bluuebunny/crossref_metadata_2025 huggingface dataset:
VSSB-Raft: A Secure and Efficient Zero Trust Consensus Algorithm for Blockchain
Authors: Tian Siben , Bai Fenhua , Shen Tao , Zhang Chi , Gong Bei
Published: August 2023

To solve the problems of vote forgery and malicious election of candidate nodes in the Raft consensus algorithm, we combine zero trust with the Raft consensus algorithm and propose a secure and efficient consensus algorithm -Verifiable Secret Sharing Byzantine Fault Tolerance Raft Consensus Algorithm (VSSB-Raft). The VSSB-Raft consensus algorithm realizes zero trust through the supervisor node and secret sharing algorithm without the invisible trust between nodes required by the algorithm. Meanwhile, the VSSB-Raft consensus algorithm uses the SM2 signature algorithm to realize the characteristics of zero trust requiring authentication before data use. In addition, by introducing the NDN network, we redesign the communication between nodes and guarantee the communication quality among nodes. The VSSB-Raft consensus algorithm proposed in this paper can make the algorithm Byzantine fault tolerant by setting a threshold for secret sharing while maintaining the algorithm’s complexity to be O(n). Experiments show that the VSSB-Raft consensus algorithm is secure and efficient with high throughput and low consensus latency.
Fraud Detection under Siege: Practical Poisoning Attacks and Defense Strategies
Authors: Paladini Tommaso , Monti Francesco , Polino Mario , Carminati Michele , Zanero Stefano
Published: August 2023

Machine learning (ML) models are vulnerable to adversarial machine learning (AML) attacks. Unlike other contexts, the fraud detection domain is characterized by inherent challenges that make conventional approaches hardly applicable. In this article, we extend the application of AML techniques to the fraud detection task by studying poisoning attacks and their possible countermeasures. First, we present a novel approach for performing poisoning attacks that overcomes the fraud detection domain-specific constraints. It generates fraudulent candidate transactions and tests them against a machine learning-based
Oracle
, which simulates the target fraud detection system aiming at evading it. Misclassified fraudulent candidate transactions are then integrated into the target detection system’s training set, poisoning its model and shifting its decision boundary. Second, we propose a novel approach that extends the adversarial training technique to mitigate AML attacks: During the training phase of the detection system, we generate artificial frauds by modifying random original legitimate transactions; then, we include them in the training set with the correct label. By doing so, we instruct our model to recognize evasive transactions before an attack occurs. Using two real bank datasets, we evaluate the security of several state-of-the-art fraud detection systems by deploying our poisoning attack with different degrees of attacker’s knowledge and attacking strategies. The experimental results show that our attack works even when the attacker has minimal knowledge of the target system. Then, we demonstrate that the proposed countermeasure can mitigate adversarial attacks by reducing the stolen amount of money up to 100%.
On Strongest Algebraic Program Invariants
Authors: Hrushovski Ehud , Ouaknine Joël , Pouly Amaury , Worrell James
Published: August 2023

A polynomial program is one in which all assignments are given by polynomial expressions and in which all branching is nondeterministic (as opposed to conditional). Given such a program, an algebraic invariant is one that is defined by polynomial equations over the program variables at each program location. Müller-Olm and Seidl have posed the question of whether one can compute the strongest algebraic invariant of a given polynomial program. In this article, we show that, while strongest algebraic invariants are not computable in general, they can be computed in the special case of affine programs, that is, programs with exclusively linear assignments. For the latter result, our main tool is an algebraic result of independent interest: Given a finite set of rational square matrices of the same dimension, we show how to compute the Zariski closure of the semigroup that they generate.
Urban Pollination Ecology
Authors: Youngsteadt Elsa , Keighron Melina C.
Published: August 2023

Pollination is an essential component of plant reproduction that is transformed by the novel environmental conditions in cities. We summarize patterns of urban plant reproduction and trace the mechanisms by which urban environments influence pollination, beginning at the level of the individual plant. We then progress through several processes unique to animal-pollinated plants, including plant–pollinator signaling, community-level effects, and emergent plant–pollinator interaction networks. Last, we review pollen movement and plant spatial mating networks. Despite a global signal of reduced pollination in urban, animal-pollinated plants, effects vary among studies, and the extent of pollen dispersal through a city remains difficult to predict. We highlight recent progress, as well as areas where new research will help crystallize our understanding of urban pollination. These advances have the potential to spur exciting new insights into network dynamics and pollen movement, and may ultimately inform the sustainable design of urban conservation and ecosystem services.
Relationships among intragastric meal distribution during gastric emptying scintigraphy, water consumption during water load satiety testing, and symptoms of gastroparesis
Authors: Parkman Henry P. , Wilson Laura A. , Silver Paul , Maurer Alan H. , Sarosiek Irene , Bulat Robert S. , Kuo Braden , Grover Madhusudan , Farrugia Gianrico , Chumpitazi Bruno P. , Shulman Robert J. , Malik Zubair , Miriel Laura A. , Tonascia James , Hamilton Frank , Abell Thomas L. , Pasricha Pankaj J. , McCallum Richard W. , Koch Kenneth L. ,   for the NIDDK Gastroparesis Clinical Research Consortium
Published: August 2023

