bluuebunny/crossref_metadata_2025 huggingface dataset:
Taking practical learning in STEM education home: Examples from do‐it‐yourself experiments in plant biology
Authors: Gya Ragnhild , Bjune Anne Elisabeth
Published: February 2021

Practical teaching can give authentic learning experiences and teach valuable skills for undergraduate students in the STEM disciplines. One of the main ways of giving students such experiences, laboratory teaching, is met with many challenges such as budget cuts, increased use of virtual learning, and currently the university lockdowns due to the COVID‐19 pandemic. We highlight how at‐home do‐it‐yourself (DIY) experiments can be a good way to include physical interaction with your study organism, system, or technique to give the students a practical, authentic learning experience. We hope that by outlining the benefits of a practical, at‐home, DIY experiment we can inspire more people to design these teaching activities in the current remote teaching situation and beyond. By contributing two examples in the field of plant biology we enrich the database on experiments to draw inspiration from for these teaching methods.
A framework for lotic macrosystem research
Authors: Thorp James H. , Dodds Walter K. , Robbins Caleb J. , Maasri Alain , Arsenault Emily R. , Lutchen Jackob A. , Tromboni Flavia , Hayford Barbara , Pyron Mark , Mathews Gregory S. , Schechner Anne , Chandra Sudeep
Published: February 2021

We analyze here the nature of research in freshwater macrosystem biology (especially lotic studies) from both conceptual and current research perspectives. The boundaries of permanent and transitional lotic macrosystems from the smallest to largest spatial extents are described. We contrast ecosystem vs. macrosystem research and macroecology vs. macrosystems ecology and provide some examples of representative aquatic macrosystems ecology projects in the USA. We recommend approaches for incorporating certain large‐scale lotic concepts developed over the last 40 yr as the bases for lotic macrosystem studies. Of these, the three most appropriate in chronological order are the River Continuum Concept, the Riverine Ecosystem Synthesis, and the Stream Biome Gradient Concept. Four other concepts would be suitable for testing macrosystem hypotheses after incorporating small to large conceptual or geographic expansions of the models. We suggest future research directions in lotic macrosystem research in areas of climate change and teleconnections among distant organisms and systems and include general recommendations for conducting macrosystem‐level research.
Doxorubicin‐induced and trastuzumab‐induced cardiotoxicity in mice is not prevented by metoprolol
Authors: Nicol Martin , Sadoune Malha , Polidano Evelyne , Launay Jean Marie , Samuel Jane Lise , Azibani Feriel , Cohen‐Solal Alain
Published: February 2021

Aims

Our objectives were to validate a murine model of chronic cardiotoxicity induced by Doxorubicin (Dox) and Trastuzumab (Trast) and to test the potential cardio‐protective effect of metoprolol.

Methods and results

Male C57Bl6 mice were intraperitoneally injected during 2 weeks with Dox (24 mg/kg) or saline, and then with Trast (10 mg/kg) or saline for two more weeks. Half of the mice received metoprolol (100 mg/kg). Cardiotoxicity was defined by a decline in left ventricular ejection fraction (LVEF) ≥ 10 points. At Day 42, Dox + Trast‐treated mice exhibited a 13‐points decline in LVEF (74 ± 2.6% vs. 87 ± 0.8% for control mice, P < 0.001) and a severe cardiac atrophy (heart weight: 105 ± 2.7 mg vs. 119 ± 3.9 mg for control mice, P < 0.01). This cardiac atrophy resulted from an excess of cardiac necrosis (assessed by plasma cardiac troponin I level: 3.2 ± 0.4 ng/L vs. 1.3 ± 0.06 ng/L for control mice, P < 0.01), an increase in apoptosis (caspase 3 activity showing a six‐fold increase for Dox + Trast‐treated mice vs. controls, P < 0.001), and cardiomyocyte atrophy (myocyte size: 0.67 ± 0.08 μm2 vs. 1.36 ± 0.10 μm2 for control mice, P < 0.001). In addition, Dox + Trast‐treated mice were shown to have an increased cardiac oxidative stress (164 ± 14 dihydroethidine‐marked nuclei per area vs. 56 ± 9.5 for control mice, P < 0.01) and increased cardiac fibrosis (the semi‐quantitative fibrosis score was three‐fold higher for Dox + Trast‐treated mice as compared with controls, P < 0.01). Metoprolol was not able to prevent either the decrease in LVEF or the severe cardiac atrophy, the cardiac necrosis, and the cardiac remodelling induced by chemotherapies.

Conclusion

A murine model of chronic cardiotoxicity induced by Dox and Trast was characterized by a decrease in cardiac function, a cardiac apoptosis and necrosis leading to cardiomyocyte atrophy. Metoprolol did not prevent this cardiotoxicity.
Non‐alcoholic fatty liver disease and heart failure with preserved ejection fraction: from pathophysiology to practical issues
Authors: Itier Romain , Guillaume Maeva , Ricci Jean‐Etienne , Roubille François , Delarche Nicolas , Picard François , Galinier Michel , Roncalli Jérôme
Published: February 2021

