Estimated public health impact of concurrent mask mandate and vaccinate-or-test requirement in Illinois, October to December 2021.

BACKGROUND: Facing a surge of COVID-19 cases in late August 2021, the U.S. state of Illinois re-enacted its COVID-19 mask mandate for the general public and issued a requirement for workers in certain professions to be vaccinated against COVID-19 or undergo weekly testing. The mask mandate required any individual, regardless of their vaccination status, to wear a well-fitting mask in an indoor setting. METHODS: We used Illinois Department of Public Health's COVID-19 confirmed case and vaccination data and investigated scenarios where masking and vaccination would have been reduced to mimic what would have happened had the mask mandate or vaccine requirement not been put in place. The study examined a range of potential reductions in masking and vaccination mimicking potential scenarios had the mask mandate or vaccine requirement not been enacted. We estimated COVID-19 cases and hospitalizations averted by changes in masking and vaccination during the period covering October 20 to December 20, 2021. RESULTS: We find that the announcement and implementation of a mask mandate are likely to correlate with a strong protective effect at reducing COVID-19 burden and the announcement of a vaccinate-or-test requirement among frontline professionals is likely to correlate with a more modest protective effect at reducing COVID-19 burden. In our most conservative scenario, we estimated that from the period of October 20 to December 20, 2021, the mask mandate likely prevented approximately 58,000 cases and 1,175 hospitalizations, while the vaccinate-or-test requirement may have prevented at most approximately 24,000 cases and 475 hospitalizations. CONCLUSION: Our results indicate that mask mandates and vaccine-or-test requirements are vital in mitigating the burden of COVID-19 during surges of the virus.

Assessment of Chemical Exposures Investigation After Fire at an Industrial Chemical Facility in Winnebago County, Illinois.

After a chemical fire, an investigation assessed health effects by using syndromic surveillance to monitor emergency department (ED) visits, a general health survey to assess the general public, and a first responders health survey to assess first responders. A total of four separate multivariable logistic regression models were developed to examine associations between reported exposure to smoke, dust, debris, or odor with any reported symptom in the general public. Syndromic surveillance identified areas with increased ED visits. Among general health survey respondents, 45.1% (911 out of 2,020) reported at least one symptom. Respondents reporting exposure to smoke, dust, debris, or odor had 4.5 (95% confidence interval (CI) [3.7, 5.5]), 4.6 (95% CI [3.6, 5.8]), 2.0 (95% CI [1.7, 2.5]), or 5.8 (95% CI [4.7, 7.3]) times the odds of reporting any symptom compared with respondents not reporting exposure to smoke, dust, debris, or odor, respectively. First responders commonly reported contact with material and being within 1 mi of the fire ≥5 hr; 10 out of 31 of first responders reported at least one symptom. There was high symptom burden reported after the fire. Results from our investigation might assist the directing of public health resources to effectively address immediate community needs and prepare for future incidents.

Measurement invariance of physical, mental, and social health PROMIS measures across individuals with spinal cord injury and traumatic brain injury.

PURPOSE: The present study tested the fit and comparability of the tripartite model of health (Physical Health, Mental Health, and Social Health) proposed by the NIH PROMIS for adults with SCI and TBI. METHODS: Participants were 630 adults with spinal cord injury (SCI; n = 336) and traumatic brain injury (TBI; n = 294) who completed 8 PROMIS short forms. The Physical Health domain is composed of the Physical Function, Pain Interference, and Fatigue scales. The Mental Health domain included the Depression, Anxiety, and Anger scales. Social Health included the Social Emotional Support scale. RESULTS: Confirmatory factor analyses supported the tripartite model of health over a unifactorial model of health for both SCI and TBI groups. Measurement invariance testing indicated the tripartite model met the level of configural and metric invariance for TBI and SCI groups, suggesting comparable structure and factor loadings. Failure to meet the level of scalar invariance indicated unequal intercepts across groups. Physical Function was identified as the source of noninvariance, and a partial scalar invariance model permitting different Physical Function intercepts across conditions was supported. CONCLUSION: Consistent with theory, findings supported construct validity of the PROMIS tripartite structure of health composed of Physical, Mental, and Social Health. PROMIS measures appeared to tap domains of health consistent with what is accepted for SCI and TBI populations, although the measurement of Physical Function was not equivalent across groups. Findings support the utility of PROMIS broadly as well as the need for condition-optimized measurement.

