Of 1,289 measles case-patients during April 2025-March 2026 in Jerusalem, Israel, 11 children died, a measles-specific mortality rate of 1.1 deaths/100,000 population. The measles-specific mortality rate among children <5 years of age was 7.7 deaths/100,000 population but 80.1 deaths/100,000 population in 6 neighborhoods populated by ultraorthodox Jews, a 47% measles-attributed death fraction.

Melatonin (MEL) is an endogenous hormone that regulates circadian rhythm, immune function and oxidative stress responses. Norepinephrine (NE), an endogenous catecholamine, increases blood pressure through the sympathetic nervous system and is commonly administered intraoperatively or in the clinically ill patient for hemodynamic support. Although endogenous NE is known to stimulate MEL synthesis, the effects of exogenous intravenous NE on plasma MEL concentration, particularly under general anaesthesia (GA), remain poorly characterised. This study examined the influence of intravenous NE on plasma MEL concentrations in healthy volunteers, both awake and under general anaesthesia. A secondary analysis was conducted using data from a prospective, single-centre, cross-over study involving volunteers who received stepwise NE infusions while awake and under total intravenous general anaesthesia. Arterial blood samples were collected to determine plasma MEL and NE concentrations. Linear mixed-effects modelling was used to assess the relationship between NE and MEL concentrations. A total of 36 healthy volunteers were enroled, yielding 417 MEL-NE samples. Intravenous NE administration was significantly associated with higher plasma MEL concentration, corresponding to an estimated 26% increase in MEL per 1 standard-deviation increase in NE concentration (Estimate = 0.230, p < 0.001). MEL concentrations were approximately 43% higher in the awake phase compared to GA (Estimate = 0.356, p < 0.001). GA did not significantly modify the NE-MEL association (Estimate = -0.02877, p = 0.528). Substantial positive correlation was observed between baseline MEL concentrations and the magnitude of the response to NE administration (r = 0.74). In conclusion, intravenous NE increases plasma MEL concentrations in both awake and anaesthetised individuals. Substantial interindividual variation in MEL response suggests underlying physiological differences. Future studies should explore the long-term effects of NE administration on MEL concentrations. Trial Registration: The study is registered in the Dutch Trial Register (NL9312).

Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome caused by germline mutations in DNA mismatch repair genes or, less commonly, EPCAM deletions. LS-associated colorectal carcinomas often present at a young age and may show unusual histomorphological patterns, posing diagnostic challenges. We report a rare case of a 29-year-old female with EPCAM-mutated LS presenting as colonic adenocarcinoma with neuroendocrine-like rosette formation. The tumor initially mimicked mixed adenoneuroendocrine carcinoma (MANEC) due to biphasic histology and the presence of multiple rosettes. However, immunohistochemistry demonstrated negativity for synaptophysin and chromogranin, excluding true neuroendocrine differentiation with diffuse Pan CK and focal CDX2, CK20 positivity along with loss of MSH2 and MSH6. Further molecular analyses confirmed EPCAM exon 5-9 deletion. The tumor was ultimately classified as an MMR-deficient adenocarcinoma with pseudoendocrine morphology. This case broadens the histomorphological spectrum of LS-associated colorectal carcinomas and introduces the concept of a possible pseudoendocrine carcinoma arising in an epithelial malignancy. Recognition of this pattern is crucial to prevent misdiagnosis as MANEC, to guide appropriate management, facilitate familial screening, and highlight that not every rosette signifies neuroendocrine differentiation; some may represent LS in disguise.

Temozolomide (TMZ) is an established therapy for gliomas with silencing of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) but is hindered by the frequent development of resistance via loss of mismatch repair (MMR) proteins. To overcome this resistance, a novel 2-fluoroethylating agent, KL-50, was designed to generate toxic DNA interstrand cross-links specifically in MGMT-deficient cells, bypassing MMR. KL-50 has shown efficacy in preclinical MGMT-silenced, TMZ-resistant glioma models. MGMT loss also occurs in a wide range of nonglioma cancers, but the ability of KL-50 to effectively treat these tumors with minimal off-target toxicity remains untested. In this study, we utilize a large-scale cell-line screen, focused panels of cancer cell lines, and tumor xenograft mouse models, including patient-derived xenografts, to interrogate the therapeutic potential of KL-50 in treating intracranial and extracranial tumors. We find that KL-50 is highly efficacious in a wide range of MGMT-deficient human tumor models, including colon cancer, melanoma, and lung cancer in vivo models. In addition, we demonstrate that KL-50 is impervious to loss of MMR and remains effective in tumors with induced TMZ resistance. Finally, we determine that KL-50 possesses higher MGMT selectivity in vitro compared with chloroethylating agents and is associated with less in vivo systemic toxicity in preclinical models. These results establish KL-50 as the first agent to maintain strong selectivity for MGMT loss while inducing tumor toxicity by an MMR-independent mechanism and support further development of 2-fluoroethylating agents for use in a tumor type-agnostic, biomarker-based strategy targeting MGMT-deficient tumors.

