tbuckley/cabot-search huggingface dataset:
Combining Atovaquone with Intensive Conventional Chemotherapy for Pediatric Acute Myeloid Leukemia (AML) Is Feasible and Well Tolerated
Authors: Alexandra McLean Stevens, Eric Schafer, Minhua Li, Maci Terrell, Raushan Rashid, Hana Paek, Allison Weisnicht, Noah J Keogh, Michelle C Alozie, Hailey H Oviedo, Alan K Gonzalez, Alicia Mangubat-Medina, Haopei Wang, Eunji Jo, Cara A Rabik, Claire Bocchini, Susan Hilsenbeck, Zachary T Ball, Todd M. Cooper, Michele Redell
Journal: Blood (2021)
Association of cardiometabolic microRNAs with COVID-19 severity and mortality
Authors: Clemens Gutmann, Kseniya Khamina, Konstantinos Theofilatos, Andreas B Diendorfer, Sean A Burnap, Adam Nabeebaccus, Matthew Fish, Mark J W McPhail, Kevin O'Gallagher, Lukas E Schmidt, Christian Cassel, Georg Auzinger, Salvatore Napoli, Salma F Mujib, Francesca Trovato, Barnaby Sanderson, Blair Merrick, Roman Roy, Jonathan D Edgeworth, Ajay M Shah, Adrian C Hayday, Ludwig Traby, Matthias Hackl, Sabine Eichinger, Manu Shankar-Hari, Manuel Mayr
Journal: Cardiovascular Research (2021)

Abstract Aims Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage. MicroRNAs (miRNAs) in blood reflect cell activation and tissue injury. We aimed to determine the association of circulating miRNAs with COVID-19 severity and 28 day intensive care unit (ICU) mortality. Methods and results We performed RNA-Seq in plasma of healthy controls (n = 11), non-severe (n = 18), and severe (n = 18) COVID-19 patients and selected 14 miRNAs according to cell- and tissue origin for measurement by reverse transcription quantitative polymerase chain reaction (RT–qPCR) in a separate cohort of mild (n = 6), moderate (n = 39), and severe (n = 16) patients. Candidates were then measured by RT–qPCR in longitudinal samples of ICU COVID-19 patients (n = 240 samples from n = 65 patients). A total of 60 miRNAs, including platelet-, endothelial-, hepatocyte-, and cardiomyocyte-derived miRNAs, were differentially expressed depending on severity, with increased miR-133a and reduced miR-122 also being associated with 28 day mortality. We leveraged mass spectrometry-based proteomics data for corresponding protein trajectories. Myocyte-derived (myomiR) miR-133a was inversely associated with neutrophil counts and positively with proteins related to neutrophil degranulation, such as myeloperoxidase. In contrast, levels of hepatocyte-derived miR-122 correlated to liver parameters and to liver-derived positive (inverse association) and negative acute phase proteins (positive association). Finally, we compared miRNAs to established markers of COVID-19 severity and outcome, i.e. SARS-CoV-2 RNAemia, age, BMI, D-dimer, and troponin. Whilst RNAemia, age and troponin were better predictors of mortality, miR-133a and miR-122 showed superior classification performance for severity. In binary and triplet combinations, miRNAs improved classification performance of established markers for severity and mortality. Conclusion Circulating miRNAs of different tissue origin, including several known cardiometabolic biomarkers, rise with COVID-19 severity. MyomiR miR-133a and liver-derived miR-122 also relate to 28 day mortality. MiR-133a reflects inflammation-induced myocyte damage, whilst miR-122 reflects the hepatic acute phase response.
