bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of New Antiepileptic Drugs on Homocysteine in Epileptic Patients: A Systematic Review and Meta-Analysis
Authors: Zheng Danyi , Bao Yaya , Gu Jiayi , Lv Tian , Yang Yue
Published: April 2023

Background. Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and new antiepileptic drugs (AEDs). In this meta-analysis, we aimed to assess the effects of new AEDs on Hcy. Methods. PubMed, Embase, Cochrane, and Web of Science databases were searched from inception to June 2022 for articles that focused on the effects of new AEDs on Hcy. A meta-analysis was performed using Stata 16.0 software. The results were presented as the mean difference (MD) and corresponding to 95% confidence intervals (CIs) comparing epileptic patients with new AEDs to the control subjects. Results. A total of 11 studies were included in the meta-analysis. Hcy was markedly increased in the new AEDs group compared with the control group (MD = 2.220, 95% CI: 0.596–3.844,

P
=
0.007

), with a high degree of heterogeneity (I2 = 99.5%). In the drugs subgroup, the oxcarbazepine (OXC) (MD = 2.30, 95% CI: −1.11–5.72,

P
=
0.187

) and lamotrigine (LTG) (MD = 1.14, 95% CI: −0.209–2.482,

P
<
0.001

) groups had no significant differences when compared with the control group. The levetiracetam (LEV) (MD = 1.81, 95% CI: 1.03–2.18,

P
<
0.001

) and topiramate (TPM) (MD = 6.922, 95% CI: 0.788–13.055,

P
=
0.027

) groups were significantly higher than the control group. Conclusions. The new AEDs, especially TPM and LEV, may increase the plasma of Hcy. The role of Hcy in patients with epilepsy who are given TPM and LEV should not be ignored in clinical situations. Patients with epilepsy who also have a high-risk vascular profile are recommended to use OXC and LTG.
Effect of Beeswax Coating on the Quality of Eggplant Fruit During Cold Storage and Optimization of Coating Conditions
Authors: Dadzie Rosemond G. , Ampofo-Asiama Jerry , Quaye Bright , Kizzie-Hayford Nazir , Amoako-Andoh Francis , Abano Ernest E. , Amoah Robert S.
Published: April 2023

Eggplants are highly nutritious and feature prominently in food recipes in the tropics. However, losses in weight, firmness, and nutrients affect the quality of the fruit after harvest. This work investigated the use of beeswax as a potential coating to improve the quality of eggplant fruit. Eggplant fruit were coated with a 3% beeswax solution alone or in combination with a citrate solution and stored at 10°C for 17 days. The coating significantly minimized weight loss, preserved firmness, and delayed colour changes. No changes in total phenols and antioxidant capacity were observed upon coating; however, ascorbate levels decreased. Using a response surface methodology approach the optimum conditions for the application of beeswax coating to improve the quality of eggplant fruit was investigated. The validated optimum coating conditions were 4.6% (w/v) coating concentration, 1% (w/v) citrate concentration, and 3 min coating duration. The validation experiment gave a high correlation coefficient (R2) of 0.93 between the predicted and measured physicochemical properties of the fruit. The optimized conditions can be useful in the preparation of a beeswax-based coating for improving the quality of eggplant fruit during cold storage.
Supplementary Table from Preclinical Development and Evaluation of Allogeneic CAR T Cells Targeting CD70 for the Treatment of Renal Cell Carcinoma
Authors: Panowski Siler H. , Srinivasan Surabhi , Tan Nguyen , Tacheva-Grigorova Silvia K. , Smith Bryan , Mak Yvonne S.L. , Ning Hongxiu , Villanueva Jonathan , Wijewarnasuriya Dinali , Lang Shanshan , Melton Zea , Ghosh Adit , Dusseaux Mathilde , Galetto Roman , Heyen Jonathan R. , Sai Tao , Van Blarcom Thomas , Chaparro-Riggers Javier , Sasu Barbra J.
Published: April 2023

Supplementary Table from Preclinical Development and Evaluation of Allogeneic CAR T Cells Targeting CD70 for the Treatment of Renal Cell Carcinoma
Supplementary Figure from Preclinical Development and Evaluation of Allogeneic CAR T Cells Targeting CD70 for the Treatment of Renal Cell Carcinoma
Authors: Panowski Siler H. , Srinivasan Surabhi , Tan Nguyen , Tacheva-Grigorova Silvia K. , Smith Bryan , Mak Yvonne S.L. , Ning Hongxiu , Villanueva Jonathan , Wijewarnasuriya Dinali , Lang Shanshan , Melton Zea , Ghosh Adit , Dusseaux Mathilde , Galetto Roman , Heyen Jonathan R. , Sai Tao , Van Blarcom Thomas , Chaparro-Riggers Javier , Sasu Barbra J.
Published: April 2023

Supplementary Figure from Preclinical Development and Evaluation of Allogeneic CAR T Cells Targeting CD70 for the Treatment of Renal Cell Carcinoma
Supplementary Data from Preclinical Development and Evaluation of Allogeneic CAR T Cells Targeting CD70 for the Treatment of Renal Cell Carcinoma
Authors: Panowski Siler H. , Srinivasan Surabhi , Tan Nguyen , Tacheva-Grigorova Silvia K. , Smith Bryan , Mak Yvonne S.L. , Ning Hongxiu , Villanueva Jonathan , Wijewarnasuriya Dinali , Lang Shanshan , Melton Zea , Ghosh Adit , Dusseaux Mathilde , Galetto Roman , Heyen Jonathan R. , Sai Tao , Van Blarcom Thomas , Chaparro-Riggers Javier , Sasu Barbra J.
Published: April 2023

Supplementary Data from Preclinical Development and Evaluation of Allogeneic CAR T Cells Targeting CD70 for the Treatment of Renal Cell Carcinoma
Supplementary Tables S1-S3 from Loss of LGR5 through Therapy-induced Downregulation or Gene Ablation Is Associated with Resistance and Enhanced MET-STAT3 Signaling in Colorectal Cancer Cells
Authors: Posey Tressie A. , Jacob Joan , Parkhurst Ashlyn , Subramanian Shraddha , Francisco Liezl E. , Liang Zhengdong , Carmon Kendra S.
Published: April 2023

