bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and radioligand‐binding assay of 2,5‐disubstituted thiadiazoles and evaluation of their anticonvulsant activities
Authors: Toolabi Mahsa , Khoramjouy Mona , Aghcheli Ayoub , Ayati Adileh , Moghimi Setareh , Firoozpour Loghman , Shahhosseini Soraya , Shojaei Rouhallah , Asadipour Ali , Divsalar Kouros , Faizi Mehrdad , Foroumadi Alireza 
Published: August 2020

AbstractIn this study, a number of 2,5‐disubstituted 1,3,4‐thiadiazoles were synthesized using an appropriate synthetic route, and their anticonvulsant activity was determined by the maximal electroshock seizure (MES) test and their neurotoxicity was evaluated by the rotarod test. Additionally, their hypnotic activity was tested using the pentobarbital‐induced sleep test. Compounds 7 (ED50 = 1.14 and 2.72 μmol/kg in the MES and sleep tests, respectively) and 11 (ED50 = 0.65 and 2.70 μmol/kg in the MES and sleep tests, respectively) were the most potent ones in the sleep test and anticonvulsant test, showing a comparable activity with diazepam as the reference drug. The results of in vivo studies, especially the antagonistic effects of flumazenil, and also the radioligand‐binding assay confirmed the involvement of benzodiazepine (BZD) receptors in the anticonvulsant and hypnotic activity of compounds 7 and 11. Finally, the docking study of compound 11 in the BZD‐binding site of the GABAA (gamma‐aminobutyric acid) receptor confirmed the possible binding of the compound to the BZD receptors. We concluded that the novel 1,3,4‐thiadiazole derivatives with appropriate substitution at positions 2 and 5 of the heterocyclic ring had a good affinity to BZD receptors and showed significant efficacy in the pharmacological tests.
Does an Audiovisual Dissection Manual Improve Medical Students' Learning in the Gross Anatomy Dissection Course?
Authors: Koop Christian F. A. , Marschollek Michael , Schmiedl Andreas , Proskynitopoulos Phileas J. , Behrends Marianne 
Published: August 2020

The gross anatomy dissection course is considered to be one of the most important subjects in medical school. Advancing technology facilitates the production of e‐learning material that can improve the learning of topographic anatomy during the course. The purpose of this study was to examine a locally produced audiovisual dissection manual's effects on performance in dissection, formal knowledge gained, motivation, emotions, learning behavior, and learning efficiency of the medical students. The results, combined with the total effort put into the production of the manual, should support decisions on further implementation of this kind of audiovisual e‐learning resource into the university's curriculum. First‐year medical students (n = 279) were randomly divided into three groups for two weeks within the regular dissection course hours during the dissection of the anterior and posterior triangles of the neck. Two groups received an audiovisual dissection manual (n = 96) or an improved written manual (n = 94) as an intervention, the control group (n = 89) received the standard dissection manual. After dissection, each student filled out tests and surveys and their dissections were evaluated. The audiovisual dissection manual did not have any significant positive effects on the examined parameters. The effects of the audiovisual dissection manual on the medical students' learning experience, as observed in this study, did not support further curriculum implementation of this kind of e‐learning resource. This study can serve as an orientation for further evaluation and design of e‐learning resources for the gross anatomy dissection course.
Recent Advances in Fluorescence Light‐Up Endogenous and Exogenous Carbon Monoxide Detection in Biology
Authors: Mukhopadhyay Sujay , Sarkar Arnab , Chattopadhyay Pabitra , Dhara Koushik 
Published: August 2020

AbstractConsiderable attention has been paid by the scientific community to detect toxic carbon monoxide (CO) in sub‐cellular organelles like mitochondria, lysosomes, nuclei, etc. due to their generation and accumulation through numerous biological processes and their role as signal transducer, therapeutics, etc. Various methods are also available for detection of CO, but fluorescence light‐up detection is considered the best due to its easy and accurate sensing capability. As of now, no review is available in the literature dedicated to fluorescent detection of only CO both in vitro and in vivo, but considering the huge amount of work reporting every year, it is necessary to have an account of all the recent significant works devoted to it. This review will give special attention to the most noteworthy development of fluorescent light‐up probes for the detection of cellular and sub‐cellular targetable CO starting from 2012 and emphasizing also the mechanism of action and the applications.
Adaptive σ‐Aromaticity in an Unsaturated Three‐Membered Ring
Authors: Huang Yuanyuan , Dai Chenshu , Zhu Jun 
Published: August 2020

