Cloned antibodies from patients with HIT provide new clues to HIT pathogenesis.

Heparin-induced thrombocytopenia (HIT) is a serious adverse drug reaction characterized by antibodies that recognize platelet factor 4/heparin complexes (PF4/H) and activate platelets to create a prothrombotic state. Although a high percentage of heparin-treated patients produce antibodies to PF4/H, only a subset also makes antibodies that are platelet activating (PA). A close correlation between PA antibodies and the likelihood of experiencing HIT has been demonstrated in clinical studies, but how PA (presumptively pathogenic) and nonactivating (NA) (presumptively benign) antibodies differ from each other at the molecular level is unknown. To address this issue, we cloned 7 PA and 47 NA PF4/H-binding antibodies from 6 patients with HIT and characterized their structural and functional properties. Findings showed that PA clones differed significantly from NA clones in possessing 1 of 2 heavy chain complementarity-determining region 3 (HCDR3) motifs, RX1-2R/KX1-2R/H (RKH) and YYYYY (Y5), in an unusually long complementarity-determining region 3 (≥20 residues). Mutagenic studies showed that modification of either motif in PA clones reduced or abolished their PA activity and that appropriate amino acid substitutions in HCDR3 of NA clones can cause them to become PA. Repertoire sequencing showed that the frequency of peripheral blood IgG+ B cells possessing RKH or Y5 was significantly higher in patients with HIT than in patients without HIT given heparin, indicating expansion of B cells possessing RKH or Y5 in HIT. These findings imply that antibodies possessing RKH or Y5 are relevant to HIT pathogenesis and suggest new approaches to diagnosis and treatment of this condition.

Off-the-shelf cryopreserved platelets for the detection of HIT and VITT antibodies.

Heparin-induced thrombocytopenia (HIT) is suspected much more often than it is confirmed. Technically simple platelet factor 4 (PF4)-polyanion enzyme-linked immunosorbent assays (ELISAs) are sensitive but nonspecific. In contrast, accurate functional tests such as the serotonin release assay, heparin-induced platelet activation assay, and PF4-dependent P-selectin expression assay require fresh platelets and have complex assay end points, limiting their availability to specialized reference laboratories. To enable broad deployment of functional testing, we sought to extend platelet viability significantly by optimizing storage conditions and developed a simple functional assay end point by measuring the release of a platelet α-granule protein, thrombospondin-1 (TSP1), in an ELISA format. Platelet cryopreservation conditions were optimized by freezing platelets at controlled cooling rates that preserve activatability. Several-month-old cryopreserved platelets were treated with PF4 or heparin and were evaluated for their ability to be activated by HIT and vaccine-induced immune thrombotic thrombocytopenia (VITT) antibodies in the TSP1 release assay (TRA). HIT and spontaneous HIT patient samples induced significantly higher TSP1 release using both PF4-treated (PF4-TRA) and heparin-treated cryopreserved platelets relative to samples from patients suspected of HIT who lacked platelet-activating antibodies. This latter group included several patients that tested strongly positive in PF4-polyanion ELISA but were not platelet-activating. Four VITT patient samples tested in the TRA activated PF4-treated, but not heparin-treated, cryopreserved platelets, consistent with recent data suggesting the requirement for PF4-treated platelets for VITT antibody detection. These findings have the potential to transform the testing paradigm in HIT and VITT, making decentralized, technically simple functional testing available for rapid and accurate in-hospital diagnosis.

Sizes of pure and doped helium droplets from single shot x-ray imaging.

Advancements in x-ray free-electron lasers on producing ultrashort, ultrabright, and coherent x-ray pulses enable single-shot imaging of fragile nanostructures, such as superfluid helium droplets. This imaging technique gives unique access to the sizes and shapes of individual droplets. In the past, such droplet characteristics have only been indirectly inferred by ensemble averaging techniques. Here, we report on the size distributions of both pure and doped droplets collected from single-shot x-ray imaging and produced from the free-jet expansion of helium through a 5 µm diameter nozzle at 20 bars and nozzle temperatures ranging from 4.2 to 9 K. This work extends the measurement of large helium nanodroplets containing 109-1011 atoms, which are shown to follow an exponential size distribution. Additionally, we demonstrate that the size distributions of the doped droplets follow those of the pure droplets at the same stagnation condition but with smaller average sizes.

