bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of sensory evaluation techniques for Hungarian wines
Authors: Guld Zsuzsanna , Nyitrainé Sárdy Diána , Gere Attila , Rácz Anita
Published: January 2020

The aim of this study was to compare different Hungarian Kadarka, Kékfrankos, and Cabernet franc wines produced and aged by the same methods and to compare two types of sensory analysis methods as well: the 100‐point OIV system and quantitative descriptive analysis (QDA). Both tests were conducted by 12 assessors of the University of Pécs, Institute for Regional Development, Faculty of Horticulture and Oenology. This study provides conclusions about the use of sensory analysis methods, highlighting the advantages and disadvantages of QDA and the OIV system. Principal component analysis, analysis of variance (ANOVA), multiple factor analysis, and partial least squares dicriminant analysis were used for the evaluation of the data. Our results showed that the sensory panel was able to discriminate the samples by both sensory methods; however, the information provided by them was significantly different. ANOVA clearly showed that the two methods have different sensitivity when comparing wines (commercial and produced wine samples) and QDA proved to be the more sensitive, as well as more detailed, method. Partial least squares discriminant analysis augmented the findings in the classification part of the different type of wine samples. In general, OIV is able to show the general quality of the wines, while QDA coupled with proper chemometric methods is able to describe why the given samples received good or bad OIV scores.
Hantzsch Ester as a Visible‐Light Photoredox Catalyst for Transition‐Metal‐Free Coupling of Arylhalides and Arylsulfinates
Authors: Zhu Da‐Liang , Wu Qi , Li Hai‐Yan , Li Hong‐Xi , Lang Jian‐Ping
Published: January 2020

Diethyl 2,6‐dimethyl‐1,4‐dihydropyridine‐3,5‐dicarboxylate (HEH) has been utilized as a visible‐light photoredox catalyst for the cross coupling of arylhalides and arylsulfinates without transition metal, sacrificial agent, and mediator. This method is compatible with various functional groups and provides diaryl sulfones in good to high yields. Mechanistic studies indicate that this reaction undergoes the stepwise light irradiation of HE−, single electron transfer (SET) in donor–acceptor complex (DAC) from *HE− to arylhalide, trapping of aryl radical with sulfinate, and SET oxidation of sulfone radical anion by HE. to sulfone by the DAC method.
Synthesis and Liver Microsomal Metabolic Stability Studies of a Fluorine‐Substituted δ‐Tocotrienol Derivative
Authors: Liu Xingui , Poddar Saikat , Song Lin , Hendrickson Howard , Zhang Xuan , Yuan Yaxia , Zhou Daohong , Zheng Guangrong
Published: January 2020

A fluoro‐substituted δ‐tocotrienol derivative, DT3‐F2, was synthesized. This compound was designed to stabilize the metabolically labile terminal methyl groups of δ‐tocotrienol by replacing one C−H bond on each of the two methyl groups with a C−F bond. However, in vitro metabolic stability studies using mouse liver microsomes revealed an unexpected rapid enzymatic C−F bond hydrolysis of DT3‐F2. To the best of our knowledge, this is the first report of an unusual metabolic hydrolysis of allylic C−F bonds.
Conductive ITO Interfaces for Optoelectronic Applications Based on Highly Ordered Inverse Opal Thin Films
Authors: Galle Lydia , Ehrling Sebastian , Lochmann Stefanie , Kaskel Stefan , Bischoff Lothar , Grothe Julia
Published: January 2020

A three‐step fabrication process for optically transparent, conducting ITO thin films with an intrinsic inverse opal structure is described. The preparation is based on colloidal crystal templating using polystyrene microspheres (100 nm–600 nm). For the realization of varying periodicities in this structure, different sphere sizes were assembled to monolayers on a substrate by spin coating and infiltrated afterwards similarly. The influence of rotation parameters as well as dispersion concentration was studied. Using this approach different geometries of the surface are accessible by systematically varying the rotation parameters and infiltration volume. The thin films show excellent anti‐reflection behavior, good transmission (>80% in the visible range) as well as a low resistance of 200 Ω/sq compared to other porous ITO interfaces. The properties are very promising for several optoelectronic applications such as in‐ or out‐coupling structures in solar cells and organic light emitting diodes.
Trusted systems of records based on Blockchain technology ‐ a prototype for mileage storing in the automotive industry
Authors: Preikschat Katarina , Böhmecke‐Schwafert Moritz , Buchwald Jan‐Paul , Stickel Carolin
Published: January 2020

Blockchain technology has the potential to bring transparency and trust to a multitude of use cases. Our research demonstrates that the technology can reduce asymmetric information in markets by bridging trust gaps. The combination of blockchain and Internet of Things technology that automatically collects sensor data, provides a feasible, decentralized technological solution for such an inefficient “Market of Lemons” coined by nobel laureate Georg Akerlof. In this paper, we develop a system prototype to reduce mileage fraud on the used car markets. Our work demonstrates the feasibility of a trusted system of records for (vehicle) data such as mileage data using a distributed database based on the public Ethereum network and smart contracts. We have identified eight requirements that are fulfilled by the prototype and the functional logic and design of thesolution can be reproduced to any other application area characterized by a lack of trust between actors or by the absence of a trusted central authority. However, the developed prototype suffers from similar limitations and challenges as the technology itself. Low throughput causes limitations in scalability and transaction costs are unpredictable. Further development of the blockchain technology and considering more cost‐efficient consensus mechanisms will address these issues.
Development of a System for Postmarketing Population Pharmacokinetic and Pharmacodynamic Studies Using Real‐World Data From Electronic Health Records
Authors: Choi Leena , Beck Cole , McNeer Elizabeth , Weeks Hannah L. , Williams Michael L. , James Nathan T. , Niu Xinnan , Abou‐Khalil Bassel W. , Birdwell Kelly A. , Roden Dan M. , Stein C. Michael , Bejan Cosmin A. , Denny Joshua C. , Van Driest Sara L.
Published: January 2020

