bluuebunny/crossref_metadata_2025 huggingface dataset:
Intellectual Property as Business Loan Collateral: A Taxonomy of Institutional and Economic Determinants
Authors: Heller David , Leitzinger Leo , Walz Uwe
Published: April 2024

As a promising strategy to secure debt financing, firms can use their intellectual property rights (IPR) as collateral. Despite an ongoing shift to a more technology-based economy, the collateralization of IPR is still trailing behind the use of more traditional asset classes. In this paper, we address the challenges and opportunities of using IPR as collateral from a legal and economic angle by also exploring the role of and consequences for IP law. We develop a new taxonomy, i.e., a classification of the key determinants of using IPR as collateral. The taxonomy defines two pillars that govern the use of IPR collateral that distinguish between institutional and economic determinants. The institutional determinants cover contract law, IPR registries, and banking regulations. The economic determinants constitute the influence of IPR characteristics on the trade-off between the economic costs and benefits of collateralizing IPR. We apply the derived taxonomy to the legal and economic status quo in several industrialized economies to identify potential impediments to IPR-backed debt financing. Taken together, our taxonomy can be viewed as providing guidance for future research in the fields of law and economics on IPR as loan collateral for businesses.
Quality improvement initiative to increase radial artery usage as a second arterial conduit in coronary artery bypass grafting
Authors: Moya-Mendez Mary E , DeLaura Isabel , Thornton Steven W , Williams Adam R , Zwischenberger Brittany A
Published: April 2024

OBJECTIVES

Use of radial artery as a second arterial graft, compared to a saphenous vein, in coronary artery bypass grafting (CABG) can improve late outcomes. However, the radial artery remains underutilized. We initiated a quality improvement (QI) initiative to increase the usage of radial artery grafts.

METHODS

During our 4-month lead period, we disseminated evidence for radial artery graft usage to surgeons, developed a radial artery decision-making algorithm and adopted endoscopic harvesting. Our QI initiative was conducted over a 6-month period and included a postoperative survey of decision-making for graft selection and obstacles to radial artery usage.

RESULTS

Over the 6-month study period, 247 patients received isolated CABG which included 98 (40%) with radial arteries as a second arterial graft and 144 (58%) with greater saphenous veins. Radial artery usage increased with QI initiative implementation by 67% compared to 6 months prior to the study period (60 radial arteries/252 isolated CABG, 24%) (P = 0.006). The survey response rate was 93% (231/247). Barriers to radial artery graft usage were poor quality target vessel or stenosis <80% (24%), patient age >75 years (20%), ejection fraction ≤35% (8%) and renal insufficiency/dialysis (7%). No patients experienced significant complications from radial artery harvest.

CONCLUSIONS

Our institutional QI initiative was successful in (i) increasing the usage of radial artery as a second arterial graft and (ii) understanding barriers to radial artery graft usage. Implementation of a QI program can improve radial artery usage in CABG with low risk of patient morbidity from radial artery harvest.
Enriching Cultural Heritage Communities: New Tools and Technologies
Authors: Dix Alan , Jones Elizabeth , Cowgill Rachel , Armstrong Charlotte , Ridgewell Rupert , Twidale Michael , Downie J Stephen , Reagan Maureen , Bashford Christina , Bainbridge David , Neads Carys-Ann , Davies Vince
Published: April 2024

This paper explores ways in which scholarly skill and expertise might be embodied in tools and sustainable practices that enable communities to create and manage their own digital archives. We focus particularly on tools and practices related to the recording and annotation of digitized materials. The paper is based on co-production practice in two very different kinds of community. Although the communities are different we find that tools designed for a specific community are valuable for others, thus offering the promise of general tools to support community-centred digitization and potentially also traditional archival practice.
Retrospective analysis of pathogens for guided creation of an EMPIRIc antibiotic prEscribing pathway (EMPIRE)
Authors: Todor Lorraine A , Hill David M
Published: April 2024

The objective of this study was to evaluate the susceptibilities of pathogens isolated from cultures within the first 7 days of admission to the burn center and in the absence of healthcare-associated infection risk factors (HAIRF) to determine if current empiric antibiotics can be narrowed for refinement of an empiric antibiotic prescribing pathway according to the suspected source. A 3-year sample of patients and cultures was utilized in hopes of obtaining at least 30 isolates of the most common pathogens and their respective susceptibilities. A total of 268 clinically relevant (e.g., deemed infectious, versus colonization) pathogens were included in the final sample with sources including wounds, respiratory, blood, urine, and bone. Of the 268 pathogens included, 45% were Gram-negative and 69% of all pathogens were isolated from wound cultures. The existing empiric pathway, vancomycin plus cefepime, covered 98% and 84% of all Gram-positive and Gram-negative pathogens, respectively. In patients without HAIRF, coverage rose to 98% and 90%, respectively. Initial use of vancomycin and cefepime remains adequate for pathogens isolated within 1 week of admission in patients without HAIRF. For pneumonias, a narrower spectrum beta-lactam would not sufficiently cover respiratory pathogens isolated within the first week of admission. Regarding early wound infections, difficult-to-treat pathogens remain as a rare isolate of wound cultures within 1 week of admission.
Trilobatin regulates glucose metabolism by ameliorating oxidative stress and insulin resistance in vivo and in vitro
Authors: He Ming , Zhang Yuqing , Zhai Yuhan , Li Yaping , Yang Guorui , Yu Shaoxuan , Xiao Haifang , Song Yuanda
Published: April 2024

Objectives

Trilobatin, a glycosylated dihydrochalcone, has been reported to have anti-diabetic properties. However, the underlying mechanism remains unexplained.