Agricultural breadbaskets shift poleward given adaptive farmer behavior under climate change.

Modern food production is spatially concentrated in global "breadbaskets." A major unresolved question is whether these peak production regions will shift poleward as the climate warms, allowing some recovery of potential climate-related losses. While agricultural impacts studies to date have focused on currently cultivated land, the Global Gridded Crop Model Intercomparison Project (GGCMI) Phase 2 experiment allows us to assess changes in both yields and the location of peak productivity regions under warming. We examine crop responses under projected end of century warming using seven process-based models simulating five major crops (maize, rice, soybeans, and spring and winter wheat) with a variety of adaptation strategies. We find that in no-adaptation cases, when planting date and cultivar choices are held fixed, regions of peak production remain stationary and yield losses can be severe, since growing seasons contract strongly with warming. When adaptations in management practices are allowed (cultivars that retain growing season length under warming and modified planting dates), peak productivity zones shift poleward and yield losses are largely recovered. While most growing-zone shifts are ultimately limited by geography, breadbaskets studied here move poleward over 600 km on average by end of the century under RCP 8.5. These results suggest that agricultural impacts assessments can be strongly biased if restricted in spatial area or in the scope of adaptive behavior considered. Accurate evaluation of food security under climate change requires global modeling and careful treatment of adaptation strategies.

Fungal Nails? DNA Facts Challenge Dystrophic Etiology.

BACKGROUND: Historically recalcitrant to treatment, infection of the nail unit is a pervasive clinical condition affecting approximately 10% to 20% of the US population; patients present with both cosmetic symptomatology and pain, with subsequent dystrophic morphology. To date, the presumptive infectious etiologies include classically reported fungal dermatophytes, nondermatophyte molds, and yeasts. Until now, the prevalence and potential contribution of bacteria to the clinical course of dystrophic nails had been relatively overlooked, if not dismissed. Previously, diagnosis had largely been made by means of clinical presentation, although microscopic examinations (potassium hydroxide) of nail scrapings to identify fungal agents and, more recently, panel-specific polymerase chain reaction assays have been used to elucidate causative infectious agents. Each of these tools suffers from test-specific limitations. METHODS: Molecular-age medicine now includes DNA-based tools to universally assess any microbe or pathogen with a known DNA sequence. This affords clinicians with rapid DNA sequencing technologies at their disposal. These sequencing-based diagnostic tools confer the accuracy of DNA-level certainty, and concurrently obviate cultivation or microbial phenotypical biases. RESULTS: Using DNA sequencing-based diagnostics, the results in this article document the first identification and quantification of significant bacterial, rather than mycotic, pathogens to the clinical manifestation of dystrophic nails. CONCLUSIONS: In direct opposition to the prevailing and presumptive mycotic-based causes, the results in this article invoke questions about the very basis for our current standards of care, including effective treatment regimens.

3D-Printed, Modular, and Parallelized Microfluidic System with Customizable Scaffold Integration to Investigate the Roles of Basement Membrane Topography on Endothelial Cells.

Because dysfunctions of endothelial cells are involved in many pathologies, in vitro endothelial cell models for pathophysiological and pharmaceutical studies have been a valuable research tool. Although numerous microfluidic-based endothelial models have been reported, they had the cells cultured on a flat surface without considering the possible three-dimensional (3D) structure of the native extracellular matrix (ECM). Endothelial cells rest on the basement membrane in vivo, which contains an aligned microfibrous topography. To better understand and model the cells, it is necessary to know if and how the fibrous topography can affect endothelial functions. With conventional fully integrated microfluidic apparatus, it is difficult to include additional topographies in a microchannel. Therefore, we developed a modular microfluidic system by 3D-printing and electrospinning, which enabled easy integration and switching of desired ECM topographies. Also, with standardized designs, the system allowed for high flow rates up to 4000 µL/min, which encompassed the full shear stress range for endothelial studies. We found that the aligned fibrous topography on the ECM altered arginine metabolism in endothelial cells and thus increased nitric oxide production. There has not been an endothelial model like this, and the new knowledge generated thereby lays a groundwork for future endothelial research and modeling.

A prospective, blinded study of a PF4-dependent assay for HIT diagnosis.

