Investigation of fast and efficient lossless compression algorithms for macromolecular crystallography experiments.

Structural biology experiments benefit significantly from state-of-the-art synchrotron data collection. One can acquire macromolecular crystallography (MX) diffraction data on large-area photon-counting pixel-array detectors at framing rates exceeding 1000 frames per second, using 200 Gbps network connectivity, or higher when available. In extreme cases this represents a raw data throughput of about 25 GB s-1, which is nearly impossible to deliver at reasonable cost without compression. Our field has used lossless compression for decades to make such data collection manageable. Many MX beamlines are now fitted with DECTRIS Eiger detectors, all of which are delivered with optimized compression algorithms by default, and they perform well with current framing rates and typical diffraction data. However, better lossless compression algorithms have been developed and are now available to the research community. Here one of the latest and most promising lossless compression algorithms is investigated on a variety of diffraction data like those routinely acquired at state-of-the-art MX beamlines.

Mechanical and Structural Properties of Articular Cartilage and Subchondral Bone in Human Osteoarthritic Knees.

Knee osteoarthritis (OA), characterized by multiple joint tissue degenerations, remains a significant clinical challenge. Recent evidence suggests that crosstalk within the osteochondral unit may drive OA progression. While structural-biomechanical properties of bone and cartilage have been studied, potential interaction within the osteochondral unit in the context of OA has yet to be investigated. We performed comprehensive structural and biomechanical quantification of the cartilage, subchondral bone plate, and subchondral trabecular bone using 101 osteochondral cores collected from tibial plateaus of 12 control human cadavers (CT, 5 male/7 female) and 19 patients undergoing total knee replacement (OA, 6 male/13 female). For each sample, we quantified subchondral bone plate microstructure, plate-and-rod morphological properties of the subchondral trabecular bone using individual trabecula segmentation, and morphological and compositional properties of the articular cartilage. We also performed indentation testing on each compartment of the osteochondral unit to extract the respective structural-mechanical properties. Cartilage thickness was lower in moderate and severe OA regions, while OARSI score was higher only in severe OA regions. GAG content did not change in any OA region. Aggregate and shear moduli were lower only in severe OA regions, while permeability was lower only in moderate OA regions. In the subchondral bone plate, thickness and TMD were higher in moderate and severe OA regions. Tissue modulus of subchondral trabecular bone was lower in moderate OA regions despite a thicker and more mineralized subchondral bone plate; this deterioration was not observed in severe OA regions. Regression analysis revealed strong correlations between cartilage and subchondral trabecular bone properties in CT; these correlations were also found in moderate OA regions but were not observed in severe OA regions. In summary, our findings comprehensively characterize the human OA osteochondral unit. Importantly, uncoupling cartilage and subchondral bone structural-mechanical properties may be a hallmark of OA.

Knee osteoarthritis (OA) is a complex condition involving the degradation of joint tissues. To better understand OA progression, we investigated the interplay between different components of the joint. Our study focused on how cartilage, subchondral bone plate, and subchondral trabecular bone interact in human knee OA samples. We observed distinct changes in these tissues in moderate and severe OA regions compared to healthy joints. In moderate to severe OA, we found that cartilage thickness decreased while the subchondral bone plate thickened. Interestingly, the strength of the subchondral trabecular bone decreased only in moderate OA regions, not in severe OA. Moreover, our analysis revealed strong correlations between cartilage and subchondral trabecular bone properties in healthy joints and moderate OA regions. However, these correlations were absent in severe OA regions, indicating a disruption in the usual relationship between these tissues. Overall, our findings shed light on the structural and biomechanical changes occurring within the knee joint in OA. Understanding these changes may offer insights into potential therapeutic strategies for managing OA.

Electrospray ionization tandem mass spectrometry of 4-aryl-3,4-dihydrocoumarins.

