bluuebunny/crossref_metadata_2025 huggingface dataset:
Bulky PNP Ligands Blocking Metal‐Ligand Cooperation Allow for Isolation of Ru(0), and Lead to Catalytically Active Ru Complexes in Acceptorless Alcohol Dehydrogenation
Authors: Deolka Shubham , Fayzullin Robert R. , Khaskin Eugene
Published: November 2021

We synthesized two 4Me−PNP ligands which block metal‐ligand cooperation (MLC) with the Ru center and compared their Ru complex chemistry to their two traditional analogues used in acceptorless alcohol dehydrogenation catalysis. The corresponding 4Me−PNP complexes, which do not undergo dearomatization upon addition of base, allowed us to obtain rare, albeit unstable, 16 electron mono‐CO Ru(0) complexes. Reactivity with CO and H2 allows for stabilization and extensive characterization of bis‐CO Ru(0) 18 electron and Ru(II) cis and trans dihydride species that were also shown to be capable of C(sp2) −H activation. Reactivity and catalysis are contrasted to non‐methylated Ru(II) species, showing that an MLC pathway is not necessary, with dramatic differences in outcomes during catalysis between iPr and tBu PNP complexes within each of the 4Me and non‐methylated backbone PNP series being observed. Unusual intermediates are characterized in one of the new and one of the traditional complexes, and a common catalysis deactivation pathway was identified.
Simple iterative trial search for the maximum independent set problem optimized for the GPUs
Authors: Imanaga Tomohiro , Nakano Koji , Yasudo Ryota , Ito Yasuaki , Kawamata Yuya , Katsuki Ryota , Tabata Yusuke , Yazane Takashi , Hamano Kenichiro
Published: November 2021

An independent set of a graph is a subset of the nodes such that no two nodes in it are adjacent. The maximum independent set (MIS) problem is an optimization problem to find a largest independent set. The main contribution of this article is to introduce a generic iterative trial search algorithm that we call iMIS for finding approximate solutions for the MIS problem. The generic algorithm iMIS is designed so that it can be implemented to run on GPUs very efficiently. Since the performance of the algorithm varies depending on its search strategy, we present a hybrid algorithm that combines three strategies of the iMIS such that best one of them for an input graph is automatically selected. We have implemented our hybrid algorithm to run on a multi‐GPU server with eight NVIDIA A100 GPUs. And evaluated the performance for 66 DIMACS benchmark graphs and 78 random graphs with up to 256M nodes. We have also evaluated the performance of three previously published algorithms for the MIS problem and an approach using Gurobi linear programming solver. The experimental results show that our hybrid algorithm can find larger independent sets for all 144 graphs compared to other methods.
Investigation on four‐port mono‐capacitor circuit with high‐pass negative group delay behavior
Authors: Fenni Sofia , Haddad Fayrouz , Jaomiary Antonio , Yazdani Samar S. , Sahoa Frank Elliot , Ramifidisoa Lucius , Guerin Mathieu , Rahajandraibe Wenceslas , Ravelo Blaise
Published: November 2021

Most of the recent studies on unfamiliar negative group delay (NGD) circuit were focused on the classes of low‐pass (LP) and bandpass (BP) topologies. So far, few research works are currently available in the literature on the high‐pass (HP) NGD class. This paper introduces an original HP‐NGD circuit theory of four‐port passive topology constituted by a single lumped capacitor. The S‐matrix equivalent model of the innovative topology is established from the admittance matrix. The basic analytical frequency‐dependent responses are expressed. Then, the GD model is derived in function of the capacitor. It was analytically found that the four‐port mono‐capacitor passive circuit is susceptible to behave as an unfamiliar class of HP‐NGD function. An innovative HP‐NGD analysis is explored in addition to the expression of synthesis design equation in function of the expected NGD cut‐off frequency which is linked to NGD optimal value. The validity of the established HP‐NGD theory is verified with a proof of concept (POC) circuit. As expected, the POC enables HP‐NGD behavior to show a good correlation between analytical model which is confirmed by the simulation.
Meta‐analysis of salt marsh vegetation impacts and recovery: a synthesis following the Deepwater Horizon oil spill
Authors: Zengel Scott , Weaver Jennifer , Mendelssohn Irving A. , Graham Sean A. , Lin Qianxin , Hester Mark W. , Willis Jonathan M. , Silliman Brian R. , Fleeger John W. , McClenachan Giovanna , Rabalais Nancy N. , Turner R. Eugene , Hughes A. Randall , Cebrian Just , Deis Donald R. , Rutherford Nicolle , Roberts Brian J.
Published: November 2021

Marine oil spills continue to be a global issue, heightened by spill events such as the 2010 Deepwater Horizon spill in the Gulf of Mexico, the largest marine oil spill in US waters and among the largest worldwide, affecting over 1,000 km of sensitive wetland shorelines, primarily salt marshes supporting numerous ecosystem functions. To synthesize the effects of the oil spill on foundational vegetation species in the salt marsh ecosystem, Spartina alterniflora and Juncus roemerianus, we performed a meta‐analysis using data from 10 studies and 255 sampling sites over seven years post‐spill. We examined the hypotheses that the oil spill reduced plant cover, stem density, vegetation height, aboveground biomass, and belowground biomass, and tracked the degree of effects temporally to estimate recovery time frames. All plant metrics indicated impacts from oiling, with 20–100% maximum reductions depending on oiling level and marsh zone. Peak reductions of ~70–90% in total plant cover, total aboveground biomass, and belowground biomass were observed for heavily oiled sites at the marsh edge. Both Spartina and Juncus were impacted, with Juncus affected to a greater degree. Most plant metrics had recovery time frames of three years or longer, including multiple metrics with incomplete recovery over the duration of our data, at least seven years post‐spill. Belowground biomass was particularly concerning, because it declined over time in contrast with recovery trends in most aboveground metrics, serving as a strong indicator of ongoing impact, limited recovery, and impaired resilience. We conclude that the Deepwater Horizon spill had multiyear impacts on salt marsh vegetation, with full recovery likely to exceed 10 years, particularly in heavily oiled marshes, where erosion may preclude full recovery. Vegetation impacts and delayed recovery is likely to have exerted substantial influences on ecosystem processes and associated species, especially along heavily oiled shorelines. Our synthesis affords a greater understanding of ecosystem impacts and recovery following the Deepwater Horizon oil spill, and informs environmental impact analysis, contingency planning, emergency response, damage assessment, and restoration efforts related to oil spills.
Life‐history strategy and extinction risk in the warm desert perennial spring ephemeral Astragalus holmgreniorum (Fabaceae)
Authors: Van Buren Renée , Searle Allyson B. , Meyer Susan E.
Published: November 2021

