bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S1 from A Cohort Study of CNS Tumors in Multiple Endocrine Neoplasia Type 1
Authors: Graillon Thomas , Romanet Pauline , Camilla Clara , Gélin Camille , Appay Romain , Roche Catherine , Lagarde Arnaud , Mougel Grégory , Farah Kaissar , Le Bras Maëlle , Engelhardt Julien , Kalamarides Michel , Peyre Matthieu , Amelot Aymeric , Emery Evelyne , Magro Elsa , Cebula Hélène , Aboukais Rabih , Bauters Catherine , Jouanneau Emmanuel , Berhouma Moncef , Cuny Thomas , Dufour Henry , Loiseau Hugues , Figarella-Branger Dominique , Bauchet Luc , Binquet Christine , Barlier Anne , Goudet Pierre
Published: July 2024

MEN1 loss of heterozygosity in meningiomas of patients #8, #15 and #16. Electropherogram of Sanger sequencing on tumor DNA showing falsely homozygous MEN1 pathogenic variants due to loss of heterozygosity at a somatic level. Patient #8: c.1037_1038delCT, p.(Thr346SerfsTer20), patient #15: c.249_252delGTCT, p.(Ile85SerfsTer33), patient #16: c.515A>T, p.(Asp172Val)
Supplementary Table S2 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: July 2024

Mutect2 called and validated variants for each subject and each tumor region from whole exome sequencing data
Supplementary Figure S6 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: July 2024

Immunohistologic images
Supplementary Table S8 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: July 2024

CIBERSORTx relative percents of deconvoluted immunocytes
Supplementary Table S7 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: July 2024

RNA-sequencing pseudo counts generated via Salmon algorithm
Supplementary Figure S9 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: July 2024

Bar graph displaying number of validated variants for each subject
Supplementary Table S4 from Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: July 2024

Peptide sequences included in each subject's personalized NeoVax peptide vaccine
Data from Safety and Efficacy of the Combination Lurbinectedin plus Doxorubicin from a Phase 1b Trial in Patients with Advanced/Metastatic Soft-Tissue Sarcoma
Authors: Cote Gregory M. , Haddox Candace L. , Choy Edwin , Merriam Priscilla A. , Mazzola Emanuele , Venkataraman Vinayak , Alcindor Thierry , Wagner Andrew J. , Demetri George D. , George Suzanne
Published: July 2024

Purpose:
While cytotoxic chemotherapy is the standard first-line treatment for patients with metastatic soft-tissue sarcoma (STS), clinical outcomes remain suboptimal. Our prior study showed lurbinectedin plus doxorubicin is well tolerated with promising clinical activity in STS. We designed this phase 1b trial to optimize dosing as the basis for a randomized trial in leiomyosarcoma and to further explore the safety profile and efficacy signal.
Patients and Methods:
Patients had advanced/metastatic STS and no prior anthracycline/lurbinectedin/trabectedin. Escalation followed a 3 + 3 design with 3-week cycles: lurbinectedin (3.2 mg/m2 day 1) and two doxorubicin levels (DL1, 25 mg/m2 day 1; DL2, 25 mg/m2 days 1 and 8). The primary objectives were to identify the maximum tolerated dose and recommended dose for subsequent randomized trials.
Results:
Ten patients were enrolled in a 6-month period. The most common treatment-emergent adverse events were grade (G) 2 fatigue and nausea, and G2 cytopenias with no febrile neutropenia events. There were two dose-limiting toxicities (DLTs) at DL2 [day 8 (G2 alanine aminotransferase [ALT]/aspartate aminotransferase increase, G3 neutropenia)], and one DLT in DL1 (G3 ALT increase). These were reversible and all patients continued the study. DL1 was chosen for further study. At the time of data cutoff, the estimated median progression-free survival is 16.5 months [95% confidence interval (CI), 6.0–ND]. The objective response rate was 60% (6/10 confirmed partial responses).
Conclusions:
In this phase 1b study, the recommended dose is lurbinectedin 3.2 mg/m2 in combination with doxorubicin 25 mg/m2 every 3 weeks. The study combination was well tolerated and demonstrated intriguing clinical activity.
Data from Cell-Free Human Papillomavirus DNA Is a Sensitive Biomarker for Prognosis and for Early Detection of Relapse in Locally Advanced Cervical Cancer
Authors: Sivars Lars , Jylhä Cecilia , Crona Guterstam Ylva , Zupancic Mark , Lindqvist Britta , Nordenskjöld Magnus , Tham Emma , Hellman Kristina
Published: July 2024

Abstract
Purpose: Human papillomavirus (HPV) is the cause of the majority of cervical cancer cases and has been showed to be released as cell-free tumor DNA (ctHPV DNA) into the circulation. Here, we analyze if ctHPV DNA could be used as a prognostic biomarker and/or to detect relapse earlier than traditional methods in locally advanced cervical cancer (LACC).

Experimental Design: A total of 74 patients with LACC were included; 66of 74 were positive for 13 high-risk HPV types on a bead-based assay of tumor biopsy samples. HPV-type–specific droplet digital PCR assays were developed. Longitudinal plasma samples were then analyzed for the biopsy-verified HPV type for each patient. In total, 418 plasma samples were analyzed. Patients were followed for a median of 37 months. Results were correlated to tumor and clinical characteristics.

Results: Of the pretreatment plasma samples, 92.4% were positive for ctHPV DNA. Persistent ctHPV DNA in end-of-treatment, early follow-up (1–2 months after end-of-treatment), or tumor evaluation (3–4 months after end-of-treatment) plasma was correlated with worse progression-free survival (P < 0.001) compared with if ctHPV DNA was not found. The positive predictive value of ctHPV status at early follow-up for predicting disease progression was 87.5%, and the negative predictive value was 89.3%. ctHPV DNA was found in plasma before relapse was diagnosed using radiology in all patients (n = 10) who experienced relapse after complete clinical response to treatment with a median 315 days lead time.