We have investigated the gas-phase fragmentation reactions of 11 synthetic 4-aryl-3,4-dihydrocoumarins by electrospray ionization tandem mass spectrometry (ESI-MS/MS) on a quadrupole-time-of flight (Q-TOF) hybrid mass spectrometer. We have also estimated thermochemical data for the protonated coumarins (precursor ion A) and product ion structures by computational chemistry at a B3LYP level of theory to establish the ion structures and to rationalize the fragmentation pathways. The most abundant ions in the product ion spectra of coumarins 1-11 resulted from C8H8O2, CO2, C4H4O3, C8H10O3, C8H8O2, and CH3OH eliminations through retro-Diels-Alder (RDA) reactions, remote hydrogen rearrangements (ß-eliminations), and ß-lactone ring contraction. Although the investigated coumarins shared most of the fragmentation pathways, formation of a benzylic product ion and its corresponding tropylium ion was diagnostic of the substituents at ring C. The thermochemical data revealed that the nature and position of the substituents at ring C played a key role in the formation of this product ion and determined its relative intensity in the product ion spectrum. The results of this study contribute to knowledge of the gas-phase ion chemistry of this important class of organic compounds.

Bragg Spot Finder (BSF): a new machine-learning-aided approach to deal with spot finding for rapidly filtering diffraction pattern images.

Macromolecular crystallography contributes significantly to understanding diseases and, more importantly, how to treat them by providing atomic resolution 3D structures of proteins. This is achieved by collecting X-ray diffraction images of protein crystals from important biological pathways. Spotfinders are used to detect the presence of crystals with usable data, and the spots from such crystals are the primary data used to solve the relevant structures. Having fast and accurate spot finding is essential, but recent advances in synchrotron beamlines used to generate X-ray diffraction images have brought us to the limits of what the best existing spotfinders can do. This bottleneck must be removed so spotfinder software can keep pace with the X-ray beamline hardware improvements and be able to see the weak or diffuse spots required to solve the most challenging problems encountered when working with diffraction images. In this paper, we first present Bragg Spot Detection (BSD), a large benchmark Bragg spot image dataset that contains 304 images with more than 66 000 spots. We then discuss the open source extensible U-Net-based spotfinder Bragg Spot Finder (BSF), with image pre-processing, a U-Net segmentation backbone, and post-processing that includes artifact removal and watershed segmentation. Finally, we perform experiments on the BSD benchmark and obtain results that are (in terms of accuracy) comparable to or better than those obtained with two popular spotfinder software packages (Dozor and DIALS), demonstrating that this is an appropriate framework to support future extensions and improvements.

Variation in TaSPL6-D confers salinity tolerance in bread wheat by activating TaHKT1;5-D while preserving yield-related traits.

Na+ exclusion from above-ground tissues via the Na+-selective transporter HKT1;5 is a major salt-tolerance mechanism in crops. Using the expression genome-wide association study and yeast-one-hybrid screening, we identified TaSPL6-D, a transcriptional suppressor of TaHKT1;5-D in bread wheat. SPL6 also targeted HKT1;5 in rice and Brachypodium. A 47-bp insertion in the first exon of TaSPL6-D resulted in a truncated peptide, TaSPL6-DIn, disrupting TaHKT1;5-D repression exhibited by TaSPL6-DDel. Overexpressing TaSPL6-DDel, but not TaSPL6-DIn, led to inhibited TaHKT1;5-D expression and increased salt sensitivity. Knockout of TaSPL6-DDel in two wheat genotypes enhanced salinity tolerance, which was attenuated by a further TaHKT1;5-D knockdown. Spike development was preserved in Taspl6-dd mutants but not in Taspl6-aabbdd mutants. TaSPL6-DIn was mainly present in landraces, and molecular-assisted introduction of TaSPL6-DIn from a landrace into a leading wheat cultivar successfully improved yield on saline soils. The SPL6-HKT1;5 module offers a target for the molecular breeding of salt-tolerant crops.

Biological mitigation of soil nitrous oxide emissions by plant metabolites.