This study of Astragalus holmgreniorum examines its adaptations to the warm desert environment and whether these adaptations will enable it to persist. Its spring ephemeral hemicryptophyte life‐history strategy is unusual in warm deserts. We used data from a 22‐year demographic study supplemented with reproductive output, seed bank, and germinant survival studies to examine the population dynamics of this species using discrete‐time stochastic matrix modeling. The model showed that A. holmgreniorum is likely to persist in the warm desert in spite of high dormant‐season mortality. It relies on a stochastically varying environment with high inter‐annual variation in precipitation for persistence, but without a long‐lived seed bank, environmental stochasticity confers no advantage. Episodic high reproductive output and frequent seedling recruitment along with a persistent seed bank are adaptations that facilitate its survival. These adaptations place its life‐history strategy further along the spectrum from “slower” to “faster” relative to other perennial spring ephemerals. The extinction risk for small populations is relatively high even though mean λs > 1 because of the high variance in year quality. This risk is also strongly dependent on seed bank starting values, creating a moving window of extinction risk that varies with population size through time. Astragalus holmgreniorum life‐history strategy combines the perennial spring ephemeral life form with features more characteristic of desert annuals. These adaptations permit persistence in the warm desert environment. A promising conclusion is that new populations of this endangered species can likely be established through direct seeding.
Primary Amine Catalyzed Activation of Carbonyl Compounds: A Study on Reaction Pathways and Reactive Intermediates by Mass Spectrometry
Authors: Iazzetti Antonia , Mazzoccanti Giulia , Bencivenni Giorgio , Righi Paolo , Calcaterra Andrea , Villani Claudio , Ciogli Alessia
Published: November 2021

The field of organocatalysis is expanding at a fast pace. Its growth is sustained by major stimuli, such as the effort toward an understanding of the mechanisms of reaction and catalytic processes in general, the elucidation of basic properties leading to stereocontrol and the search for broad applicability and scalability of the synthetic methodology. This paper reports a thorough study based on ESI‐MS spectrometry of amino‐organocatalyzed model reactions under different experimental conditions. Off‐line reaction monitoring of mixtures containing different catalytic systems, by ESI‐MSn showed the presence of several putative intermediate species, either in their protonated or sodiated forms. In addition, enantioselective chromatography of crude reactions provides the stereochemical outcome of asymmetric reactions. The bulk of the data collected offers a clue of the intricate pathways occurring in solution for the studied reactions.
Economic, Environmental and Social Impact of Carbon Tax for Iran: A Computable General Equilibrium Analysis
Authors: Moosavian Seyed Farhan , Zahedi Rahim , Hajinezhad Ahmad
Published: November 2021

The environmental taxes, such as carbon tax, also affect other economic variables in a different way in addition to the main goal of politicians. The carbon tax aims to reduce energy consumption and pollutant emissions, while it can also reduce labor tax and labor costs which are incentives to create new jobs. It is necessary to evaluate the carbon taxation policy in Iran due to the special circumstances of the budget deficit mainly caused by the decline of exports and oil revenues. The present study is based on a general equilibrium model in the form of a nonlinear equations system. The model has been calibrated for the 2017 reference year using the data table adopted from Iran's economy. It has been shown that if the carbon tax revenue is employed to decrease the labor income tax, the environmental quality will be improved by reducing pollutant emissions on the one hand, and it will lead to positive effects on the welfare and employment on the other hand. In the present paper, the effect of applying this tax on two policies with redistribution (compensation) and without redistribution (no compensation) of income tax among the households is examined. Maximum, minimum, and optimal values of pollutant emissions reduction under the influence of carbon tax policies were calculated in both scenarios. The simulation results show that the taxation without redistribution of tax revenues decreases the welfare and household's actual consumed budget by 6.2%, but in policy with compensation of tax revenue, these indices will increase by 0.8%. The gross domestic product (GDP) decreases by about 1.7% and 2.1% in both policies, respectively, while the consumer price index (CPI) in both scenarios will increase by about 6.4% and 8%, respectively. According to this research findings, carbon taxation with the redistribution of revenue is a suitable policy to reduce greenhouse gas emissions and adhere to international commitments at the same time.
T‐FACE studies reveal that increased temperature exerts an effect opposite to that of elevated CO2 on nutrient concentration and bioavailability in rice and wheat grains
Authors: Guo Xuanhe , Huang Baowei , Zhang Han , Cai Chuang , Li Gang , Li Haozheng , Zhang Yaling , Struik Paul C. , Liu Zijuan , Dong Mingming , Ni Rongbing , Pan Genxing , Liu Xiaoyu , Chen Weiping , Luo Weihong , Yin Xinyou
Published: November 2021