The prevalence of non‐alcoholic fatty liver disease (NAFLD) in heart failure (HF) preserved left ventricular ejection fraction (HFpEF) patients could reach 50%. Therefore, NAFLD is considered an emerging risk factor. In 20% of NAFLD patients, the condition progresses to non‐alcoholic steatohepatitis (NASH), the aggressive form of NAFLD characterized by the development of fibrosis in the liver, leading to cirrhosis. The purpose of this review is to provide an overview of the relationships between NAFLD and HFpEF and to discuss its impact in clinical setting. Based on international reports published during the past decade, there is growing evidence that NAFLD is associated with an increased incidence of cardiovascular diseases, including impaired cardiac structure and function, arterial hypertension, endothelial dysfunction, and early carotid atherosclerosis. NAFLD and HFpEF share common risk factors, co‐morbidities, and cardiac outcomes, in favour of a pathophysiological continuum. Currently, NAFLD and NASH are principally managed with non‐specific therapies targeting insulin resistance like sodium‐glucose co‐transporter‐2 inhibitors and liraglutide, which can effectively treat hepatic and cardiac issues. Studies including HFpEF patients are ongoing. Several specific NAFLD‐oriented therapies are currently being developed either alone or as combinations. NAFLD diagnosis is based on a chronic elevation of liver enzymes in a context of metabolic syndrome and insulin resistance, with fibrosis scores being available for clinical practice. In conclusion, identifying HF patients at risk of NAFLD is a critically important issue. As soon as NAFLD is confirmed and its severity determined, patients should be proposed a management focused on symptoms and co‐morbidities.
Monoprotected Diamines Derived from 1,5‐Disubstituted (Aza)spiro[2.3]hexane Scaffolds
Authors: Malashchuk Andrii , Chernykh Anton V. , Perebyinis Mariana Y. , Komarov Igor V. , Grygorenko Oleksandr O.
Published: February 2021

Synthesis of monoprotected diamines derived from 1,5‐disubstituted spiro[2.3]hexane and 5‐azaspiro[2.3]hexane scaffolds is described. In both cases, the method relied on the cyclopropanation of the corresponding cyclobutane or azetidine derivatives. In the case of monoprotected 1,5‐diaminospiro[2.3]hexanes, the title products were obtained as single diastereomers. X‐Ray diffraction studies supported by exit vector plot (EVP) analysis showed that the obtained building blocks are promising piperidine/cycloalkane isosteres with potential utility to drug discovery. Also, conformations observed in the crystalline state for the two different diastereomers of 1,5‐diaminospiro[2.3]hexane derivatives prompt their application in design of β‐turn and sheet‐like peptidomimetics, respectively.
Synthesis of Azepino[1,2‐a]indole‐10‐amines via [6+1] Annulation of Ynenitriles with Reformatsky Reagent
Authors: Iioka Ryoya , Yorozu Kohei , Sakai Yoko , Kawai Rika , Hatae Noriyuki , Takashima Katsuki , Tanabe Genzoh , Wasada Hiroaki , Yoshimatsu Mitsuhiro
Published: February 2021

Lewis acid‐catalyzed [6+1] annulation reactions of 2‐cyano‐1‐propargyl‐ and 2‐alkynyl‐1‐cyanomethyl‐indoles with Reformatsky reagent are described. 8‐Aryl, 8‐alkyl‐, 8‐hetaryl‐, 9‐aryl, and 9‐alkyl‐azepino[1,2‐a]indole amines were obtained through a 7‐endo‐mode cyclization of the β‐aminoacrylate intermediates. The antiproliferative activity of the azepino[1,2‐a]indoles analogs against the HCT‐116 cells were also examined.
Testing the basic socio‐structural assumptions of social identity theory in the gender context: Evidence from correlational studies on women's leadership
Authors: Scheifele Carolin , Ehrke Franziska , Viladot Maria A. , Van Laar Colette , Steffens Melanie C.
Published: February 2021

Given negative social identity, different perceptions of the structure of an intergroup relation (i.e., stability, legitimacy, permeability) should be related to different identity‐management strategies (i.e., social competition, social creativity, or individual mobility) depending on group identification. This is among the basic tenets of social identity theory (SIT). There is surprisingly little empirical support for these postulates in the context of one of the most central group identities: gender. Using a sample of female leaders in Spain in a Pilot Study (N = 649) and in Germany in the preregistered Main Study (N = 687), we tested relations between structural perceptions and identity‐management strategies. Whereas structural equation modeling yielded empirical support regarding social competition but little for other strategies in the Pilot Study, the results were even less in line with SIT's predictions in the Main Study. We discuss reasons why only weak support for SIT emerged in this intergroup context.
Novel Three‐dimensional Sensor for Rapid Detection of Pb(II) and Cd(II) in Edible Mushrooms
Authors: Yin Jiaqi , Chu Guanglei , Wang Yue , Zhai Hongguo , Wang Bao , Sun Xia , Guo Yemin , Zhang Yanyan
Published: February 2021

A sensing platform was developed based on the molybdenum disulfide‐reduced graphene oxide (MoS2‐RGO). The flower‐like MoS2‐RGO nanocomposite had a large number of active sites such as oxygen‐containing groups and highly reactive sulfur that contributed to the adsorption and preconcentration of heavy metal ions (HMIs). MoS2‐RGO was synthesized by one‐step reduction method. Under optimized conditions, the limits of detection (LODs) for Pb(II) and Cd(II) was 0.13 μg/L and 0.59 μg/L with a linear range of 4.1–207.2 μg/L and 2.2–112.4 μg/L, respectively. The modified sensors had been successfully applied to detect Pb(II) and Cd(II) in three kinds of edible mushrooms.
An appraisal of experimental designs: Application to enantioselective capillary electromigration techniques
Authors: Perovani Icaro Salgado , Serpellone Carolina Oliveira , de Oliveira Anderson Rodrigo Moraes
Published: February 2021