Plant metabolites significantly affect soil nitrogen (N) cycling, but their influence on nitrous oxide (N2O) emissions has not been quantitatively analyzed on a global scale. We conduct a comprehensive meta-analysis of 173 observations from 42 articles to evaluate global patterns of and principal factors controlling N2O emissions in the presence of root exudates and extracts. Overall, plant metabolites promoted soil N2O emissions by about 10%. However, the effects of plant metabolites on N2O emissions from soils varied with experimental conditions and properties of both metabolites and soils. Primary metabolites, such as sugars, amino acids, and organic acids, strongly stimulated soil N2O emissions, by an average of 79%, while secondary metabolites, such as phenolics, terpenoids, and flavonoids, often characterized as both biological nitrification inhibitors (BNIs) and biological denitrification inhibitors (BDIs), reduced soil N2O emissions by an average of 41%. The emission mitigation effects of BNIs/BDIs were closely associated with soil texture and pH, increasing with increasing soil clay content and soil pH on acidic and neutral soils, and with decreasing soil pH on alkaline soils. We furthermore present soil incubation experiments that show that three secondary metabolite types act as BNIs to reduce N2O emissions by 32%-45%, while three primary metabolite classes possess a stimulatory effect of 56%-63%, confirming the results of the meta-analysis. Our results highlight the potential role and application range of specific secondary metabolites in biomitigation of global N2O emissions and provide new biological parameters for N2O emission models that should help improve the accuracy of model predictions.

Enhancing Readability of Online Patient-Facing Content: The Role of AI Chatbots in Improving Cancer Information Accessibility.

BACKGROUND: Internet-based health education is increasingly vital in patient care. However, the readability of online information often exceeds the average reading level of the US population, limiting accessibility and comprehension. This study investigates the use of chatbot artificial intelligence to improve the readability of cancer-related patient-facing content. METHODS: We used ChatGPT 4.0 to rewrite content about breast, colon, lung, prostate, and pancreas cancer across 34 websites associated with NCCN Member Institutions. Readability was analyzed using Fry Readability Score, Flesch-Kincaid Grade Level, Gunning Fog Index, and Simple Measure of Gobbledygook. The primary outcome was the mean readability score for the original and artificial intelligence (AI)-generated content. As secondary outcomes, we assessed the accuracy, similarity, and quality using F1 scores, cosine similarity scores, and section 2 of the DISCERN instrument, respectively. RESULTS: The mean readability level across the 34 websites was equivalent to a university freshman level (grade 13±1.5). However, after ChatGPT's intervention, the AI-generated outputs had a mean readability score equivalent to a high school freshman education level (grade 9±0.8). The overall F1 score for the rewritten content was 0.87, the precision score was 0.934, and the recall score was 0.814. Compared with their original counterparts, the AI-rewritten content had a cosine similarity score of 0.915 (95% CI, 0.908-0.922). The improved readability was attributed to simpler words and shorter sentences. The mean DISCERN score of the random sample of AI-generated content was equivalent to "good" (28.5±5), with no significant differences compared with their original counterparts. CONCLUSIONS: Our study demonstrates the potential of AI chatbots to improve the readability of patient-facing content while maintaining content quality. The decrease in requisite literacy after AI revision emphasizes the potential of this technology to reduce health care disparities caused by a mismatch between educational resources available to a patient and their health literacy.

Liquid Chromatography Coupled to Isotope Ratio Mass Spectrometry Expanded to Include Organic Mobile Phases.

Current commercially available liquid chromatography coupled to isotope ratio mass spectrometry systems (LC-IRMS) oxidize all eluent and thus can only operate with all-aqueous mobile phases, limiting their application to a small subset of analytes and mixtures that can be separated without organic solvents. We report a novel rotating-catalytic disc desolvation device with subsequent laser-activated photocatalytic analyte combustion to create CO2 for high precision carbon isotope ratio measurements compatible with both aqueous and organic liquid mobile phases. Sucrose, glucose, androsterone, or androsterone acetate in 20% and 50% H2O-CH3OH solutions were introduced by flow injection to the interface to IRMS for sugars and steroids, respectively. Sucrose δ13CVPDB linearity was excellent over 1-10 µg (33-655 nmol C) injections, using IRMS compatible He/1%O2 oxidation gas. The limit of precise isotope analysis (LOIA) of δ13CVPDB was 1 µg (35 nmol C) for sucrose and 10 µg (655 nmol C) for androsterone with average precisions of SD(δ13C) ± 0.8‰. Calibration was performed with and bracketed the δ13CVPDB isotope ratio range using androsterone-acetate and glucose. With further development to improve sensitivity and application to chromatography, the prototype proof-of-principle LC-IRMS shows promise to resolve a major drawback in current LC-IRMS systems and may open LC-IRMS to many more compounds than currently possible.