Elevated CO2 concentration has been reported to decrease grain nutrient concentrations and thus worsen nutritional deficiency and hidden hunger. One nutritional aspect is mineral content, yet mineral bioavailability can be limited by the presence of phytic acid. Given that future climate scenarios predict elevated global temperature driven by elevated atmospheric CO2 concentrations, we used Temperature by Free‐Air CO2 Enrichment (T‐FACE) field experiments to investigate whether elevated temperature alters the effects of elevated CO2 on grain mineral concentrations, grain mineral yields, and their bioavailability in a range of wheat and rice genotypes. We found that the negative effects of elevated CO2 were compensated for by positive effects of elevated temperature. As a result, the combined elevated CO2 and elevated temperature increased concentrations of some minerals by up to ~15% in both rice and wheat relative to control conditions. Moreover, the combined elevated CO2 and elevated temperature did not significantly change total yields of some minerals despite lower grain yields. The combined CO2 and temperature elevation increased phytic acid concentration in rice by 18.1% but decreased it in wheat by 3.5%. The mineral bioavailability, estimated as the mole ratio of phytic acid to minerals in rice and wheat grains, was limited by the combined CO2 and temperature elevation in only a few cases. Our results indicate that under future climate conditions of elevated temperature and CO2, the nutritional quality of rice and wheat with respect to minerals may remain unchanged.
The effect of long‐chain alkanes on flavour release and olfactory characteristics of rose essential oil
Authors: Fu Yingjie , Zhang Yipeng , Zeng Shitong , Luo Liwen , Xi Hui , Li Peng , Wang Dingzhong , Liao Tougen , Chen Jiajia , Sun Shihao , Xie Jianping
Published: November 2021

Long‐chain alkanes (LA) are common component of rose essential oil (REO). However, the effect of LA on the olfactory characteristics of REO has not been elaborately reported to date. Herein, we utilized three kinds of REO to explore the role of LA in REO. Accordingly, the models of volatiles and LA were established and applied to investigate the effect of LA on flavour release. By addition of LA, the flavour release decreased from 24.26%~101.39% to −15.44%~9.4%, indicating that the proper constitution and proportion of LA were important factors to approach the original behaviour of REO. Moreover, the impact of LA on sensory perception of REO was also revealed by comparing the odour of flavours in the presence and absence of LA. Results showed a significant difference in Kushui samples (P < .01) and Turkish samples (P < .05). This work systematically illustrated the functions of LA which regulated the flavour release and the scent of REO, enlightening the further research on REO and rose industry production.
Global burden of NAFLD and chronic liver disease among adolescents and young adults
Authors: Paik James M. , Kabbara Khaled , Eberly Katherine E. , Younossi Youssef , Henry Linda , Younossi Zobair M.
Published: November 2021

Background and Aim

The causes of chronic liver disease (CLD) among adults have changed. Data are lacking on trends among youth. We determined the trends and changes in the global burden of CLD among adolescents and young adults using Global Burden of Disease (GBD) data (2009–2019).

Approach and Results

The GBD study estimation methods were used to assess CLD prevalence, incidence, and deaths (21 GBD regions). Annual percent change (APC) calculation by joinpoint regression modeling. Age groups were 15–19, 20–24, and 25–29 years old. Globally in 2019, the 15–29 group accounted for 17.2% (0.29 billion) of CLD prevalent cases, 11.2% (n = 232,072) CLD incident cases, and 3.8% (n = 55,515) CLD deaths. Between 2009 and 2019, CLD prevalence rate increased annually among 25–29 (APC = +0.41%, p < 0.001); remained stable among 20–24 (APC = +0.02%, p = 0.582); and decreased among 15–19 (APC = −2.13%, p < 0.001). CLD prevalence increases were driven by the proportion with NAFLD (15–19: 40.8% to 52.9%, p < 0.001); 20–24: 57.6% to 62.7%, p < 0.001); and 25–29: 66.9% to 70.1%, p < 0.001); the proportion with HBV decreased across all age groups. NAFLD prevalence worsening trend (APC ≥ 0%) was global. Overall CLD death rate decreased annually in all age groups, driven by the decrease in the proportion with HBV [aged 15–19 (from 5.90% to 5.20%, p < 0.001); aged 20–24 (from 18.62% to 16.37%, p < 0.001); and aged 25–29 (from 28.69% to 25.28%, p < 0.001)]; from 2015 to 2019, CLD death rate for HCV (APC = +1.46%) and NAFLD (APC = +2.26%) increased.

Conclusions

Over the past decade, the causes of CLD among 15–29‐year‐olds have shifted: viral hepatitis remains the most common cause of CLD deaths, but the global burden of HBV incidence is decreasing, whereas NAFLD is the main driver for increased CLD incidence.
Dissecting the Balance Between Metabolic and Oncogenic Functions of Astrocyte‐Elevated Gene‐1/Metadherin
Authors: Rajesh Yetirajam , Reghupaty Saranya Chidambaranathan , Mendoza Rachel G. , Manna Debashri , Banerjee Indranil , Subler Mark A. , Weldon Korri , Lai Zhao , Giashuddin Shah , Fisher Paul B. , Sanyal Arun J. , Martin Rebecca K. , Dozmorov Mikhail G. , Windle Jolene J. , Sarkar Devanand
Published: November 2021

