Extending Infrared Emission via Energy Transfer in a CsPbI3-Cyanine Dye Hybrid.

Directing energy flow in light harvesting assemblies of nanocrystal-chromophore hybrid systems requires a better understanding of factors that dictate excited-state processes. In this study, we explore excited-state interactions within the CsPbI3-cyanine dye (IR125) hybrid assembly through a comprehensive set of steady-state and time-resolved absorption and photoluminescence (PL) experiments. Our photoluminescence investigations reveal the quenching of CsPbI3 emission alongside the simultaneous enhancement of IR125 fluorescence, providing evidence for a singlet energy transfer. The evaluation of both photoluminescence (PL) quenching and PL decay measurements yield ∼94% energy transfer efficiency for the CsPbI3-IR125 hybrid assembly. Transient absorption spectroscopy further unveils that this singlet energy transfer process operates on an ultrafast time scale, occurring within 400 ps with a rate constant of energy transfer of 1.4 × 1010 s-1. Our findings highlight the potential of the CsPbI3-IR125 hybrid assembly to extend the emission of halide perovskites into the infrared region, paving the way for light energy harvesting and display applications.

Autosomal dominant ApoA4 mutations present as tubulointerstitial kidney disease with medullary amyloidosis.

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.L66V of the ApoA4 protein. We identified two other distantly related families from our registry with the same variant and two other distantly related families with a chr11:116693454 C>T (hg19) variant encoding the missense mutation p.D33N. Both mutations are unique to affected families, evolutionarily conserved and predicted to expand the amyloidogenic hotspot in the ApoA4 structure. Clinically affected individuals suffered from CKD with a bland urinary sediment and a mean age for kidney failure of 64.5 years. Genotyping identified 48 genetically affected individuals; 44 individuals had an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73 m2, including all 25 individuals with kidney failure. Significantly, 11 of 14 genetically unaffected individuals had an eGFR over 60 ml/min/1.73 m2. Fifteen genetically affected individuals presented with higher plasma ApoA4 concentrations. Kidney pathologic specimens from four individuals revealed amyloid deposits limited to the medulla, with the mutated ApoA4 identified by mass-spectrometry as the predominant amyloid constituent in all three available biopsies. Thus, ApoA4 mutations can cause autosomal dominant medullary amyloidosis, with marked amyloid deposition limited to the kidney medulla and presenting with autosomal dominant CKD with a bland urinary sediment. Diagnosis relies on a careful family history, APOA4 sequencing and pathologic studies.

Advancing animal tuberculosis surveillance using culture-independent long-read whole-genome sequencing.

Animal tuberculosis is a significant infectious disease affecting both livestock and wildlife populations worldwide. Effective disease surveillance and characterization of Mycobacterium bovis (M. bovis) strains are essential for understanding transmission dynamics and implementing control measures. Currently, sequencing of genomic information has relied on culture-based methods, which are time-consuming, resource-demanding, and concerning in terms of biosafety. This study explores the use of culture-independent long-read whole-genome sequencing (WGS) for a better understanding of M. bovis epidemiology in African buffaloes (Syncerus caffer). By comparing two sequencing approaches, we evaluated the efficacy of Illumina WGS performed on culture extracts and culture-independent Oxford Nanopore adaptive sampling (NAS). Our objective was to assess the potential of NAS to detect genomic variants without sample culture. In addition, culture-independent amplicon sequencing, targeting mycobacterial-specific housekeeping and full-length 16S rRNA genes, was applied to investigate the presence of microorganisms, including nontuberculous mycobacteria. The sequencing quality obtained from DNA extracted directly from tissues using NAS is comparable to the sequencing quality of reads generated from culture-derived DNA using both NAS and Illumina technologies. We present a new approach that provides complete and accurate genome sequence reconstruction, culture independently, and using an economically affordable technique.

School Nurses and Chronic Absenteeism in Schools: A Qualitative Study on Experiences, Perspectives, and Roles.