Heparin-induced thrombocytopenia (HIT) is a life-threatening, prothrombotic, antibody-mediated disorder. To maximize the likelihood of recovery, early and accurate diagnosis is critical. Widely available HIT assays, such as the platelet factor 4 (PF4) heparin enzyme-linked immunosorbent assay (ELISA) lack specificity, and the gold-standard carbon 14-labeled serotonin release assay (SRA) is of limited value for early patient management because it is available only through reference laboratories. Recent studies have demonstrated that pathogenic HIT antibodies selectively activate PF4-treated platelets and that a technically simpler assay, the PF4-dependent P-selectin expression assay (PEA), may provide an option for rapid and conclusive results. Based upon predefined criteria that combined 4Ts scores and HIT ELISA results, 409 consecutive adults suspected of having HIT were classified as disease positive, negative, or indeterminate. Patients deemed HIT indeterminate were considered disease negative in the primary analysis and disease positive in a sensitivity analysis. The ability of PEA and SRA to identify patients judged to have HIT was compared using receiver operating characteristic curve statistics. Using these predefined criteria, the diagnostic accuracy of PEA was high (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.87-1.0) and similar to that of SRA (AUC, 0.91; 95% CI, 0.82-1.0). In sensitivity analysis, the AUCs of PEA and SRA were also similar at 0.88 (95% CI, 0.78-0.98) and 0.86 (95% CI, 0.77-0.96), respectively. The PEA, a technically simple nonradioactive assay that uses ∼20-fold fewer platelets compared with the SRA, had high accuracy for diagnosing HIT. Widespread use of the PEA may facilitate timely and more effective management of patients with suspected HIT.

Microfibrous Extracellular Matrix Changes the Liver Hepatocyte Energy Metabolism via Integrins.

Cell line-based liver models are critical tools for liver-related studies. However, the conventional monolayer culture of hepatocytes, the most widely used in vitro model, does not have the extracellular matrix (ECM), which contributes to the three-dimensional (3D) arrangement of the hepatocytes in the liver. As a result, the metabolic properties of the hepatocytes in the monolayer tissue culture may not accurately reflect those of the hepatocytes in the liver. Here, we developed a modular platform for 3D hepatocyte cultures on fibrous ECMs produced by electrospinning, a technique that can turn a polymer solution to the micro/nanofibers and has been widely used to produce scaffolds for 3D cell cultures. Metabolomics quantitation by liquid chromatography-mass spectrometry (LC-MS) indicated that Huh7 hepatocytes grown in microfibers electrospun from silk fibroin exhibited reduced glycolysis and tricarboxylic acid (TCA) cycle, as compared to the cells cultured as a monolayer. Further mechanistic studies suggested that integrins were correlated to the ECM's effects. This is the first time to report how an ECM scaffold could affect the fundamental metabolism of the hepatocytes via integrins.

Carbon-Negative Biofuel Production.

Achievement of the 1.5 °C limit for global temperature increase relies on the large-scale deployment of carbon dioxide removal (CDR) technologies. In this article, we explore two CDR technologies: soil carbon sequestration (SCS), and carbon capture and storage (CCS) integrated with cellulosic biofuel production. These CDR technologies are applied as part of decentralized biorefinery systems processing corn stover and unfertilized switchgrass grown in riparian zones in the Midwestern United States. Cover crops grown on corn-producing lands are chosen from the SCS approach, and biogenic CO2 in biorefineries is captured, transported by pipeline, and injected into saline aquifers. The decentralized biorefinery system using SCS, CCS, or both can produce carbon-negative cellulosic biofuels (≤-22.2 gCO2 MJ-1). Meanwhile, biofuel selling prices increase by 15-45% due to CDR costs. Economic incentives (e.g., cover crop incentives and/or a CO2 tax credit) can mitigate price increases caused by CDR technologies. A combination of different CDR technologies in decentralized biorefinery systems is the most efficient method for greenhouse gas (GHG) mitigation, and its total GHG mitigation potential in the Midwest is 0.16 GtCO2 year-1.

A review of iodine-based compounds, with a focus on biofilms: results of an expert panel.

Biofilms play a central role in the chronicity of non-healing lesions such as venous leg ulcers and diabetic foot ulcers. Therefore, biofilm management and treatment is now considered an essential part of wound care. Many antimicrobial treatments, whether topical or systemic, have been shown to have limited efficacy in the treatment of biofilm phenotypes. The antimicrobial properties of iodine compounds rely on multiple and diverse interactions to exert their effects on microorganisms. An expert panel, held in Las Vegas during the autumn Symposium on Advanced Wound Care meeting in 2018, discussed these properties, with the focus on iodine and iodophors and their effects on biofilm prevention and treatment.

