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The prognosis of patients diagnosed with relapsed or refractory (R/R) T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has consistently been unsatisfactory, with limited treatment options. As reports, the CAG regimen can serve as a salvage treatment for R/R T-ALL/LBL, but there remains a subset of patients who do not benefit from it. Recent studies have indicated that daratumumab (Dara) and venetoclax (Ven) may offer promising therapeutic benefits for T-ALL/LBL. In light of these findings, we conducted a safety and efficacy evaluation of the enhanced treatment regimen, combining Dara and Ven with aclarubicin, cytarabine, granulocyte colony-stimulating factor, and etoposide (CAGE), in patients suffering from R/R T-ALL/LBL. The participants in this phase I trial were patients with R/R T-ALL/LBL who fail to standard treatment regimens. During each 28-day cycle, the patients were treated by Dara, Ven, cytarabine, aclarubicin, granulocyte colony-stimulating factor, etoposide. The primary endpoint of this study was the rate of remission. This report presents the prospective outcomes of 21 patients who received the salvage therapy of Dara and Ven combined with the CAGE regimen (Dara + Ven + CAGE). The objective remission rate (ORR) was determined to be 57.1%, while the complete remission (CR) rate was 47.6%. Notably, patients with the early T-cell precursor (ETP) subtype exhibited a significantly higher remission rate in the bone marrow compared to non-ETP patients (100% vs. 44.4%, p = 0.044). The Dara + Ven + CAGE regimen demonstrated a favorable remission rate in patients with R/R T-ALL/LBL. Moreover, the treatment was well-tolerated. [ABSTRACT FROM AUTHOR]

Psoriasis is characterized by inflammation and hyperproliferation of epidermal keratinocytes. Cycloastragenol (CAG) is an active molecule of Astragalus membranaceus that potentially plays a repressive role in psoriasis. Activated cell autophagy is an effective pathway for alleviating psoriasis progression. Thus, we investigated the role of CAG in the proliferation and autophagy of interleukin (IL)-22-stimulated keratinocytes. A psoriasis model was established by stimulating HaCaT cells with IL-22. Gene or protein expression levels were measured by qRT-PCR or western blot. Autophagy flux was observed with mRFP-GFP-LC3 adenovirus transfection assay under confocal microscopy. Stanniocalcin-1 (STC1) secretion levels were determined using ELISA kits. The apoptosis rate was assessed using flow cytometry. Interactions between miR-145 and STC1 or STC1 and Notch1 were validated by luciferase reporter gene assays, RIP, and Co-IP assays. CAG repressed cell proliferation and promoted apoptosis and autophagy in IL-22-stimulated HaCaT cells. Additionally, CAG promoted autophagy by enhancing miR-145. STC1 silencing ameliorated autophagy repression in IL-22-treated HaCaT cells. Moreover, miR-145 negatively regulated STC1, and STC1 was found to activate Notch1. Lastly, STC1 overexpression reversed CAG-promoted autophagy. CAG alleviated keratinocyte hyperproliferation through autophagy enhancement via regulating the miR-145/STC1/Notch1 axis in psoriasis. [ABSTRACT FROM AUTHOR]

BackgroundAchieving the 95–95–95 targets require an efficient and innovative person-centered approach, specifically community-based differentiated service delivery (DSD), to improve access to human immunodeficiency virus (HIV) services and reduce burdens on the health system. Therefore, this study aimed to assess the uptake of community-based DSD models and associated factors among people living with HIV (PLHIV).MethodsA multicenter cross-sectional study was conducted among PLHIV in public health facilities in South Ethiopia. Data were collected and entered into EpiData version 3.1 before being exported to Stata version 14 for further analysis. In the bivariable logistic regression analysis, variables with a p-value of ≤0.25 were included in the multivariable logistic regression analysis. A p-value of

