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MPI-Guided Photothermal Therapy of Prostate Cancer Using Stem Cell Delivery of Magnetotheranostic Nanoflowers
No full textThe efficacy of photothermal therapy (PTT) of cancer critically depends on widespread nanoparticle (NP) distribution and retention within the tumor. However, intratumoral (i.t.) injection of naked NPs may result in poor dispersion and backflow resulting in leakage and rapid clearance, limiting therapeutic outcome and increasing off-target toxicity. To overcome these limitations, we employed tumor-tropic human mesenchymal stem cells (hMSCs) as delivery vehicles for magnetotheranostic gold-iron oxide nanoflowers (GIONF), enabling widespread i.t. distribution and sustained retention in contrast to injection of naked GIONF. GIONF-hMSCs demonstrated superior heating performance under near-infrared laser irradiation while exhibiting a strong magnetic particle imaging (MPI) signal, allowing for noninvasive quantitative tracking of their whole body biodistribution. Laser irradiation at peak GIONF-hMSC retention resulted in complete tumor ablation without recurrence up to 90 days post-treatment. These results are a first demonstration of using MPI to evaluate the retention and leakage of i.t.-injected intracellular versus naked nanoparticles for advancing PTT with cellular magnetotheranostics
Stereotactic radiosurgery for pineal gland metastases: results from the international radiosurgery research foundation
No full textPurpose Metastases to the pineal gland are rare. Surgical excision can be associated with high rates of morbidity. Alternatively, stereotactic radiosurgery (SRS) for brain metastases in the pineal region has not been vigorously studied. Methods We performed a multi-institutional retrospective study for patients treated with SRS for pineal region metastases at treatment centers that comprise the International Radiosurgery Research Foundation (IRRF). Demographics, tumor characteristics, treatment parameters, and clinical outcomes were collected. The primary endpoint was local tumor control (LC). Secondary endpoints included: Overall survival (OS), distant tumor control (DC), and adverse radiation events (AREs). Kaplan-Meier and Cox regression analyses were performed to evaluate time to event endpoints and prognostic factors respectively. Results Twenty-six patients (16 female, 62% median age 60 years (range: 16-87) with 26 pineal metastases were managed with SRS. Primary tumor histology was lung (46.2%), breast (26.9%), melanoma (7.7%), and other (19.2%). SRS treatment was up-front in the majority of cases (61.5%), adjuvant (19.2%) or salvage therapy (19.2%). The median prescription dose was 18 Gy in a single fraction. Median follow-up was 9 months (range 3-101). LC at 3-,6-,12-, and 24-months was 100%, 94.4%, 87.7%, and 87.7% respectively. DC at the same intervals were 79.2%, 73.9%, 52.8%, and 35.2%. Median OS was 32 months (range: 6-52). No evaluated prognostic factors were significantly associated with LC, DC, or OS. Among the 13 patients with symptoms related to their pineal tumor at baseline, 7 improved and 6 remained stable following SRS. Leptomeningeal spread occurred in 7.7% of patients and no cases of post-SRS hydrocephalus were observed. Overall AREs occurred in 14 (53.8%) patients, with a median time to onset of 4 months. Conclusion SRS offers excellent local tumor control of pineal metastases with high rates of symptomatic improvement, minimal leptomeningeal spread, and limited post-SRS complications. Despite this, distant tumor control is limited in this setting and may be improved by improved systemic disease management.</p
JNK3 regulates β cell responses to incretins in human islets and mouse models
