Analyzing nursing students' mental health profiles at the onset of COVID-19.

The purpose of this descriptive-exploratory study was to identify profiles of mental health among undergraduate nursing students to understand the relationship between student's mental health profiles and relevant risk and protective factors at the onset of COVID-19. Latent Class Analysis (LCA) was employed to cull these students' mental health profiles (yielding 3 profiles) using data collected from 277 participants enrolled in a four-year BSN Program at a large, public institution in the Southeastern United States. Relational analyses of these profiles indicated that students who were the most vulnerable for mental health challenges also had the highest resilience and coping scores.

CycleGAN with mutual information loss constraint generates structurally aligned CT images from functional EIT images.

Electrical impedance tomography (EIT) has been employed in the field of medical imaging due to its cost effectiveness, safety profile and portability, but the images generated are relatively low resolution. To address these limitations, we create a novel method using EIT images to generate high resolution structurally aligned images of lungs like those from CT scans. A way to achieve this transformation is via Cycle generative adversarial networks (CycleGAN), which have demonstrated image-to-image translation capabilities across different modalities. However, a generic implementation yields images which may not be aligned with their input image. To solve this issue, we construct and incorporate a Mutual Information (MI) constraint in CycleGAN to translate functional lung EIT images to structural high resolution CT images. The CycleGAN is first trained on unpaired EIT and CT lung images. Afterwards, we generate CT image pairs from EIT images via CycleGANs constrained with MI loss and without this loss. Finally, through generating these 1560 CT image pairs and then comparing the visual results and quantitative metrics, we show that MI constrained CycleGAN produces more structurally aligned CT images, where Normalised Mutual Information (NMI) is increased to 0.2621+/- 0.0052 versus 0.2600 +/- 0.0066, p<0.0001 for non-MI constrained images. By this process, we simultaneously provide functional and structural information, and potentially enable more detailed assessment of lungs.Clinical Relevance- By establishing a structurally aligning generative process via MI Loss in CycleGAN, this study enables EIT-CT conversion, thereby providing functional and structural images for enhanced lung assessment, from just EIT images.

The Non-Invasive Prediction of Colorectal Neoplasia (NIPCON) Study 1995-2022: A Comparison of Guaiac-Based Fecal Occult Blood Test (FOBT) and an Anti-Adenoma Antibody, Adnab-9.

Given the need to improve the sensitivity of non-invasive methods to detect colorectal neoplasia, particularly adenomas, we compared a fecal test using a monoclonal antibody (Mab) raised against constituents of colonic adenomas designated Adnab-9 (Adenoma Antibody 9), recognizing an N-linked 87 kDa glycoprotein, to gFOBT, which is shown to reduce CRC mortality. p87 immunohistochemistry testing is significantly more sensitive (OR 3.64[CI 2.37-5.58]) than gFOBT (guaiac-based fecal occult blood test) for adenomas (<3 in number), advanced adenomas (OR 4.21[CI 2.47-7.15]), or a combination of the two (OR 3.35[CI 2.47-4.53]). p87 immunohistochemistry shows regional Paneth cell (PC) expression mainly in the right-sided colon and is significantly reduced in the ceca of African Americans (p < 0.0001). In a subset of patients, we obtained other body fluids such as urine, colonic effluent, and saliva. Urine tests (organ-specific neoantigen) showed a significant difference for advanced adenomas (p < 0.047). We conclude that fecal p87 testing is more sensitive than gFOBT and Adnab-9 and could be used to better direct the colonoscopy screening effort.

"The Terrors of Kingly Power": The Unusual Dental Pathology of King Pyrrhus of Epirus.

Pyrrhus of Epirus, widely respected and feared by his contemporaries, was a legendary figure in the ancient world. In this paper, we investigate Plutarch's description of the king's unique dental pathology. There are several possibilities to explain the ancient king's presentation, including several different types of developmental dysplasia. However, our conclusion is that it was likely due to a significant dental calculus overgrowth, often seen in the ancient Greek diet of the time. Whatever the underlying cause, Pyrrhus' intimidating visage helped secure the king a legacy that lasts to this day.

The Polyanionic Drug Suramin Neutralizes Histones and Prevents Endotheliopathy.

