bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk profile analysis and complications after surgery for autoimmune thyroid disease
Authors: Thomusch O , Sekulla C , Billmann F , Seifert G , Dralle H , Lorenz K , Vorländer C , Dralle H , Freitag M , Jähne J , Steinmüller T , Trupka A , Steinert F , Schabram J , Heinzmann B , Lang H , Cotte J , Hoffmann T F , Dette K , Gellert K , Henne-Bruns D , Boese-Landgraf J , Simon Evangelisches D , Kube R , Lorenz E P M , Pross M , Hartel M , Thomschke D , Pistorius G , Hopt U T , Franke C , Rose U , Steuer W , Schwenk W , Ebert K-H , Kelm C , Witzigmann H , Rampf W , Ridwelski K , Knoefel W T , Bechstein W O , Grothe D , Anthuber M , Mirow L , Probst W , Thews A , Fleck U , Kärgel W , Schimmelpenning H , Fielitz J , Rose U , Schöffauer T , Asperger W , Zaage J , Dorn H-U , Weitz J , Neubauer M , Klar E , Lautermann J , Senkal M , Lippert H , Lück R , Ziesche M , Kröll K-P , Skrobisz J , Lorenc Z , Dudesek B , Smutny S , Brauckhoff M , Längle F , Wenzl E
Published: March 2018

Background

Surgical approaches to autoimmune thyroid disease are currently hampered by concerns over postoperative complications. Risk profiles and incidences of postoperative complications have not been investigated systematically, and studies with sufficient power to show valid data have not been performed.

Methods

A prospective multicentre European study was conducted between July 2010 and December 2012. Questionnaires were used to collect data prospectively on patients who had surgery for autoimmune thyroid disease and the findings were compared with those of patients undergoing surgery for multinodular goitre. Logistic regression analysis was used to evaluate risk factors for thyroid surgery-specific complications, transient and permanent recurrent laryngeal nerve (RLN) palsy and hypoparathyroidism.

Results

Data were available for 22 011 patients, of whom 18 955 were eligible for analysis (2488 who had surgery for autoimmune thyroid disease and 16 467 for multinodular goitre). Surgery for multinodular goitre and that for autoimmune thyroid disease did not differ significantly with regard to general complications. With regard to thyroid surgery-specific complications, the rate of temporary and permanent vocal cord palsy ranged from 2·7 to 6·7 per cent (P = 0·623) and from 0·0 to 1·4 per cent (P = 0·600) respectively, whereas the range for temporary and permanent hypoparathyroidism was 12·9 to 20·0 per cent (P < 0·001) and 0·0 to 7·0 per cent (P < 0·001) respectively. In logistic regression analysis of transient and permanent vocal cord palsy, autoimmune thyroid disease was not an independent risk factor. Autoimmune thyroid disease, extent of thyroid resection, number of identified parathyroid glands and no autotransplantation were identified as independent risk factors for both transient and permanent hypoparathyroidism.

Conclusion

Surgery for autoimmune thyroid disease is safe in comparison with surgery for multinodular goitre in terms of general complications and RLN palsy. To avoid the increased risk of postoperative hypoparathyroidism, special attention needs to be paid to the parathyroid glands.
Synthesis and Characterization of a 2‐(1,1‐Dicyanomethylene) rhodanine‐based Nonfullerene Acceptor for OPVs
Authors: Koh Changwoo , Lim Eunhee
Published: March 2018

We synthesized an A–π–D–π–A‐type nonfullerene small molecule acceptor (Flu‐CNRH) based on fluorene and 2‐(1,1‐dicyanomethylene)rhodanine (CNRH) by a Knoevenagel condensation of the diformyl compound (Flu‐T‐CHO) and CNRH for the use as acceptors in organic photovoltaic cells (OPVs). Introduction of CNRH end groups effectively lowered the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels of the acceptor compared to those of the corresponding rhodanine‐based acceptor (Flu‐RH). The HOMO and LUMO levels of Flu‐CNRH are −5.71 and −3.60 eV, respectively. For comparison, Flu‐RH has HOMO and LUMO energy levels of −5.58 and −3.53 eV, respectively. This lowered LUMO energy level enables Flu‐CNRH to be combined with low bandgap polymer donors PTB7 and PTB7‐Th by providing proper LUMO offsets between donor and acceptor. OPV cells were fabricated with the device configuration of ITO/PEDOT:PSS/active layer/LiF/Al. The best power conversion efficiency of 1.47% was obtained in the P3HT:Flu‐CNRH devices at a D:A ratio of 1:1.5 and with annealing at 140°C. Moreover, Flu‐CNRH showed compatibility with low bandgap polymer donor PTB7 (1.22%) with external quantum efficiency response at a longer wavelength region up to 750 nm, while Flu‐RH had no photovoltaic behavior with PTB7 and PTB7‐Th.
Quantification of metronidazole in human plasma using a highly sensitive and rugged LC–MS/MS method for a bioequivalence study
Authors: Vanol Pravin G. , Sanyal Mallika , Shah Priyanka A. , Shrivastav Pranav S.
Published: March 2018

A highly sensitive, selective and rugged method has been described for the quantification of metronidazole (MTZ) in human plasma by liquid chromatography–tandem mass spectrometry using metronidazole‐d4 as the internal standard (IS). The analyte and the IS were extracted from 100 μL plasma by liquid–liquid extraction. The clear samples obtained were chromatographed on an ACE C18 (100 × 4.6 mm, 5 μm) column using acetonitrile and 10.0 mm ammonium formate in water, pH 4.00 (80:20, v/v) as the mobile phase. A triple quadrupole mass spectrometer system equipped with turbo ion spray source and operated in multiple reaction monitoring mode was used for the detection and quantification of MTZ. The calibration range was established from 0.01 to 10.0 μg/mL. The results of validation testing for precision and accuracy, selectivity, matrix effects, recovery and stability complied with current bioanalytical guidelines. A run time of 3.0 min permitted analysis of more than 300 samples in a day. The method was applied to a bioequivalence study with 250 mg MTZ tablet formulation in 24 healthy Indian males.
Simultaneous determination of zidebactam and cefepime in dog plasma by LC–MS/MS and its application to pre‐clinical pharmacokinetic study
Authors: Patil Kiran , Tambe Harshad , Zope Vineet , Chavan Rajesh , Yeole Ravindra , Patel Mahesh
Published: March 2018

