bluuebunny/crossref_metadata_2025 huggingface dataset:
Governance
Authors: Blowfield Michael
Published: September 2023

This chapter looks outside of business at how other sections of society are attempting to govern sustainability issues. It starts by identifying the different sectors of society, their governance roles, and some of their achievements. It then studies in more detail government initiatives at the international, regional, national, and local level. It talks about the phenomenon of multi-stakeholder governance, and how different sectors are collaborating to address sustainability challenges. Climate governance is dealt with in considerable detail, both because of the importance of the climate change challenge, and for the lessons it offers for other sustainability governance initiatives. The chapter ends with a look at the future of sustainability governance.
Decision Making
Authors: Combe Colin
Published: September 2023

This chapter explores the decision-making process in management. It starts with an explanation of the conditions that affect the decision-making process such as uncertainty, risk, and ambiguity. It presents an outline of the nature of programmed and non-programmed decision-making. The chapter includes descriptions, analysis, and examples for models of decision-making such as the rational, administrative, intuitional, political, and garbage can models. It also highlights factors leading to error or bias in decision-making. The chapter concludes with an analysis of the link between decision-making and different styles of management.
Organisational Structure
Authors: Combe Colin
Published: September 2023

This chapter presents an overview of the evolution of the formation of different forms of organizational structure from the bureaucratic formats that characterised factories during the Industrial Revolution through to virtual organisations in the twenty-first century. The chapter begins by explaining the importance of organisational structure in modern management and discusses the key determinants of organisational structure. It then provides a description, analysis, and examples of different types of structure including functional, multidivisional and strategic business units, geographical, matrix, project-team based, and virtual organisations. The discussion extends to cover the emergence of strategic alliances as a form of collaborative arrangements for achieving the stated strategic aims. Key issues discussed also include communication, authority, span of control, centralisation/decentralisation, and the role of restructuring as part of corporate strategy. The chapter analyses the effectiveness of implementing organisational structural change as a means of achieving organisational goals.
Ethics and Corporate Social Responsibility
Authors: Combe Colin
Published: September 2023

This chapter explores ethics and corporate social responsibility (CSR). It discusses some of the main philosophical approaches to ethics that have been evident through the ages. It highlights the key characteristics of the human rights approach that informs much of current thinking on ethics in business and the wider society. The advantages of adopting ethical business practices and CSR are outlined. It then focuses on the relationship between ethics, CSR, and stakeholders. The chapter outlines the means by which ethics are recognised and codified, and it identifies some of the competing responsibilities that help shape a CSR stance by managers in organisations. The implementation of CSR actions has implications for performance in organisation, and forms the basis for discussion on how this may affect profitability. It also examines how ethics and CSR can be included in mission statements and form organisational goals. Finally, the chapter analyses the CSR framework and how organisations can achieve different levels of CSR.
Clients, Procurement, and the Request for Information
Authors: O’Mahoney Joe , Markham Calvert
Published: September 2023

This chapter demonstrates the consultant–client relationship, which is central to both the theoretical understanding and the practical success of consultancy projects. It emphasizes the importance for a consultant to understand and empathize with the needs of the client. It also focuses on consultancy from the point of view of those buying and using consultancy services. The chapter analyses the processes underpinning the client–consultant relationship and the variety of roles the consultant may need to take on. It also traces the gradual shift from personal to procurement models of client engagement. It outlines the pros and cons of the procurement function for both consultants and clients and reviews the procurement process from finding and defining a project to recruiting consultants and negotiating fees.
Consulting Approaches, Methods, and Tools
Authors: O’Mahoney Joe , Markham Calvert
Published: September 2023

This chapter focuses on key approaches, methods, and tools that the consultant can draw upon in order to help their clients. It highlights what approaches, methods, and tools are and how they can be useful, but also discusses the limitations of the tools and techniques of consultancy. The chapter provides an overview of the main analytical frameworks in consultancy and explains how consultancies develop their own tools and products before classifying the different types of tools and methods consultants have developed. It discusses how consultancies and consultants create “bespoke” tools that can then be used for marketing purposes or licensed to other firms.
The Ethics of Consultancy
Authors: O’Mahoney Joe , Markham Calvert
Published: September 2023

This chapter argues that ethical practice in consulting is not getting any better, despite the burgeoning interest in corporate social responsibility, ethical codes, and other pursuits. It emphasizes how consulting ethics are increasingly made the responsibility of the individual consultant rather than the institutions and structures which envelop consulting practice. It also outlines the historical and institutional forces that led to unethical practice in the consulting industry. The chapter highlights regulatory and voluntary changes that have occurred in consulting in the past decade, suggesting that without efforts to reduce institutional conflicts of interest, ethical practice will not improve. It considers specific charges that have been made against consultants by academics and the press.
Secondary data
Authors: Bradley Nigel
Published: September 2023

