Funding Bodies Research Articles

Care and the academy: Navigating fieldwork, funding and care responsibilities

AbstractThis commentary reflects on research jointly conducted by the Development Geographies Research Group (DevGRG) and the Gender and Feminist Geographies Research Group (GFGRG) of the RGS‐IBG, which aimed to understand the challenges faced by academics with care responsibilities. We set out the effects of research funding policies and practices on researchers' ability to combine careers as academic geographers with care responsibilities, highlighting the specific effects in a field‐based subject such as Geography. We gathered data about a range of research funders' policies and how these are implemented (in various ways) in UK Geography departments. We also surveyed all UK university Geography departments to understand experiences of parental and adoption leave, including support from employers, impacts on career progression, and recommendations for support. Our data show that there is a need for a more consistent and comprehensive approach to recognising the costs of academics' caring responsibilities, to support their career progression and to mitigate the impacts disproportionately experienced by women. Funders and higher education institutes (HEIs) need to work collaboratively to develop policies and practices to address the individualised way in which (predominantly female) academics currently experience navigating the provision of funding for parental leave, and for covering costs of care during fieldwork. Our research highlights the need for consistent and progressive policies in relation to care and parental leave across all funding bodies – that can subsequently be embedded into institutional frameworks – in order to provide equity and consistency for staff across the UK higher education (HE) sector. We also emphasise the need for these policies to be more visible and transparent, making the task of navigating them more manageable for staff at an often uncertain time in their working lives.

Investigating the contribution of author- and publication-specific features to scholars’ h-index prediction

Evaluation of researchers’ output is vital for hiring committees and funding bodies, and it is usually measured via their scientific productivity, citations, or a combined metric such as the h-index. Assessing young researchers is more critical because it takes a while to get citations and increment of h-index. Hence, predicting the h-index can help to discover the researchers’ scientific impact. In addition, identifying the influential factors to predict the scientific impact is helpful for researchers and their organizations seeking solutions to improve it. This study investigates the effect of the author, paper/venue-specific features on the future h-index. For this purpose, we used a machine learning approach to predict the h-index and feature analysis techniques to advance the understanding of feature impact. Utilizing the bibliometric data in Scopus, we defined and extracted two main groups of features. The first relates to prior scientific impact, and we name it ‘prior impact-based features’ and includes the number of publications, received citations, and h-index. The second group is ‘non-prior impact-based features’ and contains the features related to author, co-authorship, paper, and venue characteristics. We explored their importance in predicting researchers’ h-index in three career phases. Also, we examined the temporal dimension of predicting performance for different feature categories to find out which features are more reliable for long- and short-term prediction. We referred to the gender of the authors to examine the role of this author’s characteristics in the prediction task. Our findings showed that gender has a very slight effect in predicting the h-index. Although the results demonstrate better performance for the models containing prior impact-based features for all researchers’ groups in the near future, we found that non-prior impact-based features are more robust predictors for younger scholars in the long term. Also, prior impact-based features lose their power to predict more than other features in the long term.

Voice, disability and ‘end of life’ research: Strategies for including people with intellectual disabilities in qualitative research related to death and dying

AbstractThis brief report proposes strategies to support qualitative research with people with intellectual disabilities on topics related to death and dying. We prepared a scoping review on methodological approaches used for qualitative research on death and dying involving participants with intellectual disabilities and a study on perceived barriers and facilitators to accessing end of life settings, conducted with co‐researchers on an online video communication platform. Through conducting these two studies, we found three strategies that we believe will increase the uptake of this research for policymakers, funding bodies and other researchers. The strategies concern research agendas, structured methodological guidance, and allocation of funds. When planning out qualitative research projects about death and dying topics, people with intellectual disabilities must be on the research agendas on topics related to death and dying. To realize this obligation, stakeholders would benefit from structured methodological guidance. The design, planning, and conduct of such studies would benefit greatly from such guidance and would ideally result in the uptake of this type of research. Additionally, proper funding taking into account needed but time‐consuming accommodations for participants is necessary. These strategy options aim to increase the amount of qualitative research that includes people with intellectual disabilities as participants.

