Investigation of Urinary Metabolites of Organophosphate Esters in Hanoi, Vietnam: Assessment Exposure and Estimated Daily Intake.

In recent years, organophosphate esters (OPEs) have become one of the most common additives in various consumer products worldwide, therefore the exposure and impact of OPEs on human health are drawing a lot of attention. In this study, three metabolites of OPEs including bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPhP) and diethyl phosphate (DEP) were investigated in first-morning void urine samples taken from a population (age range: 3-76 years old) in Hanoi, Vietnam. The most dominant urinary OPE metabolite was DEP with the geometric mean of specific gravity adjust (SG-adjusted) concentration were 1960 ng mL-1 and detected frequency (DF) of 98%. Followed by DPhP (8.01 ng mL-1, DF: 100%) and BDCIPP (2.18 ng mL-1, DF: 51%). The results indicated that gender and age might have associations with the OPE metabolites variation in urine samples. The levels of OPE metabolites in urine samples from females were slightly higher than in males. An increase in age seems to have an association with a decrease in DPhP levels in urine. Exposure doses of parent OPEs were evaluated from the unadjusted urinary concentration of corresponding OPE metabolite. The estimated exposure doses of triethyl phosphate (TEP) (mean: 534,000 ng kg-1 d-1) were significantly higher than its corresponding reference dose, suggesting the high potential risk from the current exposure doses of TEP to human health. The results of this work provided the initial information on the occurrence of three OPE metabolites in urine from Hanoi, Vietnam and estimated exposure dose of corresponding parent OPEs.

Utilizing surface plasmon resonance as a novel method for monitoring in-vitro P-glycoprotein efflux.

P-glycoprotein (Pgp) is known for its dichotomous roles as both a safeguarding efflux transporter against xenobiotics and as a catalyst for multidrug resistance. Given the susceptibility of numerous therapeutic compounds to Pgp-mediated resistance, compliance with Food and Drug Administration (FDA) guidelines mandates an in-depth in vitro transport assay during drug development. This study introduces an innovative transport assay that aligns with these regulatory imperatives but also addresses limitations in the currently established techniques. Using Pgp-reconstituted liposomes and employing surface plasmon resonance (SPR), this study developed a distinct method of measuring the relative transport rates of Pgp substrates in a controlled microenvironment. The Pgp substrates selected for this study-quinidine, methadone, and desipramine-resulted in transport ratios that corroborate with trends previously observed. To assess the kinetics of Pgp-mediated transport, the results were analyzed by fitting the data to both currently proposed Pgp substrate translocation models-the vacuum cleaner and flippase models. While the resulting kinetic analysis in this study lends support predominantly to the vacuum cleaner model, this study most notably developed a novel method of assessing Pgp-mediated transport rates and real-time kinetics using surface plasmon resonance.

How Should Health Care Organizations Limit Roles of Human Trafficking in Their Labor and Supply Chains?

There has been little attention given to roles played by human trafficking in health care organizations' supply chains. Hand sanitizers and gloves, for example, might be produced by forced labor, which tends to increase in prevalence during pandemics, mass violence, migration, or other global crises. This article considers the nature and scope of health care organizations' corporate and social responsibilities to procure products and personnel justly, offers recommendations to minimize possibilities that supplies are produced by forced labor, and advocates for a public health approach to limiting human trafficking in organizations' supply chains.

How much is invested in obesity prevention in Australia? An analysis of major research and Federal Government funding, 2013-2022.

Objective and importance of study: Overweight and obesity are the second leading risk factors for death and non-communicable disease in Australia. This study aimed to examine the Australian Federal Government funding landscape for population-level obesity prevention from 2013 to 2022. STUDY TYPE: A retrospective analysis and narrative synthesis of publicly available data on obesity prevention funding from the Federal Government and major federally funded Australian research organisations. METHODS: Searches were conducted of Australian Federal Government Budget documents and funding announcements from the National Health and Medical Research Council (NHMRC), Australian Research Council (ARC) and Medical Research Future Fund (MRFF). Funding allocations targeting obesity prevention, or the prevention of risk factors associated with obesity, were included. These were determined by the presence of keywords related to obesity, unhealthy diet, physical activity and sedentary behaviour. Data were extracted verbatim, coded and narratively synthesised by funding source. RESULTS: From 2013 to 2022, 186 funding allocations for obesity prevention in Australia were identified, totalling approximately A$778 million. The proportion of funding allocated to obesity prevention compared to the total annual budget of each funding source was relatively low: NHMRC = 1.1%; ARC = 0.2%; MRFF = 0.8%; Federal Government = 0.1% (of health budget). Funding for obesity prevention initiatives fluctuated over time. CONCLUSIONS: Findings underscore the need for strategic and ongoing funding allocation to support obesity prevention research, implementation and sustainment of evidence-based obesity prevention initiatives in Australia.

