bluuebunny/crossref_metadata_2025 huggingface dataset:
‘I Just Wanted to Get It Over and Done With’: A Grounded Theory of Psychological Need Frustration in Video Games
Authors: Ballou Nick , Deterding Sebastian
Published: October 2023

Psychological need frustration—experiences like failure, loneliness, or coercion—is emerging as a promising explanation for why people disengage with games and other entertainment media, and how media may induce dysregulated use and ill-being. However, existing research on game-related need frustration relies on general instruments with unclear content validity for games. We also do not know how need frustration arises in video games, nor how it leads to disengagement. We therefore conducted a semi-structured interview study with 12 video game players, following grounded theory methods to develop a model of need-frustrating play. We find that need frustration is a common and impactful experience in games, with distinct antecedents not fully captured in existing measures. Felt need frustration arises when observed need-frustrating events negatively violate expected need frustration or satisfaction; repeated violations update players’ expectations, which lead them to modulate or quit play to reduce expected frustration exposure.
Investigating the Effects of Tailored Gamification on Learners’ Engagement over Time in a Learning Environment
Authors: Serna Audrey , Hallifax Stuart , Lavoué Élise
Published: October 2023

Gamification has been widely used to increase learners’ motivation and engagement in digital learning environments. Various studies have highlighted the need to tailor gamification according to users’ characteristics. However, little is known about how tailoring gamification affects learners’ engagement when interacting with the environment. In this paper, we analyse learners’ behaviours in a large-scale field study in real-world classroom conditions over a six-week period. We identify three behavioural patterns and show at a global level that two of these patterns are influenced by adaptation. When we look at how learners’ engagement evolves over time, we see more differences in the adapted condition, specifically in the final lessons of the experiment. Globally learners’ engaged behaviours gradually decreased over time but tailoring the game elements to learners seemed to reduce this decrease or make it more stable, depending on the behavioural patterns.
BlueVR: Design and Evaluation of a Virtual Reality Serious Game for Promoting Understanding towards People with Color Vision Deficiency
Authors: You Ruoxin , Zhou Yihao , Zheng Weicheng , Zuo Yiran , Barrera Machuca Mayra Donaji , Tong Xin
Published: October 2023

People with color vision deficiency (CVD) often encounter color-related challenges in their daily life, which are difficult for those with non-CVD to comprehend fully. Therefore, we designed a Virtual Reality (VR) serious game,
BlueVR
, to simulate challenging scenarios encountered by people with CVD and facilitate understanding from people with non-CVD. We conducted an empirical study with thirty participants with non-CVD and six participants with CVD to evaluate the opportunities and challenges of
BlueVR
. Our findings suggest that
BlueVR
increased people with non-CVD’s understanding, awareness, and perspective-taking abilities towards people with CVD. Moreover, interviews with participants with CVD revealed that
BlueVR
accurately depicts their real-life discomforts and meets their expectations to improve potential social awareness. This research contributes valuable insights into the mechanisms underlying the effectiveness of VR serious games in promoting understanding and design implications for future game development.
If at First You Don’t Succeed: Helping Players Make Progress in Games with Breaks and Checkpoints
Authors: Johanson Colby , Piller Brandon , Gutwin Carl , Mandryk Regan L.
Published: October 2023

Developing skill and overcoming in-game challenges is of great interest to both players and game designers. Players can improve through repetition, but sometimes practice does not lead to improvement and progress stalls. It would be useful if designers could help players make progress without compromising their long-term skill development. We carried out a study to investigate how two techniques—checkpoints and breaks—affect in-game progress and player skill. Checkpoints allow multiple attempts at a challenge without having to repeat earlier sections; this aids progress, but could potentially hinder skill development. Second, breaks in gameplay have been shown to accelerate skill development, but their effectiveness is unknown when the breaks are integrated into the game's design. Our study evaluated the effects of game-integrated breaks and checkpoints on players' in-game progress (when the techniques were present) as well as two test sessions (with all techniques removed). Our results showed that both checkpoints and breaks aid progress (combining both had the largest effect) and that neither technique reduced performance in the transfer task, suggesting that skill development was not hindered. Our work provides evidence that checkpoints and breaks are valuable techniques that can assist both player progress and skill.
Informing Children about Privacy: A Review and Assessment of Age-Appropriate Information Designs in Kids-Oriented F2P Video Games
Authors: Sas Martin , Denoo Maarten , Mühlberg Jan Tobias
Published: October 2023

