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Stemphylium lycopersici is one of the causal agents of the gray spot on the tomato leaves, a recurrent and widespread pathology in tomato crops in Holguín. The in vitro antagonism of Trichoderma harzianum strains A-34, A-53 and Trichoderma viride TS-3 was evaluated against Stemphylium lycopersici. The confrontation was carried out by means of an antagonism assay in Papa Dextrose Agar PDA culture medium. The indicator evaluated was the mycelial inhibition percentage IM (%).The three strains of Trichoderma sp. showed high antagonistic effectiveness in vitro against Stemphylium lycopersici. [ABSTRACT FROM AUTHOR]

The effect of the imbibition temperature on the operational performance of the extraction stage is not fully clarified. Additionally, many criteria referred to on this issue are contradictory, inconclusive, or not supported by industrial data. Due to such limitations in knowledge, this research aims to analyze the influence of imbibition temperature on: i) temperature of the milling train juices, ii) moisture and sucrose composition of bagasse, and iii) starch composition of milling train juices. The results indicate that the imbibition temperature has no influence on the mixed juice temperature and does not allow the minimum recommended temperature for asepsis (65 °C) in all juices of the milling units to be reached. Moreover, from the experiments performed, it is established that bagasse moisture increases by 1.6–1.8 units, and sucrose extraction reduces by 12% when the imbibition temperature varies from 85 °C to 40 °C. The starch composition of the mixed juice increases by 15% when the imbibition temperature rises from 40 °C to 85 °C. The research provides new statistical evidence for a better understanding and operational control of the effect of imbibition temperature. • New statistical evidence was obtained to better understand the imbibition temperature effect. • The findings are useful for managing extraction performance. • The increase in starch extraction according to the rising imbibition temperature is determined. [ABSTRACT FROM AUTHOR]

Chordoid meningioma is a morphological variant of meningioma designated as WHO grade 2. However, the recurrence rates varied widely in different case series, and to date, a unifying molecular genetic signature has not been identified. Among 1897 meningiomas resected at our institution, we identified 12 primary chordoid meningiomas from 12 patients. Histologically, all 12 cases had predominant (> 50%) chordoid morphology. Ten were otherwise grade 1, and two were also atypical. We performed DNA global methylation profile, copy number variation analysis, and targeted next-generation sequencing on 11 chordoid meningiomas, and compared to those of 51 non-chordoid, mostly high grade meningiomas. The chordoid meningiomas demonstrated a unique methylation profile in tSNE, UMAP, and hierarchical heatmap clustering analyses of the most differentially methylated CpGs. The most common copy number variation in chordoid meningioma was loss of 1p (7/11, 64%). Three chordoid meningiomas had 2p loss, which was significantly higher than the non-chordoid control cohort (27% vs 7.2%, p = 0.035). 22q loss was only seen in the two cases with additional atypical histological features. Chordoid meningiomas were enriched in mutations in chromatin remodeling genes EP400 (8/11,73%) KMT2C (4/11, 36%) and KMT2D (4/11, 36%), and showed low or absent NF2, TERT, SMO, and AKT1 mutations. Prognosis wise, only one case recurred. This case had atypical histology and high-grade molecular features including truncating NF2 mutation, 1p, 8p, 10, 14, 22q loss, and homozygous deletion of CDKN2A/B. Progression free survival of chordoid, otherwise grade 1 meningioma was comparable to non-chordoid WHO grade 1 meningioma (p = 0.75), and significantly better than chordoid WHO grade 2 meningioma (p = 0.019). Conclusion: the chordoid histology alone may not justify a universal WHO grade 2 designation. Screening for additional atypical histological or molecular genetic features is recommended. [ABSTRACT FROM AUTHOR]