Table S1 shows IC50 values for irinotecan and anti-LGR5 ADCs in CRC cells with overexpression of STAT3-CA or LGR5; Table S2 shows IC50 values for MET and STAT3 inhibitors in CRC cells with and without loss of LGR5 expression; Table S3 shows combination index (CI) values for irinotecan or ADCs in combination with MET or STAT3 inhibitors
Supplementary Data from Tumor and Stromal Cell Targeting with Nintedanib and Alpelisib Overcomes Intrinsic Bladder Cancer Resistance
Authors: Marqués Miriam , Corral Sonia , Sánchez-Díaz María , del Pozo Natalia , Martínez de Villarreal Jaime , Schweifer Norbert , Zagorac Ivana , Hilberg Frank , Real Francisco X.
Published: April 2023

Supplementary Tables and Figures
Figure S6 from Loss of LGR5 through Therapy-induced Downregulation or Gene Ablation Is Associated with Resistance and Enhanced MET-STAT3 Signaling in Colorectal Cancer Cells
Authors: Posey Tressie A. , Jacob Joan , Parkhurst Ashlyn , Subramanian Shraddha , Francisco Liezl E. , Liang Zhengdong , Carmon Kendra S.
Published: April 2023

shows effects of combination treatment on antitumor efficacy and survival in LoVo LGR5 KD xenografts and body weights of xenografts during treatment
Table S3 from Small-Molecule–Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death
Authors: Avelar Rita A. , Armstrong Amy J. , Carvette Gracie , Gupta Riya , Puleo Noah , Colina Jose A. , Joseph Peronne , Sobeck Alexander M. , O'Connor Caitlin M. , Raines Brynne , Gandhi Agharnan , Dziubinski Michele L. , Ma Daniel S. , Resnick Kimberly , Singh Sareena , Zanotti Kristine , Nagel Christa , Waggoner Steven , Thomas Daffyd G. , Skala Stephanie L. , Zhang Junran , Narla Goutham , DiFeo Analisa
Published: April 2023

Table S3
Figure S4 from Loss of LGR5 through Therapy-induced Downregulation or Gene Ablation Is Associated with Resistance and Enhanced MET-STAT3 Signaling in Colorectal Cancer Cells
Authors: Posey Tressie A. , Jacob Joan , Parkhurst Ashlyn , Subramanian Shraddha , Francisco Liezl E. , Liang Zhengdong , Carmon Kendra S.
Published: April 2023

shows cytotoxicity of cryptotanshinone in combination with irinotecan in control and LGR5 KD LoVo cells
Table S2 from Small-Molecule–Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death
Authors: Avelar Rita A. , Armstrong Amy J. , Carvette Gracie , Gupta Riya , Puleo Noah , Colina Jose A. , Joseph Peronne , Sobeck Alexander M. , O'Connor Caitlin M. , Raines Brynne , Gandhi Agharnan , Dziubinski Michele L. , Ma Daniel S. , Resnick Kimberly , Singh Sareena , Zanotti Kristine , Nagel Christa , Waggoner Steven , Thomas Daffyd G. , Skala Stephanie L. , Zhang Junran , Narla Goutham , DiFeo Analisa
Published: April 2023

Table S2
Figure S3 from Loss of LGR5 through Therapy-induced Downregulation or Gene Ablation Is Associated with Resistance and Enhanced MET-STAT3 Signaling in Colorectal Cancer Cells
Authors: Posey Tressie A. , Jacob Joan , Parkhurst Ashlyn , Subramanian Shraddha , Francisco Liezl E. , Liang Zhengdong , Carmon Kendra S.
Published: April 2023

shows cytotoxicity of inhibitors of MET, STAT3, and Wnt in CTL and LGR5 KD/KO CRC cells
Table S1 from Small-Molecule–Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death
Authors: Avelar Rita A. , Armstrong Amy J. , Carvette Gracie , Gupta Riya , Puleo Noah , Colina Jose A. , Joseph Peronne , Sobeck Alexander M. , O'Connor Caitlin M. , Raines Brynne , Gandhi Agharnan , Dziubinski Michele L. , Ma Daniel S. , Resnick Kimberly , Singh Sareena , Zanotti Kristine , Nagel Christa , Waggoner Steven , Thomas Daffyd G. , Skala Stephanie L. , Zhang Junran , Narla Goutham , DiFeo Analisa
Published: April 2023

Table S1
Figure S2 from Loss of LGR5 through Therapy-induced Downregulation or Gene Ablation Is Associated with Resistance and Enhanced MET-STAT3 Signaling in Colorectal Cancer Cells
Authors: Posey Tressie A. , Jacob Joan , Parkhurst Ashlyn , Subramanian Shraddha , Francisco Liezl E. , Liang Zhengdong , Carmon Kendra S.
Published: April 2023

shows inhibitors of IL6/Gp130 and EGFR do not attenuate STAT3 activation in LGR5 KD/KO CRC cells, LGR5 KD in DLD-1 cells increases MET-STAT3 activation, and the effects of MET and STAT3 inhibitors at different time-points
Fig. S7 from Small-Molecule–Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death
Authors: Avelar Rita A. , Armstrong Amy J. , Carvette Gracie , Gupta Riya , Puleo Noah , Colina Jose A. , Joseph Peronne , Sobeck Alexander M. , O'Connor Caitlin M. , Raines Brynne , Gandhi Agharnan , Dziubinski Michele L. , Ma Daniel S. , Resnick Kimberly , Singh Sareena , Zanotti Kristine , Nagel Christa , Waggoner Steven , Thomas Daffyd G. , Skala Stephanie L. , Zhang Junran , Narla Goutham , DiFeo Analisa
Published: April 2023

Fig. S7
Figure S1 from Loss of LGR5 through Therapy-induced Downregulation or Gene Ablation Is Associated with Resistance and Enhanced MET-STAT3 Signaling in Colorectal Cancer Cells
Authors: Posey Tressie A. , Jacob Joan , Parkhurst Ashlyn , Subramanian Shraddha , Francisco Liezl E. , Liang Zhengdong , Carmon Kendra S.
Published: April 2023

shows effects of chemotherapies and ADC on LGR5 protein and mRNA expression and LGR5 knockdown effects on clonogenicity, signaling pathways, and expression of STAT3 target genes.
Fig. S5 from Small-Molecule–Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death
Authors: Avelar Rita A. , Armstrong Amy J. , Carvette Gracie , Gupta Riya , Puleo Noah , Colina Jose A. , Joseph Peronne , Sobeck Alexander M. , O'Connor Caitlin M. , Raines Brynne , Gandhi Agharnan , Dziubinski Michele L. , Ma Daniel S. , Resnick Kimberly , Singh Sareena , Zanotti Kristine , Nagel Christa , Waggoner Steven , Thomas Daffyd G. , Skala Stephanie L. , Zhang Junran , Narla Goutham , DiFeo Analisa
Published: April 2023