AbstractBased on Hückel's and Baird's rules, species are aromatic either in the lowest singlet state (S0) or the lowest triplet state (T1) only. Thus, species with adaptive aromaticity (with aromaticity in both the S0 and T1 states) is particularly rare. On the other hand, σ‐aromaticity in the T1 state has been underdeveloped, let alone adaptive σ‐aromaticity. Herein, via various aromaticity indices including NICS, ACID and EDDB, we demonstrate adaptive σ‐aromaticity in an unsaturated three‐membered ring, which is a traditional area dominated by π‐aromaticity. The origin of adaptive σ‐aromaticity could be attributed to the excitation mode of the T1 state formed from out‐of‐plane π molecular orbital to the π* orbitals. Thus the σ‐aromaticity of the three‐membered ring in the S0 state could hold in the T1 state. Our findings extend the concept of adaptive σ‐aromaticity into three‐membered rings and could be useful to further develop the concept of both σ‐aromaticity and adaptive aromaticity.
Recent progress of defect chemistry on 2D materials for advanced battery anodes
Authors: Khossossi Nabil , Singh Deobrat , Ainane Abdelmajid , Ahuja Rajeev 
Published: August 2020

AbstractThe rational design of anode materials plays a significant factor in harnessing energy storage. With an in‐depth insight into the relationships and mechanisms that underlie the charge and discharge process of two‐dimensional (2D) anode materials. The efficiency of rechargeable batteries has significantly been improved through the implementation of defect chemistry on anode materials. This mini review highlights the recent progress achieved in defect chemistry on 2D materials for advanced rechargeable battery electrodes, including vacancies, chemical functionalization, grain boundary, Stone Wales defects, holes and cracks, folding and wrinkling, layered von der Waals (vdW) heterostructure in 2D materials. The defect chemistry on 2D materials provides numerous features such as a more active adsorption sites, great adsorption energy, better ions‐diffusion and therefore higher ion storage, which enhances the efficiency of the battery electrode.
Interdecadal relationship between the wintertime haze frequency over Beijing and mega‐ENSO
Authors: Wang Jing , Liu Yanju , Ding Yihui 
Published: August 2020

AbstractObservational analyses suggest that natural or internal climate variability plays a crucial role in modulating wintertime haze days in Beijing (WHDBJ) on decadal timescales, which may overwhelm the effect of human emissions to some extent. This study links the variations in WHDBJ to the mega‐El Niño–Southern Oscillation (ENSO), a newly defined ENSO‐related pattern with a vaster range of variability, on decadal timescales. The mega‐ENSO delineates an apparent out‐of‐phase relationship with WHDBJ, which could be used to explain past and recent decreases in WHDBJ in 1961–1971 and 1997–2012, as well as the increase in WHDBJ in 1972–1996. The positive phase of the mega‐ENSO can induce a high dynamical scavenging efficiency of pollutants over the Beijing area through notable in situ low‐level northerly wind anomalies that are associated with a quasi‐barotropic anticyclonic anomaly centered around Lake Baikal, thus reducing the frequency of haze days on decadal timescales, and vice versa for the negative phase. The mega‐ENSO can influence interdecadal predictions of the long‐term occurrence of haze events over Beijing. Therefore, it will be focused upon in future routine operations.
Experimentelle Untersuchung eines passiven Festkörperschwingungsdämpfers für Ingenieurkonstruktionen
Authors: Reiterer Michael , Muik Joachim 
Published: August 2020

AbstractIm Aufsatz wird die Effektivität eines passiven Festkörperschwingungsdämpfers zur Reduktion der infolge dynamischer Einwirkungen ausgelösten erzwungenen Schwingungen von turmartigen Ingenieurkonstruktionen wie z. B. Windenergieanlagen experimentell an einem Modellversuchsstand untersucht und bewertet. Der Modellversuchsstand besteht aus einem mit geringer Strukturdämpfung ausgeführten eingeschossigen Stockwerkrahmen, dessen Grundeigenfrequenz auf ca. 1 Hz abgestimmt wird. Zu Vergleichszwecken wird im Modellversuchsstand auch die Effektivität eines konventionellen passiven Flüssigkeitsdämpfers untersucht und die erzielten Ergebnisse miteinander verglichen. Der Festkörperschwingungsdämpfer besteht aus einer halbkreisförmigen Bahn, in der eine zylindrische Walze eine reibungsbehaftete Rollbewegung ausführt. Der untersuchte Schwingungsdämpfer weist somit eine Analogie zum konventionellen Pendeldämpfer auf. Zu Beginn werden die theoretischen Grundlagen und die optimale Abstimmung der im Modellversuchsstand untersuchten Schwingungsdämpfertypen dargelegt. Es werden freie Schwingversuche des Stockwerkrahmens ohne und mit aktivierten Schwingungsdämpfern durchgeführt und die in den Versuchen erzielte Schwingungsdämpfungseffektivität wird für den Festkörperschwingungsdämpfer und für den Flüssigkeitsdämpfer dargelegt.
CRISPR interference of nucleotide biosynthesis improves production of a single‐domain antibody in Escherichia coli
Authors: Landberg Jenny , Wright Naia Risager , Wulff Tune , Herrgård Markus J. , Nielsen Alex Toftgaard 
Published: August 2020

