bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Plasma Cell–Free DNA Chromatin Immunoprecipitation Profiling Depicts Phenotypic and Clinical Heterogeneity in Advanced Prostate Cancer
Authors: Sipola Joonatan , Munzur Aslı D. , Kwan Edmond M. , Seo Clara C.Y. , Hauk Benjamin J. , Parekh Karan , Liao Yi Jou (Ruby) , Bernales Cecily Q. , Donnellan Gráinne , Bloise Ingrid , Fung Emily , Ng Sarah W.S. , Wang Gang , Vandekerkhove Gillian , Nykter Matti , Annala Matti , Maurice-Dror Corinne , Chi Kim N. , Herberts Cameron , Wyatt Alexander W. , Takeda David Y.
Published: February 2025

Abstract
Cell phenotype underlies prostate cancer presentation and treatment resistance and can be regulated by epigenomic features. However, the osteotropic tendency of prostate cancer limits access to metastatic tissue, meaning most prior insights into prostate cancer chromatin biology are from preclinical models that do not fully represent disease complexity. Noninvasive chromatin immunoprecipitation of histones in plasma cell–free DNA (cfDNA) in humans may enable the capture of disparate prostate cancer phenotypes. In this study, we analyzed activating promoter- and enhancer-associated H3K4me2 from cfDNA in metastatic prostate cancer enriched for divergent patterns of metastasis and diverse clinical presentation. H3K4me2 density across prostate cancer genes, accessible chromatin, and lineage-defining transcription factor–binding sites correlated strongly with ctDNA fraction—demonstrating capture of prostate cancer–specific biology and informing the development of a statistical framework to adjust for ctDNA fraction. Chromatin hallmarks mirrored synchronously measured clinicogenomic features: bone- versus liver-predominant disease, serum PSA, biopsy-confirmed histopathologic subtype, and RB1 deletions convergently indicated phenotype segregation along an axis of differential androgen receptor activity and neuroendocrine identity. Detection of lineage switching after sequential progression on systemic therapy in select patients indicates potential use for individualized resistance monitoring. Epigenomic footprints of metastasis-induced normal tissue destruction were evident in bulk cfDNA from two patients. Finally, a public epigenomic resource was generated using a distinct chromatin marker that has not been widely investigated in prostate cancer. These results provide insights into the adaptive molecular landscape of aggressive prostate cancer and endorse plasma cfDNA chromatin profiling as a biomarker source and biological discovery tool.

Significance: Plasma cell–free chromatin immunoprecipitation sequencing enables phenotypic dissection of lethal prostate cancer and is a practical tool for biomarker discovery while overcoming prior limitations of access to relevant tissue and reliance on model systems.
Data from Imlunestrant Is an Oral, Brain-Penetrant Selective Estrogen Receptor Degrader with Potent Antitumor Activity in ESR1 Wild-Type and Mutant Breast Cancer
Authors: Bhagwat Shripad V. , Mur Cecilia , Vandekopple Matthew , Zhao Baohui , Shen Weihua , Marugán Carlos , Capen Andrew , Kindler Lisa , Stephens Jennifer R. , Huber Lysiane , Castanares Mark A. , Garcia-Tapia David , Cohen Jeff D. , Bastian Jolie , Mattioni Brian , Yuen Eunice , Baker Thomas K. , Rodriguez Cruz Vivian , Fei Dongling , Manro Jason R. , Pulliam Nicholas , Dowless Michele S. , Ortiz Ruiz Maria Jesus , Yu Chunping , Puca Loredana , Klippel Anke , Bacchion Francesca , Ismail-Khan Roohi , Rodrik-Outmezguine Vanessa , Peng Sheng-Bin , Lallena María Jose , Gong Xueqian , de Dios Alfonso
Published: February 2025

Abstract
Targeting of the estrogen receptor (ER) by antiestrogens is the standard of care for patients with ER+ HER2− advanced/metastatic breast cancer. Although antiestrogens that degrade ERα (fulvestrant) or block estrogen production (aromatase inhibitors) have improved patient outcomes, clinically important challenges remain related to drug administration, limited bioavailability, lack of brain exposure, and acquired resistance due to ESR1 mutations. These limitations indicate a need for more robust ER-targeted therapies. Here, we discovered and characterized imlunestrant, a next-generation potent, brain-penetrant oral selective ER degrader. Imlunestrant degraded ERα and decreased ERα-mediated gene expression both in vitro and in vivo. Cell proliferation and tumor growth in ESR1 wild-type (WT) and mutant models were significantly inhibited by imlunestrant. Combining imlunestrant with abemaciclib (CDK4/6 inhibitor), alpelisib (PI3K inhibitor), or everolimus (mTOR inhibitor) further enhanced tumor growth inhibition, regardless of ESR1 mutational status. In an ER+ breast cancer intracranial tumor model, imlunestrant prolonged survival compared with vehicle or alternative selective ER degrader therapies. Together, these findings support the potential of imlunestrant to degrade ERα and suppress the growth of ESR1-WT and mutant breast cancer, including brain metastatic tumors.

Significance: Imlunestrant, a next-generation, brain-penetrant oral ERα degrader, displays potent activity in ESR1 wild-type and mutant breast cancer, enhances combination activity with standard-of-care agents, and inhibits growth of ER+ intracranial tumors.
Table 4 from The Prostaglandin EP4 Antagonist Vorbipiprant Combined with PD-1 Blockade for Refractory Microsatellite-Stable Metastatic Colorectal Cancer: A Phase Ib/IIa Trial
Authors: Pietrantonio Filippo , Morano Federica , Niger Monica , Ghelardi Filippo , Chiodoni Claudia , Palazzo Michele , Nichetti Federico , Manca Paolo , Cristarella Eleonora , Doldi Valentina , Zaffaroni Nadia , Sabella Giovanna , Brambilla Nadia , Benincasa Elena , Giacovelli Giampaolo , Vitalini Cristina , Girolami Federica , Rovati Lucio C.
Published: February 2025

