Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Consensus on the lung cancer management after third-generation EGFR-TKI resistance.

Lung cancer is the most prevalent malignant tumour in the Asia-Pacific region. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers. Among these, the rate of mutations in Asian patients with lung adenocarcinoma is 40-60%.

Discovery of the therapeutic potential of naltriben against glutamate-induced neurotoxicity.

Glutamate-induced neuronal death is associated with neurodegeneration including cerebral ischemia. Several μ-opioid receptor antagonists exhibit a neuroprotective activity and have been considered as a potential therapeutic option for neurodegenerative disorders. For the first time, our current study unveiled the neuroprotective activity of selective δ-opioid receptor antagonists.

Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens.

Introduction: Pandemic influenza vaccine development focuses on the hemagglutinin (HA) antigen for potency and immunogenicity. Antibody responses targeting the neuraminidase (NA) antigen, or the HA stalk domain have been implicated in protection against influenza. Responses to the NA and HA-stalk domain following pandemic inactivated influenza are not well characterized in humans.

Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.

Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.

Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.

Plasma fibronectin is a prognostic biomarker of disability in Parkinson's disease: a prospective, multicenter cohort study.

In a prospective longitudinal study with 218 Parkinson's disease (PD) patients in the discovery cohort and 84 in the validation cohort, we aimed to identify novel blood biomarkers predicting disability milestones in PD. Through Least Absolute Shrinkage and Selection Operator-Cox (Lasso-Cox) regression, developed nomogram predictive model and Linear mixed-effects models, we identified low level of plasma fibronectin (pFN) as one of the best-performing risk markers in predicting disability milestones. A low level of pFN was associated with a short milestone-free survival period in PD.

Understanding the Interplay between oHSV and the Host Immune System: Implications for Therapeutic Oncolytic Virus Development.

Oncolytic herpes simplex viruses (oHSV) preferentially replicate in cancer cells while inducing antitumor immunity, and thus, they are often referred to as in situ cancer vaccines. OHSV infection of tumors elicits diverse host immune responses comprising both innate and adaptive components. Although the innate/adaptive immune responses primarily target the tumor, they also contribute to antiviral immunity, limiting viral replication/oncolysis.

DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection.

DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2.

Leveraging domain knowledge for synthetic ultrasound image generation: a novel approach to rare disease AI detection.

Purpose: This study explores the use of deep generative models to create synthetic ultrasound images for the detection of hemarthrosis in hemophilia patients. Addressing the challenge of sparse datasets in rare disease diagnostics, the study aims to enhance AI model robustness and accuracy through the integration of domain knowledge into the synthetic image generation process.

Methods: The study employed two ultrasound datasets: a base dataset (Db) of knee recess distension images from non-hemophiliac patients and a target dataset (Dt) of hemarthrosis images from hemophiliac patients.

Optimizing immunogenicity and product presentation of a SARS-CoV-2 subunit vaccine composition: effects of delivery route, heterologous regimens with self-amplifying RNA vaccines, and lyophilization.

Introduction: Dozens of vaccines have been approved or authorized internationally in response to the ongoing SARS-CoV-2 pandemic, covering a range of modalities and routes of delivery. For example, mucosal delivery of vaccines via the intranasal (i.n.

Therapeutic potential inhibitor for dipeptidyl peptidase IV in diabetic type 2: in silico approaches.

Diabetes mellitus (DM) is a metabolic disease marked by an excessive rise in blood sugar (glucose) levels caused by a partial or total absence of insulin production, combined with alterations in the metabolism of proteins, lipids, and carbohydrates. The International Diabetes Federation estimates that 425 million individuals globally had diabetes in 2017 which will be 629 million by 2045. Several medications are used to treat DM, but they have limitations and side effects including weight gain, nausea, vomiting, and damage to blood vessels and kidneys.

Throw out an oligopeptide to catch a protein: Deep learning and natural language processing-screened tripeptide PSP promotes Osteolectin-mediated vascularized bone regeneration.

Angiogenesis is imperative for bone regeneration, yet the conventional cytokine therapies have been constrained by prohibitive costs and safety apprehensions. It is urgent to develop a safer and more efficient therapeutic alternative. Herein, utilizing the methodologies of Deep Learning (DL) and Natural Language Processing (NLP), we proposed a paradigm algorithm that amalgamates with a variant, , to deftly discern potential pro-angiogenic peptides from intrinsically disordered regions (IDRs) of 262 related proteins, where are fertile grounds for developing safer and highly promising bioactive peptides.

