An Electrosynthesis of 1,3,4-Oxadiazoles from N-Acyl Hydrazones.

The 1,3,4-oxadiazole is a widely encountered motif in the areas of pharmaceuticals, materials, and agrochemicals. This work has established a mild, mediated electrochemical synthesis of 2,5-disubstituted 1,3,4-oxadiazoles from N-acyl hydrazones. Using DABCO as the optimal redox mediator has enabled a mild oxidative cyclisation, without recourse to stoichiometric oxidants. In contrast to previous methods, this indirect electrochemical oxidation has enabled a broad range of substrates to be accessed, with yields of up to 83%, and on gram scale. The simplicity of the method has been further demonstrated by the development of a one-pot procedure, directly transforming readily available aldehydes and hydrazides into valuable heterocycles.

Interactions between neural representations of the social and spatial environment.

Even in our highly interconnected modern world, geographic factors play an important role in human social connections. Similarly, social relationships influence how and where we travel, and how we think about our spatial world. Here, we review the growing body of neuroscience research that is revealing multiple interactions between social and spatial processes in both humans and non-human animals. We review research on the cognitive and neural representation of spatial and social information, and highlight recent findings suggesting that underlying mechanisms might be common to both. We discuss how spatial factors can influence social behaviour, and how social concepts modify representations of space. In so doing, this review elucidates not only how neural representations of social and spatial information interact but also similarities in how the brain represents and operates on analogous information about its social and spatial surroundings.This article is part of the theme issue 'The spatial-social interface: a theoretical and empirical integration'.

Irreversible electroporation of localised prostate cancer downregulates immune suppression and induces systemic anti-tumour T-cell activation - IRE-IMMUNO study.

OBJECTIVES: To prospectively compare systemic anti-tumour immune responses induced by irreversible electroporation (IRE) and robot-assisted radical prostatectomy (RARP) in patients with localised intermediate-risk prostate cancer (PCa). PATIENTS AND METHODS: Between February 2021 and June 2022, before and after treatment (at 5, 14 and 30 days) peripheral blood samples of 30 patients with localised PCa were prospectively collected. Patient inclusion criteria were: International Society of Urological Pathologists Grade 2-3, clinical cancer stage ≤T2c, prostate-specific antigen level <20 ng/mL). Patients were treated with IRE (n = 20) or RARP (n = 10). Frequency and activation status of lymphocytic and myeloid immune cell subsets were determined using flow cytometry. PCa-specific T-cell responses to prostatic acid phosphatase (PSAP) and cancer testis antigen (New York oesophageal squamous cell carcinoma 1 [NY-ESO-1]) were determined by interferon-γ enzyme-linked immunospot assay (ELISpot). Repeated-measures analysis of variance and two-sided Student's t-tests were used to compare immune responses over time and between treatment cohorts. RESULTS: Patient and tumour characteristics were similar between the cohorts except for age (median 68 years [IRE] and 62 years [RARP], P = 0.01). IRE induced depletion of systemic regulatory T cells (P = 0.0001) and a simultaneous increase in activated cytotoxic T-lymphocyte antigen 4 (CTLA-4)+ cluster of differentiation (CD)4+ (P < 0.001) and CD8+ (P = 0.032) T cells, consistent with reduction of systemic immune suppression allowing for effector T-cell activation, peaking 14 days after IRE. Effects were positively correlated with tumour volume/ablation size. Accordingly, IRE induced expansion of PSAP and/or NY-ESO-1 specific T-cell responses in four of the eight immune competent patients. Temporarily increased activated myeloid derived suppressor cell frequencies (P = 0.047) were consistent with transient immunosuppression after RARP. CONCLUSIONS: Irreversible electroporation induces a PCa-specific systemic immune response in patients with localised PCa, aiding conversion of the tumour microenvironment into a more immune permissive state. Therapeutic efficacy might be further enhanced by combination with CTLA-4 checkpoint inhibition, potentially opening up a new synergistic treatment paradigm for high-risk localised or (oligo)metastatic disease.

Creating and Reliving the Moment: Using Musical Improvisation and Care Aesthetics as a Lens of Connection and Self-Expression for Younger People Living with Dementia.

