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2D metal-organic frameworks (2D-MOFs) are an important class of functional porous materials. However, the low porosity and surface area of 2D-MOFs have greatly limited their functionalities and applications. Herein, the rational synthesis of a class of mos-MOFs with molybdenum disulfide (mos) net based on the assembly of trinuclear metal clusters and 3-connected tripodal organic ligands is reported. The non-crystallographic (3,6)-connected mos net, different from the 3-connected hcb net of graphene, offers abundant intralayer voids courtesy of the split of one node into two. Indeed, mos-MOFs exhibit high apparent Brunauer-Emmett-Teller surface areas, significantly superior to those of other 2D-MOF analogs. Markedly, hydrolytically stable Cr-mos-MOF-1 displays an impressive water vapor uptake of 0.75 g g -1 at 298 K and P/P 0 = 0.9, among the highest in 2D-MOFs. The combined water adsorption and X-ray diffraction study reveal the water adsorption mechanisms, suggesting the importance of intralayer porosities of mos-MOFs for high-performance water capture. This study paves the way for a reliable approach to synthesizing 2D-MOFs with high porosity and surface areas for diverse applications., (© 2024 Wiley‐VCH GmbH.)

Abstract: We aimed to investigate the immediate effect of best practice education (with and without pain science messages) and structure-focused education on reassurance among people with rotator cuff-related shoulder pain. We conducted a 3-arm, parallel-group, randomised experiment. People with rotator cuff-related shoulder pain were randomised (1:1:1) to (1) best practice education (highlights that most shoulder pain is not serious or a good indicator of tissue damage and recommends simple self-management strategies); (2) best practice education plus pain science messages (which attempt to improve understanding of pain); and (3) structure-focused education (highlighting that structural changes are responsible for pain and should be targeted with treatment). Coprimary outcomes were self-reported reassurance that no serious condition is causing their pain and continuing with daily activities is safe. Secondary outcomes measured management intentions, credibility and relevance of the education, and similarity to previous education. Two thousand two hundred thirty-seven participants were randomised and provided primary outcome data. Best practice education increased reassurance that no serious condition is causing their pain (estimated mean effect 0.5 on a 0-10 scale, 95% confidence interval [CI] 0.2-0.7) and continuing with daily activities is safe (0.6, 95% CI 0.3-0.8) compared with structure-focused education . Adding pain science messages to best practice education slightly increased both measures of reassurance (0.2, 95% CI 0.0-0.4). Clinicians treating patients with rotator cuff-related shoulder pain should highlight that most shoulder pain is not serious or a good indicator of tissue damage and recommend simple self-management strategies. The benefit of adding pain science messages is small., (Copyright © 2023 International Association for the Study of Pain.)

Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (Csf1r ∆FIRE/∆FIRE ), we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated. Seizure susceptibility and hippocampal-prefrontal cortex coherence in awake behaving animals, processes that are disrupted in mice deficient in microglia-enriched genes, are also normal. Similarly, eye-specific segregation of inputs into the lateral geniculate nucleus proceeds normally in the absence of microglia. Single-cell and single-nucleus transcriptomic analyses of neurons and astrocytes did not uncover any substantial perturbation caused by microglial absence. Thus, the brain possesses remarkable adaptability to execute developmental synaptic refinement, maturation and connectivity in the absence of microglia., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Ladder graphs admit a maximum-symmetry embedding in which edges coincide. In folding ladders, there are no zero-length edges. We give examples of high-symmetry 3-periodic ladders, particularly emphasizing the structures of 3-periodic vertex- and edge-transitive folding ladders. For these, the coincident-edge configuration is one of maximum volume for fixed edge length and has the same coordinates as (is isomeghethic to) a higher-symmetry 3-periodic graph.