Fig. S5
Supplementary Table 1 from Novel Arginase Inhibitor, AZD0011, Demonstrates Immune Cell Stimulation and Antitumor Efficacy with Diverse Combination Partners
Authors: Doshi Aatman S. , Cantin Susan , Hernandez Marylens , Srinivasan Srimathi , Tentarelli Sharon , Griffin Matthew , Wang Yanjun , Pop-Damkov Petar , Prickett Laura B. , Kankkonen Cecilia , Shen Minhui , Martin Maryann San , Wu Song , Castaldi M. Paola , Ghadially Hormas , Varnes Jeffrey , Gales Sonya , Henry David , Hoover Clare , Mele Deanna A. , Simpson Iain , Gangl Eric T. , Mlynarski Scott N. , Finlay M. Raymond V. , Drew Lisa , Fawell Stephen E. , Shao Wenlin , Schuller Alwin G.
Published: April 2023

Supplementary Table 1
Fig. S4 from Small-Molecule–Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death
Authors: Avelar Rita A. , Armstrong Amy J. , Carvette Gracie , Gupta Riya , Puleo Noah , Colina Jose A. , Joseph Peronne , Sobeck Alexander M. , O'Connor Caitlin M. , Raines Brynne , Gandhi Agharnan , Dziubinski Michele L. , Ma Daniel S. , Resnick Kimberly , Singh Sareena , Zanotti Kristine , Nagel Christa , Waggoner Steven , Thomas Daffyd G. , Skala Stephanie L. , Zhang Junran , Narla Goutham , DiFeo Analisa
Published: April 2023

Fig. S4
Fig. S3 from Small-Molecule–Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death
Authors: Avelar Rita A. , Armstrong Amy J. , Carvette Gracie , Gupta Riya , Puleo Noah , Colina Jose A. , Joseph Peronne , Sobeck Alexander M. , O'Connor Caitlin M. , Raines Brynne , Gandhi Agharnan , Dziubinski Michele L. , Ma Daniel S. , Resnick Kimberly , Singh Sareena , Zanotti Kristine , Nagel Christa , Waggoner Steven , Thomas Daffyd G. , Skala Stephanie L. , Zhang Junran , Narla Goutham , DiFeo Analisa
Published: April 2023

Fig. S3
Supplementary Figure 4 from Novel Arginase Inhibitor, AZD0011, Demonstrates Immune Cell Stimulation and Antitumor Efficacy with Diverse Combination Partners
Authors: Doshi Aatman S. , Cantin Susan , Hernandez Marylens , Srinivasan Srimathi , Tentarelli Sharon , Griffin Matthew , Wang Yanjun , Pop-Damkov Petar , Prickett Laura B. , Kankkonen Cecilia , Shen Minhui , Martin Maryann San , Wu Song , Castaldi M. Paola , Ghadially Hormas , Varnes Jeffrey , Gales Sonya , Henry David , Hoover Clare , Mele Deanna A. , Simpson Iain , Gangl Eric T. , Mlynarski Scott N. , Finlay M. Raymond V. , Drew Lisa , Fawell Stephen E. , Shao Wenlin , Schuller Alwin G.
Published: April 2023

Supplementary Figure 4
Supplementary Figure 3 from Novel Arginase Inhibitor, AZD0011, Demonstrates Immune Cell Stimulation and Antitumor Efficacy with Diverse Combination Partners
Authors: Doshi Aatman S. , Cantin Susan , Hernandez Marylens , Srinivasan Srimathi , Tentarelli Sharon , Griffin Matthew , Wang Yanjun , Pop-Damkov Petar , Prickett Laura B. , Kankkonen Cecilia , Shen Minhui , Martin Maryann San , Wu Song , Castaldi M. Paola , Ghadially Hormas , Varnes Jeffrey , Gales Sonya , Henry David , Hoover Clare , Mele Deanna A. , Simpson Iain , Gangl Eric T. , Mlynarski Scott N. , Finlay M. Raymond V. , Drew Lisa , Fawell Stephen E. , Shao Wenlin , Schuller Alwin G.
Published: April 2023

Supplementary Figure 3
Supplementary Figure 2 from Novel Arginase Inhibitor, AZD0011, Demonstrates Immune Cell Stimulation and Antitumor Efficacy with Diverse Combination Partners
Authors: Doshi Aatman S. , Cantin Susan , Hernandez Marylens , Srinivasan Srimathi , Tentarelli Sharon , Griffin Matthew , Wang Yanjun , Pop-Damkov Petar , Prickett Laura B. , Kankkonen Cecilia , Shen Minhui , Martin Maryann San , Wu Song , Castaldi M. Paola , Ghadially Hormas , Varnes Jeffrey , Gales Sonya , Henry David , Hoover Clare , Mele Deanna A. , Simpson Iain , Gangl Eric T. , Mlynarski Scott N. , Finlay M. Raymond V. , Drew Lisa , Fawell Stephen E. , Shao Wenlin , Schuller Alwin G.
Published: April 2023

Supplementary Figure 2
Supplementary Figure 1 from Novel Arginase Inhibitor, AZD0011, Demonstrates Immune Cell Stimulation and Antitumor Efficacy with Diverse Combination Partners
Authors: Doshi Aatman S. , Cantin Susan , Hernandez Marylens , Srinivasan Srimathi , Tentarelli Sharon , Griffin Matthew , Wang Yanjun , Pop-Damkov Petar , Prickett Laura B. , Kankkonen Cecilia , Shen Minhui , Martin Maryann San , Wu Song , Castaldi M. Paola , Ghadially Hormas , Varnes Jeffrey , Gales Sonya , Henry David , Hoover Clare , Mele Deanna A. , Simpson Iain , Gangl Eric T. , Mlynarski Scott N. , Finlay M. Raymond V. , Drew Lisa , Fawell Stephen E. , Shao Wenlin , Schuller Alwin G.
Published: April 2023

Supplementary Figure 1
Data from Tumor and Stromal Cell Targeting with Nintedanib and Alpelisib Overcomes Intrinsic Bladder Cancer Resistance
Authors: Marqués Miriam , Corral Sonia , Sánchez-Díaz María , del Pozo Natalia , Martínez de Villarreal Jaime , Schweifer Norbert , Zagorac Ivana , Hilberg Frank , Real Francisco X.
Published: April 2023