Purpose: Molecular subgroups of pediatric brain tumors associated with divergent biological, clinical, and prognostic features have been identified. However, data regarding the impact of subgroup affiliation on the outcome of children with malignant brain tumors treated with radiation-sparing protocol is limited. We report long-term clinical outcomes and the molecular subgroups of malignant brain tumors in young children whose first-line treatment was high-dose chemotherapy without irradiation. Methods: Tumor subclassification was performed using the Illumina HumanMethylation450 BeadChip (450k) genome-wide methylation array profiling platform. Clinical information was obtained from chart review. Results: Methylation array profiling yielded information on molecular subgroups in 22 children. Median age at surgery was 26 months (range 1–119 months). Among medulloblastomas (MB), all 6 children in the infant sonic hedgehog (SHH) subgroup were long-term survivors, whereas all 4 children in subgroup 3 MB died. There was one long-term survivor in subgroup 4 MB. One out of five children with ependymoma was a long-term survivor (RELPOS). Both children with primitive neuroectodermal tumors died. One child with ATRT TYR and one child with choroid plexus carcinoma were long-term survivors. Conclusions: The efficacy of high-dose chemotherapy radiation-sparing treatment appears to be confined to favorable molecular subgroups of pediatric brain tumors, such as infant SHH MB. Identification of molecular subgroups that benefit from radiation-sparing therapy will aid in the design of prospective, "precision medicine"–driven clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: There is variability in survival within IDH mutant gliomas determined by chromosomal events. Copy number variation (CNV) abundance associated with survival in low-grade and IDH mutant astrocytoma has been reported. Our purpose was to correlate the extent of genome-wide CNV abundance in IDH mutant astrocytomas with MRI features. Methods: Presurgical MRI and CNV plots derived from Illumina 850k EPIC DNA methylation arrays of 18 cases of WHO grade II–IV IDH mutant astrocytomas were reviewed. IDH mutant astrocytomas were divided into CNV stable group (CNV-S) with ≤ 3 chromosomal gains or losses and lack of focal gene amplifications and CNV unstable group (CNV-U) with > 3 large chromosomal gains/losses and/or focal amplifications. The associations between MR features, relative cerebral blood volume (rCBV), CNV abundance, and time to progression were assessed. Tumor rCBV estimates were obtained using DSC T2* perfusion analysis. Results: There were nine (50%) CNV-S and nine (50%) CNV-U IDH mutant astrocytomas. CNV-U tumors showed larger mean tumor size (P = 0.004) and maximum diameter on FLAIR (P = 0.004) and also demonstrated significantly higher median rCBV than CNV-S tumors (2.62 vs 0.78, P = 0.019). CNV-U tumors tended to have shorter time to progression although without statistical significance (P = 0.393). Conclusions: Larger size/diameter and higher rCBVs were seen associated CNV-U astrocytomas, suggesting a correlation of aggressive imaging phenotype with unstable and aggressive genotype in IDH mutant astrocytomas. [ABSTRACT FROM AUTHOR]

Background: In many cancers, specific subtypes are more prevalent in specific racial backgrounds. However, little is known about the racial distribution of specific molecular types of brain tumors. Public data repositories lack data on many brain tumor subtypes as well as diagnostic annotation using the current World Health Organization classification. A better understanding of the prevalence of brain tumors in different racial backgrounds may provide insight into tumor predisposition and development, and improve prevention., Methods: We retrospectively analyzed the racial distribution of 1709 primary brain tumors classified by their methylation profiles using clinically validated whole genome DNA methylation. Self-reported race was obtained from medical records. Our cohort included 82% White, 10% Black, and 8% Asian patients with 74% of patients reporting their race., Results: There was a significant difference in the racial distribution of specific types of brain tumors. Blacks were overrepresented in pituitary adenomas (35%, P < .001), with the largest proportion of FSH/LH subtype. Whites were underrepresented at 47% of all pituitary adenoma patients ( P < .001). Glioblastoma (GBM) IDH wild-type showed an enrichment of Whites, at 90% ( P  < .001), and a significantly smaller percentage of Blacks, at 3% ( P  < .001)., Conclusions: Molecularly classified brain tumor groups and subgroups show different distributions among the three main racial backgrounds suggesting the contribution of race to brain tumor development., Competing Interests: M.S. is scientific advisor and shareholder of Heidelberg Epignostix and Halo Dx, and a scientific advisor of Arima Genomics, and InnoSIGN, and received research funding from Lilly USA. Other authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology. The 5th edition of the Central Nervous System World Health Organization (WHO) introduces CDKN2A/B homozygous deletion as a biomarker of grade 4. We sought to investigate the prognostic impact of DNA methylation-derived molecular biomarkers for IDH mutant astrocytoma., Methods: We analyzed 98 IDH mutant astrocytomas diagnosed at NYU Langone Health between 2014 and 2022. We reviewed DNA methylation subclass, CDKN2A/B homozygous deletion, and ploidy and correlated molecular biomarkers with histological grade, progression free (PFS), and overall (OS) survival. Findings were confirmed using 2 independent validation cohorts., Results: There was no significant difference in OS or PFS when stratified by histologic WHO grade alone, copy number complexity, or extent of resection. OS was significantly different when patients were stratified either by CDKN2A/B homozygous deletion or by DNA methylation subclass (P value = .0286 and .0016, respectively). None of the molecular biomarkers were associated with significantly better PFS, although DNA methylation classification showed a trend (P value = .0534)., Conclusions: The current WHO recognized grading criteria for IDH mutant astrocytomas show limited prognostic value. Stratification based on DNA methylation shows superior prognostic value for OS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