Physiological and molecular mechanisms of plant-root responses to iron toxicity.

The chemical form and physiological activity of iron (Fe) in soil are dependent on soil pH and redox potential (Eh), and Fe levels in soils are frequently elevated to the point of causing Fe toxicity in plants, with inhibition of normal physiological activities and of growth and development. In this review, we describe how iron toxicity triggers important physiological changes, including nitric-oxide (NO)-mediated potassium (K+) efflux at the tips of roots and accumulation of reactive oxygen species (ROS) and reactive nitrogen (RNS) in roots, resulting in physiological stress. We focus on the root system, as the first point of contact with Fe in soil, and describe the key processes engaged in Fe transport, distribution, binding, and other mechanisms that are drawn upon to defend against high-Fe stress. We describe the root-system regulation of key physiological processes and of morphological development through signaling substances such as ethylene, auxin, reactive oxygen species, and nitric oxide, and discuss gene-expression responses under high Fe. We especially focus on studies on the physiological and molecular mechanisms in rice and Arabidopsis under high Fe, hoping to provide a valuable theoretical basis for improving the ability of crop roots to adapt to soil Fe toxicity.

A pilot study of virtual reality for inpatients with opioid use disorder.

BACKGROUND AND OBJECTIVES: While inpatient withdrawal management/acute stabilization can improve outcomes for individuals with opioid use disorder (OUD), patients often leave treatment early due to mood, tension, and cravings associated with opioid withdrawal. The aim of this study was to evaluate the feasibility and preliminary effectiveness of a novel virtual reality (VR) based intervention; 3D Therapy Thrive (3DTT). METHODS: Subjects with OUD (N = 32) were recruited from a community acute stabilization program and received up to two sessions of 3DTT. They completed questionnaires related to their overall satisfaction with the experience and side effects; as well as those related to mood, tension, and cravings. RESULTS: There were no reported side effects and the majority of subjects (94%) reported high satisfaction with the experience. Out of 62 patients approached, 33 patients agreed to participate (53%) 33 patients completed one, and 17 of these patients (52%) completed both sessions of 3DTT, with 19 participants (58%) completing their treatment protocols. Compared to baseline, 3DTT participants reported significant reductions in depression, tension, and cravings (p's < 0.001). DISCUSSION AND CONCLUSIONS: This pilot study supports the feasibility and preliminary effectiveness of 3DTT for improving outcomes for inpatients with OUD. Future randomized controlled trials are necessary to evaluate the efficacy of 3DTT for improving retention, reducing cravings, and improving mood and tension. SCIENTIFIC SIGNIFICANCE: This is the first study to evaluate the feasibility of a psychologically informed VR intervention in inpatients with OUD.

OsEIL1 is involved in the response to heterogeneous high ammonium in rice: A split-root analysis.

Ammonium (NH4+) concentrations in rice fields show heterogeneous spatial distribution under the combined influences of nitrogen fertilizer application and modern agronomic practices. However, the characteristics and mechanisms of rice roots in response to heterogeneous NH4+ supply are not well understood. Here, we found a systemic response of rice roots to heterogeneous and high (10 mM) NH4+ supply using a split-root experiment, and show root growth on the NH4+-free (NO3-) side was also inhibited by localized high-NH4+ supply. Moreover, OsEIL1 (encoding a core transcription factor in the ethylene signaling pathway) was found to be involved in the response of rice roots to heterogeneous NH4+. OsEIL1 mutation significantly increased the inhibitory effect of localized high-NH4+ on root growth of the NO3- side, as well as significantly increased NH4+ efflux there. Furthermore, our results indicate that the mitigating effect of OsEIL1 on NH4+ efflux is related to the regulated expression of OsVTC1-3 (encoding a GDP-mannose pyrophosphorylase). These findings provide insight into the mechanisms by which OsEIL1 responds to heterogeneous high NH4+ and contribute to our understanding of rice adaptation to heterogeneous NH4+ supply.

The development of a deep learning model for automated segmentation of the robotic pancreaticojejunostomy.