A precise and accurate liquid chromatography–tandem mass spectrometric (LC–MS/MS) bioanalytical method has been developed and validated for the simultaneous quantification of zidebactam (ZID) and cefepime (FEP) in dog plasma. Ceftazidime was used as an internal standard. Protein precipitation method was used as sample preparation approach. The calibration curve obtained was linear (r ≥ 0.99) over the concentration range 0.156–80 μg/mL for ZID and 0.312–160 μg/mL for FEP. The method was validated as per US Food and Drug Administration guidelines and the results met the acceptance criteria. A run time of 3.5 min for each sample made it possible to analyze the maximum number of samples per day. The proposed method was successfully applied for pharmacokinetic study in beagle dogs.
Inhibitory effects of Danhong Injection and its major constituents on human cytochrome P450 enzymes in vitro
Authors: Ye Lin‐Hu , Zhao Xin‐Qian , Kong Ling‐Ti , Wang Li‐Sha , Tao Xue , Wu Hui , He Mei , Chang Qi
Published: March 2018

Danhong Injection (DHI) as a Chinese patent medicine is mainly used to treat ischemic encephalopathy and coronary heart disease in combination with other chemotherapy. However, the information on DHI's potential drug interactions is limited. The goal of this work was to examine the potential P450‐mediated metabolism drug interaction arising from DHI and its active components. The results showed that DHI inhibited CYP2C19, CYP2D6, CYP3A4, CYP2E1 and CYP2C9 with IC50 values of 1.26, 1.42, 1.63, 1.10 and 1.67% (v/v), respectively. Danshensu and rosmarinic acid inhibited CYP2E1 and CYP2C9 with IC50 values of 36.63 and 75.76 μm, and 34.42 and 76.89 μm, respectively. Salvianolic acid A and B inhibited CYP2D6, CYP2E1 and CYP2C9 with IC50 values of 33.79, 21.64 and 31.94 μm, and 45.47, 13.52 and 24.15 μm, respectively. The study provides some useful information for safe and effective use of DHI in clinical practice.
Sodium valproate compared to phenytoin in treatment of status epilepticus
Authors: Amiri‐Nikpour Mohammad Reza , Nazarbaghi Surena , Eftekhari Parisa , Mohammadi Sedra , Dindarian Sina , Bagheri Mahdi , Mohammadi Hozan
Published: March 2018

Background

Status epilepticus (SE) is a neurological emergency which can be life‐threatening. Several medical regimens are used in order to control it. In this study, we intended to evaluate the clinical efficacy and tolerability of sodium valproate and intravenous phenytoin (IV PHT) in the control of SE.

Methods

One hundred and ten consecutive patients suffering from benzodiazepine refractory SE who were referred to the emergency ward from March 2014 to March 2015 were randomly divided into two groups. The first group received intravenous sodium valproate, 30 mg/kg as loading dose and then 4–8 mg/kg every 8 hr as maintenance regimen. The second group received IV PHT 20 mg/kg as loading dose and then 1.5 mg/kg for 8 hr as maintenance therapy. All patients were monitored for vital signs every 2 hr up to 12 hr. The patients were also followed up for 7 days regarding drug response and adverse effects.

Results

The administration of sodium valproate and phenytoin respectively resulted in seizure control in 43 (78.18%) and 39 (70.90%) of the patients within 7 days of drug administration (p = .428). Seven‐day mortality rate was similar in both groups (12.73% vs. 12.73%; p = .612). There was no significant difference in adverse effects between two groups.

Conclusion

Sodium valproate is preferred to IV PHT for treatment and control of SE due to its higher tolerability and lower hemodynamic instability.
Effects of oral metaphors and allegories on programming problem solving
Authors: Hidalgo‐Céspedes Jeisson , Marín‐Raventós Gabriela , Lara‐Villagrán Vladimir , Villalobos‐Fernández Luis
Published: March 2018

Metaphors of ordinary concepts are intensively used in computer science for naming abstract concepts and for designing users interfaces. Metaphors are mappings from a source domain (e.g., a stream) to a target domain (e.g., a sequence of bytes). Typically computing phenomena are explained using incoherent discourses at the source domain, formed by metaphors taken from a diversity of origins. Nonetheless, versatility of metaphors allows for the creation of coherent discourses in the origin domain that map the target computing discourse, and we call themallegories. The limited number of existing studies about this topic has compared only textual allegories, visual allegories, and the traditional unconnected metaphors. Although their findings are heterogeneous, equal effectiveness is the most frequent empirical result between these three types of metaphors. Furthermore, we have not found any study about oral allegories, in spite of oral being the most used modality for metaphors in computer science education. This article experimentally compares the effects of oral allegories and oral metaphors on a complex problem‐solving task. As in previous studies, our results did not find any significant differences on support or detriment of oral allegories. Our results support new metaphor theories posing that the context significantly influences the metaphors’ efficacy, and encourages future research about the interaction between context and allegories.
The benefit and risk of nivolumab in non‐small‐cell lung cancer: a single‐arm meta‐analysis of noncomparative clinical studies and randomized controlled trials
Authors: Zhao Binghao , Zhang Wenxiong , Yu Dongliang , Xu Jianjun , Wei Yiping
Published: March 2018

