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本案例為一名75歲女性表現為肉眼可見的血尿兩天，過去病史有10年前子宮頸癌第四期接受過骨盆腔放射治療、高血壓及第2型糖尿病。病人到本院急診就醫後住院接受進一步檢查，住院後第2天膀胱鏡發現出血性膀胱炎，住院後第4天接受經尿道膀胱腫瘤切除術，病理報告顯示為膀胱急慢性發炎併出血。病人於手術後第四天出院。病人於手術後第10天出現下腹痛、肉眼可見的血尿及糞尿，安排腹部電腦斷層及腸胃道鋇劑攝影均顯示迴腸膀胱廔管。後續安排住院接受剖腹探查、廔管及迴腸切除術及膀胱修補術。病理報告顯示為迴腸憩室和潰瘍伴有急性和慢性發炎。病人於術後第7天併發膀胱出血及膀胱滲漏，經膀胱鏡清血塊及腹腔引流後，於術後第36天出院。本文討論腸道膀胱廔管的病態生理學、危險因子、常見症狀、診斷及治療、手術併發症處理等。此案例提醒基層醫師若病人有肉眼可見的血尿合併骨盆腔放射線治療的病史應鑑別診斷腸道膀胱廔管，需儘早安排腸胃道鋇劑攝影或腹部電腦斷層，以免延誤診斷時機。 The patient was a 75-year-old woman who presented with gross hematuria for two days. Her medical history included cervical cancer, stage IV treated with pelvic radiation therapy (RT) 10 years ago, hypertension, and type 2 diabetes mellitus. The patient visited the emergency department of our hospital on May 29, 2016, and was hospitalized for further evaluation. Cystoscopy on the 2nd day after admission revealed hemorrhagic cystitis. Transurethral resection of bladder tumor (TURBT) was performed on the 4th day after admission. The pathology report revealed acute and chronic bladder inflammation and bleeding. The patient was discharged on the 8th day after admission. However, the patient developed lower abdominal pain, gross hematuria, and fecaluria on the 10th postoperative day. Abdominal computed tomography (CT) and gastrointestinal tract (GI) series were performed, all of which showed an ileum-vesical fistula. Exploratory laparotomy, resection of the fistula and ileum, and bladder repair, were performed on June 17, 2016, fifteen days after her first operation. The surgeries were successful and uneventful. Pathological examination revealed a diverticulum and ulcer with transmural mixed acute and chronic inflammation. Unfortunately, the patient developed intraperitoneal bladder perforation on the 7th postoperative day. After adequate abdominal drainage and cystoscopy-assisted blood clot evacuation, she was discharged from the hospital on the 36th postoperative day. This article discusses the pathophysiology of enterovesical fistula, risk factors, common symptoms, diagnosis and treatment, and the management of surgical complications. Clinicians should keep this clinical scenario in mind if the patient has gross hematuria combined with a history of pelvic RT. This combination of symptoms and history should suggest a differential diagnosis of enterovesical fistula and arrangement of GI series or abdominal CT should be performed as soon as possible to avoid delaying the diagnosis. &nbsp

Background Chronic kidney disease (CKD) is pathologically correlated with a sophisticated milieu of innate and adaptive immune dysregulation, but the underlying immunological disturbances remain poorly understood. Methods To address this, we comprehensively interrogated cellular and soluble elements of the immune system by using high-dimensional flow cytometry to analyze peripheral blood mononuclear cells and performing cytokine/chemokine profiling of serum samples, respectively, in a cohort of 69 patients and 19 non-CKD controls. Results Altered serum levels of several cytokines/chemokines were identified, among which concentrations of stem cell factor (SCF) were found to be elevated with the progression of CKD and inversely correlated with estimated glomerular filtration rate (eGFR). Deep immunophenotyping analyses reveal a global change in immune modulation associated with CKD severity. Specifically, a decrease in the subsets of CD56dim natural killer (NK) cells (KLRG-1+CD38+CD64+CD15+CD197+) and monocytes (KLRG-1+CD38+PD-1+) was detected in severe CKD compared with controls and mild CKD. In addition, comparisons between mild and severe CKD demonstrated a loss of a mature B cell population (PD-1+CD197+IgD+HLA-DR+) in the advanced stages of disease. Further, we identified immunophenotypic markers to discriminate mild CKD from the controls, among which the portion of CD38+ monocytes was of particular value in early diagnosis. Conclusions Our data unveil severity-specific immunological signatures perturbed in CKD patients.