ORR, DCR, and PFS >4 months according to PD-L1 CPS.
Table 2 from The Prostaglandin EP4 Antagonist Vorbipiprant Combined with PD-1 Blockade for Refractory Microsatellite-Stable Metastatic Colorectal Cancer: A Phase Ib/IIa Trial
Authors: Pietrantonio Filippo , Morano Federica , Niger Monica , Ghelardi Filippo , Chiodoni Claudia , Palazzo Michele , Nichetti Federico , Manca Paolo , Cristarella Eleonora , Doldi Valentina , Zaffaroni Nadia , Sabella Giovanna , Brambilla Nadia , Benincasa Elena , Giacovelli Giampaolo , Vitalini Cristina , Girolami Federica , Rovati Lucio C.
Published: February 2025

Overview of TEAE.
Figure 2 from The Prostaglandin EP4 Antagonist Vorbipiprant Combined with PD-1 Blockade for Refractory Microsatellite-Stable Metastatic Colorectal Cancer: A Phase Ib/IIa Trial
Authors: Pietrantonio Filippo , Morano Federica , Niger Monica , Ghelardi Filippo , Chiodoni Claudia , Palazzo Michele , Nichetti Federico , Manca Paolo , Cristarella Eleonora , Doldi Valentina , Zaffaroni Nadia , Sabella Giovanna , Brambilla Nadia , Benincasa Elena , Giacovelli Giampaolo , Vitalini Cristina , Girolami Federica , Rovati Lucio C.
Published: February 2025

Gene expression signatures, immune cell enrichment and gene expression–based CMS, and association with treatment response. Treeplot depicting the results of hierarchical clustering of enriched terms from GSEA, comparing enriched pathways in patients with PFS <4 or >4 months (A). Bar plot reporting the results of the Student t test t statistics comparing inflammatory gene expression signature enrichment scores in patients with PFS >4 months vs. those with PFS <4 months (B). Heatmap of normalized enrichment scores of immune cell subtypes, comparing patients with PFS <4 or >4 months (C). DC, dendritic cells; iDC, immature dendritic cells; mDC, mature dendritic cells; MDSC, myeloid-derived suppressor cells; pDC, plasmacytoid dendritic cells; TFG, follicular helper T cells; TGD, gamma-delta T cells; Treg, regulatory T cells. Stacked barplots representing the proportion of patients assigned to gene expression CMS in patients with PFS >4 months (n = 6) and patients with PFS <4 months (n = 17; D).
Supplementary Figure S2 from The Prostaglandin EP4 Antagonist Vorbipiprant Combined with PD-1 Blockade for Refractory Microsatellite-Stable Metastatic Colorectal Cancer: A Phase Ib/IIa Trial
Authors: Pietrantonio Filippo , Morano Federica , Niger Monica , Ghelardi Filippo , Chiodoni Claudia , Palazzo Michele , Nichetti Federico , Manca Paolo , Cristarella Eleonora , Doldi Valentina , Zaffaroni Nadia , Sabella Giovanna , Brambilla Nadia , Benincasa Elena , Giacovelli Giampaolo , Vitalini Cristina , Girolami Federica , Rovati Lucio C.
Published: February 2025

Supplementary Figure S2. PBMC subpopulation at baseline and at 2 months based on PFS duration or vorbipiprant dose.
Supplementary Figure S1 from The Prostaglandin EP4 Antagonist Vorbipiprant Combined with PD-1 Blockade for Refractory Microsatellite-Stable Metastatic Colorectal Cancer: A Phase Ib/IIa Trial
Authors: Pietrantonio Filippo , Morano Federica , Niger Monica , Ghelardi Filippo , Chiodoni Claudia , Palazzo Michele , Nichetti Federico , Manca Paolo , Cristarella Eleonora , Doldi Valentina , Zaffaroni Nadia , Sabella Giovanna , Brambilla Nadia , Benincasa Elena , Giacovelli Giampaolo , Vitalini Cristina , Girolami Federica , Rovati Lucio C.
Published: February 2025

Supplementary Figure S1. Kaplan Meier plot for PFS and OS overall and stratified by presence/absence of liver metastases.
Supplementary Table S5 from Smoking-Associated Carcinogen–Induced Inflammation Promotes Lung Carcinogenesis via IRAK4 Activation
Authors: Aggarwal Ritesh K. , Sidoli Simone , Wang Jingli , Sahu Srabani , Sanawar Rahul , Gupta Varun , Aluri Srinivas , Sukrithan Vineeth , Vegivinti Charan T.R. , Zavras Phaedon D. , Verma Divij , Gordon-Mitchell Shanisha , Agarwal Beamon , Verma Tanya , Starczynowski Daniel T. , Steidl Ulrich G. , Shastri Aditi , Halmos Balazs , LaFave Lindsay M. , Cheng Haiying , Verma Amit , Zou Yiyu
Published: February 2025

Supplementary Table S5. Manuscript Figure 5 data - The Excel file has data points for easy access to infer numerical values for data presented in the manuscript. Also see Data Availability Statement.
Supplementary Table S4 from Smoking-Associated Carcinogen–Induced Inflammation Promotes Lung Carcinogenesis via IRAK4 Activation
Authors: Aggarwal Ritesh K. , Sidoli Simone , Wang Jingli , Sahu Srabani , Sanawar Rahul , Gupta Varun , Aluri Srinivas , Sukrithan Vineeth , Vegivinti Charan T.R. , Zavras Phaedon D. , Verma Divij , Gordon-Mitchell Shanisha , Agarwal Beamon , Verma Tanya , Starczynowski Daniel T. , Steidl Ulrich G. , Shastri Aditi , Halmos Balazs , LaFave Lindsay M. , Cheng Haiying , Verma Amit , Zou Yiyu
Published: February 2025