Structural and functional characterization of the IgSF21-neurexin2α complex and its related signaling pathways in the regulation of inhibitory synapse organization.

The prevailing model behind synapse development and specificity is that a multitude of adhesion molecules engage in transsynaptic interactions to induce pre- and postsynaptic assembly. How these extracellular interactions translate into intracellular signal transduction for synaptic assembly remains unclear. Here, we focus on a synapse organizing complex formed by immunoglobulin superfamily member 21 (IgSF21) and neurexin2α (Nrxn2α) that regulates GABAergic synapse development in the mouse brain. We reveal that the interaction between presynaptic Nrxn2α and postsynaptic IgSF21 is a high-affinity receptor-ligand interaction and identify a binding interface in the IgSF21-Nrxn2α complex. Despite being expressed in both dendritic and somatic regions, IgSF21 preferentially regulates dendritic GABAergic presynaptic differentiation whereas another canonical Nrxn ligand, neuroligin2 (Nlgn2), primarily regulates perisomatic presynaptic differentiation. To explore mechanisms that could underlie this compartment specificity, we targeted multiple signaling pathways pharmacologically while monitoring the synaptogenic activity of IgSF21 and Nlgn2. Interestingly, both IgSF21 and Nlgn2 require c-jun N-terminal kinase (JNK)-mediated signaling, whereas Nlgn2, but not IgSF21, additionally requires CaMKII and Src kinase activity. JNK inhibition diminished de novo presynaptic differentiation without affecting the maintenance of formed synapses. We further found that Nrxn2α knockout brains exhibit altered synaptic JNK activity in a sex-specific fashion, suggesting functional linkage between Nrxns and JNK. Thus, our study elucidates the structural and functional relationship of IgSF21 with Nrxn2α and distinct signaling pathways for IgSF21-Nrxn2α and Nlgn2-Nrxn synaptic organizing complexes in vitro. We therefore propose a revised hypothesis that Nrxns act as molecular hubs to specify synaptic properties not only through their multiple extracellular ligands but also through distinct intracellular signaling pathways of these ligands.

Field and laboratory investigation of highly pathogenic avian influenza H5N6 and H5N8 in Quang Ninh province, Vietnam, 2020 to 2021.

BACKGROUND: Avian influenza (AI) is a contagious disease that causes illness and death in poultry and humans. High pathogenicity AI (HPAI) H5N6 outbreaks commonly occur in Quang Ninh province bordering China. In June 2021, the first HPAI H5N8 outbreak occurred at a Quang Ninh chicken farm. OBJECTIVES: This study examined the risk factors associated with HPAI H5N6 and H5N8 outbreaks in Quang Ninh. METHODS: A retrospective case-control study was conducted in Quang Ninh from Nov 2021 to Jan 2022. The cases were households with susceptible poultry with two or more clinical signs and tested positive by real-time reverse transcription polymerase chain reaction. The controls were households in the same village as the cases but did not show clinical symptoms of the disease. Logistic regression models were constructed to assess the risk factors associated with HPAI outbreaks at the household level. RESULTS: There were 38 cases with H5N6 clade 2.3.4.4h viruses (n = 35) and H5N8 clade 2.3.4.4b viruses (n = 3). Compared to the 112 controls, raising poultry in uncovered or partially covered ponds (odds ratio [OR], 7.52; 95% confidence interval [CI], 1.44-39.27), poultry traders visiting the farm (OR, 8.66; 95% CI, 2.7-27.69), farms with 50-2,000 birds (OR, 3.00; 95% CI, 1.06-8-51), and farms with ≥ 2,000 birds (OR, 11.35; 95% CI, 3.07-41.94) were significantly associated with HPAI outbreaks. CONCLUSIONS: Combining biosecurity measures, such as restricting visitor entry and vaccination in farms with more than 50 birds, can enhance the control and prevention of HPAI in Quang Ninh and its spread across borders.

"Multiplexed screen identifies a Pseudomonas aeruginosa -specific small molecule targeting the outer membrane protein OprH and its interaction with LPS".

The surge of antimicrobial resistance threatens efficacy of current antibiotics, particularly against Pseudomonas aeruginosa , a highly resistant gram-negative pathogen. The asymmetric outer membrane (OM) of P. aeruginosa combined with its array of efflux pumps provide a barrier to xenobiotic accumulation, thus making antibiotic discovery challenging. We adapted PROSPECT 1 , a target-based, whole-cell screening strategy, to discover small molecule probes that kill P. aeruginosa mutants depleted for essential proteins localized at the OM. We identified BRD1401, a small molecule that has specific activity against a P. aeruginosa mutant depleted for the essential lipoprotein, OprL. Genetic and chemical biological studies identified that BRD1401 acts by targeting the OM ß-barrel protein OprH to disrupt its interaction with LPS and increase membrane fluidity. Studies with BRD1401 also revealed an interaction between OprL and OprH, directly linking the OM with peptidoglycan. Thus, a whole-cell, multiplexed screen can identify species-specific chemical probes to reveal novel pathogen biology.

Shared genetic risk between major orofacial cleft phenotypes in an African population.

Nonsyndromic orofacial clefts (NSOFCs) represent a large proportion (70%-80%) of all OFCs. They can be broadly categorized into nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO). Although NSCL/P and NSCPO are considered etiologically distinct, recent evidence suggests the presence of shared genetic risks. Thus, we investigated the genetic overlap between NSCL/P and NSCPO using African genome-wide association study (GWAS) data on NSOFCs. These data consist of 814 NSCL/P, 205 NSCPO cases, and 2159 unrelated controls. We generated common single-nucleotide variants (SNVs) association summary statistics separately for each phenotype (NSCL/P and NSCPO) under an additive genetic model. Subsequently, we employed the pleiotropic analysis under the composite null (PLACO) method to test for genetic overlap. Our analysis identified two loci with genome-wide significance (rs181737795 [p = 2.58E-08] and rs2221169 [p = 4.5E-08]) and one locus with marginal significance (rs187523265 [p = 5.22E-08]). Using mouse transcriptomics data and information from genetic phenotype databases, we identified MDN1, MAP3k7, KMT2A, ARCN1, and VADC2 as top candidate genes for the associated SNVs. These findings enhance our understanding of genetic variants associated with NSOFCs and identify potential candidate genes for further exploration.

Classification and application of metal-based nanoantioxidants in medicine and healthcare.

Antioxidants play an important role in the prevention of oxidative stress and have been widely used in medicine and healthcare. However, natural antioxidants have several limitations such as low stability, difficult long-term storage, and high cost of large-scale production. Along with significant advances in nanotechnology, nanomaterials have emerged as a promising solution to improve the limitations of natural antioxidants because of their high stability, easy storage, time effectiveness, and low cost. Among various types of nanomaterials exhibiting antioxidant activity, metal-based nanoantioxidants show excellent reactivity because of the presence of an unpaired electron in their atomic structure. In this review, we summarize some novel metal-based nanoantioxidants and classify them into two main categories, namely chain-breaking and preventive antioxidant nanomaterials. In addition, the applications of antioxidant nanomaterials in medicine and healthcare are also discussed. This review provides a deeper understanding of the mechanisms of metal-based nanoantioxidants and a guideline for using these nanomaterials in medicine and healthcare.

Utilization of Integrated Child Development Services (ICDS) and its linkages with undernutrition in India.

The Integrated Child Development Services (ICDS) programme has been the central focus of the POSHAN Abhiyaan to combat maternal and child malnutrition under the national nutrition mission in India. This paper examined the linkages between utilization of ICDS and underweight among children aged 6-59 months. The study utilized data from two recent rounds of the National Family Health Survey (NFHS-4 [2015-2016] and NFHS-5 [2019-2021]). Descriptive analyses were used to assess the change in utilization of ICDS and the prevalence of underweight at the national and state levels. Multivariable logistic regressions were performed to examine factors associated with the utilization of ICDS and underweight. Linkages between utilization of ICDS and underweight were examined using the difference-in-differences (DID) approach. Utilization of ICDS increased from 58% in 2015-2016 to 71% in 2019-2021. The prevalence of underweight decreased from 37% to 32% in the same period. Changes in ICDS utilization and underweight prevalence varied considerably across states, socioeconomic and demographic characteristics. Results from decomposition of DID models suggest that improvements in ICDS explained 9%-12% of the observed reduction in underweight children between 2016 and 2021, suggesting that ICDS made a modest but meaningful contribution in addressing undernutrition among children aged 6-59 months in this period.

Biomarker discovery with quantum neural networks: a case-study in CTLA4-activation pathways.

BACKGROUND: Biomarker discovery is a challenging task due to the massive search space. Quantum computing and quantum Artificial Intelligence (quantum AI) can be used to address the computational problem of biomarker discovery from genetic data. METHOD: We propose a Quantum Neural Networks architecture to discover genetic biomarkers for input activation pathways. The Maximum Relevance-Minimum Redundancy criteria score biomarker candidate sets. Our proposed model is economical since the neural solution can be delivered on constrained hardware. RESULTS: We demonstrate the proof of concept on four activation pathways associated with CTLA4, including (1) CTLA4-activation stand-alone, (2) CTLA4-CD8A-CD8B co-activation, (3) CTLA4-CD2 co-activation, and (4) CTLA4-CD2-CD48-CD53-CD58-CD84 co-activation. CONCLUSION: The model indicates new genetic biomarkers associated with the mutational activation of CLTA4-associated pathways, including 20 genes: CLIC4, CPE, ETS2, FAM107A, GPR116, HYOU1, LCN2, MACF1, MT1G, NAPA, NDUFS5, PAK1, PFN1, PGAP3, PPM1G, PSMD8, RNF213, SLC25A3, UBA1, and WLS. We open source the implementation at: https://github.com/namnguyen0510/Biomarker-Discovery-with-Quantum-Neural-Networks .

Poor personal protective equipment practices were associated with heat-related symptoms among Asian healthcare workers: a large-scale multi-national questionnaire survey.

BACKGROUND: It is pertinent to understand the perceptions of healthcare workers (HCWs) with their associated personal protective equipment (PPE) usage and heat strain symptoms experienced to effectively combat the negative effects of heat stress during treatment and care activities. METHODS: We evaluated the associated heat stress perceived by HCWs across Asia and validated a questionnaire on perceptions of heat stress, associated PPE usage, and heat strain symptoms experienced. The questionnaire was administered to 3,082 HCWs in six Asian regions. Factor analyses, including Cronbach's alpha, assessed the questionnaire's validity and reliability. Structural equation modelling analysed the effects of knowledge, attitudes and practices, and heat strain symptoms. RESULTS: The questionnaire was found to be reliable in assessing HCWs' knowledge, and attitudes and practices towards heat stress and PPE usage (both Cronbach's alpha = 0.9), but not heat strain symptoms (Cronbach's alpha = 0.6). Despite knowledge of heat stress, HCWs had negative attitudes and practices regarding PPE usage (ß1 = 0.6, p < 0.001). Knowledge (path coefficient = 0.2, p < 0.001), and negative attitudes and practices (path coefficient = 0.2, p < 0.001) of HCWs towards heat stress and PPE usage adversely affected symptoms experienced. CONCLUSIONS: The questionnaire was not reliable in assessing symptoms. HCWs should, nevertheless, still self-assess their symptoms for early detection of heat strain. To effectively attenuate heat strain, understanding HCWs' attitudes and practices towards PPE usage should guide policymakers in implementing targeted heat management strategies.

The Lawnmower and the Pediatric Lower Extremity: A Catastrophic Combination.