Background: Pain is the leading cause of disability and reduced quality of life worldwide. Despite the increasing burden for patients and healthcare systems, pain research remains underfunded and under focused. Having stakeholders identify and prioritize areas that need urgent attention in the field will help focus funding topics, reduce 'research waste', improve the effectiveness of pain research and therapy and promote the uptake of research evidence. In this study, the European Pain Federation (EFIC) developed a Pain Research Strategy for Europe., Methods: The study used multiple methods, including literature searches, multidisciplinary expert debate, a survey and a final consensus meeting. The cross-sectional survey was conducted among 628 European pain researchers, clinicians, educators and industry professionals to obtain the rating and hierarchy of pain research priorities. The final consensus meeting involved a multidisciplinary expert panel including people with lived experience from 23 countries. The survey results guided discussions where top priorities were agreed., Results: Content analysis identified nine survey themes, of which five emerged as top priorities: (i) understand the pathophysiology of pain; (ii) understand and address comorbidities; (iii) critically assess current therapies; (iv) develop new treatments; and (v) explore the biopsychosocial impacts of pain. Physical, psychological and social approaches were prioritized at the same level as pharmacological treatments. The top priorities were endorsed by a multidisciplinary expert panel. The panel emphasized the importance of also clearly communicating the concepts of prediction, prevention self-management and personalized pain management in the final strategy., Conclusions: The content of the final top research priorities' list reflects a holistic approach to pain management. The equal importance given to physical, psychological and social aspects alongside pharmacological treatments highlights the importance of a comprehensive biopsychosocial-orientated research strategy. The expert panel's endorsement of five top priorities, coupled with an emphasis on communicating the concepts of prediction, prevention, self-management and personalized pain management, provides a clear direction for future basic, translational and clinical research., Significance: EFIC has developed a Pain Research Strategy for Europe that identifies pain research areas deserving the most focus and financial support. Implementation and wide dissemination of this Strategy is vital to increase the conduct of urgent pain projects, pain research funding and the implementation of research findings into practice, to ultimately decrease the personal, societal and financial burden of pain., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

We report symmetric (vertex- and arc-transitive) embeddings of catenated rings, polyhedra and rods. Linked triangles form infinite families of structures, and we limit this report to only structures with each ring linked to three or six others. For linked squares, hexagons, tetrahedra, octahedra, cubes and rods, only a small number of symmetric structures were found, and all are reported.

Objectives: The increasing burden of cardiovascular diseases (CVDs) in Kenya threatens its healthcare system. There is a need for innovative models that improve equitable access to CVD prevention services. Community markets are social establishments with untapped potential to promote public health. This is a multiphased feasibility study that explores the potential of Health Kiosks in Markets (HEKIMA) to improve access to CVD prevention services. In this formative phase, the aim was to assess the readiness of primary healthcare centres (HCs) and community markets to jointly deliver CVD prevention services., Design: Mixed methods using concept mapping and readiness surveys. Concept mapping with 35 stakeholders from different sectors (health and non-health) to identify feasible priorities for HEKIMA. The readiness questionnaire contained 193 items which were based on the guidance of the WHO Handbook for Monitoring the Building Blocks of Health Systems and adapted to suit the context of a single HC., Setting: Vihiga County is located in western Kenya and has a population of 590 013. A total of 18 HCs and 19 markets were assessed, with 10 HCs and 15 markets included in the evaluation., Results: 91 statements were generated from concept mapping and distilled into 8 clusters, namely equipment and supplies, access and referral, communication, manpower, networks and linkages, practice, service delivery and health promotion. Agreed actions for HEKIMA were provision of efficient quality services, health promotion and partnerships sensitive to the local context. HCs and markets had established governance systems and basic infrastructure. The majority of the HCs lacked essential CVD medications. No HC-market interface existed but there was willingness for a partnership., Conclusion: There was strong consensus that an HC-market interface via community health worker manned kiosks could have a positive impact on health systems, markets and CVD prevention in vulnerable communities. However, significant infrastructural, technical and resource gaps were observed that need to be addressed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Musculoskeletal pain is a significant public health concern in Europe. With the advent of the digital age, online health information-seeking behaviour has become increasingly important, influencing health outcomes and the ability of individuals to make well-informed decisions regarding their own well-being or of those they are responsible for. This study protocol outlines an investigation into how individuals in five European countries (Austria, Denmark, Ireland, Italy, and Spain) seek online health information for musculoskeletal pain., Methods: The protocol adopts an exploratory and systematic two-phase approach to analyse online health information-seeking behaviour. Phase 1 involves four steps: (1) extraction of an extensive list of keywords using Google Ads Keyword Planner; (2) refinement of the list of keywords by an expert panel; (3) investigation of related topics and queries and their degree of association with keywords using Google Trends; and (4) creation of visual representations (word clouds and simplified network graphs) using R. These visual representations provide insights into how individuals search for online health information for musculoskeletal pain. Phase 2 identifies relevant online sources by conducting platform-specific searches on Google, X, Facebook, and Instagram using the refined list of keywords. These sources are then analysed and categorised with NVivo and R to understand the types of information that individuals encounter., Conclusions: This innovative protocol has significant potential to advance the state-of-the-art in digital health literacy and musculoskeletal pain through a comprehensive understanding of online health information-seeking behaviour. The results may enable the development of effective online health resources and interventions., (© The Author(s) 2024.)