Epidemiologically Linked COVID-19 Outbreaks at a Youth Camp and Men's Conference - Illinois, June-July 2021.

On June 30, 2021, the Illinois Department of Public Health (IDPH) contacted CDC concerning COVID-19 outbreaks at two events sponsored by the same organization: a 5-day overnight church camp for persons aged 14-18 years and a 2-day men's conference. Neither COVID-19 vaccination nor COVID-19 testing was required before either event. As of August 13, a total of 180 confirmed and probable cases had been identified among attendees at the two events and their close contacts. Among the 122 cases associated with the camp or the conference (primary cases), 18 were in persons who were fully vaccinated, with 38 close contacts. Eight of these 38 close contacts subsequently became infected with SARS-CoV-2, the virus that causes COVID-19 (secondary cases); among the eight close contacts with secondary cases, one half (four) were fully vaccinated. Among the 180 total persons with outbreak-associated cases, five (2.8%) were hospitalized; no deaths occurred. None of the vaccinated persons with cases were hospitalized. Approximately 1,000 persons across at least four states were exposed to SARS-CoV-2 through attendance at these events or through close contact with a person who had a primary case. This investigation underscores the impact of secondary SARS-CoV-2 transmission during large events, such as camps and conferences, when COVID-19 prevention strategies are not implemented. In Los Angeles County, California, during July 2021, when the SARS-CoV-2 B.1.617.2 (Delta) variant was predominant, unvaccinated residents were five times more likely to be infected and 29 times more likely to be hospitalized from infection than were vaccinated residents (1). Implementation of multiple prevention strategies, including vaccination and nonpharmaceutical interventions such as masking, physical distancing, and screening testing, are critical to preventing SARS-CoV-2 transmission and serious complications from COVID-19.

Geographic and demographic heterogeneity of SARS-CoV-2 diagnostic testing in Illinois, USA, March to December 2020.

BACKGROUND: Availability of SARS-CoV-2 testing in the United States (U.S.) has fluctuated through the course of the COVID-19 pandemic, including in the U.S. state of Illinois. Despite substantial ramp-up in test volume, access to SARS-CoV-2 testing remains limited, heterogeneous, and insufficient to control spread. METHODS: We compared SARS-CoV-2 testing rates across geographic regions, over time, and by demographic characteristics (i.e., age and racial/ethnic groups) in Illinois during March through December 2020. We compared age-matched case fatality ratios and infection fatality ratios through time to estimate the fraction of SARS-CoV-2 infections that have been detected through diagnostic testing. RESULTS: By the end of 2020, initial geographic differences in testing rates had closed substantially. Case fatality ratios were higher in non-Hispanic Black and Hispanic/Latino populations in Illinois relative to non-Hispanic White populations, suggesting that tests were insufficient to accurately capture the true burden of COVID-19 disease in the minority populations during the initial epidemic wave. While testing disparities decreased during 2020, Hispanic/Latino populations consistently remained the least tested at 1.87 tests per 1000 population per day compared with 2.58 and 2.87 for non-Hispanic Black and non-Hispanic White populations, respectively, at the end of 2020. Despite a large expansion in testing since the beginning of the first wave of the epidemic, we estimated that over half (50-80%) of all SARS-CoV-2 infections were not detected by diagnostic testing and continued to evade surveillance. CONCLUSIONS: Systematic methods for identifying relatively under-tested geographic regions and demographic groups may enable policymakers to regularly monitor and evaluate the shifting landscape of diagnostic testing, allowing officials to prioritize allocation of testing resources to reduce disparities in COVID-19 burden and eventually reduce SARS-CoV-2 transmission.

