bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies to Reduce the On‐Target Platelet Toxicity of Bcl‐xL Inhibitors: PROTACs, SNIPERs and Prodrug‐Based Approaches
Authors: Negi Arvind , Voisin‐Chiret Anne Sophie
Published: March 2022

Apoptosis is a highly regulated cellular process. Aberration in apoptosis is a common characteristic of various disorders. Therefore, proteins involved in apoptosis are prime targets in multiple therapies. Bcl‐xL is an antiapoptotic protein. Compared to other antiapoptotic proteins, the expression of Bcl‐xL is common in solid tumors and, to an extent, in some leukemias and lymphomas. The overexpression of Bcl‐xL is also linked to survival and chemoresistance in cancer and senescent cells. Therefore, Bcl‐xL is a promising anticancer and senolytic target. Various nanomolar range Bcl‐xL inhibitors have been developed. ABT‐263 was successfully identified as a Bcl‐xL/Bcl‐2 dual inhibitor. But it failed in the clinical trial (phase‐II) because of its on‐target platelet toxicity, which also implies an essential role of Bcl‐xL protein in the survival of human platelets. Classical Bcl‐xL inhibitor designs utilize occupancy‐driven pharmacology with typical shortcomings (such as dose‐dependent off‐target and on‐target platelet toxicities). Hence, event‐driven pharmacology‐based approaches, such as proteolysis targeting chimeras (PROTACs) and SNIPERs (specific non‐genetic IAP‐based protein erasers) have been developed. The development of Bcl‐xL based PROTACs was expected, as 600 E3‐ligases are available in humans, while some (such as cereblon (CRBN), von Hippel‐Lindau (VHL)) are relatively less expressed in platelets. Therefore, E3 ligase ligand‐based Bcl‐xL PROTACs (CRBN: XZ424, XZ739; VHL: DT2216, PZ703b, 753b) showed a significant improvement in platelet therapeutic index than their parent molecules (ABT‐263: DT2216, PZ703b, 753b, XZ739, PZ15227; A1155463: XZ424). Other than their distinctive pharmacology, PROTACs are molecularly large, which limits their cell permeability and plays a role in improving their cell selectivity. We also discuss prodrug‐based approaches, such as antibody‐drug conjugates (ABBV‐155), phosphate prodrugs (APG‐1252), dendrimer conjugate (AZD0466), and glycosylated conjugates (Nav‐Gal). Studies of in‐vitro, in‐vivo, structure‐activity relationships, biophysical characterization, and status of preclinical/clinical inhibitors derived from these strategies are also discussed in the review.
Prediction of wheat quality parameters combining Raman, fluorescence, and near‐infrared spectroscopy (NIRS)
Authors: Nagel‐Held Johannes , Kaiser Leonie , Longin Carl Friedrich Horst , Hitzmann Bernd
Published: March 2022

Background and Objectives

A high amount of the world wheat production is used for bread making. Due to its simplicity, wheat samples are traded based on protein content, although this is only an indirect measurement of baking quality. As direct bread quality traits like loaf volume, water absorption, and dough properties are cumbersome to measure along wheat supply chains and in wheat breeding programs, this study aims to predict directly dough properties and baking behavior by combining complementary information from near‐infrared, Raman, and fluorescence spectroscopy. Several proven data preprocessing and regression algorithms were evaluated, including partial least‐squares regression (PLSR) and genetic algorithm (GA).

Findings

A highly diverse sample set of 415 wheat samples from a wheat hybrid breeding program was analyzed as whole grain, whole grain flour, and extracted flour. The best predictive models yielded a 10‐fold cross‐validated coefficient of determination R2 of .973, .873, .774, .835, .369, .447, .311, .512, .536, .723, and .715 for protein content, wet gluten, loaf volume, water uptake, elongation resistance to extension, extensibility, ratio number, extensograph energy, maltose number, plant height, and grain yield, respectively.

Conclusion

The prediction accuracies are well suited for screening purposes in wheat breeding and allow better quality assessment compared to protein content along wheat supply chains.

Significance and Novelty

In this study, complementary spectroscopic techniques are combined for the first time to achieve higher prediction accuracy for a wide range of wheat quality parameters. In addition, Raman and fluorescence spectroscopy were used to predict quality data from a large sample set.
Disclosing Cyclic(Alkyl)(Amino)Carbenes as One‐Electron Reductants: Synthesis of Acyclic(Amino)(Aryl)Carbene‐Based Kekulé Diradicaloids
Authors: Maiti Avijit , Elvers Benedict J. , Bera Sachinath , Lindl Felix , Krummenacher Ivo , Ghosh Prasanta , Braunschweig Holger , Yildiz Cem B. , Schulzke Carola , Jana Anukul
Published: March 2022

Herein, we disclose cyclic(alkyl)(amino)carbenes (CAACs) to be one‐electron reductants under the formation of a transient radical cation as indicated by EPR spectroscopy. The disclosed CAAC reducing reactivity was used to synthesize acyclic(amino)(aryl)carbene‐based Thiele and Chichibabin hydrocarbons, a new class of Kekulé diradicaloids. The results demonstrate CAACs to be potent organic reductants. Notably, the acyclic(amino)(aryl)carbene‐based Chichibabin's hydrocarbon shows an appreciable population of the triplet state at room temperature, as evidenced by both variable‐temperature NMR and EPR spectroscopy.
Ligand‐Induced Donor State Destabilisation – A New Route to Panchromatically Absorbing Cu(I) Complexes
Authors: Tran Jens H. , Traber Philipp , Seidler Bianca , Görls Helmar , Gräfe Stefanie , Schulz Martin
Published: March 2022

