bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efflux pump-mediated resistance to antifungal compounds can be prevented by conjugation with triphenylphosphonium cation
Authors: Chang Wenqiang , Liu Jun , Zhang Ming , Shi Hongzhuo , Zheng Sha , Jin Xueyang , Gao Yanhui , Wang Shuqi , Ji Aiguo , Lou Hongxiang 
Published: November 2018

AbstractAntifungal resistance due to upregulation of efflux pumps is prevalent in clinical Candida isolates. Potential efflux pump substrates (PEPSs), which are active against strains deficient in efflux pumps but inactive against wild-type strains, are usually missed in routine antifungal screening. Here we present a method for identification of PEPSs, and show that conjugation with mitochondria-targeting triphenylphosphonium cation (TPP+) can enhance or restore the compounds’ antifungal activity. The screening method involves co-culturing a wild-type C. albicans strain and a Cdr efflux pump-deficient strain, labelled with different fluorescent proteins. We identify several PEPSs from a library of natural terpenes, and restore their antifungal activity against wild-type and azole-resistant C. albicans by conjugation with TPP+. The most active conjugate (IS-2-Pi-TPP) kills C. albicans cells, prevents biofilm formation and eliminates preformed biofilms, without inducing significant resistance. The antifungal activity is accompanied by mitochondrial dysfunction and increased levels of intracellular reactive oxygen species. In addition, IS-2-Pi-TPP is effective against C. albicans in a mouse model of skin infection.
Deep-learning-based inverse design model for intelligent discovery of organic molecules
Authors: Kim Kyungdoc , Kang Seokho , Yoo Jiho , Kwon Youngchun , Nam Youngmin , Lee Dongseon , Kim Inkoo , Choi Youn-Suk , Jung Yongsik , Kim Sangmo , Son Won-Joon , Son Jhunmo , Lee Hyo Sug , Kim Sunghan , Shin Jaikwang , Hwang Sungwoo 
Published: November 2018

AbstractThe discovery of high-performance functional materials is crucial for overcoming technical issues in modern industries. Extensive efforts have been devoted toward accelerating and facilitating this process, not only experimentally but also from the viewpoint of materials design. Recently, machine learning has attracted considerable attention, as it can provide rational guidelines for efficient material exploration without time-consuming iterations or prior human knowledge. In this regard, here we develop an inverse design model based on a deep encoder-decoder architecture for targeted molecular design. Inspired by neural machine language translation, the deep neural network encoder extracts hidden features between molecular structures and their material properties, while the recurrent neural network decoder reconstructs the extracted features into new molecular structures having the target properties. In material design tasks, the proposed fully data-driven methodology successfully learned design rules from the given databases and generated promising light-absorbing molecules and host materials for a phosphorescent organic light-emitting diode by creating new ligands and combinatorial rules.
The characteristic, antioxidative and multiple organ protective of acidic-extractable mycelium polysaccharides by Pleurotus eryngii var. tuoliensis on high-fat emulsion induced-hypertriglyceridemic mice
Authors: Gao Zheng , Lai Qiangqiang , Yang Qihang , Xu Nuo , Liu Wenbo , Zhao Fulan , Liu Xinchao , Zhang Chen , Zhang Jianjun , Jia Le 
Published: November 2018

AbstractThe antioxidant and multiple organ protection effects of acid- extracted mycelia polysaccharides (Ac-MPS) fromPleurotus eryngiivar. tuoliensison HFE-induced hypertriglyceridemic mice were investigated. The results showed that Ac-MPS have potential ability to relieve the hypertriglyceridemia and preventing oxidative stress by decreasing levels of TG, TC LDL-C, elevating contents of HDL-C in serum, increasing the activities of SOD, GSH-Px, CAT and T-AOC, and the down regulating MDA and LPO contents in liver, heart, kidney and spleen. And the histopathological observations also displayed that Ac-MPS could alleviate organ damage. Moreover, the GC, HPGPC, FT-IR and AFM analyses revealed the Ac-MPS possessed the typical polysaccharides structure with the molecular weights (Mw) of 2.712 × 105 Da. These conclusions indicated that the Ac-MPS had the potential to develop new drugs for hypertriglyceridemia-induced multiple organ failure.
MicroRNA cluster miR199a/214 are differentially expressed in female and male rats following nicotine self-administration
Authors: Pittenger Steven T. , Schaal Victoria L. , Moore Dalia , Guda Rahul S. , Koul Sneh , Yelamanchili Sowmya V. , Bevins Rick A. , Pendyala Gurudutt 
Published: November 2018

