bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of the ATN classification scheme in a population without dementia: Findings from the EPAD cohort
Authors: Ingala Silvia , De Boer Casper , Masselink Larissa A , Vergari Ilaria , Lorenzini Luigi , Blennow Kaj , Chételat Gaël , Di Perri Carol , Ewers Michael , van der Flier Wiesje M , Fox Nick C , Gispert Juan Domingo , Haller Sven , Molinuevo José Luís , Muniz‐Terrera Graciela , Mutsaerts Henri JMM , Ritchie Craig W , Ritchie Karen , Schmidt Mark , Schwarz Adam J , Vermunt Lisa , Waldman Adam D , Wardlaw Joanna , Wink Alle Meije , Wolz Robin , Wottschel Viktor , Scheltens Philip , Visser Pieter Jelle , Barkhof Frederik ,   the EPAD consortium
Published: April 2021

Background

We classified non‐demented European Prevention of Alzheimer's Dementia (EPAD) participants through the amyloid/tau/neurodegeneration (ATN) scheme and assessed their neuropsychological and imaging profiles.

Materials and methods

From 1500 EPAD participants, 312 were excluded. Cerebrospinal fluid cut‐offs of 1000 pg/mL for amyloid beta (Aß)1‐42 and 27 pg/mL for p‐tau181 were validated using Gaussian mixture models. Given strong correlation of p‐tau and t‐tau (R2 = 0.98, P < 0.001), neurodegeneration was defined by age‐adjusted hippocampal volume. Multinomial regressions were used to test whether neuropsychological tests and regional brain volumes could distinguish ATN stages.

Results

Age was 65 ± 7 years, with 58% females and 38% apolipoprotein E (APOE) ε4 carriers; 57.1% were A–T–N–, 32.5% were in the Alzheimer's disease (AD) continuum, and 10.4% suspected non‐Alzheimer's pathology. Age and cerebrovascular burden progressed with biomarker positivity (P < 0.001). Cognitive dysfunction appeared with T+. Paradoxically higher regional gray matter volumes were observed in A+T–N– compared to A–T–N– (P < 0.001).

Discussion

In non‐demented individuals along the AD continuum, p‐tau drives cognitive dysfunction. Memory and language domains are affected in the earliest stages.
Optimization of the cycle time of robotics resistance spot welding for automotive applications
Authors: Banga Harish Kumar , Kalra Parveen , Kumar Raman , Singh Sunpreet , Pruncu Catalin I.
Published: April 2021

In the automobile manufacturing industry, resistance spot welding (RSW) is widely used, especially to build the car's body. The RSW is a standard and wide‐ranging joining technique in several assembling ventures, showing a wide range of possibilities for a competent procedure. Robots are commonly used for spot welding in various industrial applications. After completing assembling design, interest increases to improve the designed processes, cost‐reduction, environmental impact, and increase time productivity when all is said to be done. In this paper, the robot movement between two welding points, a path followed while spotting, gripping and payload‐carrying activities, numbers of holds, moves, and a possibility to enhance interaction between four Robots were analyzed using an offline Robot simulation software “DELMIA‐V5.” The body shop assembly line of the SML ISUZU plant has four robots that perform about 209 welding spots in 532 s. The optimal model reduced the whole welding cycle time by 68 s, and after modification and proper sequencing, a12.7% reduction in cycle time was achieved. The offline Robot simulation software “DELMIA‐V5” has good potential to produce optimal algorithms while saving precious time. It enables an organization to promote higher quality and to encourage meaningful creativity by reducing design flaws.
Evaluation of a Targeted Drug‐Eluting Intravascular Nanotherapy to Prevent Neointimal Hyperplasia in an Atherosclerotic Rat Model
Authors: Newton Emily R. , Gillis David C. , Sun Kui , Dandurand Brooke R. , Siletzky Robin , Biswas Suvendu , Karver Mark R. , Tsihlis Nick D. , Stupp Samuel I. , Kibbe Melina R.
Published: April 2021

Herein the hypothesis that nitric oxide–bearing collagen‐targeted nanofibers will target vascular injury and inhibit neointimal hyperplasia in an atherosclerotic rat model is tested. Western blot confirms the apolipoprotein E (ApoE) knockout (‐/‐) status. Serum cholesterol increases threefold in Sprague Dawley (SD) ApoE‐/‐ versus wt SD rats (291.7 ± 22.3 vs 105.0 ± 3.6 mg dL−1, p < 0.05). Oxidative stress markers are elevated in SD ApoE‐/‐ vs wt SD strains (p = 0.002). Oil Red O staining shows lipid‐rich lesions in SD ApoE‐/‐ aortas. Transmission electron microscopy shows coassembled peptide amphiphiles (PA) form nanofibers. Fluorescence microscopy shows targeting of collagen‐binding peptide (CBP)‐S‐nitrosyl (SNO)‐PA nanofiber to arteries 20 min after injury, whereas uninjured carotid and nontargeted SNO‐PA nanofibers show minimal localization (3444.8 ± 282.0, 11.0 ± 2.3, and 451.4 ± 93.6 arbitrary units, respectively, p < 0.05). Two weeks after injury and injection, CBP‐SNO‐PA nanofibers inhibit neointimal hyperplasia by 67% versus injury alone (p < 0.0001). Intima/media (I/M) ratios are 0.3, 1.0, and 0.9 for CBP‐SNO‐PA nanofiber, scrambled SNO‐PA nanofiber, and injury alone, respectively (p < 0.0001). Results are durable out to 3 months (I/M 0.6 vs 1.4 for CBP‐SNO‐PA vs injury alone, p < 0.0001). Targeted drug‐eluting nanofibers localize to vascular injury, decrease neointimal hyperplasia after 2 weeks, and are durable out to 3 months in an atherosclerotic rat model.
Thermo‐responsive mixed‐matrix hollow fiber membranes
Authors: Götz Tobias , Landzettel Jan , Schiestel Thomas
Published: April 2021

