bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly Stereoselective Direct Construction of Diaryl‐Substituted Cyclobutanes†
Authors: Song Xiang‐Yang , Zhao Liu‐Peng , Wang Lijia , Tang Yong
Published: December 2019

Summary of main observation and conclusion

A copper catalyzed stereoselective [2+2] cyclization has been developed, providing a concise protocol to the direct construction of diaryl‐substituted cyclobutanes in up to 99% yield with up to >95/5 dr. Meanwhile, the enantioselective version of this reaction has also been achieved, leading to a series of optically active diaryl‐substituted cyclobutanes with up to 94% ee.
Encapsulation‐Controlled Photoisomerization of a Styryl Derivative: Stereoselective Formation of the Anti Z‐Isomer in the Cucurbit[7]uril Cavity
Authors: Chernikova Ekaterina Y. , Berdnikova Daria V. , Peregudov Alexander S. , Fedorova Olga A. , Fedorov Yuri V.
Published: December 2019

The photochemical isomerization of a styrylpyridinium dye (SP) bearing an unsymmetrically attached benzo‐15‐crown‐5 ether has been studied in aqueous solution in the absence and presence of cucurbit[7]uril (CB[7]). The detailed analysis of the UV/Vis and NMR spectra showes that the isomeric composition of the photostationary mixtures of SP can be modulated by the host‐guest complexation with CB[7]. It was found that steric hindrance caused by encapsulation of SP in the host cavity induces the exclusive formation of the anti conformer of Z‐SP in contrast with the mixture of both anti and syn conformers obtained during photoisomerization of the dye without CB[7]. Remarkably, the displacement of anti Z‐SP from CB[7] does not lead to the transformation of the anti Z‐isomer into the syn Z‐isomer pointing out the conformational memory of the system. The results provide an interesting example of the supramolecular stereorecognition by the achiral CB[7] host.
Conjugated Bifunctional Carbazole‐Based Oxime Esters: Efficient and Versatile Photoinitiators for 3D Printing under One‐ and Two‐Photon Excitation
Authors: Hu Peng , Qiu Wanwan , Naumov Sergej , Scherzer Tom , Hu Zhiyong , Chen Qidai , Knolle Wolfgang , Li Zhiquan
Published: December 2019

The rapid development of 3D printing using visible light as an irradiation source requires efficient visible light photoinitiators to realize a fast and reliable 3D printing process. Based on the photocleavage concept, a series of symmetric bifunctional photoinitiators comprising oxime‐ester moieties as latent initiation functionalities and conjugated carbazole as chromophores was synthesized. The impact of substitution position and the types of radicals on photophysical and photochemical behavior was investigated via experimental tests combined with quantum‐chemical calculations. The conjugated carbazole‐based oxime esters exhibit broad absorption bands from 250 to 400 nm and an interesting photobleaching property was observed during photolysis. Under 405 nm LED irradiation, the photoinitiation efficiency of the novel photoinitiators is comparable to that of the commercial visible light photoinitiator TPO. A vertical resolution of 50 μm was obtained when using oxime esters as photoinitiators in DLP 3D printing to fabricate delicate objects. The A‐π‐D‐π‐A core structures impart sufficient two‐photon cross sections (102–136 GM) to the oxime esters, enabling the construction of complex 3D microstructures of nanometer spatial resolution with two‐photon 3D printing technology. Notably, the threshold energy of the formulation containing 4d is lower than that of the commercial two‐photon resists IP−L. Also, the thermal stability of the PIs (>160 °C) is sufficient for daily storage.
Managing salmon for wildlife: Do fisheries limit salmon consumption by bears in small Alaskan streams?
Authors: Lincoln Alexandra E. , Hilborn Ray , Wirsing Aaron J. , Quinn Thomas P.
Published: December 2019

Ecosystem‐based management requires consideration of overlapping resource use between humans and other consumers. Pacific salmon are an important resource for both fisheries and populations of wildlife around the Pacific rim, including coastal brown bears (Ursus arctos); salmon consumption has been positively linked to bear density, body size, and reproductive rate. As a case study within the broader context of human–wildlife competition for food, we used 16–22 yr of empirical data in four different salmon‐bearing systems in southwestern Alaska to explore the relationship between sockeye salmon (Oncorhynchus nerka) availability and consumption by bears. We found a negative relationship between the annual biomass of salmon available to bears and the fraction of biomass consumed per fish, and a saturating relationship between salmon availability and the total annual biomass of salmon consumed by bears. Under modeled scenarios, bear consumption of salmon was predicted to increase only with dramatic (on the order of 50–100%) increases in prey availability. Even such large increases in salmon abundance were estimated to produce relatively modest increases in per capita salmon consumption by bears (2.4–4.8 kg·bear−1·d−1, 15–59% of the estimated daily maximum per capita intake), in part because bears did not consume salmon entirely, especially when salmon were most available. Thus, while bears catching salmon in small streams may be limited by salmon harvest in some years, current management of the systems we studied is sufficient for bear populations to reach maximum salmon consumption every 2–4 yr. Consequently, allocating more salmon for brown bear conservation would unlikely result in an ecologically significant response for bears in these systems, though other ecosystem components might benefit. Our results highlight the need for documenting empirical relationships between prey abundance and consumption, particularly in systems with partial consumption, when evaluating the ecological response of managing prey resources for wildlife populations.
Artificial light at night, in interaction with spring temperature, modulates timing of reproduction in a passerine bird
Authors: Dominoni Davide M. , Kjellberg Jensen Johan , de Jong Maaike , Visser Marcel E. , Spoelstra Kamiel
Published: December 2019