BACKGROUND: Minimally invasive surgery provides an unprecedented opportunity to review video for assessing surgical performance. Surgical video analysis is time-consuming and expensive. Deep learning provides an alternative for analysis. Robotic pancreaticoduodenectomy (RPD) is a complex and morbid operation. Surgeon technical performance of pancreaticojejunostomy (PJ) has been associated with postoperative pancreatic fistula. In this work, we aimed to utilize deep learning to automatically segment PJ RPD videos. METHODS: This was a retrospective review of prospectively collected videos from 2011 to 2022 that were in libraries at tertiary referral centers, including 111 PJ videos. Each frame of a robotic PJ video was categorized based on 6 tasks. A 3D convolutional neural network was trained for frame-level visual feature extraction and classification. All the videos were manually annotated for the start and end of each task. RESULTS: Of the 100 videos assessed, 60 videos were used for the training the model, 10 for hyperparameter optimization, and 30 for the testing of performance. All the frames were extracted (6 frames/second) and annotated. The accuracy and mean per-class F1 scores were 88.01% and 85.34% for tasks. CONCLUSION: The deep learning model performed well for automated segmentation of PJ videos. Future work will focus on skills assessment and outcome prediction.

Defining the Role of Social Vulnerability in Treatment and Survival in Localized Colon Cancer: A Retrospective Cohort Study.

OBJECTIVE: To determine whether variations in Social Vulnerability Index (SVI) are associated with disparities in colon cancer surgery and mortality. SUMMARY BACKGROUND DATA: Colon cancer mortality is influenced by health care access, which is affected by individual and community-level factors. Prior studies have not used the SVI to compare surgical access and survival in localized colon cancer patients. Further, it is unclear if those above 65 years are more vulnerable to variations in SVI. METHODS: We queried the Texas and California Cancer Registries from 2004-2017 to identify patients with localized colonic adenocarcinoma and categorized patients into <65 and ≥65 years. Our outcomes were survival and access to surgical intervention. The independent variable was census tract social vulnerability index, with higher scores indicating more social vulnerability. We used multivariable logistic regression and Cox proportional hazards for analysis. RESULTS: We included 73,923 patients with a mean age of 68.6 years (SD 13.0), mean SVI of 47.2 (SD 27.6), and 51.1% male. After adjustment, increasing SVI was associated with reduced odds of undergoing surgery (OR 0.996; 95% CI 0.995-0.997; P < 0.0001 and increased mortality (HR 1.002; 95% CI 1.001-1.002; P < 0.0001). Patients < 65 years were more sensitive to variation in SVI. CONCLUSIONS: Increased social vulnerability was associated with reduced odds of receiving surgery for early-stage colon cancer as well as increased mortality. These findings amplify the need for policy changes at the local, state, and federal level to address community-level vulnerability to improve access to surgical care and reduce mortality.

A guideline on the molecular ecosystem regulating ferroptosis.

Ferroptosis, an intricately regulated form of cell death characterized by uncontrolled lipid peroxidation, has garnered substantial interest since this term was first coined in 2012. Recent years have witnessed remarkable progress in elucidating the detailed molecular mechanisms that govern ferroptosis induction and defence, with particular emphasis on the roles of heterogeneity and plasticity. In this Review, we discuss the molecular ecosystem of ferroptosis, with implications that may inform and enable safe and effective therapeutic strategies across a broad spectrum of diseases.

Proficiency Levels and Validity Evidence for Scoring Metrics for a Virtual Reality and Inanimate Robotic Surgery Simulation Curriculum.