Up to date, preparation of thermo‐responsive mixed‐matrix membranes (MMM) has only be described as small scale flat membranes or multi‐step processes for hollow fiber membranes. In this work, the development of thermo‐responsive MMM hollow fibers composed of polyethersulfone as membrane polymer and poly(N‐isopropylacrylamide) (PNIPAM) microgel particles via the wet spinning process is presented. PNIPAM particles are synthesized with (NP‐S, zavg 20°C = 105 nm) and without (NP‐L, zavg 20°C = 250 nm) sodium dodecyl sulfate and their thermo‐responsive behavior is characterized by dynamic light scattering. Particle size (NP‐S, NP‐L), particle content (10%, 15%) and the extrusion pressure in the wet spinning process (1.0–3.0 bar) are investigated as experimental parameters. Reversible thermo‐responsive behavior of the hollow fibers is demonstrated by water permeability measurements at different temperatures (20 and 50°C). The largest switching factors (R) are observed for the hollow fibers containing NP‐L. For 15% NP‐L and 1 bar extrusion pressure, water permeances between 0.5 and 6.0 L m−2 h−1 bar−1 are observed, corresponding to R = 12 and a dextran (500 kDa) rejection of 91% at 25°C.
Synergetic effect of fly ash cenospheres and multi‐walled carbon nanotubes on mechanical and tribological properties of epoxy resin coatings
Authors: Chen Ping , Wang Yuan , Li Jianchao , Chu Weicheng
Published: April 2021

The multiform wear of friction pair components is the main cause of marine equipment failure and epoxy resin (EP) coatings have been widely used in this field. Fly ash cenospheres (FACs) and multi‐walled carbon nanotubes (MWCNTs) were used to reinforce the tribological properties of EP coatings. The synergetic effects of FACs and MWCNTs on the mechanical and tribological properties of EP coatings were studied. Experimental results show that the tensile and flexural properties of FACs‐MWCNTs/EP composites are significantly reinforced. The tribological performance of EP composite coatings under seawater conditions is improved by the synergetic effect of FACs and MWCNTs, especially, the 10 wt.% FACs‐1 wt.% MWCNTs/EP coatings behave the most excellent tribological properties. It indicates that FACs can increase the hardness of EP coatings and provide a smoother surface for the water film formation, which decreases the friction coefficient and wear volume. MWCNTs can increase the elasticity modulus of EP, and act as a rope to prevent EP matrix and FACs from being desquamated.
Chemical synthesis of NiFe2O4/NG/cellulose nanocomposite and its antibacterial potential against bacterial pathogens
Authors: Anbu Periasamy
Published: April 2021

In this work, a nickel ferrite (NiFe2O4)/nitrogen‐doped‐graphene (NG)/cellulose composite (NiFe2O4/NG/cellulose) was successfully synthesized through a facile chemical route, and its antibacterial potential was evaluated. The synthesized NiFe2O4/NG/cellulose composite was characterized by performing morphological and structural analyses. The results showed the successful formation of NiFe2O4‐nanoparticles with a spherical shape and a size ranging from 15 to 200 nm. Energy‐dispersive X‐ray results confirmed the presence of various elements (carbon, nitrogen, oxygen, iron, and nickel) in the reaction mixture. The X‐ray diffraction pattern showed the face‐centered‐cubic nature of the particles. In addition, antibacterial activity against Escherichia coli (Gram‐negative bacteria) and Bacillus subtilis (Gram‐positive bacteria) was evaluated with different concentrations of NiFe2O4/NG/cellulose composite (0–50 μg/mL). Inhibitory activity increased with increasing concentrations of NiFe2O4/NG/cellulose. The composite's inhibitory activity was slightly higher in E. coli than in B. subtilis due to the differing nature of their cell wall structures. Overall, the chemically synthesized NiFe2O4/NG/cellulose composite has the potential as an efficient antibacterial agent for controlling the growth of pathogenic bacteria.
Novel green synthesis and characterization of a chemotherapeutic supplement by silver nanoparticles containing Berberis thunbergii leaf for the treatment of human pancreatic cancer
Authors: Guo Juan , Li Yihui , Yu Zhi , Chen Lei , Chinnathambi Arunachalam , Almoallim Hesham S. , Alharbi Sulaiman Ali , Liu Linxun
Published: April 2021

In recent years, silver nanoparticles have been used as modern chemotherapeutic drugs to treat several cancers such as pancreatic, breast, prostate, and blood cancers. No previous reports demonstrated the in vitro anti‐human pancreatic cancer effects of the novel chemotherapeutic drug formulated by silver nanoparticles containing Berberis thunbergii leaf (AgNPs). The synthesized AgNPs were characterized using different techniques including UV–vis. and FT‐IR spectroscopy, X‐ray diffraction, scanning electron microscopy (SEM), and TEM. All techniques approved the synthesized silver nanoparticles. The SEM and TEM exhibited a uniform spherical morphology and an average size of about 15 nm for the biosynthesized nanoparticles, respectively. The 4‐(dimethylamino)benzaldehyde,2,2‐diphenyl‐1‐ pikrilhydrazil (DPPH) test revealed similar antioxidant potentials for B. thunbergii leaf aqueous extract, AgNPs, and butylated hydroxytoluene. AgNPs inhibited half of the DPPH molecules in the concentration of 108 μg/mL. To survey the anti‐human pancreatic cancer activities of AgNO3, B. thunbergii leaf aqueous extract, and AgNPs, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay was used on common human pancreatic cancer cell lines. AgNPs had very low cell viability and anti‐human pancreatic cancer effects dose‐dependently against PANC‐1, AsPC‐1, and MIA PaCa‐2. The IC50 values of the AgNPs were 259, 268, and 141 μg/mL against PANC‐1, AsPC‐1, and MIA PaCa‐2 cell lines, respectively. It is thought that the AgNPs obtained can be used as an anticancer drug for the diagnosis of pancreatic cancer in humans after acceptance of the above findings in clinical study trials.
Insights into the effect of hydrolysis medium on the holocellulose decomposition, furfural, and pseudo‐lignin formation
Authors: Zhang Hui , Wang Xinping , Chen Yanxi , Chen Qiuyan , Li Shaolian , Shi Yinan , Cao Shilin , Ma Xiaojuan
Published: April 2021

