bluuebunny/crossref_metadata_2025 huggingface dataset:
Wannabe Bounded Treewidth Graphs Admit a Polynomial Kernel for Directed Feedback Vertex Set
Authors: Lokshtanov Daniel , Ramanujan Maadapuzhi-Sridharan , Saurabh Saket , Sharma Roohani , Zehavi Meirav
Published: January 2025

In the
Directed Feedback Vertex Set (DFVS)
problem, given a digraph
D
and a positive integer
k
, the goal is to check if there exists a set of at most
k
vertices whose deletion from
D
results in a directed acyclic graph. The existence of a polynomial kernel for
DFVS
, parameterized by the solution size
k
, is a central open problem in kernelization. In this article, we give a polynomial kernel for
DFVS
parameterized by
k
plus
the size of a treewidth-η modulator (of the underlying undirected graph), where η is any fixed positive integer. Since the status of the existence of a polynomial kernel for
DFVS
(parameterized by the solution size) has been open for a very long time now, and it is known to not admit a polynomial kernel when the parameter is the size of a treewidth-2 modulator, solution size plus the size of the treewidth-η modulator makes for an interesting choice of parameter to study. In fact, the polynomial kernelization complexity of
DFVS
parameterized by the size of the undirected feedback vertex set (treewidth-1 modulator) in the underlying undirected graph has already been studied in literature. Our choice of parameter strictly encompasses previous positive kernelization results on
DFVS
. Our result is based on a novel application of the tool of
important separators
embedded in state-of-the-art machinery such as protrusion decompositions.
How are We Detecting Inconsistent Method Names? An Empirical Study from Code Review Perspective
Authors: Kim Kisub , Zhou Xin , Kim Dongsun , Lawall Julia , Liu Kui , Bissyandé Tegawendé F. , Klein Jacques , Lee Jaekwon , Lo David
Published: January 2025

Proper naming of methods can make program code easier to understand, and thus enhance software maintainability. Yet, developers may use inconsistent names due to poor communication or a lack of familiarity with conventions within the software development lifecycle. To address this issue, much research effort has been invested into building automatic tools that can check for method name inconsistency and recommend consistent names. However, existing datasets generally do not provide precise details about why a method name was deemed improper and required to be changed. Such information can give useful hints on how to improve the recommendation of adequate method names. Accordingly, we construct a sample method-naming benchmark, ReName4J, by matching name changes with code reviews. We then present an empirical study on how state-of-the-art techniques perform in detecting or recommending consistent and inconsistent method names based on ReName4J. The main purpose of the study is to reveal a different perspective based on reviewed names rather than proposing a complete benchmark. We find that the existing techniques underperform on our review-driven benchmark, both in inconsistent checking and the recommendation. We further identify potential biases in the evaluation of existing techniques, which future research should consider thoroughly.
Security and Privacy Challenges of Large Language Models: A Survey
Authors: Das Badhan Chandra , Amini M. Hadi , Wu Yanzhao
Published: January 2025

Large language models (LLMs) have demonstrated extraordinary capabilities and contributed to multiple fields, such as generating and summarizing text, language translation, and question-answering. Today, LLMs have become quite popular tools in natural language processing tasks, with the capability to analyze complicated linguistic patterns and provide relevant responses depending on the context. While offering significant advantages, these models are also vulnerable to security and privacy attacks, such as jailbreaking attacks, data poisoning attacks, and personally identifiable information leakage attacks. This survey provides a thorough review of the security and privacy challenges of LLMs, along with the application-based risks in various domains, such as transportation, education, and healthcare. We assess the extent of LLM vulnerabilities, investigate emerging security and privacy attacks against LLMs, and review potential defense mechanisms. Additionally, the survey outlines existing research gaps and highlights future research directions.
Automatic construction of the citation network from the medieval Jewish Responsa literature
Authors: Ben-Gigi Nati , Zhitomirsky-Geffet Maayan , Schler Jonathan , Katzoff Binyamin
Published: January 2025

This article presents a novel approach for the citation network construction from Jewish Responsa literature based on automatic extraction of references from texts. Jewish Responsa literature contains thousands of answers to questions related to Jewish law (Halachah), spanning over 1,300 years by authors from all over the world. This literature is abundant with references, but because of their high lexical and format variability their automatic identification and extraction is very challenging. In this article we present a novel, multi layered approach that splits the reference extraction task into two main subtasks: i) reference boundaries’ identification; ii) reference internal components’ identification. We experimented with several different machine learning models: CRF (Conditional Random Field) model, BERT (Bidirectional Encoder Representations from Transformers) model, and a combined approach, BERT-CRF. Additionally, we examined the influence of the training corpus on the model’s accuracy by comparing the performance of the models trained on modern Hebrew vs. Rabbinic Hebrew. We found that the best results were achieved by a BERT-CRF model trained on Rabbinic Hebrew. The constructed network can be utilized to build various tools for analyzing trends and influences in the Jewish Halachic corpus, such as the most influencing authors, the authors’ sources of authority, and their evolution over time and place.
Reasoning About Exceptional Behavior At the Level of Java Bytecode with ByteBack
Authors: Paganoni Marco , Furia Carlo A.
Published: January 2025

A program’s exceptional behavior can substantially complicate its control flow, and hence accurately reasoning about the program’s correctness. On the other hand, formally verifying realistic programs is likely to involve exceptions—a ubiquitous feature in modern programming languages.

