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1.
An. psicol ; 40(2): 265-271, May-Sep, 2024. tab
Article in English | IBECS | ID: ibc-232728

ABSTRACT

En la educación superior, pocos estudios relacionan factores contextuales en la clase, como el énfasis del profesor en la utilidad del contenido y las características motivacionales de los estudiantes. El objetivo fue probar un modelo multinivel sobre la relación entre el énfasis del docente en la utilidad del contenido durante la clase, la autonomía de los estudiantes y, a su vez, la motivación para aprender. Participaron 3033 estudiantes universitarios matriculados de 1º a 4º grado de Ciencias de la Actividad Física y del Deporte, de universidades de España (N = 602), Portugal (N = 469), México (N = 1177), Chile (N = 372), y Brasil (N = 413). Se realizó un modelo de ecuaciones estructurales multinivel, en el que los participantes respondieron preguntas sobre el énfasis del profesor en la utilidad del contenido de la clase, la autonomía y la motivación para aprender. Se hipotetizó que el énfasis del profesor en la utilidad del contenido predecía la autonomía del estudiante que, por su vez, predecía la motivación para aprender. Los resultados, a nivel grupal e individual, indican que el énfasis del docente en la utilidad del contenido predijo la autonomía del estudiante, y la autonomía predijo la motivación para aprender.(AU)


Teacher autonomy support is related to improved student learn-ing. In higher education, few studies relate classroom contextual factors, such as teacher emphasis on content usefulness, and students' motivational characteristics. The aim was to test a multilevel model about the relation between the extent of teachers’ emphasis on the usefulness of class con-tent with student autonomy, and, in turn, on motivation to learn. The par-ticipants were 3033 university students enrolled from 1st to 4th grade of Sciences of the Physical Activity and Sport, from universities in Spain (N = 602), Portugal (N = 469), Mexico (N = 1177), Chile (N = 372), and Brazil (N = 413). A multilevel structural equation model was performed, in which participants answered questions about the teacher's emphasis on the use-fulness of class content, basic psychological need for autonomy, and moti-vation to learn. At the group and individual levels, the hypothesis is that the teacher's emphasis on the usefulness of class content predict the stu-dent autonomy, in turn, student autonomy predicts student motivation to learn. Results found at the group level and at the individual level the strength of teacher emphasis on class content predicted student autonomy; student autonomy predicted student motivation to learn.(AU)


Subject(s)
Humans , Male , Female , Personal Autonomy , Universities , Teaching , Motivation
2.
Eur J Ophthalmol ; : 11206721241272239, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39109642

ABSTRACT

INTRODUCTION: To study the relationship between socioeconomic status and persistence with topical antiglaucomatous medication. METHODS: A retrospective epidemiological observational cohort study was conducted with a sample of 1563 patients. The main dependent variable was persistence (medication possession ratio), the independent variable was socioeconomic status (deprivation index). Additional independent variables were used for multivariate analysis: individual health card index, sex, age, pharmacological group, number of eye drops, preservatives, diagnosis and concurrent medications. Bivariate statistical analysis was obtained using non-parametric tests. Logistic regression was used for multivariate analysis. The level of statistical significance was set at p < 0.05. RESULTS: We obtained data showing greater persistence in the groups with a higher socioeconomic level (deprivation index 1 and 2), with medication possession ratio values of 79.97 and 75.30, respectively) as opposed to the groups at lower socioeconomic levels (deprivation index 4 and 5, with medication possession ratio values of 73.75 and 69.85, respectively. Logistic regression corroborated this difference, reaching a significant value (no persistence in deprivation index group 5 versus 1) with OR = 1.62; 95%CI: 1.13-2.31. Additionally, lower persistence was detected in males, under 60 years of age, undergoing treatment with alpha-agonists, and in patients with ocular hypertension. DISCUSSION: Low socioeconomic status of the patient was significantly associated with decreased persistence with topical antiglaucomatous therapy.