With the rise of free-to-play (F2P) games, the profitability of video-gaming apps critically depends on the ability of developers to acquire, retain, and monetize large numbers of players. In this context, most game designers have no viable alternative than massively collecting players' personal data and monitoring their behavior to target them with personalized advertising and in-game purchases. Given the risks associated with such data practices, players, in particular children, need to be aware that a video game might compromise their privacy. Game designers should therefore ensure that players receive appropriate information about the data practices associated with their games. This might, however, be challenging, especially when the game is directed at children, given the complexity of privacy information and the limited literacy capacities of children and their parents. To answer game designers' need for comprehensive guidance regarding the communication of privacy information to children, we provide a survey of the age-appropriate information design strategies which been recommended by data protection authorities, children protection organizations and the relevant scientific literature. On this occasion, we also refer to illustrative examples of designs which can be considered good practices. Finally, by using an "evaluation matrix", we reviewed and assessed the implementation of those design strategies in nine F2P mobile games committed to following Google Play's Families Policies. Our findings show that, despite being child-oriented, the reviewed games largely fail at communicating privacy information in an age-appropriate way.
Growing Up with Cerebral Palsy (CP) and Games: Case Study on the Accessible Gameplay Experiences of the Young Players with CP and Their Families through the Lens of Developmental Task Perspective
Authors: Eum Karam , Lee Seyeon , Jo Minjae , Doh Young Yim
Published: October 2023

Understanding the experiences of players with disabilities is a key research issue in game accessibility. However, less is known about the values that young players experience from games, particularly in relation to their situational context as adolescents and young adults with disabilities. We explore how the values of accessible gaming are created in players’ lives by analyzing interviews with five players with cerebral palsy (CP) (age range 13–25 years) and their parents through the lens of developmental tasks theory. Using thematic analysis, we discovered three themes that illustrated how video games’ roles changed according to their life stages: “Establishing Healthy Self in Family”, “Navigating Peer Culture”, and “Preparing Adult Life”. Our results indicated that young players with CP made active decisions in their life and developed supportive relationships from playing accessible games. The changes in their desired developmental task and social contexts influenced the values they found in games. We discuss video games as a sociocultural resource that assists young players with CP to attain the developmental tasks they desire and achieve social inclusion. We conclude with design insights for creating more inclusive gameplay experiences for young players with CP.
From Traditional to Game-Based Learning of Climate Change: A Media Comparison Experiment
Authors: Fernández Galeote Daniel , Legaki Nikoletta-Zampeta , Hamari Juho
Published: October 2023

Widespread climate change engagement is needed to confront our current environmental crises, but it remains difficult to attain. Methods such as visualizations and experiential learning activities, including games and gamification, have been proposed to engage citizens beyond what generic and one-way information sharing can, but rigorous studies comparing the effects of game-based learning with traditional methods are rare. Therefore, this study investigates the effects of a serious game vs. control on learning outcomes related to climate change concepts. We conducted an experiment involving N=105 participants randomly assigned to two treatment groups (a desktop screen-based video game and an immersive VR version of the same game) and a control (a text with charts) and investigated the differences between pre- and post-intervention measures of knowledge. The results show that all three conditions had a large effect on learning, but there were no significant improvement differences between groups. Therefore, video games, either on desktop or virtual reality, may be as effective as more traditional instructional materials. Based on detailed observations of the questionnaire data, we also provide game design recommendations. Future studies could focus on specific features of learning and cognitive engagement and expand this experimental design to affect and behavior.
Playing with Emotions: A Systematic Review Examining Emotions and Emotion Regulation in Esports Performance
Authors: Beres Nicole A. , Klarkowski Madison , Mandryk Regan L.
Published: October 2023

The massive growth of esports has vitalized the need to study human performance in competitive video gaming. The pressure of competitive play elicits a range of emotional experiences, which can affect players during and beyond a gaming session. In this work, we review the state of the literature concerning the role emotions play in esports performance as well as highlight coping strategies players use to regulate emotions during competitive play. We review the findings of N=32 peer-reviewed articles pertaining to emotions and esports, finding that the emotional experiences elicited by competitive play affect esports performance. In response, players attempt to regulate their emotions to maintain performance; however, efforts to do so vary, as they currently lack effective coping strategies. Lastly, we review the potential of technical interventions in esports training for improving emotion regulation among players. Our findings support knowledge development in esports, and present avenues towards promoting the emotional wellbeing of competitive gamers.
The Cycle of Toxicity: Exploring Relationships between Personality and Player Roles in Toxic Behavior in Multiplayer Online Battle Arena Games
Authors: Kordyaka Bastian , Laato Samuli , Jahn Katharina , Hamari Juho , Niehaves Bjoern
Published: October 2023

Toxic behavior remains a salient challenge for online gaming environments, such as multiplayer online battle arena video games (MOBAs). In this study, we sought to understand player roles and settings in which toxicity occurs using a mixed-methods approach. First, we conducted ethnographic observations and interviews with players of the most popular contemporary MOBA, League of Legends (Study 1). During the qualitative analysis three main themes emerged: (1) the fluidity of roles, (2) the subjectivity of the toxic experience, and (3) cascading effects and changing modalities of toxicity. Based on the themes, we formulated hypotheses regarding players’ experience with toxicity. To test these hypotheses, we gathered cross-sectional data from MOBA players (n = 216), which we analyzed with co-variance-based statistics (Study 2). Our quantitative findings showcase the complexity of toxicity as well as players’ ambivalence toward the topic. We found indicators of substantial influences of personality and a cycle of retaliation toxicity spread as victims retaliated against the perpetrator.
Towards Greater Inclusion and Accessibility for Physically Disabled Players in Location-Based Games
Authors: Clark Maximillian Oliver , Singh Aneesha , Barbareschi Giulia
Published: October 2023