Obesity is an enormous global health problem, and obesity‐induced nonalcoholic steatohepatitis (NASH) is contributing to a rising incidence and mortality for hepatocellular carcinoma (HCC). Increase in de novo lipogenesis and decrease in fatty acid β‐oxidation (FAO) underlie hepatic lipid accumulation in NASH. Astrocyte‐elevated gene‐1/metadherin (AEG‐1) overexpression contributes to both NASH and HCC. AEG‐1 harbors an LXXLL motif through which it blocks activation of peroxisome proliferator activated receptor α (PPARα), a key regulator of FAO. To better understand the role of LXXLL motif in mediating AEG‐1 function, using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology, we generated a mouse model (AEG‐1‐L24K/L25H) in which the LXXLL motif in AEG‐1 was mutated to LXXKH. We observed increased activation of PPARα in AEG‐1‐L24K/L25H livers providing partial protection from high‐fat diet–induced steatosis. Interestingly, even with equal gene dosage levels, compared with AEG‐1–wild‐type livers, AEG‐1‐L24K/L25H livers exhibited increase in levels of lipogenic enzymes, mitogenic activity and inflammation, which are attributes observed when AEG‐1 is overexpressed. These findings indicate that while LXXLL motif favors steatotic activity of AEG‐1, it keeps in check inflammatory and oncogenic functions, thus maintaining a homeostasis in AEG‐1 function. AEG‐1 is being increasingly appreciated as a viable target for ameliorating NASH and NASH‐HCC, and as such, in‐depth understanding of the functions and molecular attributes of this molecule is essential. Conclusion: The present study unravels the unique role of the LXXLL motif in mediating the balance between the metabolic and oncogenic functions of AEG‐1.
Are peatlands in different states with respect to their thermodynamic behaviour? A simple test of peatland energy and entropy budgets
Authors: Worrall Fred , Morrison Ross , Evans Chris , Kaduk Joerg , Page Susan , Cumming Alex , Rayment Mark , Kettridge Nicholas
Published: November 2021

Whilst all ecosystems must obey the second law of thermodynamics, these physical bounds and controls on ecosystem evolution and development are largely ignored across the ecohydrological literature. To unravel the importance of these underlying restraints on ecosystem form and function, and their power to inform our scientific understanding, we have calculated the entropy budget of a range of peat ecosystems. We hypothesize that less disturbed peatlands are ‘near equilibrium’ with respect to the second law of thermodynamics and thus respond to change by minimizing entropy production. This ‘near equilibrium’ state is best achieved by limiting evaporative losses. Alternatively, peatlands ‘far‐from‐equilibrium’ respond to a change in energy inputs by maximizing entropy production which is best achieved by increasing evapotranspiration. To test these alternatives this study examined the energy balance time series from seven peatlands across a disturbance gradient. We estimate the entropy budgets for each and determine how a change in net radiation (ΔRn) was transferred to a change in latent heat flux (ΔλE). The study showed that: (i) The transfer of net radiation to latent heat differed significantly between peatlands. One group transferred up to 64% of the change in net radiation to a change in latent heat flux, while the second transferred as little as 27%. (ii) Sites that transferred the most energy to latent heat flux were those that produced the greatest entropy. The study shows that an ecosystem could be ‘near equilibrium’ rather than ‘far from equilibrium’.
Pazopanib with 5‐FU and oxaliplatin as first line therapy in advanced gastric cancer: A randomized phase‐II study—The PaFLO trial. A study of the Arbeitsgemeinschaft Internistische Onkologie AIO‐STO‐0510
Authors: Högner Anica , Al‐Batran Salah‐Eddin , Siveke Jens T. , Lorenz Mario , Bartels Prisca , Breithaupt Kirstin , Malfertheiner Peter , Homann Nils , Stein Alexander , Gläser Dietrich , Tamm Ingo , Hinke Axel , Vogel Arndt , Thuss‐Patience Peter ,   PaFLO investigators
Published: November 2021

VEGF inhibition in gastric cancer has a proven benefit in the second line setting. Pazopanib, an oral tyrosine kinase inhibitor, selectively inhibits VEGFR‐1, ‐2 and ‐3, c‐kit and PDGF‐R resulting in inhibition of angiogenesis. This open‐label randomized phase II trial (2:1) investigated the efficacy of combining pazopanib with FLO (5‐fluorouracil, oxaliplatin) vs FLO alone (internal control arm) as first‐line treatment in patients with advanced adenocarcinoma of the stomach and gastroesophageal junction (GEJ). Eighty‐seven patients were randomized and 78 patients were eligible and evaluable (PaFLO arm 51 patients, FLO arm 27 patients). The PFS rate at 6 months (primary endpoint) was 34% in the PaFLO arm vs 30% in the FLO arm. Comparing PaFLO with FLO median PFS was 4.66 months (95% confidence interval [CI] 2.87‐6.46) vs 4.47 months (95% CI 1.79‐7.14) (95% CI, hazard ratio [HR] 0.96 (0.60‐1.55), P = .882 [exploratory]); median OS was 10.19 months (95% CI 5.46‐14.92) vs 7.33 months (95% CI 4.93‐9.73), (95% CI HR 1.01 [0.62‐1.65], P = .953, exploratory), disease control rate was 72% vs 59%. PaFLO was well tolerable, toxicities were slightly higher in the PaFLO arm. Major adverse events were loss of appetite, nausea, fatigue, diarrhea, neutropenia and thrombocytopenia. Adding pazopanib to chemotherapy shows signs of efficacy but no major improvement in this randomized phase 2 trial. The PFS at 6 months in both arms was lower than expected from the literature. Biomarkers identifying subgroups who benefit and novel combinations are needed. ClinicalTrials.gov: NCT01503372.
Sialic acids in gynecological cancer development and progression: Impact on diagnosis and treatment
Authors: Berghuis Anna Y. , Pijnenborg Johan F. A. , Boltje Thomas J. , Pijnenborg Johanna M. A.
Published: November 2021