The ecological impact of artificial light at night (ALAN) on phenological events such as reproductive timing is increasingly recognized. In birds, previous experiments under controlled conditions showed that ALAN strongly advances gonadal growth, but effects on egg‐laying date are less clear. In particular, effects of ALAN on timing of egg laying are found to be year‐dependent, suggesting an interaction with climatic conditions such as spring temperature, which is known have strong effects on the phenology of avian breeding. Thus, we hypothesized that ALAN and temperature interact to regulate timing of reproduction in wild birds. Field studies have suggested that sources of ALAN rich in short wavelengths can lead to stronger advances in egg‐laying date. We therefore tested this hypothesis in the Great Tit (Parus major), using a replicated experimental set‐up where eight previously unlit forest transects were illuminated with either white, green, or red LED light, or left dark as controls. We measured timing of egg laying for 619 breeding events spread over six consecutive years and obtained temperature data for all sites and years. We detected overall significantly earlier egg‐laying dates in the white and green light vs. the dark treatment, and similar trends for red light. However, there was a strong interannual variability in mean egg‐laying dates in all treatments, which was explained by spring temperature. We did not detect any fitness consequence of the changed timing of egg laying due to ALAN, which suggests that advancing reproduction in response to ALAN might be adaptive.
Does the leaf economic spectrum hold within plant functional types? A Bayesian multivariate trait meta‐analysis
Authors: Shiklomanov Alexey N. , Cowdery Elizabeth M. , Bahn Michael , Byun Chaeho , Jansen Steven , Kramer Koen , Minden Vanessa , Niinemets Ülo , Onoda Yusuke , Soudzilovskaia Nadejda A. , Dietze Michael C.
Published: December 2019

The leaf economic spectrum is a widely studied axis of plant trait variability that defines a trade‐off between leaf longevity and productivity. While this has been investigated at the global scale, where it is robust, and at local scales, where deviations from it are common, it has received less attention at the intermediate scale of plant functional types (PFTs). We investigated whether global leaf economic relationships are also present within the scale of plant functional types (PFTs) commonly used by Earth System models, and the extent to which this global‐PFT hierarchy can be used to constrain trait estimates. We developed a hierarchical multivariate Bayesian model that assumes separate means and covariance structures within and across PFTs and fit this model to seven leaf traits from the TRY database related to leaf longevity, morphology, biochemistry, and photosynthetic metabolism. Although patterns of trait covariation were generally consistent with the leaf economic spectrum, we found three approximate tiers to this consistency. Relationships among morphological and biochemical traits (specific leaf area [SLA], N, P) were the most robust within and across PFTs, suggesting that covariation in these traits is driven by universal leaf construction trade‐offs and stoichiometry. Relationships among metabolic traits (dark respiration [Rd], maximum RuBisCo carboxylation rate [Vc,max], maximum electron transport rate [Jmax]) were slightly less consistent, reflecting in part their much sparser sampling (especially for high‐latitude PFTs), but also pointing to more flexible plasticity in plant metabolistm. Finally, relationships involving leaf lifespan were the least consistent, indicating that leaf economic relationships related to leaf lifespan are dominated by across‐PFT differences and that within‐PFT variation in leaf lifespan is more complex and idiosyncratic. Across all traits, this covariance was an important source of information, as evidenced by the improved imputation accuracy and reduced predictive uncertainty in multivariate models compared to univariate models. Ultimately, our study reaffirms the value of studying not just individual traits but the multivariate trait space and the utility of hierarchical modeling for studying the scale dependence of trait relationships.
Rangeland sharing by cattle and bees: moderate grazing does not impair bee communities and resource availability
Authors: Shapira Tal , Henkin Zalmen , Dag Arnon , Mandelik Yael
Published: December 2019

Rangelands are a dominant anthropogenic land use and a main driver of natural habitat loss worldwide. Land sharing, the integration of agricultural production and biodiversity conservation, may provide a platform for managing rangelands to fulfill multiple ecosystem services. However, livestock grazing can greatly affect biodiversity and little is known about its effects on providers of focal ecosystem services, such as pollinators. We investigated the effect of cattle grazing on bee communities and their foraging and nesting resources in Mediterranean rangelands. Specifically, we explored the effect of moderate cattle grazing on flowering plant abundance, species richness and composition, the diversity of nesting substrates, and consequently, the possible effects on wild bee and honey bee foraging activity, species diversity, and community composition. We conducted field research in the Mediterranean rangelands of Israel during the main bee activity season, in the spring of 2012 and 2013, comparing paired cattle‐grazed and ungrazed areas. The availability of floral and nesting resources for bees was unaffected or positively affected by grazing. Similarly, wild bee abundance, species richness, and composition were not affected by grazing, but were instead shaped by spatiotemporal factors. Nor was honey bee activity level impaired by grazing. The foraging preferences of bees, as well as flower species composition and peak bloom differed between grazed and ungrazed areas. Therefore, in our studied rangelands, grazing had its main effect on the foraging choices of honey bees and wild bees, rather than on their abundance and diversity. Moreover, our results indicate the potentially important role of ungrazed patches in increasing nectar and pollen diversity and availability in rangelands for both honey bees and wild bees in the spring. Hence, maintaining a mosaic of moderately grazed and ungrazed patches is expected to provide the greatest benefits for wild bee conservation and honey bee activity in Mediterranean rangelands. Our findings support the notion of rangeland sharing by cattle and bees in Mediterranean ecosystems under moderate grazing intensities, mimicking the coexistence of honey bees, wild bees, and cattle in Mediterranean ecosystems on an evolutionary timescale.
Nickel‐Catalyzed C‐O Cross‐Coupling Reaction at Low Catalytic Loading with Weak Base Participation
Authors: Wu Fan , Zhu Kejie , Wu Guolin , Gao Yu , Chen Haijun
Published: December 2019