The intense absorption of light to covering a large part of the visible spectrum is highly desirable for solar energy conversion schemes. To this end, we have developed novel anionic bis(4H‐imidazolato)Cu(I) complexes (cuprates), which feature intense, panchromatic light absorption properties throughout the visible spectrum and into the NIR region with extinction coefficients up to 28,000 M−1 cm−1. Steady‐state absorption, (spectro)electrochemical and theoretical investigations reveal low energy (Vis to NIR) metal‐to‐ligand charge‐transfer absorption bands, which are a consequence of destabilized copper‐based donor states. These high‐lying copper‐based states are induced by the σ‐donation of the chelating anionic ligands, which also feature low energy acceptor states. The optical properties are reflected in very low, copper‐based oxidation potentials and three ligand‐based reduction events. These electronic features reveal a new route to panchromatically absorbing Cu(I) complexes.
Stereodivergent Desymmetrization of Simple Dicarboxylates via Branch‐Selective Pd/Cu Catalyzed Allylic Substitution
Authors: Li Guanlin , Zhao Ling , Luo Yicong , Peng Youbin , Xu Kai , Huo Xiaohong , Zhang Wanbin
Published: March 2022

Asymmetric desymmetrization has been demonstrated to be a powerful strategy for building stereocenters in asymmetric synthesis. Herein, a Pd/Cu catalyzed asymmetric desymmetrization reaction with a simple geminal dicarboxylate is reported. A wide scope of imino esters bearing an aryl or heteroaromatic group were compatible with this bimetallic catalytic system. The reactions proceeded smoothly, giving the desired products in good yields with high to excellent regio‐, diastereo‐, and enantioselectivity (up to 20 : 1 branched:linear, >20 : 1 dr, >99 % ee). Notably, the reaction favored branched selectivity, which is unusual for the Pd‐catalyzed allylic alkylation reaction. In addition, the standard product could be easily transformed to other valuable molecules such as chiral allylic alcohols, carbamates, and organic boron compounds. Furthermore, DFT calculations were conducted to explain the origin of the branched selectivity.
Catalytic Depolymerization of Polyolefinic Plastic Waste
Authors: Seitz Mathias , Schröter Stephan
Published: March 2022

In a circular economy, processes such as the pyrolysis of polyolefin plastic waste must be established for naphtha cracker feedstock production. However, the composition of the plastic waste used has a strong influence on the conversion process and the heteroatom content, and thus on the quality of the pyrolysis oils. In this work, the influence of critical plastic components (e.g., polyamide 6) on the catalytic cracking of polyethylene (PE‐HD) in a batch rotary kiln reactor was investigated and a cost‐effective concept for integrating chemical recycling into a steam cracking plant was proposed.
A novel feature selection with stochastic gradient descent logistic regression for multilabeled stress prediction in working employees
Authors: Anitha Swaminathan , Vanitha Muthuraman
Published: March 2022

In the recent times, stress prediction becomes a hot research area and several research works have been developed to address it. The advent of machine learning (ML) models assists the stress prediction process to understand the patterns effectively and offer effective perceptions about possible future intervention. In this view, this article presents a multi‐labeled stress prediction in working employee using extremely randomized tree (ET) based feature selection (FS) and stochastic gradient descent (SGD) with logistic regression (LR), called ETSGD‐LR model. First, the ET based FS technique can be used to compute impurity‐based feature importance, which in turn can be used to discard irrelevant features. In addition, the SGD‐LR model is used to classify the feature reduced subset into different class labels. For experimental validation, we have collected our own stress prediction dataset with 1197 records of employees collected from schools, banks, universities, and so forth from different institutions. Among them 1197 records are filtered with various diseases and work pressure. A detailed set of simulations were carried out in Python Programming tool, and the results are analyzed in terms of sensitivity, specificity, accuracy, precision, F‐score, and kappa. The obtained simulation outcome ensured the superior performance of the ETSGD‐LR model over the compared methods with the maximum sensitivity, specificity, and accuracy of 0.980, 0.900, and 0.972, respectively. The experimental results shown that the inclusion of FS process helps to improve the classification performance.
Deoxydehydration of Biomass‐Derived Polyols Over Silver‐Modified Ceria‐Supported Rhenium Catalyst with Molecular Hydrogen
Authors: Yamaguchi Kosuke , Cao Ji , Betchaku Mii , Nakagawa Yoshinao , Tamura Masazumi , Nakayama Akira , Yabushita Mizuho , Tomishige Keiichi
Published: March 2022

Olefin production from polyols via deoxydehydration (DODH) was carried out over Ag‐modified CeO2‐supported heterogeneous Re catalysts with H2 as a reducing agent. Both high DODH activity and low hydrogenation ability for C=C bonds were observed in the reaction of erythritol, giving a 1,3‐butadiene yield of up to 90 % under “solvent‐free” conditions. This catalyst is applicable to other substrates such as methyl glycosides (methyl α‐fucopyranoside: 91 % yield of DODH product; methyl β‐ribofuranoside: 88 % yield), which were difficult to be converted to the DODH products over the DODH catalysts reported previously. ReOx‐Ag/CeO2 was reused 3 times without a decrease of activity or selectivity after calcination as regeneration. Although the transmission electron microscopy energy‐dispersive X‐ray spectroscopy and X‐ray absorption fine structure analyses showed that Re species were highly dispersed and Ag was present as metal particles with various sizes from well‐dispersed species (<1 nm) to around 5 nm particles, the catalysts prepared from size‐controlled Ag nanoparticles showed similar performance, indicating that the catalytic performance is insensitive to the Ag particle size.
k‐means clustering based energy and trust management routing algorithm for mobile ad‐hoc networks
Authors: C Gopala krishnan , A.H Nishan , Theerthagiri Prasannavenkatesan
Published: March 2022