Gynecological cancers are in the top 10 of most common cancers in women. Survival and outcome are strongly related to the stage at diagnosis. Therefore, early diagnosis is essential in reducing morbidity and mortality. The high mortality rate of gynecological cancers can mainly be attributed to ovarian cancer (OC). OC is commonly diagnosed at an advanced stage due to a lack of proper screening tools allowing early detection. Endometrial cancer (EC) on the contrary, is mostly diagnosed at an early stage and has, in general, better outcomes. The incidence of nonendometrioid EC has increased in the last decade, displaying a shared tumor biology with OC and consequently significantly worse outcome. New approaches allowing detection of gynecological cancers in an early stage are therefore desired. Recent studies on cancer biology have shown the relevance of altered glycosylation in the occurrence and progression of cancer. The aberrant expression of sialic acid, a specific carbohydrate terminating glycoproteins and glycolipids on the cell‐surface, is frequently correlated with malignancy. We aimed to determine the current understanding of sialic acid function in different gynecological cancers to identify the gaps in knowledge and its potential use for new diagnostic and therapeutic avenues. Therefore we performed a review on current literature focusing on studies where sialylation was linked to gynecological cancers. The identified studies showed elevated levels of sialic acid in serum, tissue and sialylated antigens in most patients with gynecological cancers, underlining its potential for diagnosis.
Statin use and incidence and mortality of breast and gynecology cancer: A cohort study using the National Health Insurance claims database
Authors: Kim Dong‐Sook , Ahn Hyeong Sik , Kim Hyun Jung
Published: November 2021

Previous studies have reported inconsistent findings concerning the impact of statin use on cancer prevention. Our study examined the association between statin use and cancer incidence and mortality related to breast and gynecologic cancers in South Korea. A population‐based cohort study was conducted using the National Health Insurance claims database. Women aged 45 to 70 years old who had taken statins for at least 6 months were compared to statin non‐users of the same age from January 2005 to June 2013. The primary outcomes were cancer incidence and mortality related to breast cancer, total gynecologic cancers, cervix uteri cancer and ovarian cancer. Cox proportional hazards regression was conducted to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). Out of 587 705 women, there were 3591 cases of breast cancer, 2239 cases of gynecologic cancers and 565 breast and total gynecologic cancer deaths during 7.6 person‐years. The aHRs for the association between the risk of each cancer and statin use were 0.88 (95% CI 0.79‐0.97) for breast cancer and 0.83 (95% CI 0.67‐0.99) for cervix uteri cancer. Statin use was associated with decreased breast cancer mortality (HR = 0.65, 95% CI 0.43‐0.99) and total gynecologic cancer mortality (HR = 0.70, 95% CI 0.50‐0.98). A dose‐response relationship was only found for all‐cancer mortality. Statin use for at least 6 months was significantly associated with a lower risk of breast and cervix uteri cancer incidence, and with lower mortality of breast and gynecologic cancers. Further research on these associations will be needed.
BAG3 induces fibroblasts to release key cytokines involved in pancreatic cell migration
Authors: Dufrusine Beatrice , Damiani Verena , Capone Emily , Pieragostino Damiana , Dainese Enrico , De Marco Margot , Reppucci Francesca , Turco Maria C. , Rosati Alessandra , Marzullo Liberato , Sala Gianluca , Sallese Michele , De Laurenzi Vincenzo
Published: November 2021

Pancreatic ductal adenoma carcinoma (PDAC) is considered one of the deadliest solid cancers as it is usually diagnosed in advanced stages and has a poor response to treatment. The enormous effort made in the last 2 decades in the oncology field has not led to significant progress in improving early diagnosis or therapy for PDAC. The stroma of PDAC plays an active role in tumour initiation and progression and includes immune cells and stromal cells. We previously reported that Bcl2‐associated athanogene (BAG3) secreted by PDAC cells activates tumour‐associated macrophages to promote tumour growth. The disruption of this tumour–stroma axis by the anti‐BAG3 H2L4 therapeutic antibody is sufficient to delay tumour growth and limit metastatic spreading in different PDAC preclinical models. In the present study, we examined the role of BAG3 to activate human fibroblasts (HF) in releasing cytokines capable of supporting tumour progression. Treatment of fibroblasts with recombinant BAG3 induced important changes in the organisation of the cytoskeleton of these cells and stimulated the production of interleukin‐6, monocyte chemoattractant protein‐1/C–C motif chemokine ligand 2, and hepatocyte growth factor. Specifically, we observed that BAG3 triggered a depolymerisation of microtubules at the periphery of the cell while they were conserved in the perinuclear area. Conversely, the vimentin‐based intermediate filaments increased and spread to the edges of the cells. Finally, the conditioned medium (CM) collected from BAG3‐treated HF promoted the survival, proliferation, and migration of the PDAC cells. Blocking of the PDAC‐fibroblast axis by the H2L4 therapeutic anti‐BAG3 antibody, resulted in inhibition of cytokine release and, consequently, the inhibition of the migratory phenotype conferred by the CM to PDAC cells.
CIFDock: A novel CHARMM‐based flexible receptor–flexible ligand docking protocol
Authors: Vankayala Sai L. , Warrensford Luke C. , Pittman Amanda R. , Pollard Benjamin C. , Kearns Fiona L. , Larkin Joseph D. , Woodcock H. Lee
Published: November 2021