In this work, four different media including aqueous water, acetic acid (AA), HCl, and H2SO4 were used to hydrolyze holocelluloses. The decomposition of holocellulose and pseudo‐lignin formation are discussed. It was found that AA and water are almost comparable in catalyzing holocellulose (HC) decomposition but the former can promote sugar decomposition and therefore pseudo‐lignin formation. In contrast, HCl and H2SO4 are more efficient in HC decomposition and furfural formation; specifically, HCl is extremely potent for HC decomposition and furfural formation but inert for pseudo‐lignin formation. The results confirmed that both hydrogen ions and anions would affect the carbohydrate decomposition; in this case, further study revealed that only concentrated Cl− in the water system can promote the furfural formation but Cl− with relative low concentration will inhibit pseudo‐lignin formation. It is proved that, Cl− can stabilize the intermediates that facilitate the pseudo lignin formation. © 2021 Society of Industrial Chemistry and John Wiley & Sons Ltd.
OSiD: opening the conceptual design of biobased processes to a context‐sensitive sustainability analysis
Authors: Palmeros Parada Mar , van der Putten Wim , van der Wielen Luuk A M , Osseweijer Patricia , van Loosdrecht Mark , Pashaei Kamali Farahnaz , Posada John A.
Published: April 2021

Biobased production has been promoted as an alternative to fossil‐based production to mitigate climate change. However, emerging concerns over the sustainability of biobased products have shown that tensions can emerge between different objectives and concerns, like emission reduction targets and food security, and that these are dependent on local contexts. Here we present the Open Sustainability‐in‐Design (OSiD) framework, the aim of which is to integrate a context‐sensitive sustainability analysis in the conceptual design of biobased processes. The framework is illustrated, taking as an example the production of sustainable aviation fuel in southeast Brazil. The OSiD framework is a novel concept that brings the perspectives of stakeholders and considerations of the regional context to an ex ante sustainability analysis of biobased production. This work also illustrates a way to integrate methods from different scientific disciplines supporting the analysis of sustainability and the identification of tensions between different sustainability aspects. Making these tensions explicit early in the development of biobased production can make them more responsive to emerging sustainability concerns. Considering the global pressure to reduce carbon emissions, situating sustainability analyses in their socio‐technical contexts as presented here can help to explain and improve the impacts of biobased production in the transition away from fossil resources. © 2021 The Authors. Biofuels, Bioproducts and Biorefining published by Society of Industrial Chemistry and John Wiley & Sons Ltd.
The dietary carcinogen PhIP activates p53‐dependent DNA damage response in the colon of CYP1A‐humanized mice
Authors: Yang Xu , Peng Hongxia , Luo Ziyan , Luo Ailing , Cai Mansi , Xu Ling , Wang Hong
Published: April 2021

Species differences in the metabolism of xenobiotics by cytochrome P450 are critical in evaluating the use of experimental animals in studying toxic compounds relevant to human diseases. 2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), which is produced by high‐temperature cooking of fish and meat, is activated to become a carcinogen by cytochrome P4501A2 (CYP1A2) through N2‐hydroxylation in humans, but is detoxified by Cyp1a2 through 4′‐hydroxylation in mice. CYP1A‐humanized (hCYP1A) mice, in which mouse Cyp1a is replaced with human CYP1A, show constitutive human xenobiotic metabolism by hCYP1A, thereby serving as a suitable model for studying PhIP. Previous studies have demonstrated that oral administration of PhIP induces colon tumors in hCYP1A mice; however, these studies used a super‐high dose, raising concerns regarding the relevance of the mechanism to human cancer. Herein, we systematically investigated PhIP‐induced colon carcinogenesis in hCYP1A mice treated with lower doses. We found that a dose 2000 times lower than that used previously, which is comparable to human daily intake levels, could induce colon tumors, albeit at a lower incidence rate. We further investigated the transcriptome changes in the colon of hCYP1A mice treated with PhIP and identified that PhIP treatment increased the expression of Bax, Btg2, Ccng1, Cdkn1a, and Trp53inp1 and decreased the expression of Igf1 and Ccnd1. Since these genes are key components of the p53‐dependent DNA damage response, the altered expression patterns indicated PhIP‐induced DNA damage in hCYP1A mice. Together, these results prove that hCYP1A mice are suitable for studying PhIP‐induced carcinogenesis and show that PhIP is an important colorectal cancer carcinogen in human diet.
Bioengineering of a CLiP‐derived tubular biliary‐duct‐like structure for bile transport in vitro
Authors: Huang Yu , Sakai Yusuke , Hara Takanobu , Katsuda Takeshi , Ochiya Takahiro , Gu Wei‐Li , Miyamoto Daisuke , Hamada Takashi , Hidaka Masaaki , Kanetaka Kengo , Adachi Tomohiko , Eguchi Susumu
Published: April 2021

The integration of a bile drainage structure into engineered liver tissues is an important issue in the advancement of liver regenerative medicine. Primary biliary cells, which play a vital role in bile metabolite accumulation, are challenging to obtain in vitro because of their low density in the liver. In contrast, large amounts of purified hepatocytes can be easily acquired from rodents. The in vitro chemically induced liver progenitors (CLiPs) from primary mature hepatocytes offer a platform to produce biliary cells abundantly. Here, we generated a functional CLiP‐derived tubular bile duct‐like structure using the chemical conversion technology. We obtained an integrated tubule‐hepatocyte tissue via the direct coculture of hepatocytes on the established tubular biliary‐duct‐like structure. This integrated tubule‐hepatocyte tissue was able to transport the bile, as quantified by the cholyl‐lysyl‐fluorescein assay, which was not observed in the un‐cocultured structure or in the biliary cell monolayer. Furthermore, this in vitro integrated tubule‐hepatocyte tissue exhibited an upregulation of hepatic marker genes. Together, these findings demonstrated the efficiency of the CLiP‐derived tubular biliary‐duct‐like structures regarding the accumulation and transport of bile.
Antibody capture process based on magnetic beads from very high cell density suspension
Authors: Brechmann Nils A. , Schwarz Hubert , Eriksson Per‐Olov , Eriksson Kristofer , Shokri Atefeh , Chotteau Véronique
Published: April 2021

