bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Significance of SASP-Related Gene Signature of Radiation Therapy in Head and Neck Squamous Cell Carcinoma
Authors: Lee Min Kyeong , Woo Seon Rang , Noh Joo Kyung , Min Soonki , Kong Moonkyoo , Lee Young Chan , Ko Seong-Gyu , Eun Young-Gyu
Published: July 2024

In this study, we developed and validated the clinical significance of senescence-associated secretory phenotype (SASP)-related gene signature and explored its association with radiation therapy (RT) in patients with head and neck squamous cell carcinoma (HNSCC). First, we searched the three published review literature associated with SASP and selected all 81 genes to develop SASP-related gene signature. Then, 81 SASP-related genes were adapted to gene expression dataset from The Cancer Genome Atlas (TCGA). Patients with HNSCC of TCGA were classified into clusters 1 and 2 via unsupervised clustering according to SASP-related gene signature. Kaplan–Meier plot survival analysis showed that cluster 1 had a poorer prognosis than cluster 2 in 5-year overall survival and recurrence-free survival. Similarly, cluster 1 showed a worse prognosis than cluster 2 in three validation cohorts (E-MTAB-8588, FHCRC, and KHU). Cox proportional hazards regression observed that the SASP-related signature was an independent prognostic factor for patients with HNSCC. We also established a nomogram using a relevant clinical parameter and a risk score. Time-dependent receiver operating characteristic analysis was carried out to assess the accuracy of the prognostic risk model and nomogram. Senescence SASP-related gene signature was associated with the response to RT. Therefore, subsequent, in vitro experiments further validated the association between SASP-related gene signature and RT in HNSCC. In conclusion, we developed a SASP-related gene signature, which could predict survival of patients with HNSCC, and this gene signature provides new clinical evidence for the accurate diagnosis and targeted RT of HNSCC.
Supplementary Table S2 from Distinct Regulation of ASCL1 by the Cell Cycle and Chemotherapy in Small Cell Lung Cancer
Authors: Liu Yuning , Wu Qingzhe , Jiang Bin , Hou Tingting , Wu Chuanqiang , Wu Ming , Song Hai
Published: July 2024

Supplementary Table S2. Primer sequences for qRT-PCR.
Supplementary Table S4 from Low- and High-Grade Glioma-Associated Vascular Cells Differentially Regulate Tumor Growth
Authors: Muthukrishnan Sree Deepthi , Qi Haocheng , Wang David , Elahi Lubayna , Pham Amy , Alvarado Alvaro G. , Li Tie , Gao Fuying , Kawaguchi Riki , Lai Albert , Kornblum Harley I.
Published: July 2024

Differentially expressed genes between LG-, PRI- and REC-GVC vs HBEC
Supplementary Table S6 from ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3
Authors: Ebegboni Vernon Justice , Jones Tamara L. , Brownmiller Tayvia , Zhao Patrick X. , Pehrsson Erica C. , Sundara Rajan Soumya , Caplen Natasha J.
Published: July 2024

Analysis of H3K4me3 modifications
Supplementary Figure S4 from Low- and High-Grade Glioma-Associated Vascular Cells Differentially Regulate Tumor Growth
Authors: Muthukrishnan Sree Deepthi , Qi Haocheng , Wang David , Elahi Lubayna , Pham Amy , Alvarado Alvaro G. , Li Tie , Gao Fuying , Kawaguchi Riki , Lai Albert , Kornblum Harley I.
Published: July 2024

Supplementary Figure S4. LG- and HG-GVC show differential expression of growth factors, cytokines, and extracellular matrix proteoglycans
Supplementary Figure S3 from Low- and High-Grade Glioma-Associated Vascular Cells Differentially Regulate Tumor Growth
Authors: Muthukrishnan Sree Deepthi , Qi Haocheng , Wang David , Elahi Lubayna , Pham Amy , Alvarado Alvaro G. , Li Tie , Gao Fuying , Kawaguchi Riki , Lai Albert , Kornblum Harley I.
Published: July 2024

Supplementary Figure S3. LG- and HG-GVC differentially regulate the growth of mIDH astrocytoma and wIDH tumor cells
Supplementary Figure S6 from ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3
Authors: Ebegboni Vernon Justice , Jones Tamara L. , Brownmiller Tayvia , Zhao Patrick X. , Pehrsson Erica C. , Sundara Rajan Soumya , Caplen Natasha J.
Published: July 2024

EWS cells expressing ETS1 exhibit TENSIN3-dependent changes in the organization of F-actin
Supplementary Figure S2 from ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3
Authors: Ebegboni Vernon Justice , Jones Tamara L. , Brownmiller Tayvia , Zhao Patrick X. , Pehrsson Erica C. , Sundara Rajan Soumya , Caplen Natasha J.
Published: July 2024

The genome-wide binding of EWSR1::FLI1 and associated epigenetic marks.
Supplementary Figure S4 from Vasorin Exocytosed from Glioma Cells Facilitates Angiogenesis via VEGFR2/AKT Signaling Pathway
Authors: Zhong Ying , Kang Hui , Ma Ziqing , Li Jiayu , Qin Zixi , Zhang Zixuan , Li Peiwen , Zhong Ying , Wang Lihui
Published: July 2024

VASN induces tip cell phenotype transformation in HUVECs
METTL14-Mediated Bim mRNA m6A Modification Augments Osimertinib Sensitivity in EGFR-Mutant NSCLC Cells
Authors: Fan Siwen , Lv Xinwu , Zhang Chuantao , Zeng Bingbing , Liang Yanqing , Chen Danyang , Xu Zumin , Li Pan , Wu Shanshan , Liu Hao , Luo Kai , Liu Zongcai , Yi Yanmei
Published: July 2024