IMD0 and WLST were assessed for their clinical utility in assessing patients with symptoms of gastroparesis. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.
Controllability Analysis of Linear Time-Varying T-H Equation with Matrix Sequence Method
Authors: Liu Sihui , Huang Qingdao
Published: August 2023

A satellite is considered to be moving relative to a nominal elliptical orbit, whose dynamics are usually described by the Tschaunner-Hempel equation (T-H equation). In this paper, we propose to transform the second-order time-varying system represented by the linear T-H equation with a second-order matrix form into a first-order time-varying system. Then, the controllability of the first-order time-varying system is investigated with the matrix sequence method including

e
=
0

. Meanwhile, we study the observability of the first-order time-varying system with a specific form of measurement. The advantages of the matrix sequence method for controllability and observability analysis are tested by numerical examples, respectively. Dual theory is used to investigate the controllability and observability of the corresponding dual system of the T-H equation. The corresponding conclusions are obtained.
Physical Activity and Exercise as a Tool to Cure Anxiety and Posttraumatic Stress Disorder
Authors: Sabri Saima , Rashid Nadia , Mao Zhi-Xiong
Published: August 2023

Anxiety and posttraumatic stress disorder (PTSD) are the most prevalent psychiatric conditions and significant public health problems. However, research has tended to support claims that engaging in physical activity (PA) has beneficial psychological effects. The objective of this review is to examine exercise and PA therapies as a kind of PTSD and anxiety treatment. Exercise has been shown in interventional trials to be both anxiolytic and antidepressive in healthy individuals. Exercise and PA therapies have a variety of benefits and varying degrees of efficacy in treating PTSD and anxiety symptoms. PA has been shown to promote physical health; psychological health and a growing body of studies indicate that PA and general health are associated with PTSD and anxiety. These findings led to recommendations for exercise interventions as a safe, efficient, and effective therapeutic option for treating anxiety and PTSD symptoms. Studies have not, however, demonstrated that they can lower anxiety to the same degree as psychotropic drugs. Additionally, the majority of published studies have significant methodological flaws, necessitating the need for additional research to determine the ideal exercise modalities, frequency, duration, and intensity for enhancing the beneficial benefits of exercise on anxiety and PTSD.
Dihydromyricetin Alleviates Nonalcoholic Fatty Liver Disease and Its Associated Metabolic Syndrome by Inhibiting Endoplasmic Reticulum Stress in LDLR−/− Mice Fed with a High-Fat and High-Fructose Diet
Authors: Liu Lin , Shen Quan , Wang Yan , Li Hong , Zhao Jingshan
Published: August 2023

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease. Previous studies have shown that dihydromyricetin (DHM) is beneficial for NAFLD. However, whether DHM alleviates NAFLD by inhibiting liver endoplasmic reticulum (ER) stress remains unknown. Thus, this study aimed to identify the potential roles and mechanisms of DHM. Twenty-four male low-density lipoprotein receptor (LDLR−/−) knockout mice aged 8 weeks were randomly divided into normal control, control, and DHM groups. Normal control mice were fed a normal diet (ND), and the last two groups of mice were fed a high-fat and high-fructose diet (HFD) for 12 weeks, treated with or without DHM. DHM alleviated diet-induced hyperlipidemia as early as 4 weeks after and until the end of HFD feeding. HFD increased insulin resistance, and the opposite was observed in the DHM group. Compared to the control group, the body weight of the mice and adipocyte size and weight of the retroperitoneal and epididymal fat were remarkably reduced in the DHM group. The expression of genes related to lipid metabolism, such as Acox1 and Cpt1α, was significantly upregulated. Moreover, Mttp was downregulated in the two fat sits in the DHM group. DHM alleviated diet-induced lipid deposition in the liver and decreased liver triglyceride and total cholesterol content. DHM improved liver function by inhibiting ER stress, alleviating atherogenesis, and promoting vascular remodeling. In conclusion, dihydromyricetin improved NAFLD and related insulin resistance, hyperlipidemia, and atherogenesis by inhibiting liver ER stress in HFD-fed LDLR−/− mice.
Intra-Tester and Inter-Tester Reliability of the Lachmeter When Measuring Knee Joint Laxity
Authors: Oxfeldt Mikkel , Pedersen Anton B. , Hansen Mette
Published: August 2023