Methods

In this investigation, the regulation of trilobatin on glucose metabolism of insulin resistance (IR)-HepG2 cells and streptozocin (STZ)-induced mice and its mechanism were evaluated.

Key findings

Different doses of trilobatin (5, 10 and 20 μM) increased glucose consumption, glycogen content, hexokinase (HK), and pyruvate kinase (PK) activity in IR-HepG2 cells. Among them, the HK and PK activity in IR-HepG2 cells treated with 20 μM trilobatin were 1.84 and 2.05 times than those of the IR-group. The overeating, body and tissue weight, insulin levels, liver damage, and lipid accumulation of STZ-induced mice were improved after feeding with different doses of trilobatin (10, 50, and 100 mg/kg/d) for 4 weeks. Compared with STZ-induced mice, fasting blood glucose decreased by 61.11% and fasting insulin (FINS) increased by 48.6% after feeding trilobatin (100 mg/kg/d). Meanwhile, data from quantitative real-time polymerase chain reaction (qRT-PCR) revealed trilobatin ameliorated glycogen synthesis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway in IR-HepG2 cells and in STZ-induced mice. Furthermore, in vitro and in vivo experiments showed that trilobatin ameliorated oxidative stress by regulating the mRNA expression of nuclear erythroid-2 related factor 2 (Nrf2)/kelch-like ECH associated protein-1 (Keap-1) pathway as well as heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO-1).

Conclusions

Our research reveals a novel pharmacological activity of trilobatin: regulating glucose metabolism through PI3K/Akt/GSK-3β and Nrf2/Keap-1 signaling pathways, improving insulin resistance and reducing oxidative stress. Trilobatin can be used as a reliable drug resource for the treatment of glucose metabolism disorders.
Phytochemical profile and hepatoprotective potentiality of Phyllanthus genus: a review
Authors: Pratima H , Shiraguppi Anita , Joojagar Priyadarshini , Shah Kamal , Cheeraladinni Sudharani S , Singh P Shivakumar , Mendem Suresh kumar , Chauhan Nagendra Singh
Published: April 2024

The Phyllanthus genus is very important plant traded as a raw herbal medicine in India. Commonly known as ‘Bhumyamalaki’ (Phyllanthus species) has been used for the prevention and treatment of jaundice. Phyllanthus is rich in diversity of bioactive compounds such as lignans, alkaloids, terpenoids, flavonoids, and tannins. Among some metabolites such as phyllanthin, hypophyllanthin, 8, 9-epoxy brevifolin, brevifolin, quercetin, gallic acid, elagic acid, and brevifolin carboxylate have been shown to have hepatoprotective and antioxidant activity found in this genus. The basic objective of this review was to overview the hepatoprotective activity based on the other available data from various plants of the Phyllanthus species including Phyllanthus amarus, Phyllanhtus urinaria, Phyllanthus fraternus, Phyllanthus maderaspatenis, Phyllanthus simplex, Phyllanthus emblica, Phyllanthus debillis, Phyllanthus tenellus, Phyllanthus polyphyllus, Phyllanthus reticulates, Phyllanthus indofischerii, Phyllanthus acidus, Phyllanthus niruri, Phyllanthus rheedii, Phyllanthus kozhikodianus, and Phyllanthus longiflorus. These species studied had considerable hepatoprotective potential. The secondary data, each in vitro and in vivo studies confirm the capacity of Phyllanthus species used as a remedy for jaundice or liver disease in addition to having antioxidants. Furthermore, it could be concluded that herbal drugs have the least side effects and are taken into considered safe for human health, they are able to substantially alternative synthetic drugs in the future.
A diagnostic dilemma—to operate or not to operate—a rare case report
Authors: Thirumurthy Sathish Kumar , Bapat Manjiri , Ahmed Ehsan
Published: April 2024

A 41-year-old male presented with a swelling in the right flank present since 2 years. Initially, it was small in size but increased in size for the past 6 months. Examination revealed a large swelling in the right flank that was soft in consistency and attached to the deeper muscle. CT scan revealed a heterogenous complex swelling with attachment to the underlying muscle. Core biopsy of the lesion was reported as undifferentiated sarcoma. After immunohistochemistry markers, the diagnosis was revised to a malignancy of a lymphomatous origin. Gene sequencing studies and extensive higher marker studies were done and a final diagnosis of plasmacytic infiltrate of uncertain clinical significance was reported. With no further diagnostic options available, the case still remains to be a diagnostic challenge as the choice of treatment between surgical resection and nonsurgical treatment with chemotherapy and/or radiation cannot be decided upon.
The ethico-religiousness of Atwood’s “God’s Gardeners” vis-à-vis Kierkegaard’s thought
Authors: Chou Christine Hsiu-Chin
Published: April 2024

This study aims to ascertain the ethico-religiousness of “God’s Gardeners” in Atwood’s The Year of the Flood, an eco-religious cult featured by the “self-rescue effort” rather than “God-relationship”. Through examining Atwood’s secularist imagination vis-à-vis Kierkegaard’s ideas about ethico-religiousness, the relationship between Atwood’s post-Christian speculation and Christianity will be re-estimated.