From cells-on-a-chip to organs-on-a-chip: scaffolding materials for 3D cell culture in microfluidics.

It is an emerging research area to integrate scaffolding materials in microfluidic devices for 3D cell culture (organs-on-a-chip). The technology of organs-on-a-chip holds the potential to obviate the gaps between pre-clinical and clinical studies. As accumulating evidence shows the importance of extracellular matrix in in vitro cell culture, significant efforts have been made to integrate 3D ECM/scaffolding materials in microfluidics. There are two families of materials that are commonly used for this purpose: hydrogels and electrospun fibers. In this review, we briefly discuss the properties of the materials, and focus on the various technologies to obtain the materials (e.g. extraction of collagen from animal tissues) and to include the materials in microfluidic devices. Challenges and potential solutions of the current materials and technologies were also thoroughly discussed. At the end, we provide a perspective on future efforts to make these technologies more translational to broadly benefit pharmaceutical and pathophysiological research.

3D-Printed Microfluidic Devices for Enhanced Online Sampling and Direct Optical Measurements.

3D printing has emerged as a robust technique to fabricate reliable and reproducible microfluidic devices. However, a limitation of 3D-printed devices has been the low transparency even when printed in a "clear" material. There are currently no reports regarding direct optical measurements through a 3D-printed device. Here, we present for the first time that the printing orientation can affect the transparency of a 3D-printed object. With the optimal orientation, we printed a microfluidic detector that was sufficiently transparent (transmittance ≈ 80%) for optical quantitation. This finding is significant because it shows the feasibility to directly 3D-print optical components for analytical applications. In addition, we created a novel microfluidic dialysis device via 3D printing, which enabled higher flow rates (for sampling with high temporal resolution) and increased extraction efficiency than commercially available ones. By coupling the microfluidic detector and dialysis probe, we successfully measured the release kinetics of indole from biofilms in a continuous, automated, and near real-time fashion. Indole is an intercellular signaling molecule in biofilms, which may regulate antibiotic resistance. The release kinetics of this molecule had not been quantitated likely because of the lack of a suitable analytical tool. Our results fill this knowledge gap.

Human Rabies - Utah, 2018.

On November 3, 2018, the Utah Department of Health (UDOH) was notified of a suspected human rabies case in a man aged 55 years. The patient's symptoms had begun 18 days earlier, and he was hospitalized for 15 days before rabies was suspected. As his symptoms worsened, he received supportive care, but he died on November 4. On November 7, a diagnosis of rabies was confirmed by CDC. This was the first documented rabies death in a Utah resident since 1944. This report summarizes the patient's clinical course and the subsequent public health investigation, which determined that the patient had handled several bats in the weeks preceding symptom onset. Public health agencies, in partnership with affected health care facilities, identified and assessed the risk to potentially exposed persons, facilitated receipt of postexposure prophylaxis (PEP), and provided education to health care providers and the community about the risk for rabies associated with bats. Human rabies is rare and almost always fatal. The findings from this investigation highlight the importance of early recognition of rabies, improved public awareness of rabies in bats, and the use of innovative tools after mass rabies exposure events to ensure rapid and recommended risk assessment and provision of PEP.

Sustainable feedstock for bioethanol production: Impact of spatial resolution on the design of a sustainable biomass supply-chain.

This study assesses the role of spatial-resolution and spatial-variations in environmental impacts estimation and decision-making for corn-stover harvesting to produce biofuels. Geospatial corn-stover yields and environmental impacts [global warming potential (GWP), eutrophication, and soil-loss] dataset for two study areas in Wisconsin and Michigan were generated through Environmental Policy Integrated Climate (EPIC) model and aggregated at different spatial-resolutions (i.e., 100; 1000; 10,000 ha). For each spatial-resolution, decision-making was accomplished using an optimization routine to minimize different environmental impacts associated with harvesting stover to meet varied biomass demands. The results of the study showed that selective harvesting at higher-resolution (or lower-aggregation level) can result in significantly lower environmental impacts, especially at low stover demand levels. Additionally, the increased spatial resolution had more impact in minimizing the environmental impacts of corn stover harvest under a more variable landscape such as terrains and its influences are more pronounced for soil-loss and eutrophication potential compared to GWP.

