CD33-CD123 IF-THEN Gating Reduces Toxicity while Enhancing the Specificity and Memory Phenotype of AML-Targeting CAR-T Cells.

Our study demonstrates the use of "IF-THEN" SynNotch-gated CAR-T cells targeting CD33 and CD123 in AML reduces off-tumor toxicity. This strategy enhances T-cell phenotype, improves expansion, preserves HSPCs, and mitigates cytokine release syndrome-addressing critical limitations of existing AML CAR-T therapies.

COVID-19 vaccinated children, adolescents, and young adults with acute lymphoblastic leukemia show spike reactive antibodies and multifunctional T-cells.

Little is known about the efficacy of COVID-19 vaccines during acute lymphoblastic leukemia therapy (ALL); data for COVID-19 vaccine immune responses in pediatric leukemia remain sparse. We conducted a single center study of patients aged 5-25 years undergoing ALL chemotherapy who received COVID-19 vaccination. Twenty-one patients were enrolled; efficacy was evaluable in 20.

Ready, set, co(produce): a co-operative inquiry into co-producing research to explore adolescent health and wellbeing in the Born in Bradford Age of Wonder project.

Background: Co-production of research with communities and stakeholders is recognised as best practice, but despite this, transparent reporting and reflective accounts on co-producing research is lacking. Born in Bradford Age of Wonder (AoW) is a large longitudinal health research project, following the health trajectories of up to 30,000 young people across the Bradford district; moreover, AoW has been entirely co-produced with teachers, parents, and young people. This paper describes the co-production of the Born in Bradford Age of Wonder (AoW) project and shares general reflections on co-production from peer researchers involved in co-producing AoW.

Study of neoadjuvant chemotherapy in advanced malignant ovarian germ cell tumors at a tertiary center in western India.

Objective: To study clinical characters and outcomes in patients of malignant ovarian germ cell tumor (MOGCT) undergoing surgery following neoadjuvant chemotherapy (NACT).

Methods: Retrospective study of patients undergoing surgery following NACT for MOGCT at our institute. Platinum based chemotherapy was given in all patients in NACT.

COVID-19 outcomes in children, adolescents and young adults with cancer.

Pediatric oncology patients are at risk for poor outcomes with respiratory viral infections. Outcome data for COVID-19 in children and young adults with cancer are needed; data are sparse for obese/overweight and adolescent and young adult subgroups. We conducted a single center cohort study of COVID-19 outcomes in patients younger than 25 years with cancer.

Preclinical Evaluation of a Novel Dual Targeting PI3Kδ/BRD4 Inhibitor, SF2535, in B-Cell Acute Lymphoblastic Leukemia.

The PI3K/Akt pathway-and in particular PI3Kδ-is known for its role in drug resistant B-cell acute lymphoblastic leukemia (B-ALL) and it is often upregulated in refractory or relapsed B-ALL. Myc proteins are transcription factors responsible for transcribing pro-proliferative genes and c-Myc is often overexpressed in cancers. The chromatin regulator BRD4 is required for expression of c-Myc in hematologic malignancies including B-ALL.

The Metabolic Landscape of Thymic T Cell Development and .

Although metabolic pathways have been shown to control differentiation and activation in peripheral T cells, metabolic studies on thymic T cell development are still lacking, especially in human tissue. In this study, we use transcriptomics and extracellular flux analyses to investigate the metabolic profiles of primary thymic and -derived mouse and human thymocytes. Core metabolic pathways, specifically glycolysis and oxidative phosphorylation, undergo dramatic changes between the double-negative (DN), double-positive (DP), and mature single-positive (SP) stages in murine and human thymus.

Role of ultrasound-guided decompression in management of mucoid degeneration of the anterior cruciate ligament.

Objective: To assess the effectiveness of ultrasound-guided decompression in managing symptomatic mucoid degeneration of the anterior cruciate ligament (ACL).

Materials And Methods: Retrospective analysis of 55 patients who underwent ultrasound-guided ACL mucoid degeneration decompression between July 2013 and August 2019. Subjective satisfaction scores were gathered immediately post-procedure for all 55 patients; follow-up satisfaction scores (scale of 0-10, 10 being excellent) were gathered telephonically for 46 patients (83.

