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Effects of Di(2-ethylhexyl) phthalate (DEHP) and hyperoxia on cardiovascular development in newborn rats

Toor, Fatima; Sargsyan, Mane; Akselrod, Abigail; Zhao, Chunfang; Sen, Namita; Nasim, Mansoor; Stroustrup, Annemarie; Perveen, Shahana
BACKGROUND:Preterm infants encounter DEHP through medical devices and equipment. While hyperoxia is known to promote cardiac remodeling and dysfunction, the impact of early phthalate exposure is understudied. We hypothesized that independent and combined DEHP and hyperoxia exposure would impair neonatal cardiovascular development. METHODS:Newborn rats were exposed from birth to day 14 to one of four conditions: control (21% oxygen), hyperoxia (60% oxygen), DEHP (25 mg/m3), and DEHP + hyperoxia (25 mg/m3 DEHP and 60% oxygen). Cardiac tissue and serum were analyzed by histology, RT-qPCR and ELISA for markers of contractility, angiogenesis, and inflammation: myosin heavy chain 6 (Myh6), vascular endothelial growth factor (VEGF), interleukin-4 (IL-4), interleukin-10 (IL-10), and fractalkine (CX3CL1). RESULTS:Histology found increased cell size, cytoplasm per nucleus, and nuclear area in all exposures. DEHP exposure and hyperoxia exposure reduced Myh6 and VEGF gene expression. Serum VEGF was higher in the DEHP + hyperoxia group compared to hyperoxia alone. IL-10 was decreased in all exposed groups. IL-4 was reduced in the DEHP + hyperoxia group. CXC3L1 was increased in the DEHP + hyperoxia group compared to hyperoxia alone. CONCLUSION(S)/CONCLUSIONS:Independent and concurrent DEHP and hyperoxia exposure during early neonatal development significantly disrupted markers of cardiac morphology, contractility, angiogenesis, and inflammation. IMPACT/CONCLUSIONS:Key Message: Postnatal exposure to DEHP adversely impacts neonatal rat cardiovascular development. Adds to Existing Literature: This is the first study to examine concurrent long-term hyperoxia and DEHP exposure on cardiovascular development in an animal model relevant to preterm infants. Identifies a modifiable contributor, DEHP, to adverse cardiovascular development. Identifies various cardiovascular components affected by DEHP and hyperoxia, including structural, angiogenic, contractile, and inflammatory aspects. Leads to a new approach to investigate the impact of environmental toxins and the origin of cardiovascular disease in the newborn period.
PMID: 42270811
ISSN: 1530-0447
CID: 6048592

What do youth need to know about puberty? A scoping review protocol to identify puberty education competencies

Brault, Marie A; Singh, Nanki; Kakkad, Nikita; Peskin, Melissa; Betori, Anthony; Laynor, Gregory; Naiser, Emily
INTRODUCTION/BACKGROUND:Puberty is a key transition point in adolescents' lives that plays a foundational role in shaping health behaviors and outcomes across one's life course. This period holds significant potential to empower adolescents and support autonomy in health and well-being, but limited puberty education curricula exist for early adolescents (age 8-14), and those that do exist vary in content. There is a paucity of evaluations of puberty competencies and limited consensus on what competencies should be measured to assess effectiveness or even how to measure these competencies. OBJECTIVE:The objective of this scoping review is to systematically map and characterize the outcomes, domains, and instruments used to evaluate puberty education curricula for early adolescents aged 8-14 years. In accordance with PRISMA-ScR and JBI scoping review guidance, this review does not synthesize effect sizes or assess intervention efficacy, but maps the breadth of evidence to identify conceptual gaps and inform future framework development. METHODS:The review protocol is registered with the Open Science Framework (OSF). We will search PubMed, CINAHL, PsycInfo, ERIC, Education Source, Scopus, Web of Science Core Collection, ProQuest Dissertations and Theses Global, and OpenAlex for relevant sources. Two reviewers will independently screen and extract studies that meet inclusion criteria using our data extraction tool. EXPECTED OUTPUTS/UNASSIGNED:Findings from the scoping review will be synthesized to create an overarching framework that can guide approaches to the development and evaluation of puberty curricula targeted to early adolescents. Focus group discussions with adolescents, parents, and school representatives will be conducted to assess the applicability and appropriateness of identified competencies and evaluation measures prior to broader dissemination. Insights from this scoping review will ultimately be used to inform the implementation and evaluation of puberty education.
PMCID:13249200
PMID: 42263087
ISSN: 1932-6203
CID: 6048292