Parameterization-induced uncertainties and impacts of crop management harmonization in a global gridded crop model ensemble.

Global gridded crop models (GGCMs) combine agronomic or plant growth models with gridded spatial input data to estimate spatially explicit crop yields and agricultural externalities at the global scale. Differences in GGCM outputs arise from the use of different biophysical models, setups, and input data. GGCM ensembles are frequently employed to bracket uncertainties in impact studies without investigating the causes of divergence in outputs. This study explores differences in maize yield estimates from five GGCMs based on the public domain field-scale model Environmental Policy Integrated Climate (EPIC) that participate in the AgMIP Global Gridded Crop Model Intercomparison initiative. Albeit using the same crop model, the GGCMs differ in model version, input data, management assumptions, parameterization, and selection of subroutines affecting crop yield estimates via cultivar distributions, soil attributes, and hydrology among others. The analyses reveal inter-annual yield variability and absolute yield levels in the EPIC-based GGCMs to be highly sensitive to soil parameterization and crop management. All GGCMs show an intermediate performance in reproducing reported yields with a higher skill if a static soil profile is assumed or sufficient plant nutrients are supplied. An in-depth comparison of setup domains for two EPIC-based GGCMs shows that GGCM performance and plant stress responses depend substantially on soil parameters and soil process parameterization, i.e. hydrology and nutrient turnover, indicating that these often neglected domains deserve more scrutiny. For agricultural impact assessments, employing a GGCM ensemble with its widely varying assumptions in setups appears the best solution for coping with uncertainties from lack of comprehensive global data on crop management, cultivar distributions and coefficients for agro-environmental processes. However, the underlying assumptions require systematic specifications to cover representative agricultural systems and environmental conditions. Furthermore, the interlinkage of parameter sensitivity from various domains such as soil parameters, nutrient turnover coefficients, and cultivar specifications highlights that global sensitivity analyses and calibration need to be performed in an integrated manner to avoid bias resulting from disregarded core model domains. Finally, relating evaluations of the EPIC-based GGCMs to a wider ensemble based on individual core models shows that structural differences outweigh in general differences in configurations of GGCMs based on the same model, and that the ensemble mean gains higher skill from the inclusion of structurally different GGCMs. Although the members of the wider ensemble herein do not consider crop-soil-management interactions, their sensitivity to nutrient supply indicates that findings for the EPIC-based sub-ensemble will likely become relevant for other GGCMs with the progressing inclusion of such processes.

Evaporation Dynamics from Ag-Doped He Droplets upon Laser Excitation.

Silver clusters were assembled in helium droplets of different sizes ranging from 104 to 1011 atoms. The clusters were heated upon laser irradiation at 355 nm, and evaporation dynamics of He atoms were studied by quadrupole mass spectroscopy using signals from He+, He2+, and He4+ splitter ions. We found that for droplets containing less than 107 atoms the laser irradiation leads to evaporation of He atoms. However, the laser irradiation leads to the breakup of the large droplets into smaller ones.

The Global Gridded Crop Model Intercomparison phase 1 simulation dataset.

The Global Gridded Crop Model Intercomparison (GGCMI) phase 1 dataset of the Agricultural Model Intercomparison and Improvement Project (AgMIP) provides an unprecedentedly large dataset of crop model simulations covering the global ice-free land surface. The dataset consists of annual data fields at a spatial resolution of 0.5 arc-degree longitude and latitude. Fourteen crop modeling groups provided output for up to 11 historical input datasets spanning 1901 to 2012, and for up to three different management harmonization levels. Each group submitted data for up to 15 different crops and for up to 14 output variables. All simulations were conducted for purely rainfed and near-perfectly irrigated conditions on all land areas irrespective of whether the crop or irrigation system is currently used there. With the publication of the GGCMI phase 1 dataset we aim to promote further analyses and understanding of crop model performance, potential relationships between productivity and environmental impacts, and insights on how to further improve global gridded crop model frameworks. We describe dataset characteristics and individual model setup narratives.

The Renewable Fuel Standard May Limit Overall Greenhouse Gas Savings by Corn Stover-Based Cellulosic Biofuels in the U.S. Midwest: Effects of the Regulatory Approach on Projected Emissions.