Abstract
Bladder cancer is a highly prevalent tumor, requiring the urgent development of novel therapies, especially for locally advanced and metastatic disease. Nintedanib is a potent antifibrotic angio-kinase inhibitor, which has shown clinical efficacy in combination with chemotherapy in patients with locally advanced muscle-invasive bladder cancer. Nintedanib inhibits fibroblast growth factor receptors (FGFRs), validated targets in patients with bladder cancer harboring FGFR3/2 genetic alterations. Here, we aimed at studying its mechanisms of action to understand therapy resistance, identify markers predictive of response, and improve the design of future clinical trials. We have used a panel of genetically well-characterized human bladder cancer cells to identify the molecular and transcriptomic changes induced upon treatment with nintedanib, in vitro and in vivo, at the tumor and stroma cell levels. We showed that bladder cancer cells display an intrinsic resistance to nintedanib treatment in vitro, independently of their FGFR3 status. However, nintedanib has higher antitumor activity on mouse xenografts. We have identified PI3K activation as a resistance mechanism against nintedanib in bladder cancer and evidenced that the combination of nintedanib with the PI3K inhibitor alpelisib has synergistic antitumor activity. Treatment with this combination is associated with cell-cycle inhibition at the tumoral and stromal levels and potent nontumor cell autonomous effects on α-smooth muscle actin—positive tumor infiltrating cells and tumor vasculature. The combination of nintedanib with PI3K inhibitors not only reversed bladder cancer resistance to nintedanib but also enhanced its antiangiogenic effects.
Data from Small molecule mediated stabilization of PP2A modulates the Homologous Recombination pathway and potentiates DNA damage-induced cell death.
Authors: Avelar Rita A. , Armstrong Amy J. , Carvette Gracie , Gupta Riya , Puleo Noah , Colina Jose A. , Joseph Peronne , Sobeck Alexander M. , O'Connor Caitlin M. , Raines Brynne , Gandhi Agharnan , Dziubinski Michele L. , Ma Daniel S. , Resnick Kimberly , Singh Sareena , Zanotti Kristine , Nagel Christa , Waggoner Steven , Thomas Dafydd G. , Skala Stephanie L. , Zhang Junran , Narla Goutham , DiFeo Analisa
Published: April 2023

Abstract
High-Grade Serous Carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP-inhibitors (PARPi) have become the mainstay of HGSC targeted therapy, given that these tumors are driven by a high degree of genomic instability and Homologous Recombination (HR) defects. Nonetheless, ~30% of patients initially respond to treatment, ultimately relapsing with resistant disease. Thus, despite recent advances in drug development and an increased understanding of genetic alterations driving HGSC progression, mortality has not declined, highlighting the need for novel therapies. Using a Small Molecule Activator of Protein Phosphatase 2A (PP2A) (SMAP-061), we investigated the mechanism by which PP2A stabilization induces apoptosis in Patient-Derived HGSC cells and Xenograft (PDX) models alone or in combination with PARPi. We uncovered that PP2A genes essential for cellular transformation (B56,B56 and PR72) and basal phosphatase activity (PP2A-A and -C) are heterozygously lost in the majority of HGSC. Moreover, loss of these PP2A genes correlate with worse overall patient survival. We show that SMAP-061 stabilization of PP2A inhibits the homologous recombination (HR) output by targeting RAD51, leading to chronic accumulation of DNA damage and ultimately apoptosis. Furthermore, combination of SMAP-061 and PARPi leads to enhanced apoptosis in both HR-proficient and HR-deficient cells and in PDX models. Our studies identifies PP2A as a novel regulator of HR and indicates PP2A modulators as a therapeutic therapy for HGSC. In sum, our findings further emphasize the potential of PP2A modulators to overcome PARPi insensitivity, given that targeting RAD51 presents benefits in overcoming PARPi-resistance driven by BRCA1/2 mutation reversions.
Data from Small-Molecule–Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death
Authors: Avelar Rita A. , Armstrong Amy J. , Carvette Gracie , Gupta Riya , Puleo Noah , Colina Jose A. , Joseph Peronne , Sobeck Alexander M. , O'Connor Caitlin M. , Raines Brynne , Gandhi Agharnan , Dziubinski Michele L. , Ma Daniel S. , Resnick Kimberly , Singh Sareena , Zanotti Kristine , Nagel Christa , Waggoner Steven , Thomas Daffyd G. , Skala Stephanie L. , Zhang Junran , Narla Goutham , DiFeo Analisa
Published: April 2023

Abstract
High-grade serous carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP inhibitors (PARPi) have become the mainstay of HGSC-targeted therapy, given that these tumors are driven by a high degree of genomic instability (GI) and homologous recombination (HR) defects. Nonetheless, approximately 30% of patients initially respond to treatment, ultimately relapsing with resistant disease. Thus, despite recent advances in drug development and an increased understanding of genetic alterations driving HGSC progression, mortality has not declined, highlighting the need for novel therapies. Using a small-molecule activator of protein phosphatase 2A (PP2A; SMAP-061), we investigated the mechanism by which PP2A stabilization induces apoptosis in patient-derived HGSC cells and xenograft (PDX) models alone or in combination with PARPi. We uncovered that PP2A genes essential for cellular transformation (B56α, B56γ, and PR72) and basal phosphatase activity (PP2A-A and -C) are heterozygously lost in the majority of HGSC. Moreover, loss of these PP2A genes correlates with worse overall patient survival. We show that SMAP-061–induced stabilization of PP2A inhibits the HR output by targeting RAD51, leading to chronic accumulation of DNA damage and ultimately apoptosis. Furthermore, combination of SMAP-061 and PARPi leads to enhanced apoptosis in both HR-proficient and HR-deficient HGSC cells and PDX models. Our studies identify PP2A as a novel regulator of HR and indicate PP2A modulators as a therapeutic therapy for HGSC. In summary, our findings further emphasize the potential of PP2A modulators to overcome PARPi insensitivity, given that targeting RAD51 presents benefits in overcoming PARPi resistance driven by BRCA1/2 mutation reversions.
Table S2 from Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell–Secreted Cytokines
Authors: Ito Yoshinaga , Pan Deng , Zhang Wubing , Zhang Xixi , Juan Tiffany Y. , Pyrdol Jason W. , Kyrysyuk Oleksandr , Doench John G. , Liu X. Shirley , Wucherpfennig Kai W.
Published: April 2023