Enhanced Antibody Response to the Conformational Non-RBD Region DNA Prime-Protein Boost Elicits Broad Cross-Neutralization Against SARS-CoV-2 Variants.

Preventing immune escape of SARS-CoV-2 variants is crucial in vaccine development to ensure broad protection against the virus. Conformational epitopes beyond the RBD region are vital components of the spike protein but have received limited attention in the development of broadly protective SARS-CoV-2 vaccines. In this study, we used a DNA prime-protein boost regimen to evaluate the broad cross-neutralization potential of immune response targeting conformational non-RBD region against SARS-CoV-2 viruses in mice.

Specialist training in infectious diseases in Europe.

Objectives: The objectives were to determine the structure of training programmes and assessment of physicians training to become infectious disease (ID) specialists in Europe in early 2024, and to document the provision of specialists, trainees and training centres in each country.

Methods: Delegates to the ID Section and Board of the European Union of Medical Specialists (UEMS) entered national data on a web-based survey tool in late 2023-early 2024. Results were compared to UEMS recommendations on the structure and content of postgraduate training in ID in Europe (2018), and to results of a similar survey in early 2021.

Chromatin-site-specific accessibility: A microtopography-regulated door into the stem cell fate.

Biomaterials that mimic extracellular matrix topography are crucial in tissue engineering. Previous research indicates that certain biomimetic topography can guide stem cells toward multiple specific lineages. However, the mechanisms by which topographic cues direct stem cell differentiation remain unclear.

A Phase 1 randomized trial of homologous and heterologous filovirus vaccines with a late booster dose.

Filoviruses, including Ebola, Marburg, Sudan, and Taï Forest viruses, are zoonotic pathogens that can cause severe viral hemorrhagic fever and death. Developing vaccines that provide durable, broad immunity against multiple filoviruses is a high global health priority. In this Phase 1 trial, we enrolled 60 healthy U.

Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

Prognostic serum biomarkers of synaptic, neuronal and glial injury in patients with acute ischemic stroke of the anterior circulation.

Background: We aimed to investigate the prognostic role of β-synuclein in comparison to that of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) for predicting functional outcome after acute ischemic stroke (AIS).

Methods: We measured serum concentrations of β-synuclein, NfL and GFAP 24 h after hospital admission in 213 consecutive patients with moderate-to-severe AIS. We investigated the association between serum biomarkers and radiological/clinical characteristics, 3-months mortality and functional outcome on the modified Rankin Scale (mRS).

Graveyard effects of antimicrobial nanostructured titanium over prolonged exposure to drug resistant bacteria and fungi.

Innovations in nanostructured surfaces have found a practical place in the medical area with use in implant materials for post-operative infection prevention. These textured surfaces should be dual purpose: (1) bactericidal on contact and (2) resistant to biofilm formation over prolonged periods. Here, hydrothermally etched titanium surfaces were tested against two highly antimicrobial resistant microbial species, methicillin-resistant and .

SOX2-induced IL1α-mediated immune suppression drives epithelial dysplasia malignant transformation.

Squamous cell carcinomas (SCC) are often preceded by potentially malignant precursor lesions, most of which remain benign. The terminal exhaustion phenotypes of effector T-cells and the accumulation of myeloid-derived suppressor cells (MDSC) have been thoroughly characterized in established SCC. However, it is unclear what precancerous lesions harbor a bona fide high risk for malignant transformation and how precancerous epithelial dysplasia drives the immune system to the point of no return.

The human RAD52 complex undergoes phase separation and facilitates bundling and end-to-end tethering of RAD51 presynaptic filaments.

Human RAD52 is a prime target for synthetical lethality approaches to treat cancers with deficiency in homologous recombination. Among multiple cellular roles of RAD52, its functions in homologous recombination repair and protection of stalled replication forks appear to substitute those of the tumor suppressor protein BRCA2. However, the mechanistic details of how RAD52 can substitute BRCA2 functions are only beginning to emerge.

Cardiovascular Effects of Splenomegaly and Splenectomy in Beta-Thalassemia Major.

Background Beta-thalassemia major is a genetic blood disease complicated by splenomegaly, and splenectomy is a standard therapy for this medical condition. Although splenectomy results not only in the improvement of the hematological status, the long-term consequences to the cardiovascular system are still questionable. Objective The aim of the study was to assess and compare the cardiovascular impact of splenomegaly and splenectomy in patients with beta-thalassemia major.