AbstractPrevious research has established sex differences associated with nicotine intake, however a significant gap in knowledge remains regarding the molecular mechanisms that govern these differences at the transcriptional level. One critical regulator of transcription are microRNAs (miRNAs). miRNAs are a family of non-coding RNAs that regulate an array of important biological functions altered in several disease states, including neuroadaptive changes within the brain associated with drug dependence. We examined the prefrontal cortex (PFC) from male and female Sprague-Dawley rats following self-administration (22 days) of nicotine or yoked saline controls using next generation RNA-Sequencing (RNA-Seq) technology and found an array of miRNAs to be significantly and differentially regulated by nicotine self-administration. Of these, we found the expression of miR-199a and 214, which are expressed on the same cluster of chromosome 1, to be upregulated in the female rats exposed to nicotine; upregulation in this group was further validated by real time polymerase chain reaction (RT-PCR). Bioinformatics analysis to assess common targets of miR-199/214 identified Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD)- dependent deacetylase that plays a role in apoptosis, neuron survival, and stress resistance. Using western-blot, we confirmed downregulation of SIRT1 and increased cleaved caspase 3 expression in the brains of nicotine-exposed female rats and no change in expression levels in the other groups. Collectively, our findings highlight a miR-199/214 regulatory network that, through SIRT1, may be associated with nicotine seeking in females which may serve as a potential therapeutic target for sex-specific treatment approaches.
2nd-order random lasing in a multimode diode-pumped graded-index fiber
Authors: Evmenova Ekaterina A. , Kuznetsov Alexey G. , Nemov Ilya N. , Wolf Alexey A. , Dostovalov Alexandr V. , Kablukov Sergey I. , Babin Sergey A. 
Published: November 2018

AbstractRaman lasing in a graded-index fiber (GIF) attracts now great deal of attention due to the opportunity to convert high-power multimode laser diode radiation into the Stokes wave with beam quality improvement based on the Raman clean-up effect. Here we report on the cascaded Raman generation of the 2nd Stokes order in the 1.1-km long GIF with 100-μm core directly pumped by 915-nm diodes. In the studied all-fiber scheme, the 1st Stokes order is generated at 950–954 nm in a linear cavity formed at GIF ends by two fiber Bragg gratings (FBGs) securing beam quality improvement from M2 ≈ 30 to M2 ≈ 2.3 due to special transverse structure of FBGs. The 2nd Stokes wave is generated either in linear (two FBGs) or half-open (one FBG) cavity with random distributed feedback via Rayleigh backscattering. Their comparison shows that the random lasing provides better beam quality and higher slope efficiency. Nearly diffraction limited beam (M2 ≈ 1.6) with power up to 27 W at maximum gain (996 nm), and 17 W at the detuned wavelength of 978 nm has been obtained, thus demonstrating that the 2nd-order random lasing in diode-pumped GIF with FBGs provides high-efficiency high-quality beam generation in a broad wavelength range within the Raman gain spectral profile.
3D microdevices that perform sample purification and multiplex qRT-PCR for early cancer detection with confirmation of specific RNAs
Authors: Kimura Yusuke , Ikeuchi Masashi , Inoue Yoshinori , Ikuta Koji 
Published: November 2018

AbstractMicroRNA expression analysis is an important screening tool for the early detection of cancer. In this study, we developed two portable three-dimensional microdevices for multiple singleplex RNA expression analysis by microRNA purification and qRT-PCR as a prototype for point-of-care testing. These microdevices are composed of several types of modules termed ‘chemical IC chips’. We successfully reduced the heating area and fluorescence observation area, reduced the energy required for the reaction, and improved the portability of all systems in the devices. The purification microdevice could purify the microRNA from the sample using the FTA elute card system. The disposable reactor module mounted on both devices was easily fabricated by deforming a 100-μm-thick polypropylene film using an uncomplicated procedure. The qRT-PCR microdevice could perform reactions for samples of small volume. We purified microRNA from the HepG2 liver cancer cell line using the purification microdevice and confirmed the expression level of miR-224, which is a potential biomarker for liver cancer. Furthermore, we observed an increase in the fluorescence intensity when we performed qRT-PCR in the qRT-PCR microdevice. Therefore, the two developed microdevices show promise as a new portable tool for early cancer detection.
Paradoxical, causal effects of sensory gain modulation on motor inhibitory control – a tDCS, EEG-source localization study
Authors: Friedrich Julia , Beste Christian 
Published: November 2018

