bluuebunny/crossref_metadata_2025 huggingface dataset:
Transition-Translation: Andrzej Sosnowski’s Translation of Three Poems by John Ashbery
Authors: Orska Joanna
Published: August 2023

Narrative poetic forms became popular in Poland in the 1990s, and just as it is the case with other changes in poetic style and genres, this tendency can be associated with the popularization of the styles of the New York School of poetry. I would like to reflect on the poetic practice of John Ashbery and its presence in Poland. My main interest is to show how translations of his texts refresh through their formal and conceptual novelty the range of the Polish lyric poetry’s sensitivities, expanding the possibilities of poetic imagination and language. The translators of poems by the New York School poets remain to this day perhaps the most important contemporary authors, who are also most often mentioned by critics as reference points for new Polish poetry. This is the case of Andrzej Sosnowski, whose translation of Three Poems (a prose poem from 1974), published in Poland in 2012 as Cztery poematy, is undoubtedly the crowning achievement of this poet-translator. Sosnowski himself is the author of several poetic prose pieces (which may be aptly described, after Fredman, as poet’s prose), whose relationships with both Ashbery himself and the authors translated by both poets (Raymond Roussel, Arthur Rimbaud) seem to be part of a complicated “translationaltransitive” game that Sosnowski may play with Ashbery. I decided to choose this example of the very unique Polish reception of the American poet because it seems to be a wide-ranging artistic project, far exceeding the boundaries of an adventure that might be called a faithful or masterly translation.
The negative adipogenesis regulator Dlk1 is transcriptionally regulated by Ifrd1 (TIS7) and translationally by its orthologue Ifrd2 (SKMc15)
Authors: Vietor Ilja , Cikes Domagoj , Piironen Kati , Vasakou Theodora , Heimdörfer David , Gstir Ronald , Erlacher Matthias David , Tancevski Ivan , Eller Philipp , Demetz Egon , Hess Michael W , Kuhn Volker , Degenhart Gerald , Rozman Jan , Klingenspor Martin , Hrabe de Angelis Martin , Valovka Taras , Huber Lukas A
Published: August 2023

Delta-like homolog 1 (Dlk1), an inhibitor of adipogenesis, controls the cell fate of adipocyte progenitors. Experimental data presented here identify two independent regulatory mechanisms, transcriptional and translational, by which Ifrd1 (TIS7) and its orthologue Ifrd2 (SKMc15) regulate Dlk1 levels. Mice deficient in both Ifrd1 and Ifrd2 (dKO) had severely reduced adipose tissue and were resistant to high-fat diet-induced obesity. Wnt signaling, a negative regulator of adipocyte differentiation, was significantly upregulated in dKO mice. Elevated levels of the Wnt/β-catenin target protein Dlk1 inhibited the expression of adipogenesis regulators Pparg and Cebpa, and fatty acid transporter Cd36. Although both Ifrd1 and Ifrd2 contributed to this phenotype, they utilized two different mechanisms. Ifrd1 acted by controlling Wnt signaling and thereby transcriptional regulation of Dlk1. On the other hand, distinctive experimental evidence showed that Ifrd2 acts as a general translational inhibitor significantly affecting Dlk1 protein levels. Novel mechanisms of Dlk1 regulation in adipocyte differentiation involving Ifrd1 and Ifrd2 are based on experimental data presented here.
The genomic landscape of transposable elements in yeast hybrids is shaped by structural variation and genotype-specific modulation of transposition rate
Authors: Hénault Mathieu , Marsit Souhir , Charron Guillaume , Landry Christian R.
Published: August 2023

Transposable elements (TEs) are major contributors to structural genomic variation by creating interspersed duplications of themselves. In return, structural variants (SVs) can affect the genomic distribution of TE copies and shape their load. One long-standing hypothesis states that hybridization could trigger TE mobilization and thus increase TE load in hybrids. We previously tested this hypothesis by performing a large-scale evolution experiment by mutation accumulation (MA) on multiple hybrid genotypes within and between wild populations of the yeasts Saccharomyces paradoxus and Saccharomyces cerevisiae . Using aggregate measures of TE load with short-read sequencing, we found no evidence for TE load increase in hybrid MA lines. Here, we resolve the genomes of the hybrid MA lines with long-read phasing and assembly to precisely characterize the role of SVs in shaping the TE landscape. Highly contiguous phased assemblies of 127 MA lines revealed that SV types like polyploidy, aneuploidy and loss of heterozygosity have large impacts on the TE load. We characterized 18 de novo TE insertions, indicating that transposition only has a minor role in shaping the TE landscape in MA lines. Because the scarcity of TE mobilization in MA lines provided insufficient resolution to confidently dissect transposition rate variation in hybrids, we adapted an in vivo assay to measure transposition rates in various S. paradoxus hybrid backgrounds. We found that transposition rates are not increased by hybridization, but are modulated by many genotype-specific factors including initial TE load, TE sequence variants and mitochondrial DNA inheritance. Our results show the multiple scales at which TE load is shaped in hybrid genomes, being highly impacted by SV dynamics and finely modulated by genotype-specific variation in transposition rates.
Research on automatic matching of online mathematics courses and design of teaching activities based on multiobjective optimization algorithm
Authors: Li Jiafeng , Cao Lixia , Zhang Guoliang
Published: August 2023