Postmarketing population pharmacokinetic (PK) and pharmacodynamic (PD) studies can be useful to capture patient characteristics affecting PK or PD in real‐world settings. These studies require longitudinally measured dose, outcomes, and covariates in large numbers of patients; however, prospective data collection is cost‐prohibitive. Electronic health records (EHRs) can be an excellent source for such data, but there are challenges, including accurate ascertainment of drug dose. We developed a standardized system to prepare datasets from EHRs for population PK/PD studies. Our system handles a variety of tasks involving data extraction from clinical text using a natural language processing algorithm, data processing, and data building. Applying this system, we performed a fentanyl population PK analysis, resulting in comparable parameter estimates to a prior study. This new system makes the EHR data extraction and preparation process more efficient and accurate and provides a powerful tool to facilitate postmarketing population PK/PD studies using information available in EHRs.
Data Integrity in Global Clinical Trials: Discussions From Joint US Food and Drug Administration and UK Medicines and Healthcare Products Regulatory Agency Good Clinical Practice Workshop
Authors: Khin Ni A. , Francis Gail , Mulinde Jean , Grandinetti Cheryl , Skeete Rachel , Yu Bei , Ayalew Kassa , Cho Seongeun‐Julia , Fisher Andrew , Kleppinger Cynthia , Ayala Ruben , Bonapace Charles , Dasgupta Arindam , Kronstein Phillip D. , Vinter Stephen
Published: January 2020

Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording, and reporting clinical trials. Regulatory agencies conduct GCP inspections to verify the integrity of data generated in clinical trials and to assure the protection of human research subjects, in addition to ensuring that clinical trials are conducted according to the applicable regulations. The first joint GCP workshop of the US Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) and the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA‐UK) was held in October 2018 and provided the agencies’ perspectives on the importance of data quality management practices on data integrity. Regulatory perspectives on data blinding to minimize introduction of bias, and the role of audit trails in assessing data integrity in global clinical trials were discussed. This paper summarizes considerations of both agencies on these topics, along with case examples.
Impact of sorghum racial structure and diversity on genomic prediction of grain yield components
Authors: Sapkota Sirjan , Boyles Richard , Cooper Elizabeth , Brenton Zachary , Myers Matthew , Kresovich Stephen
Published: January 2020

Population structure is an important factor that affects the accuracy of estimated breeding values in genomic prediction. Natural sorghum [Sorghum bicolor (L.) Moench] populations exhibit population structure resulting from genetic and morphological differentiation due to evolutionary divergence. To study the impact of sorghum racial structure and diversity in genomic prediction, we conducted two cross‐validation (CV) experiments: CV1, proportional sampling from races; and CV2, sampling from across race (AR) or within race (WR). A diversity panel with 389 individuals with 224,007 single nucleotide polymorphisms was used for genomic prediction. Genomic heritabilities for traits were positively correlated (0.63) with their mean prediction accuracy (r) from CV1, and within‐subpopulation variance accounted for ∼80% of total genetic variance. The CV1 prediction accuracy ranged from 0.52–0.69, but r declined by 39 and 54% on average for WR and AR methods, respectively. As a predictor, race explained 30–50% of covariance for grain and panicle traits, but race was a bad predictor of plant height, as expected. Grain weight was consistently the best predicted trait across CV1 and CV2 methods except in AR. Difference in average r for WR and AR was greater in durra and caudatum, small in kafir, and nonexistent in guinea and mixed subgroups. We observed higher prevalence of minor alleles among guinea and mixed subgroups, highlighting contribution of allelic diversity towards prediction accuracy. Genomic prediction in sorghum will benefit from utilization of interracial diversity, and we emphasize the need for further investigations into the role of racial structure in genomic prediction.
Tensions in current curriculum reform and the development of teachers’ professional autonomy
Authors: Hughes Sioned , Lewis Helen
Published: January 2020

Current curriculum reform in Wales provides an opportunity for teachers to have greater freedom to develop pedagogical approaches that meet the needs of their pupils. The Successful Futures report recommends that teachers should have a greater autonomy in choosing how to deliver the curriculum, and ensuring it is done so in a manner that is meaningful and relevant to their pupils. Strengthening teachers’ agency in relation to pedagogy, however, can sometimes be difficult to achieve because, for example, of perceived issues around workload and accountability. There are many ‘off‐the‐peg’ or ready‐made solutions to the challenges of curriculum reform, and in many cases, schools are responding to such challenges using ready‐made or bespoke approaches. This paper explores the nature of the tensions between the drive to empower professional contributions to curriculum reform, and increase autonomy for teachers, and the existing professional practices. In particular, as an example of the tensions, the paper considers how and why one school selected a commercial mindfulness package to contribute to the newly defined Health and Wellbeing Area of Experience, and the implication of this choice on teacher autonomy and pedagogical practice.
Treatment of modifiable risk factors for foot ulceration in persons with diabetes: a systematic review
Authors: van Netten Jaap J. , Sacco Isabel C.N. , Lavery Lawrence A. , Monteiro‐Soares Matilde , Rasmussen Anne , Raspovic Anita , Bus Sicco A.
Published: January 2020

Background

Prevention of diabetic foot ulcers is important. Preventative treatment mostly targets and aims to improve modifiable risk factors of foot ulceration. While effectiveness of interventions in ulcer prevention has been systematically reviewed, their effectiveness in improving modifiable risk factors is unknown.