Herein, we report a nickel‐catalyzed crossing‐coupling reaction for the synthesis of diaryl ethers. The desired products are achieved by coupling heterocyclic alcohols with aryl bromides bearing strong electron withdrawing nitro group under the catalyst system of NiCl2(PPh3)2 and weak base KHCO3. This mild reaction exhibits a broad functional group tolerance. Compound 4 as an important intermediate is suitable for further structural modification of MALT1 inhibitor MI‐2.
Evaluation of electrical characteristics of biological tissue with electrical impedance spectroscopy
Authors: Yao Jiafeng , Wang Li , Liu Kai , Wu Hongtao , Wang Hao , Huang Jingshi , Li Jianping
Published: December 2019

The electrical characteristics of biological tissue is evaluated by establishing an electrical equivalent circuit with electrical impedance spectroscopy. The least squares method is used to realize electrical equivalent circuit fitting by using the developed portable electrical impedance spectroscopy system. The EIS system is used to obtain the impedance spectrum data of the measured biological tissue. In the experiment, the impedance spectrum data of eggs under different heating time were measured, and the established equivalent circuit model of eggs was fitted by nonlinear least squares fitting algorithm. Moreover, the electrical characteristics of the biological tissue are also revealed by numerical simulation with HANAI model. The experimental and simulation results show that the extracted equivalent electrical parameters can clearly characterize the variation of the internal change of components of biological tissues.
Different adsorbed gas effects on the reservoir parameters and production in coalbed methane extraction by multibranch horizontal wells
Authors: Li Qixian , Xu Jiang , Peng Shoujian , Yan Fazhi , Zhang Chaolin , Han Ende
Published: December 2019

Coalbed methane (CBM) is an efficient energy source that mainly contains CH4 and CO2. Multibranch horizontal wells (MBHWs) are widely used in CBM extraction. In the study, CH4 and CO2 were employed to perform CBM extraction experiments by MBHWs. Based on the experiments, a phenomenon occurs wherein gas from the high‐pressure production layer enters the low‐pressure production layer during the initial stage. Reservoir pressure, temperature, permeability, and instantaneous flow rate exhibit similar evolution laws. Specifically, they initially increase sharply, then declining rapidly, and finally level off in the production layer with the minimum initial pressure. Increase in the adsorption capacity lowers the increase in reservoir pressure, although the phenomenon persists longer from appearance to disappearance. The moment of permeability recovery is related to the adsorption capacity, and the moment of permeability recovery under CO2 conditions occurs after that under CH4 conditions. The instantaneous flow rate curve is divided into three categories, namely steep flow rate increase curve, flow rate inhibition curve, and backflow curve. The results are useful for CBM extraction of multiple coal seams.
Impacts of different vegetation restoration options on gully head soil resistance and soil erosion in loess tablelands
Authors: Guo Mingming , Wang Wenlong , Wang Tianchao , Wang Wenxin , Kang Hongliang
Published: December 2019

Vegetation restoration is identified as an effective approach to control soil erosion and affects soil detachment and resistance to concentrated flow on the Loess Plateau. However, the effects of vegetation restoration at gully heads in loess‐tableland remains unclear. This study was performed to investigate the effects of nine vegetation restoration types at gully heads on soil detachment rate (Dr) and soil resistance to concentrated flow (i.e. soil erodibility, Kr and critical shear stress, τc). Undisturbed soil samples were collected from nine vegetation‐restored lands and one slope cropland (as the control) and were subjected to a hydraulic flume to obtain Dr values of gully heads under six inflow discharges (0.5–3.5 L s‐1). The results showed that the Dr values of nine revegetated gully heads were 77.11% to 95.81% less than that of slope cropland, and the grassland dominated by Cleistogenes caespitosa and the shrubland dominated by Hippophae rhamnoides had a relatively greater decrease in Dr than those of other seven restoration types. The Dr value of nine revegetated gully heads could be better simulated by stream power than by flow velocity and shear stress and was also significantly affected by soil disintegration rate (positively), soil bulk density, saturated hydraulic conductivity, organic matter content, and water‐stable aggregate stability (negatively). Additionally, roots with diameters of 0 to 0.5 mm showed a greater effect on Dr than those with larger diameters. Compared to cropland, the nine restored types reduced Kr by 76.26% to 94.26% and improved τc by 1.51 to 4.68 times. The decrease in Kr and the increase in τc were significantly affected by organic matter content, water‐stable aggregate, mean weight diameter of aggregate and root mass density. The combination of grass species (Cleistogenes caespitosa) and shrub (Hippophae rhamnoides) could be considered the best vegetation restoration types for improving soil resistance of gully heads to concentrated flow. © 2019 John Wiley & Sons, Ltd.
Direct sequence spread spectrum communication narrowband interference cancelation in compressed domain
Authors: Zhang Yongshun , Zhu Weigang , Yin Canbin , Zhan Yayun
Published: December 2019

