bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into short‐ and long‐term crop‐foraging strategies in a chacma baboon (Papio ursinus) from GPS and accelerometer data
Authors: Walton Ben J. , Findlay Leah J. , Hill Russell A.
Published: January 2021

Crop‐foraging by animals is a leading cause of human–wildlife “conflict” globally, affecting farmers and resulting in the death of many animals in retaliation, including primates. Despite significant research into crop‐foraging by primates, relatively little is understood about the behavior and movements of primates in and around crop fields, largely due to the limitations of traditional observational methods. Crop‐foraging by primates in large‐scale agriculture has also received little attention. We used GPS and accelerometer bio‐loggers, along with environmental data, to gain an understanding of the spatial and temporal patterns of activity for a female in a crop‐foraging baboon group in and around commercial farms in South Africa over one year. Crop fields were avoided for most of the year, suggesting that fields are perceived as a high‐risk habitat. When field visits did occur, this was generally when plant primary productivity was low, suggesting that crops were a “fallback food”. All recorded field visits were at or before 15:00. Activity was significantly higher in crop fields than in the landscape in general, evidence that crop‐foraging is an energetically costly strategy and that fields are perceived as a risky habitat. In contrast, activity was significantly lower within 100 m of the field edge than in the rest of the landscape, suggesting that baboons wait near the field edge to assess risks before crop‐foraging. Together, this understanding of the spatiotemporal dynamics of crop‐foraging can help to inform crop protection strategies and reduce conflict between humans and baboons in South Africa.
Between T and Y: Asymmetry in the Interaction of LAu(I) with Bipy and β‐Diiminate‐like Ligands
Authors: Cataffo Andrea , de Haas Titus , Ehm Christian , Budzelaar Peter H. M.
Published: January 2021

The combination of an LAu(I) fragment with a potentially chelating ligand
can result in different coordination modes of
: strictly monodentate, symmetrically bidentate, or intermediate with asymmetric bidentate binding of
. Density Functional calculations indicate that for π‐acceptor ancillary ligands L (C2H4, CO) and bis(nitrogen) donors
(bipyridine, phenanthroline, β‐diiminate) symmetric chelate structures are obtained. With primarily σ‐donating ancillary ligands L (Me−, Cl−, MeCN) the asymmetric coordination mode is the norm. Phosphine ancillary ligands L are on the edge and display the highest sensitivity to ligand variation. Asymmetry increases when (a) going from anionic (β‐diiminate) to neutral (bipyridine, phenanthroline) bidentates
; (b) making
less electron‐rich e. g. through having aryl instead of alkyl groups at N or through introduction of CF3 substituents. Inversion of the asymmetry through “gold hopping” is remarkably facile (barrier mostly <6 kcal/mol, often ∼1 kcal/mol). The high‐temperature fluxionality reported for two (PPh3)Au(β‐diiminate) complexes is tentatively assigned to imine inversion (rather than gold hopping) as the rate‐limiting step.
Capturing seizures in clinical trials of antiseizure medications for KCNQ2‐DEE
Authors: Millichap John J. , Harden Cynthia L. , Dlugos Dennis J. , French Jacqueline A. , Butterfield Noam N. , Grayson Celene , Aycardi Ernesto , Pimstone Simon N.
Published: January 2021

Literature review of patients with KCNQ2 developmental and epileptic encephalopathy (KCNQ2‐DEE) reveals, based on 16 reports including 139 patients, a clinical phenotype that includes age‐ and disease‐specific stereotyped seizures. The typical seizure type of KCNQ2‐DEE, focal tonic, starts within 0‐5 days of life and is readily captured by video‐electroencephalography VEEG for clinical and genetic diagnosis. After initial identification, KCNQ2‐DEE seizures are clinically apparent and can be clearly identified without the use of EEG or VEEG. Therefore, we propose that the 2019 recommendations from the International League against Epilepsy (ILAE), the Pediatric Epilepsy Research Consortium (PERC), for capturing and recording seizures for clinical trials (Epilepsia Open, 4, 2019, 537) are suitable for use in KCNQ2‐DEE‒associated antiseizure medicine (ASM) treatment trials. The ILAE/PERC consensus guidance states that a caregiver‐maintained seizure diary, completed by caregivers who are trained to recognize seizures using within‐patient historical recordings, accurately captures seizures prospectively in a clinical trial. An alternative approach historically endorsed by the Food and Drug Administration (FDA) compares seizure counts captured on VEEG before and after treatment. A major advantage of the ILAE/PERC strategy is that it expands the numbers of eligible patients who meet inclusion criteria of clinical trials while maintaining accurate seizure counts (Epilepsia Open, 4, 2019, 537). Three recent phase 3 pivotal pediatric trials investigating ASMs to treat syndromic seizures in patients as young as 2 years of age (N Engl J Med, 17, 2017, 699; Lancet, 21, 2020, 2243; Lancet, 17, 2018, 1085); and ongoing phase 2 open‐label pediatric clinical trial that includes pediatric epileptic syndromes as young as 1 month of age (Am J Med Genet A, 176, 2018, 773), have already used caregiver‐maintained seizure diaries successfully. For determining the outcome of a KCNQ2‐DEE ASM treatment trial, the use of a seizure diary to count seizures by trained observers is feasible because the seizures of KCNQ2‐DEE are clinically apparent. This strategy is supported by successful precedent in clinical trials in similar age groups and has the endorsement of the international pediatric epilepsy community.
Hypolipidemic, anti‐inflammatory, and anti‐atherosclerotic effects of tea before and after microbial fermentation
Authors: Deng Xiujuan , Hou Yan , Zhou Hongjie , Li Yali , Xue Zhiqiang , Xue Xiaoting , Huang Ganghua , Huang Kunlun , He Xiaoyun , Xu Wentao
Published: January 2021

Background

Microbial fermentation significantly affects the flavor and efficacy of tea. It is generally believed that fermented tea is more effective in lowering lipids, while unfermented tea can more effectively inhibit inflammation. However, there is not sufficient evidence to support this claim. To systematically compare the hypolipidemic, anti‐inflammatory, and anti‐atherosclerotic effects of tea before and after microbial fermentation, hyperlipidemic rats and inflammatory injury cells were treated with Monascus purpureus‐fermented pu‐erh tea water extract (MPT) and sun‐dried green tea water extract (SGT), respectively.