5.
Cureus ; 16(6): e61591, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38962639

ABSTRACT

Background Early treatment of intracranial lesions in the emergency department is crucial, but it can be challenging to differentiate between them. This differentiation is essential because the treatment of each type of lesion is different. Cerebral computed tomography perfusion (CTP) imaging can help visualize the vascularity of brain lesions and provide absolute quantification of physiological parameters. Compared to magnetic resonance imaging, CTP has several advantages, such as simplicity, wide availability, and reproducibility. Purpose This study aimed to assess the effectiveness of Hounsfield units (HU) in measuring the density of hypercellular lesions and the ability of CTP to quantify hemodynamics in distinguishing intracranial space-occupying lesions. Methods A retrospective study was conducted from March 2016 to March 2022. All patients underwent CTP and CT scans, and relative cerebral blood volume (rCBV) and HU were obtained for intracranial lesions. Results We included a total of 244 patients in our study. This group consisted of 87 (35.7%) individuals with glioblastomas (GBs), 48 (19.7%) with primary central nervous system lymphoma (PCNSL), 45 (18.4%) with metastases (METs), and 64 (26.2) with abscesses. Our study showed that the HUs for METs were higher than those for GB (S 57.4% and E 88.5%). In addition, rCBV values for PCNSL and abscesses were lower than those for GB and METs. The HU in PCNSL was higher than those in abscesses (S 94.1% and E 96.6%). Conclusion PCT parameters provide valuable information for diagnosing brain lesions. A comprehensive assessment improves accuracy. Combining rCBV and HU enhances diagnostic accuracy, making it a valuable tool for distinguishing between lesions. PCT's widespread availability allows for the use of both anatomical and functional information with high spatial resolution for diagnosing and managing brain tumor patients.

6.
Front Physiol ; 15: 1410660, 2024.
Article in English | MEDLINE | ID: mdl-38966230

ABSTRACT

Somatic growth in vertebrates is mainly controlled by the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. The role of epigenetic mechanisms in regulating this axis in fish is far from being understood. This work aimed to optimize and evaluate the use of short-term culture of pituitary and liver explants from a farmed fish, the gilthead seabream Sparus aurata, for studying epigenetic mechanisms involved in GH/IGF-I axis regulation. Our results on viability, structure, proliferation, and functionality of explants support their use in short-term assays. Pituitary explants showed no variation in gh expression after exposure to the DNA methylation inhibitor decitabine (5-Aza-2'-deoxycytidine; DAC), despite responding to DAC by changing dnmt3bb and tet1 expression, and TET activity, producing an increase in overall DNA hydroxymethylation. Conversely, in liver explants, DAC had no effects on dnmt s and tet s expression or activity, but modified the expression of genes from the GH-IGF-I axis. In particular, the expression of igfbp2a was increased and that of igfbp4, ghri and ghrii was decreased by DAC as well as by genistein, which is suggestive of impaired growth. While incubation of liver explants with S-adenosylmethionine (SAM) produced no clear effects, it is proposed that nutrients must ensure the methylation milieu within the liver in the fish to sustain proper growth, which need further in vivo verification. Pituitary and liver explants from S. aurata can be further used as described herein for the screening of inhibitors or activators of epigenetic regulators, as well as for assessing epigenetic mechanisms behind GH-IGF-I variation in farmed fish.

7.
Comput Biol Med ; 180: 108890, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39068903

ABSTRACT

BACKGROUND: Breast cancer (BC) remains a prevalent health concern, with metastasis as the main driver of mortality. A detailed understanding of metastatic processes, particularly cell migration, is fundamental to improve therapeutic strategies. The wound healing assay, a traditional two-dimensional (2D) model, offers insights into cell migration but presents scalability issues due to data scarcity, arising from its manual and labor-intensive nature. METHOD: To overcome these limitations, this study introduces the Prediction Wound Progression Framework (PWPF), an innovative approach utilizing Deep Learning (DL) and artificial data generation. The PWPF comprises a DL model initially trained on artificial data that simulates wound healing in MCF-7 BC cell monolayers and spheres, which is subsequently fine-tuned on real-world data. RESULTS: Our results underscore the model's effectiveness in analyzing and predicting cell migration dynamics within the wound healing context, thus enhancing the usability of 2D models. The PWPF significantly contributes to a better understanding of cell migration processes in BC and expands the possibilities for research into wound healing mechanisms. CONCLUSIONS: These advancements in automated cell migration analysis hold the potential for more comprehensive and scalable studies in the future. Our dataset, models, and code are publicly available at https://github.com/frangam/wound-healing.

