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Conventional combinatorial anticancer therapy has shown promising outcomes; still, a significant interest in developing new methods to reinforce and possibly merge chemotherapy and immunotherapy persists. Here, a new one‐step method that immediately modifies immune cells into a targeted form of chemoimmunotherapy through spontaneous and rapid incorporation of hydrophobized antibody–drug conjugates (ADCs) on the surface of immune cells is presented. Therapeutic objectives of this approach include targeted delivery of a potent chemotherapeutic agent to avoid adverse effects, enhancing the mobilization of infused immune cells toward tumor sites, and preserving the intense cytotoxic activities of immune cells against tumor cells. The embedding of hydrophobized ADCs on the immune cell membrane using the strategy in this study provides noninvasive, nontoxic, and homogenous modifications that transiently arm immune cells with highly potent cytotoxic drugs targeted toward cancer cells. The resulting surface‐engineered immune cells with ADCs significantly suppress the tumor growth and drive the eradication of target cancer cells through combinatorial anticancer effects. This novel strategy allows convenient and timely preparation of advanced chemoimmunotherapy on a single immune cell to treat various types of cancer. Advanced natural killer (NK) cells, instantaneously prepared using a one‐step method, are surface‐engineered with antibody–drug conjugates (ADCs). Combining chemotherapy and immunotherapy in a single cell, these specialized NK cells can target specific tumor cells through antigen recognition, deliver potent chemotherapeutic agents, and destroy tumor cells. Surface engineering of NK cells with ADCs may become an “off‐the‐shelf” reagent for various types of cancer.

Challenges of health systems in Latin America and the Caribbean include accessibility, inequity, segmentation, and poverty. These challenges are similar in different countries of the region and transcend national borders. The increasing digital transformation of health care holds promise of more precise interventions, improved health outcomes, increased efficiency, and ultimately reduced health-care costs. In Latin America and the Caribbean, the adoption of digital health tools is in early stages and the quality of cancer registries, electronic health records, and structured databases are problematic. Cancer research and innovation in the region are limited due to inadequate academic resources and translational research is almost fully dependent on public funding. Regulatory complexity and extended timelines jeopardise the potential improvement in participation in international studies. Emerging technologies, artificial intelligence, big data, and cancer research represent an opportunity to address the health-care challenges in Latin America and the Caribbean collectively, by optimising national capacities, sharing and comparing best practices, and transferring scientific and technical capabilities.

Experiments suggest that biodiversity enhances the ability of ecosystems to maintain multiple functions, such as carbon storage, productivity, and the buildup of nutrient pools (multifunctionality). However, the relationship between biodiversity and multifunctionality has never been assessed globally in natural ecosystems. We report here on a global empirical study relating plant species richness and abiotic factors to multifunctionality in drylands, which collectively cover 41% of Earth's land surface and support over 38% of the human population. Multifunctionality was positively and significantly related to species richness. The best-fitting models accounted for over 55% of the variation in multifunctionality and always included species richness as a predictor variable. Our results suggest that the preservation of plant biodiversity is crucial to buffer negative effects of climate change and desertification in drylands.