The teaching of the optimization algorithm is a new kind of swarm intelligence optimization technique, which is superior in optimizing many simple functions. Still, it is not evident in processing some complex problems (group and teaching classification). Achieving automatic matching and knowledge transfer in online courses is imperative in mathematics education. This study proposes a design scheme MTCBO-LR (multiobjective capability optimizer-logistic regression), based on multitask optimization, which enables precise knowledge transfer and data interaction among many educators. It incorporates the standard TLBO algorithm to optimize, provides a variety of learning tactics for students at different stages of mathematics instruction, and is capable of adaptively adjusting these strategies in response to actual teaching needs. Experimental results on various datasets reveal that the proposed method enhances searchability and group diversity in various optimization extremes and outperforms similar methods in resolving to multitask teaching problems.
Ethanolamine-phosphate phospho-lyase (ETNPPL) contributes to the diagnosis, prognosis, and therapy of hepatocellular carcinoma
Authors: Zhang Yun , Shen Li , Wang Bojun , Wu Xiaohong
Published: August 2023

Background

Hepatocellular carcinoma (HCC) is characterized by high mortality, difficulty in early screening, relapse, and poor prognosis. This study aimed to explore the expression of ethanolamine-phosphate phospho-lyase (ETNPPL) and its clinical significance in HCC.

Methods

Differentially expressed mRNAs were screened using microarray analysis. Functional enrichment was performed using GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis. We used qRT-PCR to measure the expression of ETNPPL in HCC tissues and paired paracarcinoma tissues. A receiver operating characteristic (ROC) curve and Kaplan-Meier curve were conducted to assess the diagnostic and prognostic values. Cell behaviors were evaluated using a scratch test and transwell assay.

Results

The results showed that numerous mRNAs are abnormally expressed in HCC. ETNPPL was decreased in HCC tissues and cells. The area under curve (AUC) of ETNPPL was 0.9089, demonstrating that ETNPPL had diagnostic value. Low expression of ETNPPL was related to poor prognosis for patients with HCC. Moreover, the over-expression of ETNPPL inhibited HCC cell migration and invasion.

Conclusions

In conclusion, downregulated ETNPPL was found in HCC and is related to poor patient prognosis and the promotion of cell metastasis. This suggests that ETNPPL serves both as a promising diagnosis and prognosis biomarker, and a therapy target of HCC.
Identification of potential functional peptides involved in demyelinating injury in the central nervous system
Authors: Dong Xiaohua , Sun Shuchen , Li Jie , Shen Sen , Chen Wanting , Li Tongqi , Li Xinyuan
Published: August 2023

Multiple sclerosis (MS) is a chronic inflammatory neurologic disease characterized by the demyelinating injury of the central nervous system (CNS). It was reported that the mutant peptide came from myelin proteolipid protein (PLP) and myelin basic protein (MBP) might play a critical role in immunotherapy function of MS. However, endogenous peptides in demyelinating brain tissue of MS and their role in the pathologic process of MS have not been revealed. Here, we performed peptidomic analysis of freshly isolated corpus callosum (CC) from the brains of CPZ-treated mice and normal diet controls of male C57BL/6 mice by LC-MS/MS. Identified a total of 217 peptides were expressed at different levels in MS mice model compared with controls. By performed GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, we found that the precursor protein of these differently expressed peptides (DEPs) were associated with myelin sheath and oxidative phosphorylation. Our study is the first brain peptidomic of MS mice model, revealing the distinct features of DEPs in demyelination brain tissue. These DPEs may provide further insight into the pathogenesis and complexity of MS, which would facilitate the discovery of the potential novel and effective strategy for the treatment of MS.
Computing Y-index of Different Corona Products of Graphs
Authors: Nagarajan S. , Durga M.
Published: August 2023

The Y-index of a graph is defined by the sum of four of degrees of the vertices of a graph. Among the all topological indices the Zagreb indices have been used more considerably than any other topological indices in chemical literature. The concept of Corona Product is a recent inclusion to mathematical vocabulary. One of the most significant graph operations is the corona product of several generic and specific graphs, which is one of the most well-known graph products. In this study, we derive some explicit formulations of several corona product types, including subdivision-vertex corona, subdivision-edge corona, subdivision-vertex neighborhood corona, subdivision-edge neighborhood corona, and vertex-edge corona of two graphs.
Effects of Coral Reef Destruction on Humans and the Environment
Authors: Ranjan Devarshi , Chandravanshi Sanjay , Verma Priyanka , Singh Mayank Bhushan , Verma Durgesh Kumar , Maurya Preeti , Upadhyay Aditya Kumar , Raghunath  , Tiwari Ankit Kumar , Sahu Kanta Kumar
Published: August 2023

Coral reefs are home to a rich biodiversity and one of the most diverse ecosystems on the planet. It provides home to 35,000–60,000 species of plants and animals (over 25% of all marine life), many of which have not been described by science. It provides food, employment, and tourism to people, protecting coastal areas from storm surges; and acts as nesting grounds for many species of fish that are important for commerce. In recent years, several natural and anthropogenic disturbances have damaged the coral reefs of the world a number of events, including pollution, overfishing, destructive fishing methods, boat anchor falls, tourism, mining coral for building materials, and a warming climate, are destroying coral reefs. To reduce the destruction of coral reefs, mitigation measures, encourage sustainable fishing, following all safety precautions when visiting coral reef areas, provide alternative management plans such as coral restoration, artificial reef management, and coral nurseries to improve the coral cover in degraded areas and also increase public awareness and stewardship program related to coral reef and its associated biota, reduce plastic pollution in the ocean.
Survey, Incidence and Pathogenicity of Root Rot Disease of Cotton in Different Districts of Haryana Incited by Rhizoctonia spp
Authors: Vashisht Preeti , Yadav N. K.
Published: August 2023

Aim: Survey, incidence and pathogenicity of root rot disease of cotton in different districts of Haryana incited by Rhizoctonia spp.