Knee injuries are common among all age groups, and clinical knee examination is essential for the prognosis, follow-up, and rehabilitation process. The Lachmeter is a newly developed digitized modification of the Rolimeter, making it easier and faster for the test personnel to read the test result. In the present study, we aimed to evaluate the intra-tester and inter-tester reliability of the Lachmeter when testing healthy and traumatic knees. 24 healthy participants and a smaller sample of six ACL patients were examined with the Lachmeter by two intermediate testers and re-examined on a second visit within 21 days. All measurements were performed using two different grip techniques: a Lachman grip and an anterior drawer grip. Intra- and inter-tester reliability was evaluated using intra-class correlation coefficient (ICC), standard error of measurement (SEM), smallest detectable change (SDC), Student’s paired t-test, and Bland–Altman plots. The results showed in healthy subjects poor to good intra-tester reliability (ICC range: −0.28–0.87, SEM range: 0.33–1.14 mm, and SDC range: 0.91–3.17 mm) and inter-tester reliability (ICC range: 0.41–0.87, SEM range: 0.27–0.67 mm, and SDC range: 0.75–1.87 mm). In ACL patients, intra-tester reliability was moderate to excellent (ICC range: 0.53–0.94, SEM range: 0.14–0.88 mm, and SDC range: 0.38–2.44 mm), with the exception of one measurement (ICC: 0.26 95% CI [−3.43; 0.89]), whereas inter-tester reliability was overall good (ICC range: 0.61–0.89, SEM range: 0.29–0.71 mm, and SDC range: 0.79–1.97 mm). Reliability measures between grip techniques indicated that the Lachman grip was more reliable than the anterior drawer grip. In conclusion, the Lachmeter showed variation between reliability measures, ranging from poor to good in healthy subjects and moderate to excellent in ACL patients. Future studies are needed to validate the Lachmeter against a gold-standard knee laxity assessment.
A New Study for the Investigation of Nonlinear Fractional Drinfeld–Sokolov–Wilson Equation
Authors: Nadeem Muhammad , Alsayaad Yahya
Published: August 2023

In this paper, we present an idea of a new iterative procedure (NIP) to examine the approximate solution of the nonlinear fractional Drinfeld–Sokolov–Wilson (DSW) equation. We first use Mohand transform (MT) to the problem and obtain a recurrence relation without any assumption or restrictive variable. This relation is now very easy to handle and suitable for the study of the homotopy perturbation method (HPM). We observe that HPM produces the iterations in the form of convergence series that becomes very close to the precise solution. The fractional derivative is considered in the Caputo sense. We also demonstrate the graphical solution to show that NIP is a very simple, straightforward, and efficient tool for nonlinear problems of fractional derivatives.
Data from Targeting KDM2A Enhances T Cell Infiltration in NSD1-Deficient Head and Neck Squamous Cell Carcinoma
Authors: Chen Chen , Shin June Ho. , Fang Zhuoqing , Brennan Kevin , Horowitz Nina B. , Pfaff Kathleen L. , Welsh Emma L. , Rodig Scott J. , Gevaert Olivier , Gozani Or , Uppaluri Ravindra , Sunwoo John B.
Published: August 2023

Abstract
In head and neck squamous cell carcinoma (HNSCC), a significant proportion of tumors have inactivating mutations in the histone methyltransferase NSD1. In these tumors, NSD1 inactivation is a driver of T cell exclusion from the tumor microenvironment (TME). A better understanding of the NSD1-mediated mechanism regulating infiltration of T cells into the TME could help identify approaches to overcome immununosuppression. Here, we demonstrated that NSD1 inactivation results in lower levels of H3K36 di-methylation and higher levels of H3K27 tri-methylation, the latter being a known repressive histone mark enriched on the promoters of key T cell chemokines CXCL9 and CXCL10. HNSCC with NSD1 mutations had lower levels of these chemokines and lacked responses to PD-1 immune checkpoint blockade. Inhibition of KDM2A, the primary lysine demethylase that is selective for H3K36, reversed the altered histone marks induced by NSD1 loss and restored T cell infiltration into the TME. Importantly, KDM2A suppression decreased growth of NSD1-deficient tumors in immunocompetent, but not in immunodeficient, mice. Together, these data indicate that KDM2A is an immunotherapeutic target for overcoming immune exclusion in HNSCC.
Data from The genomic and epigenomic landscape of double-negative metastatic prostate cancer
Authors: Lundberg Arian , Zhang Meng , Aggarwal Rahul , Li Haolong , Zhang Li , Foye Adam , Sjöström Martin , Chou Jonathan , Chang Kevin , Moreno-Rodriguez Thaidy , Shrestha Raunak , Baskin Avi , Zhu Xiaolin , Weinstein Alana S. , Younger Noah , Alumkal Joshi J. , Beer Tomasz M. , Chi Kim N. , Evans Christopher P. , Gleave Martin , Lara Primo N. , Reiter Rob E. , Rettig Matthew B. , Witte Owen N. , Wyatt Alexander W. , Feng Felix Y. , Small Eric J. , Quigley David A.
Published: August 2023

