One-pot acid-catalysed synthesis of bis(1-imidazo[1,5-]pyridyl)arylmethanes and evaluation of cytotoxic activities.

A practical and efficient approach for the acid-catalysed synthesis of bis(1-imidazo[1,5-]pyridyl)arylmethane (BimPy) derivatives has been described. Interestingly, these BimPys showed potential cytotoxicity against various cancer cell lines (SK-LU-1, MCF-7, HepG2).

Factors associated with retention in Quitline counseling for smoking cessation among HIV-positive smokers receiving care at HIV outpatient clinics in Vietnam.

Background: Quitline counseling is an effective method for supporting smoking cessation, offering personalized and accessible assistance. Tobacco use is a significant public health issue among people living with HIV. In Vietnam, over 50% of men living with HIV use tobacco.

Safety and biological outcomes following a phase 1 trial of GD2-specific CAR-T cells in patients with GD2-positive metastatic melanoma and other solid cancers.

Background: Chimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and refractory B-cell malignancies. If CAR-T cell therapy for non-hematological malignancies is to achieve the same stage of clinical development, then iterative early-phase clinical testing can add value to the clinical development process for evaluating CAR-T cell products containing different CAR designs and manufactured under differing conditions.

Methods: We conducted a phase 1 trial of third-generation GD2-specific CAR-T cell therapy, which has previously been tested in neuroblastoma patients.

Depression and associated factors among HIV-positive smokers receiving care at HIV outpatient clinics in Vietnam: a cross-sectional analysis.

Objectives: To assess the prevalence of depressive symptoms and associated factors among people living with HIV (PLWH) who were current cigarette smokers and receiving treatment at HIV outpatient clinics (OPCs) in Vietnam.

Design: A cross-sectional survey of smokers living with HIV.

Setting: The study was carried out in 13 HIV OPCs located in Ha Noi, Vietnam.

GD2-targeting CAR-T cells enhanced by transgenic IL-15 expression are an effective and clinically feasible therapy for glioblastoma.

Background: Aggressive primary brain tumors such as glioblastoma are uniquely challenging to treat. The intracranial location poses barriers to therapy, and the potential for severe toxicity. Effective treatments for primary brain tumors are limited, and 5-year survival rates remain poor.

Management of Frail and Older Homebound Patients With Heart Failure: A Contemporary Virtual Ambulatory Model.

Background: Heart failure (HF) affects many patients who are older and frail, presenting multiple physical barriers to accessing specialty care in a traditional ambulatory clinic model. Here, we present an assisted virtual care model in which a home visiting nurse facilitated video visits with a HF cardiologist to follow homebound, frail, and older patients with HF.

Methods: This is a pragmatic, quasi-experimental, pre-post, single-centre study.

Effects of Chemotherapy Agents on Circulating Leukocyte Populations: Potential Implications for the Success of CAR-T Cell Therapies.

Adoptive T-cell therapy using autologous T cells genetically modified to express cancer-specific chimeric antigen receptors (CAR) has emerged as a novel approach for cancer treatment. CAR-T cell therapy has been approved in several major jurisdictions for treating refractory or relapsed cases of B-cell precursor acute lymphoblastic leukaemia and diffuse large B-cell lymphoma. However, in solid cancer patients, several clinical studies of CAR-T cell therapy have demonstrated minimal therapeutic effects, thus encouraging interest in better integrating CAR-T cells with other treatments such as conventional cytotoxic chemotherapy.

Optimization of manufacturing conditions for chimeric antigen receptor T cells to favor cells with a central memory phenotype.

Background: Chimeric antigen receptor (CAR)-T cells are genetically engineered to recognize tumor-associated antigens and have potent cytolytic activity against tumors. Adoptive therapy with CAR-T cells has been highly successful in B-cell leukemia and lymphoma. However, in solid tumor settings, CAR-T cells face a particularly hostile tumor microenvironment where multiple immune suppressive factors serve to thwart the anti-cancer immune response.

Rapid mitogenic regulation of the mTORC1 inhibitor, DEPTOR, by phosphatidic acid.

The mammalian target of rapamycin complex 1 (mTORC1) is regulated, in part, by the endogenous inhibitor DEPTOR. However, the mechanism of DEPTOR regulation with regard to rapid mTORC1 activation remains unknown. We report that DEPTOR is rapidly and temporarily dissociated from mTORC1 upon mitogenic stimulation, suggesting a mechanism underlying acute mTORC1 activation.

Regulatory T cells dynamically control the primary immune response to foreign antigen.

The population dynamics that enable a small number of regulatory T (T(R)) cells to control the immune responses to foreign Ags by the much larger conventional T cell subset were investigated. During the primary immune response, the expansion and contraction of conventional and T(R) cells occurred in synchrony. Importantly, the relative accumulation of T(R) cells at peak response significantly exceeded that of conventional T cells, reflecting extensive cell division within the T(R) cell pool.

Regulatory T cell development in the absence of functional Foxp3.

Although the development of regulatory T cells (T(reg) cells) in the thymus is defined by expression of the lineage marker Foxp3, the precise function of Foxp3 in T(reg) cell lineage commitment is unknown. Here we examined T(reg) cell development and function in mice with a Foxp3 allele that directs expression of a nonfunctional fusion protein of Foxp3 and enhanced green fluorescent protein (Foxp3DeltaEGFP). Thymocyte development in Foxp3DeltaEGFP male mice and Foxp3DeltaEGFP/+ female mice recapitulated that of wild-type mice.

Long-term memory deficits in Pavlovian fear conditioning in Ca2+/calmodulin kinase kinase alpha-deficient mice.

Signaling by the Ca(2+)/calmodulin kinase (CaMK) cascade has been implicated in neuronal gene transcription, synaptic plasticity, and long-term memory consolidation. The CaM kinase kinase alpha (CaMKKalpha) isoform is an upstream component of the CaMK cascade whose function in different behavioral and learning and memory paradigms was analyzed by targeted gene disruption in mice. CaMKKalpha mutants exhibited normal long-term spatial memory formation and cued fear conditioning but showed deficits in context fear during both conditioning and long-term follow-up testing.

Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice.

Background: Regulatory T cells have been proposed to play an important role in regulating allergic inflammation. The transcription factor Foxp3 is a master switch gene that controls the development and function of natural and adaptive CD4(+)CD25(+) regulatory T (T(R)) cells. In human subjects loss-of-function Foxp3 mutations trigger lymphoproliferation, autoimmunity, and intense allergic inflammation in a disease termed immune dysregulation polyendocrinopathy enteropathy-X-linked syndrome.

Critical function of the CD40 pathway in parvovirus B19 infection revealed by a hypomorphic CD40 ligand mutation.

Parvovirus B19-induced chronic anemia has been associated with failure to mount an effective neutralizing antibody response. We describe an adolescent male with a 13-year history of parvovirus B19-induced anemia as the primary manifestation of X-linked hyper IgM immunodeficiency (XHIM). This patient, whose serum IgG concentration was at the low end of the normal range and who mounted IgG antibody responses to T cell-dependent antigens, suffered from a nonsense mutation (R11 --> X) in the CD40 ligand (CD40L) gene.