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IntroductionIn academic breast surgery, ultrasound use tends to be limited to radiology departments, thus formal surgical resident training in breast ultrasound is sparse. Building on residents' ultrasound skills in our general surgery training program, we developed a novel curriculum to teach ultrasound-guided breast procedures (UGBPs), including core needle biopsy (CNB) and wire localization (WL). We hypothesized that learning UGBPs on cadavers would be preferred to learning with a breast phantom model using chicken breasts.MethodsResidents received a 1-h lecture on breast CNB and WL followed by a 1-h hands-on laboratory session. Olives stuffed with red pimentos were used to replicate breast masses and implanted in chicken breasts and the breasts of lightly embalmed and unembalmed female cadavers. All residents practiced UGBPs with a course instructor on both models. Residents completed anonymous prelaboratory and postlaboratory surveys utilizing five-point Likert scales.ResultsA total of 35 trainees participated in the didactics; all completed the prelaboratory survey and 28 completed the postlaboratory survey. Participant clinical year ranged from 1 to 6. Residents' confidence in describing and performing CNBs and WLs increased significantly on postlaboratory surveys, controlling for clinical year (P

Cotton (Gossypium hirsutum L.) is the key renewable fibre crop worldwide, yet its yield and fibre quality show high variability due to genotype-specific traits and complex interactions among cultivars, management practices and environmental factors. Modern breeding practices may limit future yield gains due to a narrow founding gene pool. Precision breeding and biotechnological approaches offer potential solutions, contingent on accurate cultivar-specific data. Here we address this need by generating high-quality reference genomes for three modern cotton cultivars (UGA230, UA48 and CSX8308) and updating the TM-1 cotton genetic standard reference. Despite hypothesized genetic uniformity, considerable sequence and structural variation was observed among the four genomes, which overlap with ancient and ongoing genomic introgressions from Pima cotton, gene regulatory mechanisms and phenotypic trait divergence. Differentially expressed genes across fibre development correlate with fibre production, potentially contributing to the distinctive fibre quality traits observed in modern cotton cultivars. These genomes and comparative analyses provide a valuable foundation for future genetic endeavours to enhance global cotton yield and sustainability.

BACKGROUND: Double lumen endobronchial tubes (DLTs) are frequently used to employ single lung ventilation strategies during thoracic surgical procedures. Placement of these tubes can be challenging even for experienced clinicians. We hypothesized that airway anatomy, particularly of the glottis and proximal trachea, significantly impacts the ease or difficulty in placement of these tubes. METHODS: Images from 24 randomly selected Positron Emission Tomography - Computed Tomography (PET-CT) scans were evaluated for several anatomic aspects of the upper airway, including size and angulation of the glottis and proximal tracheal using calibrated CT measurements and an online digital protractor. The anatomic issues identified were confirmed in cadaveric anatomic models. RESULTS: Proximal tracheal diameter measurements in PET-CT scans demonstrated a mean ± standard deviation of 20.4 ± 2.5 mm in 12 males and 15.5 ± 0.98 mm in 12 females (p

State wildlife agency professionals are realizing they need new mindsets and practices for collaboration with diverse stakeholders and community partners to achieve policy, management, science, and education goals. This realization led to a partnership between a state agency, a land-grant university's outreach and engagement office, and University Extension to codesign professional development certificate programs about community engagement. The authors describe the codevelopment process of both basic and advanced community engagement certificate programs, including goals, descriptions, curricula, and evaluation outcomes. Three years of programming resulted in lessons learned about moving community engagement concepts from theory to practice, the value of participant-generated case studies, and the importance of opportunities for adult learners to practice new ideas in their own professional contexts. In addition to participant impacts, the authors share how this codevelopment process and partnership has improved practices and influenced culture change in the state agency, university, and Extension.