This chapter focuses on secondary data, which forms the basis of all research projects. It also explains the nature of secondary data. It shows how to refine the approach to collecting primary data. Desk researchers looks for secondary data within the client organisation and also outside. Data are available both online and offline. Wherever the data are to be found, planning the search is essential. The chapter mainly instructs how to interpret published data and how to create search records.
Quantitative research
Authors: Bradley Nigel
Published: September 2023

This chapter examines quantitative research, a branch of research concerned with numbers and statistics. It shows the evaluation of the different elements of the marketing mix. In decision-making, managers prefer to have hard figures, and quantitative research offers precisely that. The chapter also looks at some regularly used approaches such as experimentation, hall tests, panels, and the omnibus. Quantitative research is a field that has been revolutionised by the use of computers, guidance on databases, data marts, and data warehouses. Finally, the chapter scrutinizes the role of software in data mining.
Business-to-business research
Authors: Bradley Nigel
Published: September 2023

This chapter analyses research into ‘non-consumer’ sectors. This kind of research comes under various titles such as ‘business-to-business’, ‘industrial’, ‘trade’, and ‘retail’. The chapter reviews industry structures, different classes of product, and the elements of ‘organisational buying behaviour’. It illustrates the importance of satisfaction, quality, image, and employee satisfaction studies. It brings to light the differences of this research with that used in the fast-moving consumer goods (FMCG) sector. Lastly, it describes the measurement techniques used in this type of research.
International research
Authors: Bradley Nigel
Published: September 2023

This chapter examines the execution and implementation of international research. It shows the specific challenges associated with conducting studies across different nations, languages, and cultures. It focuses on the question of whether it is possible to apply equivalent techniques to different marketplaces. It studies the implications of these differences on desk research, sampling, and instrument design, or whether the research is qualitative or quantitative in nature. Lastly, it determines what must be considered at the publication stage of international research.
Reflection and transferable skills
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

This chapter discusses learning styles. First, it highlights the importance of experience in line with David Kolb's Learning Cycle. Then, the chapter narrates how Kolb's Learning Cycle is used as a basis to design learning cycles and learning styles developed by Graham Gibbs, Peter Honey, and Alan Mumford. It lists Honey and Mumford's category of learners which include activists, reflectors, theorists, and pragmatists. The chapter also looks at the VARK model for other possible learning style models. It explains the process of locating, processing, and communicating information such as guidelines in holding a successful meeting, report writing, data searching, and reading log grids.
Enhancing your profile: standing out from the crowd
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

This chapter looks into enhancing the employability profile. It emphasizes the need to initiate extracurricular activities such as participating in societies, volunteering, part-time work, work experience, holiday internships, twelve-month placements, and activities that demonstrate global connectedness. It mentions the importance of foreign language skills. It explains Mozilla's Open Badges which could serve as evidence of a person's engagement in non-university-related projects. Moreover, the chapter acknowledges the competition in finding employment and the need to stand out. It also highlights the significance of achieving personal goals, a positive mindset, and visualized success. It suggests a reading list on keeping an optimistic outlook.
Managing projects, managing yourself
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

This chapter focuses on managing projects. It narrates the stages of a project: conception/feasibility, planning, implementation, and completion. The chapter highlights the importance of time, cost, and quality in working on a project. It mentions how communication is vital for ensuring the project’s smooth completion. Then, the chapter discusses transferable skills and techniques needed by leaders by citing delegation and performance as examples. It looks into styles of leadership such as individual, team, and task. The chapter acknowledges the inevitability of a firm’s or an individual’s need to cope with change. It explains time management techniques such as the quadrant method and Pareto Principle.
Teamwork 1: Getting started
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

This chapter introduces the concept of working with a team. It explores different types of teams and the roles people take in them in an effort to help an individual identify what type of team player they will be. Then, the chapter points out reasons why teams fail such as unclear goals, arguments, and missing details. It also highlights the impact of emotions and good communication on team dynamics. The chapter recognizes the significance of using technology when working and communicating in teams. It also explains the concept of emotional intelligence. It notes team building as a possible way to improve teamwork. The chapter looks into possible actions while working in a team such as anxiety management, identity management, and mindfulness.
Customer facing skills
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

This chapter focuses on ways to deal with customers. First, it notes important details in relation to dealing with customers such as acknowledgment, listening, building rapport, trust maintenance, informing customers, problem ownership, and cultural issues. The chapter shows methods used by businesses to deal with clients or customers even though these methods might not work in the sales industry. It points out the importance of keeping the aim of helping customers to the right path instead of selling to them. The chapter notes the importance of building rapport with customers by having emotional intelligence and a significant level of sensitivity. It emphasizes the significance of communication, appearances, and first impressions.
Preparing the evidence
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

This chapter looks into preparing application documentation such as curriculum vitaes (CVs), cover letters, and online application forms. It notes ways of making employability evidence stand out, such as using action words and highlighting extracurricular activities. The chapter explains how the STAR method helps deliver evidence of an individual's competence. It mentions how verbs could help state things in a more positive and concise way. The chapter also highlights the benefits and issues of having a digital identity ranging from e-portfolios and social media. It warns of the dangers of employers looking at a candidate's social media posts in terms of evidence of discrimination, disparaging previous employers, and false qualifications. The chapter includes different parts of application forms which vary from standard and personal sections to selection critical sections.
An elephant in the room—EU policy gaps in the regulation of moderating illegal sexual content on video-sharing platforms
Authors: Sorbán Kinga
Published: September 2023

