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Utterances containing verbal irony display prosodic particularities that distinguish them from non-ironic speech. While some prosodic features of irony have been identified in Spanish, previous studies have not accounted for different subtypes, nor have they examined this phenomenon in Chilean Spanish despite the unique intonation patterns in this dialect. This study examined the acoustic and prosodic correlates of five subtypes of irony (jocularity, rhetorical questions, understatements, hyperbole, and sarcasm) spontaneously occurring in the casual speech of sociolinguistic interviews with fifteen Chilean women. We segmented 3907 syllable nuclei from 197 spontaneously occurring instances of irony and compared the syllables within the ironic utterances to those in the pre-ironic utterances, along seven acoustic and prosodic variables: pitch range, duration, F0, F1, F2, H1*–H2*, and HNR. The results showed that the speakers favored jocularity and did not produce sarcasm or understatements, and that jocularity, hyperbole, and rhetorical questions significantly differed from the baseline utterances along a variety of acoustic and prosodic measures. We argue that these cues contributed to marking the ironic utterances as salient, allowing these women to talk about difficult real-life events with a touch of humor. Our study provides additional evidence for the connection between prosody and pragmatics in Chilean Spanish and lays the groundwork for further examination of irony and prosody in this and other Spanish dialects.

In situ hybridization techniques are powerful methods for exploring gene expression in a wide range of biological contexts, providing spatial information that is most often lost in traditional biochemical techniques. However, many in situ hybridization methods are costly and time-inefficient, particularly for screening-based projects that follow on from single-cell RNA sequencing data, which rely on of tens of custom-synthetized probes against each specific RNA of interest. Here we provide an optimized pipeline for Hybridization Chain Reaction (HCR)-based RNA visualization, including an open-source code for optimized probe design. Our method achieves high specificity and sensitivity with the option of multiplexing using only five pairs of probes, which greatly lowers the cost and time of the experiment. These features of our HCR protocol are particularly useful and convenient for projects involving screening several genes at medium throughput, especially as the method include an amplification step, which makes the signal readily visible at low magnification imaging.

Abstract: Myelodysplastic syndromes (MDS) are clonal hematologic disorders characterized by morphologic abnormalities of myeloid cells and peripheral cytopenias. Although genetic abnormalities underlie the pathogenesis of these disorders and their heterogeneity, current classifications of MDS rely predominantly on morphology. We performed genomic profiling of 3233 patients with MDS or related disorders to delineate molecular subtypes and define their clinical implications. Gene mutations, copy-number alterations, and copy-neutral loss of heterozygosity were derived from targeted sequencing of a 152-gene panel, with abnormalities identified in 91%, 43%, and 11% of patients, respectively. We characterized 16 molecular groups, encompassing 86% of patients, using information from 21 genes, 6 cytogenetic events, and loss of heterozygosity at the TP53 and TET2 loci. Two residual groups defined by negative findings (molecularly not otherwise specified, absence of recurrent drivers) comprised 14% of patients. The groups varied in size from 0.5% to 14% of patients and were associated with distinct clinical phenotypes and outcomes. The median bone marrow (BM) blast percentage across groups ranged from 1.5% to 10%, and the median overall survival ranged from 0.9 to 8.2 years. We validated 5 well-characterized entities, added further evidence to support 3 previously reported subsets, and described 8 novel groups. The prognostic influence of BM blasts depended on the genetic subtypes. Within genetic subgroups, therapy-related MDS and myelodysplastic/myeloproliferative neoplasms had comparable clinical and outcome profiles to primary MDS. In conclusion, genetically-derived subgroups of MDS are clinically relevant and might inform future classification schemas and translational therapeutic research., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The polarization of cells often involves the transport of specific mRNAs and their localized translation in distal projections. Neurons and glia are both known to contain long cytoplasmic processes, while localized transcripts have only been studied extensively in neurons, not glia, especially in intact nervous systems. Here, we predict 1,740 localized Drosophila glial transcripts by extrapolating from our meta-analysis of seven existing studies characterizing the localized transcriptomes and translatomes of synaptically associated mammalian glia. We demonstrate that the localization of mRNAs in mammalian glial projections strongly predicts the localization of their high-confidence Drosophila homologs in larval motor neuron-associated glial projections and are highly statistically enriched for genes associated with neurological diseases. We further show that some of these localized glial transcripts are specifically required in glia for structural plasticity at the nearby neuromuscular junction synapses. We conclude that peripheral glial mRNA localization is a common and conserved phenomenon and propose that it is likely to be functionally important in disease., (© 2024 Lee et al.)

