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Glioblastoma (GBM) is the deadliest form of primary brain tumor with limited treatment options. Recent studies have profiled GBM tumor heterogeneity, revealing numerous axes of variation that explain the molecular and spatial features of the tumor. Here, we seek to bridge descriptive characterization of GBM cell type heterogeneity with the functional role of individual populations within the tumor. Our lens leverages a gene program-centric meta-atlas of published transcriptomic studies to identify commonalities between diverse tumors and cell types in order to decipher the mechanisms that drive them. This approach led to the discovery of a tumor-derived stem cell population with mixed vascular and neural stem cell features, termed a neurovascular progenitor (NVP). Following in situ validation and molecular characterization of NVP cells in GBM patient samples, we characterized their function in vivo. Genetic depletion of NVP cells resulted in altered tumor cell composition, fewer cycling cells, and extended survival, underscoring their critical functional role. Clonal analysis of primary patient tumors in a human organoid tumor transplantation system demonstrated that the NVP has dual potency, generating both neuronal and vascular tumor cells. Although NVP cells comprise a small fraction of the tumor, these clonal analyses demonstrated that they strongly contribute to the total number of cycling cells in the tumor and generate a defined subset of the whole tumor. This study represents a paradigm by which cell type-specific interrogation of tumor populations can be used to study functional heterogeneity and therapeutically targetable vulnerabilities of GBM.
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Rosai-Dorfman disease (RDD) with craniocervical junction involvement is a rare clinical entity. We present herein a case of a pediatric patient with craniocervical junction RDD which was surgically treated. A 10-year-old female with a history of B-cell acute lymphoblastic leukemia (B-ALL) in remission and RDD presented with frontal migraine headaches. She previously had a right posterior chest wall lesion which was biopsy-proven RDD. She was found on imaging to have a dural-based right craniocervical junction lesion. Given her history of B-ALL, after a multidisciplinary discussion, the decision was made to proceed with resection with possible initiation of cobimetinib or clofarabine. The patient underwent a suboccipital craniotomy, C1 laminectomy, and resection of the dural-based lesion. Gross total resection was achieved, and histopathology confirmed the diagnosis of RDD. She was discharged home on postoperative day 4. No recurrence was seen on follow-up imaging at 3 months. We conducted a systematic literature review examining all cases of pediatric intracranial RDD and all cases of craniocervical junction RDD. This represents, to the best of our knowledge, only the second case of pediatric craniocervical junction RDD. Although RDD is often self-limiting, medical treatment is often considered for intracranial disease, but tissue confirmation is necessary. Surgical resection provides histopathologic diagnosis and can sometimes serve as definitive treatment for a particular lesion.
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This Data in Brief (DiB) article presents the differences in cycling behaviors related to violations, errors, and positive behaviors by region. The study data were collected by means of a structured questionnaire applied to a full sample of 7,001 participants from 19 countries, distributed over 5 continents. This paper proposes descriptive statistics, as well as common statistical tests. The aim is to enable authors to make their own analyses, not to provide precise interpretations. For further information about the macro project supporting the collection of these data, it is advised to refer to the paper titled "Cross-culturally approaching the cycling behavior questionnaire (CBQ): Evidence from 19 countries", published in Transportation Research Part F: Traffic Psychology and Behavior.
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Accurate classification of genetic variants is crucial for clinical decision-making in hereditary cancer. In Spain, genetic diagnostic laboratories have traditionally approached this task independently due to the lack of a dedicated resource. Here we present SpadaHC, a web-based database for sharing variants in hereditary cancer genes in the Spanish population. SpadaHC is implemented using a three-tier architecture consisting of a relational database, a web tool and a bioinformatics pipeline. Contributing laboratories can share variant classifications and variants from individuals in Variant Calling Format (VCF) format. The platform supports open and restricted access, flexible dataset submissions, automatic pseudo-anonymization, VCF quality control, variant normalization and liftover between genome builds. Users can flexibly explore and search data, receive automatic discrepancy notifications and access SpadaHC population frequencies based on many criteria. In February 2024, SpadaHC included 18 laboratory members, storing 1.17 million variants from 4306 patients and 16 343 laboratory classifications. In the first analysis of the shared data, we identified 84 genetic variants with clinically relevant discrepancies in their classifications and addressed them through a three-phase resolution strategy. This work highlights the importance of data sharing to promote consistency in variant classifications among laboratories, so patients and family members can benefit from more accurate clinical management. Database URL: https://spadahc.ciberisciii.es/.