OBJECTIVE: Our institution recently implemented a virtual reality (VR) skills curriculum for general surgery residents using the SimNow simulator. Based on a content alignment study, we revised the curriculum to include only 20 of 33 VR tasks and we added 3 previously validated inanimate tasks. The purpose of this study was to establish expert-derived proficiency levels for all tasks and to evaluate the validity of the scoring for the VR tasks. DESIGN: Two expert robotic surgeons performed 5 repetitions of each VR and inanimate task. The trimmed mean (lowest scoring attempt and outliers [>2 standard deviations] were eliminated) was defined as the expert level for each task. For the VR tasks, expert levels were compared to resident performance to evaluate validity. SETTING: This study was conducted at the University of Texas Southwestern Medical Center (Dallas, TX), a tertiary care academic teaching hospital. PARTICIPANTS: Two expert robotic surgeons participated in this study. The data from 42 residents (PGY2-4) who completed the original curriculum was used to represent novice performance. RESULTS: Comparison of expert levels and resident performance was statistically significant for 15 VR tasks (supporting validity) and approached significance (p = 0.06, 0.09) for 2 VR tasks; expert levels were designated as proficiency levels for these 17 tasks. Group comparisons were clearly not significant (p = 0.2-0.8) for 3 VR tasks; 2 of these 3 tasks were retained as introductory exercises (with 3 repetitions required) and 1 was excluded. For the 3 inanimate tasks, expert levels minus 2 standard deviations were designated as proficiency levels. CONCLUSIONS: This analysis generated validity evidence for 15 VR tasks and established expert-derived proficiency levels for 17 VR tasks and 3 inanimate tasks. Our proposed curriculum now consists of 19 VR and 3 inanimate tasks using the selected proficiency levels. We anticipate that this design will maximize curriculum efficiency and effectiveness.

Minimally invasive pancreaticoduodenectomy: A favorable approach for frail patients with pancreatic cancer.

BACKGROUND: Within the past decade, minimally invasive pancreaticoduodenectomy has been increasingly adopted in high-volume cancer centers. Amid broader trends of a growing older population, the numbers of frail patients with cancer are expected to increase. In this study, we compared the postoperative outcomes of open pancreaticoduodenectomy and minimally invasive pancreaticoduodenectomy in frail patients with pancreatic ductal adenocarcinoma. METHODS: Using the pancreatectomy-targeted American College of Surgeons-National Surgical Quality Improvement Program database (2014-2021), we identified pancreaticoduodenectomy cases for pancreatic ductal adenocarcinoma. Patients with a modified frailty index ≥2 were considered frail. We performed 2:1 (open pancreaticoduodenectomy to minimally invasive pancreaticoduodenectomy) optimal pair propensity score matching for both patient- and disease-specific characteristics. We evaluated baseline covariate balance for homogeneity and assessed 30-day postoperative outcomes: complications, discharge destination, major morbidity, and mortality. RESULTS: We identified 3,143 frail patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. Of those, 275 (9%) underwent minimally invasive pancreaticoduodenectomy. Minimally invasive pancreaticoduodenectomy was associated with a lower rate of any complications compared with open pancreaticoduodenectomy (43% vs 54%; P < .001), major morbidity (29% vs 35%; P = .042), and nonhome discharge (12% vs 17%; P = .022). When comparing the 2 minimally invasive pancreaticoduodenectomy approaches, robotic surgery was associated with fewer complications compared with laparoscopy (39% vs 51%; P = .040) and a lower mortality rate (1% vs 4%; P = .041) CONCLUSION: In frail patients with pancreatic cancer, minimally invasive pancreaticoduodenectomy was associated with better postoperative outcomes than open pancreaticoduodenectomy. This study builds on growing literature reporting that, when properly implemented, minimally invasive pancreaticoduodenectomy is associated with more favorable postoperative outcomes. Given the particularly high risk of complication in frail patients, implementing a preoperative frailty assessment can provide valuable insights to inform patient counseling.

Plant iron status regulates ammonium-use efficiency through protein N-glycosylation.

Improving nitrogen-use efficiency is an important path toward enhancing crop yield and alleviating the environmental impacts of fertilizer use. Ammonium (NH4+) is the energetically preferred inorganic N source for plants. The interaction of NH4+ with other nutrients is a chief determinant of ammonium-use efficiency (AUE) and of the tipping point toward ammonium toxicity, but these interactions have remained ill-defined. Here, we report that iron (Fe) accumulation is a critical factor determining AUE and have identified a substance that can enhance AUE by manipulating Fe availability. Fe accumulation under NH4+ nutrition induces NH4+ efflux in the root system, reducing both growth and AUE in Arabidopsis (Arabidopsis thaliana). Low external availability of Fe and a low plant Fe status substantially enhance protein N-glycosylation through a Vitamin C1-independent pathway, thereby reducing NH4+ efflux to increase AUE during the vegetative stage in Arabidopsis under elevated NH4+ supply. We confirm the validity of the iron-ammonium interaction in the important crop species lettuce (Lactuca sativa). We further show that dolomite can act as an effective substrate to subdue Fe accumulation under NH4+ nutrition by reducing the expression of Low Phosphate Root 2 and acidification of the rhizosphere. Our findings present a strategy to improve AUE and reveal the underlying molecular-physiological mechanism.