Results

MPT, with higher levels of theabrownins, flavonoids, gallic acid (GA), and lovastatin, was more effective in reducing serum triglyceride (TG), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), and inflammatory cytokines (TNF‐α, IL‐1β, and IL‐6), while SGT, with higher levels of tea polyphenols, amino acids, (‐)‐epigallocatechin gallate (EGCG), and theaflavins, was more effective in increasing serum high‐density lipoprotein cholesterol (HDL‐C) in hyperlipidemic rats. The foam cells on the arterial wall of the rats in the MPT group were visibly less, and the thrombosis time was longer than that in the SGT group. Cell experiments showed that MPT was more effective in protecting endothelial cells from damage than SGT.

Conclusion

Surprisingly, Monascus purpureus‐fermented pu‐erh tea not only had better hypolipidemic and anti‐atherosclerotic effects than its raw material (sun‐dried green tea), but also was superior in anti‐inflammatory effects to the latter, which was possibly attributable to the great changes in functional ingredients during microbial fermentation.
Brackish water algal reefs – facies analysis as a tool to identify palaeoenvironmental variations in Miocene deposits (Mainz‐Weisenau, Germany)
Authors: Nohl Theresa , Knoblach Julia , Teichert Sebastian
Published: January 2021

Brackish‐water carbonates are far less studied than their marine or limnic counterparts. However, their association with few, specialized species enables the documentation of fine‐scale changes in the depositional environment. The Cenozoic Mainz Basin (Germany) was only sporadically connected to the North Sea and the Paratethys, exposing several transitions from marine to fresh water influence. Focusing on one outcrop of the Rüssingen Formation of Mainz‐Weisenau (Aquitanian, Miocene), we present a detailed analysis of the faunal and sedimentological responses to changing salinities and water depth, including algal reef growth and facies development. The deposits include allochthonous limestones surrounding an autochthonous reef complex and several smaller reef patches. The allochthonous facies is dominated by the gastropod Hydrobia inflata, and the reef facies is mainly made up by the green alga Cladophorites sp. The algal thalli are overgrown by cryptocrystalline, organic precipitations, and laminated, chemical precipitations. Locally, quiver‐shaped structures of Trichoptera sp. protective cases occur. The depositional setting was a shallow, low energy, and brackish environment supersaturated by carbonate. We could not confirm a general trend of reducing salinities as reported for the Rüssingen Formation. Our results question previously reported episodic desiccation events, because apparent caliche horizons actually represent thin beds of increased Cladophorites growth. Set‐up, distribution of the reef facies, and reef debris indicate short‐time variations of temperature, salinity and water depth. We conclude that these variations are based on the geographic position at the edge of an algal reef barrier, separating the Mainz Basin from the Rhine Rift Valley.
Geochemistry and geochronology of Pengco subduction‐related ophiolites, Tibet: Implications for Dongkaco microcontinent in the Bangong–Nujiang suture zone
Authors: Shao Hua‐Sheng , Song Yang , Li Jing‐Chao , Liu Zhi‐Bo , Yuan Guo‐Li , Hu Yi‐Ling
Published: January 2021

The identification of a microcontinent in Bangong–Nujiang suture zone (BNSZ) is important to understanding the tectonic evolution of Bangong–Nujiang Tethys Ocean (BNTO). Subduction‐related ophiolite is one of the keys to discriminate a microcontinent in suture zones, which can be generated during the oceanic subduction beneath the microcontinent. Generally, ophiolites in the adjacent area of a microcontinent would show characteristics of a volcanic arc, while ophiolites in adjacent area of an ocean show characteristics of a fore‐arc. North Pengco ophiolites (NPOs) and South Pengco ophiolites (SPOs) were collected in the central section of BNSZ, and dated at 115.0–111.5 Ma by SHRIMP II. According to their trace element characteristics, NPOs were determined to have formed at a setting of subduction‐related volcanic arc and affected by slab‐derived fluids or melts. The diagram based on the Ce versus Ce/Y shows that NPOs originated from the partial melting of spinel peridotites. On the other hand, SPOs were generated from the partial melting of ultra‐depleted mantle at a setting of subduction‐related fore‐arc on the basis of extraordinarily low REEs summation and HFSEs (e.g., Zr, Ti, Nb and Ta), relatively high concentrations of compatible elements (e.g., Cr, Ni), large ratios of CaO/TiO2 (37.67–437.50) and Al2O3/TiO2 (20.78–424.50), which were also affected by slab‐derived fluids. Based on the relative location of NPOs and SPOs, it reasonably proposed that a northward subduction of a minor oceanic basin had occurred at the Early Cretaceous, trigged by the Dongkaco microcontinent (DMC). In reverse, these ophiolites provide evidence for the existence of DMC in BNTO. Combining with other subduction‐related ophiolites developed in BNSZ, BNTO might have comprised of several minor oceanic basins separated by some blocks like DMC in the central and west sections, rather than a unified ocean basin.
Spatial accessibility to healthcare facilities in coastal region of Bangladesh
Authors: Zafri Niaz Mahmud , Nurullah Md , Neema Meher Nigar , Waliullah Md
Published: January 2021