Cell clarification represents a major challenge for the intensification through very high cell density in the production of biopharmaceuticals such as monoclonal antibodies (mAbs). The present report proposes a solution to this challenge in a streamlined process where cell clarification and mAb capture are performed in a single step using magnetic beads coupled with protein A. Capture of mAb from non‐clarified CHO cell suspension showed promising results; however, it has not been demonstrated that it can handle the challenge of very high cell density as observed in intensified fed‐batch cultures. The performances of magnetic bead‐based mAb capture on non‐clarified cell suspension from intensified fed‐batch culture were studied. Capture from a culture at density larger than 100 × 106 cells/ml provided an adsorption efficiency of 99% and an overall yield of 93% with a logarithmic host cell protein (HCP) clearance of ≈2–3 and a resulting HCP concentration ≤≈5 ppm. These results show that direct capture from very high cell density cell suspension is possible without prior processing. This technology, which brings significant benefits in terms of operational cost reduction and performance improvements such as low HCP, can be a powerful tool alleviating the challenge of process intensification.
A mediating role for mental health in associations between COVID‐19‐related self‐stigma, PTSD, quality of life, and insomnia among patients recovered from COVID‐19
Authors: Mahmoudi Hosein , Saffari Mohsen , Movahedi Mahmoud , Sanaeinasab Hormoz , Rashidi‐Jahan Hojat , Pourgholami Morteza , Poorebrahim Ali , Barshan Jalal , Ghiami Milad , Khoshmanesh Saman , Potenza Marc N. , Lin Chung‐Ying , Pakpour Amir H.
Published: April 2021

Introduction

Patients with COVID‐19 often suffer from psychological problems such as post‐traumatic stress disorder (PTSD) and self‐stigmatization that may negatively impact their quality of life and sleep. This study examined mental health as a potential mediating factor linking self‐stigmatization and PTSD to quality of life and sleep.

Methods

Using a cross‐sectional design, 844 people who had recovered from COVID‐19 were called and interviewed. Data were collected using structured scales. Structural equation modeling was applied to assess fitness of a mediation model including self‐stigma and PTSD as independent factors and quality of life and insomnia as dependent variables.

Results

Mental health, COVID‐19‐related self‐stigma, and mental quality of life were associated. Insomnia, PTSD, and COVID‐19‐related self‐stigma displayed significant direct associations (r = .334 to 0.454; p < .01). A mediation model indicated satisfactory goodness of fit (CFI = 0.968, TLI = 0.950, SRMR = 0.071, RMSEA = 0.068). Mental health as a mediator had negative relationships with COVID‐19‐related self‐stigma, PTSD, and insomnia and positive associations with quality of life.

Conclusion

Mental health may mediate effects of COVID‐19‐related self‐stigma and PTSD on quality of life and insomnia. Designing programs to improve mental health among patients with COVID‐19 may include efforts to reduce negative effects of PTSD and COVID‐19‐related self‐stigma on quality of life and insomnia.
Estrogen attenuates physical and psychological stress‐induced cognitive impairments in ovariectomized rats
Authors: Khaleghi Mina , Rajizadeh Mohammad Amin , Bashiri Hamideh , Kohlmeier Kristi Anne , Mohammadi Fatemeh , Khaksari Mohammad , Shabani Mohammad
Published: April 2021

Introduction

Women are more vulnerable to stress‐related disorders than men, which is counterintuitive as female sex hormones, especially estrogen, have been shown to be protective against stress disorders.

Methods

In this study, we investigated whether two different models of stress act differently on ovariectomized (OVX) rats and the impact of estrogen on physical or psychological stress‐induced impairments in cognitive‐behaviors. Adult female Wistar rats at 21–22 weeks of age were utilized for this investigation. Sham and OVX rats were subjected to physical and psychological stress for 1 hr/day for 7 days, and cognitive performance was assessed using morris water maze (MWM) and passive avoidance (PA) tests. The open field and elevated plus maze tests (EPM) evaluated exploratory and anxiety‐like behaviors.

Results

In sham and OVX rats, both physical and psychological stressors were associated with an increase in EPM‐determined anxiety‐like behavior. OVX rats exhibited decreased explorative behavior in comparison with nonstressed sham rats (p < .05). Both physical stress and psychological stress resulted in disrupted spatial cognition as assayed in the MWM (p < .05) and impaired learning and memory as determined by the PA test when the OVX and sham groups were compared with the nonstressed sham group. Estrogen increased explorative behavior, learning and memory (p < .05), and decreased anxiety‐like behavior compared with vehicle in OVX rats exposed to either type of stressor.

Conclusions

When taken together, estrogen and both stressors had opposite effects on memory, anxiety, and PA performance in a rat model of menopause, which has important implications for potential protective effects of estrogen in postmenopausal women exposed to chronic stress.
Cost‐effectiveness analysis of primary human papillomavirus testing in cervical cancer screening: Results from the HPV FOCAL Trial
Authors: Cromwell Ian , Smith Laurie W. , van der Hoek Kim , Hedden Lindsay , Coldman Andrew J. , Cook Darrel , Franco Eduardo L. , Krajden Mel , Martin Ruth , Lee Marette H. , Stuart Gavin , van Niekerk Dirk , Ogilvie Gina , Peacock Stuart
Published: April 2021

The Human Papillomavirus FOr CervicAL cancer (HPV FOCAL) trial is a large randomized controlled trial comparing the efficacy of primary HPV testing to cytology among women in the population‐based Cervix Screening Program in British Columbia, Canada. We conducted a cost‐effectiveness analysis based on the HPV FOCAL trial to estimate the incremental cost per detected high‐grade cervical intraepithelial neoplasia of grade 2 or worse lesions (CIN2+). A total of 19,009 women aged 25 to 65 were randomized to one of two study groups. Women in the intervention group received primary HPV testing with reflex liquid‐based cytology (LBC) upon a positive finding with a screening interval of 48 months. Women in the control group received primary LBC testing, and those negative returned at 24 months for LBC and again at 48 months for exit screening. Both groups received HPV and LBC co‐testing at the 48‐month exit. Incremental costs during the course of the trial were comparable between the intervention and control groups. The intervention group had lower overall costs and detected a larger number of CIN2+ lesions, resulting in a lower mean cost per CIN2+ detected ($7551) than the control group ($8325), a difference of ‐$773 [all costs in 2018 USD]. Cost per detected lesion was sensitive to the costs of sample collection, HPV testing, and LBC testing. The HPV FOCAL Trial results suggest that primary HPV testing every 4 years produces similar outcomes to LBC‐based testing every 2 years for cervical cancer screening at a lower cost.
Phase 1b study of galunisertib and ramucirumab in patients with advanced hepatocellular carcinoma
Authors: Harding James J. , Do Richard K. , Yaqubie Amin , Cleverly Ann , Zhao Yumin , Gueorguieva Ivelina , Lahn Michael , Benhadji Karim A. , Kelley Robin K. , Abou‐Alfa Ghassan K.
Published: April 2021

Background

Preclinical data suggest that vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)‐β signaling interact to stimulate angiogenesis and suppress antitumor immune responses. Thus, combined inhibition of both pathways may offer greater antitumor activity compared with VEGF‐targeted antiangiogenic monotherapy against hepatocellular carcinoma (HCC).

Methods

This is a multicenter, open‐label, phase 1b study of galunisertib, an inhibitor of TGF‐β receptor 1, and ramucirumab, an anti‐VEGF receptor 2 antibody, in patients with advanced HCC aiming to define the maximum tolerated dose (MTD). Secondary objectives included safety, pharmacokinetics (PK), antitumor efficacy, and plasma alpha‐fetoprotein and TGF‐β kinetics. Dose escalation employed a 3 + 3 design. Patients received galunisertib at 80 mg (cohort 1) or 150 mg (cohort 2) orally twice a day on days 1–14 of a 28‐day cycle combined with ramucirumab 8 mg/kg intravenously every 2 weeks.

Results

Eight patients were enrolled: three in cohort 1 and five in cohort 2 (two patients were unevaluable due to rapid disease progression and replaced). No dose‐limiting toxicities were observed. Treatment‐related adverse events (AEs) of any grade in ≥2 patients included nausea (25%) and vomiting (25%). There was one Grade 3 treatment‐related AE, a cerebrovascular accident possibly related to ramucirumab. Galunisertib exposure was dose‐proportional and not affected by ramucirumab. The RECIST version 1.1 objective response rate and disease control rate were 0% and 12.5%, respectively.

Conclusion

Combination therapy was safe and tolerable and displayed favorable PK. The MTD was established at galunisertib at 150 mg orally twice a day and ramucirumab 8 mg/kg intravenously every 2 weeks. The results do not support the preclinical hypothesis that blocking TGFβ signaling enhances efficacy of VEGF‐targeted therapy; thus further clinical development was halted for the combination of galunisertib and ramucirumab.
Iodine‐Catalyzed Diels‐Alder Reactions
Authors: Arndt Thiemo , Wagner Philip K. , Koenig Jonas J. , Breugst Martin
Published: April 2021

The Diels‐Alder cycloaddition is the most popular pericyclic reaction with numerous applications in synthesis and catalysis. We now demonstrate that we can perform this reaction under mild and metal‐free conditions relying on molecular iodine as the catalyst. Cycloadditions with cyclohexadiene, cyclopentadiene, or isoprene with various dienophiles can be performed typically within minutes in moderate to good yields and high endo selectivity. The mechanistic studies including kinetic and DFT investigations clearly indicate a halogen‐bond activation and rule out other modes of activation. Furthermore, iodine performs equally well as typical metallic Lewis acids like AlCl3, SnCl4, or TiCl4.
Analysis of Non‐innocence of Phosphaquinodimethane Ligands when Charge and Aromaticity Come into Play
Authors: Junker Philip , Rey Planells Alicia , Espinosa Ferao Arturo , Streubel Rainer
Published: April 2021

Several phosphaquinodimethanes and their M(CO)5 complexes (M=Cr, Mo, W) and model derivatives have been theoretically investigated regarding the quest of non‐innocence. Computed structural and electronic properties of the P‐Me/NH2 substituted phosphaquinodimethanes and tungsten complexes revealed an interesting non‐innocent ligand behaviour for the radical anion complexes with distonic ion character and a strong rearomatization of the middle phenyl ring. The latter was further probed taking also geometric aromaticity (HOMA) and quinoid distortion parameters (HOMQc) into account, as well as NICS(1). Furthermore, the effect of the P‐substitution was investigated for real (or plausible) complexes and their free ligands focusing on the resulting aromaticity at the middle phenyl ring and vertical one‐electron redox processes. The best picture of ligand engagement in redox changes was provided by representing NICS(1) values versus HOMA and the new geometric distortion parameter HOMQc8.
CO2 Capture by Hydroxylated Azine‐Based Covalent Organic Frameworks
Authors: Maia Renata Avena , Lopes Oliveira Felipe , Ritleng Vincent , Wang Qiang , Louis Benoît , Mothé Esteves Pierre
Published: April 2021