MANETs (Mobile Ad‐Hoc Networks) have limited energy and are unable to energize themselves. This work aims to create a power management strategy for the MANET that saves energy. While routing based on the cluster, the cluster heads may fail or work improperly by the cause of power issues. As a result, the cluster heads experience instability when gathering information and interacting. The main focus of this research is identifying the unstable cluster heads and replacing them with other nodes that implement the self‐configurable cluster method. For defining the cluster heads successfully, we presented a k‐means protocol approach. The proposed k‐means technique identifies the abnormal or unnecessary variations of the cluster heads and the change in cluster count. A node is designated as a cluster head (CH) in MANET after the cluster value remains lesser than the existing routing threshold value. Information gathering, computing trust levels, and trust‐based configuration are the three key elements of the proposed trust management system, which communicates with each node to establish secure network connections. Finally, the testing results show that the proposed approach uses less energy and effectively manages trust in MANET.
Detection of insulin analogues and large peptides >2 kDa in urine
Authors: Cox Holly D. , Knussmann Graham N. , Moore Chad , Eichner Daniel
Published: March 2022

Insulin analogues and large bioactive peptides may be used by athletes to enhance performance and are banned by the World Anti‐Doping Agency (WADA). In addition to insulin analogues, the large peptides include a structurally diverse set of peptides including analogues of growth hormone releasing hormone (GHRH), insulin‐like growth factor‐1 (IGF‐1), and mechano‐growth factor (MGF). Detection of this class of peptides is difficult due to their absorptive losses and presence at very low concentrations in urine. In this report, a high throughput method is described that allows sensitive detection of four classes of large peptides in one assay. Sample extraction is performed by ultrafiltration to concentrate the urine followed by solid phase extraction in a 96‐well micro‐elution plate. Peptides in the urine samples are detected on a triple quadrupole mass spectrometer coupled to standard flow liquid chromatography. The method was validated and evaluated for limit of detection, limit of identification, specificity, precision, carryover, recovery, matrix interference, and post‐extraction stability. The limit of detection for insulin analogues is between 5 and 25 pg/ml and between 5 and 50 pg/ml for the other peptide classes. Specificity was good with no detection of interfering peaks in blank urine samples. Carryover from a high concentration sample was not observed and the post‐extraction stability was between 77% and 107%. The method was able to detect insulin analogues in three diabetic urine samples. Increased screening for this class of peptides will improve detection and deterrence.
Protein kinases and protein phosphatases encoded in the Ciona robusta genome
Authors: Tokuoka Miki , Kobayashi Kenji , Lemaire Patrick , Satou Yutaka
Published: March 2022

Protein kinases (PKs) and protein phosphatases (PPs) regulate the phosphorylation of proteins that are involved in a variety of biological processes. To study such biological processes systematically, it is important to know the whole repertoire of PKs and PPs encoded in a genome. In the present study, we surveyed the genome of an ascidian (Ciona robusta or Ciona intestinalis type A) to comprehensively identify the genes that encoded PKs and PPs. Because ascidians belong to the sister group of vertebrates, a comparison of the whole repertoire of PKs and PPs of ascidians with those of vertebrates may help to delineate the complements of these proteins that were present in the last common ancestor of these two groups of animals. Our results show that the repertory of PPs was much more expanded in vertebrates than the repertory of PKs. We also showed that approximately 75% of PKs and PPs were expressed during development from eggs to larvae. Thus, the present study provides catalogs for PKs and PPs encoded in the ascidian genome. These catalogs will be useful for systematic studies of biological processes that involve phosphorylation and for evolutionary studies of the origin of vertebrates.
Prevalence of type 2 diabetes and pre‐diabetes among pulmonary and extrapulmonary tuberculosis patients of Bangladesh: A cross‐sectional study
Authors: Sheuly Afsana Habib , Arefin S. M. Zahid Hassan , Barua Lingkan , Zaman Muhammed Shahriar , Chowdhury Hasina Akhter
Published: March 2022

Background

We aimed to determine the prevalence of type 2 diabetes (T2D) and pre‐diabetes (pre‐DM) among patients with pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in Bangladesh. We also examined the association between type of TB and hyperglycaemia as an adjunct to the primary objective.

Materials and Methods

This cross‐sectional analytical study recruited 350 TB patients (175 PTB and 175 EPTB) from two tertiary care hospitals specialized for TB treatment. Oral glucose tolerance tests and fasting plasma glucose measurements were carried out for unknown glycaemic status and those with previously known diabetes, respectively.

Results

Overall, the prevalence of T2D and pre‐DM was 19.1% (new 85.1%, old 14.9%) and 34.3%, respectively. Although the risk factors were highly prevalent among the patients with EPTB, a higher proportion of T2D (26.3%) and pre‐DM (34.3%) was detected among the patients with PTB. The proportion of impaired fasting glucose was low in both groups, but a high trend of impaired glucose tolerance was observed across the groups, with a higher proportion (35.4%) in the PTB group. Both pre‐DM and T2D showed significantly higher odds (pre‐DM, AOR: 4.488; CI: 2.531–7.958; p < .001 and T2D, AOR: 4.280; CI: 2.305–7.946; p < .001) for having PTB.

Conclusion

The prevalence of T2D and pre‐DM was higher among the patients with PTB, and it (PTB) appeared as a predictor of hyperglycaemia. It indicates the primary intervention should target the patients with PTB to get the maximum benefit of screening to reduce the number of risk factors, disease burden and subsequent complications.
Governing toward decarbonization: The legitimacy of national orchestration
Authors: Nasiritousi Naghmeh , Grimm Julia
Published: March 2022

Today, the world faces grand challenges that are both daunting and urgent to address. The decarbonization challenge in particular requires states to mobilize a range of actors to achieve structural changes. In this context, there has been a proliferation of orchestration attempts by states, whereby they use soft or indirect forms of steering to coordinate and engage intermediaries to achieve policy objectives. This type of steering raises a number of questions: How can such forms of steering gain legitimacy among the targeted actors and how can this legitimacy be maintained in the face of competing interests? This paper uses the case of the Fossil Free Sweden Initiative to highlight key factors and considerations in establishing and maintaining legitimacy in the orchestration of a varied set of non‐state actors with differing interests. Specifically, the paper makes two core contributions to existing literature. Theoretically, it highlights how institutional legitimacy is obtained through a balancing act of stakeholder demands at different levels. Empirically, it examines how Sweden, considered a climate leader, governs toward decarbonization through national orchestration as an important tool. The paper thereby offers new insights into the legitimacy of orchestration with significant implications for how to understand rule‐making and governance with the use of intermediaries. It particularly highlights how power and agency can create a governance dilemma for the orchestrator that may undermine legitimacy in the long term.
Heart failure with mildly reduced ejection fraction: retrospective study of ejection fraction trajectory risk
Authors: Miller Robert J.H. , Nabipoor Majid , Youngson Erik , Kotrri Gynter , Fine Nowell M. , Howlett Jonathan G. , Paterson Ian D. , Ezekowitz Justin , McAlister Finlay A.
Published: March 2022

Aims

Heart failure with mildly reduced ejection fraction (HFmrEF) is associated with a favourable prognosis compared with heart failure (HF) with reduced ejection fraction (EF). We assessed whether left ventricular ejection fraction (LVEF) trajectory can be used to identify groups of patients with HFmrEF who have different clinical outcomes in a large retrospective study of patients with serial imaging.

Methods and results

Patients with HF and ≥2 echocardiograms performed ≥6 months apart were included if the LVEF measured 40–49% on the second study. Patients were classified as HFmrEF‐Increasing if LVEF had increased ≥10% (n = 450), HFmrEF‐Decreasing if LVEF had decreased ≥10% (n = 512), or HFmrEF‐Stable if they did not meet other criteria (n = 389). The primary outcome was all‐cause mortality or cardiovascular hospitalization after the second echocardiogram. Associations with time to first event were assessed with multivariable Cox analyses adjusted for age, co‐morbidities, and medications.

In total, 1351 patients with HFmrEF (median age 74, 64.2% male) were included with 28.8% exhibiting stable LVEF. During median follow‐up of 15.3 months, the composite outcome occurred in 811 patients. During follow‐up, patients with HFmrEF‐Increasing were less likely to experience the primary outcome [adjusted hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.60–0.88, P < 0.001] compared with HFmrEF‐Stable. Patients with HFmrEF‐Decreasing were more likely to experience the composite outcome in unadjusted analyses (unadjusted HR 1.19, 95% CI 1.01–1.40, P = 0.040) but not adjusted analyses (adjusted HR 1.16, 95% CI 0.98–1.37, P = 0.092). Associations with death or HF hospitalizations were similar (HFmrEF‐Increasing: adjusted HR 0.72, 95% CI 0.59–0.88, P = 0.005; HFmrEF‐Decreasing: adjusted HR 1.20, 95% CI 1.01–1.44, P = 0.044). Patients with HFmrEF‐Decreasing had a similar risk of the composite outcome as patients with HF with reduced EF (adjusted HR 1.03, 95% CI 0.89–1.20, P = 0.670). Patients with HFmrEF‐Increasing were less likely to experience the composite outcome compared with patients with HF with preserved EF (adjusted HR 0.73, 95% CI 0.62–0.87, P < 0.001).

Conclusions

Amongst patients with HFmrEF, those exhibiting positive LVEF trajectory were less likely to experience adverse outcomes after correcting for important confounders including medical therapy. Categorizing HFmrEF patients based on LVEF trajectory provides meaningful clinical information and may assist clinicians with management decisions.
Electrochemical Hydroxylation of Electron‐Rich Arenes in Continuous Flow
Authors: Kooli Anni , Wesenberg Lars , Beslać Marko , Krech Anastasiya , Lopp Margus , Noël Timothy , Ošeka Maksim
Published: March 2022

Electrochemical hydroxylation of arenes by trifluoroacetic acid provides a straightforward access to aryl oxygen compounds under the mild and environmental benign reaction conditions. Harmful and pollutant stoichiometric amounts of oxidation reagents and the use of metal‐catalysts can be avoided. Herein, we present a novel method for the synthesis of hydroxylated products from electron‐rich arenes that was achieved by the implementation of a continuous‐flow setup. The continuous nature of the process allowed to fine‐tune the reactions conditions in order to prevent the decomposition of the sensitive products expanding the reaction scope beyond electron‐poor and neutral arenes that were previously reported in the batch processes. Thus, synthetically valuable hydroxylated arenes were obtained in good yields with the residence time just over a minute. In order to demonstrate the reliability and the efficiency of the electrochemical flow setup, a scale up experiment was also performed.
Enantioselective Pictet–Spengler Condensation to Access the Total Synthesis of (+)‐Tabertinggine
Authors: Long Dan , Zhao Gaoyuan , Liu Zhiqiang , Chen Peiqi , Ma Shiqiang , Xie Xingang , She Xuegong
Published: March 2022

A chiral phosphoric acid (CPA)‐catalyzed enantioselective Pictet–Spengler condensation/lactamization cascade reaction was established, which paved the way of the collective synthesis of iboga‐type indole alkaloids. Herein, we presented the asymmetric total synthesis of iboga‐type indole alkaloid (+)‐tabertinggine.
Antinociceptive effect of garlic, garlic preparations and derivative compounds
Authors: Hernández‐Cruz Estefani Yaquelin , Silva‐Islas Carlos Alfredo , Maldonado Perla D. , Pedraza‐Chaverri José , Carballo‐Villalobos Azucena Ibeth
Published: March 2022

Background and objective

The antinociceptive effects of garlic have shown promise in treating different chronic diseases in humans, such as knee osteoarthritis, rheumatoid arthritis and peripheral arterial occlusive disease stage II. The most common garlic products are garlic powder (dried garlic), steam distilled garlic oils, garlic oil macerate and aged garlic extract. These commercial products contain organosulphur compounds (OSCs) that have been extensively evaluated in preclinical models and some clinical assays to treat different diseases against pain. In this review, we describe the importance of some bioactive compounds found in garlic and their role in treating pain.

Materials & Methods

A systematic search of the literature in Dimensions, PubMed, Scopus, and Web of Science was performed. Terms and preselected keywords relating to garlic, its derivatives and organusulphure compounds in acute, chronic and neuropathic pain, were used to perform a systematic literature search. Two independent reviewers screened the papers for inclusion and assessed the methodological quality.

Results & Discussion

The antinociceptive activity of garlic and its OSC is related to its antioxidant and anti‐inflammatory properties, which may be explained by the ability to block the synthesis of PGs, pro‐inflammatory cytokines and interferon‐γ, by the reduction COX‐2 activity and increasing the levels of anti‐inflammatory cytokines. Besides, garlic extract is an activator of TRPA1 and TRPV1, where the principal responsible for this activation are OSC.

Conclusion

The relationship between these pathways allows a better understanding how garlic and its derivates could be carrying out its pharmacological action over the management of acute and chronic pain and provide a base by further investigations.

Significance

Antinociceptive effect of garlic and its OSCs has been extensively evaluated in preclinical models and clinical assays to treat different diseases, contributing to the modulation of inflammation as an essential factor in reducing pain. The current review emphasizes the potential therapeutic effect of garlic and its derivatives in treatment of pain and related mechanisms of action. Moreover, it provides information about the potential clinical use in patients with painful conditions.
The ECOTOXicology Knowledgebase: A Curated Database of Ecologically Relevant Toxicity Tests to Support Environmental Research and Risk Assessment
Authors: Olker Jennifer H. , Elonen Colleen M. , Pilli Anne , Anderson Arne , Kinziger Brian , Erickson Stephen , Skopinski Michael , Pomplun Anita , LaLone Carlie A. , Russom Christine L. , Hoff Dale
Published: March 2022

The need for assembled existing and new toxicity data has accelerated as the amount of chemicals introduced into commerce continues to grow and regulatory mandates require safety assessments for a greater number of chemicals. To address this evolving need, the ECOTOXicology Knowledgebase (ECOTOX) was developed starting in the 1980s and is currently the world's largest compilation of curated ecotoxicity data, providing support for assessments of chemical safety and ecological research through systematic and transparent literature review procedures. The recently released version of ECOTOX (Ver 5, www.epa.gov/ecotox) provides single-chemical ecotoxicity data for over 12,000 chemicals and ecological species with over one million test results from over 50,000 references. Presented is an overview of ECOTOX, detailing the literature review and data curation processes within the context of current systematic review practices and discussing how recent updates improve the accessibility and reusability of data to support the assessment, management, and research of environmental chemicals. Relevant and acceptable toxicity results are identified from studies in the scientific literature, with pertinent methodological details and results extracted following well-established controlled vocabularies and newly extracted toxicity data added quarterly to the public website. Release of ECOTOX, Ver 5, included an entirely redesigned user interface with enhanced data queries and retrieval options, visualizations to aid in data exploration, customizable outputs for export and use in external applications, and interoperability with chemical and toxicity databases and tools. This is a reliable source of curated ecological toxicity data for chemical assessments and research and continues to evolve with accessible and transparent state-of-the-art practices in literature data curation and increased interoperability to other relevant resources. Environ Toxicol Chem 2022;41:1520–1539. © 2022 SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
Predicting Primary Biodegradation of Petroleum Hydrocarbons in Aquatic Systems: Integrating System and Molecular Structure Parameters using a Novel Machine-Learning Framework
Authors: Davis Craig Warren , Camenzuli Louise , Redman Aaron D.
Published: March 2022

Quantitative structure–property relationship (QSPR) models for predicting primary biodegradation of petroleum hydrocarbons have been previously developed. These models use experimental data generated under widely varied conditions, the effects of which are not captured adequately within model formalisms. As a result, they exhibit variable predictive performance and are unable to incorporate the role of study design and test conditions on the assessment of environmental persistence. To address these limitations, a novel machine-learning System-Integrated Model (HC-BioSIM) is presented, which integrates chemical structure and test system variability, leading to improved prediction of primary disappearance time (DT50) values for petroleum hydrocarbons in fresh and marine water. An expanded, highly curated database of 728 experimental DT50 values (181 unique hydrocarbon structures compiled from 13 primary sources) was used to develop and validate a supervised model tree machine-learning model. Using relatively few parameters (6 system and 25 structural parameters), the model demonstrated significant improvement in predictive performance (root mean square error = 0.26, R2 = 0.67) over existing QSPR models. The model also demonstrated improved accuracy of persistence (P) categorization (i.e., “Not P/P/vP”), with an accuracy of 96.8%, and false-positive and -negative categorization rates of 0.4% and 2.7%, respectively. This significant improvement in DT50 prediction, and subsequent persistence categorization, validates the need for models that integrate experimental design and environmental system parameters into biodegradation and persistence assessment. Environ Toxicol Chem 2022;41:1359–1369. © 2022 ExxonMobil Biomedical Sciences, Inc. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Juvenile crust and mantle sources for the Nasrand intrusive rocks, the central Urumieh–Dokhtar magmatic arc, Iran: Insights from elemental and isotopic geochemistry
Authors: Sepahvand Farzaneh , Tahmasbi Zahra , Sarjoughian Fatemeh , Ebrahimi Mohammad , Ling Wenli , Zhang Zhiyong , Esmaeili Rasoul
Published: March 2022

The Oligocene Nasrand intrusive rocks (NIRs), located in the central part of the Urumieh–Dokhtar magmatic arc, are mainly composed of granite and subordinate diorite and gabbro. These rocks are characterized by the enrichment of light rare earth elements (LREEs), Nb‐Ta negative anomalies, and high LILE/HFSE, suggesting a subduction‐related origin. The felsic rocks with granite compositions have high SiO2 content (69.77–77.88 wt.%), low Mg# (0.02–0.43), low Nb/Ta, and Zr/Hf (Avg: 12.53, and 33.08, respectively). The initial 87Sr/86Sr ratio and εNd(t) values in felsic rocks range from 0.70577 to 0.70576 and 0.4 to −0.3, respectively. These data suggest that these felsic rocks originated from juvenile crust by heat rising from basaltic magmas in an orogenic setting. The mafic‐intermediate rocks and dikes are gabbro, gabbroic diorite, and monzodiorite, with low SiO2 content (48.08–56.11 wt.%) and high Mg# (0.37–0.68), with average ratios of Nb/Ta and Zr/Hf are 27.88 and 39.84, respectively. The initial 87Sr/86Sr ratio and εNd(t) values for mafic‐intermediate rocks and dikes are 0.70583 to 0.70476 and −0.1 to +2.6, respectively. These characteristics indicate magma from a mantle source that had undergone minor mixing with juvenile crust. It seems mantle‐derived juvenile magma underplating played an important role in the crustal growth in the Urumieh–Dokhtar magmatic belt during the Ediacaran to Early Cambrian, relative to other time frames.
Differences between cultured cortical neurons by trypsin and papain digestion
Authors: Hu Chang‐Yan , Du Ruo‐Lan , Xiao Qiu‐Xia , Geng Min‐Jian
Published: March 2022

The objective of this study was to compare the efficiency of trypsin and papain in neuronal digestion and determine which enzyme is more efficient. Cortical tissues were obtained from Sprague–Dawley (SD) rats. According to the different digestive enzymes, the samples were divided into the trypsin group and the papain group. After being digested by each of the two enzymes, cortical neurons were collected from the samples. Then, the morphology of the cortical neurons was determined. Moreover, the cortical neurons were transfected with the negative control (NC) lentivirus. The transfection efficiency and morphology were determined and compared. Compared with the papain group, cortical neurons in the trypsin group were more in number, had larger cell size, had longer axonal length, and had fewer impurities. The transfection efficiency of the trypsin group (57.77%) was higher than that of the papain group (53.83%). The morphology of neurons that was displayed showed that the cell body of most neurons shrank and became smaller, and the axis mutation became shorter and less in the papain group 6 days after transfection with the NC lentivirus. Trypsin is more efficient in digesting neurons because the neurons digested by this enzyme are more in number, have a larger cell body, longer axons, and greater transfection efficiency.
Effects of different injection methods of propofol anesthesia on the behavior and electroencephalography recording in mice
Authors: Luo Dan , Chen Shi‐Yu , Zhang Yu
Published: March 2022

Propofol is commonly used in mice studies on the mechanism of general anesthesia. The administration routes of propofol include intraperitoneal injection, single tail vein injection, and continuous tail vein pumping. The aim of this study is to compare the effects of the three injection methods on the behavior and electroencephalography (EEG) recording in mice. Mice were divided into an intraperitoneal injection group, a single tail vein injection group, and a continuous tail vein pumping group according to the propofol administration route. The indexes for observation were: time of loss of righting reflex (LORR), time of resumption of righting reflex (RORR), and change in the number of EEG spindle waves during anesthesia. The LORR and RORR were detected again after 1 week to determine the repeatability of the three administration routes. Death and behavioral change after anesthesia recovery in mice were recorded in the three groups. For propofol administration in mice, intraperitoneal injection induced long‐duration anesthesia, but the depth of anesthesia was shallow and there was a risk of anesthesia accidents. A small dose of propofol administered through a single tail vein can induce loss of consciousness but the LORR time was not recorded, hence the metrics during induction of anesthesia were not investigated. Continuous tail vein pumping produced stable behavior and EEG recording during anesthesia induction and recovery in mice, and the individual difference was small. Continuous tail vein pumping is an ideal administration route for studying the mechanism of loss of consciousness of propofol anesthesia in mice, which could provide reference data for future mice experiments using propofol.
Air sensitivity of electrode materials in Li/Na ion batteries: Issues and strategies
Authors: Zhang Ruiwang , Yang Sijie , Li Haobo , Zhai Tianyou , Li Huiqiao
Published: March 2022

With the development of electrode materials in lithium ion batteries—upgrading from LiCoO2 and LiFePO4 to Ni‐rich layered oxides, and the shifting of battery systems from high cost lithium ion to low cost sodium ion technology, the air sensitivity of the electrode materials has become an increasingly important issue in both production and application. Furthermore, the air sensitivity of electrode materials must be carefully considered throughout nearly all stages of their life, including material design, synthesis, production, storage, packaging, transportation, and battery assembly. Therefore, a fundamental understanding of the air degradation mechanism of electrode materials and the exploration of new methods to enhance their air stability are of great significance for the development of batteries with better performance. Herein, we provide a review of the issues related to air exposure of electrode materials in Li/Na ion batteries, including factors related to air sensitivity, degradation mechanisms, and recent progress in improving their air stability. The merits and existing challenges of different strategies are presented, and a rational design perspective as well as general principles for evaluating air stability are proposed.

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Biosafety and differentially expressed genes analysis of melanoma cells treated with cold atmospheric plasma
Authors: Zhao Lihong , Yan Cong , Kong Shuzhen , Jia Tao , Chu Zhaowei , Yang Li , Wu Jian , Geng Songmei , Guo Kun
Published: March 2022

Cold atmospheric plasma (CAP) has attracted increasing attention due to its anti‐bacterial and anti‐tumor effects. Melanoma is an aggressive malignancy with increasing incidence rate and poor prognosis. Evaluating cell viability, apoptosis rate and reactive species injection efficiency of melanoma cells and human keratinocyte cells (HaCaT) treated with CAP to analyze biological safety of CAP. RNA‐sequencing (RNA‐seq) of A875 cells before and after treatment was performed to further explore the anti‐tumor mechanism of CAP. CAP had a more significant biological effect on melanoma cells than HaCaT cells by inhibiting proliferation and promoting apoptosis. RNA‐sequencing analysis showed that besides MAPK and p53 apoptotic signaling pathways, necroptosis and autophagy also played important roles in CAP‐induced melanoma cells death. CAP can selectively kill melanoma cells and has good biosafety cytologically. Besides apoptosis, CAP can induce cell death via autophagy and necroptosis.
In situ crosslinking temperature‐responsive hydrogels with improved delivery, swelling, and elasticity for endovascular embolization
Authors: Overstreet Derek J. , Lee Elizabeth J. , Pal Amrita , Vernon Brent L.
Published: March 2022

Endovascular embolization of cerebral aneurysms is a common approach for reducing the risk of often‐fatal hemorrhage. However, currently available materials used to occlude these aneurysms provide incomplete filling (coils) or require a complicated, time‐consuming delivery procedure (solvent‐exchange precipitating polymers). The objective of this work was to develop an easily deliverable in situ forming hydrogel that can occlude the entire volume of an aneurysm. The hydrogel is formed by mixing a solution of a temperature‐responsive polymer containing pendent thiol groups (poly(NIPAAm‐co‐cysteamine) or poly(NIPAAm‐co‐cysteamine‐co‐JAAm)) with a solution of poly(ethylene glycol) diacrylate (PEGDA). Incorporation of hydrophilic grafts of polyetheramine acrylamide (JAAm) in the temperature‐responsive polymer caused weaker physical crosslinking, facilitated faster and more complete chemical crosslinking, and increased gel swelling. One formulation (30 wt % PNCJ20 + PEGDA) could be delivered for over 220 s after mixing, formed a strong and elastic hydrogel (G' > 6000 Pa) within 30 min and once set, maintained its shape and volume in a model aneurysm under flow. This gel represents a promising candidate water‐based material utilizing both physical and chemical crosslinking that warrants further investigation as an embolic agent for saccular aneurysms.
Subjective psychological impacts during COVID‐19 lockdown on older people, risk profiles and coping strategies: Results of an online survey in Spain
Authors: Doménech Sara , Blancafort‐Alias Sergi , Rojano Xavier , Salvà Antoni , Roqué Marta , Coll‐Planas Laura
Published: March 2022

This study explores the psychological impacts of lockdown among older people during the coronavirus disease 2019 pandemic in Spain, and identifies risk profiles and adaptative behaviors. A cross‐sectional online survey was disseminated by social networks through snowball sampling (April–June 2020). The survey included ad‐hoc questions about psychological impacts on subjective cognitive functioning, emotional distress, and loneliness. Open end‐questions were coded according to Lazarus and Folkman's coping strategies framework. Of the 2010 respondents, 76% experienced impact in at least one cognitive function (11% reporting severe effects), 78% frequent sadness and 13% frequent loneliness. Age 80+, women and low education increased the risk of loneliness and severe impact in memory and processing speed. Living alone was an additional risk factor for loneliness and sadness. Lockdown is associated with cognitive impacts, emotional distress, and loneliness being risk profiles related to inequality axes. Coping strategies should inform aging policies to prevent psychological impacts during the lockdown.
Effect of vitamin D monotherapy on indices of sarcopenia in community‐dwelling older adults: a systematic review and meta‐analysis
Authors: Prokopidis Konstantinos , Giannos Panagiotis , Katsikas Triantafyllidis Konstantinos , Kechagias Konstantinos S. , Mesinovic Jakub , Witard Oliver C. , Scott David
Published: March 2022

Background

Vitamin D supplementation is proposed as a potentially effective nutritional intervention to mitigate the risk of sarcopenia. The aim of this systematic review and meta‐analysis was to investigate the impact of vitamin D supplementation monotherapy on indices of sarcopenia in community‐dwelling older adults.