A respiratory health survey of a subsurface smoldering landfill.

In late 2010, a subsurface smoldering event was detected in the Bridgeton Sanitary Landfill in St. Louis County, Missouri. This was followed by complaints from nearby residents of foul odors emanating from the landfill. In 2016 a health survey was conducted of residents near the landfill and, as a comparison, other regions of St. Louis County. The survey was a two-stage cluster sample, where the first stage was census blocks, and the second stage was households within the census blocks. The health survey, which was conducted by face-to-face interviews of residents both near the landfill and away from the landfill, focused mainly on respiratory symptoms and diseases such as asthma and chronic obstructive pulmonary disease. The differences in the prevalence of asthma (26.7%, 95% CI 19.8-34.1 landfill vs 24.7%, 95% CI 15.7-33.6 comparison) and COPD (13.7%, 95% CI 7.2-20.3 landfill vs 12.5%, 95% CI 6.4-18.7 comparison) between the two groups were not statistically significant. Landfill households reported significantly more "other respiratory conditions," (17.6%, 95% CI 11.1-24.1 landfill vs 9.5%, 95% CI 4.8-14.3 comparison) and attacks of shortness of breath (33.9%, 95% CI 25.1-42.8 landfill vs 17.9%, 95% CI 12.3-23.5). Frequency of odor perceptions and level of worry about neighborhood environmental issues was higher among landfill households (p < 0.001). We conclude that the results do not support the hypothesis that people living near the Bridgeton Landfill have elevated respiratory or related illness compared to those people who live beyond the vicinity of the landfill.

Mental health and wellbeing: focus on men's health.

All nurses have a responsibility to ensure that they actively promote both mental and physical health and wellbeing. This article aims to bring together current thinking and evidence about nursing and men's mental health promotion. Key areas of concern outlined are the high rate of suicide in men, the expression of depression in men and the problems of masculinity when related to seeking help for mental health. The article highlights the importance of language and the normalising of distressing feelings when working with men and suggests that nurses need to recognise how men can experience depression differently, actively identify and address suicidal thinking, and provide gender-sensitive interventions. Additionally, nurses working with men need to demonstrate 'male-positive' values and offer future-focused and action-oriented interventions (such as solution-focused, coaching or cognitive behavioural therapy approaches) that contribute to a sense of agency, promote hope and are more engaging for many men.

Will Not Want: Self-Control Rather than Motivation Explains the Female Advantage in Report Card Grades.

Girls earn better grades than boys, but the mechanism explaining this gender difference is not well understood. We examined the relative importance of self-control and motivation in explaining the female advantage in grades. In Study 1, we surveyed middle school teachers and found they judged girls to be higher in both school motivation and self-control. In Studies 2 and 3-using self-reported motivation and teacher- and/or parent-reported self-control, and quarterly and final grades obtained from school records-we find that self-control, but not school motivation, helps to explain the gender gap in academic performance. In these studies, girls appeared to be more self-controlled than boys, but-contrary to teacher judgments in Study 1-did not appear to be more motivated to do well in school.

Detecting feigned cognitive impairment using pupillometry on the Warrington Recognition Memory Test for Words.

