Purinergic signaling in liver disease: calcium signaling and induction of inflammation.

Purinergic signaling regulates many metabolic functions and is implicated in liver physiology and pathophysiology. Liver functionality is modulated by ionotropic P2X and metabotropic P2Y receptors, specifically P2Y1, P2Y2, and P2Y6 subtypes, which physiologically exert their influence through calcium signaling, a key second messenger controlling glucose and fat metabolism in hepatocytes. Purinergic receptors, acting through calcium signaling, play an important role in a range of liver diseases. Ionotropic P2X receptors, such as the P2X7 subtype, and certain metabotropic P2Y receptors can induce aberrant intracellular calcium transients that impact normal hepatocyte function and initiate the activation of other liver cell types, including Kupffer and stellate cells. These P2Y- and P2X-dependent intracellular calcium increases are particularly relevant in hepatic disease states, where stellate and Kupffer cells respond with innate immune reactions to challenges, such as excess fat accumulation, chronic alcohol abuse, or infections, and can eventually lead to liver fibrosis. This review explores the consequences of excessive extracellular ATP accumulation, triggering calcium influx through P2X4 and P2X7 receptors, inflammasome activation, and programmed cell death. In addition, P2Y2 receptors contribute to hepatic steatosis and insulin resistance, while inhibiting the expression of P2Y6 receptors can alleviate alcoholic liver steatosis. Adenosine receptors may also contribute to fibrosis through extracellular matrix production by fibroblasts. Thus, pharmacological modulation of P1 and P2 receptors and downstream calcium signaling may open novel therapeutic avenues.

Exploring American Elderberry Compounds for Antioxidant, Antiviral, and Antibacterial Properties Through High-Throughput Screening Assays Combined with Untargeted Metabolomics.

American elderberry ( Sambucus nigra subsp. canadensis ) is a rapidly emerging new perennial crop for Missouri, recognized for its high level of bioactive compounds with significant health benefits, including antibacterial, antiviral, and antioxidant properties. A high-throughput screening assay combined with untargeted metabolomics analysis was utilized on American elderberry juice from 21 genotypes to explore and characterize these bioactive compounds. Our metabolomics study has identified 32 putative bioactive compounds in the American Elderberry juices. An array of high-throughput screening bioassays was conducted to evaluate 1) total antioxidant capacity, 2) activation of antioxidant response elements (ARE), 3) antiviral activity, and 4) antibacterial activity of the putatively identified compounds. Our results revealed that 14 of the 32 American elderberry compounds exhibited strong antioxidant activity. Four compounds (isorhamnetin 3-O-glucoside, kaempferol, quercetin, and naringenin) activated ARE activity and were found to be non-cytotoxic to cells. Notably, six of the 32 compounds demonstrated significant antiviral activity in an in vitro TZM-bl assay against two strains of HIV-1 virus, CXCR4-dependent NL4-3 virus and CCR5-dependent BaL virus. Luteolin showed the most potent anti-HIV activity against the NL4-3 virus (IC 50 = 1.49 µM), followed by isorhamnetin (IC 50 = 1.67 µM). The most potent anti-HIV compound against the BaL virus was myricetin (IC 50 = 1.14 µM), followed by luteolin (IC 50 = 4.38 µM). Additionally, six compounds were found to have antibacterial activity against gram-positive bacteria S. aureus , with cyanidin 3-O-rutinoside having the most potent antibacterial activity in vitro (IC 50 = 2.9 µM), followed by cyanidin 3-O-glucoside (IC 50 = 3.7 µM). These findings support and validate the potential health benefits of compounds found in American elderberry juices and highlight their potential for use in dietary supplements as well as innovative applications in health and medicine.

Extreme heterogeneity in the microrheology of lamellar surfactant gels analyzed with neural networks.

The heterogeneity of the viscoelasticity of a lamellar gel network based on cetyl-trimethylammonium chloride and cetostearyl alcohol was studied using particle-tracking microrheology. A recurrent neural network (RNN) architecture was used for estimating the Hurst exponent, H, on small sections of tracks of probe spheres moving with fractional Brownian motion. Thus, dynamic segmentation of tracks via neural networks was used in microrheology and it is significantly more accurate than using mean square displacements (MSDs). An ensemble of 414 particles produces a MSD that is subdiffusive in time, t, with a power law of the form t^{0.74±0.02}, indicating power law viscoelasticity. RNN analysis of the probability distributions of H, combined with detailed analysis of the time-averaged MSDs of individual tracks, revealed diverse diffusion processes belied by the simple scaling of the ensemble MSD, such as caging phenomena, which give rise to the complex viscoelasticity of lamellar gels.

