bluuebunny/crossref_metadata_2025 huggingface dataset:
Corporate social responsibility in smaller enterprises
Authors: Blowfield Michael , Murray Alan
Published: September 2023

This chapter surveys corporate social responsibility (CSR) as an aspect of business theory and management practice as it applies to small and medium-sized enterprises (SMEs). The chapter also includes an overview of the field of social entrepreneurship. The chapter discusses what is unique about SMEs in the CSR context and the distinctions between SMEs, and how these affect their behaviour. CSR as an area of opportunity and competitive advantage for SMEs is considered. How CSR is being managed in practice is also studied. The last part deals with those SMEs that are categorized as social entrepreneurs.
The future of corporate social responsibility
Authors: Blowfield Michael , Murray Alan
Published: September 2023

This chapter discusses the current trends in corporate social responsibility (CSR) and in what directions the field is moving. It examines the different pressures that drive CSR, and the consequences of each for business behaviour. It looks at the major trends that will affect what is meant by ‘CSR’ over the coming years. The chapter considers what is motivating the business transformation. Finally, it reflects on what CSR reveals about the changing business role in twenty-first century society.
Foundations of Economics
Authors: Gillespie Andrew
Published: September 2023

Foundations of Economics splits economics into two sections: microeconomics and macroeconomics. Under microeconomics, chapters cover the production possibility frontier (PPF), demand, behavioural economics, elasticity of demand, supply, and market equilibrium. This part of the book also looks at the free-market system, intervening in the market system, costs, revenues, profits, monopoly, and oligopoly. Finally, the first part touches on monopolistic competition,non-price competition, and the labour market. The second part moves on to the macroeconomic sphere. Included here are chapters on equilibrium, national income, the standard of living, influences on aggregate demand, and government objectives. This part also covers topics such as unemployment, money, inflation, trade, and government policies.
The role of institutional investors in corporate governance
Authors: Mallin Christine A.
Published: September 2023

This chapter discusses the importance of the potential influence of large shareholders. This was identified back in the 1930s with the separation of owners of the business from the control of the business, control being put instead in the hands of the directors. The chapter explores the separation of ownership and control and argues that this causes a number of problems outlined by agency theory. Agency theory explains the circumstances in which the managers of the business may not act in the best interests of the owners. Throughout the twentieth century, the pattern of ownership continued to change and, in the USA and UK in particular, individual share ownership declined and institutional share ownership increased. The chapter refers to the internationalization of cross-border portfolios and the financial crises that have occurred in many parts of the world. It also examines the rise of institutional investors and their role in corporate governance.
Corporate governance in South Africa, Egypt, India, and Brazil
Authors: Mallin Christine A.
Published: September 2023

This chapter examines corporate governance developments in a sample of countries and looks at this in a global context. The countries selected are diverse in their cultural and legal backgrounds, ownership structures, and corporate governance structures. The chapter reviews core principles that are evident in the corporate governance codes of these countries. Such principles help build or restore confidence in stock markets, ensure more transparency and disclosure, enhance protection of minority shareholders' rights, and guarantee that the company is managed in the interests of shareholders and stakeholders. The chapter emphasizes the importance of a corporate governance code and of a firm-level corporate governance. Firm-level corporate governance provisions matter more in countries with weak legal environments because firms can partially compensate for ineffective laws and enforcement by establishing good corporate governance and credible investor protection.
Trait theory—description, analysis, and use
Authors: Roe Kevin
Published: September 2023

This chapter discusses trait theory, which was the first leadership approach to be studied rigorously. Its basic premise is that leadership as observed in ‘Great Men’ arises as a result of these extraordinary people possessing innate and immutable personal qualities that preordain them for positions of high influence. Researchers used many different methods to collect their data and each researcher generated a slightly different set of conclusions that contained the ‘key traits’ needed to succeed as a leader. The consistent theme was that leadership was concerned with the study and understanding of personality. This view was challenged and disputed as it failed either to generate an agreed list of attributes or to consider the effect of circumstance and situation in terms of identifying leaders and non-leaders. Further research dwindled until recently when investigations from a more psychologically driven perspective linked some of the Big Five traits to successful leaders.
Behavioural models
Authors: Roe Kevin
Published: September 2023

This chapter examines behavioural models, considering not who a leader is, but how a leader behaves. Behavioural models began to evolve as a result of dissatisfaction with the Great Man-type theories of leadership which ascribed successful leadership to inherited traits. The belief and hope was that, with the right kind of developmental procedures and processes in place, individuals could be trained to become leaders. This belief was supported by the growing science and theories investigating how humans learn. While there was (and is) disagreement over this process, leadership writers and academics have used the underpinning philosophy—that humans can learn—to develop the behavioural and skills model. Although the approach is not without its drawbacks, the behavioural model can help both organizations and individuals define what they mean by ‘leadership’.
Followership
Authors: Roe Kevin
Published: September 2023