8.
Viruses ; 16(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39066233

ABSTRACT

Patients with COVID-19 may develop a hypercoagulable state due to tissue and endothelial injury, produced by an unbalanced immune response. Therefore, an increased number of thromboembolic events has been reported in these patients. The aim of this study is to investigate the presence of antiphospholipid antibodies (aPL) in COVID-19 patients, their role in the development of thrombosis and their relationship with the severity of the disease. In this retrospective study, serum samples from 159 COVID-19 patients and 80 healthy donors were analysed for the presence of aPL. A total of 29 patients (18.2%) and 14 healthy donors (17.5%) were positive for aPL. Nineteen COVID-19 patients (12%) but no healthy donor presented a positive percentage of the IgA isotype aPL. IgA anti-ß2-glycoprotein I antibodies (anti-ß2GPI) were the most frequent type (6.3%) in patients but was not detected in any healthy donor. The positivity of this antibody was found to be significantly elevated in patients with thromboembolic events (25% vs. 5%, p = 0.029); in fact, patients with positive IgA anti-ß2GPI had an incidence of thrombosis over six times higher than those who had normal antibody concentrations [OR (CI 95%) of 6.67 (1.5-30.2), p = 0.014]. Additionally, patients with moderate-severe disease presented a higher aPL positivity than patients with mild disease according to the Brescia (p = 0.029) and CURB-65 (p = 0.011) severity scales. A multivariate analysis showed that positivity for IgA anti-ß2GPI is significantly associated with disease severity measured by CURB-65 [OR (CI 95%) 17.8 (1.7-187), p = 0.0016]. In conclusion, COVID-19 patients have a significantly higher positive percentage of the IgA isotype aPL than healthy donors. IgA anti-ß2GPI antibodies were the most frequently detected aPL in COVID-19 patients and were associated with thrombosis and severe COVID-19 and are thus proposed as a possible marker to identify high-risk patients.


Subject(s)
Antibodies, Antiphospholipid , Biomarkers , COVID-19 , Immunoglobulin A , SARS-CoV-2 , Severity of Illness Index , Thrombosis , beta 2-Glycoprotein I , Humans , COVID-19/immunology , COVID-19/complications , COVID-19/blood , Male , beta 2-Glycoprotein I/immunology , Female , Immunoglobulin A/blood , Middle Aged , Thrombosis/immunology , Retrospective Studies , Antibodies, Antiphospholipid/blood , Adult , Aged , Biomarkers/blood , SARS-CoV-2/immunology , Aged, 80 and over
9.
Children (Basel) ; 11(7)2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39062303

ABSTRACT

Repetitive practice can become an exploratory activity where instruction and discovery are linked, allowing instruction and guidance through tasks that help to construct and acquire the knowledge and skills that make up the content. (1) Background: The aim of the study was to show how a teaching method based on guided discovery would affect the teaching of children's aquatic competence in schoolchildren with different levels of competence. (2) Methods: An observational study was conducted with 385 schoolchildren (195 boys and 189 girls) aged 3-5 years belonging to a charter kindergarten, using an Instrument for the Measurement of Aquatic Competence in Children (SMACC) consisting of 17 items grouped into three dimensions: socio-affective, cognitive, and motor. (3) Results: After measuring aquatic competence, all age groups and all variables (motor, cognitive, and socio-affective) showed differences between pre- and post-scores and a high magnitude of effect size. When the teaching intervention was analyzed according to the level of aquatic competence of the age group, improvements were found in all variables in both the low and high-competence groups. (4) Conclusions: This study describes how guided discovery instruction has equal effects at different levels of proficiency. Furthermore, when this type of instruction was used, aquatic competence was explained not only by the motor and socio-affective dimensions but also by the cognitive variable.

10.
Int J Mol Sci ; 25(14)2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39062828

ABSTRACT

The production and release of cortisol during stress responses are key regulators of growth in teleosts. Understanding the molecular responses to cortisol is crucial for the sustainable farming of rainbow trout (Oncorhynchus mykiss) and other salmonid species. While several studies have explored the genomic and non-genomic impacts of cortisol on fish growth and skeletal muscle development, the long-term effects driven by epigenetic mechanisms, such as cortisol-induced DNA methylation, remain unexplored. In this study, we analyzed the transcriptome and genome-wide DNA methylation in the skeletal muscle of rainbow trout seven days after cortisol administration. We identified 550 differentially expressed genes (DEGs) by RNA-seq and 9059 differentially methylated genes (DMGs) via whole-genome bisulfite sequencing (WGBS) analysis. KEGG enrichment analysis showed that cortisol modulates the differential expression of genes associated with nucleotide metabolism, ECM-receptor interaction, and the regulation of actin cytoskeleton pathways. Similarly, cortisol induced the differential methylation of genes associated with focal adhesion, adrenergic signaling in cardiomyocytes, and Wnt signaling. Through integrative analyses, we determined that 126 genes showed a negative correlation between up-regulated expression and down-regulated methylation. KEGG enrichment analysis of these genes indicated participation in ECM-receptor interaction, regulation of actin cytoskeleton, and focal adhesion. Using RT-qPCR, we confirmed the differential expression of lamb3, itga6, limk2, itgb4, capn2, and thbs1. This study revealed for the first time the molecular responses of skeletal muscle to cortisol at the transcriptomic and whole-genome DNA methylation levels in rainbow trout.