Design: Survey.

Place and Duration of Study: Ten major cotton growing districts in Haryana during Kharif 2021 and Kharif 2022.

Methodology: A roving survey to record cotton root rot incidence was conducted in ten major cotton growing districts of Haryana during the month of June and July for consecutive two Kharif seasons 2021 and 2022. On an average 4 growing region of cotton in each district were visited and percent disease incidence was recorded.

Results: Among all the surveyed districts of Haryana the maximum mean disease incidence was recorded in Fatehabad (18.75%) followed by Hisar (15.25 %), Sirsa (15%), While the minimum disease incidence was recorded in Nuh and Charkhi dadri 9.25 per cent in both during kharif 2021. Among all the surveyed districts of Haryana the maximum mean disease incidence was recorded in Fatehabad (18.25%) followed by Sirsa (15.25%), Hisar (15.42%), While the minimum disease incidence was recorded Charkhi dadri (9.08%).

Conclusion: The results of the current study showed that important cotton-growing regions in Haryana have root rot disease incidence. It is clear from the overall study that root rot disease is common in significant mulberry-growing regions in Haryana. As a result, resistant cotton types are urgently needed to address the grower's issue, together with the best management techniques, such as effective biocontrol agents that can significantly reduce the illness. Consequently, research should be conducted to ascertain the incidence of the disease in different places.
Effect of Sulphur and Micronutrient on Growth and Yield of Lentil (Lens culinary is Medik)
Authors: Gangwar Shashank , Singh Rajesh
Published: August 2023

A field experiment was conducted during Rabi, 2022 at Crop Research Farm, Departmentof Agronomy, SHUATS, Prayagraj (U.P). The treatment consisted of three level of Sulphur (25,35,45 kg/ha) and three level of Micro-nutrient Boron (1 kg/ha), Zinc (4 kg/ha), Molybdenum (0.4 kg/ha) and control. The experiment was laid out in Randomized Block Design with ten treatments each replicatd thrice. The soil in the experimental area was sandy loam with pH (8.0), EC (0.56 dS/m), Organic Carbon (0.62%), Available N (225 kg/ha), Available P (38.2 kg/ha), and Available K (240.7 kg/ha). Higher plant height (36.93 cm), number of nodules (16.44) higher dry weight (6.67 g/plant), maximum number of pods/plant (160.33), maximum number of seeds/pod (1.99), higher seed yield (2028.05 kg/ha) and higher stover yield (3540.60 kg/ha). However, the maximum gross return (129245.56 INR/ha), maximum net return (91679.57 INR/ha) and maximum benefit cost ratio (2.44) was obtained with same treatment-9 [Sulphur (45 kg/ha) + Molybdenum (0.4 kg/ha)].
Estimation of Costs and Returns of Groundnut in Vizianagaram Districts of Andhra Pradesh, India
Authors: Naidu K. G. K Narendra , Chandra Ram
Published: August 2023

Groundnut crop is one of the important oil seed crop grown in Vizianagaram district. Though the Groundnut is cultivated on small area but it contributes sizable share in total earnings of the cultivator. However, yield and profit from Groundnut cultivation is uncertain because it is very sensitive and it badly affects from extreme climatic conditions so it requires special attention.

The marketing of Groundnut from producer to consumer also involves various activities like transportation, loading, and storage, etc. During this process of marketing the quality as well as quantity of Groundnut get damaged and lost. The Groundnut growers face number of problems at each stage of production, marketing, and distribution like lack of technical knowledge, lack of market intelligence, inadequate transportation, and major market yard facilities.

The socio-economic characteristics of farmers i.e., size of family, educational status, land utilization pattern, cropping pattern and fixed capital investment were studied. The standard cost concepts i.e., cost 'A', and cost 'B', cost 'C' was used in present study.

Majority of groundnut respondents (36%) had farming experience of 2 – 9 years, about 37% had 10 to 20-year experience, 16% had 21-to-30-year experience, while 09% of the respondents had between 31 to 35-year experience of groundnut production. The mean years of farming experience was 17 years. This is an indication that more farmers are embracing production of the crop due to its profit advantage.

The total owned area is observed between 0.1-0.9 hectares of land, about 40% had 1 – 2 hectares, 22% had between 2 – 4 hectares and 07% had 4 – 10 hectares and none hold above 10 hectares. The average farm size is 1.5 hectares.

The cost A of groundnut cultivation was observed to be Rs.118560, Rs.115543, Rs.111606 and Rs.110040 per hectare of marginal, small, semi-medium, and medium land holding farmers.

Cost B it is the summation of Cost A, Rental Value of owned land and interest on value 67.89 of owned fixed capital.