Starting with a comparative overview of the two writers’ situatedness in their own “post-Christian” milieu, the discussion then focuses on Kierkegaard’s thought to facilitate the investigation into the religiousness of Atwood’s ethical type. Ultimately, a certain “crossroads” is testified between the secularized vision and the Christian understanding of being ethical and religious.
The impact of a top-heavy IMF on the formation and evolution of dark star clusters
Authors: Shirazi Ali Rostami , Haghi Hosein , Zonoozi Akram Hasani , Farhani Asl Ahmad , Kroupa Pavel
Published: April 2024

The Spitzer instability leads to the formation of a black hole subsystem (BHSub) at the centre of a star cluster providing energy to luminous stars (LSs) and increasing their rate of evaporation. When the self-depletion time of the BHSub exceeds the evaporation time of the LSs, a dark star cluster (DSC) will appear. Using the nbody7 code, we performed a comprehensive set of direct N-body simulations over a wide range of initial conditions to study the pure effect of the top-heaviness of the initial mass function (IMF) on the formation of the DSC phase. In the Galactic tidal field, top-heavy IMFs lead to the fast evaporation of LSs and the formation of DSCs. Therefore, DSCs can be present even in the outer region of the Milky Way (MW). To successfully transition to the DSC phase, the MW Globular Clusters (GCs) must possess an initial black hole (BH) mass fraction of $\widetilde {\mathit {M}}_\mathrm{BH}(0)\gt 0.05$. For star clusters with $\widetilde {\mathit {M}}_\mathrm{BH}(0)\gt 0.08$, the DSC phase will be created for any given initial density of the cluster and Galactocentric distance. The duration of the cluster’s lifetime spent in the DSC phase shows a negative (positive) correlation with the initial density, and Galactocentric distance of the star cluster if $\widetilde {\mathit {M}}_\mathrm{BH}(0)\le 0.12$ ($\widetilde {\mathit {M}}_\mathrm{BH}(0)\ge 0.15$). Considering the canonical IMF, it is unlikely for any MW GCs to enter the DSC phase. We discuss the BH retention fraction in view of the observed properties of the GCs of the MW.
The Impoverishing Effect of Tobacco Use in Indonesia
Authors: Swarnata Arya , Kamilah Fariza Zahra , Melinda Gea , Adrison Vid
Published: April 2024

Introduction

Smoking households in Indonesia diverted a significant share of their budget to tobacco. Tobacco expenditure is deemed unproductive, as it crowds out resources from essential commodities and increases health care expenditure driven by tobacco-induced diseases. Therefore, despite having adequate resources, some smoking families in Indonesia may spend less on basic needs, which inadvertently puts their standard of living below the poverty line.

Aims and Methods

Employing data from 2021 (March) Indonesia’s Socioeconomic Survey (SUSENAS), this research aims to quantify the impoverishing effect of tobacco consumption in Indonesia, considering spending on tobacco and tobacco-attributable health care costs as unproductive expenditure. The de facto headcount poverty rate and poverty gap index are calculated by removing tobacco expenditures and tobacco-attributable health care expenditures from the household’s total spending.

Results

Accounting for unproductive spending related to tobacco use, Indonesia’s headcount poverty ratio in March 2021 would rise by 3.22 percentage points, equivalent to an additional 8.75 million people living below the poverty line. In addition, the poverty gap index would increase by 0.77 percentage points. The impoverishment effect of tobacco is larger among rural populations than their urban counterparts. Moreover, the impoverishment is mainly driven by direct tobacco spending rather than tobacco-attributable health care expenditure.

Conclusions

Significant portions of Indonesia’s population are exposed to secondary poverty because of tobacco use. A high level of cigarette spending among smoking households is the major source of the impoverishing effect of tobacco use.

Implications

The study provides quantitative evidence of the true cost of smoking in Indonesia, where the de facto number of the poor population after accounting for tobacco-related spending is higher than what is published in the official statistics. The findings of this study support tobacco control policies in Indonesia, particularly to effectively reduce tobacco use and mitigate the impoverishing impact of tobacco use on low-income households.
A Qualitative Analysis of How Underage Adolescents Access Nicotine Vaping Products in Aotearoa New Zealand
Authors: Frost Katie , Graham-DeMello Anna , Ball Jude , Pettie (Ngāti Pūkenga) Michaela , Hoek Janet
Published: April 2024

Introduction

Despite policies setting a minimum legal sales age, youth continue to access electronic cigarettes (ECs). Evidence of rising youth vaping prevalence in many countries suggests existing measures have serious loopholes and raise important questions about how youth source vaping products.

Aims and Methods

We explored how youth source ECs using in-depth interviews with 30 adolescents aged 16–17 who vaped at least once a month and lived in Aotearoa New Zealand. Our semistructured interview guide probed participants’ vaping experiences and how they developed and used social, quasi-commercial, and commercial supply routes to access ECs. We used an inductive reflexive thematic analysis approach to interpret the data.

Results

Nearly all participants shared ECs with peers and sharing was the sole access route for some. Many used proxies, often older relatives or people they knew socially, to purchase ECs on their behalf; however, others recruited proxies by approaching previously unknown people they identified on social media. Participants also sourced ECs via quasi-commercial networks that existed within schools and on social media, and some purchased in their own right, usually from smaller retail outlets that did not ask for ID.