Rational design of intricate multicomponent reticular structures is often hindered by the lack of suitable blueprint nets. We established the merged-net approach, proffering optimal balance between designability and complexity, as a systematic solution for the rational assembly of multicomponent structures. In this work, by methodically mapping node-net relationships among 53 basic edge-transitive nets, we conceived a signature net map to identify merging net pairs, resulting in the enumeration of 53 merged nets. We developed a practical design algorithm and proposed more than 100 multicomponent metal-organic framework platforms. The effectiveness of this approach is commended by the successful synthesis of four classes of materials, which is based on merging three-periodic nets with the four possible net periodicities. The construction of multicomponent materials based on derived nets of merged nets highlights the potential of the merged-net approach in accelerating the discovery of intricate reticular materials.

Objective: Diet is a risk factor in inflammatory bowel diseases (IBD) pathogenesis. This study aims to examine the dietary patterns and beliefs of Irish patients living with IBD through an online questionnaire and subsequent open discussions with an IBD patient collaborator panel (PCP). All data presented here are selected and presented following the PCP's suggestions and views., Design: This mixed-method study included an online questionnaire using a short food frequency questionnaire examining dietary patterns, dietary opinions, beliefs and behaviours (phase I). Six in-person PCP sessions were conducted, where findings from the online questionnaire, diet and lifestyle in the context of IBD were discussed in depth (phase II)., Results: The questionnaire revealed that respondents with active IBD are associated with the consumption of high-sugar, processed and meat-based foods while reducing their consumption of high-fibre foods. Individuals with active Crohn's disease have a decrease in overall daily energy consumption and a significant reduction in intake of fibre, non-starch polysaccharides, micronutrients [B vitamins (B1, B2, and B9), vitamin C, calcium] and trace elements (iron, zinc, copper and manganese). The PCP reported that food tolerability is limited during relapse, leading patients to prefer simple carbohydrates for energy, consistent with the dietary intake data. The PCP reported that most dietary advice was received during hospitalisation (relapse), focused on food avoidance, with little follow-up during remission. The consensus among the PCP was that factors, such as disease type, psychological aspects, dietary understanding and support, can influence peoples' dietary choices., Conclusion: In summary, we show that dietary intake in people with IBD varies and may depend on several factors, not just the disease itself. This PCP desires more dietary information and professional support outside of hospitalisation to assist with disease management., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate whether sedentary behaviour is a risk or prognostic factor for spinal pain in children and adolescents. Specifically, to estimate the (1) direction and strength of the association; (2) risk of spinal pain onset and (3) effect on spinal pain prognosis., Design: Systematic review with meta-analysis., Data Sources: Electronic searches of MEDLINE, Embase, CINAHL and Web of Science up to 23 March 2023., Eligibility Criteria for Selecting Studies: Reports estimating the effect of sedentary behaviour on spinal pain in young people (≤19 years)., Results: We included 129 reports, 14 were longitudinal (n = 8 433) and 115 were cross-sectional (n > 697 590). We incorporated 86 studies into meta-analyses. (1) From cross-sectional data, we found low certainty evidence of a small positive association between sedentary behaviour and spinal pain (adjusted odds ratio 1.25 (95% CI 1.17 to 1.33), k = 44, n > 92 617). (2) From longitudinal data, we found low certainty evidence of no increased risk for the onset of spinal pain due to sedentary behaviour (adjusted risk ratio 1.07 (95% CI 0.84 to 1.35), k = 4, n = 1 292). (3) No studies assessed prognosis., Conclusion: Cross-sectional data suggest minimally higher odds of spinal pain for children and adolescents who engage in greater sedentary behaviours. However, longitudinal data do not support a causal relationship, indicating that sedentary behaviour does not increase the risk for onset of spinal pain. Due to the low certainty of evidence, these findings must be interpreted with caution. We found no evidence of the effect sedentary behaviour has on spinal pain prognosis in children and adolescents, highlighting a considerable gap in the literature., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