Supplementary Table S2: ## Raw count matrix of mini-pool CRISPR screens. ## Normalized gene scores in mini-pool screens.
Supplementary Table S3 from Nucleosome Patterns in Circulating Tumor DNA Reveal Transcriptional Regulation of Advanced Prostate Cancer Phenotypes
Authors: De Sarkar Navonil , Patton Robert D. , Doebley Anna-Lisa , Hanratty Brian , Adil Mohamed , Kreitzman Adam J. , Sarthy Jay F. , Ko Minjeong , Brahma Sandipan , Meers Michael P. , Janssens Derek H. , Ang Lisa S. , Coleman Ilsa M. , Bose Arnab , Dumpit Ruth F. , Lucas Jared M. , Nunez Talina A. , Nguyen Holly M. , McClure Heather M. , Pritchard Colin C. , Schweizer Michael T. , Morrissey Colm , Choudhury Atish D. , Baca Sylvan C. , Berchuck Jacob E. , Freedman Matthew L. , Ahmad Kami , Haffner Michael C. , Montgomery R. Bruce , Corey Eva , Henikoff Steven , Nelson Peter S. , Ha Gavin
Published: April 2023

Differential regulation metrics and values for select features
Sheet 1: Log2 fold-change, p-value, and q-value between ARPC and NEPC lines for NPS in the 47 phenotype defining gene bodies (two tailed Mann-Whitney U test, Benjamini-Hochberg adjusted).
Sheet 2: Differentially expressed list of 514 transcription factor (TF). All statistical comparison and fold change estimation was done against ARPCs.
Sheet 3: Log2 fold-change, p-value, and q-value between ARPC and NEPC lines for central mean coverage in 108 TFs overlapping RNA-Seq up/down regulated TFs (two tailed Mann-Whitney U test, Benjamini-Hochberg adjusted).
Sheet 4: Paralogous transcription factors (TFs) for each of the 38 TFs with differential RNA expression between ARPC and NEPC and differential TFBS accessibility. Paralogous TFs that are also differentially expressed by RNAseq analysis of PDX tumors are shown in red text. Paralogs were obtained from ensembl biomart human genes GRCh38.p13 (http://uswest.ensembl.org/biomart/martview/64d8bd7fe9851a2501aece9b74b03631)
Sheet 5: Mean values in ARPC, NEPC, and HD lines for central and window means for ARPC and NEPC specific open chromatin regions.
Supplementary Fig. S9 from Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell–Secreted Cytokines
Authors: Ito Yoshinaga , Pan Deng , Zhang Wubing , Zhang Xixi , Juan Tiffany Y. , Pyrdol Jason W. , Kyrysyuk Oleksandr , Doench John G. , Liu X. Shirley , Wucherpfennig Kai W.
Published: April 2023

Supplementary Fig. S9 shows enhanced IFNg and TNFa expression by T cells and NK cells in Rnf31/Atg5-dKO tumors.
Supplementary Table S2 from Nucleosome Patterns in Circulating Tumor DNA Reveal Transcriptional Regulation of Advanced Prostate Cancer Phenotypes
Authors: De Sarkar Navonil , Patton Robert D. , Doebley Anna-Lisa , Hanratty Brian , Adil Mohamed , Kreitzman Adam J. , Sarthy Jay F. , Ko Minjeong , Brahma Sandipan , Meers Michael P. , Janssens Derek H. , Ang Lisa S. , Coleman Ilsa M. , Bose Arnab , Dumpit Ruth F. , Lucas Jared M. , Nunez Talina A. , Nguyen Holly M. , McClure Heather M. , Pritchard Colin C. , Schweizer Michael T. , Morrissey Colm , Choudhury Atish D. , Baca Sylvan C. , Berchuck Jacob E. , Freedman Matthew L. , Ahmad Kami , Haffner Michael C. , Montgomery R. Bruce , Corey Eva , Henikoff Steven , Nelson Peter S. , Ha Gavin
Published: April 2023

PTM peak data and phenotype 47 fragment variability
Sheet 1: PDX sample representation in 3 histone PTM CUT&RUN nucleosome profiling assays (H3K4me1, H2K27ac and H3K27me3).
Sheet 2: Log2 fold-change, p-value, and q-value between ARPC and NEPC lines for coefficient of variation in the 47 phenotype defining gene bodies (two tailed Mann-Whitney U test, Benjamini-Hochberg adjusted).
Sheet 3: Log2 fold-change, p-value, and q-value between ARPC and NEPC lines for coefficient of variation in the 47 phenotype defining gene promoters (two tailed Mann-Whitney U test, Benjamini-Hochberg adjusted).
Supplementary Fig. S8 from Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell–Secreted Cytokines
Authors: Ito Yoshinaga , Pan Deng , Zhang Wubing , Zhang Xixi , Juan Tiffany Y. , Pyrdol Jason W. , Kyrysyuk Oleksandr , Doench John G. , Liu X. Shirley , Wucherpfennig Kai W.
Published: April 2023

Supplementary Fig. S8 shows CD8 T cell-dependent control of tumors containing a B2m-/- population with inactivated Rnf31 and Atg5 genes.
Supplementary Table S1 from Nucleosome Patterns in Circulating Tumor DNA Reveal Transcriptional Regulation of Advanced Prostate Cancer Phenotypes
Authors: De Sarkar Navonil , Patton Robert D. , Doebley Anna-Lisa , Hanratty Brian , Adil Mohamed , Kreitzman Adam J. , Sarthy Jay F. , Ko Minjeong , Brahma Sandipan , Meers Michael P. , Janssens Derek H. , Ang Lisa S. , Coleman Ilsa M. , Bose Arnab , Dumpit Ruth F. , Lucas Jared M. , Nunez Talina A. , Nguyen Holly M. , McClure Heather M. , Pritchard Colin C. , Schweizer Michael T. , Morrissey Colm , Choudhury Atish D. , Baca Sylvan C. , Berchuck Jacob E. , Freedman Matthew L. , Ahmad Kami , Haffner Michael C. , Montgomery R. Bruce , Corey Eva , Henikoff Steven , Nelson Peter S. , Ha Gavin
Published: April 2023

PDX sequencing metrics Phenotype and sequencing metrics for all PDX LuCaP lines.
Supplementary Fig. S7 from Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell–Secreted Cytokines
Authors: Ito Yoshinaga , Pan Deng , Zhang Wubing , Zhang Xixi , Juan Tiffany Y. , Pyrdol Jason W. , Kyrysyuk Oleksandr , Doench John G. , Liu X. Shirley , Wucherpfennig Kai W.
Published: April 2023

Supplementary Fig. S7 shows effect of PD-1 inhibition on treatment of tumors containing a B2m-/- population.
Supplementary Fig. S6 from Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell–Secreted Cytokines
Authors: Ito Yoshinaga , Pan Deng , Zhang Wubing , Zhang Xixi , Juan Tiffany Y. , Pyrdol Jason W. , Kyrysyuk Oleksandr , Doench John G. , Liu X. Shirley , Wucherpfennig Kai W.
Published: April 2023

