bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered structure of the vestibular cortex in patients with vestibular migraine
Authors: Zhe Xia , Gao Jie , Chen Li , Zhang Dongsheng , Tang Min , Yan Xuejiao , Bai Fuxia , Zhang Xin , Zou Ze , Chen Weibo , Lei Xiaoyan , Zhang Xiaoling
Published: March 2020

Introduction

Previous voxel‐based morphometry (VBM) studies have revealed changes in brain structure in patients with vestibular migraine (VM); these findings have improved the present understanding of pathophysiology. Few other studies have assessed the association between structural changes and the severity of dizziness in VM. This study aimed to examine the structural changes and cortical morphometric features associated with migraine and vertigo attacks in patients with VM.

Methods

Twenty patients with VM and 20 healthy normal volunteers were scanned on a 3‐tesla MRI scanner. The gray matter volume (GMV) was estimated using the automated Computational Anatomy Toolbox (CAT12). The relationship between clinical parameters and morphometric abnormalities was also analyzed in VM.

Results

Compared with controls, VM patients have decreased GMV in the prefrontal cortex (PFC), posterior insula–operculum regions, inferior parietal gyrus, and supramarginal gyrus. Moreover, patient scores on the Dizziness Handicap Inventory (DHI) score showed a negative correlation with GMV in the posterior insula–operculum regions.

Conclusion

These findings demonstrated abnormality in the central vestibular cortex and correlations between dizziness severity and GMV in core regions of the vestibular cortex of VM patients, suggesting a pathophysiological role of these core vestibular regions in VM patients.
Activation of brain‐derived neurotrophic factor signaling in the basal forebrain reverses acute sleep deprivation‐induced fear memory impairments
Authors: Ma Tao , Zhang Hao , Xu Zhi‐Peng , Lu Yan , Fu Qiang , Wang Wei , Li Guan‐Hua , Wang Ying‐Ying , Yang Yi‐Tian , Mi Wei‐Dong
Published: March 2020

Introduction

The mechanisms underlying sleep deprivation‐induced memory impairments and relevant compensatory signaling pathways remain elusive. We tested the hypothesis that increased brain‐derived neurotrophic factor (BDNF) expression in the basal forebrain following acute sleep deprivation was a compensatory mechanism to maintain fear memory performance.

Methods

Adult male Wistar rats were deprived of 6‐hr total sleep from the beginning of the light cycle. The effects of sleep deprivation on BDNF protein expression and activation of downstream tropomyosin receptor kinase B (TrkB)/phospholipase C‐γ1 (PLCγ1) signaling in the basal forebrain and fear memory consolidation were examined. BDNF or selective downstream TrkB receptor antagonist ANA‐12 was further injected into the basal forebrain bilaterally to observe the changes in fear memory consolidation in response to modulation of the BDNF/TrkB signaling.

Results

Six hours of sleep deprivation‐induced both short‐ and long‐term fear memory impairments. Increased BDNF protein expression and TrkB and PLCγ1 phosphorylation in the basal forebrain were observed after sleep deprivation. Microinjection of BDNF into the basal forebrain partly reversed fear memory deficits caused by sleep deprivation, which were accompanied by increased BDNF protein levels and TrkB/PLCγ1 activation. After ANA‐12 microinjection, sleep deprivation‐induced activation of the BDNF/TrkB pathway was inhibited and impairments of fear memory consolidation were further aggravated.

Conclusions

Acute sleep deprivation induces compensatory increase of BDNF expression in the basal forebrain. Microinjection of BDNF into the basal forebrain mitigates the fear memory impairments caused by sleep deprivation by activating TrkB/PLCγ1 signaling.
Once‐a‐week or every‐other‐day urethra‐sparing prostate cancer stereotactic body radiotherapy, a randomized phase II trial: 18 months follow‐up results
Authors: Zilli Thomas , Jorcano Sandra , Bral Samuel , Rubio Carmen , Bruynzeel Anna M.E. , Oliveira Angelo , Abacioglu Ufuk , Minn Heikki , Symon Zvi , Miralbell Raymond
Published: March 2020

Background

To present the 18 months results from a prospective multicenter phase II randomized trial of short vs protracted urethra‐sparing stereotactic body radiotherapy (SBRT) for localized prostate cancer (PCa).

Methods

Between 2012 and 2015, a total of 170 PCa patients were randomized to 36.25 Gy in 5 fractions (6.5 Gy × 5 to the urethra) delivered either every other day (EOD, arm A, n = 84) or once a week (QW, arm B, n = 86). Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v4.0 scale), IPSS, and QoL scores were assessed at baseline, at the 5th fraction (5fx), 12th weeks (12W), and every 6 months after SBRT. The primary endpoint was biochemical control at 18 months and grade ≥ 3 toxicity (including grade ≥ 2 for urinary obstruction/retention) during the first 3 months.

Results

Among the 165 patients analyzed, the toxicity stopping rule was never activated during the acute phase. Maximum acute grade 2 GU toxicity rates at 5fx were 17% and 19% for arms A and B, respectively, with only 2 cases of grade 2 GI toxicity at 5fx in arm A. At month 18, grade ≥ 2 GU and GI toxicity decreased below 5% and 2% for both arms. No changes in EORTC QLQ‐PR25 scores for GU, GI, and sexual domains were observed in both arms between baseline and month 18. Four biochemical failures were observed, 2 in each arm, rejecting the null hypothesis of an unfavorable response rate ≤ 85% in favor of an acceptable ≥ 95% rate.

