Unanswered Research Questions Research Articles

School prevention of non-consensual sexting among middle adolescents: Does sexual preoccupation awareness matter?

Although non-consensual sexting seems to concern not only adults but also middle adolescent students, with detrimental consequences on their well-being, the related research-based effective school prevention programs are almost absent. Furthermore, there is an unanswered research question as to whether sex-related issues, such as sexual preoccupation, matters in adolescents’ non-consensual sexting and its prevention. The present study investigated the effectiveness of a school-based intervention against non-consensual sexting among middle adolescents, based on the European funded program TABBY (Threat Assessment of Bullying Behavior in Youth). Furthermore, the predictive role of sexual preoccupation was examined. Overall, 280 Greek students from randomly selected junior high school responded to self-report scales on non-consensual sexting and sexual preoccupation. Based on an experimental longitudinal research design, only the experimental (N = 131), but not the control group of students (N = 149), participated in the intervention. To test the effectiveness of the intervention, both student groups completed the scales before (1st phase), immediately after (2nd phase), and six months after the intervention (3rd phase), which was implemented by trained teachers. The results showed both, the short-term and long-term effectiveness of the intervention. Also, the study highlighted the significant contribution of sexual preoccupation awareness in reducing non-consensual sexting, especially immediately after and six months after the intervention. The study implies the necessity to adapt existed prevention programs to the specific parameters of non-consensual sexting, integrating at the same time sexual preoccupation awareness activities to better address this issue.

Establishing a research partnership to investigate functional loss and rehabilitation towards the end of life.

Functional loss, the inability to perform necessary or desired tasks, is a common consequence of life-limiting illnesses and associated symptoms (pain, fatigue, breathlessness, etc.) and causes suffering for patients and families. Rehabilitation, a set of interventions designed to address functional loss, is recognised as essential within palliative care, as it can improve quality of life and reduce care costs. However, not everyone has equal access to rehabilitation. Despite limited life expectancy or uncertain ability to benefit from interventions, palliative rehabilitation services are often absent. This is partly due to a lack of high-quality research around optimal models of rehabilitation. Research in this area is methodologically challenging and requires multidisciplinary and cross-speciality collaboration. We aimed to establish and grow a United Kingdom research partnership across diverse areas, commencing with partners from Edinburgh, East Anglia, Lancashire, Leeds, London and Nottingham, around the topic area of functional loss and rehabilitation in palliative and end-of-life care. The objectives were to (1) develop a multidisciplinary, cross-speciality research partnership, (2) generate high-priority unanswered research questions with stakeholders, (3) co-design and submit high-quality competitive research proposals, including (4) sharing topic and methodological expertise, and (5) to build capacity and capability to deliver nationally generalisable studies. The partnership was established with professionals from across England and Scotland with complementary areas of expertise including complex palliative and geriatric research, physiotherapy, nursing, palliative medicine and psychology. Research questions were generated through a modified version of the Child Health and Nutrition Research Initiative, which allowed for the collation and refinement of research questions relating to functional loss and rehabilitation towards the end of life. Partnership members were supported through a series of workshops to transform research ideas into proposals for submission to stage one calls by the National Institute for Health and Care Research. The partnership not only supported students, clinicians and public members with training opportunities but also supported clinicians in securing protected time from clinical duties to allow them to focus on developing local research initiatives. Through our partnership we established a network that offered researchers, clinicians, students and public members the chance to develop novel skills and explore opportunities for personal and professional development around the topic area of functional loss and rehabilitation in palliative and end-of-life care. The partnership was crucial to foster collaboration and facilitate exchange of ideas, knowledge and experiences to build joint research study proposals. This article presents independent research funded by the National Institute for Health and Care Research (NIHR) programme as award number NIHR135171. A plain language summary of this article is available on the NIHR Journals Library website https://doi.org/10.3310/PTHC7598.

The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation.

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research suggests that they may be regulated by both distinct and shared pathways. Specifically, recent studies have indicated that both CIP and CIL utilize mechanotransduction pathways, a process that involves cells sensing and responding to mechanical forces. This review article describes the role of mechanotransduction in CI, shedding light on how mechanical forces regulate CIL and CIP. Emphasis is placed on filamin A (FLNA)-mediated mechanotransduction, elucidating how FLNA senses mechanical forces and translates them into crucial biochemical signals that regulate cell locomotion and proliferation. In addition to FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable of directly or indirectly binding to specific DNA sequences in distant genes to regulate gene expression, emerge as sensitive players in both the mechanotransduction and signaling pathways of CI. This article presents methods for identifying these TAF proteins and profiling the associated changes in chromatin structure, offering valuable insights into CI and other biological functions mediated by mechanotransduction. Finally, it addresses unanswered research questions in these fields and delineates their possible future directions.