Supplementary Table S4. Manuscript Figure 4 data - The Excel file has data points for easy access to infer numerical values for data presented in the manuscript. Also see Data Availability Statement.
Supplementary Data 1 from A Phase I Study of FHD-609, a Heterobifunctional Degrader of Bromodomain-Containing Protein 9, in Patients with Advanced Synovial Sarcoma or SMARCB1-Deficient Tumors
Authors: Livingston J. Andrew , Blay Jean-Yves , Trent Jonathan , Valverde Claudia , Agulnik Mark , Gounder Mrinal , Le Cesne Axel , McKean Meredith , Wagner Michael J. , Stacchiotti Silvia , Agresta Samuel , Quintás-Cardama Alfonso , Reilly Sarah A. , Healy Kathleen , Hickman Denice , Zhao Tina , Ballesteros-Perez Alex , Khalil Alexis , Collins Michael P. , Piel Jessica , Horrigan Kim , Lefkovith Ariel , Innis Scott , Lazar Alexander J. , Cote Gregory M. , Wagner Andrew J.
Published: February 2025

Supplementary Data ECG tracings
Supplementary Table S4 from Next-Generation Sequencing–Based MSI Scoring Predicts Benefit in Mismatch Repair–Deficient Tumors Treated with Nivolumab: Follow-up on NCI-MATCH Arm Z1D
Authors: Schoenfeld Jonathan D. , Azad Nilofer S. , Gross Jacob , Chen Li , Overman Michael J. , Kao Katrina , Jackson Latifa , Brunnquell Donna , Bu Xiangning , Coppola Christina , Guan Ping , Lee Jennifer , Sims David , Fuchs Rebecca , Weirather Jason L. , Pfaff Kathleen L. , Gunasti Lauren , Ranasinghe Srin , Hamilton Stanley R. , Wang Victoria , O’Dwyer Peter J. , Wu Catherine J. , Rodig Scott J. , Patton David R. , Harris Lyndsay
Published: February 2025

Subjects TMB, MSISensor score and clinical benefit
Supplementary Figure S3 from Bladder Preservation with Durvalumab plus Tremelimumab and Concurrent Radiotherapy in Patients with Localized Muscle-Invasive Bladder Cancer (IMMUNOPRESERVE): A Phase II Spanish Oncology GenitoUrinary Group Trial
Authors: Garcia-del-Muro Xavier , P. Valderrama Begoña , Medina-Colmenero Ana , Etxaniz Olatz , Gironés Sarrió Regina , Juan-Fita María José , Costa-García Marcel , Moreno Rafael , Miras Rodríguez Isabel , Ortiz Irene , Cuéllar Andrés , Ferrer Ferran , Vigués Francesc , de Haro Piedra Roberto , Candal Gomez Arturo , Villà Salvador , Pontones José Luis , Murria Yasmina , Lendínez-Cano Guillermo , Alemany Ramon
Published: February 2025

Supplementary Figure 3. Efficacy time-to-event endpoints in patients stratified according to PD-L1 expression. A) Bladder preserved free of tumor survival (BPFS). B) Disease-free survival (DFS). C) Relapse-free survival (RFS). Log rank p-values enclosed in each panel.
Supplementary Data 3 from Circulating Tumor DNA Dynamics and Clinical Outcome in Metastatic Colorectal Cancer Patients Undergoing Front-Line Chemotherapy
Authors: Ghidini Michele , Hahne Jens Claus , Senti Chiara , Heide Timon , Proszek Paula Z. , Shaikh Ridwan , Carter Paul , Hubank Mike , Trevisani Francesco , Garrone Ornella , Cappelletti Maria Rosa , Generali Daniele , Cattaneo Monica , Gnocchi Nicoletta , Donati Gianvito , Gobbi Angela , Grizzi Giulia , Lampis Andrea , Elghadi Raghad , Tanzi Giulia , Tomasello Gianluca , Ratti Margherita , Pinato David J. , Fassan Matteo , Vlachogiannis Georgios , Sottoriva Andrea , Cortellini Alessio , Passalacqua Rodolfo , Valeri Nicola
Published: February 2025

Supp Table S3
Supplementary Table S1 from Genomic Profiling Reveals SMARCA4 Mutations Are Associated with Shorter Overall and Intracranial Progression-Free Survival in Patients with Melanoma Brain Metastases
Authors: Fischer Grant M. , Lamba Nayan , Vogelzang Jayne , Aizer Ayal , Ligon Keith L.
Published: February 2025

Supplementary Table S1. Genes common to all versions of DFCI OncoPanel and MSK-IMPACT panel.
Data from Human Papilloma Virus Circulating Cell-Free DNA Kinetics in Patients with Cervical Cancer Undergoing Definitive Chemoradiation
Authors: Seo Aaron , Xiao Weihong , Gjyshi Olsi , Yoshida-Court Kyoko , Wei Peng , Swanson David , Cisneros Napravnik Tatiana , Grippin Adam , Venkatesan Aradhana M. , Jacobsen Megan C. , Fuentes David T. , Lynn Erica , Sammouri Julie , Jhingran Anuja , Joyner Melissa , Lin Lilie L. , Colbert Lauren E. , Gillison Maura L. , Klopp Ann H.
Published: February 2025

