Haematopoietic gene therapy of non-conditioned patients with Fanconi anaemia-A: results from open-label phase 1/2 (FANCOLEN-1) and long-term clinical trials.

Background: Allogeneic haematopoietic stem-cell transplantation is the standard treatment for bone marrow failure (BMF) in patients with Fanconi anaemia, but transplantation-associated complications such as an increased incidence of subsequent cancer are frequent. The aim of this study was to evaluate the safety and efficacy of the infusion of autologous gene-corrected haematopoietic stem cells as an alternative therapy for these patients.

Methods: This was an open-label, investigator-initiated phase 1/2 clinical trial (FANCOLEN-1) and long-term follow-up trial (up to 7 years post-treatment) in Spain.

Dyadic Coping in Aging: Linking Self-Perceptions of Aging to Depression.

Negative self-perceptions of aging have been linked to poorer health and quality of life and predict significantly depressive symptomatology. The support provided by the partner may have an impact on the effects of self-perceptions of aging on depressive symptoms; a close relationship can go along with additional stress or resources and benefits. The present study analyzes the relationship between negative self-stereotypes and depressive symptomatology, considering positive and negative dyadic coping (DC) as moderator variables in this association.

Psychometric properties of the Partner Ambivalence Scale in middle-aged and older adults.

Objectives: Ambivalent feelings in a partner relationship, characterized by simultaneous positive and negative emotional experiences, can significantly influence individuals' mental health. Traditionally measured indirectly, this study introduces the Partner Ambivalence Scale (PAS), developed for directly capturing the complexity of ambivalent emotions. This study aimed to analyze the psychometric properties of the PAS, and assess the effects of ambivalent feelings on partner relationship quality and depressive symptomatology.

Profiles of Dementia Caregivers according to Psychosocial and Resource Variables. Importance of Kinship.

The present study aims to analyze the existence of different profiles in family caregivers of people with dementia according to psychosocial and resource variables. In addition, it aims to study whether there is a greater representation of each kinship group in each of the profiles and if there are differences in emotional distress among such profiles considering the kinship with the care-recipient. Participants 288 family dementia caregivers, divided into four kinship groups (wives, husbands, sons and daughters).

Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells.

Background: Primary resistance to anti-EGFR therapies affects 40% of metastatic colorectal cancer patients harbouring wild-type RAS/RAF. YAP1 activation is associated with this resistance, prompting an investigation into AURKA's role in mediating YAP1 phosphorylation at Ser397, as observed in breast cancer.

Methods: We used transcriptomic analysis along with in vitro and in vivo models of RAS/RAF wild-type CRC to study YAP1 Ser397 phosphorylation as a potential biomarker for cetuximab resistance.

CD44 Modulates Cell Migration and Invasion in Ewing Sarcoma Cells.

The chimeric EWSR1::FLI1 transcription factor is the main oncogenic event in Ewing sarcoma. Recently, it has been proposed that EWSR1::FLI1 levels can fluctuate in Ewing sarcoma cells, giving rise to two cell populations. EWSR1::FLI1 cells present a migratory and invasive phenotype, while EWSR1::FLI1 cells are more proliferative.

Executive functions in daily living skills: A study in adults with autism spectrum disorder.

Introduction: Adults with autism and adults with schizophrenia show difficulties in adaptive skills, especially those related to daily functioning. Some studies suggest that adaptive skills are associated with deficits in executive functions (EF), while others indicate that intelligence quotient (IQ) might also play a role. Literature suggests that autistic symptoms further affect adaptive skills.

Adenine base editing efficiently restores the function of Fanconi anemia hematopoietic stem and progenitor cells.

Fanconi Anemia (FA) is a debilitating genetic disorder with a wide range of severe symptoms including bone marrow failure and predisposition to cancer. CRISPR-Cas genome editing manipulates genotypes by harnessing DNA repair and has been proposed as a potential cure for FA. But FA is caused by deficiencies in DNA repair itself, preventing the use of editing strategies such as homology directed repair.

Neuropsychological profile of executive functions in autism spectrum disorder and schizophrenia spectrum disorders: a comparative group study in adults.

As assessed by numerous neuropsychological tasks, individuals with autism spectrum disorder (ASD) and schizophrenia spectrum disorders (SSDs) have similar impairments related to executive functions (EFs). The neuropsychological profile of these two conditions was examined using the three-component EFs' framework of Miyake and Friedman (Cogn Psychol 41(1):49-100, 2000). This approach assesses Inhibition (suppression of unwanted and irrelevant information/responses), Updating (use and control of contents of working memory), and Shifting (disengagement between activities or mental tasks) using nine different tasks.

Differences in daily life executive functioning between people with autism and people with schizophrenia.

This is a comparative analysis of everyday executive functioning between individuals with Autism Spectrum Disorder (ASD), Schizophrenia Spectrum Disorders (SSD) and controls using Dysexecutive Questionnaire-Spanish (DEX-Sp), to identify patterns of difficulties. Also we assessed the relationship between EF and adaptive behavior as measured by the Vineland Adaptive Behavioral Scale-II. Common areas of everyday executive functions were established as problematic in individuals with ASD and SSD related to Disinhibition and Apathy, while Disorganization and Impulsivity was gravely affected in ASD group only.

The Transcription Factor , a Direct Target of in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes.

Ewing sarcoma is a rare pediatric tumor characterized by chromosomal translocations that give rise to aberrant chimeric transcription factors (e.g., EWSR1-FLI1).

Overcoming PLK1 inhibitor resistance by targeting mevalonate pathway to impair AXL-TWIST axis in colorectal cancer.