Decreased erythrocyte aggregation in Glenn and Fontan: univentricular circulation as a rheologic disease model.

BACKGROUND: In the Fontan palliation for single ventricle heart disease (SVHD), pulmonary blood flow is non-pulsatile/passive, low velocity, and low shear, making viscous power loss a critical determinant of cardiac output. The rheologic properties of blood in SVHD patients are essential for understanding and modulating their limited cardiac output and they have not been systematically studied. We hypothesize that viscosity is decreased in single ventricle circulation. METHODS: We evaluated whole blood viscosity, red blood cell (RBC) aggregation, and RBC deformability to evaluate changes in healthy children and SVHD patients. We altered suspending media to understand cellular and plasma differences contributing to rheologic differences. RESULTS: Whole blood viscosity was similar between SVHD and healthy at their native hematocrits, while viscosity was lower at equivalent hematocrits for SVHD patients. RBC deformability is increased, and RBC aggregation is decreased in SVHD patients. Suspending SVHD RBCs in healthy plasma resulted in increased RBC aggregation and suspending healthy RBCs in SVHD plasma resulted in lower RBC aggregation. CONCLUSIONS: Hematocrit corrected blood viscosity is lower in SVHD vs. healthy due to decreased RBC aggregation and higher RBC deformability, a viscous adaptation of blood in patients whose cardiac output is dependent on minimizing viscous power loss. IMPACT: Patients with single ventricle circulation have decreased red blood cell aggregation and increased red blood cell deformability, both of which result in a decrease in blood viscosity across a large shear rate range. Since the unique Fontan circulation has very low-shear and low velocity flow in the pulmonary arteries, blood viscosity plays an increased role in vascular resistance, therefore this work is the first to describe a novel mechanism to target pulmonary vascular resistance as a modifiable risk factor. This is a novel, modifiable risk factor in this patient population.

Effect of Hospital Cancer Designation on use of Multimodal Therapy and Survival of Metastatic Colorectal Cancer: A State-Wide Analysis.

BACKGROUND: Stage IV colorectal cancer (CRC) often requires multidisciplinary approach. However, multimodal treatment options (receipt of > 1 type of treatment) may not be uniformly delivered across health systems. We characterized the association between center-level cancer center designation and receipt of multimodal treatment and survival. METHODS: The Texas Cancer Registry was used to identify patients diagnosed with stage IV CRC from 2004-2017. We identified those who received care at either: a National Cancer Institute-designated (NCI-D), an American College of Surgeons-Commission on Cancer-designated (ACS-D), or an undesignated facility. We used multivariable logistic regression and Cox regression for analysis to assess receipt of one or more treatment modality and 5-year overall survival. RESULTS: Of 19,355 patients with stage IV CRC, 2955 (15%) received care at an NCI-D facility and 5871 (30%) received multimodal therapy. Both NCI-D (odds ratio [OR] 1.64; 95% confidence interval [CI] 1.49-1.81) and ACS-D (OR 1.37; 95% CI 1.27-1.48) were associated with increased likelihood of multimodal therapy compared with undesignated centers. NCI-D also was associated with significantly improved survival (hazard ratio [HR] 0.74; 95% CI 0.70-0.78), although ACS-D was associated with a modest improvement in survival (HR 0.95; 95% CI 0.92-0.99). Receipt of multimodal therapy was strongly associated with improved survival (HR 0.61; 95% CI 0.59-0.63). CONCLUSIONS: In patients with stage IV CRC, treatment at ACS-D and NCI-D facilities was associated with increased use of multimodality therapy and improved survival. However, only a small proportion of patients have access to these specialized centers, highlighting a need for expanded access to multimodal therapies at other centers.