Musical improvisation is a generative process of spontaneously creating music 'in the moment'. For people with young onset dementia, musical improvisation provides an extended opportunity for creative self-expression and connection to one's own body and life story. Using visual research methods, including video elicitation interviews, this paper explores the 'in the moment' musical experiences of five people living with young onset dementia who took part in a 15-week improvised music-making programme (Music in Mind). We frame the exploration of the group's musical experiences through the emerging lens of 'care aesthetics'-a concept that identifies the sensory relations and embodied practices between two (or more) people in a caring relationship. In the context of this analysis, we look to the caring practices by, with, and between people living with dementia, their family members, and the musicians who lead the programme and the relationship of these practices to feelings of self-expression and meaningful connection. Musical improvisation has the potential to support the psychological, social, and spiritual wellbeing of people living with young onset dementia. In applying a lens of care aesthetics, it is possible to observe the micro-level experiences of people living with dementia and their family carers.

Virtual Loupes: A Pilot Study on the Use of Video Passthrough Augmented Reality in Plastic Surgery.

BACKGROUND: Plastic surgeons use loupes or operative microscope to aid in tissue dissection and anastomosis of structures. These devices have their own limitations in areas of visualization and weight. Current uses of augmented and virtual reality in surgery have been limited to operative planning and simulation. We present a proof of concept that harnesses video passthrough AR technology to augment the capabilities of loupes. METHODS: We first evaluated methods of gaze-based eye tracking to enable digital magnification. Using the Varjo XR-1 mixed reality headset, we compared discrete zoom through displayed pop-up menu vs continuous zoom through eye winking. Six participants were recruited to perform skin suturing simulation and completed a survey and interview. Next we assessed the performance and limitations of AR digital magnification. Varjo XR-3 was utilized to address the hardware limitations. Participants performed anastomotic suturing tasks with progressively finer suture, then completed a survey and interview. FINDINGS: There was no strong preference between zoom methods, although participants felt the discrete zoom was easier to use. Participants had difficulty determining depth and visualizing the suture due to limitations of digital magnification. Using Wilcoxon rank sum test to examine differences in system usability scale, the Phase 2 user experience had significant difference in percentile distribution (P 0.0390). CONCLUSION: Virtual loupes may be a valuable tool for plastic surgeons, with potential for variable magnification and advanced visualization. Improvements in the hardware yielded higher ratings of system usability and user experience. Further development is needed to address the limitations of existing devices.

Genomic Discovery and Structure-Activity Exploration of a Novel Family of Enzyme-Activated Covalent Cyclin-Dependent Kinase Inhibitors.

Fungi have historically been the source of numerous important medicinal compounds, but full exploitation of their genetic potential for drug development has been hampered in traditional discovery paradigms. Here we describe a radically different approach, top-down drug discovery (TD3), starting with a massive digital search through a database of over 100,000 fully genomicized fungi to identify loci encoding molecules with a predetermined human target. We exemplify TD3 by the selection of cyclin-dependent kinases (CDKs) as targets and the discovery of two molecules, 1 and 2, which inhibit therapeutically important human CDKs. 1 and 2 exhibit a remarkable mechanism, forming a site-selective covalent bond to the CDK active site Lys. We explored the structure-activity relationship via semi- and total synthesis, generating an analog, 43, with improved kinase selectivity, bioavailability, and efficacy. This work highlights the power of TD3 to identify mechanistically and structurally novel molecules for the development of new medicines.

Has Active Surveillance for Prostate Cancer Become Safer? Lessons Learned from a Global Clinical Registry.

BACKGROUND AND OBJECTIVE: Active surveillance (AS) has evolved into a widely applied treatment strategy for many men around the world with low-risk prostate cancer (or in selected cases intermediate-risk disease). Here, we report on the safety and acceptability of AS, and treatment outcomes for low- and intermediate-risk tumours over time in 14 623 men with follow-up of over 6 yr. METHODS: Clinical data from 26 999 men on AS from 25 cohorts in 15 countries have been collected in an international database from 2000 onwards. KEY FINDINGS AND LIMITATIONS: Across our predefined four time periods of 4 yr each (covering the period 2000-2016), there was no significant change in overall survival (OS). However, metastasis-free survival (MFS) rates have improved since the second period and were excellent (>99%). Treatment-free survival rates for earlier periods showed a slightly more rapid shift to radical treatment. Over time, there was a constant proportion of 5% of men for whom anxiety was registered as the reason for treatment alteration. There was, however, also a subset of 10-15% in whom treatment was changed, for which no apparent reason was available. In a subset of men (10-15%), tumour progression was the trigger for treatment. In men who opted for radical treatment, surgery was the most common treatment modality. In those men who underwent radical treatment, 90% were free from biochemical recurrence at 5 yr after treatment. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study confirms that AS was a safe management option over the full duration in this large multicentre cohort with long-term follow-up, given the 84.1% OS and 99.4% MFS at 10 yr. The probability of treatment at 10 yr was 20% in men with initial low-risk tumours and 31% in men with intermediate-risk tumours. New diagnostic modalities may improve the acceptability of follow-up using individual risk assessments, while safely broadening the use of AS in higher-risk tumours. PATIENT SUMMARY: Active surveillance (AS) has evolved into a widely applied treatment strategy for many men with prostate cancer around the world. In this report, we show the long-term safety of following AS for men with low- and intermediate-risk prostate cancer. Our study confirms AS as a safe management option for low- and intermediate-risk prostate cancer. New diagnostic modalities may improve the acceptability of follow-up using individual risk assessments, while safely broadening the use of AS in higher-risk tumours.