Resistance to osimertinib represents a significant challenge for the successful treatment of non–small cell lung cancer (NSCLC) harboring activating mutations in EGFR. N6-methyladenosine (m6A) on mRNAs is critical for various biological processes, yet whether m6A regulates osimertinib resistance of NSCLC remains unknown. In this study, we demonstrated that developing osimertinib-resistant phenotypes depends on m6A reduction resulting from downexpression of m6A methyltransferase METTL14 in EGFR-mutant NSCLCs. Both in vitro and in vivo assays showed that specific knockdown of METTL14 was sufficient to confer osimertinib resistance and that elevated expression of METTL14 rescued the efficacy of osimertinib in the resistant NSCLC cells. Mechanistically, METTL14 promoted m6A methylation of pro-apoptotic Bim mRNA and increased Bim mRNA stability and expression, resulting in activating the Bim-dependent pro-apoptotic signaling and thereby promoting osimertinib-induced cell apoptosis. Analysis of clinical samples revealed that decreased expression of METTL14 was observed in osimertinib-resistant NSCLC tissues and significantly associated with a poor prognosis. In conclusion, our study reveals a novel regulatory mechanism by which METTL14-mediated m6A methylation of Bim mRNA inhibited osimertinib resistance of NSCLC cells. It offers more evidences for the involvement of m6A modification in regulation of osimertinib resistance and provides potential therapeutic targets for novel approaches to overcome the tolerance of osimertinib and other EGFR tyrosine kinase inhibitors.

Implications: This study offers more evidences for the involvement of METTL14-mediated N6-methyladenosine modification in regulation of osimertinib resistance and provides potential therapeutic targets for novel approaches to overcome the tolerance of osimertinib and other EGFR tyrosine kinase inhibitors.
Supplementary Table 3 from Germline Testing Identifies Pathogenic/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors
Authors: Mohindroo Chirayu , Baydogan Seyda , Agarwal Parul , Wright Robin D. , Prakash Laura R. , Mork Maureen E. , Klein Alison P. , Laheru Daniel A. , Maxwell Jessica E. , Katz Matthew H.G. , Dasari Arvind , Kim Michael P. , He Jin , McAllister Florencia , De Jesus-Acosta Ana
Published: July 2024

Supplementary Table 3: Stratified analysis of the clinical factors in the unselected cohort (MEN1 and DNA repair genes)
Supplementary Table 1 from Germline Testing Identifies Pathogenic/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors
Authors: Mohindroo Chirayu , Baydogan Seyda , Agarwal Parul , Wright Robin D. , Prakash Laura R. , Mork Maureen E. , Klein Alison P. , Laheru Daniel A. , Maxwell Jessica E. , Katz Matthew H.G. , Dasari Arvind , Kim Michael P. , He Jin , McAllister Florencia , De Jesus-Acosta Ana
Published: July 2024

Supplementary Table 1: Details of each P/LP detected in the high-risk cohort along with the high-risk criteria
Data from Germline Testing Identifies Pathogenic/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors
Authors: Mohindroo Chirayu , Baydogan Seyda , Agarwal Parul , Wright Robin D. , Prakash Laura R. , Mork Maureen E. , Klein Alison P. , Laheru Daniel A. , Maxwell Jessica E. , Katz Matthew H.G. , Dasari Arvind , Kim Michael P. , He Jin , McAllister Florencia , De Jesus-Acosta Ana
Published: July 2024

Abstract
Ten percent of pancreatic neuroendocrine tumors (pNET) are related to inherited syndromes (MEN1, MEN4, VHL, NF1, and TSC). Growing evidence suggests that clinically sporadic pNETs can also harbor germline pathogenic variants. In this study, we report the prevalence of pathologic/likely pathologic (P/LP) germline variants in a high-risk cohort and an unselected cohort. We collected clinical data of patients with pNETs seen at MD Anderson Cancer Center and Johns Hopkins Hospital. The high-risk cohort included (n = 132) patients seen at MD Anderson Cancer Center who underwent germline testing for high-risk criteria (early onset, personal or family history of cancer, and syndromic features) between 2013 and 2019. The unselected cohort included (n = 106) patients seen at Johns Hopkins Hospital who underwent germline testing following their diagnosis of pNETs between 2020 and 2022. In the high-risk cohort (n = 132), 33% (n = 44) had P/LP variants. The majority of the patients had P/LP variants in MEN1 56% (n = 25), followed by DNA repair pathways 18% (n = 8), and 7% (n = 3) in MSH2 (Lynch syndrome). Patients with P/LP were younger (45 vs. 50 years; P = 0.002). In the unselected cohort (n = 106), 21% (n = 22) had P/LP. The majority were noted in DNA repair pathways 40% (n = 9) and MEN1 36% (n = 8). Multifocal tumors correlated with the presence of P/LP (P = 0.0035). MEN1 germline P/LP variants correlated with younger age (40 vs. 56 years; P = 0.0012), presence of multifocal tumors (P < 0.0001), and World Health Organization grade 1 histology (P = 0.0078). P/LP variants are prevalent in patients with clinically sporadic pNET irrespective of high-risk features. The findings support upfront universal germline testing in all patients with pNET.

