Sex-dependent efficacy of sphingosine-1-phosphate receptor agonist FTY720 in mitigating Huntington's disease.

Huntington's disease (HD) is a debilitating neurodegenerative disorder characterized by severe motor deficits, cognitive decline and psychiatric disturbances. An early and significant morphological hallmark of HD is the activation of astrocytes triggered by mutant huntingtin, leading to the release of inflammatory mediators. Fingolimod (FTY), an FDA-approved sphingosine-1-phosphate (S1P) receptor agonist is used to treat multiple sclerosis (MS), a neuroinflammatory disease, and has shown therapeutic promise in other neurological conditions.

Cognitive and Neurobiological Correlates for Switching/Inhibition Moderate the Relations Between Word Reading and Reading Comprehension in Hebrew-Speaking Children: An fMRI Study.

The expanded Simple View of Reading model suggests language processing and word reading as contributors to reading comprehension and points at the participation of executive functions as supporting these abilities. Switching and inhibition are both executive functions (EF) contributing to reading, especially in languages with two writing systems-shallow and deep, such as Hebrew. Here, we aimed to determine the specific role of switching/inhibition both cognitively and neurobiologically in the Simple View of Reading model among 49 eight- to 12-year-old Hebrew-speaking children.

ABCC1 Is a ΔNp63 Target Gene Overexpressed in Squamous Cell Carcinoma.

The transcription factor ΔNp63 plays a pivotal role in maintaining the integrity of stratified epithelial tissues by regulating the expression of distinct target genes involved in lineage specification, cell stemness, cell proliferation and differentiation. Here, we identified the ABC transporter subfamily member as a novel ΔNp63 target gene. We found that in immortalized human keratinocytes and in squamous cell carcinoma (SCC) cells, ∆Np63 induces the expression of ABCC1 by physically occupying a p63-binding site (p63 BS) located in the first intron of the gene locus.

25-Hydroxycholesterol attenuates tumor necrosis factor alpha-induced blood-brain barrier breakdown in vitro.

Intracellular cholesterol metabolism is regulated by the SREBP-2 and LXR signaling pathways. The effects of inflammation on these molecular mechanisms remain poorly studied, especially at the blood-brain barrier (BBB) level. Tumor necrosis factor α (TNFα) is a proinflammatory cytokine associated with BBB dysfunction.

Emerging Role of ABC Transporters in Glia Cells in Health and Diseases of the Central Nervous System.

ATP-binding cassette (ABC) transporters play a crucial role for the efflux of a wide range of substrates across different cellular membranes. In the central nervous system (CNS), ABC transporters have recently gathered significant attention due to their pivotal involvement in brain physiology and neurodegenerative disorders, such as (AD). Glial cells are fundamental for normal CNS function and engage with several ABC transporters in different ways.

Clinical and Radiographic Outcomes of Mineral Trioxide Aggregate Pulpotomies in Vital Permanent Teeth with Carious Pulp Exposure: A Pioneering Retrospective Study.

Purpose: Vital partial pulpotomy (PP) or cervical pulpotomy (CP) in carious pulp-exposed permanent teeth preserves tooth vitality, promotes pulp healing, decreases treatment costs, and shortens treatment duration, which is a significant factor in treating noncooperative children. The aim of this retrospective study was to compare clinical and radiographic outcomes of partial and CP in vital carious-exposed permanent teeth.

Materials And Methods: All vital permanent teeth with carious pulp exposure, treated by pulpotomy using mineral trioxide aggregate (MTA) during 2017-2019, by two operators in one dental center, were included in the study.

Laboratory Results of a Real-Time SHM Integrated System on a P180 Full-Scale Wing-Box Section.

The final objective of the study herein reported is the preliminary evaluation of the capability of an original, real-time SHM system applied to a full-scale wing-box section as a significant aircraft component, during an experimental campaign carried out at the Piaggio Lab in Villanova D'Albenga, Italy. In previous works, the authors have shown that such a system could be applied to composite beams, to reveal damage along the bonding line between a longitudinal stiffening element and the cap. Utilizing a suitable scaling process, such work has then been exported to more complex components, in order to confirm the outcomes that were already achieved, and, possibly, expanding the considerations that should drive the project towards an actual implementation of the proposed architecture.

