Humoral and cellular immune responses after 6 months of a heterologous SARS-CoV-2 booster with the protein-based PHH-1V vaccine in a phase IIb trial.

The HIPRA-HH-2 was a multicentre, randomized, active-controlled, double-blind, non-inferiority phase IIb clinical trial comparing the immunogenicity and safety of the PHH-1V adjuvanted recombinant vaccine as a heterologous booster against homologous booster with BNT162b2. Interim results demonstrated strong humoral and cellular immune response against the SARS-CoV-2 Wuhan-Hu-1 strain and the Beta, Delta, and Omicron BA.1 variants up to day 98 post-dosing.

Safety of baricitinib in vaccinated patients with severe and critical COVID-19 sub study of the randomised Bari-SolidAct trial.

Background: The Bari-SolidAct randomized controlled trial compared baricitinib with placebo in patients with severe COVID-19. A post hoc analysis revealed a higher incidence of serious adverse events (SAEs) among SARS-CoV-2-vaccinated participants who had received baricitinib. This sub-study aimed to investigate whether vaccination influences the safety profile of baricitinib in patients with severe COVID-19.

Generation of chimeric antigen receptor T cells targeting p95HER2 in solid tumors.

The redirection of T lymphocytes against tumor-associated or tumor-specific antigens, using bispecific antibodies or chimeric antigen receptors (CAR), has shown therapeutic success against certain hematological malignancies. However, this strategy has not been effective against solid tumors. Here, we describe the development of CAR T cells targeting p95HER2, a tumor-specific antigen found in HER2-amplified solid tumors.

Partial Recovery of Telomere Length After Long-term Virologic Suppression in Persons With HIV-1.

Background: People with HIV-1 (PWH) age differently than the general population. Blood telomere length (BTL) attrition is a surrogate biomarker of immunosenescence and aging in PWH. BTL is reduced immediately after HIV-1 infection and recovers in PWH with long-term virologic suppression, but the extent of this recovery is unknown.

Immunogenicity of a third dose with mRNA-vaccines in the ChAdOx1-S/BNT162b2 vaccination regimen against SARS-CoV-2 variants.

CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months.

ERK1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility.

ERK1/2 mitogen-activated protein kinases (ERK) are key regulators of basic cellular processes, including proliferation, survival, and migration. Upon phosphorylation, ERK becomes activated and a portion of it dimerizes. The importance of ERK activation in specific cellular events is generally well documented, but the role played by dimerization is largely unknown.

The PARP1 selective inhibitor saruparib (AZD5305) elicits potent and durable antitumor activity in patient-derived BRCA1/2-associated cancer models.

Background: Poly (ADP-ribose) polymerase 1 and 2 (PARP1/2) inhibitors (PARPi) are targeted therapies approved for homologous recombination repair (HRR)-deficient breast, ovarian, pancreatic, and prostate cancers. Since inhibition of PARP1 is sufficient to cause synthetic lethality in tumors with homologous recombination deficiency (HRD), PARP1 selective inhibitors such as saruparib (AZD5305) are being developed. It is expected that selective PARP1 inhibition leads to a safer profile that facilitates its combination with other DNA damage repair inhibitors.

Generation of Metastatic Cholangiocarcinoma Patient-Derived Xenograft Models.

Cholangiocarcinoma (CCA) poses a substantial clinical hurdle as it is often detected at advanced metastatic stages with limited therapeutic options. To enhance our understanding of advanced CCA, it is imperative to establish preclinical models that faithfully recapitulate the disease's characteristics. Patient-derived xenograft (PDX) models have emerged as a valuable approach in cancer research, offering an avenue to reproduce and study the genomic, histologic, and molecular features of the original human tumors.

Non-suppressible viraemia during HIV-1 therapy: a challenge for clinicians.

In individuals receiving antiretroviral therapy (ART), persistent low-level viraemia not attributed to suboptimal ART adherence, detrimental pharmacological interactions, or drug resistance is referred to as non-suppressible viraemia (NSV). This Review presents recent findings in the virological characterisation of NSV, revealing that it consists of one or a few identical populations of plasma viruses without signs of evolution. This finding suggests that NSV originates from virus production by expanded HIV-infected cell clones, reflecting the persistence of the HIV reservoir despite ART.

Implementation of a High-Sensitivity Global Navigation Satellite System Receiver on a System-on-Chip Field-Programmable Gate Array Platform.