It is observed as Rs.100281, Rs.97489, Rs.93760 and Rs.92036per hectare of groundnut production in marginal, small, semi-medium and medium land holding farmers and the average value of cost B is Rs.95892 per hectare.

To find Cost C1 is the summation of Cost B and imputed value of family labor, family labor cost is given to be an Rs.7500, Rs.7550, Rs.7700 and Rs.8000 and got a solution of Rs.107781, Rs. 105039, Rs.101460 and Rs.100036 per hectare.

Cost C2 it includes Cost B + 10 per cent of cost B. as managerial charges as calculated as a result Rs.118560, Rs.115543, Rs.115543 and Rs.110040 and the total input cost is also considered a cost C.
Overview of Knowledge about the Importance of the First 1000 Days of Life In Indonesian Women of Reproductive Age (15 - 49 Years) in 2021
Authors: Reviani Nia , Suryanegara Wiradi , Gultom Abitmer
Published: August 2023

The first thousand days of life is a golden period from 0-2 years which is a critical period in brain growth because there is a rapid increase in the development of cells in the brain that are very vulnerable to damage. If, at this time, the child is suffering from malnutrition, it cannot be guaranteed that further development will proceed normally. This study aims to describe knowledge about the importance of of the first 1000 days of life in women of childbearing age (15-49 years) in 2021. This research is a descriptive study with purposive sampling and obtained a total sample of 115 respondents. The results showed that the description of the knowledge of women of childbearing age about the meaning of of  the first 1000 days of life  showed that most women of childbearing age had moderate knowledge of 64 people (56%), knowledge of the of  the first 1000 days of life program showed that most women of childbearing age had high knowledge of 44 people (38%), and knowledge about nutrition in of  the first 1000 days of life  shows that most women of childbearing age have moderate knowledge of 72 people (63%). Based on the results of the study, the description of knowledge about the importance of  the first 1000 days of life in women of childbearing age (15-49 years) regarding of  the first 1000 days of life  program is included in the medium category, regarding the understanding of of  the first 1000 days of life  is included in the high category, and regarding nutrition in of  the first 1000 days of life is included in the medium category.
Fortunato da Costa Family
Authors: Curto José C.
Published: August 2023

This paper reconstructs the history of the Fortunato da Costa family, from the first appearance of its constituting members in Portugal, during the Napoleonic invasion of 1808, through the nation’s political turmoil of the late 1820s and early 1830s, the family’s relocation to São Tomé and Príncipe around 1838-1839, amidst significant Creole-metropolitan tensions on the islands, as well as “intrusions” from the British Anti-Slave Trade Squadron, to its settlement in Angola during an intense period of illegal slave trading and the transition to legitimate commerce, until 1859, when the last known member passed away. The story of the Fortunato da Costa family is an odyssey stretching over half a century, marked by some of the most important processes in Atlantic history. Negotiating these historical developments was anything but easy sailing: in fact, for some it created a series of contradictions, at times leading to the kind of dark moments that families often face. Reconstructing the lives of this unique family thus also presents us with a particularly striking example of the human condition in all its frailties, with a story that is far from unilinear.
retornos à África Ocidental
Authors: Hofbauer Andreas
Published: August 2023

Existem diversas pesquisas sobre comunidades na África fundadas pelos chamados “retornados”, mas não há estudos aprofundados que busquem comparar as trajetórias desses “retornos”. O que se propõe neste ensaio é, portanto, um estudo comparativo que tem um foco específico: no centro das preocupações analíticas estarão as relações que os/as retornados/as – mais especificamente as primeiras duas gerações – estabeleceram com as populações locais. Além da identificação de semelhanças objetiva-se apontar para diferenças substanciais e relacioná-las com conjunturas e contextos específicos. As experiências em Serra Leoa, na Libéria, no Benim e em Gana servirão como exemplos que permitem reconstruir “modos” de “reinserção” de populações, sequestradas das suas comunidades de origem, em terras africanas.
Conselhos noturnos num quintal de Nampula
Authors: Silva Jaqueline de Oliveira e
Published: August 2023

Na arqueologia, escava-se por camadas em busca de fragmentos que torna possível recontar uma história. Observando a técnica de trabalho das arqueólogas, penso neste trabalho com as danças makuas como a busca por uma estratigrafia, por traçar a trajetória da dança através dos seus vestígios e diferentes níveis de profundidade: os movimentos, as narrativas e as relações entre pessoas e os objetos. Nessa escavação, encontrei fragmentos de narrativas, imagens, vídeos, textos e sons que me levaram a reconstruir sentidos, descrever e traçar movimentos. Busco compreender os ritos de iniciação femininos através do cruzamento entre a experiência vivida pelo meu corpo de mulher negra diaspórica, guiada pelas mãos das mulheres makuas e as narrativas dessas mulheres e dos homens makuas.
Performance musical como disputa político-discursiva na diáspora
Authors: Abreu Mariana
Published: August 2023