Nivolumab is a programmed cell death 1 (PD‐1) receptor inhibitor antibody that enhances immune system antitumor activity. Although it is used for treating advanced non‐small‐cell lung cancer (NSCLC), its actual efficacy has not been determined. We searched PubMed, the Cochrane Library, Embase,MEDLINE, and Web of Science for related noncomparative clinical studies and randomized controlled trials (RCTs) to assess nivolumab benefit and risk inNSCLC. The main outcomes were objective response rate (ORR), 1‐year overall survival rate (1‐yOSrate), and progression‐free survival rate at 24 weeks (PFSat 24 weeks rate), any‐grade adverse effects rate (any‐gradeAEs%), and grade 3–4AErate (grade 3–4AEs%). Relative risk (RR) was used to compareORRin patients with positive and negative programmed cell death ligand 1 (PD‐L1) expression. Random‐effects models were used to determine pooled effect size and two‐sided 95% confidence intervals (95%CI). We included 20 studies (17 noncomparative open‐label cohort studies, threeRCTs) involving 3404 patients in our meta‐analysis. The modified nivolumabORRwas 18% (95%CI: 15–20%), the 1‐yOSrate was 45% (95%CI: 40–50%),PFSat 24 weeks rate was 42% (95%CI: 37–48%), any‐gradeAEs% was 61% (95%CI: 50–73%), and grade 3–4AEs% was 12% (95%CI: 9–16%).PD‐L1 expression was related with the nivolumabORR. Nivolumab potentially causes ongoing response, long‐termPFS, and reduced treatment‐relatedAEs.PD‐L1 expression predicts the outcome of nivolumab immunotherapy. More high‐quality and well‐designedRCTs with large sample sizes are warranted to prove our findings.
NOTCH1 mutation and its prognostic significance in Chinese chronic lymphocytic leukemia: a retrospective study of 317 cases
Authors: Zou Yixin , Fan Lei , Xia Yi , Miao Yi , Wu Wei , Cao Lei , Wu Jiazhu , Zhu Huayuan , Qiao Chun , Wang Li , Xu Wei , Li Jianyong
Published: March 2018

The proto‐oncogene NOTCH1 is frequently mutated in around 10% of patients with chronic lymphocytic leukemia (CLL). This study analyzed NOTCH1 mutation status of 317 Chinese patients with CLL by Sanger sequencing. The frequencies of NOTCH1 mutation in the PEST (proline (P), glutamic acid (E), serine (S), threonine (T)‐rich protein sequence) domain and the 3′ untranslated regions (UTR) were 8.2% and 0.9%, with the most frequent mutation being c.7541_7542delCT and c.*371A>G, respectively. Clinical and biological associations were determined including NOTCH1 mutations with advanced stage (Binet stage, P = 0.010), unmutated immunoglobulin heavy‐chain variable region (IGHV) gene (P < 0.001) and trisomy 12 (+12) (P = 0.014). NOTCH1‐mutated patients had lower CD20 expression intensity than NOTCH1‐unmutated patients (P = 0.029). In addition, NOTCH1‐mutated patients had shorter overall survival (OS) (P = 0.002) and treatment‐free survival (TFS) (P = 0.002) than NOTCH1‐unmutated patients, especially for patients with NOTCH1 c.7541_7542delCT and/or c.*371A>G mutations. Patients with both mutated NOTCH1 and unmutated IGHV had shorter OS (P < 0.001) and TFS (P < 0.001) than those with unmutated NOTCH1 or mutated IGHV. These data provide a comprehensive view of the clinical relevance and prognostic impact of NOTCH1 mutations on Chinese patients with CLL.
Plasma miRNA can detect colorectal cancer, but how early?
Authors: Wikberg Maria L. , Myte Robin , Palmqvist Richard , van Guelpen Bethany , Ljuslinder Ingrid
Published: March 2018

Colorectal cancer (CRC) is a major cause of deaths worldwide but has a good prognosis if detected early. The need for efficient, preferable non‐ or minimally invasive, inexpensive screening tools is therefore critical. We analyzed 12 miRNAs in pre‐ and postdiagnostic plasma samples to evaluate their potential as CRC screening markers. We used a unique study design with two overlapping cohorts, allowing analysis of pre‐ and postdiagnostic samples from 58 patients with CRC and matched healthy controls. Plasma concentrations of miR‐15b, ‐16, ‐18a, ‐19a, 21, ‐22, ‐25, ‐26a, ‐29c, ‐142‐5p, ‐150, and ‐192 were measured by semi‐quantitative real‐time PCR. Concentrations of miR‐18a, ‐21, ‐22, and ‐25 in plasma from patients with CRC were significantly altered compared to healthy controls. Combined as a multimarker panel, they detected CRC with an AUC of 0.93. Furthermore, levels of these three miRNAs also showed different levels in the prediagnostic case samples close to diagnosis. Only miR‐21‐levels were elevated several years before diagnosis. Plasma levels of miR‐18a, ‐21, ‐22, and ‐25 show promise as screening biomarkers for CRC. However, based on our unique analysis of prediagnostic and postdiagnostic samples from the same patients, we conclude that circulating miRNAs elevated at diagnosis may not automatically be suitable for CRC screening, if the increase occurs too close to clinical diagnosis.
Liquid biopsy by NGS: differential presence of exons (DPE) in cell‐free DNA reveals different patterns in metastatic and nonmetastatic colorectal cancer
Authors: Olmedillas‐López Susana , García‐Olmo Dolores C. , García‐Arranz Mariano , Peiró‐Pastor Ramón , Aguado Begoña , García‐Olmo Damián
Published: March 2018