Due to the broad bandwidth nature of the direct sequence spread spectrum (DSSS) signal, the application of narrowband interference (NBI) cancelation algorithms based on the Nyquist‐Shannon sampling theory are limited by the high sampling rate. To solve the sampling and processing difficulty in the traditional DSSS communication interference cancelation method, we used the compressive sensing (CS) to reduce the sampling rate of the DSSS communication system, and further proposed a compressed domain NBI elimination method in this study. We proved that NBI with a certain bandwidth and DSSS signal are both sparse in specific dictionaries and proposed the corresponding sparse dictionary construction method. Detailed analysis of the compressed domain features of NBI and the DSSS signal demonstrated that it is possible to extract the strong NBI components from the compressed measurements. Two compressed domain NBI cancelation algorithms were proposed based on this idea. The extracted NBI components were filtered out from the compressed measurements directly in the first algorithm, and then we achieved the DSSS signal demodulation in compressed domain using the separated DSSS signal components with the orthogonal matching pursuit (OMP) algorithm. A proposed extraction filter block sparse Bayesian learning (EFBSBL) framework algorithm was utilized to estimate the NBI from the compressed measurements in the second algorithm. The estimated NBI was eliminated from the received signal, and then we recompressed the DSSS signal after NBI cancelation and realized the DSSS signal demodulation in compressed domain with the OMP algorithm. Simulation results support our theoretical analysis results and reveal that the two proposed algorithms are both effective for NBI cancelation and significant interference cancelation performance are achieved.
TGF‐β Signaling Plays a Pivotal Role During Developmental Biliary Atresia in Sea Lamprey (Petromyzon marinus)
Authors: Chung‐Davidson Yu‐Wen , Ren Jianfeng , Yeh Chu‐Yin , Bussy Ugo , Huerta Belinda , Davidson Peter Joseph , Whyard Steven , Li Weiming
Published: December 2019

Biliary atresia (BA) is a rare neonatal disease with unknown causes. Approximately 10% of BA cases develop in utero with other congenital defects that span a large spectrum of disease variations, including degeneration of the gall bladder and bile duct as well as malformation of the liver, intestines, and kidneys. Similar developmental alterations are manifested in a unique animal model, the sea lamprey (Petromyzon marinus), in which BA occurs naturally during metamorphosis. With the likelihood of conserved developmental mechanisms underlying organogenesis and degeneration, lamprey developmental BA may be a useful model to infer mechanisms underlying human embryonic BA. We reasoned that hepatobiliary transcriptomes regulate the transition between landmark stages of BA. Therefore, we examined sea lamprey hepatobiliary transcriptomes at four stages (M0, metamorphic stage 0 or larval stage, no BA; M2, metamorphic stage 2, onset of BA; M5, metamorphic stage 5, BA, and heightened hepatocyte proliferation and reorganization; and JV, juvenile, completion of BA) using messenger RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analyses. We found gene‐expression patterns associated with the transition between these stages. In particular, transforming growth factor β (TGF‐β), hedgehog, phosphatidylinositol‐4,5‐bisphosphate 3‐kinase‐Akt, Wnt, and mitogen‐activated protein kinase pathways were involved during biliary degeneration. Furthermore, disrupting the TGF‐β signaling pathway with antagonist or small interfering RNA treatments at the onset of BA delayed gall bladder and bile duct degeneration. Conclusion: Distinctive gene‐expression patterns are associated with the degeneration of the biliary system during developmental BA. In addition, disrupting TGF‐β signaling pathway at the onset of BA delayed biliary degeneration.
Identification of diagnostic metabolic signatures in clear cell renal cell carcinoma using mass spectrometry imaging
Authors: Vijayalakshmi Kanchustambham , Shankar Vishnu , Bain Ryan M. , Nolley Rosalie , Sonn Geoffrey A. , Kao Chia‐Sui , Zhao Hongjuan , Tibshirani Robert , Zare Richard N. , Brooks James D.
Published: December 2019

Clear cell renal cell carcinoma (ccRCC) is the most common and lethal subtype of kidney cancer. Intraoperative frozen section (IFS) analysis is used to confirm the diagnosis during partial nephrectomy. However, surgical margin evaluation using IFS analysis is time consuming and unreliable, leading to relatively low utilization. In our study, we demonstrated the use of desorption electrospray ionization mass spectrometry imaging (DESI‐MSI) as a molecular diagnostic and prognostic tool for ccRCC. DESI‐MSI was conducted on fresh‐frozen 23 normal tumor paired nephrectomy specimens of ccRCC. An independent validation cohort of 17 normal tumor pairs was analyzed. DESI‐MSI provides two‐dimensional molecular images of tissues with mass spectra representing small metabolites, fatty acids and lipids. These tissues were subjected to histopathologic evaluation. A set of metabolites that distinguish ccRCC from normal kidney were identified by performing least absolute shrinkage and selection operator (Lasso) and log‐ratio Lasso analysis. Lasso analysis with leave‐one‐patient‐out cross‐validation selected 57 peaks from over 27,000 metabolic features across 37,608 pixels obtained using DESI‐MSI of ccRCC and normal tissues. Baseline Lasso of metabolites predicted the class of each tissue to be normal or cancerous tissue with an accuracy of 94 and 76%, respectively. Combining the baseline Lasso with the ratio of glucose to arachidonic acid could potentially reduce scan time and improve accuracy to identify normal (82%) and ccRCC (88%) tissue. DESI‐MSI allows rapid detection of metabolites associated with normal and ccRCC with high accuracy. As this technology advances, it could be used for rapid intraoperative assessment of surgical margin status.
Novel engineered TRAIL‐based chimeric protein strongly inhibits tumor growth and bypasses TRAIL resistance
Authors: Rozga Piotr , Kloska Damian , Pawlak Sebastian , Teska‐Kaminska Malgorzata , Galazka Marlena , Bukato Katarzyna , Pieczykolan Anna , Jaworski Albert , Molga‐Kaczmarska Anna , Kopacz Aleksandra , Badyra Bogna , Kachamakova‐Trojanowska Neli , Zolnierkiewicz Olga , Targosz‐Korecka Marta , Poleszak Katarzyna , Szymanik Michal , Zerek Bartlomiej , Pieczykolan Jerzy , Jozkowicz Alicja , Grochot‐Przeczek Anna
Published: December 2019