T cell surface CTLA4 sequesters the costimulatory ligands CD80 and CD86 on antigen-presenting cells (APCs) to prevent autoimmunity. Therapeutic immunosuppression by recombinant CTLA4-immunoglobulin (Ig) fusion proteins, including abatacept, is also attributed to CD80/CD86 blockade. Recent studies show that CTLA4-Ig binding to APC surface cis-CD80:PD-L1 complexes can release the inhibitory ligand PD-L1, but whether this contributes to T cell inhibition remains unclear. Here, we show that PD-L1 liberation by CTLA4-Ig is strictly limited, both in extent and context, relative to PD-L1-competing anti-CD80 antibodies. At APC surface CD80:PD-L1 ratios exceeding 2:1, CTLA4-Ig therapies fail to release PD-L1 regardless of their CD80 affinity. Additionally, introducing flexibility into CTLA4-Ig by modifying its rigid homodimer interface produces biologics that retain bivalent CD80 binding without dissociating cis-bound PD-L1. These findings demonstrate that CTLA4-Ig therapies liberate PD-L1 through a CD80 reorientation mechanism that imposes a strict context dependence to their PD-1 checkpoint agonism and resultant T cell inhibition., Competing Interests: Declaration of interests E.P.O., N.J.K., K.J.G., M.M.G., and R.A.D. are inventors on International Patent Application PCT/AU2022/051296 (filed October 28, 2022) related to this work. E.P.O., N.J.K., and R.A.D. are co-founders of FLEX Immunotherapeutics. N.D.H. is CSO of oNKo-Innate Pty Ltd and declares ownership and funding not related to this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To explore patient experiences of rotator cuff-related shoulder pain, and their views on the role and value of diagnostic shoulder imaging., Materials and Methods: Semi-structured interviews were conducted with 20 patients with shoulder pain exploring the impact and management of their shoulder condition, reasons for and experiences of diagnostic imaging, and feelings about and responses to diagnostic imaging findings. Framework analysis was used to analyse the dataset., Results: Five themes were identified [1]: Lived experience and beliefs about pain and movement [2]; Contextualisation of imaging findings by health professionals is more important than the imaging report [3]; Factors influencing whether and when to have imaging [4]; Imaging can identify the actual problem and guide treatment; and [5] Treatment responses and treatment decision making., Conclusion: Patients commonly believe imaging is needed to formulate a diagnosis. There was minimal concern about potential indirect harms that could arise (e.g., inappropriate diagnosis leading to unnecessary treatments). The context of the diagnostic imaging reports (i.e., what needed to be done) was perceived as more important than the exact meaning of the imaging findings. Patients felt that the diagnostic imaging confirmed their existing biomedical beliefs, and these beliefs were not challenged by their healthcare professionals.

The cGAS-STING pathway responds to cytosolic DNA to elicit host immunity to infection. The activation of stimulator of interferon genes (STING) can trigger a number of critical cellular responses including inflammation, noncanonical autophagy, lipid metabolism, senescence, and cell death. STING-mediated immunity through the production of type I interferons (IFNs) and nuclear factor kappa B (NF-κB)-driven proinflammatory cytokines is primarily driven via the effector protein TBK1. We have previously found that IκBα kinase epsilon (IKKε), a homolog of TBK1, can also facilitate STING-NF-κB responses. Therefore, a thorough understanding of how IKKε participates in STING signaling is essential. Here, we used a combination of genetic and biochemical approaches to provide mechanistic details into how IKKε confers non-IFN (e.g., NF-κB and MAPK) STING responses in macrophages, including in the absence of TBK1. We demonstrate a conserved mechanism of STING binding between TBK1 and IKKε. These findings strengthen our understanding of cGAS-STING signaling and the preservation of host immunity in cases of TBK1-deficiency., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

The relationship between postoperative dietary intake and weight loss after bariatric surgery remains unclear. We performed a systematic review and meta-analysis of studies published between January 2000 and May 2023, reporting weight loss outcomes, and dietary intake before and after Roux-en-Y gastric bypass and sleeve gastrectomy. A total of 42 studies were included. There was no detectable difference in dietary intake between the two procedures. Roux-en-Y gastric bypass induced an average decrease in energy intake of 886 kcal/day at 12-month post-surgery; however, there was no correlation between daily energy intake and weight loss. These findings show a substantial reduction of energy intake in the first year after bariatric surgery but do not support a link between lower energy intake and greater weight loss., (© 2024. The Author(s).)