Supplementary Fig. S6 shows functional links between autophagy and cytokine signaling pathways.
Supplementary Fig. S4 from Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell–Secreted Cytokines
Authors: Ito Yoshinaga , Pan Deng , Zhang Wubing , Zhang Xixi , Juan Tiffany Y. , Pyrdol Jason W. , Kyrysyuk Oleksandr , Doench John G. , Liu X. Shirley , Wucherpfennig Kai W.
Published: April 2023

Supplementary Fig. S4 shows differentially expressed genes revealed by RNA-seq analysis.
Supplementary Fig. S3 from Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell–Secreted Cytokines
Authors: Ito Yoshinaga , Pan Deng , Zhang Wubing , Zhang Xixi , Juan Tiffany Y. , Pyrdol Jason W. , Kyrysyuk Oleksandr , Doench John G. , Liu X. Shirley , Wucherpfennig Kai W.
Published: April 2023

Supplementary Fig. S3 generation of tumor cell lines with multiple gene edits.
Supplementary Fig. S2 from Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell–Secreted Cytokines
Authors: Ito Yoshinaga , Pan Deng , Zhang Wubing , Zhang Xixi , Juan Tiffany Y. , Pyrdol Jason W. , Kyrysyuk Oleksandr , Doench John G. , Liu X. Shirley , Wucherpfennig Kai W.
Published: April 2023

Supplementary Fig. S2 shows efficiency of gene editing in tumor cell lines for co-dependency screen.
Supplementary Fig. S10 from Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell–Secreted Cytokines
Authors: Ito Yoshinaga , Pan Deng , Zhang Wubing , Zhang Xixi , Juan Tiffany Y. , Pyrdol Jason W. , Kyrysyuk Oleksandr , Doench John G. , Liu X. Shirley , Wucherpfennig Kai W.
Published: April 2023

Supplementary Fig. S10 shows pharmacological sensitization to T cell cytokines in vitro and in vivo.
Table S6 from Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis
Authors: Salem Joe-Elie , Bretagne Marie , Abbar Baptiste , Leonard-Louis Sarah , Ederhy Stéphane , Redheuil Alban , Boussouar Samia , Nguyen Lee S. , Procureur Adrien , Stein Frederic , Fenioux Charlotte , Devos Perrine , Gougis Paul , Dres Martin , Demoule Alexandre , Psimaras Dimitri , Lenglet Timothee , Maisonobe Thierry , De Chambrun Marc Pineton , Hekimian Guillaume , Straus Christian , Gonzalez-Bermejo Jesus , Klatzmann David , Rigolet Aude , Guillaume-Jugnot Perrine , Champtiaux Nicolas , Benveniste Olivier , Weiss Nicolas , Saheb Samir , Rouvier Philippe , Plu Isabelle , Gandjbakhch Estelle , Kerneis Mathieu , Hammoudi Nadjib , Zahr Noel , Llontop Claudia , Morelot-Panzini Capucine , Lehmann Lorenz , Qin Juan , Moslehi Javid J. , Rosenzwajg Michelle , Similowski Thomas , Allenbach Yves
Published: April 2023

Treatment modalities and reported adverse events by quartile of period of inclusion.
Table S5 from Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis
Authors: Salem Joe-Elie , Bretagne Marie , Abbar Baptiste , Leonard-Louis Sarah , Ederhy Stéphane , Redheuil Alban , Boussouar Samia , Nguyen Lee S. , Procureur Adrien , Stein Frederic , Fenioux Charlotte , Devos Perrine , Gougis Paul , Dres Martin , Demoule Alexandre , Psimaras Dimitri , Lenglet Timothee , Maisonobe Thierry , De Chambrun Marc Pineton , Hekimian Guillaume , Straus Christian , Gonzalez-Bermejo Jesus , Klatzmann David , Rigolet Aude , Guillaume-Jugnot Perrine , Champtiaux Nicolas , Benveniste Olivier , Weiss Nicolas , Saheb Samir , Rouvier Philippe , Plu Isabelle , Gandjbakhch Estelle , Kerneis Mathieu , Hammoudi Nadjib , Zahr Noel , Llontop Claudia , Morelot-Panzini Capucine , Lehmann Lorenz , Qin Juan , Moslehi Javid J. , Rosenzwajg Michelle , Similowski Thomas , Allenbach Yves
Published: April 2023

Proposed management algorithm for ICI-myotoxicities as a function of severity criteria grading
Table S4 from Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis
Authors: Salem Joe-Elie , Bretagne Marie , Abbar Baptiste , Leonard-Louis Sarah , Ederhy Stéphane , Redheuil Alban , Boussouar Samia , Nguyen Lee S. , Procureur Adrien , Stein Frederic , Fenioux Charlotte , Devos Perrine , Gougis Paul , Dres Martin , Demoule Alexandre , Psimaras Dimitri , Lenglet Timothee , Maisonobe Thierry , De Chambrun Marc Pineton , Hekimian Guillaume , Straus Christian , Gonzalez-Bermejo Jesus , Klatzmann David , Rigolet Aude , Guillaume-Jugnot Perrine , Champtiaux Nicolas , Benveniste Olivier , Weiss Nicolas , Saheb Samir , Rouvier Philippe , Plu Isabelle , Gandjbakhch Estelle , Kerneis Mathieu , Hammoudi Nadjib , Zahr Noel , Llontop Claudia , Morelot-Panzini Capucine , Lehmann Lorenz , Qin Juan , Moslehi Javid J. , Rosenzwajg Michelle , Similowski Thomas , Allenbach Yves
Published: April 2023

Definitions used for adjudication and grading of the different evaluated events
Supplementary Methods from Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis
Authors: Salem Joe-Elie , Bretagne Marie , Abbar Baptiste , Leonard-Louis Sarah , Ederhy Stéphane , Redheuil Alban , Boussouar Samia , Nguyen Lee S. , Procureur Adrien , Stein Frederic , Fenioux Charlotte , Devos Perrine , Gougis Paul , Dres Martin , Demoule Alexandre , Psimaras Dimitri , Lenglet Timothee , Maisonobe Thierry , De Chambrun Marc Pineton , Hekimian Guillaume , Straus Christian , Gonzalez-Bermejo Jesus , Klatzmann David , Rigolet Aude , Guillaume-Jugnot Perrine , Champtiaux Nicolas , Benveniste Olivier , Weiss Nicolas , Saheb Samir , Rouvier Philippe , Plu Isabelle , Gandjbakhch Estelle , Kerneis Mathieu , Hammoudi Nadjib , Zahr Noel , Llontop Claudia , Morelot-Panzini Capucine , Lehmann Lorenz , Qin Juan , Moslehi Javid J. , Rosenzwajg Michelle , Similowski Thomas , Allenbach Yves
Published: April 2023