Prevention Relevance: Here, we present germline data from the largest reported cohort of patients with pNET (n = 238), comprising both a high-risk cohort and an unselected cohort. In both cohorts, we identify a high number of P/LPs, including those in the DNA repair pathway. Our findings support universal germline testing in patients with pNET.
Data from Nfe2l2/NRF2 Deletion Attenuates Tumorigenesis and Increases Bacterial Diversity in a Mouse Model of Lynch Syndrome
Authors: Haller Felix , Jimenez Kristine , Baumgartner Maximilian , Lang Michaela , Klotz Anton , Jambrich Manuela , Busslinger Georg , Müllauer Leonhard , Khare Vineeta , Gasche Christoph
Published: July 2024

Abstract
Lynch syndrome (LS) is the most prevalent heritable form of colorectal cancer. Its early onset and high lifetime risk for colorectal cancer emphasize the necessity for effective chemoprevention. NFE2L2 (NRF2) is often considered a potential druggable target, and many chemopreventive compounds induce NRF2. However, although NRF2 counteracts oxidative stress, it is also overexpressed in colorectal cancer and may promote tumorigenesis. In this study, we evaluated the role of NRF2 in the prevention of LS-associated neoplasia. We found increased levels of NRF2 in intestinal epithelia of mice with intestinal epithelium–specific Msh2 deletion (MSH2ΔIEC) compared with C57BL/6 (wild-type) mice, as well as an increase in downstream NRF2 targets NAD(P)H dehydrogenase (quinone 1) and glutamate–cysteine ligase catalytic subunit. Likewise, NRF2 levels were increased in human MSH2-deficient LS tumors compared with healthy human controls. In silico analysis of a publicly accessible RNA sequencing LS dataset also found an increase in downstream NRF2 targets. Upon crossing MSH2ΔIEC with Nrf2null (MSH2ΔIECNrf2null) mice, we unexpectedly found reduced tumorigenesis in MSH2ΔIECNrf2null mice compared with MSH2ΔIEC mice after 40 weeks, which occurred despite an increase in oxidative damage in MSH2ΔIECNrf2null mice. The loss of NRF2 impaired proliferation as seen by Ki67 intestinal staining and in organoid cultures. This was accompanied by diminished WNT/β-catenin signaling, but apoptosis was unaffected. Microbial α-diversity increased over time with the loss of NRF2 based upon 16S rRNA gene amplicon sequencing of murine fecal samples. Altogether, we show that NRF2 protein levels are increased in MSH2 deficiency and associated neoplasia, but the loss of NRF2 attenuates tumorigenesis. Activation of NRF2 may not be a feasible strategy for chemoprevention in LS.

Prevention Relevance: Patients with LS have an early onset and high lifetime risk for colorectal cancer. In this study, we show that NRF2 protein levels are increased in MSH2 deficiency and associated neoplasia, but the loss of NRF2 attenuates tumorigenesis. This suggests that NRF2 may not be a tumor suppressor in this specific context.
Supplementary Figure 7 from Melanoma Clonal Heterogeneity Leads to Secondary Resistance after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes
Authors: König David , Sandholzer Michael T. , Uzun Sarp , Zingg Andreas , Ritschard Reto , Thut Helen , Glatz Katharina , Kappos Elisabeth A. , Schaefer Dirk J. , Kettelhack Christoph , Passweg Jakob R. , Holbro Andreas , Baur Katharina , Medinger Michael , Buser Andreas , Lardinois Didier , Jeker Lukas T. , Khanna Nina , Stenner Frank , Kasenda Benjamin , Homicsko Krisztian , Matter Matthias , Rodrigues Mantuano Natalia , Zippelius Alfred , Läubli Heinz
Published: July 2024

Supplementary Figure 7. MHC I expression on tumor cells in lesion used for expansion of the TIL product and the progressing lung metastasis.
Supplementary Table S5 from Small Extracellular Vesicle piR-hsa-30937 Derived from Pancreatic Neuroendocrine Neoplasms Upregulates CD276 in Macrophages to Promote Immune Evasion
Authors: Zhong Yuan , Tian Ye , Wang Yan , Bai Jian’an , Long Qin , Yan Lijun , Gong Zhihui , Gao Wei , Tang Qiyun
Published: July 2024

Differentially expressed piRNAs in serum sEVs from PNEN patients compared to healthy volunteers
Supplementary Fig. S9 from Small Extracellular Vesicle piR-hsa-30937 Derived from Pancreatic Neuroendocrine Neoplasms Upregulates CD276 in Macrophages to Promote Immune Evasion
Authors: Zhong Yuan , Tian Ye , Wang Yan , Bai Jian’an , Long Qin , Yan Lijun , Gong Zhihui , Gao Wei , Tang Qiyun
Published: July 2024

Supplementary Fig. S9 PNEN cell-derived sEV piR-hsa-30937 is transferred to macrophages and drives CD276 expression by targeting PTEN to activate the AKT signaling pathway. CD276+ macrophages suppress T-cell immunity and promote PNEN immune evasion and progression.
Supplementary Data from Melanoma Clonal Heterogeneity Leads to Secondary Resistance after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes
Authors: König David , Sandholzer Michael T. , Uzun Sarp , Zingg Andreas , Ritschard Reto , Thut Helen , Glatz Katharina , Kappos Elisabeth A. , Schaefer Dirk J. , Kettelhack Christoph , Passweg Jakob R. , Holbro Andreas , Baur Katharina , Medinger Michael , Buser Andreas , Lardinois Didier , Jeker Lukas T. , Khanna Nina , Stenner Frank , Kasenda Benjamin , Homicsko Krisztian , Matter Matthias , Rodrigues Mantuano Natalia , Zippelius Alfred , Läubli Heinz
Published: July 2024

Supplementary Data
Supplementary Table S6 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Table S6
Supplementary Table S4 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Table S4
Supplementary Figure S3 from The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells
Authors: Bianchi Matteo , Reichen Christian , Croset Amelie , Fischer Stefanie , Eggenschwiler Aline , Grübler Yvonne , Marpakwar Rajlakshmi , Looser Thamar , Spitzli Patricia , Herzog Christel , Villemagne Denis , Schiegg Dieter , Abduli Liridon , Iss Chloé , Neculcea Alexandra , Franchini Marco , Lekishvili Tamara , Ragusa Simone , Zitt Christof , Kaufmann Yvonne , Auge Alienor , Hänggi Martin , Ali Waleed , Frasconi Teresa M. , Wullschleger Stephan , Schlegel Iris , Matzner Mirela , Lüthi Ursina , Schlereth Bernd , Dawson Keith M. , Kirkin Vladimir , Ochsenbein Adrian F. , Grimm Sebastian , Reschke Nina , Riether Carsten , Steiner Daniel , Leupin Nicolas , Goubier Anne
Published: July 2024