Although tumors of Li-Fraumeni syndrome (LFS) have a premalignant or dormant phase that could be exploited by early imaging detection, this has been underevaluated in the literature. We present a case series of patients with LFS followed by imaging over time to highlight patterns of growth of tumors and hotspots of missed tumors in this population. Clinical and imaging features were available for 29 tumors of 24 carriers of a germline TP53 pathogenic variant, developed between 1999 and 2023 were retrospectively reviewed in a single tertiary pediatric center. Imaging characteristics of tumors were evaluated with MRI, CT, and radiographs. Local invasion, time interval for developing primary cancer, and/or recurrent disease and metastasis, and factors that delayed the tumor diagnosis were assessed. In patients with multiple tumors the median time intervals for development of first, second, and third primary cancers were 45.9, 79.8, and 28.1 months, respectively. Hotspots of missed tumors included superficial soft tissues, areas close to bones, on the scalp, in tissues around the adrenal region and in small hypodense lesions on brain CT. In conclusion, the pattern of growth of tumors is variable and erratic in LFS patients with some tumors presenting with a dormant pattern., Competing Interests: A.S.D. is the Principal Investigator of the following grants unrelated to the current study: Novo Nordisk (Research Grant), Terry Fox Foundation (Research Grant), PSI Foundation (Research Grant), Society of Pediatric Radiology (Research Grant), Radiological Society of North America (Education Grant). The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Calcium signaling plays an integral role in neuronal communication and muscle movement. The junctophilin family of proteins are structural components of calcium channels of the endoplasmic reticulum and are implicated in various neurodegenerative disorders. This study examined the function of jph-1 , a gene coding for a junctophilin protein in Caenorhabditis elegans ( C. elegans ), by downregulating jph-1 gene expression using RNAi through bacterial feeding. Downregulation of jph-1 altered the physical morphology and impaired thrashing locomotion in wild-type C. elegans . These results are consistent with those of others in demonstrating a role for jph-1 in muscle physiology., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Biochar obtained via microwave-assisted pyrolysis (MAP) at 720 W and 15 min from cocoa pod husk (CPH) is an efficient adsorbent of Cd 2+ (aq). Biochar of residual biomass of CPH (BCCPH) possesses favorable physicochemical and morphological properties, featuring a modest surface area yet a suitable porous structure. Adsorption, predominantly governed by physisorption, is influenced by the oxygen-containing active sites (-COOR, -C(R)O, and -CH 2 OR; R = H, alkyl). CdCO 3 formation occurs during adsorption. Experimental data were well-fitted into various kinetic models for a broad understanding of the sorption process. Langmuir model indicates a maximum adsorption capacity of 14.694 mg/g. The thermodynamic study confirms the spontaneous and endothermic sorption. Studies at the molecular level have revealed that the Cd 2+ ion tends to bind to surface aromatic carbon atoms. This sustainable approach produces BCCPH via MAP as a solution for waste transformation into water-cleaning materials., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Purpose: Uterine sarcomas are a rare group of uterine malignancies. Due to the low incidence and changes in uterine sarcoma classification, risk factors are not well characterized. Our objective was to evaluate risk factors for uterine sarcoma and compare risk factors between uterine sarcoma, malignant mixed Mullerian tumors (MMMTs), and type I endometrial carcinomas., Methods: This nested case-control study utilized linked data from population-based medical birth and cancer registries in Denmark, Finland, Norway, and Sweden. Up to 10 controls were matched on country and birth year for each uterine cancer case. Using multivariable adjusted multinomial logistic regression, estimates of the associations between pregnancy-related factors and risk of uterine sarcoma, MMMTs, and type I endometrial carcinomas were determined., Results: Having a very-low-birth-weight infant (< 1500 vs. 2500-3999 g: OR [95% CI] 2.83 [1.61-4.96]) was associated with an increased risk of uterine sarcoma. Whereas, having a more recent pregnancy was associated with reduced risks of MMMT (< 10 vs. ≥ 30 years: 0.66 [0.20-2.23]) and type 1 endometrial carcinomas (0.35 [0.30-0.41]) but not uterine sarcomas (1.33 [0.90-1.98], p-heterogeneity < 0.01)., Conclusion: Our study provides evidence that risk factors for uterine sarcoma and MMMT, previously grouped with uterine sarcomas, vary substantially. Additionally, MMMT and type I endometrial carcinomas are more similar than uterine sarcoma in that pregnancy complications like gestational hypertension and preeclampsia were associated with reduced risks of both but not uterine sarcoma, suggesting different etiologies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)