Citations

ABSTRACT Microbial colonization of plant roots involves strong selective pressures that shape the structure and function of root-associated communities. In particular, the endosphere represents a highly selective environment requiring host entry and in planta persistence. However, strain-specific microbial traits that enable endosphere colonization remain poorly understood. Here, we use a defined, genome-resolved community of 28 Variovorax strains isolated from the roots of Populus deltoides and Populus trichocarpa (poplar trees) to determine which strains partition between rhizosphere and endosphere compartments and to identify the genomic traits associated with endosphere specialization. By combining strain-resolved metagenomic profiling, comparative genomics, and functional assays, we demonstrate that dominant endosphere colonizers are enriched in genes related to nutrient metabolism, redox balance, transcriptional regulation, and a conserved L-fucose utilization pathway experimentally shown to enhance root colonization. Not all strains succeed through the same strategy. Community-wide functional profiling revealed a distinct and reduced set of traits in the endosphere, including orthogroups associated with low-abundance strains that were overlooked in strain-level analyses. These findings reveal that multiple ecological strategies, such as metabolic competition, regulatory adaptation, and niche specialization, can support endosphere colonization. Our results advance the understanding of how bacterial colonization traits are distributed and deployed within a plant microbiome and suggest that host filtering selects for distinct, and sometimes complementary, microbial strategies. This work supports a shift toward mechanistic, genome-resolved models of microbiome assembly and offers a framework for linking microbial function to host colonization success. IMPORTANCE Plants often depend on diverse microbial partners to support their growth, resilience, and adaptation to changing environments. Among these microbes, some bacteria inhabit the rhizosphere (the narrow zone around roots where microbes interact with the plant) while others are able to enter and persist within root tissues. The traits that distinguish these two lifestyles remain poorly understood. In this study, we examined a group of related Variovorax strains from poplar tree root microbiomes to ask why some rhizosphere-associated strains also become successful endosphere colonizers. We found that strains appear to succeed through different strategies: some may benefit from rapid growth on plant-derived carbon sources, while others may rely on stress tolerance or fine-tuned regulation. These results suggest that there is no single path from the rhizosphere into the root interior, but rather multiple strategies shaped by the host environment. Understanding this diversity can inform efforts to design resilient plant-microbe communities.

Abstract Exercise training improves cardiovascular health and reduces the risk for future cardiovascular events and mortality. However, emerging evidence suggests that Masters athletes may have a higher prevalence of cardiovascular abnormalities, such as atrial arrhythmias, coronary atherosclerosis, aortic dilatation, and myocardial fibrosis, compared to their less active peers. The clinical management of Masters athletes may be challenging as available guidelines for such conditions are generally based on data derived from symptomatic sedentary patients, limiting their applicability to highly trained individuals. Other unique challenges in the clinical assessment of Masters athletes include differences in symptomatic presentations compared to sedentary individuals, potential resistance to the initiation of pharmacologic treatment, and the increasing availability of consumer wearable health data that may provide relevant information on their cardiovascular health status. The purpose of this joint EAPC/ESC and ACC Clinical Consensus Statement is to provide an in-depth update on the current state of knowledge on abnormal cardiovascular findings in Masters athletes. We present an expert-based approach on the diagnostic assessment, management, and prognosis of (i) atrial fibrillation, (ii) bradyarrhythmias, (iii) ventricular arrhythmias, (iv) coronary atherosclerosis, (v) aortic dilatation, (vi) myocardial fibrosis, and (vii) exercise-induced arrhythmogenic cardiomyopathy. Clinical challenges, areas of ongoing controversy, and uncertainty and the potential underlying mechanisms are discussed. We also present future perspectives and research directives to further refine current best practice strategies. This includes the need for clinical outcome studies, dedicated randomized controlled trials in athletes, and international registries with diverse populations and longitudinal follow-up to evaluate the natural history of cardiac abnormalities and facilitate development of evidence-based approaches in the clinical management of Masters athletes with cardiovascular abnormalities.

ABSTRACT Objective With regulatory approval of HPV‐specific immunotherapy for recurrent respiratory papillomatosis (RRP) and growing experience with systemic bevacizumab, a management algorithm incorporating these medical treatments is warranted. Data Sources and Methods RRP Foundation (RRPF) Key Opinion Leaders offer a proposed management algorithm for adults with RRP considering published literature and commercial drug availability. Results Preventative HPV vaccination should be considered for all patients. Determination of HPV type and pulmonary imaging are important for contemporary RRP patient care and assist in decision making. Risks and benefits of papilloma debulking as needed versus medical management of RRP must be deliberated on a patient case‐by‐case basis. HPV ‐specific immunotherapy that induces an HPV ‐specific T cell response to target the underlying HPV infection that is the cause of RRP is safe, offers the possibility of durable disease control following a short treatment course and is the recommended first‐line medical treatment for patients who wish to avoid the risks of repeat procedural management. Papilloma disease control with systemic bevacizumab, which carries defined risks and must be continued for clinical benefit is the recommended second‐line medical treatment for patients who do not achieve a complete response with immunotherapy and wish to continue medical management. For patients who elect to be treated with debulking procedures as needed, use of locally‐administered adjuvant should be considered. Conclusion This proposed management algorithm from the RRPF serves as a contemporary resource and information guide for adult patients with RRP and their physicians considering treatment options. Level of Evidence 5