Supplementary Fig. S3. TAA quantification on healthy blood cells.
Supplementary Table 1 from Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers
Authors: Praharaj Monali , Shen Fan , Lee Alex J. , Zhao Liang , Nirschl Thomas R. , Theodros Debebe , Singh Alok K. , Wang Xiaoxu , Adusei Kenneth M. , Lombardo Kara A. , Williams Raekwon A. , Sena Laura A. , Thompson Elizabeth A. , Tam Ada , Yegnasubramanian Srinivasan , Pearce Edward J. , Leone Robert D. , Alt Jesse , Rais Rana , Slusher Barbara S. , Pardoll Drew M. , Powell Jonathan D. , Zarif Jelani C.
Published: July 2024

Supplementary Table 1
Supplementary Figure 15 from SIRT3 Negatively Regulates TFH-Cell Differentiation in Cancer
Authors: Hou Yueru , Cao Yejin , He Ying , Dong Lin , Zhao Longhao , Dong Yingjie , Niu Ruiying , Bi Yujing , Liu Guangwei
Published: July 2024

Fig. S15. SIRT3 deficiency upregulates the expression of Glut1 and p-S6 in TFH cells in tumor.
Supplementary Figure 2 from Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers
Authors: Praharaj Monali , Shen Fan , Lee Alex J. , Zhao Liang , Nirschl Thomas R. , Theodros Debebe , Singh Alok K. , Wang Xiaoxu , Adusei Kenneth M. , Lombardo Kara A. , Williams Raekwon A. , Sena Laura A. , Thompson Elizabeth A. , Tam Ada , Yegnasubramanian Srinivasan , Pearce Edward J. , Leone Robert D. , Alt Jesse , Rais Rana , Slusher Barbara S. , Pardoll Drew M. , Powell Jonathan D. , Zarif Jelani C.
Published: July 2024

Supplementary Figure 2
Supplementary Figure 1 from SIRT3 Negatively Regulates TFH-Cell Differentiation in Cancer
Authors: Hou Yueru , Cao Yejin , He Ying , Dong Lin , Zhao Longhao , Dong Yingjie , Niu Ruiying , Bi Yujing , Liu Guangwei
Published: July 2024

Fig. S1. SIRT3 expression is related to the TFH differentiation in viral infection and cancer.
Figure S8 from IL3-Driven T Cell–Basophil Crosstalk Enhances Antitumor Immunity
Authors: Wei Jian , Mayberry Colleen L. , Lv Xiaoting , Hu Fangyan , Khan Taushif , Logan Natalie A. , Wilson John J. , Sears John D. , Chaussabel Damien , Chang Chih-Hao
Published: July 2024

Enhanced T cell-basophil cross-talk by IL3 supplementation improves antitumor immunity
Figure S6 from IL3-Driven T Cell–Basophil Crosstalk Enhances Antitumor Immunity
Authors: Wei Jian , Mayberry Colleen L. , Lv Xiaoting , Hu Fangyan , Khan Taushif , Logan Natalie A. , Wilson John J. , Sears John D. , Chaussabel Damien , Chang Chih-Hao
Published: July 2024

The effect of IL4 on gene expression and activity of CD8+ T cells
Supplementary Figure 5 from PVRIG is Expressed on Stem-Like T Cells in Dendritic Cell–Rich Niches in Tumors and Its Blockade May Induce Immune Infiltration in Non-Inflamed Tumors
Authors: Alteber Zoya , Cojocaru Gady , Granit Roy Z. , Barbiro Inbal , Wool Assaf , Frenkel Masha , Novik Amit , Shuchami Adi , Liang Yu , Carmi Vered D. , Sabath Niv , Foreman Rob , Petrenko Natalia , He Jiang , Kliger Yossef , Levy-Barda Adva , Eitan Ram , Raban Oded , Sadot Eran , Sulimani Omri , Nathan Abraham Avi , Adewoye Henry , Ferre Pierre , Levine Zurit , Ophir Eran
Published: July 2024

Supplementary Figure 5
Supplementary Figure 2 from PVRIG is Expressed on Stem-Like T Cells in Dendritic Cell–Rich Niches in Tumors and Its Blockade May Induce Immune Infiltration in Non-Inflamed Tumors
Authors: Alteber Zoya , Cojocaru Gady , Granit Roy Z. , Barbiro Inbal , Wool Assaf , Frenkel Masha , Novik Amit , Shuchami Adi , Liang Yu , Carmi Vered D. , Sabath Niv , Foreman Rob , Petrenko Natalia , He Jiang , Kliger Yossef , Levy-Barda Adva , Eitan Ram , Raban Oded , Sadot Eran , Sulimani Omri , Nathan Abraham Avi , Adewoye Henry , Ferre Pierre , Levine Zurit , Ophir Eran
Published: July 2024

Supplementary Figure 2
Supplementary Figure 1 from PVRIG is Expressed on Stem-Like T Cells in Dendritic Cell–Rich Niches in Tumors and Its Blockade May Induce Immune Infiltration in Non-Inflamed Tumors
Authors: Alteber Zoya , Cojocaru Gady , Granit Roy Z. , Barbiro Inbal , Wool Assaf , Frenkel Masha , Novik Amit , Shuchami Adi , Liang Yu , Carmi Vered D. , Sabath Niv , Foreman Rob , Petrenko Natalia , He Jiang , Kliger Yossef , Levy-Barda Adva , Eitan Ram , Raban Oded , Sadot Eran , Sulimani Omri , Nathan Abraham Avi , Adewoye Henry , Ferre Pierre , Levine Zurit , Ophir Eran
Published: July 2024

