Publications by Year: 2026

The paraventricular hypothalamus (PVH) controls behavioral and physiologic processes, including appetite, social behavior, autonomic outflow, and pituitary hormone secretion. However, molecular markers for centrally projecting PVH neuron populations remain largely undefined, and a complete census of PVH cell types has not been established. Therefore, we performed extensive single-cell/nucleus RNA sequencing to catalog PVH neuron subtypes and multiplexed error-robust fluorescence in situ hybridization (MERFISH) to map them spatially. Our spatial transcriptomic atlas resolves 26 Sim1+ and 29 GABAergic neuron populations from the PVH and surrounding areas. Additionally, projection-based profiling identified neurons that project to the parabrachial region (PB) and spinal cord, helping to determine PVH populations that regulate satiety and sympathetic nervous system activity, respectively. Notably, activation of PB-projecting PVH neurons expressing Brs3 reduces food intake, and silencing them causes obesity. Together, this atlas contributes high-resolution PVH spatial and circuit-based gene expression profiles, representing a valuable resource for the field of homeostasis.

OBJECTIVES: Ethnic and racial discrimination stress is a key social determinant of sleep health, yet its day-to-day influence on Mexican-origin adolescents remains underexplored. This study focused on Mexican-origin adolescents and examined the negative effects of daily ethnic and racial discrimination stress on sleep.

METHOD: The analytic sample included 256 Mexican-origin adolescents (48.8% female, 49.7% male, 1.56% non-binary; mean age = 13.50; SD = 1.11; range = 12-16 years old) residing in a suburban area in the United States Midwest. Using multi-level models that disentangle between- and within-person effects, this study assessed daily ethnic and racial discrimination stress and self-reported same-night sleep using a 21-day daily report method. Daily sleep indicators included nighttime duration, onset latency, and quality.

RESULTS: On days when adolescents reported higher levels of discrimination stress, they also reported longer sleep onset latency. At the between-person level, youth who reported higher levels of discrimination stress reported poorer sleep quality. Possible reciprocal dynamics between stress and sleep were tested. Results showed that at the within-person level, sleep behaviors were not associated with next-day racial discrimination. At the between-person level, adolescents who reported higher sleep quality or longer sleep duration the prior night also reported lower levels of next-day discrimination, suggesting that sleep disturbances may be associated with stress experiences.

CONCLUSION: This study highlights the importance of targeted support for Mexican-origin adolescents' sleep health especially on days when they experience ethnic and racial discrimination.

This study examined whether frailty mediates the relationship between sexual and gender minority (SGM) status and three types of outpatient healthcare utilization among adults aged 50 and older in the All of Us Research Program (2017-2022). We estimated controlled direct effects of SGM status across generalist, specialist, and mental health visits. Healthcare utilization and SGM status were self-reported, and frailty was measured using a survey-based deficit accumulation index. Both SGM status and frailty were independently associated with increased rates of all outpatient visit types. Regarding mediation, our results suggest that if all participants were robust, SGM adults would still have higher healthcare utilization compared to cisgender heterosexual older adults. This indicates that factors beyond frailty influence patterns of healthcare use in this population and highlights the importance of identifying additional determinants to ensure that older SGM adults receive appropriate and responsive care.

BACKGROUND AND AIMS: The triglyceride-glucose (TyG) index (ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]) is a novel, simple, and inexpensive biomarker of insulin resistance with growing evidence in support of its diagnostic and prognostic value for cardiovascular disease (CVD). We examined the relationship of baseline TyG index with incident CVD, coronary heart disease (CHD), and cerebrovascular disease during up to 32 years of follow-up among postmenopausal women, before and after stratifying by the cardiovascular-kidney-metabolic (CKM) syndrome and socioeconomic status (SES) at baseline.

METHODS: 11,769 participants from Women's Health Initiative (5074 with CKM vs. 6695 without CKM; 4149 low SES vs. 5958 medium SES vs. 1662 high SES) were analyzed.

RESULTS: On average, the TyG index increased with decreasing SES and was higher in women with vs. without CKM. Cox regression and multistate Markov models adjusting for demographic, lifestyle, and health characteristics at baseline were constructed to estimate hazard ratios (HR) and 95 % confidence intervals (CI). A 1-unit increase in the TyG index was associated with greater CVD risk (CVD: HR = 1.54, 95 % CI: 1.39, 1.71; CHD: HR = 1.74, 95 % CI: 1.52, 1.99; Cerebrovascular disease: HR=1.32, 95% CI: 1.15, 1.53). The TyG index was positively associated with probabilities of transitions from a healthy state to CHD, cerebrovascular disease, and death, as well as transitions between CHD or cerebrovascular disease and death. These relationships did not vary by CKM syndrome or SES.

CONCLUSIONS: Among postmenopausal women, irrespective of CKM syndrome or SES, the TyG index is a valuable diagnostic and prognostic tool for CVD outcomes.

BACKGROUND: Over the past decade, lung cancer management has been reshaped by advances in early detection, treatment, and prevention. Prevention now extends beyond tobacco control to include recognition of non-tobacco risk factors, screening, and incidental nodule programs. Yet progress in primary prevention remains uneven, with marked regional disparities. Smoking prevalence continues to decline and measures to reduce particulate matter exposure are expanding, but the overall global impact remains inconsistent.