Abstract
Systemic targeted therapy in prostate cancer is primarily focused on ablating androgen signaling. Androgen deprivation therapy and second-generation androgen receptor (AR)-targeted therapy selectively favor the development of treatment-resistant subtypes of metastatic castration-resistant prostate cancer (mCRPC), defined by AR and neuroendocrine (NE) markers. Molecular drivers of double-negative (AR-/NE-) mCRPC are poorly defined. In this study, we comprehensively characterized treatment-emergent mCRPC by integrating matched RNA sequencing, whole-genome sequencing, and whole-genome bisulfite sequencing from 210 tumors. AR-/NE- tumors were clinically and molecularly distinct from other mCRPC subtypes, with the shortest survival, amplification of the chromatin remodeler CHD7, and PTEN loss. Methylation changes in CHD7 candidate enhancers were linked to elevated CHD7 expression in AR-/NE+ tumors. Genome-wide methylation analysis nominated KLF5 as a driver of the AR-/NE- phenotype, and KLF5 activity was linked to RB1 loss. These observations reveal the aggressiveness of AR-/NE- mCRPC and could facilitate the identification of therapeutic targets in this highly aggressive disease.
Data from Tumor-derived Small Extracellular Vesicles Inhibit the Efficacy of CAR T Cells against Solid Tumors
Authors: Zhong Wenqun , Xiao Zebin , Qin Zhiyuan , Yang Jingbo , Wen Yi , Yu Ziyan , Li Yumei , Sheppard Neil C. , Fuchs Serge Y. , Xu Xiaowei , Herlyn Meenhard , June Carl H. , Pure Ellen , Guo Wei
Published: August 2023

Abstract
Chimeric antigen receptor (CAR) T cell therapy has shown remarkable success in the treatment of hematologic malignancies. Unfortunately, it has limited efficacy against solid tumors, even when the targeted antigens are well expressed. A better understanding of the underlying mechanisms of CAR T cell therapy resistance in solid tumors is necessary to develop strategies to improve efficacy. Here we report that solid tumors release small extracellular vesicles (sEVs) that carry both targeted tumor antigens and the immune checkpoint protein PD-L1. These sEVs acted as cell-free functional units to preferentially interact with cognate CAR T cells and efficiently inhibited their proliferation, migration, and function. In syngeneic mouse tumor models, blocking tumor sEV secretion not only boosted the infiltration and anti-tumor activity of CAR T cells but also improved endogenous anti-tumor immunity. These results suggest that solid tumors use sEVs as an active defense mechanism to resist CAR T cells and implicate tumor sEVs as a potential therapeutic target to optimize CAR T cell therapy against solid tumors.
Data from Temozolomide sensitizes ARID1A-mutated cancers to PARP inhibitors
Authors: Yu Zheng-Cheng , Li Tianhe , Tully Ellen , Huang Peng , Chen Chih-Ning , Oberdoerffer Philipp , Gaillard Stephanie , Shih Ie-Ming , Wang Tian-Li
Published: August 2023

Abstract
ARID1A is a subunit of SWI/SNF chromatin remodeling complexes and is mutated in many types of human cancers, especially those derived from endometrial epithelium, including ovarian and uterine clear cell carcinoma (CCC) and endometrioid carcinoma (EMCA). Loss-of-function mutations in ARID1A alter epigenetic regulation of transcription, cell cycle checkpoint control, and DNA damage repair. We report here that mammalian cells with ARID1A deficiency harbor accumulated DNA base lesions and increased abasic (AP) sites, products of glycosylase in the first step of base excision repair (BER). ARID1A mutations also delayed recruitment kinetics of BER long-patch repair effectors. Although ARID1A-deficient tumors were not sensitive to monotherapy with DNA-methylating temozolomide (TMZ), the combination of TMZ with PARP inhibitors (PARPi) potently elicited double strand DNA breaks, replication stress, and replication fork instability in ARID1A-deficient cells. The TMZ and PARPi combination also significantly delayed in vivo growth of ovarian tumor xenografts carrying ARID1A mutations and induced apoptosis and replication stress in xenograft tumors. Together, these findings identified a synthetic lethal strategy to enhance the response of ARID1A-mutated cancers to PARP inhibition, which warrants further experimental exploration and clinical trial validation.
Supplementary Figure S1 from A Phase I, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients with Advanced Gastrointestinal Stromal Tumor
Authors: George Suzanne , Heinrich Michael C. , Somaiah Neeta , Oppelt Peter , McLeod Robert , Nishioka Satoshi , Kundu Madan G. , Qian Xiaozhong , Kumar Prasanna , Laadem Abderrahmane , Lau Yvonne , Tran Brittany P. , Fallon Maura , Dosunmu Ololade , Shi Julia , Naito Yoichi
Published: August 2023

Supplementary Figure S1. Swimmer plot of tumor response over time
Supplementary Table S1 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: August 2023

