bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery and antiproliferative evaluation of new quinoxalines as potential DNA intercalators and topoisomerase II inhibitors
Authors: Eissa Ibrahim H. , Metwaly Ahmed M. , Belal Amany , Mehany Ahmed B.M. , Ayyad Rezk R. , El‐Adl Khaled , Mahdy Hazem A. , Taghour Mohammed S. , El‐Gamal Kamal M.A. , El‐Sawah Mohamad E. , Elmetwally Souad A. , Elhendawy Mostafa. A. , Radwan Mohamed M. , ElSohly Mahmoud A.
Published: August 2019

In continuation of our previous work on the design and synthesis of topoisomerase II (Topo II) inhibitors and DNA intercalators, a new series of quinoxaline derivatives were designed and synthesized. The synthesized compounds were evaluated for their cytotoxic activities against a panel of three cancer cell lines (Hep G‐2, Hep‐2, and Caco‐2). Compounds 18b, 19b, 23, 25b, and 26 showed strong potencies against all tested cell lines with IC50 values ranging from 0.26 ± 0.1 to 2.91 ± 0.1 µM, comparable with those of doxorubicin (IC50 values ranging from 0.65 ± 0.1 to 0.81 ± 0.1 µM). The most active compounds were further evaluated for their Topo II inhibitory activities and DNA intercalating affinities. Compounds 19b and 19c exhibited high activities against Topo II (IC50 = 0.97 ± 0.1 and 1.10 ± 0.1 µM, respectively) and bound the DNA at concentrations of 43.51 ± 2.0 and 49.11 ± 1.8 µM, respectively, whereas compound 28b exhibited a significant affinity to bind the DNA with an IC50 value of 37.06 ± 1.8 µM. Moreover, apoptosis and cell‐cycle tests of the most promising compound 19b were carried out. It was found that 19b can significantly induce apoptosis in Hep G‐2 cells. It has revealed cell‐cycle arrest at the G2/M phase. Moreover, compound 19b downregulated the Bcl‐2 levels, indicating its potential to enhance apoptosis. Furthermore, molecular docking studies were carried out against the DNA–Topo II complex to examine the binding patterns of the synthesized compounds.
Visible‐Light‐Promoted Cascade Radical Cyclization: Synthesis of 1,4‐Diketones Containing Chroman‐4‐One Skeletons
Authors: He Xiang‐Kui , Cai Bao‐Gui , Yang Qing‐Qing , Wang Long , Xuan Jun
Published: August 2019

A visible‐light‐induced cascade radical cyclization of aroyl chlorides with 2‐(allyloxy)‐benzaldehyde derivatives has been developed. The method takes advantages of unactivated C=C bonds as the acyl radical acceptors and offers a mild and green approach for the synthesis of 1,4‐diketones bearing biologically important chroman‐4‐one skeletons with moderate to good yields.
A comprehensive psychometric analysis of autism‐spectrum quotient factor models using two large samples: Model recommendations and the influence of divergent traits on total‐scale scores
Authors: English Michael C. W. , Gignac Gilles E. , Visser Troy A. W. , Whitehouse Andrew J. O. , Maybery Murray T.
Published: August 2019

The Autism‐Spectrum Quotient (AQ) is a psychometric scale that is commonly used to assess autistic‐like traits and behaviors expressed by neurotypical individuals. A potential strength of the AQ is that it provides subscale scores that are specific to certain dimensions associated with autism such as social difficulty and restricted interests. However, multiple psychometric evaluations of the AQ have led to substantial disagreement as to how many factors exist in the scale, and how these factors are defined. These challenges have been exacerbated by limitations in study designs, such as insufficient sample sizes as well as a reliance on Pearson, rather than polychoric, correlations. In addition, several proposed models of the AQ suggest that some factors are uncorrelated, or negatively correlated, which has ramifications for whether total‐scale scores are meaningfully interpretable—an issue not raised by previous work. The aims of the current study were to provide: (a) guidance as to which models of the AQ are viable for research purposes, and (b) evidence as to whether total‐scale scores are adequately interpretable for research purposes. We conducted a comprehensive series of confirmatory factor analyses on 11 competing AQ models using two large samples drawn from an undergraduate population (n = 1,702) and the general population (n = 1,280). Psychometric evidence largely supported using the three‐factor model described by Russell‐Smith et al. [Personality and Individual Differences 51(2), 128–132 (2011)], but did not support the use of total‐scale scores. We recommend that researchers consider using AQ subscale scores instead of total‐scale scores. Autism Res 2020, 13: 45–60. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

We examined 11 different ways of scoring subscales in the popular Autism‐Spectrum Quotient (AQ) questionnaire in two large samples of participants (i.e., general population and undergraduate students). We found that a three‐subscale model that used “Social Skill,” “Patterns/Details,” and “Communication/Mindreading” subscales was the best way to examine specific types of autistic traits in the AQ. We also found some weak associations between the three subscales—for example, being high on the “Patterns/Details” subscale was not predictive of scores on the other subscales. This means that meaningful interpretation of overall scores on the AQ is limited.
Analysis of the Unbalanced Two‐Period Cross‐Over Design with Negligible Residual Effects
Authors: Gomez‐Marin O. , McHugh R. B.
Published: August 2019

The analysis of variance proposed by Grizzle (1965) for the unbalanced two‐period crossover design when residual effects are omitted is shown to be appropriate only when the numbers of subjects in both treatment sequences, A : B and B : A, are equal. Following a general linear model approach, a valid analysis of variance is developed for the general unbalanced case.