This chapter assesses followership. Organizations should examine their employees for good followership potential as well as for their leadership potential. Both of these are roles rather than positions, and as such need to be viewed with the same level of interest. Leader�member exchange theory gives a map for examining the individual relationship between two people in two different roles. It goes on to suggest that relationships of different quality emerge between a leader and followers. This quality, in turn, affects the perceptions of the leader, who may view some individuals as trustworthy and competent and others as lazy and unreliable. These judgements may be affected by a leader's past experiences as well as impression management on the part of the followers. However, trying to predict the likely outcome of any follower—leader interaction may be challenging.
Ethical leadership
Authors: Roe Kevin
Published: September 2023

This chapter explores different ethical frameworks, reviews the nascent literature surrounding ‘ethical leadership’, and examines related ideas such as whistle-blowing. In considering what is ‘right’ and ‘wrong’, the main challenge for leaders is tied up in the very nature of leadership and its ‘essentially contested nature’. However, leadership occupies a social space—meaning that it is defined by those who engage in it—and that it forms part of the broader social experience. Consequently, as a leader’s social environment changes, so does the definition of leadership—and by inference, ‘good’ leadership. Ethics, morals, and values are linked to a broad consistent framework so that in any situation a leader should know what should or should not be done. In terms of moral development, regardless of the initial position adopted, a person can evolve in terms of their moral judgement as they gain wisdom and a broader understanding of human nature.
Consumer Behaviour
Authors: Szmigin Isabelle , Piacentini Maria
Published: September 2023

Consumer Behaviour consists of four parts. The first part looks at the historical and current perspectives on consumption. The second part presents a micro-view of consumption which includes examinations of decision-making and involvement, learning and memory, perceptual processes, attitude theory and behaviour change, and personality and motivation. The third part turns to a macro-view of consumption and considers groups, social processes, communication, culture, and patterns of buyer behaviour. The last part focuses on future trends in consumer behaviour.
Qualitative Data Analysis
Authors: Bell Emma , Bryman Alan , Harley Bill
Published: September 2023

This chapter describes the concept of qualitative data analysis. It discusses the main features, processes, and outcomes of the most widely used strategies of qualitative data analysis: thematic analysis and grounded theory. Moreover, coding is the starting point for most forms of qualitative data analysis. The chapter notes the software packages available to assist in the analysis of qualitative data in an effort to simplify and enhance the time-consuming task of manual coding and retrieving data. It shows that despite the software, the analyst must still make theoretically informed decisions about what to code and how to interpret the data.
Human resource management in an organizational context
Authors: Preece David
Published: September 2023

The This chapter studies how the organizational context influences HR practices and how HR practices play a part in shaping organizations. It focuses on the inner or internal contexts of organizations. It begins by tackling the structure and design of organizations, and perspectives on organizational change. Then, it analyses the various approaches to managing and organizing work, including teamworking and empowerment initiatives. The chapter also looks at culture, power, and politics in organizations, before concluding.
Global Marketing Management
Authors: Lee Kiefer , Carter Steve
Published: September 2023

Global Marketing Management is composed of three parts. Part One is about understanding the global marketing environment. It includes discussions on changes and new challenges; the global marketing environment; understanding globalization; understanding global cultures and buyer behaviours; understanding global social and ethical issues; and opportunity analysis. The second part covers the development of global marketing strategies. This includes looking at market entry strategies and competitive advantage. This second part also looks at product and brand management, global services marketing, global communications, global supply chains and distribution, marketing relationships, and global pricing. The last part is about implementing and coordinating global market operations.
Change Management and Innovation
Authors: Combe Colin
Published: September 2023

This chapter discusses change management and innovation. It first sets out a rationale for the reasons why change is necessary in modern organisations. Then, it outlines detailed accounts of types of organisational change, such as incremental, step change, and business reengineering. It discusses management issues relating to the change process such as identifying areas of change, design, implementation of change, and managing resistance to change. The chapter introduces the concept of innovation with an emphasis on managing and influencing the development of innovation. It also includes a deeper discussion on influential contributions from academic writers on information systems as a catalyst for change. Finally, the chapter identifies barriers to change and discusses how to manage resistance to change.
Types of Management Consultancy
Authors: O’Mahoney Joe , Markham Calvert
Published: September 2023

This chapter introduces different types of management consultancy and seeks to categorize the industry according to different perspectives. It examines different business models of consultancy, consulting services, and sectors which consulting firms serve. It also gives an overview of the primary characteristics of different categories and implications of trends for the segmentation of the consulting industry. The chapter elaborates how strategy consultancies are moving downstream and doing management work, while IT and outsourcing consultancies are trying to move upstream into the same area. It refers to companies that added consulting divisions to maximize the economies of scope, help set the clients' purchasing agendas, and lever more business.
The Consulting Life-Cycle
Authors: O’Mahoney Joe , Markham Calvert
Published: September 2023

This chapter explains the consultancy life-cycle and introduces the concept of the five stages it incorporates: pre-sales, sales, research, delivery, and exit. It provides a realistic and practice-informed overview of consultancy work to give real insights into the day-to-day lives of consultants. It also reviews the different sales approaches that consultancies utilize and determines how to write and manage proposals. The chapter describes the main research skills used by consultants to find and analyse data and clarifies how consultancy projects are planned, controlled, and delivered. It concludes that the life-cycle is a way of describing most of the work that consultants perform, but advises considering it as a simplification that should be treated as a guide rather than a rule.
The Consultancy Career
Authors: O’Mahoney Joe , Markham Calvert
Published: September 2023