INTRODUCTION: In two-stage exchange for periprosthetic joint infection (PJI), adding antibiotics to cement spacers is the standard of care; however, little is known about optimal dosage. There is emphasis on using >3.6 g of total antibiotic, including ≥2.0 g of vancomycin, per 40 g of cement, but these recommendations lack clinical evidence. We examined whether recommended antibiotic spacer doses affect treatment success. METHODS: This was a retrospective review of 202 patients who underwent two-stage exchange for PJI from 2004 to 2020 with at least 1-year follow-up. Patients were separated into high (>3.6 g of total antibiotic per 40 g of cement) and low-dose spacer groups. Primary outcomes were overall and infectious failure. RESULTS: High-dose spacers were used in 80% (162/202) of patients. High-dose spacers had a reduced risk of overall (OR, 0.37; P = 0.024) and infectious (OR, 0.35; P = 0.020) failure for infected primary arthroplasties, but not revisions. In multivariate analysis, vancomycin dose ≥2.0 g decreased the risk of infectious failure (OR, 0.31; P = 0.016), although not overall failure (OR, 0.51; P = 0.147). CONCLUSION: During two-stage exchange for PJI, spacers with greater than 3.6 g of total antibiotic may reduce overall and infectious failure for infected primary arthroplasties. Furthermore, using at least 2.0 g of vancomycin could independently decrease the risk of infectious failure.

The Strongyloides genus of parasitic nematodes have a fascinating life cycle and biology, but are also important pathogens of people and a World Health Organization-defined neglected tropical disease. Here, a community of Strongyloides researchers have posed thirteen major questions about Strongyloides biology and infection that sets a Strongyloides research agenda for the future. This article is part of the Theo Murphy meeting issue Strongyloides: omics to worm-free populations.

Abstract Northern regions are warming faster than the rest of the globe. It is difficult to predict ecosystem responses to warming because the thermal sensitivity of their biophysical components varies. Here, we present an analysis of the authors’ expert judgment regarding the sensitivity of six ecosystem components – permafrost, peatlands, lakes, snowpack, vegetation, and endothermic vertebrates – across northern landscapes ranging from boreal to polar biomes. We identified 28 discontinuous component states across a 3700 km latitudinal gradient in northeastern North America and quantified sensitivity as the transition time from an initial to a contrasting state following a theoretical step change increase in mean annual air temperature of 5 °C. We infer that multiple interconnected state shifts are likely to occur within a narrow subarctic latitudinal band at timescales of 10 to more than 100 years, and response times decrease with latitude. Response times differ between components and across latitudes, which is likely to impair the integrity of ecosystems.

Abstract Continuous exposure to environmental hypoxia (11% O2) has been shown to markedly slow the progressive degeneration of retinal ganglion cells (RGCs) in a mouse model of mitochondrial optic neuropathy with RGC-specific deletion of the key mitochondrial complex I accessory subunit ndufs4. As a first step toward identifying the therapeutic mechanism of hypoxia in this model, we conducted a series of experiments to investigate the role of the hypoxia-inducible factor (HIF) regulatory pathway in RGC neuroprotection. Vglut2-Cre; ndufs4 loxP/loxP mice were crossed with strains bearing floxed alleles of the negative HIF regulatory vhl or of the two major HIF α-subunit isoforms, Hif1α and Hif2α. Deletion of vhl within ndufs4-deficient RGCs failed to prevent RGC degeneration under normoxia, indicating that HIF activation is not sufficient to achieve RGC rescue. Furthermore, the rescue of ndufs4-deficient RGCs by hypoxia remained robust despite genetic inactivation of Hif1α and Hif2α. Our findings demonstrate that the HIF pathway is entirely dispensable to the rescue of RGCs by hypoxia. Future efforts to uncover key HIF-independent molecular pathways induced by hypoxia in this mouse model may be of therapeutic relevance to mitochondrial optic neuropathies such as Leber hereditary optic neuropathy.

Abstract Background Despite the growing interest in the use of human genomic data for drug target identification and validation, the extent to which the spectrum of human disease has been addressed by genome-wide association studies (GWAS), or by drug development, and the degree to which these efforts overlap remain unclear. Methods In this study we harmonize and integrate different data sources to create a sample space of all the human drug targets and diseases and identify points of convergence or divergence of GWAS and drug development efforts. Results We show that only 612 of 11,158 diseases listed in Human Disease Ontology have an approved drug treatment in at least one region of the world. Of the 1414 diseases that are the subject of preclinical or clinical phase drug development, only 666 have been investigated in GWAS. Conversely, of the 1914 human diseases that have been the subject of GWAS, 1121 have yet to be investigated in drug development. Conclusions We produce target-disease indication lists to help the pharmaceutical industry to prioritize future drug development efforts based on genetic evidence, academia to prioritize future GWAS for diseases without effective treatments, and both sectors to harness genetic evidence to expand the indications for licensed drugs or to identify repurposing opportunities for clinical candidates that failed in their originally intended indication.