Though equal and easy accessibility to healthcare facilities are a fundamental right, people of the coastal region often get poor accessibility to healthcare facilities. This research aimed to assess the spatial accessibility to healthcare facilities in the coastal region of Bangladesh. Patuakhali district was selected as the study area. Accessibility to three levels of healthcare facilities: Community Clinic (CC), Upazila Health Complex (UHC) and District Hospital (DH) was measured individually using Geographic Information System (GIS) adopting the simple distance measures. Finally, overall accessibility to healthcare facilities was measured by overlaying accessibility to all three levels of healthcare facilities according to their relative importance. The findings of this study showed that a significant portion (70%) of Patuakhali district had high accessibility to CC; whereas, almost 60% and 40% of the area had poor accessibility to UHC and DH, respectively. Furthermore, 40% and 28% of the area of Patuakhali district had low and high accessibility to overall healthcare facilities, respectively. Furthermore, accessibility to healthcare facilities was found very poor in rural areas, char areas, and seashore. Thereafter, it is recommended to provide an UHC in every upazila and a DH in the southern part of Galachipa upazila to ensure high spatial accessibility of healthcare facilities.
Uncovered equity returns parity in non‐euro Central European EU member countries
Authors: Orlowski Lucjan , Soper Carolyne , Sywak Monika
Published: January 2021

This paper examines a nexus between euro values of local currencies and returns to equities in non‐euro Central European countries (CECs) relative to returns in a global equity market. In essence, it analyses whether the uncovered equity returns parity (UERP) condition holds in these countries. In theory, the UERP condition holds if higher returns in a local equity market relative to the global market returns are offset by the local currency depreciation. The underlying UERP model examines the relationship between local currencies in euro and CEC equity returns relative to a global market index proxied by Wilshire5000 index. We assume that the UERP relationship is country‐sensitive, time‐dependent and state‐dependent, that is, it varies among countries and depends on economic and financial market conditions. The model is tested with the Bai–Perron multiple breakpoint regressions for structural breaks, as well as the two‐state Markov switching test for state dependence, during the January 4, 1999–February 25, 2020 sample period. We find that UERP condition holds in CECs mainly at times of financial distress, including the peak and the aftermath of the 2008–2010 global financial crisis.
Whether rising tide has lifted all the boats? Effect of inter‐governmental transfers on household income inequality in Pakistan
Authors: Ain Qurat ul , Jie Yan , Ivașcu Larisa , Shah Syed Ghulam Meran , Yousaf Tahir
Published: January 2021

Though income distribution is mainly the responsibility of the central government but the intergovernmental system can either improve or deteriorate the equity in the redistribution of resources. Income redistribution depends upon how the process of devolution is premeditated and implemented. This study reveals the empirical evidences on the effect of different types of intergovernmental transfers/grants, under NFC awards, on household income inequality using a sample of panel data of provincial units in Pakistan from 1990 to 2015. Empirical underpinnings contemplate that straight transfers and non‐development grants have taken on the greater change in reducing income inequality and thus have made the utmost attempt to guarantee the equal distribution of revenues among the federating units. On contrary, the divisible pool transfers, augment the income inequality. Remarkably, even if devolution could be attractive due to efficiency reasons, it may have uninvited consequences on the income distribution. Further development grants indicate no relation to household income inequality. These results also have obvious policy implications as the normative scheme governs intergovernmental regional transfers in case of divisible pool transfers in Pakistan which must be revised, and focus should be given on implementation, if the objective is to confer the country' greater territorial cohesion.
Pinocembrin attenuates benzo(a)pyrene‐induced CYP1A1 expression through multiple pathways: An in vitro and in vivo study
Authors: Alzahrani Abdullah M. , Rajendran Peramaiyan
Published: January 2021

Benzo(a)pyrene [B(a)P], which is a carcinogen, is a substance most typically known in cigarette smoke and considered as an important intermediary of lung cancer. The enzyme CYP1A1 is crucial for the metabolic conversion of B(a)P into the intermediates that induce carcinogenesis. Stimulation of the aryl hydrocarbon receptor, which is regulated by B(a)P, is thought to induce numerous signaling cascades. Interruption in the mitogen‐activated protein kinase (MAPK) pathway causes changes in cellular processes and may alter the AhR pathway. The aim of this investigation is to examine the potential ability of a flavonoid pinocembrin (PCB) to alleviate B(a)P toxicity and analyze the underlying molecular mechanisms. We found that PCB inhibited DNA adduct formation by attenuating CYP1A1 expression through the suppression of the AhR/Src/ERK pathways. PCB mitigated the B(a)P‐stimulated DNA damage, inhibited Src and ERK1/2 expression, decreased CYP1A1 expression, and reduced the B(a)P‐induced stimulation of NF‐κB and MAPK signaling in lung epithelial cells. Finally, the activity of CYP1A1 and Src in lung tissues from mice supplemented with PCB was noticeably decreased and lower than that in lung tissues from mice supplemented with B(a)P alone. Collectively, these data suggest that PCB may alleviate the toxic effects of PAHs, which are important environmental pollutants.
IL‐6/STAT3‐mediated autophagy participates in the development of age‐related glomerulosclerosis
Authors: Zhu Xinwang , Zhang Congxiao , Shi Mai , Li Huimin , Jiang Xue , Wang Lining
Published: January 2021