Enantioresolution processes are vital tools for investigating the enantioselectivities of chiral compounds. An analyst resolves to optimize enantioresolution conditions once they are determined. Generally, optimization is conducted by a one‐factor‐at‐a‐time (OFAT) approach. Although this approach may determine an adequate condition for the method, it does not often allow the estimation of the real optimum condition. Experimental designs are conducive for the optimization of enantioresolution methods via capillary electromigration techniques (CETs). They can efficiently extract information from the behavior of a method and enable the estimation of the real optimum condition. Furthermore, the application of the analytical quality by design (AQbD) approach to the development of CET‐based enantioselective methods is a trend. This article (i) offers an overview of the application of experimental designs to the development of enantioselective methods from 2015 to mid‐2020, (ii) reveals the experimental designs that are presently employed in CET‐based enantioresolutions, and (iii) offers a critical point of view on how the different experimental designs can aid the optimization of enantioresolution processes by considering the method parameters.
Mixotrophic cultivation of Chlorella vulgaris in sugarcane molasses preceding nitrogen starvation: Biomass productivity, lipid content, and fatty acid analyses
Authors: Laraib Natasha , Manzoor Maleeha , Javid Arshad , Jabeen Faiza , Bukhari Syed Mohsin , Ali Waqas , Hussain Ali
Published: February 2021

In the present study, a precharacterized oleaginous microalgal species (Chlorella vulgaris) was exploited for its biomass productivity, lipid yield, and fatty acid analysis under mixotrophic and photoautotrophic conditions. For the purpose, the microalgal biomass was raised mixotrophically as well photoautotrophically. For mixotrophic cultivation, molasses was used as additional source of carbon and energy, while for photoautotrophic cultivation, atmospheric CO2 was the sole source of carbon and energy. The microalgal biomass raised thus was then harvested following 5 days of nitrogen starvation. Mixotrophic cultivation depicted remarkably higher biomass productivity (137.43 ± 13.3 mg L−1 day−1) than that of photoautotrophic cultivation (91.57 ± 7.9 mg L−1 day−1). About 39% (w/w) of total lipid content was obtained from the dried biomass raised mixotrophically. Lipidomic analysis of the extracted oil depicted higher concentrations of polyunsaturated fatty acids (palmitic and oleic acids). The significant availability of polyunsaturated fatty acids (60 mg g−1 of dried algal biomass) ensured the production of high quality biofuel.
Benthic species as mud patrol ‐ modelled effects of bioturbators and biofilms on large‐scale estuarine mud and morphology
Authors: Brückner Muriel Z.M. , Schwarz Christian , Coco Giovanni , Baar Anne , Boechat Albernaz Márcio , Kleinhans Maarten G.
Published: February 2021

Sediment‐stabilizing and ‐destabilizing organisms, i.e. microphytobenthos (biofilms) and macrozoobenthos (bioturbators), affect the erodibility of muddy sediments, potentially altering large‐scale estuarine morphology. Using a novel eco‐morphodynamic model of an idealized estuary, we investigate eco‐engineering effects of microphytobenthos and two macrozoobenthic bioturbators. Local mud erodibility is based on species pattern predicted through hydrodynamics, soil mud content, competition and grazing.

Mud resuspension and export is enhanced under bioturbation and prevented under biostabilization through respective exposure and protection of the supra‐ and intertidal. Bioturbation decreases mud thickness and bed elevations, which increases net mud fluxes. Microphytobenthos reduces erosion, leading to a local mud increase of intertidal sediments.

In multi‐species scenarios, an effective mud‐prone bioturbator strongly alters morphology, exceeding that of a more abundant sand‐prone moderate species, showing that morphological change depends on species traits as opposed to abundance. Altering their habitat, the effective mud‐prone bioturbator facilitates expansion of the sand‐prone moderate bioturbator. Grazing and species competition favor species distributions of dominant bioturbators. Consequently, eco‐engineering affects habitat conditions while species interactions determine species dominance.

Our results show that eco‐engineering species determine the mud content of the estuary, which suggests large effects on the morphology of estuaries with aggravating habitat degradation.
Paleoseismology of the 2016 MW 6.1 Petermann earthquake source: Implications for intraplate earthquake behaviour and the geomorphic longevity of bedrock fault scarps in a low strain‐rate cratonic region
Authors: King Tamarah Rosellen , Quigley Mark , Clark Dan , Zondervan Albert , May Jan‐Hendrik , Alimanovic Abaz
Published: February 2021

The 20 May 2016 MW 6.1 Petermann earthquake in central Australia generated a 21 km surface rupture with 0.1 to 1 m vertical displacements across a low‐relief landscape. No paleo‐scarps or potentially analogous topographic features are evident in pre‐earthquake Worldview‐1 and Worldview‐2 satellite data. Two excavations across the surface rupture expose near‐surface fault geometry and mixed aeolian‐sheetwash sediment faulted only in the 2016 earthquake. A 10.6 ± 0.4 ka optically stimulated luminescence (OSL) age of sheetwash sediment provides a minimum estimate for the period of quiescence prior to 2016 rupture. Seven cosmogenic beryllium‐10 (10Be) bedrock erosion rates are derived for samples < 5 km distance from the surface rupture on the hanging‐wall and foot‐wall, and three from samples 19 to 50 km from the surface rupture. No distinction is found between fault proximal rates (1.3 ± 0.1 to 2.6 ± 0.2 m Myr−1) and distal samples (1.4 ± 0.1 to 2.3 ± 0.2 m Myr−1). The thickness of rock fragments (2–5 cm) coseismically displaced in the Petermann earthquake perturbs the steady‐state bedrock erosion rate by only 1 to 3%, less than the erosion rate uncertainty estimated for each sample (7–12%). Using 10Be erosion rates and scarp height measurements we estimate approximately 0.5 to 1 Myr of differential erosion is required to return to pre‐earthquake topography. By inference any pre‐2016 fault‐related topography likely required a similar time for removal. We conclude that the Petermann earthquake was the first on this fault in the last ca. 0.5–1 Myr. Extrapolating single nuclide erosion rates across this timescale introduces large uncertainties, and we cannot resolve whether 2016 represents the first ever surface rupture on this fault, or a > 1 Myr interseismic period. Either option reinforces the importance of including distributed earthquake sources in fault displacement and seismic hazard analyses.
Agricultural commodity price dynamics and their determinants: A comprehensive econometric approach
Authors: Crespo Cuaresma Jesus , Hlouskova Jaroslava , Obersteiner Michael
Published: February 2021