Mind the gap: Development and validation of an evolutionary mismatched lifestyle scale and its impact on health and wellbeing.

Identifying an integrative framework that could appropriately delineate underlying mechanisms and individual risk/protective factors for human health has remained elusive. Evolutionary mismatch theory provides a comprehensive, integrative model for understanding the underlying causes and mechanisms of a wide range of modern health and well-being problems, ranging from obesity to depression. Despite growing interest regarding its importance though, no psychometrically-sound measure of evolutionary mismatch yet exists to facilitate research and intervention. To construct such a scale, aimed at gauging individual differences in the extent to which people's modern lifestyles are mismatched with ancestral conditions, we conducted four studies (a pilot study, followed by 3 main studies, with a final sample of 1901 participants across the main studies). Results from exploratory and confirmatory factor analyses have produced a 36-item evolutionary mismatched lifestyle scale (EMLS) with 7 subdomains of mismatched behaviours (e.g., diet, physical activity, relationships, social media use) that is psychometrically sound. Further, the EMLS is associated with physical, mental and subjective health. We explore the potential of the EMLS as a tool for examining interpersonal and cultural variations in health and wellbeing, while also discussing the limitations of the scale and future directions in relation to further psychometric examinations.

Auditing the microbiological quality of the air in operating theatres.

The critical relationship between airborne microbiological contamination in an operating theatre and surgical site infection (SSI) is well known. The aim of this annotation is to explain the scientific basis of using settle plates to audit the quality of air, and to provide information about the practicalities of using them for the purposes of clinical audit. The microbiological quality of the air in most guidance is defined by volumetric sampling, but this method is difficult for surgical departments to use on a routine basis. Settle plate sampling, which mimics the mechanism of deposition of airborne microbes onto open wounds and sterile instruments, is a good alternative method of assessing the quality of the air. Current practice is not to sample the air in an operating theatre during surgery, but to rely on testing the engineering systems which deliver the clean air. This is, however, not good practice and microbiological testing should be carried out routinely during operations as part of clinical audit.

Analysis of the airflow features and ventilation efficiency of an Ultra-Clean-Air operating theatre by qDNS simulations and experimental validation.

Ultra-Clean-Air (UCA) operating theatres aim to minimise surgical instrument contamination and wound infection through high flow rates of ultra-clean air, reducing the presence of Microbe Carrying Particles (MCPs). This study investigates the airflow patterns and ventilation characteristics of a UCA operating theatre (OT) under standard ventilation system operating conditions, considering both empty and partially occupied scenarios. Utilising a precise computational model, quasi-Direct Numerical Simulations (qDNS) were conducted to delineate flow velocity profiles, energy spectra, distributions of turbulent kinetic energy, energy dissipation rate, local Kolmogorov scales, and pressure-based coherent structures. These results were also complemented by a tracer gas decay analysis following ASHRAE standard guidelines. Simulations showed that contrary to the intended laminar regime, the OT's geometry inherently fosters a predominantly turbulent airflow, sustained until evacuation through the exhaust vents, and facilitating recirculation zones irrespective of occupancy level. Notably, the occupied scenario demonstrated superior ventilation efficiency, a phenomenon attributed to enhanced kinetic energy induced by the additional obstructions. The findings underscore the critical role of UCA-OT design in mitigating MCP dissemination, highlighting the potential to augment the design to optimise airflow across a broader theatre spectrum, thereby diminishing recirculation zones and consequently reducing the propensity for Surgical Site Infections (SSIs). The study advocates for design refinements to harness the turbulent dynamics beneficially, steering towards a safer surgical environment.

Income and Sex Moderate the Association Between Population Density and Reproduction: A Multilevel Analysis of Life History Strategies Across 23 Nations.