Risk of second primary malignancies in patients with follicular lymphoma: a population-based study in the Netherlands, 1989-2018
Authors: Manette A. W. Dinnessen, Otto Visser, Sanne H. Tonino, Eduardus F. M. Posthuma, Nicole M. A. Blijlevens, Marie José Kersten, Pieternella J. Lugtenburg, Avinash G. Dinmohamed
Journal: Blood Cancer Journal (2021)
Precision Co-Targeting of the Thymic Stromal Lymphopoietin Receptor in Childhood <i>CRLF2</i>-Rearranged Acute Lymphoblastic Leukemia
Authors: Asen Bagashev, Joseph Patrick Loftus, Savannah Ross, Lisa M Niswander, Haiying Qin, Terry J. Fry, Sarah K Tasian
Journal: Blood (2021)
Percutaneous Kidney Puncture with Three-dimensional Mixed-reality Hologram Guidance: From Preoperative Planning to Intraoperative Navigation
Authors: Francesco Porpiglia, Enrico Checcucci, Daniele Amparore, Dario Peretti, Federico Piramide, Sabrina De Cillis, Alberto Piana, Gabriel Niculescu, Paolo Verri, Matteo Manfredi, Massimiliano Poggio, Ilaria Stura, Giuseppe Migliaretti, Marco Cossu, Cristian Fiori
Journal: European Urology (2021)
<i>In Vivo</i> Delivery of a CD20 CAR Using a CD8-Targeted Fusosome in Southern Pig-Tail Macaques (<i>M. nemestrina</i>) Results in B Cell Depletion
Authors: Justine Cunningham, Sundeep Chandra, Akinola Emmanuel, Allyse Mazzarelli, Carmela Passaro, Paige Baldwin, Michelle Nguyen-McCarty, Carrie Rocca, Shannon Joyce, Joohwan Kim, Vasily Vagin, James Kaczmarek, Hemant Chavan, Heather Jewell, Yonatan Lipsitz, Misha Shamashkin, Kelan Hlavaty, Jason Rodriguez, Carl Co, Pattie Cruite, Hanane Ennajdaoui, Victoria Duback, Jess Elman, Shirisha Amatya, Caspian Harding, Sergey Lyubinetsky, Vidur Patel, Lauren Pepper, Albert Ruzo, Salvatore Iovino, Bindu Varghese, Aaron E. Foster, Boris Gorovits, Kutlu Elpek, Michael Laska, Trevor McGill, Jagesh V Shah, Terry J. Fry, Donna Dambach
Journal: Blood (2021)
The Impact of T Cell Immunity on Chemotherapy Response in Childhood Acute Lymphoblastic Leukemia
Authors: Yizhen Li, Xu Yang, Yu Sun, Wentao Yang, Wenjian Yang, Bensheng Ju, John Easton, Shawn Lee, Ching-Hon Pui, Jiyang Yu, Hongbo Chi, Jun J. Yang
Journal: Blood (2021)
Abstract 14056: Evaluation Of A Non-invasive Left Ventricular Pressure-volume Loop Approximation Method Based On Arterial Blood Pressure Values And Cardiac MRI
Authors: Jing Liu, Niema M Pahlevan
Journal: Circulation (2021)

Introduction: Left ventricle (LV) pressure-volume loop (LVPVL) is an informative manifestation of LV mechanical dynamics. Seemann et al. (Circulation: Cardiovascular Imaging. 2019;12(1): e008493) proposed a novel non-invasive LVPVL approximation method using brachial blood pressure and cardiac MRI with the double-Hill model characterizing the time-varying LV elastance. However, their clinical validation was performed on a small population with a significant age difference between the control and HF groups. Methods: We evaluated the noninvasive LVPVL method on the iPhone-HMRI study cohort that includes non-HF (N = 102) and HF (N =25) participants. (Pahlevan et al. Critical Care Medicine ,2017 PMID: 28441235) Mean[range] of age (years) were 53[20-92] and 55[26-88] for the non-HF and the HF groups, respectively. Stroke work, potential energy, external power, energy per ejected volume, contractility, and LV efficiency from the estimated loops were compared between the non-HF and HF groups. Results: The estimated LVPVLs for HF group yielded significantly higher mechanical potential energy and energy per ejected volume, but significantly lower ventricular efficiency and contractility (p&lt;0.0001). There were no significant differences between groups for stroke work (p=0.09) and mean external power (p=0.86). Conclusions: Our results with an age-matching control group agree with the previously reported results. However, since this method uses a fixed guesses of LV end-diastolic pressure, it is suspected that the resultant estimated LVPVL cannot effectively characterize the variation along the pressure axis and the loop-area for features such as stroke work and mean external power. Improvements are needed to leverage hemodynamic information in arterial pressure waveforms (i.e., carotid) to enhance the sensitivity of such non-invasive LVPVL determination based on time-varying LV elastance model and arterial waveforms measured using tonometry.