We present a comprehensive modelling framework aimed at quantifying the response of agricultural commodity prices to changes in their potential determinants. The problem of model uncertainty is assessed explicitly by concentrating on specification selection based on the quality of short‐term out‐of‐sample forecasts (1 to 12 months ahead) for the price of wheat, soybeans and corn. Univariate and multivariate autoregressive models (autoregressive [AR], vector autoregressive [VAR] and vector error correction [VEC] specifications, estimated using frequentist and Bayesian methods), specifications with heteroskedastic errors (AR conditional heteroskedastic [ARCH] and generalized AR conditional heteroskedastic [GARCH] models) and combinations of these are entertained, including information about market fundamentals, macroeconomic and financial developments, and climatic variables. In addition, we assess potential non‐linearities in the commodity price dynamics along the business cycle. Our results indicate that variables measuring market fundamentals and macroeconomic developments (and, to a lesser extent, financial developments) contain systematic predictive information for out‐of‐sample forecasting of commodity prices and that agricultural commodity prices react robustly to shocks in international competitiveness, as measured by changes in the real exchange rate.
A literature survey of matrix methods for data science
Authors: Stoll Martin
Published: February 2021

Efficient numerical linear algebra is a core ingredient in many applications across almost all scientific and industrial disciplines. With this survey we want to illustrate that numerical linear algebra has played and is playing a crucial role in enabling and improving data science computations with many new developments being fueled by the availability of data and computing resources. We highlight the role of various different factorizations and the power of changing the representation of the data as well as discussing topics such as randomized algorithms, functions of matrices, and high‐dimensional problems. We briefly touch upon the role of techniques from numerical linear algebra used within deep learning.
Feasibility study of CO2/N2 separation intensification on supported ionic liquid membranes by commonly used impregnation methods
Authors: Ziobrowski Zenon , Rotkegel Adam
Published: February 2021

This work presents the experimental research on feasible intensification of CO2/N2 separation by utilization of the developed supported ionic liquid membranes (SILMs). SILMs were developed through specific impregnation of commercially available ceramic microfiltration/ultrafiltration membranes made by INOPOR and polydimethylsiloxane (PDMS) membranes made by Pervatech BV with chosen imidazolium based ionic liquids (ILs). The effects of operating parameters, impregnation method, and SILM thickness were analyzed.

The impregnation was performed by coating and soaking methods at normal pressure and under vacuum. The proper impregnation of the ceramic support, especially in case of commercial PDMS membranes, allows to achieve two distinct, stable, highly selective separation layers. The comparison of separation efficiency of the investigated SILMs shows that SILM based on PDMS membrane prepared by coating with 1‐ethyl‐3‐methylimidazolium acetate ([Emim][Ac]) has very good stability, high CO2/N2 ideal separation factor of 152 and permeability of 2400 barrer. It was found that optimum operating conditions were feed temperature of 20°C and pressure below 200 kPa.

The obtained results represent an interesting low cost alternative in the gas separation, especially when the choice of selectivity is the first priority. The comparison with literature data and upper bond Robeson correlation (2008) suggests, that applying an additional active separating IL layer and an appropriate impregnating method to the commercial ceramic membranes may result in significant improvement of separation efficiency. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd.
Activated carbon‐based composites for capturing CO2: a review
Authors: Wang Junya , Pu Qiuyun , Ning Ping , Lu Shijian
Published: February 2021

Activated carbon is widely regarded as a potential CO2 adsorbent because of its special texture. Activated carbon captures CO2 mainly through physical adsorption due to the characteristics of surface structure and pore structure, which makes the adsorbent sensitive to temperature and relatively low in selectivity. In order to solve these problems, much effort has been made in new developments, including synthesis activated carbon‐based composites, which can not only improve its CO2 capture capacity and stability, but also improve its selectivity. This paper reviews the recent research focused on the activated carbon‐based composites using in postcombustion CO2 capture. The status and development of activated carbon‐based composites are presented in four parts as activated carbon/metal composite, activated carbon/zeolite composite, activated carbon/metal organic framework composite, and activated carbon/carbon material composite. The details of synthesis method, synthesis condition, modification method, and CO2 adsorption performance are introduced. Simultaneously, the characteristics, advantages, and potential challenges of the composites are also summarized. This work will provide important parameters in the applications of activated carbon‐based adsorbents for postcombustion CO2 capture and give suggestions on future research efforts. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd.
Experimental study on in situ dissociation kinetics of CO2 hydrate in pure water and water/sediments systems
Authors: Wang Jie , Li Airong , Liu Faping , Luo Zedong
Published: February 2021

Recently, hydrate technology as a newly emerging field has been attracting more and more attention. To support its potential applications, the dissociation behaviors and kinetics of CO2 hydrate in pure water and water/sediments systems at specified temperatures were studied experimentally by depressurization method. This work reveals two novel aspects of CO2 hydrate dissociation. Firstly, it is remarkable that the dissociation rate of CO2 hydrate in water/sediments is faster than that of CO2 hydrate in pure water, which has not been conscious previously. Secondly, a pseudo first‐order kinetic equation including the kinetic constant and activation energy was formulated to describe the dissociation process. Temperature plays an important role and the dissociation rate constant () and activation energy () were obtained through the dissociation experiments at different temperatures. For CO2 hydrate in pure water, the dissociation rate constant increased from 0.02 to 0.13 mol/(dm2⋅MPa⋅min) at the temperature from 273.86 to 276.11 K, and the activation energy was 469.06 kJ mol−1. For CO2 hydrate in water/sediments, the dissociation rate constant was from 0.03 to 0.15 mol/(dm2⋅MPa⋅min) at the temperature ranging from 273.45 to 276.11 K, and the activation energy was 346.30 kJ mol−1. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd.
Unusual location of a second branchial cleft cyst presenting in the suprasternal notch
Authors: Xing Monica H. , Mundi Neil , Govindan Aparna , Khorsandi Azita , Urken Mark L.
Published: February 2021