Conclusions: ctHPV DNA in follow-up plasma is a promising prognostic biomarker in patients with LACC, useful for analysis of response to therapy and for early detection of relapse.
Data from A Cohort Study of CNS Tumors in Multiple Endocrine Neoplasia Type 1
Authors: Graillon Thomas , Romanet Pauline , Camilla Clara , Gélin Camille , Appay Romain , Roche Catherine , Lagarde Arnaud , Mougel Grégory , Farah Kaissar , Le Bras Maëlle , Engelhardt Julien , Kalamarides Michel , Peyre Matthieu , Amelot Aymeric , Emery Evelyne , Magro Elsa , Cebula Hélène , Aboukais Rabih , Bauters Catherine , Jouanneau Emmanuel , Berhouma Moncef , Cuny Thomas , Dufour Henry , Loiseau Hugues , Figarella-Branger Dominique , Bauchet Luc , Binquet Christine , Barlier Anne , Goudet Pierre
Published: July 2024

AbstractPurpose:
Multiple endocrine neoplasia type 1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Thus, we aimed to describe the frequency, incidence, and specific clinical and histological features of central nervous system (CNS) tumors in the MEN1 population (except pituitary tumors).
Experimental Design:
The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990 and followed up in the French MEN1 national cohort. The standardized incidence ratio (SIR) was calculated based on the French Gironde CNS Tumor Registry. Genomic analyses were performed on somatic DNA from seven CNS tumors, including meningiomas and ependymomas from patients with MEN1, and then on 50 sporadic meningiomas and ependymomas.
Results:
A total of 29 CNS tumors were found among the 1,498 symptomatic patients (2%; incidence = 47.4/100,000 person-years; SIR = 4.5), including 12 meningiomas (0.8%; incidence = 16.2/100,000; SIR = 2.5), 8 ependymomas (0.5%; incidence = 10.8/100,000; SIR = 17.6), 5 astrocytomas (0.3%; incidence = 6.7/100,000; SIR = 5.8), and 4 schwannomas (0.3%; incidence = 5.4/100,000; SIR = 12.7). Meningiomas in patients with MEN1 were benign, mostly meningothelial, with 11 years earlier onset compared with the sporadic population and an F/M ratio of 1/1. Spinal and cranial ependymomas were mostly classified as World Health Organization grade 2. A biallelic MEN1 inactivation was observed in 4/5 ependymomas and 1/2 meningiomas from patients with MEN1, whereas MEN1 deletion in one allele was present in 3/41 and 0/9 sporadic meningiomas and ependymomas, respectively.
Conclusions:
The incidence of each CNS tumor was higher in the MEN1 population than in the French general population. Meningiomas and ependymomas should be considered part of the MEN1 syndrome, but somatic molecular data are missing to conclude for astrocytomas and schwannomas.
Supplementary Figure 9 from CD8-Targeted IL2 Unleashes Tumor-Specific Immunity in Human Cancer Tissue by Reviving the Dysfunctional T-cell Pool
Authors: Kaptein Paulien , Slingerland Nadine , Metoikidou Christina , Prinz Felix , Brokamp Simone , Machuca-Ostos Mercedes , de Roo Guido , Schumacher Ton N.M. , Yeung Yik A. , Moynihan Kelly D. , Djuretic Ivana M. , Thommen Daniela S.
Published: July 2024

Development and expression of different gene programs capturing the CD8- IL2 induced effects.
Supplementary Figure 12 from CD8-Targeted IL2 Unleashes Tumor-Specific Immunity in Human Cancer Tissue by Reviving the Dysfunctional T-cell Pool
Authors: Kaptein Paulien , Slingerland Nadine , Metoikidou Christina , Prinz Felix , Brokamp Simone , Machuca-Ostos Mercedes , de Roo Guido , Schumacher Ton N.M. , Yeung Yik A. , Moynihan Kelly D. , Djuretic Ivana M. , Thommen Daniela S.
Published: July 2024

Characterization of LCKi-induced effects.
Supplementary Figure 1 from CD8-Targeted IL2 Unleashes Tumor-Specific Immunity in Human Cancer Tissue by Reviving the Dysfunctional T-cell Pool
Authors: Kaptein Paulien , Slingerland Nadine , Metoikidou Christina , Prinz Felix , Brokamp Simone , Machuca-Ostos Mercedes , de Roo Guido , Schumacher Ton N.M. , Yeung Yik A. , Moynihan Kelly D. , Djuretic Ivana M. , Thommen Daniela S.
Published: July 2024

CD8-IL2 activates CD8+ T cells in human tumor samples with high specificity.
Supplementary Data File 1 from CD8-Targeted IL2 Unleashes Tumor-Specific Immunity in Human Cancer Tissue by Reviving the Dysfunctional T-cell Pool
Authors: Kaptein Paulien , Slingerland Nadine , Metoikidou Christina , Prinz Felix , Brokamp Simone , Machuca-Ostos Mercedes , de Roo Guido , Schumacher Ton N.M. , Yeung Yik A. , Moynihan Kelly D. , Djuretic Ivana M. , Thommen Daniela S.
Published: July 2024

IL2 and TCR gene programs
Supplementary Table S2 from IL2 Targeted to CD8+ T Cells Promotes Robust Effector T-cell Responses and Potent Antitumor Immunity
Authors: Moynihan Kelly D. , Kumar Manu P. , Sultan Hussein , Pappas Danielle C. , Park Terrence , Chin S. Michael , Bessette Paul , Lan Ruth Y. , Nguyen Henry C. , Mathewson Nathan D. , Ni Irene , Chen Wei , Lee Yonghee , Liao-Chan Sindy , Chen Jessie , Schumacher Ton N.M. , Schreiber Robert D. , Yeung Yik A. , Djuretic Ivana M.
Published: July 2024