Targeting of the TRAIL‐DR4/5 pathway was proposed as a promising approach for specific induction of apoptosis in cancer cells. Clinical trials, however, showed inadequate efficiency of TRAIL as a monotherapy. It is a widely held view that the application of multifunctional molecules or combination therapy may lead to substantial improvement. Here, we demonstrate the effectiveness and safety of a novel chimeric protein, AD‐O51.4, which is a TRAIL equipped with positively charged VEGFA‐derived effector peptides. The study was performed in multiple cancer cell line‐ and patient‐derived xenografts. A pharmacokinetic profile was established in monkeys. AD‐O51.4 strongly inhibits tumor growth, even leading to complete long‐term tumor remission. Neither mice nor monkeys treated with AD‐O51.4 demonstrate symptoms of drug toxicity. AD‐O51.4 exhibits a satisfactory half‐life in plasma and accumulates preferentially in tumors. The cellular mechanism of AD‐O51.4 activity involves both cytotoxic effects in tumor cells and antiangiogenic effects on the endothelium. The presence of DRs in cancer cells is crucial for AD‐O51.4‐driven apoptosis execution. The TRAIL component of the fusion molecule serves as an apoptosis inducer and a cellular anchor for the effector peptides in TRAIL‐sensitive and TRAIL‐resistant cancer cells, respectively. The FADD‐dependent pathway, however, seems to be not indispensable in death signal transduction; thus, AD‐O51.4 is capable of bypassing the refractoriness of TRAIL. AD‐O51.4‐driven cell death, which exceeds TRAIL activity, is achieved due to the N‐terminally fused polypeptide, containing VEGFA‐derived effector peptides. The high anticancer efficiency of AD‐O51.4 combined with its safety has led to the entry of AD‐O51.4 into toxicological studies.
An ecological investigation of resilience among rural‐urban migrant adolescents of low socioeconomic status families in China
Authors: Gao Yunjiao , Xie Shenghua , Frost Caren J.
Published: December 2019

The present study aims to explore the mechanism of resilience among rural‐urban migrant adolescents of low socioeconomic status (SES) families in China with the ecological system perspective. Selecting 946 rural‐urban migrant adolescents from the China Education Panel Survey, we used latent class analyses to distinguish different levels of resilience among migrant adolescents from low‐SES families, and logistic regressions to identify factors associated with resilience and to examine the cumulative risk and protection models. The findings show that parental expectation, teacher support and organised neighbourhood are salient resilience‐promoting factors; and resilience happens only if protective factors accumulate enough at multiple systems to compensate the negative effect of cumulative community risk. The study describes the importance of a protective environment in the domains of family, school and neighbourhood on the resilience of this group, and suggest intervention programmes should extend the paradigm from child‐centred approach to environment‐focused approach to potentiate the positive development of this population.
Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology
Authors: Garnham Jack O. , Roberts Lee D. , Espino‐Gonzalez Ever , Whitehead Anna , Swoboda Peter P. , Koshy Aaron , Gierula John , Paton Maria F. , Cubbon Richard M. , Kearney Mark T. , Egginton Stuart , Bowen T. Scott , Witte Klaus K.
Published: December 2019

Background

Patients with coexistent chronic heart failure (CHF) and diabetes mellitus (DM) demonstrate greater exercise limitation and worse prognosis compared with CHF patients without DM, even when corrected for cardiac dysfunction. Understanding the origins of symptoms in this subgroup may facilitate development of targeted treatments. We therefore characterized the skeletal muscle phenotype and its relationship to exercise limitation in patients with diabetic heart failure (D‐HF).

Methods

In one of the largest muscle sampling studies in a CHF population, pectoralis major biopsies were taken from age‐matched controls (n = 25), DM (n = 10), CHF (n = 52), and D‐HF (n = 28) patients. In situ mitochondrial function and reactive oxygen species, fibre morphology, capillarity, and gene expression analyses were performed and correlated to whole‐body exercise capacity.

Results

Mitochondrial respiration, content, coupling efficiency, and intrinsic function were lower in D‐HF patients compared with other groups (P < 0.05). A unique mitochondrial complex I dysfunction was present in D‐HF patients only (P < 0.05), which strongly correlated to exercise capacity (R2 = 0.64; P < 0.001). Mitochondrial impairments in D‐HF corresponded to higher levels of mitochondrial reactive oxygen species (P < 0.05) and lower gene expression of anti‐oxidative enzyme superoxide dismutase 2 (P < 0.05) and complex I subunit NDUFS1 (P < 0.05). D‐HF was also associated with severe fibre atrophy (P < 0.05) and reduced local fibre capillarity (P < 0.05).

Conclusions

Patients with D‐HF develop a specific skeletal muscle pathology, characterized by mitochondrial impairments, fibre atrophy, and derangements in the capillary network that are linked to exercise intolerance. These novel preliminary data support skeletal muscle as a potential therapeutic target for treating patients with D‐HF.
Clinical impact of normal alanine aminotransferase on direct‐acting antiviral outcome in patients with chronic hepatitis C virus infection
Authors: Joshita Satoru , Sugiura Ayumi , Umemura Takeji , Yamazaki Tomoo , Fujimori Naoyuki , Matsumoto Akihiro , Usami Yoko , Tanaka Eiji
Published: December 2019

Background and Aims

This study aimed to clarify the clinical picture of hepatitis C virus (HCV) carriers with normal alanine aminotransferase (CNALT) and those with ALT elevation (non‐CNALT) under direct‐acting antivirals (DAAs).