Background

Second branchial cleft cysts (SBCCs) are congenital benign tumors that comprise up to 90% of all branchial cleft anomalies. SBCCs typically present in the lateral neck along the anterior border of the upper third of the sternocleidomastoid muscle. We describe a case of a SBCC presenting in an unusual location in the lower neck close to midline.

Methods

An 18‐year‐old male presented with a 2‐year history of a neck mass in the suprasternal notch. Imaging findings were reviewed with a head and neck radiologist who felt that the findings were highly suggestive of a fourth branchial cleft cyst.

Results

The patient underwent surgical excision of the mass. Final pathologic evaluation confirmed the diagnosis of a second branchial cleft cyst.

Conclusions

Though extremely uncommon, second branchial cleft cysts can extend to the suprasternal notch and should not be excluded from the differential diagnoses of lower neck masses.
Mitogen‐activated protein kinase inhibition‐induced modulation of epidermal growth factor receptor signaling in human head and neck squamous cell carcinoma
Authors: Xie Guiqin , Zhu Ailin , Gu Xinbin
Published: February 2021

Background

Epidermal growth factor receptor (EGFR) overexpression is one of the most notable characteristics in head and neck squamous cell carcinoma (HNSCC). The MAPK kinase (MEK) inhibitor trametinib has shown efficacy to treat HNSCC; however, the molecular mechanism remains unclear.

Methods

HNSCC lines, mouse models, Western blot, and flow cytometry were employed to analyze the anticancer effects of trametinib.

Results

The JHU‐011, JHU‐022, and JHU‐029 HNSCC cells with different genetic alterations were highly susceptible to trametinib. Trametinib effectively reduced EGFR expression, which was accompanied by the reduction of pro‐survival protein MYC, and the increased expression of a MYC‐targeted cyclin‐dependent kinase inhibitor p27kip1 and pro‐apoptotic protein BIM. Trametinib resulted in G1 arrest of the cells, markedly reduced cell numbers in S phase, and significantly increased apoptosis. In mouse models, trametinib strongly inhibited tumors growth.

Conclusions

The MAPK–ERK signaling inhibition by trametinib may target EGFR and the downstream proteins against HNSCC.
Nuclear factor erythroid 2–related factor 2 and β‐Catenin Coactivation in Hepatocellular Cancer: Biological and Therapeutic Implications
Authors: Tao Junyan , Krutsenko Yekaterina , Moghe Akshata , Singh Sucha , Poddar Minakshi , Bell Aaron , Oertel Michael , Singhi Aatur D. , Geller David , Chen Xin , Lujambio Amaia , Liu Silvia , Monga Satdarshan P.
Published: February 2021

Background and Aims

HCC remains a major unmet clinical need. Although activating catenin beta‐1 (CTNNB1) mutations are observed in prominent subsets of HCC cases, these by themselves are insufficient for hepatocarcinogenesis. Coexpression of mutant CTNNB1 with clinically relevant co‐occurrence has yielded HCCs. Here, we identify cooperation between β‐catenin and nuclear factor erythroid 2–related factor 2 (Nrf2) signaling in HCC.

Approach and Results

Public HCC data sets were assessed for concomitant presence of CTNNB1 mutations and either mutations in nuclear factor erythroid‐2–related factor‐2 (NFE2L2) or Kelch like‐ECH‐associated protein 1 (KEAP1), or Nrf2 activation by gene signature. HCC development in mice and similarity to human HCC subsets was assessed following coexpression of T41A‐CTNNB1 with either wild‐type (WT)‐, G31A‐, or T80K‐NFE2L2. Based on mammalian target of rapamycin complex 1 activation in CTNNB1‐mutated HCCs, response of preclinical HCC to mammalian target of rapamycin (mTOR) inhibitor was investigated. Overall, 9% of HCC cases showed concomitant CTNNB1 mutations and Nrf2 activation, subsets of which were attributable to mutations in NFE2L2/KEAP1. Coexpression of mutated CTNNB1 with mutant NFE2L2, but not WT‐NFE2L2, led to HCC development and mortality by 12‐14 weeks. These HCCs were positive for β‐catenin targets, like glutamine synthetase and cyclin‐D1, and Nrf2 targets, like NAD(P)H quinone dehydrogenase 1 and peroxiredoxin 1. RNA‐sequencing and pathway analysis showed high concordance of preclinical HCC to human HCC subset showing activation of unique (iron homeostasis and glioblastoma multiforme signaling) and expected (glutamine metabolism) pathways. NFE2L2‐CTNNB1 HCC mice were treated with mTOR inhibitor everolimus (5‐mg/kg diet ad libitum), which led to >50% decrease in tumor burden.