Drugs are needed to protect against the neutrophil-derived histones responsible for endothelial injury in acute inflammatory conditions such as trauma and sepsis. Heparin and other polyanions can neutralize histones but challenges with dosing or side effects such as bleeding limit clinical application. In this study, we demonstrate that suramin, a widely available polyanionic drug, completely neutralizes the toxic effects of individual histones, but not citrullinated histones from neutrophil extracellular traps. The sulfate groups on suramin form stable electrostatic interactions with hydrogen bonds in the histone octamer with a dissociation constant of 250 nM. In cultured endothelial cells (Ea.Hy926), histone-induced thrombin generation was significantly decreased by suramin. In isolated murine blood vessels, suramin abolished aberrant endothelial cell calcium signals and rescued impaired endothelial-dependent vasodilation caused by histones. Suramin significantly decreased pulmonary endothelial cell ICAM-1 expression and neutrophil recruitment caused by infusion of sublethal doses of histones in vivo. Suramin also prevented histone-induced lung endothelial cell cytotoxicity in vitro and lung edema, intra-alveolar hemorrhage, and mortality in mice receiving a lethal dose of histones. Protection of vascular endothelial function from histone-induced damage is a novel mechanism of action for suramin with therapeutic implications for conditions characterized by elevated histone levels.

In the SARS-CoV-2 Pandora Pandemic: Can the Stance of Premorbid Intestinal Innate Immune System as Measured by Fecal Adnab-9 Binding of p87:Blood Ferritin, Yielding the FERAD Ratio, Predict COVID-19 Susceptibility and Survival in a Prospective Population Database?

SARS-CoV-2 severity predictions are feasible, though individual susceptibility is not. The latter prediction allows for planning vaccination strategies and the quarantine of vulnerable targets. Ironically, the innate immune response (InImS) is both an antiviral defense and the potential cause of adverse immune outcomes. The competition for iron has been recognized between both the immune system and invading pathogens and expressed in a ratio of ferritin divided by p87 (as defined by the Adnab-9 ELISA stool-binding optical density, minus the background), known as the FERAD ratio. Associations with the FERAD ratio may allow predictive modeling for the susceptibility and severity of disease. We evaluated other potential COVID-19 biomarkers prospectively. Patients with PCR+ COVID-19 tests (Group 1; n = 28) were compared to three other groups. In Group 2 (n = 36), and 13 patients displayed COVID-19-like symptoms but had negative PCR or negative antibody tests. Group 3 (n = 90) had no symptoms and were negative when routinely PCR-tested before medical procedures. Group 4 (n = 2129) comprised a pool of patients who had stool tests and symptoms, but their COVID-19 diagnoses were unknown; therefore, they were chosen to represent the general population. Twenty percent of the Group 4 patients (n = 432) had sufficient data to calculate their FERAD ratios, which were inversely correlated with the risk of COVID-19 in the future. In a case report of a neonate, we studied three biomarkers implicated in COVID-19, including p87, Src (cellular-p60-sarcoma antigen), and Abl (ABL-proto-oncogene 2). The InImS of the first two were positively correlated. An inverse correlation was found between ferritin and lysozyme in serum (p < 0.05), suggesting that iron could have impaired an important innate immune system anti-viral effector and could partially explain future COVID-19 susceptibility.

Dynamics of release factor recycling during translation termination in bacteria.

In bacteria, release of newly synthesized proteins from ribosomes during translation termination is catalyzed by class-I release factors (RFs) RF1 or RF2, reading UAA and UAG or UAA and UGA codons, respectively. Class-I RFs are recycled from the post-termination ribosome by a class-II RF, the GTPase RF3, which accelerates ribosome intersubunit rotation and class-I RF dissociation. How conformational states of the ribosome are coupled to the binding and dissociation of the RFs remains unclear and the importance of ribosome-catalyzed guanine nucleotide exchange on RF3 for RF3 recycling in vivo has been disputed. Here, we profile these molecular events using a single-molecule fluorescence assay to clarify the timings of RF3 binding and ribosome intersubunit rotation that trigger class-I RF dissociation, GTP hydrolysis, and RF3 dissociation. These findings in conjunction with quantitative modeling of intracellular termination flows reveal rapid ribosome-dependent guanine nucleotide exchange to be crucial for RF3 action in vivo.

Improvement of Therapeutic Value of Quercetin with Chitosan Nanoparticle Delivery Systems and Potential Applications.