Next‐generation sequencing (NGS) has been proposed as a suitable tool for liquid biopsy in colorectal cancer (CRC), although most studies to date have focused almost exclusively on sequencing of panels of potential clinically actionable genes. We evaluated the clinical value of whole‐exome sequencing (WES) of cell‐free DNA (cfDNA) circulating in plasma, with the goal of identifying differential clinical profiles in patients with CRC. To this end, we applied an original concept, “differential presence of exons” (DPE). We determined differences in levels of 379 exons in plasma cfDNA and used DPE analysis to cluster and classify patients with disseminated and localized disease. The resultant bioinformatics analysis pipeline allowed us to design a predictive DPE algorithm in a small subset of patients that could not be initially classified based on the selection criteria. This DPE suggests that these nucleic acids could be actively released by both tumor and nontumor cells as a means of intercellular communication and might thus play a role in the process of malignant transformation. DPE is a new technique for the study of plasma cfDNA by WES that might have predictive and prognostic value in patients with CRC.
Prognostic significance of the infiltration of CD163+ macrophages combined with CD66b+ neutrophils in gastric cancer
Authors: Huang Xiaopei , Pan Yamin , Ma Jun , Kang Zhengchun , Xu Xiaowen , Zhu Yan , Chen Jikuai , Zhang Wei , Chang Wenjun , Zhu Jiangbo
Published: March 2018

The polarization of tumor‐associated macrophages (TAMs) and tumor‐associated neutrophils (TANs), especially from the antitumoral phenotype to the protumoral phenotype under certain conditions, has an important influence on the progression of tumors. However, the interactions and combined prognosis of these cells are poorly known. Here, we detected the infiltration of CD68+ TAMs, CD163+ TAMs, and CD66b+ TANs in the specimens from 662 patients with GC by immunohistochemistry. The results showed that the infiltration of each of CD163+, CD68+, and CD66b+ cells in GC tissue was significantly increased and independently associated with GC prognosis. Strong collinearity (r = 0.690, P < 0.001) was found between the infiltration of CD163+ and CD68+ cells in GC, and multivariate Cox analysis confirmed the infiltration of CD163+ cells was a better predictor for prognosis than that of CD68+ cells. The combination of the infiltration of CD163+ and CD66b+ cells provided more accurate survival prediction than any individual marker. Patient subgroups with CD66blowCD163low (hazard ratio (HR) = 2.161; 95% confidence interval (CI)  = 1.266–3.688; P < 0.001), CD66bhighCD163high (HR = 3.575; 95% CI = 2.155–5.933; P < 0.001), and CD66blowCD163high (HR = 7.514; 95% CI = 4.583–12.312; P < 0.001) were gradually associated with shorter DFS when compared with the subgroup with CD66bhighCD163low. The similar result was also for DSS among the subgroups. Moreover, the two‐marker model could more effectively discriminate the prognosis among the patients with chemotherapy than that among those without chemotherapy. We concluded that CD163+ TAMs were a more valuable prognostic marker than CD68+ TAMs, and CD163+ TAMs combined with CD66b+ TANs could more precisely predict the prognosis of patients with GC.
Intake of bean fiber, beans, and grains and reduced risk of hormone receptor‐negative breast cancer: the San Francisco Bay Area Breast Cancer Study
Authors: Sangaramoorthy Meera , Koo Jocelyn , John Esther M.
Published: March 2018

High dietary fiber intake has been associated with reduced breast cancer risk, but few studies considered tumor subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status or included racial/ethnic minority populations who vary in their fiber intake. We analyzed food frequency data from a population‐based case–control study, including 2135 breast cancer cases (1070 Hispanics, 493 African Americans, and 572 non‐Hispanic Whites (NHWs)) and 2571 controls (1391 Hispanics, 557 African Americans, and 623 NHWs). Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer associated with fiber intake were calculated using unconditional logistic regression. Breast cancer risk associated with high intake (high vs. low quartile) of bean fiber (p‐trend = 0.01), total beans (p‐trend = 0.03), or total grains (p‐trend = 0.05) was reduced by 20%. Inverse associations were strongest for ER‐PR‐ breast cancer, with risk reductions associated with high intake ranging from 28 to 36%. For bean fiber, risk was reduced among foreign‐born Hispanics only, who had the highest fiber intake, whereas for grain intake, inverse associations were found among NHWs only. There was no evidence of association with fiber intake from vegetables and fruits or total intake of vegetables and fruits. A high dietary intake of bean fiber and fiber‐rich foods such as beans and grains may lower the risk of ER‐PR‐ breast cancer, an aggressive breast cancer subtype for which few risk factors have been identified.
Describing symptoms using the Symptom Screening in Pediatrics Tool in hospitalized children with cancer and hematopoietic stem cell transplant recipients
Authors: Johnston Donna L. , Hyslop Shannon , Tomlinson Deborah , Baggott Christina , Gibson Paul , Orsey Andrea , Dix David , Price Vicky , Vanan Magimairajan , Portwine Carol , Kuczynski Susan , Spiegler Brenda , Tomlinson George A. , Dupuis Laura Lee , Sung Lillian
Published: March 2018

Objectives were to describe any bothersome symptom and severely bothersome symptoms in inpatient children with cancer and hematopoietic stem cell transplant (HSCT) recipients. We included children 8–18 years of age with cancer or HSCT recipients who were receiving active treatment for cancer, admitted to hospital, and expected to be in hospital 3 days later. We administered the self‐report Symptom Screening in Pediatrics Tool (SSPedi). We described those who identified any degree of symptom bother (at least “a little”) and those who rated the degree of bother as severe (“a lot” or “extremely”). Factors associated with severe symptoms and total SSPedi scores were examined using multiple logistic and linear regression. Among the 302 patients, 298 (98.7%) reported having any bothersome symptom and 181 (59.9%) had at least one severely bothersome symptom. In multiple regression, older children were significantly more likely to have at least one severely bothersome symptom (15–18 and 11–14 years vs. 8–10 years; P = 0.008) and to have higher total SSPedi scores (P = 0.0003). Those with relapsed disease were more likely to have at least one severely bothersome symptom (odds ratio 2.1, 95% confidence interval 1.1–4.3; P = 0.037) and HSCT recipients were more likely to have higher symptom scores (β = 3.48, standard error = 1.6; P = 0.030). Almost all children receiving cancer therapies experience bothersome symptoms and 60% have at least one severely bothersome symptom. Older children experienced more severely bothersome symptoms and higher symptom scores. Future studies should follow children longitudinally to better understand the symptom trajectory and should institute interventions to manage symptoms.
Targeting LMW‐PTP to sensitize melanoma cancer cells toward chemo‐ and radiotherapy
Authors: Lori Giulia , Paoli Paolo , Caselli Anna , Cirri Paolo , Marzocchini Riccardo , Mangoni Monica , Talamonti Cinzia , Livi Lorenzo , Raugei Giovanni
Published: March 2018

