Association between life's essential 8 and male biochemical androgen deficiency: evidence from NHANES 2013-2016.

Purpose: To evaluate the association of Life's Essential 8 (LE8) and its subscales with male biochemical androgen deficiency (MBAD) and total testosterone based on the data from the national health and nutrition examination survey (NHANES) database. Methods: Data of males aged 20 years or older from NHANES of 2013-2016 were extracted. LE8 score was calculated based on American Heart Association definitions. Total testosterone (TT) values were measured in NHANES using precise isotope dilution liquid chromatography. MBAD was defined as serum TT of <300 ng/dL. Univariate and multivariable analyses were conducted. Propensity score matching (PSM) and weighted regression after matching were added as sensitivity analyses. The generalized additive model, smooth curve fitting, and the recursive algorithm were used to determine the potential inflection points. Piecewise regression models with log-likelihood ratio test were used to quantify nonlinear effects. Results: A total of 3094 participants who were males and aged 20 years or above were included. Out of them, 805 males were diagnosed with MBAD. After adjusting the confounders in the multivariable model, LE8 was independently associated with MBAD (OR 0.96, P < 0.001) and TT (ß 2.7, P < 0.001). The association remained robust even after PSM. The non-linear relationship of LE8 behaviors score with MBAD and TT was revealed. Conclusion: LE8 was an independent protective factor of MBAD and a feasible approach to promote male endocrine sexual function.

Preparation of an injectable zinc-containing hydrogel with double dynamic bond and its potential application in the treatment of periodontitis.

Periodontal tissue regeneration continues to face significant clinical challenges. Periodontitis leads to alveolar bone resorption and even tooth loss due to persistent microbial infection and persistent inflammatory response. As a promising topical drug delivery system, the application of hydrogels in the controlled release of periodontal bioactive drugs has aroused great interest. Therefore, the design and preparation of an injectable hydrogel with self-repairing properties for periodontitis treatment is still in great demand. In this study, polysaccharide-based self-healing hydrogels with antimicrobial osteogenic properties were developed. Zinc ions are introduced into a dynamic cross-linking network formed by dynamic Schiff bases between carboxymethyl chitosan and oxidized hyaluronic acid via coordination bonds. The OC-Zn hydrogels exhibited good tissue adhesion, good fatigue resistance, excellent self-healing ability, low cytotoxicity, good broad-spectrum antimicrobial activity, and osteogenic activity. Therefore, the designed hydrogels allow the development of drug delivery systems as a potential treatment for periodontitis.

CXCL10 could be a prognostic and immunological biomarker in bladder cancer.

INTRODUCTION: As proteins that promote immune cell differentiation, chemokines have attracted great interest regarding their role in anti-tumor immune responses within the cancer environment. However, the exact role of CXCL10, a chemokine, in bladder cancer (BLCA) is still not fully elucidated. METHOD: In the present study, we employed bioinformatics approaches to examine the expression pattern, prognostic value, and immune infiltration of CXCL10 in BLCA. Furthermore, we focused on examining the impact of CXCL10 on immune therapy in BLCA. Additionally, we validated the expression of CXCL10 in various BLCA cell lines using PCR techniques. RESULTS: We observed an upregulation of CXCL10 in BLCA tissues as well as in different cell lines. Additionally, upregulation of CXCL10 indicates a better prognosis for BLCA patients. ESTIMATE and CIBERSORT algorithms suggest that CXCL10 is closely associated with the immune microenvironment of BLCA. Through multiple immune therapy cohorts, we also identified that CXCL10 has shown promising predictive value for assessing the efficacy of immune therapy in in BLCA. CONCLUSION: Our study indicates that CXCL10 has the potential to serve as a favorable prognostic factor and is strongly associated with immune infiltration in BLCA.

Using machine learning to identify proteomic and metabolomic signatures of stroke in atrial fibrillation.

