bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hybrid Approach for Solving Constrained Multi-Objective Mixed-Discrete Nonlinear Programming Engineering Problems
Authors: Roy Satadru , A. Crossley William , Jain Samarth
Published: April 2021

Several complex engineering design problems have multiple, conflicting objectives and constraints that are nonlinear, along with mixed discrete and continuous design variables; these problems are inherently difficult to solve. This chapter presents a novel hybrid approach to find solutions to a constrained multi-objective mixed-discrete nonlinear programming problem that combines a two-branch genetic algorithm as a global search tool with a gradient-based approach for the local search. Hybridizing two algorithms can provide a search approach that outperforms the individual algorithms; however, hybridizing the two algorithms, in the traditional way, often does not offer advantages other than the computational efficiency of the gradient-based algorithms and global exploring capability of the evolutionary-based algorithms. The approach here presents a hybridization approach combining genetic algorithm and a gradient-based approach with improved information sharing between the two algorithms. The hybrid approach is implemented to solve three engineering design problems of different complexities to demonstrate the effectiveness of the approach in solving constrained multi-objective mixed-discrete nonlinear programming problems.
Participation in the National Collaborating Centre for Methods and Tools’ Knowledge Broker Mentoring Program: a public health inspector perspective
Authors: Powers Andrea , Pelletier T. , Ray R. , Reynolds A. , Howarth C. , Dobbins M.
Published: April 2021

Although evidence-informed decision making is an important part of the field of public health inspection, finding the time to stay informed of current research can be a challenge amidst day-to-day job expectations. This article will explore how two Public Health Inspectors (PHIs) from Ottawa Public Health, a municipal public health unit in Ontario, incorporated evidence-informed decision making (EIDM) into their work. They built their EIDM skills through participating in the 18-month Knowledge Broker (KB) Mentoring Program offered by the National Collaborating Centre for Methods and Tools. The program required a substantial time commitment, including nine in-person workshop days and dedicated hours to practice research appraisal skills and to complete a rapid review. The inspectors were approved and supported to spend the necessary time; however, they still found it difficult to designate hours for learning while balancing their frontline inspection workload. This article will share observations about the PHI’s involvement, including benefits and challenges as well as factors that facilitated their successful completion of the KB Mentoring Program.
Silenciar el discurso del odio
Authors: Martínez Martínez Silvia
Published: April 2021

Marzo marcó un nuevo hito en la guerra para acabar con la propagación del discurso del odio en internet. La presentación de un protocolo que cuenta con la adhesión de actores diversos favorece la colaboración para atajar estos mensajes, que constituyen un delito. Un discurso del odio que, más allá del ámbito penal y el efecto directo sobre las personas o colectivos a los que se dirige, tiene consecuencias en la dinámica y el funcionamiento democráticos, así como en el mantenimiento de una convivencia tolerante y pacífica.
Can colchicine prevent acute myocardial infarction? Systematic review and meta-analysis
Authors: Masson Walter , Lobo Martín , Lavalle Cobo Augusto , Molinero Graciela
Published: April 2021

Objective: The association between the use of colchicine and the incidence of acute myocardial infarction (AMI) is inconsistent. The main objective of this study was to evaluate the effect of colchicine on the incidence of AMI. Assessment of the incidence of stroke and cardiovascular mortality were secondary endpoints. Methods: A meta-analysis of randomized studies that evaluated the use of colchicine in patients with atherosclerotic disease and reported cardiovascular events was performed, after searching the PubMed/MEDLINE, Embase, Scielo and Cochrane Controlled Trials databases. A fixed or random effects model were used depending on the heterogeneity observed. Results: Seven studies were selected for the analysis of the primary end point (5966 subjects in the colchicine arm and 5948 patients in the control arm). This meta-analysis demonstrated that colchicine therapy was associated with a lower risk of AMI (OR: 0.76, 95% CI: 0.62-0.92; I2 = 15%). Likewise, a significant reduction in the incidence of stroke was observed without a significant effect on cardiovascular mortality with pharmacological intervention. Conclusion: The use of colchicine in patients with atherosclerotic cardiovascular disease was associated with a significant reduction in the incidence of AMI. The incorporation of colchicine into the therapeutic arsenal of cardiovascular disease should be considered by future clinical practice guidelines.
Current Status of Cardiac Rehabilitation in Argentina
Authors: Zeballos Cecilia , Iglesias Diego , Paz Ivana , Bustamante Julieta , González Naya Enrique , Castiello Gustavo , Davolos Ignacio
Published: April 2021

Background: Cardiac rehabilitation is a well-known strategy for secondary prevention in several heart diseases and includes a set of strategies based on education of a healthy lifestyle, management of cardiovascular risk factors, psychosocial counseling, and prescription of supervised physical exercise. Several clinical trials, systematic reviews and meta-analyses have documented its efficacy and safety. Nevertheless, cardiac rehabilitation remains underused. There is information available describing the current status of cardiac rehabilitation and the characteristics of centers in some European countries and North America. There are pooled data from South America in 2014, along with reports from Brazil, Colombia, and Uruguay, but there are few data from our country. Therefore, the aim of this study was to determine the current status of cardiac rehabilitation programs in Argentina. Methods: We conducted a descriptive study using a virtual questionnaire to evaluate the structure and characteristics of rehabilitation programs in our country and the potential barriers to achieve efficient rehabilitation. Results: Seventy-two centers responded. The main results show a high concentration of centers in urban areas (69.23% in AMBA), predominance of private centers (66.67%), inclusion of patients with the so-called classic cardiovascular diseases (coronary artery disease, heart failure, postoperative heart valve surgery, peripheral vascular disease, and after cardiac transplantation and device implantation), and a majority of centers with an exercise-centered strategy. The main difficulty for the inclusion of patients in the centers was poor referral of candidates. Conclusions: The data from this survey allow for a diagnosis of the situation and can be the starting point for developing improvement strategies to implement quality standards and future accreditation programs for the centers.
Slow Release Fertilizer has no Effect on Soil and Plant Nitrogen and Fruit Yield in Bell Pepper (Capsicum annum L.)
Authors: Díaz-Pérez Juan Carlos
Published: April 2021

