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Natural killer (NK) cells play a crucial role in the immune system's response against cancer. However, the challenge of obtaining the required quantity of NK cells for effective therapeutic response necessitates the development of strategies for their ex vivo expansion. This study aimed to develop a novel feeder cell line, K562.Clone1, capable of promoting the ex vivo expansion of NK cells while preserving their cytotoxic potential. he K562 leukemic cell line was transduced with mbIL-21 and 4-1BBL proteins to generate K562.Clone1 cells. NK cells were then co-cultured with these feeder cells, and their expansion rate was monitored over 14 days. The cytotoxic potential of the expanded NK cells was evaluated against acute myeloid leukemia blasts and tumor cell lines of leukemia and glial origin. Statistical analysis was performed to determine the significance of the results. The K562.Clone1 co-cultured with peripheral NK showed a significant increase in cell count, with an approximate 94-fold expansion over 14 days. Expanded NK cells demonstrated cytotoxicity against the tested tumor cell lines, indicating preservation of their cytotoxic characteristics. Additionally, the CD56, CD16, inhibitory KIRs, and activation receptors were conserved and present in a well-balanced manner. The study successfully developed a feeder cell line, K562.Clone1, that effectively promotes the expansion of NK cells ex vivo while maintaining their cytotoxic potential. This development could significantly contribute to the advancement of NK cell therapy, especially in Brazil.

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Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-acute sequela of SARS-CoV-2 infection. The highly diverse clinical features of MIS-C necessities characterizing its features by subphenotypes for improved recognition and treatment. However, jointly identifying subphenotypes in multi-site settings can be challenging. We propose a distributed multi-site latent class analysis (dMLCA) approach to jointly learn MIS-C subphenotypes using data across multiple institutions. Methods: We used data from the electronic health records (EHR) systems across nine U.S. children's hospitals. Among the 3,549,894 patients, we extracted 864 patients < 21 years of age who had received a diagnosis of MIS-C during an inpatient stay or up to one day before admission. Using MIS-C conditions, laboratory results, and procedure information as input features for the patients, we applied our dMLCA algorithm and identified three MIS-C subphenotypes. As validation, we characterized and compared more granular features across subphenotypes. To evaluate the specificity of the identified subphenotypes, we further compared them with the general subphenotypes identified in the COVID-19 infected patients. Findings: Subphenotype 1 (46.1%) represents patients with a mild manifestation of MIS-C not requiring intensive care, with minimal cardiac involvement. Subphenotype 2 (25.3%) is associated with a high risk of shock, cardiac and renal involvement, and an intermediate risk of respiratory symptoms. Subphenotype 3 (28.6%) represents patients requiring intensive care, with a high risk of shock and cardiac involvement, accompanied by a high risk of >4 organ system being impacted. Importantly, for hospital-specific clinical decision-making, our algorithm also revealed a substantial heterogeneity in relative proportions of these three subtypes across hospitals. Properly accounting for such heterogeneity can lead to accurate characterization of the subphenotypes at the patient-level. Interpretation: Our identified three MIS-C subphenotypes have profound implications for personalized treatment strategies, potentially influencing clinical outcomes. Further, the proposed algorithm facilitates federated subphenotyping while accounting for the heterogeneity across hospitals.

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Waste collection services are uncommon in rural areas of low-resource countries, causing waste accumulation and subsequent dumping and burning of garbage. Air pollution from household garbage burning, including plastics, has been observed in Jalapa, Guatemala in addition to household air pollution (HAP) from cooking. Adolescent girls often help with these cooking and household tasks, but little is known about their exposures. We characterized 24-h exposures to HAP and household garbage burning in adolescent girls by measuring fine particulate matter (PM2.5), black carbon (BC), urinary biomarkers of polycyclic aromatic hydrocarbons (PAHs), bisphenol A (BPA), and phthalates. We recruited 60 girls between 13 and 17 years of age who helped with cooking activities and lived with participants of the Household Air Pollution Intervention Network (HAPIN) trial. We recruited n = 30 girls each from the control (wood-burning stove) and intervention (liquefied petroleum gas stove) arms. We also measured real-time kitchen concentrations of BC in 20 homes (33%). PM2.5 and BC were measured in n = 21 control and n = 20 intervention participants. Median concentrations of personal PM2.5 and BC and kitchen BC were lower (p < 0.05) in the intervention arm by 87%, 80%, and 85%, respectively. PAH metabolite concentrations were lower (p < 0.001) for all nine metabolites in intervention (n = 26) compared to control participants (n = 29). Urinary BPA concentrations were 66% higher in participants who reported using cosmetics (p = 0.02), and phthalate concentrations were 63% higher in participants who had reported using hair products during the sample period (p = 0.05). Our results suggest that gas stoves can reduce HAP exposures among adolescents who are not primary cooks at home. Biomarkers of plastic exposure were not associated with intervention status, but some were elevated compared to age- and sex-matched participants of the National Health and Nutrition Examination Survey (NHANES).