Covalent organic frameworks (COFs) RIO‐13, RIO‐12, RIO‐11, and RIO‐11m were investigated towards their CO2 capture properties by thermogravimetric analysis at 1 atm and 40 °C. These microporous COFs bear in common the azine backbone composed of hydroxy‐benzene moieties but differ in the relative number of hydroxyl groups present in each material. Thus, their sorption capacities were studied as a function of their textural and chemical properties. Their maximum CO2 uptake values showed a strong correlation with an increasing specific surface area, but that property alone could not fully explain the CO2 uptake data. Hence, the specific CO2 uptake, combined with DFT calculations, indicated that the relative number of hydroxyl groups in the COF backbone acts as an adsorption threshold, as the hydroxyl groups were indeed identified as relevant adsorption sites in all the studied COFs. Additionally, the best performing COF was thoroughly investigated, experimentally and theoretically, for its CO2 capture properties in a variety of CO2 concentrations and temperatures, and showed excellent isothermal recyclability up to 3 cycles.
DNA‐Encoded Libraries: Hydrazide as a Pluripotent Precursor for On‐DNA Synthesis of Various Azole Derivatives
Authors: Ma Fei , Li Jie , Zhang Shuning , Gu Yuang , Tan Tingting , Chen Wanting , Wang Shuyue , Ma Peixiang , Xu Hongtao , Yang Guang , Lerner Richard A.
Published: April 2021

DNA‐encoded combinatorial chemical library (DEL) technology, an approach that combines the power of genetics and chemistry, has emerged as an invaluable tool in drug discovery. Skeletal diversity plays a fundamental importance in DEL applications, and relies heavily on novel DNA‐compatible chemical reactions. We report herein a phylogenic chemical transformation strategy using DNA‐conjugated benzoyl hydrazine as a common versatile precursor in azole chemical expansion of DELs. DNA‐compatible reactions deriving from the common benzoyl hydrazine precursor showed excellent functional group tolerance with exceptional efficiency in the synthesis of various azoles, including oxadiazoles, thiadiazoles, and triazoles, under mild reaction conditions. The phylogenic chemical transformation strategy provides DELs a facile way to expand into various unique chemical spaces with privileged scaffolds and pharmacophores.
Die Vorzüge der selbst kompensierenden Messung
Authors: Kasper Stefan
Published: April 2021

Nach Ankunft des Rohöls muss das Wasser aus der Emulsion entfernt werden. Vegaflex‐Sensoren helfen, dass die Trennung der Wasser‐ und Ölschicht effektiv abläuft.
Neue Lösung für vorausschauende Wartung
Authors: Huber Cornelia
Published: April 2021

Bei der Echtzeit‐Datenanalyse identifiziert ABB Ability Condition Monitoring for measurement devices Probleme von Messgeräten frühzeitig und macht so auf wichtige oder unerwünschte Änderungen des Gerätezustands aufmerksam.
Funktionale Sicherheit für Tankanlagen
Authors: Garbsch Matthias
Published: April 2021

Die Themen SIL (Safety Integrity Level) und PL (Performance Level) gewinnen in der Prozessindustrie und im Maschinen‐ und Anlagenbau eine immer wesentlichere Bedeutung. Doch Anwender stehen in der Praxis hier oft vor komplexen Herausforderungen. JUMO bünd
Wertvolle Unterstützung
Authors: Schulte Manfred
Published: April 2021

Im Zusammenhang mit der CE‐Kennzeichnung einer Gesamtheit von Maschinen, die für den Eigengebrauch hergestellt wird, stellt sich oftmals die Frage, wie die rechtlichen Anforderungen der Richtlinie 2006/42/EG für Maschinen (MRL) eingehalten sowie damit ver
Kleine Box mit großem Inhalt
Authors: Krause Peter
Published: April 2021

Mit digital vernetzter Filtertechnik lassen sich optimale Prozesse gestalten und Mehrwertdienste generieren. Dazu notwendig ist ein Filtercontroller, der in Kombination mit zusätzlicher Sensorik und einer IT‐Infrastruktur Prozessparameter in Echtzeit visu
Fördergeld für Energiesparer
Authors: Jeschabek Ralph
Published: April 2021

Die Firma Ziegler fertigt hochpräzise Komponenten für die Flugzeug‐ und Automobilindustrie. Druckluft ist dabei in allen Maschinen im Einsatz. Weil deren Anzahl mit den Jahren zunahm, stießen die bisherigen vier Schraubenkompressoren an ihre Grenzen. ALMi
Latente Talente
Authors: Ruppelt Erwin
Published: April 2021

Vielen ist inzwischen bekannt, dass Druckluft, die in der Industrie eingesetzt wird, aus wirtschaftlichen Gesichtspunkten so gut wie immer aufbereitet werden sollte. Kältetrocknung ist dabei das wichtigste Aufbereitungsverfahren. Neue Technologien ermögli
Druckluft ohne Kompromisse
Authors: Hilton Britta
Published: April 2021

CompAir hat neue ölgeschmierten Schraubenkompressoren der L‐Serie eingeführt. Verglichen mit Vorgängern arbeiten sie 8 % effizienter und erzielen 5 % höhere Liefermengen.
Variantenreich
Authors: Meißler Sebastian
Published: April 2021

Auch bei der Steuerung von Gebläsen und Kompressoren bietet die Integration digitaler Anwendungen ein großes Potenzial zur Steigerung der Maschinenverfügbarkeit, Ausfallsicherheit und Informationstransparenz in der übergeordneten Steuerung des Maschinenbe
Design, Synthesis and Biological Evaluation of Novel α‐Acyloxycarboxamide‐Based Derivatives as c‐Met Inhibitors
Authors: Feng Yu‐juan , Ren Yu‐Lin , Zhao Li‐Ming , Xue Guo‐Qiang , Yu Wen‐Hao , Yang Jia‐Qi , Liu Jun‐Wei
Published: April 2021