Distinct HLA associations with autoantibody-defined subgroups in idiopathic inflammatory myopathies

In patients with idiopathic inflammatory myopathies (IIM), autoantibodies are associated with specific clinical phenotypes suggesting a pathogenic role of adaptive immunity. We explored if autoantibody profiles are associated with specific HLA genetic variants and clinical manifestations in IIM. We included 1348 IIM patients and determined the occurrence of 14 myositis-specific or -associated autoantibodies. We used unsupervised cluster analysis to identify autoantibody-defined subgroups and logistic regression to estimate associations with clinical manifestations, HLA-DRB1, HLA-DQA1, HLA-DQB1 alleles, and amino acids imputed from genetic information of HLA class II and I molecules. We identified eight subgroups with the following dominant autoantibodies: anti-Ro52, -U1RNP, -PM/Scl, -Mi2, -Jo1, -Jo1/Ro52, -TIF1γ or negative for all analysed autoantibodies. Associations with HLA-DRB1∗11, HLA-DRB1∗15, HLA-DQA1∗03, and HLA-DQB1∗03 were present in the anti-U1RNP-dominated subgroup. HLA-DRB1∗03, HLA-DQA1∗05, and HLA-DQB1∗02 alleles were overrepresented in the anti-PM/Scl and anti-Jo1/Ro52-dominated subgroups. HLA-DRB1∗16, HLA-DRB1∗07 alleles were most frequent in anti-Mi2 and HLA-DRB1∗01 and HLA-DRB1∗07 alleles in the anti-TIF1γ subgroup. The HLA-DRB1∗13, HLA-DQA1∗01 and HLA-DQB1∗06 alleles were overrepresented in the negative subgroup. Significant signals from variations in class I molecules were detected in the subgroups dominated by anti-Mi2, anti-Jo1/Ro52, anti-TIF1γ, and the negative subgroup. Distinct HLA class II and I associations were observed for almost all autoantibody-defined subgroups. The associations support autoantibody profiles use for classifying IIM which would likely reflect underlying pathogenic mechanisms better than classifications based on clinical symptoms and/or histopathological features. See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript.

Youth participation processes in longitudinal out of home care research

AbstractWhile there is growing recognition of the importance of meaningful youth participation in activities and decisions which impact their lives, facilitating such engagement within different forums requires varied approaches. A programme of youth research at one Western Australian university has sought to embed pathways for ongoing youth participation in longitudinal research. In particular, we discuss Navigating Through Life, a large‐scale WA research project comprising three sub‐studies exploring young people's transitions from out of home care (OOHC) to independence. We established a youth advisory group to run alongside the project and employed peer researchers to conduct research tasks. In this paper, we seek to explicate the development and various iterations of youth participation in the project. We utilise our reflections, interview data and documentation from YAG meetings and feedback sessions with the peer researchers to illustrate the processes of transformation and flexibility required to develop and maintain youth participation in various ways across the project's life. Drawing on our findings and current literature, we highlight how funding bodies and researchers must consider the additional needs, unique and changeable life circumstances of young people to best facilitate their involvement in research.

Recruiting a Hard-to-Reach, Hidden and Vulnerable Population: The Methodological and Practical Pitfalls of Researching Vaccine-Hesitant Parents.

While recruitment is an essential aspect of any research project, its challenges are rarely acknowledged. We intend to address this gap by discussing the challenges to the participation of vaccine-hesitant parents defined here as a hard-to-reach, hidden and vulnerable population drawing on extensive empirical qualitative evidence from seven European countries. The difficulties in reaching vaccine-hesitant parents were very much related to issues concerning trust, as there appears to be a growing distrust in experts, which is extended to the work developed by researchers and their funding bodies. These difficulties have been accentuated by the public debate around COVID-19 vaccination, as it seems to have increased parents' hesitancy to participate. Findings from recruiting 167 vaccine-hesitant parents in seven European countries suggest that reflexive and sensible recruitment approaches should be developed.