The standard of age‐related glomerulosclerosis is unclear. Both signal transducer and activator of transcription 3 (STAT3) and autophagy are involved in age‐related kidney disease. Therefore, we aimed to explore the standard, as well as the potential mechanism(s). A total of 44 patients who underwent radical nephrectomy were enrolled. Pearson analysis was performed to investigate the parameters with ages. The patients were divided into the young‐ and aged‐kidney groups. Kidney morphological changes were evaluated by histology staining, senescence was evaluated by senescence‐associated‐β‐galactosidase (SA‐β‐gal) staining, and autophagosome was measured by transmission electron microscopy. Moreover, Western blot and/or immunohistochemistry were accomplished to assess the expression of p16, STAT3, and glycoprotein130 (GP130) and autophagy‐related proteins. Furthermore, human glomerular mesangial cells were administrated with tocilizumab (TCZ) and/or IL‐6, and then the above indexes were tested again. Sclerotic glomerular density and glomerular sclerosis rate were significantly higher in individuals more than 40 years old, and they were strongly correlated with ages. Moreover, the expression of p16, STAT3, GP130, and p62 was significantly increased, while LC3II and autophagosome were statistically decreased in the aged‐kidney. Glomeruli were hardly to stain with SA‐β‐gal. For the in vitro experiments, we observed that IL‐6 significantly increased p16, STAT3, GP130, and p62, induced higher SA‐β‐gal staining, while downregulated LC3II and autophagosome. Furthermore, TCZ statistically reversed the effects of IL‐6 on the above expression of proteins. Glomerular sclerosis rate might be one standard for natural renal aging, and IL‐6/STAT3‐mediated autophagy may participate in the development of age‐related glomerulosclerosis.
Epigallocatechin gallate and coenzyme Q10 attenuate cisplatin‐induced hepatotoxicity in rats via targeting mitochondrial stress and apoptosis
Authors: Fatima Sabiha , Suhail Nida , Alrashed May , Wasi Samina , Aljaser Feda S. , AlSubki Roua A. , Alsharidah Ashwag S. , Banu Naheed
Published: January 2021

Despite the extensive use of cisplatin (CP) as a chemotherapeutic agent, its clinical use is often restricted by undesirable side effects, such as toxicity to normal tissues. The aim of this study was to probe the effect of a combinatorial treatment of low multiple doses of antioxidants on CP‐induced toxicity and the mitochondrial apoptotic pathway in hepatocytes. Animals received a single toxic dose of CP (7.5 mg/kg body weight) with or without combined multiple doses of epigallocatechin gallate (EGCG) and coenzyme Q10 (CoQ10) (15 and 5 mg/kg body weight, respectively). CP‐treated animals showed altered biochemical parameters, denoting hepatotoxicity, which was markedly improved by the multidose treatment with EGCG + CoQ10. The increased levels of oxidants found in the cytosolic and mitochondrial fractions isolated from the liver of CP‐administered rats were significantly attenuated by the combinatorial doses of antioxidants. EGCG + CoQ10 ameliorated the CP‐induced compromised antioxidant defenses, oxidative modification of macromolecules, decreased activities of respiratory chain enzymes, altered membrane depolarization, and swelling of liver mitochondria. Furthermore, EGCG + CoQ10 treatment inhibited CP‐induced apoptosis by suppressing the activation and mitochondrial accumulation of proapoptotic proteins and preventing the inhibition of antiapoptotic protein expression, cytochrome c efflux, caspase‐3 activation, and DNA fragmentation. Histological findings further confirmed the protective effects of EGCG + CoQ10 against CP‐induced cellular injury. Our findings revealed that the combination of EGCG and CoQ10, owing to their individual antioxidant properties, can be an effective remedy, which by maintaining redox hemostasis attenuate the mitochondrial stress‐mediated molecular and cellular processes involved in CP‐induced liver toxicity and cell death.
Coaction of hepatic thioredoxin and glutathione systems in iron overload‐induced oxidative stress
Authors: Sönmez Aydın Feyza , Hukkamlı Berna , Budak Harun
Published: January 2021

In the present study, we demonstrate the coaction of thioredoxin and glutathione (GSH) systems in mouse liver against iron overload‐induced oxidative stress (OS). Mice were injected intraperitoneally with an iron dextran solution twice a week for 3 weeks. Iron accumulation in mouse liver was demonstrated spectroscopically. To confirm the iron overload model in the liver, the increased gene expression levels of hepcidin (Hamp), ferroportin (Fpn1), and ferritin (Fth1), which regulate iron trafficking, were observed by a quantitative polymerase chain reaction. In the case of iron overload, the GSH level and the reduced glutathione/oxidized glutathione ratio, which represents a marker of OS, decreased significantly. An increase in the malondialdehyde level, one of the final products of the lipid peroxidation process, was observed. The gene expression of the thioredoxin system, including thioredoxin (Trx1) and thioredoxin reductase (TrxR1), was examined. Though TrxR1 expression decreased, no changes were observed in Trx1. The enzyme activity and semiquantitative protein expression of TRXR1 increased. The activity of GSH reductase and GSH peroxidase increased in the iron overload group. The gene and protein expressions of thioredoxininteracting protein, which is an indicator of the commitment of the cell to apoptosis, were elevated significantly. The increased protein expression of Bcl‐2‐related X protein and CASPASE‐3, which is an indicator of apoptosis, increased significantly. In conclusion, excess iron accumulation in mouse liver tissue causes OS, which affects the redox state of the thioredoxin and GSH systems, inducing cell apoptosis and also ferroptosis due to increased lipid peroxidation and the depletion of GSH level.
The transcriptional cofactor Jab1/Cops5 is crucial for BMP‐mediated mouse chondrocyte differentiation by repressing p53 activity
Authors: Mamidi Murali K. , Samsa William E. , Bashur Lindsay A. , Chen Yuqing , Chan Ricky , Lee Brendan , Zhou Guang
Published: January 2021