Most research on Location-Based Games (LBGs) has been conducted on non-disabled players, meaning the experiences of disabled players are not well understood and potentially overlooked. As such, this research aimed to address the following questions: 1). What are the barriers and needs of disabled LBGs players? 2). How can LBGs be made more inclusive and accessible? To address these questions, two studies were conducted in the form of an online qualitative questionnaire and a series of co-design workshops. Results articulate the needs, barriers, and desired features of 60 participants. Based on our findings and through the collaborative work with disabled players we articulate 4 guidelines for game designers and developers aimed at improving the accessibility of LBGs: 1) Adding avatar features that better represent disabled characteristics, 2). Providing different input options for phone interactions, 3) Allowing for disabled specific accounts and 4) Introducing a messenger feature to LBGs.
A Ruse by Any Other Name: Comparing Loot Boxes and Collectible Card Games Using Magic Arena
Authors: Mattinen Topias , Macey Joseph , Hamari Juho
Published: October 2023

The convergence of gaming and gambling, known as "gamblification", has been a topic of increasing interest in recent years. Loot boxes, i.e., rewards offering randomized content in exchange for money or time, have been a particular focal point. Research has shown links between excessive loot box consumption and problematic consumption behaviors, leading to several attempts to regulate loot boxes. Arguments against regulation have been that loot boxes are conceptually and structurally akin to other unregulated game formats, such as collectible card games. However, this discourse is often without deeper analysis of the mechanics of different products at the center of convergence. Therefore, to add to this knowledge, this article examines the similarities and differences between booster packs in Magic Arena, their physical counterparts in Magic: The Gathering, and loot boxes included in digital games. Particular attention is paid to the ways in which these booster packs compare to loot boxes in terms of consumption patterns, visual appearance, contextual factors, and regulation. Analysis reveals that digital booster packs in Magic Arena differ from both loot boxes and physical card packs, both due to their direct impact on gameplay, and their unique features afforded by the digital environment in which they exist.
Investigating Players’ Perceptions of Deceptive Design Practices within a 3D Gameplay Context
Authors: King John , Fitton Dan , Cassidy Brendan
Published: October 2023

Deceptive design practices have been identified and studied in games but, to date, there have been no substantial explorations of deceptive design practices within 3D environments typically found in PC games. These offer a new set of affordances for interacting with the player, and game developers may be able to utilize these in order to shape gameplay experiences. The goal of this work was to explore users’ perceptions of deceptive design present in a popular free-to-play 3D game. A survey was carried out with 259 adult respondents identifying and explaining instances of deceptive design within video clips of gameplay from a popular Roblox game. Thematic analysis of the responses revealed six new categories of deceptive design pattern within a 3D gameplay context:
Predatory Monetization
,
Default to Purchase
,
UI Misdirection
,
Emotional Interpersonal Persuasion
,
Physical Placement
, and
Narrative Obligation
. Through our work we hope to highlight the use of deceptive design both within current 3D games and future 3D gaming environments. This work is particularly important as 3D and VR gaming grow in popularity alongside game publishers increasingly moving towards “freemium” monetization models for income.
Let’s Play Together through Channels: Understanding the Practices and Experience of Danmaku Participation Game Players in China
Authors: Wang PiaoHong , Lu Zhicong
Published: October 2023

Live streaming is becoming increasingly popular in recent years, as most channels prioritize the delivery of engaging content to their viewers. Among various live streaming channels,
Danmaku participation game
(DPG) has emerged in China as a mixture of live streaming and online gaming, offering an immersive gaming experience to players. Although prior research has explored
audience participation games
(APGs) in North America and Europe, it primarily focuses on discussing prototypes and lacks observation of players in natural settings. Little is known about how players perceive DPGs and their player experience. To fill the research gap, we observed a series of DPG channels and conducted an interview-based study to gain insights into the practices and experiences of DPG players. Our work reveals that DPGs can effectively synergize live streaming and online games, amplifying both player engagement and a profound sense of accomplishment to players.
Understanding Player’s Gesture-Based Communicative Behavior in MOBA Games
Authors: Zheng Keyang , Farzan Rosta
Published: October 2023

Prior research has shown that gesture-based communication plays an integral role in online multiplayer games, especially for teams consisting of strangers with no prior common experiences. What motivates a particular form of in-game communication and its impact, especially promptly after a communication attempt, on team performance is less explored. In this paper, we present a framework for studying individual communication attempts using a gestured-based tool, "Ping", in a popular MOBA game, Heroes of the Storm. We design a framework to capture the game's situational context prior to the communication, the communication attempt, and its immediate impact. Using this framework, we analyze and identify game factors that influence players' decisions to communicate and their choice of communication. We also present how communication has an immediate positive effect on the team's performance. Our findings further the discussion of studying communication behaviors for virtual teams engaging in synchronous, collaborative work with shared visual spaces.
Emotional Virtual Characters for Improving Motivation and Performance in VR Exergames
Authors: Graf Linda , Abramowski Sophie , Born Felix , Masuch Maic
Published: October 2023