Paclitaxel liposome, cisplatin and 5-fluorouracil-based induction chemotherapy followed by de-escalated intensity-modulated radiotherapy with concurrent cisplatin in stage IVA–IVB childhood nasopharyngeal carcinoma in endemic area: a phase II, single-arm trial

Previous studies demonstrated that induction chemotherapy (IC) followed by de-escalated chemoradiotherapy adapted to tumor response was effective in treating childhood nasopharyngeal carcinoma (NPC), but the toxicity profile of this treatment strategy, and whether childhood patients with advanced stages can obtain enough benefits from it requires further investigation. We conducted a single-center phase II trial (NCT03020329). All participants received 3 cycles of paclitaxel liposome, cisplatin and 5-fluorouracil (TPF)-based IC. Patients who showed complete or partial response received de-escalated radiotherapy of 60Gy with 3 cycles of concurrent cisplatin, and those who showed stable or progressive disease received standard-dose radiotherapy of 70Gy with concurrent cisplatin. The primary endpoint was the complete response (CR) rate at the end of concurrent chemoradiotherapy (CCRT). From November 2016 to March 2021, 44 patients were recruited in the cohort. The CR rate was 80% (35/44, 95% CI, 65-90) of the whole cohort. All patients achieved CR 3 months after CCRT. By the last follow-up, the 3-year progression-free survival and overall survival were 91% (95% CI, 82-99) and 100% respectively. Dry mouth was the most common late toxicity, with an incidence of 41% (18/44), followed by skin fibrosis and hearing impairment. No patient suffered from severe late toxicity and growth retardation. Our results proved the efficacy and safety of TPF regimen followed by de-escalated radiotherapy with concurrent cisplatin in treating stage IVa-b childhood NPC patients. A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

A Free Art Calls for a Free Society: On the Freedom of Art and Autonomy as Project

In recent years, the far right “culture war” has to an increasing extent been allowed to set the terms for cultural policy debates, in Sweden and internationally. In the Swedish context, empty accusations against public cultural institutions of “wokeist” bias and “cancel culture” have found support in a public report from the governmental Agency for Cultural Policy Analysis, which claims that national public funding bodies are imposing politically correct demands on their applicants, with a “detrimental influence” on the freedom of art. This article shows that the ACPA lacks grounds for these claims. Taking its cue from the ACPA’s report, it instead focuses on the fundamental and contested concept of the freedom or the autonomy of art. It seeks to outline what would need to characterise a critical concept of the autonomy of art today, and asks what the political implications would be of a rigorous understanding of such a concept. It argues that cultural policy should be understood as a project of cultural democratization, which should in turn be understood as a project of autonomy.

The viral fitness and intrinsic pathogenicity of dominant SARS-CoV-2 Omicron sublineages BA.1, BA.2, and BA.5