Explicit general expressions, both in algebraic and matrix form, are presented and a numerical example is given to illustrate the details of the analysis.
One Degree of Freedom for Interaction in a Two‐Way Classification without Replications
Authors: Onukogu Ike B.
Published: August 2019

The paper developsF‐tests with single numerator degree of freedom (d.f.) for interaction in a two‐way crossed classification with one observation per cell. Thus, a convenient and possibly more powerful alternative to the Johnson and Graybill (1972) test is provided.
A New Class of Matrices with Application in Experimental Designs
Authors: Gupta S. C.
Published: August 2019

A very general class of balanced matrices is defined in this paper. These matrices are generalisations of the balanced orthogonal designs of Rao (1970) and generalised balanced matrices of Dey and Midha (1976). Some methods of construction of these balanced matrices are discussed. An application of these matrices in experimental designs is also given.
Redirection of the Glycolytic Flux Enhances Isoprenoid Production in Saccharomyces cerevisiae
Authors: Kwak Suryang , Yun Eun Ju , Lane Stephan , Oh Eun Joong , Kim Kyoung Heon , Jin Yong‐Su
Published: August 2019

Sufficient supply of reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a prerequisite of the overproduction of isoprenoids and related bioproducts in Saccharomyces cerevisiae. Although S. cerevisiae highly depends on the oxidative pentose phosphate (PP) pathway to produce NADPH, its metabolic flux toward the oxidative PP pathway is limited due to the rigid glycolysis flux. To maximize NADPH supply for the isoprenoid production in yeast, upper glycolytic metabolic fluxes are reduced by introducing mutations into phosphofructokinase (PFK) along with overexpression of ZWF1 encoding glucose‐6‐phosphate (G6P) dehydrogenase. The PFK mutations (Pfk1 S724D and Pfk2 S718D) result in less glycerol production and more accumulation of G6P, which is a gateway metabolite toward the oxidative PP pathway. When combined with the PFK mutations, overexpression of ZWF1 caused substantial increases of [NADPH]/[NADP+] ratios whereas the effect of ZWF1 overexpression alone in the wild‐type strain is not noticeable. Also, the introduction of ZWF1 overexpression and the PFK mutations into engineered yeast overexpressing acetyl‐CoA C‐acetyltransferase (ERG10), truncated HMG‐CoA reductase isozyme 1 (tHMG1), and amorphadiene synthase (ADS) leads to a titer of 497 mg L–1 of amorphadiene (3.7‐fold over the parental strain). These results suggest that perturbation of upper glycolytic fluxes, in addition to ZWF1 overexpression, is necessary for efficient NADPH supply through the oxidative PP pathway and enhanced production of isoprenoids by engineered S. cerevisiae.
Determination, residue and risk assessment of trifloxystrobin, trifloxystrobin acid and tebuconazole in Chinese rice consumption
Authors: Luo Xiaoshuang , Qin Xinxian , Liu Zhengyi , Chen Dan , Yu Weiwei , Zhang Kankan , Hu Deyu
Published: August 2019

A simple and rapid analytical method for the detection of trifloxystrobin, trifloxystrobin acid and tebuconazole in soil, brown rice, paddy plants and rice hulls was established and validated by liquid chromatography with tandem mass spectrometry. Acceptable linearity (R2 > 0.99), accuracy (average recoveries of 74.3–108.5%) and precision (intra‐ and inter‐day relative standard deviations of 0.9–8.8%) were obtained using the developed determination approach. In the field trial, the half‐lives of trifloxystrobin and tebuconazole in paddy plants were 5.7–8.3 days in three locations throughout China, and the terminal residue concentrations of trifloxystrobin and tebuconazole were <100 and 500 μg/kg (maximum residue limits set by China), respectively, at harvest, which indicated that, based on the recommended application procedure, trifloxystrobin and tebuconazole are safe for use on rice. The risk assessment results demonstrated that, owing to risk quotient values of both fungicides being <100%, the potential risk of trifloxystrobin and tebuconazole on rice was acceptable for Chinese consumers. These data could provide supporting information for the proper use and safety evaluation of trifloxystrobin and tebuconazole in rice.
G‐Spot Anatomy and its Clinical Significance: A Systematic Review
Authors: Ostrzenski Adam
Published: August 2019