Methods

The available medical scientific literature in PubMed, Excerpta Medica Database, and the Cochrane database was searched for original research studies on six interventions to treat modifiable risk factors for diabetic foot ulceration (ie, education for patients; education for professionals; self‐management; pre‐ulcer treatment; orthotic interventions; and foot‐ and mobility‐related exercises). We assessed interventions for eight outcomes (ie, patients' knowledge; treatment adherence; professionals' knowledge; pre‐ulcers; mechanical stress; neuropathy symptoms; foot/ankle joint mobility; and foot function). Both controlled and noncontrolled studies were selected. Data from controlled studies were assessed for methodological quality by two independent reviewers and extracted and presented in evidence and risk of bias tables.

Results

We included 72 publications (26 with a controlled study design and 46 noncontrolled). We found that structured education may improve foot self‐care behaviour of patients, yearly foot examinations, and foot disease knowledge of health care professionals. Callus removal reduces peak plantar pressure. Custom‐made therapeutic footwear can be effective in reducing plantar pressure and may reduce callus. Foot‐ and mobility‐related exercises may improve neuropathy symptoms and foot and ankle joint range of motion, while they do not seem to reduce peak plantar pressure; evidence for their effect on foot strength is conflicting.

Conclusions

Structured education for patients and health care professionals, callus removal, custom‐made therapeutic footwear, and foot‐ and mobility‐related exercises may be beneficial for improving modifiable risk factors for foot ulceration. However, we generally found low quality of evidence for interventions targeting modifiable risk factors for ulceration in persons with diabetes, with frequently inconsistent or limited results available per intervention and outcome.
Long‐term survival probability, not current habitat quality, predicts dispersal distance in a stream salamander
Authors: Addis Brett R. , Lowe Winsor H.
Published: January 2020

Dispersal evolves as an adaptive mechanism to optimize individual fitness across the landscape. Specifically, dispersal represents a mechanism to escape fitness costs resulting from changes in environmental conditions. Decades of empirical work suggest that individuals use local habitat cues to make movement decisions, but theory predicts that dispersal can also evolve as a fixed trait, independent of local conditions, in environments characterized by a history of stochastic spatiotemporal variation. Until now, however, both conditional and fixed models of dispersal evolution have primarily been evaluated using emigration data (stay vs. leave), and not dispersal distances: a more comprehensive measure of dispersal. Our goal was to test whether conditional or fixed models of dispersal evolution predict variation in dispersal distance in the stream salamanderGyrinophilus porphyriticus.We quantified variation in habitat conditions using measures of salamander performance from 4 yr of spatially explicit, capture–mark–recapture (CMR) data across three headwater streams in the Hubbard Brook Experimental Forest in central New Hampshire, USA. We used body condition as an index of local habitat quality that individuals may use to make dispersal decisions, and survival probability estimated from multistate CMR models as an index of mortality risk resulting from the long‐term history of environmental variation. We found that dispersal distances increased with declining survival probability, indicating that salamanders disperse further in risky environments. Dispersal distances were unrelated to spatial variation in body condition, suggesting that salamanders do not base dispersal distance decisions on local habitat quality. Our study provides the first empirical support for fixed models of dispersal evolution, which predict that dispersal evolves in response to a history of spatiotemporal environmental variation, rather than as a conditional response to current habitat conditions. More broadly, this study underscores the value of assessing alternative scales of environmental variation to gain a more complete and balanced understanding of dispersal evolution.
Disturbance legacies increase and synchronize nutrient concentrations and bacterial productivity in coastal ecosystems
Authors: Kominoski John S. , Gaiser Evelyn E. , Castañeda‐Moya Edward , Davis Stephen E. , Dessu Shimelis B. , Julian Paul , Lee Dong Yoon , Marazzi Luca , Rivera‐Monroy Victor H. , Sola Andres , Stingl Ulrich , Stumpf Sandro , Surratt Donatto , Travieso Rafael , Troxler Tiffany G.
Published: January 2020

Long‐term ecological research can resolve effects of disturbance on ecosystem dynamics by capturing the scale of disturbance and interactions with environmental changes. To quantify how disturbances interact with long‐term directional changes (sea‐level rise, freshwater restoration), we studied 17 yr of monthly dissolved organic carbon (DOC), total nitrogen (TN), and phosphorus (TP) concentrations and bacterioplankton productivity across freshwater‐to‐marine estuary gradients exposed to multiple disturbance events (e.g., droughts, fire, hurricanes, and low‐temperature anomalies) and long‐term increases in water levels. By studying two neighboring drainages that differ in hydrologic connectivity, we additionally tested how disturbance legacies are shaped by hydrologic connectivity. We predicted that disturbance events would interact with long‐term increases in water levels in freshwater and marine ecosystems to increase spatiotemporal similarity (i.e., synchrony) of organic matter, nutrients, and microbial activities. Wetlands along the larger, deeper, and tidally influenced Shark River Slough (SRS) drainage had higher and more variable DOC, TN, and TP concentrations than wetlands along the smaller, shallower, tidally restricted Taylor River Slough/Panhandle (TS/Ph) drainage. Along SRS, DOC concentrations declined with proximity to coast, and increased in magnitude and variability following drought and flooding in 2015 and a hurricane in 2017. Along TS/Ph, DOC concentrations varied by site (higher in marine than freshwater wetlands) but not year. In both drainages, increases in TN from upstream freshwater marshes occurred following fire in 2008 and droughts in 2010 and 2015, whereas downstream increases in TP occurred with coastal storm surge from hurricanes in 2005 and 2017. Decreases in DOC:TN and DOC:TP were explained by increased TN and TP. Increases in bacterioplankton productivity occurred throughout both drainages following low‐temperature events (2010 and 2011) and a hurricane (2017). Long‐term TN and TP concentrations and bacterioplankton productivity were correlated (r > 0.5) across a range of sampling distances (1–50 km), indicating spatiotemporal synchrony. DOC concentrations were not synchronized across space or time. Our study advances disturbance ecology theory by illustrating how disturbance events interact with long‐term environmental changes and hydrologic connectivity to determine the magnitude and extent of disturbance legacies. Understanding disturbance legacies will enhance prediction and enable more effective management of rapidly changing ecosystems.
Electrocatalytic Reduction of Oxygen at Glassy Carbon Electrodes Coated with Diazonium‐derived Porphyrin/Metalloporphyrin Films
Authors: Kudas Zuleyha , Atmaca Ufuk , Saruhan Tuba , Celik Murat , Ekinci Duygu
Published: January 2020