Among the Omicron sublineages that have emerged, BA.1, BA.2, BA.5, and their related sublineages have resulted in the largest number of infections. While recent studies demonstrated that all Omicron sublineages robustly escape neutralizing antibody response, it remains unclear on whether these Omicron sublineages share any pattern of evolutionary trajectory on their replication efficiency and intrinsic pathogenicity along the respiratory tract. We compared the virological features, replication capacity of dominant Omicron sublineages BA.1, BA.2 and BA.5 in the human nasal epithelium, and characterized their pathogenicity in K18-hACE2, A129, young C57BL/6, and aged C57BL/6 mice. We found that BA.5 replicated most robustly, followed by BA.2 and BA.1, in the differentiated human nasal epithelium. Consistently, BA.5 infection resulted in higher viral gene copies, infectious viral titres and more abundant viral antigen expression in the nasal turbinates of the infected K18-hACE2 transgenic mice. In contrast, the Omicron sublineages are continuously attenuated in lungs of infected K18-hACE2 and C57BL/6 mice, leading to decreased pathogenicity. Nevertheless, lung manifestations remain severe in Omicron sublineages-infected A129 and aged C57BL/6 mice. Our results suggested that the Omicron sublineages might be gaining intrinsic replication fitness in the upper respiratory tract, therefore highlighting the importance of global surveillance of the emergence of hyper-transmissive Omicron sublineages. On the contrary, replication and intrinsic pathogenicity of Omicron is suggested to be further attenuated in the lower respiratory tract. Effective vaccination and other precautions should be in place to prevent severe infections in the immunocompromised populations at risk. A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Barriers and Enablers to Evaluating Outcomes From Public Involvement in Health Service Design: An Interpretive Description.

While health services are expected to have public involvement in service (re)design, there is a dearth of evaluation of outcomes to inform policy and practice. There are major gaps in understanding why outcome evaluation is under-utilised. The aims of this interpretive descriptive study were to explore researcher participants' experiences of and/or attitudes towards evaluating health service outcomes from public involvement in health service design in high-income countries. Additionally, the aims were to explore barriers and enablers of evaluation, and reasons for the use of evaluation tools or frameworks. Semi-structured interviews (n = 13) were conducted with researchers of published studies where the public was involved in designing health services. Using framework analysis, four themes were developed that captured participants' experiences: Public involvement is hard - evaluation is harder; power, a diversity of agendas, and the invisible public; practical and methodological challenges; and genuineness and authenticity matter. Evaluation is driven by stakeholder requirements, including decision-makers, funding bodies, researchers, and academics, and evaluation tools are rarely used. The public is largely absent from the outcome evaluation agenda. There is a lack of commitment and clarity of purpose of public involvement and its evaluation. Outcome evaluation must be multi-layered and localised and reflect the purpose of public involvement, what constitutes success (and to whom), and use the most appropriate methods. Multi-level supports should include increased resources, such as funding, time, and expertise. Without improved evaluation, outcomes of investment in public involvement in health service design/redesign remain unknown.

Alterations of hepatic energy metabolism in murine models of obesity, diabetes and fatty liver diseases.

Disturbed hepatic energy metabolism contributes to non-alcoholic fatty liver (NAFLD), but the development of changes over time and obesity- or diabetes-related mechanisms remained unclear. Two-day old male C57BL/6j mice received streptozotocin (STZ) or placebo (PLC) and then high-fat (HFD) or regular chow diet (RCD) from week 4 (W4) to either W8 or W16, yielding control [CTRL=PLC+RCD], diabetes [DIAB=STZ+RCD], obesity [OBES=PLC+HFD] and diabetes-related non-alcoholic steatohepatitis [NASH=STZ+HFD] models. Mitochondrial respiration was measured by high-resolution respirometry and insulin-sensitive glucose metabolism by hyperinsulinemic-euglycemic clamps with stable isotope dilution. NASH showed higher steatosis and NAFLD activity already at W8 and liver fibrosis at W16 (all p<0.01 vs CTRL). Ballooning was increased in DIAB and NASH at W16 (p<0.01 vs CTRL). At W16, insulin sensitivity was 47%, 58% and 75% lower in DIAB, NASH and OBES (p<0.001 vs CTRL). Hepatic uncoupled fatty acid oxidation (FAO)-associated respiration was reduced in OBES at W8, but doubled in DIAB and NASH at W16 (p<0.01 vs CTRL) and correlated with biomarkers of unfolded protein response (UPR), oxidative stress and hepatic expression of certain enzymes (acetyl-CoA carboxylase 2, Acc2; carnitine palmitoyltransferase I, Cpt1a). Tricarboxylic acid cycle (TCA)-driven respiration was lower in OBES at W8 and doubled in DIAB at W16 (p<0.0001 vs CTRL), which positively correlated with expression of genes related to lipolysis. Hepatic mitochondria adapt to various metabolic challenges with increasing FAO-driven respiration, which is linked to dysfunctional UPR, systemic oxidative stress, insulin resistance and altered lipid metabolism. In a diabetes model, higher TCA-linked respiration reflected mitochondrial adaptation to greater hepatic lipid turnover. Funding bodies that contributed to this study were listed in the acknowledgements section.