Docking studies play a critical role in the current workflow of drug discovery. However, limitations may often arise through factors including inadequate ligand sampling, a lack of protein flexibility, scoring function inadequacies (e.g., due to metals, co‐factors, etc.), and difficulty in retaining explicit water molecules. Herein, we present a novel CHARMM‐based induced fit docking (CIFDock) workflow that can circumvent these limitations by employing all‐atom force fields coupled to enhanced sampling molecular dynamics procedures. Self‐guided Langevin dynamics simulations are used to effectively sample relevant ligand conformations, side chain orientations, crystal water positions, and active site residue motion. Protein flexibility is further enhanced by dynamic sampling of side chain orientations using an expandable rotamer library. Steps in the procedure consisting of fixing individual components (e.g., the ligand) while sampling the other components (e.g., the residues in the active site of the protein) allow for the complex to adapt to conformational changes. Ultimately, all components of the complex—the protein, ligand, and waters—are sampled simultaneously and unrestrained with SGLD to capture any induced fit effects. This modular flexible docking procedure is automated using CHARMM scripting, interfaced with SLURM array processing, and parallelized to use the desired number of processors. We validated the CIFDock procedure by performing cross‐docking studies using a data set comprised of 21 pharmaceutically relevant proteins. Five variants of the CHARMM‐based SWISSDOCK scoring functions were created to quantify the results of the final generated poses. Results obtained were comparable to, or in some cases improved upon, commercial docking program data.
Comprehensive analysis of N6‐methyladenosine‐related long non‐coding RNAs for prognosis prediction in liver hepatocellular carcinoma
Authors: Zhu Hong‐Xu , Lu Wen‐Jie , Zhu Wei‐Ping , Yu Song
Published: November 2021

Background

Liver hepatocellular carcinoma (LIHC) is a lethal cancer. This study aimed to identify the N6‐methyladenosine (m6A)‐targeted long non‐coding RNA (lncRNA) related to LIHC prognosis and to develop an m6A‐targeted lncRNA model for prognosis prediction in LIHC.

Methods

The expression matrix of mRNA and lncRNA was obtained, and differentially expressed (DE) mRNAs and lncRNAs between tumor and normal samples were identified. Univariate Cox and pathway enrichment analyses were performed on the m6A‐targeted lncRNAs and the LIHC prognosis‐related m6A‐targeted lncRNAs. Prognostic analysis, immune infiltration, and gene DE analyses were performed on LIHC subgroups, which were obtained from unsupervised clustering analysis. Additionally, a multi‐factor Cox analysis was used to construct a prognostic risk model based on the lncRNAs from the LASSO Cox model. Univariate and multivariate Cox analyses were used to assess prognostic independence.

Results

A total of 5031 significant DEmRNAs and 292 significant DElncRNAs were screened, and 72 LIHC‐specific m6A‐targeted binding lncRNAs were screened. Moreover, a total of 29 LIHC prognosis‐related m6A‐targeted lncRNAs were obtained and enriched in cytoskeletal, spliceosome, and cell cycle pathways. An 11‐m6A‐lncRNA prognostic model was constructed and verified; the top 10 lncRNAs included LINC00152, RP6‐65G23.3, RP11‐620J15.3, RP11‐290F5.1, RP11‐147L13.13, RP11‐923I11.6, AC092171.4, KB‐1460A1.5, LINC00339, and RP11‐119D9.1. Additionally, the two LIHC subgroups, Cluster 1 and Cluster 2, showed significant differences in the immune microenvironment, m6A enzyme genes, and prognosis of LIHC.

Conclusion

The m6A‐lncRNA prognostic model accurately and effectively predicted the prognostic survival of LIHC. Immune cells, immune checkpoints (ICs), and m6A enzyme genes could act as novel therapeutic targets for LIHC.
Ensemble classification of autism spectrum disorder using structural magnetic resonance imaging features
Authors: Zhang‐James Yanli , Buitelaar Jan K. ,   The ENIGMA‐ASD Working Group, van Rooij Daan , Faraone Stephen V.
Published: November 2021

Background

Autism spectrum disorder (ASD) is characterized by a spectrum of social and communication impairments and rigid and stereotyped behaviors that have a neurodevelopmental origin. Although many imaging studies have reported structural and functional alterations in multiple brain regions, clinically useful diagnostic imaging biomarkers for ASD remain unavailable.

Methods

In this study, we applied machine learning (ML) models to regional volumetric and cortical thickness data from the largest structural magnetic resonance imaging (sMRI) dataset available from the Enhancing Neuro Imaging Genetics Through Meta‐Analysis (ENIGMA) consortium (1833 subjects with ASD and 1838 without ASD; age range: 1.5–64; average age: 15.6; male/female ratio: 4.2:1).

Results

The highest classification accuracy on a hold‐out test set was achieved using a stacked Extra Tree Classifier. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.62 (95% confidence interval [CI]: 0.57, 0.68) and the area under the precision‐recall curve was 0.58. Learning curve analysis showed the good fit of the model and suggests that more training examples will not likely benefit model performance.

Conclusions

Our results suggest that sMRI volumetric and cortical thickness data alone may not provide clinically sufficient useful diagnostic biomarkers for ASD. Developing clinically useful imaging classifiers for ASD will benefit from combining other data modalities or feature types, such as functional MRI data and raw images that can leverage other machine learning (ML) techniques such as convolutional neural networks.
Gender diversity and senior leadership in academic dentistry: Female representation at the dean position in the United States
Authors: Bompolaki Despoina , Pokala Sai Vishnu , Koka Sreenivas
Published: November 2021

Purpose/objectives

The purpose of this study was to calculate the male to female dean ratio in the US dental schools, assess whether the dean's gender is affected by specific school characteristics (such as geographic location or class size), and determine whether the dean's gender affects the percent of women in the school leadership team.

Methods

Each US school's website was reviewed to capture the name and gender of each dean and others holding assistant, associate or vice dean positions. All data were entered in an Excel database (Microsoft Excel 2016) and analyzed using a statistical analysis software program (IBM SPSS Statistics, v26; IBM Corp). The level of significance was set to α = 0.05.