Atrial fibrillation (AF) is a common cardiac arrhythmia, with stroke being its most detrimental comorbidity. The exact mechanism of AF related stroke (AFS) still needs to be explored. In this study, we integrated proteomics and metabolomics platform to explore disordered plasma proteins and metabolites between AF patients and AFS patients. There were 22 up-regulated and 31 down-regulated differentially expressed proteins (DEPs) in AFS plasma samples. Moreover, 63 up-regulated and 51 down-regulated differentially expressed metabolites (DEMs) were discovered in AFS plasma samples. We integrated proteomics and metabolomics based on the topological interactions of DEPs and DEMs, which yielded revealed several related pathways such as arachidonic acid metabolism, serotonergic synapse, purine metabolism, tyrosine metabolism and steroid hormone biosynthesis. We then performed a machine learning model to identify potential biomarkers of stroke in AF. Finally, we selected 6 proteins and 6 metabolites as candidate biomarkers for predicting stroke in AF by random forest, the area under the curve being 0.976. In conclusion, this study provides new perspectives for understanding the progressive mechanisms of AF related stroke and discovering innovative biomarkers for determining the prognosis of stroke in AF.

Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage of both eyes after COVID-19 infection: a case report.

BACKGROUND: Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage is commonly observed in myopia with tilted optic disc. It presents with typical features on the fundus and follows a self-limiting course. However, due to its complex etiology, clinicians sometimes lack sufficient understanding of it which can easily lead to misdiagnosis or overtreatment. In this case report, we describe a rare case of intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage in both eyes. CASE PRESENTATION: An 18-year-old female who has no past medical history experienced sudden black shadow blocking of her right eye in the right eye for the past 2 days after a 5-day history of COVID-19 infection. The best corrected visual acuity is 0.5 in the right eye and 0.6 in the left eye. Optical coherence tomography (OCT) showed tilted optic discs in both eyes, bulged nasal optic discs, and the presence of strong reflective material under the parafoveal retina of the optic discs. Fundus fluorescein angiography (FFA) showed subretinal fluorescence occlusion above and nasolateral to the optic disc in the right eye, with hypofluorescence below the optic disc; the subretinal below the optic disc was obscured by vitreous hemorrhage; hypofluorescence was seen in the optic disc region of the left eye.COVID-19 antigen was positive. The patient was in the early stage of the third COVID-19 infection when the disease occurred. We speculate that it may be related to it. After 5 months of conservative treatment, the patient's hemorrhage disappeared in both eyes and her best corrected visual acuity returned to normal. CONCLUSIONS: Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage usually occurs in myopia with tilted optic disc. In most patients, the cause of the bleeding is unknown, but it can gradually resolve under clinical observation or conservative treatment.

Circulating exosome long non-coding RNAs are associated with atrial structural remodeling by increasing systemic inflammation in atrial fibrillation patients.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia with severe clinical sequelae, but its genetic characteristic implicated in pathogenesis has not been completely clarified. Accumulating evidence has indicated that circulating exosomes and their carried cargoes, such as long non-coding RNAs (lncRNAs), involve in the progress of multiple cardiovascular diseases. However, their potential role as clinical biomarkers in AF diagnosis and prognosis remains unknown. Methods: Herein, we conducted the sequence and bioinformatic analysis of circulating exosomes harvested from AF and sinus rhythm patients. Results: A total of 53 differentially expressed lncRNAs were identified, and a total of 6 significantly changed lncRNAs (fold change > 2.0), including NR0046235, NR003045, NONHSAT167247.1, NONHSAT202361.1, NONHSAT205820.1 and NONHSAT200958.1, were verified by qRT-PCR in 215 participants. Moreover, these circulating exosome lncRNA levels were different between paroxysmal and persistent AF patients, which were dramatically associated with abnormal hemodynamics and atrial diameter. Furthermore, we observed that the area under ROC curve (AUC) of six lncRNAs combination for diagnosis of persistent AF was 80.34%. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment pathway analysis indicated these exosome lncRNAs mainly concerning response to chemokine-chemokine receptor interaction, which induced activated inflammation and structural remodeling. In addition, increased plasma levels of CXCR3 ligands, including CXCL4, CXCL9, CXCL10 and CXCL11, were accumulated in AF patient tissues. Conclusion: Our study provides the transcriptome profile revealing pattern of circulating exosome lncRNAs in atrial structural remodeling, which bring valuable insights into improving prognosis and therapeutic targets for AF.

The highs and lows of cyclic thrombocytopenia.