Regular attendance is integral for students' academic success; it also affects adolescents' physical and mental health. Very few studies consider (a) differences between partial- and full-day absences regarding chronic absenteeism (CA; missing school ≥15 days in an academic year); or (b) roles of school nurses in addressing student absenteeism. This study describes school nurses' perceptions of factors related to CA and differences between partial- and full-day absences by analyzing qualitative data from six focus groups with 21 Midwestern school nurses. Four themes emerged: Absenteeism at the intersection of family and health; Absenteeism at the intersection of family and school; Absenteeism at the intersection of family and ecological systems; and School nurse roles in supporting chronically absent students. Findings highlight the importance of school nurses by describing their role in identifying students who are at risk for CA, allowing for effective assessment and intervention with students before patterns of CA become habitual.

Expanding Our Understanding of Traffickers and Their Operations: A Review of the Literature and Path Forward.

Human trafficking is a serious crime and violation of human rights that results in numerous harms. Although the phenomenon is not new, scholarship on the issue has grown substantially since the first legal framework was passed in 2000. However, the existing literature has been criticized for its skewed focus on victims, among other things. The dearth of information on traffickers and their operations limits our ability to reduce or prevent perpetration. The current study presents a comprehensive and critical review of the existing literature focused on traffickers to synthesize what is already known and highlight the key gaps. Twenty-nine articles met the inclusion criteria of (1) focusing on traffickers and their operations and (2) relying on data either directly from traffickers or sources that contained detailed information about criminal cases against traffickers. We used an iterative process to identify relevant studies, which included collecting articles of which we were already familiar or were identified in existing reviews, searching their reference lists, and conducting cited-by searches until saturation was reached. Topics found in the extant literature included: characteristics of traffickers, relationships between traffickers and victims, organizational characteristics and networks, operations, connections with other crimes, motivations, perceptions of behavior, and risks associated with trafficking. It concludes with recommendations for future research and a discussion of how bridging gaps in the literature could support more rigorous mathematical modeling that is needed to identify and assess promising perpetration prevention and intervention strategies.

Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease.

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an increasingly recognized cause of chronic kidney disease. ADTKD pregnancy outcomes have not previously been described. Methods: A cross-sectional survey was sent to women from ADTKD families. Results: Information was obtained from 85 afffected women (164 term pregnancies) and 23 controls (50 pregnancies). Only 16.5% of genetically affected women knew they had ADTKD during pregnancy. Eighteen percent of ADTKD mothers had hypertension during pregnancy versus 12% in controls (p = 0.54) and >40% in comparative studies of chronic kidney disease in pregnancy. Eleven percent of births of ADTKD mothers were <37 weeks versus 0 in controls (p < 0.0001). Cesarean section occurred in 19% of pregnancies in affected women versus 38% of unaffected individuals (p = 0.06). Only 12% of babies required a neonatal intensive care unit stay. Conclusions: ADTKD pregnancies had lower rates of hypertension during pregnancy versus other forms of chronic kidney disease, which may have contributed to good maternal and fetal outcomes.

Early-in-life isoflurane exposure alters resting-state functional connectivity in juvenile non-human primates.

BACKGROUND: Clinical studies suggest that anaesthesia exposure early in life affects neurobehavioural development. We designed a non-human primate (NHP) study to evaluate cognitive, behavioural, and brain functional and structural alterations after isoflurane exposure during infancy. These NHPs displayed decreased close social behaviour and increased astrogliosis in specific brain regions, most notably in the amygdala. Here we hypothesise that resting-state functional connectivity MRI can detect alterations in connectivity of brain areas that relate to these social behaviours and astrogliosis. METHODS: Imaging was performed in 2-yr-old NHPs under light anaesthesia, after early-in-life (postnatal days 6-12) exposure to 5 h of isoflurane either one or three times, or to room air. Brain images were segmented into 82 regions of interest; the amygdala and the posterior cingulate cortex were chosen for a seed-based resting-state functional connectivity MRI analysis. RESULTS: We found differences between groups in resting-state functional connectivity of the amygdala and the auditory cortices, medial premotor cortex, and posterior cingulate cortex. There were also alterations in resting-state functional connectivity between the posterior cingulate cortex and secondary auditory, polar prefrontal, and temporal cortices, and the anterior insula. Relationships were identified between resting-state functional connectivity alterations and the decrease in close social behaviour and increased astrogliosis. CONCLUSIONS: Early-in-life anaesthesia exposure in NHPs is associated with resting-state functional connectivity alterations of the amygdala and the posterior cingulate cortex with other brain regions, evident at the juvenile age of 2 yr. These changes in resting-state functional connectivity correlate with the decrease in close social behaviour and increased astrogliosis. Using resting-state functional connectivity MRI to study the neuronal underpinnings of early-in-life anaesthesia-induced behavioural alterations could facilitate development of a biomarker for anaesthesia-induced developmental neurotoxicity.