AbstractGrowth decoupling can be used to optimize the production of biochemicals and proteins in cell factories. Inhibition of excess biomass formation allows for carbon to be utilized efficiently for product formation instead of growth, resulting in increased product yields and titers. Here, we used CRISPR interference to increase the production of a single‐domain antibody (sdAb) by inhibiting growth during production. First, we screened 21 sgRNA targets in the purine and pyrimidine biosynthesis pathways and found that the repression of 11 pathway genes led to the increased green fluorescent protein production and decreased growth. The sgRNA targets pyrF, pyrG, and cmk were selected and further used to improve the production of two versions of an expression‐optimized sdAb. Proteomics analysis of the sdAb‐producing pyrF, pyrG, and cmk growth decoupling strains showed significantly decreased RpoS levels and an increase of ribosome‐associated proteins, indicating that the growth decoupling strains do not enter stationary phase and maintain their capacity for protein synthesis upon growth inhibition. Finally, sdAb production was scaled up to shake‐flask fermentation where the product yield was improved 2.6‐fold compared to the control strain with no sgRNA target sequence. An sdAb content of 14.6% was reached in the best‐performing pyrG growth decoupling strain.
Single‐step purification of a small non‐mAb biologic by peptide‐ELP‐based affinity precipitation
Authors: Mullerpatan Akshat , Kane Erin , Ghosh Ronit , Nascimento André , Andersen Henrik , Cramer Steven , Karande Pankaj 
Published: August 2020

AbstractAffinity precipitation using stimulus‐responsive biopolymers such as elastin‐like polypeptides (ELPs) have been successfully employed for the purification of monoclonal antibodies. In the current work, we extend these studies to the development of an ELP‐peptide fusion for the affinity precipitation of the therapeutically relevant small non‐mAb biologic, AdP. A 12‐mer affinity peptide ligand (P10) was identified by a primary phage biopanning followed by a secondary in‐solution fluorescence polarization screen. Peptide P10 and AdP interacted with a KD of 19.5 µM. A fusion of P10 with ELP was then shown to be successful in selectively capturing the biologic from a crude mixture. While pH shifts alone were not sufficient for product elution, the use of pH in concert with fluid‐phase modifiers such as NaCl, arginine, or ethylene glycol was effective. In particular, the use of pH 8.5 and an arginine concentration of 500 mM enabled >80% product recovery. The overall process performance evaluated by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and reversed‐phase ultra‐performance liquid chromatography analyses indicated successful single‐step purification of the biologic from an Escherichia coli lysate resulting in ∼90% purity and >80% recovery. These results demonstrate that phage display can be readily employed to identify a peptide ligand capable of successfully carrying out the purification of a non‐antibody biological product using ELP‐based affinity precipitation.
Variability in body weight precedes diagnosis in dementia: A nationwide cohort study
Authors: Ha Jane , Kwon Yeongkeun , Kwon Ye‐Ji , Kim DaHye , Han Kyungdo , Jang Mi , Park Sungsoo , Nam Ga Eun , Kim Yang Hyun , Kim Do Hoon , Park Yong Gyu , Cho Kyung‐Hwan 
Published: August 2020