Methods

We enrolled 1002 patients with HCV (427 men, median age: 69 years) who had received DAAs for comparisons between CNALT (ALT ≤33 U/L in males and ≤25 U/L in females; n = 374) and non‐CNALT (n = 628) groups.

Results

CNALT patients displayed a higher platelet count (PLT) (170 000 vs 146 000/μL, P < 0.0001) and albumin (4.1 vs 4.1 g/dL, P = 0.0006) but lower AST (25 vs 51 U/L, P < 0.0001), alpha fetoprotein (3.2 vs 5.4 ng/mL, P < 0.0001), and liver fibrosis marker scores (all P < 0.0001). The sustained virologic response rate was comparable between the CNALT and non‐CNALT groups (97.8 vs 95.3%, P = 0.106). The cumulative incidence of hepatocellular carcinoma (HCC) after DAA treatment was comparable between the CNALT and non‐CNALT groups (P = 0.117, log‐rank test). In CNALT patients with HCC history, PLT ≥150 000/μL was an independent risk factor of HCC recurrence (P = 0.019). In non‐CNALT patients without HCC history, male gender (P = 0.021) and albumin <4.0 g/dL (P = 0.007) were independent risk factors, while PLT < 150 000/μL (P = 0.081) was a marginal risk factor of HCC occurrence.

Conclusion

CNALT patients displayed a milder degree of liver fibrosis. Combinations of CNALT and PLT status might be useful as markers for HCC occurrence or recurrence surveillance.
Synthesis of some novel pyrazolopyrimidotriazepine, pyrazolotriazolopyrimidine, and pyrazolopyrimidotetrazine derivatives
Authors: Hassan Aisha Y. , Abdel‐Aziem Anhar , Hussain Aisha O.
Published: December 2019

Reaction of ethyl 5‐amino‐1‐phenyl‐1H‐pyrazole‐4‐carboxylate with thiocarbohydrazide yielded 5‐amino‐6‐hydrazinyl‐1‐phenyl‐1H‐pyrazolo[3,4‐d]pyrimidine‐4‐(5H)one (1), which used as precursor to synthesize pyrazolopyrimidotriazepine 2, pyrazolopyrimidotriazines 5‐7, pyrazolotriazolopyrimidines 8‐14, pyrazolopyrimidotetrazines 17. The structures of the newly synthesized compounds were confirmed by spectral data (IR, NMR, elemental analysis, and mass spectra).
Diastereoselective synthesis of pyrrolo[1, 2‐c]imidazoles using chiral thiohydantoins, malononitrile, and aldehydes and evaluation of their antioxidant and antibacterial activities
Authors: Mollanejad Khadijeh , Asghari Sakineh , Jadidi Khosrow
Published: December 2019

Diastereoselective synthesis of pyrrolo[1,2‐c]imidazoles is reported from three‐component reaction of chiral thiohydantoins, aldehydes, and malononitrile in the presence of NEt3. The antioxidant properties of the obtained products were evaluated by 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging assay. Among the products, compound 4l possessing NH2 and NH groups and bromine atom at 4‐position of the aromatic ring displayed the highest antioxidant activity (90%). Also, their antibacterial activities were explored against gram‐positive and gram‐negative bacteria using disc diffusion method. Among the synthesized compounds, 4a with chlorine atom at para position of the aromatic ring, and methyl group (the smallest alkyl group) at 7‐position, displayed the best antibacterial activity against the tested gram‐positive bacteria.
Recognition of gluconeogenic enzymes; Icl1, Fbp1, and Mdh2 by Gid4 ligase: A molecular docking study
Authors: Elfiky Abdo A. , Ismail Alaa M. , Elshemey Wael M.
Published: December 2019

The pro/N‐degron pathway is an evolved protein degradation pathway through the ubiquitin‐proteasome system. It is a vital pathway to attain protein homeostasis inside the liver cells with varying glucose levels. N‐terminal proline exists in more than 300 proteins in Saccharomyces cerevisiae, but only three of them are the gluconeogenic enzymes; isocitrate lyase (Icl1), fructose‐1,6‐bisphosphatase (Fbp1), and malate dehydrogenase (Mdh2). The present in silico study aims to structurally illustrate the binding of Icl1 enzyme to Gid4 ligase concerning its peers; Fbp1 and Mdh2. Based on the molecular docking scores and interactions, one can attribute the binding stability of Gid4 with degrons, to peptides of length six up to eight from the N‐terminal. Moreover, the percent change in the docking score provides a rationale for the unique Gid4‐Icl11‐4 interaction. The present study provides insights on the binding attitude of Gid4 ligase to degrons of different lengths, so one will consider in designing peptidomimetics to target Gid4 ligase.
Molecular causes of sex‐specific deficits in rodent models of neurodevelopmental disorders
Authors: Mossa Adele , Manzini M. Chiara
Published: December 2019