Cyclic thrombocytopenia (CTP) is characterized by periodic platelet oscillation with substantial amplitude. Most CTP cases have a thrombocytopenic background and are often misdiagnosed as immune thrombocytopenia with erratically effective treatment choices. CTP also occurs during hydroxyurea treatment in patients with myeloproliferative diseases. While the aetiology of CTP remains uncertain, here we evaluate historical, theoretical and clinical findings to provide a framework for understanding CTP pathophysiology. CTP retains the intrinsic oscillatory factors defined by the homeostatic regulation of platelet count, presenting as reciprocal platelet/thrombopoietin oscillations and stable oscillation periodicity. Moreover, CTP patients possess pathogenic factors destabilizing the platelet homeostatic system thereby creating opportunities for external perturbations to initiate and sustain the exaggerated platelet oscillations. Beyond humoral and cell-mediated autoimmunity, we propose recently uncovered germline and somatic genetic variants, such as those of MPL, STAT3 or DNMT3A, as pathogenic factors in thrombocytopenia-related CTP. Likewise, the JAK2 V617F or BCR::ABL1 translocation that drives underlying myeloproliferative diseases may also play a pathogenic role in hydroxyurea-induced CTP, where hydroxyurea treatment can serve as both a trigger and a pathogenic factor of platelet oscillation. Elucidating the pathogenic landscape of CTP provides an opportunity for targeted therapeutic approaches in the future.

Imaging process matched neural network for complex wavefront retrieval with a higher space-bandwidth product.

Recently, deep learning (DL) has shown great potential in complex wavefront retrieval (CWR). However, the application of DL in CWR does not match well with the physical diffraction process. The state-of-the-art DL-based CWR methods crop full-size diffraction patterns down to a smaller size to save computational resources. However, cropping reduces the space-bandwidth product (SBP). In order to solve the trade-off between computational resources and SBP, we propose an imaging process matched neural network (IPMnet). IPMnet accepts full-size diffraction patterns with a larger SBP as inputs and retrieves a higher resolution and a larger field of view of the complex wavefront. We verify the effectiveness of the proposed IPMnet through simulations and experiments.

Different microbial assemblage colonized on microplastics and clay particles in aerobic sludge treatment.

In this study, a combination of property analysis and high-throughput sequencing was used to investigate the microbial colonization ability and their community structures and functions in polypropylene microplastics (PPMPs), polystyrene microplastics (PSMPs) and montmorillonite (MMT), respectively as the representatives of artificial and natural substrates in aerobic sludge treatment. After 45 d of incubation, the surface properties of substrates were altered with the increased oxygen functional groups and surface roughness, indicating microbial settlement. Moreover, MPs had different microbial structures from that of MMT, and PSMPs exhibited higher microbial diversity and abundance than PPMPs and MMT. Also, these substrates changed the inherent ecological niche in sludge. Especially, the abundance of some pathogens (e.g., Pseudomonas, Klebsiella and Flavobacterium) was increased in MPs, and the disease risk of Kyoto Encyclopedia of Genes and Genomes metabolic pathway (e.g., Infectious diseases: Bacterial, Infectious diseases: Parasitic and Immune diseases) was higher. Also, the presence of MPs inhibited the decomposition of organic matter including soluble chemical oxygen demand and protein compared to natural substrates. The findings revealed the crucial vector role of MPs for microbes and the effect on aerobic sludge treatment, highlighting the necessity of MP removal in sludge.

Extended autofocusing in dual-wavelength digital holography.

In single-wavelength digital holography (DH), the phase wrapping phenomenon limits the total object depth that can be measured due to the requirement for well-resolved phase fringes. To address this limitation, dual-wavelength DH is proposed, enabling measurement of much deeper objects. In single-wavelength DH, because the object depth is limited, the depth of focus (DOF) of DH's optical system at a reconstruction distance is sufficient to cover the object depth. To date, many autofocusing algorithms have been proposed to obtain a correct reconstruction distance. However, in dual-wavelength DH, because the object depth is extended, the DOF at a reconstruction distance cannot cover the extended object depth. The extended object depth can span multiple DOFs, causing partially out of focus object depth. Therefore, in dual-wavelength DH, relying solely on autofocusing algorithms for a single distance is insufficient. But extended autofocusing algorithms, which can autofocus objects through multiple DOFs, are demanded. However, there are no such extended autofocusing algorithms in dual-wavelength DH. Therefore, we propose an extended autofocusing algorithm for dual-wavelength DH based on a correlation coefficient. The proposed algorithm is able to focus the whole object depth when the depth spans multiple DOFs. Through theoretical analysis, simulations, and experiments, the necessity and effectiveness of the proposed algorithm are verified.

Microplastics exhibit lower carrying effects on the bioaccessibility and cytotoxicity of lead than montmorillonite clay particles.

