bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 925: Continuing anti-EGFR treatment prolonged survival in mCRC patients receiving conversion liver resection
Authors: Hsieh Yao-Yu , Tsai Chin-Wen ,   T-CARE Group, Liang Yi-Hsieh 
Published: March 2024

Abstract
Introduction: Anti-EGFR monoclonal antibody plus doublet chemotherapy is the mainstay of first-line treatment of RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients. Some of these patients might undergo secondary resection. However, there is no standardized suggestion on whether colorectal cancer liver metastasis patients should keep target therapy after secondary resection. NCCN guidelines suggest chemotherapy only in patients receiving primary liver resection. Whether we could spare the use of target therapy after secondary resection is the main aim of our study.
Methods: Using Taiwan's National Health Insurance Research Database, we established a cohort of KRAS wild-type mCRC patients treated with first-line anti-EGFR therapy plus doublet chemotherapy between 2013 and 2018. Secondary surgery was defined as either resection of liver metastases or radiofrequency ablation.
Results: 5694 stage IV mCRC patients received anti-EGFR MAb plus doublet chemotherapy as a first-line treatment between 2013 and 2018. 174 patients were enrolled in the final analysis, with 153 continuing anti-EGFR MAb after secondary resection and 21 patients without anti-EGFR MAb. Compared with those who without anti-EGFR therapy after secondary resection, patients who continued anti-EGFR MAb exhibited significantly longer overall survival (OS; median, 43.8 vs. 31.9 months, p = 0.031) but not in time to treatment failure (TTF; median, 22.2 vs. 26.6 months, p = 0.841). The OS benefits of continuing anti-EGFR MAb remained regardless of left-sided or right-sided primary tumors (40.9 vs. 43.0 months, p = 0.980). The patient cohort from 2016 to 2018 showed more prolonged survival than from 2012 to 2015 (not reached vs. 40.450, p = 0.0305). TTF has no statistical difference when considering patient cohort or primary tumor location. In multivariate analyses, continuing first-line anti-EGFR MAb therapy after secondary resection remained an independent predictor of longer OS.
Conclusion: For mCRC patients who received secondary resection after first-line anti-EGFR and doublet chemotherapy, continuing anti-EGFR MAb after resection was associated with significantly longer OS regardless of primary tumor sidedness.
Citation Format: Yao-Yu Hsieh, Chin-Wen Tsai, T-CARE Group, Yi-Hsieh Liang. Continuing anti-EGFR treatment prolonged survival in mCRC patients receiving conversion liver resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 925.
Abstract 942: Response to systemic therapies in patient-derived cell lines from primary and recurrent adult granulosa cell tumors
Authors: Brink Geertruid , Hami Nizar , Mertens Sander , Hofhuis Ward , Piek Jurgen , de Kroon Cor , Lok Christianne , Roes Eva Maria , van Lonkhuijzen Luc , Nijman Hans , Snippert Hugo , Groeneweg Jolijn , Witteveen Petronella , Zweemer Ronald 
Published: March 2024

Abstract
Introduction: In patients with adult-type granulosa cell tumor (aGCT), a rare subtype of ovarian cancer, surgery is the preferred treatment for both primary and recurrent disease. However, the probability of complete resection decreases after multiple recurrences, in which case systemic treatment is an alternative option. Response rates of systemic therapy are variable, resistance is a problem and it is difficult to predict which therapy will work in which patient. Drug screen testing on patient-derived aGCT cell lines may offer a solution.
Methods: In a national prospective study on aGCT, fresh tissue was collected immediately after surgery. Tumor tissue was cultured and developed into 2D cell lines. Both clinically applicable and experimental drugs were tested on the patient-derived cell lines and two control cell lines. Dose-response curves and synergy were calculated using GraphPad Prism and Compusyn software.
Results: We cultured 34 patient-derived cell lines from tissue of seven patients with primary aGCT and from 13 patients with recurrence. In eight patients multiple sites were cultured. A total of 27 drugs were tested, including 10 monotherapies and 17 combinations. Carboplatin/gemcitabine showed efficacy and synergy 33 of 34 patient-derived cell lines (97%), in contrast to the regular carboplatin/paclitaxel and carboplatin/etoposide combinations (50% and 74%, respectively). The experimental combinations alpelisib/fulvestrant and alpelisib/gemcitabine showed efficacy of more than 75%. Testing of anti-hormonal therapy was not sufficiently reliable with this technique.
Conclusion: Drug screening on patient-derived tumor cell lines adequately reflects the reality of the variable response to systemic therapy in aGCT. In future research, this technique could be used to personalize the systemic treatment of aGCT patients. The response to carboplatin/gemcitabine in our patient-derived cell lines is striking.
Citation Format: Geertruid Brink, Nizar Hami, Sander Mertens, Ward Hofhuis, Jurgen Piek, Cor de Kroon, Christianne Lok, Eva Maria Roes, Luc van Lonkhuijzen, Hans Nijman, Hugo Snippert, Jolijn Groeneweg, Petronella Witteveen, Ronald Zweemer. Response to systemic therapies in patient-derived cell lines from primary and recurrent adult granulosa cell tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 942.
Abstract 948: A novel combinatorial therapy for lethal neuroendocrine prostate cancer
Authors: Wang Mu-En , Tu Wei-Ling , Lu Yi , Wu Jinjin , Bawcom Alyssa , Armstrong Andrew J. , Wang Qianben , Wang Yuzhuo , Huang Jiaoti , Chen Ming 
Published: March 2024