No full textThe c-Jun N-terminal kinases (JNKs) regulate diverse physiological processes. Whereas JNK1 and JNK2 are broadly expressed and associated with insulin resistance, inflammation, and stress responses, JNK3 is largely restricted to central nervous system neurons and pancreatic β cells, and its physiological role in β cells remains poorly defined. To investigate its function, we generated mice lacking JNK3 specifically in β cells (βJNK3-KO). These mice displayed glucose intolerance and defective insulin secretion, particularly after oral glucose challenge, indicating impaired incretin responses. Consistently, Exendin-4-stimulated (Ex4-stimulated) insulin secretion was blunted in βJNK3-KO islets, accompanied by reduced GLP-1R expression. Similar findings were observed in human islets treated with a selective JNK3 inhibitor (iJNK3). Downstream of GLP-1R, Ex4-induced CREB phosphorylation was diminished in βJNK3-KO islets, indicating impaired canonical signaling. Moreover, activation of the GLP-1R/CREB/IRS2 pathway, a key regulator of β cell survival, was reduced in βJNK3-KO islets and iJNK3-treated human islets. As a consequence, the protective effects of Ex4 were lost in cytokine-treated βJNK3-KO and human islets, and Ex4-mediated protection was partially attenuated in βJNK3-KO mice exposed to multiple low-dose streptozotocin. These findings identify JNK3 as a regulator of β cell function and survival and suggest that targeting this pathway may enhance incretin-based therapies
Serum metabolomic signatures of relapse recovery in early multiple sclerosis
No full textBackground: Relapses in relapsing-remitting multiple sclerosis (RRMS) are acute neuroinflammatory events that shape long-term disease trajectory. Yet, the molecular events during the early recovery period remain poorly characterized, particularly in early, treatment-free disease. Defining these molecular dynamics may clarify mechanisms of repair relevant for understanding early disease progression.Objective: Identify serum metabolomic signatures that discriminate early-stage, untreated RRMS by time from last clinical relapse and capture trends in the recovery period.Methods: Using a cross-sectional cohort study design, we performed untargeted serum metabolomic profiling in 79 RRMS cases (24 weeks) relapse used supervised machine learning (random forest and partial least squares-discriminant analysis) and rank-based tests. Machine learning and rank-based correlation identified monotonic changes across five relapse proximity stages (24 weeks).Results: Multiple metabolites distinguished recent from non-recent relapse (p < 0.05; AUCs 0.72–0.85) and were significantly lower near relapse, including medium-chain acylcarnitines (C6-C10), fatty acid conjugates (hexanoylglycine), microbial-derived aromatics (3-phenylpropionate, 4-vinylcatechol sulfate), and conjugated steroids. Forty-two metabolites had monotonic changes with increasing time from relapse, including 30 decreased and 12 elevated near relapse (p < 0.05). Perturbed pathways involved mitochondrial β-oxidation, tricarboxylic acid cycle flux, membrane lipid remodeling, phase II conjugation, steroid metabolism, and gut-microbial fermentation of polyphenols and aromatic amino acids.Conclusions: Serum metabolomic profiles in early RRMS reflected coordinated biochemical changes following clinical relapse, implicating mitochondrial dysfunction, membrane remodeling, and microbial co-metabolism
Cross-Institutional Investigation of Faculty Publishing in the United States, 2021-2022
No full textThe objectives of this study were to ascertain the knowledge and attitudes of university faculty in the United States concerning journal publication, and specifically, the phenomenon known as "predatory publishing." The research questions that guided the development of the survey were:
How do university faculty determine where to submit journal article manuscripts for publication?
Are university faculty aware of the terminology, tools, and strategies related to predatory publishing and assessing the quality of journals?
How is a faculty member's awareness or attitudes related to their prior experience in academia?
Does a faculty member's knowledge of predatory journals affect which publishers they publish with and how they view the work of other scholars?
This study was exploratory in nature, and the survey instrument developed for this purpose was not formally validated. The investigators designed the survey through a pilot study and consequently refined and expanded it to investigate a broader population. The resulting survey consists of 47 closed- and open-ended items with 136 total variables. The questions are organized into five sections: demographics, environment/department culture, history/experience, journal criteria, and predatory publishing.