Conclusions

Disrupting social supply will be challenging, though reducing ECs’ availability, appeal, and affordability could make social supply, including sharing and proxy purchasing, more difficult. Reports that youth purchase ECs from commercial retailers known to waive age verification suggest stronger monitoring and enforcement, along with escalating retailer penalties, are required.

Implications

Vaping access routes sit on a continuum from informal, spontaneous sharing to carefully planned commercial purchases. While supply via friends, siblings and other social contacts is an important means of access, nicotine dependence drives some to use riskier access routes, including approaching unknown people to act as proxy purchasers. Evidence young people identify noncompliant retailers suggests policy makers should monitor and enforce existing measures more stringently and consider additional penalties for recidivist underage suppliers. A more comprehensive response that reduces the appeal, addictiveness, affordability, and availability of vaping products would address factors fostering and maintaining youth vaping.
Administrative Justice in the Modern Mixed Administrative State: Moving Beyond Taxonomies
Authors: Boughey Janina
Published: April 2024

The challenges that government outsourcing presents for administrative law were the topic of considerable scholarly discussion in the 1990s and early 2000s, with broad agreement amongst public lawyers that outsourcing should not result in a loss of the particular kind of accountability with which administrative justice is concerned. Yet, over the past two decades, while government outsourcing has continued and evolved, very little has been done to address these challenges. This article explores the question of when non-court-based administrative justice accountability mechanisms ought to extend to outsourced government functions. I argue that much of the focus of administrative lawyers to date has been on the approaches that courts should take, which has led governments and legislatures to adopt tests and taxonomies largely developed in or for the courts, which distinguish between ‘public’ and ‘private’ functions. I show that these taxonomies are not well adapted to administrative justice mechanisms outside of the courts, are not fit for purpose in many modern government outsourcing arrangements and have resulted in significant accountability gaps. I propose a different starting point for thinking about administrative justice in the modern mixed administrative state, based on normative principles as opposed to categories.
Delays in presentation, diagnosis, and treatment in Sudanese women with breast cancer: a cross-sectional study
Authors: Alfadul Esraa S A , Tebaig Badria , Alrawa Salma S , Elgadi Ammar Tarig , Margani Ensaf E M A , Adam Maab E B , Mohamoud Mawaheb Sh Adem , Elhassan Safa A M , Elhassan Moawia Mohammed Ali
Published: April 2024

Background

The poor prognosis of breast cancer in Sudan could be due to delayed treatment and diagnosis at an advanced stage. Our study aimed to assess the extent of delays from onset of symptoms to treatment in Sudanese women with breast cancer, as well as identify factors contributing to these delays.

Materials and Methods

We conducted a multi-center cross sectional study between March and April 2023. Data were collected from the medical records and interviews with women with breast cancer in the two main oncology centers in Sudan. Linear regression was used to identify the predictors of delayed presentation.

Results

We interviewed 601 women with breast cancer. The majority of women (50.1%) were diagnosed at locally advanced or metastatic disease. The median interval from the onset of symptoms to receiving oncologic treatment was 221 days (IQR = 92, 496). The longest delay was the presentation delay 61 (31 244) days. The median duration for diagnosis delay and treatment delay was 21 (10.57) days and 27 (10.64) days, respectively. Predictors of early presentation included, being young (β = −5.3; 95% CI = 0.06 to 10), married (β = −264; 95% CI = −427 to −101), divorced (β = −306; 95% CI = −549 to −63), or widowed (β = −320; 95% CI = −-543 to −97), urban residence (β = −107; 95% CI = −213 to −2.3), and seeking traditional healer (β = −204; 95% CI = −383 to −26).

Conclusion

Most Sudanese women with breast cancer experience significant patient delays, often presenting at advanced stages. Factors like being single, older, and living in rural areas contribute to these delays. Increasing breast cancer education, improving healthcare access and addressing sociodemographic barriers can potentially expedite diagnosis and improve outcomes.
On Möbius Functions from Automorphic Forms and a Generalized Sarnak’s Conjecture
Authors: Wei Zhining , Zhao Shifan
Published: April 2024

In this paper, we consider generalized Möbius functions associated with two types of L-functions: Rankin–Selberg L-functions of symmetric powers of distinct holomorphic cusp forms and L-functions derived from Maass cusp forms. We show that these generalized Möbius functions are weakly orthogonal to bounded sequences. As a direct corollary, a generalized Sarnak’s conjecture holds for these two types of Möbius functions.
Notch1 hyperactivity drives ubiquitination of NOX2 and dysfunction of CD8+ regulatory T cells in patients with systemic lupus erythematosus
Authors: Yuan Zixin , Liu Mengdi , Zhang Lei , Jia Li , Hao Siao , Su Danhua , Tang Longhai , Wang Chunhong , Wang Mingyuan , Wen Zhenke
Published: April 2024

Objectives

Patients with SLE display heightened immune activation and elevated IgG autoantibody levels, indicating compromised regulatory T cell (Tregs) function. Our recent findings pinpoint CD8+ Tregs as crucial regulators within secondary lymphoid organs, operating in a NOX2-dependent mechanism. However, the specific involvement of CD8+ Tregs in SLE pathogenesis and the mechanisms underlying their role remain uncertain.

