Sarah K.

Global fertility rates continue to decline despite advancements in assisted reproductive technologies, highlighting a significant gap in our understanding of the mechanisms underlying preconception physiology. In this commentary, we review a growing body of work demonstrating that the microbiome plays a crucial yet underexplored role in women’s reproductive health. This work has shown that microbial communities produce substrates that support metabolic, immune, and hormonal functions during this critical period, affecting fertility, pregnancy outcomes, and offspring health. Women with reproductive disorders, including endometriosis, polycystic ovarian syndrome, primary ovarian insufficiency, and recurrent pregnancy loss, harbor distinct microbial signatures. Animal studies provide key mechanistic insights, showing that disruption of microbiota accelerates ovarian aging, but translating these findings to human preconception health requires careful consideration. While these findings are compelling, this emerging field currently lacks a clear understanding of how microbial signals affect reproductive tissues through metabolites, immune responses, or hormonal pathways. We outline criteria for establishing microbial causation in preconception health, including sufficiency, necessity, specificity, and timing. Moving beyond correlations involves selecting appropriate models, focusing on key developmental windows, conducting longitudinal studies before conception, and investigating how specific microbial metabolites influence reproductive outcomes. Incorporating microbiome research into preconception care could lead to the development of new therapies and interventions. While the principles outlined here primarily address preconception reproductive health, they also offer a framework for microbiome research in general, emphasizing the need for a mechanistic understanding, timely interventions, and progress from association to causation in this rapidly evolving field.

Hosseinzadeh et al. demonstrate use of a publicly accessible automated machine learning platform to differentiate between a common benign tumor and malignant transformation of it within the paranasal sinuses. This AI algorithm beat prior human prediction, and showed that physicians with no coding background can effectively utilize this tool.

Background Community pharmacists are the most publicly accessible health professionals in high-income countries. There is increasing interest in conducting randomised controlled trials (RCT)—the benchmark of original evidence in the medical field—in community pharmacies. However, little evidence exists examining the challenges and opportunities of conducting RCTs in pharmacies, particularly with respect to project management. In this work, we aim to provide a narrative of lessons learned in conducting two RCTs in community pharmacies in two high-income countries. Methods We retrospectively reviewed multiple data sources including administrative and trial activity records. We conducted face-to-face and online sessions to create a list of lessons learned from our experiences and created a stakeholder map for the trials examined. We framed our findings using the Project Managements Institute’s model of the project life cycle, and descriptive statistics were used to estimate the outcomes reported. Results Ninety-six pharmacies were recruited. Across the project phases, seven high-level tasks within Initiation; 30 within Planning, 43 within Execution/Monitoring and Controlling, and 14 in Closure, were identified. Recruitment of pharmacies, developing documentation for trial drug supply, participant recruitment, and negotiation with pharmacy contracting bodies took longest to complete. Eight key stakeholder groups were identified, including public services/agencies; community pharmacies, communications actors; funders/sponsors; universities/research institutes; healthcare providers; suppliers; and regulators. Thirty lessons were identified, most critically across engaging and managing stakeholders; selecting and supporting trial sites; streamlining trial processes to minimise burden; optimising data collection and accuracy; and considering pharmacy constraints and costs. Conclusions Conducting RCTs in community pharmacies presents unique challenges across the project life cycle. Key lessons include the importance of early planning, streamlining processes to reduce staff burden, and addressing pharmacy constraints. The complexity of the work necessitates dedicated and well-resourced trial management staff to enhance stakeholder management and offer tailored supports where required. Trial registration. Not applicable.

Cryo-EM structures of the stabilized prefusion conformation of the glycoprotein B ectodomain—the HSV-1 entry machine—identify a prefusion-specific neutralizing antibody and reveal how prefusion glycoprotein B may evade antibody-mediated neutralization.

Lipocalin-2 (LCN2) is a 25 kDa glycoprotein that has been shown to be a multifunctional player in the metastasis of triple-negative breast cancer (TNBC). In physiological contexts, LCN2 exhibits bacteriostatic properties and plays key roles in iron homeostasis and the transport of hydrophobic molecules. However, several studies have shown that aberrant LCN2 expression is associated with poor prognosis in various malignancies, including breast cancer, which is the most common cancer in women worldwide and can be classified into four molecular subtypes. Among these, TNBC represents a disproportionately aggressive subtype characterized by poor prognosis and high metastatic potential. Although LCN2 has been extensively studied in breast cancer overall, its specific role in TNBC progression and metastasis is only beginning to be understood. Recent evidence suggests that LCN2 contributes to several tumor-promoting processes such as angiogenesis, therapy resistance and modulation of the tumor microenvironment. Moreover, LCN2 appears to influence organ-specific metastasis, particularly to the lung and brain, while its role in liver and bone dissemination remains unclear. Collectively, current data identify LCN2 as a critical mediator of TNBC progression and highlight its potential as a prognostic factor and modulator of disease progression. This review aims to summarize insights from both in vitro and in vivo studies, with particular focus on the role of LCN2 in the metastatic cascade, while also addressing existing research gaps and critically evaluating the current findings.

CAR T cell therapies are effective but costly and difficult to manufacture. Here, authors develop a novel approach using retargeted and functionalized lentiviral vectors that selectively reprogram T cells in vivo, evade immune clearance, and generate functional CAR T cells with therapeutic efficacy.

PfCoronin is a stage-restricted regulator that links host-cell haemoglobin uptake to artemisinin action, showing how non-essential parasite proteins can strongly influence malaria drug response and shape the evolution of artemisinin resistance.

Project SCORE (Student-Centered Outcomes Research Experiences) is a community-engaged after school science education program designed to address persistent inequities in health, education, and biomedical career access among Mississippi youth. Grounded in youth participatory action research and leveraging near-peer mentoring (NPM), the program engages teens in public health education, research skill development, and mentored inquiry led by undergraduate and graduate health sciences students. Program components include weekly workshops during the academic year and a one-week residential summer campus experience focused on health literacy, scientific thinking, research communication, and college-readiness. An evaluation assessed implementation and short-term outcomes. Pre/post survey data indicate increases in STEM self-efficacy, career interest in STEM careers, and public health communication skills. Students reported strong engagement, belonging, and program satisfaction, and summer participants described an enhanced interest in college and health science careers. The lessons learned highlight the importance of robust NPM support, flexible program adaptation, and strong community partnerships. Early findings demonstrate that Project SCORE is a feasible, acceptable, and replicable model for engaging historically excluded youth in STEM and public health through community-based, student-centered research experiences.