Motivation and high effort in exergames are still open to optimization. In reality, coaches can stimulate athletes' engagement by infecting them with their emotions. However, whether these emotion-influencing effects also occur with virtual coaches remains unclear. In the present study, we measured the emotional state, motivation, and performance (punch speed) of 47 participants playing a VR exergame with an emotional (happy/angry) or neutral virtual coach. Results show that the happy and angry coach significantly affected the players' emotions. Furthermore, interacting with the emotional coaches leads to higher motivation, whereas the angry coach causes a reduction of feeling related.
Also, we found a significant positive correlation between the increase in anger and punch speed. Our results show that adding an emotional component to virtual coaches into exergames is promising for increasing motivation and performance. This study highlights the positive effects of emotional virtual characters for improving VR exergames and, therefore, players' health.
The Consistency of Gamification User Types: A Study on the Change of Preferences over Time
Authors: Santos Ana Cláudia Guimarães , Oliveira Wilk , Hamari Juho , Joaquim Sivaldo , Isotani Seiji
Published: October 2023

In recent decades, several studies have suggested and validated user models (e.g., Bartle, and Hexad) to represent different user profiles in games and gamified environments. However, when applying these user models in practice (e.g., to personalize gamification), several studies reported contradictory outcomes. Recently, some studies outlined that one of the possible explanations for these contradictory findings is that people can present changes in their user profiles over time. In this study (N = 118), we present an analysis of the consistency of gamification user orientations after six months of the initial identification, by analyzing the association between user orientations in the first and second data collection. Overall, our results corroborate prior research demonstrating that user orientations can not be considered stable over time and also that the strongest tendency of the users might not be sufficient to determine how users change. Furthermore, we were able to identify that some user orientations can be more stable than others and model some relationships between their profiles after six months. Based on the results, we indicate a research agenda that can further the knowledge about the topic, as well as indicate a set of suggestions on how to model user profiles based on our results.
“I Feel My Abs”: Exploring Non-standing VR Locomotion
Authors: Kontio Reetu , Laattala Markus , Welsch Robin , Hämäläinen Perttu
Published: October 2023

Virtual Reality (VR) games and experiences predominantly have the users interact while standing or seated. However, this only represents a fraction of the full diversity of human movement. In this paper, we explore a novel non-standing approach to VR locomotion where the user performs locomotion movements in the air or only slightly touching the ground with their feet. For instance, the user may lie supine on the ground, reminiscent of the Bicycle Crunch, a core training movement common in Pilates and other forms of bodyweight exercise. Although this cannot generally replace traditional VR locomotion, it provides two benefits that we believe can be of use for specific application domains such as VR exergames: First, the user's lower body movement is not impeded by a small real-life space, allowing versatile navigation of large virtual worlds using walking, running, strafing, and jumping. Second, we allow new ways to activate parts of the body that remain passive in most existing VR interactions. We describe and discuss four different variants of the approach, and investigate two prototypes further in a qualitative user study, to better understand their strengths, weaknesses, and application potential.
“I’m the leader and I’m going to save the world”: Characterizing Empowering and Disempowering Game Experiences
Authors: Vornhagen Jan B. , Bennett Dan , Murphy Dooley , Mekler Elisa D.
Published: October 2023

Empowering people through technology is a core concern of HCI, yet little is known about how players experience empowerment or disempowerment through videogames. We surveyed 250 participants about their dis-/empowering videogame experiences, investigating why they felt dis-/empowered, and how these experiences related to core player experience constructs including emotion and basic needs satisfaction. While empowering experiences were often positive, and disempowering experiences often negative, we found meaningful exceptions to this, and a surprising complexity in player accounts. We capture this diversity in seven themes. These range from ”heroic victories” which follow long periods of failure, to positive experiences of disempowerment, which were appreciated for their narrative meaning. By articulating these complex experiences, and relating them to quantitative measures we provide a foundation for understanding of the role of dis-/empowerment in player experience, and highlight avenues for future work. Data and analyses are available at https://osf.io/zhtu8/
Efficient Low-Resource Medical Information Processing Based on Semantic Analysis and Granular Computing
Authors: Cheng Yuting , Zhang Chao , Sangaiah Arun Kumar , Fan Xueqing , Wang Anna , Wang Liyin , Liu Yixin
Published: October 2023

The rise of the digital economy and e-commerce has fostered a movement towards efficient low-resource medical information processing, a trend that holds great importance in the healthcare sector. Diabetes, being a widespread chronic condition, has witnessed the introduction of glucometers, which offer patients a convenient method of monitoring their blood sugar levels. However, it is worth noting that a considerable proportion of online comments may be subject to emotional bias or contain inaccurate information. Furthermore, the performance of glucometers can be influenced by several attributes, including price, accuracy and portability, thereby potentially complicating the decision-making process for consumers. Semantic analysis can be employed to acquire valuable information, aiding consumers in reasonably choosing the suitable glucometer. This paper utilizes the benefits of granular computing, an emerging computing paradigm, to effectively handle incomplete and uncertain medical information. It employs generalized fuzzy sets, rough sets and three-way decisions (TWD) techniques to boost the accuracy and reliability of medical information fusion. Subsequently, the MABAC (Multi-Attribute Border Approximation Area Comparison) method is utilized to evaluate the reviews of every glucometer, calculate their aggregated scores, and rank and compare them. Ultimately, in light of consumers’ needs and trade-offs, the glucometer with the highest score can be selected. The proposed approach comprehensively considers the weight and priority of multiple attributes, reduces information overload and mitigates selection difficulties, thereby enhancing the accuracy and reliability of low-resource medical information processing.
Decidability of the Satisfiability Problem for Boolean Set Theory with the Unordered Cartesian Product Operator
Authors: Cantone Domenico , Ursino Pietro
Published: October 2023