Neurodevelopmental disorders (NDDs) such as intellectual disability and autism spectrum disorder consistently show a male bias in prevalence, but it remains unclear why males and females are affected with different frequency. While many behavioral studies of transgenic NDD models have focused only on males, the requirement by the National Institutes of Health to consider sex as a biological variable has promoted the comparison of male and female performance in wild‐type and mutant animals. Here, we review examples of rodent models of NDDs in which sex‐specific deficits were identified in molecular, physiological, and/or behavioral responses, showing sex differences in susceptibility to disruption of genes mutated in NDDs. Haploinsufficiency in genes involved in mechanisms such as synaptic function (GABRB3 and NRXN1), chromatin remodeling (CHD8, EMHT1, and ADNP), and intracellular signaling (CC2D1A and ERK1) lead to more severe behavioral outcomes in males. However, in the absence of behavioral deficits, females can still present with cellular and electrophysiological changes that could be due to compensatory mechanisms or differential allocation of molecular and cellular functions in the two sexes. By contrasting these findings with mouse models where females are more severely affected (MTHFR and AMBRA1), we propose a framework to approach the study of sex‐specific deficits possibly leading to sex bias in NDDs.
Effects of AO on the interdecadal oscillating relationship between the ENSO and East Asian winter monsoon
Authors: Chen Dong , Sun Jianqi , Gao Ya
Published: December 2019

Based on the Twentieth Century Reanalysis version 2 datasets (1871–2010), this article first analyzes the relationships of the Arctic Oscillation (AO) and the El Niño‐Southern Oscillation (ENSO) with the East Asian winter monsoon (EAWM) and further investigates the changes in the relationships between the ENSO (AO) and EAWM before and after removing the AO (ENSO) signal. As revealed by previous studies, an interdecadal oscillating relationship is found between the ENSO and EAWM. This oscillation disappears when the AO signal is removed; however, the ENSO–EAWM relationship has exhibited a stable and significant negative correlation over the past 140 years. In contrast, the oscillating relationship (with a period of approximately 60 years) between the AO and EAWM shows little differences when the ENSO signal is removed. Further analysis reveals the main reasons for the strengthening of the ENSO–EAWM relationship by removing the AO signal. The results show that after removing the AO signal, the ENSO‐induced anomalous sinking branch of the Walker circulation over the western Pacific shifts northwestward, and the ENSO‐related anomalous anticyclone in the northern part of the western Pacific strengthens. Such circulation anomalies are conducive to the establishment of the East Asia–North Pacific teleconnection, which is favourable for the ENSO–EAWM relationship. The above results reveal that there is an interdecadal oscillation in the AO–EAWM relationship and the ENSO–EAWM relationship may be relatively stable, the interdecadal oscillation only occurs under the influence of the AO. These results may improve the use of ENSO for predicting the EAWM on seasonal time scale in the future.
Sunshine duration in Poland from ground‐ and satellite‐based data
Authors: Matuszko Dorota , Bartoszek Krzysztof , Soroka Jakub , Węglarczyk Stanisław
Published: December 2019

The aim of the study is to characterise the spatial variability of sunshine duration in Poland. The study used ground‐based and satellite‐based data from 1983 to 2018 multi‐annual period, from the territory of Poland. The ground‐based data include daily sums of sunshine duration from 29 Institute of Meteorology and Water Management—National Research Institute stations and two stations of the Jagiellonian University. Satellite‐based data from the product “SDU ‐ Sunshine Duration, v003” were used with a resolution of 0.05° × 0.05°, coming from the nearest pixel of a given meteorological station. These values were obtained from the SARAH‐2.1 database, published by The European Organization for the Exploitation of Meteorological Satellites (EUMETSAT). It was found that the mean annual sums of sunshine duration calculated on the basis of ground‐based data in Poland range from about 1,460–1,500 hr in the south and south‐west of the country (mountain areas) to 1,800–1,830 hr in the north—the region of the eastern Baltic coast. Satellite‐based data are in line with ground‐based data in relation to the dependence of sunshine duration on latitude, that is, the increase in sunshine duration from the south to the north in the summer and in the spring, and the decrease in the winter. In the autumn, the spatial variability based on satellite data is more latitudinal than in the case of ground‐based data. Moreover, in the autumn and winter, the sums of sunshine duration based on satellite data are overestimated and, in the summer, especially since the turn of the 20th and 21st century, they have been underestimated. The performed analysis has shown that there is some conformity of the results, but the accuracy of matching satellite‐based data and ground‐based data depends on the location of the station and is subject to fluctuations in the annual and multi‐annual cycle.
Multi‐scale features of the co‐variability between global sea surface temperature anomalies and daily extreme rainfall in Argentina
Authors: Robledo Federico , Vera Carolina , Penalba Olga
Published: December 2019

The goal of this study is to provide a better understanding of the trends and dominant oscillations characterizing the co‐variability between global sea surface temperature (SST) anomalies and daily extreme rainfall in Argentina. A singular value decomposition was performed between daily extreme rainfall monthly index in Argentina and global SST without removing the trends. The three leading modes explain 70.5% of the co‐variability, while the two leading modes explain more than 66% of the variability. The two leading modes exhibit significant variability on inter‐annual timescales related to tropical Pacific and Indian oceans, and specifically with El Niño–Southern Oscillation and the Indian Ocean Dipole. On decadal timescales, the leading mode activity is related to the Pacific Decadal Oscillation, whereas the second leading mode is associated with the Atlantic Multi‐decadal Oscillation (AMO). The third leading mode show co‐variability between the SST of the tropical Atlantic and the Indian ocean and extreme rainfall in the eastern‐centre of Argentina; this mode distinguishes phases of AMO. In addition, the two leading modes show positive trends, being largely non‐linear for leading one. The fact that extreme rainfall changes in Argentina observed in the last decades, are significantly influenced by the combination of the multi‐decadal variability and long‐term trends associated with the tropical oceans, is valuable knowledge to assess them in the future.
Predictors of chemotherapy and its effects in early stage squamous cell carcinoma of the larynx
Authors: Jayakrishnan Thejus T. , White Richard J. , Greenberg Larisa , Colonias Athanasios , Wegner Rodney E.
Published: December 2019

Background

Squamous cell carcinoma (SCC) of larynx is a common head and neck cancer. For cases that are node negative, the role of definitive concurrent chemoradiation is unclear and not supported by guidelines but used at provider discretion. To address this knowledge gap, we examined the oncological outcomes with additional chemotherapy and factors correlated with the chemotherapy administration.