While previous studies guided by evolutionary life history theory have revealed several important socioecological moderators of the influence of population density (PD) on reproduction, absent is an understanding of how individual-level factors such as personal resources and sex differences might interact and play a role. Using data from a large sample of clients (N = 4,432,440) of an online dating company spanning 317 states nested within 23 countries, we contributed a robust multilevel analysis of life history effects by assessing the interaction between state-level PD and individual-level income on offspring quantity, and we further qualified this analysis by sex. Consistent with previous research, PD was negatively correlated with having children. Consistent with our novel hypotheses, this negative relationship was moderated by income such that the link between PD and low fertility became weaker with increasing levels of income and these patterns were stronger for men than for women. These results held despite controlling for a variety of country-level, state-level, and individual-level confounds. Findings are discussed together with theoretical and practical implications for the management of fertility based on evolutionary life history perspectives.

Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome.

The gut microbiota influences the clinical responses of cancer patients to immunecheckpoint inhibitors (ICIs). However, there is no consensus definition of detrimental dysbiosis. Based on metagenomics (MG) sequencing of 245 non-small cell lung cancer (NSCLC) patient feces, we constructed species-level co-abundance networks that were clustered into species-interacting groups (SIGs) correlating with overall survival. Thirty-seven and forty-five MG species (MGSs) were associated with resistance (SIG1) and response (SIG2) to ICIs, respectively. When combined with the quantification of Akkermansia species, this procedure allowed a person-based calculation of a topological score (TOPOSCORE) that was validated in an additional 254 NSCLC patients and in 216 genitourinary cancer patients. Finally, this TOPOSCORE was translated into a 21-bacterial probe set-based qPCR scoring that was validated in a prospective cohort of NSCLC patients as well as in colorectal and melanoma patients. This approach could represent a dynamic diagnosis tool for intestinal dysbiosis to guide personalized microbiota-centered interventions.

Impact of Matrix Gel Variations on Primary Culture of Microvascular Endothelial Cell Function.

OBJECTIVE: The endothelium regulates crucial aspects of vascular function, including hemostasis, vasomotor tone, proliferation, immune cell adhesion, and microvascular permeability. Endothelial cells (ECs), especially in arterioles, are pivotal for flow distribution and peripheral resistance regulation. Investigating vascular endothelium physiology, particularly in microvascular ECs, demands precise isolation and culturing techniques. METHODS: Freshly isolated ECs are vital for examining protein expression, ion channel behavior, and calcium dynamics. Establishing primary endothelial cell cultures is crucial for unraveling vascular functions and understanding intact microvessel endothelium roles. Despite the significance, detailed protocols and comparisons with intact vessels are scarce in microvascular research. We developed a reproducible method to isolate microvascular ECs, assessing substrate influence by cultivating cells on fibronectin and gelatin matrix gels. This comparative approach enhances our understanding of microvascular endothelial cell biology. RESULTS: Microvascular mesenteric ECs expressed key markers (VE-cadherin and eNOS) in both matrix gels, confirming cell culture purity. Under uncoated conditions, ECs were undetected, whereas proteins linked to smooth muscle cells and fibroblasts were evident. Examining endothelial cell (EC) physiological dynamics on distinct matrix substrates revealed comparable cell length, shape, and Ca2+ elevations in both male and female ECs on gelatin and fibronectin matrix gels. Gelatin-cultured ECs exhibited analogous membrane potential responses to acetylcholine (ACh) or adenosine triphosphate (ATP), contrasting with their fibronectin-cultured counterparts. In the absence of stimulation, fibronectin-cultured ECs displayed a more depolarized resting membrane potential than gelatin-cultured ECs. CONCLUSIONS: Gelatin-cultured ECs demonstrated electrical behaviors akin to intact endothelium from mouse mesenteric arteries, thus advancing our understanding of endothelial cell behavior within diverse microenvironments.

Spatial organisation of fungi in soil biocrusts of the Kalahari is related to bacterial community structure and may indicate ecological functions of fungi in drylands.