The Renewable Fuel Standard (RFS) program specifies a greenhouse gas (GHG) reduction threshold for cellulosic biofuels, while the Low Carbon Fuel Standard (LCFS) program in California does not. Here, we investigate the effects of the GHG threshold under the RFS on projected GHG savings from two corn stover-based biofuel supply chain systems in the United States Midwest. The analysis is based on a techno-economic framework that minimizes ethanol selling price. The GHG threshold lowers the lifecycle GHG of ethanol: 34.39 ± 4.92 gCO2 MJ-1 in the RFS-compliant system and 46.30 ± 10.05 gCO2 MJ-1 in the non RFS-compliant system. However, hypothetical biorefinery systems complying with the RFS will not process the more GHG-intensive corn stover, and thus much less biofuel will be produced compared to the non RFS-compliant system. Thus, taken as a whole, the non RFS-compliant system would achieve more GHG savings than an RFS-compliant system: 10.7 TgCO2 year-1 in the non RFS-compliant system compared with 4.4 TgCO2 year-1 in the RFS-compliant system. These results suggest that the current RFS GHG reduction threshold may not be the most efficient way to carry out the purposes of the Energy Security and Independence Act in the corn stover-based biofuel system: relaxing the threshold could actually increase the overall GHG savings from corn stover-based biofuels. Therefore, the LCFS-type regulatory approach is recommended for the corn stover-based cellulosic biofuel system under the RFS program. In addition, our calculation of the GHG balance for stover-based biofuel accounts for SOC losses, while the current RFS estimates do not include effects on SOC.

Global wheat production with 1.5 and 2.0°C above pre-industrial warming.

Efforts to limit global warming to below 2°C in relation to the pre-industrial level are under way, in accordance with the 2015 Paris Agreement. However, most impact research on agriculture to date has focused on impacts of warming >2°C on mean crop yields, and many previous studies did not focus sufficiently on extreme events and yield interannual variability. Here, with the latest climate scenarios from the Half a degree Additional warming, Prognosis and Projected Impacts (HAPPI) project, we evaluated the impacts of the 2015 Paris Agreement range of global warming (1.5 and 2.0°C warming above the pre-industrial period) on global wheat production and local yield variability. A multi-crop and multi-climate model ensemble over a global network of sites developed by the Agricultural Model Intercomparison and Improvement Project (AgMIP) for Wheat was used to represent major rainfed and irrigated wheat cropping systems. Results show that projected global wheat production will change by -2.3% to 7.0% under the 1.5°C scenario and -2.4% to 10.5% under the 2.0°C scenario, compared to a baseline of 1980-2010, when considering changes in local temperature, rainfall, and global atmospheric CO2 concentration, but no changes in management or wheat cultivars. The projected impact on wheat production varies spatially; a larger increase is projected for temperate high rainfall regions than for moderate hot low rainfall and irrigated regions. Grain yields in warmer regions are more likely to be reduced than in cooler regions. Despite mostly positive impacts on global average grain yields, the frequency of extremely low yields (bottom 5 percentile of baseline distribution) and yield inter-annual variability will increase under both warming scenarios for some of the hot growing locations, including locations from the second largest global wheat producer-India, which supplies more than 14% of global wheat. The projected global impact of warming <2°C on wheat production is therefore not evenly distributed and will affect regional food security across the globe as well as food prices and trade.

Climate change impact and adaptation for wheat protein.

Wheat grain protein concentration is an important determinant of wheat quality for human nutrition that is often overlooked in efforts to improve crop production. We tested and applied a 32-multi-model ensemble to simulate global wheat yield and quality in a changing climate. Potential benefits of elevated atmospheric CO2 concentration by 2050 on global wheat grain and protein yield are likely to be negated by impacts from rising temperature and changes in rainfall, but with considerable disparities between regions. Grain and protein yields are expected to be lower and more variable in most low-rainfall regions, with nitrogen availability limiting growth stimulus from elevated CO2 . Introducing genotypes adapted to warmer temperatures (and also considering changes in CO2 and rainfall) could boost global wheat yield by 7% and protein yield by 2%, but grain protein concentration would be reduced by -1.1 percentage points, representing a relative change of -8.6%. Climate change adaptations that benefit grain yield are not always positive for grain quality, putting additional pressure on global wheat production.