Aims: To evaluate the effects of combining slow release fertilizer (SRF) with conventional N fertilizer on the levels of soil nitrogen (N), leaf N, and yield of bell pepper plants.

Study Design:  The design was a randomized complete block with a factorial arrangement.  There were four treatments [2 N fertilizers x 2 N rates (200 kg/ha N and 280 kg/ha N)] and four replications. The N fertilizers treatments were calcium nitrate + SRF and calcium nitrate (CN) alone as the control. The rate treatments were 200 and 280 kg/ha N.

Place and Duration of Study: Horticulture Farm, Department of Horticulture, Tifton Campus, University of Georgia, spring of 2008.

Methodology: Bell pepper ‘Heritage’ (Harris Moran, Modesto, Calif., U.S.) transplants were planted on 10 Apr. 2008 in two rows of plants per bed, with a distance between plants of 0.30 m. Soil and leaf nitrogen and other nutrients were monitored during the season.

Results: There were no consistent differences in the concentrations of NH4+-N  and NO3--N at both 0-30 cm and 30-60 cm soil depth between CN + SRF and CN alone. Leaf N concentrations 40 DAT and 68 DAT were higher in plants fertilized with CN + SRF compared to the control, while there were no differences in leaf N concentration 98 DAT. Leaf N concentration was increased at the highest N fertilization rate. Marketable and total fruit yields and individual fruit weight were unaffected by fertilizer treatment and N rate.

Conclusion: Utilization of a slow-release fertilizer (combined with calcium nitrate) had no benefit in reducing soil N losses or in increasing leaf N status and bell pepper fruit yields.
Effects of Aqueous Stem Bark Extract of Stereospermum kunthianum on Carbon Tetrachloride - Induced Hepatotoxicity in Rats
Authors: Jada Mahmoud Suleiman , Sulaiman Mohammed Aliyu , Abdulmalik Muktar
Published: April 2021

Aim: This study is aimed at evaluating the effects of the aqueous stem bark extract of Stereospermum kunthianum on CCl4-induced hepatotoxicity in rats.

Methodology: Analysis of qualitative phytochemical components and antioxidant activity were carried out. Experimental rats were randomly divided into six groups of five rats each. Group 1: served as the normal control group. Group 2: was administered with CCl4 only at a dose of 3 ml/kg b.wt by single intraperitoneal administration. Group 3: served as the standard control group.   Group 4: was administered with 200 mg/kg b.wt of the aqueous stem bark extract + CCl4. Group 5: was administered with 400 mg/kg b.wt of the aqueous stem bark extract + CCl4. Group 6: was administered with 600 mg/kg b.wt of the aqueous stem bark extract+ CCl4.

Results: The phytochemical analysis showed the presence of flavonoid, phenols, saponins, and terpenoid while tannins and alkaloids were absent. The antioxidant activity showed that the extract significantly (P<0.05) inhibits Ferric Reducing Antioxidant Power (FRAP) and Thiobarbituric Acid Reactive Substances (TBARS), giving high activity as the concentration of the extract increases. The elevated levels of ALT and AST coupled with Conjugated bilirubin, Total bilirubin, and total protein caused by CCl4 administration were all reduced significantly (P<0.05) by the extract in dose dependent manner.

Conclusion: These findings demonstrated that stem bark extract of Stereospernmum kunthianum could be an alternative medication for liver injury.
Comparative Efficacy of Antidermatophyte Creams Formulated from Ethanol Extracts of Cassia Occidentalis and Cassia Alata Leaves
Authors: Oyedeji F. O. , Fawehinmi A. B. , Etatuvie S. O. , Lawal Hassan
Published: April 2021

Incidence of drug resistance by dermatophytes is a worldwide concern. Researchers search for natural and better drugs to arrest the ugly situation. This study aims to formulate antidermatophyte Creams with ethanol extracts of the leaves of cassia alata and cassia occidentalis against four selected dermatophytes namely Trichophyton mentagrophtes, Microsporum audounii, Epidermophyton floccosum  and Malassezia furfur. Wistar rats were used in determining the efficacy of the formulated herbal creams by examining the biopsies of the skin of the infected rats for presence of fungal hyphae, tissue destruction, Inflammation of the skin, absence of sebaceous gland and also absence of hair follicles. Dekeratinization of the skin layer was also measured. From the result obtained, it was observed that the efficacy of the creams is concentration dependent. Cassia alata cream formulation was particularly effective against three of the dermatophytes namelyTrichophyton mentagrophtes (30.71± 0.51 µm) Microsporum audounii (36.17± 0.59 µm), and Epidermophyton floccosum (37.49± 0.18 µm) while Cassia occidentalis cream was effective against Malassezia furfur (33.22± 0.16 µm). The results showed that the plants ethanol extracts can be utilized in the management of dermatophytosis when formulated as a cream for topical use.
Mass Spectrometry and Drug Discovery
Authors: van Breemen Richard B. , Newsome Andrew G. , Dahl Jeffrey H. , Muchiri Ruth N.
Published: April 2021