Do German winegrowers see a connection between biodiversity and wine tourism?

Abstract German winegrowers are increasingly creating habitats in wine landscapes that are necessary for the preservation of biodiversity. Since biodiversity in the landscape can have a positive impact on tourism attractiveness, one might assume that winemakers are also promoting tourism by doing so, but are they aware of this? The aim of this study is to explore whether German winegrowers see a link between biodiversity and tourism in wine regions and what this link might look like. For this purpose, 52 qualitative interviews were conducted with German winegrowers from all 13 German wine regions. The results show that German winemakers are aware of the central importance of the landscape in attracting tourists and that the clear majority of the interviewed winegrowers believe that a biodiverse landscape has a positive impact on tourism in wine regions. This work reveals unanswered research questions and opens a wide field for researchers to address the topic. Promoting biodiversity could be one of the most important factors contributing to the appeal of wine landscapes and could thus increase the attractiveness of wine regions for potential visitors. Ultimately, tourism flows could be optimized and the predominantly rural German wine regions could preserve their cultural heritage and develop into new aspects of sustainability.

Can bitcoin mining empower energy transition and fuel sustainable development goals in the US?

The transition to renewable energy in the US, vital for Sustainable Development Goals (SDGs) 7 and 13, faces economic obstacles, leaving a knowledge gap regarding potential innovative solutions to accelerate this shift. Simultaneously, the energy-intensive nature of blockchain applications like bitcoin mining is a cause for climate concerns. This work addresses the previously unanswered research question of whether bitcoin mining can be strategically used to harness surplus renewable energy from forthcoming clean energy installations, bridging the gap between economic viability and SDGs. Specifically, we conduct a comprehensive analysis, comparing the economic returns of bitcoin mining with three alternative chemical-based energy storage systems, including hydrogen, ammonia, and methanol, all powered by planned renewable sources. Mixed-integer linear programs were formulated to determine the maximum profits that can be obtained based on power utilization from planned renewable installations using varying alternatives. Results suggest that bitcoin mining is profitable in 80 out of 83 examined planned installations, generating a maximum profit of $7.68 million and harnessing 62% of the available renewable energy. Therefore, integrating bitcoin mining with planned renewable installations offers a dual solution of bolstering investments in the renewable energy sector while addressing climate concerns associated with conventional mining operations.

Multiscale Structure and Function of the Aortic Valve Apparatus.

While studying the aortic valve in isolation has facilitated the development of life-saving procedures and technologies, the dynamic interplay of the aortic valve and its surrounding structures is vital to preserving their function across the wide range of conditions encountered in an active lifestyle. Our view is that these structures should be viewed as an integrated functional unit, herein referred to as the aortic valve apparatus (AVA). The coupling of the aortic valve and root, left ventricular outflow tract, and blood circulation is crucial for AVA's functions: unidirectional flow out of the left ventricle, coronary perfusion, reservoir function, and supporting left ventricular function. In this review, we explore the multiscale biological and physical phenomena that underly the simultaneous fulfilment of these functions. A brief overview of the tools used to investigate the AVA is included, such as: medical imaging modalities, experimental methods, and computational modelling, specifically fluid-structure interaction (FSI) simulations, is included. Some pathologies affecting the AVA are explored, and insights are provided on treatments and interventions that aim to maintain quality of life. The concepts explained in this paper support the idea of AVA being an integrated functional unit and help identify unanswered research questions. Incorporating phenomena through the molecular, micro, meso and whole tissue scales is crucial for understanding the sophisticated normal functions and diseases of the AVA.

Highly Selective Inhibitors of Dipeptidyl Peptidase 9 (DPP9) Derived from the Clinically Used DPP4-Inhibitor Vildagliptin.