In Vivo Cerebral Imaging of Mutant Huntingtin Aggregates Using 11C-CHDI-180R PET in a Nonhuman Primate Model of Huntington Disease.

Huntington disease (HD) is a neurodegenerative disorder caused by an expanded polyglutamine (CAG) trinucleotide expansion in the huntingtin (HTT) gene that encodes the mutant huntingtin protein (mHTT). Visualization and quantification of cerebral mHTT will provide a proxy for target engagement and a means to evaluate therapeutic interventions aimed at lowering mHTT in the brain. Here, we validated the novel radioligand 11C-labeled 6-(5-((5-methoxypyridin-2-yl)methoxy)benzo[d]oxazol-2-yl)-2-methylpyridazin-3(2H)-one (11C-CHDI-180R) using PET imaging to quantify cerebral mHTT aggregates in a macaque model of HD. Methods: Rhesus macaques received MRI-guided intrastriatal delivery of a mixture of AAV2 and AAV2.retro viral vectors expressing an HTT fragment bearing 85 CAG repeats (85Q, n = 5), a control HTT fragment bearing 10 CAG repeats (10Q, n = 4), or vector diluent only (phosphate-buffered saline, n = 5). Thirty months after surgery, 90-min dynamic PET/CT imaging was used to investigate 11C-CHDI-180R brain kinetics, along with serial blood sampling to measure input function and stability of the radioligand. The total volume of distribution was calculated using a 2-tissue-compartment model as well as Logan graphical analysis for regional quantification. Immunostaining for mHTT was performed to corroborate the in vivo findings. Results: 11C-CHDI-180R displayed good metabolic stability (51.4% ± 4.0% parent in plasma at 60 min after injection). Regional time-activity curves displayed rapid uptake and reversible binding, which were described by a 2-tissue-compartment model. Logan graphical analysis was associated with the 2-tissue-compartment model (r 2 = 0.96, P < 0.0001) and used to generate parametric volume of distribution maps. Compared with controls, animals administered the 85Q fragment exhibited significantly increased 11C-CHDI-180R binding in several cortical and subcortical brain regions (group effect, P < 0.0001). No difference in 11C-CHDI-180R binding was observed between buffer and 10Q animals. The presence of mHTT aggregates in the 85Q animals was confirmed histologically. Conclusion: We validated 11C-CHDI-180R as a radioligand to visualize and quantify mHTT aggregated species in a HD macaque model. These findings corroborate our previous work in rodent HD models and show that 11C-CHDI-180R is a promising tool to assess the mHTT aggregate load and the efficacy of therapeutic strategies.

Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5Δ32/Δ32) can cure HIV, yet mechanisms remain speculative. To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV+, anti-retroviral therapy (ART)-suppressed Mauritian cynomolgus macaques (MCMs) and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.5 years after stopping ART, in other cases, it was insufficient without protection of engrafting cells afforded by CCR5-deficiency, as CCR5-tropic virus spread to donor CD4+ T cells despite full ART suppression. These data demonstrate the individual contributions of allogeneic immunity and CCR5 deficiency to HIV cure and support defining targets of alloimmunity for curative strategies independent of HSCT.

Sex Trading Among Adolescent Cisgender Boys.

OBJECTIVES: Cisgender girls and boys report trading sex for something of value at roughly equal proportions; yet, boys are understudied and underserved. We compare boys who reported trading sex to those who never traded sex to address this gap in knowledge and practice. METHODS: The study is a secondary analysis of the Minnesota Student Survey, a triannual, census-style survey. The sample included 32 311 cisgender boy students in ninth and 11th grades who answered a question about sex trading. Bivariate descriptive statistics and multivariate logistic models were used to identify associated factors and determine the odds of trading sex on the basis of specific experiences. RESULTS: We found that 1.2% of boys reported trading sex. In bivariate analyses, boys who reported trading sex were more likely than those who did not to: identify as Black or Indigenous; report a marginalized gender identity or sexual expression; have had sexual intercourse; have experienced sexual harassment and harassment on the basis of sexual identity and race, ethnicity, and national origin; and to have experienced homelessness, food insecurity, foster care, and substance treatment (P < .001). In multivariate models, we found increased odds of trading sex for some variables, including a marginalized sexual identity, identifying as Black, and experiences of unstable housing, foster care, substance treatment, sexual harassment, and harassment based on gender (P < .001). CONCLUSIONS: These findings contribute new knowledge about boys who trade sex using a large, population-based sample and counter false assumptions and stereotypes. These data suggest new avenues of research, intervention, and prevention.

