Publications by authors named "B-L Silva"

CD70 has emerged as a promising target in acute myeloid leukemia (AML), and we have previously demonstrated the potency of an optimized CD70-targeted ligand-based chimeric antigen receptor (CAR). However, here, we identify in vivo CD70 antigen escape as a limitation of single-antigen targeting. Combination targeting of CD70 and CD33 may overcome AML antigen heterogeneity.

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Background And Objectives: Whether the outcome of patients with spontaneous intracerebral hemorrhage (ICH) differs depending on the type of hospital where they are admitted is uncertain. The objective of this study was to determine influence of hospital type at admission (telestroke center [TSC], primary stroke center [PSC], or comprehensive stroke center [CSC]) on outcome for patients with ICH. We hypothesized that outcomes may be better for patients admitted to a CSC.

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Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs.

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  • PPM1D is a phosphatase frequently activated in cancer, especially in therapy-related myeloid neoplasms, but its role in blood cell formation and tumor growth is not fully understood.
  • Research using conditional mouse models reveals that PPM1D is crucial for hematopoiesis by influencing the fitness and self-renewal of hematopoietic stem cells, and while it grants some resistance to chemotherapy, it's less effective than losing p53.
  • Loss of PPM1D makes leukemias more sensitive to chemotherapy, and inhibiting it may be beneficial across various cancers, suggesting that targeting PPM1D could be a promising new therapy for cancer treatment without major side effects in mice.
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Background And Objectives: Neurologic disorders are common medical conditions. However, even with a higher demand for neurologic care, the capacity to train neurologists is impaired. The fear of neurosciences/neurology by medical students, known as neurophobia, may cause multiple adverse effects in neurologic assistance.

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The complete blood count (CBC) is a highly requested test that is generally restricted to centralized laboratories, which are limited by high cost, being maintenance-demanding, and requiring costly equipment. The Hilab System (HS) is a small, handheld hematological platform that uses microscopy and chromatography techniques, combined with machine learning (ML) and artificial intelligence (AI), to perform a CBC test. This platform uses ML and AI techniques to add higher accuracy and reliability to the results besides allowing for faster reporting.

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Background: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens.

Methods: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy.

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  • The study investigates the effectiveness of venetoclax combined with anti-CD20 antibodies in fit patients with advanced chronic lymphocytic leukemia (CLL), compared to traditional chemoimmunotherapy.
  • In a phase 3 trial with 926 participants, various treatment regimens were compared, emphasizing the primary goals of achieving undetectable minimal residual disease and prolonging progression-free survival.
  • Results showed that venetoclax combinations significantly outperformed chemoimmunotherapy in terms of undetectable minimal residual disease rates and 3-year progression-free survival, especially in the venetoclax-obinutuzumab-ibrutinib group.
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Background: Despite their unique contributions to heart failure (HF) care, home healthcare workers (HHWs) have unmet educational needs and many lack HF caregiving self-efficacy. To address this, we used a community-partnered approach to develop and pilot a HF training course for HHWs.

Methods: We partnered with the Training and Employment Fund, a benefit fund of the largest healthcare union in the United States, to develop a 2-hour virtual HF training course that met HHWs' job-specific needs.

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Background And Objectives: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).

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Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematologic malignancies. Approximately half of patients with refractory large B cell lymphomas achieve durable responses from CD19-targeting CAR-T treatment; however, failure mechanisms are identified in only a fraction of cases. To gain new insights into the basis of clinical response, we performed single-cell transcriptome sequencing of 105 pretreatment and post-treatment peripheral blood mononuclear cell samples, and infusion products collected from 32 individuals with large B cell lymphoma treated with either of two CD19 CAR-T products: axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel).

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  • To address the HIV epidemic and threats like SARS-CoV-2, new vaccine strategies are needed to enhance mucosal immunity, particularly through airway surfaces.
  • The study introduces a method called "albumin hitchhiking," utilizing a modified vaccine combining protein immunogens with an albumin-binding polymer to improve uptake in the nasal mucosa.
  • The results showed that this approach significantly increased immune responses in mice and nonhuman primates, suggesting its potential effectiveness in fighting diseases such as HIV and SARS-CoV-2.
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Background: In the trial of Minocycline in Clinically Isolated Syndrome (MinoCIS), minocycline significantly reduced the risk of conversion to clinically definite multiple sclerosis (CDMS). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are emerging biomarkers in MS, and minocycline modulates matrix metalloproteinases (MMPs).

Objective: To assess the value of blood NfL and GFAP as a biomarker of baseline and future disease activity and its utility to monitor treatment response in minocycline-treated patients with clinically isolated syndrome (CIS).