We previously reported that the evolutionary conserved transcriptional cofactor Jab1/Cops5 is critical for mouse chondrocyte differentiation by selectively repressing BMP signaling. In this study, we first uncovered that the endogenous Jab1 interacts with endogenous Smad1/5/8. Furthermore, although Jab1 did not directly interact with Acvr1 (Alk2), a key Type I BMP receptor, the interaction between endogenous Smad1/5/8 and Acvr1 was increased in Jab1‐null chondrocytes. Thus, Jab1 might negatively regulate BMP signaling during chondrocyte differentiation in part by sequestering Smad1/5/8 away from Acvr1. Next, to identity Jab1 downstream targets in chondrocytes, we performed RNA‐sequencing analysis of Jab1‐null chondrocytes and discovered a total of 1993 differentially expressed genes. Gene set enrichment analysis revealed that key targets inhibited by Jab1 includes p53, BMP/transforming growth factor beta, and apoptosis pathways. We confirmed that endogenous Jab1 interacts with endogenous p53. There was significantly elevated p53 reporter activity, an enhanced expression of phospho‐p53, and an increased expression of a key p53 downstream target, Puma, in Jab1‐null chondrocytes. Moreover, treatments with a p53‐specific inhibitor and/or a BMP Type I receptor‐specific inhibitor reversed the elevated p53 and BMP signaling activities in Jab1‐null chondrocytes and partially restored columnar growth plate structure in E17.5 Jab1‐null mouse tibia explant cultures. Finally, we demonstrated that the chondrocyte‐specific Jab1 overexpression in mice resulted in smaller‐sized embryos with disorganized growth plates. In conclusion, our data showed that the delicate Jab1‐mediated crosstalk between BMP and p53 pathways is crucial to maintain proper chondrocyte survival and differentiation. Moreover, the appropriate Jab1 expression level is essential for proper skeletal development.
Effects and mechanism of lncRNA‐27785.1 that regulates TGF‐β1 of Sika deer on antler cell proliferation
Authors: Chen Dan‐Yang , Li Yan‐jun , Jiang Ren‐feng , Li Yu‐ting , Feng Jiang , Hu Wei
Published: January 2021

Transforming growth factor (TGF‐β) plays an important role in the development of deer antlers. The purpose of this study was to investigate the role of long noncoding RNA in the transcriptional regulation of TGF‐β1 and its relationship with the proliferation and differentiation of antler chondrocytes. High‐throughput sequencing was used to screen lncRNAs related to TGF‐β1. Next, the overexpression plasmid and interference sequence of target lncRNA27785.1 were constructed and transfected into chondrocytes. We found that lncRNA27785.1 inhibited the proliferation and migration of chondrocytes and delayed the transition of cells from G1 to S phase. qRT‐PCR and Western blot analysis indicated that the overexpression of lncRNA27785.1 may downregulate mRNA and protein expression of TGF‐BR2, Smad3, pSmad3, and Smad4. Our findings highlight lncRNA27785.1 as an inhibitor of chondrocytes proliferation and differentiation by negatively regulating the TGF‐β/Smad signaling pathway; this implicates an important regulatory role for long noncoding RNA in the regeneration of antler.
Assessing uncertainty for decision‐making in climate adaptation and risk mitigation
Authors: Reggiani Paolo , Todini Ezio , Boyko Oleksiy , Buizza Roberto
Published: January 2021

Future water availability or crop yield studies, tied to statistics of river flow, precipitation, temperature or evaporation over medium to long‐term horizons, are becoming frequent in climate impact and risk analysis. During the last two decades, access to multi‐system integration of climate models has given rise to the concept of using model ensembles to issue probabilistic climatological projections. These probabilistic projections have not yet been exploited to the full extent in decision support, and are still used to mainly quantify uncertainty bands only for selected climate variables and indicators. One of the reasons of this limited use is the fact that the multi‐system ensemble dispersion is sub‐optimal and does not provide an accurate and reliable representation of the predictive probability density, which is essential for rational decision support under uncertain conditions. The aims of this paper are twofold. First, it seeks to highlight the potential benefits of using climate projections in conjunction with Bayesian paradigms towards educated decision‐making. Second, it discusses how to appropriately formulate probabilistic forecasts by coherently integrating information contained in climate projection ensembles with observations to improve the estimation of the probability density function of future climate states. The results show that the proposed Bayesian approach yields unbiased and sharper predictive distributions for temperature with respect to using the unprocessed ensemble distribution. It also yields improved predictive densities with respect to the Reliability Ensemble Averaging (REA) method.
Adenosine triphosphate (ATP) as a metric of microbial biomass in aquatic systems: new simplified protocols, laboratory validation, and a reflection on data from the literature
Authors: Bochdansky Alexander B. , Stouffer Alison N. , Washington NyJaee N.
Published: January 2021

The use of adenosine triphosphate (ATP) as a universal biomass indicator is built on the premise that ATP concentration tracks biomass rather than the physiological condition of cells. However, reportedly high variability in ATP in response to environmental conditions is the main reason the method has not found widespread application. To test possible sources of this variability, we used the diatom Thalassiosira weissflogii as a model and manipulated its growth rate through nutrient limitation and through exposure to three different temperatures (15°C, 20°C, and 25°C). We simplified the ATP protocol with hot‐water or chemical extraction methods, modified a commercially available luciferin‐luciferase assay, and employed single‐photon counting in a scintillation counter, all of which increased sensitivity and throughput. Per‐cell ATP levels remained relatively constant despite changes in growth rates by approximately 10‐fold in the batch culture (i.e., nutrient limitation) experiments, and approximately 2‐fold in response to temperature. The re‐examination of related literature values revealed that average cellular ATP levels differed little among taxonomic groups of aquatic microbes, even at the domain level, and correlated well with bulk properties such as elemental carbon or nitrogen. Fulfilling multiple cellular functions in addition to being the universal energy currency requires ATP to be maintained in a millimolar concentration range. Consequently, ATP relates directly to live cytoplasm volume, while elemental carbon and nitrogen are constrained by an indeterminate pool of detrital material and intracellular storage compounds. The ATP‐biomass indicator is sensitive, economical, and can be readily standardized among laboratories and across environments.
Development and Characterization of PLGA‐Based Multistage Delivery System for Enhanced Payload Delivery to Targeted Vascular Endothelium
Authors: Palma‐Chavez Jorge A. , Fuentes Kevin , Applegate Brian E. , Jo Javier A. , Charoenphol Phapanin
Published: January 2021