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Bases de Dados Genéticas , Humanos , Espanha , Variação Genética , Neoplasias/genética , Genes Neoplásicos , Predisposição Genética para DoençaRESUMO
In this case report, the diagnostic challenge and emergency management of a Bochdalek hernia in adults in Mexico are outlined. This case report can help the medical community to consider the clinical presentation in adults and the importance of early diagnosis and management. We present a 57-year-old female patient with a history of arterial hypertension who, following a bout of abdominal pain, was diagnosed with a Bochdalek hernia. Following emergency surgery, there was an increase in intra-abdominal pressure, which was continuously monitored due to the possibility of compartment syndrome, potentially necessitating a second emergency surgery.
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This study provides a comprehensive perspective on the deregulated pathways and impaired biological functions prevalent in human glioblastoma (GBM). In order to characterize differences in gene expression between individuals diagnosed with GBM and healthy brain tissue, we have designed and manufactured a specific, custom DNA microarray. The results obtained from differential gene expression analysis were validated by RT-qPCR. The datasets obtained from the analysis of common differential expressed genes in our cohort of patients were used to generate protein-protein interaction networks of functionally enriched genes and their biological functions. This network analysis, let us to identify 16 genes that exhibited either up-regulation (CDK4, MYC, FOXM1, FN1, E2F7, HDAC1, TNC, LAMC1, EIF4EBP1 and ITGB3) or down-regulation (PRKACB, MEF2C, CAMK2B, MAPK3, MAP2K1 and PENK) in all GBM patients. Further investigation of these genes and enriched pathways uncovered in this investigation promises to serve as a foundational step in advancing our comprehension of the molecular mechanisms underpinning GBM pathogenesis. Consequently, the present work emphasizes the critical role that the unveiled molecular pathways likely play in shaping innovative therapeutic approaches for GBM management. We finally proposed in this study a list of compounds that target hub of GBM-related genes, some of which are already in clinical use, underscoring the potential of those genes as targets for GBM treatment.
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Neoplasias Encefálicas , Glioblastoma , Análise de Sequência com Séries de Oligonucleotídeos , Humanos , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/terapia , Glioblastoma/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica , Masculino , Feminino , Mapas de Interação de Proteínas/genética , Pessoa de Meia-IdadeRESUMO
The Woven Endobridge (WEB) intrasaccular flow diversion device (Microvention, Inc.) is commonly used to treat both unruptured and ruptured wide-necked bifurcation aneurysms.1 Despite its relative safety and comparable rates of aneurysm occlusion, the device may compress over time resulting in aneurysm recurrence.2 In this video, we demonstrate the microsurgical retreatment of a large anterior communicating artery (ACoA) aneurysm previously treated with WEB. A 53-year-old patient with hypertension and current tobacco use presented with a ruptured ACoA aneurysm measuring 8.4 mm × 8 mm × 7 mm. She was urgently treated with a 9 mm × 5 mm WEB SL and made a full recovery. At 6 months, cerebral angiography showed a significant recurrence secondary to WEB compression. We considered both endovascular and microsurgical approaches; however, the anatomy was unfavorable for endovascular treatment.3 Although previous reports have documented clipping as a retreatment strategy, a minority of these aneurysms were ACoA aneurysms.4-7 The patient consented to the surgical procedure. This operative video illustrates the in vivo appearance of the WEB device and the surgical technique used to treat this unusual situation. The WEB device was firm and not as compressible as previously reported, but clipping was still possible.4,6 We highlight the use of temporary clipping, fenestrated clips, and intraoperative angiography in treatment. The aneurysm was occluded, and the patient remained without deficits. In summary, clip ligation can be an excellent option for ACoA aneurysms in the setting of WEB recurrence. The patient consented to this report; Institutional Review Board/ethics committee approval was not required.