Microplastics (MPs) in the environment are always colonized by microbes, which may have implications for carrying effect of pollutants and exposure risk in organisms. We present the crucial impacts and mechanisms of microbial colonization on the bioaccessibility and toxicity of Pb(II) loaded in disposable box-derived polypropylene (PP) and polystyrene (PS) MPs and montmorillonite (MMT) clay particles. After 45 d incubation, higher biomass measured by crystal violet staining were detected in MMT (1.23) than in PP and PS (0.400 and 0.721) indicating preferential colonization of microbes in clay particles. Microbial colonization further enhanced the sorption ability toward Pb(II), but inhibited the desorption and bioaccessibility of enriched Pb(II) in zebrafish and decreased the toxicity to gastric epithelial cells in an order of MMT > PS ≈ PP. The crucial effects were mainly because microbe-colonized substrates possessed higher oxygen functional groups and specific surface area and exhibited stronger interactions with Pb(II) and digestive component (i.e., pepsin) than pure substrates. This decreased the available soluble pepsin for complexing with sorbed Pb(II). The findings highlight the role of microbial colonization in modulating the exposure risks of artificial and natural substrate-associated pollutants and suggest that the risks of MPs may be overestimated compared to clay particles.

Short-term effects of air pollution and weather changes on the occurrence of acute aortic dissection in a cold region.

Background: Air pollution and severe weather conditions can adversely affect cardiovascular disease emergencies. Nevertheless, it remains unclear whether air pollutants and low ambient temperature can trigger the occurrence of acute aortic dissection (AAD) in cold regions. Methods: We applied a retrospective analysis to assess the short-term effects of air pollution and ambient temperature on the occurrence of AAD in Harbin, China. A total of 564 AAD patients were enrolled from a major hospital in Harbin between January 1, 2017, and February 5, 2021. Weather condition data and air pollutant concentrations, including fine particulate matter smaller than 10 µm (PM10) and 2.5 µm in diameter (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3), were collected every day. Conditional logistic regressions and correlation analysis were applied to analyze the relationship of environmental and atmospheric parameters with AAD occurrence at lags of 0 to 7 days. Specifically, we appraised the air quality index, CO, NO2, SO2, O3, PM10, PM2.5, temperature, dew point temperature, atmospheric pressure, and cloud amount. Results: A total of 1,496 days at risk were assessed, of which 564 patients developed AAD. Specifically, AAD did not occur on 1,043 (69.72%) days, while 1 or more cases occurred on 453 (30.28%) days. Several pollution and weather predictors for AAD were confirmed by multilevel modeling. The air quality index (p = 0.0012), cloud amount (p = 0.0001), and concentrations of PM2.5 (p = 0.0004), PM10 (p = 0.0013), NO2 (p = 0.0007) and O3 (p = 0.0001) predicted AAD as early as 7 days before the incident (lag of 7 days) in the study period. However, only concentrations of the air pollutants NO2 (p = 0.0468) and O3 (p = 0.011) predicted the occurrence of AAD after the COVID-19 outbreak. Similar predictive effects were observed for temperature, dew point temperature, and atmospheric pressure (all p < 0.05) on all days. Conclusion: The risk of AAD is closely related to air pollution and weather characteristics in Harbin. While causation was not determined, the impact of air pollutants on the risk of AAD was reduced after the COVID-19 outbreak.

Burden of Lung Cancer in China, 1990-2019: Findings from the Global Burden of Disease Study 2019.

BACKGROUND: Lung cancer is one of the most common malignant tumors in the world. It has become an increasingly important public health problem in China. In this study, we systematically assessed the lung cancer situation in China from 1990 to 2019 and provided an epidemiological knowledge base for the revision of health policies. The relevant data were extracted from the Global Burden of Disease (GBD) database. METHODS: Based on GBD 2019 data, we evaluated the incidence, prevalence, and death rates of lung cancer in China and their change trends from 1990 to 2019, making comparisons by gender and age. RESULTS: The age-standardized incidence and death rates (ASIR and ASDR, respectively) of lung cancer in China were higher than the average levels in Asia, Africa, Europe, and Oceania and also higher than those of neighboring Asian countries. Lung cancer rose from the seventh leading cause of death in 1990 to the fourth leading one in 2019, indicating that the disease burden of lung cancer is increasing. In 2019, the incidence, prevalence, and death rates of lung cancer were all higher in men than in women across all age groups. All three indices were lower in men and women <50 years old than in men and women >50 years. From 1990 to 2019, the ASIR, age-standardized prevalence rate (ASPR), and ASDR showed trends of increase (P < .05), and the rise in the ASPR (average annual percentage change [AAPC] = 1.9) was greater than those in the ASIR (AAPC = 1) and ASDR (AAPC = .8). CONCLUSIONS: From 1990 to 2019, the incidence, prevalence, and death rates of lung cancer continued to increase in China. To reduce this burden, prevention and management of known risk factors should be promoted through national policies.