Abstract Background The importance of parental diet in relation to eventual offspring health is increasing in prominence due to the increased frequency of parents of reproductive age consuming poor diets. Whilst maternal health and offspring outcome have been studied in some detail, the paternal impacts are not as well understood. A father’s poor nutritional status has been shown to have negative consequences on foetal growth and development and ultimately impact the long-term adult health of the offspring. In this study, we examined sperm- and seminal vesicle fluid-mediated mechanisms of preimplantation embryo development alterations in response to sub-optimal paternal diets. Results Male mice were fed a diet to model either under (low-protein diet (LPD)) or over (high-fat/sugar ‘Western’ diet (WD)) nutrition, LPD or WD supplemented with methyl donors or a control diet (CD) before mating with age-matched females. Male metabolic health was influenced by WD and MD-WD, with significant changes in multiple serum lipid classes and hepatic 1-carbon metabolites. Sperm RNA sequencing revealed significant changes to mRNA profiles in all groups when compared to CD (LPD: 32, MD-LPD: 17, WD: 53, MD-WD: 35 transcripts). Separate analysis of the seminal vesicle fluid proteome revealed a significant number of differentially expressed proteins in all groups (LPD: 13, MD-LPD: 27, WD: 24, MD-WD: 19) when compared to control. Following mating, in vitro time-lapse imaging of preimplantation embryos revealed a significant increase in the timing of development in all experimental groups when compared to CD embryos. Finally, qPCR analysis of uterine tissue at the time of implantation identified perturbed expression of Cd14 and Ptgs1 following mating with WD-fed males. Conclusions Our current study shows that paternal nutritional status has the potential to influence male metabolic and reproductive health, impacting on embryonic development and the maternal reproductive tract. This study highlights potential direct (sperm-mediated) and indirect (seminal vesicle fluid-mediated) pathways in which a father’s poor diet could shape the long-term health of his offspring.

Abstract Monocytes, the circulating macrophage precursors, contribute to diseases like atherosclerosis and asthma. Long non-coding RNAs (lncRNAs) have been shown to modulate the phenotype and inflammatory capacity of monocytes. We previously discovered the lncRNA SMANTIS, which contributes to cellular phenotype expression by controlling BRG1 in mesenchymal cells. Here, we report that SMANTIS is particularly highly expressed in monocytes and lost during differentiation into macrophages. Moreover, different types of myeloid leukemia presented specific SMANTIS expression patterns. Interaction studies revealed that SMANTIS binds RUNX1, a transcription factor frequently mutated in AML, primarily through its Alu-element on the RUNT domain. RNA-seq after CRISPR/Cas9-mediated deletion of SMANTIS or RUNX1 revealed an association with cell adhesion and both limited the monocyte adhesion to endothelial cells. Mechanistically, SMANTIS KO reduced RUNX1 genomic binding and altered the interaction of RUNX1 with EP300 and CBFB. Collectively, SMANTIS interacts with RUNX1 and attenuates monocyte adhesion, which might limit monocyte vascular egress.

Abstract Nanomechanical oscillators are an alternative platform for computation in harsh environments. However, external perturbations arising from such environments may hinder information processing by introducing errors into the computing system. Here, we simulate the dynamics of three coupled Duffing oscillators whose multiple equilibrium states can be used for information processing and storage. Our analysis reveals that, within experimentally relevant parameters, error correcting dynamics can emerge, wherein the system’s state is robust against random external impulses. We find that oscillators in this configuration have several surprising and attractive features, including dynamic isolation of resonators exposed to extreme impulses and the ability to correct simultaneous errors.

Summary: Dupuytren's disease continues to present many challenges for the surgeon. A variety of surgical approaches and their variations have been described in the literature, further complicated by the degree of skin shortage and/or the need for local flap procedures or a full thickness skin graft. In the face of all these decisions – none of which is supported by Level 1 evidence – it can be very difficult to plan the best incision(s). We describe a safe and reproducible technique to plan fasciectomy incisions in primary or recurrent Dupuytren's disease. Our short communication and accompanying artwork demonstrates the anatomical landmarks and a simple decision-making algorithm based on just 3 key stages: (1) Proximal incision planning and execution of the palmar release(s); (2) Extension distally into the digit(s) based on the tissue quality, with either with zigzag (Brunner's) or a midline longitudinal (McIndoe) incision(s); (3) Flap assisted closure or coverage with a full thickness skin graft where required.