This paper presents the design, proof-of-concept implementation, and preliminary performance assessment of an affordable real-time High-Sensitivity (HS) Global Navigation Satellite System (GNSS) receiver. Specifically tailored to capture and track weak Galileo E1b/c signals, this receiver aims to support research endeavors focused on advancing GNSS signal processing algorithms, particularly in scenarios characterized by pronounced signal attenuation. Leveraging System-on-Chip Field-Programmable Gate Array (SoC-FPGA) technology, this design merges the adaptability of Software Defined Radio (SDR) concepts with the the robust hardware processing capabilities of FPGAs.

The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2.

Chemotherapy often generates intratumoral senescent cancer cells that strongly modify the tumor microenvironment, favoring immunosuppression and tumor growth. We discovered, through an unbiased proteomics screen, that the immune checkpoint inhibitor programmed cell death 1 ligand 2 (PD-L2) is highly upregulated upon induction of senescence in different types of cancer cells. PD-L2 is not required for cells to undergo senescence, but it is critical for senescent cells to evade the immune system and persist intratumorally.

Three Years of the Coronavirus Disease 2019 Pandemic in a European Region: A Population-Based Longitudinal Assessment in Madrid Between 2020 and 2022.

Background: Our objective was to assess the health impact of coronavirus disease 2019 (COVID-19) during 2020-2022 in the Madrid region.

Methods: We included all individuals registered in the Madrid Health System Registry as of 31 December 2019, and followed them until 31 December 2022. Using a unique personal identifier, we linked the databases of primary care, hospitals, pharmacies, certified laboratories performing diagnostic tests, vaccines, and mortality.

A Flexible System-on-Chip Field-Programmable Gate Array Architecture for Prototyping Experimental Global Navigation Satellite System Receivers.

Global navigation satellite system (GNSS) technology is evolving at a rapid pace. The rapid advancement demands rapid prototyping tools to conduct research on new and innovative signals and systems. However, researchers need to deal with the increasing complexity and integration level of GNSS integrated circuits (IC), resulting in limited access to modify or inspect any internal aspect of the receiver.

Interactions between BRD4S, LOXL2, and MED1 drive cell cycle transcription in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) often develops resistance to single-agent treatment, which can be circumvented using targeted combinatorial approaches. Here, we demonstrate that the simultaneous inhibition of LOXL2 and BRD4 synergistically limits TNBC proliferation in vitro and in vivo. Mechanistically, LOXL2 interacts in the nucleus with the short isoform of BRD4 (BRD4S), MED1, and the cell cycle transcriptional regulator B-MyB.

AXL - a new player in resistance to HER2 blockade.

HER2 is a driver in solid tumors, mainly breast, oesophageal and gastric cancer, through activation of oncogenic signaling pathways such as PI3K or MAPK. HER2 overexpression associates with aggressive disease and poor prognosis. Despite targeted anti-HER2 therapy has improved outcomes and is the current standard of care, resistance emerge in some patients, requiring additional therapeutic strategies.

Three-dimensional cell culture of chimeric antigen receptor T cells originated from peripheral blood mononuclear cells towards cellular therapies.

Background Aims: With the objective of improving the ex vivo production of therapeutic chimeric antigen receptor (CAR) T cells, we explored the addition of three-dimensional (3D) polystyrene scaffolds to standard suspension cell cultures.

Methods: We aimed to mimic the structural support given by the lymph nodes during in vivo lymphocyte expansion.

Results: We observed an increase in cell proliferation compared with standard suspension systems as well as an enhanced cytotoxicity toward cancer cells.

Monocyte Activation and Ageing Biomarkers in the Development of Cardiovascular Ischaemic Events or Diabetes in People with HIV.

We investigated whether blood telomere length (TL), epigenetic age acceleration (EAA), and soluble inflammatory monocyte cytokines are associated with cardiovascular events or diabetes (DM) in people living with HIV (PLHIV). This was a case-control study nested in the Spanish HIV/AIDS Cohort (CoRIS). Cases with myocardial infarction, stroke, sudden death, or diabetes after starting antiretroviral therapy were included with the available samples and controls matched for sex, age, tobacco use, pre-ART CD4 cell count, viral load, and sample time-point.

Evaluation of triple negative breast cancer with heterogeneous immune infiltration.

Introduction: Tumor infiltrating lymphocytes (TILs) are known to be a prognostic and predictive biomarker in breast cancer, particularly in triple negative breast cancer (TNBC) patients. International guidelines have been proposed to evaluate them in the clinical setting as a continuous variable, without a clear defined cut-off. However, there are scenarios where the immune infiltration is heterogeneous that some areas of the patient's tumour have high numbers of TILs while other areas completely lack them.