Vascular‐targeted drug delivery remains an attractive platform for therapeutic and diagnostic interventions in human diseases. This work focuses on the development of a poly‐lactic‐co‐glycolic‐acid (PLGA)‐based multistage delivery system (MDS). MDS consists of two stages: a micron‐sized PLGA outer shell and encapsulated drug‐loaded PLGA nanoparticles. Nanoparticles with average diameters of 76, 119, and 193 nm are successfully encapsulated into 3–6 µm MDS. Sustained in vitro release of nanoparticles from MDS is observed for up to 7 days. Both MDS and nanoparticles arebiocompatible with human endothelial cells. Sialyl‐Lewis‐A (sLeA) is successfully immobilized on the MDS and nanoparticle surfaces to enable specific targeting of inflamed endothelium. Functionalized MDS demonstrates a 2.7‐fold improvement in endothelial binding compared to PLGA nanoparticles from human blood laminar flow. Overall, the presented results demonstrate successful development and characterization of MDS and suggest that MDS can serve as an effective drug carrier, which can enhance the margination of nanoparticles to the targeted vascular wall.
Rating or sorting: Terminology matters
Authors: Colorni Alberto , Tsoukiàs Alexis
Published: January 2021

In this article, we argue that the term “sorting” (in MCDA), although established within a well‐defined community, is unappropriate for linguistic, scientific and pragmatic reasons. We present and discuss such reasons and we suggest the use of the term “rating”, since fitting better both the foundational part of this class of methods and the necessity to improve the visibility of our community.
The relationship between obsessive–compulsive spectrum disorders and DSM‐5 dysfunctional personality domains in a nonclinical sample of Italian women
Authors: Somma Antonella , LeBeau Richard T. , Krueger Robert F. , Markon Kristian E. , Gialdi Giulia , Frau Claudia , Boscaro Linda , Liberatore Giada , Fossati Andrea
Published: January 2021

To evaluate the usefulness of the DSM‐5 maladaptive personality domains in explaining the similarities and differences among four disorders included in the obsessive–compulsive spectrum, 428 Italian community‐dwelling women (mean age = 31.96 years, SD = 12.30 years) were administered the Obsessive–Compulsive Spectrum Disorder Scales and the Personality Inventory for DSM‐5‐Short Form as part of an ongoing online survey on women's health. Multiple Indicators Multiple Causes (MIMIC) confirmatory bifactor analysis results showed that the OCSD general factor (i.e., obsessive–compulsive spectrum factor) was positively associated with Negative Affectivity, whereas Body Dysmorphic Disorder (BDD), Hoarding Disorder (HD), and Skin‐Picking Disorder (SPD) specific factors showed significant and substantial differential relationships with dysfunctional personality domains. Specifically, BDD was positively associated with Negative Affectivity, Detachment and Psychoticism domains; HD was associated with high Negative Affectivity and Psychoticism; and SPD was associated with Detachment. © 2020 John Wiley & Sons, Ltd.
A novel ISM‐SAM strategy, based on gas chromatography/mass spectrometry analysis, to compensate for matrix effects in the determination of pyruvic acid
Authors: Zhao Jinhui , Zhang Mingjia , Guo Jing , Meng Fanyu , Liu Xiaowei , Yu Jiaying , Liu Liyan
Published: January 2021

Rationale

The matrix effect is tricky in gas chromatography/mass spectrometry (GC/MS) analyses. Although several methods have been proposed to solve this problem, the results were unsatisfactory. Even fewer studies have assessed the performance of corrective methods. Hence, our study focused on assessing several common corrective methods, and then proposed a new strategy to correct for the matrix effect in GC/MS analyses.

Methods

In GC/MS analyses, the internal standard method (ISM) was employed to overcome the matrix effect during the detection of pyruvic acid (PA) in serum samples from a healthy adult female. The accuracy of the ISM was evaluated by comparing it with the standard addition method (SAM). To employ the ISM‐SAM strategy, correction factors (CFs) were established by combining the ISM and the SAM based on different groups. The CFs were used to normalize data onto the results of subsequent analyses.

Results

When using the ISM to detect levels of PA, a serious bias is observed, thereby affecting the conclusions reached. In contrast, more reliable data can be obtained after normalizing results by undertaking the ISM‐SAM strategy. The feasibility of this strategy was verified by comparing it with the results of the SAM alone. The ISM‐SAM strategy was successfully applied to quantify the PA levels in healthy people and nephrotic syndrome patients.