Physiological and perceptual auditory consequences of hunting-related recreational firearm noise exposure in young adults with normal hearing sensitivity.

Purpose: The objective of the current study was to describe outcomes on physiological and perceptual measures of auditory function in human listeners with and without a history of recreational firearm noise exposure related to hunting. Design: This study assessed the effects of hunting-related recreational firearm noise exposure on audiometric thresholds, oto-acoustic emissions (OAEs), brainstem neural representation of fundamental frequency (F0) in frequency following responses (FFRs), tonal middle-ear muscle reflex (MEMR) thresholds, and behavioral tests of auditory processing in 20 young adults with normal hearing sensitivity. Results: Performance on both physiological (FFR, MEMR) and perceptual (behavioral auditory processing tests) measures of auditory function were largely similar across participants, regardless of hunting-related recreational noise exposure. On both behavioral and neural measures including different listening conditions, performance degraded as difficulty of listening condition increased for both nonhunter and hunter participants. A right-ear advantage was observed in tests of dichotic listening for both nonhunter and hunter participants. Conclusion: The null results in the current study could reflect an absence of cochlear synaptopathy in the participating cohort, variability related to participant characteristics and/or test protocols, or an insensitivity of the selected physiological and behavioral auditory measures to noise-induced synaptopathy.

Using the RE-AIM framework to evaluate physical activity-based fall prevention interventions in older adults with chronic conditions: A systematic review.

Falls are a serious public health problem, especially for older adults with chronic conditions. The purpose of this systematic review was to evaluate the translational potential of physical activity-based balance interventions for older adults with common chronic conditions guided by the Reach, Effectiveness/Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework. Databases were searched (2011-2021) to identify studies with physical activity-based fall prevention interventions for older adults with chronic conditions. Data were collected using the RE-AIM coding guide and Mixed Methods Appraisal Tool for evidence quality. The search yielded 122 articles, of which 14 distinct studies were included. The most reported RE-AIM dimensions across the studies were Reach (46.2%) and Implementation (40.5%), with Effectiveness/Efficacy (29.4%), Adoption (2.0%), and Maintenance (5.4%) being the least reported. Studies were largely conducted in controlled research environments with minimal staff involvement and without long-term follow-up periods. While studies found that physical activity-based programs were effective in improving balance, information on representativeness and adoption/maintenance of programs was lacking. Studies included sufficient details about the intervention (content, dosage, progression). External validity RE-AIM indicators were reported less frequently than internal validity indicators. The studies were of moderate quality overall. Studies often lacked information on indicators critical for understanding how to implement these programs. This review signals the need to investigate the translation of these interventions from controlled research settings to clinical settings to improve the public impact of fall prevention for this population.

Falls are a serious public health problem, especially for older adults with chronic diseases who have a higher risk of falling. For this review paper, we gathered similar research articles that looked at the effects of balance exercise programs in older adults with a variety of chronic diseases and reviewed how likely they could be used in real-world settings using a guide. We found fourteen studies that met our criteria. The most common elements that authors included in their reports were how research subjects were identified and details about the exercise program design/delivery. The least common elements were the scientific outcomes of the program, how/where the program was incorporated, and the long-term effects of the program. While these balance exercise programs for older adults with chronic diseases were successful in these individual research studies, this general area of fall research is somewhat underdeveloped. Researchers should put more consideration into surroundings where these programs could take place and study how these programs could be successful in real-world settings long-term.

"It could bring down Greek life as a whole": Greek life members' perspectives on party culture, safety, responsibilities and consequences.