New therapeutic targets are revolutionizing colorectal cancer clinical management, opening new horizons in metastatic patients' outcome. Polo Like Kinase1 (PLK1) inhibitors have high potential as antitumoral agents, however, the emergence of drug resistance is a major challenge for their use in clinical practice. Overcoming this challenge represents a hot topic in current drug discovery research.

Therapeutic Potential of Inactivation by CRISPR/Cas9 in Ewing Sarcoma.

Ewing sarcoma is an aggressive bone cancer affecting children and young adults. The main molecular hallmark of Ewing sarcoma are chromosomal translocations that produce chimeric oncogenic transcription factors, the most frequent of which is the aberrant transcription factor EWSR1-FLI1. Because this is the principal oncogenic driver of Ewing sarcoma, its inactivation should be the best therapeutic strategy to block tumor growth.

A Higher Proportion of Eicosapentaenoic Acid (EPA) When Combined with Docosahexaenoic Acid (DHA) in Omega-3 Dietary Supplements Provides Higher Antioxidant Effects in Human Retinal Cells.

Retinal pigment epithelium (RPE) is a key regulator of retinal function and is directly related to the transport, delivery, and metabolism of long-chain n-3 polyunsaturated fatty acids (n3-PUFA), in the retina. Due to their functions and location, RPE cells are constantly exposed to oxidative stress. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown to have antioxidant effects by different mechanisms.

Targeting Galectin-1 by Aflibercept Strongly Enhances Its Antitumor Effect in Neuroendocrine Carcinomas.

Background: Galectin-1 (Gal-1) plays major roles in cancer by modulating different processes leading to tumor development and progression. In the last years, it has been suggested as a promising target for anticancer therapy. Recently, aflibercept has shown high affinity for Gal-1.

Preclinical Evaluation of a Cell-Based Gene Therapy Using the Sleeping Beauty Transposon System in Choroidal Neovascularization.

Age-related macular degeneration (AMD) is a progressive retinal disorder characterized by imbalanced pro- and antiangiogenic signals. The aim of this study was to evaluate the effect of cell-based gene therapy with stable expression of human pigment epithelium-derived factor (PEDF) release using the non-viral () transposon system delivered by miniplasmids free of antibiotic resistance markers (pFAR4). Retinal pigment epithelial (RPE) cells and iris pigment epithelial (IPE) cells were co-transfected with pFAR4-inverted terminal repeats (ITRs) CMV-PEDF-BGH and pFAR4-CMV--SV40 plasmids.

Strong Antitumor Activity of Bevacizumab and Aflibercept in Neuroendocrine Carcinomas: In-Depth Preclinical Study.

Background: Neuroendocrine carcinoma (NEC) is a rare and very aggressive tumor. It has been greatly understudied, and very little is known about optimal treatment strategy for patients with this disease. The purpose of this study was to evaluate in vivo whether anti-vascular endothelial growth factor (VEGF) drugs could be a therapeutic alternative for these tumors with a poor prognosis.

Prognostic significance of neutrophil-to lymphocyte ratio and platelet-to lymphocyte ratio in older patients with metastatic colorectal cancer.

Unlabelled: Aging is associated with a higher risk of cancer, >70% of cancer-related deaths occur in aged patients; however, this population is underrepresented in clinical trials, therefore, clinical information regarding this age group is rather limited.

Objectives: Neutrophil-to lymphocyte ratio (NLR) and platelet-to lymphocyte ratio (PLR) have been described as biomarkers in cancer, thus, we have assessed their impact in an aged cohort of patients with metastatic colorectal cancer (mCRC).

Patients And Methods: 110 patients with a mean age of 72.

Long-Term PEDF Release in Rat Iris and Retinal Epithelial Cells after Sleeping Beauty Transposon-Mediated Gene Delivery.

Pigment epithelium derived factor (PEDF) is a potent antiangiogenic, neurotrophic, and neuroprotective molecule that is the endogenous inhibitor of vascular endothelial growth factor (VEGF) in the retina. An ex vivo gene therapy approach based on transgenic overexpression of PEDF in the eye is assumed to rebalance the angiogenic-antiangiogenic milieu of the retina, resulting in growth regression of choroidal blood vessels, the hallmark of neovascular age-related macular degeneration. Here, we show that rat pigment epithelial cells can be efficiently transfected with the PEDF-expressing non-viral hyperactive Sleeping Beauty transposon system delivered in a form free of antibiotic resistance marker miniplasmids.

Evaluation of 10 AMD Associated Polymorphisms as a Cause of Choroidal Neovascularization in Highly Myopic Eyes.

Choroidal neovascularization (CNV) commonly occurs in age related macular degeneration and pathological myopia patients. In this study we conducted a case-control prospective study including 431 participants. The aim of this study was to determine the potential association between 10 single nucleotide polymorphisms (SNPs) located in 4 different genetic regions (CFI, COL8A1, LIPC, and APOE), and choroidal neovascularization in age-related macular degeneration and the development of choroidal neovascularization in highly myopic eyes of a Caucasian population.

Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice.

We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS)-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids) on choroidal neovascularization (CNV). Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced) murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline), group S (oral supplement, intravitreal saline), group V + aVEGF (oral vehicle, intravitreal anti-VEGF), and group S + aVEGF (oral supplement, intravitreal anti-VEGF).

Varicella vaccination coverage inverse correlation with varicella hospitalizations in Spain.

Varicella vaccines available in Spain were marketed in 1998 and 2003 for non-routine use. Since 2006 some regions included universal varicella vaccination in their regional routine vaccination programs at 15-18 months of age. Regions without universal vaccination in toddlers, but instead with the strategy of vaccinating susceptible adolescents, reached different varicella vaccination coverage through private market.