Efficacy outcomes of CDK4/6 inhibitors in combination with endocrine therapy treatment in hormone receptor-positive/HER2-negative advanced breast cancer according to PAM50 intrinsic subtype: Primary results of SOLTI-1801 CDK-PREDICT study.

Introduction: The prognostic value of PAM50 intrinsic subtypes (IS), cell cycle, and immune-related gene expression in HR+ /HER2- advanced breast cancer (BC) treated with CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) in a first-line metastatic setting is unclear. This study evaluates these biomarkers in metastatic biopsies from patients diagnosed with HR+ /HER2- advanced BC.

Methods: CDK-PREDICT study is a multicentric, ambispective observational cohort study conducted in six Spanish hospitals.

Dual harm among patients in the Ontario forensic mental health system.

Background: Dual harm involves the unfortunate experience of harm to self and others/objects. Safeguarding individuals in forensic psychiatric settings against all forms of harm to self and others is sacrosanct. While understanding dual harm is crucial in the care and rehabilitation of patients in forensic psychiatric settings, only a few studies have explored this phenomenon.

Left ventricular diastolic dysfunction is prevalent but not associated with mortality in patients with septic shock.

Purpose: Prognostic impact of left ventricular diastolic dysfunction (LVDD) in septic shock patients has not been determined using current diagnostic guidelines. We assessed the relation between LVDD during the first 3 days following intensive care unit (ICU) admission for septic shock and Day-28 mortality.

Methods: This prospective, multicenter, observational study enrolled 402 patients (age: 63 ± 13 year; 59% male; SAPS II: 59 ± 20; SOFA: 9.

Linking tumor immune infiltration to enhanced longevity in recurrence-free breast cancer.

Background: The infiltration of tumor-infiltrating B cells and plasma cells in early-stage breast cancer has been associated with a reduced risk of distant metastasis. However, the influence of B-cell tumor infiltration on overall patient survival remains unclear.

Materials And Methods: This study explored the relationship between an antitumor immune response, measured by a 14-gene B-cell/immunoglobulin (IGG) signature, and mortality risk in 9638 breast cancer patients across three datasets.

Chromatin accessibility and gene expression in the parasite Trichomonas vaginalis.

, the most common non-viral sexually transmitted parasite, causes more than 270 million infections annually. The infection's outcome varies greatly depending on different factors that include variation in human immune responses, the vaginal microbiome, and the inherent virulence of the strain. Although the pathogenicity of the different strains depends, at least partially, on differential gene expression of virulence genes; the regulatory mechanisms governing this transcriptional control remain incompletely understood.

Efficient evacuation - enhanced survival: Insights from Gaza conflict trauma care.

Background: Combat-related injuries have evolved in urban warfare because of close-contact engagements and high-energy blast injuries, with rapid medical evacuation improving survival rates. This study analyzes injury patterns and outcomes in the Gaza conflict, emphasizing the need to optimize trauma care protocols in modern combat environments, particularly because of the unique proximity of conflict zones to tertiary trauma centers.

Methods: A retrospective study was conducted at a single center involving 189 patients evacuated by helicopter to a Level I tertiary trauma center.

Parenteral lipid emulsions: the state of the art.

Purpose Of Review: Several types of injectable lipid emulsions (ILEs) have become available for parenteral nutrition. The purpose of this review is to highlight the most recent and interesting articles in the field of ILEs.

Recent Findings: Recent literature has compared ILEs in various clinical scenarios (e.

HER2DX genomic test in early-stage HER2-positive breast cancer.

Therapies targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer significantly impact patient outcomes, quality of life, and health care systems. While chemotherapy and trastuzumab improve survival in early-stage HER2-positive breast cancer, variability in clinical and biological characteristics leads to different response to therapies and outcomes. Clinical guidelines provide general recommendations, but significant uncertainty persists in identifying an optimal treatment plan for individual patients.

Prognostic value of residual disease (RD) biology and gene expression changes during the neoadjuvant treatment in patients with HER2+ early breast cancer (EBC).

Background: In HER2+ early breast cancer (EBC), we investigated tumor and immune changes during neoadjuvant treatment and their impact on residual disease (RD) biology and prognostic implications across 4 neoadjuvant studies of trastuzumab with or without lapatinib, and with or without chemotherapy: CALGB 40601, PAMELA, NeoALTTO and NSABP B-41.

Patients And Methods: We compared tumor and immune gene expression changes during neoadjuvant treatment and their association with with event-free survival (EFS) by uni- and multivariable Cox regression models in different cohorts and timepoints: 452 RD samples at baseline including 169 with a paired RD, and biomarker changes during neoadjuvant therapy, evaluating model performance via the c-index.

Results: Analysis of 169 paired tumor samples revealed a shift in intrinsic subtype proportions from HER2-Enriched at baseline (50.

Widespread gene-environment interactions shape the immune response to SARS-CoV-2 infection in hospitalized COVID-19 patients.

Genome-wide association studies performed in patients with coronavirus disease 2019 (COVID-19) have uncovered various loci significantly associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity. However, the underlying -regulatory genetic factors that contribute to heterogeneity in the response to SARS-CoV-2 infection and their impact on clinical phenotypes remain enigmatic. Here, we used single-cell RNA-sequencing to quantify genetic contributions to -regulatory variation in 361,119 peripheral blood mononuclear cells across 63 COVID-19 patients during acute infection, 39 samples collected in the convalescent phase, and 106 healthy controls.

ADHD and Academic Performance in College Students: A Systematic Review.