Traditional Chinese medicine polysaccharides is a biologically active ingredient that is not easy to be digested. It is fermented by intestinal microflora to promote qualitative and selective changes in the composition of the intestinal microbiome, which often result in beneficial effects on the health of the host. People call it "prebiotics". In this review, we systematically summarized the anti-diabetic effect of traditional Chinese medicine polysaccharides. These polysaccharides regulate the metabolism of sugar and lipids by inter-influence with the intestinal microflora, and maintain human health, while improving type 2 diabetes-like symptoms such as high blood glucose, and abnormal glucose and lipid metabolism.

Ultrasensitive and specific detection of cocaine is of great significance for monitoring cocaine abuse. Herein, a fluorescent aptasensor via coupling CRISPR-Cas12a, with magnetic nanoparticles (MNPs), split-aptamer, and terminal deoxynucleotidyl transferase (TdT), was developed for the detection of cocaine. In short, the complete cocaine aptamer is split into two parts, one is modified on magnetic nanoparticles (MNPs) and the other is free. The presence of cocaine will mediate the binding of these two segments. Then TdT will mediate the extension to form an ultra-long sequence that can bind with multiple CRISPR-Cas12a resulting in the trans-cleavage activity of CRISPR-Cas12a being triggered. Thence, the DNA reporter which is bi-labeled with fluorophore and quencher is cleaved resulting in the generation of a fluorescence signal. The developed fluorescent aptasensor realizes the detection of cocaine with excellent sensitivity and specificity. The detection limit is low down to 33 pM, and the linear range is from 330 to 1.65 × 10

Background Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. Methods We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0). Results Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio [HR], 6.59; 95% confidence interval [CI], 6.1–7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79–8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98–11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9–8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4. Conclusions Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients. Clinical Trials Registration NCT04647695.

A higher number of socially anxious users were found as more users joined social network sites. Since social commerce has become an important issue, this study investigated the effect of social anxiety on online users’ social commerce intention. Online social interactions are hypothesized to influence social commerce intention directly or indirectly through online social support. 427 effective samples were collected from Facebook users, and the results confirmed most of the causal effects. The study also tested the moderating effect of social anxiety on the causal effects. Of the eight relationships, social anxiety significantly moderates six of them. The relationships between online social interaction and emotional support and between online social interaction and social commerce intention are stronger for users with higher social anxiety. For users with lower social anxiety, the relationship between social support and the receiving of social commerce intention is stronger. The research findings lead to significant theoretical contributions and managerial implications.

Rutin, a flavonoid found in fruits and vegetables, is a potential anticancer compound with strong anticancer activity. Therefore, electrochemical sensor was developed for the detection of rutin. In this study, CoWO4 nanosheets were synthesized via a hydrothermal method, and porous carbon (PC) was prepared via high-temperature pyrolysis. Successful preparation of the materials was confirmed, and characterization was performed by transmission electron microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin. The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability. PC has a high surface-to-volume ratio and superior conductivity. Moreover, the hydrophobicity of PC allows large amounts of rutin to be adsorbed, there by increasing the concentration of rutin at the electrode surface. Owing to the synergistic effect of the 3D CoWO4 nanosheets and PC, the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity. The sensor showed a good linear range (5–5000 ng/mL) with a detection limit of 0.45 ng/mL. The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