In this study, the influence of the film structure was investigated on the electrocatalytic oxygen reduction at GC electrodes covered with porphyrin and metalloporphyrin rings via the diazonium modification method. For that purpose, primarily, tetraphenylporphyrin (TPP) films on GC electrode surfaces were prepared by electroreduction of in situ generated diazonium salts of 5‐(4‐aminophenyl)‐10,15,20‐triphenylporphyrin (APP) and 5,10,15,20‐tetrakis(4‐aminophenyl)porphyrin (TAPP) molecules. Next, the formation of metalloporphyrin films on the modified surfaces was accomplished through the complexation reactions of surface porphyrin rings with metal ions in the salt solutions containing Mn(II), Fe(III) and Co(II) ions. The resulting porphyrin and metalloporphyrin layers were identified with XPS and ICP‐MS. The electrochemical barrier properties of the films on GC surfaces were examined by cyclic voltammetry in K3Fe(CN)6 aqueous solution. The electrocatalytic abilities of the resulting films were also investigated for the oxygen electrochemical reduction by employing cyclic voltammetry in PBS solutions saturated with oxygen. The results showed that the oxygen reduction potentials on modified GC electrodes were shifted to less negative potentials compared to that of bare GC electrode. Also, it was obtained that the oxygen reduction reaction was more effective on the GC electrodes modified with TPP rings by using TAPP molecules than those prepared by using APP molecules.
The effect of atmospheric pressure cold plasma on the inactivation ofEscherichia coliin sour cherry juice and its qualitative properties
Authors: Hosseini Seyed Mehdi , Rostami Sajad , Hosseinzadeh Samani Bahram , Lorigooini Zahra
Published: January 2020

One of the nonthermal methods is the atmospheric pressure cold plasma (APCP). In this study, the effect of cold plasma on the reduction ofEscherichia colibacteria and qualitative properties of sour cherry juice, including total phenolic content (TPC), total anthocyanin content (TAC), and vitamin C, were investigated. Independent variables included plasma exposure time (1, 5, and 9 min), applied field intensity (25, 37.5, and 50 kV/cm), feeding gas oxygen content (0%, 0.5%, and 1%), and sample depth (0.5, 1, and 1.5 cm). The results show that increased oxygen content in argon has the greatest effect on the reduction of bacteria, and plasma exposure decreased 6 logarithmic periods ofE. colibacteria in sour cherry juice. Optimization results showed when all bacteria were eliminated by plasma, TPC remained unchanged, and TAC and vitamin C decreased by 4% and 21%, respectively, while thermal methods increased TPC by 23% and decreased TAC and vitamin C by 26% and 77%, respectively. These results indicate that, compared with conventional thermal methods, sour cherry juice pasteurization using APCP has little effect on the juice qualitative properties, and this method can serve as a suitable alternative to conventional thermal methods.
Emerging technologies to study glial cells
Authors: Hirbec Hélène , Déglon Nicole , Foo Lynette C. , Goshen Inbal , Grutzendler Jaime , Hangen Emilie , Kreisel Tirzah , Linck Nathalie , Muffat Julien , Regio Sara , Rion Sybille , Escartin Carole
Published: January 2020

Development, physiological functions, and pathologies of the brain depend on tight interactions between neurons and different types of glial cells, such as astrocytes, microglia, oligodendrocytes, and oligodendrocyte precursor cells. Assessing the relative contribution of different glial cell types is required for the full understanding of brain function and dysfunction. Over the recent years, several technological breakthroughs were achieved, allowing “glio‐scientists” to address new challenging biological questions. These technical developments make it possible to study the roles of specific cell types with medium or high‐content workflows and perform fine analysis of their mutual interactions in a preserved environment. This review illustrates the potency of several cutting‐edge experimental approaches (advanced cell cultures, induced pluripotent stem cell (iPSC)‐derived human glial cells, viral vectors, in situ glia imaging, opto‐ and chemogenetic approaches, and high‐content molecular analysis) to unravel the role of glial cells in specific brain functions or diseases. It also illustrates the translation of some techniques to the clinics, to monitor glial cells in patients, through specific brain imaging methods. The advantages, pitfalls, and future developments are discussed for each technique, and selected examples are provided to illustrate how specific “gliobiological” questions can now be tackled.
Predictors of mortality in Māori, Pacific Island, and European patients diagnosed with dementia at a New Zealand Memory Service
Authors: Cullum Sarah , Varghese Chris , Coomarasamy Christin , Whittington Rosie , Hadfield Laura , Rajay Aakash , Yeom Brian , Liu Bonnie , Christie Madeline , Appleton Kerry , Yates Susan , Cheung Gary
Published: January 2020

Background

As the economic impact of dementia on health and social care increases, governments require disease‐specific epidemiological data that will help inform spending and policy decisions. The aim of this study is to examine predictors of mortality in dementia in consecutive referrals to a New Zealand (NZ) memory service that includes Māori, Pacific Islander, and NZ European patients.