Supplementary Figure 1
Supplementary Fig. S4 from Orchestrated Codelivery of Peptide Antigen and Adjuvant to Antigen-Presenting Cells by Using an Engineered Chimeric Peptide Enhances Antitumor T-Cell Immunity
Authors: Pan Haifeng , Yu Siyuan , Zhuang Haoyun , Yang Han , Jiang Jinlu , Yang Haihui , Ren Shuling , Luo Guoxing , Yu Xuan , Chen Shuping , Lin Yanhua , Sheng Roufang , Zhang Shiyin , Yuan Quan , Huang Chenghao , Zhang Tianying , Li Tingdong , Ge Shengxiang , Zhang Jun , Xia Ningshao
Published: July 2024

Supplementary Fig. S4. Flow cytometry gating strategy for the analysis of Ag+ DCs or Ag+ macrophages after subcutaneous injection at tail base in C57BL/6 mice.
Supplementary Fig. S14 from Orchestrated Codelivery of Peptide Antigen and Adjuvant to Antigen-Presenting Cells by Using an Engineered Chimeric Peptide Enhances Antitumor T-Cell Immunity
Authors: Pan Haifeng , Yu Siyuan , Zhuang Haoyun , Yang Han , Jiang Jinlu , Yang Haihui , Ren Shuling , Luo Guoxing , Yu Xuan , Chen Shuping , Lin Yanhua , Sheng Roufang , Zhang Shiyin , Yuan Quan , Huang Chenghao , Zhang Tianying , Li Tingdong , Ge Shengxiang , Zhang Jun , Xia Ningshao
Published: July 2024

Supplementary Fig. S14. Detection of liver and kidney damage biomarkers and H&E staining of major organs.
Data from Melanoma Clonal Heterogeneity Leads to Secondary Resistance after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes
Authors: König David , Sandholzer Michael T. , Uzun Sarp , Zingg Andreas , Ritschard Reto , Thut Helen , Glatz Katharina , Kappos Elisabeth A. , Schaefer Dirk J. , Kettelhack Christoph , Passweg Jakob R. , Holbro Andreas , Baur Katharina , Medinger Michael , Buser Andreas , Lardinois Didier , Jeker Lukas T. , Khanna Nina , Stenner Frank , Kasenda Benjamin , Homicsko Krisztian , Matter Matthias , Rodrigues Mantuano Natalia , Zippelius Alfred , Läubli Heinz
Published: July 2024

Abstract
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in patients with melanoma, although long-term responses seem restricted in patients who have complete remissions. Many patients develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. In this study, we describe a case of secondary resistance to TIL-ACT possibly due to intratumoral heterogeneity and selection of a resistant tumor cell clone by the transferred T cells. To the best our knowledge, this is the first case of clonal selection of a pre-existing nondominant tumor cell clone; this report demonstrates the mechanism involved in secondary resistance to TIL-ACT that can potentially change current clinical practice because it advocates for T-cell collection from multiple tumor sites and analysis of tumor heterogeneity before treatment with TIL-ACT.
Data from IL3-Driven T Cell–Basophil Crosstalk Enhances Antitumor Immunity
Authors: Wei Jian , Mayberry Colleen L. , Lv Xiaoting , Hu Fangyan , Khan Taushif , Logan Natalie A. , Wilson John J. , Sears John D. , Chaussabel Damien , Chang Chih-Hao
Published: July 2024

Abstract
Cytotoxic T lymphocytes (CTL) are pivotal in combating cancer, yet their efficacy is often hindered by the immunosuppressive tumor microenvironment, resulting in CTL exhaustion. This study investigates the role of interleukin-3 (IL3) in orchestrating antitumor immunity through CTL modulation. We found that intratumoral CTLs exhibited a progressive decline in IL3 production, which was correlated with impaired cytotoxic function. Augmenting IL3 supplementation, through intraperitoneal administration of recombinant IL3, IL3-expressing tumor cells, or IL3-engineered CD8+ T cells, conferred protection against tumor progression, concomitant with increased CTL activity. CTLs were critical for this therapeutic efficacy as IL3 demonstrated no impact on tumor growth in Rag1 knockout mice or following CD8+ T-cell depletion. Rather than acting directly, CTL-derived IL3 exerted its influence on basophils, concomitantly amplifying antitumor immunity within CTLs. Introducing IL3-activated basophils retarded tumor progression, whereas basophil depletion diminished the effectiveness of IL3 supplementation. Furthermore, IL3 prompted basophils to produce IL4, which subsequently elevated CTL IFNγ production and viability. Further, the importance of basophil-derived IL4 was evident from the absence of benefits of IL3 supplementation in IL4 knockout tumor-bearing mice. Overall, this research has unveiled a role for IL3-mediated CTL–basophil cross-talk in regulating antitumor immunity and suggests harnessing IL3 sustenance as a promising approach for optimizing and enhancing cancer immunotherapy.

