Intermolecular (United States)

Spatial biology has advanced our understanding of cancer biology and shed light on the immense transcriptomic and proteomic heterogeneity that exists within the tumor-immune microenvironment (TiME). To date, most analytical and diagnostic approaches only provide one type of biological readout per tissue section, and the generation of true multi-omic data has remained challenging. We developed a workflow that allows the integration of multiple omic modalities on a single section. The workflow is centered around a new signal removal strategy, EpicIF™ technology, which effectively and rapidly removes fluorophores while leaving tissue and probe chemistries unaffected. Using this workflow on the CellScape™ platform, we iteratively performed spatial proteomic, transcriptomic, and interactomic assays all on the same tissue sections. Formalin-fixed, paraffin-embedded tissue sections were subjected to standard histological processing and then incubated with primary antibodies against PD1 and PD-L1, which were then treated with oligonucleotide-modified secondary probes designed for an in situ Proximity Ligation Assay (isPLA) to detect PD1 and PD-L1 interactions. Next, the detection of RNA targets was accomplished by adding 12 HCR™ HiFi RNA-ISH probes, which were visualized by addition of target-specific fluorescently labeled HCR™ Gold amplifiers (RNA-FISH). Lastly, spatial proteomic labeling was conducted with VistaPlex™ multiplex immunofluorescence (mIF) panels targeting 30+ biomarkers. We deployed this tri-omic assay on samples of primary CNS lymphoma (PCNSL), a rare and aggressive form of B-cell lymphoma that remains an area of unmet clinical need, with over half of diagnosed patients succumbing to the disease. Unlike diffuse large b-cell lymphoma (DLBCL), its morphologically identical systemic counterpart, PCNSL shows sensitivity to PD1 checkpoint inhibition. We investigated if our assay could describe unique interactions between the PD1-PDL1 axis and the lymphoma TiME in PCNSL (n=24), in comparison to DLBCL (n=152) cases. High-resolution imaging with the CellScape platform allowed for precise detection and quantification of isPLA, RNA-FISH and mIF signals on the same slide. The combined assay showed differential biomarker expression and interaction profiles associated with immune-regulatory processes in the interrogated tumor samples, revealing remarkable inter- and intra-tumoral heterogeneity. This spatial multi-omics approach allows for a more comprehensive insight into the complex interplay of immune and non-immune cell populations in the TiME. Citation Format: Arne Christians, Jannik Boog, Daniel Jimenez Sanchez, Sara Bodbin, Agata Wicher, Subham Basu, Aneesh Acharya, Randy Chen, Hong Liang, Shruti Shridar, Tan Char Loo, Ng Siok Bian, Michelle Poon, Anand Jeyasekharan, Oliver Braubach. Development of a novel tri-omic spatial biology assay that provides in-depth immune profiling of the tumor immune microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2084.

RNA editing analysis in single lung adenocarcinoma cells uncovers RNA mutations that correlate with tumor mutation burden and cancer innate immunity and reveals the amount of RNA mutations that strongly predicts patient survival. See related commentary by Luo and Liang, p. 351.

Intelligent Transportation Systems (ITS) are an emerging sector of the urban transportation research area. The increased cognitive capability of ITS is expected to create future cities and environments in which people are safer and have a better quality of life, as well as offering more efficient use of resources and improved safety.

In this research, a new depside of the lichen Everniopsis trulla has been isolated. The extraction was carried out to 400 g of dry sample and ground with ethanol for 3 repetitions, then, it was fractionated by applying column chromatography with the CHCl3-MeOH system and purified by recrystallization with MeOH-Acetone (1: 1); Finally, white crystals in the form of needles (solid C) with a melting point of 198 ° C were obtained, whose structure was elucidated based on spectroscopic data (UV-Visible, IR, NMR-H1, NMR-C13, mass spectrometry and single crystal X-ray diffraction). According to the Science Finder databases, it is a new depside, called trullarin, and it is observed that molecular packing is influenced by both intramolecular and intermolecular forces. Intermolecular hydrogen bonds of O - H -O type binds neighboring molecules forming dimers.

A interação entre educador e educando afasta-se, cada vez mais, das práticas conservadorasde ensino. As metodologias ativas possibilitam o envolvimento e o interesse do aluno, bem como promovem a atitude ativa na aprendizagem, o que é ainda mais desejável na Educação a Distância. A gamificação é um dos recursos didáticos possíveis no ambiente virtual de aprendizagem. No presente estudo, adotou-se uma pesquisa aplicada com abordagem quali-quantitativa, com observação participante, na aplicação de Júri Simulado com alunos do curso Técnico em Multimeios Didáticos, em uma instituição pública de ensino. A prática buscou avaliar o uso da gamificação para aproximar os alunos do conteúdo, desenvolver aargumentação, motivar e tornar a aula virtual mais propícia à interação. A maioria dos alunos (87%) afirmou motivação no desenvolvimento da atividade. Os resultados apontam que a metodologia utilizada favoreceu o engajamento, a interação e a aprendizagem dos alunos.