Mass spectrometry has become an essential analytical tool at every stage of the drug discovery and development process. Although mass spectrometry is essential for the characterization of biologics such as therapeutic antibodies and RNA‐based therapeutic agents, this article focuses on small molecule drugs. Applications of mass spectrometry to drug discovery include support for combinatorial chemistry, mass spectrometry‐based high‐throughput screening, and lead optimization. In the case of natural products, mass spectrometry facilitates rapid and accurate activity screening, characterization, dereplication, and identification of active compounds. Mass spectrometry provides rapid, reliable, sensitive, and selective analysis of combinatorial libraries for structure confirmation, purity analysis, and library deconvolution. In addition, mass spectrometric screening methods have been developed and applied to drug discovery and development. In support of drug development, high‐throughput LC‐MS methods have become routine for solubility and bioavailability testing and metabolite screening to ensure that only high‐quality lead compounds are advanced to expensive clinical testing.
Chirality and Drug Discovery
Authors: Hagen Timothy J. , Helgren Travis R.
Published: April 2021

The relationship between chirality and biological is extremely important to the pharmaceutical and biopharmaceutical areas as evidenced by the number of single enantiomer new drugs that have been developed and approved. This article covers several areas of importance for the design and synthesis of novel small molecules drugs to medicinal chemists. The chirality includes atropisomers and the impact of these chiral molecules and their biological implications are discussed. In addition to chirality at carbon, examples of chiral compounds involving chirality at non‐carbon atoms are included. A section titled “chiral switch” covers recent drug development and marketed of single enantiomers.
Combinatorial Chemistry and Its Associated Technologies
Authors: Klus Nicholas J. , Mitscher Lester A. , Aubé Jeffrey
Published: April 2021

Combinatorial chemistry comprises a range of technologies used to produce compound collections, known as “libraries,” which may be used to identify biologically useful compounds. These techniques include synthesis of compounds as mixtures, parallel synthesis of unique organic compounds, display technologies, and technologies needed for handling and using compound libraries. The article describes the principles of library construction with special interest in those that have demonstrated practicality and success in producing biologically relevant molecules. Where relevant, practical concerns of techniques are discussed and selected applications described.
Drug Transport and Membrane Transport Proteins
Authors: Welch Matthew , Swaan Peter W.
Published: April 2021

In order to exert their intended therapeutic goal, drugs need to cross epithelial barriers to reach their site of action. Transport proteins have critical physiological roles in nutrient absorption and transport of endogenous compounds. These systems can serve as useful pharmacological targets and may be utilized as a mechanism to increase drug absorption. However, there is little understanding of these proteins at the molecular level due to their resistance to crystallization.
In vitro
and computational approaches have been applied to gain some insight into these transporters and their substrate specificities. This represents an opportunity for optimizing molecules as substrates for solute transporters and providing a further screening system for drug discovery. This article will demonstrate that future growth in knowledge of transporter function will be led by integrated
in vitro
and
in silico
approaches.
Large‐Scale Synthesis
Authors: Cole Kevin P.
Published: April 2021

Large‐scale synthesis enables drug discovery, clinical development, and commercialization for new small molecule medicines. Several key disciplines collaborate to develop and define chemical processes, and ensure that they are suitable for large‐scale manufacturing activities. This article will discuss how new drugs transition from the medicinal chemistry laboratory, to kilo‐scale facilities, to pilot, and eventually to commercial scale. Important topics along the way include route selection, process safety, environmental considerations, equipment and facility types, scale‐dependent phenomenon, continuous processing, outsourcing, development models, and regulatory considerations. The article concludes with recent two case studies that highlight some of the topics covered and exemplify the power of process development and large‐scale production for modern small molecule drugs.
Hematopoietic Agents
Authors: Hoggatt Jonathan , Datari Shruti , Pelus Louis M.
Published: April 2021

Higher organisms maintain adequate numbers of blood cells to meet the normal physiological requirements of blood cell turnover as well as respond to needs for increased demand (e.g. infection). This lifelong process of continuous formation and turnover of blood cells is termed “hematopoiesis” and is regulated in both stochastic and instructive fashion.
Estrogen Receptor Modulators
Authors: Rosales Carlo I. , Gutgesell Lauren M. , Ratia Kiira M. , Thatcher Gregory R.J.
Published: April 2021

The estrogen receptor (ER) has historically played and continues to play a prominent role in drug discovery as a target for medicinal chemists. The first targeted cancer therapy was directed at ERα and the first clinical drug that is a proteolysis targeting small molecule is also an ER ligand used to treat metastatic breast cancer. The last decade has been described as a renaissance in the medicinal chemistry of endocrine therapy, therefore, this article focuses on design of small molecule ERα ligands for treatment of hormone‐dependent breast cancer. As our understanding of the role of ER in resistance to endocrine therapy increases, further opportunities will be presented for medicinal chemists to design therapeutic agents for metastatic disease. Beyond breast cancer, ER, whether nuclear or extranuclear remains largely unexploited as a target for small molecule drug design, which is partly explained by the complexity of the underlying biology and partly by the cooling influence of the initial Women's Health Initiative outcomes on estrogen replacement therapy. Old and new concepts of ligand binding and signal transduction by ER are presented to stimulate the interests of medicinal chemists; accompanied by a catalogue of newer small molecule ligands reported in the literature and their interactions with ER.
Essential Micronutrients: Vitamins and Essential Fatty Acids
Authors: H. Block John
Published: April 2021

Biochemical processes cannot operate without what traditionally are called vitamins. The cell membranes cannot be maintained and production of crucial cytokines cannot occur without the two essential fatty acids. Vitamins have a variety of functions with some having dual roles ranging from regulators of cell division, structural components of key tissues, coenzymes, and antioxidants Vitamins A and D have provided the medicinal chemist with the basic structure to develop pharmacologically active molecules indicated for a variety of diseases. Some of the vitamins are toxic when taken in excess and have defined tolerable upper intake levels. Long‐chain fatty acids are essential because of human's inability to introduce double bonds on the third or sixth carbon from the terminal end of the chain. Linoleic acid is the precursor to prostaglandins, thromboxanes, leukotrienes, and lipoxins, and α‐linolenic acid is the precursor of long‐chain acids that are components of lipid membranes. Recent meta‐analyses and recent double blind studies on large numbers of human subjects indicate that taking vitamin and fatty acid supplements appear to not be beneficial providing a balanced diet is consumed.
Therapeutic and Diagnostic Agents for Parkinson's Disease
Authors: Ghoneim Ola A.M. , Booth Raymond G.
Published: April 2021

This article summarizes the neurobiology of Parkinson's disease and medicinal chemistry relevant to treatment of this neurodegenerative disorder with neuropsychiatric complications. The article also surveys basic clinical features of Parkinson's disease, its neuropathophysiology and etiology. Considered are genetic, maturational, metabolic, and environmental contributors to risk for the disease. Pharmacotherapy for Parkinson's disease includes
l
‐dopa to counter cerebral dopamine deficiency, direct dopaminergic agonists, and agents that prolong the actions of
l
‐dopa or dopamine by preventing their metabolism by peripheral aromatic amino acid decarboxylase, catechol‐
O
‐methyltransferase, or monoamine oxidase. Additional drugs acting on nondopaminergic systems include muscarinic acetylcholine, adenosine, and
l
‐glutamate antagonists, as well as serotonin (5‐hydroxytryptamine) agonists. Agents used to diagnose Parkinson's disease and monitor its progression include radioactive compounds used to image brain
l
‐dopa and dopamine neurotransporters and dopamine receptors. Finally, potential contributions are considered of medicinal chemistry to improve pharmacotherapy of Parkinson's disease.
Microbes to Man: From Soils and the Depths to Drugs
Authors: Newman David J.
Published: April 2021

This article covers microbially sourced antibiotics and anticancer agents that have either been approved by regulatory agencies (US and EU), are awaiting approval or are generally in Phases I–Phase III (cancer) or Phase I–IV (antibiotics). Also included are discussions of compounds that have been “developed” by synthetic chemists using as their templates, materials originally from microbes. Included are discussions on developments with genetic analyses of as yet uncultured (perhaps unculturable in the case of some symbionts), including use of environmental DNA (eDNA) as routes to novel agents where the microbe is unknown, even “unknowable.” In addition, examples are given of how agents that are too toxic to act as pharmaceutical agents in their own right, have now become major components of novel treatments for cancer treatment by linking these “toxins” to monoclonal antibodies directed to particular epitopes on cancerous cells, thus delivering highly toxic and effective agents directly to the site(s) needed. Comments have also been made about the lack of new antimicrobials, in particular directed toward fungal infections and the ESKAPE pathogen series, where agents long out of use, are now acting as templates upon which to design novel potent compounds.
Structure Alerts
Authors: Norman Bryan
Published: April 2021

Structure alerts are classes of chemicals, functional groups, or substructures that, when present in drugs or drug candidates, have been linked to preclinical toxicity and/or adverse drug reactions (ADRs) in humans. The assignment of structure alerts, which includes a wide variety of structural types, has mostly emerged from retrospective analyses of drug or drug candidates that have demonstrated toxicity. Some compounds are inherently toxic, while others containing structure alerts manifest toxicity due to metabolism and formation of reactive metabolites. In many cases, the mechanisms associated with toxicity have been hypothesized to be the result of covalent binding of a drug or metabolite to endogenous nucleophiles in proteins and nucleic acids. Strategies to mitigate toxicity due to structure alerts have generally focused on avoidance and/or replacement of the structure alert. However, as many safe and successful drugs contain structure alerts, there is no industry‐wide alignment on which should always be avoided or replaced. It has been demonstrated that ADRs are more likely to occur in higher dose drugs (>100 mg) and more lipophilic drugs (LogP >3). The inclusion of structure alerts in drug candidates that have these liabilities may increase the risk of toxicity.
Structure‐Based Drug Design
Authors: Ferreira Leonardo L.G. , Andricopulo Adriano D.
Published: April 2021

Structure‐based drug design (SBDD) is the backbone of modern pharmaceutical research and development. Its origins date back to the 1950s and 1960s when the first X‐ray protein structures and pioneering studies correlating ligand–receptor binding and drug activity came out. With this foundation, seminal work on computer graphics enabled the first visualization and manipulation of virtual protein structures. These milestones opened the avenues for the growth of protein crystallography and molecular modeling, which thenceforth evolved side by side to culminate in modern SBDD. Today, SBDD can handle molecular targets previously regarded as intractable or undruggable, such as protein–protein interactions. Another advance coming from SBDD, fragment‐based drug discovery has excelled in optimizing weak ligands into drug‐like compounds. SBDD has provided groundbreaking drugs for many therapeutic areas, including highly complex conditions and diseases that were previously considered a death sentence. In fact, a substantial fraction of the drugs approved recently have been developed with the support of structural data. This article provides a perspective on the central aspects of this exciting field and explores the fundamentals of molecular modeling and its integration with X‐ray diffraction. The discussion of key concepts is followed by representative examples of the practice of SBDD.
Improving Strength and Electromagnetic Shielding Effectiveness of Mg–Sn–Zn–Ca–Ce Alloy by Sn Addition
Authors: Ye Junliu , Chen Xianhua , Luo Zhu , Li Jianbo , Yuan Yuan , Tan Jun , Pan Fusheng
Published: April 2021

The strength and electromagnetic shielding capability are two essential requirements for lightweight metallic materials as shielding materials. However, it is still a challenge to develop magnesium (Mg) alloys with both high strength and favorable electromagnetic shielding capability. Herein, the results show that alloying with Sn in Mg–xSn–Zn–Ca–Ce alloys simultaneously increases both strength and electromagnetic shielding effectiveness (SE). After Sn alloying, the average grain size of the alloys is greatly reduced, whereas the intensity of basal texture is enhanced, and the precipitation of Mg2Sn phase is promoted. The Mg–3Sn–Zn–Ca–Ce alloy attains best comprehensive mechanical properties and electromagnetic SE (ultimate tensile strength (UTS) of 337 MPa and SE of 91–114 dB) in Sn containing alloys. The increase in strength is attributed to the combination of grain refinement, texture strengthening, and precipitation strengthening. The great electromagnetic SE is mainly due to the regularly arranged Mg2Sn precipitates in the basal plane.
Recent Advances in Catalyst Structure and Composition Engineering Strategies for Regulating CO2 Electrochemical Reduction
Authors: Zhu Shangqian , Delmo Ernest Pahuyo , Li Tiehuai , Qin Xueping , Tian Jian , Zhang Lili , Shao Minhua
Published: April 2021

Electrochemical CO2 reduction has been recognized as a promising solution in tackling energy‐ and environment‐related challenges of human society. In the past few years, the rapid development of advanced electrocatalysts has significantly improved the efficiency of this reaction and accelerated the practical applications of this technology. Herein, representative catalyst structures and composition engineering strategies in regulating the CO2 reduction selectivity and activity toward various products including carbon monoxide, formate, methane, methanol, ethylene, and ethanol are summarized. An overview of in situ/operando characterizations and advanced computational modeling in deepening the understanding of the reaction mechanisms and accelerating catalyst design are also provided. To conclude, future challenges and opportunities in this research field are discussed.
Engineering a Hydrogen‐Sulfide‐Based Nanomodulator to Normalize Hyperactive Photothermal Immunogenicity for Combination Cancer Therapy
Authors: Li Jie , Xie Lisi , Li Bei , Yin Chao , Wang Guohao , Sang Wei , Li Wenxi , Tian Hao , Zhang Zhan , Zhang Xuanjun , Fan Quli , Dai Yunlu
Published: April 2021

Photothermal therapy (PTT), one of the most‐potent cancer therapeutic strategies known, is highlighted with excessive inflammatory response, while ablating cancer with immunogenic death. This hyperactive immune response may override PTT‐triggered immunogenicity, exacerbate skin empyrosis, and incur permanent tissue injury and high‐profile tumor regeneration. Therefore, an anticancer balance between pathological and protective immune response is urgently needed for an advanced photothermal therapeutic tactic. Herein, a gas‐modulated photothermal immunogenicity strategy is proposed by integrating an amphiphilic‐conjugated polymer with a polysulfide‐based hydrogen sulfide (H2S) donor (2,2′‐dipyridyl tetrasulfide@CP‐PEG) (where CP = conjugated polymer and PEG = poly(ethylene glycol)). The CP is endowed with NIR‐II fluorescence capacity and favorable photothermal effect, tracing the tumor for precise therapeutics. The polysulfide donor can release H2S triggered by intracellular glutathione, which elicits mitochondrial dysfunction and robust anti‐inflammation effect. Ultimately, this gas‐modulated PTT strategy inhibits tumor growth remarkably and limits the magnitude of PTT‐induced proinflammatory tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1beta (IL‐1β) cytokines. Moreover, the regulated inflammation accelerates PTT‐induced wound healing. A H2S‐modulated PTT with adaptive immune response is thus recommended as an advanced strategy to cancer therapeutics.
Surfactant and irrigation impacts on soil water content and leachate of soils and greenhouse substrates
Authors: Abagandura Gandura Omar , Park Dara , Bridges William C.
Published: April 2021

Water retentionx is considered an important characteristic for determining the efficiency and effectiveness of soils and greenhouse substrates. Surfactants have the potential to improve water infiltration and distribution uniformity throughout the soil profile. In addition, efficient irrigation can improve the wettability of soils. The objective of this study was to determine how surfactants and irrigation influence soil water content (SWC), leachate volume, and pH in soils and greenhouse substrates. This study was conducted at Clemson University, SC, on two soils (sandy loam and sand) and two substrates (Fafard 3B‐SURF and 80% sand, 20% peat). Four surfactants (a) 10% oleic acid esters of block copolymers (OAC), (b) 30% alkoxylated polyols and 21% glucoethers (APG), (c) 50% nonionic polyols and 5% 1,2‐propanediol (NIPP), and (d) water control (CNT) with two irrigation regimes (ONCE and SPLIT) were applied to PVC columns. Based on the leachate results, applying irrigation volume as SPLIT in conjunction with using a surfactant reduced leachate up to 75%. The soils retained more water when OAC and NIPP surfactants were applied. When the soil was left to dry out, the SWC was 5 and 9% higher from SPLIT irrigation compared with ONCE irrigation in the sand–peat and the sand soils, respectively. Surfactants can increase SWC, and combining split irrigation with surfactants can play an important role in reducing leaching from soils and greenhouse substrates, resulting in water quality and quantity conservation, and an economic advantage to the grower.
Low‐Temperature Nickel‐Catalyzed C−N Cross‐Coupling via Kinetic Resolution Enabled by a Bulky and Flexible Chiral N‐Heterocyclic Carbene Ligand
Authors: Wang Zi‐Chao , Xie Pei‐Pei , Xu Youjun , Hong Xin , Shi Shi‐Liang
Published: April 2021

The transition‐metal‐catalyzed C−N cross‐coupling has revolutionized the construction of amines. Despite the innovations of multiple generations of ligands to modulate the reactivity of the metal center, ligands for the low‐temperature enantioselective amination of aryl halides remain a coveted target of catalyst engineering. Designs that promote one elementary reaction often create bottlenecks at other steps. We here report an unprecedented low‐temperature (as low as −50 °C), enantioselective Ni‐catalyzed C−N cross‐coupling of aryl chlorides with sterically hindered secondary amines via a kinetic resolution process (s factor up to >300). A bulky yet flexible chiral N‐heterocyclic carbene (NHC) ligand is leveraged to drive both oxidative addition and reductive elimination with low barriers and control the enantioselectivity. Computational studies indicate that the rotations of multiple σ‐bonds on the C2‐symmetric chiral ligand adapt to the changing needs of catalytic processes. We expect this design would be widely applicable to diverse transition states to achieve other challenging metal‐catalyzed asymmetric cross‐coupling reactions.
Socrates on the Farm: Agricultural Improvement and Rural Knowledge in Eighteenth‐Century Germany and Switzerland
Authors: Phillips Denise
Published: April 2021

In many eighteenth‐century agricultural texts, peasants were depicted as an impediment to agrarian improvement, superstitious and resistant to novelty. That was the stereotype one often encountered, in any case, in more programmatic writing about agriculture from this period. A closer look at the era's technical literature tells a more complicated story, however. Much as traveling European naturalists relied on local intermediaries in far corners of the globe, elite agricultural improvers back home relied on local rural knowledge as they drafted a new technical literature on farming. This article looks at Jacob Guyer (also known as Kleinjogg), a Swiss farmer who became an enlightened celebrity after the Zurich doctor Hans Caspar Hirzel published a biography of him in 1761. Hirzel called Kleinjogg a “philosophical farmer”; the article explores the implications of this title, and examines the various ways that elite eighteenth‐century authors used contact with rural people and direct experience of farming as a source of authority.
Ultra‐sensitive detection of ATP in serum and lysates based on nitrogen‐doped carbon dots
Authors: Qin Yaning , Yan Zhaoyue , Liu Rui , Qu Chaojie , Mao Haichen , Qu Lingbo , Yang Ran
Published: April 2021

In this work, novel types of nitrogen‐doped carbon dots (N‐CDs) were prepared from citric acid and glycine (GLY) as precursors through a simple pyrolysis method. The GLY‐CDs showed strong fluorescence with a fluorescence quantum yield as high as 33.34% and good water solubility. The fluorescence of GLY‐CDs could be selectively quenched by iron(III) ion (Fe3+) resulting in the non‐fluorescent complex. Due to the high affinity of Fe3+ to adenosine‐5′‐triphosphate (ATP), the fluorescence of the GLY‐CDs in GLY‐CDs‐Fe3+ could be recovered by ATP. Thereby, quantitatively fluorescent turn‐on detection of ATP could be achieved. The fluorescence recovery ratio was linearly proportional to the concentration of ATP with a detection limit as low as 15.0 nM, indicating the CDs have high sensitivity. The GLY‐CDs were successfully employed in the detection of ATP in serum and cell lysates.
Surface Roughness Effects of Pd‐loaded Magnetic Microspheres on Reduction Kinetics of Nitroaromatics
Authors: An Seonghwi , Manivannan Shanmugam , Viji Mayavan , Shim Min Suk , Hwang Byeong Hee , Kim Kyuwon
Published: April 2021

Metal nanoparticles decoration on magnetically active semiconductor materials is a common strategy to improve the colloidal stability, catalyst harvesting, and reuse. In this study, a surfactant‐free solvothermal method followed by a heat treatment to prepare highly surface roughened α‐Fe2O3 (Hematite)/Pd microspheres (MSPs) is reported. Amine‐functionalized silicate sol‐gel matrix is used as a stabilizing agent for the solvothermal synthesis of Prussian blue (PB) MSPs using HCl at 80 °C for 20 h. It is observed that modulating HCl concentration in a medium led to a high degree of improvement in surface roughness. Employing heat treatment at 350 °C for 6 h, PB MSPs are transformed into α‐Fe2O3, Hematite phase. Fabricated Hematite/Pd MSPs have shown high catalytic reduction activity over p‐nitrophenol. Reduction kinetics of nitroaromatics is monitored using UV‐vis absorption spectroscopy and product formation is confirmed by 1H and 13C NMR analyses.
Carbo‐mer of Barrelene: A Rigid 3D‐Carbon‐Expanded Molecular Barrel
Authors: Zhu Chongwei , Poater Albert , Duhayon Carine , Kauffmann Brice , Saquet Alix , Rives Arnaud , Maraval Valérie , Chauvin Remi
Published: April 2021

After extensive studies of 1D and 2D skeletal carbo‐mers based on C8 π‐conjugating dialkynylbutatriene units (DABs: ∼C≡C−(R)C=C=C=C(R)−C≡C∼) bridging sp or sp2 centers in carbo‐butene, carbo‐xylylene or carbo‐benzene derivatives, 3D versions are envisaged through carbo‐barrelenes and partially reduced derivatives thereof where two or three DAB blades span a bridge between sp3 carbinol vertices or ether thereof. For R=Ph, stable representatives were synthesized through a pivotal [6]pericyclynedione, and extensively characterized by spectroscopic, electrochemical and crystallographic methods. Density functional theory calculations allow detailed analysis of structural and electronic features of the 7 Å high C26 barrel‐shaped molecules, and show that they can behave as cages for ionic species. Beyond aesthetical concerns, the results could open prospects of applications in host‐guest supramolecular chemistry and single molecule charge transport.
Morphology Engineering of Fullerene[C70] Microcrystals: From Perfect Cubes, Defective Hoppers to Novel Cruciform‐Pillars
Authors: Xu Ting , Chen Ning , He Zhimin , Yu Pengwei , Shen Wangqiang , Akasaka Takeshi , Lu Xing
Published: April 2021

Controlled crystallization of fullerene molecules into ordered molecular assemblies is important for their applications. However, the morphology engineering of fullerene[C70] assemblies is challenging, and complicated architectures have rarely been reported due to the low molecular symmetry of C70molecules, which makes their crystallization difficult to control and the low production yield as well. Herein, with the assistance of solvent intercalation, a general reprecipitation approach is reported to prepare morphologically controllable C70microcrystals with mesitylene as a good solvent andn‐propanol as a poor solvent in one solvent system without replacing specific solvents. A series of C70microcrystals with high uniformity from perfect cubes and defective hoppers to novel cruciform‐pillars are obtained by intentionally tuning C70concentration and the volume ratio of mesitylene ton‐propanol. Among them, novel cruciform‐pillar‐shaped microcrystals are obtained for the first time by further decreasing the amount of mesitylene in the solvent‐intercalated microcrystals. Notably, the C70concentration is a key parameter for the selective growth of C70hopper, rather than the volume ratio of mesitylene ton‐propanol. Interestingly, the hopper‐shaped microcrystals exhibit excellent photoluminescence properties relative to those of cubes and cruciform‐pillars owing to the enhanced light absorption, proving their potential applications in optoelectronic devices. This study offers new insights into the morphology‐controlled synthesis of other micro/nanostructured organic microcrystals and the fine tuning of photoluminescence properties of organic crystals.
Thermally Activated Delayed Fluorescence and Phosphorescence Quenching in Iminophosphonamide Copper and Zinc Complexes
Authors: Goswami Bhupendra , Feuerstein Thomas J. , Yadav Ravi , Lebedkin Sergei , Boden Pit J. , Steiger Sophie T. , Niedner‐Schatteburg Gereon , Gerhards Markus , Kappes Manfred M. , Roesky Peter W.
Published: April 2021

The synthesis of copper and zinc complexes of four variably substituted iminophosphonamide ligands is presented. While the copper complexes form ligand‐bridged dimers, the zinc compounds are monomeric. Due to different steric demand of the ligand the arrangement of the ligands within the dimeric complexes varies. Similar to the structurally related iminophosphonamide complexes of alkali metals and calcium, the steady‐state and time‐resolved photoluminescence (PL) of four of the seven compounds studied here as solids in a temperature range of 5–295 K can be described within the scheme of thermally activated delayed fluorescence (TADF). Accordingly, they exhibit bright blue‐green phosphorescence at low temperatures (<100 K), which turns into delayed fluorescence by increasing the temperature. However, unusually, the fluorescence is practically absent in two copper complexes which otherwise still conform to the TADF scheme. In these cases, the excited singlet states decay essentially non‐radiatively and their thermal population from the corresponding low‐lying triplet states efficiently quenches PL (phosphorescence). Three other copper and zinc complexes only exhibit prompt fluorescence, evidencing a wide variation of photophysical properties in this class of compounds. The excited states of the copper complex with especially pronounced phosphorescence quenching were also investigated by low‐temperature time‐resolved infrared spectroscopy and quantum chemical calculations.
Self‐Assembled Porphyrinoids: One‐Component Nanostructured Photomedicines
Authors: Paramio Irene , Torres Tomás , de la Torre Gema
Published: April 2021