See related Spotlight, p. 798
E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network
Authors: Poliaková Turan Michaela , Riedo Rahel , Medo Matúš , Pozzato Chiara , Friese-Hamim Manja , Koch Jonas P. , Coggins Si’Ana A. , Li Qun , Kim Baek , Albers Joachim , Aebersold Daniel M. , Zamboni Nicola , Zimmer Yitzhak , Medová Michaela
Published: July 2024

Various lines of investigation support a signaling interphase shared by receptor tyrosine kinases and the DNA damage response. However, the underlying network nodes and their contribution to the maintenance of DNA integrity remain unknown. We explored MET-related metabolic pathways in which interruption compromises proper resolution of DNA damage. Discovery metabolomics combined with transcriptomics identified changes in pathways relevant to DNA repair following MET inhibition (METi). METi by tepotinib was associated with the formation of γH2AX foci and with significant alterations in major metabolic circuits such as glycolysis, gluconeogenesis, and purine, pyrimidine, amino acid, and lipid metabolism. 5′-Phosphoribosyl-N-formylglycinamide, a de novo purine synthesis pathway metabolite, was consistently decreased in in vitro and in vivo MET-dependent models, and METi-related depletion of dNTPs was observed. METi instigated the downregulation of critical purine synthesis enzymes including phosphoribosylglycinamide formyltransferase, which catalyzes 5′-phosphoribosyl-N-formylglycinamide synthesis. Genes encoding these enzymes are regulated through E2F1, whose levels decrease upon METi in MET-driven cells and xenografts. Transient E2F1 overexpression prevented dNTP depletion and the concomitant METi-associated DNA damage in MET-driven cells. We conclude that DNA damage following METi results from dNTP reduction via downregulation of E2F1 and a consequent decline of de novo purine synthesis.

Significance:

Maintenance of genome stability prevents disease and affiliates with growth factor receptor tyrosine kinases. We identified de novo purine synthesis as a pathway in which key enzymatic players are regulated through MET receptor and whose depletion via MET targeting explains MET inhibition-associated formation of DNA double-strand breaks. The mechanistic importance of MET inhibition-dependent E2F1 downregulation for interference with DNA integrity has translational implications for MET-targeting-based treatment of malignancies.
High‐Density Lipoprotein Particle Concentration and Size Predict Incident Coronary Artery Disease Events in a Cohort With Type 1 Diabetes
Authors: Costacou Tina , Vaisar Tomas , Miller Rachel G. , Davidson W. Sean , Heinecke Jay W. , Orchard Trevor J. , Bornfeldt Karin E.
Published: July 2024

Background

The cholesterol efflux capacity of high density lipoprotein (HDL) is negatively associated with cardiovascular risk. Small HDL particles account almost quantitatively for cholesterol efflux capacity, perhaps mediated through efflux of cholesterol and outer leaflet plasma membrane phospholipids by ABCA1 (ATP binding cassette subfamily A member 1). People with type 1 diabetes are at increased coronary artery disease (CAD) risk despite normal HDL‐cholesterol concentrations. We therefore tested the hypothesis that small HDL particles (HDL‐P)—rather than HDL‐cholesterol—predict incident CAD in type 1 diabetes.

Methods and Results

Incident CAD (CAD death, myocardial infarction, or coronary revascularization) was determined in 550 individuals with childhood‐onset type 1 diabetes. HDL‐P was quantified by calibrated ion mobility analysis and cholesterol efflux capacity was quantified with validated assays. During a median follow‐up of 26 years, 36.5% of the participants developed incident CAD, for an incidence density of 181.3 per 10 000 person‐years. In multivariable Cox models, neither HDL‐cholesterol nor apolipoprotein A1 concentration was significantly associated with CAD risk. In contrast, higher extra‐small HDL‐P concentrations were significantly associated with decreased CAD risk (hazard ratio [HR], 0.26 [95% CI, 0.14–0.50]). Weaker associations were observed for total HDL‐P (HR, 0.88 [95% CI, 0.83–0.93]), small HDL (HR, 0.83 [95% CI, 0.68–1.02]), medium HDL (HR, 0.79 [95% CI, 0.71–0.89]), and large HDL (HR, 0.72 [95% CI, 0.59–0.89]). Although cholesterol efflux capacity was negatively associated with incident CAD, this association was no longer significant after adjustment for total HDL‐P.

Conclusions

Lower concentrations of total HDL‐P and HDL subpopulations were positively associated with incident CAD independently of HDL‐cholesterol, apolipoprotein A1, and other common CVD risk factors. Extra‐small HDL was a much stronger predictor of risk than the other HDLs. Our data are consistent with the proposal that extra‐small HDL plays a critical role in cardioprotection in type 1 diabetes, mediated by macrophage cholesterol efflux by the ABCA1 pathway.
Moral Engagement in Design: Five Considerations for Unpacking the Ethical Dimensions of Design Methods
Authors: Ozkaramanli Deger , Nagenborg Michael
Published: July 2024

What society experiences today as morally questionable design—from gendered toys for children to public benches that prevent sleeping—can be considered the aftermath of an underdeveloped foundation for systematic ethical reflection in design methodologies. Although designing is an inherently moral activity, research on how to recognize and handle ethical questions and moral dilemmas in early (conceptual) design activities is scarce. In this article, we use an interdisciplinary lens to analyze and respond to the challenges of bridging moral psychology, ethics of technology, and design methodologies. For this, we introduce the concept of moral engagement in design, which is inspired by Moral Disengagement Theory. Finally, we propose five preliminary considerations for enacting moral engagement in design practices. These considerations form an interdisciplinary bridge to help us reflect on the moral dimensions of methodological choices in conceptual design practices.
Ngan mayla gen. et sp. nov, a new blind potamid cave crab from Borneo, Kalimantan (Crustacea: Decapoda: Brachyura: Potamoidea, Potamidae), and three other unidentified cave crabs from the same region
Authors: GUINOT DANIÈLE , MORENO PAULA A. RODRÍGUEZ
Published: July 2024