Subject(s)
DNA Methylation , Hydrocortisone , Muscle, Skeletal , Oncorhynchus mykiss , Stress, Physiological , Transcriptome , Animals , Oncorhynchus mykiss/genetics , Oncorhynchus mykiss/metabolism , Hydrocortisone/metabolism , Hydrocortisone/pharmacology , Muscle, Skeletal/metabolism , Muscle, Skeletal/drug effects , Stress, Physiological/genetics , Epigenesis, Genetic , Epigenomics/methods , Gene Expression Profiling , Fish Proteins/genetics , Fish Proteins/metabolism
11.
Int J Mol Sci ; 25(14)2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39063032

ABSTRACT

Combined gene and cell therapy are promising strategies for cancer treatment. Given the complexity of cancer, several approaches are actively studied to fight this disease. Using mesenchymal stem cells (MSCs) has demonstrated dual antitumor and protumor effects as they exert massive immune/regulatory effects on the tissue microenvironment. MSCs have been widely investigated to exploit their antitumor target delivery system. They can be genetically modified to overexpress genes and selectively or more efficiently eliminate tumor cells. Current approaches tend to produce more effective and safer therapies using MSCs or derivatives; however, the effect achieved by engineered MSCs in solid tumors is still limited and depends on several factors such as the cell source, transgene, and tumor target. This review describes the progress of gene and cell therapy focused on MSCs as a cornerstone against solid tumors, addressing the different MSC-engineering methods that have been approached over decades of research. Furthermore, we summarize the main objectives of engineered MSCs against the most common cancers and discuss the challenges, limitations, risks, and advantages of targeted treatments combined with conventional ones.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Neoplasms , Humans , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Neoplasms/therapy , Mesenchymal Stem Cell Transplantation/methods , Animals , Genetic Therapy/methods , Tumor Microenvironment
12.
Sci Total Environ ; : 174802, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39009149

ABSTRACT

This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found athttps://www.elsevier.com/about/policies/article-withdrawal.

13.
Epidemiologia (Basel) ; 5(3): 318-329, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-39051202

ABSTRACT

OBJECTIVE: To comp+are levels of physical fitness between Ecuador and Spain and identify whether breastfeeding period, walking onset, and abdominal obesity are determinants of physical performance in schoolchildren from Ecuador and Spain. METHODS: a total of 352 schoolchildren (6-12 years old) from Ecuador (n = 176) and Spain (n = 176) joined in this study. Anthropometric measures, socio-demographic characteristics, and physical fitness were evaluated. RESULTS: Spanish schoolchildren showed better performance in handgrip strength, standing long jump, and 25 m sprint (p = 0.021; p < 0.001; p < 0.001; p < 0.001, respectively). Furthermore, Spanish children showed better cardiorespiratory fitness (p < 0.001) and a higher VO2 max (p = 0.002) with regards to their peers. In addition, children from Ecuador and Spain showed an influence of breastfeeding period (p ranged from <0.001 to 0.043) and walking onset (p ranged from <0.001 to 0.032) on physical performance. Moreover, physical fitness components were protective factors of abdominal obesity in Ecuadorian and Spanish schoolchildren (p ranged from =0.001 to 0.049). CONCLUSIONS: Our findings revealed the influence of the infancy period and the onset of walking on children's physical performance, highlighting the importance of these factors in motor development during early childhood and also their influence in middle childhood and throughout adulthood.

14.
Neuro Oncol ; 2024 07 01.
Article in English | MEDLINE | ID: mdl-38946469

ABSTRACT

BACKGROUND: Encorafenib plus binimetinib (EB) is a standard of care treatment for advanced BRAFV600-mutant melanoma. We assessed efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response. METHODS: E-BRAIN/GEM1802 was a prospective, multicenter, single arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression.Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%. RESULTS: The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After two months, icRR was 70.8% (95% CI: 55.9-83.1); 10.4% complete response. Median intracranial PFS and OS were 8.5 (95% CI: 6.4-11.8) and 15.9 (95% CI: 10.7-21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grade 3-4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%). CONCLUSION: Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response.