We give a positive solution to the decidability problem for the fragment of set theory, dubbed
BST
⊗, consisting of quantifier-free formulae involving the Boolean set operators of union, intersection, and set difference, along with the unordered Cartesian product operator ⊗ (where

\(s \otimes t := \big \lbrace \lbrace u,v\rbrace \,\texttt {|}\:u \in s \wedge v \in t \big \rbrace\)

), and the equality predicate, but no membership. Specifically, we provide nondeterministic exponential decision procedures for both the ordinary and the finite satisfiability problems for
BST
⊗. We expect that these decision procedures can be adapted for the standard Cartesian product and, with added technicalities, to the cases involving membership, providing a solution to a longstanding problem in computable set theory.
Optimizing the Operational Parameters Used in Preparing Anodic Aluminum Oxide (AAO) Templates from Low-purity Aluminum
Authors: Castro Lina M. , Canny David , Castro Posada John Henry , Araque-Marín Pedronel , Ostos Carlos
Published: October 2023

Anodized aluminum oxide (AAO) templates with well-defined geometric pore features and uniform nanoporous arrays were successfully obtained from recyclable low-cost, low-purity (99.16%) aluminum via a two-step anodizing process. The templates were characterized by scanning electron microscopy (SEM) and operating parameters were optimized using a Box-Behnken experimental design. The best conditions were found for an oxalic acid electrolyte concentration of 0.6 M, an anodizing potential of 46 V, and a bath temperature of 10 °C. This process resulted in an averaged regularity ratio (ravg) value of 2.66 which compares very favorably with previously reported values obtained from higher-purity aluminum (99.5%). Templates developed from low-purity aluminum are more suitable for high-volume industrial applications where there is a practical trade-off between cost and the quality of the geometric pores.
Impact of maternal dietary folic acid or choline dietary deficiencies on vascular function in young and middle-aged female mouse offspring after ischemic stroke
Authors: Pull Kasey , Folk Robert , Kang Jeemin , Jackson Shaley , Gusek Brikena , Esfandiarei Mitra , Jadavji Nafisa M.
Published: October 2023

We demonstrate that a maternal dietary deficiency in one-carbon (1C) metabolites result in reduced cerebral blood flow in adult female offspring after ischemic stroke, but the long-term effects are not present. This result points to the key role of the maternal diet in early life neuroprogramming, while emphasizing its effects on both fetal development and long-term cerebrovascular health.
Using Street View Images to Examine the Impact of Built Environment on Street Property Crimes in the Old District of CA City, China
Authors: Chen Xiliang , Li Gang , Mehmood Muhammad Sajid , Jin Annan , Du Mengjia , Xue Yutong
Published: October 2023

Property crimes on the street are common in cities, posing a certain threat to people’s daily life safety and social stability. Therefore, it is essential to analyze the characteristics and spatial patterns of street property crimes in the built environment to make cities safe. Based on environmental criminological theories, this study takes the MC old district in CA City as a case study and uses a negative binomial regression model to analyze the influencing factors of street property crimes in different periods. The results show the temporal and spatial differentiation in street property crimes. In terms of time, the number of crime cases presents the features of “three peaks and two troughs.” In terms of space, crime cases show spatial clustering patterns, mainly concentrated in the commercial and prosperous areas where the main roads of the city are located. During the whole day, openness, banks, bars, and restaurants have a significant positive effect on crime occurrence; closeness, police cameras, grocery stores, and distance to the nearest police patrol station had a significant negative effect on crime occurrence. There are two explanations for the positive and negative correlations of some environmental variables with a crime before dawn, daytime, and nighttime. This study explored the spatial-temporal distribution and factors that influence the old district street property crimes by extracting physical environmental characteristics from street view images using deep learning algorithms and providing a reference base for police departments to prevent and combat crime.
Cardiac Tuberculoma Presenting as Sudden Cardiac Death in an Immunocompetent Young Man: A Case Report and Literature Review
Authors: Lema Alemayehu Shiferaw
Published: October 2023

