bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B020: Development of novel Src-targeting strategies to block bladder cancer invasive progression
Authors: Jerome Nicole A. , Wang Yin , Henderson Marian L. , Broses Luke , Day Kathleen C. , Day Mark L. , Soellner Matthew B. , Palmbos Phillip L. 
Published: May 2024

Abstract
Background: Treatment of muscle-invasive bladder cancer remains challenging and, BCG, one of the few treatments that prevents progression of high-risk non-muscle invasive tumors to invasive metastatic disease, is difficult to obtain. Thus, development of new treatment approaches to block progression to muscle invasive disease is essential. We find that TRIM29 (tripartite motif containing 29, also known as ATDC), drives bladder cancer invasive progression through modulation of focal adhesions containing FAK and c-Src (Src). Despite this, literature has reported conflicting effects of Src knockdown and Src kinase inhibition on migration, perhaps due to separable pro- and anti-invasive functions of Src in bladder cancer. Hypothesis: Src drives bladder cancer invasive progression specifically through its tyrosine kinase activity within focal adhesions. Methods: We used 2D live cell migration assays and 3D spheroid invasion assays to test dasatinib, highly specific, novel conformation inhibitors of Src, a novel Src PROTAC, and siRNA against Src on bladder cancer migration and invasion. Results: Dasatinib and our novel conformation-specific inhibitors inhibited Src kinase activity and both siRNA and the novel PROTAC reduced total Src expression in vitro. Neither dasatinib, conformation inhibitors, siRNA, nor the PROTAC impacted bladder cancer cell viability in UM-UC5, UM-UC9 or UM-UC14 cell lines. Interestingly, we found that inhibiting Src’s kinase activity with either dasatinib or conformation-specific inhibitors abrogated bladder cancer migration. Conclusion: These results point to the selective importance of Src in regulating bladder cancer migration and invasion. They also suggest that novel Src targeting agents have potential clinical utility in the prevention of bladder cancer invasive progression.
Citation Format: Nicole A. Jerome, Yin Wang, Marian L. Henderson, Luke Broses, Kathleen C. Day, Mark L. Day, Matthew B. Soellner, Phillip L. Palmbos. Development of novel Src-targeting strategies to block bladder cancer invasive progression [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B020.
Abstract IA003: Molecular subtypes and clinical benefit from neoadjuvant chemotherapy: A ten-year update
Authors: McConkey David J 
Published: May 2024

Abstract
Ten years ago TCGA and two private groups reported that muscle-invasive bladder cancers (MIBCs) could be grouped into basal and luminal molecular subtypes that shared features with the corresponding subtypes of breast cancer. These and earlier studies by the group at Lund University demonstrated that molecular subtype membership was prognostic: patients whose tumors were assigned to basal/squamous subtypes had shorter survival than did patients whose tumors were assigned to the luminal subtypes, and these relationships were confirmed in subsequent studies. In addition, one of the studies included tumors from patients treated with neoadjuvant cisplatin-based combination chemotherapy (NAC), where patients whose tumors were infiltrated with smooth muscle cells and fibroblasts (the MD Anderson p53-like subtype) had the lowest response rates. Parallel comparisons of patients who either did or did not receive NAC concluded that patients with basal tumors derived the most clinical benefit in terms of disease-specific or overall survival. Thus, in addition to being prognostic, there was a suggestion that molecular subtypes might also be used to predict resistance to NAC. This work led to the design of two large collaborative projects that were designed to validate these observations and the conclusion that inactivating mutations in several DNA damage and repair (DDR) genes were also associated with response. One leveraged the S1314 Phase-2 “CoXEN” trial that was designed to prospectively validate another gene expression-based biomarker, and the other exploited pretreatment samples from the CALGB/Alliance 90601 Phase-3 trial of gemcitabine/cisplatin with or without bevacizumab in patients with advanced or metastatic disease. Comparisons of response rates as a function of molecular subtype membership in S1314 failed to validate the original link between the MD Anderson p53-like subtype and resistance, and patients with basal/squamous tumors in 90601 did not have better outcomes than did patients with luminal tumors. Thus, while the prognostic value of molecular subtype membership was confirmed, the predictive value was not. Developing biomarkers to predict response to chemotherapy remains a challenge not only for bladder cancer but also for other solid and hematopoietic malignancies. It seems likely that success will require the integration of measurements using multiple platforms, including liquid biopsies and others. The exciting results of the EV-302 clinical trial of enfortumab vedotin plus pembrolizumab have shifted the focus of biomarker work to these and other novel agents.
Citation Format: David J McConkey. Molecular subtypes and clinical benefit from neoadjuvant chemotherapy: A ten-year update [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr IA003.
Abstract IA012: Novel approaches to the management of non-muscle invasive bladder cancer
Authors: Kamat Ashish M. 
Published: May 2024