Conclusions

At 18 months, urethra‐sparing SBRT showed a low toxicity profile, with minimal impact on QoL and favorable biochemical control rates, regardless of overall treatment time (EOD vs QW).
Inferior prognosis of gastric involvement in patients with gastrointestinal Burkitt Lymphoma
Authors: Xie Yi , Jia Mengyu , Shi Jumei , Tao Yi
Published: March 2020

Due to limited information reported on the clinical characteristics and outcomes of Burkitt lymphoma (BL) patients with gastrointestinal (GI) involvement, here we used the Surveillance, Epidemiology, and End Results (SEER) database to perform our study in a population‐based scale. Extranodal GI involvement was categorized into gastric and intestinal primary sites. A total of 477 BL patients with GI involvement extracted from the SEER database between 2004 and 2015 were included in this study, 112 (23.5%) with the stomach and 365 (76.5%) with the intestine. Our study demonstrated that gastric involvement, older age, male gender, black race, advanced‐stage III/IV, no‐chemotherapy, and earlier years of diagnosis were associated with a significantly worse overall survival (OS) in GI BL patients after adjustment in multivariate analysis, whereas marital status did not significantly influence OS. Notably, BL Patients with gastric involvement had a significantly inferior 5‐year OS in both univariate and multivariate analysis, as compared to those with intestinal involvement (37.8% vs. 70.2%; Univariate: HR = 2.637, P < .001; Multivariate: HR = 1.489, P = .016). In subgroup analysis, we demonstrated that gastric BL patients had a consistently worse OS than intestinal patients regardless of gender, clinical stage and year of diagnosis. Hopefully, with the advances in modern therapy, improved survival has been found in BL patients with GI involvement as a whole, specifically those with gastric involvement (HR = 0.529, P = .011) in recent years of diagnosis. In conclusion, despite the improved survival achieved in recent years, the prognosis of BL patients with gastric involvement is still poor. Novel personalized therapies and better access to intensive care remain to be needed.
Distribution of heparan sulfate correlated with the expression of heparanase‐1 and matrix metalloproteinase‐9 in an ovariectomized rats skin
Authors: Veridiano Juliana M. , Theodoro Thérèse R. , Negrete Bárbara R. , Petri Giuliana , da Silva Pinhal Maria A. , de Toledo Olga Maria S.
Published: March 2020

There are few studies on heparan sulfate (HS) in the skin, during aging, when estrogen is suppressed. The enzyme heparanase‐1 (HPSE‐1), has its 17β‐estrogen‐regulated expression in pathological conditions such as cancer and chronic inflammatory diseases. HPSE‐1 is correlated with the matrix metalloproteinase‐9 (MMP‐9), an endopeptidase that also undergoes estrogen action. We investigated the distribution of HS, expression HPSE‐1 and MMP‐9 in the skin of adult rats at different ages and in the age‐matched ovariectomized rats to evaluate the influence of low estrogen on the distribution of HS. Thirty female Wistar rats were used. Rats underwent to a sham surgery (ctr, n = 15) or to a bilateral ovariectomy (ovx, n = 15) and were euthanized after 45, 75, and 90 days after ovariectomy. Morphological, morphometric, biochemical, and reverse transcriptase polymerase chain reaction (RT‐PCR) methodologies were used. A significant decrease (P < 0.001) in total skin thickness was observed in the ctr and ovx animals, being higher in the older animals. The thickness of the epidermis and dermis decreased; however, the proportion in the total skin remained similar comparing ctr and ovx. An increase of HS with increasing age and ovariectomy was observed. The expression of the HPSE‐1 and MMP‐9 enzymes decreased, being higher in old animals. A correlation between the increase of HS and the decrease of the HPSE‐1 was demonstrated in both groups. Overall, these data suggested that estrogen acts in the regulation of the expression of the HPSE‐1, not only in pathological states, as already established, but also in aging.
The enduring legacy of Koji Nakanishi's research on bioorganic chemistry and natural products. Part 1: Isolation, structure determination and mode of action
Authors: Ellestad George , Zask Arie , Berova Nina
Published: March 2020

In this brief review on Koji Nakanishi's remarkable career in natural products chemistry, we have highlighted a number of his accomplishments that illustrate the broad diversity of his interests. These include the isolation, structure determination, and biological mechanism of action of many natural products including the triterpenoid pristimerin; the diterpenoid ginkgolides; insect and crustacean molting hormones; phytoalexins; the toxic red tide principle brevetoxin; the vanadium tunicate pigments; philanthotoxin from killer wasps; antisickling agents; mitomycin DNA adducts; insect antifeedants; a mitotic hormone, the small molecule fish attractants from the sea anemone; new isolation and purification technologies; molecular chemistry of vision; age‐related macular degeneration; and the development of the exciton circular dichroism (CD) chirality method for microscale determination of absolute configuration of natural products and chirality of other chiral molecules and supramolecular assembly.
Synthesis of Meta Symmetric 1T’‐WTe2 Using an Edge‐Induced Mechanism
Authors: Xiao Yao , Zhou Mengyue , Liu Jinglu , Wei Bin , Yue Shuanglin , Zhou Yuan , Yang Kena , Zhang Tao , Zeng Mengqi , Wang Zhongchang , Fu Lei
Published: March 2020