Conclusions

Our results indicated that a false outcome was presented when only the ISM was used to adjust the data, and important information would be missed if the correction strategy was not carried out. Therefore, ISM‐SAM, as an available correction method, should be adapted to improve the reliability of research results.
The antimammary tumor effects of ethanolic extract of propolis from Adamawa region (Cameroon) are by apoptosis via reactive oxygen species‐mediated mitochondrial pathway
Authors: Zingue Stéphane , Cisilotto Julia , Fogang Robinson Charly Mbe , Tchoupang Edwige Nana , Ndinteh Derek Tantoh , Tchuenguem Fohouo Nestor‐Fernand , Njamen Dieudonné , Creczynski‐Pasa Tânia Beatriz
Published: January 2021

Identification of novel natural treatment to combat cancer is a current need. This study was aimed at assessing the anticancer effects of ethanol‐extracted Cameroonian propolis (EEP). The antitumor effect of EPP was evaluated in vitro by measuring; cell viability, cell cycle, cell death mechanism, cell migration/invasion, reactive oxygen species (ROS), mitochondrial potential (ΔΨm), caspase activity, and apoptosis‐regulating proteins (Bcl‐2 and Bcl‐XL) in cell lines. In vivo, the effect of EEP against 7,12 dimethylbenz(a)anthracene (DMBA)‐induced breast tumorigenesis in rats was assessed. EEP was found to induce cytotoxicity against ER negative MDA‐MB‐231 breast cancer cells by activating apoptosis through ROS‐mediated mitochondrial pathway. The extract equally triggered caspase‐3 and caspase‐9, increment of ROS level, disruption of ΔΨm and down‐regulation of Bcl‐XL and Bcl‐2 proteins. Besides, EPP prevented migration and invasion activities by inhibiting MMP‐2 activity. At all doses it prevented breast tumor incidence (20% in EEP 150 mg/kg vs 70% in DMBA) as well as tumor burden. Tumor sections from EEP‐treated rats showed middle proliferation of mammary ducts with weak inflammatory responses. In summary, Cameroonian propolis exhibited antimammary tumor effects via the intrinsic pathway of apoptosis.
(Info)Graphically Inclined: A framework of infographic learning
Authors: Smith Jennifer M. , Robertson Marla K.
Published: January 2021

Infographics are appearing in children’s magazines, picture books, and informational texts. Understanding, and ultimately creating, these complex visual representations of information or data requires higher level thinking skills to analyze and understand how the text and graphics work together to convey meaning. The authors provide a framework for infographic exploration, investigation, creation, and integration into larger writing pieces. Each phase of the framework includes specific considerations to assist teachers in scaffolding their students’ infographic learning. Providing students with support through exposure to many types of infographics and modeling infographic interpretation prepares students to critically examine and use infographics as they encounter them both in and out of school.
Mixed NNLO QCD×electroweak corrections of $$ \mathcal{O} $$(Nfαsα) to single-W/Z production at the LHC
Authors: Dittmaier Stefan , Schmidt Timo , Schwarz Jan
Published: January 2021

Abstract

First results on the radiative corrections of order $$ \mathcal{O} $$
O
(Nfαsα) are presented for the off-shell production of W or Z bosons at the LHC, where Nf is the number of fermion flavours. These corrections comprise all diagrams at $$ \mathcal{O} $$
O
(αsα) with closed fermion loops, form a gauge-invariant part of the next-to-next-to-leading-order corrections of mixed QCD×electroweak type, and are the ones that concern the issue of mass renormalization of the W and Z resonances. The occurring irreducible two-loop diagrams, which involve only self-energy insertions, are calculated with current standard techniques, and explicit analytical results on the electroweak gauge-boson self-energies at $$ \mathcal{O} $$
O
(αsα) are given. Moreover, the generalization of the complex-mass scheme for a gauge-invariant treatment of the W/Z resonances is described for the order $$ \mathcal{O} $$
O
(αsα). While the corrections, which are implemented in the Monte Carlo program Rady, are negligible for observables that are dominated by resonant W/Z bosons, they affect invariant-mass distributions at the level of up to 2% for invariant masses of ≳ 500 GeV and are, thus, phenomenologically relevant. The impact on transverse-momentum distributions is similar, taking into account that leading-order predictions to those distributions underestimate the spectrum.
Effect of ceritinib on the pharmacokinetics of coadministered CYP3A and 2C9 substrates: a phase I, multicenter, drug–drug interaction study in patients with ALK + advanced tumors
Authors: Hurtado Felipe K. , de Braud Filippo , De Castro Carpeño Javier , de Miguel Luken Maria Jose , Wang Ding , Scott Jeffrey , Lau Yvonne Y. , McCulloch Tracey , Mau-Sorensen Morten
Published: January 2021

Purpose

Ceritinib is an ALK receptor tyrosine kinase inhibitor approved as first- and second-line treatment in adult patients with ALK + metastatic non-small cell lung cancer (NSCLC). The study investigated the drug–drug interaction (DDI) potential of ceritinib when coadministered with midazolam and warfarin as probe substrates for CYP3A and CYP2C9 activity, respectively.

Methods

This was a phase I, multicenter, open-label, single sequence, crossover DDI study in 33 adult patients with ALK + NSCLC or other advanced tumors. A single dose of a cocktail consisting of midazolam and warfarin was administered with and without concomitant administration of ceritinib. The primary objective was to evaluate the pharmacokinetics of midazolam and warfarin. Secondary objectives included pharmacokinetics, safety, tolerability, overall response rate (ORR), and duration of response (DOR) of ceritinib 750 mg once daily.

Results

Ceritinib inhibited CYP3A-mediated metabolism of midazolam, resulting in a markedly increased AUC (geometric mean ratio [90% confidence interval]) by 5.4-fold (4.6, 6.3). Ceritinib also led to an increase in the AUC of S-warfarin by 54% (36%, 75%). The pharmacokinetics and safety profile of ceritinib in this study are consistent with previous reports and no new safety signals were reported. Among the 19 patients with NSCLC, efficacy (ORR: 42.1% and DCR: 63.2%) was similar to that reported previously in studies of pretreated patients with ALK + NSCLC.