The discovery of the G‐spot and verification of its anatomy and histology paved the way to better understanding. Until 2012, the G‐spot was defined as a physiological sexual response phenomenon with no identifiable anatomical correlate. The weakness of this definition is that a physiological response cannot exist without an anatomical basis, so the question motivating the present study was formulated: Are current scientific‐clinical data sufficient to resolve the controversy about the anatomical existence of a G‐spot? It is important to stipulate that no systematic review of the G‐spot has hitherto been published. Manual and electronic searches revealed postmortem and in vivo studies describing the G‐spot and findings reported within PRISMA‐IPD guidelines. The objective of the present review was to provide evidence‐based information related to the G‐spot. Articles were quality‐assessed using validated instruments. Publications on the G‐spot from 1950 to May 2019 were reviewed. Of the 279 full‐text articles examined, 30 met the eligibility criteria. The findings indicate that there are reliable scientific‐clinical data to support the existence of an anatomical G‐spot structure. Transient anterior‐distal vaginal wall engorgement is caused by blood entrapment within the G‐spot structure. Histological examination effectively ruled out the G‐spot as the organ cannot be responsible for female ejaculation since no glandular tissue was identifiable. Finally, the results of this study could assist in developing new therapeutic, surgical interventions to treat secondary G‐spot dysfunction. Additionally, this review indicates ample opportunities for further scientific‐clinical investigations and has thereby moved the field forward. Clin. Anat. 32:1094–1101, 2019. © 2019 Wiley Periodicals, Inc.
Phytochemical Content, Antidiabetic, Anticholinergic, and Antioxidant Activities of Endemic Lecokia cretica Extracts
Authors: Aras Abdülmelik , Bursal Ercan , Türkan Fikret , Tohma Hatice , Kılıç Ömer , Gülçin İlhami , Köksal Ekrem
Published: August 2019

The aim of this work was to investigate the enzyme inhibition, antioxidant activity, and phenolic compounds of Lecokia cretica (Lam.) DC. Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α‐glycosidase enzymes were strongly inhibited by the L. cretica extracts. IC50 values for the three enzymes were found as 3.21 mg/mL, 2.1 mg/mL, and 2.07 mg/mL, respectively. Antioxidant activities were examined in both aqueous and ethanol (EtOH) extracts using CUPRAC, FRAP, and DPPH method. Also, the phenolic compounds of the endemic plant were identified and quantified by using HPLC/MS/MS. According to the results, the extracts have remarkable antioxidant activities. The most abundant phenolic acids of L. cretica in EtOH extract were determined as quinic acid (12.76 mg/kg of crude extract), chlorogenic acid (3.39 mg/kg), and malic acid (2.38 mg/kg).
Three‐dimensional Polypyrrole Derived N‐doped Carbon Nanotube Aerogel as a High‐performance Metal‐free Catalyst for Oxygen Reduction Reaction
Authors: Zhang Chuang , Ma Ben , Zhou Yingke
Published: August 2019

A novel N‐doped carbon nanotube aerogel has been synthesized by pyrolysis of the three‐dimensional tubular polypyrrole networks and evaluated as a metal‐free electrocatalyst for the oxygen reduction reaction. The carbon aerogel catalysts are pyrolyzed at 500 °C (PPy/C‐500), 700 °C (PPy/C‐700), 900 °C (PPy/C‐900) and 1050 °C (PPy/C‐1050), and display the pyrolyzed temperature‐dependent activity and stability. The catalytic activity is increased with the increase of pyrolysis temperature from 500 °C to 1050 °C, ascribed to the high electronically conductive graphitic phases, the thin wall of the three‐dimensional tubular carbon aerogel framework and the increased effective active sites. The nitrogen content is reduced with the increase of pyrolysis temperature, and which plays an important role in the stability of the pyrolyzed catalyst. After 1500 cycles, the PPy/C‐1050 catalyst shows more positive half‐wave potential than the commercial Pt/C catalyst, and displays a quasi‐four‐electron pathway toward the oxygen reduction reaction in the acid solution. This work provides an effective strategy for preparing the low cost and metal‐free N‐doped carbon aerogel catalyst from the conjugated conducting polymer, to achieve high activity and stability.
k‐nearest reliable neighbor search in crowdsourced LBSs
Authors: Jang Hong‐Jun , Kim Byoungwook , Jung Soon‐Young
Published: August 2019

To improve the quality of spatial information in a location‐based services (LBS), crowdsourced LBS (cLBS) applications that receive additional information such as the visit time of static spatial objects from users have appeared. In this paper, we propose a new type of nearest neighbor (NN) query called the k‐nearest reliable neighbor (kNRN) query, which searches for objects that are likely to exist. Suppose that in cLBSs, the user wants to find a restaurant that is likely to exist and is close to the user. In such a case, a kNRN query is highly recommended. In this paper, we formally define a data model in cLBSs and define reliable objects and a kNRN problem. As a brute‐force approach to this problem in a massive dataset that has large computational and I/O costs, we propose a 3DR‐tree‐based baseline algorithm, 2DR‐tree‐based incremental algorithm, and an a3DR‐tree‐based branch‐and‐bound algorithm for kNRN queries. A performance study is conducted on both synthetic and real datasets. Our experimental results show the efficiency of our proposed methods.
Probiotics for the treatment of type 2 diabetes: A review of randomized controlled trials
Authors: Tiderencel Kelly A. , Hutcheon Deborah A. , Ziegler Jane
Published: August 2019

With the increasing prevalence of type 2 diabetes mellitus (T2DM), there is increased interest in probiotic supplementation for improving glycaemic control. This review evaluates nine randomized controlled trials that tested the effects of probiotics on glycaemic outcomes including fasting plasma glucose, fasting plasma insulin, haemoglobin A1c, and homeostatic model assessment of insulin resistance among adults with T2DM. Based on the evidence reviewed, multistrain probiotics that contain seven million to 100 billion colony forming units ofLactobacillus acidophilus,Streptococcus thermophilus,Lactobacillus bulgaricus, and/orBifidobacterium lactisadministered for 6 to 12 weeks may be efficacious for improving glycaemic control in adults with T2DM. Further research is needed to understand the role of the gut microbiota and the probiotic dose, medium, and duration of exposure that is most effective for disease management.
Early‐onset type 2 diabetes is associated with genetic variants of β‐cell function in the Chinese Han population
Authors: Kong Xiaomu , Xing Xiaoyan , Zhang Xuelian , Hong Jing , Yang Wenying
Published: August 2019

Aims

To investigate the genetic factors contributing to early‐onset type 2 diabetes (EOD) in the Chinese Hans populations.