Conclusions

Coactivation of β‐catenin and Nrf2 is evident in 9% of all human HCCs. Coexpression of mutant NFE2L2 and mutant CTNNB1 led to clinically relevant HCC development in mice, which responded to mTOR inhibitors. Thus, this model has both biological and therapeutic implications.
The Impact of Direct‐Acting Antiviral Therapy on End‐Stage Liver Disease Among Individuals with Chronic Hepatitis C and Substance Use Disorders
Authors: Park Haesuk , Jiang Xinyi , Song Hyun Jin , Lo Re Vincent , Childs‐Kean Lindsey M. , Lo‐Ciganic Wei‐Hsuan , Cook Robert L. , Nelson David R.
Published: February 2021

Background and Aims

Our aim was to evaluate the impact of direct‐acting antivirals (DAAs) on decompensated cirrhosis (DCC) and HCC in patients with chronic HCV and substance use disorder (SUD) compared with those without an SUD.

Approach and Results

This retrospective cohort study used the MarketScan database (2013‐2018) to identify 29,228 patients with chronic HCV, where 22% (n = 6,385) had ≥1 SUD diagnosis. The inverse probability of treatment weighted multivariable Cox proportional hazard models were used to compare the risk of developing DCC and HCC. Among the those who were noncirrhotic, treatment reduced the DCC risk among SUD (adjusted hazard ratio [aHR] 0.13; 95% CI, 0.06‐0.30) and non‐SUD (aHR 0.11; 95% CI, 0.07‐0.18), whereas the risk for HCC was not reduced for the SUD group (aHR 0.91; 95% CI, 0.33‐2.48). For those with cirrhosis, compared with patients who were untreated, treatment reduced the HCC risk among SUD (aHR, 0.33; 95% CI, 0.13‐0.88) and non‐SUD (aHR, 0.40; 95% CI, 0.25‐0.65), whereas the risk for DCC was not reduced for the SUD group (aHR, 0.64; 95% CI, 0.37‐1.13). Among patients with cirrhosis who were untreated, the SUD group had a higher risk of DCC (aHR, 1.52; 95% CI, 1.03‐2.24) and HCC (aHR, 1.69; 95% CI, 1.05‐2.72) compared with non‐SUD group.

Conclusions

Among the HCV SUD group, DAA treatment reduced the risk of DCC but not HCC for those who were noncirrhotic, whereas DAA treatment reduced the risk of HCC but not DCC for those with cirrhosis. Among the nontreated, patients with an SUD had a significantly higher risk of DCC and HCC compared with those without an SUD. Thus, DAA treatment should be considered for all patients with HCV and an SUD while also addressing the SUD.
Sleep Disturbance Is Associated With the Presence of Portosystemic Collaterals in Patients With Compensated Cirrhosis
Authors: Balakrishnan Maya , Falker Caroline , Conley Samantha , Ciarleglio Maria , Deng Yanhong , Redeker Nancy S. , Garcia‐Tsao Guadalupe
Published: February 2021

Disturbed sleep is common among patients with cirrhosis. The extent to which this is associated with the different stages of compensated cirrhosis is unknown. This study examines whether the presence of portosystemic collaterals, an indicator of clinically significant portal hypertension, is associated with sleep disturbance in compensated cirrhosis. We conducted a cross‐sectional study among patients with compensated cirrhosis, comparing sleep characteristics, sleep quality, and excessive daytime sleepiness between 21 patients without and 21 patients with portosystemic collaterals. Patients were assessed with wrist actigraphy, Pittsburgh Sleep Quality Index, and the Epworth Sleepiness Scale. Collateral presence was determined by imaging and esophagogastroduodenoscopy. Differences in sleep characteristics were analyzed using t tests and computed effect sizes. Multivariable linear regression analysis was used to evaluate the association between collaterals and sleep disturbance while controlling for possible confounders. The group of patients with collaterals had greater beta‐blocker and tobacco use, lower albumin, and higher international normalized ratio compared to the group without collaterals. Patients with collaterals had more sleep fragmentation (Cohen’s d = −0.86), lower sleep efficiency (Cohen’s d = 0.59), and lower total sleep time (Cohen’s d = 0.75) than patients without collaterals. The presence of collaterals was independently associated with greater sleep fragmentation (P = 0.046) and greater daytime sleepiness (P = 0.030). Conclusion: Patients with compensated cirrhosis complicated by portosystemic collaterals experienced more sleep disturbance than those without collaterals.
Relationship between social cohesion and the care burden of primary family caregivers in central Tokyo, Japan
Authors: Naganuma Yuki , Yamaoka Kazue , Takahashi Kenzo
Published: February 2021

Objectives

To clarify how the care burden of primary family caregivers is associated with social cohesion in an urban area of Tokyo, Japan.

Study design

Cross‐sectional study.

Methods

A questionnaire survey of primary family caregivers was conducted in Tokyo in 2015. Social cohesion was examined using the social capital indicators of Kondo et al, and the care burden of primary family caregivers was assessed by the Zarit Care Burden Interview Scale in Japanese short version (J‐ZBI_8). Data were analyzed by multiple regression models. Ethics approval was obtained to carry out this research.

Results

Seventy‐nine caregivers responded to the questionnaires. After excluding 6 caregivers who did not respond appropriately to the questionnaire, 73 caregivers were included in the analyses. The average age of the primary family caregivers was 68.9 ± 12.7 years old, and that of the patients receiving care was 83.1 ± 10.0 years old. “Receipt of instrumental support” was significantly associated with reduced burden of care for family caregivers as assessed by the J‐ZBI_8 score (P = .027).