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Glyphosate is a broad spectrum and non-selective herbicide employed to control different weeds in agricultural and urban zones and to facilitate the harvest of various crops. Currently, glyphosate-based formulations are the most employed herbicides in agriculture worldwide. Extensive use of glyphosate has been related to environmental pollution events and adverse effects on non-target organisms, including humans. Reducing the presence of glyphosate in the environment and its potential adverse effects requires the development of remediation and treatment alternatives. Bioremediation with microorganisms has been proposed as a feasible alternative for treating glyphosate pollution. The present study reports the glyphosate resistance profile and degradation capacity of the bacterial strain Burkholderia cenocepacia CEIB S5-2, isolated from an agricultural field in Morelos-México. According to the agar plates and the liquid media inhibition assays, the bacterial strain can resist glyphosate exposure at high concentrations, 2000 mg·L-1. In the degradation assays, the bacterial strain was capable of fast degrading glyphosate (50 mg·L-1) and the primary degradation metabolite aminomethylphosphonic acid (AMPA) in just eight hours. The analysis of the genomic data of B. cenocepacia CEIB S5-2 revealed the presence of genes that encode enzymes implicated in glyphosate biodegradation through the two metabolic pathways reported, sarcosine and AMPA. This investigation provides novel information about the potential of species of the genus Burkholderia in the degradation of the herbicide glyphosate and its main degradation metabolite (AMPA). Furthermore, the analysis of genomic information allowed us to propose for the first time a metabolic route related to the degradation of glyphosate in this bacterial group. According to the findings of this study, B. cenocepacia CEIB S5-2 displays a great glyphosate biodegradation capability and has the potential to be implemented in glyphosate bioremediation approaches.
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Biodegradação Ambiental , Burkholderia cenocepacia , Glicina , Glifosato , Herbicidas , Glicina/análogos & derivados , Burkholderia cenocepacia/metabolismo , Herbicidas/metabolismoRESUMO
BACKGROUND: Pulmonary hypertension (PH) accompanying COPD (PH-COPD) is associated with worse outcomes than COPD alone. There are currently no approved therapies to treat PH-COPD. The PERFECT study (ClinicalTrials.gov: NCT03496623) evaluated the safety and efficacy of inhaled treprostinil (iTRE) in this patient population. METHODS: Patients with PH-COPD (mean pulmonary arterial pressure ≥30â mmHg and pulmonary vascular resistance ≥4â WU) were enrolled in a multicentre, randomised (1:1), double-blind, placebo-controlled, 12-week, crossover study. A contingent parallel design was also prespecified and implemented, based on a blinded interim analysis of missing data. Patients received treatment with iTRE up to 12 breaths (72â µg) 4 times daily or placebo. The primary efficacy end-point was change in peak 6-min walk distance (6MWD) at week 12. RESULTS: In total, 76 patients were randomised, 64 in the original crossover design and 12 in the contingent parallel design; 66 patients received iTRE and 58 received placebo. The study was terminated early at the recommendation of the data and safety monitoring committee based on the totality of evidence that iTRE increased the risk of serious adverse events and suggestive evidence of an increased risk of mortality. The change in 6MWD was numerically worse with iTRE exposure than with placebo exposure. CONCLUSIONS: The risk-benefit observations associated with iTRE in patients with PH-COPD did not support continuation of the PERFECT study. The results of this study do not support iTRE as a viable treatment option in patients with PH-COPD.
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Anti-Hipertensivos , Estudos Cross-Over , Epoprostenol , Hipertensão Pulmonar , Doença Pulmonar Obstrutiva Crônica , Teste de Caminhada , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/complicações , Epoprostenol/análogos & derivados , Epoprostenol/administração & dosagem , Epoprostenol/uso terapêutico , Feminino , Masculino , Hipertensão Pulmonar/tratamento farmacológico , Administração por Inalação , Idoso , Pessoa de Meia-Idade , Método Duplo-Cego , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Resultado do TratamentoRESUMO
(1) Background: Parenteral nutrition (PN) is a technique used for the administration of nutrients to patients for whom traditional routes cannot be used. It is performed using solutions with extremely complex compositions, which can give rise to a large number of interactions. These interactions can impact their stability and put the patient's life at risk. The aim of this study is to determine how changes in composition and storage protocol affect the stability of NP solutions. (2) Methods: Twenty-three samples were prepared according to routine clinical practice, with modifications to the concentration of some components. The samples were stored at room temperature (RT) and refrigerated (4 °C). Measurements of the droplet diameter, pH, density and viscosity were performed for both storage protocols on days 1, 3, 10 and 14. (3) Results: The samples with the lowest concentration of lipids (PN13-17) and proteins (PN18-22) showed a larger droplet diameter than the rest of the samples throughout the experiments. The USP limits were exceeded for some of the measurements of these sample groups. The pH density and viscosity remained relatively constant under the conditions studied. (4) Conclusions: The PN samples were considered stable and safe for administration under real-world conditions, but the samples with the lowest concentrations of lipids and proteins showed a tendency towards emulsion instability.