List of GEP70 genes located on chromosome 1 and their cytoband location. Cytoband
Supplemental Figure 5 from Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors
Authors: Gallois Claire , Landi Matteo , Taieb Julien , Sroussi Marine , Saberzadeh-Ardestani Bahar , Cazelles Antoine , Lonardi Sara , Bergamo Francesca , Intini Rossana , Maddalena Giulia , Pietrantonio Filippo , Corti Francesca , Ambrosini Margherita , Martinetti Antonia , Germani Marco Maria , Boccaccio Chiara , Vetere Guglielmo , Mouillet-Richard Sophie , de Reynies Aurélien , Sinicrope Frank A. , Cremolini Chiara , Laurent-Puig Pierre
Published: August 2023

Kaplan Meier curves for progression-free survival according to the three unsupervised clusters in the validation cohort
Supplemental Figure 4 from Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors
Authors: Gallois Claire , Landi Matteo , Taieb Julien , Sroussi Marine , Saberzadeh-Ardestani Bahar , Cazelles Antoine , Lonardi Sara , Bergamo Francesca , Intini Rossana , Maddalena Giulia , Pietrantonio Filippo , Corti Francesca , Ambrosini Margherita , Martinetti Antonia , Germani Marco Maria , Boccaccio Chiara , Vetere Guglielmo , Mouillet-Richard Sophie , de Reynies Aurélien , Sinicrope Frank A. , Cremolini Chiara , Laurent-Puig Pierre
Published: August 2023

Heatmap with unsupervised clustering in the validation cohort
Supplementary Spreadsheet S8 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: August 2023

Supplemental Spreadsheet 8: Differential expression between normal chr1 and whole-arm gains group MM patients
Supplementary Spreadsheet S6 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: August 2023

Differential expression between normal chr1 and gain(1q) MM patients with t(11;14) translocation
Supplementary Figures 1 from Poor Outcome in Postpartum Breast Cancer Patients Is Associated with Distinct Molecular and Immunologic Features
Authors: Lefrère Hanne , Moore Kat , Floris Giuseppe , Sanders Joyce , Seignette Iris M. , Bismeijer Tycho , Peters Dennis , Broeks Annegien , Hooijberg Erik , Van Calsteren Kristel , Neven Patrick , Warner Ellen , Peccatori Fedro Alessandro , Loibl Sibylle , Maggen Charlotte , Han Sileny N. , Jerzak Katarzyna J. , Annibali Daniela , Lambrechts Diether , de Visser Karin E. , Wessels Lodewyk , Lenaerts Liesbeth , Amant Frédéric
Published: August 2023

Supplmeentary Figures S1-S28
Supplementary Spreadsheet S2 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: August 2023

Correlation coefficient outbut between genetic variables Corrrelation analysis between deletion region, gain regions, and other genetic events
Supplementary Figure S9 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: August 2023

Impact of additional chromosome 1 structural events on outcome A.Effect of amp(1q) with or without a total (TT) gain on PFS B. Effect of amp(1q) on OS
Supplementary Figure S2 from Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression
Authors: Lheureux Stephanie , Prokopec Stephenie D. , Oldfield Leslie E. , Gonzalez-Ochoa Eduardo , Bruce Jeffrey P. , Wong Derek , Danesh Arnavaz , Torti Dax , Torchia Jonathan , Fortuna Alexander , Singh Sharanjit , Irving Matthew , Marsh Kayla , Lam Bernard , Speers Vanessa , Yosifova Aleksandra , Oaknin Ana , Madariaga Ainhoa , Dhani Neesha C. , Bowering Valerie , Oza Amit M. , Pugh Trevor J.
Published: August 2023

Supplementary Figure 2: Estimated tumour content in plasma DNA
Supplementary Figure S5 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: August 2023

Hi-C interaction and TAD map of CT1, TI1, D7 regions. The chromatin confirmation of the region encompassing CT1, TI1, and D7 across the 3 HMCLs (U266, RPMI8226, and KMS11) and PC for comparison. The region shows significant variability in the TAD strucure at the TENT5C locus across all samples in comparision to PC which could explain its dysregulation
Supplementary Figure S1 from Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression
Authors: Lheureux Stephanie , Prokopec Stephenie D. , Oldfield Leslie E. , Gonzalez-Ochoa Eduardo , Bruce Jeffrey P. , Wong Derek , Danesh Arnavaz , Torti Dax , Torchia Jonathan , Fortuna Alexander , Singh Sharanjit , Irving Matthew , Marsh Kayla , Lam Bernard , Speers Vanessa , Yosifova Aleksandra , Oaknin Ana , Madariaga Ainhoa , Dhani Neesha C. , Bowering Valerie , Oza Amit M. , Pugh Trevor J.
Published: August 2023

Supplementary Figure 1: Establishment of limit of detection (LOD) for targeted sequencing panel on ctDNA
Supplementary Figure S2 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: August 2023