Biological soil crusts, or biocrusts, are microbial communities found in soil surfaces in drylands and in other locations where vascular plant cover is incomplete. They are functionally significant for numerous ecosystem services, most notably in the C fixation and storage due to the ubiquity of photosynthetic microbes. Whereas carbon fixation and storage have been well studied in biocrusts, the composition, function and characteristics of other organisms in the biocrust such as heterotrophic bacteria and especially fungi are considerably less studied and this limits our ability to gain a holistic understanding of biocrust ecology and function. In this research we characterised the fungal community in biocrusts developed on Kalahari Sand soils from a site in southwest Botswana, and combined these data with previously published bacterial community data from the same site. By identifying organisational patterns in the community structure of fungi and bacteria, we found fungi that were either significantly associated with biocrust or the soil beneath biocrusts, leading to the conclusion that they likely perform functions related to the spatial organisation observed. Furthermore, we showed that within biocrusts bacterial and fungal community structures are correlated with each other i.e., a change in the bacterial community is reflected by a corresponding change in the fungal community. Importantly, this correlation but that this correlation does not occur in nearby soils. We propose that different fungi engage in short-range and long-range interactions with dryland soil surface bacteria. We have identified fungi which are candidates for further studies into their potential roles in biocrust ecology at short ranges (e.g., processing of complex compounds for waste management and resource provisioning) and longer ranges (e.g., translocation of resources such as water and the fungal loop model). This research shows that fungi are likely to have a greater contribution to biocrust function and dryland ecology than has generally been recognised.

Correction: Identifying areas of Australia with high out-of-hospital cardiac arrest incidence and low bystander cardiopulmonary resuscitation rates: A retrospective, observational study.

[This corrects the article DOI: 10.1371/journal.pone.0301176.].

Feasibility and Preliminary Efficacy of American Elderberry Juice for Improving Cognition and Inflammation in Patients with Mild Cognitive Impairment.

Despite data showing that nutritional interventions high in antioxidant/anti-inflammatory properties (anthocyanin-rich foods, such as blueberries/elderberries) may decrease risk of memory loss and cognitive decline, evidence for such effects in mild cognitive impairment (MCI) is limited. This study examined preliminary effects of American elderberry (Sambucus nigra subsp. canadensis) juice on cognition and inflammatory markers in patients with MCI. In a randomized, double-blind, placebo-controlled trial, patients with MCI (n = 24, Mage = 76.33 ± 6.95) received American elderberry (n = 11) or placebo (n = 13) juice (5 mL orally 3 times a day) for 6 months. At baseline, 3 months, and 6 months, patients completed tasks measuring global cognition, verbal memory, language, visuospatial cognitive flexibility/problem solving, and memory. A subsample (n = 12, 7 elderberry/5 placebo) provided blood samples to measure serum inflammatory markers. Multilevel models examined effects of the condition (elderberry/placebo), time (baseline/3 months/6 months), and condition by time interactions on cognition/inflammation outcomes. Attrition rates for elderberry (18%) and placebo (15%) conditions were fairly low. The dosage compliance (elderberry-97%; placebo-97%) and completion of cognitive (elderberry-88%; placebo-87%) and blood-based (elderberry-100%; placebo-100%) assessments was high. Elderberry (not placebo) trended (p = 0.09) towards faster visuospatial problem solving performance from baseline to 6 months. For the elderberry condition, there were significant or significantly trending decreases over time across several markers of low-grade peripheral inflammation, including vasorin, prenylcysteine oxidase 1, and complement Factor D. Only one inflammatory marker showed an increase over time (alpha-2-macroglobin). In contrast, for the placebo, several inflammatory marker levels increased across time (L-lactate dehydrogenase B chain, complement Factor D), with one showing deceased levels over time (L-lactate dehydrogenase A chain). Daily elderberry juice consumption in patients with MCI is feasible and well tolerated and may provide some benefit to visuospatial cognitive flexibility. Preliminary findings suggest elderberry juice may reduce low-grade inflammation compared to a placebo-control. These promising findings support the need for larger, more definitive prospective studies with longer follow-ups to better understand mechanisms of action and the clinical utility of elderberries for potentially mitigating cognitive decline.

Comparative benefits and harms of perioperative interventions to prevent chronic pain after orthopedic surgery: a systematic review and network meta-analysis of randomized trials.