Methods

SLE and healthy individuals were enlisted to assess the quantity and efficacy of Tregs. CD8+CD45RA+CCR7+ Tregs were generated ex vivo, and their suppressive capability was gauged by measuring pZAP70 levels in targeted T cells. Notch1 activity was evaluated by examining activated Notch1 and HES1, with manipulation of Notch1 accomplished with Notch inhibitor DAPT, Notch1 shRNA, and Notch1-ICD. To create humanized SLE chimaeras, immune-deficient NSG mice were engrafted with PBMCs from SLE patients.

Results

We observed a reduced frequency and impaired functionality of CD8+ Tregs in SLE patients. There was a downregulation of NOX2 in CD8+ Tregs from SLE patients, leading to a dysfunction. Mechanistically, the reduction of NOX2 in SLE CD8+ Tregs occurred at a post-translational level rather than at the transcriptional level. SLE CD8+ Tregs exhibited heightened Notch1 activity, resulting in increased expression of STUB1, an E3 ubiquitin ligase that binds to NOX2 and facilitates its ubiquitination. Consequently, restoring NOX2 levels and inhibiting Notch1 activity could alleviate the severity of the disease in humanized SLE chimaeras.

Conclusion

Notch1 is the cell-intrinsic mechanism underlying NOX2 deficiency and CD8+ Treg dysfunction, serving as a therapeutic target for the clinical management of SLE.
Psychiatry, Modernity and the Politics of the Individual: The Historical Contours of Mental Hygiene
Authors: Dufaud Grégory , Henckes Nicolas , Scarfone Marianna
Published: April 2024

This introduction to this special issue devoted to mental hygiene movements in Europe examines the issues and problems facing their historical study. While the definition of mental hygiene was obvious to contemporaries, it referred to highly divergent projects in different socio-political contexts. As a result, historians have struggled to come up with a unified definition of mental hygiene as a category for analysis. After outlining historiographical responses to this question, this essay suggests that mental hygiene can best be understood as a specific way of articulating four dimensions of the psychiatric discipline, namely its organization and its relationship to the state, individuals and science. The final section provides an overview of the themes developed by the articles in this special issue.
My voyage in the enchanted world of sleep
Authors: Lavie Peretz
Published: April 2024

In this paper, I describe my 45-year career in sleep research. I started my undergraduate studies at Tel Aviv University, where I was first introduced to the enchanted world of sleep, continued to my graduate studies with Wilse B. Webb at the University of Florida, and then to post-doctoral training with Dan Kripke at the University of California at San Diego. Then, I describe the evolution of my academic career at the Technion-Israel Institute of Technology, where I started in 1975 as an Assistant Professor and retired in 2019 as the President of the Institute. I describe the areas of research that I pursued and how the research developed, emphasizing unexpected results that guided me and my lab team in new directions. This includes my early studies on ultradian rhythms, inspired by Nathaniel Kleitman’s Basic Rest Activity Cyle hypothesis, utilizing the ultrashort sleep–wake paradigm to chart the 24-hour sleep propensity function, and how these studies led us to explore the role of melatonin in sleep regulation. I also explain why we directed our attention to sleep apnea, and how clinical observations led to the provocative hypothesis that sleep apnea—typically seen as a disorder—may also play a protective role. Under the leadership of my research partner and wife, Lena, we confirmed this hypothesis. Also in this article, I describe my enthusiasm for the history of our field and, as derived from my experience as a Dean of Medicine and President of a university, I share my philosophy about the role of members of academia in society. I emphasize that none of my achievements could have been accomplished without the hard work and motivation of my students and research partners, who shared my enthusiasm and passion for the enchanted world of sleep.

This paper is part of the Living Legends in Sleep Research series, which is sponsored by Idorsia Pharmaceuticals and Jazz Pharmaceuticals.
Incorporating diverse values of nature in decision-making—theory and practice
Authors: Vatn A. , Pascual U. , Chaplin-Kramer R. , Termansen M. , Arias-Arévalo P. , Balvanera P. , Athayde S. , Hahn T. , Lazos E.
Published: April 2024

Values play a significant role in decision-making, especially regarding nature. Decisions impact people and nature in complex ways and understanding which values are prioritised, and which are left out is an important task for improving the equity and effectiveness of decision-making. Based on work done for the IPBES Values Assessment, this paper develops a framework to support analyses of how decision-making influences nature as well as whose values get prioritised. The framework is used to analyse key areas of environmental policy: a) the present model for nature protection in market economies, b) the role of valuation in bringing nature values into decisions, and c) values embedded in environmental policy instruments, exemplified by protected areas for nature conservation and payments for ecosystem services. The analyses show that environmental policies have been established as mere additions to decision-making structures that foster economic expansion, which undermines a wide range of nature's values. Moreover, environmental policies themselves are also focused on a limited set of nature's diverse values.

This article is part of the theme issue ‘Bringing nature into decision-making’.
Cities in nature
Authors: Chan Lena
Published: April 2024

More than half of the world's population live in cities, and they have benefitted from the ecosystem services provided by urban biodiversity. International conventions like the Convention on Biological Diversity have provided recommendations on how to engage local governments and cities in the implementation of their strategic plans. In parallel, recognizing this, cities conserve, restore and enhance biodiversity in many practical ways. A list of general strategies adopted by cities is presented. The rich and diverse experiences of eleven cities, i.e. Abu Dhabi, Auckland, Durban, Edinburgh, Edmonton, Hyderabad, Los Angeles, São Paulo, Singapore, Toluca and Vitoria-Gasteiz, which have successfully conserved biodiversity in urbanized landscape across the globe, are shared. These cities have all applied the Singapore Index on Cities' Biodiversity as an evaluation and monitoring tool for biodiversity conservation efforts, in addition to using it innovatively for other purposes. Cities can play a pivotal role in ensuring that Target 12 of the Kunming–Montreal Global Biodiversity Framework will be achieved. Upscaling cities’ models of success would require a worldwide concerted effort involving everyone, i.e. all levels of stakeholders. Mainstreaming of biodiversity into all sectors, including commercial, economic, financial, industrial and technological, and the incorporation of biodiversity into decision-making in urban planning and management would be a game-changer.