Supplementary Table S2, Antibodies used in this study
Supplementary Figure S7 from IL2 Targeted to CD8+ T Cells Promotes Robust Effector T-cell Responses and Potent Antitumor Immunity
Authors: Moynihan Kelly D. , Kumar Manu P. , Sultan Hussein , Pappas Danielle C. , Park Terrence , Chin S. Michael , Bessette Paul , Lan Ruth Y. , Nguyen Henry C. , Mathewson Nathan D. , Ni Irene , Chen Wei , Lee Yonghee , Liao-Chan Sindy , Chen Jessie , Schumacher Ton N.M. , Schreiber Robert D. , Yeung Yik A. , Djuretic Ivana M.
Published: July 2024

Supplementary Figure S7: Sub-clustering of naïve-like/recently activated cluster and characterization of clonal expansion and antigen.
Supplementary Figures and Tables from Combining TIGIT Blockade with MDSC Inhibition Hinders Breast Cancer Bone Metastasis by Activating Antitumor Immunity
Authors: Monteran Lea , Ershaid Nour , Scharff Ye’ela , Zoabi Yazeed , Sanalla Tamer , Ding Yunfeng , Pavlovsky Anna , Zait Yael , Langer Marva , Caller Tal , Eldar-Boock Anat , Avivi Camila , Sonnenblick Amir , Satchi-Fainaro Ronit , Barshack Iris , Shomron Noam , Zhang Xiang H.-F. , Erez Neta
Published: July 2024

Supplementary Figure 1: Bone metastasis immunosuppressive microenvironment. Supplementary Figure 2: Gating strategy for RNA sequencing. Supplementary Figure 3: Differentially expressed genes during breast cancer bone metastasis progression. Supplementary Figure 4: Metastasis-infiltrating T cells are profoundly altered by metastatic progression. Supplementary Figure 5: Immune Checkpoint Receptors (ICRs) are expressed by metastasis-infiltrating T cells. Supplementary Figure 6: Targeting TIGIT results in activation of T cell mediated anti-tumor immunity. Supplementary Figure 7: (a) Spinal Cord Compression occurrence in treated mice. P-values were calculated using two-sided Chi square test. Supplementary Figure 8: TIGIT is highly expressed in human bone metastasis. Supplementary Table 1: Patient cohort data. Supplementary Table 2: Primers sequences.
Table S5 from Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy
Authors: Dias Matheus Henrique , Friskes Anoek , Wang Siying , Fernandes Neto Joao M. , van Gemert Frank , Mourragui Soufiane , Papagianni Chrysa , Kuiken Hendrik J. , Mainardi Sara , Alvarez-Villanueva Daniel , Lieftink Cor , Morris Ben , Dekker Anna , van Dijk Emma , Wilms Lieke H.S. , da Silva Marcelo S. , Jansen Robin A. , Mulero-Sánchez Antonio , Malzer Elke , Vidal August , Santos Cristina , Salazar Ramón , Wailemann Rosangela A.M. , Torres Thompson E.P. , De Conti Giulia , Raaijmakers Jonne A. , Snaebjornsson Petur , Yuan Shengxian , Qin Wenxin , Kovach John S. , Armelin Hugo A. , te Riele Hein , van Oudenaarden Alexander , Jin Haojie , Beijersbergen Roderick L. , Villanueva Alberto , Medema Rene H. , Bernards Rene
Published: July 2024

Supplementary table 5: Stress-focused drug screens AUC differences in HT-29 cells Area Under the Curve (AUC) from each compound of the stress-focused drug screen in the presence or absence of LB-100. Compounds are ranked by the difference in the AUC between LB-100-treated and untreated samples.
Table S4 from Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy
Authors: Dias Matheus Henrique , Friskes Anoek , Wang Siying , Fernandes Neto Joao M. , van Gemert Frank , Mourragui Soufiane , Papagianni Chrysa , Kuiken Hendrik J. , Mainardi Sara , Alvarez-Villanueva Daniel , Lieftink Cor , Morris Ben , Dekker Anna , van Dijk Emma , Wilms Lieke H.S. , da Silva Marcelo S. , Jansen Robin A. , Mulero-Sánchez Antonio , Malzer Elke , Vidal August , Santos Cristina , Salazar Ramón , Wailemann Rosangela A.M. , Torres Thompson E.P. , De Conti Giulia , Raaijmakers Jonne A. , Snaebjornsson Petur , Yuan Shengxian , Qin Wenxin , Kovach John S. , Armelin Hugo A. , te Riele Hein , van Oudenaarden Alexander , Jin Haojie , Beijersbergen Roderick L. , Villanueva Alberto , Medema Rene H. , Bernards Rene
Published: July 2024

Supplementary table 4: The composition of the stress-focused drug library Compounds comprising the stress-focused drug library with their respective targets.
Figure S6 from Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy
Authors: Dias Matheus Henrique , Friskes Anoek , Wang Siying , Fernandes Neto Joao M. , van Gemert Frank , Mourragui Soufiane , Papagianni Chrysa , Kuiken Hendrik J. , Mainardi Sara , Alvarez-Villanueva Daniel , Lieftink Cor , Morris Ben , Dekker Anna , van Dijk Emma , Wilms Lieke H.S. , da Silva Marcelo S. , Jansen Robin A. , Mulero-Sánchez Antonio , Malzer Elke , Vidal August , Santos Cristina , Salazar Ramón , Wailemann Rosangela A.M. , Torres Thompson E.P. , De Conti Giulia , Raaijmakers Jonne A. , Snaebjornsson Petur , Yuan Shengxian , Qin Wenxin , Kovach John S. , Armelin Hugo A. , te Riele Hein , van Oudenaarden Alexander , Jin Haojie , Beijersbergen Roderick L. , Villanueva Alberto , Medema Rene H. , Bernards Rene
Published: July 2024