Safety and Effectiveness of Venetoclax/Rituximab in Bcri-Naïve and Bcri-Exposed Patients with Relapsed/Refractory CLL Under Real-Life Conditions - Data from the Observational Verve Study
Authors: Davide Rossi, Holger Hebart, Christoph Losem, Thomas Wolff, Xenia Schmidt, Kirsten Famulla, Burkhard Schmidt, Thomas Noesslinger, Ingo Schwaner
Journal: Blood (2021)
Non-Infectious Morbidity during Pediatric Acute Myeloid Leukemia Chemotherapy in the Netherlands: A 15-Year Overview
Authors: Emily R. Schwartz, Kim Klein, Valerie De Haas, Natasja Dors, Marry M. van den Heuvel-Eibrink, Rutger R.G. Knops, Wim J.E. Tissing, Birgitta Versluijs, C. Michel Zwaan, Raphaele R.L. van Litsenburg, Gertjan J.L. Kaspers
Journal: Blood (2021)
Effect of adjunctive vitamin C, glucocorticoids, and vitamin B1 on longer-term mortality in adults with sepsis or septic shock: a systematic review and a component network meta-analysis
Authors: Tomoko Fujii, Georgia Salanti, Alessandro Belletti, Rinaldo Bellomo, Anitra Carr, Toshi A. Furukawa, Nora Luethi, Yan Luo, Alessandro Putzu, Chiara Sartini, Yasushi Tsujimoto, Andrew A. Udy, Fumitaka Yanase, Paul J. Young
Journal: Intensive Care Medicine (2021)

We aimed to compare the effects of vitamin C, glucocorticoids, vitamin B1, combinations of these drugs, and placebo or usual care on longer-term mortality in adults with sepsis or septic shock. MEDLINE, Embase, CENTRAL, ClinicalTrials.gov and WHO-ICTRP were searched. The final search was carried out on September 3rd, 2021. Multiple reviewers independently selected randomized controlled trials (RCTs) comparing very-high-dose vitamin C (≥ 12 g/day), high-dose vitamin C (< 12, ≥ 6 g/day), vitamin C (< 6 g/day), glucocorticoid (< 400 mg/day of hydrocortisone), vitamin B1, combinations of these drugs, and placebo/usual care. We performed random-effects network meta-analysis and, where applicable, a random-effects component network meta-analysis. We used the Confidence in Network Meta-Analysis framework to assess the degree of treatment effect certainty. The primary outcome was longer-term mortality (90-days to 1-year). Secondary outcomes were severity of organ dysfunction over 72 h, time to cessation of vasopressor therapy, and length of stay in intensive care unit (ICU). Forty-three RCTs (10,257 patients) were eligible. There were no significant differences in longer-term mortality between treatments and placebo/usual care or between treatments (10 RCTs, 7,096 patients, moderate to very-low-certainty). We did not find any evidence that vitamin C or B1 affect organ dysfunction or ICU length of stay. Adding glucocorticoid to other treatments shortened duration of vasopressor therapy (incremental mean difference, − 29.8 h [95% CI − 44.1 to − 15.5]) and ICU stay (incremental mean difference, − 1.3 days [95% CI − 2.2 to − 0.3]). Metabolic resuscitation with vitamin C, glucocorticoids, vitamin B1, or combinations of these drugs was not significantly associated with a decrease in longer-term mortality.