We here report on freshwater cave crabs of the families Potamidae and Gecarcinucidae in East Kalimantan, Sarawak, Indonesia in Borneo. A new genus and species of potamid crab, Ngan mayla, is described from Lubang Gedung Cave in the Merabu Karst. With its bullet-shaped eyes, Ngan mayla gen. et sp. nov. is totally blind and also displays the characters associated with an obligate cave-dwelling life, namely that it is dolichopod and fully depigmented. The closest genus and species is Cerberusa caeca Holthuis, 1979, from northern Sarawak. Highly modified, Ngan mayla gen. et sp. nov. proves to be among the most troglobitic of the known subterranean potamids, of which there were currently only seven in the Old World, with only four simultaneously being completely blind, entirely depigmented and dolichopod (Cerberusa caeca Holthuis, 1979, Diyutamon cereum Huang, Shih & Ng, 2017 and Phasmon typhlops Huang, Ahyong & Shih, 2020, to which must be added today Ngan mayla gen. et sp. nov.). Ngan mayla gen. et sp. nov. is easily distinguished from other potamid genera by its chelipeds bearing numerous acute teeth, spines (some horn-tipped) and short simple setae or spine-like setae on all articles. Two young female crabs collected in 2010 at the same area (Merabu Karst) but from a different cave, the Lubang Tebot Cave, could not be identified to specific level: an Isolapotamon sp., and a gecarcinucid with very long legs, pale colouration and slightly modified but black-pigmented eyes, close to Balssiathelphusa Bott, 1969, could possibly belong to a new genus. Some information on New World troglobitic crabs is provided.
Confirming the occurrence of two fiddler crabs, Tubuca dussumieri (H. Milne Edwards, 1852) and T. coarctata (H. Milne Edwards, 1852) (Crustacea: Decapoda: Ocypodidae), in Hong Kong by DNA barcoding and morphology
Authors: JIMENEZ PEDRO JULIÃO , CHANG KAI , SHIH HSI-TE , YASUHARA MORIAKI
Published: July 2024

The Indo-West Pacific region has a rich fiddler crab fauna. In East Asia, some species of fiddler crabs, such as Tubuca coarctata (H. Milne Edwards, 1852) and T. dussumieri (H. Milne Edwards, 1852), are considered insular, being present in the Philippines, Taiwan, and Ryukyus, but with no consistent record on continental China. Although T. dussumieri has been previously recorded in continental China, these records were considered dubious or misidentified. The nature of the Kuroshio Current and the colder waters of the China Coastal Current, compared to the currents along the eastern coasts of the Philippines and Taiwan, are considered barriers to the entrance of larvae of these species into the region. Nonetheless, using the cytochrome oxidase subunit I (COI) gene and morphological evidence, we present the first record of T. coarctata and show the presence of a T. dussumieri population in Hong Kong SAR, China. We hypothesize that the newly found T. coarctata in Hong Kong may be related to water temperature increases due to anthropogenic climate change, which allows its larvae to survive in this region and develop into adult crabs. Furthermore, our findings corroborate previous records of T. dussumieri in continental China. The restricted distribution of T. dussumieri in China and the smaller size of individuals, however, may indicate suboptimal habitats for arriving larvae. The limited presence of the two crabs on Chinese shores indicates that the intense coastal development in the country, such as in Hong Kong, may destroy suitable habitats and render these species susceptible to local extinction.
On the genus Flabellamon Ng, 1996, with descriptions of two new species (Crustacea: Brachyura: Potamidae)
Authors: TAN ZHI WAN , YEO DARREN C. J.
Published: July 2024

The history, taxonomy and nomenclatural issues revolving around the genus Flabellamon Ng, 1996, are reviewed. The genus of late contained two species, F. kuehnelti (Pretzmann, 1963) and F. wanchaii Takeda, Sanpool & Intapan, 2019. In the process of this review, two new species of this genus were uncovered from historical materials that were previously misidentified, and described herein as, F. ngankee sp. nov. (from northwestern Thailand) and F. mulayit sp. nov. (from southeastern Myanmar). Flabellamon ngankee sp. nov. is most similar superficially to F. wanchaii but can be distinguished easily by morphological differences in carapace armature, external orbital tooth, male pleonal margins and male gonopod. Flabellamon mulayit sp. nov. on the other hand, is more similar morphologically to F. kuehnelti, but can also be distinguished easily by epibranchial tooth and male gonopod characters. An identification key to the species of Flabellamon is provided.
Interannual Variation of Summer Compound Hot and Drought Events in Xinjiang and Its Relationship with the North Atlantic Sea Surface Temperature
Authors: Zhang Xiaolu , Miao Jiapeng , Wang Xiaoxin , Zhou Botao
Published: July 2024

Xinjiang suffers compound hot and drought events under global warming. However, less attention has been paid to physical mechanisms of the variability of compound hot and drought events in this region. This article investigates the interannual variation of summer (June–August) compound hot and drought events in Xinjiang and its relationship with the sea surface temperature (SST) over the North Atlantic. The results show that its first empirical orthogonal function (EOF) mode features a spatially homogenous pattern. This mode is closely connected with the simultaneous meridional negative–positive–negative SST anomalies over the North Atlantic. The summer North Atlantic tripole SST anomalies can trigger a remarkable wave train extending from the North Atlantic to Eurasia, consequently inducing an anomalous high pressure system over the Iran–Pamir Plateau, which is conducive to the increase in air temperature from the surface to the upper troposphere over Xinjiang. The warmer troposphere further strengthens the western Asian subtropical meridional temperature gradient and thereby enhances the westerly wind to the north flank of the West Asian subtropical westerly jet (WASWJ). As a result, the WASWJ is displaced northward, which intensifies the sinking motion and prevents the water vapor transport to Xinjiang, leading to a decrease in precipitation in the target region. The higher temperature and less precipitation contribute to the occurrence of compound hot and drought events over Xinjiang. Numerical simulations based on the Community Atmosphere Model, version 4 (CAM4), further confirm the relationship between the North Atlantic tripole SST anomalies and compound hot and drought events in Xinjiang during summer on the interannual time scale.