With the availability of broadband internet and a significant increase in storage capacity, people are sharing a dynamically growing amount of multimedia content on video-sharing platforms, including sexually explicit content. While sexual content on the internet is not illegal per se and remains in the domain of economic services, there are certain forms of sexually explicit content that are criminally unlawful, such as child pornography or non-consensual pornography. This article explores why the current business-oriented regulatory environment fails to provide effective tools to combat illegal sexual content: first, from the perspective of content moderation on video-sharing platforms, and then from the perspective of substantive criminal law. After mapping the gaps in policy at all levels of content regulation, the article offers recommendations to address these issues, open up a policy debate and influence policy makers.
Wheat crop traits conferring high yield potential may also improve yield stability under climate change
Authors: Stella Tommaso , Webber Heidi , Eyshi Rezaei Ehsan , Asseng Senthold , Martre Pierre , Dueri Sibylle , Rafael Guarin Jose , Pequeno Diego N L , Calderini Daniel F , Reynolds Matthew , Molero Gemma , Miralles Daniel , Garcia Guillermo , Slafer Gustavo , Giunta Francesco , Kim Yean-Uk , Wang Chenzhi , Ruane Alex C , Ewert Frank
Published: September 2023

Increasing genetic wheat yield potential is considered by many as critical to increasing global wheat yields and production, baring major changes in consumption patterns. Climate change challenges breeding by making target environments less predictable, altering regional productivity and potentially increasing yield variability. Here we used a crop simulation model solution in the SIMPLACE framework to explore yield sensitivity to select trait characteristics (radiation use efficiency [RUE], fruiting efficiency and light extinction coefficient) across 34 locations representing the world’s wheat-producing environments, determining their relationship to increasing yields, yield variability and cultivar performance. The magnitude of the yield increase was trait-dependent and differed between irrigated and rainfed environments. RUE had the most prominent marginal effect on yield, which increased by about 45 % and 33 % in irrigated and rainfed sites, respectively, between the minimum and maximum value of the trait. Altered values of light extinction coefficient had the least effect on yield levels. Higher yields from improved traits were generally associated with increased inter-annual yield variability (measured by standard deviation), but the relative yield variability (as coefficient of variation) remained largely unchanged between base and improved genotypes. This was true under both current and future climate scenarios. In this context, our study suggests higher wheat yields from these traits would not increase climate risk for farmers and the adoption of cultivars with these traits would not be associated with increased yield variability.
Treaty influencers: a computational analysis of the development of international investment law
Authors: Lie Runar Hilleren
Published: September 2023

This article uses computational methods to analyse the development of the international investment law regime, seeking to understand how, when, and by whom change in treaty language occurs. The study uses a novel computational method to explore the influence of different states on the language of international investment treaties and the spread of language patterns. The analysis reveals a hegemony of Western European, rather than North American influence, and further highlights a clear early mover advantage for obtaining language spread. The article discusses the implications of these findings for the investment treaty system, particularly the limited impact of hard negotiating power compared to early entrance and convincing legal language.
Recruitment of a Middling Promiscuous Enzyme Drives Adaptive Metabolic Evolution in Escherichia coli
Authors: Campbell Ryan P , Whittington A Carl , Zorio Diego A R , Miller Brian G
Published: September 2023

A key step in metabolic pathway evolution is the recruitment of promiscuous enzymes to perform new functions. Despite the recognition that promiscuity is widespread in biology, factors dictating the preferential recruitment of one promiscuous enzyme over other candidates are unknown. Escherichia coli contains four sugar kinases that are candidates for recruitment when the native glucokinase machinery is deleted—allokinase (AlsK), manno(fructo)kinase (Mak), N-acetylmannosamine kinase (NanK), and N-acetylglucosamine kinase (NagK). The catalytic efficiencies of these enzymes are 103- to 105-fold lower than native glucokinases, ranging from 2,400 M−1 s−1 for the most active candidate, NagK, to 15 M−1 s−1 for the least active candidate, AlsK. To investigate the relationship between catalytic activities of promiscuous enzymes and their recruitment, we performed adaptive evolution of a glucokinase-deficient E. coli strain to restore glycolytic metabolism. We observed preferential recruitment of NanK via a trajectory involving early mutations that facilitate glucose uptake and amplify nanK transcription, followed by nonsynonymous substitutions in NanK that enhance the enzyme's promiscuous glucokinase activity. These substitutions reduced the native activity of NanK and reduced organismal fitness during growth on an N-acetylated carbon source, indicating that enzyme recruitment comes at a cost for growth on other substrates. Notably, the two most active candidates, NagK and Mak, were not recruited, suggesting that catalytic activity alone does not dictate evolutionary outcomes. The results highlight our lack of knowledge regarding biological drivers of enzyme recruitment and emphasize the need for a systems-wide approach to identify factors facilitating or constraining this important adaptive process.
Heating of the neck or elbows alleviates Raynaud’s phenomenon but has different effects on different types of patients with systemic sclerosis
Authors: Shima Yoshihito , Watanabe Akane , Inoue Nobuto , Maruyama Tetsuya , Kunitomo Eiji , Kumanogoh Atsushi
Published: September 2023