Background: Despite literature recognising the huge potential of co-production as a positive approach to evidence creation, there is a dearth of evidence about how co-production principles can problematise knowledge exchange, specifically in evaluation work. Aims: To critically examine three evaluation projects commissioned by voluntary sector stakeholders to illustrate challenges in knowledge exchange linked to the co-production of evidence exchange. Methods: We critically compare the challenges experienced in co-producing evidence across three evaluations, reflecting on power dynamics, co-productive ways of working and emotions, which all impact upon successful knowledge exchange. Findings: In Project 1, internal monitoring data required for reporting was not shared. In Project 2, the commissioners' need to evidence success resulted in limited knowledge sharing, with valuable learning about partnership issues and service delivery held internally. In Project 3, evidence demonstrating the failure of a local authority model of area management for community members was partially discredited by statutory stakeholders (state actors). Discussion and conclusions: Bias in evaluation reporting and academic publication can arise from current knowledge exchange processes, including co-production. Voluntary sector funding is problematic as stakeholders delivering programmes also commission evaluations. Knowledge exchange is influenced by vested interests arising from the political context in which data is gathered. Evaluators can face aggression, challenge and unfair treatment resulting in damaged relationships, and failures in knowledge exchange. The emotional elements of knowledge exchange remain under-reported. Varying and shifting power dynamics also limit knowledge exchange. Changing research practice, to support power sharing, needs further exploration to facilitate improved knowledge exchange.

Increasing the numbers of Indigenous people enrolled in research higher degrees in Australia is important for building the Indigenous academic workforce, broadening the scope of knowledge production in academic institutions and ensuring effective research outcomes for Indigenous Australians. While the numbers of Indigenous research higher degree students are increasing, universities still have a lot to do to bring that number up to parity. In this paper, we explore the value of a pre-doctoral program developed for Indigenous people interested in doing a PhD that provides them the information they need to inform their choices about undertaking a doctoral project. As the only program of this kind in Australia, this research contributes to the emerging literature on the factors that have an influence on why Indigenous people choose to undertake PhD programs and the effectiveness of initiatives to support their pathway to higher degree research. The research outcomes build on the evidence base for improving initiatives across the university sector, highlighting the need for tailored, Indigenous-led pre-doctoral support programs for Indigenous students, the value of cohort experiences and the importance of universities that value Indigenous people and their knowledge systems.

This paper explores linguistic life-histories from five participants in a larger interview study with U.S.-based adults. These five interviewees were middle-class White women from monolingual English-speaking families who pursued multilingual learning trajectories in young adulthood. Having previously attained proficiency in one language through academic study, all five recounted similar pivotal decisions to deprioritize that language, and instead invest in another language that they now saw as more socially relevant. Through discursive analysis of the emotionality and (lack of) agency in their narratives of linguistic decision-making, the paper demonstrates how all five women, in dialogue with the interviewer, co-constructed ideologies of linguistic solidarity across lines of social difference. Drawing on Bakhtinian theory to analyze identity development as ideological becoming, the research explores elite contestation of dominant language ideologies within interview dialogues.

Abstract: Over recent decades, our understanding of climate change has accelerated greatly, but unfortunately, observable impacts have increased in tandem. Both mitigation and adaptation have not progressed at the level or scale warranted by our collective knowledge on climate change. More effective approaches to engage people on current and future anthropogenic climate change effects are urgently needed. Here, we show how species whose distributions are shifting in response to climate change, that is, ‘species‐on‐the‐move’, present an opportunity to engage people with climate change by linking to human values, and our deep connections with the places in which we live, in a locally relevant yet globally coherent narrative. Species‐on‐the‐move can impact ecosystem structure and function, food security, human health, livelihoods, culture and even the climate itself through feedback to the climate system, presenting a wide variety of potential pathways for people to understand that climate change affects them personally as individuals. Citizen science focussed on documenting changes in biodiversity is one approach to foster a deeper engagement on climate change. However, other possible avenues, which may offer potential to engage people currently unconnected with nature, include arts, games or collaborations with rural agriculture (e.g. new occurrences of pest species) or fisheries organisations (e.g. shifting stocks) or healthcare providers (e.g. changing distributions of disease vectors). Through the importance we place on the aspects of life impacted by the redistribution of species around us, species‐on‐the‐move offer emotional pathways to connect with people on the complex issue of climate change in profound ways that have the potential to engender interest and action on climate change. Read the free Plain Language Summary for this article on the Journal blog.