Materials and methods

For 2734 newly diagnosed type 2 diabetes patients and 4041 normal glycemic controls, 25 single nucleotide polymorphisms from 24 genomic loci linked to diabetes were successfully genotyped. Three genetic risk scores (GRSs) were constructed, including the weighted type 2 diabetes‐related GRS (wT‐GRS), the weighted β‐cell function‐related GRS (wB‐GRS), and the weighted GRS constructed by risk alleles not related to β‐cell function (wNB‐GRS). For patients with diabetes, EOD, middle‐age‐onset type 2 diabetes (MOD), and late‐onset type 2 diabetes (LOD) were defined by onset ages ≤40, 40 to 60, and ≥60 years, respectively.

Results

From single marker analysis, different gene profiles were identified between EOD and LOD patients. EOD patients had greater wT‐GRS and wB‐GRS values than LOD patients. After adjustment for sex, elevated wT‐GRS and wB‐GRS values were significantly associated with an increased risk for EOD by 1.11‐ and 1.21‐fold per allele (P = 1.69 × 10−7; 6.07 × 10−8). The wT‐GRS and wNB‐GRS were nominally related to an increased risk of LOD by 1.03‐fold per allele (P = 1.03 × 10−2, 1.78 × 10−2). In patients with diabetes, higher wT‐GRS and wB‐GRS were associated with younger onset age [wT‐GRS: β (SE) = –0.0033(0.0016), P = 3.74 × 10−2; wB‐GRS: −0.0076(0.0028), 7.45 × 10−3] and decreased insulinogenic index [wT‐GRS: –0.0384(0.0098), 9.39 × 10−5; wB‐GRS: −0.0722(0.0176), 4.21 × 10−5].

Conclusion

Our findings indicate a strong genetic predisposition for EOD, which can be mainly attributed to genetic variants linked to β‐cell function, suggesting the β‐cell dysfunction plays a key role in the pathogenesis of EOD in Chinese Han individuals.
Thirty years after Balbina Dam: Diversity and floristic composition of the downstream floodplain forest, Central Amazon, Brazil
Authors: da Rocha Maíra , de Assis Rafael Leandro , Piedade Maria Teresa Fernandez , Feitosa Yuri Oliveira , Householder John Ethan , Lobo Guilherme de Sousa , Demarchi Layon Oreste , Albuquerque Bianca Weiss , Quaresma Adriano Costa , Ramos José Ferreira , Schöngart Jochen , Wittmann Florian
Published: August 2019

The construction of hydroelectric dams causes changes in the diversity and floristic composition of floodplain forests due to the irregularity of the hydrological regime in rivers downstream from the dams. In the Amazon Basin, plans for the construction of dams are threatening the igapós, forests flooded by blackwater rivers. In these floodplains, the distribution of tree species is synchronized with periodic flood events of the topographic gradient. Previous studies on the Balbina Dam show an altered flood pulse downstream. This work discusses the potential long‐term impacts on the diversity and floristic composition of an igapó downstream of the dam (Uatumã River) and compares it with an area unaffected by the dam (Abacate River). An evaluation of the vegetation strata—adults, saplings, and seedlings—showed that for all strata, diversity was greater in the high igapó (higher topographies) in the Uatumã area. This may be due to the near‐total absence of flooding in the high igapó and to the extent of flooding in the low igapó (low topographies). Thus, in the Uatumã area, seeds of species typical of flooded areas cannot reach the high igapó by water and, thus, tend to be replaced by upland forest species (mainly seedlings). In the low igapó, the typical species have difficulty establishing. Therefore, the Uatumã vegetation forms two different communities, which does not occur in the Abacate area. These effects of the dam led to irreversible changes in the diversity and floristic composition across all strata throughout the entire topography in the downstream region.
Discovery of an unrecorded population of Yamato salamander (Hynobius vandenburghi) by GIS and eDNA analysis
Authors: Sakai Yusuke , Kusakabe Ayane , Tsuchida Kota , Tsuzuku Yuka , Okada Shogo , Kitamura Takuto , Tomita Sei , Mukai Takahiko , Tagami Masataka , Takagi Masaki , Yaoi Yuichi , Minamoto Toshifumi
Published: August 2019

Background

Biodiversity loss is a serious environmental problem, and human activities might be primarily responsible for the marked decline in animal populations globally. Amphibians, in particular, have significantly decreased in number in recent decades. One example is the endangered Yamato salamander (Hynobius vandenburghi), which is distributed in Central Japan and has a very restricted distribution in Gifu Prefecture.

Aims

We aimed to discover new populations of H. vandenburghi using a combination of GIS and environmental DNA (eDNA) analysis.