Abstract
Non-muscle invasive bladder cancer (NMIBC) is a prevalent disease with a high recurrence rate and the potential to progress to muscle-invasive stages. While transurethral resection and bacillus Calmette-Guerin (BCG) immunotherapy remain the mainstay of treatment, limitations exist, particularly for high-grade and BCG-unresponsive NMIBC. This necessitates the exploration of novel therapeutic strategies. This talk will explore promising avenues in NMIBC management, including combination intravesical therapies, enhanced delivery methods for existing treatments, and emerging fields like gene therapy, targeted therapy, immunotherapy variants, and photodynamic therapy. These approaches hold the potential to improve bladder preservation rates, reduce recurrence, and ultimately enhance patient outcomes across the entire spectrum of NMIBC disease.
Citation Format: Ashish M. Kamat. Novel approaches to the management of non-muscle invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr IA012.
Colon Age: A Metric for Whether and How to Screen Male Veterans for Early-Onset Colorectal Cancer
Authors: Imperiale Thomas F. , Myers Laura J. , Barker Barry C. , Stump Timothy E. , Daggy Joanne K. 
Published: May 2024

Abstract
We aimed to develop a metric for estimating risk for early-onset colorectal cancer (EOCRC) to help decide whether and how to screen persons &lt; age 50. We used risk prediction models derived and validated on male veterans to calculate the RRs for six scenarios: one low-risk scenario (no risk factors present), four intermediate risk scenarios (some risk factors present), and one high-risk scenario (all risk factors present) for three age groups (35–39, 40–44, and 45–49 years). For each scenario, we estimated absolute colorectal cancer risk using Surveillance Epidemiology and End Results colorectal cancer incidence rates and each scenario’s RR. We identified the current Surveillance Epidemiology and End Results 5-year age group to which the revised estimate was closest and refer to the midpoint of this group as the “colon age.” When the revised estimate equals or exceeds that for 50- to 54-year-olds and for 70- to 74-year-olds, respective recommendations were made for (any) colorectal cancer screening and screening with colonoscopy. Among the scenarios, there was inconsistency between the two models for the 35 to 39 and 40 to 44 age groups, with only the 15-variable model recommending screening for the higher-risk 35- to 39-year-olds. Both models recommended screening for some intermediate risk and high-risk 40- to 44-year-olds. The models were well aligned on whether and how to screen most 45- to 49-year-olds. Using risk factors for EOCRC with colorectal cancer incidence rates, “colon age” may be useful for shared decision-making about whether and how to screen male veterans &lt;50 years. For 45- to 49-year-olds, the 7-variable model may be preferred by patients, providers, and health systems.
Prevention Relevance: A new metric known as “colon age” expresses risk of EOCRC based on biological risk and may be useful for providers to explain and for patients to understand colorectal cancer risk when considering whether and how to be screened for colorectal cancer prior to age 45 or 50.
Prognostic Impact of Heart Rhythm Shockability Trajectory in Out-of-Hospital Cardiac Arrest: A Multicenter Retrospective Study
Authors: Wang Chih-Hung , Lu Tsung-Chien , Tay Joyce , Wu Cheng-Yi , Wu Meng-Che , Su Pei-I. , Huang Chun-Yen , Tsai Chu-Lin , Huang Chien-Hua , Chen Wen-Jone 
Published: May 2024

BACKGROUND:
This study aimed to investigate the association between the temporal transitions in heart rhythms during cardiopulmonary resuscitation (CPR) and outcomes after out-of-hospital cardiac arrest.

