ABSTRACTIntroductionChlorophyllin (CHL) effectively decreases the side effects of radiotherapy (RT) by scavenging radiation‐induced free radicals and reactive oxygen species in preclinical trials. This study aims to assess the efficacy of oral CHL for the treatment of brain radionecrosis in patients with diffuse glioma.MethodsThis is a phase 2 trial prospective, interventional study. Adults (> 18 years) with a histological diagnosis of diffuse glioma developing radionecrosis will be eligible for the study. Radionecrosis will be identified using standard imaging protocols with magnetic resonance imaging (MRI) with or without positron emission tomography (PET). Patients will be accrued in two strata: symptomatic (stratum A) and asymptomatic (stratum B). Chlorophyllin will be prescribed to all patients using a morning oral dose of 750 mg before breakfast for 3 months. In addition, participants in stratum A will be given a tapering dose of dexamethasone for 1 month, while stratum B will not be receiving any steroids. Imaging with an MRI brain protocol and PET scan will be planned at 1 month and MRI at 3 months after starting CHL. The primary endpoint is the clinical‐radiological response at 1 month. Secondary endpoints include response at 3 months, biological responses, survival analysis, and quality‐of‐life scores. The total sample size is 118 (60 and 58 in stratum A and B, respectively), with one interim analysis planned.DiscussionRadionecrosis leads to significant morbidity and is usually treated with corticosteroids, which can lead to several side effects from both acute and long‐term use. Refractory radionecrosis requires treatment with bevacizumab or surgical resection. Chlorophyllin is a cheap, safe, and readily available phytopharmaceutical drug, which is being investigated in the phase 2 study and, if proven effective, can be considered an alternative for treating radionecrosis.Trial Registration: Clinical Trial Registry India (CTRI): CTRI/2023/08/056166; ClinicalTrials.gov: NCT06016452

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ABSTRACTBackgroundNational social determinant of health (SDoH) studies on gastrointestinal cancers (GIC) have observed single GIC‐types for surgery but not across all GIC‐types, non‐surgical treatments outcomes, or mortality. The Social Vulnerability Index (SVI), a validated large‐data SDoH‐tool, quantifiably characterizes the interrelatedness of SDoH‐impact through dynamic, region‐contextualized measures.MethodsThis retrospective cohort study assessed GIC patients (20+ years) between 2013 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database for total and subcomponent social vulnerability associations across 15 SDoH‐variables encompassing themes of socioeconomic status, minority‐language status, household composition, and housing‐transportation measured by the Social Vulnerability Index (SVI). These are measured and contextualized from all US counties. Univariate logistic and linear regressions of these vulnerability associations with treatment receipt (chemotherapy, radiation, primary surgery) and survival were performed for the entire cohort and across race/ethnicity strata.ResultsWith increasing overall social vulnerability, 287,248 patients (162,387 [56.5%] male; 185,250 [64.6%] white) demonstrated decreased receipt of chemotherapy (lowest, pancreas‐OR, 0.90; 95% CI, 0.88–0.93), radiotherapy (hepatic‐OR, 0.87; 95% CI, 0.85–0.89) and surgery (esophagus‐OR, 0.90; 95% CI, 0.87–0.92) for 13/14, 10/14, and 8/14 GIC‐types, respectively. Survival period decreases upwards of 21.3% (biliary tract: 6.9–5.4 months) were observed across 7/14 GICs. Treatment receipt and survival decreases were exacerbated for non‐White patients for 9/14 GICs. Socioeconomic status, minority‐language, household composition, and housing‐transportation vulnerabilities differentially contributed to these trends.DiscussionSocial vulnerability was associated with worse prognostic and treatment disparities, with certain SDoH‐types differentially contributing to these detrimental trends per GIC‐type while associations were exacerbated among non‐White race/ethnic patients. These real‐world contexts present actionable targets for further initiatives to combat GIC disparities.