Tumor resistance to apoptosis is one the main causes of anticancer treatment failure. Previous studies showed that LMW‐PTP overexpression enhances resistance of cancer cells to traditional anticancer drugs. Today, the role of LMW‐PTP in inducing resistance to apoptosis in melanoma cells remains to be elucidated. Experimental setting include MTT assay, Annexin V/Pi method, and colony assay to assess whether silencing of LMW‐PTP improves the sensitivity of A375 to dacarbazine, 5‐FU, and radiotherapy. Pharmacological targeting of LMW‐PTP was obtained using Morin, a LMW‐PTP inhibitor. The ability of Morin to improve the effectiveness of anticancer drugs and radiotherapy was also studied. Moreover, PC3 cells were used as an alternative cellular model to confirm the data obtained with melanoma cells. We found that LMW‐PTP silencing improves the effectiveness of dacarbazine, 5‐FU, and radiotherapy. Identical results were obtained in vivo when Morin was used to target LMW‐PTP. We demonstrated that Morin synergizes with dacarbazine, improving its cytotoxic activity. However, we showed that the combined treatment, Morin‐anticancer drug, does not affect the viability of noncancerous cells. Knockdown of LMW‐PTP sensitizes also PC3 cells to docetaxel and radiotherapy. In conclusion, we showed that LMW‐PTP targeting improves effectiveness of anticancer drugs used for treatment of melanoma. Moreover, our results suggest that Morin could be used as adjuvant to improve the outcome of patients affected by metastatic melanoma.
Anti‐tumor effects of a nonsteroidal anti‐inflammatory drug zaltoprofen on chondrosarcoma via activating peroxisome proliferator‐activated receptor gamma and suppressing matrix metalloproteinase‐2 expression
Authors: Higuchi Takashi , Takeuchi Akihiko , Munesue Seiichi , Yamamoto Norio , Hayashi Katsuhiro , Kimura Hiroaki , Miwa Shinji , Inatani Hiroyuki , Shimozaki Shingo , Kato Takashi , Aoki Yu , Abe Kensaku , Taniguchi Yuta , Aiba Hisaki , Murakami Hideki , Harashima Ai , Yamamoto Yasuhiko , Tsuchiya Hiroyuki
Published: March 2018

Surgical resection is the only treatment for chondrosarcomas, because of their resistance to chemotherapy and radiotherapy; therefore, additional strategies are crucial to treat chondrosarcomas. Peroxisome proliferator‐activated receptor gamma (PPARγ) is a ligand‐activated transcription factor, which has been reported as a possible therapeutic target in certain malignancies including chondrosarcomas. In this study, we demonstrated that a nonsteroidal anti‐inflammatory drug, zaltoprofen, could induce PPARγ activation and elicit anti‐tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce expressions of PPARγ mRNA and protein in human chondrosarcoma SW1353 and OUMS27 cells, and induce PPARγ‐responsible promoter reporter activities. Inhibitory effects of zaltoprofen were observed on cell viability, proliferation, migration, and invasion, and the activity of matrix metalloproteinase‐2 (MMP2); these effects were dependent on PPARγ activation and evidenced by silencing PPARγ. Moreover, we showed a case of a patient with cervical chondrosarcoma (grade 2), who was treated with zaltoprofen and has been free from disease progression for more than 2 years. Histopathological findings revealed enhanced expression of PPARγ and reduced expression of MMP2 after administration of zaltoprofen. These findings demonstrate that zaltoprofen could be a promising drug against the malignant phenotypes in chondrosarcomas via activation of PPARγ and inhibition of MMP2 activity.
Identification of transcriptome signature for predicting clinical response to bevacizumab in recurrent glioblastoma
Authors: Choi Seung Won , Shin Hyemi , Sa Jason K. , Cho Hee Jin , Koo Harim , Kong Doo‐Sik , Seol Ho Jun , Nam Do‐Hyun
Published: March 2018

Glioblastomas are among the most fatal brain tumors. Although no effective treatment option is available for recurrent glioblastomas (GBMs), a subset of patients evidently derived clinical benefit from bevacizumab, a monoclonal antibody against vascular endothelial growth factor. We retrospectively reviewed patients with recurrent GBM who received bevacizumab to identify biomarkers for predicting clinical response to bevacizumab. Following defined criteria, the patients were categorized into two clinical response groups, and their genetic and transcriptomic results were compared. Angiogenesis‐related gene sets were upregulated in both responders and nonresponders, whereas genes for each corresponding angiogenesis pathway were distinct from one another. Two gene sets were made, namely, the nonresponder angiogenesis gene set (NAG) and responder angiogenesis gene set (RAG), and then implemented in independent GBM cohort to validate our dataset. A similar association between the corresponding gene set and survival was observed. In NAG, COL4A2 was associated with a poor clinical outcome in bevacizumab‐treated patients. This study demonstrates that angiogenesis‐associated gene sets are composed of distinct subsets with diverse biological roles and they represent different clinical responses to anti‐angiogenic therapy. Enrichment of a distinct angiogenesis pathway may serve as a biomarker to predict patients who will derive a clinical benefit from bevacizumab.
Efatutazone and T0901317 exert synergistically therapeutic effects in acquired gefitinib‐resistant lung adenocarcinoma cells
Authors: Ni Jie , Zhou Lei‐lei , Ding Li , Zhang Xue‐qin , Zhao Xia , Li Huizi , Cao Haixia , Liu Siwen , Wang Zhuo , Ma Rong , Wu Jianzhong , Feng Jifeng
Published: March 2018