Perfluorodecanoic acid (PFDoA) is a widely distributed environmental pollutant that can affect the functions of many organs. However, systematic evaluations of the effects of PFDoA on testicular functions are lacking. The aim of this study was to investigate the effects of PFDoA on mouse testicular functions, including spermatogenesis, testosterone synthesis, and stem Leydig cells (SLCs) in the interstitial tissue of the testis. PFDoA (0, 2, 5, 10 mg/kg/d) was administered via gavage to 2-month-old mice for 4 weeks. Serum hormone levels and sperm quality were assayed. Furthermore, to investigate the mechanisms by which PFDoA affects testosterone synthesis and spermatogenesis in vivo, the expression of StAR and P450scc in testicular tissue was measured by immunofluorescence staining and quantitative real-time PCR. In addition, the levels of SLC markers, including nestin and CD51, were studied. PFDoA decreased the luteinizing hormone concentration and sperm quality. Although the difference was not statistically significant, mean testosterone levels showed a downward trend. The expression of StAR, P450scc, CD51, and nestin was also suppressed in the PFDoA-treated groups compared with the control group. Our study suggested that PFDoA exposure can decrease testosterone biosynthesis, and even reduce the number of SLCs. These results indicated that PFDoA suppressed the main functions of testis, and further researches are required to identify strategies for preventing or reducing the effect of PFDoA on testicular function.

Pancreatic cancer (PC) is one of the most fatal cancers with a very poor prognosis. Here, we found that N(6)-methyladenosine (m(6)A) RNA demethylase fat mass and obesity-related protein (FTO) promote the growth, migration and invasion of PC. FTO expression level is increased in human PC and is associated with poor prognosis of PC patients. Knockdown of FTO increases m(6)A methylation of TFPI-2 mRNA in PC cells, thereby increasing mRNA stability via the m(6)A reader YTHDF1, resulting in up-regulation of TFPI-2 expression, and inhibits PC proliferation, colony formation, sphere formation, migration and invasion in vitro, as well as tumour growth in vivo. Rescue assay further confirms that FTO facilitates cancer progression by reducing the expression of TFPI-2. Mechanistically, FTO promotes the progression of PC at least partially through reducing m(6)A/YTHDF1 mediated TFPI-2 mRNA stability. Our findings reveal that FTO, as an m(6)A demethylase, plays a critical role in promoting PC growth, migration and invasion, suggesting that FTO may be a potential therapeutic target for treating PC.

Cell segmentation’s low precision due to the intensity differences hinders widespread use of whole brain microscopy imaging. Previous studies used ResNet or CNN to account for this problem, but are unapplicable to immunolabeled signals across samples. Here we present a semiauto ground truth generation and weakly-supervised U-Net-based Deep-learning precise segmentation pipeline for whole brain immunopositive c-FOS signals, which reveals the distinct neural activity maps with different social motivations.

Astaxanthin (AST), a super antioxidant with coloring and medical properties, renders it a beneficial feed additive for shrimp. This study conducted a white shrimp feeding trial of 3S, 3’S isoform AST, which was derived from metabolic-engineered Kluyveromyces marxianus fermented broth (TB) and its extract (TE) compared to sources from two chemically synthetic ASTs (Carophyll Pink [CP] and Lucantin Pink [LP]), which contain 3S, 3’S, 3R, 3’S (3S, 3’R) and 3R, 3’R isoforms ratio of 1:2:1. The effects on red coloration, immune parameters and resistance to Vibrio infection were evaluated. Four AST sources were incorporated into the diets at concentrations of 0 (control), 100 mg kg−1 (TB100, TE100, CP100, and LP100), and 200 mg kg−1 (TB200, TE200, CP200, and LP200). Results revealed that in week 4, shrimps that received AST-supplemented feeds, especially TB100, TB200, and TE200, significantly increased redness (a*) values. Immune responses including phagocytosis activity, superoxide-anion production, phenoloxidase activity, and immune-related genes were examined on days 0, 1, 2, 4, 7, 14, 21, and 28. Generally, shrimps that received AST-supplemented feeds exhibited higher immune responses on days 7 and 14 than the control feed. Gene expression levels of superoxide dismutase and glutathione peroxidase were significantly upregulated on days 7 and 14 in shrimps that received AST-supplemented feeds, while genes of penaeidins, antilipopolysaccharide factor, and lysozyme were upregulated on days 4, 7, and 14, especially received TB200 and TE200. Furthermore, shrimps that received TB100, TE100, CP100, and LP100 7 days were then challenged with Vibrio parahaemolyticus and the result demonstrated higher survival rates especially TB100 at 168 h than the control feed. In conclusion, incorporating AST into the diets enhanced shrimp red coloration, immune parameters, and resistance against V. parahaemolyticus infection. The K. marxianus-derived AST exhibited higher performance than did chemical AST to be a potential feed additive in shrimp aquaculture.