Dipeptidyl peptidase 9 (DPP9) is a proline-selective serine protease that plays a key role in NLRP1- and CARD8-mediated inflammatory cell death (pyroptosis). No selective inhibitors have hitherto been reported for the enzyme: all published molecules have grossly comparable affinities for DPP8 and 9 because of the highly similar architecture of these enzymes' active sites. Selective DPP9 inhibitors would be highly instrumental to address unanswered research questions on the enzyme's role in pyroptosis, and they could also be investigated as therapeutics for acute myeloid leukemias. Compounds presented in this manuscript (42 and 47) combine low nanomolar DPP9 affinities with unprecedented DPP9-to-DPP8 selectivity indices up to 175 and selectivity indices >1000 toward all other proline-selective proteases. To rationalize experimentally obtained data, a molecular dynamics study was performed. We also provide in vivo pharmacokinetics data for compound 42.

Early cancer detection in primary care in Ireland: a protocol for a research prioritisation exercise

Background: Cancer is a significant cause of morbidity, mortality, and economic loss in Ireland. It is important that cancer research funding is directed in accordance with the values of a wide variety of stakeholders, so as to ultimately deliver tangible benefits to cancer patients. The aim of this study is to achieve consensus among key stakeholders (including patients, caregivers, healthcare professionals, policymakers and academics) regarding research priorities in the area of early detection of cancer in primary care in Ireland. Methods: A research prioritisation exercise adapted from the James Lind Alliance (JLA) consensus framework will be used to enable all key stakeholders to identify and prioritise research questions. This involves the following stages: (1) setting up a steering group and priority setting partnership, (2) gathering potential research questions via an online survey, (3) processing, categorising, and summarising these research questions, (4) identifying the unanswered research questions, (5) determining the top 10 research priorities via a consensus workshop. Results: The following outcomes will be reported: (1) a “Top 10” list of the most important research questions in early cancer detection in primary care; (2) a list of unanswered research questions which ranked outside of the Top 10; (3) a list of research questions which were proposed but considered to be already answered by a panel of academics working in the field. Conclusions: The co-production of consensus derived research questions in early cancer detection will provide a platform for both funders and researchers to concentrate on the most significant issues to stakeholders, especially patients and their doctors.

A bibliometric review of portfolio diversification literature

Portfolio diversification (PD) is attracting increasing attention, as it is becoming more difficult to optimize portfolios due to growing financial markets integration. To highlight the evolution of PD literature, we perform a meta-literature review on 242 articles published between 1974 and 2022. We identify the most influential aspects of the literature and perform co-authorship, cartographic and co-citation analyses. We identify four main research clusters, as well as the most influential articles in the field. We map the different streams of the literature, visualizing different focus areas and trends, and identify more than 60 unanswered research questions. Findings will facilitate scholars focusing on under-investigated areas.

Results of the Eighth Scientific Workshop of ECCO: Pathophysiology and risk factors of postoperative Crohn's disease recurrence after an ileocolic resection.

Postoperative recurrence (POR) after an ileocolonic resection with ileocolonic anastomosis is frequently encountered in patients with Crohn's disease. The 8 th Scientific Workshop of ECCO reviewed the available evidence on pathophysiology and risk factors for POR. In this manuscript, we will discuss published data on the role of the microbiome, the mesentery, the immune system, and the genetic background. In addition to the investigation of causative mechanisms of POR, identification of risk factors is essential to tailor preventive strategies. Potential clinical, surgical and histological risk factors are presented along with their limitations. Emphasis is placed on unanswered research questions, guiding prevention of POR based on individual patient profiles.

Mycotoxins: Emerging toxic mechanisms, and unanswered research questions.

Recently, a series of toxic mechanisms have been explored in mycotoxins. Emerging evidence show that mycotoxins may induce human neurodegenerative diseases (ND); however, this idea is still unproven. Besides to identify this hypothesis, some questions, for example, how the mycotoxins induce this disease and what the molecular mechanism is, as well as whether the brain-gut axis is involved in this context, should be answered. Very recent studies further reported an "immune evasion" mechanism in trichothecenes; moreover, hypoxia seems to play important function in this process; nevertheless, whether this "immune evasion" process is present in other mycotoxins, especially in aflatoxins, should be tested. In this work, we mainly discussed some key scientific questions that need to be answered in the toxic mechanisms of mycotoxins. We especially focused on the research questions in the key signaling pathways, balance mechanism of immunostimulatory and immunosuppressive effects, and the relationship between autophagy and apoptosis. Interesting topics such as mycotoxins and aging, cytoskeleton and immunotoxicity are also discussed. More importantly, we compile a special issue: "New insight into mycotoxins and bacterial toxins: toxicity assessment, molecular mechanism and food safety" for Food and Chemical Toxicology. Researchers are encouraged to submit their newest work to this special issue.