In this paper, we present a novel approach to verify the exceptional behavior of Java programs, which extends our previous work on
Byte Back
.
Byte Back
works on a program’s bytecode, while providing means to specify the intended behavior at the source-code level; this approach sets
Byte Back
apart from most state-of-the-art verifiers that target source code. To explicitly model a program’s exceptional behavior in a way that is amenable to formal reasoning, we introduce Vimp: a high-level bytecode representation that extends the Soot framework’s Jimple with verification-oriented features, thus serving as an intermediate layer between bytecode and the Boogie intermediate verification language. Working on bytecode through this intermediate layer brings flexibility and adaptability to new language versions and variants: as our experiments demonstrate,
Byte Back
can verify programs involving exceptional behavior in all versions of Java, as well as in Scala and Kotlin (two other popular JVM languages).
Comparative response of casein protein hydrolysate-fed young and older human serum on in vitro muscle protein metabolism and myotube size
Authors: Pauk Martina , Amigo-Benavent Miryam , Patel Bijal , Jakeman Philip M. , Carson Brian P.
Published: January 2025

This study extended previously developed coculture models and found that treating skeletal muscle cells with ex vivo human serum following feeding with a casein protein hydrolysate resulted in greater protein signaling, muscle protein synthesis, muscle growth, and lower expression of genes related to muscle protein breakdown compared with feeding with a nonessential amino acid control. These findings were similar using serum from young and older adults.
Effect of exogenous β-hydroxybutyrate on BDNF signaling, cognition, and amyloid precursor protein processing in humans with T2D and insulin-resistant rodents
Authors: Baranowski B. J. , Oliveira B. F. , Falkenhain K. , Little J. P. , Mohammad A. , Beaudette S. M. , Finch M. S. , Caldwell H. G. , Neudorf H. , MacPherson R. E. K. , Walsh J. J.
Published: January 2025

Ketone supplementation does not alter circulating BDNF levels or cognition in humans with T2D. Acute and chronic ketone supplementation in C57BL/6J mice did not change BDNF protein content or improve recognition memory. Ketone supplementation in C57BL/6J mice positively modulated β-site amyloid precursor protein cleaving enzyme 1 (BACE1) activity, providing a potential future therapeutic strategy.
Constitutive loss of kynurenine-3-monooxygenase changes circulating kynurenine metabolites without affecting systemic energy metabolism
Authors: Dumont Kyle D. , Jannig Paulo R. , Porsmyr-Palmertz Margareta , Ruas Jorge L.
Published: January 2025

The kynurenine pathway of tryptophan degradation is influenced by metabolic stressors: exercise raises circulating KYNA levels, while obesity is linked to increased QUIN. We investigated whether a mouse model lacking KMO—leading to increased circulating KYNA and decreased QUIN—would exhibit changes in energy metabolism. We found that energy metabolism was largely unaffected despite robust changes in circulating kynurenine metabolites, suggesting that systemic KMO inhibition may not have widespread metabolic effects.
The Developmental Assets Model for Positive Youth Development and Social Contribution: A Qualitative Study of Spanish Undergraduates
Authors: Gomez-Baya Diego , Martin-Barrado Antonio-David , Grasmeijer Anna Jean , Martin-Gomez Carmen , Palacios-Galvez Maria Soledad , Morales-Marente Elena
Published: January 2025

Relational developmental systems theory integrates a positive youth development (PYD) perspective on the transition to adulthood. Meanwhile, the developmental assets (DAs) model describes the personal and contextual resources that nurture PYD. This study examined the fulfillment of DAs and experience of social contribution in a sample of 23 Spanish undergraduates from seven universities (age range 18–25, Mage = 20.57, SD = 2.06). Data were collected from seven focus groups, each comprising undergraduate students from different academic years, universities, and degree programs. All interviews were conducted in Spanish for 50–65 min and comprised eight questions divided into three sections (internal assets, external assets, and social contribution and barriers). The results indicated that among internal assets, positive values, social competencies, and positive identity were important for adolescents. Additionally, the external asset of social support was a highly relevant resource. Regarding social contribution, the participants showed empathy towards the needs of the community and reported that helping others was rewarding. Clearly, the youth’s perspectives on their development should be considered while creating prevention and promotion programs that foster internal and external assets.
Imperatorin’s Effect on Myocardial Infarction Based on Network Pharmacology and Molecular Docking
Authors: Zhang Ruizhe , Wang Peng , Jin Yao , Xie Qingya , Xiao Pingxi
Published: January 2025

Purpose: Myocardial infarction (MI), a severe cardiovascular disease, is the result of insufficient blood supply to the myocardium. Despite the improvements of conventional therapies, new approaches are needed to improve the outcome post‐MI. Imperatorin is a natural compound with multiple pharmacological properties and potential cardioprotective effects. Therefore, this work investigated imperatorin’s therapeutic effects and its mechanism of action in an MI mouse model.

Methods: Network pharmacology, molecular docking, and experimental validation were performed for exploring the pharmacokinetic properties, therapeutic effects, and molecular targets of imperatorin in MI. Permanent ligation of the left anterior descending artery was performed in male C57BL/6 mice to induce MI before treatment with imperatorin once per day for 1 week. Echocardiography, heart histology, RNA sequencing, and quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR) as well as western blotting were carried out for evaluating cardiac function and structure, as well as gene and protein expression.

Results: Imperatorin significantly improved cardiac function, preserved cardiac structure, attenuated cardiac remodeling and fibrosis, and reduced cardiomyocyte apoptosis in MI mice. Eight differentially expressed genes overlapping with key target genes were found, two upregulated and six downregulated. A key target in signaling pathways associated with imperatorin effect in MI was angiotensin‐converting enzyme (ACE). Imperatorin inhibited ACE–angiotensin II (Ang II)–angiotensin II Type 1 receptor (AT1R) axis in MI mice.