Summary of main observation and conclusion

Lattice symmetry is vital to the properties of two‐dimensional (2D) materials, yet their fixed symmetry cannot meet the increasing requirements in highly efficient and programmable electrical transport. If the structural diversity of 2D materials, as demonstrated by 1T’‐WTe2, is improved without any phase transition or structural reconstruction, excellent metallic 1T’‐WTe2 would be possibly used for integrated devices. Here, we realized meta symmetry of 1T’‐WTe2 by using an edge‐induced mechanism, which is recognized as the combination of the intrinsic C2v symmetry and sixfold axes. On account of the dynamically controlled growth, the meta symmetric 1T’‐WTe2 with ~94.9% purity is obtained for the first time. Meta symmetry will also keep the intrinsic electrical properties of 1T’‐WTe2 over the node. Such meta symmetry could not only enrich the structural diversity of 1T’‐WTe2, but also be extended to other low‐symmetry 2D materials, which would be promising for customized circuits and devices.
Synthesis and Biological Screening of New Lawson Derivatives as Selective Substrate‐Based Inhibitors of Cytochrome bo3 Ubiquinol Oxidase from Escherichia coli
Authors: Elamri Isam , Radloff Melanie , Hohmann Katharina F. , Nimbarte Vijaykumar D. , Nasiri Hamid R. , Bolte Michael , Safarian Schara , Michel Hartmut , Schwalbe Harald
Published: March 2020

The respiratory chain of Escherichia coli contains two different types of terminal oxidase that are differentially regulated as a response to changing environmental conditions. These oxidoreductases catalyze the reduction of molecular oxygen to water and contribute to the proton motive force. The cytochrome bo3 oxidase (cyt bo3) acts as the primary terminal oxidase under atmospheric oxygen levels, whereas the bd‐type oxidase is most abundant under microaerobic conditions. In E. coli, both types of respiratory terminal oxidase (HCO and bd‐type) use ubiquinol‐8 as electron donor. Here, we assess the inhibitory potential of newly designed and synthesized 3‐alkylated Lawson derivatives through L‐proline‐catalyzed three‐component reductive alkylation (TCRA). The inhibitory effects of these Lawson derivatives on the terminal oxidases of E. coli (cyt bo3 and cyt bd‐I) were tested potentiometrically. Four compounds were able to reduce the oxidoreductase activity of cyt bo3 by more than 50 % without affecting the cyt bd‐I activity. Moreover, two inhibitors for both cyt bo3 and cyt bd‐I oxidase could be identified. Based on molecular‐docking simulations, we propose binding modes of the new Lawson inhibitors. The molecular fragment benzyl enhances the inhibitory potential and selectivity for cyt bo3, whereas heterocycles reduce this effect. This work extends the library of 3‐alkylated Lawson derivatives as selective inhibitors for respiratory oxidases and provides molecular probes for detailed investigations of the mechanisms of respiratory‐chain enzymes of E. coli.
Small‐Molecule Inhibitors of METTL3, the Major Human Epitranscriptomic Writer
Authors: Bedi Rajiv K. , Huang Danzhi , Eberle Stefanie A. , Wiedmer Lars , Śledź Pawel , Caflisch Amedeo
Published: March 2020

The RNA methylase METTL3 catalyzes the transfer of a methyl group from the cofactor S‐adenosyl‐L‐methionine (SAM) to the N6 atom of adenine. We have screened a library of 4000 analogues and derivatives of the adenosine moiety of SAM by high‐throughput docking into METTL3. Two series of adenine derivatives were identified in silico, and the binding mode of six of the predicted inhibitors was validated by protein crystallography. Two compounds, one for each series, show good ligand efficiency. We propose a route for their further development into potent and selective inhibitors of METTL3.
Use of immunotherapy and surgery for stage IV melanoma
Authors: Molina George , Kasumova Gyulnara G. , Qadan Motaz , Boland Genevieve M.
Published: March 2020

Background

Immunotherapy for stage IV melanoma has dramatically changed the overall prognosis and treatment strategies. The aim of this study was to evaluate whether changes in systemic immunotherapy options have significantly altered surgical resection rates for patients with stage IV melanoma.

Methods

The National Cancer Database (2004‐2015) was used to perform a difference‐in‐difference analysis to evaluate whether the rate of surgical resection of metastatic disease for stage IV melanoma differed with the use of immunotherapy in the checkpoint inhibitor era in comparison with the use of immunotherapy in the pre–checkpoint inhibitor era. An adjusted difference‐in‐difference analysis stratified by facility type was performed. An adjusted Poisson regression analysis evaluated predictors of surgical resection in patients with stage IV melanoma who received immunotherapy.

Results

There were 14,433 patients with stage IV melanoma (median age, 66 years [interquartile range, 56‐76 years]; female, 31.7%), and of all patients in the checkpoint inhibitor era (n = 7,524), 25% (n = 1,879) received immunotherapy. Patients with stage IV disease who received immunotherapy in the checkpoint inhibitor era were more likely to be younger, be healthier, have private insurance, come from upper income quartiles, and be treated at academic programs. A difference‐in‐difference analysis revealed similar rates of surgical resection of metastatic disease with the use of immunotherapy in the checkpoint inhibitor era and the pre–checkpoint inhibitor era, regardless of facility type.