Background The application of advanced imaging in pediatric research trials introduces the challenge of how to effectively handle and communicate incidental and reportable findings. This challenge is amplified in underserved populations that experience disparities in access to healthcare as recommendations for follow-up care may be difficult to coordinate. Therefore, the purpose of the present report is to describe the process for identifying and communicating findings from a research MRI to low-income Latino children and families. Methods Latino adolescents ( n  = 86) aged 12–16 years old with obesity and prediabetes underwent a research MRI (3 Tesla Philips Ingenia®) as part of a randomized controlled diabetes prevention trial. The research MRIs were performed at baseline and 6 months to assess changes in whole-abdominal fat distribution and organ fat in response to the intervention. An institutional pathway was developed for identifying and reporting findings to participants and families. The pathway was developed through a collaborative process with hospital administration, research compliance, radiology, and the research team. All research images were reviewed by a board-certified pediatric radiologist who conveyed findings to the study pediatrician for determination of clinical actionability and reportability to children and families. Pediatric sub-specialists were consulted as necessary and a primary care practitioner (PCP) from a free community health clinic agreed to receive referrals for uninsured participants. Results A total of 139 images (86 pre- and 53 post-intervention) were reviewed with 31 findings identified and 23 deemed clinically actionable and reportable. The only reportable finding was severely elevated liver fat (> 10%, n  = 14) with the most common and concerning incidental findings being horseshoe kidney (n = 1) and lung lesion (n = 1). The remainder ( n  = 7) were less serious. Of youth with a reportable or incidental finding, 18 had a PCP but only 7 scheduled a follow-up appointment. Seven participants without a PCP were referred to a safety-net clinic for follow-up. Conclusions With the increased utilization of high-resolution imaging in pediatric research, additional standardization is needed on what, when, and how to return incidental and reportable findings to participants, particularly among historically underrepresented populations that may be underserved in the community. Trial registration Preventing Diabetes in Latino Youth, NCT02615353

Soil samples collected from 224 dryland sites around the world show that aridity affects the concentration of organic carbon and total nitrogen differently from the concentration of inorganic phosphorus, suggesting that any predicted increase in aridity with climate change could uncouple the carbon, nitrogen and phosphorus cycles in drylands and negatively affect the services provided by these ecosystems. Aridity threatens nutrient balance in dry ecosystems It is thought likely that climatic change, such as the increased aridity predicted for many drylands, could disrupt the biogeochemical cycles of carbon, nitrogen and phosphorus during the twenty-first century. These elements are essential nutrients for biomass production in terrestrial ecosystems. This study finds that aridity has a negative effect on the concentration of global dryland soil organic carbon and nitrogen, but a positive effect on the concentration of inorganic phosphorus. This suggests a decoupling of nutrient cycles in response to an increase in aridity that could have a negative impact on biogeochemical reactions that control key ecosystem functions such as primary productivity. The biogeochemical cycles of carbon (C), nitrogen (N) and phosphorus (P) are interlinked by primary production, respiration and decomposition in terrestrial ecosystems 1 . It has been suggested that the C, N and P cycles could become uncoupled under rapid climate change because of the different degrees of control exerted on the supply of these elements by biological and geochemical processes 1 , 2 , 3 , 4 , 5 . Climatic controls on biogeochemical cycles are particularly relevant in arid, semi-arid and dry sub-humid ecosystems (drylands) because their biological activity is mainly driven by water availability 6 , 7 , 8 . The increase in aridity predicted for the twenty-first century in many drylands worldwide 9 , 10 , 11 may therefore threaten the balance between these cycles, differentially affecting the availability of essential nutrients 12 , 13 , 14 . Here we evaluate how aridity affects the balance between C, N and P in soils collected from 224 dryland sites from all continents except Antarctica. We find a negative effect of aridity on the concentration of soil organic C and total N, but a positive effect on the concentration of inorganic P. Aridity is negatively related to plant cover, which may favour the dominance of physical processes such as rock weathering, a major source of P to ecosystems, over biological processes that provide more C and N, such as litter decomposition 12 , 13 , 14 . Our findings suggest that any predicted increase in aridity with climate change will probably reduce the concentrations of N and C in global drylands, but increase that of P. These changes would uncouple the C, N and P cycles in drylands and could negatively affect the provision of key services provided by these ecosystems.

Germline mutations in BUB1 and BUB3 have been reported to increase the risk of developing colorectal cancer (CRC) at young age, in presence of variegated aneuploidy and reminiscent dysmorphic traits of mosaic variegated aneuploidy syndrome. We performed a mutational analysis of BUB1 and BUB3 in 456 uncharacterized mismatch repair-proficient hereditary non-polyposis CRC families and 88 polyposis cases. Four novel or rare germline variants, one splice-site and three missense, were identified in four families. Neither variegated aneuploidy nor dysmorphic traits were observed in carriers. Evident functional effects in the heterozygous form were observed for c.1965-1G>A, but not for c.2296G>A (p.E766K), in spite of the positive co-segregation in the family. BUB1 c.2473C>T (p.P825S) and BUB3 c.77C>T (p.T26I) remained as variants of uncertain significance. As of today, the rarity of functionally relevant mutations identified in familial and/or early onset series does not support the inclusion of BUB1 and BUB3 testing in routine genetic diagnostics of familial CRC.