Photodynamic therapy (PDT) is becoming a promising way to treat various kinds of cancers, with few side effects. Porphyrinoids are the most relevant photosensitizers (PS) in PDT, because they present high extinction coefficients, biocompatibility, and excellent photochemical behavior. To maximize therapeutic effects, polymer‐PS conjugates, and PS‐loaded nanoparticles have been developed, with insights in improving tumor delivery. However, some drawbacks such as non‐biodegradability, multistep fabrication, and low reagent loadings limit their clinical application. A novel strategy, noted by some authors as the “one‐for‐all” approach, is emerging to circumvent the use of additional delivery agents. This approach relies on the self‐assembly of amphiphilic PS to fabricate nanostructures with improved transport properties. In this review we focus on different rational designs of porphyrinoid PS to achieve some of the following attributes in nanoassembly: i) selective uptake, through the incorporation of recognizable biological vectors; ii) responsiveness to stimuli; iii) combination of imaging and therapeutic functions; and iv) multimodal therapy, including photothermal or chemotherapy abilities.
Financial toxicity, mental health, and gynecologic cancer treatment: The effect of the COVID‐19 pandemic among low‐income women in New York City
Authors: Chen Yiting Stefanie , Zhou Zhen Ni , Glynn Shannon M. , Frey Melissa K. , Balogun Onyinye D. , Kanis Margaux , Holcomb Kevin , Gorelick Constantine , Thomas Charlene , Christos Paul J. , Chapman‐Davis Eloise
Published: April 2021

BACKGROUND

New York City (NYC) emerged as an epicenter of the COVID‐19 pandemic, and marginalized populations were affected at disproportionate rates. The authors sought to determine the impact of COVID‐19 on cancer treatment, anxiety, and financial distress among low‐income patients with gynecologic cancer during the peak of the NYC pandemic.

METHODS

Medicaid‐insured women who were receiving gynecologic oncology care at 2 affiliated centers were contacted by telephone interviews between March 15 and April 15, 2020. Demographics and clinical characteristics were obtained through self‐report and retrospective chart review. Financial toxicity, anxiety, and cancer worry were assessed using modified, validated surveys.

RESULTS

In total, 100 patients completed the telephone interview. The median age was 60 years (range, 19‐86 years), and 71% had an annual income <$40,000. A change in employment status and early stage cancer (stage I and II) were associated with an increase in financial distress (P < .001 and P = .008, respectively). Early stage cancer and telehealth participation were significantly associated with increased worry about future finances (P = .017 and P = .04, respectively). Lower annual income (<$40,000) was associated with increased cancer worry and anxiety compared with higher annual income (>$40,000; P = .036 and P = .017, respectively). When controlling for telehealth participation, income, primary language, and residence in a high COVID‐19 prevalence area, a delay in medical care resulted in a 4‐fold increased rate of anxiety (P = .023, 95% CI, 1.278‐14.50). Race was not significantly associated with increased financial distress, cancer worry, or anxiety.

CONCLUSIONS

Low socioeconomic status was the most common risk factor for increased financial distress, cancer worry, and anxiety. Interventions aimed at improving access to timely oncology care should be implemented during this ongoing pandemic.
Impact of molecular testing on detecting mimics of oncocytic neoplasms in thyroid fine‐needle aspirates diagnosed as follicular neoplasm of Hürthle cell (oncocytic) type
Authors: Landau Michael S. , Nikiforov Yuri E. , Ohori N. Paul , Chiosea Simion I.
Published: April 2021

Background

Some thyroid nodules cytologically presenting as follicular neoplasm, Hürthle cell (Oncocytic) type (FNHCT), are not oncocytic tumors and represent autonomously functioning thyroid nodules (AFTNs) with TSHR, GNAS, and EZH1 mutations or oncocytic metaplasia. A to be defined subset of FNHCT harbors genome haploidisation‐type DNA copy number alterations (GH‐CNA). Molecular profiling of FNHCT may distinguish oncocytic neoplasms from its mimics.

Methods

Consecutive fine‐needle aspirates of 180 thyroid nodules over 37 months diagnosed as FNHCT and tested by ThyroSeq v3 were identified. Histologic follow‐up was available for 79 of 180 nodules (44%).

Results

No molecular alterations were found in 76 of 180 nodules (42%), of which 15 were resected (oncocytic metaplasia, n = 7; follicular oncocytic adenoma, n = 8). Of nodules followed without surgery, 17 of 101 (17%) showed TSHR, EZH1, and GNAS mutations of AFTNs. Papillary thyroid carcinoma was identified by BRAF V600E (n = 2) and hyalinizing trabecular adenoma by PAX8‐GLIS3 (n = 1). GH‐CNA alone was detected in 42 of 180 FNHCT nodules (23%), of which 29 were resected and histologically diagnosed as follicular oncocytic neoplasms. All remaining resected nodules were histologically proven oncocytic neoplasms: 1) RAS‐like alterations without GH‐CNA (n = 25) and 2) TERT and/or TP53 mutations co‐occurring with GH‐CNA (n = 6), including anaplastic thyroid carcinoma arising from follicular oncocytic carcinoma with TP53, TERT mutations with GH‐CNA (n = 2).

Conclusions

A proportion of FNHCT nodules are AFTNs and oncocytic metaplasias, which can be suspected based on characteristic mutations or lack of alterations on molecular testing. Among resected FNHCTs, GH‐CNAs characterize approximately half of histologically confirmed follicular oncocytic neoplasms.