Methods

Date of birth, sex, ethnicity, living situation, cognitive function, dementia subtype, dementia severity, physical comorbidity, and medication data were collected from electronic health records. The resulting data set was linked to administrative data on mortality and last hospital contact dates to allow time‐dependent survival analyses.

Results

The risk of death in people with dementia was increased by age (adjusted HR per year 1.08, 95%CI:1.05‐1.12) and lower cognitive score at baseline (adjusted HR for severe impairment:2.54, 95% CI:1.25‐5.16), and was reduced by cholinesterase inhibitors (adjusted HR:0.54, 95% CI:0.34‐0.88). Compared to NZ Europeans (HR:1.19, 95% CI:0.63‐2.25), antipsychotics increased the risk of death three‐fold in Māori (adjusted HR:3.62, 95% CI:0.79‐16.7) and Pacific Islanders (adjusted HR:2.54, 95%CI:1.10‐5.85).

Conclusions

Further research is required to elucidate the mechanisms underlying the survival rates in Māori and Pacific Islanders living with dementia in NZ,and their increased risk of death if antipsychotics are used.
Neural correlates of intonation and lexical tone in tonal and non‐tonal language speakers
Authors: Chien Pei‐Ju , Friederici Angela D. , Hartwigsen Gesa , Sammler Daniela
Published: January 2020

Intonation, the modulation of pitch in speech, is a crucial aspect of language that is processed in right‐hemispheric regions, beyond the classical left‐hemispheric language system. Whether or not this notion generalises across languages remains, however, unclear. Particularly, tonal languages are an interesting test case because of the dual linguistic function of pitch that conveys lexical meaning in form of tone, in addition to intonation. To date, only few studies have explored how intonation is processed in tonal languages, how this compares to tone and between tonal and non‐tonal language speakers. The present fMRI study addressed these questions by testing Mandarin and German speakers with Mandarin material. Both groups categorised mono‐syllabic Mandarin words in terms of intonation, tone, and voice gender. Systematic comparisons of brain activity of the two groups between the three tasks showed large cross‐linguistic commonalities in the neural processing of intonation in left fronto‐parietal, right frontal, and bilateral cingulo‐opercular regions. These areas are associated with general phonological, specific prosodic, and controlled categorical decision‐making processes, respectively. Tone processing overlapped with intonation processing in left fronto‐parietal areas, in both groups, but evoked additional activity in bilateral temporo‐parietal semantic regions and subcortical areas in Mandarin speakers only. Together, these findings confirm cross‐linguistic commonalities in the neural implementation of intonation processing but dissociations for semantic processing of tone only in tonal language speakers.
BRCA1 c.5470_5477del, a founder mutation in Chinese Han breast cancer patients
Authors: Meng Hua , Yao Lu , Yuan Hua , Xu Ye , Ouyang Tao , Li Jinfeng , Wang Tianfeng , Fan Zhaoqing , Fan Tie , Lin Benyao , Xie Yuntao
Published: January 2020

The spectrum and frequency of BRCA1/2 pathogenic variants may be ethnicity‐specific. Whether high‐frequency founder mutations are present in Chinese women remains largely unknown. In the current study, germline pathogenic variants in the BRCA1/2 genes were determined in 9,505 unselected Chinese Han breast cancer (BC) patients by next‐generation and/ or Sanger sequencing. Four hundred and seventy‐one (5.0%) BC patients carried BRCA1/2 pathogenic variants in this cohort. A total of 25 recurrent pathogenic variants (at least found in four unrelated patients) were identified in this cohort (8 BRCA1 and 17 BRCA2 recurrent pathogenic variants), 161 patients carried one of these recurrent pathogenic variants in this cohort of 9,505 patients. All of these 25 recurrent pathogenic variants were further explored whether they had founder effect through haplotype analysis. The most common pathogenic variant, BRCA1 c.5470_5477del, was found in 30 BC patients from 29 unrelated families. Twenty‐seven of these 29 unrelated patients who carried this BRCA1 c.5470_5477del mutation shared an identical haplotype, indicating that BRCA1 c.5470_5477del was a founder mutation in the Chinese Han population. Furthermore, BRCA1 c.5470_5477del mutation carriers had a significantly worse survival than noncarriers (disease‐free survival, p = 0.049; overall survival, p = 0.029). Taken together, our data suggested that BRCA1 c.5470_5477del is a founder mutation in the Chinese Han population and BRCA1 c.5470_5477del mutation carriers have a poor survival.
Upregulation of 6‐phosphofructo‐2‐kinase (PFKFB3) by hyperactivated mammalian target of rapamycin complex 1 is critical for tumor growth in tuberous sclerosis complex
Authors: Wang Yani , Tang Sisi , Wu Yuncui , Wan Xiaofeng , Zhou Meng , Li Hongwu , Zha Xiaojun
Published: January 2020