Conclusions

The distribution of immunotherapy was unequal among patients with stage IV melanoma. Across all facilities, the rates of surgical resection of metastatic disease for stage IV melanoma did not differ with the use of immunotherapy between the checkpoint inhibitor era and the pre–checkpoint inhibitor era.
Impression space model for the evaluation of Internet advertising effectiveness
Authors: Song Yongqiang , Wang Hong , Zhang Changyong , Wang Lutong
Published: March 2020

The evaluation of Internet advertising effectiveness plays an important role in network marketing at this stage. The evaluation criteria of Internet advertising effectiveness mostly use proceeds as an indicator, ignoring the brand effect generated by Internet advertising, making it difficult for researchers to further study the effect of Internet advertising. With the updating and iteration of technical theory, it is an urgent task to find a new criteria to measure Internet advertising effectiveness. At present, the research on Internet advertising effectiveness research is based on the analysis of nondifferentiation category. The research on user click behavior is a holistic analysis of the whole web page. This global coverage research is difficult to present the behavior characteristics of users in the web page. In response to the above problems, the impression space is proposed to measure Internet advertising effectiveness. Firstly, the fuzzy classification theory is used to digitize the user category data, the user type is divided by probability distribution, and the distribution of web page interest regions is divided by gaze time and page layout to further study the click‐and‐effect relationship of different users and the user browsing time series.Then, establish multimodal multifactors to build an impression space model to measure Internet advertising effectiveness. The experimental results show that the accuracy of the constructed impression space model for the evaluation of Internet advertising effectiveness reaches 92.4%, and the impression space is more effective as the evaluation of Internet advertising effectiveness.
Load‐balanced data gathering in Internet of Things using an energy‐aware cuckoo‐search algorithm
Authors: Sadeghi Fahimeh , Avokh Avid
Published: March 2020

This paper deals with the lifetime problem in the Internet of Things. We first propose an efficient cluster‐based scheme named “Cuckoo‐search Clustering with Two‐hop Routing Tree (CC‐TRT)” to develop a two‐hop load‐balanced data aggregation routing tree in the network. CC‐TRT uses a modified energy‐aware cuckoo‐search algorithm to fairly select the best cluster head (CH) for each cluster. The applied cuckoo‐search algorithm makes the CH role to rotate between different sensors round by round. Subsequently, we extend the CC‐TRT scheme to present two methods for constructing multi‐hop data aggregation routing trees, named “Cuckoo‐search Clustering with Multi‐Hop Routing Tree (CC‐MRT)” and “Cuckoo‐search Clustering with Weighted Multi‐hop Routing Tree (CC‐WMRT).” Both CC‐MRT and CC‐WMRT rely on a two‐level structure; they not only use an energy‐aware cuckoo‐search algorithm to fairly select the best CHs but also adopt a load‐balanced high‐level routing tree to route the aggregated data of CHs to the sink node. However, CC‐WMRT slightly has a better performance thanks to its low‐level routing strategy. As an advantage, the proposed schemes balance the energy consumption among different sensors. Numerical results show the efficiency of the CC‐TRT, CC‐MRT, and CC‐WMRT algorithms in terms of the number of transmissions, remaining energy, energy consumption variance, and network lifetime.
Bacterial vaginosis, representation of endocervical and/or metaplastic cells, and cytological abnormalities in different age groups: Association study
Authors: dos Passos Eva Nayssa , Ribeiro Andrea A. , Tavares Suelene Brito do Nascimento , de Souza Nadja Lindany Alves , Batista Maria de Lourdes Siqueira , Cardoso Filho Leonardo Izidório , de Aquino Érika Carvalho , Rabelo‐Santos Sílvia Helena
Published: March 2020

Background

Studies have indicated that bacterial vaginosis (BV) might be a cofactor for the acquisition and persistence of high‐risk papillomavirus, enabling the development of cytological abnormalities. The presence of endocervical and metaplastic cells makes the smear more adequate for the detection of these abnormalities once these cell types are representative of the transformation zone, a site of increased susceptibility to viral infection.

Methods

The purpose of this study was to evaluate the patterns of vaginal microbiota, the representation of endocervical and/or metaplastic cells, and the detection of cytological abnormalities in cervical smears from women 15 to 64 years old. Results from satisfactory cytological smears performed in a laboratory school from the Federal University of Goiás were analyzed. The degree of association between the categorical variables was evaluated by the χ2 test, Fisher's Exact test, and stratified analysis through the estimation of the prevalence ratio, with 95% confidence intervals and 5% statistical significance level (P < .05).

Results

The global prevalence of BV and cytological abnormalities was 22.02% and 8.21%, respectively. BV and the representation of endocervical and/or metaplastic cells were independently associated with the detection of high‐grade cytological abnormalities in the cervical smears of women between 25 and 64 years old.

Conclusions

BV and representation of endocervical and/or metaplastic cells were independently associated with the detection of high‐grade cytological abnormalities reinforcing the importance of specimen adequacy and microbiota in the cervical microenvironment.
Integrating genetics, biophysical, and demographic insights identifies critical sites for seagrass conservation
Authors: Jahnke Marlene , Moksnes Per‐Olav , Olsen Jeanine L. , Serra Serra Núria , Nilsson Jacobi Martin , Kuusemäe Kadri , Corell Hanna , Jonsson Per R.
Published: March 2020

The eelgrass Zostera marina is an important foundation species of coastal areas in the Northern Hemisphere, but is continuing to decline, despite management actions. The development of new management tools is therefore urgent in order to prioritize limited resources for protecting meadows most vulnerable to local extinctions and identifying most valuable present and historic meadows to protect and restore, respectively. We assessed 377 eelgrass meadows along the complex coastlines of two fjord regions on the Swedish west coast—one is currently healthy and the other is substantially degraded. Shoot dispersal for all meadows was assessed with Lagrangian biophysical modeling (scale: 100–1,000 m) and used for barrier analysis and clustering; a subset (n = 22) was also assessed with population genetic methods (20 microsatellites) including diversity, structure, and network connectivity. Both approaches were in very good agreement, resulting in seven subpopulation groupings or management units (MUs). The MUs correspond to a spatial scale appropriate for coastal management of “waterbodies” used in the European Water Framework Directive. Adding demographic modeling based on the genetic and biophysical data as a third approach, we are able to assess past, present, and future metapopulation dynamics to identify especially vulnerable and valuable meadows. In a further application, we show how the biophysical approach, using eigenvalue perturbation theory (EPT) and distribution records from the 1980s, can be used to identify lost meadows where restoration would best benefit the present metapopulation. The combination of methods, presented here as a toolbox, allows the assessment of different temporal and spatial scales at the same time, as well as ranking of specific meadows according to key genetic, demographic and ecological metrics. It could be applied to any species or region, and we exemplify its versatility as a management guide for eelgrass along the Swedish west coast.
Identification and population genetic comparison of three ascidian species based on mtDNA sequences
Authors: Bhattachan Punit , Qiao Runyu , Dong Bo
Published: March 2020