Tuberculosis is one of several preventable and curable communicable diseases that is a major cause of morbidity and one of the top ten causes of death worldwide. Cardiac tuberculosis frequently affects the pericardium. Although rare, most cases of tuberculosis involving the myocardium and endocardium present as sudden cardiac death in asymptomatic cases. Information about the myocardial involvement of tuberculosis appears in the literature once in a blue moon. As a result, there is a knowledge gap about cardiac tuberculosis among health professionals. Here, a case of sudden cardiac death from tuberculoma of the right atrium with a secondary thrombus causing bicaval obstruction that is observed in an asymptomatic immunocompetent young man is presented. Furthermore, challenges related to the diagnosis and management of cardiac tuberculosis are discussed, and an overview of the relevant literature is provided to break new ground in early diagnosis and therapy.
Canine Parvovirus 2C Identified in Dog Feces from Poop Bags Collected from Outdoor Waste Bins in Arizona USA, June 2022
Authors: Faleye Temitope O. C. , Driver Erin M. , Bowes Devin A. , Smith Abriana , Kaiser Nicole A. , Wright Jillian M. , Chapman Ainsley R. , Halden Rolf U. , Varsani Arvind , Scotch Matthew
Published: October 2023

Canine parvoviruses (CPVs) are a major cause of morbidity and mortality in dogs. However, surveillance has been largely limited to clinically manifest cases, resulting in a dearth of CPV genomic information on virus type, abundance, and diversity, limiting our understanding of its evolutionary dynamics. We tested the feasibility of using dog feces in poop bags collected from outdoor waste bins as a source for environmental surveillance of CPV. After polymerase chain reaction, long-read sequencing, and bioinformatics, we identified that CPV-2c was present in Arizona, USA, in June 2022 and documented variants with amino acid substitutions 530E and 101K in NS1 and NS2, respectively. Based on publicly available sequence data in GenBank as of January 2023, the CPV genome described here represents the only CPV genome described in the USA from the 2022 season, despite news of CPV outbreak-associated fatalities in dogs in the USA. This highlights the need for more studies that document CPV complete or near complete genomes, as well as experimental studies, to further our understanding of its evolutionary process.
Reproductive Behavior of Bubalus arnee (Kerr, 1792) (Mammalia: Artiodactyla: Bovidae) in Koshi Tappu Wildlife Reserve and Chitwan National Park, Nepal
Authors: Bhattarai Ram Krishna , Joshi Rajeev , Gautam Jeetendra , Kandel Birendra , Singh Bikram
Published: October 2023

The Asiatic wild water buffalo (Bubalus arnee Kerr), an endangered species featured on the IUCN Red List, is distributed across Nepal, India, Sri Lanka, Myanmar, Bhutan, Cambodia, and Thailand. This investigation delves into the reproductive and certain social behaviors exhibited by Bubalus arnee across distinct habitats and herd types within Nepal’s Koshi Tappu Wildlife Reserve (KTWR) and Chitwan National Park (CNP) during the premonsoon and postmonsoon spans of 2018. The data were amassed through direct observations employing focal animal sampling, continuous sampling, and scan sampling methodologies. Eight primary behavioral activities were noted: chasing, courtship, grazing, mating, mowing, sniffing, urination, and wallowing. We carefully structured the gathered data and input it into a Microsoft Excel spreadsheet to facilitate analysis. For a more comprehensive visualization of reproductive behavior, we utilized the ggplot2 package within R-studio, enabling the creation of informative graphical depictions. During the premonsoon phase, Bull A exhibited six reproductive behaviors in KTWR. Notably, sniffing was the most frequently observed behavior, recorded six times (37.5%) daily, succeeded by fighting and urination with four (25%) and three (18.35%) daily observations, respectively. Chasing, mating, and courtship were each observed once (6.25%) daily. In contrast, during both seasons, Bulls B, M, and J were not observed partaking in mating activities. When analyzing the postmonsoon reproductive behavior of the observed B. arnee in KTWR and CNP, a notable distinction emerged. In KTWR, there were four more instances of sniffing behavior compared to CNP. In addition, courtship behavior was slightly more frequent in KTWR, occurring three times, whereas it was observed only twice in CNP. Similarly, urination activity was recorded twice as often in KTWR as compared to CNP. As a suggestion for future research, exploring the specific factors influencing the observed variations in reproductive behaviors and habitat preferences of Bubalus arnee could provide valuable insights into the conservation and management of these endangered species.
Correlation between Treatment Outcomes and Serum Vitamin D Levels As Well As Infliximab Trough Concentration among Chinese Patients with Crohn’s Disease
Authors: Song Xiaomei , Zhang Huihui , Wang Hao , Li Zhongyue , Zhou Xiaoqin , Guo Hong
Published: October 2023

Background. The relationship between vitamin D (vit-D) levels and the effectiveness of infliximab (IFX) in patients with Crohn’s disease (CD) remains controversial. Objective. To evaluate the interaction between vit-D levels and the response to IFX therapy in patients with CD. Methods. This was a retrospective cohort study. Serum vit-D and IFX trough concentrations (TC) were measured in 84 patients, and statistical analyses were performed. Results. The total vit-D deficiency rate at enrollment, at week 14 and week 38, was 64.3%, 41.67%, and 37.5%, respectively (

P
<
0.001

). CD activity index (CDAI) (120, range, 93–142.75) and simplified endoscopic activity score for CD (SES-CD) (2, range, 0–4) at week 14 were lower than that of enrollment (CDAI, 136.5, range, 101.25–196; SES-CD 13, range, 5–23) (