Objectives

We previously reported that heating of the neck or elbows alleviated Raynaud’s phenomenon in patients with systemic sclerosis and upregulated capillary extension factor angiopoietin-1 (Angpt-1) in the fingertips. In this study, we investigated which cases responded better to the effect of heating of the neck or elbows.

Methods

The pre- to postheating change in the visual analogue scale (ΔVAS) for Raynaud’s phenomenon was examined for correlation with age, disease duration, autoantibodies, disease types, corticosteroid dose, capillaroscopic nailfold capillary damage, fingertip Angpt-1 concentrations at baseline, and increased rate of Angpt-1 concentration.

Results

The ΔVAS for elbow heating correlated positively with the baseline Angpt-1 concentration, whereas opposite correlation was observed for neck heating. The other items did not significantly correlate with the ΔVAS; however, the ΔVAS for elbow heating tended to be larger in patients with advanced capillary damage, whereas an opposite trend was observed for neck heating.

Conclusions

Elbow and neck heating alleviated Raynaud’s phenomenon to a similar extent, but their mechanism was different. Heating of the elbows had a greater effect on patients with advanced capillary damage and lower fingertip Angpt-1 concentrations.
Karnofsky Performance Status and quality of life in patients with relapsed or refractory primary CNS lymphoma from a phase I/II study of tirabrutinib
Authors: Arakawa Yoshiki , Narita Yoshitaka , Nagane Motoo , Mishima Kazuhiko , Terui Yasuhito , Yonezawa Hajime , Asai Katsunori , Fukuhara Noriko , Sugiyama Kazuhiko , Shinojima Naoki , Aoi Arata , Nishikawa Ryo
Published: September 2023

Background

Tirabrutinib, a second-generation inhibitor of Bruton’s tyrosine kinase, was approved in March 2020 for the treatment of relapsed or refractory primary central nervous system lymphoma (r/r PCNSL) based on phase I/II studies in Japan. We previously reported the overall response rate and safety profile. We describe Karnofsky Performance Status (KPS) and the quality of life (QoL) in patients with r/r PCNSL receiving tirabrutinib based on more than 1-year follow-up data.

Methods

Patients with r/r PCNSL, age ≥20 years, and KPS ≥70 were treated with tirabrutinib once daily at a dose of 320, 480, or 480 mg under fasted conditions. QoL was assessed using questionnaires issued by the European Organization for Research and Treatment of Cancer (EORTC), namely EORTC QLQ-C30, EORTC QLQ-BN20, and EuroQol 5 dimensions 3-level (EQ-5D-3L) along with KPS.

Results

Forty-four patients (mean age, 60 years [range 29–86]) were enrolled. The median follow-up period was 14.9 months (range, 1.4–27.7). The median KPS of the patients at baseline was 80.0 (range, 70–100), and this remained constant during the treatment. The global health status/QoL in the QLQ-C30 showed significant improvements from baseline through cycles 3–17 and remained relatively constant thereafter until cycle 23. Improvements were also seen in emotional functioning and constipation in the QLQ-C30 segments. Other items of QLQ-C30 and QLQ-BN20, EQ-5D visual analog scales, and EQ-5D index were maintained during the treatment.

Conclusions

Tirabrutinib generally maintains KPS and QoL scores with some improvements in specific QoL items in patients with r/r PCNSL.
A rare presentation of dengue fever: bilateral psoas muscle hematoma, intrahepatic cholestatic hepatitis, pancreatitis and pancytopenia
Authors: Islam Jemima , Mondal Karimulla , Ghosh Sumit Kumar , Datta Anup Kumar , Ghosh Soumitra
Published: September 2023

Dengue is the foremost cause of arthropod-borne viral disease in the world. It is and commonly found in tropical and subtropical parts of the world. Dengue fever is caused by one of the four distinct serotypes (DENV 1–4) of single-stranded RNA Flavivirus genus and transmitted through Aedes mosquito. Infection caused by one serotype develops lifelong immunity to that serotype, but not to others. Dengue fever (DF) presents with high fever, headache, myalgia, and arthralgia, and rash. Severe dengue, dengue haemorrhagic fever (DHF), and dengue shock syndrome (DSS) are accompanied by thrombocytopenia, vascular leakage, and hypotension. DSS is characterized by shock, which can be fatal with case fatality high as 12% to 44%. There are few atypical manifestations of dengue fever growing with rising disease burden, often missed and sometimes difficult to diagnosis. In this case report, we will discuss atypical manifestations of bilateral psoas muscle hematoma, intrahepatic cholestatic hepatitis, pancreatitis and pancytopenia observed in dengue fever patient.
Construction of a Diagnostic Model for Small Cell Lung Cancer Combining Metabolomics and Integrated Machine Learning
Authors: Shang Xiaoling , Zhang Chenyue , Kong Ronghua , Zhao Chenglong , Wang Haiyong
Published: September 2023

Background

To date, no study has systematically explored the potential role of serum metabolites and lipids in the diagnosis of small cell lung cancer (SCLC). Therefore, we aimed to conduct a case-cohort study that included 191 cases of SCLC, 91 patients with lung adenocarcinoma, 82 patients with squamous cell carcinoma, and 97 healthy controls.