This article is part of the theme issue ‘Bringing nature into decision-making’.
Shaping nature outcomes in corporate settings
Authors: Bebbington Jan , Blasiak Robert , Larrinaga Carlos , Russell Shona , Sobkowiak Madlen , Jouffray Jean-Baptiste , Österblom Henrik
Published: April 2024

Transnational companies have substantive impacts on nature: a hallmark of living in the Anthropocene. Understanding these impacts through company provision of information is a precursor to holding them accountable for nature outcomes. The effect of increasing disclosures (of varying quality) is predicated on ‘information governance’, an approach that uses disclosure requirements to drive company behaviour. However, its efficacy is not guaranteed. We argue that three conditions are required before disclosures have the possibility to shape nature outcomes, namely: (1) radical traceability that links company actions to outcomes in particular settings; (2) developing organizational routines, tools and approaches that translate strategic intent to on-the-ground behaviour; and (3) mobilizing and aligning financial actors with corporate nature ambitions. While disclosure is key to each of these conditions, its limits must be taken into account and it must be nested in governance approaches that shape action, not just reporting.

This article is part of the theme issue ‘Bringing nature into decision-making’.
Using the Red List of Ecosystems and the Nature-based Solutions Global Standard as an integrated process for climate change adaptation in the Andean high mountains
Authors: Vasseur L. , Andrade A.
Published: April 2024

Under anthropogenic pressures and climate change, most ecosystems are showing signs of reduced resilience. Unfortunately, some are more at risk of collapse and, without interventions, they may lose biodiversity, ecological integrity and ecosystem services. Here, we describe two tools that were developed under the auspices of the International Union for Conservation of Nature, the Red List of Ecosystems and the Nature-based Solutions Global Standard, and their capacity to first identify the ecosystems at risk of collapse in a nation and then develop solutions based on nature to improve their resilience. Nature-based solutions include, for example ecosystem-based adaptation, where solutions are developed to meet the needs of the local people while protecting nature to ensure greater resilience of the social–ecological system, not only the natural ecosystem. We discuss through a case study in the Andean high mountains and páramo social–ecological system how these approaches have been used in Colombia. We then discuss lessons learned and challenges that may reduce the capacity of a community to initiate such interventions, such as national policies and funding restrictions. We also discuss through another early case in Ecuador the importance to adapt these types of interventions to the geographical and cultural context of the social–ecological systems.

This article is part of the theme issue ‘Bringing nature into decision-making’.
Natural capital approaches for the optimal design of policies for nature recovery
Authors: Day Brett , Mancini Mattia , Bateman Ian J. , Binner Amy , Cho Frankie , de Gol Anthony , Ferguson-Gow Henry , Fezzi Carlo , Lee Christopher , Liuzzo Lorena , Lovett Andrew , Owen Nathan , Pearson Richard G. , Smith Greg
Published: April 2024

By embedding a spatially explicit ecosystem services modelling tool within a policy simulator we examine the insights that natural capital analysis can bring to the design of policies for nature recovery. Our study is illustrated through a case example of policies incentivising the establishment of new natural habitat in England. We find that a policy mirroring the current practice of offering payments per hectare of habitat creation fails to break even, delivering less value in improved flows of ecosystem services than public money spent and only 26% of that which is theoretically achievable. Using optimization methods, we discover that progressively more efficient outcomes are delivered by policies that optimally price activities (34%), quantities of environmental change (55%) and ecosystem service value flows (81%). Further, we show that additionally attaining targets for unmonetized ecosystem services (in our case, biodiversity) demands trade-offs in delivery of monetized services. For some policy instruments it is not even possible to achieve the targets. Finally, we establish that extending policy instruments to offer payments for unmonetized services delivers target-achieving and value-maximizing policy designs. Our findings reveal that policy design is of first-order importance in determining the efficiency and efficacy of programmes pursuing nature recovery.

This article is part of the theme issue ‘Bringing nature into decision-making’.
Leveraging natural capital accounting to support businesses with nature-related risk assessments and disclosures
Authors: Ingram Jane Carter , McKenzie Emily J. , Bagstad Kenneth J. , Finisdore John , van den Berg Rayne , Fenichel Eli , Vardon Michael , Posner Stephen , Santamaria Marta , Mandle Lisa , Barker Richard , Spurgeon James
Published: April 2024

Nature loss threatens businesses, the global economy and financial stability. Understanding and addressing these risks for business will require credible measurement approaches and data. This paper explores how natural capital accounting (NCA) can support business data and information needs related to nature, including disclosures aligned with the Taskforce on Nature-related Financial Disclosures recommendations. As businesses seek to measure, manage and disclose their nature-related risks and opportunities, they will need well-organized, consistent and high-quality information regarding their dependencies and impacts on nature, which few businesses currently collect or track in-house. NCA may be useful for these purposes but has not been widely used or applied by businesses. National NCA guided by the U.N. System of Environmental-Economic Accounting may provide: (i) a useful framework for businesses in conceptualizing, organizing and managing nature-related data and statistics; and (ii) data and information that can directly support business disclosures, corporate NCA and other business applications. This paper explores these opportunities as well as synergies between national and corporate natural capital accounts. In addition, the paper discusses key barriers to advancing the wider use and benefits of NCA for business, including: awareness of NCA, data access, business capabilities related to NCA, spatial and temporal scales of data, audit and assurance considerations, potential risks, and costs and incentives.