Abstract
Background: Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer that can arise de novo, but more commonly develops after hormone therapies for advanced prostate adenocarcinoma. Current treatment options for NEPC are only palliative, and most patients die within several months. Additionally, single-agent clinical trials targeting NEPC so far have only produced disappointing results, highlighting the clear need to develop effective combinatorial therapies for NEPC. RB1 loss, a pivotal event in the development of NEPC, can sensitize cancer cells to ferroptosis in multiple cancer cell types, including prostate cancer. Here, we aim to identify an optimal combinatorial therapy for NEPC based on targeting ferroptosis.
Methods: We determined the cell-killing efficacy of ferroptosis inducers and several current and emerging treatment regimens for NEPC as single agents, then performed drug synergism analyses of the above two potent treatments. Lastly, we investigated the molecular mechanisms of drug synergism by examining the major types of cell death induced by combinatorial treatment through molecular and biochemical assays.
Results: Our results demonstrated that both ferroptosis inducers and BCL2 inhibitors as single agents led to robust cell death in NEPC cell lines tested. In contrast, cisplatin, the standard of care for NEPC, and Aurora kinase A inhibitor showed modest to no cell-killing effect. Furthermore, suboptimal doses of ferroptosis inducers and BCL-2 inhibitors synergistically induced cell death in NEPC cell lines. Unexpectedly, we found that low-dose ferroptosis inducer led to increased production of mitochondria ROS, which in turn exacerbated BCL-2 suppression-induced apoptosis.
Conclusions: Our findings reveal a novel combinatorial therapy for NEPC. Based on our in vitro data, we will further test the in vivo therapeutic efficacy of ferroptosis inducers combined with BCL-2 inhibitors against NEPC growth.
Citation Format: Mu-En Wang, Wei-Ling Tu, Yi Lu, Jinjin Wu, Alyssa Bawcom, Andrew J. Armstrong, Qianben Wang, Yuzhuo Wang, Jiaoti Huang, Ming Chen. A novel combinatorial therapy for lethal neuroendocrine prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 948.
Incremental Value of a Metabolic Risk Score for Heart Failure Mortality: A Population-Based Study
Authors: Joo Jungnam , Shearer Joseph J. , Wolska Anna , Remaley Alan T. , Otvos James D. , Connelly Margery A. , Sampson Maureen , Bielinski Suzette J. , Larson Nicholas B. , Park Hoyoung , Conners Katherine M. , Turecamo Sarah , Roger Véronique L. 
Published: March 2024

BACKGROUND:
Heart failure is heterogeneous syndrome with persistently high mortality. Nuclear magnetic resonance spectroscopy enables high-throughput metabolomics, suitable for precision phenotyping. We aimed to use targeted metabolomics to derive a metabolic risk score (MRS) that improved mortality risk stratification in heart failure.

METHODS:
Nuclear magnetic resonance was used to measure 21 metabolites (lipoprotein subspecies, branched-chain amino acids, alanine, GlycA (glycoprotein acetylation), ketone bodies, glucose, and citrate) in plasma collected from a heart failure community cohort. The MRS was derived using least absolute shrinkage and selection operator penalized Cox regression and temporal validation. The association between the MRS and mortality and whether risk stratification was improved over the Meta-Analysis Global Group in Chronic Heart Failure clinical risk score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels were assessed.

RESULTS:
The study included 1382 patients (median age, 78 years, 52% men, 43% reduced ejection fraction) with a 5-year survival rate of 48% (95% CI, 46%–51%). The MRS included 9 metabolites measured. In the validation data set, a 1 standard deviation increase in the MRS was associated with a large increased rate of death (hazard ratio, 2.2 [95% CI, 1.9–2.5]) that remained after adjustment for Meta-Analysis Global Group in Chronic Heart Failure score and NT-proBNP (hazard ratio, 1.6 [95% CI, 1.3–1.9]). These associations did not differ by ejection fraction. The integrated discrimination and net reclassification indices, and Uno’s C statistic, indicated that the addition of the MRS improved discrimination over Meta-Analysis Global Group in Chronic Heart Failure and NT-proBNP.

CONCLUSIONS:
This MRS developed in a heart failure community cohort was associated with a large excess risk of death and improved risk stratification beyond an established risk score and clinical markers.
Game Engines for Immersive Visualization: Using Unreal Engine Beyond Entertainment
Authors: Krüger Marcel , Gilbert David , Kuhlen Torsten W. , Gerrits Tim 
Published: March 2024

Abstract
One core aspect of immersive visualization labs is to develop and provide powerful tools and applications that allow for efficient analysis and exploration of scientific data. As the requirements for such applications are often diverse and complex, the same applies to the development process. This has led to a myriad of different tools, frameworks, and approaches that grew and developed over time. The steady advance of commercial off-the-shelf game engines such as Unreal Engine has made them a valuable option for development in immersive visualization labs. In this work, we share our experience of migrating to Unreal Engine as a primary developing environment for immersive visualization applications. We share our considerations on requirements, present use cases developed in our lab to communicate advantages and challenges experienced, discuss implications on our research and development environments, and aim to provide guidance for others within our community facing similar challenges.
The Common Good According to Whom?
Authors: Howard Dana 
Published: March 2024

Abstract
Alex John London’s new book, For the Common Good: Philosophical Foundations of Research Ethics highlights the fact that establishing just social arrangements is not only a matter of incentivizing popular will to act for the common good; it also requires filling in informational gaps about which policies, arrangements, and interventions will advance the basic interests of members in an equitable, effective and efficient manner. Promoting justice requires, in part, acquiring the knowledge for how to do so. In developing this point, London carefully traces these missteps in the main philosophical debates and then resuscitates the importance of questions of justice at the heart of research ethics. In doing so, it provides a transformative corrective for the field. This review critically examines one of the central pillars of London’s egalitarian research imperative approach: the way in which the social value of research is closely linked with minimizing uncertainty among reasonable experts.
The Legal Status and Targeting of Hacker Groups in the Russia-Ukraine Cyber Conflict
Authors: Biggio Giacomo 
Published: March 2024

Abstract
The armed conflict between Russia and Ukraine has been characterized by a considerable number of cyber operations by States and non-State actors in support to either party to the conflict. One year since the Russian invasion of Ukraine, the ‘Russia-Ukraine cyber conflict’ offers valuable insights for estimating the effectiveness of International Humanitarian Law in regulating the status and the conduct of individuals engaging in cyberspace operations during wartime. By discussing the status of hackers groups and individuals who have conducted cyber operations in support of Ukraine, this Article claims that the relevance of the concept of combatancy is diminished in the cyber domain, and that the notion of direct participation in hostilities must be adapted to the specific features of cyberspace. Furthermore, the article focuses on the issues relating to the targeting of individual who directly participate in hostilities by conducting cyber operations in support of Ukraine. By doing so, the Article argues that cyber direct participants place themselves at an increased risk of being attacked, even though the Russian armed forces are limited in their targeting decisions by the principles of proportionality and precaution.
Hebrew Loanwords in Two Rural Dialects of Arabic in Israel
Authors: Abu Elhija Duaa 
Published: March 2024