Conclusion: Imperatorin attenuated MI by inhibiting the ACE–Ang II–AT1R axis. Thus, imperatorin might be considered a potential therapeutic agent to cure MI.
The Role of Ursodeoxycholic Acid Administration During the COVID‐19 Pandemic: A Questionnaire Survey
Authors: Zhou Cheng , Jia Ran , Yang Jinqiu , Liu Tong , Liu Xiaoyan , Yang Lin , Zhao Wenxia
Published: January 2025

In December 2022, China classified COVID‐19 as a category B infectious disease. This ended 2 years of close epidemiological surveillance of COVID‐19. The objective of this questionnaire was to assess the infection status in the COVID‐19 pandemic since December in Henan Province, China, and the prevalence of infection in people who were taking ursodeoxycholic acid (UDCA) during this period. We distributed questionnaires to patients attending the gastroenterology clinic at the First Affiliated Hospital of Henan University of Chinese Medicine. The questionnaire lasted for 3 weeks and a total of 660 were collected, of which the number of people taking UDCA was 70. This is the first investigation into the rate of infection among those taking UDCA during the time of the COVID‐19 pandemic. Our results showed that the overall infection rate among those taking UDCA was 71.43% (n = 50), with a 10% (n = 7) rate of asymptomatic infections, which was significantly lower than the 85.42% (n = 504) and 6.27% (n = 37) rates among respondents who did not take. The administration of UDCA showed a trend toward reducing the rate of COVID‐19 infection, but the difference was not statistically significant when compared to patients with shorter durations of medication use. While less than 30% of participants remained uninfected during the study period, indicating a potential protective effect, it is important to note that complete prevention of SARS‐CoV‐2 infection by UDCA was not observed.
Therapeutic Efficacy of Reward Circuit‐Targeted Transcranial Magnetic Stimulation (TMS) on Suicidal Ideation in Depressed Patients: A Sham‐Controlled Trial of Two TMS Protocols
Authors: Huang Xinyu , Xi Chunhua , Fang Ya , Ye Rong , Wang Xin , Zhang Shu , Cui Yuqiu , Guo Yang , Zhang Jingyi , Ji Gong-Jun , Zhu Chunyan , Luo Yuejia , Chen Xiaofen , Wang Kai , Tian Yanghua , Yu Fengqiong
Published: January 2025

Background: Suicide is one of the leading causes of premature death, and dysfunctional reward processing may serve as a potential mechanism. However, effective treatment targeting reward circuits is rarely reported.

Objective: The present study investigated the therapeutic efficacy of two individualized protocols, repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS), targeting the left dorsolateral prefrontal cortex (lDLPFC)–nucleus accumbens (NAcc) circuit on suicidal ideation among patients with major depressive disorder (MDD).

Methods: Here, 40 healthy controls (HCs) and 70 MDD patients (MDDs) were recruited for this double‐blinded, sham‐controlled clinical trial. The reward learning process during the Iowa gambling task (IGT) was initially measured at the baseline. Further, 62 MDDs were assigned to receive 15 daily sessions of individualized rTMS (n = 25), iTBS (n = 15), or sham treatment (n = 22) to the site of strongest lDLPFC–NAcc connectivity.

Results: We found MDDs demonstrated abnormalities in both IGT performance and reward‐associated event‐related potential (ERP) components compared to HCs. MDDs in the rTMS and iTBS groups showed significant improvements in suicidal ideation and anhedonia symptoms compared to the sham group. The rTMS group also exhibited a more negative‐going N170 and feedback‐related negativity (FRN) after treatment, and the increase in N170 absolute amplitude posttreatment showed a trend of correlation with improved Temporal Experience Pleasure Scales (TEPSs) and TEPS‐anticipatory (TEPS‐ant) scores.

Conclusion: The current study indicates that reward circuit‐based rTMS and iTBS showed comparable antisuicidal effects in depressive patients, suggesting that the lDLPFC–NAcc pathway may serve as a potential treatment target.

Trial Registration: ClinicalTrials.gov identifier: NCT03991572
Blow‐Up Results for a Weakly Coupled System of Semilinear Wave Equations in de Sitter Spacetime
Authors: Yang Jie , Ma Xia , Liu Caiyun
Published: January 2025

The main goal of this paper is to study blow‐up of solutions of a weakly coupled system for semilinear wave equations with damping terms and mass terms in the de Sitter spacetime. The exponential, polynomial, and logarithmic growth of time‐dependent factors in nonlinear terms are investigated by using iterative methods, respectively. Upper bound lifespan estimates of solutions to the problem are established. To the best of our knowledge, the results in Theorems 1.1–1.3 are new. In particular, the critical curve for exponents (p, q) in nonlinear terms in this problem is same as the critical curve for a weakly coupled system of semilinear wave equations with power nonlinearities. In addition, wave trends are expressed by numerical simulation.
Area‐Specific Assessment of Stratum Corneum Hydration and Transepidermal Water Loss in Pediatric Patients With Atopic Dermatitis
Authors: Kwon Bo Yeon , Kim Dohyeong , Shim Kyungmin , Nguyen Cindy , Lee Hee Chul , Kang Daeshik , Kim Hohyun , Seo SungChul
Published: January 2025

SCORring atopic dermatitis (SCORAD) is widely used to assess the severity of atopic eczema, but score systems based on the entire body may be limited in effective monitoring and intervention. It is crucial to monitor moisture levels in each affected body part, but empirical research is still lacking. The objective of this study was to analyze the levels of stratum corneum hydration (SCH) and transepidermal water loss (TEWL) in atopic dermatitis (AD) patients, focusing on the presence and location of atopic lesions at different body sites. The levels of TEWL and SCH were measured using the AF200 AquaFlux and the Corneometer, respectively, at 15 body sites. 98 children under the age of 10 were measured, including 83 AD patients and 15 in the control group. Patients were also assessed with SCORAD and for the presence of atopic lesions at each body site. 58.7% of AD patients had lesions in the antecubital fossa and popliteal fossa, with corresponding low SCH levels and high TEWL in the upper body. The differences in TEWL between the control group and AD patients were confirmed significant in the neck and antecubital fossa regions, while differences in SCH were identified in the face, antecubital fossa, and popliteal fossa regions. A higher TEWL was found among AD patients with atopic lesions in the face and ankle. This study suggests that continuous monitoring of SCH and TEWL levels at specific body sites can provide insights into identifying vulnerable body areas to AD and supplement the SCORAD system for more effective clinical intervention and prevention strategies.
Exposing the Forgery Clues of DeepFakes via Exploring the Inconsistent Expression Cues
Authors: Liu Jiatong , Wang Lina , Wang Run , Ke Jianpeng , Ye Xi , Wu Yadi
Published: January 2025