Methods

Metabolomics and lipidomics were applied to analyze different metabolites and lipids in the serum of these patients. The SCLC diagnosis model (d-model) was constructed using an integrated machine learning technology and a training cohort (n = 323) and was validated in a testing cohort (n=138).

Results

Eight metabolites, including 1-mristoyl-sn-glycero-3-phosphocholine, 16b-hydroxyestradiol, 3-phosphoserine, cholesteryl sulfate, D-lyxose, dioctyl phthalate, DL-lactate and Leu-Phe, were successfully selected to distinguish SCLC from controls. The d-model was constructed based on these 8 metabolites and showed improved diagnostic performance for SCLC, with the area under curve (AUC) of 0.933 in the training cohort and 0.922 in the testing cohort. Importantly, the d-model still had an excellent diagnostic performance after adjusting the stage and related clinical variables and, combined with the progastrin-releasing peptide (ProGRP), showed the best diagnostic performance with 0.975 of AUC for limited-stage patients.

Conclusion

This study is the first to analyze the difference between metabolomics and lipidomics and to construct a d-model to detect SCLC using integrated machine learning. This study may be of great significance for the screening and early diagnosis of SCLC patients.
Metabolomic Analysis of the Desert Moss Syntrichia caninervis Provides Insights into Plant Dehydration and Rehydration Response
Authors: Yang Qilin , Yang Ruirui , Gao Bei , Liang Yuqing , Liu Xiujin , Li Xiaoshuang , Zhang Daoyuan
Published: September 2023

Desiccation-tolerant (DT) plants can survive extreme dehydration and tolerate the loss of up to 95% of their water content, making them ideal systems to determine the mechanism behind extreme drought stress and identify potential approaches for developing drought-tolerant crops. The desert moss Syntrichia caninervis is an emerging model for extreme desiccation tolerance that has benefited from high-throughput sequencing analyses, allowing identification of stress-tolerant genes; however, its metabolic response to desiccation is unknown. A liquid chromatography–mass spectrometry analysis of S. caninervis at six dehydration–rehydration stages revealed 912 differentially abundant compounds, belonging to 93 metabolic classes. Many (256) metabolites accumulated during rehydration in S. caninervis, whereas only 71 accumulated during the dehydration period, in contrast to the pattern observed in vascular DT plants. During dehydration, nitrogenous amino acids (l-glutamic acid and cysteinylglycine), alkaloids (vinleurosine) and steroids (physalin D) accumulated, whereas glucose 6-phosphate decreased. During rehydration, γ-aminobutyric acid, glucose 6-phosphate and flavonoids (karanjin and aromadendrin) accumulated, as did the plant hormones 12-oxo phytodienoic acid (12-OPDA) and trans-zeatin riboside. The contents ofl-arginine, maltose, turanose, lactulose and sucrose remained high throughout dehydration–rehydration. Syntrichia caninervis thus accumulates antioxidants to scavenge reactive oxygen species, accumulating nitrogenous amino acids and cytoprotective metabolites and decreasing energy metabolism to enter a protective state from dehydration-induced damage. During subsequent rehydration, many metabolites rapidly accumulated to prevent oxidative stress and restore physiological activities while repairing cells, representing a more elaborate rehydration repair mechanism than vascular DT plants, with a faster and greater accumulation of metabolites. This metabolic kinetics analysis in S. caninervis deepens our understanding of its dehydration mechanisms and provides new insights into the different strategies of plant responses to dehydration and rehydration.
The limits of human mobility traces to predict the spread of COVID-19: A transfer entropy approach
Authors: Delussu Federico , Tizzoni Michele , Gauvin Laetitia
Published: September 2023

Mobile phone data have been widely used to model the spread of COVID-19; however, quantifying and comparing their predictive value across different settings is challenging. Their quality is affected by various factors and their relationship with epidemiological indicators varies over time. Here, we adopt a model-free approach based on transfer entropy to quantify the relationship between mobile phone-derived mobility metrics and COVID-19 cases and deaths in more than 200 European subnational regions. Using multiple data sources over a one-year period, we found that past knowledge of mobility does not systematically provide statistically significant information on COVID-19 spread. Our approach allows us to determine the best metric for predicting disease incidence in a particular location, at different spatial scales. Additionally, we identify geographic and demographic factors, such as users’ coverage and commuting patterns, that explain the (non)observed relationship between mobility and epidemic patterns. Our work provides epidemiologists and public health officials with a general—not limited to COVID-19—framework to evaluate the usefulness of human mobility data in responding to epidemics.
Physics-based approach to extend a de novo TIM barrel with rationally designed helix-loop-helix motifs
Authors: Kordes Sina , Beck Julian , Shanmugaratnam Sooruban , Flecks Merle , Höcker Birte
Published: September 2023