Research priorities relating to the delivery of cardiovascular prevention and rehabilitation programmes: results of a modified Delphi process

ObjectiveThe purpose of this British Association for Cardiovascular Prevention and Rehabilitation (BACPR) research priority setting project (PSP) was to identify a top 10 list of priority research questions for cardiovascular...

A journey to understand SFRT.

This article tells the story of a medical physicist's journey to understand SFRT which started by accident more than 15 years ago. For decades, clinical application and preclinical research have shown that spatially fractionated radiation therapy (SFRT) can achieve a magically high therapeutic index. However, only recently, SFRT received well-deserved attention from mainstream radiation oncology. Today, our understanding of SFRT remains limited, which significantly hinders the advancement of SFRT for patient care. In this article, the author intends to shed some light on several important but unanswered SFRT research questions, including what is the essence of SFRT, which dosimetric parameters have clinical relevance and which do not, how does SFRT spare normal tissue but not tumor, and why radiobiological models developed for conventional radiation therapy may not be suitable for SFRT.

Setting the research agenda for medically not yet explained symptoms (MNYES): a priority-setting partnership of patients, caregivers and clinicians

IntroductionThis study establishes research priorities for Medically Not Yet Explained Symptoms (MNYES). A significant number of patients suffer from these symptoms, also known as MUS, that are likely to cause work disability and impact on quality of life. Research into MNYES in general has been poorly funded over the years, has been primarily researcher-led, and was sometimes controversial.ObjectivesTo identify research priorities from the perspective of patients, caregivers and clinicians, following the James Lind Alliance (JLA) priority setting partnership (PSP) method.MethodsThe PSP Steering Group termed these symptoms Medically Not Yet Explained Symptoms (MNYES). This was an operational definition not intended to add to or replace other definitions already in use, that was constructed to embrace the views of all stakeholders. The nomenclature MNYES was chosen to indicate our incomplete understanding of these conditions. This could pertain to biological, psychological and social factors, as well as factors involving the trajectory of patients through various healthcare settings.The study involved five key stages: defining the appropriate term for the conditions under study by the PSP Steering Group; gathering questions on MNYES from patients, caregivers and clinicians in a publicly accessible survey; checking these research questions against existing evidence; interim prioritisation in a second survey; and a final multi-stakeholder consensus meeting to determine the top 10 unanswered research questions using the modified nominal group methodology.ResultsOver 700 responses from UK patients, caregivers and clinicians were identified in two surveys from a broad range of medical specialities and primary care. Patients prioritised research questions regarding diagnosis and aetiology; clinicians and caregivers prioritised outcomes and treatment, relatively.The top 10 unanswered research questions cover the domains of: treatment; the role of clinicians; symptoms and outcomes; and recovery.ConclusionsThis JLA PSP may well be the first attempt at capturing the thoughts of a wide group of medical professionals, patients and caregivers in one place with the aim eventually of standardising care and reducing unhelpful variability in the management of MNYES. Following the JLA approach is a strength of the study. The choice of the term MNYES conveys a message of hope, which responds to a need identified by patients, carers and clinicians alike for vigorous research in this domain. The research priorities are expected to generate much-needed, relevant and impactful research into MNYES. Better funding possibilities for MNYES are urgently needed.Disclosure of InterestNone Declared

Consumer and Healthcare Professional Led Priority Setting for Quality Use of Medicines in People with Dementia: Gathering Unanswered Research Questions.

Historically, research questions have been posed by the pharmaceutical industry or researchers, with little involvement of consumers and healthcare professionals. To determine what questions about medicine use are important to people living with dementia and their care team and whether they have been previously answered by research. The James Lind Alliance Priority Setting Partnership process was followed. A national Australian qualitative survey on medicine use in people living with dementia was conducted with consumers (people living with dementia and their carers including family,and friends) and healthcare professionals. Survey findings were supplemented with key informant interviews and relevant published documents (identified by the research team). Conventional content analysis was used to generate summary questions. Finally, evidence checking was conducted to determine if the summary questions were 'unanswered'. A total of 545 questions were submitted by 228 survey participants (151 consumers and 77 healthcare professionals). Eight interviews were conducted with key informants and four relevant published documents were identified and reviewed. Overall, analysis resulted in 68 research questions, grouped into 13 themes. Themes with the greatest number of questions were related to co-morbidities, adverse drug reactions, treatment of dementia, and polypharmacy. Evidence checking resulted in 67 unanswered questions. A wide variety of unanswered research questions were identified. Addressing unanswered research questions identified by consumers and healthcare professionals through this process will ensure that areas of priority are targeted in future research to achieve optimal health outcomes through quality use of medicines.