Florida's proposal to remove vaccine mandates in the state raises urgent questions about the state's vulnerability to measles resurgence. We develop and analyze an age-structured measles transmission model with heterogeneous contact patterns between children and adults, calibrated using data from the 2025 measles outbreak in Gaines County, Texas, and applied to Florida using state-specific demographic structure and measles-mumps-rubella (MMR) vaccination coverage. Using Florida-specific mixing patterns and demographic composition, we estimate the state's vaccine-induced herd immunity threshold and find that current MMR coverage already falls below the level required to prevent sustained measles transmission. Simulated declines in MMR vaccination coverage following removal of school-entry requirements further increase outbreak potential, producing epidemic sizes not seen since prevaccine eras and projecting a significant number of pediatric deaths within five years. Sensitivity analyses highlight that small reductions in child vaccination rates yield disproportionately large increases in outbreak magnitude, especially under strong assortative mixing among children. These findings indicate that Florida's vaccination policies are approaching a critical tipping point: Maintaining or improving MMR vaccination coverage is essential to prevent measles from reestablishing endemic circulation within the state and potentially spreading to the broader United States.

Free-text narratives in vaccine adverse event reports contain symptom descriptions and contextual wording that can be characterized using text mining. However, lexicon-based sentiment scores in medical narratives should be interpreted as vocabulary patterns rather than direct measures of patients' emotional states. We evaluated sex-specific and vaccine-specific patterns in sentiment-scored and emotion-category assignment vocabulary in Vaccine Adverse Event Reporting System (VAERS) narratives for coronavirus disease 2019 (COVID-19), influenza, human papillomavirus (HPV), and measles-mumps-rubella (MMR) vaccines. Public VAERS reports received from 2010 to 2024 were analyzed. VAERSDATA, VAERSVAX, and VAERSSYMPTOMS were linked by VAERS_ID, with duplicate records removed. Report-level AFINN scores were normalized per 100 words. Sensitivity analyses excluded common clinical and symptom-related terms. Effect sizes, 95% confidence intervals, adjusted linear regression models with HC3 robust standard errors, and NRC emotion-category assignment profiles were evaluated. After duplicate handling, 1022460 COVID-19, 148489 influenza, 41212 HPV, and 47459 MMR reports were analyzed. Female-associated reports generally showed slightly lower primary AFINN scores than male-associated reports, although effect sizes were negligible. Excluding clinical and symptom-related terms attenuated or reversed these differences. Adjusted regression models showed only small associations between sex and AFINN scores. NRC analyses demonstrated clearer vaccine-specific than sex-specific vocabulary patterns. VAERS narratives showed only small sex-related differences but distinct vaccine-specific patterns in sentiment-scored and emotion-category assignment vocabulary. These findings should be interpreted as lexicon-derived vocabulary patterns rather than direct measures of psychological responses, vaccine perceptions, or clinical outcomes.

Background and Objectives: Despite long-standing MMR vaccination programmes, outbreaks of vaccine-preventable diseases continue to occur worldwide, raising concerns regarding waning immunity and susceptibility gaps in adult populations. Between 2017 and 2019 alone, WHO reported over 880,000 measles cases globally-a fourfold increase over the preceding two years-with outbreaks in both low- and high-income countries despite high childhood vaccination coverage. This study evaluated the seroepidemiology of measles, mumps, and rubella among adults in Türkiye over a nine-year period. Materials and Methods: A retrospective laboratory-based study was conducted using ELISA IgM and IgG results obtained between 2014 and 2022 at a tertiary-care university hospital. Seropositivity rates were analysed by year, age group, and sex. Temporal trends were assessed using the Cochran-Armitage trend test; factors associated with IgG seropositivity were assessed using multivariable logistic regression. Results: Among 10,407 adult test records, overall IgG seropositivity was 75.8% for measles, 94.9% for rubella, and 86.3% for mumps; IgM positivity remained low throughout (0.9%, 0.4%, and 1.9%, respectively). Measles IgG declined significantly from 78.4% in 2014-2019 to 62.6% in 2022 (p < 0.001), whereas Rubella IgG remained stable (93.2-95.7%) and Mumps IgG showed no significant temporal change. Seropositivity increased markedly with age for measles (18-29 years: 70.2% vs. ≥50 years: 93.4%; p < 0.001) and mumps (p = 0.030). Multivariable analysis confirmed that Measles IgG seropositivity was substantially lower in 2022 than in the pooled 2014-2019 period (OR = 0.432, 95% CI: 0.319-0.584, p < 0.001). Rubella seroprotection among women of reproductive age was 94.7% (95% CI: 93.9-95.5%), close to but not statistically distinguishable from the 95% population immunity benchmark used in rubella elimination frameworks. Conclusions: A significant measles immunity gap exists among younger adults in Türkiye, with Measles IgG seropositivity declining from 78.4% in 2014-2019 to 62.6% in 2022, consistent with a cohort effect whereby vaccine-era cohorts exhibit lower protection than older adults with naturally acquired immunity. Rubella immunity, by contrast, remained close to the 95% elimination benchmark throughout. These findings underscore the importance of targeted serological surveillance and evidence-based booster vaccination strategies.