Single intravenous administration of oncolytic adenovirus TILT-123 results in systemic tumor transduction and immune response in patients with advanced solid tumors.

Background: A limitation of approved oncolytic viruses is their requirement for intratumoral (i.t.) injection.

Overcoming effector T cell exhaustion in ovarian cancer ascites with a novel adenovirus encoding for a MUC1 bispecific antibody engager and IL-2 cytokine.

T cell-focused cancer immunotherapy including checkpoint inhibitors and cell therapies has been rapidly evolving over the past decade. Nevertheless, there remains a major unmet medical need in oncology generally and immuno-oncology specifically. We have constructed an oncolytic adenovirus, Ad5/3-E2F-d24-aMUC1aCD3-IL-2 (TILT-322), which is armed with a human aMUC1aCD3 T cell engager and IL-2.

Diagnostic Accuracy of Cone Beam Computed Tomography and Periapical Radiography for Detecting Apical Root Resorption in Retention Phase of Orthodontic Patients: A Cross-Sectional Study.

This clinical study aimed to evaluate and compare the diagnostic accuracy of intraoral periapical radiography (PR) and cone beam computed tomography (CBCT) in detecting external apical root resorption (EARR) in orthodontic patients during the retention phase. The research involved 41 Caucasian patients who had undergone comprehensive orthodontic treatment, with a total of 328 teeth analyzed. The Kappa values for inter- and intra-examiner agreement were high for both PR and CBCT, indicating a robust level of agreement among examiners.

Safety, Efficacy, and Biological Data of T-Cell-Enabling Oncolytic Adenovirus TILT-123 in Advanced Solid Cancers from the TUNIMO Monotherapy Phase I Trial.

Purpose: TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with TNFa and IL2, designed to induce T-cell infiltration and cytotoxicity in solid tumors.

Patients And Methods: TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose-escalation trial designed to assess the safety of TILT-123 in advanced solid cancers refractory to standard therapy. Patients received intravenous and intratumoral TILT-123.

Effects of endodontic irrigation solutions on structural, chemical, and mechanical properties of coronal dentin: A scoping review.

Objective: This review aims to assess structural, chemical, and mechanical properties of coronal dentin after endodontic irrigation.

Materials And Methods: Reporting followed the PRISMA extension for scoping reviews. An electronic search was carried out in PubMed, Embase, and Cochrane Library.

Effective intravenous delivery of adenovirus armed with TNFα and IL-2 improves anti-PD-1 checkpoint blockade in non-small cell lung cancer.

Lung cancer remains among the most difficult-to-treat malignancies and is the leading cause of cancer-related deaths worldwide. The introduction of targeted therapies and checkpoint inhibitors has improved treatment outcomes; however, most patients with advanced-stage non-small cell lung cancer (NSCLC) eventually fail these therapies. Therefore, there is a major unmet clinical need for checkpoint refractory/resistant NSCLC.

An oncolytic adenovirus coding for a variant interleukin 2 cytokine improves response to chemotherapy through enhancement of effector lymphocyte cytotoxicity, fibroblast compartment modulation and mitotic slippage.

Pancreatic ductal adenocarcinoma (PDAC) is a highly treatment-resistant cancer. Currently, the only curative treatment for PDAC is surgery, but most patients are diagnosed with metastatic disease and thus outside the scope of surgery. The majority of metastatic patients receive chemotherapy, but responses are limited.

Development of a Syrian hamster anti-PD-L1 monoclonal antibody enables oncolytic adenoviral immunotherapy modelling in an immunocompetent virus replication permissive setting.

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, but preclinical testing of hypotheses such as combination therapies has been complicated, in part due to species incompatibility issues. For example, one of few known permissive animal models for oncolytic adenoviruses is the Syrian hamster, for which an ICI, mainly an anti-PD-L1 monoclonal antibody (mAb) was not previously available. In this study, we developed an anti-Syrian hamster PD-L1 mAb to enable the evaluation of safety and efficacy, when combining anti-PD-L1 with an oncolytic adenovirus encoding tumour necrosis factor alpha (TNFα) and interleukin-2 (IL-2) (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2 or TILT-123).

Oncolytic adenovirus coding for bispecific T cell engager against human MUC-1 potentiates T cell response against solid tumors.

Immunotherapy with bispecific T cell engagers has shown efficacy in patients with hematologic malignancies and uveal melanoma. Antitumor effects of bispecific T cell engagers in most solid tumors are limited due to their short serum half-life and insufficient tumor concentration. We designed a novel serotype 5/3 oncolytic adenovirus encoding a human mucin1 antibody and the human CD3 receptor, Ad5/3-E2F-d24-aMUC1aCD3 (TILT-321).

Development and validation of the facilitative interpersonal skills scale for clients.

Objective: Psychotherapy studies have revealed that therapist characteristics are responsible for 5% to 9% of outcome variance. The therapist-facilitative interpersonal skills (FIS) have been shown to predict both alliance and outcomes, indicating that higher FIS therapists are more effective than lower FIS therapists. The current study focused on the development and validation of the FIS-client version (FIS-C) instrument, aimed at collecting the clients' perspectives on relevant therapist characteristics.

Persona preparedness: a survey instrument for measuring the organizational readiness for deploying personas.

Unlabelled: User-centric design within organizations is crucial for developing information technology that offers optimal usability and user experience. Personas are a central user-centered design technique that puts people before technology and helps decision makers understand the needs and wants of the end-user segments of their products, systems, and services. However, it is not clear how ready organizations are to adopt persona thinking.

Intentional Replantation as a Starting Approach for a Multidisciplinary Treatment of a Mandibular Second Molar: A Case Report.

Intentional replantation (IR) may offer a solution for persistent periapical lesions associated with endodontically treated teeth. A 35-year-old male patient presented with pain associated with the left mandibular second molar and hypoesthesia. Upon clinical examination, increased probing pocket depth in the mid-buccal surface was detected.

Effective Combination Immunotherapy with Oncolytic Adenovirus and Anti-PD-1 for Treatment of Human and Murine Ovarian Cancers.

Ovarian cancer (OvCa) is one of the most common gynecological cancers and has the highest mortality in this category. Tumors are often detected late, and unfortunately over 70% of OvCa patients experience relapse after first-line treatments. OvCa has shown low response rates to immune checkpoint inhibitor (ICI) treatments, thus leaving room for improvement.

Local delivery of interleukin 7 with an oncolytic adenovirus activates tumor-infiltrating lymphocytes and causes tumor regression.

Cytokines have proven to be effective for cancer therapy, however whilst low-dose monotherapy with cytokines provides limited therapeutic benefit, high-dose treatment can lead to a number of adverse events. Interleukin 7 has shown promising results in clinical trials, but anti-cancer effect was limited, in part due to a low concentration of the cytokine within the tumor. We hypothesized that arming an oncolytic adenovirus with Interleukin 7, enabling high expression localized to the tumor microenvironment, would overcome systemic delivery issues and improve therapeutic efficacy.

Long-Term Outcome of Nonvital Immature Permanent Teeth Treated With Apexification and Corono-Radicular Adhesive Restoration: A Case Series.

Introduction: This study aimed to evaluate the long-term outcome of 16 permanent maxillary central incisors with nonvital pulps and open apices treated with apexification and corono-radicular adhesive restorations, within a follow-up span of 5 to 22 years.

Methods: Fourteen patients providing a total of 16 teeth treated with mineral trioxide aggregate (n = 12), Biodentine (n = 3), or β-tricalcium phosphate (n = 1) apical barrier and corono-radicular restoration, with or without fiberglass post, were included. Clinical and radiographic criteria were defined for assessment at recall.

Delayed Cutaneous Adverse Reaction of the AstraZeneca COVID-19 Vaccine in a Breastfed Female Infant: A Coincidence or a Rare Effect?

The ChAdOx1 nCoV-19 vector vaccine (Vaxzevria, AstraZeneca, Cambridge, UK) was developed at Oxford University and is considered safe for the administration in lactating mothers. Nevertheless, as a novel vaccine, there are gaps in the knowledge regarding possible adverse events in breastfeeding infants of vaccinated mothers. This case report provides first-time data on a possible delayed, cutaneous, adverse reaction in a breastfed, 16-month-old female infant after the first administration of the AstraZeneca vaccine to her 33-year-old mother.

Adenovirus Encoding Tumor Necrosis Factor Alpha and Interleukin 2 Induces a Tertiary Lymphoid Structure Signature in Immune Checkpoint Inhibitor Refractory Head and Neck Cancer.

Immune checkpoint inhibitors (ICI) have provided significant improvement in clinical outcomes for some patients with solid tumors. However, for patients with head and neck cancer, the response rate to ICI monotherapy remains low, leading to the exploration of combinatorial treatment strategies. In this preclinical study, we use an oncolytic adenovirus (Ad5/3) encoding hTNFα and hIL-2 and non-replicate adenoviruses (Ad5) encoding mTNFα and mIL-2 with ICI to achieve superior tumor growth control and improved survival outcomes.

Lossless Coding of Light Fields Based on 4D Minimum Rate Predictors.

Common representations of light fields use four-dimensional data structures, where a given pixel is closely related not only to its spatial neighbours within the same view, but also to its angular neighbours, co-located in adjacent views. Such structure presents increased redundancy between pixels, when compared with regular single-view images. Then, these redundancies are exploited to obtain compressed representations of the light field, using prediction algorithms specifically tailored to estimate pixel values based on both spatial and angular references.

Local therapy with an engineered oncolytic adenovirus enables antitumor response in non-injected melanoma tumors in mice treated with aPD-1.

Intratumoral immunotherapies are entering clinical use but concerns remain regarding their effects on non-injected tumors. Here, we studied the impact of local treatment with an adenovirus coding for TNFa and IL-2 on systemic antitumor response in animals receiving aPD-1 (anti-programmed cell death protein 1) therapy. Using bilateral murine melanoma models, we tested systemic tumor response to combined therapy with anti-PD-1 and an adenovirus coding for TNFa and IL-2 ("virus").

Thrombus in transit through a patent foramen ovale: catch it if you can-a case report.

Background: Patent foramen ovale (PFO) is one of the most common congenital heart defects, but the finding of a thrombus in transit (TIT) through a PFO is extremely rare. It is a therapeutic challenge, and systemic anticoagulation, cardiac surgery, or fibrinolysis should be considered.

Case Summary: A 43-year-old woman was admitted with intermediate-high-risk pulmonary embolism.

Açaí extract powder as natural antioxidant on pork patties during the refrigerated storage.

The current trends among consumers are pushing for the use of natural antioxidants options. Açaí fruit is rich on polyphenolic components but no studies have been carried out to evaluate their effect in meat products. The objective was to investigate the effect of açaí extract on refrigerated pork patties quality.

Impact of Periodontal Attachment Loss on the Outcome of Endodontic Microsurgery: A Systematic Review and Meta-Analysis.

: Endodontic microsurgery (EMS) aims to eradicate the sources of infection once the apical root resection removes most of the infected anatomical structures and repairs potential procedural errors in the apical region. An endodontic-periodontal lesion yields a pathological communication between the pulp and the periodontium. The purpose of this systematic review and meta-analysis is to evaluate the impact of periodontal attachment loss on the outcome of teeth submitted to EMS.