Canadian nurse initiated analgesia protocol to reduce delays in the emergency department: A quality improvement study.

BACKGROUND: Australian literature supports nurse-initiated opioid analgesia protocols may be effective, but this practice is not yet widely adopted in Canada. LOCAL PROBLEM: Previous quality audits of Emergency Departments (EDs) in Victoria (Canada) indicate long delays to administration of analgesia. METHODS: Two tertiary care hospitals in a Canadian city of approximately 400,000 people were chosen for a quality improvement initiative. A manual retrospective chart review was conducted on a total of 122 patients which was compared to data from 125 patients from a previous audit in 2019. INTERVENTIONS: ED nursing staff both hospitals were provided education and daily reminders to document pain score at triage, and to flag an acute analgesia opioid order set on the charts of patients with moderate or severe pain (greater than 4 out of 10 in the Numerical Rating Scale (NRS) or by triage nurse's clinical judgment). At Victoria General Hospital (VGH), nurses had the option of finding an emergency physician (EP) to sign the acute analgesia opioid order set, or independently administer IV opioids from a presigned order set without consulting an EP. At Royal Jubilee Hospital (RJH), nursing staff could only administer IV opioids from the order set after an EP was consulted. Median time to opioid analgesia after the intervention was compared to 2019 data for each hospital. RESULTS: Each hospital significantly reduced median time to administration of opioids: VGH achieved 45.6 % reduction (1 h 8 min improvement, p = 0.001) and RJH achieved a 62.5 % reduction (2 h 11 min improvement, p < 0.001). Secondary outcomes indicated patients may receive analgesia faster when the opioid protocol was nurse initiated (median 43 minutes) vs physician initiated (median 1 h 1 min) at VGH. Pain score documentation at triage improved from <10 % in 2019 to >50 % in 2020 at both sites. Approximately 95 % of EP and nursing staff thought nurse-initiated opioids are safe, effective, and should be supported by regulatory boards. CONCLUSION: Implementing a new triage protocol to expedite initiation of an analgesic protocol was associated with significantly reduced time to analgesia for patients with moderate to severe pain. Time reductions may be greater with nurse-initiated analgesia before physician assessment.

Robotic-Assisted Bladder Diverticulectomy: Indications, Technique, and Outcomes-A Case Series.

Purpose: This case series describes the experiences and outcomes of multiple Australian surgeons performing robotic-assisted bladder diverticulectomy (RABD), highlighting the procedural effectiveness and safety, for both benign and malignant indications for diverticulectomy. Methods: Outcomes were analyzed from 13 experienced Australian urologists who performed RABD between 2016 and 2023. Retrospective analysis was performed on prospectively collected data, which included patient demographics, diverticulum characteristics, surgical approaches, and post-operative outcomes. Surgical techniques included the extravesical and intravesical approaches, with the focus on maintaining oncological principles in cases of malignancy. Results: A total of 28 patients underwent RABD, with the majority being male and a mean age of 63.9 years. All surgeons utilized a four-port transperitoneal approach and opted for the extravesical dissection of the diverticular neck; one case utilized both an extravesical and a trans-diverticular approach. Functional outcomes demonstrated symptomatic resolution in patients with nonmalignant diverticula, whereas oncological outcomes indicated clear margins in 90% of malignant cases. The average length of the procedure was 106 minutes, with minimal blood loss and a mean hospital stay of 2.67 days. Early complications occurred in 14% with the majority Clavien-Dindo grade II. Conclusion: Robotic bladder diverticulectomy, predominantly via the transperitoneal extravesical approach, has emerged as a safe, effective, and reliable surgical intervention for both malignant and nonmalignant bladder diverticula. The consistent surgical approach and excellent outcomes demonstrated in this case series reinforce the procedure's potential as a safe option, even in the setting of malignancy within a diverticulum.