Main observation and conclusion

Dysregulated HGF/c‐Met signalling has been associated with many human cancers, poor clinical outcomes, and even resistance acquisition to some approved targeted therapies. As such, c‐Met kinase has emerged as an attractive target for anticancer drug discovery. Herein, a series of 6,7‐disubstitued‐4‐(2‐fluorophenoxy)quinoline derivatives bearing α‐acyloxycarboxamide moiety were designed, synthesized via Passerini reaction as the key step, and evaluated for their in vitro biological activities against c‐Met kinase and five selected cancer cell lines. The preliminary structure‐activity relationship demonstrated that α‐acyloxycarboxamide as the 5‐atom linker maintained the potent antitumor potency. Among these compounds, compound 25s (c‐Met IC50 = 4.06 nmol/L) was identified as the most promising lead compound and displayed the most potent antiproliferative activities against A549, HT‐29 and MDA‐MB‐231 cell lines with IC50 of 0.39, 0.20, and 0.58 μmol/L, which were 1.3‐, 1.4‐ and 1.2‐fold superior to foretinib, respectively. The further studies indicated that compound 25s can induce apoptosis of A549 cells and arrest efficiently the cell cycle distribution in G2/M phase of A549 cells. Moreover, compound 25s can also inhibit c‐Met phosphorylation in A549 cells by a dose‐dependent manner. Collectively, these results indicated that compound 25s could be a potential anticancer lead compound deserving for further development.
Natural and Synthetic Fiber‐Based Adsorbents for Water Remediation
Authors: Candido Iuri Custodio Montes , Pires Indira Carolina Brito , de Oliveira Helinando Pequeno
Published: April 2021

The use of unmodified and chemically treated natural fibers for water remediation (removal of chemical residues/oil spills and organic wastewater from water) is a significant and low‐cost strategy to reduce the contamination of aquifers with metal ions, as well as marine environments with oil spills and water bodies with organic dyes. Furthermore, synthetic fibers exhibit a superior performance owing to their tunable surface area and superhydrophobic/swelling properties. This review summarizes the most recent advances in natural fiber‐based biosorbents and synthetic fiber mats since the efficient removal of toxic compounds depend on adequate incorporation of functional groups on the fiber surface for mutual electrostatic and diffusion of contaminants into the fibrils. The most relevant results in the removal of oil, trace metal ions, and organic dyes are presented and evaluated. The evaluation is done according to the strategies for chemical modification of raw materials by the reuse of plastics or conventional electrospinning techniques to support the hierarchical growth of more complex chemical structures.
Influence of Metalaxyl and CGA 62828 Adsorption on the Leaching Behavior of Metal‐Contaminated Soils
Authors: Bassil Joseph , Azzi Valérie , Naveau Aude , Menhem Tony , Rizk Ibtihaj , El Samrani Antoine G.
Published: April 2021

Pesticides’ degradation in the environment affects their persistence and their environmental impact. In this study, batch experiments are performed to investigate 1) the adsorption of a fungicide, metalaxyl, and its main acid metabolite (CGA 62828) onto the surface of two different soils collected in the metal‐contaminated bay of an industrial area and 2) the influence of these two molecules on the leaching of soluble bases, iron and zinc, from the studied soils. In ultrapure water, adsorption isotherms show that the amount of CGA 62828 adsorbed by the soil particles are higher than the amount of metalaxyl. Furthermore, higher amount of these two molecules are adsorbed at a slower rate by the well‐drained soil in comparison with the more polluted saline anthroposol. In contrary to metalaxyl, CGA 62828 favors the release of the bases K, Na, and Ca by the saline soil in contact with ultrapure water. CGA 62828 also tends to limit the Fe and Zn release which are favored in the presence of metalaxyl. The composition of the local tap water did not significantly influence the adsorbed quantities of metalaxyl and CGA 62828 despite its impact on the Fe and Zn leaching.
Science's Response to CoVID‐19
Authors: Long Marcus J. C. , Aye Yimon
Published: April 2021

CoVID‐19 is a multi‐symptomatic disease which has made a global impact due to its ability to spread rapidly, and its relatively high mortality rate. Beyond the heroic efforts to develop vaccines, which we do not discuss herein, the response of scientists and clinicians to this complex problem has reflected the need to detect CoVID‐19 rapidly, to diagnose patients likely to show adverse symptoms, and to treat severe and critical CoVID‐19. Here we aim to encapsulate these varied and sometimes conflicting approaches and the resulting data in terms of chemistry and biology. In the process we highlight emerging concepts, and potential future applications that may arise out of this immense effort.
A NIR fluorescent smart probe for imaging tumor hypoxia
Authors: Hettie Kenneth S. , Klockow Jessica L. , Moon Eui Jung , Giaccia Amato J. , Chin Frederick T.
Published: April 2021

Background

Tumor hypoxia is a characteristic of paramount importance due to low oxygenation levels in tissue negatively correlating with resistance to traditional therapies. The ability to noninvasively identify such could provide for personalized treatment(s) and enhance survival rates. Accordingly, we recently developed an NIR fluorescent hypoxia‐sensitive smart probe (NO2‐Rosol) for identifying hypoxia via selectively imaging nitroreductase (NTR) activity, which could correlate to oxygen deprivation levels in cells, thereby serving as a proxy. We demonstrated proof of concept by subjecting a glioblastoma (GBM) cell line to extreme stress by evaluating such under radiobiological hypoxic (pO2 ≤ ~0.5%) conditions, which is a far cry from representative levels for hypoxia for brain glioma (pO2 = ~1.7%) which fluctuate little from physiological hypoxic (pO2 = 1.0‐3.0%) conditions.

Aim

We aimed to evaluate the robustness, suitability, and feasibility of NO2‐Rosol for imaging hypoxia in vitro and in vivo via assessing NTR activity in diverse GBM models under relevant oxygenation levels (pO2 = 2.0%) within physiological hypoxic conditions that mimic oxygenation levels in GBM tumor tissue in the brain.