The pervasive prevalence of DeepFakes poses a profound threat to individual privacy and the stability of society. Believing the synthetic videos of a celebrity and trumping up impersonated forgery videos as authentic are just a few consequences generated by DeepFakes. We investigate current detectors that blindly deploy deep learning techniques that are not effective in capturing subtle clues of forgery when generative models produce remarkably realistic faces. Inspired by the fact that synthetic operations inevitably modify the regions of eyes and mouth to match the target face with the identity or expression of the source face, we conjecture that the continuity of facial movement patterns representing expressions that existed in the veritable faces will be disrupted or completely broken in synthetic faces, making it a potentially formidable indicator for DeepFake detection. To prove this conjecture, we utilize a dual‐branch network to capture the inconsistent patterns of facial movements within eyes and mouth regions separately. Extensive experiments on popular FaceForensics++, Celeb‐DF‐v1, Celeb‐DF‐v2, and DFDC‐Preview datasets have demonstrated not only effectiveness but also the robust capability of our method to outperform the state‐of‐the‐art baselines. Moreover, this work represents greater robustness against adversarial attacks, achieving ASR of 54.8% in the I‐FGSM attack and 43.1% in the PGD attack on the DeepFakes dataset of FaceForensics++, respectively.
Water Physicochemical Properties Influence the Production, Nutritional Composition, and Antioxidant Activity of Gracilaria tenuistipitata From the Northern Bay of Bengal, Bangladesh
Authors: Ullah Md. Rahamat , Haque Mohammed Ashraful , Hasan Md. Monjurul , Yasmin Farhana , Bosu Aovijite , Islam Md. Amirul , Tanu Mohosena Begum
Published: January 2025

This study investigates the influence of water physicochemical properties on the growth, production, nutritional composition, and antioxidant properties of Gracilaria tenuistipitata, cultivated at two different sites (Gangamati and Hazipur) along the northern Bay of Bengal, Bangladesh. The water quality parameters were monitored weekly. Results revealed that the Gangamati site is characterized by significantly higher (p < 0.05) salinity (14.75 ± 4.89 ppt), transparency (60.50 ± 9.57 cm), and total dissolved solids (6154.90 ± 1492.50 mg/L) compared to the Hazipur site. The Gangamati site significantly (p < 0.05) outperformed the Hazipur site in terms of daily growth rate and production. Furthermore, proximate composition analysis indicated significantly higher (p < 0.05) protein (25.06 ± 0.90% DW), lipid (1.22 ± 0.05% DW), fiber (7.03 ± 0.76% DW), and carbohydrate (38.41 ± 0.80% DW) contents in seaweed from the Gangamati site. The mineral content of G. tenuistipitata was also influenced by the culture site significantly (p < 0.05). Amino acid analysis demonstrated superior protein quality in Gangamati seaweed, with significantly higher levels of essential (77.286 ± 0.06 mg/g) and nonessential (95.243 ± 0.07 mg/g) amino acids than the Hazipur site. The fatty acid profiles varied significantly between the two sites, with seaweed from the Gangamati site exhibiting higher levels of unsaturated fatty acids (41.27 ± 0.05%) compared to Hazipur, indicating superior nutritional lipid quality indices. Bioactive compounds were significantly higher (p < 0.05) in Gangamati seaweed, along with higher antioxidant activity. Overall, these results indicate that the Gangamati estuary provides a better environment for the cultivation of G. tenuistipitata, resulting in seaweed with superior nutritional and bioactive properties.
Real‐Time Reverse Transcription Multienzyme Isothermal Rapid Amplification for Rapid Detection of African Horse Sickness Virus
Authors: Huang Chaohua , Wang Jianchang , Ruan Zhouxi , Wu Jiang , Lin Yanxing , Cao Chenfu , Yang Junxing , Weng Qiaoyu , Jin Ye , Chen Peng , Hua Qunyi
Published: January 2025

African horse sickness (AHS) is an acute infectious disease of equids caused by the AHS virus (AHSV), which can cause up to 90% mortality in naive horses. Reliable and rapid diagnosis is crucial for the surveillance and control of AHSV. As one of the AHSV detection methods recommended by World Organization for Animal Health (WOAH), the RT‐qPCR assay has the drawbacks such as complex operation, expensive instruments, and long detecting time, which limit its application in simple laboratories or outdoors. In this study, a real‐time reverse transcription multienzyme isothermal rapid amplification (RT‐MIRA) assay was established to detect AHSV. Primers and exo‐probes were designed, synthesized, and screened based on the conserved regions of the AHSV Seg-7 gene. A series of experiments were conducted to evaluate the performances of the established real‐time RT‐MIRA for detecting AHSV. The valid testing results showed that this method was highly specific for the detection of AHSV, without exhibiting any cross‐reactivity towards other equine viruses or other Orbivirus; its limit of detection (LOD) was 10 copies/μL, which was consistent with that of RT‐qPCR, meaning it had good sensitivity for detecting AHSV. Furthermore, the real‐time RT‐MIRA for AHSV performed good repeatability, and its standard curve exhibited good linearity with a correlation coefficient of R2 = 0.9898, which indicated that the established method could be used for the quantitative detection of ASHV. As no AHS infection cases have been reported in China, 120 simulated clinical samples were tested by the real‐time RT‐MIRA and RT‐qPCR for AHSV, which results showed there was a significant correlation between the two assays, with a κ value of 0.966 and an R2 value of 0.9576. Parallel detection of 396 equine blood samples and 1760 Culicoides by this method and the RT‐qPCR showed that all samples were negative for AHSV. Furthermore, the results of the real‐time RT‐MIRA could be judged by naked eyes under a portable equipment with blue light (480 nm). In conclusion, the real‐time RT‐MIRA for AHSV was specific and sensitive and had the advantages of convenient operation, visualization, no need for special equipment, and could be a reliable tool for rapid screening and detection of AHSV in field or border ports.
Investigating the Multidomain Impact of Palliative Care on End‐of‐Life Patients: A Comprehensive Evaluation
Authors: Abu Hasheesh Mohammad O.
Published: January 2025

Background: Palliative care is recognized for its holistic approach in improving the quality of life for patients and their families, focusing on pain relief, symptom management, and addressing emotional, social, and spiritual needs. However, the field is evolving due to increasing demand for these specialized services, emphasizing the need for the ongoing research into palliative care practices.

Research Purpose: Is to investigate the multidomain impact of palliative care on end‐of‐life patients and evaluate their effectiveness on these domains.

Method: A quantitative descriptive design was adopted for conducting the current study. Approval obtained from a designated hospital in Amman, Jordan, and official permission to carry out the study. The study’s participants consisted primarily of physicians and nurses who were involved in providing care to terminally ill patients. The research tool employed in this study is a standardized palliative care assessment that was used in Australia, with modifications based on the literature review. The validity and reliability of the adapted tool have been ensured through rigorous testing procedures.

Results: Findings indicated that the implementation of standardized practical palliative care exhibited an average level across all domains, specifically, the spiritual domain received the highest mean score (1.80), while the structural domain had the lowest (1.69). There were significant differences in palliative care provision across specialized work sites, with radiotherapy and blood disease sites scoring higher (M = 2.04 and M = 1.87, respectively). Educational levels significantly influenced care perceptions, favoring BSc holders. Age did not significantly affect palliative care provision, probably because of standardized care protocols and sample size. In addition, nurses rated palliative care higher than physicians, likely due to their more direct patient involvement.

Conclusion: In light of the results, it is evident that there is a pressing need to consistently evaluate the healthcare services offered to meet the needs of the increasing population of terminally ill patients.
Supplementary Table S8 from AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers
Authors: Belmontes Brian , Slemmons Katherine K. , Su Chun , Liu Siyuan , Policheni Antonia N. , Moriguchi Jodi , Tan Hong , Xie Fang , Aiello Daniel Andrew , Yang Yajing , Lazaro Raul , Aeffner Famke , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Vestergaard Mikkel , Cowland Sanne , Andersson Jan , Sarvary Ian , Chen Qing , Sharma Pooja , Lopez Patricia , Tamayo Nuria , Pettus Liping H. , Ghimire-Rijal Sudipa , Mukund Susmith , Allen Jennifer R. , DeVoss Jason , Coxon Angela , Rodon Jordi , Ghiringhelli François , Penel Nicolas , Prenen Hans , Glad Sanne , Chuang Chen-Hua , Keyvanjah Kiana , Townsley Danielle M. , Butler John R. , Bourbeau Matthew P. , Caenepeel Sean , Hughes Paul E.
Published: January 2025

Supplementary Table S8: Antibodies for ELISA and Western Blot
Supplementary Table S6 from AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers
Authors: Belmontes Brian , Slemmons Katherine K. , Su Chun , Liu Siyuan , Policheni Antonia N. , Moriguchi Jodi , Tan Hong , Xie Fang , Aiello Daniel Andrew , Yang Yajing , Lazaro Raul , Aeffner Famke , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Vestergaard Mikkel , Cowland Sanne , Andersson Jan , Sarvary Ian , Chen Qing , Sharma Pooja , Lopez Patricia , Tamayo Nuria , Pettus Liping H. , Ghimire-Rijal Sudipa , Mukund Susmith , Allen Jennifer R. , DeVoss Jason , Coxon Angela , Rodon Jordi , Ghiringhelli François , Penel Nicolas , Prenen Hans , Glad Sanne , Chuang Chen-Hua , Keyvanjah Kiana , Townsley Danielle M. , Butler John R. , Bourbeau Matthew P. , Caenepeel Sean , Hughes Paul E.
Published: January 2025

Supplementary Table S6: Significant AMG 193-associated splicing events
Supplementary Table S5 from Cancer Prevalence across Vertebrates
Authors: Compton Zachary T. , Mellon Walker , Harris Valerie K. , Rupp Shawn , Mallo Diego , Kapsetaki Stefania E. , Wilmot Mallory , Kennington Ryan , Noble Kathleen , Baciu Cristina , Ramirez Lucia N. , Peraza Ashley , Martins Brian , Sudhakar Sushil , Aksoy Selin , Furukawa Gabriela , Vincze Orsolya , Giraudeau Mathieu , Duke Elizabeth G. , Spiro Simon , Flach Edmund , Davidson Hannah , Li Christopher I. , Zehnder Ashley , Graham Trevor A. , Troan Brigid V. , Harrison Tara M. , Tollis Marc , Schiffman Joshua D. , Aktipis C. Athena , Abegglen Lisa M. , Maley Carlo C. , Boddy Amy M.
Published: January 2025

Model fitting results for the phenotype evolution models
Supplementary Table S3 from Cancer Prevalence across Vertebrates
Authors: Compton Zachary T. , Mellon Walker , Harris Valerie K. , Rupp Shawn , Mallo Diego , Kapsetaki Stefania E. , Wilmot Mallory , Kennington Ryan , Noble Kathleen , Baciu Cristina , Ramirez Lucia N. , Peraza Ashley , Martins Brian , Sudhakar Sushil , Aksoy Selin , Furukawa Gabriela , Vincze Orsolya , Giraudeau Mathieu , Duke Elizabeth G. , Spiro Simon , Flach Edmund , Davidson Hannah , Li Christopher I. , Zehnder Ashley , Graham Trevor A. , Troan Brigid V. , Harrison Tara M. , Tollis Marc , Schiffman Joshua D. , Aktipis C. Athena , Abegglen Lisa M. , Maley Carlo C. , Boddy Amy M.
Published: January 2025

Most common cancer types
Supplementary Table S1 from AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers
Authors: Belmontes Brian , Slemmons Katherine K. , Su Chun , Liu Siyuan , Policheni Antonia N. , Moriguchi Jodi , Tan Hong , Xie Fang , Aiello Daniel Andrew , Yang Yajing , Lazaro Raul , Aeffner Famke , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Vestergaard Mikkel , Cowland Sanne , Andersson Jan , Sarvary Ian , Chen Qing , Sharma Pooja , Lopez Patricia , Tamayo Nuria , Pettus Liping H. , Ghimire-Rijal Sudipa , Mukund Susmith , Allen Jennifer R. , DeVoss Jason , Coxon Angela , Rodon Jordi , Ghiringhelli François , Penel Nicolas , Prenen Hans , Glad Sanne , Chuang Chen-Hua , Keyvanjah Kiana , Townsley Danielle M. , Butler John R. , Bourbeau Matthew P. , Caenepeel Sean , Hughes Paul E.
Published: January 2025

Supplementary Table S1: Plasma protein binding and PK profile of AM-9747 and AMG 193
Supplementary Figure 7 from Zongertinib (BI 1810631), an Irreversible HER2 TKI, Spares EGFR Signaling and Improves Therapeutic Response in Preclinical Models and Patients with HER2-Driven Cancers
Authors: Wilding Birgit , Woelflingseder Lydia , Baum Anke , Chylinski Krzysztof , Vainorius Gintautas , Gibson Neil , Waizenegger Irene C. , Gerlach Daniel , Augsten Martin , Spreitzer Fiona , Shirai Yukina , Ikegami Masachika , Tilandyová Sylvia , Scharn Dirk , Pearson Mark A. , Popow Johannes , Obenauf Anna C. , Yamamoto Noboru , Kondo Shunsuke , Opdam Frans L. , Bruining Annemarie , Kohsaka Shinji , Kraut Norbert , Heymach John V. , Solca Flavio , Neumüller Ralph A.
Published: January 2025

In vivo tumor responses for zongertinib monotherapy or combinations.
Supplementary Figure S11 from AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers
Authors: Belmontes Brian , Slemmons Katherine K. , Su Chun , Liu Siyuan , Policheni Antonia N. , Moriguchi Jodi , Tan Hong , Xie Fang , Aiello Daniel Andrew , Yang Yajing , Lazaro Raul , Aeffner Famke , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Vestergaard Mikkel , Cowland Sanne , Andersson Jan , Sarvary Ian , Chen Qing , Sharma Pooja , Lopez Patricia , Tamayo Nuria , Pettus Liping H. , Ghimire-Rijal Sudipa , Mukund Susmith , Allen Jennifer R. , DeVoss Jason , Coxon Angela , Rodon Jordi , Ghiringhelli François , Penel Nicolas , Prenen Hans , Glad Sanne , Chuang Chen-Hua , Keyvanjah Kiana , Townsley Danielle M. , Butler John R. , Bourbeau Matthew P. , Caenepeel Sean , Hughes Paul E.
Published: January 2025

Supplementary Figure S11: AMG 193 treatment of patients with MTAP-deleted cancers results in inhibition of serum SDMA
Supplementary Data Table 2 from Zongertinib (BI 1810631), an Irreversible HER2 TKI, Spares EGFR Signaling and Improves Therapeutic Response in Preclinical Models and Patients with HER2-Driven Cancers
Authors: Wilding Birgit , Woelflingseder Lydia , Baum Anke , Chylinski Krzysztof , Vainorius Gintautas , Gibson Neil , Waizenegger Irene C. , Gerlach Daniel , Augsten Martin , Spreitzer Fiona , Shirai Yukina , Ikegami Masachika , Tilandyová Sylvia , Scharn Dirk , Pearson Mark A. , Popow Johannes , Obenauf Anna C. , Yamamoto Noboru , Kondo Shunsuke , Opdam Frans L. , Bruining Annemarie , Kohsaka Shinji , Kraut Norbert , Heymach John V. , Solca Flavio , Neumüller Ralph A.
Published: January 2025

PRISM screen raw data.
Figure 4 from Chromothripsis-Mediated Small Cell Lung Carcinoma
Authors: Rekhtman Natasha , Tischfield Sam E. , Febres-Aldana Christopher A. , Lee Jake June-Koo , Chang Jason C. , Herzberg Benjamin O. , Selenica Pier , Woo Hyung Jun , Vanderbilt Chad M. , Yang Soo-Ryum , Xu Fei , Bowman Anita S. , da Silva Edaise M. , Noronha Anne Marie , Mandelker Diana L. , Mehine Miika , Mukherjee Semanti , Blanco-Heredia Juan , Orgera John J. , Nanjangud Gouri J. , Baine Marina K. , Aly Rania G. , Sauter Jennifer L. , Travis William D. , Savari Omid , Moreira Andre L. , Falcon Christina J. , Bodd Francis M. , Wilson Christina E. , Sienty Jacklynn V. , Manoj Parvathy , Sridhar Harsha , Wang Lu , Choudhury Noura J. , Offin Michael , Yu Helena A. , Quintanal-Villalonga Alvaro , Berger Michael F. , Ladanyi Marc , Donoghue Mark T.A. , Reis-Filho Jorge S. , Rudin Charles M.
Published: January 2025