Figure S6: LB-100 and adavosertib induce histological response in orthotopic CRC PDXs (A) Representative Hematoxylin & Eosin (H&E) stainings at endpoint from PDOX2 and PDOX3 treated as indicated. Original magnification middle images: 15x, scale bar 1000 µm; right images: 200x. S indicates stroma, and the arrows point to the tumor-cell component. (B) Mice body weight variation of the 3 CRC PDXs across the experiments.
Figure S3 from Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy
Authors: Dias Matheus Henrique , Friskes Anoek , Wang Siying , Fernandes Neto Joao M. , van Gemert Frank , Mourragui Soufiane , Papagianni Chrysa , Kuiken Hendrik J. , Mainardi Sara , Alvarez-Villanueva Daniel , Lieftink Cor , Morris Ben , Dekker Anna , van Dijk Emma , Wilms Lieke H.S. , da Silva Marcelo S. , Jansen Robin A. , Mulero-Sánchez Antonio , Malzer Elke , Vidal August , Santos Cristina , Salazar Ramón , Wailemann Rosangela A.M. , Torres Thompson E.P. , De Conti Giulia , Raaijmakers Jonne A. , Snaebjornsson Petur , Yuan Shengxian , Qin Wenxin , Kovach John S. , Armelin Hugo A. , te Riele Hein , van Oudenaarden Alexander , Jin Haojie , Beijersbergen Roderick L. , Villanueva Alberto , Medema Rene H. , Bernards Rene
Published: July 2024

Figure S3: High N-Myc levels sensitize neuroblastoma cells to LB-100, and PP2A knockdown sensitizes CRC cells to WEE1 inhibition (A) Western blots comparing N-Myc levels in isogenic neuroblastoma models. GAPDH was used as a loading control. (B) long-term viability assays compares the toxicity of LB-100 across these neuroblastoma models. LB-100 was refreshed every 2-3 days, and the cells were grown for 10 days before fixing, staining, and imaging. (C) Western blots show the knockdown of PPP2R1A in HT-29 and SW-480 cells. GAPDH was used as a loading control. (D) Dose-response assays show the effect of Adavosertib after PPP2R1A knockdown compared to a control shRNA in HT-29 and SW-480 cells. Cell viability was estimated by resazurin fluorescence after 5 days in the presence of the drug or DMSO control. The normalized values are plotted. (E) The heat map shows all “Hallmarks” and “KEGG” molecular signatures significantly enriched by LB-100 (4 µM), calyculin A (5 nM), or okadaic acid (10 nM) in HT-29 and SW-480 cells after 8 hours. Asterisks indicate significance level (* p-value <0.05, ** p-value <0.01, *** p-value <0.001).
Figure S2 from Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy
Authors: Dias Matheus Henrique , Friskes Anoek , Wang Siying , Fernandes Neto Joao M. , van Gemert Frank , Mourragui Soufiane , Papagianni Chrysa , Kuiken Hendrik J. , Mainardi Sara , Alvarez-Villanueva Daniel , Lieftink Cor , Morris Ben , Dekker Anna , van Dijk Emma , Wilms Lieke H.S. , da Silva Marcelo S. , Jansen Robin A. , Mulero-Sánchez Antonio , Malzer Elke , Vidal August , Santos Cristina , Salazar Ramón , Wailemann Rosangela A.M. , Torres Thompson E.P. , De Conti Giulia , Raaijmakers Jonne A. , Snaebjornsson Petur , Yuan Shengxian , Qin Wenxin , Kovach John S. , Armelin Hugo A. , te Riele Hein , van Oudenaarden Alexander , Jin Haojie , Beijersbergen Roderick L. , Villanueva Alberto , Medema Rene H. , Bernards Rene
Published: July 2024

Figure S1: LB-100 engages stress-related, inflammatory response, and mitogenic signaling transcriptional programs in CRC cells (A) Dose-response assays show the effect of LB-100 in 7 CRC models. Cell viability was estimated by resazurin fluorescence after 5 days in the presence of the drug or DMSO control. The normalized values are plotted. (B) The heat map shows all “Hallmarks” and “KEGG” molecular signatures significantly enriched by LB-100 (4 µM) in both HT-29 and SW-480 cells in at least one of the addressed time points. Asterisks indicate significance level (* p-value <0.05, ** p-value <0.01, *** p-value <0.001)
Figure S10 from Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy
Authors: Dias Matheus Henrique , Friskes Anoek , Wang Siying , Fernandes Neto Joao M. , van Gemert Frank , Mourragui Soufiane , Papagianni Chrysa , Kuiken Hendrik J. , Mainardi Sara , Alvarez-Villanueva Daniel , Lieftink Cor , Morris Ben , Dekker Anna , van Dijk Emma , Wilms Lieke H.S. , da Silva Marcelo S. , Jansen Robin A. , Mulero-Sánchez Antonio , Malzer Elke , Vidal August , Santos Cristina , Salazar Ramón , Wailemann Rosangela A.M. , Torres Thompson E.P. , De Conti Giulia , Raaijmakers Jonne A. , Snaebjornsson Petur , Yuan Shengxian , Qin Wenxin , Kovach John S. , Armelin Hugo A. , te Riele Hein , van Oudenaarden Alexander , Jin Haojie , Beijersbergen Roderick L. , Villanueva Alberto , Medema Rene H. , Bernards Rene
Published: July 2024

Figure S10: Acquired resistance to the combination of LB-100 and Adavosertib suppress anchorage-independent and tumor growth in CRC models (A) Endpoint proliferation of HT-29 and SW-480 parental and resistant cells growing attached or in anchorage-independent conditions. Cells were plated in the same density on regular or cell-repellent culture plates in the absence of drugs and grown for 5-6 days. Proliferation was addressed by CellTiter-Glo 3D® and is expressed as fold change over T0. (B) Growth curves of the individual tumors from SW-480 parental and resistant cells measured 3 times per week. The dashed line indicates the 1500 mm3 ethical sacrifice.
Table S4 from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy
Authors: Mo George , Lee Sang Y. , Coffey David G. , Voillet Valentin , Kirsch Ilan R. , Gottardo Raphael , Smythe Kimberly S. , Yeung Cecilia C.S. , Greenbaum Adam , Green Damian J. , Maloney David G. , Till Brian G.
Published: July 2024