General-purpose large language models outperform specialized clinical AI tools on medical benchmarks

Vishwanath, Krithik; Alyakin, Anton; Ghosh, Mrigayu; Hage, Ali; Neifert, Sean N; Orillac, Cordelia; Mandelberg, Nataniel J; Khan, Hammad A; Lee, Jin Vivian; Yao, Jie J; Small, William Robert; Varma, Aakaash; Hewitt, D Brock; Aphinyanaphongs, Yindalon; Alber, Daniel Alexander; Oermann, Eric Karl
Specialized clinical artificial intelligence (AI) tools are entering medical practice despite scarce independent evaluation. We quantitatively evaluate two clinical AI tools, OpenEvidence and UpToDate Expert AI, built on large language models (LLMs) against three frontier LLMs: GPT-5.2, Gemini 3.1 Pro and Claude Opus 4.6. Our evaluation has three stages: (1) 500 MedQA questions testing medical knowledge, (2) 500 HealthBench items measuring alignment with clinicians and (3) the real clinical queries (RCQ) benchmark, built from 100 de-identified queries from physicians to a general-purpose language model in a live clinical environment. For the RCQ benchmark, 12 US clinicians performed randomized, blinded review of model outputs, producing 1,800 model-question annotations. Frontier LLMs outperformed clinical AI tools in all three evaluations. Clinical AI tools performed comparably to auto-enabled Google Search AI Overview on the RCQ. These findings highlight the need for independent, real-world evaluation of AI tools before they enter clinical settings.
PMID: 42286322
ISSN: 1546-170x
CID: 6049082

Racial, gender and language based disparities in sepsis: a public health perspective

Gill, Harman S; Khandelwal, Krishnakant; Amini, Masoud; Ortego, Alexandra
Existence of linguistic, gender and ethno-racial differences in patients with sepsis remains relatively unknown, especially in the public health domain. Retrospective analysis of data reported by a hospital in South Brooklyn to a New York State sepsis registry was undertaken over a 24-month period. Inclusion criteria were age over 18, available linguistic, gender and ethno-racial data, and registration in the New York State sepsis registry. Patients with missing data fields were excluded from the study. Primary outcome was the correlation of gender, race, ethnic & language-based differences with overall sepsis-based mortality. Secondary outcomes were the correlation of the same demographic variables with rates of mechanical ventilation, vasopressor use, intensive care unit (ICU) admission rates & overall incidence of sepsis and septic shock. Results: 677 patients were included in the final analysis in this single center retrospective observational cohort study and multiple statistically significant primary and secondary outcomes were found. Non-English-speaking patients had a higher incidence rate of sepsis-based mortality when compared to their English-speaking cohorts. The incidence rate difference is -0.36 (95% CI -0.49 to -0.22), with a P-value < 0.0001. A higher rate of vasopressor use was noted among non-English speaking patients when compared to their English speaking counterparts. The difference in incidence rates was -0.35, (95% CI -0.46 to -0.25) with a P-value of < 0.0001. Non-English-speaking patients had a higher incidence of receiving mechanical ventilation when compared to English-speaking cohorts. The incidence rate difference is -0.35 (95% CI -0.48 to -0.22), with a P-value < 0.0001. Non-English-speaking patients had a higher ICU admission rate with an incidence rate difference of -0.30, at a P value < 0.0001. Non-English-speaking patients had a higher sepsis incidence rate (0.70, 95% CI 0.63 to 0.78) compared to English-speaking patients (0.30, 95% CI 0.25 to 0.36), with a P-value of < 0.0001. Non-English-speaking patients experienced a higher incidence of septic shock (0.70, 95% CI 0.63 to 0.78) compared to English-speaking patients (0.30, 95% CI 0.25 to 0.36), with a P-value of < 0.0001. Caucasians showed statistically significant and higher rates across all primary and secondary outcomes albeit with greater statistical fragility. No significant differences were noted with regards to the impact of gender on all outcomes. Conclusion: Significant and multiple linguistic and ethno-racial differences were noted in this single center study with regards to sepsis-based morbidity and mortality outcomes. These differences need to be validated in larger, multi-center trials and could inform future efforts focused on identifying higher risk subsets in patients presenting with sepsis and septic shock in a public health setting.
PMID: 42251623
ISSN: 1970-9366
CID: 6047972