Chromatin state of different gain region. The regions of gain tend to fall within active chromatin regions with G3, G4, G5, G6, and G8 lying exclusively within A-compartments (100%) across B-cell differentiation states and MM cell lines (U266, RPMI8226, and KMS11). The G1 region also followed this pattern with the exception of KMS11 (where A-compartment represented only 78% of the region). The G2 region showed variability between the normal and malignant phenotype, with moderate switching from to B-compartments of 24%, 21%, and 37% in U266, RPMI8226, and KMS11 respectively. The compartment profile of the G7 region is interesting as each sample contained considerable B-compartment percentage (range 16-82%) but within the conserved A-compartment across all samples lies the well characterised oncogene ABL2. The G9 region showed the greatest variability across all samples and was shifted more towards inactive chromatin (range 45-97%). NBC=Naïve B-cell, MBC=Memory B-cell, GCBC=Germinal Center B-cell, PC=plasma cell.
Supplementary Figure 2 from Development and Multicenter Case–Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction
Authors: Salari Keyan , Sundi Debasish , Lee Jason J. , Wu Shulin , Wu Chin-Lee , DiFiore Gabrielle , Yan Q. Robert , Pienkny Andrew , Lee Chi K. , Oberlin Daniel , Barme Greg , Piser Joel , Kahn Robert , Collins Edward , Phillips Kevin G. , Caruso Vincent M. , Goudarzi Mahdi , Garcia-Ransom Monica , Lentz Peter S. , Evans-Holm Martha E. , MacBride Andrew R. , Fischer Daniel S. , Haddadzadeh Iden J. , Mazzarella Brian C. , Gray Joe W. , Koppie Theresa M. , Bicocca Vincent T. , Levin Trevor G. , Lotan Yair , Feldman Adam S.
Published: August 2023

Supplemental Figure 2. uCGP Predicted Recurrence Risk by Subgroup.
Supplementary Materials 1 from A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma
Authors: Lee Yun Bin , Nam Joon Yeul , Cho Eun Ju , Lee Jeong-Hoon , Yu Su Jong , Kim Hyo-Cheol , Paeng Jin Chul , Yoon Jung-Hwan , Kim Yoon Jun
Published: August 2023

Supplementary Materials. Study Protocol
Supplementary Data 3 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , García-Silva Susana , Santos Vanesa , Sánchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto Jose L. , Fernández-Rodríguez Juana , Pérez-Portabella Cleofé Romagosa , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: August 2023

Dual inhibition of ENG and MEK efficiently blocks ENG-Smad1/5 and MAPK/ERK pathway activation in ST88-14 cells.
Supplementary Table S7 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

MMR-D cases
Supplementary Data 1 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , García-Silva Susana , Santos Vanesa , Sánchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto Jose L. , Fernández-Rodríguez Juana , Pérez-Portabella Cleofé Romagosa , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: August 2023

Taqman probes used for quantitative PCR.
Suppl. Figure 1 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , García-Silva Susana , Santos Vanesa , Sánchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto Jose L. , Fernández-Rodríguez Juana , Pérez-Portabella Cleofé Romagosa , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: August 2023

Analysis of ENG expression and plasma circulating sEVs in human PNSTs.
Supplementary Figure S6 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

MAPK amplifications are alternative drivers in KRAS WT pancreatic cancer
Supplementary Figure S1 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

KRAS WT pancreatic cancer cohort curation and variant filtering
Data from Poor outcome in postpartum breast cancer patients is associated with distinct molecular and immunological features
Authors: Lefrère Hanne , Moore Kat , Floris Giuseppe , Sanders Joyce , Seignette Iris M. , Bismeijer Tycho , Peters Dennis , Broeks Annegien , Hooijberg Erik , Van Calsteren Kristel , Neven Patrick , Warner Ellen , Peccatori Fedro Alessandro. , Loibl Sibylle , Maggen Charlotte , Han Sileny N. , Jerzak Katarzyna J. , Annibali Daniela , Lambrechts Diether , de Visser Karin E. , Wessels Lodewyk , Lenaerts Liesbeth , Amant Frédéric
Published: August 2023