Materials & Methods

Firstly, we designed two primer sets for amplifying Hynobius species targeting mitochondrial 12S rRNA and cytochrome b genes. Next, we performed aquarium experiments to detect H. vandenburghi DNA in aquarium water. We also conducted sequential eDNA detection surveys in five known habitats in Gifu City, Japan, 17 times from January to August 2016. Following these basic eDNA studies, we used GIS to characterize the vegetation and topography of known habitats of H. vandenburghi. We collected water samples in the potential habitats identified by GIS and analyzed eDNA for the presence of H. vandenburghi using the designed primers. Finally, we conducted physical collection surveys in these potential habitats.

Results

We successfully developed two Hynobius‐specific primer sets and detected H. vandenburghi eDNA in aquarium water. The eDNA of the target species was detected in almost all (94%–100%) samples from four habitats, whereas only 29% of samples were positive for one habitat. We identified five potential habitats by GIS analysis. The DNA of H. vandenburghi was detected in three of five potential habitats. Finally, we discovered a new population in one of the potential sites.

Discussion

Our approach combining GIS and eDNA enabled the detection of novel population of an endangered amphibian species. This study was conducted by high school students under the supervision of teachers with the help of university researchers, suggesting the applicability of eDNA studies as a tool of citizen science.

Conclusion

The combination of GIS and eDNA will allow to detect cryptic populations on which conservation efforts may be focused and to alert people to the need for conservation action.
Use of Beta Cyclodextrin to Remove Cholesterol and Increase Astaxanthin Content in Shrimp Oil
Authors: Raju Navaneethan , Benjakul Soottawat
Published: August 2019

Shrimp oil is extracted from shrimp (Litopenaeus vannamei) cephalothorax and subjected to the removal of cholesterol by β‐cyclodextrin (βCD). Different oil/βCD ratios (1:2, 1:3, and 1:4, w/w) and homogenization times (1, 10, and 20 min) are used. Cholesterol deduction is attained with increasing βCD levels and homogenization time. Astaxanthin content is augmented, while cholesterol concentration is reduced. Nevertheless, oil yield and astaxanthin concentration of treated oil are decreased as βCD levels are increased. To increase the oil yield, the used βCD is further extracted for three times with ethyl acetate at 1:10 (w/v) ratio, in which yield is increased from 44.6% to 64%. Cholesterol removal of 95% is obtained, while astaxanthin content is increased. Lipid oxidation is lowered as indicated by the lower TOTOX value, peroxide value, thiobarbituric acid reactive substances, and p‐anisidine value. However, lipid hydrolysis is slightly increased after treatment. Volatiles, especially aldehydes and alcohols, are decreased after treatment. FTIR spectra confirm the removal of phospholipid, which might be associated with the decreased oil yield after treatment. With the developed process, total fatty acid is increased by 15.6%, in which monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) are augmented. βCD could remove cholesterol, increase astaxanthin and fatty acid content.

Practical Applications: Shrimp oil has been known to be a rich source of astaxanthin and PUFAs with health benefit. However, it also contains cholesterol, which can be a drawback for consumption as the supplement. The removal of cholesterol, while maintaining PUFA and astaxanthin could pave a way for promoting the intake of shrimp oil. Use of βCD for oil treatment with subsequent extraction of remaining oil in the used βCD could be implemented with ease. Another advantage of the developed process is to increase both fatty acid and astaxanthin contents in the resulting oil. As a consequence, shrimp oil with lowered cholesterol can be directly used as food ingredient and also for neutraceutical purpose.
Selfing ability and drift load evolve with range expansion
Authors: Koski Matthew H. , Layman Nathan C. , Prior Carly J. , Busch Jeremiah W. , Galloway Laura F.
Published: August 2019

Colonization at expanding range edges often involves few founders, reducing effective population size. This process can promote the evolution of self-fertilization, but implicating historical processes as drivers of trait evolution is often difficult and requires an explicit model of biogeographic history. In plants, contemporary limits to outcrossing are often invoked as evolutionary drivers of self-fertilization, but historical expansions may shape mating system diversity, with leading-edge populations evolving elevated selfing ability. In a widespread plant, Campanula americana, we identified a glacial refugium in the southern Appalachian Mountains from spatial patterns of genetic drift among 24 populations. Populations farther from this refugium have smaller effective sizes and fewer rare alleles. They also displayed elevated heterosis in among-population crosses, reflecting the accumulation of deleterious mutations during range expansion. Although populations with elevated heterosis had reduced segregating mutation load, the magnitude of inbreeding depression lacked geographic pattern. The ability to self-fertilize was strongly positively correlated with the distance from the refugium and mutation accumulation—a pattern that contrasts sharply with contemporary mate and pollinator limitation. In this and other species, diversity in sexual systems may reflect the legacy of evolution in small, colonizing populations, with little or no relation to the ecology of modern populations.
The role of monitoring, documentary and archival records for coastal shallow lake management
Authors: Roberts Lucy R. , Sayer Carl D. , Hoare Daniel , Tomlinson Mark , Holmes Jonathan A. , Horne David J. , Kelly Andrea
Published: August 2019