Large depth-of-field ultra-compact microscope by progressive optimization and deep learning.

The optical microscope is customarily an instrument of substantial size and expense but limited performance. Here we report an integrated microscope that achieves optical performance beyond a commercial microscope with a 5×, NA 0.1 objective but only at 0.15 cm3 and 0.5 g, whose size is five orders of magnitude smaller than that of a conventional microscope. To achieve this, a progressive optimization pipeline is proposed which systematically optimizes both aspherical lenses and diffractive optical elements with over 30 times memory reduction compared to the end-to-end optimization. By designing a simulation-supervision deep neural network for spatially varying deconvolution during optical design, we accomplish over 10 times improvement in the depth-of-field compared to traditional microscopes with great generalization in a wide variety of samples. To show the unique advantages, the integrated microscope is equipped in a cell phone without any accessories for the application of portable diagnostics. We believe our method provides a new framework for the design of miniaturized high-performance imaging systems by integrating aspherical optics, computational optics, and deep learning.

A novel stemness classification in acute myeloid leukemia by the stemness index and the identification of cancer stem cell-related biomarkers.

Background: Stem cells play an important role in acute myeloid leukemia (AML). However, their precise effect on AML tumorigenesis and progression remains unclear. Methods: The present study aimed to characterize stem cell-related gene expression and identify stemness biomarker genes in AML. We calculated the stemness index (mRNAsi) based on transcription data using the one-class logistic regression (OCLR) algorithm for patients in the training set. According to the mRNAsi score, we performed consensus clustering and identified two stemness subgroups. Eight stemness-related genes were identified as stemness biomarkers through gene selection by three machine learning methods. Results: We found that patients in stemness subgroup I had a poor prognosis and benefited from nilotinib, MK-2206 and axitinib treatment. In addition, the mutation profiles of these two stemness subgroups were different, which suggested that patients in different subgroups had different biological processes. There was a strong significant negative correlation between mRNAsi and the immune score (r= -0.43, p<0.001). Furthermore, we identified eight stemness-related genes that have potential to be biomarkers, including SLC43A2, CYBB, CFP, GRN, CST3, TIMP1, CFD and IGLL1. These genes, except IGLL1, had a negative correlation with mRNAsi. SLC43A2 is expected to be a potential stemness-related biomarker in AML. Conclusion: Overall, we established a novel stemness classification using the mRNAsi score and eight stemness-related genes that may be biomarkers. Clinical decision-making should be guided by this new signature in prospective studies.

A case of acute myocarditis induced by PD-1 inhibitor (sintilimab) in the treatment of large cell neuroendocrine carcinoma.

The combination of Sintilimab with pemetrexed/platinum has become the first-line treatment for non-squamous non-small-cell lung carcinoma (NSCLC). Here, we report a patient with metastatic large cell neuroendocrine carcinoma (LCNEC) treated with Sintilimab for five cycles who developed shortness of breath after activity. The level of creatine kinase (CK), creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT) were significantly increased. The cardiac MR suggested that heart function was slightly decreased. Considering that the patient did not take any illicit drugs, without history of autoimmune disease, coronary heart disease, arrhythmia, or chronic heart failure, we diagnosed the patient with Sintilimab-induced myocarditis. The symptoms alleviated after rapid use of glucocorticoids. Myocarditis is a rare immune-related adverse events (irAEs), especially myocarditis induced by programmed cell death receptor-1 (PD-1) inhibitor in the treatment of LCNEC.

Bread staling prediction with a multiobjective particle swarm optimization-based bread constitutive modeling method.