Mediation Analysis of Racial Disparity for Infant Mortality Using Bayesian Estimation of Potential Outcomes.

Background/Objectives: While the overall rate of infant mortality in the United States has been decreasing over decades, the racial disparity, defined as the difference between races, has increased. Even though a person's race cannot change, it may be possible to identify factors that mediate or cause this racial disparity. Evaluating the factors that mediate or cause racial disparity is imperative because current clinical recommendations could be based on preventative modalities that are more effective for white women and their children. Methods: A Bayesian approach modeled the data from the full United States National Natality Database for the years 2016 to 2018. The binomial rate parameters for each combination of race and mediators provided the potential outcomes. Estimating the mediation outcomes, including total effect, controlled direct effect, mediated effect, and proportion mediated used common counterfactual definitions for these probabilities. Results: Maternal smoking, low birthweight, and teenage maternity interacted in causing racial disparity for infant mortality. The proportion of racial disparity attributable to low birthweight was approximately 0.73, with only small variations attributable to maternal smoking and teenage maternity. Conclusions: The novel approach facilitated modeling of multiple mediators. Low birthweight caused racial disparity for infant mortality. The model can be extended to evaluate additional mediational factors with the objective of identifying the preventable causes.

Beyond Prostate Imaging Reporting and Data System: Combining Magnetic Resonance Imaging Prostate Imaging Reporting and Data System and Prostate-Specific Membrane Antigen-Positron Emission Tomography/Computed Tomography PRIMARY Score in a Composite (P) Score for More Accurate Diagnosis of Clinically Significant Prostate Cancer.

PURPOSE: The Prostate Imaging Reporting and Data System (PI-RADS) score is standard of care for clinically significant prostate cancer (csPCa) diagnosis. The PRIMARY score (prostate-specific membrane antigen [PSMA]-positron emission tomography [PET]/CT) also has high diagnostic accuracy for csPCa. This study aimed to develop an easily calculated combined (P) score for csPCa detection (International Society of Urological Pathology [ISUP] ≥2) incorporating separately read PI-RADS and PRIMARY scores, with external validation. MATERIALS AND METHODS: Two datasets of men with suspected PCa, no prior biopsy, recent MRI and 68Ga-PSMA-11-PET/CT, and subsequent transperineal biopsy were evaluated. These included the development sample (n = 291, 56% csPCa) a prospective trial and the validation sample (n = 227, 67% csPCa) a multicenter retrospective database. Primary outcome was detection of csPCa (ISUP ≥2), with ISUP ≥ 3 cancer detection a secondary outcome. Score performance was evaluated by area under the curve, sensitivity, specificity, and decision curve analysis. RESULTS: The 5-point combined (P) score was developed in a prospective dataset. In the validation dataset, csPCa was identified in 0%, 20%, 52%, 96%, and 100% for P score 1 to 5. The area under the curve was 0.93 (95% CI: 0.90-0.96), higher than PI-RADS 0.89 (95% CI: 0.85-0.93, P = .039) and PRIMARY score alone 0.84 (95% CI: 0.79-0.89, P < .001). Splitting scores at 1/2 (negative) vs 3/4/5 (positive), P score sensitivity was 94% (95% CI: 89-97) compared to PI-RADS 89% (95% CI: 83-93) and PRIMARY score 86% (95% CI: 79-91). For ISUP ≥ 3, P score sensitivity was 99% (95% CI: 95-100) vs 94% (95% CI: 88-98) and 92% (95% CI: 85-97) for PI-RADS and PRIMARY scores respectively. A maximum standardized uptake value > 12 (P score 5) was ISUP ≥ 2 in all cases with 93% ISUP ≥ 3. CONCLUSIONS: The P score is easily calculated and improves accuracy for csPCa over both PI-RADS and PRIMARY scores. It should be considered when PSMA-PET is undertaken for diagnosis.

Responding to the real problem of sustainable resuscitation skills with real assessment. Mixed-methods evaluation of an authentic assessment programme.