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.

Renewable energy sources are an environmentally attractive idea, but they require a proper control scheme to guarantee optimal operation. In this work, we tune different controllers for an Interleaved Boost Converter (IBC) powered by a photovoltaic array using three metaheuristics: Genetic Algorithm, Particle Swarm Optimization, and Gray Wolf Optimization. We also develop several controllers for a second simulated scenario where the IBC is plugged into an existing microgrid (MG) as this can provide relevant data for real-life applications. In both cases, we consider hybrid controllers based on a Linear Quadratic Regulator (LQR). However, we hybridize it with an Integral action (I-LQR) in the first scenario to compare our data against previously published controllers. In the second one, we add a Proportional-Integral technique (PI-LQR) as we do not have previous data to compare against to provide a more robust controller than I-LQR. To validate our approach, we run extensive simulations with each metaheuristic and compare the resulting data. We focus on two fronts: the performance of the controllers and the computing cost of the solvers when facing practical issues. Our results demonstrate that the approach proposed for tuning controllers is a feasible strategy. The controllers tuned with the metaheuristics outperformed previously proposed strategies, yielding solutions thrice faster with virtually no overshoot and a voltage ripple seven times smaller. Not only this, but our controllers could correct some issues liaised to the IBC when it is plugged into an MG. We are confident that these insights can help migrate this approach to a more diverse set of MGs with different renewable sources and escalate it to real-life experiments.

There is a paucity of adequate mouse models and cell lines available to study lung squamous cell carcinoma (LUSC). We have generated and characterized two models of phenotypically different transplantable LUSC cell lines, i.e. UN-SCC679 and UN-SCC680, derived from A/J mice that had been chemically induced with N-nitroso-tris-chloroethylurea (NTCU). Furthermore, we genetically characterized and compared both LUSC cell lines by performing whole-exome and RNA sequencing. These experiments revealed similar genetic and transcriptomic patterns that may correspond to the classic LUSC human subtype. In addition, we compared the immune landscape generated by both tumor cells lines in vivo and assessed their response to immune checkpoint inhibition. The differences between the two cell lines are a good model for the remarkable heterogeneity of human squamous cell carcinoma. Study of the metastatic potential of these models revealed that both cell lines represent the organotropism of LUSC in humans, i.e. affinity to the brain, bones, liver and adrenal glands. In summary, we have generated valuable cell line tools for LUSC research, which recapitulates the complexity of the human disease.

The Colombian Tropical Andes are one of the regions with highest bird diversity on Earth. However, information on bird morphology, reproductive phenology, and molt is particularly scarce in this region. Also, this region is heavily impacted by deforestation, and it is vulnerable to climate change. Hence, providing baseline information on life history and morphological traits will be essential to support future research on functional diversity, climate change effects, conservation, evolution, and phenology. To fill this gap, we have compiled information on bird distribution, morphology, molt, and reproductive phenology at 52 localities of the Department of Caldas, covering an elevation range between 148 and 3845 m. This compilation comprises a wide range of habitats, including native forests, forestry plantations, croplands, and paramo. Our database presents information for 3,398 records belonging to 379 bird species (representing 23 orders, 53 families, and 258 genera). From those records, 2,843 correspond to information collected in the field between 2008 and 2019, and the remaining 555 records correspond to specimens deposited in the Natural History Museum of the Caldas University, collected between 1969 and 2014. We measured nine morphological traits from all specimens: total culmen, gape, bill width, bill depth, tarsus, wing length, tail length, total length, and mass. We also have reproductive condition information for 257 species and molt information available for 378 species. The information contained in this data set represents ~20% of the Colombian avifauna and ~11% of the bird species richness in South America. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA).