Where are we with fractionation schedules and prescriptions in high-dose-rate 3D planning vaginal cuff brachytherapy?

Purpose: Currently, there are many schedules for exclusive vaginal cuff brachytherapy (VCB). In 3D treatment planning for VCB dosimetry, parameters have not been analyzed. The aim of this study was to compare the most common schedules using dose-volume histogram metrics.

Reirradiation Practice in Gynecological Cancer: Insights from a National Survey in Spain.

Purpose: Given the lack of standardisation in gynecological cancer reirradiation, the Gyneacologial Radiation Oncology (GINECOR) working group on behalf of the Spanish Society of Radiation Oncology (SEOR), works towards to inquire the current state of reirradiation practices among the radiation oncology departments in Spain.

Methods: An online 37-question survey was sent to all GINECOR members, representing most Spanish centers. The survey addressed general aspects of reirradiation, including experience, reirradiation sites, and techniques used.

A novel proxy for energy flux in multi-era wildfire reconstruction.

Escalations in wildfire activity are of significant global concern, particularly within vulnerable wetland ecosystems integral to natural carbon sequestration and climate change mitigation. Our understanding and management of future wildfire activity may be better contextualised through the study of historic and ancient fire records, independent of human influence. Methods of study include 'geothermometry' - approximating ancient fire intensity from temperature-dependent changes in the chemistry of fossil charcoal.

Updates in diagnosis and treatment of pediatric antiphospholipid syndrome.

Purpose Of Review: This review offers an overview of the most important recent articles on pediatric APS.

Recent Findings: Non-thrombotic extra criteria manifestations were prevalent in pediatric APS. Pregnancy morbidity has been described as the first manifestation of APS at youth age, impairing gestational outcomes.

Non-consecutive enzyme interactions within TCA cycle supramolecular assembly regulate carbon-nitrogen metabolism.

Enzymes of the central metabolism tend to assemble into transient supramolecular complexes. However, the functional significance of the interactions, particularly between enzymes catalyzing non-consecutive reactions, remains unclear. Here, by co-localizing two non-consecutive enzymes of the TCA cycle from Bacillus subtilis, malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICD), in phase separated droplets we show that MDH-ICD interaction leads to enzyme agglomeration with a concomitant enhancement of ICD catalytic rate and an apparent sequestration of its reaction product, 2-oxoglutarate.

Interstitial needles versus intracavitary applicators only for locally advanced cervical cancer: results from real-life dosimetric comparisons.

Background And Purpose: Image-guided adapted brachytherapy (IGABT) is superior to other radiotherapy techniques in the treatment of locally advanced cervical cancer (LACC). We aimed to investigate the benefit of interstitial needles (IN) for a combined intracavitary/interstitial (IC/IS) approach using IGABT over the intracavitary approach (IC) alone in patients with LACC after concomitant external beam radiotherapy (EBRT) and chemotherapy.

Materials And Methods: We included consecutive patients with LACC who were treated with IC/IS IGABT after radiochemotherapy (RCT) in our retrospective, observational study.

Cell proliferation and Notch signaling coordinate the formation of epithelial folds in the Drosophila leg.

The formation of complex three-dimensional organs during development requires precise coordination between patterning networks and mechanical forces. In particular, tissue folding is a crucial process that relies on a combination of local and tissue-wide mechanical forces. Here, we investigate the contribution of cell proliferation to epithelial morphogenesis using the Drosophila leg tarsal folds as a model.

Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies.

Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells limits the efficacy of immunotherapeutic approaches. The T cell receptor expresses one of two highly homologous chains [T cell receptor β-chain constant (TRBC) domains 1 and 2] in a mutually exclusive manner, making it a promising target.

Designer Small-Molecule Control System Based on Minocycline-Induced Disruption of Protein-Protein Interaction.

A versatile, safe, and effective small-molecule control system is highly desirable for clinical cell therapy applications. Therefore, we developed a two-component small-molecule control system based on the disruption of protein-protein interactions using minocycline, an FDA-approved antibiotic with wide availability, excellent biodistribution, and low toxicity. The system comprises an anti-minocycline single-domain antibody (sdAb) and a minocycline-displaceable cyclic peptide.

Is There a Place for Brachytherapy in Vulvar Cancer? A Narrative Review.

Vulvar cancer is a relatively rare neoplasm. The essential treatment is surgery for the primary tumour. However, postoperative recurrence rates are high, even in early-stage disease when tumour-free surgical margins are achieved or in the absence of associated risk factors (lymph node metastases, deep stromal invasion or invasion of the lymphatic vascular space).