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Systems modeling offers a valuable tool to support strategic decision-making for complex problems because it considers the causal inter-relationships that drive population health outcomes. This tool can be used to simulate policies and initiatives to determine which combinations are likely to deliver the greatest impacts and returns on investment. Systems modeling benefits from participatory approaches where a multidisciplinary stakeholder group actively engages in mapping and contextualizing causal mechanisms driving complex system behaviors. Such approaches can have significant advantages, including that they may improve connection and coordination of the network of stakeholders operating across the system; however, these are often observed in practice as colloquial anecdotes and seldom formally assessed. We used a basic social network analysis to explore the impact on the configuration of the network of mental health providers, decision-makers, and other stakeholders in Bogota, Colombia active in a series of three workshops throughout 2021 and 2022. Overall, our analysis suggests that the participatory process of the systems dynamics exercise impacts the social network's structure, relationships, and dynamics.

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Using an electronic health record-based algorithm, we identified children with Coronavirus disease 2019 (COVID-19) based exclusively on serologic testing between March 2020 and April 2022. Compared with the 131 537 polymerase chain reaction-positive children, the 2714 serology-positive children were more likely to be inpatients (24% vs 2%), to have a chronic condition (37% vs 24%), and to have a diagnosis of multisystem inflammatory syndrome in children (23% vs <1%). Identification of children who could have been asymptomatic or paucisymptomatic and not tested is critical to define the burden of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection in children.

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INTRODUCTION: The second best conduit for coronary artery bypass grafting is uncertain. The objective of this study is to determine the second best conduit according to graft patency results from randomized controlled trials using a network meta-analysis. METHODS: A systematic literature search was conducted for randomized controlled trials comparing the angiographic patency rate of the no-touch saphenous vein (NT-SV), the radial artery (RA), the right internal thoracic artery (RITA), and the gastroepiploic artery (GEA) in reference to the conventionally harvested saphenous vein (CON-SV). The primary outcome was graft occlusion, and the secondary outcome was all-cause mortality. RESULTS: A total of 859 studies were retrieved, of which 18 were included. A total of 6,543 patients and 8,272 grafts were analyzed. The weighted mean angiographic follow-up time was 3.5 years. Compared with CON-SV, RA (incidence rate ratio [IRR] 0.56; 95% confidence interval [CI], 0.43-0.74) and NT-SV (IRR 0.56; 95% CI, 0.44-0.70) demonstrated lower graft occlusion. NT-SV and RA were ranked as the best conduits (rank score for NT-SV 0.88 vs. 0.87 for RA, 0.29 for GEA, 0.27 for CON-SV, and 0.20 for RITA). There was no significant difference in late mortality between different conduit types. CONCLUSION: RA and NT-SV are associated with significantly lower graft occlusion rates and are comparably ranked as the best conduit for patency.