The effective management and restoration of aquatic ecosystems rely on the establishment of “reference conditions,” defined as the conditions expected in the absence of anthropogenic impacts, and require a thorough understanding of the natural variability within a system. However, at least in Europe, most systematic surveys post‐date the onset of human‐induced pressures on aquatic ecosystems, and thus fail to capture earlier degradation to water chemistry and flora and fauna, which were already advanced. Paleolimnological methods can be used to assess a range of anthropogenic stressors, but variability within a system is often smoothed to give long‐term patterns. Here, we compile monitoring, documentary, and archival records from a range of sources to extend our understanding of centennial‐scale lake ecosystem change and recovery from increasing salinity. We use a case study of the Thurne Broads shallow lake coastal wetland system (Broads National Park, UK), which has been subjected to multiple pressures of anthropogenic land drainage and North Sea storm surges (primarily in 1938 and 1953 CE) that have influenced salinity. Although there are still periods with significant data gaps and the interactions with eutrophication remain unclear, we demonstrate that historical data sources can be used in combination to observe seasonal patterns and extend knowledge on past salinity change and macrophyte community structure back to the 1800s. A demonstrable change in the ecosystem is observed after the sea flood of 1938 CE, when salinity levels in parts of the Thurne Broads were close, or equivalent, to seawater. With the added anthropogenic pressures of the late 1900s, the system has failed to fully recover. Future management, whilst balancing the needs of multiple users, should focus on the current large seasonal fluctuations in salinity and the vulnerability of the system to future large salinity increases.
Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity
Authors: Kato Daisuke , Wake Hiroaki , Lee Philip R. , Tachibana Yoshihisa , Ono Riho , Sugio Shouta , Tsuji Yukio , Tanaka Yasuyo H. , Tanaka Yasuhiro R. , Masamizu Yoshito , Hira Riichiro , Moorhouse Andrew J. , Tamamaki Nobuaki , Ikenaka Kazuhiro , Matsukawa Noriyuki , Fields R. Douglas , Nabekura Junichi , Matsuzaki Masanori
Published: August 2019

Myelination increases the conduction velocity in long‐range axons and is prerequisite for many brain functions. Impaired myelin regulation or impairment of myelin itself is frequently associated with deficits in learning and cognition in neurological and psychiatric disorders. However, it has not been revealed what perturbation of neural activity induced by myelin impairment causes learning deficits. Here, we measured neural activity in the motor cortex during motor learning in transgenic mice with a subtle impairment of their myelin. This deficit in myelin impaired motor learning, and was accompanied by a decrease in the amplitude of movement‐related activity and an increase in the frequency of spontaneous activity. Thalamocortical axons showed variability in axonal conduction with a large spread in the timing of postsynaptic cortical responses. Repetitive pairing of forelimb movements with optogenetic stimulation of thalamocortical axon terminals restored motor learning. Thus, myelin regulation helps to maintain the synchrony of cortical spike‐time arrivals through long‐range axons, facilitating the propagation of the information required for learning. Our results revealed the pathological neuronal circuit activity with impaired myelin and suggest the possibility that pairing of noninvasive brain stimulation with relevant behaviors may ameliorate cognitive and behavioral abnormalities in diseases with impaired myelination.
Enhancement of indirect functional connections with shortest path length in the adult autistic brain
Authors: Guo Xiaonan , Simas Tiago , Lai Meng‐Chuan , Lombardo Michael V. , Chakrabarti Bhismadev , Ruigrok Amber N. V. , Bullmore Edward T. , Baron‐Cohen Simon , Chen Huafu , Suckling John ,   MRC AIMS Consortium
Published: August 2019

Autism is a neurodevelopmental condition characterized by atypical brain functional organization. Here we investigated the intrinsic indirect (semi‐metric) connectivity of the functional connectome associated with autism. Resting‐state functional magnetic resonance imaging scans were acquired from 65 neurotypical adults (33 males/32 females) and 61 autistic adults (30 males/31 females). From functional connectivity networks, semi‐metric percentages (SMPs) were calculated to assess the proportion of indirect shortest functional pathways at global, hemisphere, network, and node levels. Group comparisons were then conducted to ascertain differences between autism and neurotypical control groups. Finally, the strength and length of edges were examined to explore the patterns of semi‐metric connections associated with autism. Compared with neurotypical controls, autistic adults displayed significantly higher SMP at all spatial scales, similar to prior observations in adolescents. Differences were primarily in weaker, longer‐distance edges in the majority between networks. However, no significant diagnosis‐by‐sex interaction effects were observed on global SMP. These findings suggest increased indirect functional connectivity in the autistic brain is persistent from adolescence to adulthood and is indicative of reduced functional network integration.
Elevated Fatty Liver Index as a Risk Factor for All‐Cause Mortality in Human Immunodeficiency Virus–Hepatitis C Virus–Coinfected Patients (ANRS CO13 HEPAVIH Cohort Study)
Authors: Barré Tangui , Protopopescu Camelia , Bani‐Sadr Firouzé , Piroth Lionel , Rojas Rojas Teresa , Salmon‐Ceron Dominique , Wittkop Linda , Esterle Laure , Sogni Philippe , Lacombe Karine , Chas Julie , Zaegel Olivia , Chaix Marie‐Laure , Miailhes Patrick , Serfaty Lawrence , Marcellin Fabienne , Carrieri Maria Patrizia ,   ANRS CO13 HEPAVIH Study Group
Published: August 2019

Background and Aims

Human immunodeficiency virus (HIV)–hepatitis C virus (HCV)–coinfected patients are at high risk of metabolic complications and liver‐related events, which are both associated with hepatic steatosis and its progressive form, nonalcoholic steatohepatitis, a known risk factor for mortality. The fatty liver index (FLI), a noninvasive steatosis biomarker, has recently drawn attention for its clinical prognostic value, although its capacity to predict mortality risk in HIV–HCV‐coinfected patients has never been investigated. Using a Cox proportional hazards model for mortality from all causes, with data from the French National Agency for Research on Aids and Viral Hepatitis CO13 HEPAVIH cohort (983 patients, 4,432 visits), we tested whether elevated FLI (≥60) was associated with all‐cause mortality.