A edição de 2022 do halftime show do Super Bowl, promovido pela National Football League (NFL) dos Estados Unidos (EUA), causou debates por se tratar da primeira edição em que o evento foi dedicado à cultura hip-hop do país. O que poderia parecer uma celebração da cultura negra foi, também, um palco de disputas políticas e discursivas atravessadas na performance. A NFL é objeto de crítica em função do tratamento conferido às pautas raciais, de maneira que os artistas tiveram que buscar estratégias para transmitir na performance a mensagem central do rap: a crítica à opressão racial e a celebração de vidas negras. Neste artigo, proponho analisar as dinâmicas de disputas discursivas que se articulam na construção dessa performance musical, entendendo a raça como uma categoria analítica central e retomando elementos da história e da estrutura do rap para entender de que forma a política performática se deu no show.
Escrevendo a diferença
Authors: Araújo Melvina Afra Mendes de
Published: August 2023

Neste artigo são descritas práticas de atores envolvidos na reabertura das antigas escolas independentes no Quênia após 1957, fechadas em 1952 por serem consideradas “celeiros de guerrilheiros”, e a construção de novas escolas sob a direção de missionários da Consolata. A escolha destes missionários para dirigi-las e os esforços para construir novas escolas são fruto de relações que foram se constituindo ao longo do período da guerrilha, iniciada em 1952, em que a maior parte dos kikuyus, maior grupo populacional do Quênia, ficou aprisionada em campos de concentração ou detenção. Para a análise basear-me-ei em dados colhidos em pesquisas de campo, documental e bibliográfica, analisados a partir de uma perspectiva focada em processos relacionais.
Unique Device Identifiers for Medical Devices at 10 Years
Authors: Dhruva Sanket S. , Ross Joseph S. , Wilson Natalia A.
Published: August 2023

This Viewpoint discusses the next steps to realize the public health promise of using unique device identifiers in health information data and outlines the progress and challenges in implementation over the past 10 years.
Groundwater flow and heterogeneous discharge into a seepage lake: Combined use of physical methods and hydrochemical tracers
Authors: Kazmierczak J. , Müller S. , Nilsson B. , Postma D. , Czekaj J. , Sebok E. , Jessen S. , Karan S. , Stenvig Jensen C. , Edelvang K. , Engesgaard P.
Published: August 2023

Groundwater discharge into a seepage lake was investigated by combining flux measurements, hydrochemical tracers, geological information, and a telescopic modeling approach using first two‐dimensional (2‐D) regional then 2‐D local flow and flow path models. Discharge measurements and hydrochemical tracers supplement each other. Discharge measurements yield flux estimates but rarely provide information about the origin and flow path of the water. Hydrochemical tracers may reveal the origin and flow path of the water but rarely provide any information about the flux. While aquifer interacting with the lake remained under seemingly steady state conditions across seasons, a high spatial and temporal heterogeneity in the discharge to the lake was observed. The results showed that part of the groundwater flowing from the west passes beneath the lake and discharges at the eastern shore, where groundwater springs and high discharge zones (HDZs) are observed at the lake bottom and at seepage faces adjacent to the lake. In the 2‐D cross section, surface runoff from the seepage faces delivers 64% of the total groundwater inputs to the lake, and a 2 m wide offshore HDZ delivers 13%. Presence of HDZs may control nutrient fluxes to the lake.
Carboamination and Alkylative Cyclization withCNBond Formation in Stereoselective Syntheses
Authors: Ghorai Manas K. , Halder Sandipan , Samanta Sauvik
Published: August 2023

The carboamination reaction can be considered an important and fascinating tool for atom‐economic and convergent construction toward the functionalizedN‐containing cyclic compounds. Because the aza‐cycle is frequently found in almost all members of the alkaloid family with immense synthetic and pharmacological activities, the formation of this ring system is a highly demanding task for synthetic organic chemists. As a result, several rational techniques have been developed including intramolecular SN2 reactions, reductive amination reactions, conjugate addition reactions, metal‐ and acid‐catalyzed cyclizations, and ring‐closing olefin metathesis reactions. Despite the many available routes, the carboamination strategy could be one of the best techniques considering stereoselectivity and the step economic path toward the formation of ring compounds in an elegant way.Alkylative cyclization with CN bond formation (N‐alkylation) is one of the most important methods in organic synthesis for the construction of aza‐cycles. Many well‐known name reactions (e.g., aza‐Diels‐Alder, aza‐Michael, aza‐Mannich, aza‐Henry reactions, etc.), which are generally being employed in the intramolecular CN bond formation step, can be treated as CN alkylative cyclization. It is an extremely powerful method for the stereoselective synthesis ofN‐heterocycles like aziridines, azetidines, lactams, pyrrolidines, piperidines, amino sugars, and many more, which are the basic structural units present in many natural products and biologically active compounds.
Stereoselective Synthesis of Halogenated Natural Products
Authors: Yoshimitsu Takehiko
Published: August 2023

Halogen functionalities often influence the physical, chemical, and biological properties of organic molecules, creating molecular diversity. Because of their significant biological properties, organohalogens have attracted considerable attention as invaluable medicinal resources. As a result, the synthesis of organohalogens is a topic of immense interest and it has motivated us to develop new halogenation methodologies.