Abstract
This study examines loanwords from Hebrew into Arabic in the spoken language of people from Iksal village, in the lower Galilee and Um Al-Fahm city, in the Triangle region in Israel. The current study specifically examines borrowing in spoken language, with a comparison of the current findings with a previous research by Abu Elhija (2017), where the data was taken from online writings on Facebook. The research questions the frequency of loanword items from Hebrew into two rural dialects, the domains that appear with Hebrew loanwords, the phonological representations of the loanwords, and the reasons for these words to be borrowed. The main findings show that more loanwords were found in the spoken corpus than in the social media corpus in Abu Elhija (2017). There are more loanwords in synchronous communication compared to asynchronous. The findings also show that topics like education, employment, and technology had the most extensive loanwords. Moreover, in the case of loanwords used by Arabs in Israel, a word can be considered a loanword regardless of its phonology.
The IL-7R antagonist lusvertikimab reduces leukemic burden in xenograft ALL via antibody-dependent cellular phagocytosis
Authors: Lenk Lennart , Baccelli Irène , Laqua Anna , Heymann Julia , Reimer Claas , Dietterle Anna , Winterberg Dorothee , Mary Caroline , Corallo Frédérique , Taurelle Julien , Narbeburu Emma , Neyton Stéphanie , Déramé Mylène , Pengam Sabrina , Vogiatzi Fotini , Bornhauser Beat , Bourquin Jean-Pierre , Raffel Simon , Dovhan Vladyslava , Schüler Thomas , Escherich Gabriele , den Boer Monique L. , Boer Judith M. , Wessels Wiebke , Peipp Matthias , Alten Julia , Antić Željko , Bergmann Anke K. , Schrappe Martin , Cario Gunnar , Brüggemann Monika , Poirier Nicolas , Schewe Denis M. 
Published: March 2024

Abstract
Acute lymphoblastic leukemia (ALL) arises from the uncontrolled proliferation of B-cell precursors (BCP-ALL) or T cells (T-ALL). Current treatment protocols obtain high cure rates in children but are based on toxic polychemotherapy. Novel therapies are urgently needed, especially in relapsed/refractory (R/R) disease, high-risk (HR) leukemias and T-ALL, in which immunotherapy approaches remain scarce. Although the interleukin-7 receptor (IL-7R) plays a pivotal role in ALL development, no IL-7R–targeting immunotherapy has yet reached clinical application in ALL. The IL-7Rα chain (CD127)–targeting IgG4 antibody lusvertikimab (LUSV; formerly OSE-127) is a full antagonist of the IL-7R pathway, showing a good safety profile in healthy volunteers. Here, we show that ∼85% of ALL cases express surface CD127. We demonstrate significant in vivo efficacy of LUSV immunotherapy in a heterogeneous cohort of BCP- and T-ALL patient-derived xenografts (PDX) in minimal residual disease (MRD) and overt leukemia models, including R/R and HR leukemias. Importantly, LUSV was particularly effective when combined with polychemotherapy in a phase 2-like PDX study with CD127high samples leading to MRD-negativity in &gt;50% of mice treated with combination therapy. Mechanistically, LUSV targeted ALL cells via a dual mode of action comprising direct IL-7R antagonistic activity and induction of macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). LUSV–mediated in vitro ADCP levels significantly correlated with CD127 expression levels and the reduction of leukemia burden upon treatment of PDX animals in vivo. Altogether, through its dual mode of action and good safety profile, LUSV may represent a novel immunotherapy option for any CD127+ ALL, particularly in combination with standard-of-care polychemotherapy.
Endothelial ZIP8 plays a minor role in BMP6 regulation by iron in mice
Authors: Fisher Allison L. , Phillips Sydney , Wang Chia-Yu , Paulo Joao A. , Xiao Xia , Moschetta Gillian A. , Sridhar Adhvaith , Mancias Joseph D. , Babitt Jodie L. 
Published: March 2024

Abstract
Iron-mediated induction of bone morphogenetic protein (BMP)6 expression by liver endothelial cells is essential for iron homeostasis regulation. We used multiple dietary and genetic mouse cohorts to demonstrate a minor functional role for the metal-ion transporter ZIP8 in regulating BMP6 expression under high-iron conditions.
Vascular smooth muscle cells in response to cholesterol crystals modulates inflammatory cytokines release and promotes neutrophil extracellular trap formation
Authors: Thazhathveettil Jishamol , Kumawat Ashok Kumar , Demirel Isak , Sirsjö Allan , Paramel Geena Varghese 
Published: March 2024

Abstract
Background
The formation and accumulation of cholesterol crystals (CC) at the lesion site is a hallmark of atherosclerosis. Although studies have shown the importance of vascular smooth muscle cells (VSMCs) in the disease atherosclerosis, little is known about the molecular mechanism behind the uptake of CC in VSMCs and their role in modulating immune response.