Methods

We evaluated multiple GBM cell lines to determine their relative sensitivity to oxygenation levels via measuring carbonic anhydrase IX (CAIX) levels, which is a surrogate marker for indirectly identifying hypoxia by reporting on oxygen deprivation levels and upregulated NTR activity. We evaluated for hypoxia via measuring NTR activity when employing NO2‐Rosol in in vitro and tumor hypoxia imaging studies in vivo.

Results

The GBM39 cell line demonstrated the highest CAIX expression under hypoxic conditions representing that of GBM in the brain. NO2‐Rosol displayed an 8‐fold fluorescence enhancement when evaluated in GBM39 cells (pO2 = 2.0%), thereby establishing its robustness and suitability for imaging hypoxia under relevant physiological conditions. We demonstrated the feasibility of NO2‐Rosol to afford tumor hypoxia imaging in vivo via it demonstrating a tumor‐to‐background of 5 upon (i) diffusion throughout, (ii) bioreductive activation by NTR activity in, and (iii) retention within, GBM39 tumor tissue.

Conclusion

We established the robustness, suitability, and feasibility of NO2‐Rosol for imaging hypoxia under relevant oxygenation levels in vitro and in vivo via assessing NTR activity in GBM39 models.
Security mechanism for maritime territory and frontier surveillance in naval operations using wireless sensor networks
Authors: Jain Usha , Hussain Muzzammil
Published: April 2021

In an underwater environment, wireless sensor networks (WSNs) have more potential applications such as homeland safety, naval surveillance, and pollution & exploration monitoring. Underwater wireless sensor networks (UWSNs) help in decreasing the rate of causalities and provide efficient ways for monitoring the underwater activities of the other countries. UWSNs can be efficiently used by the navy to monitor suspicious activities and also to counter‐attack any terrorist or enemy attacks. As usual, deploying wireless sensor networks underwater is not only challenging due to environment and constrained resources but also is vulnerable to security attacks. Thus, security is an unexplored and crucial aspect of UWSNs. Here, we define a node authentication mechanism for UWSNs for securing frontier lines, maritime territory, and naval surveillance. The proposed authentication protocol is based on symmetric‐key cryptography and secures against impersonation, masquerade, Sybil, and many more other attacks. We have analyzed the proposed protocol both formally and automatedly and were unable to find any possible security attack on the proposed protocol. The experimental analysis of the mechanism proved that the proposed mechanism consumes less energy compared to the existing mechanisms. Hence, the proposed mechanism can be easily adopted for maintaining the security of maritime territory and reduce the causalities in naval operations.
Accelerating real‐time object detection in high‐resolution video surveillance
Authors: Wang Yuefeng , Mao Kuang , Chen Tong , Yin Yanglong , He Shuibing , Chen Gang
Published: April 2021

As various algorithms and models spring up, object detection‐based deep learning for image analysis has become an established technology in the field of computer vision. Furthermore, object detection for high‐resolution videos derived from ubiquitous surveillance cameras draws many researchers' attention due to its practical significance and the challenge on detecting accuracy and speed. Existing object detection methods mainly resize and compress each frame in the video and then apply the detection algorithm, but with the method, the detection for small objects in dense scenes is far from satisfactory in terms of accuracy because small objects are reduced to pixel‐level sizes in compressed frame images. In order to fix this issue, we propose AROD, a parallel detection framework based on adaptive image cropping. Unlike the traditional first‐compression‐and‐then‐detection methods, AROD adopts adaptive image cropping for distributed parallel detection. In this way, AROD significantly improves the accuracy of small object detection in dense scenes with acceptable overhead. In our experimental evaluation, YOLOv2‐tiny model equipped with AROD reaches 29.29 FPS along with high detection accuracy. Experimental results verify that AROD ensures the high throughput of real‐time video analytics while maintaining high detection accuracy.
Bi4O5BrI Solid Solution towards Boosted Photocatalytic Reduction and Oxidation Activities Induced by Efficient Carrier Separation
Authors: Zhang Jia , Wang Zhen , Liu Lu , Hu Baorong , Zhao Yilei , Zhao Shuang , Zhao Wenting , Li Shuang , Chen Xi , Hai Xin
Published: April 2021

Semiconductor photocatalysis is considered a promising technology for destroying pollutants, while the faint carrier separation efficiency of the photocatalyst is one of the main limitations for obtaining high performance. This study reports a solid solution strategy to achieve effective carrier separation in Bi4O5BrxI2−x. The solid solution structure endows Bi4O5BrxI2−x with proper light adsorption, tunable band gap, and effective separation of photogenerated electrons and holes. As a result, Bi4O5BrxI2−x exhibits reduction and oxidation activities for highly efficient photocatalytic Cr(VI) reduction and tetracycline hydrochloride (HTC) degradation under visible light irradiation, with the activity reaching the maximum at x = 1. Within 30 min, the removal rates of Cr(VI) and HTC reach 90% and 100%, respectively. This study not only provides an effective strategy to increase the carrier separation of bismuth‐based semiconductors, but also opens new opportunities to rationally design other solid solution catalysts with high performance in wastewater treatment.
Advances in Versatile Nanoscale Catalyst for the Reductive Catalytic Fractionation of Lignin
Authors: Zhang Haichuan , Fu Shiyu , Du Xu , Deng Yulin
Published: April 2021

In the past five years, biomass‐derived biofuels and biochemicals were widely studied both in academia and industry as promising alternatives to petroleum. In this Review, the latest progress of the synthesis and fabrication of porous nanocatalysts that are used in catalytic transformations involving hydrogenolysis of lignin is reviewed in terms of their textural properties, catalytic activities, and stabilities. A particular emphasis is made with regard to the catalyst design for the hydrogenolysis of lignin and/or lignin model compounds. Furthermore, the effects of different supports on the lignin hydrogenolysis/hydrogenation are discussed in detail. Finally, the challenges and future opportunities of lignin hydrogenolysis over nanomaterial‐supported catalysts are also presented.