Methods

We queried the National Cancer Database for patients with early stage (T2N0M0) laryngeal SCC treated nonsurgically. Multivariable logistic regression identified predictors of chemotherapy. Multivariable Cox regression evaluated predictors of survival. Propensity matching accounted for indication biases.

Results

We identified 7181 patients meeting the eligibility criteria, of which 1568 (22%) patients received chemotherapy in addition to radiation. Predictors of chemotherapy use included younger age, Caucasian race, more remote year of treatment, higher grade, sites other than glottis, treatment at a community cancer center, and use of intensity‐modulated radiation therapy. Median overall survival was not significantly different in the two arms analyzed—65 months (95% confidence interval [CI] 60, 72months) with chemotherapy compared to 70 months without chemotherapy (95% CI 66, 75 months,P<.37). Predictors for survival on propensity‐matched multivariable analysis were increased age, male sex, less education, lower income, higher comorbidity score, receipt of treatment at a community center, and nonglottic sites.

Conclusions

This study shows no clear survival benefit with chemotherapy in early stage disease. Although this implies that chemotherapy should not be routinely delivered, individualized judgment and prospective studies are recommended as the biology behind this interesting finding is undefined.

Level of Evidence

2C (Outcomes Research).
Clinical Outcomes of Portosystemic Shunts on the Outcome of Liver Transplantation
Authors: Rodriguez Eduardo A. , Perez Rachel , Zhang Nan , Lim Elisabeth S. , Miller Christopher , Schwartz Michael A. , McGirr Aidan J. , Srinivasan Ananth , Hewitt Winston , Silva Alvin C. , Rakela Jorge , Vargas Hugo E.
Published: December 2019

Spontaneous portosystemic shunts (SPSSs) have been associated with worse clinical outcomes in the pre–liver transplantation (LT) setting, but little is known about their post‐LT impacts. Our aim was to compare LT candidates with and without SPSSs and assess the impact of SPSSs on patient mortality and graft survival in the post‐LT setting. Patients 18 years or older with abdominal imaging done prior to LT were included. Exclusion criteria were the presence of pre‐LT surgical shunts, LT indications other than cirrhosis, and combined solid organ transplantations. SPSSs were classified as absent, small, or large according to their maximum diameter (8 mm). Multiple variables that could influence the post‐LT course were extracted for analysis. Patient and graft survival were estimated using the Kaplan‐Meier method and were compared between groups using a log‐rank test. The project received institutional review board approval. We extracted data from 326 patients. After comparing patients without SPSS or with small or large SPSSs, no statistical difference was found for overall patient survival: no SPSS (n = 8/63), reference; small SPSS (n = 18/150), hazard ratio (HR), 1.05 (95% confidence interval [CI], 0.45‐2.46); and large SPSS (n = 6/113), HR, 0.60 (95% CI, 0.20‐1.78); P = 0.20. Also, no difference was found for graft survival: no SPSS (n = 11/63), reference; small SPSS (n = 21/150), HR, 0.80 (95% CI, 0.38‐1.70); large SPSS (n = 11/113), HR, 0.59 (95% CI, 0.25‐1.40); P = 0.48. Similarly, no statistical significance was found for these variables when comparing if the graft used was procured from a donation after circulatory death donor versus a donation after brain death donor. In conclusion, the previously described association between SPSSs and worse clinical outcomes in pre‐LT patients seems not to persist once patients undergo LT. This study suggests that no steps to correct SPSS intraoperatively are necessary.
A report of 2 cases of Cornelia de Lange syndrome (CdLS) and an analysis of clinical and genetic characteristics in a Chinese CdLS cohort
Authors: Li Shuo , Miao Hui , Yang Hongbo , Wang Linjie , Gong Fengying , Chen Shi , Zhu Huijuan , Pan Hui
Published: December 2019

Background

Cornelia de Lange syndrome (CdLS) is a rare dominantly inherited developmental disorder with an estimated prevalence of 0.5–10:100,000 and no racial disparity in prevalence. The aim of this study was to present two unrelated Chinese CdLS individuals with mutations in NIPBL and to perform a comprehensive analysis of a Chinese cohort with CdLS.

Subjects and methods

Two unrelated Chinese patients complaining of short stature were referred to the outpatient department of Peking Union Medical College Hospital (PUMCH). Their clinical data at birth and at the most recent assessment were collected. Mutation analysis was carried out by whole exome sequencing. Twenty‐four Chinese cases with CdLS were identified through a systematic review of the literature published between 1987 and 2017.

Results

Two patients presented with typical phenotypes, characteristic complications of CdLS and mutations in the NIPBL gene. The average age at diagnosis of the 26 Chinese cases was higher than that of other cohorts. The frequencies of characteristic manifestations of CdLS were similar with those of other populations.

Conclusions

By investigating 26 Chinese cases of CdLS, we observed that the clinical data and gene variants in the Chinese cohort of CdLS patients were generally in accordance with those of other populations.