Prophylactic Treatment of Severe Haemophilia Á Patients with Inhibitors to FVIII with Peglip-FVIII
Authors: Margarita Timofeeva, Nadezhda I. Zozulya, Tatiana Pospelova, Marina V Kosinova, Igor Kurtov, Edward Tuddenham, Gavin Ling
Journal: Blood (2021)
A Phase 2 Study of Pemigatinib (FIGHT-203; INCB054828) in Patients with Myeloid/Lymphoid Neoplasms (MLNs) with Fibroblast Growth Factor Receptor 1 (FGFR1) Rearrangement (MLN <i>FGFR1</i>)
Authors: Jason Gotlib, Jean-Jacques Kiladjian, Alessandro Vannucchi, Alessandro Rambaldi, Andreas Reiter, William Shomali, Tracy I. George, Jay L. Patel, Philomena Colucci, Chris Walker, Huiling Zhen, Srdan Verstovsek
Journal: Blood (2021)
318 Enforced tumor specific MHC-I heterogeneity in triple negative breast cancer drives immunotherapy resistance
Authors: Brandie Taylor, Justin Balko, Melinda Sanders, Paula Gonzalez-Ericsson, Violeta Sanchez
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Despite the broad success of immune checkpoint inhibition (ICI e.g. anti-Programmed Death Ligand-1 [PD-L1]) in cancer treatment, tumor-intrinsic factors leading to intrinsic and acquired resistance are poorly understood. Tumor specific MHC-I expression is indispensable for anti-PD-1/L1 response as complete loss of MHC-I via B2M deletion results in inability of CD8+ T cells to recognize tumor-associated antigens. However, MHC-I is heterogeneously downregulated or lost in many tumor types. Tumor cell destruction can also occur through non-synaptic mechanisms, in a so-called ‘field effect’. Therefore, we modeled heterogeneous loss of MHC-I expression in breast cancer and experimentally evaluated how heterogeneous MHC-I loss affects response to anti-PD-L1 therapy. Methods We performed quantitative immunofluorescence for MHC-I and Pan-CK on breast cancer tumors (n=410). To determine the functional effect of MHC-I heterogeneity on anti-PD-L1 response, we used an immunocompetent EMT6 orthotopic mammary tumor model which ubiquitously expresses MHC-I at baseline. Using CRISPR/Cas9, we engineered EMT6 cells with B2m loci excision resulting in complete knockout of MHC-I on the cell surface. We then orthotopically implanted B2m-comtetent and B2m-KO cells at varying inoculum ratios (100:0, 90:10, 50:50, 10:90, 0:100) into syngeneic Balb/C mice and assessed immune responsiveness and efficacy of checkpoint inhibition. Additionally, to look at how loss of MHC-I affects the tumor microenvironment we will use the PanCancer Immune NanoString panel (n=770 genes) to evaluate gene expression patterns in tumor cells and infiltrating immune cells. Results In patient samples, we identified high diversity in MHC-I expression across all clinical subtypes, with triple negative breast cancer (TNBC) having the highest MHC-I expression. Chemotherapy-treated tumors had higher MHC-I levels than untreated tumors. In mice when 10% of cells were B2m-KO, we observed a 50% reduction in complete eradication of EMT6 tumors with aPD-L1 treatment and reduced disease-stabilization and no complete responses when a 50% mixture of MHC-I deficient cells. An increasing percentage of B2m KO leads to worse outcomes overall and a decrease in infiltrating T cells. Conclusions Our work suggests that there is an ICI-responsive phenotype that is driven by heterogeneity in MHC-I expression levels. As little as 10% of tumor specific MHC-I loss can lead to therapeutic resistance and a decrease in complete responders. This represents that early TNBC may be less responsive to single-agent PD-L1 due to specific percentages of MHC-I loss. MHC-I expression can influence therapy outcomes and potentially lead to novel observations of how to overcome lack of, or limited, MHC-I expression.
Myeloid cyclooxygenase-2/prostaglandin E2/E-type prostanoid receptor 4 promotes transcription factor MafB-dependent inflammatory resolution in acute kidney injury
Authors: Yu Pan, Shirong Cao, Andrew S. Terker, Jiaqi Tang, Kensuke Sasaki, Yinqiu Wang, Aolei Niu, Wentian Luo, Dhouha Daassi, Xiaofeng Fan, Suwan Wang, Matthew H. Wilson, Ming-Zhi Zhang, Raymond C. Harris
Journal: Kidney International (2021)
Right atrial function is associated with right venticular diastolic stiffness: RA–RV interaction in pulmonary arterial hypertension
Authors: Jeroen N. Wessels, Sophia A. Mouratoglou, Jessie van Wezenbeek, M. Louis Handoko, J. Tim Marcus, Lilian J. Meijboom, Berend E. Westerhof, Harm Jan Bogaard, Gustav J. Strijkers, Anton Vonk Noordegraaf, Frances S. de Man
Journal: European Respiratory Journal (2021)

Background Pulmonary arterial hypertension (PAH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness. This study assessed the impact of RV diastolic stiffness on RA–RV interaction. Methods PAH patients with low or high end-diastolic elastance (E ed ) (n=94) were compared with controls (n=31). Treatment response was evaluated in 62 patients. RV and RA longitudinal strain, RA emptying and RV filling were determined and diastole was divided into a passive and active phase. Vena cava backflow was calculated as RA active emptying−RV active filling and RA stroke work as RA active emptying×RV end-diastolic pressure. Results With increased E ed , RA and RV passive strain were reduced while active strain was preserved. In comparison to controls, patients had lower RV passive filling but higher RA active emptying and RA stroke work. RV active filling was lower in patients with high E ed , resulting in higher vena cava backflow. Upon treatment, E ed was reduced in ~50% of the patients with high E ed , which coincided with larger reductions in afterload, RV mass and vena cava backflow and greater improvements in RV active filling and stroke volume in comparison with patients in whom E ed remained high. Conclusions In PAH, RA function is associated with changes in RV function. Despite increased RA stroke work, severe RV diastolic stiffness is associated with reduced RV active filling and increased vena cava backflow. In 50% of patients with high baseline E ed , diastolic stiffness remained high, despite treatment. A reduction in E ed coincided with a large reduction in afterload, increased RV active filling and decreased vena cava backflow.