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Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for a variety of hematological diseases. Allogenic HSCT requires hematopoietic stem cells (HSCs) from matched donors and comes with cytotoxicity and mortality. Recent advances in genome modification of HSCs have demonstrated the possibility of using autologous HSCT-based gene therapy to alleviate hematologic symptoms in monogenic diseases, such as the inherited bone marrow failure (BMF) syndrome Fanconi anemia (FA). However, for FA and other BMF syndromes, insufficient HSC numbers with functional defects results in delayed hematopoietic recovery and increased risk of graft failure. We and others previously identified the adaptor protein LNK (SH2B3) as a critical negative regulator of murine HSC homeostasis. However, whether LNK controls human HSCs has not been studied. Here, we demonstrate that depletion of LNK via lentiviral expression of miR30-based short hairpin RNAs results in robust expansion of transplantable human HSCs that provided balanced multilineage reconstitution in primary and secondary mouse recipients. Importantly, LNK depletion enhances cytokine-mediated JAK/STAT activation in CD34+ hematopoietic stem and progenitor cells (HSPCs). Moreover, we demonstrate that LNK depletion expands primary HSPCs associated with FA. In xenotransplant, engraftment of FANCD2-depleted FA-like HSCs was markedly improved by LNK inhibition. Finally, targeting LNK in primary bone marrow HSPCs from FA patients enhanced their colony forming potential in vitro. Together, these results demonstrate the potential of targeting LNK to expand HSCs to improve HSCT and HSCT-based gene therapy.

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ABSTRACT Introduction: The second best conduit for coronary artery bypass grafting is uncertain. The objective of this study is to determine the second best conduit according to graft patency results from randomized controlled trials using a network meta-analysis. Methods: A systematic literature search was conducted for randomized controlled trials comparing the angiographic patency rate of the no-touch saphenous vein (NT-SV), the radial artery (RA), the right internal thoracic artery (RITA), and the gastroepiploic artery (GEA) in reference to the conventionally harvested saphenous vein (CON-SV). The primary outcome was graft occlusion, and the secondary outcome was all-cause mortality. Results: A total of 859 studies were retrieved, of which 18 were included. A total of 6,543 patients and 8,272 grafts were analyzed. The weighted mean angiographic follow-up time was 3.5 years. Compared with CON-SV, RA (incidence rate ratio [IRR] 0.56; 95% confidence interval [CI], 0.43-0.74) and NT-SV (IRR 0.56; 95% CI, 0.44-0.70) demonstrated lower graft occlusion. NT-SV and RA were ranked as the best conduits (rank score for NT-SV 0.88 vs. 0.87 for RA, 0.29 for GEA, 0.27 for CON-SV, and 0.20 for RITA). There was no significant difference in late mortality between different conduit types. Conclusion: RA and NT-SV are associated with significantly lower graft occlusion rates and are comparably ranked as the best conduit for patency.

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PURPOSE: Type 2 diabetes mellitus (T2DM) is an urgent public health problem and disproportionately affects Mexican Americans. The gut microbiome contributes to the pathophysiology of diabetes; however, no studies have examined this association in Mexican-Americans. The objective of this study was to compare gut microbiome composition between Mexican-Americans with and without T2DM. METHODS: This was a cross-sectional study of volunteers from San Antonio, TX. Subjects were 18 years or older and self-identified as Mexican American. Subjects were grouped by prior T2DM diagnosis. Eligible subjects attended a clinic visit to provide demographic and medical information. Thereafter, subjects recorded their dietary intake for three days and collected a stool sample on the fourth day. Stool 16s rRNA sequences were classified into operational taxonomic units (OTUs) via the mothur bayesian classifier and referenced to the Greengenes database. Shannon diversity and bacterial taxa relative abundance were compared between groups using the Wilcoxon rank sum test. Beta diversity was estimated using Bray-Curtis indices and compared between groups using PERMANOVA. RESULTS: Thirty-seven subjects were included, 14 (38%) with diabetes and 23 (62%) without diabetes. Groups were well-matched by body mass index and comorbid conditions. Shannon diversity was not significantly different between those with and without T2DM (3.26 vs. 3.31; p = 0.341). Beta diversity was not significantly associated with T2DM diagnosis (p = 0.201). The relative abundance of the most common bacterial phyla and families did not significantly differ between groups; however, 16 OTUs were significantly different between groups. CONCLUSIONS: Although alpha diversity was not significantly different between diabetic and non-diabetic Mexican Americans, the abundance of certain bacterial taxa were significantly different between groups.

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Kidney paired exchange (KPE) constitutes 12% of all living donor kidney transplantations (LDKTs) in the United States. The success of KPE programs has prompted many in the liver transplant community to consider the possibility of liver paired exchange (LPE). Though the idea seems promising, the application has been limited to a handful of centers in Asia. In this article, we consider the indications, logistical issues, and ethics for establishing a LPE program in the United States with reference to the principles and advances developed from experience with KPE. Liver Transplantation 24 677-686 2018 AASLD.

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