A celastrol-based nanodrug with reduced hepatotoxicity for primary and metastatic cancer treatment.

Cancer is the world's leading cause of death and a key hindrance to extending life expectancy. Celastrol, a bioactive compound derived from Tripterygium wilfordii, has been shown to have excellent antitumor activity, but its poor solubility and severe organ toxicity side effects have hampered its clinical application. In this study, a self-assembled nanodrug (PLC-NP) was designed to deliver celastrol to tumor sites while efficiently reducing its side effects by conjugating celastrol with the bioactive material LMWH and P-selectin targeting peptide (PSN). Extensive invitro and invivo experiments were performed to investigate both therapeutic efficacy and adverse effects. Furthermore, the specific mechanism of the antitumor activity has also been explored. The PLC-NP nanodrugs were spherical in shape, with a mean particle size of 115.83±6.93nm. PLC-NP was sufficiently stable during blood circulation, with a selective target to P-selectin-highly expressed tumor cells, followed by releasing the containing celastrol under acidic environment and high levels of esterase in tumor cells. Both invitro and invivo results confirmed that celastrol's antitumor and anti-metastatic abilities were not attenuated and were actually strengthened after being formed into nanodrugs. More importantly, the organ toxicities of the modified celastrol nanodrug were dramatically reduced. Mechanistic study indicated that the inactivation of PI3K/Akt/mTOR signaling pathway and ROS-mediated mitochondrial dysfunction play critical roles in celastrol-mediated autophagy and apoptosis. Our findings could offer a potential strategy for the translation of toxic compounds into clinical therapeutic nanomedicine. See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript.

Current status of global research on pericardial diseases: a bibliometric analysis of the top 100 from Web of Science

IntroductionBibliometric studies can help guide researchers and funding bodies toward fields where more research activity is warranted. Bibliometric analyses have previously been published in many specialties and sub-specialties. Our literature search did not show a bibliometric analysis on pericardial diseases. We performed a bibliometric analysis of the top 100 cited manuscripts on pericardial diseases to identify knowledge.Material and MethodsBibliometric analysis is a quantitative method to assess research performance and analyze publication trends. Web of Science was searched in April 2020 to identify the top 100 cited manuscripts in pericardial diseases.ResultsTwenty-six out of the top 100 cited manuscripts were published between 2000 and 2009. These manuscripts were cited on average189 times (range: 110–743) since publication. Only two manuscripts were cited &gt; 500 times. Among the top-ten cited manuscripts, there were 6 original articles, 1 case series, and 3 review articles. Of the 3 review articles, 2 were society guidelines. 90% of the authors had written just 1 manuscript. There were ten manuscripts with women as first authors with a significant association between gender of the first and corresponding author (odds ratio = 44, p &lt; 0.001). Only 20% of manuscripts were funded. Most publications came from institutions in the United States (n = 40), Italy (n = 10), and Spain (n = 5).ConclusionsOur study provides an insight into the characteristics and quality of the highly cited literature in the field of pericardial diseases. This can be used to guide further research in the field of pericardial diseases.