Table S4. Staining panel used for multiplex immunohistochemistry
Table S2 from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy
Authors: Mo George , Lee Sang Y. , Coffey David G. , Voillet Valentin , Kirsch Ilan R. , Gottardo Raphael , Smythe Kimberly S. , Yeung Cecilia C.S. , Greenbaum Adam , Green Damian J. , Maloney David G. , Till Brian G.
Published: July 2024

Table S2. Differentially expressed TCR-β CDR3 sequences increased at 3 and/or 35 month timepoints in patient UPN-04
Table S1 from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy
Authors: Mo George , Lee Sang Y. , Coffey David G. , Voillet Valentin , Kirsch Ilan R. , Gottardo Raphael , Smythe Kimberly S. , Yeung Cecilia C.S. , Greenbaum Adam , Green Damian J. , Maloney David G. , Till Brian G.
Published: July 2024

Table S1. Baseline cytokine levels (prior to lymphodepletion) for UPN-03 and UPN-04.
Supplementary Figures from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy
Authors: Mo George , Lee Sang Y. , Coffey David G. , Voillet Valentin , Kirsch Ilan R. , Gottardo Raphael , Smythe Kimberly S. , Yeung Cecilia C.S. , Greenbaum Adam , Green Damian J. , Maloney David G. , Till Brian G.
Published: July 2024

Figure S1. Cellular composition of the post-treatment tumor biopsy of patient UPN-03. Figure S2. Gating strategy for multiparameter flow cytometry for UPN-03. Figure S3. Gating strategy for multiparameter flow cytometry for UPN-04.
Supplementary Table S8 from Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC–Alarmin Axis
Authors: Vincelette Nicole D. , Yu Xiaoqing , Kuykendall Andrew T. , Moon Jungwon , Su Siyuan , Cheng Chia-Ho , Sammut Rinzine , Razabdouski Tiffany N. , Nguyen Hai V. , Eksioglu Erika A. , Chan Onyee , Al Ali Najla , Patel Parth C. , Lee Dae H. , Nakanishi Shima , Ferreira Renan B. , Hyjek Elizabeth , Mo Qianxing , Cory Suzanne , Lawrence Harshani R. , Zhang Ling , Murphy Daniel J. , Komrokji Rami S. , Lee Daesung , Kaufmann Scott H. , Cleveland John L. , Yun Seongseok
Published: July 2024

Comparison of gene expression profiles of Mx1-Cre+/-;Rosa26LSL-MYC/LSL-MYC vs. Mx1-Cre+/-;Rosa26+/+ mouse.
Table S3 from Genotoxicity Associated with Retroviral CAR Transduction of ATM-Deficient T Cells
Authors: Rozenbaum Meir , Fluss Reut , Marcu-Malina Victoria , Sarouk Ifat , Meir Amilia , Elitzur Sarah , Zinger Tal , Jacob-Hirsch Jasmine , Saar Efrat G. , Rechavi Gideon , Jacoby Elad
Published: July 2024

Cytogenetic analysis of ATM-/- transduced with GFP or CAR
Table S2 from Genotoxicity Associated with Retroviral CAR Transduction of ATM-Deficient T Cells
Authors: Rozenbaum Meir , Fluss Reut , Marcu-Malina Victoria , Sarouk Ifat , Meir Amilia , Elitzur Sarah , Zinger Tal , Jacob-Hirsch Jasmine , Saar Efrat G. , Rechavi Gideon , Jacoby Elad
Published: July 2024

Detailed cytogenetic analysis of CAR-T and untransduced activated cells
Figure 2 from Cancer-Related Fatigue and the Additive Effect of Treatment in the Context of Lymphoma: An Analysis of the Lymphoma Coalition’s 2022 Global Patient Survey
Authors: Kalloger Steve E. , Watson Amanda , Sajkowski Shawn , Warwick Lorna
Published: July 2024

The effect of age and biological sex on the probability of experiencing CRF as a symptom, side effect, or both. A and B, For patients with DLBCL, the probability of experiencing CRF as both a symptom and side effect increases by a factor of 1.37 for females relative to males given a static age of 50 years. C and D, Similar but milder phenomenon for patients with follicular lymphoma. Increasing age was also associated with experiencing CRF as both a symptom and side effect. In contrast, the way CRF was experienced by patients with mantle cell lymphoma was not influenced by biological sex but rather age. A 30-year increase in age saw the increase in the probability of experiencing CRF as both a symptom and a side effect by a factor of 2.21 (E and F).
N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma
Authors: Geroyska Sofia , Mejia Isabel , Chan Alfred A. , Navarrete Marian , Pandey Vijaya , Kharpatin Samuel , Noguti Juliana , Wang Feng , Srole Daniel , Chou Tsui-Fen , Wohlschlegel James , Nemeth Elizabeta , Damoiseaux Robert , Shackelford David B. , Lee Delphine J. , Díaz Begoña
Published: July 2024

Myristoylation is a type of protein acylation by which the fatty acid myristate is added to the N-terminus of target proteins, a process mediated by N-myristoyltransferases (NMT). Myristoylation is emerging as a promising cancer therapeutic target; however, the molecular determinants of sensitivity to NMT inhibition or the mechanism by which it induces cancer cell death are not completely understood. We report that NMTs are a novel therapeutic target in lung carcinoma cells with LKB1 and/or KEAP1 mutations in a KRAS-mutant background. Inhibition of myristoylation decreases cell viability in vitro and tumor growth in vivo. Inhibition of myristoylation causes mitochondrial ferrous iron overload, oxidative stress, elevated protein poly (ADP)-ribosylation, and death by parthanatos. Furthermore, NMT inhibitors sensitized lung carcinoma cells to platinum-based chemotherapy. Unexpectedly, the mitochondrial transporter translocase of inner mitochondrial membrane 17 homolog A (TIM17A) is a critical target of myristoylation inhibitors in these cells. TIM17A silencing recapitulated the effects of NMT inhibition at inducing mitochondrial ferrous iron overload and parthanatos. Furthermore, sensitivity of lung carcinoma cells to myristoylation inhibition correlated with their dependency on TIM17A. This study reveals the unexpected connection between protein myristoylation, the mitochondrial import machinery, and iron homeostasis. It also uncovers myristoylation inhibitors as novel inducers of parthanatos in cancer, and the novel axis NMT-TIM17A as a potential therapeutic target in highly aggressive lung carcinomas.