Optimizing Systemic Therapy in Advanced Gastrointestinal Malignancies: Strategies to Minimize Toxicity and Maximize Tolerability

Bulancea, Sabrina; Grewal, Udhayvir S; Wronska, Marta; Vadehra, Deepak; Hornstein, Nicholas; Brown, Timothy J; Shusterman, Michael
Advanced gastrointestinal cancers remain a major global health challenge, with rising incidence especially among younger populations. Systemic chemotherapy continues to be the mainstay of care for most patients, but balancing treatment benefit with tolerability is an ongoing concern. Many patients, especially older adults and those with significant medical comorbidities, may struggle with standard dosing due to side effects, yet they are often underrepresented in clinical trials. As a result, real-world practice often relies on adjusting drug doses and schedules to reduce toxicity without compromising outcomes. Personalizing systemic therapy based on patient factors like age, fitness, and individual response can help improve tolerability and maintain quality of life. Emerging evidence supports the use of modified dosing and frequency, but prospective data remain limited. In this review, we discuss current approaches to optimizing systemic therapy for advanced gastrointestinal cancers and the need for practical, patient-centered care pathways.
PMID: 42270485
ISSN: 1938-0674
CID: 6048582

Cross-subject decoding of internal mental states using predictive time-series modeling

Wang, Zi-Han; Chen, Xiao; Lu, Bin; Wang, Yu-Wei; Li, Xue-Ying; Li, Hui-Xian; Liao, Yi-Fan; Hu, Zheng-Jiayi; Wu, Chen-Nan; Wang, Han-Lin; Gao, Qing-Lin; Liu, Hai-Long; Liu, Yan-Song; Thompson, Paul M; Xavier Castellanos, F; Cao, Li-Ping; Chen, Guan-Mao; Chen, Jian-Shan; Chen, Tao; Chen, Tao-Lin; Cheng, Yu-Qi; Chu, Zhao-Song; Cui, Xi-Long; Gong, Qi-Yong; Guo, Wen-Bin; He, Can-Can; Huang, Qian; Ji, Xin-Lei; Jia, Feng-Nan; Kuang, Li; Li, Bao-Juan; Li, Feng; Li, Tao; Liu, Xiao-Yun; Liu, Zhe-Ning; Long, Yi-Cheng; Lu, Jian-Ping; Qiu, Jiang; Shan, Xiao-Xiao; Si, Tian-Mei; Sun, Peng-Feng; Wang, Chuan-Yue; Wang, Hua-Ning; Wang, Xiang; Wang, Ying; Wu, Xiao-Ping; Wu, Xin-Ran; Wu, Yan-Kun; Xie, Chun-Ming; Xie, Guang-Rong; Xie, Peng; Xu, Xiu-Feng; Xue, Zhen-Peng; Yang, Hong; Yang, Jian; Yu, Hua; Yu, Yong-Qiang; Yuan, Min-Lan; Yuan, Yong-Gui; Zhang, Ai-Xia; Zhang, Ke-Rang; Zhang, Wei; Zhao, Jing-Ping; Zhu, Jia-Jia; ,; Yan, Chao-Gan
PMID: 42285800
ISSN: 2095-9281
CID: 6049072

Back to basics in critical care: Can hematological ratios refine sepsis risk stratification? [Editorial]

Gupta, Bikram Kumar; Prakash, Jay; Ortego, Alexandra
PMCID:13252669
PMID: 42281817
ISSN: 2229-5151
CID: 6048792

Alexander von Humboldt and the little women of Loja

Saenger, Paul H; Mejia-Corletto, Jorge
Alexander von Humboldt's early nineteenth-century explorations of the Andes established foundational methods in biogeography and environmental science, emphasizing measurement, spatial integration, and the interdependence of natural systems. Nearly two centuries later, southern Ecuador became the site of a landmark discovery in endocrine genetics: a population with growth hormone receptor deficiency (Laron syndrome) characterized by severe insulin-like growth factor-1 (IGF-1) deficiency. This article examines the historical and scientific continuity of observation in the Ecuadorian Andes, linking Humboldt's integrative natural philosophy with modern approaches to human molecular physiology. While no direct historical connection exists between Humboldt's writings and the later identification of this endocrine condition, the shared geographic setting underscores the enduring scientific value of place-based investigation.
PMID: 42275780
ISSN: 1532-2238
CID: 6048692