15.
Biomed Pharmacother ; 177: 117051, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38959608

ABSTRACT

Due to the limitations of the current skin wound treatments, it is highly valuable to have a wound healing formulation that mimics the extracellular matrix (ECM) and mechanical properties of natural skin tissue. Here, a novel biomimetic hydrogel formulation has been developed based on a mixture of Agarose-Collagen Type I (AC) combined with skin ECM-related components: Dermatan sulfate (DS), Hyaluronic acid (HA), and Elastin (EL) for its application in skin tissue engineering (TE). Different formulations were designed by combining AC hydrogels with DS, HA, and EL. Cell viability, hemocompatibility, physicochemical, mechanical, and wound healing properties were investigated. Finally, a bilayered hydrogel loaded with fibroblasts and mesenchymal stromal cells was developed using the Ag-Col I-DS-HA-EL (ACDHE) formulation. The ACDHE hydrogel displayed the best in vitro results and acceptable physicochemical properties. Also, it behaved mechanically close to human native skin and exhibited good cytocompatibility. Environmental scanning electron microscopy (ESEM) analysis revealed a porous microstructure that allows the maintenance of cell growth and ECM-like structure production. These findings demonstrate the potential of the ACDHE hydrogel formulation for applications such as an injectable hydrogel or a bioink to create cell-laden structures for skin TE.


Subject(s)
Biomimetic Materials , Hydrogels , Tissue Engineering , Hydrogels/chemistry , Humans , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Tissue Engineering/methods , Cell Survival/drug effects , Mesenchymal Stem Cells/drug effects , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Wound Healing/drug effects , Collagen Type I/metabolism , Skin/drug effects , Skin/metabolism , Dermatan Sulfate/chemistry , Dermatan Sulfate/pharmacology , Fibroblasts/drug effects , Elastin/chemistry , Extracellular Matrix/metabolism , Biomimetics/methods , Sepharose/chemistry , Dermis/drug effects , Dermis/metabolism , Dermis/cytology , Animals
16.
Cureus ; 16(6): e61854, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38978946

ABSTRACT

Cutaneous squamous cell carcinoma is the second most common neoplasm among non-melanoma skin cancers. When associated with perineural invasion of the cranial nerves, with clinical features often observed in trigeminal and facial nerves due to their cutaneous extension, it may lead to a worse prognosis. This paper introduces a rare case of an 81-year-old male, with a history of a moderately differentiated invasive carcinoma of the left frontal region with perineural invasion on the left trigeminal cranial nerve. The case underscores the aggressive nature of the intraneural infiltration by squamous cell carcinoma and the challenges in managing such advanced malignancies.

17.
Eur J Emerg Med ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38985840

ABSTRACT

OBJECTIVE/BACKGROUND: Intravenous digoxin is still used in emergency departments (EDs) to treat patients with acute heart failure (AHF), especially in those with rapid atrial fibrillation. We investigated whether intravenous digoxin used to treat rapid atrial fibrillation in patients with AHF may influence mortality. METHODS: A secondary analysis of patients included in the Spanish EAHFE (Epidemiology of Acute Heart Failure in Emergency Departments) cohort, which includes patients diagnosed with AHF in 45 Spanish EDs. The relationships between age, estimated glomerular filtration rate, and potassium with 30-day mortality were investigated using restricted cubic spline models adjusted for relevant patient and episode variables. RESULTS: From the 19 947 patients included, we analyzed 2194 patients with AHF and rapid atrial fibrillation that not receiving digoxin at home, divided according to whether they were or were not treated with intravenous digoxin in the ED. The median age of the patients was 82 years (interquartile range=76-87), 61.4% were women and 65.2% had previous episodes of atrial fibrillation. Digoxin and no digoxin groups were formed by 864 (39.4%) and 1330 (60.6%) patients, respectively. There were 191 deaths within the 30-day follow-up period (8.9%), with no differences between patients receiving or not receiving digoxin (8.5 vs. 9.1%, P = 0.636). Although analysis of restricted cubic spline curves showed that death was associated with advanced age, worse renal function, and hypokalemia and hyperkalemia, the use of intravenous digoxin did not interact with any of these relationships (P = 0.156 for age, P = 0.156 for estimated glomerular filtration rate, P = 0.429 for potassium). CONCLUSION: The use of intravenous digoxin in the ED was not associated with significant changes in 30-day mortality, which was confirmed irrespective of patient age or the existence of renal dysfunction or serum potassium disturbances.