P
<
0.001

). The biochemical remission (BR), clinical remission (CR), endoscopic remission (ER), and response (ERe) rates of week 38 were 76.1%, 88.5%, 22.4%, and 67.2%, respectively. vit-D levels at enrollment were positively correlated with CDAI at week 38 (

P
=
0.024

). IFX serum TC was related to BR (

P
=
0.036

), CR (

P
=
0.032

) at week 14, and ERe (

P
=
0.009

) at week 38. Conclusion. Among Chinese patients with CD, vit-D levels prior to IFX therapy are related to CDAI scores, and IFX serum TC is associated with BR, CR, and ERe.
Epidemiology of a Hybrid Swarm: Evidence of 11 Feline Infectious Agents Circulating in a Population of Sympatric European Wildcat Hybrids and Free-Living Domestic Cats, in Scotland
Authors: Alves Beatriz S. G. , Bacon Alice , Langridge Keri , Papasouliotis Kostas , Handel Ian , Anderson Neil E. , Meredith Anna L.
Published: October 2023

Hybridisation between wild and domestic species poses a serious challenge to conservation management and can, potentially, lead to extinction. Alongside it, disease transmission will inevitably occur. However, the link between these two phenomena has historically been neglected. In Scotland, the European wildcat is particularly threatened by hybridisation with the domestic cat, a process promoted by long-term habitat loss, human encroachment, and persecution. Between 2015 and 2019, free-living cats (n = 120) were captured in six conservation priority areas of northern Scotland. Samples were collected for infectious disease screening (feline immunodeficiency virus, feline leukaemia virus, feline calicivirus, feline herpesvirus, Chlamydia felis, Mycoplasma felis, Bordetella bronchiseptica, Mycoplasma haemofelis, Candidatus Mycoplasma haemominutum, Candidatus Mycoplasma turicensis, and Tritrichomonas foetus) and genetic analysis. Polymerase chain reaction and reverse transcriptionPCR were used to detect infectious DNA or RNA, respectively. The hybrid score (Q) for each individual cat was determined using a 35-SNP-marker test. Statistical analysis investigated the association between Q and probability of infection, accounting for spatial clustering. The results confirmed the presence of 11 infectious agents circulating in the free-living cat population of northern Scotland, which consists of a hybrid swarm between F. silvestris and F. catus. For eight of them (feline leukaemia virus, feline herpesvirus C. felis, B. bronchiseptica, M. felis, M. haemofelis, Ca. M. haemominutum, and T. foetus), there was no significant association between infection probability and Q, supporting our hypothesis that the hybrid swarm may be functioning as a single epidemiological unit. Considering the impact of infectious diseases on health, welfare, and population dynamics of domestic cats, their presence in the extremely fragile and hybridised population of F. silvestris in Scotland could be population limiting or, potentially, contribute to local extinction. Comprehensive disease surveillance, risk analysis, and domestic cat management will be essential for the European wildcat conservation, particularly where hybridisation is increasing and anthropogenic factors are prevalent.
Stroma-Mediated Breast Cancer Cell Proliferation Indirectly Drives Chemoresistance by Accelerating Tumor Recovery between Chemotherapy Cycles
Authors: Miroshnychenko Daria , Miti Tatiana , Kumar Pragya , Miller Anna , Laurie Mark , Giraldo Nathalia , Bui Marilyn M. , Altrock Philipp M. , Basanta David , Marusyk Andriy
Published: October 2023

The ability of tumors to survive therapy reflects both cell-intrinsic and microenvironmental mechanisms. Across many cancers, including triple-negative breast cancer (TNBC), a high stroma/tumor ratio correlates with poor survival. In many contexts, this correlation can be explained by the direct reduction of therapy sensitivity induced by stroma-produced paracrine factors. We sought to explore whether this direct effect contributes to the link between stroma and poor responses to chemotherapies. In vitro studies with panels of TNBC cell line models and stromal isolates failed to detect a direct modulation of chemoresistance. At the same time, consistent with prior studies, fibroblast-produced secreted factors stimulated treatment-independent enhancement of tumor cell proliferation. Spatial analyses indicated that proximity to stroma is often associated with enhanced tumor cell proliferation in vivo. These observations suggested an indirect link between stroma and chemoresistance, where stroma-augmented proliferation potentiates the recovery of residual tumors between chemotherapy cycles. To evaluate this hypothesis, a spatial agent–based model of stroma impact on proliferation/death dynamics was developed that was quantitatively parameterized using inferences from histologic analyses and experimental studies. The model demonstrated that the observed enhancement of tumor cell proliferation within stroma-proximal niches could enable tumors to avoid elimination over multiple chemotherapy cycles. Therefore, this study supports the existence of an indirect mechanism of environment-mediated chemoresistance that might contribute to the negative correlation between stromal content and poor therapy outcomes.

Significance:

Integration of experimental research with mathematical modeling reveals an indirect microenvironmental chemoresistance mechanism by which stromal cells stimulate breast cancer cell proliferation and highlights the importance of consideration of proliferation/death dynamics.