Methods

A comprehensive search of the literature was conducted in PubMed, Web of Science, Scopus, and Cochrane Library. Eligible randomized controlled trials (RCTs) compared the effect of vitamin D supplementation (as monotherapy) with placebo on indices of sarcopenia in older (>50 years) adults. Using the random effects inverse‐variance model, we calculated the mean difference (MD) in handgrip strength (HGS), short physical performance battery (SPPB), timed up and go (TUG), and appendicular lean mass (ALM) between groups. We also calculated the standardized mean difference (SMD) in general muscle strength and general physical performance (composite plot of all muscle strength and physical performance outcomes, respectively) between groups.

Results

Ten RCTs were included in the meta‐analysis. A significant decrease in SPPB scores was observed with vitamin D supplementation compared with placebo (MD: −0.23; 95% CI −0.40 to −0.06; I2 = 0%; P = 0.007). Vitamin D supplementation conferred no effect on HGS (MD: −0.07 kg; 95% CI −0.70 to 0.55; I2 = 51%, P = 0.82), TUG (MD: 0.07 s; 95% CI −0.08 to 0.22; I2 = 0%, P = 0.35), ALM (MD: 0.06 kg/m2; 95% CI: −0.32 to 0.44; I2 = 73%, P = 0.77), general muscle strength (SMD: −0.01; 95% CI −0.17 to 0.15; I2 = 42%, P = 0.90), or general physical performance (SMD: −0.02; 95% CI −0.23 to 0.18; I2 = 71%, P = 0.83).

Conclusions

Vitamin D supplementation did not improve any sarcopenia indices in community‐dwelling older adults and may compromise some aspects of physical performance. Future studies are warranted to investigate the impact of vitamin D supplementation on individual indices of SPPB, including mobility and balance, in older adults.
Incidence of congenital and postnatal cytomegalovirus infection during the first year of life in Mexican preterm infants
Authors: Cadena‐Mota Sandra , Muñoz‐Escalante Juan C. , Martínez‐Rodríguez Luz E. , Bernal‐Silva Sofía , Tello‐Martínez Nallely , de la Torre‐Rodríguez Ileana , Hernández‐Sánchez Pedro G. , Castillo‐Martínez Fernanda , Escalante‐Padrón Francisco , Lima‐Rogel Victoria , González‐Ortiz Ana M. , Noyola Daniel E.
Published: March 2022

Cytomegalovirus infection occurs commonly during infancy. Postnatal infection in term infants is usually asymptomatic; however, infection in preterm infants can be associated with clinical manifestations during the neonatal period. Nevertheless, few studies to assess the frequency of cytomegalovirus infection in preterm infants have been performed outside of high‐income countries. We analyzed the incidence of congenital and postnatal cytomegalovirus infection in a cohort of preterm infants. Cytomegalovirus infection was detected during the neonatal period in four of 178 infants; in three of them, the virus was detected during the first 3 weeks of life and, therefore, congenital infection was confirmed (1.7% incidence). Postnatal infection was detected in 44 (36.4%) of 121 infants who were assessed after discharge from the neonatal intensive care unit. Cytomegalovirus infection was significantly associated with the duration of breastfeeding. In addition, we characterized cytomegalovirus strains detected in infants together with sequences available at GenBank, based on sequences of the UL18 gene. Cytomegalovirus UL18‐sequences clustered in five distinct clades (A–E), and sequences obtained from infants in our study were distributed in four of the five clades; 44.4% of these sequences were included in clade E. Breastfeeding duration was shorter on average (5.6 months) in infants with sequences in clade E compared to infants with sequences in the other three clades (8.2 months; p = .07). In conclusion, we provide information regarding the high incidence of cytomegalovirus infection in preterm infants. Further studies are warranted to assess if cytomegalovirus strain characteristics are associated with the risk of infection acquisition during infancy.
Molecular identification and characterization of measles virus genotypes circulating in Afghanistan, 2008–2018
Authors: Rana Muhammad S. , Usman Muhammad , Ikram Aamer , Alam Muhammad M. , Salman Muhammad , Zaidi Syed S. Z. , Umair Massab , Stanikzai Nasir , Shakoor Abdul , Afghan Fazel
Published: March 2022

The measles virus (MV) remains a leading cause of morbidity and mortality in children under 5 years of age. Molecular identification of circulating wild‐type MV) strains is a vital component of the measles elimination program. We received 159 oral swab samples from Afghanistan during 2008–2018. Viral RNA was extracted, followed by one‐step RT‐PCR and positive amplicons were subject to sequencing for genotype identification. Out of 159 total samples, 52% (83/159) were detected positive by RT‐PCR. Genotype D4 was identified from 2.4% (2/83), genotype H1, 4.8% (4/83), and genotype B3, 92.7% (77/83) cases, respectively.