INTRODUCTION: The retention of resuscitation skills is a widespread concern, with a rapid decay in competence frequently following training. Meanwhile, training programmes continue to be disconnected with real-world expectations and assessment designs remain in conflict with the evidence for sustainable learning. This study aimed to evaluate a programmatic assessment pedagogy which employed entrustment decision and the principles of authentic and sustainable assessment (SA). METHODS: We conducted a prospective sequential explanatory mixed methods study to understand and address the sustainable learning challenges faced by final-year undergraduate paramedic students. We introduced a programme of five authentic assessments based on actual resuscitation cases, each integrating contextual elements that featured in these real-life events. The student-tutor consensus assessment (STCA) tool was configured to accommodate an entrustment scale framework. Each test produced dual student led and assessor scores. Students and assessors were surveyed about their experiences with the assessment methodologies and asked to evaluate the programme using the Ottawa Good Assessment Criteria. RESULTS: Eighty-four students participated in five assessments, generating dual assessor-only and student-led results. There was a reported mean score increase of 9% across the five tests and an 18% reduction in borderline or below scores. No statistical significance was observed among the scores from eight assessors across 420 unique tests. The mean student consensus remained above 91% in all 420 tests. Both student and assessor participant groups expressed broad agreement that the Ottawa criteria were well-represented in the design, and they shared their preference for the authentic methodology over traditional approaches. CONCLUSION: In addition to confirming local sustainability issues, this study has highlighted the validity concerns that exist with conventional resuscitation training designs. We have successfully demonstrated an alternative pedagogy which responds to these concerns, and which embodies the principles of SA, quality in assessment practice, and the real-world expectations of professionals.

Momentum-exchange interactions in a Bragg atom interferometer suppress Doppler dephasing.

Large ensembles of laser-cooled atoms interacting through infinite-range photon-mediated interactions are powerful platforms for quantum simulation and sensing. Here we realize momentum-exchange interactions in which pairs of atoms exchange their momentum states by collective emission and absorption of photons from a common cavity mode, a process equivalent to a spin-exchange or XX collective Heisenberg interaction. The momentum-exchange interaction leads to an observed all-to-all Ising-like interaction in a matter-wave interferometer. A many-body energy gap also emerges, effectively binding interferometer matter-wave packets together to suppress Doppler dephasing in analogy to Mössbauer spectroscopy. The tunable momentum-exchange interaction expands the capabilities of quantum interaction-enhanced matter-wave interferometry and may enable the realization of exotic behaviors, including simulations of superconductors and dynamical gauge fields.

Forensic geoscience non-invasive detection and characterisation of underground clandestine complexes, bunkers, tunnels and firing ranges.

Recent events in conflict zones have emphasized that the successful detection and characterisation of buried clandestine complexes, bunkers and tunnels is vitally important for forensic investigators globally, to reduce or solve criminal activities, address national security threats and avoid potential terrorist attacks. However, this can often prove very difficult, particularly in urban areas, with potentially both below-ground non target items and above-ground infrastructures present, that can interfere with detecting target(s). Here we provide selected successful case studies where forensic geoscience techniques were used to detect and characterise buried clandestine complexes, bunkers and tunnels using different geophysical techniques. Generally, desktop studies assessing pre-existing information, including local geology, soils, historical/modern remote sensing, maps and photographs inform appropriate geophysical survey technique(s) selection. Subsequent near-surface geophysical techniques are then employed to produce accurate plans of sub-surface targets, with numerical modelling and correction for the interfering effects of above ground infrastructure, enabling the calibration of geophysical datasets to provide confidence in their respective interpretations. All forensic investigations are, of course, unique to every site, and thus require an individual approach to their respective ground conditions. Investigations should be both phased and iterative, with techniques tailored to local conditions: the selection of geophysical method(s) is crucial to improve successful detection rates of such important buried targets.

Heritability and genome-wide association study of vaccine-induced immune response in Beagles: A pilot study.