This paper reviews recent studies investigating chitosan nanoparticles as drug delivery systems for quercetin. The therapeutic properties of quercetin include antioxidant, antibacterial and anti-cancer potential, but its therapeutic value is limited by its hydrophobic nature, low bioavailability and fast metabolism. Quercetin may also act synergistically with other stronger drugs for specific disease states. The encapsulation of quercetin in nanoparticles may increase its therapeutic value. Chitosan nanoparticles are a popular candidate in preliminary research, but the complex nature of chitosan makes standardisation difficult. Recent studies have used in-vitro, and in-vivo experiments to study the delivery of quercetin alone or in combination with another active pharmaceutical ingredient encapsulated in chitosan nanoparticles. These studies were compared with the administration of non-encapsulated quercetin formulation. Results suggest that encapsulated nanoparticle formulations are better. In-vivo or animal models simulated the type of disease required to be treated. The types of diseases were breast, lung, liver and colon cancers, mechanical and UVB-induced skin damage, cataracts and general oxidative stress. The reviewed studies included various routes of administration: oral, intravenous and transdermal routes. Although toxicity tests were often included, it is believed that the toxicity of loaded nanoparticles needs to be further researched, especially when not orally administered.

A Case of Esophago-Respiratory Fistula due to Inhalation Smoke Injury Diagnosed by Upper Endoscopy.

Esophago-respiratory fistula (ERF) refers to the formation of a pathological connection between the esophagus and respiratory tract. Acquired ERF is a rare but life-threatening diagnosis in adults. We describe a 79-year-old male who was admitted with an inhalation smoke injury. He was diagnosed with ERF by endoscopic visualization and sampling of the hyaline cartilage within the wall of the esophagus. Percutaneous endoscopic gastrostomy placement and conservative measures were effective in the management of ERF.

Two closely related ureotelic fish species of the genus Alcolapia express different levels of ammonium transporters in gills.

Most fish excrete their nitrogenous waste across the gills as ammonia through the activity of the Rhesus glycoprotein ammonium transporters. In contrast, fish of the subgenus Alcolapia (Oreochromis) are the only vertebrates that survive the extreme conditions of the soda lakes of Natron and Magadi in East Africa and have evolved adaptations to the highly alkaline waters including the ability to excrete their nitrogenous waste as urea. Nevertheless, Alcolapia retain the Rhesus glycoprotein genes in their genomes and using two heterologous expression systems, we demonstrate that Alcolapia Rhbg is capable of moving ammonia. Comparing ammonia and urea excretion from two closely related Alcolapia species from the same aquarium, we found that while Alcolapia grahami remains fully ureotelic after many generations in lab conditions, Alcolapia alcalica excretes some of its nitrogenous waste as ammonia. Using in situ hybridisation, we demonstrate robust, localised gene expression of Rhbg, rhcg1 and rhcg2 in the gill tissue in both A. alcalica embryos and adults, similar to that in other ammoniotelic fish. In contrast, the expression of these genes in A. grahami gills is much lower than in A. alcalica, suggesting the rapid evolution of a molecular mechanism underlying the complete ureotelism of A. grahami.

Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy.

BACKGROUND: Trauma patients with abnormal fibrinolysis have increased morbidity and mortality. Knowledge of mechanisms differentiating fibrinolytic phenotypes is important to optimize treatment. We hypothesized that subjects with abnormal fibrinolysis identified by whole blood viscoelastometry can also be distinguished by plasma thrombin generation, clot structure, fibrin formation, and plasmin generation measurements. METHODS: Platelet-poor plasma (PPP) from an observational cross-sectional trauma cohort with fibrinolysis shutdown (% lysis at 30 minutes [LY30] < 0.9, n = 11) or hyperfibrinolysis (LY30 > 3%, n = 9) defined by whole blood thromboelastography were studied. Noninjured control subjects provided comparative samples. Thrombin generation, fibrin structure and formation, and plasmin generation were measured by fluorescence, confocal microscopy, turbidity, and a fluorescence-calibrated plasmin assay, respectively, in the absence/presence of tissue factor or tissue plasminogen activator (tPA). RESULTS: Whereas spontaneous thrombin generation was not detected in PPP from control subjects, PPP from hyperfibrinolysis or shutdown patients demonstrated spontaneous thrombin generation, and the lag time was shorter in hyperfibrinolysis versus shutdown. Addition of tissue factor masked this difference but revealed increased thrombin generation in hyperfibrinolysis samples. Compared with shutdown, hyperfibrinolysis PPP formed denser fibrin networks. In the absence of tPA, the fibrin formation rate was faster in shutdown than hyperfibrinolysis, but hyperfibrinolysis clots lysed spontaneously; these differences were masked by addition of tPA. Tissue plasminogen activator-stimulated plasmin generation was similar in hyperfibrinolysis and shutdown samples. Differences in LY30, fibrin structure, and lysis correlated with pH. CONCLUSION: This exploratory study using PPP-based assays identified differences in thrombin generation, fibrin formation and structure, and lysis in hyperfibrinolysis and shutdown subgroups. These groups did not differ in their ability to promote tPA-triggered plasmin generation. The ability to characterize these activities in PPP facilitates studies to identify mechanisms that promote adverse outcomes in trauma. LEVEL OF EVIDENCE: Prognostic/Epidemiological; Level III.