The well-posedness of stochastic Navier–Stokes equations with various noises is a hot topic in the area of stochastic partial differential equations. Recently, the consideration of stochastic Navier–Stokes equations involving fractional Laplacian has received more and more attention. Due to the scaling-invariant property of the fractional stochastic equations concerned, it is natural and also very important to study the well-posedness of stochastic fractional Navier–Stokes equations in the associated critical Fourier–Besov spaces. In this paper, we are concerned with the three-dimensional stochastic fractional Navier–Stokes equation driven by multiplicative noise. We aim to establish the well-posedness of solutions of the concerned equation. To this end, by utilising the Fourier localisation technique, we first establish the local existence and uniqueness of the solutions in the critical Fourier–Besov space $$\dot{\mathcal {B}}^{4-2\alpha -\frac{3}{p}}_{p,r}$$ B ˙ p , r 4 - 2 α - 3 p . Then, under the condition that the initial date is sufficiently small, we show the global existence of the solutions in the probabilistic sense.

Hydrocephalus is a common complication of hemorrhagic stroke and has been reported to contribute to poor neurological outcomes. Herein, we aimed to investigate the validity of cerebrospinal fluid (CSF) data in predicting shunt-dependent hydrocephalus (SDHC) in patients with hemorrhagic stroke. PubMed, CENTRAL, and Embase databases were searched for relevant studies published through July 31, 2021. The 16 studies with 1505 patient included those in which CSF data predicted risk for SDHC and reports on CSF parameters in patients in whom SDHC or hydrocephalus that was not shunt-dependent developed following hemorrhagic stroke. We appraised the study quality using Newcastle-Ottawa Scale and conducted a meta-analysis of the pooled estimates of the CSF predictors. The meta-analysis revealed three significant CSF predictors for shunt dependency, i.e., higher protein levels (mean difference [MD] = 32.09 mg/dL, 95% confidence interval [CI] = 25.48-38.70, I

The emergence and spread of multidrug-resistant bacteria highlight the need for new antibacterial interventions. A screening of 24 newly synthesized dibenzoxazepines identified a small molecule compound, SW14, with potent inhibitory activity against intracellular multidrug-resistant and fluoroquinolone-resistant strains of

[Au(O4NCS2)]2 underwent structural transformation by heating to give [Au(O4NCS2)]6. Moreover, [Ag(O4NCS2)]n and [Cu(O4NCS2)]4 can be isolated, and notably [Cu(O4NCS2)]4 structurally transformed to [Cu(O4NCS2)]8 by heating can be also observed.

Inspired by crab exoskeleton, fused deposition modeling (FDM) was used to control local deposition of acrylonitrile‐butadiene‐styrene (ABS) polymer and local porosity. Effects of four different meso-scale structures on the stochastic mechanical properties were investigated. Tensile tests showed that the biomimetic Bouligand structure increases strength, strain at break, toughness, and mechanical reliability of additively manufactured porous ABS. Change in meso-scale structures impacted variations in mechanical properties. Weibull moduli--as an indication of variation in properties--ranged from 17 to 54 for fracture strength. Variations in strain at break were higher compared to strength with a Weibull modulus between 6 and 16. Finite element simulations captured the experimental fracture behavior of porous structures. Simulations revealed significant damage accumulation in porous Bouligand structures.