This article is part of the theme issue ‘Bringing nature into decision-making’.
Consensus Guideline for the Management of Gastric Cancer with Synchronous Peritoneal Metastases
Authors:   PSM Writing Group,   PSM Consortium Group, Turaga Kiran K
Published: April 2024

Background

Gastric cancer with synchronous peritoneal metastases (GCPM) is a debilitating disease with limited treatment options. This manuscript describes an update of the 2018 Chicago Consensus Guidelines addressing the management of GCPM in line with most recent evidence.

Methods

A clinical management pathway was updated through two rounds of a Delphi Consensus to assess agreement levels with pathway blocks. Supporting evidence underwent evaluation via a rapid literature review. Meta-analyses were performed where appropriate.

Results

Overall, level of evidence in this disease subset was low to moderate. Of 124 participants in the first round, 109 (88%) responded in the second round. Strong consensus (>90%) was achieved in 6/8 (75%) blocks in round I and II. A multidisciplinary preoperative assessment and diagnostic laparoscopy should be offered all patients, while patients with a high burden of disease or progression should undergo non-surgical management. Patients with stable/responsive disease and low peritoneal carcinomatosis index should subsequently be offered treatment with regional therapeutic interventions and cytoreductive surgery. In patients who are cytology positive, systemic therapy can be used to convert these patients to cytology negative, with subsequent surgery offered per the patient’s goals of care. Meta-analysis of observational and randomized control trials revealed a survival benefit with the addition of intraperitoneal chemotherapy to cytoreductive surgery (HR 0.52).

Conclusion

The consensus-driven clinical pathway for GCPMs offers vital clinical guidance for practitioners. There is a growing body of high-quality evidence to support management strategies and future clinical trials are eagerly awaited.
Combinatorial miRNA1a/15b interference drives adult cardiac regeneration
Authors: Yuan Ting , Wu Meiqian , Zhu Chaonan , Yu Hao , Pham Minh Duc , Bottermann Katharina , Mao Yijie , Langner Mathias , Peitzsch Mirko , Das Arka Provo , Ward Jonathan , Mirtschink Peter , Zeiher Andreas , Dimmeler Stefanie , Krishnan Jaya
Published: April 2024

BACKGROUND

Despite its promise, cardiac regenerative therapy remains clinically elusive due to the difficulty of spatio-temporal control of proliferative induction, and the need to coordinately reprogram multiple regulatory pathways to overcome the strict post-mitotic state of human adult cardiomyocytes. The present study was designed to identify a novel combinatorial miRNA therapy to address this unmet therapeutic need.

METHODS

We performed a combinatorial miRNA interference screen specifically targeting cardiac-predominant miRNAs regulating key aspects of cardiomyocyte mitotic induction to cell-cycle completion, including sarcomerogenesis, metabolic and cell-cycle control pathways. Cardiomyocyte proliferation and cardiac function were assessed in human cardiac biopsies, human cardiac tissue mimetics and in mouse disease models.

RESULTS

We identified combinatorial interference of miR-1a and miR-15b (LNA-1a/15b) as drivers of adult cardiomyocyte proliferation. Due to miR-1a/15b function on multiple processes modulating adult cardiomyocyte mitosis, its inhibition augmented adult cardiomyocyte cell-cycle completion and daughter cell formation, and improved contractility inin vitro2D and 3D ischemic models, and in a mouse model of ST-segment elevation myocardial infarction (STEMI). Due to the cardiac-restricted pattern of miR-1a/15b expression, this strategy provides a feasible strategy for specific cardiomyocyte proliferative induction with minimal risk of neoplasm formation and off-target toxicity.

CONCLUSIONS

Combinatorial miR-1a/15b inhibition drives mitotic re-entry in adult cardiomyocytes and improves cardiac function in response to myocardial infarction. Our data provides a novel and clinically feasible LNA-based anti-miR-1a/15b strategy to attenuate heart failure and highlights an underutilized therapeutic strategy for simultaneous co-regulation of multiple disease pathways through combinatorial miRNA interference.
Second-line tenofovir alafenamide for children with HIV in Africa
Authors: Musiime Victor , Szubert Alexander J , Mujuru Hilda A , Kityo Cissy , Doerholt Katja , Makumbi Shafic , Mulenga Veronica , Ndebele Wedu , Mwamabazi Mwate , McIlleron Helen , Bwakura-Dangarembizi Mutsa , Natukunda Eva , Linda Kyomuhendo Jovia , Monkiewicz Lara , Kapasa Monica , Nyathi Mary , Nduna Bwendo , South Annabelle , Musoro Godfrey , Zyambo Khozya , Zhang Yingying , Walker Simon , Turkova Anna , Walker A Sarah , Bamford Alasdair , Gibb Diana M ,   CHAPAS-4 Trial Team
Published: April 2024

Background

Children living with HIV have few second-line antiretroviral therapy(ART) options, especially fixed-dose-combinations(FDC).