This chapter describes the consultancy career and the options associated with it, including the access points to consultancy and measures to take to be recruited successfully. It describes the challenges of moving up the consultancy ladder and highlights the reasons why consultants leave and the options available when doing so. It also addresses questions that students frequently ask when facing the challenge of applying to consultancies. The chapter covers the consulting career structure and the salaries that can be expected, as well as the different entry points to the career. It elaborates how to succeed in the recruitment process and how best to land a promotion after getting into the consulting profession.
Developing Employability for Business
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

Developing Employability for Business contains three sections. The first section is about identifying and building employability assets. It considers transferable skills and how to enhance a profile. The second section is on developing essential employability assets. It looks at managing projects, team work, and customer facing skills. The last section is about going into work and considers finding a job, career management, and success in the workplace.
Sex, Science, and Society: Reckonings and Responsibilities for Biologists
Authors: Lewis A Kelsey , Sharpe Sam L
Published: September 2023

Synopsis

Individuals who may not fit European colonial ideas of dichotomous male or female bodies—those who are intersex—have been known across cultures and throughout human history. Unfortunately, acknowledgement of and engagement with this aspect of human biological diversity and the ongoing impact of binary misunderstandings of sex have been largely contained within the humanities and social sciences, while sex diversity beyond an assumed male/female binary has been either ignored or pathologized in the medical and biological sciences. The perceived social threat of intersex variation to the sex and gender binary has led to institutional and medical regulation of intersex people’s bodies, which has been the subject of increasing spotlight recently. Given the historical and ongoing role of the biological sciences in the pathologization of human sex variation and the deployment of medical technologies attempting to suppress this variation, we must actively acknowledge that our work does not exist and is not produced in a vacuum. Biological data demonstrate that sex is diverse and variable in animals, plants, and fungi. Despite this, the paradigm of binary sex has labeled diverse and variable sex as anomalous, especially in human populations. It is far past time to address this paradigm by actively examining the ways that our research, teaching, and communication engage with, articulate, and make legible particular narratives of sex diversity and variation.
Minireview: Glucocorticoid−Leptin Crosstalk: Role of Glucocorticoid–Leptin Counterregulation in Metabolic Homeostasis and Normal Development
Authors: Paul Bidisha , Buchholz Daniel R
Published: September 2023

Synopsis

Glucocorticoids and leptin are two important hormones that regulate metabolic homeostasis by controlling appetite and energy expenditure in adult mammals. Also, glucocorticoids and leptin strongly counterregulate each other, such that chronic stress-induced glucocorticoids upregulate the production of leptin and leptin suppresses glucocorticoid production directly via action on endocrine organs and indirectly via action on food intake. Altered glucocorticoid or leptin levels during development can impair organ development and increase the risk of chronic diseases in adults, but there are limited studies depicting the significance of glucocorticoid-leptin interaction during development and its impact on developmental programming. In mammals, leptin-induced suppression of glucocorticoid production is critical during development, where leptin prevents stress-induced glucocorticoid production by inducing a period of short-hyporesponsiveness when the adrenal glands fail to respond to certain mild to moderate stressors. Conversely, reduced or absent leptin signaling increases glucocorticoid levels beyond what is appropriate for normal organogenesis. The counterregulatory interactions between leptin and glucocorticoids suggest the potential significant involvement of leptin in disorders that occur from stress during development.
“Death” and Its Discontents
Authors: Sparks Nicholas
Published: September 2023

“Death” sits at the center of this issue of the Journal of Medicine and Philosophy. Each article, in its own fashion, touches on the problems of thinking about the nature of death in the light of contemporary scientific and medical advances. Three articles explicitly center on the ongoing debate over the Uniform Determination of Death Act, and three center on thematic issues surrounding death. Despite the topic, the discussion is lively and thoughtful. After introducing each article and sketching their contours, I offer some closing remarks on a central issue dredged up by these articles: the role of evaluative commitments and other interests in selecting criteria for the determination of death. These articles raise interesting questions about the relationship between the nature of “death” and ethical, epistemic, social-political, and economic values. This further opens up interesting lines of inquiry into medical epistemology. Finally, they broach deep questions about the nature of “function” and the relationship between organic and artificially sustained function.
ATMOSPHERIX: I- an open source high-resolution transmission spectroscopy pipeline for exoplanets atmospheres with SPIRou
Authors: Klein Baptiste , Debras Florian , Donati Jean-François , Hood Thea , Moutou Claire , Carmona Andres , Ould-elkhim Merwan , Bézard Bruno , Charnay Benjamin , Fouqué Pascal , Masson Adrien , Vinatier Sandrine , Baruteau Clément , Boisse Isabelle , Bonfils Xavier , Chiavassa Andrea , Delfosse Xavier , Dethier William , Hebrard Guillaume , Kiefer Flavien , Leconte Jérémy , Martioli Eder , Parmentier Vivien , Petit Pascal , Pluriel William , Selsis Franck , Teinturier Lucas , Tremblin Pascal , Turbet Martin , Venot Olivia , Wyttenbach Aurélien
Published: September 2023