Computational protein design promises the ability to build tailor-made proteins de novo. While a range of de novo proteins have been constructed so far, the majority of these designs have idealized topologies that lack larger cavities which are necessary for the incorporation of small molecule binding sites or enzymatic functions. One attractive target for enzyme design is the TIM-barrel fold, due to its ubiquity in nature and capability to host versatile functions. With the successful de novo design of a 4-fold symmetric TIM barrel, sTIM11, an idealized, minimalistic scaffold was created. In this work, we attempted to extend this de novo TIM barrel by incorporating a helix-loop-helix motif into its βα-loops by applying a physics-based modular design approach using Rosetta. Further diversification was performed by exploiting the symmetry of the scaffold to integrate two helix-loop-helix motifs into the scaffold. Analysis with AlphaFold2 and biochemical characterization demonstrate the formation of additional α-helical secondary structure elements supporting the successful extension as intended.
Micro-porous PLGA/β-TCP/TPU scaffolds prepared by solvent-based 3D printing for bone tissue engineering purposes
Authors: Hatt Luan P , Wirth Sylvie , Ristaniemi Aapo , Ciric Daniel J , Thompson Keith , Eglin David , Stoddart Martin J , Armiento Angela R
Published: September 2023

The 3D printing process of fused deposition modelling is an attractive fabrication approach to create tissue-engineered bone substitutes to regenerate large mandibular bone defects, but often lacks desired surface porosity for enhanced protein adsorption and cell adhesion. Solvent-based printing leads to the spontaneous formation of micropores on the scaffold’s surface upon solvent removal, without the need for further post processing. Our aim is to create and characterize porous scaffolds using a new formulation composed of mechanically stable poly(lactic-co-glycol acid) and osteoconductive β-tricalcium phosphate with and without the addition of elastic thermoplastic polyurethane prepared by solvent-based 3D-printing technique. Large-scale regenerative scaffolds can be 3D-printed with adequate fidelity and show porosity at multiple levels analysed via micro-computer tomography, scanning electron microscopy and N2 sorption. Superior mechanical properties compared to a commercially available calcium phosphate ink are demonstrated in compression and screw pull out tests. Biological assessments including cell activity assay and live-dead staining prove the scaffold’s cytocompatibility. Osteoconductive properties are demonstrated by performing an osteogenic differentiation assay with primary human bone marrow mesenchymal stromal cells. We propose a versatile fabrication process to create porous 3D-printed scaffolds with adequate mechanical stability and osteoconductivity, both important characteristics for segmental mandibular bone reconstruction.
Female sexual medicine: an assessment of medical school curricula in a major United States city
Authors: Codispoti Nicolette , Negris Olivia , Myers Monica C , Petersen Anna , Nico Elsa , Romanello Jennifer P , Rubin Rachel S
Published: September 2023

Background

Although approximately 41% of women experience sexual dysfunction, limited education on female sexual medicine (FSM) in medical school results in underpreparedness among physicians when addressing these bothersome conditions.

Aim

This study aims to evaluate the extent to which FSM is represented in medical education by examining current preclinical and clinical curricula.

Methods

Preclinical curriculum materials on female sexual anatomy, physiology, and pathology, as well as obstetrics and gynecology clinical materials (syllabi, lecture materials, and supplemental resources), were collected from medical schools in the Chicago area. We utilized previous literature to identify specific components of medical school content to evaluate.

Outcomes

Upon reviewing each institution’s curricula, we evaluated materials for topic saturation and assessed goals of each syllabus in terms of required content.

Results

Curriculum materials were collected from 7 medical schools. In the preclinical assessment, 1 institution identified all anatomic components of the clitoris in our review, 4 discussed the physiology of the female orgasm, 3 highlighted the prevalence and epidemiology of female sexual dysfunction (FSD), 3 addressed treatments for FSD, and 1 instructed a genitourinary physical exam specific to assessing FSD. When assessing obstetrics and gynecology clinical materials, 5 institutions included topics related to FSM. Of these, only 1 institution had corresponding required synchronous clerkship time dedicated to these topics as a 1-hour lecture, in addition to an optional online training to third-year clinical students in comprehensive sexual history–taking practices, including screening for FSD. One other institution offered supplemental case-based gynecology modules including vulvovaginal diseases and chronic pelvic pain, though sexual pleasure, arousal, and libido were not included.

Clinical Implications

The results of this study highlight the need for the inclusion of standardized curricula related to FSM in medical education to equip future physicians to treat patients with sexual dysfunction.