OBJECTIVE: Pupillometry provides information about physiological and psychological processes related to cognitive load, familiarity, and deception, and it is outside of conscious control. This study examined pupillary dilation patterns during a performance validity test (PVT) among adults with true and feigned impairment of traumatic brain injury (TBI). PARTICIPANTS AND METHODS: Participants were 214 adults in three groups: adults with bona fide moderate to severe TBI (TBI; n = 51), healthy comparisons instructed to perform their best (HC; n = 72), and healthy adults instructed and incentivized to simulate cognitive impairment due to TBI (SIM; n = 91). The Recognition Memory Test (RMT) was administered in the context of a comprehensive neuropsychological battery. Three pupillary indices were evaluated. Two pure pupil dilation (PD) indices assessed a simple measure of baseline arousal (PD-Baseline) and a nuanced measure of dynamic engagement (PD-Range). A pupillary-behavioral index was also evaluated. Dilation-response inconsistency (DRI) captured the frequency with which examinees displayed a pupillary familiarity response to the correct answer but selected the unfamiliar stimulus (incorrect answer). RESULTS: All three indices differed significantly among the groups, with medium-to-large effect sizes. PD-Baseline appeared sensitive to oculomotor dysfunction due to TBI; adults with TBI displayed significantly lower chronic arousal as compared to the two groups of healthy adults (SIM, HC). Dynamic engagement (PD-Range) yielded a hierarchical structure such that SIM were more dynamically engaged than TBI followed by HC. As predicted, simulators engaged in DRI significantly more frequently than other groups. Moreover, subgroup analyses indicated that DRI differed significantly for simulators who scored in the invalid range on the RMT (n = 45) versus adults with genuine TBI who scored invalidly (n = 15). CONCLUSIONS: The findings support continued research on the application of pupillometry to performance validity assessment: Overall, the findings highlight the promise of biometric indices in multimethod assessments of performance validity.

Sensitivity of the African neuropsychology battery memory subtests and learning slopes in discriminating APOE 4 and amyloid pathology in adult individuals in the Democratic Republic of Congo.

Background: The current study examined the sensitivity of two memory subtests and their corresponding learning slope metrics derived from the African Neuropsychology Battery (ANB) to detect amyloid pathology and APOEε4 status in adults from Kinshasa, the Democratic Republic of the Congo. Methods: 85 participants were classified for the presence of ß-amyloid pathology and based on allelic presence of APOEε4 using Simoa. All participants were screened using CSID and AQ, underwent verbal and visuospatial memory testing from ANB, and provided blood samples for plasma Aß42, Aß40, and APOE proteotype. Pearson correlation, linear and logistic regression were conducted to compare amyloid pathology and APOEε4 status with derived learning scores, including initial learning, raw learning score, learning over trials, and learning ratio. Results: Our sample included 35 amyloid positive and 44 amyloid negative individuals as well as 42 without and 39 with APOEε4. All ROC AUC ranges for the prediction of amyloid pathology based on learning scores were low, ranging between 0.56-0.70 (95% CI ranging from 0.44-0.82). The sensitivity of all the scores ranged between 54.3-88.6, with some learning metrics demonstrating good sensitivity. Regarding APOEε4 prediction, all AUC values ranged between 0.60-0.69, with all sensitivity measures ranging between 53.8-89.7. There were minimal differences in the AUC values across learning slope metrics, largely due to the lack of ceiling effects in this sample. Discussion: This study demonstrates that some ANB memory subtests and learning slope metrics can discriminate those that are normal from those with amyloid pathology and those with and without APOEε4, consistent with findings reported in Western populations.

Semantic clustering on common list-learning tasks: a systematic review of the state of the literature and recommendations for future directions.