Methods concerning Immune-checkpoint proteins profiling on peripheral blood mononuclear cells and Circulating immune checkpoint agents drug monitoring
Figure S4 from Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis
Authors: Salem Joe-Elie , Bretagne Marie , Abbar Baptiste , Leonard-Louis Sarah , Ederhy Stéphane , Redheuil Alban , Boussouar Samia , Nguyen Lee S. , Procureur Adrien , Stein Frederic , Fenioux Charlotte , Devos Perrine , Gougis Paul , Dres Martin , Demoule Alexandre , Psimaras Dimitri , Lenglet Timothee , Maisonobe Thierry , De Chambrun Marc Pineton , Hekimian Guillaume , Straus Christian , Gonzalez-Bermejo Jesus , Klatzmann David , Rigolet Aude , Guillaume-Jugnot Perrine , Champtiaux Nicolas , Benveniste Olivier , Weiss Nicolas , Saheb Samir , Rouvier Philippe , Plu Isabelle , Gandjbakhch Estelle , Kerneis Mathieu , Hammoudi Nadjib , Zahr Noel , Llontop Claudia , Morelot-Panzini Capucine , Lehmann Lorenz , Qin Juan , Moslehi Javid J. , Rosenzwajg Michelle , Similowski Thomas , Allenbach Yves
Published: April 2023

Example of the first severe ICI-myocarditis case treated with abatacept guided by real-time immune-monitoring assessment of CD86RO (CD86 receptor occupancy) on circulating monocytes.
Figure S3 from Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis
Authors: Salem Joe-Elie , Bretagne Marie , Abbar Baptiste , Leonard-Louis Sarah , Ederhy Stéphane , Redheuil Alban , Boussouar Samia , Nguyen Lee S. , Procureur Adrien , Stein Frederic , Fenioux Charlotte , Devos Perrine , Gougis Paul , Dres Martin , Demoule Alexandre , Psimaras Dimitri , Lenglet Timothee , Maisonobe Thierry , De Chambrun Marc Pineton , Hekimian Guillaume , Straus Christian , Gonzalez-Bermejo Jesus , Klatzmann David , Rigolet Aude , Guillaume-Jugnot Perrine , Champtiaux Nicolas , Benveniste Olivier , Weiss Nicolas , Saheb Samir , Rouvier Philippe , Plu Isabelle , Gandjbakhch Estelle , Kerneis Mathieu , Hammoudi Nadjib , Zahr Noel , Llontop Claudia , Morelot-Panzini Capucine , Lehmann Lorenz , Qin Juan , Moslehi Javid J. , Rosenzwajg Michelle , Similowski Thomas , Allenbach Yves
Published: April 2023

Effect of plasmapheresis on ICI circulating levels in the 10 patients receiving plasmapheresis in our cohort.
Figure S2 from Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis
Authors: Salem Joe-Elie , Bretagne Marie , Abbar Baptiste , Leonard-Louis Sarah , Ederhy Stéphane , Redheuil Alban , Boussouar Samia , Nguyen Lee S. , Procureur Adrien , Stein Frederic , Fenioux Charlotte , Devos Perrine , Gougis Paul , Dres Martin , Demoule Alexandre , Psimaras Dimitri , Lenglet Timothee , Maisonobe Thierry , De Chambrun Marc Pineton , Hekimian Guillaume , Straus Christian , Gonzalez-Bermejo Jesus , Klatzmann David , Rigolet Aude , Guillaume-Jugnot Perrine , Champtiaux Nicolas , Benveniste Olivier , Weiss Nicolas , Saheb Samir , Rouvier Philippe , Plu Isabelle , Gandjbakhch Estelle , Kerneis Mathieu , Hammoudi Nadjib , Zahr Noel , Llontop Claudia , Morelot-Panzini Capucine , Lehmann Lorenz , Qin Juan , Moslehi Javid J. , Rosenzwajg Michelle , Similowski Thomas , Allenbach Yves
Published: April 2023

Delay between presentation for ICI myocarditis, appearance of life-threatening myotoxicity criteria (severity grade 4, Supplementary Table 5 for details concerning grading) and start of the immunosuppressive treatments (with dose) in severe ICI-myocarditis patients requiring abatacept.
Figure S1 from Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis
Authors: Salem Joe-Elie , Bretagne Marie , Abbar Baptiste , Leonard-Louis Sarah , Ederhy Stéphane , Redheuil Alban , Boussouar Samia , Nguyen Lee S. , Procureur Adrien , Stein Frederic , Fenioux Charlotte , Devos Perrine , Gougis Paul , Dres Martin , Demoule Alexandre , Psimaras Dimitri , Lenglet Timothee , Maisonobe Thierry , De Chambrun Marc Pineton , Hekimian Guillaume , Straus Christian , Gonzalez-Bermejo Jesus , Klatzmann David , Rigolet Aude , Guillaume-Jugnot Perrine , Champtiaux Nicolas , Benveniste Olivier , Weiss Nicolas , Saheb Samir , Rouvier Philippe , Plu Isabelle , Gandjbakhch Estelle , Kerneis Mathieu , Hammoudi Nadjib , Zahr Noel , Llontop Claudia , Morelot-Panzini Capucine , Lehmann Lorenz , Qin Juan , Moslehi Javid J. , Rosenzwajg Michelle , Similowski Thomas , Allenbach Yves
Published: April 2023

Examples of cardiac and skeletal muscle pathology findings on autopsies of 2 patients
Data from Nucleosome Patterns in Circulating Tumor DNA Reveal Transcriptional Regulation of Advanced Prostate Cancer Phenotypes
Authors: De Sarkar Navonil , Patton Robert D. , Doebley Anna-Lisa , Hanratty Brian , Adil Mohamed , Kreitzman Adam J. , Sarthy Jay F. , Ko Minjeong , Brahma Sandipan , Meers Michael P. , Janssens Derek H. , Ang Lisa S. , Coleman Ilsa M. , Bose Arnab , Dumpit Ruth F. , Lucas Jared M. , Nunez Talina A. , Nguyen Holly M. , McClure Heather M. , Pritchard Colin C. , Schweizer Michael T. , Morrissey Colm , Choudhury Atish D. , Baca Sylvan C. , Berchuck Jacob E. , Freedman Matthew L. , Ahmad Kami , Haffner Michael C. , Montgomery R. Bruce , Corey Eva , Henikoff Steven , Nelson Peter S. , Ha Gavin
Published: April 2023