Guidelines to improve internationalization in the psychological sciences

AbstractConversations about the internationalization of psychological sciences have occurred over a few decades with very little progress. Previous work shows up to 95% of participants in the studies published in mainstream journals are from Western, Educated, Industrialized, Rich, Democratic nations. Similarly, a large proportion of authors are based in North America. This imbalance is well‐documented across a range of subfields in psychology, yet the specific steps and best practices to bridge publication and data gaps across world regions are still unclear. To address this issue, we conducted a hackathon at the Society for the Improvement of Psychological Science 2021 conference to develop guidelines to improve international representation of authors and participants, adapted for various stakeholders in the production of psychological knowledge. Based on this hackathon, we discuss specific guidelines and practices that funding bodies, academic institutions, professional academic societies, journal editors and reviewers, and researchers should engage with to ensure psychology is the scientific discipline of human behavior and cognition across the world. These recommendations will help us develop a more valid and fairer science of human sociality.

A Small Jordanian Adventure Tourism Tour Operator with Big Ambitions

Summary Small inbound tour operators, around the world, live in a competitive environment. They fight to carve out a profitable business niche. The success of this normally depends on collaboration with other operators and good relations with their local tourism authority. Experience Jordan Adventures (EJA), based in Amman, moved beyond this, reaching out to international organizations for support. In particular, they have taken advantage of their membership of the Adventure Travel and Tourism Association (ATTA) to make contacts and establish relationships with funding bodies such as the United States Agency for International Development (USAID) and the Jordanian Action for the Development of Enterprises (JADE). With their partners’ help, EJA has become a driver and developer of new adventure products, such as the Jordan Trail, a long-distance walking route, and the Jordan Bike Trail. These have brought economic value to remoter communities in Jordan. Information © The Authors 2023

Systems thinking for general surveillance programs – using leverage points to guide program management

With the increasing threat of pests, weeds and diseases to agriculture, the environment and our way of life, governments are becoming more reliant on general surveillance to fill biosecurity surveillance gaps. That is, engaging people from all walks of life in the monitoring and reporting of pests, weeds and diseases. It is often thought that instigating a general surveillance program simply requires the development of reporting tools and creating awareness of the program among intended target groups, but this is a simplistic view. This paper explores whether a broader approach identifies better ways to implement general surveillance programs to meet their goals and remain sustainable over the long-term, and therefore assist in program management. A systems thinking approach was used to identify the components within general surveillance programs, and their interactions. These components are the actors or people involved and their relationships; infrastructure like reporting tools and resources; formal and informal rules; and species or diseases of interest and their environment (included to account for the biophysical context). We explored what helped and hindered the design and implementation of general surveillance programs, drawing on international literature and the experiences of people in nine case studies from across Australia and New Zealand. Systems thinking helped to identify leverage points in the case studies, including feedback loops and information flow paths, and facilitated thought on how they can be used to improve programs. For example, sharing knowledge and experiences of actors from throughout the program being notifiers (i.e. the people who report pests, weeds and diseases), laboratory or herbarium staff, funding bodies, policy makers and others, built trust and ownership in the program and facilitated learning and self-organisation. This increased the capacity for innovation, adaptation, and continual improvement, leading to ongoing program benefits. Approaching program management using systems thinking helps structure program monitoring and evaluation and better target effort and resources to improve performance. However, this requires a dedicated program coordinator (or coordination team) with adequate resources to identify challenges and opportunities and adapt the program accordingly.

Intermediating climate change: the evolving strategies, interactions and impacts of neglected “climate intermediaries”

ABSTRACT Climate change governance systems comprise a wide variety of actors. Here, we introduce “climate intermediaries” as one potentially influential yet often neglected type of actor, behaving as “go-betweens” that connect different types of actors and/or governance levels. This Special Issue analyses two under-researched forms of climate intermediaries: those that exist for reasons unconnected to climate change, and new or uncommon forms of climate intermediaries that have yet to be examined. In this Introduction article, we present the conceptual framework employed within our Special Issue. We begin by problematizing the definition of intermediaries within climate research before clarifying our own relational understanding of “climate intermediaries”. A climate intermediary is thus a role, assumed by any type of actor, while potentially assuming other roles when interacting with other actors. Second, we summarize the existing research on the strategies of intermediaries, the interactions that may exist between them, and the impacts of these actors on the climate policy process. These three foci then guide our three research questions for the Special Issue. Third, we examine existing research on myriad types of intermediaries, such as interest groups, faith-based actors, and funding bodies. Finally, we provide an overview of the contributions included within the issue.