AbstractPurpose:
Human papillomavirus (HPV) is a significant cause of cervical cancer. We hypothesized that detecting viral cell-free HPV DNA (cfDNA) before, during, and after chemoradiation (chemoRT) could provide insights into disease extent, clinical staging, and treatment response.
Experimental Design:
A total of 66 patients with locally advanced cervical cancer were enrolled between 2017 and 2023, with 49 receiving standard-of-care treatment and 17 participating in a clinical trial combining a therapeutic HPV vaccine (PDS0101; IMMUNOCERV). Plasma was collected at baseline, weeks 1, 3, and 5 of chemoRT, and 3 to 4 months after chemoRT. HPV cfDNA was quantified using droplet digital PCR targeting the HPV E6/E7 oncogenes of 13 high-risk types. MRI was performed at baseline and before brachytherapy.
Results:
The median follow-up was 23 months, with recurrence-free survival (RFS) of 78.4% at 2 years. Baseline nodal disease extent correlated with HPV cfDNA levels. HPV cfDNA levels peaked in week 1 of radiation and decreased through treatment. Patients receiving the PDS0101 vaccine had a higher rate of undetectable HPV type 16 cfDNA compared with those who received standard-of-care therapy. HPV cfDNA clearance correlated with better 2-year RFS (92.9% vs. 30%, log-rank; P = 0.0067). The strongest predictor of RFS was HPV cfDNA clearance in follow-up achieving a concordance index score of 0.83, which improved when combined with MRI response (concordance index, 0.88).
Conclusions:
HPV cfDNA levels change dynamically during chemoRT. HPV cfDNA levels at follow-up predict RFS, and delivery of therapeutic HPV vaccine with chemoRT was linked to rapid HPV cfDNA decline. Monitoring HPV cfDNA during and after chemoRT may guide tailoring of personalized treatment.
Data from HMGA2 Expression Predicts Subtype, Survival, and Treatment Outcome in Pancreatic Ductal Adenocarcinoma
Authors: Yamamoto Naomi , Dobersch Stephanie , Loveless Ian , Samraj Annie N. , Jang Gun Ho , Haraguchi Miki , Kang Liang-I. , Ruzinova Marianna B. , Vij Kiran R. , Mudd Jacqueline L. , Walsh Thomas , Safyan Rachael A. , Chiorean Elena Gabriela , Hingorani Sunil R. , Bolton Nathan M. , Li Li , Fields Ryan C. , DeNardo David G. , Notta Faiyaz , Crawford Howard C. , Steele Nina G. , Kugel Sita
Published: February 2025

AbstractPurpose:
The purpose of this study was to establish HMGA2 as a marker of basal-like disease in pancreatic ductal adenocarcinoma (PDAC) and explore its use as a biomarker for prognosis and treatment resistance.
Experimental Design:
We identified high-mobility group A2 (HMGA2) protein expression in basal PDAC cells in a single-cell RNA sequencing (RNA-seq) atlas of 172 patient samples. We then analyzed HMGA2 expression, along with expression of the classic marker GATA-binding factor 6 (GATA6), in a cohort of 580 PDAC samples with multiplex IHC. We further supplemented these data with an additional 30 diverse patient samples and multiple independent single-cell RNA-seq databases.
Results:
We found that expression of HMGA2, but not previously described basal markers cytokeratins 5 or 17, predicted overall survival in our cohort. Combining HMGA2 and GATA6 statuses allowed for the identification of two key study groups: an HMGA2+/GATA6− cohort with worse survival, low tumor-infiltrating CD8+ T cells, increased FAP+ fibroblasts, and poorer response to gemcitabine-based chemotherapies (n = 94, median survival = 11.2 months after surgery) and an HMGA2−/GATA6+ cohort with improved survival, increased CD8+ T-cell infiltrate, decreased FAP+ fibroblasts, and improved survival with gemcitabine-based chemotherapy (n = 198, median survival = 21.7 months after surgery). HMGA2 was also prognostic for overall survival in RNA-seq from an independent cohort.
Conclusions:
IHC stratification of primary tumors by HMGA2 and GATA6 statuses in pancreatic cancer is associated with differential outcomes, survival following chemotherapy, and tumor microenvironments. As a nuclear marker for basal disease, HMGA2 complements GATA6 to identify disease subtypes in PDAC.
Data from Phase I/II Trial of Exportin 1 Inhibitor Selinexor plus Docetaxel in Previously Treated, Advanced KRAS-Mutant Non–Small Cell Lung Cancer
Authors: von Itzstein Mitchell S. , Burns Timothy F. , Dowell Jonathan E. , Horn Leora , Camidge D. Ross , York Sally J. , Eaton Keith D. , Kyle Kelly , Fattah Farjana , Liu Jialiang , Mu-Mosley Hong , Gupta Arjun , Nadeem Urooba , Gao Ang , Zhang Song , Gerber David E.
Published: February 2025

AbstractPurpose:
Patients with Kirsten rat sarcoma viral oncogene (KRAS)–mutant non–small cell lung cancer (NSCLC) have limited therapeutic options. Based on the activity of nuclear export inhibition in preclinical models, we evaluated this strategy in previously treated, advanced KRAS-mutant NSCLC.
Patients and Methods:
The primary outcomes of this multicenter phase I/II dose-escalation trial of selinexor plus docetaxel were safety and tolerability. Selinexor was started 1 week before docetaxel to permit monotherapy pharmacodynamic assessment.
Results:
Among 40 enrolled patients, the median age was 66 years, 55% were female, and 85% were White. The MTD was selinexor 60 mg orally weekly plus docetaxel 75 mg/m2 every 3 weeks. The most common adverse events were nausea (73%, 8% grade ≥3), fatigue (70%, 5% grade ≥3), neutropenia (65%, 60% grade ≥3), and diarrhea (58%, 10% grade ≥3). Of 32 efficacy-evaluable patients, 7 (22%) had partial responses and 18 (56%) had stable disease. Outcomes were not associated with KRAS mutation type but were significantly better in cases with wild-type TP53 (42%), including response and disease control rates (27% and 80% vs. 9% and 27%, respectively; P = 0.03) and progression-free survival (median 7.4 vs. 1.8 months; HR, 0.2; 95% confidence interval, 0.07–0.67; P = 0.003). After selinexor initiation and prior to docetaxel administration, serum lactate dehydrogenase levels increased an average of 51 U/L in TP53-altered cases and decreased an average of 48 U/L in TP53 wild-type cases (P = 0.06).
Conclusions:
Selinexor plus docetaxel was relatively well tolerated in patients with advanced KRAS-mutant NSCLC. The regimen has promising efficacy in TP53 wild-type cases, in which selinexor monotherapy may also have activity.
High Glucose Contribution to the TCA Cycle Is a Feature of Aggressive Non–Small Cell Lung Cancer in Patients
Authors: Cai Ling , Hammond Nia G. , Tasdogan Alpaslan , Alsamraae Massar , Yang Chendong , Cameron Robert B. , Quan Peiran , Solmonson Ashley , Gu Wen , Pachnis Panayotis , Kaur Mayher , Chang Brianna K. , Zhou Qin , Hensley Christopher T. , Do Quyen N. , Martins Nascentes Melo Luiza , Ubellacker Jessalyn M. , Kaushik Akash , Clare Maia G. , Alcazar Isabel N. , Kurylowicz Katarzyna , Marcuccilli Joseph D. , Allies Gabriele , Kutritz Andrea , Klode Joachim , Ramesh Vijayashree , Rogers Thomas J. , Rao Aparna D. , Crentsil Hannah E. , Li Hong , Brister Fang , McDaniel Phyllis , Xu Xiaohong , Evers Bret M. , Zacharias Lauren G. , Sudderth Jessica , Xu Jian , Mathews Thomas P. , Oliver Dwight , Minna John D. , Waters John , Morrison Sean J. , Kernstine Kemp H. , Faubert Brandon , DeBerardinis Ralph J.
Published: February 2025