OBJECTIVE: Describe Greek life students' perspectives of party culture, safety, and College Sexual Violence (CSV) prevention. PARTICIPANTS: 27 US undergraduates: 5 fraternity underclassmen, 6 fraternity upperclassmen, 10 sorority underclassmen, 6 sorority upperclassmen. METHODS: Students participated in one of four focus groups, separately by gender and academic year. Facilitation guide addressed partying, sexual violence, and safety. RESULTS: Greek life members described partying preferences, perceived safety threats, and actions they took to party safely. University efforts to support safe partying were not universally viewed as helpful. CONCLUSIONS: Although Greek life students strive to create safe partying environments, there remain missed opportunities to mitigate risks related to CSV. The responsibility to ensure safe partying falls too heavily on students, resulting in universities missing opportunities to provide measures that promote safety while mitigating risks and potentially serious harms.

The combined impact of testosterone and Western-style diet on endometriosis severity and progression in rhesus macaques†.

Polycystic ovary syndrome (PCOS) is associated with irregular menstrual cycles, hyperandrogenemia, and obesity. It is currently accepted that women with PCOS are also at risk for endometriosis, but the effect of androgen and obesity on endometriosis has been underexplored. The goal of this study was to determine how testosterone (T) and an obesogenic diet impact the progression of endometriosis in a nonhuman primate (NHP) model. Female rhesus macaques were treated with T (serum levels approximately 1.35 ng/ml), Western-style diet (WSD; 36% of calories from fat compared to 16% in standard monkey chow) or the combination (T + WSD) at the time of menarche as part of a longitudinal study for ~7 years. Severity of endometriosis was determined based on American Society for Reproductive Medicine (ASRM) revised criteria, and staged 1-4. Stages 1 and 2 were associated with extent of abdominal adhesions, while stages 3 and 4 were associated with presence of chocolate cysts. The combined treatment of T + WSD resulted in earlier onset of endometriosis and more severe types associated with large chocolate cysts compared to all other treatments. There was a strong correlation between glucose clearance, homeostatic model assessment for insulin resistance (HOMA-IR), and total percentage of body fat with presence of cysts, indicating possible indirect contribution of hyperandrogenemia via metabolic dysfunction. An RNA-seq analysis of omental adipose tissue revealed significant impacts on a number of inflammatory signaling pathways. The interactions between obesity, hyperandrogenemia, and abdominal inflammation deserve additional investigation in NHP model species.

The effect of dietary fat consumption on Alzheimer's disease pathogenesis in mouse models.

Alzheimer's disease (AD) is a fatal cognitive disorder with proteinaceous brain deposits, neuroinflammation, cerebrovascular dysfunction, and extensive neuronal loss over time. AD is a multifactorial disease, and lifestyle factors, including diet, are likely associated with the development of AD pathology. Since obesity and diabetes are recognized as risk factors for AD, it might be predicted that a high-fat diet (HFD) would worsen AD pathology. However, modeling HFD-induced obesity in AD animal models has yielded inconclusive results. Some studies report a deleterious effect of HFD on Aß accumulation, neuroinflammation, and cognitive function, while others report that HFD worsens memory without affecting AD brain pathology. Moreover, several studies report no major effect of HFD on AD-related phenotypes in mice, while other studies show that HFD might, in fact, be protective. The lack of a clear association between dietary fat consumption and AD-related pathology and cognitive function in AD mouse models might be explained by experimental variations, including AD mouse model, sex and age of the animals, composition of the HFD, and timeline of HFD consumption. In this review, we summarize recent studies that aimed at elucidating the effect of HFD-induced obesity on AD-related pathology in mice and provide an overview of the factors that may have contributed to the results reported in these studies. Based on the heterogeneity of these animal model studies and given that the human population itself is quite disparate, it is likely that people will benefit most from individualized nutritional plans based on their medical history and clinical profiles.

Cost of pre-surgical evaluation for epilepsy surgery: A single-center experience.