BACKGROUND: Chronic postsurgical pain (CPSP) is common following musculoskeletal and orthopedic surgeries and is associated with impairment and reduced quality of life. Several interventions have been proposed to reduce CPSP; however, there remains uncertainty regarding which, if any, are most effective. We will perform a systematic review and network meta-analysis of randomised trials to assess the comparative benefits and harms of perioperative pharmacological and psychological interventions directed at preventing chronic pain after musculoskeletal and orthopedic surgeries. METHODS: We will search MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to present, without language restrictions. We will include randomised controlled trials that as follows: (1) enrolled adult patients undergoing musculoskeletal or orthopedic surgeries; (2) randomized them to any pharmacological or psychological interventions, or their combination directed at reducing CPSP, placebo, or usual care; and (3) assessed pain at 3 months or more after surgery. Screening for eligible trials, data extraction, and risk-of-bias assessment using revised Cochrane risk-of-bias tool (RoB 2.0) will be performed in duplicate and independently. Our main outcome of interest will be the proportion of surgical patients reporting any pain at ≥ 3 months after surgery. We will also collect data on other patient important outcomes, including pain severity, physical functioning, emotional functioning, dropout rate due to treatment-related adverse event, and overall dropout rate. We will perform a frequentist random-effects network meta-analysis to determine the relative treatment effects. When possible, the modifying effect of sex, surgery type and duration, anesthesia type, and veteran status on the effectiveness of interventions will be investigated using network meta-regression. We will use the GRADE approach to assess the certainty evidence and categorize interventions from most to least beneficial using GRADE minimally contextualised approach. DISCUSSION: This network meta-analysis will assess the comparative effectiveness of pharmacological and psychological interventions directed at preventing CPSP after orthopedic surgery. Our findings will inform clinical decision-making and identify promising interventions for future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023432503.

Identifying areas of Australia with high out-of-hospital cardiac arrest incidence and low bystander cardiopulmonary resuscitation rates: A retrospective, observational study.

AIM: This study aims to explore regional variation and identify regions within Australia with high incidence of out-of-hospital cardiac arrest (OHCA) and low rates of bystander cardiopulmonary resuscitation (CPR). METHOD: Adult OHCAs of presumed medical aetiology occurring across Australia between 2017 and 2019 were mapped onto local government areas (LGA) using the location of arrest coordinates. Bayesian spatial models were applied to provide "smoothed" estimates of OHCA incidence and bystander CPR rates (for bystander-witnessed OHCAs) for each LGA. For each state and territory, high-risk LGAs were defined as those with an incidence rate greater than the state or territory's 75th percentile and a bystander CPR rate less than the state or territory's 25th percentile. RESULTS: A total of 62,579 OHCA cases attended by emergency medical services across 543 LGAs nationwide were included in the study. Nationally, the OHCA incidence rate across LGA ranged from 58.5 to 198.3 persons per 100,000, while bystander CPR rates ranged from 45% to 75%. We identified 60 high-risk LGAs, which were predominantly located in the state of New South Wales. Within each region, high-risk LGAs were typically located in regional and remote areas of the country, except for four metropolitan areas-two in Adelaide and two in Perth. CONCLUSIONS: We have identified high-risk LGAs, characterised by high incidence and low bystander CPR rates, which are predominantly in regional and remote areas of Australia. Strategies for reducing OHCA and improving bystander response may be best targeted at these regions.

"It's beautiful and it's messy and it's tragic": exploring the role of compassion in the eating disorder recovery processes of 2S/LGBTQ + Canadians.

This research explores experiences of compassion among 2S/LGBTQ + Canadians living with eating disorders in the context of eating disorder treatment and community support. There is a growing body of scholarship showing disparities in eating disorder care for those within 2S/LGBTQ + communities. Among the reported concerns is a potential lack of compassion in eating disorder treatment and recovery settings, something which may serve to exacerbate feelings of isolation and perpetuate misunderstandings of 2S/LGBTQ + people's experiences. In an effort to understand these dynamics more deeply, we conducted semi-structured interviews with 2S/LGBTQ + Canadians who have experienced eating disorder care. The data collected were then subjected to Foucauldian discourse analysis, which produced three interconnected discursive considerations: feeling lack of structural compassion, 2S/LGBTQ + communities as places of respite, and 2S/LGBTQ + caregiving. One of the common threads among these discursive considerations was cis-heteronormativity ingrained in eating disorder treatment settings and health care systems more broadly. Our findings underscore the critical need for more enhanced compassion for 2S/LGBTQ + patients in eating disorder care settings. We conclude that compassion, when implemented on the levels of individual clinicians, policy and procedure, and institutions, may represent an avenue toward disrupting ingrained cis-heteronormativity and the associated discursive power structures contained in health care systems.