Conclusion

Ceritinib is a strong CYP3A inhibitor and a weak CYP2C9 inhibitor. These findings should be reflected as actionable clinical recommendations in the prescribing information for ceritinib with regards to concomitant medications whose pharmacokinetics may be altered by ceritinib.
Molekularpathologie bei urologischen Tumoren
Authors: Hommerding Oliver , Allory Yves , Argani Pedram , Bismar Tarek A. , Bubendorf Lukas , Canete-Portillo Sofía , Chaux Alcides , Chen Ying-Bei , Cheng Liang , Cubilla Antonio L. , Egevad Lars , Gill Anthony J. , Grignon David J. , Hartmann Arndt , Hes Ondrej , Idrees Muhammad T. , Kao Chia-Sui , Knowles Margaret A. , Looijenga Leendert H. J. , Lotan Tamara L. , Pritchard Colin C. , Rubin Mark A. , Tomlins Scott A. , Van der Kwast Theodorus H. , Velazquez Elsa F. , Warrick Joshua I. , Williamson Sean R. , Kristiansen Glen
Published: January 2021

Das zunehmende Verständnis molekularer Grundlagen von Tumoren sowie der Fortschritt in der Diversifizierung der onkologischen Therapien versprechen individualisierte Therapieoptionen, welche bislang jedoch nur ansatzweise in die Therapieplanung von urologischen Tumoren eingegangen sind. Daher hat die Internationale Gesellschaft für Urologische Pathologie (ISUP) im März 2019 eine Konsenskonferenz zur Erarbeitung evidenzbasierter Handlungsempfehlungen zur molekularpathologischen Diagnostik beim Urothelkarzinom, Nierenzellkarzinom, Prostatakarzinom, Peniskarzinom und testikulären Keimzelltumoren durchgeführt. Die auf dieser Konsenskonferenz erarbeiteten Empfehlungen sind kürzlich in 5 separaten Manuskripten veröffentlich worden und werden in der vorliegenden Arbeit zusammengefasst.

Im Rahmen der Konferenzvorbereitung wurde eine umfassende Umfrage zur derzeitigen Praxis molekularer Testungen bei urogenitalen Tumoren unter den Mitgliedern der ISUP durchgeführt. Auf der Konferenz wurden die Ergebnisse und die entsprechenden Hintergrundinformationen durch 5 Arbeitsgruppen präsentiert und Handlungsempfehlungen für die Diagnostik erarbeitet. Eine Übereinstimmung von 66 % der Konferenzteilnehmer wurde als Konsens definiert.
Fractional Matchings, Component-Factors and Edge-Chromatic Critical Graphs
Authors: Klopp Antje , Steffen Eckhard
Published: January 2021

The first part of the paper studies star-cycle factors of graphs. It characterizes star-cycle factors of a graphGand proves upper bounds for the minimum number of$$K_{1,2}$$K1,2-components in a$$\{K_{1,1}, K_{1,2}, C_n:n\ge 3\}$${K1,1,K1,2,Cn:n≥3}-factor of a graphG. Furthermore, it shows where these components are located with respect to the Gallai–Edmonds decomposition ofGand it characterizes the edges which are not contained in any$$\{K_{1,1}, K_{1,2}, C_n:n\ge 3\}$${K1,1,K1,2,Cn:n≥3}-factor ofG. The second part of the paper proves that every edge-chromatic critical graphGhas a$$\{K_{1,1}, K_{1,2}, C_n:n\ge 3\}$${K1,1,K1,2,Cn:n≥3}-factor, and the number of$$K_{1,2}$$K1,2-components is bounded in terms of its fractional matching number. Furthermore, it shows that for every edgeeofG, there is a$$\{K_{1,1}, K_{1,2}, C_n:n\ge 3\}$${K1,1,K1,2,Cn:n≥3}-factorFwith$$e \in E(F)$$e∈E(F). Consequences of these results for Vizing’s critical graph conjectures are discussed.
Dydrogesterone in the treatment of endometriosis: evidence mapping and meta-analysis
Authors: Peng Chao , Huang Yan , Zhou Yingfang
Published: January 2021

Purpose

Endometriosis is a common, chronic gynecological disease that affects women’s fertility potential. Dydrogesterone is an effective and safe drug that is under-utilized due to limited clinical research. The purpose of this evidence mapping is to identify, describe, and analyze the current available evidence regarding dydrogesterone for the treatment of endometriosis.

Materials and methods

We performed a search in electronic databases: Medline, The Cochrane Library, EMBASE, PubMed, CNKI, Wanfang, VIP, and CBM. We also hand-searched google for relevant studies. Our primary outcomes included changes in pain relief including pelvic pain, dysmenorrhea, and dyspareunia. Secondary outcomes included pregnancy rate, frequency of analgesic use, and other reported outcomes according to specific settings in the studies.

Results

Of 377 references screened, 19 studies were included in the data synthesis involving 1709 female participants. Nearly three-quarters were either randomized control trials or clinical control trials. Compared with gestrinone, dydrogesterone relieved dysmenorrhea, increased the pregnancy rate, and reduced the risk of certain adverse events. Compared with GnRH-a, dydrogesterone also lowered the risk of endometriosis recurrence and elevated transaminase levels. Whether there was any difference in efficacy between dydrogesterone and leuprolide acetate, letrozole or traditional Chinese medicine remains unclear due to insufficient data.

Conclusions

The amount and quality of evidence evaluating the effects of dydrogesterone for the treatment of endometriosis is generally very low. Limited evidence suggests that dydrogesterone may have some advantages over gestrinone, GnRH agonists, and other therapeutic interventions in treating endometriosis. However, this conclusion should be interpreted with caution.