Abstract
Purpose: Postpartum breast cancer patients diagnosed after cessation of breastfeeding (post-weaning, PP-BCPW), have a particularly poor prognosis compared to patients diagnosed during lactation (PP-BCDL), or to pregnant (Pr-BC) and nulliparous (NP-BC) patients, irrespective of standard prognostic characteristics. Animal studies point to a role of the involution process in stimulation of tumor growth in the mammary gland. However, in women, the molecular mechanisms that underlie this poor prognosis of PP-BCPW patients remain vastly underexplored, due to of lack of adequate patient numbers and outcome data. Experimental Design: We explored whether distinct prognostic features, common to all breast cancer molecular subtypes, exist in postpartum tumor tissue. Using detailed breastfeeding data, we delineated the post-weaning period in PP-BC as a surrogate for mammary gland involution and performed whole transcriptome sequencing, immunohistochemical and (multiplex) immunofluorescent analyses on tumor tissue of PP-BCPW, PP-BCDL, Pr-BC and NP-BC patients. Results: We found that PP-BCPW patients having a low expression level of an immunoglobulin gene signature, but high infiltration of plasma B-cells, have an increased risk for metastasis and death. Although PP-BCPW tumor tissue was also characterized by an increase in CD8+ cytotoxic T-cells and reduced distance among these cell types, these parameters were not associated with differential clinical outcomes among groups. Conclusion: These data point to the importance of plasma B-cells in the post-weaning mammary tumor microenvironment regarding the poor prognosis of PP-BCPW patients. Future prospective and in-depth research needs to further explore the role of B-cell immunobiology in this specific group of young breast cancer patients.
Data from Identification of a Novel FUS/ETV4 Fusion and Comparative Analysis with Other Ewing Sarcoma Fusion Proteins
Authors: Boone Megann A. , Taslim Cenny , Crow Jesse C. , Selich-Anderson Julia , Watson Mike , Heppner Peter , Hamill James , Wood Andrew C. , Lessnick Stephen L. , Winstanley Mark
Published: August 2023

Abstract
Ewing sarcoma is a pediatric bone cancer defined by a chromosomal translocation fusing one of the FET family members to an ETS transcription factor. There have been seven reported chromosomal translocations, with the most recent reported over a decade ago. We now report a novel FET/ETS translocation involving FUS and ETV4 detected in a patient with Ewing sarcoma. Here, we characterized FUS/ETV4 by performing genomic localization and transcriptional regulatory studies on numerous FET/ETS fusions in a Ewing sarcoma cellular model. Through this comparative analysis, we demonstrate significant similarities across these fusions, and in doing so, validate FUS/ETV4 as a bona fide Ewing sarcoma translocation. This study presents the first genomic comparison of Ewing sarcoma–associated translocations and reveals that the FET/ETS fusions share highly similar, but not identical, genomic localization and transcriptional regulation patterns. These data strengthen the notion that FET/ETS fusions are key drivers of, and thus pathognomonic for, Ewing sarcoma.
Implications:
Identification and initial characterization of the novel Ewing sarcoma fusion, FUS/ETV4, expands the family of Ewing fusions and extends the diagnostic possibilities for this aggressive tumor of adolescents and young adults.
TABLE 1C from Dual Blockade of EP2 and EP4 Signaling is Required for Optimal Immune Activation and Antitumor Activity Against Prostaglandin-Expressing Tumors
Authors: Francica Brian J. , Holtz Anja , Lopez Justine , Freund David , Chen Austin , Wang Dingzhi , Powell David , Kipper Franciele , Panigrahy Dipak , Dubois Raymond N. , Whiting Chan C. , Prasit Peppi , Dubensky Thomas W.
Published: August 2023

Antibodies used for IHC of CT26 tumors
FIGURE 4 from Dual Blockade of EP2 and EP4 Signaling is Required for Optimal Immune Activation and Antitumor Activity Against Prostaglandin-Expressing Tumors
Authors: Francica Brian J. , Holtz Anja , Lopez Justine , Freund David , Chen Austin , Wang Dingzhi , Powell David , Kipper Franciele , Panigrahy Dipak , Dubois Raymond N. , Whiting Chan C. , Prasit Peppi , Dubensky Thomas W.
Published: August 2023

TPST-1495 confers therapeutic efficacy in mice bearing PGE2-producing tumors. A, PGE2 detected by mass spectrometry in cell culture fluids of tumor cells lines after 24 hours in culture. Results depict six technical replicates. B, PGEM detected by mass spectrometry in urine of tumor-bearing mice from untreated animals (shown in C) approximately 17 days after tumor implantation. Results are representative of one experiment with five biological replicates. Tumor outgrowth (C) and percent TGI [TGI = 100*(Control Volume − Treatment Volume)/Control Volume] (D) measured in mice bearing flank implanted tumors of tumor types shown in the figure. A total of 1 × 106 cells were implanted on day 0 and treatment in mice randomized to assigned groups was initiated when average tumor volume within a tumor line reached approximately 80–100 mm3. Mice were treated with TPST-1495 (100 mg/kg twice a day, orally), E7046 (150 mg/kg every day, orally), PF04418948 (100 mg/kg every day, orally), or Celecoxib (60 mg/kg every day, orally) and followed for outgrowth until vehicle mice reached humane endpoints. Results are representative of two experiments with N = 5 mice per group. Mean and SD are depicted in all graphs and the Student two-sided t test was used to assess significance between individual groups at the last timepoint before mice were sacrificed. **, P < 0.01; *, P < 0.05. Flow cytometry (E) or IHC (F) from CT26 tumors after 14 days of treatment. A total of 1 × 106 CT26 cells were implanted in the flanks of animals and followed until the average was 80–100 mm3. Mice were then treated for 14 days at which time tumors were resected and stained. Results depict one experiment with 8 mice, representative of more than three similar experiments. G and H, Flow cytometry from CT26 tumors resected after 17 days of treatment. Tumors were implanted as in E, treated for 17 days with TPST-1495, and then time tumors were resected and stained for DC1+ dendritic cells (G) or macrophages (H). Results shown in G represent one experiment with 10 mice, representative of multiple similar experiments with an average of 2-fold increase over vehicle, but data depicted are the only replicate that met P < 0.05 statistical cutoff. One datapoint in G met the Gibbs criteria for outliers and was excluded. Results in H represent one experiment of two similar experiments with at least 8 mice. Mean and SD are depicted in all graphs and the Student two-sided t test was used to assess significance between individual groups. ****, P < 0.0001; **, P < 0.01; *, P < 0.05.
FIGURE 3 from Dual Blockade of EP2 and EP4 Signaling is Required for Optimal Immune Activation and Antitumor Activity Against Prostaglandin-Expressing Tumors
Authors: Francica Brian J. , Holtz Anja , Lopez Justine , Freund David , Chen Austin , Wang Dingzhi , Powell David , Kipper Franciele , Panigrahy Dipak , Dubois Raymond N. , Whiting Chan C. , Prasit Peppi , Dubensky Thomas W.
Published: August 2023

