abolished the effects of lenti-CXCL1, and the CXCR2 inhibitor SB265610 prevented chronic stress-induced depression-like behaviors, inhibited GSK3β activity, blocked apoptosis pathways, and restored BDNF expression. The CXCL1/CXCR2 axis appears to play a critical role in stress-induced depression, and CXCR2 is a potential novel therapeutic target for patients with depression.-Chai, H.-H., Fu, X.-C., Ma, L., Sun, H.-T., Chen, G.-Z., Song, M.-Y., Chen, W.-X., Chen, Y.-S., Tan, M.-X., Guo, Y.-W., Li, S.-P. The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress-induced depression in mice.

Background Damage to the endothelium due to ischemia reperfusion injury (IRI) leads to a disruption of the microvasculature, which could be influenced by angiopoietin 1 via its effects on endothelium. We investigated the physiological and therapeutic roles of angiopoietin 1 in renal IRI using angiopoietin 1 knockout and over-expression mice. Methods Renal IRI was induced by clamping the right renal artery seven days after left uninephrectomy for 25 min followed by reperfusion. A whole body angiopoietin 1 knockout was achieved by induction with tamoxifen. The renal tubule over-expression of angiopoietin 1 was induced by doxycycline. Results In the normal mice, the renal expression of angiopoietin 1 increased 7 days to 14 days after IRI. The angiopoietin 1 knockout caused a delay in the recovery of renal function, less tubular regeneration and more residual tubular necrosis. The endothelial density was lower and the VE-cadherin protein loss was greater in the knockout mice. The over-expression of angiopoietin 1 attenuated the tubular necrosis and renal function impairment 1 and 3 days after IRI. The loss of the endothelium was ameliorated in the over-expression mice. This protective effect was associated with the up-regulation of the gene expression of epidermal growth factor, hepatocyte growth factor, and insulin like growth factor-1 and less tubular apoptosis. The over-expression of angiopoietin 1 stimulated tumor necrosis factor-α, C-C chemokine receptor type 2 and CX3C chemokine receptor 1 inflammatory gene expression, but did not influence macrophage infiltration. Conclusions Altogether, the augmentation and downregulation of angiopoietin 1 attenuated renal damage and impaired renal recovery, respectively, by influencing the survival/regeneration of the endothelium. The manipulation of angiopoietin 1 represents a novel therapeutic approach for the treatment of ischemic kidney injury. Electronic supplementary material The online version of this article (10.1186/s10020-019-0072-7) contains supplementary material, which is available to authorized users.

Three D–A π-conjugated copolymers PnTIF (where n = 2, 4, or 6), composed of isoindigo electron acceptor units and difluorinated bithiophene (BTF) electron donor units, were synthesized and characterized. The HOMO and LUMO energy levels, solubility (and miscibility with PCBM), crystallinity (and crystalline orientation) and PnTIF:PCBM thin film morphology (nano-fibrillar network and phase separation) of the copolymers could be adjusted by the number (0 for P2TIF, 1 for P4TIF, 2 for P6TIF) of flexible 3-dodecylthiophene spacers between the isoindigo and BTF units. From the tested polymer solar cells fabricated with PnTIF:PCBM bulk heterojunctions, P4TIF:PC61BM solar cells exhibited a remarkably high short-circuit current density of ∼22 mA cm−2 together with a fill factor of ∼61% and an open-circuit voltage >0.80 volt, resulting in a power conversion efficiency of 10.7%, making it one of the highest among PC61BM-based polymer solar cells.

Objective To focus on the potential beneficial effects of the pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP4is) on attenuating progression of diabetic kidney disease in reducing the long-term effect of the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Patients and Methods Data from the National Health Insurance Research Database from January 1, 1999, to July 31, 2011, were analyzed, and patients with diabetes weaning from dialysis-requiring AKI were identified. Cox proportional hazards models and inverse-weighted estimates of the probability of treatment were used to adjust for treatment selection bias. The outcomes were incident end-stage renal disease (ESRD) and mortality, major adverse cardiovascular events, and hospitalized heart failure. Results Of a total of 6165 patients with diabetes weaning from dialysis-requiring AKI identified, 5635 (91.4%) patients were DPP4i nonusers and 530 (8.6%) patients were DPP4i users. Compared with DPP4i nonusers, DPP4i users had a lower risk of ESRD (hazard ratio, 0.81; 95% CI, 0.70-0.94; P=.04) and all-cause mortality (hazard ratio, 0.28; 95% CI, 0.23-0.34; P