AbstractResponse inhibition is a key component of executive functioning, but the role of perceptual processes has only recently been focused. Although the interrelation of incoming information and resulting behavioural (motor) effects is well-known to depend on gain control mechanisms, the causal role of sensory gain modulation for response inhibition is elusive. We investigate it using a somatosensory response inhibition (Go/Nogo) task and examine the effects of parietal (somatosensory) cathodal and sham tDCS stimulation on a behavioural and neurophysiological level. For the latter, we combine event-related potential (ERP) and source localization analyses. Behavioural results reveal that cathodal stimulation leads to superior inhibition performance as compared to sham stimulation depending on the intensity of tDCS stimulation. The neurophysiological data show that an early (perceptual) subprocess of the Nogo-N2 ERP-component is differentially modulated by the type of stimulation but not a later (response-related) Nogo-N2 subcomponent. Under cathodal stimulation, the early N2 amplitude is reduced and the right inferior frontal gyrus (BA45) is less active. Cathodal tDCS likely enhances inhibition performance via decreasing the efficiency of gain control and the impact of sensory stimuli to trigger prepotent responses. Thereby, response inhibition processes, associated with structures of the response inhibition network, become less demanded.
A gold(i) biscarbene complex with improved activity as a TrxR inhibitor and cytotoxic drug: comparative studies with different gold metallodrugs
Authors: Schmidt Claudia , Albrecht Lucia , Balasupramaniam Shantheya , Misgeld Rainer , Karge Bianka , Brönstrup Mark , Prokop Aram , Baumann Knut , Reichl Stephan , Ott Ingo 
Published: November 2018

AbstractGold complexes with N-heterocyclic carbene (NHC) ligands have been attracting major attention in medicinal inorganic chemistry based on their favorable antiproliferative effects and the structural versatility of the coordinated NHC ligands. Here we present a novel complex of the type (NHC)2Au+, which represents a substantially improved and selective TrxR inhibitor compared to close structural analogues. The complex is highly stable in various solutions over 96 hours, however, comparative cellular uptake studies indicate metabolic transformations inside cells over time. A portfolio of other gold complexes (e.g. Auranofin) has been used as references in key biological assays, showing that the novel (NHC)2Au+ complex exhibits substantially lower protein binding in combination with a strongly enhanced cytotoxic activity.
A Comparison of Personal Sound Amplification Products and Hearing Aids in Ecologically Relevant Test Environments
Authors: Brody Lisa , Wu Yu-Hsiang , Stangl Elizabeth 
Published: November 2018

Purpose
The aim of this study was to compare the benefit of self-adjusted personal sound amplification products (PSAPs) to audiologist-fitted hearing aids based on speech recognition, listening effort, and sound quality in ecologically relevant test conditions to estimate real-world effectiveness.

Method
Twenty-five older adults with bilateral mild-to-moderate hearing loss completed the single-blinded, crossover study. Participants underwent aided testing using 3 PSAPs and a traditional hearing aid, as well as unaided testing. PSAPs were adjusted based on participant preference, whereas the hearing aid was configured using best-practice verification protocols. Audibility provided by the devices was quantified using the Speech Intelligibility Index (American National Standards Institute, 2012). Outcome measures assessing speech recognition, listening effort, and sound quality were administered in ecologically relevant laboratory conditions designed to represent real-world speech listening situations.

Results
All devices significantly improved Speech Intelligibility Index compared to unaided listening, with the hearing aid providing more audibility than all PSAPs. Results further revealed that, in general, the hearing aid improved speech recognition performance and reduced listening effort significantly more than all PSAPs. Few differences in sound quality were observed between devices. All PSAPs improved speech recognition and listening effort compared to unaided testing.