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(1) Background: parenteral nutrition (PN) is indispensable for patients unable to receive oral or enteral feeding. However, the complexity of PN solutions presents challenges regarding stability and compatibility. Precipitation reactions may occur. The most frequent is the formation of calcium phosphate (Ca-P). The different factors influencing these reactions must be considered to ensure patient safety. (2) Methods: eight paediatric PN solutions were prepared, following standard protocols. Samples were stored at room temperature and in a refrigerator. Electron microscopy, coupled with energy dispersive X-ray spectroscopy (EDS), was employed. Precipitates were analysed for composition and morphology. (3) Results: precipitates were observed in all samples, even at day 0. Crystalline structures, predominantly composed of calcium or magnesium, sometimes associated with chlorine or phosphorus, were detected. Additionally, amorphous precipitates, contained heterogeneous compositions, including unexpected elements, were identified. (4) Conclusions: various precipitates, primarily calcium- or magnesium-based, can form in PN solutions, although it is not expected that they can form under the real conditions of use. Calcium oxalate precipitation has been characterised, but the use of organic calcium and phosphate salts appears to mitigate calcium phosphate precipitation. Electron microscopy provides interesting results on NP precipitation, but sample preparation may present technical limitations that affect the interpretation of the results.
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Fosfatos de Cálcio , Precipitação Química , Estabilidade de Medicamentos , Soluções de Nutrição Parenteral , Soluções de Nutrição Parenteral/química , Fosfatos de Cálcio/química , Humanos , Nutrição Parenteral , Espectrometria por Raios X , Microscopia Eletrônica , Magnésio/química , Cálcio/química , Cálcio/análiseRESUMO
Constitutional heterozygous pathogenic variants in the exonuclease domain of POLE and POLD1, which affect the proofreading activity of the corresponding polymerases, cause a cancer predisposition syndrome characterized by increased risk of gastrointestinal polyposis, colorectal cancer, endometrial cancer and other tumor types. The generally accepted explanation for the connection between the disruption of the proofreading activity of polymerases epsilon and delta and cancer development is through an increase in the somatic mutation rate. Here we studied an extended family with multiple members heterozygous for the pathogenic POLD1 variant c.1421T>C p.(Leu474Pro), which segregates with the polyposis and cancer phenotypes. Through the analysis of mutational patterns of patient-derived fibroblasts colonies and de novo mutations obtained by parent-offspring comparisons, we concluded that heterozygous POLD1 L474P just subtly increases the somatic and germline mutation burden. In contrast, tumors developed in individuals with a heterozygous mutation in the exonuclease domain of POLD1, including L474P, have an extremely high mutation rate (>100 mut/Mb) associated with signature SBS10d. We solved this contradiction through the observation that tumorigenesis involves somatic inactivation of the wildtype POLD1 allele. These results imply that exonuclease deficiency of polymerase delta has a recessive effect on mutation rate.
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DNA Polimerase III , Humanos , DNA Polimerase III/genética , DNA Polimerase III/metabolismo , Feminino , Masculino , Linhagem , Heterozigoto , Genes Recessivos , Neoplasias/genética , Neoplasias/patologia , Mutação , Mutação em Linhagem Germinativa , AdultoRESUMO
Occupational protection could be improved in interventional radiology. The monthly personal dosimetry cannot alert on some occupational doses with anomalous values for certain procedures. Active electronic personal dosimeters linked wireless to a dose management system (DMS), allow for the measurement of occupational doses per procedure, integrating this information with patient dose indicators and with technical and geometrical conditions of the procedures. We analysed around 3100 occupational dose values for individual procedures collected during the last two years, in an interventional radiology laboratory of a University Hospital and two groups, with patient doses higher than 100 Gy.cm2, and lower than 30 Gy.cm2. An unshielded reference dosimeter located at the C-arm registers the ambient dose equivalent (ADE) per procedure to be compared with the personal dose equivalent (PDE) over the apron. The ratio between both values PDE/ADE is a good indication of occupational protection. Alerts for occupational protection optimisation are suggested. For the full sample, 8.4 % of occupational doses measured over the protective apron of the interventionists were higher than 100 µSv and 3.8 % higher than 200 µSv per procedure. Occupational protection for complex procedures (>100 Gy.cm2) had median values of 46 µSv for PDE and 3.3 % for PDE/ADE. However, for simple procedures, (<30 Gy.cm2) the median values were 10 µSv and 28.4 %. This last percentage is 9 times higher than the value for complex procedures. This lack of protection should be corrected and the need to reduce some occupational doses reinforced in radiation protection training programmes for interventionists.