OP13 Postoperative Crohn’s disease recurrence: unanswered questions and future directions in diagnosis, pathophysiology, prevention and treatment. Conclusions from the 8th ECCO Scientific workshop.

Abstract Background Despite the increased availability of biological therapies, postoperative recurrence (POR) after an ileocolonic resection with ileocolonic anastomosis frequently occurs in patients with Crohn’s disease. Methods Over the last two years, a mixed panel of 24 gastroenterologists and colorectal surgeons collaborated within the 8th Scientific Workshop of ECCO. The available evidence on diagnosis, pathophysiology and risk factors, prevention and treatment of POR was reviewed and unanswered research questions were listed. Results In recent years, surgeons have been utilising innovative surgical techniques to reduce POR. Whilst the side-to-side anastomosis has become more common, the benefits of newer procedures such as Kono-S anastomosis or over-the-valve strictureplasty remain unproven. Consistency in describing and reporting POR is crucial both in routine practice and in clinical research. Ileocolonoscopy six to twelve months after ileocolonic anastomosis remains the gold standard to diagnose POR. However, an effort to adapt the Rutgeerts score to surgical techniques different from end-to-end anastomosis is required. Significance of isolated ulcers of the anastomotic line, specifically in case of stapled anastomoses, is still debated. In the coming years, intestinal ultrasound combined to faecal calprotectin may ultimately decrease the reliance on ileocolonoscopy. Research on the microbiome and genetic background of patients with POR is promising although not applicable in daily clinical practice yet. Smoking is the only risk factor clearly identified in POR, whereas previous ileocolonic resection or penetrating disease have not been validated in prospective studies. Stronger emphasis on smoking cessation for all patients should include specific active measures to make it successful. The prevailing gap in accurate predictors of POR disempowers clinicians from stratifying between systematic prophylaxis and endoscopy-driven approach. Immediate prophylaxis therapy may lead to overtreatment.Ongoing randomized controlled trials comparing (i) systematic prophylaxis and endoscopy-guided introduction of biological therapy (NCT05169593), and (ii) therapy escalation to status quo in patients with moderate endoscopic POR (NCT05072782) should be informative. Conclusion Despite important progress in the field of POR in the last 30 years, POR management remains a challenge. The IBD community should strive to optimise diagnostic procedures of POR including ileocolonoscopy and non-invasive techniques, define patients at high risk of POR using microbiome and/or genetic profiling and clarify the optimal medical treatment strategy after surgery.

Negative symptoms of schizophrenia: Trying to answer unanswered research questions

My research has focused on unmet needs in caring for people with schizophrenia. In particular, I focused on negative symptoms, a complex psychopathological dimension of the disorder, with a significant impact on the disease outcome, and not effectively addressed by existing treatments.In the present commentary, I summarize the trajectory of my research activity. I start with the description of my initial attempts to define the role of the dorsolateral prefrontal cortex in the pathogenesis of broadly defined negative symptoms. Then, I report on the evidence that led me to realize that no progress in research on schizophrenia negative symptoms could occur without considering the heterogeneity and complexity of the construct. Finally, I illustrate my attempts to succeed in this direction and the most pressing unsolved issues in this research field.

The top 10 research priorities in psoriatic arthritis: a James Lind Alliance Priority Setting Partnership.

To identify and prioritize the top 10 research questions for PsA. The British Psoriatic Arthritis Consortium (BritPACT) formed a Priority Setting Partnership (PSP) comprising of people living with PsA, carers and clinicians, supported by the James Lind Alliance (JLA). This PSP followed the established three-stage JLA process: first, an online survey of people living with PsA, carers and clinicians to identify PsA questions, asking, 'What do you think are the most important unanswered questions in psoriatic arthritis research?' The questions were checked against existing evidence to establish 'true uncertainties' and grouped as 'indicative questions' reflecting the overarching themes. Then a second online survey ranked the 'true uncertainties' by importance. Finally, a workshop including people living with PsA and clinician stakeholders finalized the top 10 research priorities. The initial survey attracted 317 respondents (69% people living with PsA, 15% carers), with 988 questions. This generated 46 indicative questions. In the second survey, 422 respondents (78% people living with PsA, 4% carers) prioritized these. Eighteen questions were taken forward to the final online workshop. The top unanswered PsA research question was 'What is the best strategy for managing patients with psoriatic arthritis including non-drug and drug treatments?' Other top 10 priorities covered diagnosis, prognosis, outcome assessment, flares, comorbidities and other aspects of treatment (https://www.jla.nihr.ac.uk). The top 10 priorities will guide PsA research and enable PsA researchers and those who fund research to know the most important questions for people living with PsA.