In patients with non–small cell lung cancer (NSCLC), the relationship between tumor metabolism and clinical outcomes is unknown. Here, 13C-labeled nutrients were intraoperatively infused into more than 90 patients with surgically resectable pulmonary lesions, and metabolic properties of resected tumors were correlated with survival. In NSCLCs infused with 13C-glucose, high 13C enrichment in tricarboxylic acid (TCA) cycle intermediates conferred a HR of 3.8 for early death, typically with metastasis. To test whether these features reflect requirements for metastasis, we generated patient-derived xenografts that spontaneously metastasize to multiple organs. Treatment with an electron transport chain (ETC) inhibitor reduced glucose-derived TCA cycle labeling but did not suppress subcutaneous tumor growth. However, ETC blockade reduced the abundance of circulating cancer cells and suppressed xenograft metastatic burden in distant organs. Our data demonstrate that isotope labeling can identify metabolic properties associated with metastasis in patients and that blocking the ETC suppresses metastasis in mice.

Significance:

Intraoperative 13C-glucose infusions in patients with NSCLC show that tumors with high labeling of TCA cycle intermediates progress rapidly, resulting in metastasis and early death. Blocking this pathway suppresses metastasis of human NSCLC cells in mice.
Surgical Preferences and Fears:
Misconceptions About Robotic-Assisted Surgery
Authors: Hirtsiefer Christopher , Ehrt Mandy , Herout Roman , Mehralivand Sherif , Vilimas Juozas , Baunacke Martin , Thomas Christian
Published: February 2025

Introduction and objective
Robotic-assisted surgery (RAS) is widely adopted across surgical fields, notably urology, but patient knowledge remains limited, often shaped by misconceptions. Previous research indicates factors like age, profession, and technology use influence RAS perceptions. This study investigates public knowledge, preferences, and misconceptions about RAS within a German cohort.
Methods
A cross-sectional survey at a university hospital’s open house gathered responses from 339 participants prior to an RAS exhibition. The questionnaire assessed demographics, surgical preferences, and RAS knowledge. Statistical analyses, including t-tests, chi-squared tests, ANOVA, and multivariate logistic regression, identified key associations.
Results
Results showed 71% (234) of participants favored RAS over conventional surgery, yet misconceptions persisted in 38% (122), particularly among pensioners (48% (46) , p < 0.01). Misconceptions were linked to a preference for conventional surgery (43% (52) vs. 19% (36), p < 0.01). Surgical preference emerged as a significant predictor of misconception. Concerns included surgeon skill (41%, 141) and machine malfunction (39%, 132), with younger participants fearing human error and older individuals fearing technical failure (p < 0.01).
Conclusion
This local study reveals strong public support for RAS but underscores prevalent misconceptions, especially among older adults, suggesting that addressing misconceptions could foster acceptance and informed decision-making.
Pengaruh Pola Hidup Sehat pada Pasien Hipertensi dengan Pendekatan Social Cognitive Theory di Wilayah Kerja Puskesmas Tlogosadang
Authors: Amalia Diah Amini
Published: February 2025

This study aims to analyze the influence of individual characteristics, personal factors and environmental factors on a healthy lifestyle in hypertensive patients. This research is a quantitative research with a descriptive verification design. The sampling technique was carried out by purposive sampling and the sample in this study totaled 300 people (hypertensive patients). The data used in this research is primary data collected through a questionnaire survey. Data analysis used path analysis, correlation coefficient, determination coefficient, and multiple linear regression tests.
The research results obtained: 1) Individual characteristics consisting of: (age with p=0.114), (gender with p=0.000), (education with p=0.000), (family history with p=0.031), (perception of disease with p=0.000); 2) Personal factors consisting of: (self-efficacy with p=0.011), (self-regulation with p=0.000); 3) Environmental factors consisting of: (friend support with p=0.000), (family support with p=0.452), (health worker support with p=0.000); 4) The independent variables, namely individual characteristics, personal factors and environmental factors jointly affect the dependent variable, namely a healthy lifestyle in hypertensive patients (p=0.000; F=231.524; R2=88.9%).
Peranan Capital Budgeting terhadap Ekspansi Perusahaan PT. Fajar Mitra Krida Abadi
Authors: Patrawan Rizky , Rochani Sri , Zulfikar Taufik
Published: February 2025

Penelitian ini bertujuan untuk mengetahui kelayakan ekspansi usaha yang akan dilakukan oleh PT. Fajar Mitra Krida Abadi. Ekspansi usaha yang akan dilakukan oleh PT. Fajar Mitra Krida Abadi dalam bentuk penambahan kantor. Penilaian dilakukan dengan menggunakan analisis capital budgeting. Penelitian ini dilakukan pada kantor pusat dari PT. Fajar Mitra Krida Abadi yang terletak di Jl. Taman Bintaro No.10, RT.7/RW.11, Bintaro, Kec. Pesanggrahan, Kota Jakarta Selatan, Daerah Khusus Ibukota Jakarta.
Sampel penelitian yang digunakan yaitu laporan keuangan PT. Fajar Mitra Krida Abadi selama 10 tahun (2012-2021), dimana metode yang digunakan adalah purposive sampling yaitu suatu metode pengambilan sampel yang mengambil obyek dengan kriteria tertentu, yaitu PT. Fajar Mitra Krida Abadi menerbitkan laporan keuangan yang telah diaudit yang berakhir pada 31 desember.
Kriteria penilaian investasi yang digunakan yaitu metode Net Present Value (NPV), Internal Rate of Return (IRR), dan Profitability Index (PI). Hasil akhir dari penelitian ini adalah ekspansi usaha yang dilakukan oleh PT. Fajar Mitra Krida Abadi dinyatakan layak karena NPV>0, IRR>biaya modal, dan PI>1. Ekspansi yang di lakukan PT. Fajar Mitra Krida layak untuk dilakukan.
The Influence of Toll Laut Ship on Seaweed Eucheuma Cottoni Trade in Nunukan Border Area
Authors: Basran  , Herlina  , Harianti  , Helena Wilybroda
Published: February 2025