The dataset resulting from this study consists of 1167 cases and 152 variables. The target population was faculty of any discipline who worked at a university in the United States and who were required to conduct and publish research as part of their position. The survey was sent to approximately 19,400 faculty at 17 doctoral-granting universities between September 2021 and May 2022
Sleep Duration Associated with Subjective Cognitive Decline: Influence of Age, Sex, Race and Ethnicity
No full textObjectives: To investigate the relationship between short and long sleep duration and subjective cognitive decline (SCD) in a diverse cohort of cognitively normal mid- to older-age adults. Methods: We conducted a cross-sectional analysis of the 2022 Behavioral Risk Factor Surveillance System (BRFSS) data, including 63,948 adults aged 40-70. SCD was assessed using BRFSS survey queries. Multivariable logistic regression models examined the association between sleep duration ( = 8 hours) and SCD, adjusting for age, sex, race/ethnicity, education, and history of depression. Results: Both short and long sleep durations were associated with higher odds of SCD. The association between short sleep and SCD was strongest among individuals in their 40s at the start of midlife. Findings were consistent across all ages for non-Hispanic Whites (NHW) and for Hispanics/Latinos in their 50s and 70s. Black/African American (B/AA) adults exhibited a stronger relationship between both short and long sleep duration and SCD as they aged from midlife into their 80s, compared to NHWs. Conclusions: Short sleep duration is more strongly associated with subjective cognitive decline in midlife, particularly among B/AA adults. Addressing sleep disparities may help mitigate the risk of SCD
An Implementation Science Study of a Community-Based PrEP Navigation Intervention for Men in South Florida
No full textPreexposure prophylaxis (PrEP) is effective for HIV prevention, yet PrEP-eligible men face structural, social, and cultural barriers to access. In this implementation science study, we evaluated a community-tailored PrEP navigation program to identify modifiable factors influencing adoption and implementation. Using staff interviews and participatory Photovoice with clients, we uncovered multilevel barriers to and facilitators of PrEP uptake. Findings were shared with a community-based organization to inform program improvements. This study highlights the value of participatory, implementation-focused approaches to equitable HIV prevention. (
. 2026;116(S1):S28-S31. https://doi.org/10.2105/AJPH.2025.308344)
Tyrosine-Peptide Analog Modulates Extracellular Vesicles miRNAs Cargo from Mesenchymal Stem/Stromal and Cancer Cells to Drive Immunoregeneration and Tumor Suppression
No full textSoft tissue sarcoma remains challenging to treat due to its heterogeneity, stemness-associated survival programs, and resistance to conventional therapies. Extracellular vesicles (EVs) mediate tumor-stroma communication, yet how stemness-targeted therapies reshape EVs-associated miRNAs networks remains unclear. This study profiled EVs miRNAs cargo from infrapatellar fat pad mesenchymal stem/stromal cells (IFP-MSCs) and sarcoma cells (SCs) under basal conditions and following treatment with a synthetic tyrosine peptide analog (TPA). EVs were isolated, characterized, and subjected to miRNAs profiling and pathway enrichment analyses. TPA induced ≥2-fold regulation of 182 miRNAs, including 49 upregulated and 24 downregulated in IFP-MSC-EVs and 86 upregulated and 23 downregulated in SC-EVs. A conserved core of 149 miRNAs (67.1%) was shared across all EVs groups. Abundant species included miR-3960 and miR-21-5p, while TPA reduced tumor-associated miRNAs such as miR-1246 (~10-fold decrease in IFP-MSC-EVs). Pathway enrichment revealed consistent targeting of cancer, MAPK, Wnt, TGF-β, and immune signaling pathways, with modest increases in mapped gene coverage following TPA treatment. In silico analysis identified distinct EVs miRNA-gene interaction profiles, with VEGFA emerging as a recurrent predicted target. These results demonstrate that stemness-targeted modulation quantitatively reprograms EVs miRNA cargo in a cell-type-dependent manner, reshaping vesicle-mediated signaling networks in sarcoma