Ascidians are sessile marine chordate invertebrates found along seashores worldwide and are typically regarded as invasive organisms. Knowledge concerning their global genetic structure and subsequent invasive potential is limited. Here, we identified three ascidians—Ciona robusta, Ciona savignyi, and Styela clava from the northeast region of China using morphological characteristics and mitochondrial cytochrome c oxidase subunit I (cox1) as genetic marker. We additionally used phylogenetics to aid in the identification of these three species. The results of a population genetic analysis showed that among the three species, the level of haplotype diversity was particularly high within C. savignyi, and nucleotide diversity varied moderately. We divided the three species separately into native and invasive populations using 170 cox1 sequences from global resources to explore population genetic structure and invasive potential. Although in the network analysis Ciona spp. formed haplogroups of native and invasive populations, some haplotypes were still shared. We found that the haplotypes did not cluster within the network of S. clava. Our AMOVA results also showed that Ciona spp. had a weak genetic structure, and less genetic differentiation was present in S. clava. These data suggest that there are extensive incursions of these three ascidians into different geographical regions. Global comparisons of ascidian populations will help in the understanding of their population genetic structure and invasive potential, hence providing important insights regarding conservation as well as management.
Acute correction of electromechanical dyssynchrony and response to cardiac resynchronization therapy
Authors: Moubarak Ghassan , Viart Guillaume , Anselme Frédéric
Published: March 2020

Aims

Echocardiographic measures of dyssynchrony at baseline have not demonstrated a good ability to predict response to cardiac resynchronization therapy (CRT). The purpose of this study was to determine if the acute correction of electromechanical dyssynchrony, assessed by the change in simple pulsed‐Doppler measures, was related to CRT response at 6 months.

Methods and results

Echocardiography was performed at baseline and at pre‐discharge after CRT implantation. Intraventricular, interventricular, and atrioventricular dyssynchrony were evaluated by the left pre‐ejection interval (LPEI), the interventricular mechanical delay, and the ratio of left ventricular filling time to RR interval, respectivelxy. A patient was considered responder if he/she was alive without hospitalization for heart failure and had an absolute increase of left ventricular ejection fraction (LVEF) >5 points. Forty‐eight patients (mean age 67 ± 11 years, 73% male, mean LVEF 30 ± 5%) were included. CRT led to an acute correction of intraventricular and interventricular dyssynchrony but not to an acute correction of atrioventricular dyssynchrony. There were 31 (65%) responders at 6 months. Two factors were independently associated with CRT response in multivariate analysis: ischemic cardiomyopathy (odds ratio 0.19, 95% confidence interval 0.04–0.87; P= 0.032) and delta LPEI (odds ratio 1.03 per 1 ms decrease, 95% confidence interval 1.01–1.05; P = 0.007). By receiver operating characteristic analysis, the optimal cut‐off value of delta LPEI was −16 ms. The proportion of responders in patients without ischemic cardiomyopathy and with a delta LPEI greater than −16 ms was 85%.

Conclusions

Acute correction of intraventricular electromechanical dyssynchrony evaluated by the LPEI predicted CRT response at 6 months.
Outpatient treatment of worsening heart failure with intravenous and subcutaneous diuretics: a systematic review of the literature
Authors: Wierda Eric , Dickhoff Cathelijne , Handoko Martin Louis , Oosterom Liane , Kok Wouter Emmanuel , de Rover Y. , de Mol B.A.J.M. , van Heerebeek Loek , Schroeder‐Tanka Jutta Maria
Published: March 2020

Aims

In the coming decade, heart failure (HF) represents a major global healthcare challenge due to an ageing population and rising prevalence combined with scarcity of medical resources and increasing healthcare costs. A transitional care strategy within the period of clinical worsening of HF before hospitalization may offer a solution to prevent hospitalization. The outpatient treatment of worsening HF with intravenous or subcutaneous diuretics as an alternative strategy for hospitalization has been described in the literature.

Methods and results

In this systematic review, the available evidence for the efficacy and safety of outpatient treatment with intravenous or subcutaneous diuretics of patients with worsening HF is analysed. A search was performed in the electronic databases MEDLINE and EMBASE. Of the 11 included studies 10 were single‐centre, using non‐randomized, observational registries of treatment with intravenous or subcutaneous diuretics for patients with worsening HF with highly variable selection criteria, baseline characteristics, and treatment design. One study was a randomized study comparing subcutaneous furosemide with intravenous furosemide. In a total of 984 unique individual patients treated in the reviewed studies, only a few adverse events were reported. Re‐hospitalization rates for HF at 30 and 180 days were 28 and 46%, respectively. All‐cause re‐hospitalization rates at 30 and 60 days were 18–37 and 22%, respectively. The highest HF re‐hospitalization was 52% in 30 days in the subcutaneous diuretic group and 42% in 30 days in the intravenous diuretic group.