TPST-1495 is more effective than a single EP4 or EP2 antagonists in overcoming PGE2-mediated immune suppression of recovery of cytokine production from human monocytes and T cells. TNFα ELISA from PGE2 blockade assay performed using human whole blood treated with TPST-1495 (A) or E7046 (B) in the presence of 10 nmol/L or 500 nmol/L PGE2. Graphs show one representative donor of 3 donors tested. C–E, IFNγ concentration in supernatants of PGE2 blockade assay performed on magnetically enriched T cells from human PBMC. Cells were treated with various concentrations of EP receptor inhibitors TPST-1495 (C), E7046 (D), or PF04418948 (E), followed by concentrations of PGE2 and CEF peptides as shown in C and D. Cytokine levels in supernatants were determined by bead-based cytokine array analysis. Graphs show data with N = 4 technical replicates from one of four independent experiments. Two different healthy donors were used across these experiments. F, Percent IFNγ production rescue, as normalized to the control (DMSO), from PGE2 Blockade assay supernatants. Magnetically enriched T Cells from human PBMC were treated with increasing amounts of EP1 (Ono-8130) and EP3 (L-798106) inhibitors and subjected to 333 nmol/L PGE2 before stimulation with CEF peptides. Each datapoint represents the average percent recovery from one experiment, with four total experiments shown. G, Percent IFNγ production rescue, as normalized to control with 0 nmol/L PGE2 and 0 nmol/L TPST-1495. Cells obtained as in C–F were treated with increasing TPST-1495 in the presence or absence of 10 mmol/L EP1 inhibitor and 10 mmol/L EP3 inhibitor. Each datapoint represents the average percent recovery from one experiment, with four total experiments shown. Mean and SD are depicted in all graphs and the Student two-sided t test was used to assess significance between individual groups. ****, P < 0.0001; ***, P < 0.001; **, P < 0.01; *, P < 0.05.
LncRNA PMS2L2 Is Downregulated in Sepsis-Induced Acute Kidney Injury and Inhibits LPS-Induced Apoptosis of Podocytes
Authors: Zhang Fengxiang , Luo Xigang , Wang Yi , Ma Lingling , Sun Dapeng
Published: August 2023

Introduction: Long noncoding RNA PMS2L2 can inhibit inflammation induced by LPS, while LPS plays an important role in sepsis, indicating the possible involvement of PMS2L2 in sepsis. Methods: Expressions of miR-21 and PMS2L2 in patients with acute kidney injury (AKI), sepsis patients without induced AKI, and healthy controls were determined by performing RT-qPCR. Overexpression assay was performed to explore the crosstalk between miR-21 and PMS2L2. Methylation-specific PCR (MSP) was performed to explore the role of PMS2L2 in regulating the methylation of miR-21 gene. The role of miR-21 and PMS2L2 in the apoptosis of CIHP-1 cells induced by LPS was assessed by cell apoptosis assay. Results: PMS2L2 was downregulated in AKI patients induced by sepsis compared to sepsis patients without AKI and healthy controls. MiR-21 was also downregulated in AKI induced by sepsis and positively correlated with PMS2L2. In addition, in cells of human podocyte cell line (CIHP-1), overexpression of PMS2L2 promoted the expression of miR-21, while miR-21 did not affect the expression of PMS2L2. MSP analysis showed that overexpression of PMS2L2 decreased methylation of miR-21. LPS treatment downregulated PMS2L2 and miR-21 in a time-dependent manner. PMS2L2 and miR-21 decreased the apoptosis of CIHP-1 cells induced by LPS, and co-overexpression of PMS2L2 and miR-21 showed stronger inhibitory effect. Conclusion: PMS2L2 is downregulated in AKI induced by sepsis and inhibits LPS-induced apoptosis of podocytes.