METHODS:
This was an analysis of the prospectively collected databases in 3 academic hospitals in northern and central Taiwan. Adult patients with out-of-hospital cardiac arrest transported by emergency medical service between 2015 and 2022 were included. Favorable neurological recovery and survival to hospital discharge were the primary and secondary outcomes, respectively. Time-specific heart rhythm shockability was defined as the probability of shockable rhythms at a particular time point during CPR. The temporal changes in the time-specific heart rhythm shockability were calculated by group-based trajectory modeling. Multivariable logistic regression analyses were performed to examine the association between the trajectory group and outcomes. Subgroup analyses examined the effects of extracorporeal CPR in different trajectories.

RESULTS:
The study comprised 2118 patients. The median patient age was 69.1 years, and 1376 (65.0%) patients were male. Three distinct trajectories were identified: high-shockability (52 patients; 2.5%), intermediate-shockability (262 patients; 12.4%), and low-shockability (1804 patients; 85.2%) trajectories. The median proportion of shockable rhythms over the course of CPR for the 3 trajectories was 81.7% (interquartile range, 73.2%–100.0%), 26.7% (interquartile range, 16.7%–37.5%), and 0% (interquartile range, 0%–0%), respectively. The multivariable analysis indicated both intermediate- and high-shockability trajectories were associated with favorable neurological recovery (intermediate-shockability: adjusted odds ratio [aOR], 4.98 [95% CI, 2.34–10.59]; high-shockability: aOR, 5.40 [95% CI, 2.03–14.32]) and survival (intermediate-shockability: aOR, 2.46 [95% CI, 1.44–4.18]; high-shockability: aOR, 2.76 [95% CI, 1.20–6.38]). The subgroup analysis further indicated extracorporeal CPR was significantly associated with favorable neurological outcomes (aOR, 4.06 [95% CI, 1.11–14.81]) only in the intermediate-shockability trajectory.

CONCLUSIONS:
Heart rhythm shockability trajectories were associated with out-of-hospital cardiac arrest outcomes, which may be a supplementary factor in guiding the allocation of medical resources, such as extracorporeal CPR.
Instruction on the Scientific Method Provides (Some) Protection Against Illusions of Causality
Authors: Chow Julie Y. L. , Goldwater Micah B. , Colagiuri Ben , Livesey Evan J. 
Published: May 2024

Abstract
People tend to overestimate the efficacy of an ineffective treatment when they experience the treatment and its supposed outcome co-occurring frequently. This is referred to as the outcome density effect. Here, we attempted to improve the accuracy of participants’ assessments of an ineffective treatment by instructing them about the scientific practice of comparing treatment effects against a relevant base-rate, i.e., when no treatment is delivered. The effect of these instructions was assessed in both a trial-by-trial contingency learning task, where cue administration was either decided by the participant (Experiments 1 & 2) or pre-determined by the experimenter (Experiment 3), as well as in summary format where all information was presented on a single screen (Experiment 4). Overall, we found two means by which base-rate instructions influence efficacy ratings for the ineffective treatment: 1) When information was presented sequentially, the benefit of base-rate instructions on illusory belief was mediated by reduced sampling of cue-present trials, and 2) When information was presented in summary format, we found a direct effect of base-rate instruction on reducing causal illusion. Together, these findings suggest that simple instructions on the scientific method were able to decrease participants’ (over-)weighting of cue-outcome coincidences when making causal judgements, as well as decrease their tendency to over-sample cue-present events. However, the effect of base-rate instructions on correcting illusory beliefs was incomplete, and participants still showed illusory causal judgements when the probability of the outcome occurring was high. Thus, simple textual information about assessing causal relationships is partially effective in influencing people’s judgements of treatment efficacy, suggesting an important role of scientific instruction in debiasing cognitive errors.
How Do You Know If You Were Mind Wandering? Dissociating Explicit Memories of Off Task Thought From Subjective Feelings of Inattention
Authors: Mathews Nathan K. , Bin Faiz Umer , Brosowsky Nicholaus P. 
Published: May 2024