Fertility-sparing progestin therapy is highly effective in selected young women with endometrial cancer. In present study, we attempted to evaluate the role of prolonged medication and identify factors predicting successful treatment, and also assess fertility outcomes among young women with early stage endometrial endometrioid carcinoma (EC).We retrospectively reviewed clinical data from patients aged45 years with well-differentiated EC at presumed stage IA (without myometrial invasion) who wished to preserve fertility. They were managed with oral progestin at Kaohsiung Chang Gung Memorial Hospital between June 2005 and June 2019.Forty-five patients were included with a median follow-up of 53.5 months (range 12-170 months). Forty-one patients (91.1%) had complete remission, the cumulative complete response (CR) rates at 3, 6, 9, 12, and12 months were 17.7%, 48.9%, 60.0%, 68.9% and 91.1%, respectively. Among the 41 responders, 23 attempted to conceive and nine (39.1%) achieved pregnancy with 12 live newborn infants. Eleven (27.5%) responders experienced recurrence at a median of 22 months from CR (range 3-54 months). Multivariate Cox regression analysis revealed that non-diabetes (HR: 4.59; 95% CI: 1.62-12.98) and endometrial thickness2 cm (HR: 0.39; 95% CI: 1.41-17.67) were significantly factors associated with treatment response.We concluded that prolonged oral progestin treatment was possible with a certain proportion of responders (24.4%) being responded after one year. Diabetes controlled on metformin and endometrial thickness2 cm could be used as surrogate markers to predict better treatment response.

Background: To explore the clinical characteristics of acute myocardial infarction (AMI) with ventricular septal perforation (VSR) and the prognosis comparison of different treatment methods, as well as the analysis of related risk factors.Methods: From January 2006 to February 2020, 29 patients with AMI and VSR diagnosed in the people's Hospital of Peking University were selected as the study object, among them, 16 cases were male (55.2%), 13 cases were female (44.8%), the average age was 64.69 ± 10.32 years old, and they were divided into survival group (n=16) and non-survival group (n=13) according to whether they survive within 30 days of surgical or drug conservative treatment.The clinical characteristics, coronary angiography and treatment of the two groups were summarized, and the prognosis and related risk factors were analyzed.Results: There was no significant difference in the basic clinical characteristics between the two groups(P>0.05)；Compared with the results of coronary angiography in the two groups, the proportion of the culprit vessel which was a simple anterior descending branch in the non-survival group was higher than that in the survival group, there was a statistical difference between the two groups(PConclusions: Whether complete revascularization and recanalization of culprit vessels or not are independent risk factors for 30 day mortality in patients with AMI and VSR；the long-term survival rate of patients after surgery and complete revascularization is significantly higher than that of patients with conservative medical treatment and incomplete revascularization. Surgery and complete revascularization are important factors affecting the long-term prognosis of patients with AMI and VSR.

Background: Intensive care unit (ICU) admission following a short-term emergency department (ED) revisit has been considered a particularly undesirable outcome among return-visit patients, although their in-hospital prognosis has not been discussed. We aimed to compare clinical outcomes between adult patients admitted to the ICU after unscheduled ED revisits and those admitted during index ED visits. Method: This retrospective study was conducted at two tertiary medical centers in Taiwan from 1 January 2016 to 31 December 2017. All adult non-trauma patients admitted to the ICU directly via the ED during the study period were included and divided into two comparison groups: patients admitted to the ICU during index ED visits and those admitted to the ICU during return ED visits. The outcomes of interest included in-hospital mortality, mechanical ventilation (MV) support, profound shock, hospital length of stay (HLOS), and total medical cost. Results: Altogether, 12,075 patients with a mean (standard deviation) age of 64.6 (15.7) years were included. Among these, 5.3% were admitted to the ICU following a return ED visit within 14 days and 3.1% were admitted following a return ED visit within 7 days. After adjusting for confounding factors for multivariate regression analysis, ICU admission following an ED revisit within 14 days was not associated with an increased mortality rate (adjusted odds ratio (aOR): 1.08, 95% confidence interval (CI): 0.89 to 1.32), MV support (aOR: 1.06, 95% CI: 0.89 to 1.26), profound shock (aOR: 0.99, 95% CI: 0.84 to 1.18), prolonged HLOS (difference: 0.04 days, 95% CI: −1.02 to 1.09), and increased total medical cost (difference: USD 361, 95% CI: −303 to 1025). Similar results were observed after the regression analysis in patients that had a 7-day return visit. Conclusion: ICU admission following a return ED visit was not associated with major in-hospital outcomes including mortality, MV support, shock, increased HLOS, or medical cost. Although ICU admissions following ED revisits are considered serious adverse events, they may not indicate poor prognosis in ED practice.