Results

The male to female dean ratio (approximately 5:1) differed significantly from the hypothesized ratio 1:1 (z = 5.22, p < 0.001). Mean class size (χ2 = 0.869, p = 0.351) and school funding source (χ2 = 0.430, p = 0.512) did not differ between schools with a male versus female dean. The percentage of women in the school's leadership team was higher in schools with a female dean (U = 151, p = 0.004).

Conclusions

In the US dental schools, there is one female dean for every five deans who are male, indicating underrepresentation of women at the highest role in academic leadership. Schools with female deans tend to have more women in other administrative roles as well. Change is needed in order to promote equity, diversity, and inclusion in academic dentistry.
Improving Sensitivity of Arterial Spin Labeling Perfusion MRI in Alzheimer's Disease Using Transfer Learning of Deep Learning‐Based ASL Denoising
Authors: Zhang Lei , Xie Danfeng , Li Yiran , Camargo Aldo , Song Donghui , Lu Tong , Jeudy Jean , Dreizin David , Melhem Elias R. , Wang Ze ,   Alzheimer's Disease Neuroimaging Initiative
Published: November 2021

Background

Arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) denoising through deep learning (DL) often faces insufficient training data from patients. One solution is to train DL models using healthy subjects' data which are more widely available and transfer them to patients' data.

Purpose

To evaluate the transferability of a DL‐based ASL MRI denoising method (DLASL).

Study Type

Retrospective.

Subjects

Four hundred and twenty‐eight subjects (189 females) from three cohorts.

Field Strength/Sequence

3 T two‐dimensional (2D) echo‐planar imaging (EPI)‐based pseudo‐continuous ASL (PCASL) and 2D EPI‐based pulsed ASL (PASL) sequences.

Assessment

DLASL was trained using young healthy adults' PCASL data (Dataset 1: 250/30 subjects as training/validation set) and was directly transferred (DTF) to PCASL data from Dataset 2 (45 subjects test set) of normal controls (NC) and Alzheimer's disease (AD) groups. DLASL was fine‐tuned (DLASLFT) and tested on PASL data from Dataset 3 (103 subjects test set) of NC and AD. An existing non‐DL method (NonDL) was used for comparison. Cerebral blood flow (CBF) images from ASL MRI were compared between NC and AD to assess characteristic hypoperfusion (lower CBF) patterns in AD. CBF image quality and CBF map sensitivity for detecting hypoperfusion using peak t‐value and suprathreshold cluster size are outcome measures.

Statistical Tests

Paired t‐test, two‐sample t‐test, one‐way analysis of variance, and Tukey honestly significant difference, and linear mixed‐effects models were used. P < 0.05 was considered statistically significant.

Results

Mean contrast‐to‐noise ratio (CNR) of Dataset 2 showed that DTF outperformed NonDL (AD: 3.38 vs. 2.64, NC: 3.80 vs. 3.36). On Dataset 3, DLASLFT outperformed NonDL measured by mean CNR (AD: 2.45 vs. 1.87, NC: 2.54 vs. 2.17) and mean radiologic score (2.86 vs. 2.44). Image quality improvement was significant on both test sets. DTF and DLASLFT improved sensitivity for detecting AD‐related hypoperfusion patterns compared with NonDL.

Data Conclusion

We demonstrated the DLASL's transferability across different ASL sequences and different populations.

Level of Evidence

3

Technical Efficacy

Stage 2
Antioxidant capacity and fragmentation features of C‐glycoside isoflavones by high‐resolution electrospray ionization tandem mass spectrometry using collision‐induced and high‐energy collisional dissociation techniques
Authors: de Moura Patricia Homobono Brito , Porzel Andrea , Nunes Rafaela Machado , Baratto Leopoldo Clemente , Wessjohann Ludger A. , Martins Roberto Carlos Campos , Leal Ivana Correa Ramos
Published: November 2021

The rapid annotation and identification by mass spectrometry techniques of flavonoids remains a challenge, due to their structural diversity and the limited availability of reference standards. This study applies a workflow to characterize two isoflavonoids, the orobol‐C‐glycosides analogs, using high‐energy collisional dissociation (HCD)‐ and collision‐induced dissociation (CID)‐type fragmentation patterns, and also to evaluate the antioxidant effects of these compounds by ferric reducing antioxidant power (FRAP), 2,2′‐azino‐bis(3‐ethylbenzothiazolin acid) 6‐sulfonic acid (ABTS), and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) methods. By the CID‐type fragmentation, in positive mode and at all high‐resolution mass spectrometry (HRMS) multiple stage, there were shown differences in the annotation of the compounds, mainly concerning some ratios of relative abundance. At CID‐MS2 20 eV, the compounds could be efficiently characterized, because they present distinct base peaks [M + H]+ and [M + H–H2O]+ for the orobol‐8‐C‐ and orobol‐6‐C‐glycoside, respectively. Similarly, by the HCD‐type fragmentation, in HRMS2 stage, differences between orobol analogs in both mode of ionization were observed. However, the HR HCD‐MS2 at 80 eV, in positive mode, generated more ions and each isomer presented different base peaks ions, [0,2X]+ for the orobol‐8‐C‐glycoside and [0,3X]+ for the orobol‐6‐C‐glycoside. By the DPPH, the 8‐C‐derivative showed a very close value compared with the standard rutin and, in the ABTS method, a higher radical‐scavenging activity. In both methods, the EC50 of orobol‐8‐C‐glycoside was almost twice better compared with orobol‐6‐C‐glycoside. In FRAP, both C‐glycosides showed a good capacity as Fe+3 reducing agents. We could realize that combined MS techniques, highlighting the positive mode of ionization, can be used to evaluate the isoflavones analogs being useful to differentiate between the isomeric flavones; therefore, these data are important to mass spectrometry dereplication studies become more efficient.