The development of acquired EGFR‐TKI therapeutic resistance is still a serious clinical problem in the management of lung adenocarcinoma. Peroxisome proliferator activated receptor gamma (PPARγ) agonists may exhibit anti‐tumor activity by transactivating genes which are closely associated with cell proliferation, apoptosis, and differentiation. However, it remains not clear whether efatutazone has similar roles in lung adenocarcinoma cells of gefitinib resistant such as HCC827‐GR and PC9‐GR. It has been demonstrated by us that efatutazone prominently increased the mRNA and protein expression of PPARγ, liver X receptor alpha (LXRα),as well as ATP binding cassette subfamily A member 1 (ABCA1). In the presence of GW9662 (a specific antagonist of PPARγ) or GGPP (a specific antagonist of LXRα), efatutazone (40 μmol/L) restored the proliferation of both HCC827‐GR and PC9‐GR cells and obviously inhibited the increased protein and mRNA expression of PPAR‐gamma, LXR‐alpha, and ABCA1 induced by efatutazone. LXRα knockdown by siRNA (si‐LXRα) significantly promoted the HCC827‐GR and PC9‐GR cells proliferation, whereas incubation efatutazone with si‐LXRα restored the proliferation ability compared with the control group. In addition, combination of efatutazone and LXRα agonist T0901317 showed a synergistic therapeutic effect on lung adenocarcinoma cell proliferation and PPAR gamma, LXR A and ABCA1 protein expression. These results indicate that efatutazone could inhibit the cells proliferation of HCC827‐GR and PC9‐GR through PPARγ/LXRα/ABCA1 pathway, and synergistic therapeutic effect is achieved when combined with T0901317.
Two New Anti‐Proliferative C18‐Norditerpenes from the Roots of Podocarpus macrophyllus
Authors: Qi Yan‐Yan , Su Jia , Zhang Zhi‐Jun , Li Lai‐Wei , Fan Min , Zhu Yu , Wu Xing‐De , Zhao Qin‐Shi
Published: March 2018

Activity‐guided fractionation strategy was used to investigate chemical constituents from the roots of Podocarpus macrophyllus. Successfully, two new norditerpenes, 2β‐hydroxymakilactone A (1) and 3β‐hydroxymakilactone A (2), along with ten known analogues (3 – 12) were isolated. The structures of 1 and 2 were elucidated by spectroscopic analysis including 1D‐, 2D‐NMR, and HR‐ESI‐MS data. The previously reported structure of 2,3‐dihydro‐2α‐hydroxypodolide was revised as 2,3‐dihydro‐2β‐hydroxypodolide (3) by spectroscopic analysis, and was further confirmed by X‐ray crystallographic analysis. Cytotoxic activities of all isolated compounds against five human solid tumour cell lines (AGS, HeLa, MDA‐MB‐231, HepG‐2, and PANC‐1) were evaluated. All of them exhibited anti‐proliferative activities (IC50 = 0.3 – 27 μm), except for 10. Compounds 1, 4, 5, 6, and 8 exhibited potent inhibitory activities with IC50 < 1 μm against HeLa and AGS cells.
Reconfigurable DNA Nanoswitches for Graphical Readout of Molecular Signals
Authors: Chandrasekaran Arun Richard
Published: March 2018

This study reports a DNA nanoswitch that can be used for visual display of outputs resulting from hybridization events of specific molecular inputs. Conformational changes of the DNA nanoswitch triggered by input DNA strands yield different “pixels” that collectively produce a graphical output on an agarose gel. This system has potential in molecular computation and biosensing approaches in which individual binding results can be translated into macromolecular visual readouts.
Liver kinase B1 suppresses growth of lung cancer cells through sonic hedgehog signaling pathway
Authors: Song Kuiyuan , Zheng Guanqun , Zhao Yue
Published: March 2018

Lung cancer is one of life‐threatening cancers in the worldwide. Liver kinase B1 (LKB1) has been reported to be closely related to cancers; however, the underlying mechanism of LKB1 in lung cancer remains unclear. In our study, a LKB1 specific shRNA was employed to down‐regulate LKB1 levels and a LKB1 over‐expression plasmid was constructed to up‐regulate LKB1 levels. Thereafter, growth of lung cancer cells was assessed by MTT assay and flow cytometry. Effects of LKB1 on the activation of sonic hedgehog (Shh) signaling pathway were detected by Western blot. Effects of LKB1 on lung cancer growth and Shh signaling pathway activation were also assessed in vivo. Our results showed that LKB1 inhibited proliferation of lung cancer cells and induced their apoptosis. Moreover, LKB1 inhibited Shh signaling pathway activation. Our in vivo study also showed that LKB1 inhibited lung cancer growth in vivo and modulated Shh signaling pathway. Treatment with cyclopamine, a Shh signaling pathway inhibitor, reversed the effects of LKB1 silencing and enhanced the effects of LKB1 over‐expression. Results of our study demonstrate that LKB1 inhibits lung cancer growth in vitro and in vivo through Shh signaling pathway.
CO2 Adducts of Carbodicarbenes: Robust and Versatile Organocatalysts for Chemical Transformation of Carbon Dioxide into Heterocyclic Compounds
Authors: Liu An‐Hua , Dang Ya‐Li , Zhou Hui , Zhang Jin‐Ju , Lu Xiao‐Bing
Published: March 2018