Significance Statement

Xinjiang, located in northwest China, suffers from frequent and intense compound hot and drought events in recent decades. It is thus urgent to understand the physical mechanisms associated with its occurrence in order for disaster prevention and mitigation. In this study, we reveal that the leading mode of summer compound hot and drought events over Xinjiang, featuring a spatially homogenous pattern, is closely correlated with the simultaneous meridional negative–positive–negative SST anomalies over the North Atlantic. The North Atlantic tripole SST anomalies can lead to an anomalous high pressure system over the Iran–Pamir Plateau and a northward shift of the West Asian subtropical westerly jet through exciting a wave train propagating from the North Atlantic to Eurasia, which consequently contributes to the occurrence of compound hot and drought events over Xinjiang.
Infection and the microbiome in bronchiectasis
Authors: Mac Aogáin Micheál , Dicker Alison J. , Mertsch Pontus , Chotirmall Sanjay H.
Published: July 2024

Bronchiectasis is marked by bronchial dilatation, recurrent infections and significant morbidity, underpinned by a complex interplay between microbial dysbiosis and immune dysregulation. The identification of distinct endophenotypes have refined our understanding of its pathogenesis, including its heterogeneous disease mechanisms that influence treatment and prognosis responses. Next-generation sequencing (NGS) has revolutionised the way we view airway microbiology, allowing insights into the “unculturable”. Understanding the bronchiectasis microbiome through targeted amplicon sequencing and/or shotgun metagenomics has provided key information on the interplay of the microbiome and host immunity, a central feature of disease progression. The rapid increase in translational and clinical studies in bronchiectasis now provides scope for the application of precision medicine and a better understanding of the efficacy of interventions aimed at restoring microbial balance and/or modulating immune responses. Holistic integration of these insights is driving an evolving paradigm shift in our understanding of bronchiectasis, which includes the critical role of the microbiome and its unique interplay with clinical, inflammatory, immunological and metabolic factors. Here, we review the current state of infection and the microbiome in bronchiectasis and provide views on the future directions in this field.
Genetic diversity and population structure of wheat landraces in Southern Winter Wheat Region of China
Authors: Liu Ying , Fu Bisheng , Zhang Qiaofeng , Cai Jin , Guo Wei , Zhai Wenling , Wu Jizhong
Published: July 2024

Background

Wheat landraces are considered a valuable source of genetic diversity for breeding programs. It is useful to evaluate the genetic diversity in breeding studies such as marker-assisted selection (MAS), genome-wide association studies (GWAS), and genomic selection. In addition, constructing a core germplasm set that represents the genetic diversity of the entire variety set is of great significance for the efficient conservation and utilization of wheat landrace germplasms.

Results

To understand the genetic diversity in wheat landrace, 2,023 accessions in the Jiangsu Provincial Crop Germplasm Resource Bank were used to explore the molecular diversity and population structure using the Illumina 15 K single nucleotide polymorphism (SNP) chip. These accessions were divided into five subpopulations based on population structure, principal coordinate and kinship analysis. A significant variation was found within and among the subpopulations based on the molecular variance analysis (AMOVA). Subpopulation 3 showed more genetic variability based on the different allelic patterns (Na, Ne and I). The M strategy as implemented in MStratv 4.1 software was used to construct the representative core collection. A core collection with a total of 311 accessions (15.37%) was selected from the entire landrace germplasm based on genotype and 12 different phenotypic traits. Compared to the initial landrace collections, the core collection displayed higher gene diversity (0.31) and polymorphism information content (PIC) (0.25), and represented almost all phenotypic variation.

Conclusions

A core collection comprising 311 accessions containing 100% of the genetic variation in the initial population was developed. This collection provides a germplasm base for effective management, conservation, and utilization of the variation in the original set.
Integrated transcriptome and microRNA analysis reveals molecular responses to high-temperature stress in the liver of American shad (Alosa sapidissima)
Authors: Liu Ying , Liang Zhengyuan , Li Yulin , Zhu Wenbin , Feng Bingbing , Xu Wei , Fu Jianjun , Wei Panpan , Luo Mingkun , Dong Zaijie
Published: July 2024

Background

Fish reproduction, development and growth are directly affected by temperature, investigating the regulatory mechanisms behind high temperature stress is helpful to construct a finer molecular network. In this study, we systematically analyzed the transcriptome and miRNA information of American shad (Alosa sapidissima) liver tissues at different cultivation temperatures of 24 ℃ (Low), 27 ℃ (Mid) and 30 ℃ (High) based on a high-throughput sequencing platform.

Results

The results showed that there were 1594 differentially expressed genes (DEGs) and 660 differentially expressed miRNAs (DEMs) in the LowLi vs. MidLi comparison group, 473 DEGs and 84 DEMs in the MidLi vs. HighLi group, 914 DEGs and 442 DEMs in the LowLi vs. HighLi group. These included some important genes and miRNAs such as calr, hsp90b1, hsp70, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p. The DEGs were mainly enriched in the protein folding, processing and export pathways of the endoplasmic reticulum; the target genes of the DEMs were mainly enriched in the focal adhesion pathway. Furthermore, the association analysis revealed that the key genes were mainly enriched in the metabolic pathway. Interestingly, we found a significant increase in the number of genes and miRNAs involved in the regulation of heat stress during the temperature change from 24 °C to 27 °C. In addition, we examined the tissue expression characteristics of some key genes and miRNAs by qPCR, and found that calr, hsp90b1 and dre-miR-125b-2-3p were significantly highly expressed in the liver at 27 ℃, while novel-m0481-5p, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p had the highest expression in the heart at 30℃. Finally, the quantitative expression trends of 10 randomly selected DEGs and 10 DEMs were consistent with the sequencing data, indicating the reliability of the results.

Conclusions

In summary, this study provides some fundamental data for subsequent in-depth research into the molecular regulatory mechanisms of A. sapidissima response to heat stress, and for the selective breeding of high temperature tolerant varieties.