Conclusion

This study suggested that social cohesion was significantly associated with reduced burden of care for primary family caregivers. Especially, the results suggested that “social support: receipt of instrumental support” was associated with a lower burden of care after adjustment for confounding factors. It is important to understand family structure and social community differences such as informal social support for future policy making.
Estimating water balance components in irrigated agriculture using a combined approach of soil moisture and energy balance monitoring, and numerical modelling
Authors: Schulz Stephan , Becker Rike , Richard‐Cerda Juan Carlos , Usman Muhammad , aus der Beek Tim , Merz Ralf , Schüth Christoph
Published: February 2021

Information on water balance components such as evapotranspiration and groundwater recharge are crucial for water management. Due to differences in physical conditions, but also due to limited budgets, there is not one universal best practice, but a wide range of different methods with specific advantages and disadvantages. In this study, we propose an approach to quantify actual evapotranspiration, groundwater recharge and water inflow, i.e. precipitation and irrigation, that considers the specific conditions of irrigated agriculture in warm, arid environments. This approach does not require direct measurements of precipitation or irrigation quantities and is therefore suitable for sites with an uncertain data basis. For this purpose, we combine soil moisture and energy balance monitoring, remote sensing data analysis and numerical modelling using Hydrus. Energy balance data and routine weather data serve to estimate ET0. Surface reflectance data from satellite images (Sentinel‐2) are used to derive leaf area indices, which help to partition ET0 into energy limited evaporation and transpiration. Subsequently, first approximations of water inflow are derived based on observed soil moisture changes. These inflow estimates are used in a series of forward simulations that produce initial estimates of drainage and ETact, which in turn help improve the estimate of water inflow. Finally, the improved inflow estimates are incorporated into the model and then a parameter optimization is performed using the observed soil moisture as the reference figure. Forward simulations with calibrated soil parameters result in final estimates for ETact and groundwater recharge. The presented method is applied to an agricultural test site with a crop rotation of cotton and wheat in Punjab, Pakistan. The final model results, with an RMSE of 2.2% in volumetric water content, suggest a cumulative ETact and groundwater recharge of 769 and 297 mm over a period of 281 days, respectively. The total estimated water inflow accounts for 946 mm, of which 77% originates from irrigation.
Variation and attribution of water use efficiency in sunflower and maize fields in an irrigated semi‐arid area
Authors: Wang Weishu , Wang Xingwang , Huo Zailin , Rong Yao , Huang Quanzhong , Huang Guanhua
Published: February 2021

Water use efficiency (WUE) links carbon and water exchanges between farmlands and the atmosphere. Understanding the variation and attribution of WUE is essential to reveal the physiological and ecological adaptation mechanisms of crops to the changing environment, and to better allocate, regulate and conserve water resources. However, few studies on the variation and attribution of WUE have been conducted in irrigated arid or semi‐arid farmlands. Therefore, in this study, water and carbon fluxes were measured using eddy covariance systems in two farmlands (one sunflower field and one maize field) in a semi‐arid irrigation district in China. It was found that the average WUE of sunflower during its full growth period was 1.72 g C kg−1 H2O, much lower than that of maize (4.07 g C kg−1 H2O). At each growth stage, the WUE of both crops were negatively correlated with vapour pressure deficit (VPD), net radiation (Rn) and soil water content (SWC). The negative correlations could be attributed to the arid meteorological condition and the relatively abundant soil moisture due to irrigation and shallow groundwater levels. VPD was the main factor affecting WUE, followed by Rn and SWC. It was also found that the response of WUE to crop leaf area index (LAI) and to canopy conductance (gc) depended on the VPD ranges: when VPD increased, the response of WUE to LAI and to gc decreased. Our findings could improve the understanding of the coupling effect of water and carbon fluxes over farmland ecosystems in arid and semi‐arid irrigation areas and help improve agricultural production and save water resources in such areas.
Ruxolitinib inhibits poly(I:C) and type 2 cytokines‐induced CCL5 production in bronchial epithelial cells: A potential therapeutic agent for severe eosinophilic asthma
Authors: Sada Mitsuru , Watanabe Masato , Inui Toshiya , Nakamoto Keitaro , Hirata Aya , Nakamura Masuo , Honda Kojiro , Saraya Takeshi , Kurai Daisuke , Kimura Hirokazu , Ishii Haruyuki , Takizawa Hajime
Published: February 2021

Rationale

Severe eosinophilic asthma is characterized by airway eosinophilia and corticosteroid‐resistance, commonly overlapping with type 2 inflammation. It has been reported that chemokine (C‐C motif) ligand 5 (CCL5) is involved in the exacerbation of asthma by RNA virus infections. Indeed, treatment with a virus‐associated ligand and a T helper type 2 cell (Th2) cytokine can synergistically stimulate CCL5 production in bronchial epithelial cells. We aimed to evaluate the mechanisms underlying CCL5 production in this in vitro model and to assess the potential of Janus kinase 1 (JAK1) as a novel therapeutic target via the use of ruxolitinib.

Methods

We stimulated primary normal human bronchial epithelial (NHBE) cells and BEAS‐2B cells with poly(I:C) along with interleukin‐13 (IL‐13) or IL‐4, and assessed CCL5 production. We also evaluated the signals involved in virus‐ and Th2‐cytokine‐induced CCL5 production and explored a therapeutic agent that attenuates the CCL5 production.

Results

Poly(I:C) stimulated NHBE and BEAS‐2B cells to produce CCL5. Poly(I:C) and IL‐13 increased CCL5 production. Poly(I:C)‐induced CCL5 production occurred via the TLR3–IRF3 and IFNAR/JAK1–phosphoinositide 3‐kinase (PI3K) pathways, but not the IFNAR/JAK1–STATs pathway. In addition, IL‐13 did not augment poly(I:C)‐induced CCL5 production via the canonical IL‐13R/IL‐4R/JAK1–STAT6 pathway but likely via subsequent TLR3‐IRF3‐IFNAR/JAK1‐PI3K pathways. JAK1 was identified to be a potential therapeutic target for severe eosinophilic asthma. The JAK1/2 inhibitor, ruxolitinib, was demonstrated to more effectively decrease CCL5 production in BEAS‐2B cells than fluticasone propionate.