This chapter will highlight synthetic approaches to selected bioactive organohalogens to which unique methods of carbon–halogen bond formation have been applied. Furthermore, recent developments in methodology, particularly in catalysis, for enantioselective halogenation with great potential for future applications to natural organohalogen synthesis will be briefly overviewed.
Enzymatic Halogenation in Stereoselective Synthesis
Authors: Murphy Cormac D. , Clark Benjamin R.
Published: August 2023

Halogenation of biologically active compounds is an attractive method for moderating their properties. Although there are numerous synthetic methodologies for halogen incorporation, biological alternatives are attractive because of the characteristics of enzyme‐catalyzed reactions, such as mild conditions of temperature and pH, and the avoidance of noxious reagents. In recent years, our understanding of the enzymology of halogenation has increased dramatically, and several new classes of enzymes catalyzing electrophilic, nucleophilic, and free radical halogenations have been identified. Furthermore, advances in molecular biology and genome sequencing have widened the possibilities of employing microorganisms to elaborate novel halogenated compounds with valuable medicinal properties.
Aberrant Signaling Pathways in Cancer
Authors: Grumolato Luca , Aaronson Stuart A.
Published: August 2023

Overview

Most, if not all, human cancers harbor aberrant activation of one or several signaling pathways, contributing to tumor initiation and/or progression. In this chapter, we describe how growth factors signal to receptors with intrinsic tyrosine kinase activity to promote cell proliferation and survival, largely through activation of the phosphatidylinositol‐3′‐kinase(PI‐3‐K)/Akt and Ras/MAP kinase pathways. Using different paradigmatic examples of oncogenic alterations in growth factor signaling, we discuss functional implications and relevance of these pathways for human cancer. General cell signaling principles in both normal and tumor cells will be addressed, and we briefly discuss how the initiation and progression of specific cancer types can be affected by the deregulation of certain other pathways, including those mediated by cytokines, the transforming growth factor‐β (TGFβ) family, Wnt, Hedgehog, Notch, and nuclear receptors.

Finally, we discuss the concepts of oncogene addiction and targeted therapy and provide a few representative examples to illustrate how increased understanding of the mechanisms underlying signaling pathway aberrations in cancer can been translated to the clinic.
Cancer Stem Cells
Authors: Deol Yadwinder S. , Granger Jill , Wicha Max S.
Published: August 2023

Overview

There is substantial evidence that many if not most tumors contain a subpopulation of cells that display stem cell properties. These “cancer stem cells” (CSCs) play an important role in tumor initiation and propagation. Furthermore, these cells may mediate resistance to cancer therapeutic agents and therefore play a fundamental role in cancer relapse. This highlights the importance of developing therapeutic approaches to target this cell population. In this chapter, we will review current thoughts on the role of tissue stem cells in carcinogenesis, the pathways that regulate these cells, and current progress in development of CSC targeting therapeutic agents. We will then review clinical implications of CSC models.
Cancer and Cell Death
Authors: Reed John C.
Published: August 2023

Overview

Cell death is a normal facet of human physiology, ensuring tissue homeostasis by offsetting cell production with cell demise. Neoplasms arise in part because of defects in physiological cell death mechanisms, contributing to pathological cell expansion when genetic or epigenetic alternations impart a selective survival advantage to premalignant or malignant cells. Defects in normal cell death pathways also contribute to cancer progression by permitting progressively aberrant cell behaviors, while also desensitizing tumor cells to immune‐mediated attack, radiation, and chemotherapy. Multiple mechanisms that account for dysregulation of cell death mechanisms in human malignancies have been identified, providing insights into cancer pathogenesis and suggesting targets for therapeutic intervention based on the concept of restoring sensitivity to natural pathways for triggering cell suicide.
RNATumor Viruses
Authors: Gallo Robert C. , Reitz Marvin S.
Published: August 2023

Overview

Retroviruses are enveloped viruses that contain a diploid RNA genome and are defined by the presence of reverse transcriptase, a DNA polymerase that transcribes RNA into DNA, which is then inserted into the host cell chromosome. These processes often lead to the capture and/or alteration of genetic material and the transfer of information between cells, with neoplastic transformation of the infected cell being an occasional outcome of infection. Retroviruses are also associated with immunodeficiencies and with neurologic diseases, although infection is often asymptomatic. Retroviruses can also enter the germ line and be present as a part of the genetic complement of all members of a species. These viruses are called endogenous retroviruses. Although most retroviral malignancies occur as leukemia/lymphomas in nonhuman species, human T‐cell leukemia virus type I (HTLV‐I) causes adult T‐cell leukemia/lymphoma in a minority of infected humans, as well as a neurologic disease and a variety of other pathologies. Human immunodeficiency virus type 1 (HIV‐1), although not considered a tumor virus, is associated with an increased incidence of several types of tumors, especially those caused by viruses such as human papillomavirus and Epstein–Barr virus.
Principles of Imaging
Authors: Schwartz Lawrence H.
Published: August 2023

Overview

Imaging is an indispensable component of clinical oncology. Computed tomography (CT) is usually more informative than plain X‐rays. Metabolic imaging with
18
F‐fluorodeoxyglucose is best combined with anatomical verification by CT. Evolving studies of function linking magnetic resonance to CT imaging is another advance for precision assessment. Targeting specific molecules with labeled agents is an evolving sector. Invasive procedures performed under radiologic imaging have substantially displaced open surgery, with benefits to patients in comfort, time and costs.
Principles of Surgical Oncology
Authors: Bloomston Mark , Tanabe Kenneth K. , Pollock Raphael E. , Morton Donald L.
Published: August 2023