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Exposição Ocupacional , Proteção Radiológica , Radiologia Intervencionista , Exposição Ocupacional/análise , Exposição Ocupacional/prevenção & controle , Humanos , Doses de RadiaçãoRESUMO
Huanglongbing (HLB) is a disease caused by the phloem- limited Candidatus Liberibacter asiaticus (CLas) that affects the citrus industry worldwide. To date, only indirect strategies have been implemented to eradicate HLB. Included among these is the population control of the psyllid vector (Diaphorina citri), which usually provides inconsistent results. Even though strategies for direct CLas suppression seem a priori more promising, only a handful of reports have been focused on a confrontation of the pathogen. Recent developments in polymer chemistry have allowed the design of polycationic self-assembled block copolymers with outstanding antibacterial capabilities. Here, we report the use of polymeric nano-sized bactericide particles (PNB) to control CLas directly in the phloem vasculature. The field experiments were performed in Rioverde, San Luis Potosí, and is one of the most important citrusproducing regions in Mexico. An average 52% reduction in the bacterial population was produced when PNB was injected directly into the trunk of 20 infected trees, although, in some cases, reduction levels reached 97%. These results position PNB as a novel and promising nanotechnological tool for citrus crop protection against CLas and other related pathogens.
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(1) Background: parenteral nutrition (PN) solutions are an extremely complex mixture. It is composed of a multitude of chemical elements that can give rise to a large number of interactions that condition its stability and safety. The aim of this study was to evaluate the stability of PN solutions for preterm infants. (2) Methods: eight samples were prepared according to the protocol for prescribing PN in preterm infants. Samples PN1-PN7 had the normal progression of macronutrients and standard amounts of micronutrients for a 1 kg preterm infant. The PN8 sample had a high concentration of electrolytes, with the idea of forcing stability limits. Samples were stored both at room temperature and under refrigeration. Measurements of globule size, pH, density, and viscosity were performed in both storage protocols on different days after processing. (3) Results: the changes in the composition of the samples did not affect the evolution of the stability at the different measurement times and temperatures. Viscosity was affected by the compositional changes made in the PN samples, but no alterations due to time or temperature were observed. Density and pH remained stable, without significant changes due to time, storage temperature, or different composition. (4) Conclusion: all samples remained stable during the study period and did not undergo significant alterations due to compositional changes or different experimental conditions.
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Drug development is a complex, costly, and time-consuming endeavor. While high-throughput screening (HTS) plays a critical role in the discovery stage, it is one of many factors contributing to these challenges. In certain contexts, virtual screening can complement the HTS, potentially offering a more streamlined approach in the initial stages of drug discovery. Molecular docking is an example of a popular virtual screening technique that is often used for this purpose; however, its effectiveness can vary greatly. This has led to the use of consensus docking approaches that combine results from different docking methods to improve the identification of active compounds and reduce the occurrence of false positives. However, many of these methods do not fully leverage the latest advancements in molecular docking. In response, we present ESSENCE-Dock (Effective Structural Screening ENrichment ConsEnsus Dock), a new consensus docking workflow aimed at decreasing false positives and increasing the discovery of active compounds. By utilizing a combination of novel docking algorithms, we improve the selection process for potential active compounds. ESSENCE-Dock has been made to be user-friendly, requiring only a few simple commands to perform a complete screening while also being designed for use in high-performance computing (HPC) environments.