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the benign tumor formation in multiple organs. The main etiology of TSC is the loss‐of‐function mutation of TSC1 or TSC2 gene, which leads to aberrant activation of mammalian target of rapamycin complex 1 (mTORC1). In this research, we found a significant increase of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase 3 (PFKFB3) expression in Tsc1−/− and Tsc2−/− mouse embryonic fibroblasts (MEFs) compared with the control cells. Inhibition of mTORC1 led to a dramatic decrease of PFKFB3 expression, indicating PFKFB3 regulation by mTORC1. Moreover, suppression of mTORC1 inhibited the expression of PFKFB3 in rat uterine leiomyoma‐derived Tsc2‐null ELT3 cells and human tumor cells. Furthermore, we identified hypoxia‐inducible factor 1α (HIF‐1α) as a mediator transmitting the signal from mTORC1 to PFKFB3. Depletion of PFKFB3 inhibited proliferation and tumorigenicity of Tsc1‐ or Tsc2‐deficient cells. In addition, combination of rapamycin with PFK15, a PFKFB3 inhibitor, exerts a stronger inhibitory effect on cell proliferation of Tsc1‐ or Tsc2‐null MEFs than treatment with single drug. We conclude that loss of TSC1 or TSC2 led to upregulated expression of PFKFB3 through activation of mTORC1/HIF‐1α signaling pathway and co‐administration of rapamycin and PFK15 may be a promising strategy for the treatment of TSC tumors as well as other hyperactivated mTORC1‐related tumors.
Rational design of thiolated polyenes as trifunctional Raman reporter molecules in surface‐enhanced Raman scattering nanotags for cytokine detection in a lateral flow assay
Authors: Keller Thomas , Brem Svetlana , Tran Vi , Sritharan Oliver , Schäfer Daniel , Schlücker Sebastian
Published: January 2020

The characteristic vibrational spectroscopic fingerprint of Raman reporter molecules adsorbed on noble metal nanoparticles is employed for the identification of target proteins by the corresponding surface‐enhanced Raman scattering (SERS) nanotag‐labeled antibodies. Here, we present the modular synthesis of thiolated polyenes with two to five C═C double bonds introduced via stepwise Wittig reactions. The experimental characterization of their electronic and vibrational properties is complemented by density functional theory calculations. Highly SERS‐active nanotags are generated by using the thiolated polyenes as Raman reporter molecules in Au/Au core/satellite supraparticles with multiple hot spots. The cytokines IL‐1β and IFN‐γ are detected in a duplex SERS‐based lateral flow assay on a nitrocellulose test strip by Raman microscopy. The thiolated polyenes are suitable for use in immuno‐SERS applications such as point‐of‐care testing as well as cellular and tissue imaging.
Long noncoding RNA PVT1 acts as an oncogenic driver in human pan‐cancer
Authors: You Zilong , Xu Shouping , Pang Da
Published: January 2020

Increasing evidence indicates that long noncoding RNAs (lncRNAs) play pivotal roles during tumorigenesis in multiple types of cancers. However, little is known about the exact role of plasmacytoma variant translocation 1 (PVT1) in human pan‐cancer. Here, we report the oncogenic role and function of PVT1 in human pan‐cancer, including breast cancer. The expression of PVT1 in human tumor tissues and nontumor tissues, the upstream regulation of PVT1 and the relationship between its expression and prognosis and chemoresistance were examined by using The Cancer Genome Atlas data. PVT1 expression is higher in human cancer tissues compared with adjacent noncancerous tissues, and patients with high levels of PVT1 expression usually have tumors with a higher TNM stage. High PVT1 expression is also associated with worse disease outcomes in patients with cancer. Hypomethylation and transcription factor binding in the PVT1 promoter locus activates its transcriptional expression. Guilt by association analysis revealed that PVT1 may be involved in processes associated with tumorigenesis. Moreover, PVT1 may trigger chemoresistance in human cancer. These results indicated that PVT1 may act as an oncogenic driver and maybe a potential therapeutic target in human cancer.
US‐based risk stratification “guidelines” for thyroid nodules: Quō Vādis?
Authors: Alexander Archie A.
Published: January 2020

Purpose

This rapid scoping review addresses the commentary titled the ACR TI‐RADS™: An Advance in the Management of Thyroid Nodules or Pandora's Box of Surveillance? suggesting that the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI‐RADS™‐2017) adds to a plethora of existing guidelines, incorporates an inconsistent lexicon, and potentially contradicts recommendations.

Materials and Methods

The author performed a rapid scoping review using a combination of English keywords to identify and review peer reviewed articles contained in electronic databases (e‐databases) comparing 2 or more guidelines for managing adult thyroid nodules (GMTNs) with (UGMTNs) and without (non‐UGMTNs) ultrasound. E‐databases included Medline (PubMed), EBSCO, Google, and Google Scholar published (2010‐2019).

Results

The search returned 28 articles, where the author identified 12 different guidelines. Most articles evaluated diagnostic performance (N = 26), not quality (N = 2) measures. The most commonly reviewed UGMTNs were in descending order ATA‐2015, ACR TI‐RADS™‐2017, South Korean, and EU TI‐RADS. No article reviewed all GMTNs or identified a generally accepted UGMTNs or non‐UGMTNs. Primary origin continents were: North America (U.S.A), Asia (Japan, South Korea, Thailand), Europe (France, Italy, U.K.), and South America (Chile).