Abstract
Mind wandering is a common experience in which your attention drifts away from the task at hand and toward task-unrelated thoughts. To measure mind wandering we typically use experience sampling and retrospective self-reports, which require participants to make metacognitive judgments about their immediately preceding attentional states. In the current study, we aimed to better understand how people come to make such judgments by introducing a novel distinction between explicit memories of off task thought and subjective feelings of inattention. Across two preregistered experiments, we found that participants often indicated they were “off task” and yet had no memory of the content of their thoughts—though, they were less common than remembered experiences. Critically, remembered experiences of mind wandering and subjective feelings of inattention differed in their behavioral correlates. In Experiment 1, we found that only the frequency of remembered mind wandering varied with task demands. In contrast, only subjective feelings of inattention were associated with poor performance (Experiments 1 and 2) and individual differences in executive functioning (Experiment 2). These results suggest that the phenomenology of mind wandering may differ depending on how the experiences are brought about (e.g., executive functioning errors versus excess attentional resources), and provide preliminary evidence of the importance of measuring subjective feelings of inattention when assessing mind wandering.
Toward the Emergence of Intelligent Control: Episodic Generalization and Optimization
Authors: Giallanza Tyler , Campbell Declan , Cohen Jonathan D. 
Published: May 2024

Abstract
Human cognition is unique in its ability to perform a wide range of tasks and to learn new tasks quickly. Both abilities have long been associated with the acquisition of knowledge that can generalize across tasks and the flexible use of that knowledge to execute goal-directed behavior. We investigate how this emerges in a neural network by describing and testing the Episodic Generalization and Optimization (EGO) framework. The framework consists of an episodic memory module, which rapidly learns relationships between stimuli; a semantic pathway, which more slowly learns how stimuli map to responses; and a recurrent context module, which maintains a representation of task-relevant context information, integrates this over time, and uses it both to recall context-relevant memories (in episodic memory) and to bias processing in favor of context-relevant features and responses (in the semantic pathway). We use the framework to address empirical phenomena across reinforcement learning, event segmentation, and category learning, showing in simulations that the same set of underlying mechanisms accounts for human performance in all three domains. The results demonstrate how the components of the EGO framework can efficiently learn knowledge that can be flexibly generalized across tasks, furthering our understanding of how humans can quickly learn how to perform a wide range of tasks—a capability that is fundamental to human intelligence.
Orbitacolax kyphosi sp. nov. (Copepoda, Cyclopoida, Bomolochidae) recovered from the brassy chub Kyphosus vaigiensis (Quoy & Gaimard, 1825) (Actinopterygii) in Japan
Authors: Izawa Kunihiko 
Published: May 2024

Abstract
Orbitacolax kyphosi sp. nov. is described based on a single specimen of the female recovered from washing fluid of the brassy chub Kyphosus vaigiensis (Quoy & Gaimard, 1825) (Centrachiformes, Kyphosidae) in Japan. K. vaigiensis is a new host and Kyphosidae is a new host group for the genus.
On the identity of Paranotonyx curtipes Nobili, 1906 (Brachyura, Thoracotremata, Varunidae)
Authors: Ng Peter K. L. , Davie Peter J. F. 
Published: May 2024