Chromosomal architecture of chromothripsis and amplifications. A, Integrated SV and CNA analysis in two representative cases confirming the hallmark features of chromothripsis and suggesting formation of ecDNA and micronucleation as a mechanism of gene amplification and chromothripsis (see “Results”). Allele-specific CN for each genomic segment is shown on the left y-axis. Genomic segments in which the CN is greater than 5 times of chromosomal baseline are indicated as orange shades to highlight the most significant amplification events. Vertical lines and arcs indicate genomic breakpoints and connections of SVs, of which the number of supporting read fragments is shown on the right y-axis. Colors of the SVs are based on the orientation of paired reads. All cases are shown in Supplementary Fig. S10. B, Conceptual diagram explaining the mechanism of chromothripsis and oncogene amplification in aSCLC. C, FISH analysis of case A07 with 3-color probes: MDM2 (red), CDK4 (green), and CCND2 (orange), revealing ecDNA location of amplified genes (so-called “double-minutes”). Sample is of a metaphase spread from a patient-derived xenograft (see “Methods”). D, Summary of FISH results for all tested samples.
Table S3 from Combined KRAS Inhibition and Immune Therapy Generates Durable Complete Responses in an Autochthonous PDAC Model
Authors: Liu Yonghong , Han Jincheng , Hsu Wen-Hao , LaBella Kyle A. , Deng Pingna , Shang Xiaoying , Tallón de Lara Paulino , Cai Li , Jiang Shan , DePinho Ronald A.
Published: January 2025

Significantly enriched GO and pathway terms identified by GO and pathway enrichment analysis of the 291 downregulated genes identified in macrophages treated with MRTX1133 plus triple immunotherapy compared to all other treatment groups.
Table S1 from Combined KRAS Inhibition and Immune Therapy Generates Durable Complete Responses in an Autochthonous PDAC Model
Authors: Liu Yonghong , Han Jincheng , Hsu Wen-Hao , LaBella Kyle A. , Deng Pingna , Shang Xiaoying , Tallón de Lara Paulino , Cai Li , Jiang Shan , DePinho Ronald A.
Published: January 2025

Differential gene expression analysis of the macrophage population identified 216 significantly upregulated and 291 signficantly downregulated genes in iKPC PDAC tumors treated with MRTX1133 plus triple immunotherapy compared to all other treatment groups.
Figure S4 from Combined KRAS Inhibition and Immune Therapy Generates Durable Complete Responses in an Autochthonous PDAC Model
Authors: Liu Yonghong , Han Jincheng , Hsu Wen-Hao , LaBella Kyle A. , Deng Pingna , Shang Xiaoying , Tallón de Lara Paulino , Cai Li , Jiang Shan , DePinho Ronald A.
Published: January 2025

Single cell RNA-seq analysis of iKPC autochthonous PDAC tumors identified cancer and stromal cell populations.
Table S11 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells
Authors: Priego Neibla , de Pablos-Aragoneses Ana , Perea-García María , Pieri Valentina , Hernández-Oliver Carolina , Álvaro-Espinosa Laura , Rojas Andrea , Sánchez Oliva , Steindl Ariane , Caleiras Eduardo , García Fernando , García-Martín Santiago , Graña-Castro Osvaldo , García-Mulero Sandra , Serrano Diego , Velasco-Beltrán Paloma , Jiménez-Lasheras Borja , Egia-Mendikute Leire , Rupp Luise , Stammberger Antonia , Meinhardt Matthias , Chaachou-Charradi Anas , Martínez-Saez Elena , Bertero Luca , Cassoni Paola , Mangherini Luca , Pellerino Alessia , Rudà Roberta , Soffietti Riccardo , Al-Shahrour Fatima , Saftig Paul , Sanz-Pamplona Rebeca , Schmitz Marc , Crocker Stephen J. , Calvo Alfonso , Palazón Asís , Valiente Manuel
Published: January 2025

GSEA of CD8+ T cells incubated with pSTAT3+ conditioned media. Gene set enrichment analysis (GSEA) of top 25 upregulated and downregulated signatures and NES of Biological Process (GOBP) pathways related to T cell function comparing CD8+ in vitro cultures incubated with the pSTAT3- (d1) or pSTAT3+ (d2) secretome. The table contains information corresponding to Figure 2B.
Figure S4 from TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells
Authors: Priego Neibla , de Pablos-Aragoneses Ana , Perea-García María , Pieri Valentina , Hernández-Oliver Carolina , Álvaro-Espinosa Laura , Rojas Andrea , Sánchez Oliva , Steindl Ariane , Caleiras Eduardo , García Fernando , García-Martín Santiago , Graña-Castro Osvaldo , García-Mulero Sandra , Serrano Diego , Velasco-Beltrán Paloma , Jiménez-Lasheras Borja , Egia-Mendikute Leire , Rupp Luise , Stammberger Antonia , Meinhardt Matthias , Chaachou-Charradi Anas , Martínez-Saez Elena , Bertero Luca , Cassoni Paola , Mangherini Luca , Pellerino Alessia , Rudà Roberta , Soffietti Riccardo , Al-Shahrour Fatima , Saftig Paul , Sanz-Pamplona Rebeca , Schmitz Marc , Crocker Stephen J. , Calvo Alfonso , Palazón Asís , Valiente Manuel
Published: January 2025

Local immunosuppression could explain immunotherapy failure in high immune cluster symptomatic brain metastasis. Supplementary Figure 4 shows additional data corresponding to Figure 3.
Conquering Overtreatment of DCIS: Lessons from PRECISION
Authors: Bhattacharjee Proteeti , Lips Esther H. , Sawyer Elinor J. , Hwang E. Shelley , Thompson Alastair M. , Wesseling Jelle ,   the Cancer Grand Challenges PRECISION Consortium, Behbod Fariba , Bhattacharjee Proteeti , Collyar Deborah , Davies Helen , Futreal Andrew , Hwang E. Shelley , Jonkers Jos , Lips Esther H. , Navin Nicholas , Nik-Zainal Serena , Pinto Donna , Rea Daniel , Sawyer Elinor J. , Schmidt Marjanka , Stobart Hilary , Thompson Alastair , van Oirsouw Marja , van Rheenen Jacco , Verschuur Ellen , Wesseling Jelle , Wessels Lodewyk F.A.
Published: January 2025

As we cannot reliably distinguish indolent, low-risk ductal carcinoma in situ (DCIS) from potentially progressive, high-risk DCIS, all women with DCIS diagnosis undergo intensive treatment without any benefit. The PREvent ductal Carcinoma In Situ Invasive Overtreatment Now team was established to unravel DCIS biology and develop new multidisciplinary approaches for accurate risk stratification to tackle the global problem of DCIS overdiagnosis and overtreatment.