Overview

The discipline of surgical oncology describes a surgical super specialty to which a board certification process is now attached in the United States. A cognitive as well as technical surgical focus, the surgical oncologist is an oncology specialist who uses surgery as his or her mainstay therapeutic modality in treating tumor problems. As such, the surgical oncologist has a thorough grounding in the natural history of solid malignancy, extensive experience in tumor biopsy and staging approaches, the knowledge needed to orchestrate a multidisciplinary solid tumor treatment program, and the commitment, via vigorous personal participation, in the many relevant research opportunities by which we will advance comprehensive care of the cancer patient.
Principles of Cancer Rehabilitation Medicine
Authors: Stubblefield Michael D. , Thomas David C. , Ragnarsson Kristjan T.
Published: August 2023

Overview

Many of the more than 14 million cancer survivors in the United States suffer from complications of disease and treatments such as surgery, chemotherapy, and radiotherapy. Restoring and maintaining the cancer survivors' function and quality of life often requires specialized rehabilitative services. The cancer rehabilitation specialist is dedicated to the identification, evaluation, and rehabilitation of neuromuscular, musculoskeletal, pain, and functional disorders associated with cancer and its treatment. This discusses the principles and practice of rehabilitation in this challenging group of patients.
Pyrimidine and Purine Antimetabolites
Authors: Diasio Robert B.
Published: August 2023

Overview

The development of pyrimidine and purine antimetabolite drugs has been based on the rationale that nucleic acids are critical to cell replication and, therefore, the pyrimidine and purine bases (and their nucleosides) that are the “building blocks” necessary to synthesize nucleic acids are themselves potential sites for designing drugs that could be effective in inhibiting nucleic acid synthesis, whether that be in bacteria, viruses, or tumor cells. In this chapter, the various antimetabolites or analogs of uracil/thymine, cytidine/deoxycytidine, hypoxanthine/guanine, and adenosine that are currently used in the management of cancer are presented and reviewed with regard to metabolism, mechanism of action, clinical pharmacology, clinical activity, and toxicity.
Endocrine Therapy for Hormone Receptor‐Positive Breast Cancer
Authors: Buzdar Aman U. , Dawood Shaheenah , Harvey Harold A. , Craig Jordan Virgil
Published: August 2023

Overview

The importance of the reproductive endocrine system in breast cancer treatment began to be appreciated at the turn of nineteenth century. It was around this time that it was realized that approximately one‐third of premenopausal women with advanced breast cancer would respond to oophorectomy. However, it was only when the estrogen receptor (ER) was discovered that it was possible to fully appreciate the mechanisms underlying the activity of ovarian ablation and other associated treatments for breast cancer such as ovarian irradiation, adrenalectomy, and hypophysectomy. Research into both the estrogen and progesterone pathways not only provided a deeper understanding of the underlying mechanism of the carcinogenic pathway involved in the development of breast cancer but also allowed identification of potential targets for therapeutic intervention.

This chapter discusses recent advances in the molecular biology and physiology underlying the estrogen and progesterone receptor (PR) pathways and potential targets for intervention. In addition it examines and compares the pharmacology and efficacy of the different endocrine agents used in the management of both early and advanced stage breast cancer.
Neoplasms of the Esophagus
Authors: Sung Max W. , Litle Virginia R. , Chmura Steven J. , Swisher Stephen G. , Rice David C. , Ajani Jaffer A. , Komaki Ritsuko K. , Ferguson Mark K.
Published: August 2023

Overview

Esophageal cancer remains a leading cause of cancer deaths worldwide, sixth in men and ninth in women. In the past quarter century, esophageal cancer has changed from predominantly squamous‐cell carcinoma to adenocarcinoma, but only in North America and Europe. The concurrent increase in cancers of the gastroesophageal junction has led to its currently inclusion in the AJCC TNM (tumor, node, metastasis) staging of esophageal cancer. Treatment options have expanded to include endoscopic mucosal resection for early‐stage disease and neoadjuvant chemoradiation followed by surgery for intermediate stage disease. Surgical techniques have also evolved to include less invasive approaches using thoracoscopy and laparoscopy. Advances in systemic chemotherapy have also been reported, with the inclusion of hormonal and targeted therapies, for esophageal adenocarcinomas. A lethal disease when diagnosed in advanced stage, continued progress in therapeutic interventions can be anticipated with early‐stage detection in high‐risk patients, and the incorporation of molecular strategies in the treatment of advanced stage disease.
Neoplasms of the Exocrine Pancreas
Authors: Wolff Robert A. , Crane Christopher H. , Li Donghui , Evans Douglas B. , Maitra Anirban , Tsai Susan
Published: August 2023

Overview

Adenocarcinoma of the pancreas is one of the most morbid and lethal malignancies. Worldwide, it accounts for 330,000 deaths annually. Smoking and obesity are both risk factors for pancreatic cancer and current estimates suggest half of all cases may be preventable. Genetic predisposition to pancreatic cancer is associated with some genetic syndromes to include BRCA1 or BRCA2 germline mutations, Peutz–Jeghers syndrome, and hereditary nonpolyposis colon cancer. Somatic mutations in KRAS, CDKN2A/INK4A, TP53, and SMAD4/DPC4 are common. Pancreatic cancer is often diagnosed when the primary tumor is inoperable or there is metastatic spread rendering the cancer incurable. At present, clinical staging defines the malignancy as resectable (and potentially curable), borderline resectable, locally advanced, or metastatic. Surgery with curative intent is possible for patients with resectable disease and for a subset of patients with borderline resectable disease. While chemotherapy has been proved to prolong survival as a component of adjuvant therapy, and as therapy for locally advanced or metastatic disease, the role of radiation therapy in treatment is less‐well defined and not universally accepted. Thus far, molecular targeted therapy has shown no clinically meaningful benefit. Adjuvant and neoadjuvant approaches are employed in patients with resectable and borderline resectable disease. Intense research in the molecular biology of pancreatic cancer continues with increasing interest in the role of the tumor microenvironment in invasion, metastatic potential, and resistance. Novel therapeutic strategies that focus on stromal modification and immunologic manipulation are at the forefront of clinical and translational research efforts.
Renal Cell Carcinoma
Authors: Burgess Earle F. , Riggs Stephen B. , Rini Brian I. , Raghavan Derek
Published: August 2023