Conclusions
Hearing aids fitted using best-practice verification protocols were capable of providing more aided audibility, better speech recognition performance, and lower listening effort compared to the PSAPs tested in the current study. Differences in sound quality between the devices were minimal. However, because all PSAPs tested in the study significantly improved participants' speech recognition performance and reduced listening effort compared to unaided listening, PSAPs could serve as a budget-friendly option for those who cannot afford traditional amplification.
Clinical Progression in Four Cases of Primary Progressive Apraxia of Speech
Authors: Utianski Rene L. , Duffy Joseph R. , Clark Heather M. , Strand Edythe A. , Boland Sarah M. , Machulda Mary M. , Whitwell Jennifer L. , Josephs Keith A. 
Published: November 2018

Purpose
This case series details the clinical progression of patients with primary progressive apraxia of speech (PPAOS) to illustrate, using several methods and supplemental material examples, the changes that occur in speech and language functioning in this patient population.

Method

Four patients who presented with PPAOS were followed between 5 and 6 years. Two patients had predominant articulatory abnormalities (termed
phonetic PPAOS
), 1 had predominant prosodic abnormalities (prosodic PPAOS), and 1 had relatively equal articulatory and prosodic abnormalities (mixed PPAOS). Detailed speech (including acoustics), language, neurologic, and neuropsychological data were collected.

Results
At initial exam, the patients ranged from 60 to 77 years old, with presenting disease duration of 1.5–10 years. Although all patients presented with an isolated apraxia of speech, all developed varying degrees of aphasia and dysarthria. Patients with phonetic PPAOS developed relatively more severe aphasia than the other 2 patients. All patients eventually had severe functional communication limitations and required alternative or augmentative means of communication, although at varying times postonset of their initial speech problem. Two patients developed dysphagia, 3 showed mild–moderate Parkinsonism, and 2 developed depression. For all patients, simple temporal acoustic measurements documented slowed speech rate over time.

Conclusions
This case series demonstrates that patients who initially present with PPAOS may develop aphasia and dysarthria, cognitive and behavioral changes, and other neurologic signs. Whether these changes can be predicted by the perceptual characteristics of the apraxia of speech is yet to be determined. The detailed longitudinal profiles provide valuable clinical insight into the progression of disease in people with PPAOS.

Supplemental Material

https://doi.org/10.23641/asha.7051616
Echinococcus granulosus sensu stricto: silencing of thioredoxin peroxidase impairs the differentiation of protoscoleces into metacestodes
Authors: Wang Hui , Li Jun , Zhang Chuanshan , Guo Baoping , Wei Qin , Li Liang , Yang Ning , Peter McManus Donald , Gao Xiaoli , Zhang Wenbao , Wen Hao 
Published: November 2018

Cystic echinococcosis (CE) is a cosmopolitan parasitic disease caused by infection with the larval stage of Echinococcus granulosus sensu lato. Thioredoxin peroxidase (TPx) may play an essential role in the antioxidant defence system of E. granulosus s.l. as neither catalase nor glutathione peroxidase activities have been detected in the parasite. However, it is not known whether TPx affects the survival and growth of E. granulosus s.l. during development. In this study, three fragments of siRNA specific for EgTPx (siRNA-1/2/3) were designed and transfected into protoscoleces of E. granulosus sensu stricto by electroporation. Quantitative real-time PCR and Western blotting analysis showed that siRNA-3 significantly reduced the expression of EgTPx. Coincidentally, knockdown of EgTPx expression in protoscoleces with siRNA-3 significantly reduced the viability of the parasite under oxidative stress induced by 0.6 mM H2O2. In vitro culture studies showed that protoscoleces treated with siRNA-3 reduced pre-microcyst formation. In vivo experiments showed that injecting mice intraperitoneally with protoscoleces treated with siRNA-3 resulted in a significant reduction in the number, size and weight of CE cysts compared with those of control animals. Silencing of EgTPx led to the impairment of growth of E. granulosus s.s. both in vitro and in vivo, indicating that EgTPx is an important factor for protoscoleces survival and plays an important role in the antioxidant defence against the host during development.
Molecular characterization and protective efficacy of the microneme 2 protein fromEimeria tenella
Authors: Yan Ming , Cui Xiaoxia , Zhao Qiping , Zhu Shunhai , Huang Bing , Wang Lu , Zhao Huanzhi , Liu Guiling , Li Zhihang , Han Hongyu , Dong Hui 
Published: November 2018