Atmospheric characterization of exoplanets from the ground is an actively growing field of research. In this context, we have created the ATMOSPHERIX consortium: a research project aimed at characterizing exoplanets atmospheres using ground-based high-resolution spectroscopy. This paper presents the publicly available data analysis pipeline and demonstrates the robustness of the recovered planetary parameters from synthetic data. Simulating planetary transits using synthetic transmission spectra of a hot Jupiter that were injected into real SPIRou observations of the non-transiting system Gl 15 A, we show that our pipeline is successful at recovering the planetary signal and input atmospheric parameters. We also introduce a deep learning algorithm to optimize data reduction which proves to be a reliable, alternative tool to the commonly used principal component analysis. We estimate the level of uncertainties and possible biases when retrieving parameters such as temperature and composition and hence the level of confidence in the case of retrieval from real data. Finally, we apply our pipeline onto two real transits of HD 189733 b observed with SPIRou and obtain similar results than in the literature. In summary, we have developed a publicly available and robust pipeline for the forthcoming studies of the targets to be observed in the framework of the ATMOSPHERIX consortium, which can easily be adapted to other high resolution instruments than SPIRou (e.g. VLT-CRIRES, MAROON-X, ELT-ANDES).
Unravelling the nuclear dust morphology of NGC 1365: a two-phase polar–RAT model for the ultraviolet to infrared spectral energy distribution
Authors: Swain Subhashree , Shalima P , Latha K V P
Published: September 2023

We present a 3D radiative transfer model for the spectral energy distribution (SED) of NGC 1365, which is a ‘changing look’ Seyfert 1.8 type active galactic nucleus (AGN). The SED from the ultraviolet (UV) to the infrared (IR) is constructed using archival data from the Ultra-Violet Imaging Telescope (UVIT) onboard AstroSat, along with IR data from the literature. The skirt radiative transfer code is used to model the SED and derive the geometry and composition of dust in this AGN. Similar to our earlier SED model of NGC 4151, the nuclear region of NGC 1365 is assumed to contain a ring or disc-like structure concentric to the accretion disc, composed of large (0.1–1 $\mu$m) graphite grains in addition to the two-phase dusty torus made up of interstellar-medium-type grains (Ring And Torus or RAT model). We also include, for the first time, an additional component of dusty wind in the form of a bipolar cone. We carry out a detailed analysis and derive the best-fitting parameters from a χ2 test to be Rin, r = 0.03 pc, σ = 26°, and τtotal = 20 for the assumed ring–torus–polar wind geometry. Our results suggest the presence of hot dust at a temperature T ∼ 1216 K at the location of the ring that absorbs and scatters the incident UV radiation and emits in the near-IR. In the mid-IR, the major contributors are the polar cone and warm dust with T ∼ 914 K at Rin, t = 0.1 pc. Not only are our model radii in agreement with IR interferometric observations, but also our study reiterates the role of high-resolution UV observations in constraining the dust grain size distribution in the nuclear regions of AGN.
Supermassive black holes in a mass-limited galaxy sample
Authors: Byrne Zachary , Drinkwater Michael J , Baumgardt Holger , Blyth David , Côté Patrick , Lüetzgendorf Nora , Spengler Chelsea , Ferrarese Laura , Mahajan Smriti , Pfeffer Joel , Sweet Sarah
Published: September 2023

The observed scaling relations between supermassive black hole masses and their host galaxy properties indicate that supermassive black holes influence the evolution of galaxies. However, the scaling relations may be affected by selection biases. We propose to measure black hole masses in a mass-limited galaxy sample including all non-detections to inprove constraints on galaxy mass – black hole mass scaling relations and test for selection bias. We use high-spatial resolution spectroscopy from the Keck and Gemini telescopes, and the Jeans Anisotropic Modelling method to measure black hole masses in early-type galaxies from the Virgo Cluster. We present four new black hole masses and one upper limit in our mass-selected sample of galaxies of galaxy mass (1.0–3.2) $\times 10^{10} \, \mathrm{M}_\odot$. This brings the total measured to 11 galaxies out of a full sample of 18 galaxies, allowing us to constrain scaling relations. We calculate a lower limit for the average black hole mass in our sample of $3.7 \times 10^{7} \, \mathrm{M}_\odot$. This is at an average galaxy stellar mass of $(1.81 \pm 0.14)\times 10^{10} \, \mathrm{M}_\odot$ and an average bulge mass of $(1.31 \pm 0.15) \times 10^{10} \, \mathrm{M}_\odot$. This lower limit shows that black hole masses in early-type galaxies are not strongly affected by selection biases.
Molecular and ionized gas in tidal dwarf galaxies: the spatially resolved star formation relation
Authors: Kovakkuni N , Lelli F , Duc P-A , Boquien M , Braine J , Brinks E , Charmandaris V , Combes F , Fensch J , Lisenfeld U , McGaugh S S , Mihos J C , Pawlowski M S , Revaz Y , Weilbacher P M
Published: September 2023