Objectives: To explore how people perceive three different forms of advice for acute low back pain (LBP)., Design: Content analysis of qualitative data collected in a three-arm randomised experiment., Participants: 2200 participants with acute LBP (ie, pain duration for ≤6 weeks) were randomly assigned to receive three types of advice: guideline advice and guideline advice with the addition of either brief pain science or ergonomics messages., Primary and Secondary Outcomes: After receiving the advice, participants answered two questions: 'If your health professional gave you this advice, how would it make you feel?' and 'If your health professional gave you this advice, what treatments (if any) do you think you would need?' Two researchers coded responses using deductive content analysis., Results: We analysed 4400 free-text responses from 2200 participants. There were little to no differences in participants' feelings, thoughts and expectations after receiving three types of advice for acute LBP. Participants most commonly expressed feeling positive about the advice (38%-35%), reassured (23%-22%) and empowered (10%-8%). Some expressed being unhappy or being frustrated with the advice (4%-3%). Participants most commonly thought they needed no treatment apart from staying active, followed by exercise and medication., Conclusions: Guideline advice with or without the addition of brief pain science or ergonomics messages generated positive feelings, reassurance or a sense of empowerment in many people with acute LBP, with no difference between types of advice., Trial Registration Number: ACTRN12623000364673., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Purpose: An online randomised experiment found that the labels lumbar sprain, non-specific low back pain (LBP), and episode of back pain reduced perceived need for imaging, surgery and second opinions compared to disc bulge, degeneration, and arthritis among 1447 participants with and without LBP. They also reduced perceived seriousness of LBP and increased recovery expectations., Methods: In this study we report the results of a content analysis of free-text data collected in our experiment. We used two questions: 1. When you hear the term [one of the six labels], what words or feelings does this make you think of? and 2. What treatment (s) (if any) do you think a person with [one of the six labels] needs? Two independent reviewers analysed 2546 responses., Results: Ten themes emerged for Question1. Poor prognosis emerged for disc bulge, degeneration, and arthritis, while good prognosis emerged for lumbar sprain, non-specific LBP, and episode of back pain. Thoughts of tissue damage were less common for non-specific LBP and episode of back pain. Feelings of uncertainty frequently emerged for non-specific LBP. Twenty-eight treatments emerged for Question2. Surgery emerged for disc bulge, degeneration, and arthritis compared to lumbar sprain, non-specific LBP, and episode of back pain. Surgery did not emerge for non-specific LBP and episode of back pain., Conclusion: Our results suggest that clinicians should consider avoiding the labels disc bulge, degeneration and arthritis and opt for labels that are associated with positive beliefs and less preference for surgery, when communicating with patients with LBP., (© 2022. The Author(s).)

Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet + subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11c + CD80 + cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post-infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Persistent pain is a major public health issue-estimated to affect a quarter of the world's population. Public understanding of persistent pain is based on outdated biomedical models, laden with misconceptions that are contrary to best evidence. This understanding is a barrier to effective pain management. Thus, there have been calls for public health-based interventions to address these misconceptions. Previous pain-focussed public education campaigns have targeted pain beliefs and behaviours that are thought to promote recovery, such as staying active. However, prevailing pain-related misconceptions render many of these approaches counter-intuitive, at best. Pain Science Education improves understanding of 'how pain works' and has been demonstrated to improve pain and disability outcomes. Extending Pain Science Education beyond the clinic to the wider community seems warranted. Learning from previous back pain-focussed and other public health educational campaigns could optimise the potential benefit of such a Pain Science Education campaign. Pain Science Education-grounded campaigns have been delivered in Australia and the UK and show promise, but robust evaluations are needed before any firm conclusions on their population impact can be made. Several challenges exist going forward. Not least is the need to ensure all stakeholders are involved in the development and implementation of Pain Science Education public messaging campaigns. Furthermore, it is crucial that campaigns are undertaken through a health equity lens, incorporating underrepresented communities to ensure that any intervention does not widen existing health inequalities associated with persistent pain. PERSPECTIVE: Public misconceptions about pain are a significant public health challenge and a viable intervention target to reduce the personal, social, and economic burden of persistent pain. Adaptation of Pain Science Education, which improves misconceptions in a clinical setting, into the public health setting seems a promising approach to explore., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)