Both genetic and non-genetic factors contribute to individual variation in the immune response to vaccination. Understanding how genetic background influences variation in both magnitude and persistence of vaccine-induced immunity is vital for improving vaccine development and identifying possible causes of vaccine failure. Dogs provide a relevant biomedical model for investigating mammalian vaccine genetics; canine breed structure and long linkage disequilibrium simplify genetic studies in this species compared to humans. The objective of this study was to estimate the heritability of the antibody response to vaccination against viral and bacterial pathogens, and to identify genes driving variation of the immune response to vaccination in Beagles. Sixty puppies were immunized following a standard vaccination schedule with an attenuated combination vaccine containing antigens for canine adenovirus type 2, canine distemper virus, canine parainfluenza virus, canine parvovirus, and four strains of Leptospira bacteria. Serum antibody measurements for each viral and bacterial component were measured at multiple time points. Heritability estimations and GWAS were conducted using SNP genotypes at 279,902 markers together with serum antibody titer phenotypes. The heritability estimates were: (1) to Leptospira antigens, ranging from 0.178 to 0.628; and (2) to viral antigens, ranging from 0.199 to 0.588. There was not a significant difference between overall heritability of vaccine-induced immune response to Leptospira antigens compared to viral antigens. Genetic architecture indicates that SNPs of low to high effect contribute to immune response to vaccination. GWAS identified two genetic markers associated with vaccine-induced immune response phenotypes. Collectively, these findings indicate that genetic regulation of the immune response to vaccination is antigen-specific and influenced by multiple genes of small effect.

Innovative, combinatorial and high-throughput approaches to degrader synthesis.

Targeted protein degraders such as PROTACs and molecular glues are a rapidly emerging therapeutic modality within industry and academia. Degraders possess unique mechanisms of action that lead to the removal of specific proteins by co-opting the cell's natural degradation mechanisms via induced proximity. Their optimisation thus far has often been largely empirical, requiring the synthesis and screening of a large number of analogues. In addition, the synthesis and development of degraders is often challenging, leading to lengthy optimisation campaigns to deliver candidate-quality compounds. This review highlights how the synthesis of degraders has evolved in recent years, in particular focusing on means of applying high-throughput chemistry and screening approaches to expedite these timelines, which we anticipate to be valuable in shaping the future of degrader optimisation campaigns.

Patient-Derived Xenografts: Historical Evolution, Immunocompromised Host Models, and Translational Significance.

Patient-derived xenografts (PDXs) represent a critical advancement in preclinical cancer research, wherein human tumor samples are implanted into animal models for evaluation of therapeutic responses. PDXs have emerged as indispensable tools in translational cancer research, facilitating investigation into tumor microenvironments and personalized medicine. This chapter elucidates the historical evolution of PDXs, from early attempts in the eighteenth century to contemporary immunocompromised host models that enhance engraftment success.

Hunter-Gatherer children's close-proximity networks: Similarities and differences with cooperative and communal breeding systems.

Among vertebrates, allomothering (non-maternal care) is classified as cooperative breeding (help from sexually mature non-breeders, usually close relatives) or communal breeding (shared care between multiple breeders who are not necessarily related). Humans have been described with both labels, most frequently as cooperative breeders. However, few studies have quantified the relative contributions of allomothers according to whether they are (a) sexually mature and reproductively active and (b) related or unrelated. We constructed close-proximity networks of Agta and BaYaka hunter-gatherers. We used portable remote-sensing devices to quantify the proportion of time children under the age of 4 spent in close proximity to different categories of potential allomother. Both related and unrelated, and reproductively active and inactive, campmates had substantial involvement in children's close-proximity networks. Unrelated campmates, siblings and subadults were the most involved in both populations, whereas the involvement of fathers and grandmothers was the most variable between the two populations. Finally, the involvement of sexually mature, reproductively inactive adults was low. Where possible, we compared our findings with studies of other hunter-gatherer societies, and observed numerous consistent trends. Based on our results we discuss why hunter-gatherer allomothering cannot be fully characterised as cooperative or communal breeding.

Convergently evolved placental villi show multiscale structural adaptations to differential placental invasiveness.

Despite having a single evolutionary origin and conserved function, the mammalian placenta exhibits radical structural diversity. The evolutionary drivers and functional consequences of placental structural diversity are poorly understood. Humans and equids both display treelike placental villi, however these villi evolved independently and exhibit starkly different levels of invasiveness into maternal tissue (i.e. the number of maternal tissue layers between placental tissue and maternal blood). The villi in these species therefore serve as a compelling evolutionary case study to explore whether placentas have developed structural adaptations to respond to the challenge of reduced nutrient availability in less invasive placentas. Here, we use three-dimensional X-ray microfocus computed tomography and electron microscopy to quantitatively evaluate key structures involved in exchange in human and equid placental villi. We find that equid villi have a higher surface area to volume ratio and deeper trophoblastic vessel indentation than human villi. Using illustrative computational models, we propose that these structural adaptations have evolved in equids to boost nutrient transfer to compensate for reduced invasiveness into maternal tissue. We discuss these findings in relation to the 'maternal-fetal conflict hypothesis' of placental evolution.