Tidal dwarf galaxies (TDGs) are low-mass objects that form within tidal and/or collisional debris ejected from more massive interacting galaxies. We use CO(1–0) observations from Atacama Large Millimeter/submillimeter Array and integral-field spectroscopy from Multi-Unit Spectroscopic Explorer to study molecular and ionized gas in three TDGs: two around the collisional galaxy NGC 5291 and one in the late-stage merger NGC 7252. The CO and H α emission is more compact than the H i emission and displaced from the H i dynamical centre, so these gas phases cannot be used to study the internal dynamics of TDGs. We use CO, H i, and H α data to measure the surface densities of molecular gas (Σmol), atomic gas (Σatom), and star formation rate (ΣSFR), respectively. We confirm that TDGs follow the same spatially integrated ΣSFR–Σgas relation of regular galaxies, where Σgas = Σmol + Σatom, even though they are H i dominated. We find a more complex behaviour in terms of the spatially resolved ΣSFR–Σmol relation on subkpc scales. The majority ($\sim 60~{{\ \rm per\ cent}}$) of star-forming regions in TDGs lie on the same ΣSFR–Σmol relation of normal spiral galaxies but show a higher dispersion around the mean. The remaining fraction of star-forming regions ($\sim 40~{{\ \rm per\ cent}}$) lie in the starburst region and are associated with the formation of massive super star clusters, as shown by Hubble Space Telescope images. We conclude that the local star formation activity in TDGs proceeds in a hybrid fashion, with some regions comparable to normal spiral galaxies and others to extreme starbursts.
Interploidy Introgression Shaped Adaptation during the Origin and Domestication History of Brassica napus
Authors: Wang Tianpeng , van Dijk Aalt D J , Bucher Johan , Liang Jianli , Wu Jian , Bonnema Guusje , Wang Xiaowu
Published: September 2023

Polyploidy is recurrent across the tree of life and known as an evolutionary driving force in plant diversification and crop domestication. How polyploid plants adapt to various habitats has been a fundamental question that remained largely unanswered. Brassica napus is a major crop cultivated worldwide, resulting from allopolyploidy between unknown accessions of diploid B. rapa and B. oleracea. Here, we used whole-genome resequencing data of accessions representing the majority of morphotypes and ecotypes from the species B. rapa, B. oleracea, and B. napus to investigate the role of polyploidy during domestication. To do so, we first reconstructed the phylogenetic history of B. napus, which supported the hypothesis that the emergence of B. napus derived from the hybridization of European turnip of B. rapa and wild B. oleracea. These analyses also showed that morphotypes of swede and Siberian kale (used as vegetable and fodder) were domesticated before rapeseed (oil crop). We next observed that frequent interploidy introgressions from sympatric diploids were prominent throughout the domestication history of B. napus. Introgressed genomic regions were shown to increase the overall genetic diversity and tend to be localized in regions of high recombination. We detected numerous candidate adaptive introgressed regions and found evidence that some of the genes in these regions contributed to phenotypic diversification and adaptation of different morphotypes. Overall, our results shed light on the origin and domestication of B. napus and demonstrate interploidy introgression as an important mechanism that fuels rapid diversification in polyploid species.
NLGN4X TCR transgenic T cells to treat gliomas
Authors: Krämer Christoper , Kilian Michael , Chih Yu-Chan , Kourtesakis Alexandros , Hoffmann Dirk C , Boschert Tamara , Koopmann Philipp , Sanghvi Khwab , De Roia Alice , Jung Stefanie , Jähne Kristine , Day Bryan , Shultz Lenny D , Ratliff Miriam , Harbottle Richard , Green Edward W , Will Rainer , Wick Wolfgang , Platten Michael , Bunse Lukas
Published: September 2023

Background

Neuroligin 4 X-linked (NLGN4X) harbors a human leukocyte antigen (HLA)-A*02-restricted tumor-associated antigen, overexpressed in human gliomas, that was found to induce specific cytotoxic T cell responses following multi-peptide vaccination in patients with newly diagnosed glioblastoma.

Methods

T cell receptor (TCR) discovery was performed using droplet-based single-cell TCR sequencing of NLGN4X-tetramer-sorted T cells postvaccination. The identified TCR was delivered to Jurkat T cells and primary human T cells (NLGN4X-TCR-T). Functional profiling of NLGN4X-TCR-T was performed by flow cytometry and cytotoxicity assays. Therapeutic efficacy of intracerebroventricular NLGN4X-TCR-T was assessed in NOD scid gamma (NSG) major histocompatibility complex (MHC) I/II knockout (KO) (NSG MHC I/II KO) mice bearing NLGN4X-expressing experimental gliomas.

Results

An HLA-A*02-restricted vaccine-induced T cell receptor specifically binding NLGN4X131–139 was applied for preclinical therapeutic use. Reactivity, cytotoxicity, and polyfunctionality of this NLGN4X-specific TCR are demonstrated in various cellular models. Intracerebroventricular administration of NLGN4X-TCR-T prolongs survival and leads to an objective response rate of 44.4% in experimental glioma-bearing NSG MHC I/II KO mice compared to 0.0% in control groups.

Conclusion

NLGN4X-TCR-T demonstrate efficacy in a preclinical glioblastoma model. On a global scale, we provide the first evidence for the therapeutic retrieval of vaccine-induced human TCRs for the off-the-shelf treatment of glioblastoma patients.Keywords cell therapy | glioblastoma | T cell receptor | tumor antigen
Improved early outcome prediction by MRI-based 3D tumor volume assessment in patients with CNS lymphomas
Authors: Lauer Eliza M , Riegler Ella , Mutter Jurik A , Alig Stefan K , Bleul Sabine , Kuehn Julia , Ranganathan Lavanya , Klingler Christian , Demerath Theo , Würtemberger Urs , Rau Alexander , Weiß Jakob , Eisenblaetter Michel , Bamberg Fabian , Prinz Marco , Finke Jürgen , Duyster Justus , Illerhaus Gerald , Diehn Maximilian , Alizadeh Ash A , Schorb Elisabeth , Reinacher Peter C , Scherer Florian
Published: September 2023

Background

Central nervous system lymphomas (CNSL) display remarkable clinical heterogeneity, yet accurate prediction of outcomes remains challenging. The IPCG criteria are widely used in routine practice for the assessment of treatment response. However, the value of the IPCG criteria for ultimate outcome prediction is largely unclear, mainly due to the uncertainty in delineating complete from partial responses during and after treatment.

Methods

We explored various MRI features including semi-automated 3D tumor volume measurements at different disease milestones and their association with survival in 93 CNSL patients undergoing curative-intent treatment.

Results

At diagnosis, patients with more than 3 lymphoma lesions, periventricular involvement, and high 3D tumor volumes showed significantly unfavorable PFS and OS. At first interim MRI during treatment, the IPCG criteria failed to discriminate outcomes in responding patients. Therefore, we randomized these patients into training and validation cohorts to investigate whether 3D tumor volumetry could improve outcome prediction. We identified a 3D tumor volume reduction of ≥97% as the optimal threshold for risk stratification (=3D early response, 3D_ER). Applied to the validation cohort, patients achieving 3D_ER had significantly superior outcomes. In multivariate analyses, 3D_ER was independently prognostic of PFS and OS. Finally, we leveraged prognostic information from 3D MRI features and circulating biomarkers to build a composite metric that further improved outcome prediction in CNSL.

Conclusions

We developed semi-automated 3D tumor volume measurements as strong and independent early predictors of clinical outcomes in CNSL patients. These radiologic features could help improve risk stratification and help guide future treatment approaches.
In Reply to “Pathogenic/Likely Pathogenic Somatic CDK12 Mutations in Black Men With Prostate Cancer”
Authors: Valle Luca F , Nickols Nicholas G , Yamoah Kosj , Garraway Isla P , Maxwell Kara N , Lynch Julie A
Published: September 2023

This letter to the editor responds to comments by Sartor et al regarding recent findings on the clinical relevance of CDK12 pathogenic mutations.
Experimental reduction of a primary nest predator fails to decrease nest predation rates of sagebrush songbirds
Authors: Rhea Ashleigh M , Chalfoun Anna D
Published: September 2023

Predator removal comprises one management strategy to increase the reproductive success of a prey species of concern, particularly within human-altered landscapes. The efficacy of such an approach, however, depends partly on the extent to which predation risk is additive or compensatory, which remains unknown for many systems. We experimentally reduced the local abundance of deer mice (Peromyscus maniculatus), a primary nest predator of three sagebrush-obligate songbirds—Brewer’s Sparrow (Spizella breweri), Sagebrush Sparrow (Artemisiospiza nevadensis), and Sage Thrasher (Oreoscoptus montanus)—during May to August 2019 in western Wyoming, USA, to assess whether nest predation risk was additive or compensatory, and whether nest predator removal could comprise a potentially effective management tool. Deer mouse removal did not affect the daily nest survival of songbirds between experimental and control plots, despite a reduction of 68%–85% in deer mouse abundance within treatment areas. Therefore, nest predation in this system likely operated in a compensatory way, in which deer mice that escaped removal, new immigrants, or other species of nest predator maintained similar levels of nest predation risk regardless of the prevalence of a primary predator. We caution that predator removal may not be an effective management tool in systems that lack barriers to predator immigration or have several alternative species of predators, even when a single species typically is responsible for the majority of predation events.
Protoplast transient expression-based RNA-sequencing: A simple method to screen transcriptional regulation in plants
Authors: Zhu Jiameng , Li Suzhen , Jiang Haiyang , Lv Di , Ma Shuai , Wang Baobao , Lu Xiangyu , Yang Wenzhu , Chen Rumei , Zhou Xiaojin
Published: September 2023

Protoplast transient expression-based RNA-sequencing identifies Opaque2 targets supported by molecular evidence and expression quantitative trait loci.
Soil–root interface hydraulic conductance determines responses of photosynthesis to drought in rice and wheat
Authors: Yang Yuhan , Ma Xiaolin , Yan Lu , Li Yingchao , Wei Suhan , Teng Zhipeng , Zhang Hong , Tang Wei , Peng Shaobing , Li Yong
Published: September 2023

Rice (Oryza sativa) production consumes a huge amount of fresh water, and improvement of drought tolerance in rice is important to conserve water resources and minimize yield loss under drought. However, processes to improve drought tolerance in rice have not been fully explored, and a comparative study between rice and wheat (Triticum aestivum) is an effective method to understand the mechanisms determining drought tolerance capacity. In the present study, we applied short-term drought stress to Shanyou 63 rice and Yannong 19 wheat to create a range of water potentials and investigated the responses of gas exchange, plant hydraulic conductance, and root morphological and anatomical traits to soil drought. We found that photosynthesis in rice was more sensitive to drought stress than that in wheat, which was related to differences in the decline of stomatal conductance and plant hydraulic conductance (Kplant). The decline of Kplant under drought was mainly driven by the decrease of soil–root interface hydraulic conductance (Ki) because Ki was more sensitive to drought than root and shoot hydraulic conductance and the soil–root interface contributed to >40% of whole-plant hydraulic resistance in both crops. Root shrinkage in response to drought was more severe in rice than that in wheat, which explains the larger depression of Ki and Kplant under drought stress in rice. We concluded that the decline of Ki drives the depression of Kplant and photosynthesis in both crops, and the plasticity of root morphology and anatomy is important in determining drought tolerance capacity.
Sequencing, Functional Annotation, and Interaction Prediction of mRNAs and Candidate Long Noncoding RNAs Originating from Tea Leaves During Infection by the Fungal Pathogen Causing Tea Leaf Spot, Didymella bellidis
Authors: Huang Honglin , Huang Hongke , Xia Zhongqiu , Yang Yuqin , Jiang Xinyue , Huang Chen , Yang Yuanyou , Wang Delu , Chen Zhuo
Published: September 2023

Tea leaf spot caused by Didymella bellidis can seriously reduce the productivity and quality of tea (Camellia sinensis var. sinensis) leaves in Guizhou Province, southwest China. Analysis of the relationship between messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) of tea could provide insights into the plant-pathogen interaction. In this study, high-throughput sequencing of mRNAs and lncRNAs from tea leaves during infection by D. bellidis was conducted using the Illumina Novaseq 6000 platform. Infection by D. bellidis hyphae resulted in up- or downregulation of 553 and 191 of the differentially expressed mRNAs (DEmRNAs), respectively. As the S gene number (total number of genes with significantly differential expression annotated in the specified Gene Ontology [GO] database), three were enriched with respect to the defense response to the fungus at the biological process level. Expression of the DEmRNAs peroxidase 21 (TEA000222.1) and mcht-2 (TEA013240.1) originating from tea leaves were upregulated during challenge by D. bellidis hyphae, whereas expression of the LRR receptor-like serine/threonine-protein kinase ERECTA (TEA016781.1) gene was downregulated. The infection of D. bellidis hyphae resulted in up- or downregulation of 227 and 958 of the differentially expressed lncRNAs (DElncRNAs). The DEmRNAs associated with uncharacterized LOC101499401 (TEA015626.1), uncharacterized protein (TEA014125.1), structural maintenance of chromosomes protein 1 (TEA001660.1), and uncharacterized protein (TEA017727.1) occurred as a result of cis regulation by DElncRNAs MSTRG.20036, MSTRG.3843, MSTRG.26132, and MSTRG.56701, respectively. The expression profiling and lncRNA/mRNA association prediction in the tea leaves infected by D. bellidis will provide a valuable resource for further research into disease resistance.
Practical Interpretation of 18F PSMA PET/CT: Spectrum of Findings
Authors: Huynh Kenneth N. , Kong Min , Liou Harris , Nguyen Ba D.
Published: September 2023

Prostate cancer imaging has evolved significantly with the introduction of 18F DCFPyL positron emission tomography/computed tomography (PET/CT), a novel radiotracer targeting the prostate-specific membrane antigen (PSMA). This promising imaging modality has demonstrated superior sensitivity and specificity for detecting local, regional, and distant recurrences compared with conventional imaging modalities. This article aims to provide a comprehensive overview of the practical interpretation of 18F DCFPyL PET/CT in the management of prostate cancer, including its advantages, potential pitfalls, and comparison to other imaging techniques. Through a better understanding of 18F DCFPyL PET/CT, clinicians can more effectively incorporate this advanced imaging tool into routine clinical practice, ultimately optimizing prostate cancer diagnosis, staging, and management.
Validation of a Simulation-Based Resuscitation Curriculum for Maternal Cardiac Arrest
Authors: Shields Andrea D. , Vidosh Jacqueline , Thomson Brook A. , Minard Charles , Annis-Brayne Kristen , Kavanagh Laurie , Roth Cheryl K. , Lutgendorf Monica A. , Rahm Stephen J. , Becker Les R. , Mosesso Vincent N. , Schaeffer Brian , Gresens Andrea , Epley Sondie , Wagner Richard , Streitz Matthew J. , Bhalala Utpal S. , Melvin Lissa M. , Deering Shad , Nielsen Peter E.
Published: September 2023

OBJECTIVE:

To assess the knowledge, skills, and self-efficacy of health care participants completing a simulation-based blended learning training curriculum on managing maternal medical emergencies and maternal cardiac arrest (Obstetric Life Support).

METHODS:

A formative assessment of the Obstetric Life Support curriculum was performed with a prehospital cohort comprising emergency medical services professionals and a hospital-based cohort comprising health care professionals who work primarily in hospital or urgent care settings and respond to maternal medical emergencies. The training consisted of self-guided precourse work and an instructor-led simulation course using a customized low-fidelity simulator. Baseline and postcourse assessments included multiple-choice cognitive test, self-efficacy questionnaire, and graded Megacode assessment of the team leader. Megacode scores and pass rates were analyzed descriptively. Pre– and post–self-confidence assessments were compared with an exact binomial test, and cognitive scores were compared with generalized linear mixed models.

RESULTS:

The training was offered to 88 participants between December 2019 and November 2021. Eighty-five participants consented to participation; 77 participants completed the training over eight sessions. At baseline, fewer than half of participants were able to achieve a passing score on the cognitive assessment as determined by the expert panel. After the course, mean cognitive assessment scores improved by 13 points, from 69.4% at baseline to 82.4% after the course (95% CI 10.9–15.1, P<.001). Megacode scores averaged 90.7±6.4%. The Megacode pass rate was 96.1%. There were significant improvements in participant self-efficacy, and the majority of participants (92.6%) agreed or strongly agreed that the course met its educational objectives.

CONCLUSION:

After completing a simulation-based blended learning program focused on managing maternal cardiac arrest using a customized low-fidelity simulator, most participants achieved a defensible passing Megacode score and significantly improved their knowledge, skills, and self-efficacy.
Human Papillomavirus Detectability and Cervical Cancer Prognosis
Authors: Volesky-Avellaneda Karena D. , Laurie Cassandra , Tsyruk-Romano Olga , El-Zein Mariam , Franco Eduardo L.
Published: September 2023

OBJECTIVE:

To evaluate whether testing positive for human papillomavirus (HPV) before treatment is associated with cervical cancer recurrence and disease-free, cancer-specific, and overall survival and to report the relationship of HPV to cervical cancer histology, stage, grade, tumor size, lymph node involvement, and treatment response.

DATA SOURCES:

EMBASE and MEDLINE were searched from inception to January 27, 2022, with the use of MeSH terms and keywords relating to cervical cancer, HPV, and prognosis. ClinicalTrials.gov was not searched because of the nature of our review question.

METHODS OF STUDY SELECTION:

Studies must have assessed HPV DNA or RNA in cervical pretreatment biopsies or cells from 20 or more patients with invasive cervical cancer followed up for any length of time and reported the effect of testing positive or negative for HPV on cervical cancer recurrence, disease-free survival, cancer-specific survival, or overall survival. We extracted data on HPV-detection methods, patient and tumor characteristics, and clinical outcomes.

TABULATION, INTEGRATION, AND RESULTS:

Hazard ratios (HRs) and 95% CIs were pooled with a random-effects model. Meta-regression was performed to explore heterogeneity. Of 11,179 titles or abstracts and 474 full-text articles reviewed, 77 studies were included in the systematic review. Among these 77 studies, 30 reported on the relationship of HPV status to histology, 39 to cancer stage, 13 to tumor grade, 17 to tumor size, 23 to lymph node involvement, and four to treatment response. Testing positive for HPV was associated with better disease-free survival (HR 0.38, 95% CI 0.25–0.57; 15 studies with 2,564 cases), cancer-specific survival (HR 0.56, 95% CI 0.44–0.71; nine studies with 1,398 cases), and overall survival (HR 0.59, 95% CI 0.47–0.74; 36 studies with 9,169 cases), but not recurrence (HR 0.59, 95% CI 0.33–1.07; eight studies with 1,313 cases). Meta-regression revealed that the number of cases, tumor grade, specimen type, gene target, and HPV prevalence together explained 73.8% of the between-study heterogeneity.

CONCLUSION:

This review indicates that HPV detectability in cervical cancer is associated with a better clinical prognosis.

SYSTEMATIC REVIEW REGISTRATION:

https://osf.io/dtyeb.
Primary Human Papillomavirus Testing and Other New Technologies for Cervical Cancer Screening
Authors: Einstein Mark H. , Zhou Nancy , Gabor Lisa , Sahasrabuddhe Vikrant V.
Published: September 2023

Cervical cancer screening has saved the lives of millions in regions where routine gynecologic care is readily accessible. As screening continues to evolve away from cervical cytology to primary human papillomavirus (HPV) testing, robust prospective cohort data have allowed for precise risk stratification and improved our ability to identify those at greatest risk of high-grade dysplasia and decrease unnecessary diagnostic procedures. New technologies such as p16/Ki-67 dual stain testing and HPV methylation panels, which offer comparable performance to co-testing and can be developed into high-throughput workflows, could lead to a fully molecular Pap test. Self-sampling in the United States, where the initial screen can be done in the home, in conjunction with new screening technologies, may decrease the existing hurdles of routine cervical cancer screening. Implementation barriers include issues with workflow, workforce, and cost. These need to be addressed to achieve an improved and more equitable cervical cancer screening program in the United States.