Significance:

KRAS-mutant lung carcinomas with LKB1 and/or KEAP1 co-mutations have intrinsic therapeutic resistance. We show that these tumors are sensitive to NMT inhibitors, which slow tumor growth in vivo and sensitize cells to platinum-based chemotherapy in vitro. Inhibition of myristoylation causes death by parthanatos and thus has the potential to kill apoptosis and ferroptosis-resistant cancer cells. Our findings warrant investigation of NMT as a therapeutic target in highly aggressive lung carcinomas.
HybridCSF model for magnetic resonance image based brain tumor segmentation
Authors: Kataria Jyoti , Panda Supriya P.
Published: July 2024

The human brain comprises a complex interconnection of nerve cells and vital organs, which regulates crucial bodily processes. Although neurons commonly undergo developmental stages, they may occasionally experience abnormalities, leading to abnormal growths known as brain tumors. The objective of brain tumor segmentation is to produce precise boundaries of brain tumor regions. This study extensively analyzes deep learning methods for brain tumor detection, evaluating their effectiveness across diverse datasets. It introduces a hybrid model, which is proposed by the name HybriCSF: hybrid convolutional-SVM-fuzzy C-means model combining convolutional neural network (CNN) with the classifier support vector machine (SVM) and clustering technique fuzzy C-means (FCM). The proposed model was implemented on Br35H, BraTs 2020 and BraTs2021 datasets. The suggested model outperformed the existing methods by achieving 98.6% of accuracy on Br35H dataset and dice score of 0.63, 0.87, 0.81 on BraTs 2020 dataset for enhancing tumor (ET), whole tumor (WT), and tumor core (TC), respectively. The achieved dice scores on the BraTs 2021datasets are 0.89, 0.95, and 0.89 for ET, WT, and TC, respectively. The results show that the suggested model HybriCSF outperforms the other CNN-based models in terms of accuracy.
Taxonomic re-evaluation of the subspecies of Hebius vibakari (Boie, 1826) (Reptilia: Serpentes: Natricidae), with new evidence from central and northern China
Authors: GAO ZONG-YUAN , HUANG JUN-JIE , DING LI , JIANG KE , MAO JIE , REN JIN-LONG
Published: July 2024

Hebius vibakari (Boie, 1826), the type species of the genus Hebius, currently includes three subspecies: Hebius vibakari vibakari, endemic to Japan except for the Hokkaido region; Hebius vibakari ruthveni (Van Denburgh, 1923), found in the Korean Peninsula, northeastern China, and eastern Russia; and Hebius vibakari danjoensis (Toriba, 1986), native to the Oshima Island, Danjo Islands, Japan. However, the taxonomic status of three subspecies has not been evaluated for many years. Integrating data from previous studies and new records from central and northern China, we evaluated the systematic positions of H. v. vibakari and H. v. ruthveni based on comparative morphology and molecular phylogenetics. Analysis recovered H. vibakari as a monophyletic group, composed of three major clades that could not correspond to the nominative subspecies. As molecular and morphological evidence could not distinguish H. v. ruthveni from H. v. vibakari, we synonymized the junior nomen H. v. ruthveni with H. v. vibakari. A detailed description of Hebius vibakari is provided, including hemipenial morphology, and the taxonomic status of the subspecies H. v. danjoensis is discussed.
Dynamics of Two Episodes of High Winds Produced by an Unusually Long-Lived Quasi-Linear Convective System in South China
Authors: Xu Xin , Ju Yuanyuan , Liu Qiqing , Zhao Kun , Xue Ming , Zhang Shushi , Zhou Ang , Wang Yuan , Tang Ying
Published: July 2024

Using radar observation and convection-permitting simulation, this work studies the storm-scale dynamics governing the generation of two episodes of high winds by an unusually long-lived quasi-linear convective system (QLCS) in South China on 21 April 2017. The first episode of high winds occurred at the apex of a bowing segment in the southern QLCS due to the downward transport of high momentum by a descending rear-inflow jet (RIJ). The RIJ was initially elevated which was generated as low-frequency gravity wave response to the thermal forcing in the QLCS leading convective line. It descended to the surface owing to the enhancement of low-level diabatic cooling which strengthened the downdrafts at the RIJ leading edge. The vertical momentum budget revealed that the downdrafts were initiated by the negative buoyancy of the cold pool and strengthened by the weakened buoyancy-induced upward pressure gradient force in the boundary layer and enhanced hydrometeor loading above. The second episode of high winds occurred in the decaying stage of the QLCS which, however, redeveloped as its northern part interacted with an intensifying large-scale shear line to the east. A zonal convective line developed along the shear line and finally merged with the QLCS. The merger greatly enhanced the low-level convergence, leading to the downward development of the line-end vortex via vertical stretching of vertical vorticity. The area of high winds was notably increased by the superposition of the ambient translational wind with the vortex rotational flow. The findings provide new insights into the generation of high winds by the QLCS-MCS merger, highlighting the importance of low-level vortices in addition to the RIJ.