Gain-of-function mutations in RPA1 cause a syndrome with short telomeres and somatic genetic rescue
Authors: Richa Sharma, Sushree S. Sahoo, Masayoshi Honda, Sophie L. Granger, Charnise Goodings, Louis Sanchez, Axel Künstner, Hauke Busch, Fabian Beier, Shondra M. Pruett-Miller, Marcus B. Valentine, Alfonso G. Fernandez, Ti-Cheng Chang, Vincent Géli, Dmitri Churikov, Sandrine Hirschi, Victor B. Pastor, Melanie Boerries, Melchior Lauten, Charikleia Kelaidi, Megan A. Cooper, Sarah Nicholas, Jill A. Rosenfeld, Sophia Polychronopoulou, Caroline Kannengiesser, Carole Saintomé, Charlotte M. Niemeyer, Patrick Revy, Marc S. Wold, Maria Spies, Miriam Erlacher, Stéphane Coulon, Marcin W. Wlodarski
Journal: Blood (2021)

Human telomere biology disorders (TBD)/short telomere syndromes (STS) are heterogeneous disorders caused by inherited loss-of-function mutations in telomere-associated genes. Here, we identify 3 germline heterozygous missense variants in the RPA1 gene in 4 unrelated probands presenting with short telomeres and varying clinical features of TBD/STS, including bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopenia, pulmonary fibrosis, or skin manifestations. All variants cluster to DNA-binding domain A of RPA1 protein. RPA1 is a single-strand DNA-binding protein required for DNA replication and repair and involved in telomere maintenance. We showed that RPA1E240K and RPA1V227A proteins exhibit increased binding to single-strand and telomeric DNA, implying a gain in DNA-binding function, whereas RPA1T270A has binding properties similar to wild-type protein. To study the mutational effect in a cellular system, CRISPR/Cas9 was used to knock-in the RPA1E240K mutation into healthy inducible pluripotent stem cells. This resulted in severe telomere shortening and impaired hematopoietic differentiation. Furthermore, in patients with RPA1E240K, we discovered somatic genetic rescue in hematopoietic cells due to an acquired truncating cis RPA1 mutation or a uniparental isodisomy 17p with loss of mutant allele, coinciding with stabilized blood counts. Using single-cell sequencing, the 2 somatic genetic rescue events were proven to be independently acquired in hematopoietic stem cells. In summary, we describe the first human disease caused by germline RPA1 variants in individuals with TBD/STS.
