Double-jeopardy: scRNA-seq doublet/multiplet detection using multi-omic profiling.

The computational detection and exclusion of cellular doublets and/or multiplets is a cornerstone for the identification the true biological signals from single-cell RNA sequencing (scRNA-seq) data. Current methods do not sensitively identify both heterotypic and homotypic doublets and/or multiplets. Here, we describe a machine learning approach for doublet/multiplet detection utilizing VDJ-seq and/or CITE-seq data to predict their presence based on transcriptional features associated with identified hybrid droplets. This approach highlights the utility of leveraging multi-omic single-cell information for the generation of high-quality datasets. Our method has high sensitivity and specificity in inflammatory-cell-dominant scRNA-seq samples, thus presenting a powerful approach to ensuring high-quality scRNA-seq data.

Contributions to the American Society of Hematology Meeting From Low- and Middle-Income Countries: An In-Depth Analysis and Call to Action.

PURPOSE: Establishing research capacity in low- and middle-income countries (LMICs) is key for improving the outcomes of patients with hematologic diseases globally. Few studies have analyzed the contributions of LMICs to global hematology. The American Society of Hematology Meeting (ASH) is the largest international academic event where peer-reviewed contributions in our field are presented. METHODS: In this cross-sectional analysis, all abstracts accepted to ASH 2018 selected for a poster or oral presentation were reviewed. Those that had a contributing author from an LMIC were identified. The proportion of LMIC abstracts across categories was analyzed. Country of origin, high-income country participation, the presence of a conflict of interest (COI), and sponsorship were determined. RESULTS: From 4,871 abstracts reviewed, 506 had a contributing author from an LMIC (10.4%), with 277 (54.7%) contributions in partnership with a high-income country. LMIC-independent contributions corresponded to 19 of 1,026 oral abstracts (1.9%) and 209 of 3,845 posters (5.4%). Most abstracts from LMICs were clinical (n = 311; 61.5%) and multicentric in nature (n = 353; 69.8%). COI statements with the pharmaceutical industry were common (n = 214; 42.3%). Collaboration between LMICs was infrequent (n = 33; 6.5%). Upper-middle-income countries had 466 participations (81.5%), in comparison with 96 (16.8%) in low-middle-income and 10 (1.7%) in low-income countries. CONCLUSION: LMICs were responsible for a small fraction of abstracts at ASH18; low-income countries were practically absent. Almost half of accepted works represented a form of international collaboration, with clinical, multicenter studies predominating and COI disclosures a frequent and unexpected feature, reflecting the instrumental nature of LMIC participation and a lack of independent, robust, locally developed hematology research.

The helminth-derived peptide GK-1 induces an anti-tumoral CD8 T cell response associated with downregulation of the PD-1/PD-L1 pathway.

CD8 T cells can kill malignant cells in an antigen-specific manner. However, anti-tumoral responses are usually limited by suppressive factors that curb the effector responses of tumor-infiltrating CD8 T cells. Therapeutic strategies to overcome intra-tumoral T cell suppression, for example immune checkpoint inhibition, have been clinically effective in patients with cancer. Here, we provide data that demonstrates that GK-1, a peptide derived from the parasite Taenia crassiceps, promotes an anti-melanoma CD8 T cell response with heightened effector characteristics that leads to an increased amount of tumor-infiltrating CD44+ IFN-γ-producing CD8 T cells. The response induced by GK-1 was associated with a reduction in the expression of PD-1 and PD-L1 on tumor-infiltrating CD8 and dendritic cells, respectively, effects that led to a dramatic decrease in tumor burden. Our results suggest that the immunomodulatory properties of GK-1 may promote a CD8 T cell response that may be therapeutically useful in the setting of cancer.

Efficacy of three filgrastim-intended copies for hematopoietic stem cell mobilization in healthy adult and pediatric donors in Mexico.