Highlights

The MS2, in positive mode of ionization, at low CID energies (15 and 20 eV) and at high HCD energies (50 eV), was suitable to characterize orobol 8 and 6‐C‐derivatives.

Positive mode of ionization was effective to rapid annotation of each orobol C‐glycoside.

The orobol C‐derivatives showed high radical scavenging effects. Orobol‐8‐C‐glycoside showed higher antioxidant capacity.
Cost‐effectiveness analysis of nasojejunal tube feeding for the prevention of pneumonia in adults who are critically ill
Authors: Wang Hongmei , Huang Chun , Yang Yang , Kong Lingxi , Zheng Xiaoying , Shan Xuefeng
Published: November 2021

Background

Nasojejunal tube (NJT) feeding has demonstrated value in reducing pneumonia in adults who are critically ill who require enteral nutrition (EN) support. This study discusses whether EN support via NJT feeding is more cost‐effective than nasogastric tube (NGT) feeding in reducing pneumonia.

Methods

A decision‐tree model was created. The analysis was based on data from a health care provider in China. Model inputs were derived from published data. The end points included incremental cost per pneumonia infection avoided, incremental cost‐effectiveness ratio (ICER), net monetary benefit (NMB), and incremental NMB (INMB) associated with prevention of pneumonia. The uncertainty was assessed through one‐way and probabilistic sensitivity analysis.

Results

The base case analysis showed that EN support via NJT feeding resulted in 0.7453 quality‐adjusted life years (QALYs) at a cost of $3018.83 compared with NGT feeding, which resulted in 0.7354 QALYs at a cost of $4788.76. NJT feeding was better than NGT feeding, providing an INMB of $2075.09 and an ICER of –$178,813.96 per QALY gained, and the cost per pneumonia infection prevented was $16,808.51. The probabilistic sensitivity analysis indicated that NJT feeding was more cost‐effective in 83.4% of the cases, with a cost below the WTP threshold. The NMB and INMB estimation for different WTP thresholds also indicated that NJT feeding is the optimal strategy.

Conclusions

EN support via NJT feeding was a more cost‐effective strategy than NGT feeding in preventing pneumonia in adults who are critically ill.
Water kefir for weaned piglets: A pilot study on its farm‐scale production, its palatability and its effects on growth performance
Authors: Gangnat Isabelle D. M. , Kreuzer Michael
Published: November 2021

BACKGROUND

Water kefir is a beverage with potential benefits for weaned piglets, including increasing feed intake and being a source of probiotics and organic acids. However, experimental confirmation of this potential is lacking. The aim of this pilot experiment was to develop a method for producing and delivering water kefir to weaned piglets at farm scale, assess its palatability and identify potential side effects in piglets varying in weight.

RESULTS

The method described here is applicable to farm practice, as it could produce >50 L water kefir per day with little investment and time. The lactic acid concentration and pH in the water kefir remained stable between batches, while the acetic acid concentration was more variable. Piglets consumed the total quantity offered, which represented about 1 L per piglet per day. No clinical signs of disease were observed requiring medication administration to the piglets. However, a trend of reduced growth was observed when water kefir was offered, especially in the lighter piglets.

CONCLUSIONS

In addition to its applicability on farms, the water kefir production method facilitates experiments in young livestock under farm‐scale conditions. The health‐promoting potential of water kefir may be increased by elevating the nutrient supply in the culture medium. No critical issue was identified that would prevent the distribution of water kefir to weaned piglets. However, the reason for the trend toward reduced growth and whether this trend would be reversed in situations with greater disease pressure remain unclear.
Preparation of chitosan grafted caffeic acid coating and its effect on pompano (Trachinotus ovatus) preservation
Authors: Sun Yuqing , Lan Weiqing , Liu Shucheng , Guan Yuan , Zhu Shengyun , Xie Jing
Published: November 2021

BACKGROUND

The present study aimed to investigate the preservative effect of chitosan‐caffeic acid grafts coating (CS‐g‐CA) on the quality and microbial characteristics of pompano (Trachinotus ovatus) during iced storage. CS‐g‐CA was prepared by a 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimidehydro/N‐hydroxysuccinimide coupling reaction. The grafting of CS‐g‐CA was confirmed by UV‐visible and Fourier‐transform infrared spectra. Samples were treated with distilled water (control), chitosan (CS), caffeic acid (CA) and CS‐g‐CA for 10 min, respectively. Microbiological [total viable count (TVC), H2S‐producing bacteria count, Pseudomonas bacteria count], physicochemical indicators [water holding capacity (WHC), cooking loss, pH, total volatile basic nitrogen (TVB‐N), thiobarbituric acid (TBA), texture profile analysis, free amino acids] and sensory evaluation were investigated during ice storage at 4 °C for up to 27 days.

RESULTS

The results showed that the antioxidant and antibacterial activities of CS could be improved by grafting CA onto CS. CS‐g‐CA coating could greatly slow down the speed of water loss and maintain WHC. Furthermore, CS‐g‐CA coating showed superior antibacterial activities by inhibiting the growth of TVC, delayed the decline of flavor amino acids and reduced sensory change. In addition, CS‐g‐CA coating reduced lipid oxidation and protein degradation as indicated by the decrease in TBA and TVB‐N, possibly as a result of the addition of CA into CS membrane significantly improving the antioxidant activity of CS.

CONCLUSION

Compared with the control group, CS‐g‐CA coating had the optimal effect and could enhance the shelf‐life of Trachinotus ovatus for at least another 9 days. © 2021 Society of Chemical Industry.