Two-Spirit, lesbian, gay, bisexual, transgender, queer and other sexually or gender diverse (2S/LGBTQ+) are at increased risk for eating disorders often related to minority stress, discrimination, and heteronormative gender expectations. Compassion is believed to be a fundamental aspect of healthcare that builds human connections and enhances positive outcomes. Healthcare, however, is steeped in heteronormative assumptions that may further isolate many 2S/LGBTQ+ patients. This study explored how 2S/LGBTQ+ Canadians living with eating disorders felt about their care and the role of compassion in their recovery journeys. We found that these individuals often felt misunderstood and isolated during treatment. However, they often experienced understanding by connecting with other 2S/LGBTQ+ people both in care and in the community, which provided the compassionate spaces lacking in their healthcare experiences. These findings highlight a need for making healthcare more compassionate for 2S/LGBTQ+ people. This can be done by changing policies, mandatory training for healthcare professionals, and treatment that recognizes and discusses minority stresses, uses trauma-informed practices, and gender-affirming approaches. By doing such items, standard norms can be challenged and the care for 2S/LGBTQ+ people living with eating disorders can be improved.

Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma.

Multiple clinical trials targeting the gut microbiome are being conducted to optimize treatment outcomes for immune checkpoint blockade (ICB). To improve the success of these interventions, understanding gut microbiome changes during ICB is urgently needed. Here through longitudinal microbiome profiling of 175 patients treated with ICB for advanced melanoma, we show that several microbial species-level genome bins (SGBs) and pathways exhibit distinct patterns from baseline in patients achieving progression-free survival (PFS) of 12 months or longer (PFS ≥12) versus patients with PFS shorter than 12 months (PFS <12). Out of 99 SGBs that could discriminate between these two groups, 20 were differentially abundant only at baseline, while 42 were differentially abundant only after treatment initiation. We identify five and four SGBs that had consistently higher abundances in patients with PFS ≥12 and <12 months, respectively. Constructing a log ratio of these SGBs, we find an association with overall survival. Finally, we find different microbial dynamics in different clinical contexts including the type of ICB regimen, development of immune-related adverse events and concomitant medication use. Insights into the longitudinal dynamics of the gut microbiome in association with host factors and treatment regimens will be critical for guiding rational microbiome-targeted therapies aimed at enhancing ICB efficacy.

A systematic review of literature examining the application of a social model of health and wellbeing.

BACKGROUND: Following years of sustained pressure on the UK health service, there is recognition amongst health professionals and stakeholders that current models of healthcare are likely to be inadequate going forward. Therefore, a fundamental review of existing social models of healthcare is needed to ascertain current thinking in this area, and whether there is a need to change perspective on current thinking. METHOD: Through a systematic research review, this paper seeks to address how previous literature has conceptualized a social model of healthcare and, how implementation of the models has been evaluated. Analysis and data were extracted from 222 publications and explored the country of origin, methodological approach, and the health and social care contexts which they were set. RESULTS: The publications predominantly drawn from the USA, UK, Australia, Canada and Europe identified five themes namely: the lack of a clear and unified definition of a social model of health and wellbeing; the need to understand context; the need for cultural change; improved integration and collaboration towards a holistic and person-centred approach; measuring and evaluating the performance of a social model of health. CONCLUSION: The review identified a need for a clear definition of a social model of health and wellbeing. Furthermore, consideration is needed on how a model integrates with current models and whether it will act as a descriptive framework or, will be developed into an operational model. The review highlights the importance of engagement with users and partner organizations in the co-creation of a model of healthcare.

The harm hypothesis: How perceived harm to women shapes reactions to research on sex differences.

Past research suggests that reactions to research on sex differences are often less positive when the findings put men in a better light than women, especially when the lead researcher is a man. The factors underlying this effect, however, are not yet fully understood. The present study aimed to provide the first experimental test of the hypothesis that the key variable is perceived harm to women. Participants (214 men and 219 women) evaluated a bogus popular-science article reporting fictional research finding either a female- or a male-favouring sex difference in intelligence, attributed to either a female or a male lead researcher. To examine the effects of perceived harm, the introduction to the task highlighted either the potential benefits or potential drawbacks of sex-differences research in general. Consistent with past research, participants reacted less positively to the male-favouring difference, especially for male-led research. Consistent with the harm hypothesis, the effect was stronger after highlighting the potential drawbacks of sex-differences research than after highlighting the potential benefits. Our findings suggest that perceptions of harm to women underpin the aversion to male-favouring findings.