See related commentary by Wall and Echeverria, p. 3667
Prostate Cancer Progression Relies on the Mitotic Kinase Citron Kinase
Authors: Rawat Chitra , Ben-Salem Salma , Singh Nidhi , Chauhan Gaurav , Rabljenovic Anja , Vaghela Vishwa , Venkadakrishnan Varadha Balaji , Macdonald Jonathan D. , Dahiya Ujjwal R. , Ghanem Yara , Bachour Salam , Su Yixue , DePriest Adam D. , Lee Sanghee , Muldong Michelle , Kim Hyun-Tae , Kumari Sangeeta , Valenzuela Malyn May , Zhang Dingxiao , Hu Qiang , Cortes Gomez Eduardo , Dehm Scott M. , Zoubeidi Amina , Jamieson Christina A.M. , Nicolas Marlo , McKenney Jesse , Willard Belinda , Klein Eric A. , Magi-Galluzzi Cristina , Stauffer Shaun R. , Liu Song , Heemers Hannelore V.
Published: October 2023

Prostate cancer remains the second leading cause of cancer death in men in Western cultures. A deeper understanding of the mechanisms by which prostate cancer cells divide to support tumor growth could help devise strategies to overcome treatment resistance and improve survival. Here, we identified that the mitotic AGC family protein kinase citron kinase (CIT) is a pivotal regulator of prostate cancer growth that mediates prostate cancer cell interphase progression. Increased CIT expression correlated with prostate cancer growth induction and aggressive prostate cancer progression, and CIT was overexpressed in prostate cancer compared with benign prostate tissue. CIT overexpression was controlled by an E2F2–Skp2–p27 signaling axis and conferred resistance to androgen-targeted treatment strategies. The effects of CIT relied entirely on its kinase activity. Conversely, CIT silencing inhibited the growth of cell lines and xenografts representing different stages of prostate cancer progression and treatment resistance but did not affect benign epithelial prostate cells or nonprostatic normal cells, indicating a potential therapeutic window for CIT inhibition. CIT kinase activity was identified as druggable and was potently inhibited by the multikinase inhibitor OTS-167, which decreased the proliferation of treatment-resistant prostate cancer cells and patient-derived organoids. Isolation of the in vivo CIT substrates identified proteins involved in diverse cellular functions ranging from proliferation to alternative splicing events that are enriched in treatment-resistant prostate cancer. These findings provide insights into the regulation of aggressive prostate cancer cell behavior by CIT and identify CIT as a functionally diverse and druggable driver of prostate cancer progression.

Significance:

The poorly characterized protein kinase citron kinase is a therapeutic target in prostate cancer that drives tumor growth by regulating diverse substrates, which control several hallmarks of aggressive prostate cancer progression.

See related commentary by Mishra et al., p. 4008
XPO1 Enables Adaptive Regulation of mRNA Export Required for Genotoxic Stress Tolerance in Cancer Cells
Authors: Marullo Rossella , Rutherford Sarah C. , Revuelta Maria V. , Zamponi Nahuel , Culjkovic-Kraljacic Biljana , Kotlov Nikita , Di Siervi Nicolás , Lara-Garcia Juan , Allan John N. , Ruan Jia , Furman Richard R. , Chen Zhengming , Shore Tsiporah B. , Phillips Adrienne A. , Mayer Sebastian , Hsu Jingmei , van Besien Koen , Leonard John P. , Borden Katherine L.B. , Inghirami Giorgio , Martin Peter , Cerchietti Leandro
Published: October 2023

Exportin-1 (XPO1), the main soluble nuclear export receptor in eukaryotic cells, is frequently overexpressed in diffuse large B-cell lymphoma (DLBCL). A selective XPO1 inhibitor, selinexor, received approval as single agent for relapsed or refractory (R/R) DLBCL. Elucidating the mechanisms by which XPO1 overexpression supports cancer cells could facilitate further clinical development of XPO1 inhibitors. We uncovered here that XPO1 overexpression increases tolerance to genotoxic stress, leading to a poor response to chemoimmunotherapy. Upon DNA damage induced by MYC expression or exogenous compounds, XPO1 bound and exported EIF4E and THOC4 carrying DNA damage repair mRNAs, thereby increasing synthesis of DNA damage repair proteins under conditions of increased turnover. Consequently, XPO1 inhibition decreased the capacity of lymphoma cells to repair DNA damage and ultimately resulted in increased cytotoxicity. In a phase I clinical trial conducted in R/R DLBCL, the combination of selinexor with second-line chemoimmunotherapy was tolerated with early indication of efficacy. Overall, this study reveals that XPO1 overexpression plays a critical role in the increased tolerance of cancer cells to DNA damage while providing new insights to optimize the clinical development of XPO1 inhibitors.

Significance:

XPO1 regulates the dynamic ribonucleoprotein nuclear export in response to genotoxic stress to support tolerance and can be targeted to enhance the sensitivity of cancer cells to endogenous and exogenous DNA damage.

See related commentary by Knittel and Reinhardt, p. 3