Whole-Genome CRISPR Screening Identifies <i>N</i>-Glycosylation As an Essential Pathway and a Potential Novel Therapeutic Target in <i>CALR</i>-Mutant MPN
Authors: Anna E. Marneth, Jonas S. Jutzi, Angel Guerra-Moreno, Michele Ciboddo, María José Jiménez Santos, Anastasia Kosmidou, Rebecca Hamel, Patricia Lozano, Elisa Rumi, John G. Doench, Jason Gotlib, Anandi Krishnan, Shannon Elf, Fatima Al-Shahrour, Ann Mullally
Journal: Blood (2021)
Ultrathin tellurium nanosheets for simultaneous cancer thermo-chemotherapy
Authors: Wen Pan, Chuang Liu, Yunhui Li, Yang Yang, Wenliang Li, Chan Feng, Leijiao Li
Journal: Bioactive Materials (2021)

The emerging two-dimensional monoelemental materials (2D Xenes) have been commonly supposed as promising drug delivery carriers, photothermal and photodynamic therapeutic agents, biosensors, theranostics, and some other candidates for biomedical applications. Here, high-performance and bioactive ultrathin 2D Tellurium nanosheets (Te NSs) are prepared by a simple but efficient liquid-phase exfoliation approach. The as-obtained Te NSs possess a mean size of ∼90 nm and a mean thickness of ∼5.43 nm. The pegylation Te NSs (Te-PEG NSs) possess excellent biocompatibility and stability. The Te-PEG NSs could generate local hyperthermia with a remarkable photothermal conversion efficiency of about 55% under 808 nm laser irradiation. Additionally, Te-PEG NSs exhibit an extremely high loading capacity of chemo drug (∼162%) owing to their ultra-high surface area and tumor microenvironment-triggered drug release superiority. The results of in vivo experiments show that the Te-PEG NSs have higher tumor elimination efficiency via the combination of photothermal and chemotherapy, comparing to any other single therapeutic modalities. Therefore, our work not only highlights the promising potentials of tellurene as an ideal anti-cancer platform but also expands the application of 2D Te for cancer nanomedicine.
Priming Death Receptor Mediated Apoptosis with Arginine Starvation Sensitises Arginine Auxotrophic B-ALL to CAR-T
Authors: Michael J Austin, Leena Halim, Farideh Miraki-Moud, David Taussig, John Bomalaski, John Maher, John Gribben, Peter Szlosarek, Bela Wrench
Journal: Blood (2021)
Radical or not, NICE makes evidence based recommendations
Authors: Gillian Leng
Journal: BMJ (2021)

Godlee’s call for the National Institute for Health and Care Excellence to keep close to its radical roots is interesting, not least because NICE has never claimed this for itself.1 Radical or not, NICE applies thorough and robust approaches to assessing health technologies. This helps patients access innovative treatments that help them live longer, better quality lives while providing value for money.

The …
False-Negative Centromere 15 Probe Results in Association with African Ancestry in Plasma Cell Dyscrasias
Authors: Alaa Koleilat, Hongwei Tang, James B Smadbeck, Neeraj Sharma, Kathryn E. Pearce, Eran Elhaik, Michael L. Baird, Yan Asmann, Patricia Greipp, Jess F Peterson, Rhett P. Ketterling, S. Vincent Rajkumar, Shaji Kumar, Linda B Baughn
Journal: Blood (2021)
CD98-induced CD147 signaling stabilizes the Foxp3 protein to maintain tissue homeostasis
Authors: JieJie Geng, Ruo Chen, Feng-fan Yang, Peng Lin, Yu-meng Zhu, Xianghui Fu, Ke Wang, Zhuan Feng, Jiao Wu, Hai Zhang, Qi-jing Li, Zhi-Nan Chen, Ping Zhu
Journal: Cellular and Molecular Immunology (2021)

Abstract Regulatory T cell (Treg) stability is necessary for the proper control of immune activity and tissue homeostasis. However, it remains unclear whether Treg stability must be continually reinforced or is established during development under physiological conditions. Foxp3 has been characterized as a central mediator of the genetic program that governs Treg stability. Here, we demonstrate that to maintain Foxp3 protein expression, Tregs require cell-to-cell contact, which is mediated by the CD147-CD98 interaction. As Tregs are produced, CD147, which is expressed on their surface, is stimulated by CD98, which is widely expressed in the physiological environment. As a result, CD147’s intracellular domain binds to CDK2 and retains it near the membrane, leading to Foxp3 dephosphorylation and the prevention of Foxp3 degradation. In addition, the optimal distribution of Foxp3+ Tregs under both pathological and physiological conditions depends on CD98 expression. Thus, our study provides direct evidence that Foxp3-dependent Treg stability is reinforced in the periphery by the interaction between CD147 and CD98 in the surrounding environment. More importantly, Tregs with high CD147 expression effectively inhibit inflammatory responses and maintain Foxp3 stability, which has guiding significance for the application of Tregs in immunotherapy.