Genetic mutations in the androgen receptor (AR) gene have been identified as the cause of androgen insensitivity syndrome. These mutations are linked to inconsistent development of the Wolffian duct and may result in conditions such as micropenis, hypospadias, and cryptorchidism. The androgen receptor has two polymorphic sites located in exon 1, which consists of varying amounts of CAG and GGN repeats. These repetitions lead to the formation of polyglutamine and polyglycine stretches of varied lengths. Increased CAG repeats lead to a decrease in androgen receptor transcriptional activity, but the impact of GGN triplets is less well understood. This research examined the CAG and GGN repeat lengths in males who had a past medical record of cryptorchidism. Prospective and retrospective observational studies from PubMed, Science Direct, and Embase were systematically searched up to 15th November 2020. Primary outcomes were analyzed using a fixed or random effect model regarding its heterogeneity and continued with multilevel modeling of each polymorphism and ethnicity. CAG and GGN repeat polymorphism was found to be significantly different compared to control in contributing to cryptorchidism (CAG: 0.55 [CI 95%=0.19-0.91]; p-value=0.003 and GGN 0.90 [CI95%=0.65-1.15]; p value

It is essential that communities at risk from TB are involved in TB research. Community advisory groups (CAGs) are one mechanism for involving communities in research and creating platforms for discussions between researchers and community members. We organised a CAG meeting with community members and people with lived experience in Ho Chi Minh City, Vietnam, to explore the community’s knowledge about TB and their perspectives on different diagnostic tests in Vietnam, a low-middle-income country with a high TB burden. Researchers shared basic information and addressed questions about TB. CAG members commented on preference of TB screening tests, and suggested that chest X-rays and blood tests were more acceptable than sputum tests because of the difficulty in sputum expectoration. In addition, clinical studies that required fewer visits to the hospitals would be preferred, even if this meant a greater reliance on blood sampling.

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a highly aggressive subtype of T-ALL. No standard chemotherapy regimen exists for patients with recurrent/refractory (R/R) ETP-ALL; in these patients, the primary goal of salvage therapy is to achieve remission as a foundation for consolidation and intensification treatments. This study reports cases of two patients with R/R ETP-ALL who underwent salvage therapy of venetoclax combined with the CAG regimen and achieved complete remission in the bone marrow. Flow cytometry results were negative for minimal residual disease. Both patients were bridged to allogeneic hematopoietic stem cell transplantation (HSCT) and in complete remission over a 3-year follow-up period. These cases show that the use of venetoclax combined with the CAG regimen may offer patients with R/R ETP-ALL an opportunity for allogeneic HSCT.

Background: Achieving the 95-95-95 targets require an efficient and innovative person-centered approach, specifically community-based differentiated service delivery (DSD), to improve access to human immunodeficiency virus (HIV) services and reduce burdens on the health system. Therefore, this study aimed to assess the uptake of community-based DSD models and associated factors among people living with HIV (PLHIV)., Methods: A multicenter cross-sectional study was conducted among PLHIV in public health facilities in South Ethiopia. Data were collected and entered into EpiData version 3.1 before being exported to Stata version 14 for further analysis. In the bivariable logistic regression analysis, variables with a p -value of ≤0.25 were included in the multivariable logistic regression analysis. A p -value of <0.05 was used to identify statistically significant factors., Results: Among 381 stable PLHIV, 55.91% were women. The median age (interquartile range) was 40 years (27-53). The uptake of community-based DSD models was 19.16%. Residence and disclosure were the two independent factors significantly associated with the uptake of community-based DSD models., Conclusion: One out of five stable PLHIV on antiretroviral therapy uptake the community-based DSD models. Improvement in uptake is needed in Ethiopia's resource-limited healthcare system to better achieve the 95-95-95 targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Merid, Toma, Anbesie and Guyo.)

It is essential that communities at risk from TB are involved in TB research. Community advisory groups (CAGs) are one mechanism for involving communities in research and creating platforms for discussions between researchers and community members. We organised a CAG meeting with community members and people with lived experience in Ho Chi Minh City, Vietnam, to explore the community's knowledge about TB and their perspectives on different diagnostic tests in Vietnam, a low-middle-income country with a high TB burden. Researchers shared basic information and addressed questions about TB. CAG members commented on preference of TB screening tests, and suggested that chest X-rays and blood tests were more acceptable than sputum tests because of the difficulty in sputum expectoration. In addition, clinical studies that required fewer visits to the hospitals would be preferred, even if this meant a greater reliance on blood sampling., Competing Interests: Conflicts of interest: none declared., (© 2024 The Authors.)