Efficacy of the scatter correction algorithm in portable chest radiography.

PURPOSE: Portable chest radiographs (CXRs) continue to be a vital diagnostic tool for emergency and critical care medicine. The scatter correction algorithm (SCA) is a post-processing algorithm aiming to reduce scatter within portable images. This study aimed to assess whether the SCA improved image quality (IQ) in portable CXRs. METHODS: Objective and subjective IQ assessments were undertaken on both phantom and clinical images, respectively. For objective analysis, attenuators were placed on the anterior surface of the patient's thorax to simulate pathologies present within uniform regions of the phantom's lung and heart. Phantom CXRs were acquired with three different tube-current-times (mAs). Phantom images were processed with different SCA strengths. Contrast to noise ratios (CNR) within the attenuator were determined for each algorithm strength and compared to non-SCA images. For subjective analysis, two independent radiologists graded 30 clinical images with and without the SCA activated. The images were graded for IQ in different anatomical structures and overall diagnostic confidence. RESULTS: Objectively, most strengths of the SCA improved the CNR in both regions. However, a detrimental effect was recorded for some algorithm strengths in regions of high contrast. Subjectively, both observers recorded the SCA significantly improved IQ in clinical CXRs in all anatomical regions. Observers indicated the greatest improvement in the lung and hilar regions, and least improvement in the chest wall and bone. All images with and without the SCA were deemed diagnostic. CONCLUSION: This study shows the potential radiation dose neutral IQ improvement when using an SCA in clinical patient CXRs.

Attention deficit hyperactivity disorder medications and bone mineral density of adults in the United States.

Introduction: Several medications used to treat attention deficit hyperactivity disorder (ADHD) have been associated with diminished bone mineral density (BMD) in children. The objective of this study was to determine if evidence exists for a similar association among adults. Materials and methods: A retrospective cross-sectional analysis was conducted using data collected by the National Health Nutrition Examination Survey 2013-2018. Data from 7961 individuals aged 18 to 50, 79 of whom were taking medications to treat ADHD. Dual-energy X-ray absorptiometry scans provided measure of body composition. Linear regression models were used to examine associations between ADHD medication use and body composition. Results: Stimulant ADHD medication usage was found to be associated with decreased BMD in both the skull (-6.6%; 95% CI 5.9-7.2) (P < 0.05) and thoracic spine (-6.0%; 95% CI 5.1-7.0) (P < 0.05). No difference in BMD was seen in any other skeletal region based on stimulant ADHD medication use (P > 0.05). We found no evidence to suggest that duration of use affected the observed decreases in BMD, P > 0.05. Conclusion: This study using a nationally representative sample assessed whether stimulant medication use in adults with ADHD was associated with decreased BMD. The overall results are inconclusive. Further study is needed to better evaluate if ADHD and/or stimulant medication use is independently associated with bone health.

Comparison of organ and effective dose estimations from different Monte Carlo simulation-based software methods in infant CT and comparison with direct phantom measurements.