Approach and Results

After multiple adjustment, individuals with FLI ≥ 60 had almost double the risk of all‐cause mortality (adjusted hazard ratio [95% confidence interval], 1.91 [1.17‐3.12], P = 0.009), independently of the following factors: HCV cure (0.21 [0.07‐0.61], P = 0.004), advanced fibrosis (1.77 [1.00‐3.14], P = 0.05), history of hepatocellular carcinoma and/or liver transplantation (7.74 [3.82‐15.69], P < 10−3), history of indirect clinical signs of cirrhosis (2.80 [1.22‐6.41], P = 0.015), and HIV Centers for Disease Control and Prevention clinical stage C (2.88 [1.74‐4.79], P < 10−3).

Conclusions

An elevated FLI (≥60) is a risk factor for all‐cause mortality in HIV–HCV‐coinfected patients independently of liver fibrosis and HCV cure. In the present era of nearly 100% HCV cure rates thanks to direct‐acting antivirals, these findings encourage the more systematic use of noninvasive steatosis biomarkers to help identify coinfected patients with higher mortality risk.
The lenalidomide/bortezomib/dexamethasone regimen for the treatment of blastic plasmacytoid dendritic cell neoplasm
Authors: Marmouset Vincent , Joris Magalie , Merlusca Lavinia , Beaumont Marie , Charbonnier Amandine , Marolleau Jean‐Pierre , Gruson Bérengère
Published: August 2019

We describe the use and value of a lenalidomide/bortezomib/dexamethasone regimen for the treatment of three patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN, a disease that lacks a consensus treatment). After five cycles of chemotherapy, we observed two complete responses and one clinical remission. Together with the encouraging literature data on the effects of lenalidomide and bortezomib on BPDCN cells, our results might prompt further investigations of this regimen's value in BPDCN.
Challenges facing oncology nurses in Jordan: A qualitative study
Authors: Al zoubi Ahmad M. , Saifan Ahmad Rajeh , Alrimawi Intima , Aljabery Mohannad A.
Published: August 2019

Background

The literature shows that oncology nurses have more stressors than nurses in other units. They face many challenges both within and outside the work environment that affect them negatively. Most of the reviewed studies concerning these challenges were conducted in developed countries.

Aim

The purpose of this study was to explore the challenges experienced by oncology nurses in Jordan during their daily practice.

Method

A qualitative descriptive approach was adopted. Semistructured individual face‐to‐face interviews were conducted with 24 nurses. Participants were selected from oncology departments in one of the biggest governmental hospitals in Jordan.

Results

Two main themes were drawn from the data analysis. The first discussed the personal challenges that oncology nurses encountered. These included emotional attachment to patients and difficulties in separating work and personal life. The second related to organizational challenges in the work environment, which included the nurses' lack of authority to inform patients about their diseases, nursing staff and supply shortages, and a lack of orientation programs. All of these factors affected the psychological status of the nurses.

Conclusions

The results of this study indicated that the working environment for oncology nurses is highly stressful and demanding and these nurses face many challenges in their work. The understanding and consideration of these challenges by stakeholders, managers, and organizational leaders would lead to improvements in the nurses' psychological state, thereby enhancing the quality of care in these units and helping with staff retention.
Searching for prognostic biomarkers for small renal masses in the urinary proteome
Authors: Di Meo Ashley , Batruch Ihor , Brown Marshall D. , Yang Chuance , Finelli Antonio , Jewett Michael A. , Diamandis Eleftherios P. , Yousef George M.
Published: August 2019

Renal cell carcinoma (RCC) is frequently diagnosed incidentally as an early‐stage small renal mass (SRM; pT1a, ≤4 cm). Overtreatment of patients with benign or clinically indolent SRMs is increasingly common and has resulted in a recent shift in treatment recommendations. There are currently no available biomarkers that can accurately predict clinical behavior. Therefore, we set out to identify early biomarkers of RCC progression. We employed a quantitative label‐free liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS) proteomics approach and targeted parallel‐reaction monitoring to identify and validate early, noninvasive urinary biomarkers for RCC‐SRMs. In total, we evaluated 115 urine samples, including 33 renal oncocytoma (≤4 cm) cases, 30 progressive and 26 nonprogressive clear cell RCC (ccRCC)‐SRM cases, in addition to 26 healthy controls. We identified six proteins, which displayed significantly elevated expression in clear cell RCC‐SRMs (ccRCC‐SRMs) relative to healthy controls. Proteins C12ORF49 and EHD4 showed significantly elevated expression in ccRCC‐SRMs compared to renal oncocytoma (≤4 cm). Additionally, proteins EPS8L2, CHMP2A, PDCD6IP, CNDP2 and CEACAM1 displayed significantly elevated expression in progressive relative to nonprogressive ccRCC‐SRMs. A two‐protein signature (EPS8L2 and CCT6A) showed significant discriminatory ability (areas under the curve: 0.81, 95% CI: 0.70–0.93) in distinguishing progressive from nonprogressive ccRCC‐SRMs. Patients (Stage I–IV) with EPS8L2 and CCT6A mRNA alterations showed significantly shorter overall survival (p = 1.407 × 10−6) compared to patients with no alterations. Our in‐depth proteomic analysis identified novel biomarkers for early‐stage RCC‐SRMs. Pretreatment characterization of urinary proteins may provide insight into early RCC progression and could potentially help assign patients to appropriate management strategies.
The NTP Report on Carcinogens: A valuable resource for public health, a challenge for regulatory science
Authors: Suarez‐Torres Jose Daniel , Alzate Juan Pablo , Orjuela‐Ramirez Maria Erley
Published: August 2019