Objectives: The present study performed a systematic review of the scientific literature that deals with the academic performance of university students with ADHD, collecting the research conducted between 2018 and 2024. Likewise, we aimed to know the factors that influence on academic performance and evaluate the tools used in the collection of ADHD symptoms and educational data.

Methods: The electronic databases PubMed, PsycInfo, and Scopus were used to search studies using PRISMA guidelines.

Disease-modifying treatment and disability progression in subclasses of patients with primary progressive MS: results from the Big MS Data Network.

Background: Effectiveness of disease-modifying treatment (DMT) in people affected by primary progressive multiple sclerosis (PPMS) is limited. Whether specific subgroups may benefit more from DMT in a real-world setting remains unclear. Our aim was to investigate the potential effect of DMT on disability worsening among patients with PPMS stratified by different disability trajectories.

Parental Assessment of Infantile Hemangioma Cosmetic Clinical Outcomes: Results of the Spanish Hemangioma Nationwide Prospective Cohort.

Background: Functional impairment is the main consideration when it comes to choosing therapy for infantile hemangiomas (IH). However, since most hemangiomas are treated for cosmetic reasons, it is important to know the cosmetic outcome assessed by the parents.

Objective: To evaluate the aesthetic outcomes of IH, considering the characteristics of the lesions and the treatments used.

Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study.

Background: Alpelisib, a PI3Kα-selective inhibitor and degrader, plus fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in SOLAR-1; limited data are available in the post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess alpelisib plus endocrine therapy in this setting in three cohorts defined by immediate previous treatment; here, we report results from cohort A.

Methods: This ongoing, phase 2, multicentre, open-label, non-comparative study enrolled patients with hormone receptor-positive, HER2-negative, advanced breast cancer with tumour PIK3CA mutation, following progression on or after previous therapy, including CDK4/6 inhibitors, from 114 study locations (cancer centres, medical centres, university hospitals, and hospitals) in 18 countries worldwide.

Experimental Demonstration of Mode-Coupled and High-Brightness Self-Amplified Spontaneous Emission in an X-Ray Free-Electron Laser.

X-ray free-electron lasers (FELs) are modern research tools with applications in multiple scientific fields. Standard x-ray FEL pulses are produced by the self-amplified spontaneous emission (SASE) mechanism. SASE-FEL pulses have high power, short duration, and excellent transverse coherence but exhibit poor temporal coherence with power and spectral profiles consisting of multiple randomly distributed spikes.

Identifying predictors of treatment response and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-negative breast cancer: the NEOENDO translational study.

Background: Predictors of response to neoadjuvant chemotherapy (NACT) and endocrine therapy (NET) in hormone receptor-positive (HoR+)/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) are required. Also, pathological and molecular changes induced by both strategies and their impact on patients' outcomes have not been reported so far.

Patients And Methods: In a cohort of 186 patients with early-stage HoR+/HER2-negative BC treated with NACT or NET, we assessed the association of baseline main clinicopathological features and PAM50 gene expression (GE), intrinsic subtypes (IS) and risk-of-relapse (ROR-P) score with pathological outcomes according to treatment strategy.

Palbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy.

With the incorporation of cyclin-dependent kinase inhibitors in early breast cancer (BC), a better identification of biomarkers is needed. The PROMETEO II trial aimed to evaluate the antitumor activity of palbociclib plus letrozole and to identify response biomarkers in patients with operable HR+/HER2- BC and residual disease after neoadjuvant chemotherapy (NAC). The primary endpoint was the rate of complete cell cycle arrest (CCCA), centrally determined by Ki67 ≤ 2.

Accelerated hit identification with target evaluation, deep learning and automated labs: prospective validation in IRAK1.

Background: Target identification and hit identification can be transformed through the application of biomedical knowledge analysis, AI-driven virtual screening and robotic cloud lab systems. However there are few prospective studies that evaluate the efficacy of such integrated approaches.

Results: We synergistically integrate our in-house-developed target evaluation (SpectraView) and deep-learning-driven virtual screening (HydraScreen) tools with an automated robotic cloud lab designed explicitly for ultra-high-throughput screening, enabling us to validate these platforms experimentally.

Gestational breast cancer: distinctive molecular and clinico-epidemiological features.

Gestational breast cancer (GBC), defined as breast cancer (BC) diagnosed during pregnancy or the first-year post-partum, accounts for 6-15% of BC cases in women aged 20-44 years. GBC has worse prognosis than non-GBC, but reasons behind are not clear. The GEICAM/2012-03 Study (Molecular Characterization of Gestational Breast Cancer) is a multicenter prospective/retrospective observational registry of patients diagnosed with GBC.

Prognostic Expression Signature of , , and Genes in Patients with Metastatic Hormone-sensitive Prostate Cancer Treated with Androgen Receptor Pathway Inhibitors.

Unlabelled: Alterations in the tumor suppressor genes (TSGs) , , and are associated with treatment resistance, worse survival, and aggressive variants of prostate cancer (AVPC). We previously developed and validated a signature reflecting low TSG expression (TSG) that was associated with poor outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) ± docetaxel. The aim of this multicenter retrospective study was to validate the TSG signature in patients with mHSPC treated with ADT and an androgen receptor pathway inhibitor (ARPI) and to explore clinical characteristics at progression according to TSG status.

StCDF1: A 'jack of all trades' clock output with a central role in regulating potato nitrate reduction activity.

Transcription factors of the CYCLING DOF FACTOR (CDF) family activate in potato the SP6A FT tuberization signal in leaves. In modern cultivars, truncated StCDF1.2 alleles override strict SD control by stabilizing the StCDF1 protein, which leads to StCOL1 suppression and impaired activation of the antagonic SP5G paralog.