Significance Statement

Quasi-linear convective systems (QLCSs) are prolific producers of high winds at the surface. While conceptual models have been established for high winds produced by single QLCSs, this is not the case for the high winds generated by QLCSs merging with other convective systems. This work revealed different dynamics for two episodes of high winds produced by a long-lived QLCS merging with an MCS in South China. The first episode resulted from the descending rear-inflow jet (RIJ) as in the case of single QLCSs. The second and stronger one was due to the superposition of ambient flow with a line-end vortex that developed downward given the enhanced low-level convergence by the merger. This finding sheds light on the importance of mergers in high-wind generation which has even greater damaging potential than the RIJ.
Effects of Turbulence on Upper-Tropospheric Ice Supersaturation
Authors: Kärcher B. , Hoffmann F. , Podglajen A. , Hertzog A. , Pluogonven R. , Atlas R. , Corcos M. , Grabowski W. W. , Gasparini B.
Published: July 2024

Effects of turbulence on ice supersaturation at cirrus heights (>8 km) remain unexplored. Small-scale mixing processes become important for high Reynolds number flows, which may develop below the buoyancy length scale (10–100 m). The current study couples a stochastic turbulent mixing model with reduced dimensionality to an entraining parcel model to investigate, in large-ensemble simulations, how supersaturation evolves due to homogeneous turbulence in the stably stratified, cloud-free upper troposphere. The rising parcel is forced by a mesoscale updraft. The perturbation of an initially homogeneous vertical distribution of supersaturation is studied after a 36-m ascent in a baseline case and several sensitivity scenarios. Turbulent mixing and associated temperature fluctuations alone lead to changes in ensemble-mean distributions with standard deviations in the range 0.001–0.006, while mean values are hardly affected. Large case-to-case variability in the supersaturation field is predicted with fluctuation amplitudes of up to 0.03, although such large values are rare. A vertical gradient of supersaturation (≈10−3 m−1) is generated for high turbulence intensities due to the development of a dry-adiabatic lapse rate. Entrainment of slightly warmer (less than 0.1 K) environmental air into the parcel decreases the mean supersaturation by less than 0.01. Supersaturation fluctuations are substantially larger after entrainment events with an additional small offset in absolute humidity (by ±3.5%) between the parcel and environmental air. The predicted perturbations of ice supersaturation are significant enough to motivate studies of turbulence–ice nucleation interactions during cirrus formation that abandon the assumption of instantaneous mixing inherent to traditional parcel models.

Significance Statement

The purpose of our study is to investigate the effects of microscale turbulence on ice supersaturation in the upper troposphere. The associated variability in temperature and moisture fields is not resolved in cloud models and cannot easily be represented in terms of large-scale flow variables. We specify the conditions in which turbulent mixing and entrainment cause substantial variations in distributions of supersaturation. These include high turbulence intensity, strong atmospheric stability, and large moisture gradients. Our results suggest that turbulence may affect the strongly supersaturation-dependent ice formation processes in high-altitude clouds, pointing to the need to investigate cirrus formation in the presence of turbulence.
Use of HSC-targeted LNP to generate a mouse model of lethal α-thalassemia and treatment via lentiviral gene therapy
Authors: Chappell Maxwell E. , Breda Laura , Tricoli Lucas , Guerra Amaliris , Jarocha Danuta , Castruccio Castracani Carlo , Papp Tyler E. , Tanaka Naoto , Hamilton Nolan , Triebwasser Michael P. , Ghiaccio Valentina , Fedorky Megan T. , Gollomp Kandace L. , Bochenek Veronica , Roche Aoife M. , Everett John K. , Cook Emma J. , Bushman Frederic D. , Teawtrakul Nattiya , Glentis Stavros , Kattamis Antonis , Mui Barbara L. , Tam Ying K. , Weissman Drew , Abdulmalik Osheiza , Parhiz Hamideh , Rivella Stefano
Published: July 2024

α-Thalassemia (AT) is one of the most commonly occurring inherited hematological diseases. However, few treatments are available, and allogeneic bone marrow transplantation is the only available therapeutic option for patients with severe AT. Research into AT has remained limited because of a lack of adult mouse models, with severe AT typically resulting in in utero lethality. By using a lipid nanoparticle (LNP) targeting the receptor CD117 and delivering a Cre messenger RNA (mRNACreLNPCD117), we were able to delete floxed α-globin genes at high efficiency in hematopoietic stem cells (HSC) ex vivo. These cells were then engrafted in the absence or presence of a novel α-globin–expressing lentiviral vector (ALS20αI). Myeloablated mice infused with mRNACreLNPCD117–treated HSC showed a complete knock out (KO) of α-globin genes. They showed a phenotype characterized by the synthesis of hemoglobin H (HbH; also known as β-tetramers or β4), aberrant erythropoiesis, and abnormal organ morphology, culminating in lethality ∼8 weeks after engraftment. Mice infused with mRNACreLNPCD117–treated HSC with at least 1 copy of ALS20αI survived long term with normalization of erythropoiesis, decreased production of HbH, and amelioration of the abnormal organ morphology. Furthermore, we tested ALS20αI in erythroid progenitors derived from α-globin–KO CD34+ cells and cells isolated from patients with both deletional and nondeletional HbH disease, demonstrating improvement in α-globin/β-globin mRNA ratio and reduction in the formation of HbH by high-performance liquid chromatography. Our results demonstrate the broad applicability of LNP for disease modeling, characterization of a novel mouse model of severe AT, and the efficacy of ALS20αI for treating AT.
Microplastic and plastic pollution: impact on respiratory disease and health
Authors: Vasse Gwenda F. , Melgert Barbro N.
Published: July 2024