Background: Large language models (LLMs) are increasingly integrated into clinical documentation, decision support, and patient-facing applications across healthcare, including plastic and reconstructive surgery. Yet, their evaluation remains bottlenecked by costly, time-consuming human review. This has given rise to LLM-as-a-judge, in which LLMs are used to evaluate the outputs of other AI systems. Methods: This review examines LLM-as-a-judge in healthcare with particular attention to judging architectures, validation strategies, and emerging applications. A narrative review of the literature was conducted, synthesizing LLM judge methodologies as well as judging paradigms, including those applied to clinical documentation, medical question-answering systems, and clinical conversation assessment. Results: Across tasks, LLM judges align most closely with clinicians on objective criteria (e.g., factuality, grammaticality, internal consistency), benefit from structured evaluation and chain-of-thought prompting, and can approach or exceed inter-clinician agreement, but remain limited for subjective or affective judgments and by dataset quality and task specificity. Conclusions: The literature indicates that LLM judges can enable efficient, standardized evaluation in controlled settings; however, their appropriate role remains supportive rather than substitutive, and their performance may not generalize to complex plastic surgery environments. Their safe use depends on rigorous human oversight and explicit governance structures.

ABSTRACT Advanced chronic diseases, or multicomplexity in older adults presents unique challenges. Transthyretin cardiac amyloidosis (ATTR‐CA) is one such scenario where heart failure is a common presentation, and management remains challenging. We describe the challenges involved in the diagnosis of ATTR‐CA in older adults, which has implications on treatment options. We discuss the application of comprehensive geriatric assessment (CGA) and shared decision making (SDM) in the context of these challenges. Based on geriatric medicine principles, an innovative framework for applying SDM in ATTR‐CA patients is proposed, including consideration of the patient priorities care approach. The proposed framework emphasizes assessing functionality, frailty, and life expectancy to help categorize risk. This framework can be applied in various advanced chronic diseases or multicomplexity. Based on risk categorization, treatment burden, and alignment with values and preferences, management pathways are suggested for each risk category. Incorporating CGA and SDM, the proposed framework supports patient‐centered care, ensuring that clinical recommendations are tailored to each older adult's unique needs and goals. In ATTR‐CA, a collaboration between cardiology and geriatric medicine provides significant value in managing older adults. The need to prevent age‐related bias in clinical decision‐making exists across all health conditions, and the proposed framework allows for a thorough evaluation of multimorbidity, frailty, disability, and patient preferences. While ATTR‐CA is used as a prototype, this integrated approach can be applied across all health conditions and is essential for delivering holistic care, improving communication, and aligning treatment plans with patient values.

Abstract Background Fever and worsening rigidity in Parkinson's disease (PD) may resemble neuroleptic malignant syndrome (NMS). We examined PD patients diagnosed with NMS—regardless of whether diagnostic criteria were used—to establish the clinical characteristics and etiology. Cases Among 15 cases, 40% (6/15) required ICU admission, 27% (4/15) required mechanical ventilation, 80% (12/15) recovered, and 20% (3/15) died. 27% (4/15) had a reduction in carbidopa‐levodopa as the primary trigger, 27% (4/15) had sepsis in addition to concurrent reductions in carbidopa‐levodopa, 7% (1/15) had sepsis alone, 33% (5/15) were exposed to new or increased antidopaminergic drugs, and 7% (1/15) had deep brain stimulator (DBS) malfunction. Literature Review Several terms to describe exacerbation of parkinsonism including NMS‐like state and parkinsonism hyperpyrexia syndrome (PHS) have been proposed over the years but may be restrictive in their definitions and confounders exist. Conclusions Acute parkinsonism dopamine depletion syndrome (APDDS) might be a more encompassing term to describe to an acute exacerbation of preexisting parkinsonism resulting from recent reduction in dopaminergic or other Parkinson's therapy (eg, DBS failure), or exposure to antidopaminergics. Symptoms include increased rigidity, encephalopathy, hyperthermia, or autonomic instability. Sepsis is a frequent confounder and may be associated with concurrent reduction or discontinuation of carbidopa‐levodopa.