Background: Lower extremity (LE) trauma within the pediatric population may be debilitating and have different implications and etiologies than in adults. Specifically, lawnmower injuries can cause catastrophic sequelae to the lower extremities, often requiring complex reconstruction or resulting in amputation. This study aims to present our experience with pediatric LE lawnmower injuries at one of the busiest level 1 trauma centers in the United States. Methods: An IRB-approved retrospective analysis was performed studying pediatric patients (age <18 years) who experienced LE trauma due to a lawnmower injury over a 5-year period (2012-2017). Patient demographics, perioperative data, and types of reconstruction were reviewed. Univariate analysis of the data was performed to examine trends in exposure and management of pediatric LE lawnmower injuries. Results: Twenty-three patients were identified with pediatric LE lawnmower injuries, of whom 82.6% were male. The patients had a median age of 6 years and a median Injury Severity Score (ISS) of 4. Over one-third (34.8%) of this cohort required immediate amputation. Additionally, 26.1% and 8.7% required local and free flap reconstruction, respectively. In comparison, only 3.6% and 2.3% of all traumatic pediatric LE injuries from the same time frame required local and free flaps, respectively. Conclusions: Lawnmower injuries to the LE can be devastating, causing long-term physical, emotional, and psychosocial consequences for pediatric patients and their families. The data in this study suggest that pediatric LE injuries from lawnmowers more often require complex reconstruction than other traumatic LE injuries. Rapid and effective decision-making by experienced surgeons is necessary to optimize the potential for limb salvage in pediatric LE lawnmower injuries. An algorithm of recommendations on when to transfer these types of injuries to more experienced tertiary centers is provided. Additional resources should be dedicated toward improving public awareness and industrial safety features to help prevent lawnmower injuries in pediatric patients.

Growth patterns of preterm and small for gestational age children during the first 10 years of life.

Background: Preterm and small for gestational age (SGA) remain significant public health concerns worldwide. Yet limited evidence exists on their growth patterns during childhood from low-or middle-income countries. Objectives: We investigated the postnatal growth patterns of preterm and SGA compared to term appropriate for gestational age (AGA) children from birth to 10-11y, and examined the impact of birth status on child nutritional status during the school age years. Methods: Children born to women who participated in a double-blinded randomized controlled trial of preconception micronutrient supplementation in Vietnam were classified into three groups: preterm AGA (n = 130), full-term SGA (n = 165) and full-term AGA (n = 1,072). Anthropometric data (weight and height) were collected prospectively at birth, 3, 6, 12, 18, 24 months and at 6-7 and 10-11y. We used ANOVA and multiple regression models to examine the differences in growth patterns from birth to 10-11y as well as child undernutrition and overnutrition by birth status. Results: Children who were born preterm exhibited rapid postnatal growth, but still had lower HAZ at 1y and 2y and showed catch up to the AGA group at 6y. Compared to those born AGA, SGA infants had higher risk of thinness (BMIZ < -2) at 2y and 6y (adjusted Odds Ratio, AOR [95% CI] 2.5 [1.0, 6.1] and 2.6 [1.4, 4.6], respectively); this risk reduced at 10-11y (1.6 [0.9, 2.8]). The risk of stunting (HAZ < -2) was also 2.4 [1.5, 3.8] and 2.3 times [1.2, 4.1] higher in SGA than AGA group at ages 2y and 6-7y, respectively, with no differences at 10y. Although preterm children had higher rates of thinness and stunting at 2y compared to AGA children, these differences were not statistically significant. No associations were found between preterm or SGA and overweight /obesity at age 10-11y. Conclusion: Children who were born term-SGA continued to demonstrate deficits in weight and height during childhood whereas those born preterm showed catch-up growth by age 6-7y. Additional efforts to reduce the burden of these conditions are needed, particularly during school-age and early adolescents when children are exposed to challenging environments and have higher demands for nutrition.

Postoperative Radiologic Imaging in Secondary Alveolar Bone Grafting for Cleft Lip and Palate: A Systematic Review and Meta-Analysis.

INTRODUCTION: Radiographs (XRs), computed tomography (CT) scans, and cone-beam CT (CBCT) scans are utilized for assessment of secondary alveolar bone graft (SABG) in patients with cleft lip and palate (CLP). However, the optimal choice for imaging modality remains unclear. This study compares the image fidelity and safety profile for XR, CT, and CBCT in the assessment of patients with CLP who have undergone SABG. METHODS: Articles from MEDLINE and Elsevier Embase were screened. The primary outcome was graft success rate. Secondary outcomes were percent-by-volume of graft maintained and patient safety, defined by radiation exposure. A random effects model was used to calculate the pooled outcomes for each imaging modality. Chi-squared analysis was used to compare pooled outcomes between different imaging modalities. RESULTS: Of the 149 articles identified initially, 14 were included. Computed tomography exhibited a significantly higher image fidelity demonstrated by a lower graft success rate (62.0%) compared with both XR (72.6%, P<0.01) and CBCT (69.8%, P<0.01). Cone-beam CT had the lowest reported percent-by-volume of graft maintained (32.1%). Computed tomography had a higher mean radiation dosage (39.7 milligray) than what has been reported for both XR and CBCT. CONCLUSION: Computed tomography demonstrated lower graft success rates than both XR and CBCT, possibly indicating a higher image fidelity. However, compared with CBCT, CT may have a higher radiation exposure. Randomized trials and longitudinal studies are necessary to perform a direct comparison between CT and CBCT and to correlate the image fidelity of these modalities with clinical outcomes.