Divergence Between Net Fluid and Weight-Based Evaluation in Calculating Cumulative Fluid Balance

Shinnick, Finley J; Hasson, Denise C; Kothari, Ulka; Shah, Ami; Odum, James D; Braun, Chloe G; Dixon, Celeste G; Fitzgerald, Julie C; Martin, Susan D; Terry, Nina; Dziorny, Adam C; ,
OBJECTIVE:Although efforts have been made to standardize fluid balance calculations in the ICU, there is a limited understanding of how different calculation methods relate to one another across an ICU admission. We quantified the agreement between the cumulative fluid balance calculated from fluid intake and output (CFBf) and cumulative fluid balance calculated from serial weights (CFBw) in critically ill children during the first week of ICU admission. DESIGN/METHODS:Retrospective, multicenter, federated observational study. SETTING/METHODS:Four pediatric medical-SICUs (PICU) and two pediatric cardiac ICUs (PCICU) from four tertiary care centers. PATIENTS/METHODS:Analysis included 8,895 pediatric patients (younger than 19 yr) representing 12,388 ICU encounters from 2023 to 2024. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:A patient's anchor weight was the weight closest to ICU admission. CFBf and CFBw were calculated at the time of new weight measurements. We assessed agreement between CFBf and CFBw using Bland-Altman analyses, stratified by ICU day and patient subgroups (neonates, early anchor weights [weight on ICU day 0], and encounters with unmeasured urine occurrences). Across all units and subgroups, CFBf exceeded CFBw (mean difference: all patients = 4.7 %CFB, early anchor weight = 4.7 %CFB, neonates = 5.9 %CFB). The mean difference increased significantly over time (days 0-3: 2.7% vs. days 4-7: 8.1%, p < 0.05), with greater divergence in neonates and those with early anchor weights. CONCLUSIONS:CFBf consistently exceeded CFBw across all subgroups, with a greater divergence on ICU days 4-7. Clinicians should understand these differences, prioritizing early and frequent patient weights throughout ICU admission. Future studies should assess each method's association with patient outcomes to identify the most clinically informative CFB method.
PMID: 42267872
ISSN: 2639-8028
CID: 6048492

Interrater Reliability of Point-of-Care Ultrasound for Predicting Post-Extubation Stridor in Pediatrics

Slamowitz, April; Moriarty, Shannon; Taylor, Matthew; Cerise, Jane; Glater-Welt, Lily; Murphy, Kristina
OBJECTIVES/OBJECTIVE:Post-extubation stridor (PES) is a serious complication in pediatric patients following endotracheal intubation and is linked to laryngeal edema. Prior studies suggest that the laryngeal air column width difference (LACWD), measured by point-of-care ultrasound (POCUS), may predict PES. There is a critical need to evaluate whether such techniques can be reliably reproduced among typical providers in the pediatric critical care setting. We aimed to assess the predictive value of LACWD for PES, examine its correlation with endotracheal tube (ETT) cuff pressure, and determine whether LACWD can be measured consistently by multiple POCUS-trained providers. METHODS:We conducted a prospective observational study of 51 mechanically ventilated pediatric patients aged 0-18 years. LACWD was measured using bedside POCUS. A subset underwent duplicate scans by different providers to assess interrater reliability. PES was defined by the presence of inspiratory stridor. Intra- and interrater reliability were evaluated using intraclass correlation coefficients (ICCs). RESULTS:PES occurred in 14% of patients. There was no significant difference in LACWD between PES and non-PES groups. LACWD showed no correlation with ETT cuff pressure. Intrarater reliability for LACWD measurements was excellent (ICC >0.95), but interrater reliability was poor (ICC = 0.27 for LACWD). CONCLUSIONS:LACWD did not reliably predict PES and showed poor interrater reliability, raising concerns about its practical utility in pediatrics. While POCUS remains an appealing non-invasive tool, our study demonstrates that the current technique lacks the reproducibility required for clinical application across providers. Future advancements may improve feasibility, but current methods are not yet suitable for routine bedside use.
PMID: 41708494
ISSN: 1550-9613
CID: 6045332