Four CO2 adducts of carbodicarbenes (CDCs) were first synthesized and structurally characterized by means of NMR spectroscopy, high‐resolution mass spectrometry, and FTIR spectroscopy. The introduction of 13C‐labelled CO2 confirmed the formation of the corresponding carboxylated species. Thermogravimetric analysis (TGA) provided detailed information on their thermal decarboxylation processes. The novel CDC–CO2 adducts were subsequently applied as robust and versatile organocatalysts for the carboxylative cyclization of CO2 with aziridines, epoxides, or propargylic alcohols, affording 2‐oxazolidinones and cyclic carbonates in good to excellent yields (51–99 %) and high functional group tolerance. TGA results together with control experiments indicate that the in situ formed free CDC by decarboxylation of the corresponding CDC–CO2 adducts plays the key role to activate the substrates by its strong Lewis basicity.
Autoamplification‐Enhanced Oxidative Kinetic Resolution of sec‐Alcohols and Alkyl Mandelates, and its Kinetic Model
Authors: Talsi Evgenii P. , Bryliakov Konstantin P.
Published: March 2018

In this contribution, the new dynamic nonlinear effect in asymmetric catalysis is discussed, manifesting itself in the oxidative kinetic resolution (OKR) of racemic secondary benzylic alcohols and alkyl mandelates with H2O2 in the presence of chiral Mn‐based catalyst, with the apparent selectivity factor (krel) of the resolution being nonconstant over the reaction course. Typically, the initial growth of krel is changed into decay at high conversions. In this contribution, we demonstrate the oxidative kinetic resolution of various substrates bearing sec‐alcoholic moieties, with the krel varying in different manners with increasing substrate conversion. We also present the predictive kinetic model of OKR with participation of asymmetric autoamplification. The influence of substrate and catalyst structure, as well as solvents and additives, on the behavior of krel variation, is discussed.
Formic Acid Decomposition over ZnPd—Implications for Methanol Steam Reforming
Authors: Kriegel René , Ivarsson Dennis C. A. , Armbrüster Marc
Published: March 2018

Single‐phase ZnPd with different elemental composition as well as ZnO‐supported ZnPd nanoparticles were prepared and tested concerning their catalytic properties in the formic acid decomposition with the aim to investigate a possible formate pathway in the steam reforming of methanol (MSR). Pd‐rich ZnPd showed higher catalytic activity than ZnPd with lower Pd content. All samples showed high and stable CO2 selectivity. The stability of the materials was investigated both ex situ by powder X‐ray diffraction (XRD), scanning electron microscopy (SEM), and Raman spectroscopy after formic acid decomposition as well as by in situ X‐ray photoelectron spectroscopy (in situ XPS) and operando differential thermal analysis–thermogravimetry (DTA/TG). Samples with higher Pd content exhibited higher stability against oxidation, corroborating earlier observations under MSR conditions. The supported ZnPd/ZnO material and Zn‐rich bulk ZnPd samples showed a strong modification after reaction, which is attributed to zinc formate formation during formic acid decomposition. Kinetic data give strong indications to exclude dehydrogenation of a formate intermediate as rate‐limiting step in MSR.
Ni‐Ce/Zeolites for CO2 Hydrogenation to CH4: Effect of the Metal Incorporation Order
Authors: Bacariza M. Carmen , Graça Inês , Lopes José M. , Henriques Carlos
Published: March 2018

The effect of the metal incorporation order used in the preparation of bimetallic ultrastable Y (USY) zeolite catalysts for CO2 methanation has been studied. First, a Na‐USY(3) zeolite was impregnated with 5 % of Ni and 3 % of Ce in three ways: Ni before Ce (Ce/Ni), Ce before Ni (Ni/Ce), and co‐impregnation (Ni‐Ce). Stronger interactions between Ni and Ce species are established when Ni is incorporated after or simultaneously with Ce, enhancing the reducibility of the Ni species and decreasing the Ni0 average size to approximately 2.5 nm. However, the CO2 adsorption capacity is smaller for the sample in which Ce is incorporated before Ni. Even though larger Ni0 particles (13.3 nm) are formed when Ni is impregnated first, a good CO2 adsorption capacity was also observed for this sample. Co impregnation was finally found as the best preparation method, the results being confirmed for an optimized USY catalyst in terms of Ni content, Si/Al ratio, and compensating cation.
Tin(IV) Sulfide Greatly Improves the Catalytic Performance of UiO‐66 for Carbon Dioxide Cycloaddition
Authors: Cheng Xiuyan , Zhang Bingxing , Shi Jinbiao , Zhang Jianling , Zheng Lirong , Zhang Jing , Shao Dan , Tan Xiuniang , Han Buxing , Yang Guanying
Published: March 2018

To overcome the limitations of metal–organic frameworks (MOFs) for catalysis (e.g., low catalytic activities resulting from blockage of the active metal centers by organic linkers) is of great importance. Herein, we demonstrate the formation of UiO‐66 nanoparticles with ultrasmall size and linker defects with the aid of SnS2 nanosheets. The UiO‐66 nanoparticles supported by SnS2 nanosheets were found to exhibit excellent catalytic activity for the cycloaddition reaction of CO2 with propylene oxide under solvent‐free and co‐catalyst‐free conditions. Outstandingly, the catalytic activity was 11 times higher than that of the pure UiO‐66 catalyst under optimum conditions. We thus provide a promising route to modify MOF particles thus to promote their catalytic performance.
Continuous Downstream Processing of Amino Acids in a Modular Miniplant
Authors: Hohmann Lukas , Löbnitz Lisa , Menke Christina , Santhirakumaran Bavatharani , Stier Patrick , Stenger Frank , Dufour Fabrice , Wiese Georg , zur Horst-Meyer Santer zur , Kusserow Burkhard , Zang Werner , Nirschl Hermann , Kockmann Norbert
Published: March 2018