BACKGROUNDThis study is focused to identify the risk factors of shunt-dependent hydrocephalus (SDHC) after aneurysmal subarachnoid hemorrhage (aSAH) and develop a model to predict its incidence.METHODSMedical records of 118 consecutive patients with aSAH treated in our institution from January 2013 to October 2021 were reviewed retrospectively, 109 of them were enrolled in this cohort, the following data were analyzed based on presence or absence of SDHC: age, gender, body mass index, Fisher grade, Hunt and Hess scale (HHS), aneurysm location, treatment modality, new neurological deficits after aneurysm treatment, estimated glomerular filtration rate (eGFR), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and platelet-neutrophil ratio (PNR). We conducted univariate and multivariate logistic regression analyses to illustrate a nomogram for predicting SDHC risk.RESULTSThe stepwise logistic regression analysis with backward selection revealed three independent predictive factors of SDHC: age ≥65 (odds ratio, 3.94; 95% CI, 1.4–11.00;p= 0.009), treatment modality (odds ratio, 4.36; 95% CI, 1.81–10.53;p= 0.001), and HHS ≥3 (odds ratio, 3.59; 95% CI, 1.50–8.61;p= 0.004). A nomogram for SDHC risk prediction was developed based on the weight of these 3 factors.CONCLUSIONSAge, treatment modality (clipping vs coiling), and HHS are predictive for SDHC after aSAH. Endovascular embolization of aneurysm plays an important role in reducing risk of SDHC after aSAH.

This paper describes our system for the low-resource domain adaptation track (Track 3) in Spoken Language Understanding Grand Challenge, which is a part of ICASSP Signal Processing Grand Challenge 2023. In the track, we adopt a pipeline approach of ASR and NLU. For ASR, we fine-tune Whisper for each domain with upsampling. For NLU, we fine-tune BART on all the Track3 data and then on low-resource domain data. We apply masked LM (MLM) -based data augmentation, where some of input tokens and corresponding target labels are replaced using MLM. We also apply a retrieval-based approach, where model input is augmented with similar training samples. As a result, we achieved exact match (EM) accuracy 63.3/75.0 (average: 69.15) for reminder/weather domain, and won the 1st place at the challenge., Comment: To appear at ICASSP2023

Recently there have been efforts to introduce new benchmark tasks for spoken language understanding (SLU), like semantic parsing. In this paper, we describe our proposed spoken semantic parsing system for the quality track (Track 1) in Spoken Language Understanding Grand Challenge which is part of ICASSP Signal Processing Grand Challenge 2023. We experiment with both end-to-end and pipeline systems for this task. Strong automatic speech recognition (ASR) models like Whisper and pretrained Language models (LM) like BART are utilized inside our SLU framework to boost performance. We also investigate the output level combination of various models to get an exact match accuracy of 80.8, which won the 1st place at the challenge., Comment: First Place in Track 1 of STOP Challenge, which is part of ICASSP Signal Processing Grand Challenge 2023

Similarity measures are very effective and meaningful tool used for evaluating the closeness between any two attributes which are very important and valuable to manage awkward and complex information in real-life problems. Therefore, for better handing of fuzzy information in real life, Ullah et al. (Complex Intell Syst 6(1): 15–27, 2020) recently introduced the concept of complex Pythagorean fuzzy set (CPyFS) and also described valuable and dominant measures, called various types of distance measures (DisMs) based on CPyFSs. The theory of CPyFS is the essential modification of Pythagorean fuzzy set to handle awkward and complicated in real-life problems. Keeping the advantages of the CPyFS, in this paper, we first construct an example to illustrate that a DisM proposed by Ullah et al. does not satisfy the axiomatic definition of complex Pythagorean fuzzy DisM. Then, combining the 3D Hamming distance with the Hausdorff distance, we propose a new DisM for CPyFSs, which is proved to satisfy the axiomatic definition of complex Pythagorean fuzzy DisM. Moreover, similarly to some DisMs for intuitionistic fuzzy sets, we present some other new complex Pythagorean fuzzy DisMs. Finally, we apply our proposed DisMs to a building material recognition problem and a medical diagnosis problem to illustrate the effectiveness of our DisMs. Finally, we aim to compare the proposed work with some existing measures is to enhance the worth of the derived measures.