Conclusion

A plethora of UGMTNs may exist. No guideline enjoys general acceptance and evaluations of performance and quality vary.
Predicting nitrous oxide emissions after the application of solid manure to grassland in the United Kingdom
Authors: Melaku Nigus Demelash , Shrestha Narayan Kumar , Wang Junye , Thorman Rachel E.
Published: January 2020

Nitrous oxide (N2O) emission from agricultural soils represents a significant source of greenhouse gas to the atmosphere. We evaluated the suitability of a modified Soil and Water Assessment Tool (SWAT) model to estimate the N2O flux from the application of solid manure at two grassland sites (North Wyke [NW] and Pwllpeiran [PW]) in the United Kingdom. The simulated N2O emissions were validated against field observations measured in 2011 and 2012 for model calibration and validation, respectively. The SWAT model predicts water‐filled pore space (WFPS) very well with Nash–Sutcliffe efficiency (NSE), R2, RMSE, and percentage bias (PBIAS) values of 0.67, .72, 0.06, and 3.64, respectively, during the calibration period for NW site, whereas it gives 0.68, .69, 0.07, and 3.04, respectively during the validation period. At PW, the model predicted the NSE, R2, RMSE, and PBIAS of 0.55, .69, 0.04, and −4.5, respectively, during calibration and 0.63, .71, 0.05, and −2.6, respectively, during the validation period. Compared with WFPS, the model resulted in a slightly lower fit for N2O emissions for NW (NSE = 0.47, R2 = .63 during calibration, and NSE = 0.55, R2 = .58 during validation) and for PW (NSE = 0.54, R2 = .71 for calibration, and NSE = 0.47, R2 = .69 for validation). Results revealed that the SWAT model performed reasonably well in representing the dynamics of N2O emissions after solid manure application to grassland.
RPE65 and retinal dystrophy: Report of new and recurrent mutations
Authors: Safari Shamsi , Zare‐Abdollahi Davood , Bushehri Ata , Safari Mohammad Reza , Dehghani Azadeh , Tahmasebi Zahra , Khorram Khorshid Hamid Reza , Ghadami Mohsen
Published: January 2020

Bachground

Leber congenital amaurosis (LCA) is a severe and congenital or early onset form of inherited retinitis pigmentosa (RP). To date, approximately 25 genes have been introduced in relation to LCA. In this regard, retinal pigment epithelium‐specific 65 kDa (RPE65) is a well‐known gene mutation that plays a role in the pathogenesis of 5–10% of LCA cases.

Methos

Two individuals fromseparate families were subjected to ehole exome sequencing (WES). Causativevariants were searched further assessed using Sanger sequencing.

Results

Here, two families with mutations in the RPE65 gene show severe and early onset LCA, as expected. In addition to the characterization of the phenotype, by reporting a new mutation (c.1451‐1G>A), we further expand the mutation spectrum of RPE65. Likewise, as an interesting aspect of our study, we report on a previously reported RP‐linked mutation associated with severe early onset LCA (c.T200G:p.L67R).

Conclusions

Considering this variant in different populations, it is likely that it represents a hotspot and affects the function of the coded protein. The variable expressivity of the phenotype can be assumed by the presence of the modifier allele(s) as a result of a different genetic background or the effect of different environments on phenotype expression.
Treatment and outcomes of extrahepatic malignancy incidentally diagnosed during pretransplant evaluation for living donor liver transplantation
Authors: Park Gil‐Chun , Hwang Shin , Song Gi‐Won , Jung Dong‐Hwan , Moon Deok‐Bog , Ahn Chul‐Soo , Kim Ki‐Hun , Ha Tae‐Yong , Yoon Young‐In , Lee Sung‐Gyu
Published: January 2020

Background

This study analyzed treatment and outcomes in patients with primary extrahepatic malignancy (EHM) incidentally diagnosed during pretransplant evaluation for living donor liver transplantation (LDLT).

Methods

Of 4621 adult patients undergoing LDLT over 19 years, 41 were diagnosed with EHM shortly before LDLT (incidental malignancy group), and 92 had been treated for EHM more than 6 months before LDLT (treated malignancy group).

Results

Most common EHMs were colorectal, thyroid, and stomach cancers in the incidental malignancy group; and stomach, breast, thyroid, colorectal, and renal cell cancers and lymphoma in the treated malignancy group. Mean interval between EHM diagnosis and LDLT in the incidental malignancy group was 1.5 ± 1.6 months. Of the 41 patients in this group, 15 (35.6%), seven (17.1%), and 16 (39.0%) underwent EHM treatment before, during, and after LDLT, respectively, whereas three (7.3%) underwent observation alone. During a mean follow‐up of 70.1 ± 50.8 months, six (14.6%) patients showed tumor recurrence, and three (7.3%) died of tumor progression. All recurrences developed in patients with tumor stages higher than the earliest stage. The mean interval between EHM diagnosis and LDLT in treated malignancy group was 79.8 ± 79.6 months. During a mean follow‐up of 63.2 ± 54.1 months, three (3.3%) patients showed tumor recurrence and one (1.1%) died of tumor progression. The incidence of EHM recurrence was significantly higher (P = .025), and the overall post‐transplant patient survival rate was significantly lower (P = .046), in the incidental malignancy than in the treated malignancy group.

Conclusions

Only patients with earliest‐stage EHM detected shortly before LDLT are indicated for upfront LDLT combined with peritransplant EHM treatment.
Mortality from HIV‐associated meningitis in sub‐Saharan Africa: a systematic review and meta‐analysis
Authors: Tenforde Mark W , Gertz Alida M , Lawrence David S , Wills Nicola K , Guthrie Brandon L , Farquhar Carey , Jarvis Joseph N
Published: January 2020

Introduction

HIV‐associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub‐Saharan Africa (SSA). We performed a systematic review and meta‐analysis with the primary aim of estimating mortality from major causes of adult meningitis in routine care settings, and to contrast this with outcomes from clinical trial settings.