Global competition leads to a need for a fast time to market and increased resource efficiency. Continuous processing, module‐based plant design, and multipurpose equipment are recently discussed approaches for the fine‐chemical industry. As a representative, the downstream process of amino acid production is discussed herein. A conventional batch procedure was transferred to a continuous process and realized in a modular miniplant, which comprised of evaporation in a wiped‐film evaporator, seeded cooling crystallization in a coiled tubular crystallizer, and solid/liquid separation on a vacuum belt filter. The operations were realized on‐skid with individual automation systems and integrated sensors. L‐Alanine was successfully processed in steady‐state operation.
Particle Size Distributions and Performance of Preferential Crystallization of L‐Asparagine·H2O with Tailor‐Made Additives
Authors: Kongsamai Peetikamol , Flood Chalongsri , ter Horst Joop H. , Flood Adrian E.
Published: March 2018

Preferential crystallization (PC) is a process to separate enantiomers. The efficiency of seeded, isothermal PC was enhanced using tailor‐made additives to inhibit the crystallization of the counter‐enantiomer. The inhibition of D‐asparagine (D‐Asn) monohydrate using D‐glutamic acid (D‐Glu) and D‐aspartic acid (D‐Asp) as additives in PC was investigated by comparing the purity, yield, and particle size distribution after PC of L‐Asn·H2O from DL‐Asn·H2O. The amount of pure L‐Asn·H2O solid product that can be produced before crystallization of the counter‐enantiomer is higher when using the additives D‐Asp and D‐Glu. However, the crystal size of L‐Asn·H2O increases faster in PC without additives than in PC with additives. This means that the additives inhibit not only the crystallization of D‐Asn·H2O but also the crystal growth of L‐Asn·H2O.
Hierarchical Mesoporous Organosilica–Silica Core–Shell Nanoparticles Capable of Controlled Fungicide Release
Authors: Luo Leilei , Liang Yucang , Erichsen Egil Severin , Anwander Reiner
Published: March 2018

A new class of hierarchically structured mesoporous silica core–shell nanoparticles (HSMSCSNs) with a periodic mesoporous organosilica (PMO) core and a mesoporous silica (MS) shell is reported. The applied one‐pot, two‐step strategy allows rational control over the core/shell chemical composition, topology, and pore/particle size, simply by adjusting the reaction conditions in the presence of cetyltrimethylammonium bromide (CTAB) as structure‐directing agent under basic conditions. The spherical, ethylene‐ or methylene‐bridged PMO cores feature hexagonal (p6mm) or cage‐like cubic symmetry (Pm
n) depending on the organosilica precursor. The hexagonal MS shell was obtained by n‐hexane‐induced controlled hydrolysis of TEOS followed by directional co‐assembly/condensation of silicate/CTAB composites at the PMO cores. The HSMSCSNs feature a hierarchical pore structure with pore diameters of about 2.7 and 5.6 nm in the core and shell domains, respectively. The core sizes and shell thicknesses are adjustable in the ranges of 90–275 and 15–50 nm, respectively, and the surface areas (max. 1300 m2 g−1) and pore volumes (max. 1.83 cm3 g−1) are among the highest reported for core–shell nanoparticles. The adsorption and controlled release of the fungicide propiconazole by the HSMSCSNs showed a three‐stage release profile.
Influence of Filler Pore Structure and Polymer on the Performance of MOF‐Based Mixed‐Matrix Membranes for CO2 Capture
Authors: Sabetghadam Anahid , Liu Xinlei , Benzaqui Marvin , Gkaniatsou Effrosyni , Orsi Angelica , Lozinska Magdalena M. , Sicard Clemence , Johnson Timothy , Steunou Nathalie , Wright Paul A. , Serre Christian , Gascon Jorge , Kapteijn Freek
Published: March 2018

To gain insight into the influence of metal–organic framework (MOF) fillers and polymers on membrane performance, eight different composites were studied by combining four MOFs and two polymers. MOF materials (NH2‐MIL‐53(Al), MIL‐69(Al), MIL‐96(Al) and ZIF‐94) with various chemical functionalities, topologies, and dimensionalities of porosity were employed as fillers, and two typical polymers with different permeability‐selectivity properties (6FDA‐DAM and Pebax) were selected as matrices. The best‐performing MOF–polymer composites were prepared by loading 25 wt % of MIL‐96(Al) as filler, which improved the permeability and selectivity of 6FDA‐DAM to 32 and 10 %, while for Pebax they were enhanced to 25 and 18 %, respectively. The observed differences in membrane performance in the separation of CO2 from N2 are explained on the basis of gas solubility, diffusivity properties, and compatibility between the filler and polymer phases.
Intracellular Chemistry: Integrating Molecular Inorganic Catalysts with Living Systems
Authors: Ngo Anh H. , Bose Sohini , Do Loi H.
Published: March 2018

This concept article focuses on the rapid growth of intracellular chemistry dedicated to the integration of small‐molecule metal catalysts with living cells and organisms. Although biological systems contain a plethora of biomolecules that can deactivate inorganic species, researchers have shown that small‐molecule metal catalysts could be engineered to operate in heterogeneous aqueous environments. Synthetic intracellular reactions have recently been reported for olefin hydrogenation, hydrolysis/oxidative cleavage, azide‐alkyne cycloaddition, allylcarbamate cleavage, C−C bond cross coupling, and transfer hydrogenation. Other promising targets for new biocompatible reaction discovery will also be discussed, with a special emphasis on how such innovations could lead to the development of novel technologies and chemical tools.
Phosphorescence Through Hindered Motion of Pure Organic Emitters
Authors: Hayduk Matthias , Riebe Steffen , Voskuhl Jens
Published: March 2018

This minireview deals with the phenomenon of room‐temperature phosphorescence induced by aggregation or crystallisation. Recent achievements, as well as novel classes of these unique luminophores, are put in to focus. In this fashion, different compounds, which reveal delayed fluorescence or phosphorescence upon fixation in a crystal lattice or within aggregates are described. Furthermore, the photophysical properties, the origin of the long‐lived triplet states, and the possible applications of these fascinating classes of molecules are also discussed. To conclude, a short overview about the state of art in the field of pure organic phosphors at room temperature is presented.