Aiming at the complex and cumbersome problems of current bread staling detection technology, a food constitutive modeling method based on the multiobjective particle swarm optimization (MOPSO) was proposed, which can quickly and efficiently identify the creep test parameters for bread, and predict the viscoelastic parameters of bread staling using the analyzed viscoelastic parameters, resulting in convenient and efficient detection of bread staling. Firstly, airflow-laser detection technology was used to carry out rapid, efficient, and non-destructive bread rheological tests to obtain bread creep test data. The MOPSO based on the Pareto set was then used to identify the generalized Kelvin model, and the discrimination accuracy was evaluated by using the inversion results established by the viscoelastic parameters, which resulted in efficient discrimination of creep test data of starch-based products represented by bread. Finally, using extreme learning machine regression (ELM), a prediction model between the analysis results and the moisture content of bread staling was established, and the prediction effect of the analysis results on bread staling was verified. The experimental results show that, when compared to finite element analysis (FEA) and non-linear regression (NLR) to identify creep parameters, the MOPSO overcomes the shortcomings of easy falling into the local optimal solution, is easy to implement, has strong global search ability, and is suitable for the analysis of high-dimensional viscoelastic models of complex foods. The correlation coefficient (R) of the prediction set established by the 12-membered viscoelastic parameters in the prediction model established by multi-element viscoelastic parameters and bread moisture content was 0.847, and the root mean square error (RMSE) was 0.021. This demonstrated that, when combined with MOPSO, airflow-laser detection technology could effectively identify the viscoelastic parameters of bread and establish a method suitable for monitoring bread staling in industrial production. The results of this study provide a reference for the identification of viscoelastic parameters of complex foods and to detect bread staling quickly and efficiently.

Twenty-three medication-taking traits and stroke: A comprehensive Mendelian randomization study.

Background: Certain medication categories may increase the risk of stroke. Nonetheless, the evidence regarding the causal relationship of medication-taking in promoting stroke and subtypes is deficient. Methods: We evaluated the causal effect of a genetic predisposition for certain medication categories on stroke and subtypes (ischemic and hemorrhagic categories) by a two-sample Mendelian randomization (MR) analysis. Data for 23 medication categories were gathered from a genome-wide association study (GWAS) involving 318,177 patients. The Medical Research Council Integrative Epidemiology Unit Open GWAS database and the FinnGen consortium were used to gather GWAS data for stroke and subtypes. Inverse variance weighted, MR-Egger, and weighted median were used for the estimation of causal effects. Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were used for sensitivity analyses. Results: Ten medication categories were linked to a high stroke risk. Nine categories were linked to a high-risk ischemic stroke. Five categories were associated with small vessel ischemic stroke. Nine categories were positively associated with large artery atherosclerotic ischemic stroke. Three categories causally increased the possibility of cardioembolic ischemic stroke. Four categories were associated with intracerebral hemorrhage. Four categories were associated with nontraumatic intracranial hemorrhage. Three categories were causally associated with subarachnoid hemorrhage (SAH). Four categories were associated with the combination of SAH, unruptured cerebral aneurysm, and aneurysm operations SAH. Conclusions: This study confirms that some medication categories lead to a greater risk of strokes. Meanwhile, it has an implication for stroke screening as well as direct clinical significance in the design of conduction of future randomized controlled trials.

The role of CD8+ T-cell clones in immune thrombocytopenia.

Immune thrombocytopenia (ITP) is traditionally considered an antibody-mediated disease. However, a number of features suggest alternative mechanisms of platelet destruction. In this study, we use a multidimensional approach to explore the role of cytotoxic CD8+ T cells in ITP. We characterized patients with ITP and compared them with age-matched controls using immunophenotyping, next-generation sequencing of T-cell receptor (TCR) genes, single-cell RNA sequencing, and functional T-cell and platelet assays. We found that adults with chronic ITP have increased polyfunctional, terminally differentiated effector memory CD8+ T cells (CD45RA+CD62L-) expressing intracellular interferon gamma, tumor necrosis factor α, and granzyme B, defining them as TEMRA cells. These TEMRA cells expand when the platelet count falls and show no evidence of physiological exhaustion. Deep sequencing of the TCR showed expanded T-cell clones in patients with ITP. T-cell clones persisted over many years, were more prominent in patients with refractory disease, and expanded when the platelet count was low. Combined single-cell RNA and TCR sequencing of CD8+ T cells confirmed that the expanded clones are TEMRA cells. Using in vitro model systems, we show that CD8+ T cells from patients with ITP form aggregates with autologous platelets, release interferon gamma, and trigger platelet activation and apoptosis via the TCR-mediated release of cytotoxic granules. These findings of clonally expanded CD8+ T cells causing platelet activation and apoptosis provide an antibody-independent mechanism of platelet destruction, indicating that targeting specific T-cell clones could be a novel therapeutic approach for patients with refractory ITP.