Methods
Human aortic smooth muscle cells were cultured and treated with CC. CC uptake and CC mediated signaling pathway and protein induction were studied using flow cytometry, confocal microscopy, western blot and Olink proteomics. Conditioned medium from CC treated VSMCs was used to study neutrophil adhesion, ROS production and phagocytosis. Neutrophil extracellular traps (NETs) formations were visualized using confocal microscopy.

Results
VSMCs and macrophages were found around CC clefts in human carotid plaques. CC uptake in VSMCs are largely through micropinocytosis and phagocytosis via PI3K–AkT dependent pathway. The uptake of CC in VSMCs induce the release inflammatory proteins, including IL-33, an alarming cytokine. Conditioned medium from CC treated VSMCs can induce neutrophil adhesion, neutrophil reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) formation. IL-33 neutralization in conditioned medium from CC treated VSMCs inhibited neutrophil ROS production and NETs formation.

Conclusion
We demonstrate that VSMCs due to its vicinity to CC clefts in human atherosclerotic lesion can modulate local immune response and we further reveal that the interaction between CC and VSMCs impart an inflammatory milieu in the atherosclerotic microenvironment by promoting IL-33 dependent neutrophil influx and NETs formation.
A case of Lomentospora prolificans endophthalmitis treated with the novel antifungal agent Olorofim
Authors: Dong Michael , Pearce Fiona , Singh Nandini , Lin Ming-Lee 
Published: March 2024

Abstract
Purpose
To report a case of endogenous Lomentospora prolificans endophthalmitis treated with the novel antifungal agent Olorofim.

Case report
A 57-year-old man developed disseminated Lomentospora prolificans with right endophthalmitis on the background of immunosuppression following lung transplantation for interstitial lung disease. He was treated with early vitrectomy, intravitreal voriconazole, and systemic Olorofim, voriconazole and terbinafine. His symptoms improved and remained stable in the right eye. Eight weeks later the patient represented with Lomentopora prolificans endophthalmitis in the left eye when systemic voriconazole and terbinafine treatment were withdrawn. Despite aggressive treatment he ultimately succumbed due to vascular complications of extensive disseminated disease.

Conclusion
We report a rare case of disseminated Lomentosporosis with panophthalmitis in an immunocompromised host with prolonged survival on systemic Olorofim, voriconazole and terbinafine in conjunction with pars plana vitrectomy and intravitreal voriconazole. Early suspicion of an opportunistic fungal infection is critical, as managing disseminated disease is often unsuccessful. Despite presumed inherent resistance, intravitreal and systemic voriconazole appeared to limit disease progression in the right eye. The potential synergistic effects of combined antifungal therapy with orotomides warrant further investigation.
An evolutionary view of the Fusarium core genome
Authors: Gomez-Chavarria Daniel A. , Rua-Giraldo Alvaro L. , Alzate Juan F. 
Published: March 2024

AbstractFusarium, a member of the Ascomycota fungi, encompasses several pathogenic species significant to plants and animals. Some phytopathogenic species have received special attention due to their negative economic impact on the agricultural industry around the world. Traditionally, identification and taxonomic analysis of Fusarium have relied on morphological and phenotypic features, including the fungal host, leading to taxonomic conflicts that have been solved using molecular systematic technologies. In this work, we applied a phylogenomic approach that allowed us to resolve the evolutionary history of the species complexes of the genus and present evidence that supports the F. ventricosum species complex as the most basal lineage of the genus. Additionally, we present evidence that proposes modifications to the previous hypothesis of the evolutionary history of the F. staphyleae, F. newnesense, F. nisikadoi, F. oxysporum, and F. fujikuroi species complexes. Evolutionary analysis showed that the genome GC content tends to be lower in more modern lineages, in both, the whole-genome and core-genome coding DNA sequences. In contrast, genome size gain and losses are present during the evolution of the genus. Interestingly, core genome duplication events positively correlate with genome size. Evolutionary and genome conservation analysis supports the F3 hypothesis of Fusarium as a more compact and conserved group in terms of genome conservation. By contrast, outside of the F3 hypothesis, the most basal clades only share 8.8% of its genomic sequences with the F3 clade.