Human papillomavirus: footprints in the population of western India.

Objectives: Cancer is a multi-factorial disease, with various intrinsic and environmental factors contributing to its occurrence. Human papillomavirus (HPV) has been associated with the occurrence of many cancers. India severely suffers from 3 HPV-associated cancers (cervical cancer, oral cancer, and oropharyngeal cancer).

Processing Human Thymic Tissue for Single Cell RNA-Seq.

Single cell RNA sequencing of human thymic cells is dependent on isolation of highly pure and viable cell populations. This protocol describes the isolation of CD34 progenitor and more differentiated CD34 fractions from post-natal thymic tissue to study thymopoiesis. CD34 cells represent <1% of thymic cells, so this protocol uses magnetic- followed by fluorescence-activated cell separation to isolate highly enriched CD34 cells.

Single-Cell RNA-Seq Mapping of Human Thymopoiesis Reveals Lineage Specification Trajectories and a Commitment Spectrum in T Cell Development.

The challenges in recapitulating in vivo human T cell development in laboratory models have posed a barrier to understanding human thymopoiesis. Here, we used single-cell RNA sequencing (sRNA-seq) to interrogate the rare CD34 progenitor and the more differentiated CD34 fractions in the human postnatal thymus. CD34 thymic progenitors were comprised of a spectrum of specification and commitment states characterized by multilineage priming followed by gradual T cell commitment.

Female genital tract melanoma: Analysis from a regional cancer institute.

Objective: Malignant melanoma of the genital tract comprises 3% of all melanomas afflicting females. They are characterized by poor prognosis with 5-year survival of 0-25% and high incidence for distant metastasis. This study was performed to assess various clinical features, treatment options, and thre management of genital melanomas.

Integrin α6 mediates the drug resistance of acute lymphoblastic B-cell leukemia.

Resistance to multimodal chemotherapy continues to limit the prognosis of acute lymphoblastic leukemia (ALL). This occurs in part through a process called adhesion-mediated drug resistance, which depends on ALL cell adhesion to the stroma through adhesion molecules, including integrins. Integrin α6 has been implicated in minimal residual disease in ALL and in the migration of ALL cells to the central nervous system.

Prognostic value of lymph node ratio in surgically treated cases of vulvar cancer: a tertiary care centre experience.

Objective: This study aimed to study the patterns of recurrence in surgically treated cases of vulvar cancer (VC) and determine the factors associated with recurrence, with a special emphasis on lymph node ratio (LNR).

Methods: This retrospective study examined VC patients primarily treated with surgery at our institute from January 2005 to December 2015. Demographic data, clinical characteristics, surgicohistopathological data, adjuvant treatment, follow up, and recurrence site and treatment were studied.

Retrospective Analysis of 32 Cases of Ovarian Granulosa Cell Tumours.

Introduction: Granulosa cell tumour (GCT) comprises 2-5% of ovarian malignancies. They are hormonally active tumours and may present with menstrual complaints, abdominal distension or infertility. Prognosis is generally favourable because of the early stage at diagnosis and less aggressive behaviour.

The PI3Kδ Inhibitor Idelalisib Inhibits Homing in an in Vitro and in Vivo Model of B ALL.

The quest continues for targeted therapies to reduce the morbidity of chemotherapy and to improve the response of resistant leukemia. Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stromal cells triggers intracellular signals that promote cell-adhesion-mediated drug resistance (CAM-DR). Idelalisib, an U.

Association of clinical trial enrollment and survival using contemporary therapy for pediatric acute lymphoblastic leukemia.

While early studies reported superior survival for cancer patients enrolled on clinical trials, recent findings are inconclusive. We investigated the association between enrollment on contemporary trials and event-free survival (EFS) in pediatric B-cell acute lymphoblastic leukemia (B-ALL). In a retrospective cohort of 274 children (1-21 years) treated for B-ALL from 2008 to 2015, 55.

The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation.

The initial stages of T-cell differentiation are characterized by a progressive commitment to the T-cell lineage, a process that involves the loss of alternative (myelo-erythroid, NK, B) lineage potentials. Aberrant differentiation during these stages can result in T-cell acute lymphoblastic leukemia (T-ALL). However, the mechanisms regulating the initial stages of human T-cell differentiation are obscure.