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AbstractA large fraction of newly transcribed RNA is degraded in the nucleus, but nuclear mRNA degradation pathways remain largely understudied. The yeast nuclear endonuclease Rnt1 has a well-characterized role in the maturation of many ncRNA precursors. However, the scope and consequence of its function in mRNA degradation pathways is much less defined. Here, we take a whole-transcriptome approach to identify Rnt1 cleavage sites throughout the yeast transcriptome in vivo, at single-nucleotide resolution. We discover previously unknown Rnt1 cleavage sites in many protein-coding regions and find that the sequences and structures necessary for cleavage mirror those required for the cleavage of known targets. We show that the nuclear localization of Rnt1 functions as an additional layer of target selection control and that cleaved mRNAs are likely exported to the cytoplasm to be degraded by Xrn1. Further, we find that several mRNAs rely heavily on Rnt1 for turnover, and strikingly, mutations in one of these targets,YDR514C, suppress the growth defect of aRNT1deletion. This suggests that Rnt1 limits the expression ofYDR514Cto maintain proper cellular homeostasis. This study uncovers a broader target range and function for the well-known RNase III enzyme.

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Context.— In 2018, an evidence-based guideline was published by the College of American Pathologists to develop recommendations for the testing, application, interpretation, and reporting of high-risk human papillomavirus and surrogate marker tests in head and neck carcinomas. Substantial new evidence has prompted a review, including data on human papillomavirus (HPV) in nonoropharyngeal anatomic sites, HPV global rates, p16 immunohistochemistry, and HPV testing performance in cytology specimens, and performance of p16 immunohistochemistry as a surrogate marker. Objective.— To assess research published since the release of the original 2018 guideline and to update evidence-based recommendations for HPV testing in head and neck carcinomas. Design.— The College of American Pathologists convened a panel of experts to update the guideline following the standards established by the National Academy of Medicine for developing trustworthy clinical practice guidelines. The expert panel defined the key questions and performed a systematic review of the literature. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, recommendations were updated on the basis of available evidence, certainty of that evidence, and key judgments. Results.— Seven strong recommendations, 4 conditional recommendations, and 5 good practice statements are offered in the guideline update. Conclusions.— The updated guideline statements provide direction on the nature of HPV testing in various head and neck specimens (including key updates based on new research on sinonasal squamous cell carcinoma) and expanded guidance on specific scenarios and practice settings. The goal is to improve and standardize, where possible, HPV testing across diverse pathology practice settings and different countries.

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Abstract Fennel and dill are well-known aromatic plants and are widely used commercially. They have also been recognized as a medicinal herb with numerous pharmacological activities. Thus, the interest in dill and fennel has been growing, and their industrial use is becoming more important. In this study, seeds of fennel and dill were extracted and analyzed using nuclear magnetic resonance (NMR) spectroscopy and ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC–QTOF/MS)-based metabolomics. Through 1D and 2D NMR analysis, a total of 34 primary metabolites were identified, and using UPLC–QTOF/MS, different chromatograms of dill and fennel were obtained in less than 20 min. In the multivariate statistical analysis of data obtained from NMR and MS, it was confirmed that seeds of dill and fennel discriminated clearly. Sugars and organic acids were identified as the primary metabolites contributing to significant differentiation of fennel and dill. Also, flavonoids, which were identified as secondary metabolites, significantly differentiated dill and fennel.

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Abstract With the development of space exploration and exploitation, it is imperative to address the potential threats posed to space objects, particularly ground-based infrared observation. However, in the extreme space environment, achieving infrared camouflage across different bands with simultaneous thermal management is challenging and has so far slipped out of concern. Here, we propose the space-to-ground infrared camouflage strategy, compatible with radiative heat dissipation. Camouflage in the H, K, mid-wave-infrared (MWIR), and long-wave-infrared (LWIR) bands is achieved through a multilayer structure, with radiative heat dissipation in the very-long-wave-infrared (VLWIR) band. High absorptivity (0.839/0.633) in the H/K bands minimizes the reflected signal of solar radiation and low emissivity (0.132/0.142) in the MWIR/LWIR bands suppresses the thermal radiation signal. Additionally, high emissivity (0.798) in the VLWIR band ensures efficient thermal management, resulting in a temperature decrement of 39.8 °C to the metal reference in the simulated space environment (with 1200 W m− 2 thermal input). This work inspires sophisticated spectral manipulation in extreme environments and guides the development of camouflage and radiative heat dissipation techniques for space objects.

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