Dietary metabolome profiles of a Healthy Australian Diet and a Typical Australian Diet: protocol for a randomised cross-over feeding study in Australian adults

IntroductionTraditional dietary assessment methods such as 24-hour recalls and food frequency questionnaires rely on self-reported data and are prone to error, bias and inaccuracy. Identification of dietary metabolites associated with...

Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases.

Recent advances in digital pathology have enabled accurate and standardised enumeration of tumour-infiltrating lymphocytes (TILs). Here, we aim to evaluate TILs as a percentage electronic TIL score (eTILs) and investigate its prognostic and predictive relevance in cutaneous melanoma. We included stage I to IV cutaneous melanoma patients and used hematoxylin-eosin-stained slides for TIL analysis. We assessed eTILs as a continuous and categorical variable using the published cut-off of 16.6% and applied Cox regression models to evaluate associations of eTILs with relapse-free, distant metastasis-free, and overall survival. We compared eTILs of the primaries with matched metastasis. Moreover, we assessed the predictive relevance of eTILs in therapy-naïve metastases according to the first-line therapy. We analysed 321 primary cutaneous melanomas and 191 metastatic samples. In simple Cox regression, tumour thickness (p<0.0001), presence of ulceration (p=0.0001) and eTILs ≤16.6% (p=0.0012) were found to be significant unfavourable prognostic factors for RFS. In multiple Cox regression, eTILs ≤16.6% (p=0.0161) remained significant and downgraded the current staging. Lower eTILs in the primary tissue was associated with unfavourable relapse-free (p=0.0014) and distant metastasis-free survival (p=0.0056). In multiple Cox regression adjusted for tumour thickness and ulceration, eTILs as continuous remained significant (p=0.019). When comparing TILs in primary tissue and corresponding metastasis of the same patient, eTILs in metastases was lower than in primary melanomas (p<0.0001). In therapy-naïve metastases, an eTILs >12.2% was associated with longer progression-free survival (p=0.037) and melanoma-specific survival (p=0.0038) in patients treated with anti-PD-1-based immunotherapy. In multiple Cox regression, lactate dehydrogenase (p<0.0001) and eTILs ≤12.2% (p=0.0130) were significantly associated with unfavourable melanoma-specific survival. Assessment of TILs is prognostic in primary melanoma samples, and the eTILs complements staging. In therapy-naïve metastases, eTILs ≤12.2% is predictive of unfavourable survival outcomes in patients receiving anti-PD-1-based therapy. See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript.

Replacing academic journals.

Replacing traditional journals with a more modern solution is not a new idea. Here, we propose ways to overcome the social dilemma underlying the decades of inaction. Any solution needs to not only resolve the current problems but also be capable of preventing takeover by corporations: it needs to replace traditional journals with a decentralized, resilient, evolvable network that is interconnected by open standards and open-source norms under the governance of the scholarly community. It needs to replace the monopolies connected to journals with a genuine, functioning and well-regulated market. In this new market, substitutable service providers compete and innovate according to the conditions of the scholarly community, avoiding sustained vendor lock-in. Therefore, a standards body needs to form under the governance of the scholarly community to allow the development of open scholarly infrastructures servicing the entire research workflow. We propose a redirection of money from legacy publishers to the new network by funding bodies broadening their minimal infrastructure requirements at recipient institutions to include modern infrastructure components replacing and complementing journal functionalities. Such updated eligibility criteria by funding agencies would help realign the financial incentives for recipient institutions with public and scholarly interest.