Throughout their lifecycle, from production to use and upon disposal, plastics release chemicals and particles known as micro- and nanoplastics (MNPs) that can accumulate in the environment. MNPs have been detected in different locations of the human body, including in our lungs. This is likely a consequence of MNP exposure through the air we breathe. Yet, we still lack a comprehensive understanding of the impact that MNP exposure may have on respiratory disease and health. In this review, we have collated the current body of evidence on the implications of MNP inhalation on human lung health fromin vitro,in vivoand occupational exposure studies. We focused on interactions between MNP pollution and different specific lung-resident cells and respiratory diseases. We conclude that it is evident that MNPs possess the capacity to affect lung tissue in disease and health. Yet, it remains unclear to which extent this occurs upon exposure to ambient levels of MNPs, emphasising the need for a more comprehensive evaluation of environmental MNP exposure levels in everyday life.
fENko-Kae01 is a flagellum-specific jumbo phage infecting Klebsiella aerogenes
Authors: Ranta Kira , Skurnik Mikael , Kiljunen Saija
Published: July 2024

Background

Klebsiella aerogenes is an opportunistic pathogen that causes a wide variety of infections. Due to the rising problem of antibiotic resistance, novel antibiotics and strategies to combat bacterial infections are needed. Host-specific bacteriophages are natural enemies of bacteria and can be used in phage therapy as an alternative form of treatment against bacterial infections. Jumbo phages are defined as phages with genomes larger than 200 kb. Relatively few studies have been done on jumbo phages compared to smaller phages.

Results

A novel phage, fENko-Kae01, was isolated from a commercial phage cocktail. Genomic analysis revealed that fENko-Kae01 is a lytic jumbo phage with a 360 kb genome encoding 578 predicted genes. No highly similar phage genomes were identified and fENko-Kae01 may be a completely new genus representative. No known genes associated with lysogenic life cycle, bacterial virulence, or antibiotic resistance were identified. The phage had myovirus morphology and a narrow host range. Phage resistant bacterial mutants emerged under phage selection. Whole genome sequencing revealed that the biogenesis of the flagellum was affected in four mutants and the lack of functional flagellum was confirmed in motility assays. Furthermore, phage fENKo-Kae01 failed to adsorb on the non-motile mutants indicating that the bacterial flagellum is the phage-binding receptor.

Conclusions

fENko-Kae01 is a novel jumbo bacteriophage that is considered safe for phage therapy. fENko-Kae01 uses the flagellum as the phage-binding receptor and may represent a completely novel genus.
High resolution mapping of a novel non-transgressive hybrid susceptibility locus in barley exploited by P. teres f. maculata
Authors: Clare Shaun J. , Alhashel Abdullah F. , Li Mengyuan , Effertz Karl M. , Poudel Roshan Sharma , Zhang Jianwei , Brueggeman Robert S.
Published: July 2024

Hybrid genotypes can provide significant yield gains over conventional inbred varieties due to heterosis or hybrid vigor. However, hybrids can also display unintended negative attributes or phenotypes such as extreme pathogen susceptibility. The necrotrophic pathogen Pyrenophora teres f. maculata (Ptm) causes spot form net blotch, which has caused significant yield losses to barley worldwide. Here, we report on a non-transgressive hybrid susceptibility locus in barley identified between the three parental lines CI5791, Tifang and Golden Promise that are resistant to Ptm isolate 13IM.3. However, F2 progeny from CI5791 × Tifang and CI5791 × Golden Promise crosses exhibited extreme susceptibility. The susceptible phenotype segregated in a ratio of 1 resistant:1 susceptible representing a genetic segregation ratio of 1 parental (res):2 heterozygous (sus):1 parental (res) suggesting a single hybrid susceptibility locus. Genetic mapping using a total of 715 CI5791 × Tifang F2 individuals (1430 recombinant gametes) and 149 targeted SNPs delimited the hybrid susceptibility locus designated Susceptibility to Pyrenophora teres 2 (Spt2) to an ~ 198 kb region on chromosome 5H of the Morex V3 reference assembly. This single locus was independently mapped with 83 CI5791 × Golden Promise F2 individuals (166 recombinant gametes) and 180 genome wide SNPs that colocalized to the same Spt2 locus. The CI5791 genome was sequenced using PacBio Continuous Long Read technology and comparative analysis between CI5791 and the publicly available Golden Promise genome assembly determined that the delimited region contained a single high confidence Spt2 candidate gene predicted to encode a pentatricopeptide repeat-containing protein.
Application of slow-controlled release fertilizer coordinates the carbon flow in carbon-nitrogen metabolism to effect rice quality
Authors: Jiang Zhengrong , Chen Qiuli , Liu Dun , Tao Weike , Gao Shen , Li Jiaqi , Lin Chunhao , Zhu Meichen , Ding Yanfeng , Li Weiwei , Li Ganghua , Sakr Soulaiman , Xue Lihong
Published: July 2024

Slow-controlled release fertilizers are experiencing a popularity in rice cultivation due to their effectiveness in yield and quality with low environmental costs. However, the underlying mechanism by which these fertilizers regulate grain quality remains inadequately understood. This study investigated the effects of five fertilizer management practices on rice yield and quality in a two-year field experiment: CK, conventional fertilization, and four applications of slow-controlled release fertilizer (UF, urea formaldehyde; SCU, sulfur-coated urea; PCU, polymer-coated urea; BBF, controlled-release bulk blending fertilizer). In 2020 and 2021, the yields of UF and SCU groups showed significant decreases when compared to conventional fertilization, accompanied by a decline in nutritional quality. Additionally, PCU group exhibited poorer cooking and eating qualities. However, BBF group achieved increases in both yield (10.8 t hm−2 and 11.0 t hm−2) and grain quality reaching the level of CK group. The adequate nitrogen supply in PCU group during the grain-filling stage led to a greater capacity for the accumulation of proteins and amino acids in the PCU group compared to starch accumulation. Intriguingly, BBF group showed better carbon–nitrogen metabolism than that of PCU group. The optimal nitrogen supply present in BBF group suitable boosted the synthesis of amino acids involved in the glycolysis/ tricarboxylic acid cycle, thereby effectively coordinating carbon–nitrogen metabolism. The application of the new slow-controlled release fertilizer, BBF, is advantageous in regulating the carbon flow in the carbon–nitrogen metabolism to enhance rice quality.