DNA methylation is an essential molecular assay for central nervous system (CNS) tumor diagnostics. While some fusions define specific brain tumors, others occur across many different diagnoses. We performed a retrospective analysis of 219 primary CNS tumors with whole genome DNA methylation and RNA next-generation sequencing. DNA methylation profiling results were compared with RNAseq detected gene fusions. We detected 105 rare fusions involving 31 driver genes, including 23 fusions previously not implicated in brain tumors. In addition, we identified 6 multi-fusion tumors. Rare fusions and multi-fusion events can impact the diagnostic accuracy of DNA methylation by decreasing confidence in the result, such as BRAF, RAF, or FGFR1 fusions, or result in a complete mismatch, such as NTRK, EWSR1, FGFR, and ALK fusions., Implications: DNA methylation signatures need to be interpreted in the context of pathology and discordant results warrant testing for novel and rare gene fusions., (©2023 American Association for Cancer Research.)

Background: Survival for patients with high-risk neuroblastoma (HRNB) remains poor despite aggressive multimodal therapies., Aims: To study the feasibility and safety of incorporating a genomic-based targeted agent to induction therapy for HRNB as well as the feasibility and safety of adding difluoromethylornithine (DFMO) to anti-GD2 immunotherapy., Methods: Twenty newly diagnosed HRNB patients were treated on this multicenter pilot trial. Molecular tumor boards selected one of six targeted agents based on tumor-normal whole exome sequencing and tumor RNA-sequencing results. Treatment followed standard upfront HRNB chemotherapy with the addition of the selected targeted agent to cycles 3-6 of induction. Following consolidation, DFMO (750 mg/m 2 twice daily) was added to maintenance with dinutuximab and isotretinoin, followed by continuation of DFMO alone for 2 years. DNA methylation analysis was performed retrospectively and compared to RNA expression., Results: Of the 20 subjects enrolled, 19 started targeted therapy during cycle 3 and 1 started during cycle 5. Eighty-five percent of subjects met feasibility criteria (receiving 75% of targeted agent doses). Addition of targeted agents did not result in toxicities requiring dose reduction of chemotherapy or permanent discontinuation of targeted agent. Following standard consolidation, 15 subjects continued onto immunotherapy with DFMO. This combination was well-tolerated and resulted in no unexpected adverse events related to DFMO., Conclusion: This study demonstrates the safety and feasibility of adding targeted agents to standard induction therapy and adding DFMO to immunotherapy for HRNB. This treatment regimen has been expanded to a Phase II trial to evaluate efficacy., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

We analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an SV amplifying a MYC enhancer in 12% of diffuse midline gliomas (DMG), indicating an underappreciated role for MYC in pHGG. SV signature analysis revealed that tumors with simple signatures were TP53 wild type (TP53 WT ) but showed alterations in TP53 pathway members PPM1D and MDM4. Complex signatures were associated with direct aberrations in TP53, CDKN2A and RB1 early in tumor evolution and with later-occurring extrachromosomal amplicons. All pHGGs exhibited at least one simple-SV signature, but complex-SV signatures were primarily restricted to subsets of H3.3 K27M DMGs and hemispheric pHGGs. Importantly, DMGs with complex-SV signatures were associated with shorter overall survival independent of histone mutation and TP53 status. These data provide insight into the impact of SVs on gliomagenesis and the mechanisms that shape them., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The immature physiology of cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) limits their utility for drug screening and disease modelling. Here we show that suitable combinations of mechanical stimuli and metabolic cues can enhance the maturation of hiPSC-derived cardiomyocytes, and that the maturation-inducing cues have phenotype-dependent effects on the cells' action-potential morphology and calcium handling. By using microfluidic chips that enhanced the alignment and extracellular-matrix production of cardiac microtissues derived from genetically distinct sources of hiPSC-derived cardiomyocytes, we identified fatty-acid-enriched maturation media that improved the cells' mitochondrial structure and calcium handling, and observed divergent cell-source-dependent effects on action-potential duration (APD). Specifically, in the presence of maturation media, tissues with abnormally prolonged APDs exhibited shorter APDs, and tissues with aberrantly short APDs displayed prolonged APDs. Regardless of cell source, tissue maturation reduced variabilities in spontaneous beat rate and in APD, and led to converging cell phenotypes (with APDs within the 300-450 ms range characteristic of human left ventricular cardiomyocytes) that improved the modelling of the effects of pro-arrhythmic drugs on cardiac tissue., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)