Identification of gene function based on models capturing natural variability of Arabidopsis thaliana lipid metabolism.

Lipids play fundamental roles in regulating agronomically important traits. Advances in plant lipid metabolism have until recently largely been based on reductionist approaches, although modulation of its components can have system-wide effects. However, existing models of plant lipid metabolism provide lumped representations, hindering detailed study of component modulation.

Types of Carabidae (Insecta: Coleoptera) deposited at the entomological collection of Instituto- Fundación Miguel Lillo, Tucumán, Argentina.

The Carabidae (Insecta: Coleoptera) type species of Entomological Collection of the Entomology Institute housed in the Zoology Area of Miguel Lillo Foundation (FML), Tucumán, Argentina, were examined and listed. This collection is considered one of the most prestigious collections in Argentina and South America. The Carabidae family is represented by 545 species, with ten holotypes, one allotype, 12 cotypes, and 65 paratypes, which correspond to 35 species.

Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T-cell therapy.

Background: We used a proliferating ligand (APRIL) to construct a ligand-based third generation chimeric antigen receptor (CAR) able to target two myeloma antigens, B-cell maturation antigen (BCMA) and transmembrane activator and CAML interactor.

Methods: The APRIL CAR was evaluated in a Phase 1 clinical trial (NCT03287804, AUTO2) in patients with relapsed, refractory multiple myeloma. Eleven patients received 13 doses, the first 15×10 CARs, and subsequent patients received 75,225,600 and 900×10 CARs in a 3+3 escalation design.

Enhancing CAR T-cell Therapy Using Fab-Based Constitutively Heterodimeric Cytokine Receptors.

Adoptive T-cell therapy aims to achieve lasting tumor clearance, requiring enhanced engraftment and survival of the immune cells. Cytokines are paramount modulators of T-cell survival and proliferation. Cytokine receptors signal via ligand-induced dimerization, and this principle has been hijacked utilizing nonnative dimerization domains.

Novel Fas-TNFR chimeras that prevent Fas ligand-mediated kill and signal synergistically to enhance CAR T cell efficacy.

The hostile tumor microenvironment limits the efficacy of adoptive cell therapies. Activation of the Fas death receptor initiates apoptosis and disrupting these receptors could be key to increasing CAR T cell efficacy. We screened a library of Fas-TNFR proteins identifying several novel chimeras that not only prevented Fas ligand-mediated kill, but also enhanced CAR T cell efficacy by signaling synergistically with the CAR.

Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR.

CAR T cells recognizing CD19 effectively treat relapsed and refractory B-ALL and DLBCL. However, CD19 loss is a frequent cause of relapse. Simultaneously targeting a second antigen, CD22, may decrease antigen escape, but is challenging: its density is approximately 10-fold less than CD19, and its large structure may hamper immune synapse formation.

Successful pharmacological intervention at different levels of the complement system in an in vitro complement fixation model for bullous pemphigoid.

Bullous pemphigoid (BP) is characterized by deposition of immunoglobulins and complement along the epidermal basement membrane (BM). In humans, there is a lack of functional studies targeting the complement system (CS). This study investigates activation of all complement pathways in BP skin biopsies.

Genotypic Diversity and Antifungal Susceptibility of Clinical Isolates of Cryptococcus Gattii Species Complex from Argentina.

The aim of this study was to determine the genotypic diversity of 22 Cryptococcus gattii species complex clinical isolates from Argentina and to place these genotypes within the diversity of clinical, veterinary and environmental isolates from Latin America. Mating type and antifungal susceptibility of the isolates were also determined. By URA5-RFLP, nine isolates were identified as molecular type VGI, 10 as VGII, one as VGIII and two as VGIV.

Scedosporium aurantiacum: First isolation in Argentina from a previously healthy patient after traumatic inoculation.

Scedosporium/Lomentospora species are widely distributed in nature. They are generally saprophytes, but can cause opportunistic infections in immunocompromised patients and occasionally in immunocompetent patients that are difficult to treat due to high levels of antifungal resistance. The distribution of Scedosporium/Lomentospora species shows regional differences.

A compact and simple method of achieving differential transgene expression by exploiting translational readthrough.

The development of multicistronic vectors enabling differential transgene expression is a goal of gene therapy and poses a significant engineering challenge. Current approaches rely on the insertion of long regulatory sequences that occupy valuable space in vectors, which have a finite and limited packaging capacity. Here we describe a simple method of achieving differential transgene expression by inserting stop codons and translational readthrough motifs (TRMs) to suppress stop codon termination.