Conclusions

The reviewed studies present practice‐based results of treatment of patients with worsening HF with intravenous or subcutaneous diuretics in an outpatient HF care unit and report that it is effective by relieving symptoms with a low risk of adverse events. The studies do not provide satisfactory evidence for reduction in rates of re‐hospitalization or improvement in mortality or quality of life. The conclusions drawn from these studies are limited by the quality of the individual studies. Prospective randomized studies are needed to determine the safety and effectiveness of outpatient intravenous or subcutaneous diuretic treatment for patient with worsening HF.
Substrate or Solvent‐Controlled PdII‐Catalyzed Regioselective Arylation of Quinolin‐4(1H)‐ones Using Diaryliodonium Salts: Facile Access to Benzoxocine and Aaptamine Analogues
Authors: Mehra Manish K. , Sharma Shivani , Rangan Krishnan , Kumar Dalip
Published: March 2020

Regioselective C3, C5, and C8 arylation of quinolin‐4(1H)‐ones have been accomplished either by substrate‐control or by tuning the reaction solvent. A variety of aryl(mesityl)iodonium triflates could smoothly deliver arylated products in good to excellent yields. Additionally, it offers great flexibility by arylating medicinally potent quinolone related heterocycles such as acridin‐9(10H)‐one, and phenanthridin‐6(5H)‐one under standard reaction conditions. This strategy was further extended with diphenyleneiodonium triflate to access oxacine fused quinolines. The post‐modifications of synthesized products enhance the further utility of this protocol in organic synthesis. To the best of our knowledge, this is the first report on C5 arylation of quinolin‐4(1H)‐ones using iodine(III) reagents.
The First Synthesis of (–)‐Agelasine F; an Antimycobacterial Natural Product Found in Marine Sponges in the Agelas Genus
Authors: Paulsen Britt , Gundersen Lise‐Lotte
Published: March 2020

(–)‐Agelasine F (also known as ageline A) is a diterpene‐adenine hybrid natural product isolated from marine sponges (Agelas species) and this compound is known to display cytotoxic activity against a variety of cancer cell lines as well as microorganisms. We herein report the first total synthesis of (–)‐agelasine F. The commercially available and inexpensive monoterpenoid (S)‐carvone was found to be a highly suitable starting material for the construction of the terpenoid part of the desired agelasine and controlling the stereochemistry of the target compound. Two alternative strategies from (S)‐carvone were evaluated. Key‐intermediates in the (–)‐agelasine F synthesis are believed also to be valuable starting materials for total syntheses of other bioactive marine sponge metabolites. The synthetic route to (–)‐agelasine F described herein is more efficient than previously published syntheses of racemic or ent‐agelasine F.
Dynamic simulation and assessment of the ecological benefits of hydropower as an alternative energy for thermal power under ecological civilization construction: A case study of Fujian, China
Authors: Zhang Lihui , Chai Jianxue , Zhu Jinrong , Zhao Zhenli
Published: March 2020

As ecological civilization construction receives growing attention in China, the eco‐friendliness of the power supply structure is becoming increasingly important. Thermal power and hydropower are the two major power sources in China. Hydropower has both positive and negative effects on the ecosystem. However, there are few studies on the comprehensive impact of hydropower on the ecosystem. Therefore, the main innovation of this article is to integrally and comprehensively study the impact of hydropower to propose recommendations for hydropower development. The study of hydropower's effects on the overall ecosystem including resources, the environment, and economic society reflects the integrity, and the simultaneous study of hydropower's positive and negative effects reflects the comprehensiveness. First, this paper constructs a system dynamics (SD) model that can analyze the impact of replacing thermal power with hydropower on the ecosystem and proposes an improved coupling coordination degree (CCD) model. Then, this paper takes the province of Fujian as an example for SD scenario simulation and proposes recommendations for each indicator in the ecology subsystem. Finally, this paper performs CCD analysis on subsystems of the ecology subsystem in different policy scenarios and provides suggestions for future hydropower development in Fujian. Results show that hydropower technology improvement and efficiency increase (HTIEI) is more conducive to the development of the overall ecosystem. The scientificity of the current hydropower policy in Fujian is proven through theoretical analysis, and further hydropower development proposals are proposed. This paper provides a basis for the formulation of power generation policies and promotes ecological civilization construction for Fujian. The proposed methods in this paper can also provide tools for policy research on clean energy power generation.
Orthogonal frequency division multiplexing with subcarrier power modulation for doubling the spectral efficiency of 6G and beyond networks
Authors: Hamamreh Jehad M. , Hajar Abdulwahab , Abewa Mohamedou
Published: March 2020

With the emergence of new applications (eg, extended reality [XR] and haptics), which require to be simultaneously served not just with low latency and sufficient reliability, but also with high spectral efficiency, future networks (ie, 6G and beyond) should be capable of meeting this demand by introducing new effective transmission designs. Motivated by this, a novel modulation technique termed as orthogonal frequency division multiplexing with subcarrier power modulation (OFDM‐SPM) is proposed for providing highly spectral‐efficient data transmission with low‐latency and less‐complexity for future 6G wireless communication systems. OFDM‐SPM utilizes the power of subcarriers in OFDM blocks as a third dimension to convey extra information bits while reducing both complexity and latency compared to conventional schemes. In this article, the concept of OFDM‐SPM is introduced and its validity as a future adopted modulation technique is investigated over a wireless multipath Rayleigh fading channel. The proposed system structure is explained, an analytical expression of the bit error rate (BER) is derived, and numerical simulations of BER and throughput performances of OFDM‐SPM are carried out. OFDM‐SPM is found to greatly enhance the spectral efficiency where it is capable of doubling it. In addition, OFDM‐SPM introduces negligible complexity to the system, does not exhibit error propagation, reduces the transmission delay, and decreases the transmission power by
half.
Assessing the potential and safety of Myrtus communis flower essential oils as efficient natural preservatives against Listeria monocytogenes growth in minced beef under refrigeration
Authors: Dhifi Wissal , Jazi Sabrine , El Beyrouthy Marc , Sadaka Carmen , Mnif Wissem
Published: March 2020