PURPOSE: Computational dosimetry software is routinely used to evaluate the organ and effective doses from computed tomography (CT) examinations. Studies have shown a significant variation in dose estimates between software in adult cohorts, and few studies have evaluated software for pediatric dose estimates. This study aims to compare the primary organ and effective doses estimated by four commercially available CT dosimetry software to thermoluminescent dosimeter (TLD) measurements in a 1-year-old phantom. METHODS: One hundred fifteen calibrated LiF (Mg, Cu, P)-TLD 100-H chips were embedded within an anthropomorphic phantom representing a 1-year-old child at positions that matched the approximate location of organs within an infant. The phantom was scanned under three protocols, each with whole-body coverage. The mean absorbed doses from 25 radiosensitive organs and skeletal tissues were determined from the TLD readings. Effective doses for each of the protocols were subsequently calculated using ICRP 103 formalism. Dose estimates by the four Monte Carlo-based dose calculation systems were determined and compared to the directly measured doses. RESULTS: Most organ doses determined by computation dosimetry software aligned to phantom measurements within 20%. Additionally, comparisons between effective doses are calculated using computational and direct measurement methods aligned within 20% across the three protocols. Significant variances were found in bone surface dose estimations among dosimetry methods, likely caused by differences in bone tissue modeling. CONCLUSION: All four-dosimetry software evaluated in this study provide adequate primary organ and effective dose estimations. Users should be aware, however, of the possible estimated uncertainty associated with each of the programs.

A positive feedback loop involving the Spa2 SHD domain contributes to focal polarization.

Focal polarization is necessary for finely arranged cell-cell interactions. The yeast mating projection, with its punctate polarisome, is a good model system for this process. We explored the critical role of the polarisome scaffold protein Spa2 during yeast mating with a hypothesis motivated by mathematical modeling and tested by in vivo experiments. Our simulations predicted that two positive feedback loops generate focal polarization, including a novel feedback pathway involving the N-terminal domain of Spa2. We characterized the latter using loss-of-function and gain-of-function mutants. The N-terminal region contains a Spa2 Homology Domain (SHD) which is conserved from yeast to humans, and when mutated largely reproduced the spa2Δ phenotype. Our work together with published data show that the SHD domain recruits Msb3/4 that stimulates Sec4-mediated transport of Bud6 to the polarisome. There, Bud6 activates Bni1-catalyzed actin cable formation, recruiting more Spa2 and completing the positive feedback loop. We demonstrate that disrupting this loop at any point results in morphological defects. Gain-of-function perturbations partially restored focal polarization in a spa2 loss-of-function mutant without restoring localization of upstream components, thus supporting the pathway order. Thus, we have collected data consistent with a novel positive feedback loop that contributes to focal polarization during pheromone-induced polarization in yeast.

COVID-19 pandemic and the effect of increased utilisation of mobile X-ray examinations on radiation dose to radiographers.

INTRODUCTION: The use of ionising radiation results in occupational exposure to medical imaging professionals, requiring routine monitoring. This study aims to assess the effect of increased utilisation of mobile X-ray units, mobile imaging of non-routine body regions and radiographer work practice changes for impact on staff radiation dose during the early stages of the COVID-19 pandemic. METHODS: A retrospective analysis of general radiology departments across two metropolitan hospitals was performed. Personal radiation monitor exposure reports between January 2019 and December 2020 were analysed. Statistical analysis was conducted using a Mann-Whitney U test when comparing each quarter, from 2019 to 2020. Categorical data were compared using a Chi-squared test. RESULTS: Mobile X-ray use during the pandemic increased approximately 1.7-fold, with the peak usage observed in September 2020. The mobile imaging rate per month of non-routine body regions increased from approximately 6.0-7.8%. Reported doses marginally increased during Q2, Q3 and Q4 of 2020 (in comparison to 2019 data), though was not statistically significant (Q2: P = 0.13; Q3: P = 0.31 and Q4 P = 0.32). In Q1, doses marginally decreased and were not statistically significant (P = 0.22). CONCLUSION: Increased utilisation and work practice changes had no significant effect on reported staff radiation dose. The average reported dose remained significantly lower than the occupational dose limits for radiation workers of 20 mSv.

Using Computed Tomography skeletal surveys to evaluate for occult bony injury in suspected non-accidental injury cases - A preliminary experience.