Cancer cells exploit the unfolded protein response (UPR) to mitigate endoplasmic reticulum (ER) stress caused by cellular oncogene activation and a hostile tumor microenvironment (TME). The key UPR sensor IRE1α resides in the ER and deploys a cytoplasmic kinase-endoribonuclease module to activate the transcription factor XBP1s, which facilitates ER-mediated protein folding. Studies of triple-negative breast cancer (TNBC)-a highly aggressive malignancy with a dismal posttreatment prognosis-implicate XBP1s in promoting tumor vascularization and progression. However, it remains unknown whether IRE1α adapts the ER in TNBC cells and modulates their TME, and whether IRE1α inhibition can enhance antiangiogenic therapy-previously found to be ineffective in patients with TNBC. To gauge IRE1α function, we defined an XBP1s-dependent gene signature, which revealed significant IRE1α pathway activation in multiple solid cancers, including TNBC. IRE1α knockout in TNBC cells markedly reversed substantial ultrastructural expansion of their ER upon growth in vivo. IRE1α disruption also led to significant remodeling of the cellular TME, increasing pericyte numbers while decreasing cancer-associated fibroblasts and myeloid-derived suppressor cells. Pharmacologic IRE1α kinase inhibition strongly attenuated growth of cell line-based and patient-derived TNBC xenografts in mice and synergized with anti-VEGFA treatment to cause tumor stasis or regression. Thus, TNBC cells critically rely on IRE1α to adapt their ER to in vivo stress and to adjust the TME to facilitate malignant growth. TNBC reliance on IRE1α is an important vulnerability that can be uniquely exploited in combination with antiangiogenic therapy as a promising new biologic approach to combat this lethal disease. SIGNIFICANCE: Pharmacologic IRE1α kinase inhibition reverses ultrastructural distension of the ER, normalizes the tumor vasculature, and remodels the cellular TME, attenuating TNBC growth in mice.

Atomic layer deposition (ALD) of chalcogenide amorphous films has attracted attention, thanks to its ability to deposit highly conformal and uniform thin films on three-dimensional structures; these film properties are critical for the development of ultrahigh-density integrated electronic circuits such as nanoscale 3D cross-point memory stacks. Control over the composition of chalcogenide compounds is indispensable for fabricating functional electronic devices. In this work, the authors used trichlorogermane (HGeCl3) and bis(trimethylsilyl)telluride [(Me3Si)2Te] as ALD precursors to develop conformal and uniform germanium telluride (GeTe) films at low temperature (60 °C). The growth of GeTe resulted in moderately Ge rich films independently of the ALD precursor injection time and the use of single or discrete (Me3Si)2Te doses. To achieve control over the GeTe film composition, the authors developed a unique ALD of elemental tellurium (Te) using tellurium ethoxide [Te(OEt)4] and (Me3Si)2Te as precursors. Combining GeTe and elemental Te in an ALD supercycle fashion, they obtained GeTex films with a controllable Te content showing a uniform and conformal morphology on high aspect ratio trench structures. A detailed analysis of the variations in Ge and Te contents upon exposure of GeTex films to Te(OEt)4 revealed that an interfacial replacement of Ge atoms to form volatile Ge(OEt)2 takes place and produces a decrease in Ge and an increase in Te content. The ALD studies of GeTe and Te films described in this work provide a facile route for deposition of GeTe with controllable composition. This material system is important for the development of ovonic threshold switching selectors and phase change memories.

Abstract As clinical data are digitized in electronic medical records (EMR), the amount of historical data becomes a challenge for utilization and outcomes studies. An automated approach for structuring clinical data into machine-readable format is essential due to scale. We previously developed MMPower, an ElasticSearch-based technology platform for named entity extraction defined by SNOMED conditions, >2,000 Entrez Genes, >900,000 cancer alterations, and ~7,000 FDA-approved and experimental therapeutics/progression that enables clinical trials search. In a pilot study, MMPower was applied to characterize and index oncology EMR for elucidating clinical histories and identifying clinical trial participants. 52,509 individual EMR were collated by Medical Record Number (MRN) across facets including Demographics, Providers/Sites, Diagnosis, Medication, Imaging, Lab results, Pathology, Performance status, and Encounter with Physician Notes. Applying MMPower yielded a total cohort of 43,987 (83.8% of EMR received) EMR with searchable, structured metadata profiles. We found that 39,317 (89.4%) of the total cohort had a cancer diagnosis as defined by SNOMED cancer types. We also extracted an Entrez gene from 36,152 (82.2%) EMR, while cancer alterations or stratification biomarkers such as ER/PR status, ALK fusions, IGH-BCL1, EGFR exon 19 deletion, CDKN2A loss, etc., were identified in 25,208 (57.3%) EMR. Furthermore, we found that the majority of EMR (69.7%) with identifiable genes also contained a cancer alteration. Interestingly, although most EMR (39,615 or 90% of total cohort) held identifiable cancer therapeutics, only 1.7% of the total cohort were flagged as cases of progression. We then determined the feasibility of matching EMR to clinical trials and found that, strikingly, 16.7% of the total cohort were potentially eligible for institution-specific clinical trials. Finally, we sought to enrich individual EMR with molecular alterations data from external lab reports, so we developed a PDF to JSON transform that enables mapping of report results by MRN to our cancer alterations model, yielding a single searchable record from multiple data sources. These results suggest that the ability to structure machine-readable clinical and molecular data for individuals from EMR at scale would accelerate translational research by promoting more efficient clinical trials accrual and could be extended to prevalence calculations, evidence-backed treatment guidance through molecular assertions, biomarkers discovery, and outcomes studies of therapeutic efficacy. Citation Format: Ryan Duren, Ryan Smith, Nick Tackes, Shane Neeley, James Welsh, Xuan Shirley Li. Scalable assembly of individual patient profiles for clinical trials accrual and research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3677.