Conclusion

We have demonstrated that JAK1 is a possible therapeutic target for severe corticosteroid‐resistant asthma with airway eosinophilia and persistent Th2‐type inflammation, and that ruxolitinib has potential as an alternative pharmacotherapy.
Early response by MR imaging and ultrasound as predictor of pathologic complete response to 12‐week neoadjuvant therapy for different early breast cancer subtypes: Combined analysis from the WSG ADAPT subtrials
Authors: Graeser Monika , Schrading Simone , Gluz Oleg , Strobel Kevin , Würstlein Rachel , Kümmel Sherko , Schumacher Claudia , Grischke Eva‐Maria , Forstbauer Helmut , Braun Michael , Christgen Matthias , Adams Jascha , Nitzsche Henrik , Just Marianne , Fischer Hans Holger , Aktas Bahriye , Potenberg Jochem , von Schumann Raquel , Kolberg‐Liedtke Cornelia , Harbeck Nadia , Kuhl Christiane K. , Nitz Ulrike
Published: February 2021

We evaluated the role of early response after 3 weeks of neoadjuvant treatment (NAT) assessed by ultrasound (US), magnetic resonance imaging (MRI) and Ki‐67 dynamics for prediction of pathologic complete response (pCR) in different early breast cancer subtypes. Patients with HR+/HER2+, HR−/HER2− and HR−/HER2+ tumors enrolled into three neoadjuvant WSG ADAPT subtrials underwent US, MRI and Ki‐67 assessment at diagnosis and after 3 weeks of NAT. Early response was defined as complete or partial response (US, MRI) and ≥30% proliferation decrease or <500 invasive tumor cells (Ki‐67). Predictive values and area under the receiver operating characteristic (AUC) curves for prediction of pCR (ypT0/is ypN0) after 12‐week NAT were calculated. Two hundred twenty‐six had MRI and 401 US; 107 underwent both MRI and US. All three methods yielded a similar AUC in HR+/HER2+ (0.66‐0.67) and HR−/HER2− tumors (0.53‐0.63), while MRI and Ki‐67 performed better than US in HR−/HER2+ tumors (0.83 and 0.79 vs 0.56). Adding MRI+/‐Ki‐67 increased AUC of US in HR−/HER2+ tumors to 0.64 to 0.75. MRI and Ki‐67 demonstrated highest sensitivity in HR−/HER2− (0.8‐1) and HR−/HER2+ tumors (1, both). Negative predictive value was similar for all methods in HR+/HER2+ (0.71‐0.74) and HR−/HER2− tumors (0.85‐1), while it was higher for MRI and Ki‐67 compared to US in HR−/HER2+ subtype (1 vs 0.5). Early response assessed by US, MRI and Ki‐67 is a strong predictor for pCR after 12‐week NAT. Strength of pCR prediction varies according to tumor subtype. Adding MRI+/‐Ki‐67 to US did not improve pCR prediction in majority of our patients.
Cross‐sectional survey of the impact of the COVID‐19 pandemic on cancer screening programs in selected low‐ and middle‐income countries: Study from the IARC COVID‐19 impact study group
Authors: Villain Patricia , Carvalho Andre L. , Lucas Eric , Mosquera Isabel , Zhang Li , Muwonge Richard , Selmouni Farida , Sauvaget Catherine , Basu Partha ,   for the IARC COVID‐19 Impact Study Group
Published: February 2021

We conducted a study to document the impact of COVID‐19 pandemic on cancer screening continuum in selected low‐ and middle‐income countries (LMICs). LMICs having an operational cancer control plan committed to screen eligible individuals were selected. Managers/supervisors of cancer screening programs were invited to participate in an online survey and subsequent in‐depth interview. Managers/supervisors from 18 programs in 17 countries participated. Lockdown was imposed in all countries except Brazil. Screening was suspended for at least 30 days in 13 countries, while diagnostic‐services for screen‐positives were suspended in 9 countries. All countries except Cameroon, Bangladesh, India, Honduras and China managed to continue with cancer treatment throughout the outbreak. The participants rated service availability compared to pre‐COVID days on a scale of 0 (no activities) to 100 (same as before). A rating of ≤50 was given for screening services by 61.1%, diagnostic services by 44.4% and treatment services by 22.2% participants. At least 70% participants strongly agreed that increased noncompliance of screen‐positive individuals and staff being overloaded or overwhelmed with backlogs would deeply impact screening programs in the next 6 months at least. Although many of the LMICs were deficient in following the “best practices” to minimize service disruptions, at least some of them made significant efforts to improve screening participation, treatment compliance and program organization. A well‐coordinated effort is needed to reinitiate screening services in the LMICs, starting with a situational analysis. Innovative strategies adopted by the programs to keep services on‐track should be mutually shared.
On the effect of oil price in the context of Covid‐19
Authors: Jawadi Fredj , Sellami Mohamed
Published: February 2021

This article studies the impact of oil price change on the stock market, the exchange rate and the real estate market in the US over the last decade. To this end, we model the dynamics of the returns for these markets and test the effect of oil market volatility on their dynamics. Through different econometric investigations, we show, in the context of Covid‐19, that oil price has experienced significant effects on the US stock market and the US dollar exchange rate, while it has no significant impact on the US real estate market. In particular, we highlight, first, a positive and significant reaction of the stock market toward an oil price shock, which might be explained by the effect of high oil financialization over the last decade. Second, we show an adverse effect of the oil price change on the US dollar, suggesting a negative relationship between the oil price and the US dollar. Accordingly, the information provided by the oil sector might help to improve the forecast of the Dow Jones and the US$\€ exchange rate.