INTRODUCTION: This case series summarises our institution's preliminary experience of using computed tomography skeletal surveys (CT-SS) for the assessment of infants with suspected non-accidental injury (NAI) who were unable to undergo radiographic skeletal surveys (SS). This paper describes our experience using CT-SS in terms of radiation doses achieved, occult bony injury detection and forensic utility. METHODS: Ten infants aged between two weeks and ten months underwent a CT-SS. The results of the CT-SS were compared with concurrent imaging results where available. Radiation doses from imaging procedures were calculated for each patient. RESULTS: Six infants had abnormalities identified on CT-SS. Two patients had both an ante-mortem CT-SS and post-mortem imaging. All fractures identified on alternate imaging modalities were visible on at least one CT-SS reconstruction. The radiation dose associated with CT-SS imaging ranged from 0.73 to 1.46mSv. CONCLUSION: The radiation dose received by the ten infants in this study was greater than the two skeletal survey approach but was less than the dose received during a bone scintigraphy examination, sometimes used to assess for occult bony injury in this setting. While CT-SS imaging results could not be compared with those obtained with current contemporaneous gold standard imaging techniques, CT-SS identified all fractures observed on the radiographic images where performed. CT-SS also identified additional rib fractures in two patients. Our preliminary findings indicate the need for future prospective studies to clarify the ability of CT-SS to detect metaphyseal fractures reliably.

Increased histone-DNA complexes and endothelial-dependent thrombin generation in severe COVID-19.

Coagulopathy in severe COVID-19 is common but poorly understood. The purpose of this study was to determine how SARS-CoV-2 infection impacts histone levels, fibrin structure, and endogenous thrombin potential in the presence and absence of endothelial cells. We studied individuals with SARS-CoV-2 infection and acute respiratory distress syndrome at the time of initiation of mechanical ventilation compared to healthy controls. Circulating histone-DNA complexes were elevated in the plasma of COVID-19 patients relative to healthy controls (n=6, each group). Using calibrated automated thrombography, thrombin generation was altered in COVID-19 patient plasma samples. Despite having increased endogenous thrombin potential, patient plasma samples exhibited prolonged lag times and times to peak thrombin in the presence of added tissue factor and PCPS. Strikingly different results were observed when endothelial cells were used in place of tissue factor and PCPS. While healthy control plasma samples did not generate measurable thrombin after 60 min, plasma samples from COVID-19+ patients formed thrombin (mean lag time ~20 min). Consistent with the observed alterations in thrombin generation, clots from COVID-19 subjects exhibited a denser fibrin network, thinner fibers and lower fibrin resolvability. Elevated histones, aberrant fibrin formation, and increased endothelial-dependent thrombin generation may contribute to coagulopathy in COVID-19.

A review of current imaging techniques used for the detection of occult bony fractures in young children suspected of sustaining non-accidental injury.

Non-accidental injuries remain a leading cause of preventable morbidity and mortality in young children. The accurate identification of the full spectrum of injuries in children presenting with suspected abuse is essential to ensure the appropriate protective intervention is taken. The identification of occult bone fractures in this cohort is important as it raises the level of concern about the mechanism of injury and maintaining the child's safety. Radiographic imaging remains the modality of choice for skeletal assessment; however, current studies report concerns regarding the ability of radiographs to detect certain fractures in the acute stage. As such, alternative modalities for the detection of fractures have been proposed. This article reviews the current literature regarding fracture detectability and radiation dose burden of imaging modalities currently used for the assessment of occult bony injury in young children in whom non-accidental injury is suspected.

High-Dimensional Precision Medicine From Patient-Derived Xenografts.

The complexity of human cancer often results in significant heterogeneity in response to treatment. Precision medicine offers the potential to improve patient outcomes by leveraging this heterogeneity. Individualized treatment rules (ITRs) formalize precision medicine as maps from the patient covariate space into the space of allowable treatments. The optimal ITR is that which maximizes the mean of a clinical outcome in a population of interest. Patient-derived xenograft (PDX) studies permit the evaluation of multiple treatments within a single tumor, and thus are ideally suited for estimating optimal ITRs. PDX data are characterized by correlated outcomes, a high-dimensional feature space, and a large number of treatments. Here we explore machine learning methods for estimating optimal ITRs from PDX data. We analyze data from a large PDX study to identify biomarkers that are informative for developing personalized treatment recommendations in multiple cancers. We estimate optimal ITRs using regression-based (Q-learning) and direct-search methods (outcome weighted learning). Finally, we implement a superlearner approach to combine multiple estimated ITRs and show that the resulting ITR performs better than any of the input ITRs, mitigating uncertainty regarding user choice. Our results indicate that PDX data are a valuable resource for developing individualized treatment strategies in oncology. Supplementary materials for this article are available online.