Abstract FLT3 ITD, a prognostic marker and drug target, is present in ~19% of AML patients. FLT3 ITD is a tandem repeat of the entire or partial exon 13-15 region. FLT3 ITDs range in size from 3bp to above 300bp and impact RTK signaling. Recent publications have shown that FLT3 ITD can be detected at single nucleotide resolution by NGS panels. However, detection of large FLT3 ITD and accurate reporting of ITD frequency remain challenging for NGS methods. False negative ITD results or inaccurate mutant/wild type allele ratio measurements could negatively alter treatment decisions for AML patients. The Illumina TruSight Myeloid panel (TMP) is a commercial NGS assay that covers 54 genes involved in myeloid malignancies. Although the TMP assay can detect SBS and small indel, medium to large size FLT3 ITD cannot be detected. Here we present an enhanced workflow to overcome these challenges. Positive controls, dynamic range, accuracy, and inter-run reproducibility were validated for the detection of SBS, indel, and FLT3 ITD using reference standards and DNA extracted from cell lines and AML patient EDTA blood and bone marrow aspirate samples. NGS libraries were prepared following Illumina's standard protocol. 275bp X2 sequencing instead of the standard 150bp X2 was run on MiSeq flowcell v3. Data analysis was performed using a MolecularMD custom pipeline. The analysis of FLT3 ITD was conducted using three methods including two off-the-shelf programs, Pindel and ITDseek, as well as Cigar, a MolecularMD developed ITD detection algorithm. FLT3 ITDs at 126 bp and 21 bp in PL-21 and MOLM-13 cell lines, respectively, were detected by TMP assay using the three algorithms. In contrast to ITDseek which only reports ITD sequence without frequency information, Pindel and Cigar report both ITD sequence and frequency. Compared to Pindel, ITD frequency reported by the custom algorithm is closer to that determined by the fragment analysis. Serial dilution of the 126bp ITD into wild type DNA showed the 0.55% ITD (from fragment analysis) can be reproducibly detected at ~0.6% by the Cigar algorithm. FLT3 ITDs ranging in size from 6bp to 300bp were detected in clinical AML samples using the enhanced TMP workflow and confirmed by a fragment analysis method. Limit of detection, reproducibility and accuracy of SBS and indel detection in other key genes by the TMP assay have also been validated. Low-level mutations, i.e. NRAS G12D at 1.7%, NRAS G13D at 2%, and IDH2 R140Q at 1.4%, were detected by TMP panel from AML samples and further confirmed with an independent assay. A long deletion (52bp) in exon 9 of CALR was also detected by the custom pipeline. In summary, the enhanced TMP workflow allows for accurate detection and reporting of SBS, indel and FLT3 ITDs including large duplications. Optimized detection of FLT3 ITDs will improve AML patient selection for targeted therapy. Citation Format: Xiaodong Wang, Zhenyu Yan, Peng Fang, Weihua Liu, Scott Glynn, Jennifer Biroschak, Chad Galderisi, Cindy Spittle, Jin Li. An optimized NGS workflow for detection of FLT3 internal tandem duplication (ITD) in AML samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4522.

A Dismorfia Muscular é um termo médico que não foi catalogado no último DSM, pode ser compreendida como Transtorno Dismórfico Corporal. É mais prevalente nos homens do que nas mulheres, embora os números sejam difíceis de estimar. Abuso de Esteróides Anabolizantes e Dependência de Exercícios estão relacionados com a Dismorfia Muscular. Esse artigo fez uma revisão bibliográfica do tema nos últimos dez anos (1997 – 2007) e discorre sobre o papel do Psicólogo do Esporte. Trata-se de um tema pouco pesquisado, considera-se dessa maneira um amplo campo de investigação para as Ciências do Esporte.