This study discusses (1) The Positive Impact of the Sea Toll (2) The Bene-fits for Seaweed Swordsmen. The research method used in this study is qualitative, which produces primary data and secondary data. This data collection technique is using observation and documentation techniques. The results of this study show (1) the potential impact of the sea toll pro-gram for entrepreneurs in sending dried seaweed crops outside the city of Nunukan for production, the negative impact of the sometimes erratic sea toll ship jadawal makes some entrepreneurs choose to use private ships even though the price is more expensive. (2) Benefits of sea tolls for seaweed traders Better accessibility: With a connected sea route, mer-chants can send their seaweed products to domestic and international markets faster and more smoothly. Lower transportation costs: seaweed entrepreneurs in Nunukan Regency can reduce their transportation costs. This can increase the competitiveness of seaweed products and provide financial benefits for traders.
β-Hydroxybutyrate Facilitates Postinfarction Cardiac Repair via Targeting PHD2
Authors: Wang Cheng , Xu Wenjing , Jiang Shushu , Wu Yichen , Shu Jiangchen , Gao Xinyuan , Huang Kai
Published: February 2025

BACKGROUND:

Acute myocardial infarction (MI) remains one of the major causes of death worldwide, and innovative treatment strategies for MI represent a major challenge in cardiovascular medicine. Caloric restriction (CR) is the most potent nonpharmacological intervention known to prevent age-related disorders and extend lifespan. CR reduces glycolysis and elevates ketone body metabolism. However, whether and how CR or ketone body prevents the progression of MI remains poorly defined.

METHODS:

Mice treated with CR and β-hydroxybutyrate (β-OHB) underwent MI induced by ligation of the left anterior descending coronary artery. Cardiac function was assessed by echocardiographic measurements. Histological analysis, fluorescence-activated cell sorting, and immunofluorescence were used to assess myocardial neovascularization and macrophage filtration. The interaction and modification of β-OHB on PHD2 were analyzed by molecular docking, cellular thermal shift assay, liquid chromatography with tandem mass spectrometry, and coimmunoprecipitation. Macrophage-specific PHD2 K239R and K385R knock-in mice were used to determine the functional significance of β-OHB/PHD2 axis in vivo.

RESULTS:

Twelve weeks of CR markedly rescued postinfarction cardiac function by enhancing neovascularization. CR significantly increased circulating and cardiac ketone bodies, including β-OHB and acetoacetate. We identified β-OHB but not acetoacetate selectively targeted macrophages to stimulate VEGF (vascular endothelial growth factor) production in the peri-infarct area to promote neovascularization and cardiac repair. Mechanistically, β-OHB binds to and induces lysine β-hydroxybutyrylation of PHD2 at lysines 239 and 385, thus blocking its function in the hydroxylation of HIF-1α (hypoxia-inducible factor 1α) and resulting in enhanced HIF1α-dependent VEGF transcription and secretion. More importantly, specific PHD2 lys239 and lys385 mutations in macrophages abolished the preventive effects of exogenous β-OHB on MI in mice.

CONCLUSIONS:

These data reveal a novel regulation of lysine β-hydroxybutyrylation on PHD2 and demonstrate a promising and therapeutic role for β-OHB/PHD2 in effectively accelerating neovascularization and preserving heart function after cardiac ischemia.
The type specimens of Atelopus moreirae Miranda-Ribeiro, 1920 , with notes on the taxonomic status of Atelopus moreirae massarti Cochran, 1948 (Amphibia, Anura, Bufonidae)
Authors: CARAMASCHI ULISSES , JR. JOSÉ P. POMBAL
Published: February 2025

Atelopus moreirae [currently Melanophryniscus moreirae (Miranda-Ribeiro, 1920)] was described on basis of an undefined number of specimens collected in the “Itatiaya”. The type series has not been designated in the original description, and the type locality of the species was referred only in a vague manner. In this paper we revise the specimens examined by Miranda-Ribeiro and define the type series of A. moreirae. In order to better define the type series of the species, a lectotype is designated and the paralectotypes are defined; the type locality is defined and georeferenced. The known distribution of the species is mapped. Additionally, the taxonomic status of Atelopus moreirae massarti Cochran, 1948 is analysed and its synonymy under Melanophryniscus moreirae (Miranda-Ribeiro, 1920) is confirmed, resulting in the conclusion that it should not be considered a valid species or subspecies.
Evaluation of Hematological and Biochemical Parameters that Predict the No-reflow Phenomenon in Patients Undergoing Primary Percutaneous Coronary Intervention
Authors: Aydemir Selim , Aydın Sidar Şiyar , Altınkaya Onur , Aksakal Emrah , Özmen Murat
Published: February 2025

Acute coronary syndromes (ACS) are one of the most common causes of morbidity and mortality worldwide. Primary percutaneous coronary intervention (pPCI) is the main treatment strategy to restore myocardial perfusion. However, the no-reflow phenomenon (NRP) may block coronary flow. The present study focused on assessing and contrasting predictive parameters for NRP in ACS patients. Our research is a retrospective analysis. We assessed the parameters significantly associated with NRP using Cox regression and Receiver operating characteristic (ROC) Curve analysis. The study included 5122 patients who met the criteria. The average age of the patients was 63.9 + 13.2, and 74.4% were male. It was observed that NRP developed in 1.8% of all patients. Age, hemoglobin (Hb), white blood cell (WBC), glucose and low density lipoprotein cholesterol (LDL-C) were determined to be independent predictors of NRP. The power of these parameters to predict NRP was similar, and WBC was the most predictive (Area Under Curve (AUC): 0.605 95% CI: 0.539–0.671, P = .001). We believe that the use of these simple, practical, and routinely used hematological and biochemical parameters will help us predict the risk of developing NRP before pPCI. This information should improve management.
Intelligent backstepping control of power grid-connected wind power generation system using two five-phase PMSGs controlled through the fifteen-switch rectifier
Authors: Sakouchi Abderrahim , Djahbar Abdelkader , Bounadja Elhadj , Moualdia Abdelhafidh
Published: February 2025