In this research, the chemical composition and biological properties of Tunisian Myrtus communis (McEO) flowers were investigated. The antibacterial effect of McEO toward some bacteria was assessed, alone and in combination with nisin. The major components of McEO were α‐pinene, 1,8‐cineol, limonene, and linalool. McEO exhibited cytotoxicity toward HepG2 and MCF‐7 cell lines. The microbiological data showed that Gram‐positive bacteria were more susceptible to McEO. McEO had a bactericidal effect against L. monocytogenes. McEO is able to prevent lipid oxidation, microbial development at noncytotoxic concentrations, when used alone or in combination with nisin. It can improve sensory attributes within acceptable limits and improve the conservation of shelf life of minced beef meat during the 4°C storage period. The most potent preservative effect was obtained with the mixture: 0.8% McEO with 500 IU/g of nisin. This combination may be a good alternative for the development of natural preservatives.
Two extensional events in the early evolution of the Yangtze Block, South China: Geochemical and isotopic evidence from two sets of Paleoproterozoic alkali porphyry in the Northern Kongling terrane
Authors: Li Haiquan , Zhou Wenxiao , Wei Yunxu , Chang Feng , Wang Bo , Tan Mantang , Hu Zhengxiang , Xu Daliang , Liu Hao
Published: March 2020

A set of granite porphyry (grnt‐porphyry) and sub‐rhyolite porphyry (rhy‐porphyry) with specific blue quartz phenocrysts was disintegrated in the northern Kongling terrane, China. Geochemical and isotopic analyses were performed on samples from Kongziqiao (KZQ) and Baizhuping (BZP). In terms of major elements, both are rich in silicon and alkalis, but depleted in calcium and magnesium. Their trace element contents are also similar, exhibiting negative anomalies for large‐ion lithophile elements (LILEs) such as K, Rb and Sr but positive anomalies for high‐field‐strength elements (HFSEs) such as Hf, Ce and Lu. Other elements such as Nb, Ti, P, Sm, Ho, Y and Yb show negative anomalies; however, the KZQ grnt‐porphyry is characterized by positive Ba and negative Zr anomalies; whereas the BZP sub rhy‐porphyry has negative Ba, U and Ta anomalies. The overall geochemistry is characteristic of A‐type granite formed in an extensional environment (A2‐type). Yield ages of the KZQ grnt‐porphyry are (2,239 Ma) and that of the BZP (1,895 Ma) sub rhy‐porphyry are Paleoproterozoic. Analysis of Hf isotopes shows that both have negative ε Hf (t) values, but the εHf (t) value of the KZQ grnt‐porphyry is slightly more positive (minimum −12.4; mean − 8.8) and its depleted mantle model age (TDM1 = 2.85–3.06 Ga, mean 2.92 Ga) is slightly older than the BZP sub rhy‐porphyry (minimum ε Hf (t) = −17.1, mean − 14.9; TDM1 = 2.79–2.92 Ga, mean 2.85 Ga). This suggests that they are derived from partial melting of different generations of ancient crustal material, which implies significant stratification in the Archean crust. The ε Nd (t) values of two samples of each rock type also indicate that both were derived from Ca. 2.9 Ga ancient crust (εNd (t) KZQ = −5.58, −4.74; εNd (t)BZP = −8.55, −8.22). The petrogenesis of both rock types is related to deep crustal extensional collapse caused by post‐orogenic extension before 2.2 Ga and after 1.9 Ga. The formation of two porphyries represents the changes in tectonic system of the Yangtze Block, and this tectonic evolution may have contributed to the reconstruction of the Columbia supercontinent.
Preliminary investigation on a new natural based poly(gamma‐glutamic acid)/Chitosan bioink
Authors: Pisani Silvia , Dorati Rossella , Scocozza Franca , Mariotti Camilla , Chiesa Enrica , Bruni Giovanna , Genta Ida , Auricchio Ferdinando , Conti Michele , Conti Bice
Published: March 2020

The study aims to investigate a novel bioink made from Chitosan (Cs)/ poly(gamma‐glutamic acid) (Gamma‐PGA) hydrogel that takes advantage of the two biodegradable and biocompatible polymers meeting most of the requirements for biomedical applications. The bioink could be an alternative to other materials commonly used in 3D‐bioprinting such as gelatin or alginate. Cs/ Gamma‐PGA hydrogel was prepared by double extrusion of Gamma‐PGA and Cs solutions, where 2 × 105 human adult fibroblasts per ml Cs solution had been loaded, through Cellink 3D‐Bioprinter at 37°C. A computer aided design model was used to get 3D‐bioprinting of a four layers grid hydrogel construct with 70% infill. Hydrogel characterization involved rheology, FTIR analysis, stability study (mass loss [ML], fluid uptake [FU]), and cell retaining ability into hydrogel. 3D‐bioprinted hydrogel gelation time resulted to be <60 s, hydrogel structure was maintained up to 36.79 Pa shear stress, FTIR analysis demonstrated Gamma‐PGA/Cs interpolyelectrolyte complex formation. The 3D‐bioprinted hydrogel was stable for 35 days (35% ML) in cell culture medium, with increasing FU. Cell loaded 3D‐bioprinted Cs 6% hydrogel was able to retain 70% of cells which survived to printing process and cell viability was maintained during 14 days incubation.
Correlation of sex‐determining region Y‐box 30 with tumor characteristics and its prognostic value in breast cancer
Authors: Peng Hui , Luo Yang , Wu Jing , Yin Wanling
Published: March 2020

Objective

Sex‐determining region Y‐box 30 (SOX30) suppresses progression of several cancers, whereas its role in breast cancer is unclear. Therefore, we aimed to determine the correlation of SOX30 with tumor characteristics and prognosis in breast cancer patients.