INTRODUCTION: The use of filgrastim biosimilars for healthy adult and pediatric donor mobilization in hematopoietic stem cell transplantation has been met with increased safety and efficacy concerns in contrast to generic small molecule drugs. In Mexico, several filgrastim-intended copies (FIC) have been available and marketed since 2001, while no clinical comparability studies to evaluate their use in this setting have been published and thus are not considered to be true biosimilars. In this study, we report our experience using three different FIC products currently available (Filatil, Dextrifyl, and Biofilgran). METHODS: We retrospectively evaluated 118 related donors of all ages who received any brand 5 µg/kg subcutaneously twice daily for 4 days and were harvested in a single apheresis system on day 5. RESULTS: Donors had a median age of 38 years (range, 1-69). A successful harvest defined as ≥2 × 106 CD34+ cells/kg of recipient weight was achieved in 95.8% of cases, with a median CD34+ cell dose of 9.4 × 106 /kg (range 1-42.8). A single apheresis session was performed in 89.8% of cases. No significant difference in cell yield between each brand was observed. All pediatric donors had a successful harvest with similar results to adult donors. No immediate severe adverse effects were documented in any case. CONCLUSIONS: In conclusion, three FICs available in Mexico were efficacious and without immediate severe adverse effects, resulting in significant cost savings. Evaluation of immunogenicity and establishment of a pharmacovigilance program with the use of FICs is warranted.

Clinical presentation in thrombotic thrombocytopenic purpura: Real-world data from two Mexican institutions.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease that can be fatal if not treated early. We aimed to describe the clinical characteristics of Mexican patients with idiopathic TTP. STUDY DESIGN AND METHODS: We conducted a retrospective study, including all adult patients diagnosed with idiopathic TTP from 2011 to 2017 in two Mexican centers. We further compared our results with the published literature. RESULTS: Twenty patients were included; 70% were female, with a median age of 38.5 years at diagnosis (range 16-63). The median time from onset of symptoms to hospital admission was 1.5 days (range 0-16). Most patients (85%) presented with at least one systemic manifestation at admission (including fever) and 90% had neurological symptoms, most of them major (70%) including loss of consciousness, transient focal abnormalities, headache, and confusion. Only one patient (5%) had the classical pentad at the time of admission. Kidney failure was present in 25% of patients and hemorrhagic symptoms in 60%. Digestive and cardiorespiratory symptoms were less common (45% and 15%, respectively). Median platelet count and lactate dehydrogenase were 10 500/µL and 1319 IU/L, respectively. Eighty percent of patients achieved remission following treatment. Patients admitted within the first 48 hours (after the onset of symptoms) tended to have better overall survival. CONCLUSION: Clinical presentation in Mexican TTP patients is similar to that in other countries. Early admission and a high suspicion for the disease will avoid delays in the initial work-up and initiation of therapy, further improving prognosis.

Soft tissue angiosarcoma of the breast in a patient with Klippel-Trenaunay-Weber syndrome.

Angiosarcomas are neoplasms of blood or lymphatic vessels with aggressive behavior. We report the coexistence of this malignancy within soft tissue of the breast in a 49-year-old woman who was diagnosed with Klippel-Trenaunay-Weber syndrome (KTW-S) during childhood. The patient has no previous history of radiation therapy on the chest and does not have any known risk factor for developing angiosarcoma, except for her congenital disease. To the best of our knowledge, the association between soft tissue angiosarcoma of the breast and KTW-S has never been previously reported.

Los angiosarcomas son neoplasias de los vasos sanguíneos y linfáticos con comportamiento agresivo. Reportamos la coexistencia de esta malignidad dentro del tejido blando de la mama en una mujer de 49 años que fue diagnosticada de síndrome de Klippel-Trenaunay-Weber desde la infancia. La paciente no tiene antecedentes de radioterapia en el tórax ni factores de riesgo conocidos para desarrollar angiosarcoma, a excepción de su enfermedad congénita. A nuestro saber, la asociación entre el angiosarcoma del tejido blando de la mama y el síndrome de Klippel-Trenaunay-Weber no había sido reportada previamente.