The Report on Carcinogens (RoC), from the National Toxicology Program of the USA, is one of the world‐leading programs for the identification and acknowledgment of substances that represent a hazard of cancer to humans. RoC covers several essential topics concerning environmental, occupational, and pharmaceutical agents that are known to be, or reasonably anticipated to be carcinogenic to humans. To promote the highest exploitation by its potential users, several RoC aspects and features were put together into one article. For doing so, a comprehensive description is provided regarding RoC history, scope, general features, listing criteria, contents, handbook, and website. Secondary and tertiary aims for this work were (a) to point out some improvement opportunities for the RoC, and (b) to discuss pending issues in regulatory science and cancer hazard assessments. In this regard, for agents classified as probably, likely, reasonably anticipated, possibly or suspected to be a human carcinogen, there is a lack of quantitative knowledge concerning the likelihood of those agents actually being carcinogenic to humans. Elucidating these probabilities is necessary, because the duration of current regulations and the arrival of new acts may depend on it. On the other hand, there is a dramatic imbalance in priorities toward carcinogens, compared with non‐carcinogens, in current cancer hazard identification programs. That vision may ignore that the availability on the market of chemicals classified as probably not carcinogenic to humans can also be important for the employment, alimentation, economy, quality of life of consumers, and human health.
Distinguishing structural features between Crohn's disease and gastrointestinal luminal tuberculosis using Mueller matrix derived parameters
Authors: Liu Teng , Lu Min , Chen Binguo , Zhong Qinsong , Li Jingyu , He Honghui , Mao Hua , Ma Hui
Published: August 2019

Recently, the incidence of inflammatory bowel diseases, especially the Crohn's disease (CD) and gastrointestinal luminal tuberculosis (ITB), has grown rapidly worldwide. Currently there is no general gold standard to distinguish between CD and ITB tissues, which both have tuberculosis and surrounding fibrous structures. Mueller matrix imaging technique is suitable for describing the location, density and distribution behavior of such fibrous structures. In this study, we apply the Mueller matrix microscopic imaging to the CD and ITB tissue samples. The 2D Mueller matrix images of the CD and ITB tissue slices are measured using the Mueller matrix microscope developed in our previous study, then the Mueller matrix polar decomposition and Mueller matrix transformation parameters are calculated. To evaluate the distribution features of the fibrous structures surrounding the tuberculosis areas more quantitatively and precisely, we analyze the retardance related Mueller matrix derived parameters, which show clear different distribution behaviors between the CD and ITB tissues, using the Tamura image processing method. It is demonstrated that the Mueller matrix derived parameters can reveal the structural features of tuberculosis areas and be used as quantitative indicators to distinguish between CD and ITB tissues, which may be useful for the clinical diagnosis.
A preliminary study on the differential expression of long noncoding RNAs and messenger RNAs in obese and control mice
Authors: Li Ping , Chen Xiaoyu , Chang Xuelian , Tang Tiantian , Qi Kemin
Published: August 2019

Obesity has become one of the public health problems that threatens children's health, but its specific etiology and pathogenesis are still unclear. Recently, many long noncoding RNAs (lncRNAs) have been shown to be involved in the occurrence of obesity. However, their roles are still poorly understood. Thus, the aim of this study was to discover the profiles of the lncRNAs and messenger RNAs (mRNAs) altered in obesity. Epididymal fat samples were collected from mice fed with control and high‐fat diets (HFD) for 16 weeks to investigate the differentially expressed lncRNAs and mRNAs by lncRNA microarray, after which seven lncRNAs and nine mRNAs were validated using reverse‐transcription polymerase chain reaction (RT‐PCR). Bioinformatics analysis and predictions were used to determine the potential biofunctions of these differentially expressed lncRNAs. Then a coexpression network was constructed to determine the transcriptional regulatory relationship of the differentially expressed lncRNAs and mRNAs between the control and HFD groups. The body weight of the HFD group was much higher than that of the control group, as a result of the increased energy intake. In total, 8421 differentially expressed lncRNAs and 6840 mRNAs were profiled using the lncRNAs microarray. Bioinformatics predictions and the coexpression network all indicated that the occurrence of obesity was attributed to those differentially expressed lncRNAs and mRNAs associated with energy metabolism, cell differentiation, and oxidative phosphorylation. The expression levels of Cyp2e1, Atp5b, Hibch, Cnbp, Frmd6, Ptchd3, ENSMUST00000155948, AK140152, ENSMUST00000135194, and ENSMUST00000180861 were significantly different between the control and HFD groups. All these Results suggested that obesity was partially attributed to those lncRNAs associated with energy metabolism, cell differentiation, and oxidative phosphorylation.