INTRODUCTION: On some list-learning tasks, such as the California Verbal Learning Test (CVLT) or Hopkins Verbal Learning Test (HVLT), examinees have the opportunity to group words based on semantically related categories (i.e., semantic clustering). Semantic clustering (SC) is often considered the most efficient organizational strategy and adopting SC is presumed to improve learning and memory. In addition, SC is conceptualized as reflecting higher-order executive functioning skills. Although SC measures have intuitive appeal, to date, there are no comprehensive reviews of the SC literature base that summarize its psychometric utility. In this systematic review, we synthesize the literature to judge the validity of SC scores. METHOD: We conducted a systematic literature search for empirical articles reporting SC from the CVLT and HVLT. We qualitatively described the relationship of SC with other list-learning and cognitive test scores and clinical diagnoses, contrasting SC with serial clustering and total learning scores when possible. RESULTS: SC was inversely correlated with serial clustering. Higher SC was strongly associated with better learning and memory performances. When compared with cognitive tests, SC tended to have the strongest relationships with other memory measures and modest relationships with tests of executive functioning. SC had negligible to small relationships with most other cognitive domains. Traditional memory scores yielded stronger relationships to cognitive test performances than did SC. SC across clinical groups varied widely, but clinical groups tended to use SC less often than healthy comparison groups. CONCLUSION: Our comprehensive review of the literature revealed that SC is strongly related to measures of learning and memory on the CVLT and HVLT and is correlated with a wide range of cognitive functions. SC has been understudied in relevant populations and additional research is needed to test the degree to which it adds incremental validity beyond traditional measures of learning and memory.

A quantitative review of competing learning slope metrics: effects of age, sex, and clinical diagnosis.

INTRODUCTION: In learning and memory tests that involve multiple presentations of the same material, learning slope refers to the degree to which examinees improve performances over successive learning trials. We aimed to quantitatively review the traditional raw learning slope (RLS), and the newly created learning ratio (LR) to understand the effects of demographic variables and clinical diagnoses on learning slope (e.g., limited improvement over multiple trials), and to develop demographically sensitive norms. METHOD: A systematic literature search was conducted to evaluate the potential for these aims to be examined across the most popular contemporary multi-trial learning tests. Two databases were searched. Following this, hierarchical linear modeling was used to examine how demographic variables predict learning slope indices. These results were in turn used to contrast the performance of clinical groups with the predicted performance of demographically similar healthy controls. Finally, preliminary normative estimates for learning slope indices were presented. RESULTS: A total of 82 studies met criteria for inclusion in this study. However, the Rey Auditory Verbal Learning Test (RAVLT) was the only test to have sufficient trial-level learning and demographic data. Fifty-eight samples from 19 studies were quantitatively examined. Hierarchical linear models provided evidence of sex differences and a curvilinear decline in learning slope with age, with strongest and most consistent effects for LR relative to RLS. Regression-based norms for demographically corrected RLS and LR scores for the RAVLT are presented. The effect of clinical diagnoses was consistently stronger for LR, and Alzheimer's disease had the strongest effect, followed by invalid performances, severe traumatic brain injury, and seizures/epilepsy. CONCLUSION: Overall, LR enjoys both conceptual and demonstrated psychometric advantages over RLS. Replication of these findings can be completed by reanalyzing existing datasets. Further work may focus on the utility of using LR in diagnosis and prediction of clinical prognosis.

Clinical recognition and management of tularemia in Missouri: a retrospective records review of 121 cases.

BACKGROUND: Clinical recognition of tularemia is essential for prompt initiation of appropriate antibiotic treatment. Although fluoroquinolones have desirable attributes as a treatment option, limited data on efficacy in the US setting exist. METHODS: To define the epidemiology of tularemia in Missouri, and to evaluate practices and outcomes of tularemia management in general, we conducted a detailed retrospective review and analysis of clinical records for patients reported to the state from 2000 to 2007. RESULTS: We reviewed records of 121 of 190 patients (64%) reported with tularemia; 79 (65%) were males; the median age was 37 years. Most patients presented with ulceroglandular (37%) and glandular (25%) forms of tularemia, followed by pneumonic (12%), typhoidal (10%), oculoglandular (3%), and oropharyngeal (2%) forms. Most cases (69%) were attributed to tick bites. Median incubation period was 3 days (range, 1-9 days), and patients sought care after a median of 3 days of illness (range, 0-44 days). Systemic disease occurred more commonly in older patients. Patients were prescribed tetracyclines (49%), aminoglycosides (47%), and fluoroquinolones (41%). Nine of 10 patients treated with ciprofloxacin for ≥10 days recovered uneventfully, without accompanying aminoglycosides or tetracyclines. CONCLUSIONS: Tularemia is frequently initially misdiagnosed. A thorough exposure history, particularly for tick bites, and awareness of clinical features may prompt clinicians to consider tularemia and facilitate appropriate testing. Promising success with oral fluoroquinolones could provide an acceptable alternative to intravenous aminoglycosides or long courses of tetracyclines where clinically appropriate.