Methods

The tumor samples of 510 breast cancer patients who underwent resection were obtained, and SOX30 expression was analyzed by immunohistochemistry. Clinical characteristics, disease‐free survival (DFS), and overall survival (OS) of breast cancer patients were recorded.

Results

There were 368 breast cancer patients in SOX30 low‐expression group and 142 in SOX30 high‐expression group. SOX30 was negatively correlated with tumor size (P = .010), tumor (T) stage (P < .001), node (N) stage (P = .001), and tumor, node, metastasis (TNM) stage (P < .001) in breast cancer patients. For prognosis, patients in SOX30 high‐expression group had prolonged DFS (P = .011) and OS (P = .002); moreover, increased SOX30 grade (assessed by semi‐quantitative scoring method assessment) was correlated with better DFS (P = .015) and OS (P = .014). Univariate Cox's regression analysis disclosed that SOX30 high expression was correlated with enhanced DFS (P = .012, hazard ratio (HR) = 0.582) and OS (P = .002, HR = 0.389); however, multivariate Cox's regression analysis revealed that SOX30 could not independently predict DFS (P = .224, HR = 0.766) or OS (P = .087, HR = 0.582) in breast cancer patients, indicating it might interact with other independent predictive factors (such as pathological differentiation, T stage, and N stage) to influence DFS and OS in breast cancer patients.

Conclusion

Sex‐determining region Y‐box 30 is a potential prognostic biomarker in breast cancer, which might contribute to the better outcome of breast cancer patients.
Operative and nonoperative management of anterior cruciate ligament injury: Differences in gait biomechanics at 5 years
Authors: Wellsandt Elizabeth , Khandha Ashutosh , Capin Jacob , Buchanan Thomas S. , Snyder‐Mackler Lynn
Published: March 2020

Gait biomechanics after anterior cruciate ligament (ACL) injury are associated with functional outcomes and the development of posttraumatic knee osteoarthritis. However, biomechanical outcomes between patients treated nonoperatively compared with operatively are not well understood. The primary purpose of this study was to compare knee joint contact forces, angles, and moments during loading response of gait between individuals treated with operative compared with nonoperative management at 5 years after ACL injury. Forty athletes treated operatively and 17 athletes treated nonoperatively completed gait analysis at 5 years after ACL reconstruction or completion of nonoperative rehabilitation. Medial compartment joint contact forces were estimated using a previously validated, patient‐specific electromyography‐driven musculoskeletal model. Knee joint contact forces, angles, and moments were compared between the operative and nonoperative group using mixed model 2 × 2 analyses of variance. Peak medial compartment contact forces were larger in the involved limb of the nonoperative group (Op: 2.37 ± 0.47 BW, Non‐Op: 3.03 ± 0.53 BW; effect size: 1.36). Peak external knee adduction moment was also larger in the involved limb of the nonoperative group (Op: 0.25 ± 0.08 Nm/kg·m, Non‐Op: 0.32 ± 0.09 Nm/kg·m; effect size: 0.89). No differences in radiographic tibiofemoral osteoarthritis were present between the operative and nonoperative groups. Overall, participants treated nonoperatively walked with greater measures of medial compartment joint loading than those treated operatively, while sagittal plane group differences were not present. Statement of clinical relevance: The differences in medial knee joint loading at 5 years after operative and nonoperative management of ACL injury may have implications on the development of posttraumatic knee osteoarthritis.
Evaluation of hydrophobic‐interaction chromatography resins for purification of antibody‐drug conjugates using a mimetic model with adjustable hydrophobicity
Authors: Müller Egbert , Sevilla Manuela , Endres Patrick
Published: March 2020

Antibody drug conjugates are cytotoxic pharmaceuticals, designed to destroy malignant cells. A cytotoxic molecule is attached to an antibody that binds specific to a cancer‐cell surface. Given the high toxicity of the drugs, strict safety standards have to be kept. For this reason, an antibody drug conjugates model was developed with fluorescein 5‐isothiocyanate as the nontoxic payload surrogate. Due to the similar hydrophobicity, this model is used to establish a suitable purification process and characterization method for antibody drug conjugates. Because of the pH dependent solubility of fluorescein, the hydrophobicity of conjugates can be modulated by the pH value. Based on the complex heterogeneity and hydrophobicity of the conjugates a chromatographic purification is challenging. Hydrophobic interaction chromatography is used for analytical as well as for preparative separation. Because of the increased hydrophobicity of the conjugates compared to native antibody, hydrophobic interaction chromatography often suffer from resolution and recovery problems. Conjugates were separated differing on the number of payloads attached to the antibody. For this matter, the drug–antibody ratio is determined and used as a quantitative term. The conjugates are purified at high recoveries and resolution by step gradients using suitable resins, allowing the separation of the target drug–antibody ratio.