Strengths and Limitations

The strengths of this study include that it is the first of its kind to complete a comprehensive review of FSM curricula at a cohort of undergraduate medical institutions. Its limitations include a small sample size of 7 medical schools limited to 1 geographical area.

Conclusion

Our focused needs assessment of medical schools in the Chicago area reveals inconsistencies in outlined institution-specific course goals related to FSM and thus highlights the need for restructuring the curricula to prepare future physicians to recognize and treat patients with sexual dysfunction.
Phase-amplitude coupling of Go/Nogo task-related neuronal oscillation decreases for humans with insufficient sleep
Authors: Zhang Peng , Sun Chuancai , Liu Zhongqi , Zhou Qianxiang
Published: September 2023

Phase-amplitude coupling (PAC) across frequency might be associated with the long-range synchronization of brain networks, facilitating the spatiotemporal integration of multiple cell assemblies for information transmission during inhibitory control. However, sleep problems may affect these cortical information transmissions based on cross-frequency PAC, especially when humans work in environments of social isolation. This study aimed to evaluate changes in the theta–beta/gamma PAC of task-related electroencephalography (EEG) for humans with insufficient sleep. Here, we monitored the EEG signals of 60 healthy volunteers and 18 soldiers in the normal environment, performing a Go/Nogo task. Soldiers also participated in the same test in isolated cabins. These measures demonstrated theta–beta PACs between the frontal and central-parietal, and robust theta–gamma PACs between the frontal and occipital cortex. Unfortunately, these PACs significantly decreased when humans experienced insufficient sleep, which was positively correlated with the behavioral performance of inhibitory control. The evaluation of theta–beta/gamma PAC of Go/Nogo task-related EEG is necessary to help understand the different influences of sleep problems in humans.
Sleep disturbances and change in multiple cognitive domains among older adults: a multicenter study of five Nordic cohorts
Authors: Overton Marieclaire , Skoog Johan , Laukka Erika J , Bodin Timothy Hadarsson , Mattsson Alexander Darin , Sjöberg Linnea , Hofer Scott M , Johansson Lena , Kulmala Jenni , Kivipelto Miia , Solomon Alina , Skoog Ingmar , Kåreholt Ingemar , Sindi Shireen
Published: September 2023

Study Objectives

We examined and compared cross-sectional and longitudinal associations between self-reported sleep disturbances and various cognitive domains in five separate Nordic European longitudinal aging studies (baseline N = 5631, mean age = 77.7, mean follow-up = 4.16 years).

Methods

Comparable sleep parameters across studies included reduced sleep duration/quality, insomnia symptoms (sleep latency, waking up at night, and early awakenings), short and long sleep duration, and daytime napping. The cognitive domains were episodic memory, verbal fluency, perceptual speed, executive functioning, and global cognition (aggregated measure). A series of mixed linear models were run separately in each study and then compared to assess the level and rate of change in cognitive functioning across each sleep disturbance parameter. Models were adjusted for age, sex, education, hypnotic usage, depressive symptoms, lifestyle factors, cardiovascular, and metabolic conditions. By using a coordinated analytic approach, comparable construct-level measurements were generated, and results from identical statistical models were qualitatively compared across studies.

Results

While the pattern of statistically significant results varied across studies, subjective sleep disturbances were consistently associated with worse cognition and steeper cognitive decline. Insomnia symptoms were associated with poorer episodic memory and participants sleeping less or more than 7–8 hours had a steeper decline in perceptual speed. In addition, daytime napping (>2 hours) was cross-sectionally and longitudinally associated with all examined cognitive domains. Most observed associations were study-specific (except for daytime napping), and a majority of association estimates remained significant after adjusting for covariates.

Conclusion

This rigorous multicenter investigation further supports the importance of sleep disturbance, including insomnia, long and short sleep duration, and daytime napping on baseline cognitive functioning and rate of change among older adults. These sleep factors may be targeted in future lifestyle interventions to reduce cognitive decline.
Evaluation of protected benzoic acid on growth performance, nutrient digestibility, and gut health indices in starter pigs
Authors: Outlaw Alex , Gachman Alexandra , Kim Haejin , Xu Xiangyi , Tan Zhigang , Qin Zhonghua , Peng Xianfeng , Rudar Marko
Published: September 2023