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Chimeric antigen receptor (CAR) T cell therapy is effective in lymphoid malignancies, but there has been limited data in myeloid cancers. Here, we start with a CD27-based CAR to target CD70 ("native") in acute myeloid leukemia (AML), and we find modest efficacy in vivo, consistent with prior reports. We then use orthogonal approaches to increase binding on both the tumor and CAR-T cell sides of the immune synapse: a pharmacologic approach (azacitidine) to increase antigen density of CD70 in myeloid tumors, and an engineering approach to stabilize binding of the CAR to CD70.

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  • Visceral leishmaniasis patients treated with liposomal amphotericin B (L-AMB) may experience nephrotoxicity, prompting a study to assess renal damage through specific biomarkers.
  • A prospective study with 17 patients analyzed various kidney function tests and biomarkers before and during L-AMB treatment.
  • Findings indicated that while traditional kidney function metrics remained stable, specific inflammatory and urinary biomarkers increased, particularly in patients who developed acute kidney injury, highlighting the need for close monitoring during treatment.
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Mucormycosis is a rare opportunistic fungal infection commonly affecting immunocompromised individuals. There has been a surge in the number of these cases during the second wave of the Coronavirus Disease 2019 (COVID-19) in India. Mucormycosis has been reported to occur concurrently or a few weeks post-recovery from COVID-19.

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  • The study examined the role of lysosomal cathepsins B, L, and D in digestion across three beetle species, focusing on gene expression in the midgut and carcasses.
  • The researchers identified digestive cathepsin genes in Tenebrio molitor and Zabrotes subfasciatus but found no such genes in Dermestes maculatus, highlighting evolutionary differences.
  • Molecular modeling suggested that variations in enzyme structures may be adaptations for digestion, with pollen-feeding acting as a potential driving force for the recruitment of these cathepsins as digestive enzymes in certain beetles.
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Cowpea [ (L.) Walp] is cultivated in tropical and subtropical regions worldwide, but its production is usually limited by boron (B) deficiency, which can be mitigated by applying B foliar spraying. In plants with nutrient mobility, the residual effect of foliar fertilization increases, which might improve its efficiency.

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Background Previous studies suggest that use of artificial intelligence (AI) algorithms as diagnostic aids may improve the quality of skeletal age assessment, though these studies lack evidence from clinical practice. Purpose To compare the accuracy and interpretation time of skeletal age assessment on hand radiograph examinations with and without the use of an AI algorithm as a diagnostic aid. Materials and Methods In this prospective randomized controlled trial, the accuracy of skeletal age assessment on hand radiograph examinations was performed with ( = 792) and without ( = 739) the AI algorithm as a diagnostic aid.

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  • A clinical trial investigated whether therapeutic-dose anticoagulation could improve outcomes for critically ill patients with severe Covid-19 compared to standard thromboprophylaxis.
  • The study found no significant difference in organ support-free days between the two groups, with the anticoagulation group showing a median of 1 day compared to 4 days for the usual-care group.
  • The trial was halted due to a high probability of futility, with similar hospital discharge survival rates and a slightly higher occurrence of major bleeding in the anticoagulation group.
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Background: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.

Methods: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis.

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  • Glycogen Storage Disease 1a (GSD1a) is a rare genetic disorder caused by a deficiency in the enzyme glucose 6-phosphatase (G6Pase-α), leading to severe low blood sugar and liver complications like tumors.
  • Current treatments focus on managing hypoglycemia but do not prevent serious liver issues, and options like enzyme replacement or gene therapy face significant hurdles.
  • Researchers have explored a new treatment using lipid nanoparticles to deliver engineered mRNAs for G6Pase-α, showing promise in a mouse model that mimics the disease, suggesting a potential breakthrough for GSD1a patients.
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Around fifteen thousand fieldworkers annually count breeding birds using standardized protocols in 28 European countries. The observations are collected by using country-specific and standardized protocols, validated, summarized and finally used for the production of continent-wide annual and long-term indices of population size changes of 170 species. Here, we present the database and provide a detailed summary of the methodology used for fieldwork and calculation of the relative population size change estimates.

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This study aimed to investigate the effects of administering photobiomodulation therapy (PBM) with bovine bone matrix on critical size defects in rats. Seventy-two adult male rats (albinus, Wistar), 90 days old, were used. Defect of 5 mm in diameter was made in their calvaria.

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Run-of-river dams are often considered to have lower environmental impacts than storage dams due to their smaller reservoirs and low potential for flow alteration. However, this has been questioned for projects recently built on large rivers around the world. Two of the world's largest run-of-river dams-Santo Antônio and Jirau-were recently constructed on the Madeira River, a major tributary to the Amazon River in Brazil.

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