Microneme proteins play an important role in the adherence of apicomplexan parasites to host cells during the invasion process. In this study, the microneme 2 protein from the protozoan parasiteEimeria tenella(EtMIC2) was cloned, characterized, and its protective efficacy as a DNA vaccine investigated. The EtMIC2 gene, which codes for a 35.07 kDa protein inE. tenellasporulated oocysts, was cloned and recombinant EtMIC2 protein (rEtMIC2) was produced in anEscherichia coliexpression system. Immunostaining with an anti-rEtMIC2 antibody showed that the EtMIC2 protein mainly localized in the anterior region and membrane of sporozoites, in the cytoplasm of first- and second-generation merozoites, and was strongly expressed during first-stage schizogony. In addition, incubation with specific antibodies against EtMIC2 was found to efficiently reduce the ability ofE. tenellasporozoites to invade host cells. Furthermore, animal-challenge experiments demonstrated that immunization with pcDNA3.1(+)-EtMIC2 significantly increased average body weight gain, while decreasing the mean lesion score and oocyst output in chickens. Taken together, these results suggest that EtMIC2 plays an important role in parasite cell invasion and may be a viable candidate for the development of new vaccines againstE. tenellainfection in chickens.
Update Breast Cancer 2018 (Part 3) – Genomics, Individualized Medicine and Immune Therapies – in the Middle of a New Era: Prevention and Treatment Strategies for Early Breast Cancer
Authors: Wöckel Achim , Lux Michael , Janni Wolfgang , Hartkopf Andreas , Nabieva Naiba , Taran Florin-Andrei , Overkamp Friedrich , Hadji Peyman , Tesch Hans , Ettl Johannes , Lüftner Diana , Müller Volkmar , Welslau Manfred , Belleville Erik , Brucker Sara , Schütz Florian , Fasching Peter , Fehm Tanja , Schneeweiss Andreas , Kolberg Hans-Christian 
Published: November 2018

AbstractIn primary early breast cancer, the aim of treatment planning is to obtain an increasingly better understanding of the disease. The identification of patients with an excellent prognosis could help this group avoid unnecessary treatments. Furthermore, the planning of treatment is becoming increasingly patient-focussed. There is a growing understanding of those patients who benefit particularly from chemotherapy, as well as of those who could benefit from immunotherapy. Studies conducted on immunotherapies will be published shortly. Smaller individual studies offer an initial insight into the efficacy of checkpoint inhibitors (anti-PD1/PDL1 therapies). Not least, one of the largest breast cancer studies of all times has recently come to an end. The use of a multigene test has shown that it is sufficient to identify patients with such a good prognosis that chemotherapy is unnecessary. This review article is intended to summarise the current studies and give an outlook on current developments.
Update Breast Cancer 2018 (Part 4) – Genomics, Individualized Medicine and Immune Therapies – in the Middle of a New Era: Treatment Strategies for Advanced Breast Cancer
Authors: Müller Volkmar , Wöckel Achim , Lux Michael , Janni Wolfgang , Hartkopf Andreas , Nabieva Naiba , Taran Florin-Andrei , Hadji Peyman , Tesch Hans , Ettl Johannes , Lüftner Diana , Welslau Manfred , Belleville Erik , Brucker Sara , Schütz Florian , Fasching Peter , Fehm Tanja , Kolberg Hans-Christian , Schneeweiss Andreas , Overkamp Friedrich 
Published: November 2018

AbstractNew therapeutic developments aimed at treating women with advanced breast cancer currently focus both on identifying patients eligible for targeted therapeutic concepts and on the continuing development of immune therapies. The data on CDK4/6 inhibitors are now complete and consistent in this class of substances (palbociclib, ribociclib and abemaciclib). Further pathways under investigation are PI3K and AKT signalling pathways along with diverse approaches to their inhibition. Initial study results were also presented recently on both mechanisms of action. Insights into the PARP inhibitors, moreover, are increasing; studies in this respect are also examining in which population they can be used most effectively. This review offers a summary of the recent studies and an outline of the latest developments.