Benzoic acid is a common alternative for antibiotic and zinc oxide use in nursery diets. Free benzoic acid (BZA) is often supplied, but this form is absorbed before it can exert any effect on distal segments of the gut. The study aimed to evaluate the effects of protected benzoic acid on growth performance, nutrient digestibility, plasma metabolites, and gut health indices in starter pigs. A total of 192 pigs were weaned at 28 ± 1 d age (initial body weight, 8.72 ± 1.13 kg). Pens were assigned to one of four treatment diets (n = 8 pens per treatment): (1) no additive (NC), (2) free benzoic acid (BZA; 0.6%), (3) protected benzoic acid (BC50; 0.2%, supplied at a ratio of one to three equivalents of BZA), and (4) antibiotic growth promoter (AGP; Carbadox, 50 ppm). Diets were fed for three weeks over two periods (period 1, 7 d; period 2, 14 d). Body weight and feed intake were measured for each period. Feces were collected at the end of each period to determine apparent total tract digestibility (ATTD) of organic matter (OM), gross energy (GE), and crude protein (CP). One pig per pen was euthanized per period to determine plasma metabolites; jejunum and ileum morphology; jejunum, ileum, and colon cytokine abundance; and jejunum, ileum, and colon tight junction protein expression. The AGP group had increased average daily gain (ADG) and average daily feed intake (ADFI) compared to other groups in period 1 and overall (P < 0.05); however, ADG and ADFI of the BC50 group was intermediate between the NC and BZA groups and the AGP group in period 2. The ATTD of OM, GE, and CP were greater in the AGP group compared to the NC and BC50 groups (P < 0.05), whereas the BZA group was intermediate. Jejunum and ileum villus height and crypt depth increased from period 1 to period 2 (P < 0.01) but were similar across groups. Ileum and colon tumor necrosis factor-α (TNF-α) abundances were greater, whereas colon interleukin (IL)-1β and colon and ileum IL-8 abundances were less, in the AGP group compared to the BZA group (P < 0.05); the NC and BC50 groups exhibited intermediate TNF-α, IL-1β, and IL-8 abundance in the ileum and colon. Jejunum cytokine abundance did not vary among groups but declined from period 1 to period 2 (P < 0.05). Tight junction protein expression also did not vary among groups. In summary, protected BZA supported a slight increase in growth performance in starter pigs, suggesting its potential as an alternative feed additive in nursery diets.
Serum inflammation and oxidative DNA damage amelioration in cocks-fed supplemental Vernonia amygdalina and zinc in aflatoxin B1 contaminated diets
Authors: Olarotimi Olumuyiwa J , Gbore Francis A , Oloruntola Olugbenga D , Jimoh Olatunji A
Published: September 2023

The objective of the study was to assess the comparative effects of Vernonia amygdalina leaf meal (VALM) and zinc (Zn) on the serum proinflammatory and anti-inflammatory cytokines as well as DNA damage of cocks-fed aflatoxin B1 (AFB1) contaminated diets. A total of 250 sexually mature Isa White cocks of 24 weeks old were randomly distributed into five groups (treatments) with each containing 50 birds, which was replicated five times with 10 birds per replicate. Cocks in group A were fed basal diet only, group B was fed basal diet contaminated with 1 mg AFB1/kg diet, group C received diet B (basal + 1 mg/kg AFB1) with 50 mg/kg Zn, group D was fed diet B with 2.5 g/kg VALM, and group E received diet B with 5.0 g/kg VALM, respectively. Feed and water were supplied ad libitum with fresh feed added to the feed troughs at 6:00 a.m. and 6:00 p.m., respectively. While serum tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), 8-hydroxy-2ʹ-deoxyguanosine (8-OHdG), and nuclear factor kappa B (NF-κB) were significantly (P < 0.05) elevated among the cocks on diet B, significant (P < 0.05) reductions were recorded among cocks on diets C, D, and E. Conversely, birds in group B had significant (P < 0.05) depression in serum interleukin 4 (IL-4) and interleukin 10 (IL-10) while improvements (P < 0.05) were recorded among cocks in groups C, D, and E, respectively. Therefore, the inclusion of VALM offset the adverse physiological effects of AFB1 observed among group B birds. The effects were comparable with the results presented by the cocksfed diet containing Zn.
Interpretable predictive models of genome-wide aryl hydrocarbon receptor-DNA binding reveal tissue-specific binding determinants
Authors: Filipovic David , Qi Wenjie , Kana Omar , Marri Daniel , LeCluyse Edward L , Andersen Melvin E , Cuddapah Suresh , Bhattacharya Sudin
Published: September 2023

The aryl hydrocarbon receptor (AhR) is an inducible transcription factor whose ligands include the potent environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Ligand-activated AhR binds to DNA at dioxin response elements (DREs) containing the core motif 5′-GCGTG-3′. However, AhR binding is highly tissue specific. Most DREs in accessible chromatin are not bound by TCDD-activated AhR, and DREs accessible in multiple tissues can be bound in some and unbound in others. As such, AhR functions similarly to many nuclear receptors. Given that AhR possesses a strong core motif, it is suited for a motif-centered analysis of its binding. We developed interpretable machine learning models predicting the AhR binding status of DREs in MCF-7, GM17212, and HepG2 cells, as well as primary human hepatocytes. Cross-tissue models predicting transcription factor (TF)-DNA binding generally perform poorly. However, reasons for the low performance remain unexplored. By interpreting the results of individual within-tissue models and by examining the features leading to low cross-tissue performance, we identified sequence and chromatin context patterns correlated with AhR binding. We conclude that AhR binding is driven by a complex interplay of tissue-agnostic DRE flanking DNA sequence and tissue-specific local chromatin context. Additionally, we demonstrate that interpretable machine learning models can provide novel and experimentally testable mechanistic insights into DNA binding by inducible TFs.