Methods

We searched PubMed, EMBASE and the Cochrane Library for published clinical trials (defined as randomized‐controlled trials (RCTs) or investigator‐managed prospective cohorts) and observational studies that evaluated outcomes of adult meningitis in SSA from 1 January 1990 through 15 September 2019. We performed random effects modelling to estimate pooled mortality, both in clinical trial and routine care settings. Outcomes were stratified as short‐term (in‐hospital or two weeks), medium‐term (up to 10 weeks) and long‐term (up to six months).

Results and discussion

Seventy‐nine studies met inclusion criteria. In routine care settings, pooled short‐term mortality from cryptococcal meningitis was 44% (95% confidence interval (95% CI):39% to 49%, 40 studies), which did not differ between amphotericin (either alone or with fluconazole) and fluconazole‐based induction regimens, and was twofold higher than pooled mortality in clinical trials using amphotericin based treatment (21% (95% CI:17% to 25%), 17 studies). Pooled short‐term mortality of TB meningitis was 46% (95% CI: 33% to 59%, 11 studies, all routine care). For pneumococcal meningitis, pooled short‐term mortality was 54% in routine care settings (95% CI:44% to 64%, nine studies), with similar mortality reported in two included randomized‐controlled trials. Few studies evaluated long‐term outcomes.

Conclusions

Mortality rates from HIV‐associated meningitis in SSA are very high under routine care conditions. Better strategies are needed to reduce mortality from HIV‐associated meningitis in the region.
Rapid and sensitive detection of pesticide residues using dynamic surface‐enhanced Raman spectroscopy
Authors: Chen Wanling , Long Feng , Song Guofen , Chen Jing , Peng Shuai , Li Penghui
Published: January 2020

Pesticide residues are one of the major food safety concerns for consumers all over the world, and it is crucial to develop simple, rapid, and effective method for the detection of pesticide residues. In the study, we report the sensitive detection of pesticides with the dynamic surface‐enhanced Raman spectroscopy (dynamic SERS) method. The dynamic SERS method provides excellent detection sensitivity at the metastable state of plasmonic nanoparticles in the sessile drop, which is a critical state between the wet state and dry state during the volatilization process. With this simple and rapid method, the SERS performance towards four pesticides, paraquat, thiabendazole, tricyclazole, and isocarbophos, is investigated with silver nanoparticles (AgNPs) as the enhancing reagents. The characteristic SERS spectra of paraquat, thiabendazole, tricyclazole, and isocarbophos can be detected at concentrations down to 1 × 10−9 M, 5 × 10−9 M, 5.28 × 10−9 M, and 3.45 × 10−7 M, respectively. The pesticides are also discriminable at the same concentrations as the standard solution counterparts from the pesticides spiked vegetable extracts, and linear relationship can be drawn from the characteristic peak intensities and negative logarithm of concentrations of the four pesticides. Therefore, the simple and rapid dynamic SERS method shows great potential in the practical detection of pesticide residues.
A single‐cell‐gap transflective blue‐phase liquid crystal display based on fringe in‐plane switching electrodes
Authors: Zhou Xiang‐Yu , Chu Fan , Tian Li‐Lan , Li Rui , Hou Wen‐Yi , Gu Xiao‐Qing , Wang Qiong‐Hua
Published: January 2020

A transflective blue‐phase liquid crystal display (TRBP‐LCD) based on fringe in‐plane switching (FIS) electrodes is proposed. The proposed structure generates combined fringe and in‐plane electric fields that cause more liquid crystal (LC) molecules to reorient almost in plane above and between the pixel electrodes. The fringe field is mainly generated in the transmissive (T) region, and the horizontal electric field is mainly generated in the reflective (R) region. By optimizing the width of the pixel electrodes and the gap between two adjacent pixel electrodes, the different electric field intensity in the T and R regions contribute to balance the optical phase retardation between the T and R regions. As a result, the proposed TRBP‐LCD exhibits a low operating voltage and high optical efficiency, while it preserves a relatively simple fabrication process.
Fabric phase sorptive extraction for the determination of 17 multiclass fungicides in environmental water by gas chromatography‐tandem mass spectrometry
Authors: Celeiro Maria , Vazquez Lua , Nurerk Piyaluk , Kabir Abuzar , Furton Kenneth G. , Dagnac Thierry , Llompart Maria
Published: January 2020

A rapid environmental pollution screening and monitoring workflow based on fabric phase sorptive extraction‐gas chromatography‐tandem mass spectrometry (FPSE‐GC‐MS/MS) is proposed for the first time for the analysis of 17 widespread used fungicides (metalaxyl, cyprodinil, tolylfluanid, procymidone, folpet, fludioxonil, myclobutanil, kresoxim methyl, iprovalicarb, benalaxyl, trifloxystrobin, fenhexamid, tebuconazole, iprodione, pyraclostrobin, azoxystrobin and dimethomorph) in environmental waters. The most critical parameters affecting FPSE, such as sample volume, matrix pH, desorption solvent and time, and ionic strength were optimized by statistical design of experiment to obtain the highest extraction efficiency. Under the optimized conditions, the proposed FPSE‐GC‐MS/MS method was validated in terms of linearity, repeatability, reproducibility, accuracy and precision. To assess matrix effects, recovery studies were performed employing different water matrices including ultrapure, fountain, river, spring, and tap water at 4 different concentration levels (0.1, 0.5, 1 and 5 µg/L). Recoveries were quantitative with values ranging between 70–115%, and relative standard deviation values lower than 14%. Limits of quantification were at the low ng/L for all the target fungicides. Finally, the validated FPSE‐GC‐MS/MS method was applied to real water samples, revealing the presence of 11 out of the 17 target fungicides.