AbstractBackgroundWhile there have been disagreements concerning whether obesity and increase in body weight elevate the risk of dementia, variability in body weight has been recently recognized as a new biometric associated with a high risk for a number of diseases. This nationwide, population‐based cohort study examined the association between body weight variability and dementia.MethodsA total of 2,812,245 adults (mean age, 51.7 years; standard deviation, 8.6) without a history of dementia who underwent at least three health examinations between 2005 and 2012 in a nationwide cohort were followed‐up until the date of dementia diagnosis (based on prescribed drugs and disease code) or until 2016 (median follow‐up duration, 5.38 years; interquartile range, 5.16–5.61). Cox regression models were used to evaluate the risk of Alzheimer's disease and vascular dementia according to body weight variability.ResultsThe hazard ratios (95% confidence intervals) of the highest quartiles of variability were 1.42 (1.35–1.49) for Alzheimer's disease and 1.47 (1.32–1.63) for vascular dementia compared to the lowest quartile group as a reference. This association was consistent in various subgroup analyses and sensitivity analyses.ConclusionsBody weight variability could predict Alzheimer's disease and vascular dementia, which may provide new insights into the prevention and management of dementia.
Oxysophocarpine suppresses hepatocellular carcinoma growth and sensitizes the therapeutic blockade of anti‐Lag‐3 via reducing FGL1 expression
Authors: Wang Jianchu , Wei Wang , Tang Qianli , Lu Libai , Luo Zongjiang , Li Wenchuan , Lu Yuan , Pu Jian 
Published: August 2020

AbstractHepatocellular carcinoma (HCC) is an aggressive malignancy with limited effective treatments and ranks as the second most lethal tumor. Immunotherapy has brought great hope for HCC treatment. Oxysophocarpine is a bioactive alkaloid which poses various pharmacological functions including neuroprotective, anti‐virus, anti‐convulsant, and anti‐nociception. However, there is little systematic study of Oxysophocarpine against HCC and its underlying potential and mechanism combined with immunotherapy in HCC treatment remain poorly unknown. This study was aimed to investigate whether Oxysophocarpine can distinctly suppress HCC cells and sensitize the immunotherapy of CD8+ T cells against HCC. We used HepG2, Hepa1‐6, and primary CD8+ T cells to perform in vitro assays and Hepa1‐6 subcutaneous tumor to conduct in vivo assay. Oxysophocarpine inhibited the proliferation and increased the apoptosis of HepG2 and Hepa1‐6 cells, meanwhile suppressed the migration of HepG2 and Hepa1‐6 cells. Oxysophocarpine sensitized the Lag‐3 immunotherapy effect of CD8+ T cells against HCC in vivo and in vitro by decreasing Fibrinogen‐like protein 1 (FGL1) expression through downregulating IL‐6‐mediated JAK2/STAT3 signaling, whereas Oxysophocarpine treatment had a little effect of CD8+ T cells cytotoxicity function against HCC with PD‐1, Tim‐3, or TIGIT blockade. Our studies provided preclinical basis for clinical application of Oxysophocarpine.
EBV‐LMP1 induces APOBEC3s and mitochondrial DNA hypermutation in nasopharyngeal cancer
Authors: Wakae Kousho , Kondo Satoru , Pham Hai Thanh , Wakisaka Naohiro , Que Lusheng , Li Yingfang , Zheng Xin , Fukano Kento , Kitamura Kouichi , Watashi Koichi , Aizaki Hideki , Ueno Takayoshi , Moriyama‐Kita Makiko , Ishikawa Kazuya , Nakanishi Yosuke , Endo Kazuhira , Muramatsu Masamichi , Yoshizaki Tomokazu 
Published: August 2020

AbstractAn Epstein‐Barr virus (EBV)—encoded latent membrane protein 1 (LMP1) is a principal oncogene that plays a pivotal role in EBV‐associated malignant tumors including nasopharyngeal cancer (NPC). Recent genomic landscape studies revealed that NPC also contained many genomic mutations, suggesting the role of LMP1 as a driver gene for the induction of these genomic mutations. Nonetheless, its exact mechanism has not been investigated. In this study, we report that LMP1 alters the expression profile of APOBEC3s(A3s), host deaminases that introduce consecutive C‐to‐U mutations (hypermutation). In vitro, LMP1 induces APOBEC3B (A3B) and 3F(A3F), in a nasopharyngeal cell line, AdAH. Overexpression of LMP1, A3B, or A3F induces mtDNA hypermutation, which is also detectable from NPC specimens. Expression of LMP1 and A3B in NPC was correlated with neck metastasis. These results provide evidence as to which LMP1 induces A3s and mtDNA hypermutation, and how LMP1 facilitates metastasis is also discussed.
Clinical implications of next‐generation sequencing‐based panel tests for malignant ovarian tumors
Authors: Saotome Keiko , Chiyoda Tatsuyuki , Aimono Eriko , Nakamura Kohei , Tanishima Shigeki , Nohara Sachio , Okada Chihiro , Hayashi Hideyuki , Kuroda Yuka , Nomura Hiroyuki , Susumu Nobuyuki , Iwata Takashi , Yamagami Wataru , Kataoka Fumio , Nishihara Hiroshi , Aoki Daisuke 
Published: August 2020

