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Transgender and gender diverse (TGD) people experience disparities in cancer care, including more late-stage diagnoses, worse cancer-related outcomes, and an increased number of unaddressed and more severe symptoms related to cancer and cancer-directed therapy. This article outlines plans to address the unique needs of TGD people through a TGD-focused oncology clinic. Such a clinic could be structured by upholding the following tenets: (1) champion a supportive, gender-affirming environment that seeks to continuously improve, (2) include a transdisciplinary team of specialists who are dedicated to TGD cancer care, and (3) initiate and embrace TGD-patient-centric research on health outcomes and health care delivery.

Abstract Background Preterm birth is a major cause of infant mortality and morbidity and accounts for 7–8% of births in the UK. It is more common in women from socially deprived areas and from minority ethnic groups, but the reasons for this disparity are poorly understood. To inform interventions to improve child survival and their quality of life, this study examined the socioeconomic and ethnic inequalities in preterm births (

Transgender and gender-diverse (TGD) persons represent a small but growing population in the United States. Accessing inclusive, equitable, and evidence-based healthcare remains a challenge for this patient population. Many TGD persons seek gender-affirming care, including gender-affirming hormonal therapy (GAHT) and gender-affirming surgery (GAS), to help ameliorate the physical and mental aspects of their gender incongruence. Both GAHT and GAS induce clinically important histopathologic and anatomic changes in breast tissue. Consequently, breast care in TGD persons has become an increasingly recognized topic of importance in gender-affirming care. However, there remains a scarce but growing base of literature specifically addressing the unique healthcare needs of breast care in TGD patients. This article will review how to establish trusting patient–provider relationships for TGD patients, gender inclusivity in breast clinics and imaging centers, the influence of GAHT and GAS on breast tissue, breast cancer screening recommendations and barriers, and breast cancer risk and treatment considerations in TGD persons.

DNA methyltransferase 1 (DNMT1) is the enzyme primarily responsible for propagation of the methylation pattern in cells. Mutations in DNMT1 have been linked to the development of adult-onset neurodegenerative disorders; these disease-associated mutations occur in the regulatory replication foci-targeting sequence (RFTS) domain of the protein. The RFTS domain is an endogenous inhibitor of DNMT1 activity that binds to the active site and prevents DNA binding. Here, we examine the impact of the disease-associated mutation A554V on normal RFTS-mediated inhibition of DNMT1. Wild-type and mutant proteins were expressed and purified to homogeneity for biochemical characterization. The mutation increased DNA binding affinity ~8-fold. In addition, the mutant enzyme exhibited increased DNA methylation activity. Circular dichroism (CD) spectroscopy revealed that the mutation does not significantly impact the secondary structure or relative thermal stability of the isolated RFTS domain. However, the mutation resulted in changes in the CD spectrum in the context of the larger protein; a decrease in relative thermal stability was also observed. Collectively, this evidence suggests that A554V disrupts normal RFTS-mediated autoinhibition of DNMT1, resulting in a hyperactive mutant enzyme. While the disease-associated mutation does not significantly impact the isolated RFTS domain, the mutation results in a weakening of the interdomain stabilizing interactions generating a more open, active conformation of DNMT1. Hyperactive mutant DNMT1 could be responsible for the increased DNA methylation observed in affected individuals.

The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns.

William F. Carroll, vice president, Chlorovinyl Issues for Occidental Chemical Corp. (OxyChem), has received the Roy T. Gottesman Leadership Award from the Vinyl Institute in recognition of exemplary service to [...]

Identifying refugia— specifically places where species can persist during periods of regionally unsuitable climate— is increasingly important for conservation practitioners and land managers charged with protecting biodiversity in a rapidly warming world. Currently, many researchers assist in this process by building models to predict areas of refugia using climate data projected into the future under different climate scenarios; however, the coarse spatial scale of future climate data can be orders of magnitude larger than the scale of refugia on the landscape. Conservation paleobiology is an emerging field that can contribute to the identification of climate refugia by looking at the macrofossil records contained in sediments to better understand the response of species to past climate change within a small area, and allows us to ground-truth hypotheses about specific areas functioning as climate refugia. Here, we present a conservation paleobiology case study to update vulnerability assessments for subalpine plant species in Acadia National Park and locate potential future refugia on the landscape. We analyzed plant macrofossils in a sediment core from Sargent Mountain Pond in Acadia National Park (Maine, United States) at a fine spatiotemporal resolution to test the hypothesis that the area served as a past climate refugium for the subalpine species it currently hosts. We found that, when compared to a pollen record from a forest hollow core collected on Mount Desert Island, the macrofossils reflect a more stable presence of subalpine taxa throughout the Holocene Climatic Optimum (8,000–5,000 BP) than was observed at lower elevations. Our results indicate the importance of a complementary approach that combines plant macrofossils and pollen in addition to modeling to identify refugia and better understand the vulnerability of species and communities to climate change.

Cartilage has poor regenerative capacity and thus damage to the joint surfaces presents a major clinical challenge. Recent research has focussed on the development of tissue-engineered and cell-based approaches for the treatment of cartilage and osteochondral injuries, with current clinically available cell-based approaches including autologous chondrocyte implantation and matrix-assisted autologous chondrocyte implantation. However, these approaches have significant disadvantages due to the requirement for a two-stage surgical procedure and an in vitro chondrocyte expansion phase which increases logistical challenges, hospital times and costs. In this study, we hypothesized that seeding biomimetic tri-layered scaffolds, with proven regenerative potential, with chondrocyte/infrapatellar fat pad stromal cell co-cultures would improve their regenerative capacity compared to scaffolds implanted cell-free. Rapid cell isolation techniques, without the requirement for long term in vitro culture, were utilised to achieve co-cultures of chondrocytes and stromal cells and thus overcome the limitations of existing cell-based techniques. Cell-free and cell-seeded scaffolds were implanted in osteochondral defects, created within the femoral condyle and trochlear ridge, in a translational large animal goat model. While analysis showed trends towards delayed subchondral bone healing in the cell-seeded scaffold group, by the 12 month timepoint the cell-free and cell-seeded groups yield cartilage and bone tissue with comparable quality and quantity. The results of the study reinforce the potential of the biomimetic tri-layered scaffold to repair joint defects but failed to demonstrate a clear benefit from the addition of the CC/FPMSC co-culture to this scaffold. Taking into consideration the additional cost and complexity associated with the cell-seeded scaffold approach, this study demonstrates that the treatment of osteochondral defects using cell-free tri-layered scaffolds may represent a more prudent clinical approach.