PATIENTS AND METHODS: This article draws upon the discussions and expert recommendations presented at the New York Lung Cancer Foundation Summit 2025, integrating perspectives on prevention, screening, therapeutic innovation, and health system challenges across diverse health care settings.

RESULTS: Screening programs, now active in >40 countries, achieve lower false-positive rates and earlier-stage diagnoses, although lung cancer incidence is rising among individuals who never used any tobacco products in some regions. Therapeutic innovations-including perioperative immunotherapy, targeted treatments for oncogene-driven non-small-cell lung cancer, and antibody-drug conjugates (ADCs)-have markedly improved survival outcomes. Persistent challenges include refining patient selection, sequencing multimodal therapies, managing toxicity, and understanding mechanisms of resistance. Systemic barriers such as unequal progress in tobacco and vaping prevention, limited screening uptake, delayed molecular testing, and restricted access to multidisciplinary care continue to blunt these gains. Ongoing research on novel immunotherapies, ADCs, and bispecific antibodies aims to overcome therapeutic resistance. In small-cell lung cancer, consolidation immunotherapy and delta-like ligand 3-targeted approaches have improved outcomes and are redefining treatment paradigms. Persistent disparities in access and trial participation underscore the need for more equitable study designs, stronger international collaboration, and clearer communication with the public.

CONCLUSIONS: This article summarizes current advances and strategic priorities in lung cancer research and care, reflecting the discussions and recommendations of the New York Lung Cancer Foundation Summit 2025.

INTRODUCTION: Diagnostic overshadowing, a type of cognitive bias, happens when a pre-existing medical condition overshadows the evaluation of other potential diagnoses. This study aimed to explore diagnostic overshadowing in trauma due to the impact of substance and alcohol use disorder (SUD) on time to diagnosis and management in patients with blunt splenic injury.

METHODS: The 2017-2020 American College of Surgeons Trauma Quality Improvement Project database was used to identify patients ≥18 y with blunt splenic injury who underwent splenectomy. Patients were stratified into those with and without SUD. Delayed diagnosis (time to abdominal computed tomography scan >1 h) and delayed splenectomy (>2 h) were defined using median-based thresholds to measure distributional shifts in care timeliness between groups. Multivariable logistic regression examined the impact of SUD on delayed diagnosis, delayed splenectomy, and outcomes (e.g., mortality, postoperative complications). A sensitivity analysis was conducted by excluding patients with a positive alcohol screen on admission.

RESULTS: Nine thousand two hundred thirty-seven patients were included: 1739 (19%) SUD and 7498 (81%) non-SUD. The median time to splenectomy was 2.4 h (interquartile range = 1.2-7.1) in SUD patients compared with 2 h (interquartile range = 1.1-4.9) in non-SUD patients (P < 0.001). On multivariable analyses, SUD patients were more likely to experience delayed diagnosis (adjusted odds ratio [aOR] = 1.13, 95% confidence interval [CI] = 1.04-1.23), delayed splenectomy (aOR = 1.25, 95% CI = 1.09-1.42), and composite complications (aOR = 1.14, 95% CI = 1.01-1.31) compared with non-SUD patients. After excluding intoxicated patients, those with SUD were still more likely to have delayed diagnosis and management, with a greater risk of delayed splenectomy compared with the overall cohort.

CONCLUSIONS: Diagnostic overshadowing, exemplified in blunt splenic injury patients with SUD, can be measured and can negatively impact patient care. Further studies are needed to explore the prevalence and impact of diagnostic overshadowing in trauma patients.

Microbiota exist virtually on every surface of the human body and plays a vital role in maintaining human health. As a significant public health issue, infertility poses a great risk to the physical and mental health of the couple and their future quality of life. Over the past decade, intensive research on the microbiota of the reproductive tract has led to the identification of microbiota in the vagina, uterus, cervix, and male testes that play a vital role in maintaining a normal pregnancy. Additionally, dysbiosis of the gut microbiota has been linked to infertility. This review summarizes the mechanisms by which dysbiosis of the reproductive tract and gut microbiota triggers infertility, focusing on dysbiosis of bacterial ecological ratios, microbiota-mediated imbalance of the immune system, inflammatory responses, and effects on signaling pathways. In addition, we discuss the significant capacity of gender-specific microbiota for diagnosis, prognosis, and treatment of infertility-associated reproductive disorders, respectively. Finally, we extensively analyze therapeutic strategies targeting the microbiota to prevent or treat infertility, laying the foundation for future customized precision medicine.

The field of durable mechanical circulatory support (MCS) has experienced remarkable progress in both advancements in technology and patient management over the past few decades. Left ventricular assist devices have evolved from bulky, pulsatile flow devices plagued by short durability and high adverse events to compact, fully magnetically levitated, continuous flow pumps with a significantly lower risk of adverse events and providing high rates of long-term survival. Yet, multiple opportunities for refinement in pump design, patient selection, and management strategies remain. The ideal MCS device would provide untethered, physiologically responsive support, minimize need for anticoagulation, and be adaptable to a wide range of patient and cardiac anatomies. In this review, we summarize emerging technological developments within various domains of pump design which will continue to shape the future of this field.