Abstract
Advanced prostate cancers comprise distinct phenotypes, but tumor classification remains clinically challenging. Here, we harnessed circulating tumor DNA (ctDNA) to study tumor phenotypes by ascertaining nucleosome positioning patterns associated with transcription regulation. We sequenced plasma ctDNA whole genomes from patient-derived xenografts representing a spectrum of androgen receptor active (ARPC) and neuroendocrine (NEPC) prostate cancers. Nucleosome patterns associated with transcriptional activity were reflected in ctDNA at regions of genes, promoters, histone modifications, transcription factor binding, and accessible chromatin. We identified the activity of key phenotype-defining transcriptional regulators from ctDNA, including AR, ASCL1, HOXB13, HNF4G, and GATA2. To distinguish NEPC and ARPC in patient plasma samples, we developed prediction models that achieved accuracies of 97% for dominant phenotypes and 87% for mixed clinical phenotypes. Although phenotype classification is typically assessed by IHC or transcriptome profiling from tumor biopsies, we demonstrate that ctDNA provides comparable results with diagnostic advantages for precision oncology.
Significance:
This study provides insights into the dynamics of nucleosome positioning and gene regulation associated with cancer phenotypes that can be ascertained from ctDNA. New methods for classification in phenotype mixtures extend the utility of ctDNA beyond assessments of somatic DNA alterations with important implications for molecular classification and precision oncology.

This article is highlighted in the In This Issue feature, p. 517
Data from Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell-secreted Cytokines
Authors: Ito Yoshinaga , Pan Deng , Zhang Wubing , Zhang Xixi , Juan Tiffany Y. , Pyrdol Jason W. , Kyrysyuk Oleksandr , Doench John G. , Liu X. Shirley , Wucherpfennig Kai W.
Published: April 2023

Abstract
Tumor heterogeneity is a major barrier to cancer therapy, including immunotherapy. Activated T cells can efficiently kill tumor cells following recognition of MHC class I (MHC-I) bound peptides, but this selection pressure favors outgrowth of MHC-I deficient tumor cells. We performed a genome-scale screen to discover alternative pathways for T cell-mediated killing of MHC-I deficient tumor cells. Autophagy and TNF signaling emerged as top pathways, and inactivation of Rnf31 (TNF signaling) and Atg5 (autophagy) sensitized MHC-I deficient tumor cells to apoptosis by T cell-derived cytokines. Mechanistic studies demonstrated that inhibition of autophagy amplified pro-apoptotic effects of cytokines in tumor cells. Antigens from apoptotic MHC-I deficient tumor cells were efficiently cross-presented by dendritic cells, resulting in heightened tumor infiltration by IFNa and TNFg-producing T cells. Tumors with a substantial population of MHC-I deficient cancer cells could be controlled by T cells when both pathways were targeted using genetic or pharmacological approaches.
Causes of Early Mortality After Catheter Ablation of Atrial Fibrillation
Authors: Tan Min Choon , Rattanawong Pattara , Karikalan Suganya , Deshmukh Abhishek J. , Srivathsan Komandoor , Scott Luis R. , McLeod Christopher J. , Asirvatham Samuel J. , Noseworthy Peter A. , Mulpuru Siva K. , Cha Yong-Mei , Munger Thomas M. , Lee Justin Z.
Published: April 2023

Background:

Recognition of the causes of early mortality after atrial fibrillation (AF) catheter ablation is essential for the improvement of patient safety. This study sought to determine the causes of early mortality (≤90 days) after AF ablation.

Methods:

We performed a retrospective analysis of AF ablation from January 1, 2013, to December 1, 2021 at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). Causes of death were identified through a comprehensive chart review of the electronic health record from within the Mayo Clinic system and outside records when available.

Results:

A total of 6723 patients were included in the study. The 90-day all-cause mortality rate was 0.22% (n=15). Among all 90-day deaths, majority of the deaths (73.3%) did not have a direct relationship with the procedure. Sudden death was the most common cause of early death (20%), followed by peri-procedural stroke (13%), respiratory failure (13%), atrioesophageal fistula (13%), infection (7%), heart failure (7%), and traumatic brain injury (7%). The 90-day mortality rate directly due to AF ablation procedural complications was 0.06% (n=4).

Conclusions:

AF ablation procedure has a 90-day mortality of 0.22%, and the most common cause of early mortality was sudden death. The majority (73.3%) of early mortality was not directly associated with a procedural complication, and the mortality rate due to complications associated with the AF ablation procedure was low at 0.06%. Further studies are required to investigate causes and risk factors associated with sudden death in this patient population.
A taxonomic revision of the Palaearctic genus Roeseliana (Orthoptera: Tettigoniidae: Tettigoniinae: Platycleidini): a case of ongoing Mediterranean speciation
Authors: MASSA BRUNO , TAGLIAVIA MARCELLO , BUZZETTI FILIPPO MARIA , FONTANA PAOLO , CAROTTI GIOVANNI , BARDIANI MARCO , LEANDRI FAUSTO , SCHERINI ROBERTO , VERDE GABRIELLA LO
Published: April 2023

The genus Roeseliana presently includes 10 specific or subspecific taxa, but following different authors some of them are considered synonyms. However, the authors who have treated these taxa often did not agree with the synonymies, in particular, concerning some taxa, such as R. fedtschenkoi (Saussure, 1874) and R. roeselii (Hagenbach, 1822). The present authors examined hundreds of specimens of different taxa, for the first time were able to obtain the translation from the Russian of the description of R. fedtschenkoi, compared the main morphological characters used to discriminate different taxa, biometrics, bioacoustics and genetics of some taxa. This allowed them to conclude that it is possible to recognize the following taxa: 1) Roeseliana roeselii (Hagenbach, 1822) widespread in the Palaearctic Region and imported in North America; 2) Roeseliana fedtschenkoi (Saussure, 1874) in Uzbekistan and Turkmenistan; 3) Roeseliana pylnovi (Uvarov, 1924) in the Caucasian region; 4) Roeseliana bispina (Bolívar, 1899) in Turkey; 5) Roeseliana azami (Finot, 1892) from the Mediterranean France through Italian peninsula (formerly R. azami minor Nadig, 1961); 6) R. ambitiosa (Uvarov, 1924) on the Balkan peninsula; 7) Roeseliana n. sp. Lemonnier-Darcemont & Darcemont, (in press) on Epirus (Greece and Albania); 8) Roeseliana brunneri Ramme 1951 in north east Italy (Veneto, Friuli and Po Valley); 9) Roeseliana oporina (Bolívar, 1887) in Spain.