Preliminary Results of a Structural Health Monitoring System Application for Real-Time Debonding Detection on a Full-Scale Composite Spar.

The present paper reports the outcomes of activities concerning a real-time SHM system for debonding flaw detection based on ground testing of an aircraft structural component as a basis for condition-based maintenance. In this application, a damage detection method unrelated to structural or load models is investigated. In the reported application, the system is applied for real-time detection of two flaws, kissing bond type, artificially deployed over a full-scale composite spar under the action of external bending loads.

First-Line Efficacy of Anti-HER2 Treatments in Previously Treated HER2-Positive Metastatic Breast Cancer Patients: A Retrospective Observational Study Investigating the Efficacy of Re-Exposure to Anti-HER2 Therapy for HER2-Positive Metastatic Breast Cancer Patients in Comparison with Naïve Patients.

Background: Most patients with HER2-positive metastatic breast cancer (MBC) receive first-line treatment with anti-HER2 agents and have already received anti-HER2 therapy as adjuvant or neoadjuvant therapy in the local setting of their disease presentation. Despite that, they constitute only a minority among clinical trials, and their response to reintroduction to anti-HER2 treatments is inconclusive based upon conflicting studies. We aimed to examine if previous exposure influences the clinical outcome of patients treated with anti-HER2 treatments compared to patients who were naïve to anti-HER2 agents.

Sparsity through evolutionary pruning prevents neuronal networks from overfitting.

Modern Machine learning techniques take advantage of the exponentially rising calculation power in new generation processor units. Thus, the number of parameters which are trained to solve complex tasks was highly increased over the last decades. However, still the networks fail - in contrast to our brain - to develop general intelligence in the sense of being able to solve several complex tasks with only one network architecture.

Cost-effectiveness of diabetic retinopathy screening programs using telemedicine: a systematic review.

Background: Diabetic retinopathy (DR) is a significant global public health and economic burden. DR accounts for approximately 15-17% of all cases of total blindness in the USA and Europe. Telemedicine is a new intervention for DR screening, however, there is not enough evidence to support its cost-effectiveness.

Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT.

Background: Experience using post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis in allogeneic stem cell transplantation (HSCT) from matched sibling donors (MSD) or unrelated donors (UD) is limited and with controversial results. The study aim was to evaluate PT-Cy as GVHD prophylaxis post-HSCT from MSD and UD transplants. We analyzed 423 patients with acute leukemia who received PT-Cy alone or in combination with other immunosuppressive (IS) drugs as GVHD prophylaxis.

Novel strategies for improving hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation or intensive chemotherapy.

High-dose conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) as well as intensive poly-chemotherapy for acute myeloid leukemia (AML) induce prolonged periods of neutropenia. The duration of the neutropenia is particularly long following umbilical cord blood transplantation (UCBT). Areas covered: After briefly reviewing the impact of hematopoietic growth factors administration to hasten hematologic reconstitution after allo-HCT or intensive AML chemotherapy, this article summarizes recent approaches that have been investigated to prompt hematologic reconstruction after UCBT or intensive AML chemotherapy.

Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus-host disease prophylaxis in haploidentical transplant.

Severe graft-versus-host disease is a major barrier for non-T-cell-depleted haploidentical stem cell transplantation. There is no consensus on the optimal graft-versus-host disease prophylaxis. This study compared the two most commonly used graft-versus-host disease prophylaxis regimens (post-transplant cyclophosphamide-based vs.

Methods of ex vivo expansion of human cord blood cells: challenges, successes and clinical implications.

More than 40,000 unrelated cord blood transplantations (UCBT) have been performed worldwide as treatment for patients with malignant or non-malignant life threatening hematologic disorders. However, low absolute numbers of hematopoietic stem and progenitor cells (HSPCs) within a single cord blood unit has remained a limiting factor for this transplantation modality, particularly in adult recipients. Further, because UCB contains low numbers of mostly naïve T cells, immune recovery after UCBT is slow, predisposing patients to severe infections.