Abstract
Paranotonyx curtipes Nobili, 1906a, has not been reported since it was described from the Red Sea. Originally placed in the Goneplacidae, the genus has been associated with the Rhizopinae Stimpson, 1858 (Pilumnidae), since Tesch (1918). A re-examination of the holotype female shows that Paranotonyx is actually a member of the Gaeticinae Davie & N.K. Ng, 2007 (Varunidae). Records from Madagascar and Pakistan previously doubtfully referred to “Acmaeopleura balssi Shen, 1932” are here shown to be conspecific with P. curtipes. Paranotonyx is redescribed and figured, and compared with the allied Acmaeopleura Stimpson, 1858, and Sestrostoma Davie & N.K. Ng, 2007, genera that are restricted to the western Pacific.
Surface drag on deformed topographic boundaries: Tests using a semi-idealized model
Authors: Li Yi , Epifanio Craig 
Published: May 2024

Abstract
The physics of the surface drag (or surface stress) boundary condition is explored
in the context of semi-idealized flows past realistic terrain. Numerical experiments are presented to explore the impact of the drag condition on flows past a region of complex topography, with a particular focus on the dependence on terrain geometry. Arguments are presented to show that the drag condition depends on the geometry of the terrain in two respects: (i) a dependence on terrain slope, as represented by a normal gradient term; and (ii) a dependence on the curvature, which appears in the drag condition as a Dirichlet term. The dependence on the geometry is illustrated through a series of numerical experiments in which simulations using the full form of the drag condition are compared to companion simulations using one of two widely used approximations: (a) the normal gradient condition, which accounts for the terrain slope but neglects curvature; and (b) the flat boundary assumption, which neglects both slope and curvature. The results show that the role of the terrain geometry in the drag condition is strongly dependent on grid spacing, with more highly resolved topography leading to a stronger dependence on the slope and curvature. For sufficiently high resolutions, the dependence on the geometry becomes significant, to the extent that simulations using the approximate drag conditions fail to capture important aspects of the flow. Some basic implications of these results for the problem of high resolution wind energy forecasting are discussed.
Large-Scale Climate Modes Drive Low-Frequency Regional Arctic Sea Ice Variability
Authors: Wyburn-Powell Christopher , Jahn Alexandra 
Published: May 2024

Abstract
Summer Arctic sea ice is declining rapidly but with superimposed variability on multiple time scales that introduces large uncertainties in projections of future sea ice loss. To better understand what drives at least part of this variability, we show how a simple linear model can link dominant modes of climate variability to low-frequency regional Arctic sea ice concentration (SIC) anomalies. Focusing on September, we find skillful projections from global climate models (GCMs) from phase 6 of the Coupled Model Intercomparison Project (CMIP6) at lead times of 4–20 years, with up to 60% of observed low-frequency variability explained at a 5-yr lead time. The dominant driver of low-frequency SIC variability is the interdecadal Pacific oscillation (IPO) which is positively correlated with SIC anomalies in all regions up to a lead time of 15 years but with large uncertainty between GCMs and internal variability realization. The Niño-3.4 index and Atlantic multidecadal oscillation have better agreement between GCMs of being positively and negatively related, respectively, with low-frequency SIC anomalies for at least 10-yr lead times. The large variations between GCMs and between members within large ensembles indicate the diverse simulation of teleconnections between the tropics and Arctic sea ice and the dependence on the initial climate state. Further, the influence of the Niño-3.4 index was found to be sensitive to the background climate. Our results suggest that, based on the 2022 phases of dominant climate variability modes, enhanced loss of sea ice area across the Arctic is likely during the next decade.

Significance Statement
The purpose of this study is to better understand the drivers of low-frequency variability of Arctic sea ice. Teasing out the complicated relationships within the climate system takes a large number of examples. Here, we use 42 of the latest generation of global climate models to construct a simple linear model based on dominant named climate features to predict regional low-frequency sea ice anomalies at a lead time of 2–20 years. In 2022, these modes of variability happen to be in the phases most conducive to low Arctic sea ice concentration anomalies. Given the context of the longer-term trend of sea ice loss due to global warming, our results suggest accelerated Arctic sea ice loss in the next decade.