Methods

Children from Uganda, Zambia, Zimbabwe were randomised to second-line tenofovir alafenamide(TAF)/emtricitabine(FTC) or standard-of-care(SOC) backbone (abacavir(ABC) or zidovudine(ZDV) with lamivudine(3TC)) in the factorial CHAPAS-4 trial. The second randomisation (reported elsewhere) was to dolutegravir(DTG), ritonavir-boosted darunavir(DRV/r), atazanavir(ATV/r) or lopinavir(LPV/r) as anchor drug. All drugs were dosed using WHO weight-bands and children <25kg received a new paediatric TAF/FTC(15/120mg) FDC tablet. The primary endpoint was viral load(VL)<400copies/ml at week-96, analysed using logistic regression, hypothesising that TAF/FTC would be non-inferior to SOC (10% margin). Secondary endpoints included safety and immunological outcomes. Analyses were intention-to-treat.

Results

919 children 3–15years, 497(54%) male, median[IQR] baseline viral load(VL) 17,573copies/ml [5549-55,700] and CD4 count 669cells/mm3[413-971], spent 99% of time on allocated NRTI backbone. At week-96, 406/454(89.4%) receiving TAF/FTC vs. 378/454(83.3%) receiving SOC had VL<400copies/mL (adjusted difference[95%CI]: 6.3%[2.0%,10.6%], p=0.004), with no evidence that this varied by ABC/3TC or ZDV/3TC SOC. CD4 count improved similarly in both arms. Growth was better with TAF/FTC vs. SOC, without evidence of excess weight-gain with any backbone/anchor drug combination (including DTG±TAF/FTC, interaction p=0.51). Bone health parameters were similar between arms, irrespective of anchor drug. One child died (treatment-unrelated); 29(3%) had serious adverse events without differences between arms.

Conclusions

TAF/FTC was virologically superior to SOC ZDV/3TC or ABC/3TC with a favourable safety profile, irrespective of anchor drug. Development of child-friendly TAF/FTC FDCs (±anchor drug) would increase cost-effective ART options for children and reduce drug access gaps between children and adults.(ISRCTN22964075)
Positivity in serum MMP-3 after clinical remission or low disease activity at 52 weeks leads to future joint destruction in patients with rheumatoid arthritis
Authors: Konishi Hiroe , Morimoto Mai , Murakami Kosaku , Onizawa Hideo , Onishi Akira , Fujii Takayuki , Murata Koichi , Tanaka Masao , Morinobu Akio , Nakano Masayoshi , Koshiba Masahiro
Published: April 2024

Introduction

This study aimed to evaluate whether a long-term increase in serum matrix metalloproteinase-3 (MMP-3) levels leads to joint destruction in rheumatoid arthritis (RA) patients with negative serum C-reactive protein (CRP) values after methotrexate (MTX) therapy.

Methods

Patients with RA (n = 182) whose CRP values became negative due to MTX therapy were divided into two groups based on their MMP-3 positivity at the end of the observation period, and the 1-year progression of joint destruction was retrospectively compared. Radiological joint destruction was assessed using the modified van der Heijde total sharp score (mTSS).

Results

Among 109 (MMP-3(−), n = 63; MMP-3(+), n = 46) patients who achieved low disease activity or clinical remission (28 joint disease activity score erythrocyte sedimentation rate < 2.6), joint destruction (ΔmTSS ≥ 0.5) progressed in 24.6% and 48.9% of the MMP-3(−) and MMP-3(+) groups (p < 0.01), respectively. Prednisolone-induced increases in serum MMP-3 levels also resulted in joint destruction.

Conclusion

To prevent progressive joint destruction, the target MMP-3 value is 49.7 ng/mL in female patients, which is below the current MMP-3 cutoff value of 59.7 ng/mL. Residual MMP-3 activity may lead to the progression of joint destruction in patients with RA, even after CRP normalization by successful treatment with MTX.
Pushing the Isotopic Envelope: When carrier channels pollute their neighbors’ signals
Authors: Peterson Connor , Boekweg Hannah , Presley Eilenora , Payne Samuel H.
Published: April 2024

Individual cells are the foundational unit of biology, and understanding their functions and interactions is critical to advancing our understanding of health and disease. Single cell proteomics has seen intense interest from mass spectrometrists, with a goal of quantifying the proteome of single cells by adapting current techniques used in bulk samples. To date, most method optimizations research has worked towards increasing the proteome coverage of single cells. One prominent technique multiplexes many individual cells into a single data acquisition event using isobaric labels. Accompanying the single cells, one label is typically used for a mixed set of many cells, called a carrier or boost channel. Although this improves peptide identification rates, several groups have examined the impact on quantitative accuracy as more cells are included in the carrier channel, e.g. 100x or 500x. This manuscript explores how impurities in the multiplexing reagent can lead to inaccurate quantification observed as a measurable signal in the wrong channel. We discover that the severe abundance differential between carrier and single cell, combined with the reagent impurities, can overshadow several channels typically used for single cells. For carrier amounts 100x and above, this contamination can be as abundant as true signal from a single cell. Therefore, we suggest limiting the carrier channel to a minimal amount and balance the goals of identification and quantification.