The Patient Health Questionnaire (PHQ-9) as a tool to screen for depression in people with multiple sclerosis: a cross-sectional validation study.

BACKGROUND: Depression has a point prevalence of 25% and lifetime prevalence of 50% in people with multiple sclerosis (pwMS). Due to accessibility and brevity, the 9-item Patient Health Questionnaire (PHQ-9) may be a useful tool in clinical practice for screening and monitoring of depressive symptoms in people with MS (pwMS). METHODS: The objective of this study was to evaluate the reliability, validity and acceptability of the PHQ-9 as a screening tool for depressive symptoms in pwMS. PwMS completed online questionnaires at 3 time-points over 4-weeks. The PHQ-9, Multiple Sclerosis Impact Scale (MSIS-29), Centre for Disease Control Health-Related Quality of Life Measure (CDC-HQOL-4) and clinical history. RESULTS: 103 participants completed the PHQ-9 at three time points, 43% were categorised as depressed on at least one response. The PHQ-9 exhibited high internal reliability (Cronbach's α = 0.89), and test-re-test agreement (ICC 0.89, 95% CI 0.85-0.91). Convergent validity was indicated through positive correlation with the mental health items on the MSIS-29 (r = 0.46 and r = 0.50) and CDC-HQOL-4 (r = 0.79 and r = 0.73) at both assessment points. Positive correlations between the PHQ-9 and the MSIS-29 (r = 0.86 and r = 0.84) and CDC-HQOL-4 (r = 0.55 and r = 0.37) physical symptom sub-scores did not indicate divergent validity. 93% of ratings evaluated the PHQ-9 as "Very" or "Completely" acceptable. CONCLUSION: The PHQ-9 is a reliable and valid measure of depressive symptoms in people with MS. Given its accessibility, ease of administration, and acceptability, we recommend the PHQ-9 as a tool to screen for depressive symptoms in people with MS.

Utility of WAIS-IV Digit Span indices as measures of performance validity in moderate to severe traumatic brain injury.

Objective: The addition of Sequencing to WAIS-IV Digit Span (DS) brought about new Reliable Digit Span (RDS) indices and an Age-Corrected Scaled Score that includes Sequencing trials. Reports have indicated that these new performance validity tests (PVTs) are superior to the traditional RDS; however, comparisons in the context of known neurocognitive impairment are sparse. This study compared DS-derived PVT classification accuracies in a design that included adults with verified TBI. Methods: Participants included 64 adults with moderate-to-severe TBI (TBI), 51 healthy adults coached to simulate TBI (SIM), and 78 healthy comparisons (HC). Participants completed the WAIS-IV DS subtest in the context of a larger test battery. Results: Kruskal-Wallis tests indicated that all DS indices differed significantly across groups. Post hoc contrasts revealed that only RDS Forward and the traditional RDS differed significantly between SIM and TBI. ROC analyses indicated that RDS variables were comparable predictors of SIM vs. HC; however, the traditional RDS showed the highest sensitivity when approximating 90% specificity for SIM vs. TBI. A greater percentage of TBI scored RDS Sequencing < 1 compared to SIM and HC. Conclusion: In the context of moderate-to-severe TBI, the DS-derived PVTs showed comparable discriminability. However, the Greiffenstein et al. traditional RDS demonstrated the best classification accuracy with respect to specificity/sensitivity balance. This relative superiority may reflect that individuals with verified TBI are more likely to perseverate on prior instructions during DS Sequencing. Findings highlight the importance of including individuals with verified TBI when evaluating and developing PVTs.