AbstractPrecision medicine based on cancer genomics is being applied in clinical practice. However, patients do not always derive benefits from genomic testing. Here, we performed targeted amplicon exome sequencing‐based panel tests, including 160 cancer‐related genes (PleSSision‐160), on 88 malignant ovarian tumors (high‐grade serous carcinoma, 27; endometrioid carcinoma, 15; clear cell carcinoma, 30; mucinous carcinoma, 6; undifferentiated carcinoma, 4; and others, 6 (immature teratoma, 1; carcinosarcoma, 3; squamous cell carcinoma, 1; and mixed, 1)), to assess treatment strategies and useful biomarkers for malignant ovarian tumors. Overall, actionable gene variants were found in 90.9%, and druggable gene variants were found in 40.9% of the cases. ActionableBRCA1andBRCA2variants were found in 4.5% of each of the cases.ERBB2amplification was found in 33.3% of mucinous carcinoma cases. Druggable hypermutation/ultramutation (tumor mutation burden ≥ 10 SNVs/Mbp) was found in 7.4% of high‐grade serous carcinoma, 46.7% of endometrioid carcinoma, 10% of clear cell carcinoma, 0% of mucinous carcinoma, 25% of undifferentiated carcinoma, and 33.3% of the other cancer cases. Copy number alterations were significantly higher in high‐grade serous carcinoma (P < .005) than in other histologic subtypes; some clear cell carcinoma showed high copy number alterations that were correlated with advanced stage (P < .05) and worse survival (P < .01). A high count of copy number alteration was associated with worse survival in all malignant ovarian tumors (P < .05). Our study shows that targeted agents can be detected in approximately 40% of malignant ovarian tumors via multigene panel testing, and copy number alteration count can be a useful marker to help assess risks in malignant ovarian tumor patients.
Phase II trial of S‐1 treatment as palliative‐intent chemotherapy for previously treated advanced thymic carcinoma
Authors: Okuma Yusuke , Goto Yasushi , Ohyanagi Fumiyoshi , Sunami Kuniko , Nakahara Yoshiro , Kitazono Satoru , Kudo Keita , Tambo Yuichi , Kanda Shintaro , Yanagitani Noriko , Horiike Atsushi , Horinouchi Hidehito , Fujiwara Yutaka , Nokihara Hiroshi , Yamamoto Noboru , Nishio Makoto , Ohe Yuichiro , Hosomi Yukio 
Published: August 2020

AbstractThymic carcinoma (TC) is a rare cancer with minimal evidence of survival following palliative‐intent chemotherapy. Sunitinib, everolimus, and pembrolizumab have been proposed as active agents based on previous phase II trials. In this phase II study, TC patients previously treated with platinum‐based chemotherapy were enrolled. The patients received S‐1 orally twice daily at a dose of 40‐60 mg/m2 for 4 weeks, followed by 2 weeks off until the progression of the disease or the presence of unacceptable toxicities. The primary endpoint was the objective response rate (ORR), and secondary endpoints were progression‐free survival (PFS), overall survival (OS), and safety. The sample size of 26 patients was planned to reject the ORR of 10% under the expectation of 30% with a power of 0.80 and a type I error of 0.05 (one‐sided). Twenty‐six patients were recruited between 2013 and 2016; 23 patients had squamous cell carcinoma and 10 had an ECOG performance status of 0. One patient showed complete response and seven patients showed partial responses, resulting in a 30.8% response rate (90% confidence interval [CI], 18.3‐46.9) and an 80.8% disease control rate (90% CI, 65.4‐90.3). The median PFS was 4.3 months (95% CI, 2.3‐10.3 months) and median OS was 27.4 months (95% CI, 16.6‐34.3). Adverse events of grade ≥ 3 included neutropenia (12%), skin rash (8%), elevated alanine aminotransferase, and fatigue (4%). No treatment‐related death was observed. S‐1 confirmed clinical activity with tolerability in patients with previously treated TC. (UMIN000010736).