Background/Objectives The purpose of this study was to present an association among different morphologic subtypes of diabetic macular edema (DME) and their response and changes in morphological features of spectral domain optical coherence tomography (SD-OCT) over time after intravitreal ranibizumab (IVR) injections. Subjects/Methods This retrospective study included 228 eyes of 150 subjects received IVR for DME and were observed for at least 2 years. Medical charts and SD-OCT image of consecutive patients were reviewed at designated time points after first IVR treatment. Results For a total of 228 eyes, 42 eyes (18.4%) were classified as group 1 (with OCT morphological changes) and 186 eyes (81.6%) classified as group 2 (without OCT morphological changes). The baseline best-corrected visual acuity and 2nd year central macula thickness were significantly different between two groups (p=0.035, p=0.001), with group 1 a poor BCVA (log MAR) 0.84±0.39 and greater CMT at 2nd year (354.21±89.02). Vitreomacular interface abnormalities (VIMA) was the most common type of change and developed in 14.9% of patients with DME who received intravitreal injection of ranibizumab treatment during a follow-up period of 24 months. Stroke was found as a risk factor for developing into another DME subtypes with odds ratio 6.381 (p= 0.038). Conclusions Macula edema disappeared rapidly after IVR treatment and might recur or even evolve to other subtypes over time, which may indicate a disease progression with poor outcome. VIMA was the most common type of change and presented in all eyes with DME irrespective of the type of macular edema as classified by SD-OCT.

Many marine alkaloids possess interesting structures and antitumor activities. Thus, we have synthesized (2 E,4 E)-4-arylidene-2-styryl-5-oxopyrrolidine derivatives of the marine alkaloids, rhopaladins A–D. The cytotoxicities of these derivatives against C-33A, CaSki, SiHa, HeLa, HepG2, and LO2 cells are evaluated by MTT assays. The results show that (2 E,4 E)-2-(4-chlorostyryl)-4-benzylidene- N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide significantly inhibits cancer cell proliferation, with IC50 values against C-33A, CaSki, SiHa, HeLa, and HepG2 cells of 5.56, 9.15, 12.5, 21.4, and 14.5 μM, respectively, and an IC50 value of 86.77 μM against the normal LO2 cell line.

Though TCRs have been subject to limited engineering in the context of therapeutic design and optimization, they are used largely as found in nature. On the other hand, CARs are artificial, composed of different segments of proteins that function in the immune system. This characteristic raises the possibility of altered response to immune regulatory stimuli. Here we describe a large-scale, systematic comparison of CARs and TCRs across 5 different pMHC targets, with a total of 19 constructs examined in vitro. These functional measurements include CAR- and TCR-mediated activation, proliferation, and cytotoxicity in both acute and chronic settings. Surprisingly, we find no consistent difference between CARs and TCRs as receptor classes with respect to their relative sensitivity to major regulators of T cell activation: PD-L1, CD80/86 and IL-2. Though TCRs often emerge from human blood directly as potent, selective receptors, CARs must be heavily optimized to attain these properties for pMHC targets. Nonetheless, when iteratively improved and compared head to head in functional tests, CARs appear remarkably similar to TCRs with respect to immune modulation.

Supplemental Digital Content is available in the text., Next-generation T-cell therapies will likely continue to utilize T-cell receptors (TCRs) and chimeric antigen receptors (CARs) because each receptor type has advantages. TCRs often possess exceptional properties even when tested unmodified from patients’ T cells. CARs are generally less sensitive, possibly because their ligand-binding domains are grafted from antibodies selected for binding affinity or avidity and not broadly optimized for a functional response. Because of the disconnect between binding and function among these receptor types, the ultimate potential of CARs optimized for sensitivity and selectivity is not clear. Here, we focus on a thoroughly studied immuno-oncology target, the HLA-A*02/HPV-E629–38 complex, and show that CARs can be optimized by a combination of high-throughput binding screens and low-throughput functional assays to have comparable activity to clinical TCRs in acute assays in vitro. These results provide a case study for the challenges and opportunities of optimizing high-performing CARs, especially in the context of targets utilized naturally by TCRs.