Overview

Renal cell carcinoma occurs in 64,000 new patients each year in the United States and results in about 14,000 deaths. For localized disease, cure is achieved by nephrectomy. Meticulous surgical staging is crucial. With improved imaging techniques, active surveillance has become an option for small, asymptomatic renal masses. Modifications in surgical technique, including laparoscopic and robotic approaches, have contributed to reduced morbidity. In more advanced disease, with locoregional or metastatic spread, immune response is a governor of outcome and survival, and immune modulation via interleukin‐2 or PDL‐1 inhibition results in sustained responses. Cytotoxic chemotherapy has negligible activity, but targeted therapies, such as tyrosine kinase and mammalian target of rapamycin inhibitors, often cause dramatic regressions. Uncommon cancers of the kidney represent about 10% of incident cases, and a general approach to their management is reviewed in this chapter.
Gynecologic Sarcomas
Authors: Rahaman Jamal , Cohen Carmel J.
Published: August 2023

Overview

Sarcomas are extremely rare and account for less than 1.5% of gynecologic cancers. Carcinosarcoma and leiomyosarcoma each account for 35–40% of uterine sarcomas, with endometrial stromal sarcoma (ESS) accounting for 10–15% and other sarcomas including adenosarcomas comprising 5–10%. Uterine carcinosarcoma should be classified as a metaplastic carcinoma of the uterus. Most adenosarcomas and ESSs have good prognosis and respond to hormonal therapy. Undifferentiated endometrial sarcoma (UES) and adenosarcomas with sarcomatous overgrowth are rare and have poor prognosis and require chemotherapy. ESS are histologically and clinically distinct from UES and each have distinct gene rearrangements. More than 50% of Stage I leiomyosarcomas (LMSs) and carcinosarcomas patients will recur. Chemotherapy is required for advanced or recurrent disease. In LMSs, the active drugs are doxorubicin, ifosfamide, gemcitabine, and docetaxel. For uterine carcinosarcomas, the drugs of choice are ifosfamide, cisplatin/carboplatin, and paclitaxel. Adjuvant radiation therapy may provide locoregional control in select cases of uterine carcinosarcomas. Hormonal therapy, including progestational agents, GnRH analogues, and aromatase inhibitors, has a role in the treatment of advanced or recurrent low‐grade ESSs and adenosarcomas.
Neoplasms of the Breast
Authors: Rugo Hope S. , Majure Melanie , Dragun Anthony , Buxton Meredith , Esserman Laura
Published: August 2023

Overview

Breast cancer in women remains a major medical problem with significant public health and societal ramifications, including issues related to screening, risk factors, prevention, diagnosis, treatment, and survival following diagnosis. Major advances have markedly improved the understanding of clinical phenotypes, as well as the biologic pathways that drive tumor growth and resistance. This research has led to dramatic changes in treatment that have contributed to a significant reduction in breast cancer mortality over the last two decades, and is the basis of ongoing clinical research. Molecular profiling has provided insights into the heterogeneity of breast cancer subtypes; combining biology and tumor burden has allowed stratification of both risk and treatment to begin the process of individualizing screening, prevention, and treatment. As new information accumulates, new paradigms of management become the standard of care reflected in international guidelines. Our challenge is to apply new formation and treatment appropriately and effectively, and to understand both response and resistance. Information obtained from molecular, biologic, and pathologic investigations and clinical trials provides the major focus of this chapter.
Other Skin Cancers
Authors: Stebbins William G. , Millican Eric A. , Neel Victor A.
Published: August 2023

Overview

Several more common types of nonmelanoma skin cancer are presented with attention to etiology and current treatment options.
Chronic Lymphocytic Leukemia
Authors: Rai Kanti R. , Barrientos Jacqueline C.
Published: August 2023

Overview

Chronic lymphocytic leukemia (CLL) is an indolent B‐cell neoplasia characterized by a progressive accumulation of small functionally incompetent lymphocytes in the blood, marrow, and lymphoid tissues. Given its indolent presentation, initiation of therapy is deferred until patients become symptomatic. CLL primarily affects the elderly population who generally has clinically significant coexisting conditions. The use of traditional chemoimmunotherapy regimens has been historically limited to fit patients able to tolerate the known toxicities from such regimens. A major shift in the management of CLL is currently taking place with the approval of several new targeted agents with unprecedented clinical activity in patients with poor prognostic markers and high‐risk disease. New drug combinations are being evaluated with the goal to optimize treatment approaches based on the clinical and biological profile of the CLL patient.