74 Patient-oriented research priorities for pediatric hospital care in Canada: a James Lind Alliance Priority Setting Partnership

Abstract Background The largest population of paediatric patients cared for in hospital are those with medical conditions managed in general paediatric inpatient units (GPIUs). Despite the large burden, there is a lack of high-quality research focused on the care of children and youth admitted to GPIUs. The Canadian Paediatric Inpatient Research Network (PIRN) was launched in 2019 to generate evidence to improve the care and outcomes for hospitalized children in GPIUs. To help establish a future research agenda, PIRN brought together clinicians, youth, patients and caregivers to identify important clinical management questions about the care of children in hospital. Objectives To conduct a research priority setting study to identify the most important unanswered clinical management research questions about paediatric hospital care in GPIUs that are important to patients, caregivers, and clinicians. Design/Methods Established James Lind Alliance Priority Setting Partnership methodology was utilized for this project, which was overseen by a Steering Group composed of patient partners, (youth, parents of patients) and clinicians (nurses, and paediatricians) (n=10), facilitated by a JLA Adviser. In phase 1, an online REDCap survey was administered to collect unanswered research questions regarding paediatric hospital care via 3 open-ended questions. Responses from the phase 1 survey went through a detailed evidence checking process. Subsequently, unanswered research questions were brought forward to a phase 2 interim prioritization online REDCap survey. A final list of top 10 unanswered research questions pertaining to paediatric hospital care was established at the final priority setting workshop. Results The phase 1 survey was completed by 188 participants and generated 495 unanswered research questions and comments, of which 58 were deemed out of scope. The remaining 437 responses were grouped into themes (e.g., hospital policy, communication, shared-decision making, health service delivery and health service management), and then refined to 75 unanswered research questions. Of these 75, 4 questions had sufficient evidence, and 21 were submitted by only one respondent. Fifty unanswered research questions were included in the phase 2 survey, which was completed by 201 participants. The top 16 questions – the top 10 from both patient partners (youth, parents of patients) and clinicians respectively – were presented at the final priority setting workshop and the top 10 questions were prioritized (Table 1). The top 10 questions focus on the care of special inpatient populations (e.g. children with medical complexity), communication, shared-decision making, support strategies, mental health supports, shortening length of stay, and supporting Indigenous patients, parents and families. Conclusion The top 10 unanswered questions on paediatric hospital care will help guide future research. PIRN will use these prioritized questions to generate scientific knowledge to improve the outcomes of hospitalized children and youth in GPIUs through the conduct of patient-oriented research.

Priority III: top 10 rapid review methodology research priorities identified using a James Lind Alliance Priority Setting Partnership

ObjectivesA rapid review is a form of evidence synthesis considered a resource-efficient alternative to the conventional systematic review. Despite a dramatic rise in the number of rapid reviews commissioned and conducted in response to the coronavirus disease 2019 pandemic, published evidence on the optimal methods of planning, doing, and sharing the results of these reviews is lacking. The Priority III study aimed to identify the top 10 unanswered questions on rapid review methodology to be addressed by future research. Study Design and SettingA modified James Lind Alliance Priority Setting Partnership approach was adopted. This approach used two online surveys and a virtual prioritization workshop with patients and the public, reviewers, researchers, clinicians, policymakers, and funders to identify and prioritize unanswered questions. ResultsPatients and the public, researchers, reviewers, clinicians, policymakers, and funders identified and prioritized the top 10 unanswered research questions about rapid review methodology. Priorities were identified throughout the entire review process, from stakeholder involvement and formulating the question, to the methods of a systematic review that are appropriate to use, through to the dissemination of results. ConclusionThe results of the Priority III study will inform the future research agenda on rapid review methodology. We hope this will enhance the quality of evidence produced by rapid reviews, which will ultimately inform decision-making in the context of healthcare.