See related article by Bressan et al., p. 16

See related article by Stratton et al., p. 22

See related article by Goodwin et al., p. 34
Atypical Small Cell Lung Cancer: A New Malignancy Characterized by Chromothripsis, Carcinoid Tumors, and Wild-type RB1 and TP53
Authors: Nadeem Urooba , Drapkin Benjamin J.
Published: January 2025

Small cell lung cancer (SCLC) and pulmonary carcinoid tumors are traditionally seen as unrelated, with SCLC linked to smoking and characterized by biallelic loss of RB1 and TP53 and rapid progression. Rekhtman and colleagues upend these assumptions by discovering an “atypical” SCLC that arises in nonsmokers with intact RB1 and TP53 loci, chromothripsis-induced oncogene amplifications on extrachromosomal DNA, and frequent synchronous carcinoid tumors.

See related article by Rekhtman et al., p. 83
Peto’s Paradox Is Dead. Long Live Peto’s Paradox
Authors: Metzger Michael J.
Published: January 2025

In this issue, Compton and colleagues report the prevalence of neoplasia and malignant cancer in 292 species, based on 16,049 necropsy records, shedding light on susceptibility to cancer and the evolution of mechanisms that protect against cancer across a broad array of vertebrates.

See related article by Compton et al., p. 227
Increased Clonal Hematopoiesis in Long-term Survivors of Pediatric Hematopoietic Cell Transplantation
Authors: Müskens Konradin F. , Wieringa Nienke , van Bergen Maaike G.J.M. , Bense Joëll E. , te Pas Brigit M. , de Pagter Anne P.J. , Lankester Arjan C. , Bierings Marc B. , Neuberg Donna S. , Haitjema Saskia , Kremer Leontien C.M. , Huls Gerwin A. , Nierkens Stefan , Jansen Joop H. , Lindemans Caroline A. , de Graaf Aniek O. , Belderbos Mirjam E.
Published: January 2025

In pediatric hematopoietic cell transplantation (HCT) recipients, transplanted donor cells may need to function far beyond normal human lifespan. In this study, we investigated the risk of clonal hematopoiesis (CH) in 144 pediatric long-term HCT survivors and 258 nontransplanted controls. CH was detected in 16% of HCT recipients and 8% of controls at variant allele frequencies of 0.01 to 0.31. Mutations were predominantly in DNMT3A (80%) and TET2 (20%). Older hematopoietic age (OR: 1.07; P < 0.001) and the HCT procedure (OR: 2.53; P = 0.02) independently increased the risk of CH, indicating both aging- and transplantation-induced effects. Large clones (variant allele frequency >0.10) were found exclusively in HCT recipients. Notably, CH was also detected within 15 years after a cord blood HCT. Inflammatory processes around graft infusion were associated with CH presence. Future studies are required to track the evolution of posttransplant CH and its impact on future cardiovascular diseases, second malignancies, and overall survival.

Significance:

As survival of HCT recipients continues to improve, late treatment effects gain importance. We demonstrate that pediatric HCT recipients show increased risk of CH compared with age-matched controls. Prospective studies are crucial to understand the clinical implications of posttransplant CH in this young population.
Suppl Figure 8 from Preclinical Development of Tuspetinib for the Treatment of Acute Myeloid Leukemia
Authors: Sonowal Himangshu , Rice William G. , Bejar Raphael , Byun Joo-Yun , Jung Seung Hyun , Sinha Ranjeet , Howell Stephen B.
Published: January 2025

Supplementary Figure 8
Suppl Figure 2 from Preclinical Development of Tuspetinib for the Treatment of Acute Myeloid Leukemia
Authors: Sonowal Himangshu , Rice William G. , Bejar Raphael , Byun Joo-Yun , Jung Seung Hyun , Sinha Ranjeet , Howell Stephen B.
Published: January 2025

Supplementary Figure 2
Figure 5 from Preclinical Development of Tuspetinib for the Treatment of Acute Myeloid Leukemia
Authors: Sonowal Himangshu , Rice William G. , Bejar Raphael , Byun Joo-Yun , Jung Seung Hyun , Sinha Ranjeet , Howell Stephen B.
Published: January 2025

Resistance to TUS creates a synthetic lethal hypersensitivity to VEN. Growth inhibition curves documenting the effect of VEN on parental MOLM-14 and four sublines selected for growth in 75 nmol/L TUS. Data are presented as mean ± SEM from three-independent experiments; P < 0.001 vs. MOLM-14 parental cells for all 4 TUS/R lines.
Figure 3 from Preclinical Development of Tuspetinib for the Treatment of Acute Myeloid Leukemia
Authors: Sonowal Himangshu , Rice William G. , Bejar Raphael , Byun Joo-Yun , Jung Seung Hyun , Sinha Ranjeet , Howell Stephen B.
Published: January 2025

Effect of TUS alone on survival of mice orthotopically inoculated with FLT3-ITD-mutant AML cell lines; (A) MV-4-11; (B) MOLM-13; and, (C) MOLM-14. Efficacy of TUS in combination with VEN or AZA in mice inoculated subcutaneously with AML cell lines; (D) MV-4-11 tumors treated with either TUS (orally, every day), VEX (orally, every day), or the combination; (E) MOLM-14 FLT3-ITD/F691L tumors treated with either TUS, AZA (3 mg/kg i.v. days 0–4), or the combination. Data are presented as mean ± SEM.