Effective activation of peroxymonosulfate by CoCr-LDH for removing organic contaminants in water: from lab-scale to practical applications.

In this study, CoCr layered double hydroxide material (CoCr-LDH) was prepared and used as an effective catalyst for peroxymonosulfate (PMS) activation to degrade organics in water. The prepared CoCr-LDH material had a crystalline structure and relatively porous structure, as determined by various surface analyses. In Rhodamine B (RhB) removal, the most outstanding PMS activation ability belongs to the material with a Co:Cr molar ratio of 2:1. The removal of RhB follows pseudo-first-order kinetics (R2 > 0.99) with an activation energy of 38.23 kJ/mol and efficiency of 98% after 7 min of treatment, and the total organic carbon of the solution reduced 47.2% after 10 min. The activation and oxidation mechanisms were proposed and the RhB degradation pathways were suggested with the key contribution of O2•- and 1O2. Notably, CoCr-LDH can activate PMS over a wide pH range of 4 - 9, and apply to a wide range of organic pollutants and aqueous environments. The material has high stability and good recovery, which can be reused for 5 cycles with a stable efficiency of above 88%, suggesting a high potential for practical recalcitrant water treatment via PMS activation by heterogeneous catalysts.

The complete mitochondrial genome of Gobionotothen gibberifrons (Perciformes, Nototheniidae).

The humped rockcod, Gobionotothen gibberifrons, is an Antarctic fish of the genus Gobionotothen in the family Nototheniidae and order Perciformes. To date, little biological information has been recorded about the genus Gobionotothen. Here, we report the first complete mitogenome of the genus Gobionotothen. The mitochondrial genome of G. gibberifrons is 18,631 bp in length, comprising 13 protein-coding genes, 24 tRNA genes (trnP-UGG and trnT-UGU were duplicated), 2 rRNA genes, and non-coding control regions. The base composition was 53.74% for A + T and 46.26% for G + C. This new mitochondrial genome of G. gibberifrons provides basic information for further phylogenetic analysis, suggesting the necessity to exploit a variety of newly discovered mitogenome sequences to infer inconclusive evolutionary relationships in Antarctic fishes.

Multiple Sclerosis: Clinical Update and Clinically-Oriented Radiologic Reporting.

Multiple sclerosis (MS) is a chronic inflammatory disease of the nervous system. MR imaging findings play an integral part in establishing diagnostic hallmarks of the disease during initial diagnosis and evaluating disease status. Multiple iterations of diagnostic criteria and consensus guidelines are put forth by various expert groups incorporating imaging of the brain and spine, and efforts have been made to standardize imaging protocols for MS. Emerging ancillary imaging findings have also attracted increasing interests and should be sought for on radiologic examination. In this paper, the authors review the clinical guidelines and approach to imaging of MS and related disorders, focusing on clinically impactful image interpretation and MR imaging reporting.

DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma.

Fibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in FLC is its driver mutation, a conserved DNAJB1-PRKACA gene fusion that could be an ideal target neoantigen for immunotherapy. In this study, we aim to define endogenous CD8 T cell responses to this fusion in FLC patients and evaluate fusion-specific T cell receptors (TCRs) for use in cellular immunotherapies. We observe that fusion-specific CD8 T cells are rare and that FLC patient TCR repertoires lack large clusters of related TCR sequences characteristic of potent antigen-specific responses, potentially explaining why endogenous immune responses are insufficient to clear FLC tumors. Nevertheless, we define two functional fusion-specific TCRs, one of which has strong anti-tumor activity in vivo. Together, our results provide insights into the fragmented nature of neoantigen-specific repertoires in humans and indicate routes for clinical development of successful immunotherapies for FLC.