This scholarly paper offers a wind power generation system (WPGS) that utilizes a configuration of parallel five-phase permanent magnet synchronous generators (PMSGs). The control mechanism for this system is based on a fifteen-switch rectifier (FSR) topology, which is specifically designed for grid-connected applications. To enhance the control performance of the proposed wind system, an Adaptive Neuro-Fuzzy Inference System (ANFIS)-based Backstepping control (BSC) methodology is utilized for both the generators-side and grid-side converters. The suggested control strategy’s effectiveness is assessed by conducting simulations at varying wind velocities and comparing it to a BSC-based control system. The simulation findings demonstrate that the suggested control system consistently ensures precise tracking of the controlled variables. Furthermore, several aspects of the system’s performance show significant improvements. Specifically, the control method successfully reduces power ripples by 30.5%, DC bus voltage overshoot by 3%, and speed overshoot by 100%. Moreover, the proposed technique reduces the overall harmonic distortion of the network current by 44.44% compared to the BSC method. Additionally, the system’s efficiency is enhanced to 96.5%, surpassing the 96% achieved by the BSC method. Compared to good nonlinear control methods, the results indicate that the suggested strategy outperforms.
Continuous finite-time integral sliding mode control of robotic manipulator with input deadzone and disturbance/uncertainty compensation
Authors: Rauf Arshad , Javaid Umair , Ilyas Muhammad , Khan Awais
Published: February 2025

This paper focuses on tracking trajectory for robotic manipulator, considering external disruptions and internal uncertainties. Robotic manipulators are highly versatile and efficient, finding extensive applications in both industry and research. Accurate control is vital for these manipulators to work properly. But, system uncertainties and disturbances make achieving this accuracy challenging. The proposed controller can manage system uncertainties and disturbances, making it reliable and effective for real-world use. An elegant control approach that combines an integral terminal sliding surface with an observer to achieve chattering-free control, is proposed. Moreover, Lyapunov stability theory is used to prove that it can globally track robotic systems in finite-time. This controller offers clear advantages: it is easy to implement, ensures smooth operation without chattering, achieves fast response, and maintains high tracking accuracy. The simulation results demonstrate that the proposed algorithm is effective in terms of tracking accuracy and resilience.
Cultural variation in trust and acceptability of artificial intelligence diagnostics for dementia
Authors: Chandra Avinash , Senthilvel Kaviya , Anjum Rifah , Uchegbu Ijeoma , Smith Laura J , Beaumont Helen , Punjabi Reshma , Begum Samina , Marshall Charles R
Published: February 2025

Digital health innovations hold diagnostic and therapeutic promise but may be subject to biases for underrepresented groups. We explored perceptions of using artificial intelligence (AI) diagnostics for dementia through a focus group as part of the Automated Brain Image Analysis for Timely and Equitable Dementia Diagnosis (ABATED) study. Qualitative feedback from a diverse public engagement group indicated that cultural variations in trust and acceptability of AI diagnostics may be an unrecognised source of real-world inequity. Efforts focused on the adoption of AI diagnostics in memory clinic pathways should aim to recognise and account for this issue.
Isolated and Invisible: The Barriers to Implementing Constructive Resettlement Approaches in Two English Young Offenders Institutions
Authors: Day Anne-Marie
Published: February 2025

The custodial estate for children aged 10–17 years across England and Wales faces a number of challenges. This article focuses on the perceptions of Resettlement Officers in two Young Offender’s Institutions (YOIs) in England on the challenges of their role: successfully reintegrating children from custody into the community using ‘Constructive Resettlement’ approaches. The findings will present a range of internal barriers encountered by Resettlement Officers that leave them feeling isolated, invisible and misunderstood. Finally, implications for future policy and practice will be considered.
Cross-Disciplinary Methods in Peace Studies Research: Agency, Uncertainty and Emancipation
Authors: Hearnden Scott Robert
Published: February 2025

Cross-disciplinary peace research frequently focuses on social and political power differentials between people. Like the tradition found in the broader social sciences, peace studies seeks to raise consciousness about, and address, unequal relationships and lends itself to the application of cross-disciplinary methodologies. It is concerned with relational inequities and how they might be remedied, including those between the researcher and research participants. This article discusses a suite of methods developed for a peace research agenda about Sri Lanka including intersectionality, social interactionism, semi and unstructured interviews, and interpretative phenomenological analysis. The methods were informed by Sri Lanka’s conflicted social and political spaces. Through the creation of spaces influenced by democracy and rights-based approaches, the methods sought to enable the exercise of participants’ democratic entitlements whilst extinguishing the potential for harm. Through the individual experiences of 22 participants, the methods selected helped to crystalise with greater clarity the structural barriers frustrating people’s agency and the reasons behind their resulting marginalisations. The article affirms that with patience and resources, ground constraints can be overcome, harm mitigated, bias reflexivity and positionality managed, and a set of methods constructed consistent with achieving a peace research agenda.
Inclusion and Participation: A View of TANF and Higher Education Through Extended Case Analysis
Authors: Sosulski Marya R.
Published: February 2025