OBJECTIVE: To estimate the cost and time taken to evaluate adults with drug-resistant focal epilepsy for potentially curative surgery. METHODS: We reviewed data on 100 consecutive individuals at a tertiary referral center evaluated for epilepsy surgery in 2017. The time elapsed between referral and either surgery or a definitive decision not to progress was measured. National Health Service tariffs applicable to our setting were used to estimate the total cost of evaluation for individuals following different routes through the pre-surgical pathway. After surgery, self-reported seizure freedom rates were obtained from each individual to assess the approximate cost of pre-surgical evaluation per additional person seizure-free. RESULTS: Of 100 individuals evaluated, 27 had surgery, 63 had a definitive decision not to have surgery, and ten were awaiting further investigations. The median duration of the pre-surgical evaluation was 29.7 months (IQR 18.6-44.1 months), with a median cost per person of £9138 (IQR £6984-£14,868). Those who proceeded to Stage Two investigations (including fluorodeoxyglucose positron emission tomography, ictal single-photon emission computerized tomography and intracranial electroencephalography) had a higher cost and extended evaluation length. After a median of 3.1 (IQR 2.3-3.7) years, 15/27 people who had surgery were seizure-free. This equated to an approximate cost of £123,500 spent per additional person seizure-free. CONCLUSION: Pre-surgical evaluation is long and costly, particularly for those who require icEEG. For those with drug-resistant focal epilepsy, surgery is, however, associated with a greater chance of seizure freedom. The suitability and risk-benefit ratio of surgery should be considered at each step of the pre-surgical pathway.

Mental Health and Protective Factors for Transgender and Gender-Diverse Youths Who Trade Sex: A Minnesota Statewide School-Based Study, 2019.

Objectives. To describe the prevalence of sex trading by gender and by associations with mental health concerns and protective factors. Methods. We used data from 9th and 11th graders who completed the 2019 Minnesota Student Survey. The analytic sample (n = 67 806) included transgender and gender-diverse (TGD) youths and cisgender youths who reported trading sex. Data on 7 mental health measures and 4 school-related and health care-related protective factors were collected. Results. The prevalence of sex trading (5.9%) was 5 times higher among TGD students than cisgender students (1.2%). In addition, the prevalence of all mental health concerns was high among TGD students who traded sex (e.g., 75.9% reported a lifetime suicide attempt, as compared with 45.9% of cisgender students who traded sex). Fewer statistical differences were found across protective factors. When TGD students who traded sex were compared according to sex assigned at birth, no statistically significant differences were found. Conclusions. Our findings support strong calls for increased competence regarding gender and sex trading or exploitation in clinical and school-based settings to decrease health disparities among TGD youths. Public Health Implications. In this study, we have presented unique prevalence estimates of mental health disparities among TGD students in the United States who trade sex. Our results indicate that TGD students who trade sex are at risk for mental health symptoms and that sensitivity to both gender and sex trading or exploitation will be critical to meeting the needs of this group in clinical as well as school-based settings.

Targeting an alternate Wilms' tumor antigen 1 peptide bypasses immunoproteasome dependency.

Designing effective antileukemic immunotherapy will require understanding mechanisms underlying tumor control or resistance. Here, we report a mechanism of escape from immunologic targeting in an acute myeloid leukemia (AML) patient, who relapsed 1 year after immunotherapy with engineered T cells expressing a human leukocyte antigen A*02 (HLA-A2)-restricted T cell receptor (TCR) specific for a Wilms' tumor antigen 1 epitope, WT1126-134 (TTCR-C4). Resistance occurred despite persistence of functional therapeutic T cells and continuous expression of WT1 and HLA-A2 by the patient's AML cells. Analysis of the recurrent AML revealed expression of the standard proteasome, but limited expression of the immunoproteasome, specifically the beta subunit 1i (ß1i), which is required for presentation of WT1126-134. An analysis of a second patient treated with TTCR-C4 demonstrated specific loss of AML cells coexpressing ß1i and WT1. To determine whether the WT1 protein continued to be processed and presented in the absence of immunoproteasome processing, we identified and tested a TCR targeting an alternative, HLA-A2-restricted WT137-45 epitope that was generated by immunoproteasome-deficient cells, including WT1-expressing solid tumor lines. T cells expressing this TCR (TTCR37-45) killed the first patients' relapsed AML resistant to WT1126-134 targeting, as well as other primary AML, in vitro. TTCR37-45 controlled solid tumor lines lacking immunoproteasome subunits both in vitro and in an NSG mouse model. As proteasome composition can vary in AML, defining and preferentially targeting these proteasome-independent epitopes may maximize therapeutic efficacy and potentially circumvent AML immune evasion by proteasome-related immunoediting.