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Algoritmos , Descoberta de Drogas , Simulação de Acoplamento Molecular , Consenso , Descoberta de Drogas/métodos , Ensaios de Triagem em Larga Escala , LigantesRESUMO
OBJECTIVES: Despite recent advances, the prognosis for primary malignant brain tumors (PMBTs) remains poor. Some commonly prescribed medications may exhibit anti-tumor properties in various cancers, and neurodegenerative diseases may activate pathways that counteract gliomagenesis. Our study is focused on determining if there is a correlation between the use of metformin, beta-blockers, angiotensin converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), or the presence of Parkinson's disease (PD), and the survival rates following a diagnosis of a PMBT. METHODS: This analysis of the 100% Texas Medicare Database identified patients aged 66+ years diagnosed with a supratentorial PMBT from 2014-2017. Cox proportional hazards regression was employed to analyze survival following diagnosis and associations of survival with surgical intervention, radiation, PD diagnosis, and prescription of metformin, beta-blockers, ACEIs, or ARBs. RESULTS: There were 1,943 patients who met study criteria, and the median age was 74 years. When medication utilization was stratified by none, pre-diagnosis only, post-diagnosis only, or both pre- and post-diagnosis (continuous), continuous utilization of metformin, beta-blockers, ACEIs, or ARBs was associated with prolonged survival compared to no utilization (hazard ratio [HR]:0.45, 95% CI:0.33-0.62; HR:0.71. 95% CI:0.59-0.86; HR:0.59, 95% CI:0.48-0.72; and HR:0.45, 95% CI:0.35-0.58 respectively). PD was also associated with longer survival (HR:0.59-0.63 across the four models). DISCUSSION: Our study suggests that metformin, beta-blockers, ACEIs, ARBs, and comorbid PD are associated with a survival benefit among geriatric Medicare patients with supratentorial PMBTs.
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Medicare , Humanos , Idoso , Masculino , Feminino , Estados Unidos/epidemiologia , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Neoplasias Supratentoriais/mortalidade , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos de Coortes , Antagonistas Adrenérgicos beta/uso terapêutico , Metformina/uso terapêutico , Texas/epidemiologia , Doença de Parkinson/mortalidade , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Taxa de SobrevidaRESUMO
The pacaya palm (Chamaedorea tepejilote Liebm) is an important food that is commonly consumed in Mexico and Central America due to its nutritive value. It is also used as a nutraceutical food against some chronic diseases, such as hypertension and hyperglycemia. However, few reports have indicated its possible potential. For this reason, the goal of this research was to evaluate the effects of the enzymatic activity of the pacaya palm inflorescence rachis on both hypertension and hyperglycemia and the effects of thermal treatments on the enzymatic activity. The enzymatic inhibition of ACE (angiotensin-converting enzyme), DPP-IV (dipeptidyl peptidase-IV), α-glucosidase and α-amylase were evaluated, all with powder extracts of pacaya palm inflorescences rachis. The results indicated that thermally treated rachis showed increased enzymatic inhibitory activity against α-amylase and DPP-IV. However, all rachis, both with and without thermal treatment, showed low- or no enzymatic activity against α-glucosidase and ACE. Apparently, the mechanism of action of the antidiabetic effect of rachis is mediated by the inhibition of α-amylase and DPP-IV and does not contribute with a significant effect on enzymes involved in the hypertension mechanism. Finally, the properties of the extract were modified via the extraction method and the temperature tested.
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OBJECTIVE: Emotions play a critical role in health risk behaviors, including substance use. However, current research often focuses exclusively on average levels of positive and negative affect, neglecting the complexity of daily emotional patterns. By capturing multiple dimensions of affect, including arousal and discrete states, we can improve our understanding of proximal predictors of substance use. The present study demonstrates the utility of a novel methodological approach for assessing affect patterns in daily life in relation to alcohol and cannabis use. METHOD: Daily diary data from N = 154 young adults who reported recent heavy episodic drinking and simultaneous use of alcohol and cannabis were analyzed using a mixed-indicator latent profile analysis to identify and describe day-level affective patterns and outcomes. RESULTS: Results revealed five distinct day-level profiles of affect: undifferentiated negative affect days, undifferentiated positive affect days, high-arousal positive affect days, mixed affect days, and low reactivity days. Undifferentiated positive affect days, high-arousal positive affect days, and low reactivity days were associated with significantly greater odds of same-day alcohol use compared to days characterized by undifferentiated negative affect (χ² = 10.55, p = .032). CONCLUSIONS: Findings suggest that daily affect patterns differentially impact alcohol use and can inform the development of interventions for problematic substance use. Additionally, the innovative methodological approach employed herein could be applicable for investigating the role of emotion in other health behaviors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).