Modeling robust COVID-19 intensive care unit occupancy thresholds for imposing mitigation to prevent exceeding capacities.

In non-pharmaceutical management of COVID-19, occupancy of intensive care units (ICU) is often used as an indicator to inform when to intensify mitigation and thus reduce SARS-CoV-2 transmission, strain on ICUs, and deaths. However, ICU occupancy thresholds at which action should be taken are often selected arbitrarily. We propose a quantitative approach using mathematical modeling to identify ICU occupancy thresholds at which mitigation should be triggered to avoid exceeding the ICU capacity available for COVID-19 patients and demonstrate this approach for the United States city of Chicago. We used a stochastic compartmental model to simulate SARS-CoV-2 transmission and disease progression, including critical cases that would require intensive care. We calibrated the model using daily COVID-19 ICU and hospital census data between March and August 2020. We projected various possible ICU occupancy trajectories from September 2020 to May 2021 with two possible levels of transmission increase and uncertainty in core model parameters. The effect of combined mitigation measures was modeled as a decrease in the transmission rate that took effect when projected ICU occupancy reached a specified threshold. We found that mitigation did not immediately eliminate the risk of exceeding ICU capacity. Delaying action by 7 days increased the probability of exceeding ICU capacity by 10-60% and this increase could not be counteracted by stronger mitigation. Even under modest transmission increase, a threshold occupancy no higher than 60% was required when mitigation reduced the reproductive number Rt to just below 1. At higher transmission increase, a threshold of at most 40% was required with mitigation that reduced Rt below 0.75 within the first two weeks after mitigation. Our analysis demonstrates a quantitative approach for the selection of ICU occupancy thresholds that considers parameter uncertainty and compares relevant mitigation and transmission scenarios. An appropriate threshold will depend on the location, number of ICU beds available for COVID-19, available mitigation options, feasible mitigation strengths, and tolerated durations of intensified mitigation.

Nonclinical Efficacy and Safety of CX-2029, an Anti-CD71 Probody-Drug Conjugate.

Probody therapeutics (Pb-Txs) are conditionally activated antibody-drug conjugates (ADCs) designed to remain inactive until proteolytically activated in the tumor microenvironment, enabling safer targeting of antigens expressed in both tumor and normal tissue. Previous attempts to target CD71, a highly expressed tumor antigen, have failed to establish an acceptable therapeutic window due to widespread normal tissue expression. This study evaluated whether a probody-drug conjugate targeting CD71 can demonstrate a favorable efficacy and tolerability profile in preclinical studies for the treatment of cancer. CX-2029, a Pb-Tx conjugated to maleimido-caproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E, was developed as a novel cancer therapeutic targeting CD71. Preclinical studies were performed to evaluate the efficacy and safety of this anti-CD71 PDC in patient-derived xenograft (PDX) mouse models and cynomolgus monkeys, respectively. CD71 expression was detected at high levels by IHC across a broad range of tumor and normal tissues. In vitro, the masked Pb-Tx form of the anti-CD71 PDC displayed a >50-fold reduced affinity for binding to CD71 on cells compared with protease-activated, unmasked anti-CD71 PDC. Potent in vivo tumor growth inhibition (stasis or regression) was observed in >80% of PDX models (28/34) at 3 or 6 mg/kg. Anti-CD71 PDC remained mostly masked (>80%) in circulation throughout dosing in cynomolgus monkeys at 2, 6, and 12 mg/kg and displayed a 10-fold improvement in tolerability compared with an anti-CD71 ADC, which was lethal. Preclinically, anti-CD71 PDC exhibits a highly efficacious and acceptable safety profile that demonstrates the utility of the Pb-Tx platform to target CD71, an otherwise undruggable target. These data support further clinical development of the anti-CD71 PDC CX-2029 as a novel cancer therapeutic.