18.
Nat Commun ; 15(1): 5826, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992028

ABSTRACT

Patritumab deruxtecan (HER3-DXd) exhibits promising efficacy in breast cancer, with its activity not directly correlated to baseline ERBB3/HER3 levels. This research investigates the genetic factors affecting HER3-DXd's response in women with early-stage hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. In the SOLTI-1805 TOT-HER3 trial, a single HER3-DXd dose was administered to 98 patients across two parts: 78 patients received 6.4 mg/kg (Part A), and 44 received a lower 5.6 mg/kg dose (Part B). The CelTIL score, measuring tumor cellularity and infiltrating lymphocytes from baseline to day 21, was used to assess drug activity. Part A demonstrated increased CelTIL score after one dose of HER3-DXd. Here we report CelTIL score and safety for Part B. In addition, the exploratory analyses of part A involve a comprehensive study of gene expression, somatic mutations, copy-number segments, and DNA-based subtypes, while Part B focuses on validating gene expression. RNA analyses show significant correlations between CelTIL responses, high proliferation genes (e.g., CCNE1, MKI67), and low expression of luminal genes (e.g., NAT1, SLC39A6). DNA findings indicate that CelTIL response is significantly associated with TP53 mutations, proliferation, non-luminal signatures, and a distinct DNA-based subtype (DNADX cluster-3). Critically, low HER2DX ERBB2 mRNA, correlates with increased HER3-DXd activity, which is validated through in vivo patient-derived xenograft  models. This study proposes chemosensitivity determinants, DNA-based subtype classification, and low ERBB2 expression as potential markers for HER3-DXd activity in HER2-negative breast cancer.


Subject(s)
Antibodies, Monoclonal, Humanized , Breast Neoplasms , Receptor, ErbB-2 , Receptor, ErbB-3 , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Receptor, ErbB-3/metabolism , Receptor, ErbB-3/genetics , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/genetics , Antibodies, Monoclonal, Humanized/therapeutic use , Broadly Neutralizing Antibodies/therapeutic use , Middle Aged , Antibodies, Monoclonal/therapeutic use , Adult , Aged , Animals , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Mutation , Mice , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Treatment Outcome , Trastuzumab , Camptothecin/analogs & derivatives , Immunoconjugates
19.
Proteomics ; : e2300385, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39001627

ABSTRACT

The mzIdentML data format, originally developed by the Proteomics Standards Initiative in 2011, is the open XML data standard for peptide and protein identification results coming from mass spectrometry. We present mzIdentML version 1.3.0, which introduces new functionality and support for additional use cases. First of all, a new mechanism for encoding identifications based on multiple spectra has been introduced. Furthermore, the main mzIdentML specification document can now be supplemented by extension documents which provide further guidance for encoding specific use cases for different proteomics subfields. One extension document has been added, covering additional use cases for the encoding of crosslinked peptide identifications. The ability to add extension documents facilitates keeping the mzIdentML standard up to date with advances in the proteomics field, without having to change the main specification document. The crosslinking extension document provides further explanation of the crosslinking use cases already supported in mzIdentML version 1.2.0, and provides support for encoding additional scenarios that are critical to reflect developments in the crosslinking field and facilitate its integration in structural biology. These are: (i) support for cleavable crosslinkers, (ii) support for internally linked peptides, (iii) support for noncovalently associated peptides, and (iv) improved support for encoding scores and the corresponding thresholds.

20.
Environ Geochem Health ; 46(9): 332, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023801

ABSTRACT

In this work, the effect of microwave-assisted acid treatments on the morphological and crystallochemical characteristics of chrysotile fibers is investigated. A low concentration of nitric acid (0.2 N) is used to remove Mg2+-species located in the octahedral sheet of its structure, thereby causing a crystallo-chemical change forming a skeleton of non-crystalline amorphous silica. This skeleton maintains an elongated morphology but characterized by rounded -not sharp-edges and porous surfaces whose physical resistance under stress is reduced when compared with the initial fibers of chrysotile, favoring a lower pathogenicity of the fibers. Thus, microwave-assisted acid treatment rise as a low-cost, fast and effective option in avoiding the dangerousness associated with asbestos waste management.


Subject(s)
Asbestos, Serpentine , Microwaves , Nitric Acid , Asbestos, Serpentine/chemistry , Nitric Acid/chemistry , Waste Management/methods , X-Ray Diffraction , Microscopy, Electron, Scanning
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