This paper presents an analysis of three focal cases embedded in a larger study of Welfare Reform and higher education using extended case methods, examining alternative paths to exiting welfare, finding employment, and leaving poverty via education and training. The results show how Welfare Reform’s signature “work-first” approach affects pursuit of educational goals and the role of policy in helping meet families’ needs. Two main themes were revealed: “Authority/Resistance” and “The Culture of Despair” in welfare. Relationships among identity, oppression, and welfare recipients’ ability to advocate to acquire information and resources to achieve educational goals are uncovered, revealing how recipients’ critical analysis of their situations and structural flaws endemic to welfare helps create unique pathways toward their objectives. The culture of welfare can change to be more inclusive, promising hope rather than engendering despair, by shifting focus from culturally bound rules around work toward support for recipients’ self-determination and inclusion.
Evaluation of anti-CD38 monoclonal antibody-based immunotherapy in multiple myeloma with renal insufficiency: a systematic review and meta-analysis
Authors: Bai Hexiang , Zhang Chunlan , Zhao Ailin , Tang Wenjiao , Zhang Li
Published: February 2025

Background:

Renal impairment is one of the common characteristics of multiple myeloma (MM) and makes management of MM more complicated. Even though monoclonal antibodies targeting CD38 have wildly succeeded in treating MM, the addition of anti-CD38 monoclonal antibodies to standard therapy to treat MM patients with renal insufficiency is still poorly studied.

Objectives:

This study aims to evaluate whether using anti-CD38 monoclonal antibody-based immunotherapy would improve the prognosis of MM patients with renal insufficiency.

Design:

This is a systematic review and meta-analysis.

Data sources and methods:

We searched Scopus, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase, and Web of Science Core Collection for randomized controlled trials that enrolled patients with MM who received CD38-targeting monoclonal antibody regimens and reported the efficacy and survival of MM with renal insufficiency. We then performed a meta-analysis to estimate the efficacy of adding anti-CD38 monoclonal antibodies to backbone regimens in MM with renal insufficiency.

Results:

In 7594 studies screened, 12 phase III trials were eligible, including 5 trials for newly diagnosed MM (NDMM; 3194 patients; 1261 with renal insufficiency) and 7 trials for relapsed refractory MM (RRMM; 2657 patients; 648 with renal insufficiency). Among NDMM patients with renal insufficiency, the addition of anti-CD38 monoclonal antibody to backbone regimens was associated with improved progression-free survival (PFS; pooled HR, 0.50; 95% CI, 0.38–0.67; p < 0.001), with little evidence of heterogeneity (Cochran Q, p = 0.19; I2 = 34.7%). Similar results were seen among RRMM patients with renal insufficiency (pooled HR, 0.46; 95% CI, 0.37–0.57; p < 0.001), with no evidence of heterogeneity (Cochran Q, p = 0.89; I2 = 0%). Similarly, the addition of anti-CD38 monoclonal antibody in RRMM among patients with renal insufficiency was associated with improved overall survival (OS; pooled HR, 0.70; 95% CI, 0.57–0.88; p = 0.002), with no significant heterogeneity (Cochran Q, p = 0.69; I2 = 0%).

Conclusion:

This meta-analysis suggests that the addition of anti-CD38 monoclonal antibodies benefits PFS in both NDMM and RRMM with renal insufficiency and OS in RRMM patients with renal insufficiency.
Profiling antimalarial drug-resistant haplotypes in Pfcrt, Pfmdr1, Pfdhps and Pfdhfr genes in Plasmodium falciparum causing malaria in the Central Region of Ghana: a multicentre cross-sectional study
Authors: Dakorah Mavis Puopelle , Aninagyei Enoch , Attoh Juliana , Adzakpah Godwin , Tukwarlba Isaac , Acheampong Desmond Omane
Published: February 2025

Background:

The proliferation of Plasmodium parasites resistant to antimalarial drugs poses a serious threat to human life and remains an obstacle to managing and eradicating Plasmodium falciparum. The surveillance of molecular markers has become necessary to monitor the spread of resistant haplotypes and discover emerging mutations.

Objective:

This molecular epidemiological study aimed to evaluate the prevalence of known mutations in the drug resistance genes Pfcrt, Pfmdr1, Pfdhfr and Pfdhps in the Central Region of Ghana.

Design:

A multi-centre cross-sectional study.

Methods:

This prospective study utilised dried blood spots from individuals with P. falciparum-infection from five districts in the Central Region of Ghana. Selective Whole Genome Amplification (sWGA) and Single Nucleotide Polymorphisms (SNPs) in P. falciparum chloroquine transporter genes ( Pfcrt), P. falciparum multidrug resistance 1 ( Pfmdr1), P. falciparum dihydropteroate synthase ( Pfdhps) and P. falciparum dihydrofolate reductase ( Pfdhfr) were analysed.

Results:

Whole genome sequencing was carried out on 522 samples. Of these, 409 (78%) samples were successfully sequenced. Six (6) of the sequenced samples were of co-infection of other parasite species with P. falciparum and excluded from the analysis. Analysis of the Pfcrt gene revealed 0.5% were CVIET (C72, V73, M74I, N75E, K76T) while the Pfcrt CVMNK (C72, V73, M74, N75, K76) wild-type haplotypes were 97% with (2.5%) (CV[M/I][N/E][K/T]) being mixed haplotypes. In the Pfmdr1 gene, monoclonal haplotypes; NFD (N86, Y184F, D1246) and YFN (N86Y, Y184F, D1246N) occurred at 44% and 9.8%, respectively, whereas mixed- haplotypes (N[Y/F]D and [N/Y][Y/F]D) were 23.5% and 0.3%, respectively. Combined Pfdhfr/ Pfdhps genes yielded about 88% Pfdhfr IRNI (N51I, C59R, S108N, I164) +  Pfdhps A437G haplotypes (conferring partial resistance to Sulphadoxine-Pyrimethamine (SP)) while 9% of the parasites had Pfhdfr IRNI +  Pfdhps A437G + K540E haplotypes (conferring full resistance to SP). The wild-type haplotype, Pfdhfr (N51, C59, S108, I164) and Pfdhps (S436, A437, K540, A581, A613) was not observed.

Conclusion:

The findings show a low prevalence of CVIET and relatively higher rates for Pfmdr1 NFD and parasites with Pfdhfr IRNI (N51I, C59R, S108N, I164) +  Pfdhps A437G haplotypes. These observations advocate for enhanced surveillance which is inimical to malaria management in an endemic area.