bluuebunny/crossref_metadata_2025 huggingface dataset:
Lessons from Homebrewed Hybridity: Designing Hybrid Digital Boardgames for Distanced Play
Authors: Sparrow Lucy A. , Rogerson Melissa J.
Published: October 2023

In 2020–2021, under the restrictions associated with the COVID-19 pandemic, boardgame players around the world sought out ways to play physical boardgames with each other despite being physically apart. Their creative appropriations of digital technologies and physical tools to allow for hybrid distanced play demonstrate not only the resilience of boardgaming as a hobby, but also provide important insights into the design of novel distanced hybrid digital boardgames (DHDBs). Through a survey of over 1300 respondents, this paper explores the ways distanced players engaged in homebrew practices to make physical boardgame play possible. Through reflexive thematic analysis, we identify three themes that reflect the practical issues players grappled with, including game choice, game mode or setup, and technical implementation. Reflecting on the challenges and opportunities associated with these issues, we consider their implications for DHDB design more generally. In doing so, we present the DHYE (Distanced Hybrid plaY Experience) framework, a practical set of design considerations that emphasises an understanding of distance not simply as an obstacle to enjoyable boardgame play but as an inspiration for novel and meaningful design.
A Matter of Perspective: Designing Immersive Character Transitions for Virtual Reality Games
Authors: Cmentowski Sebastian , Karaosmanoglu Sukran , Kievelitz Fabian , Steinicke Frank , Krüger Jens
Published: October 2023

Virtual reality (VR) games intensify storytelling experiences by letting players take the role of a character. However, in contrast to films, novels, or games, VR experiences often remain centered around one single character without using the potential of complex multiprotagonist plots. Our work engages in this critical topic by investigating the design of immersive and natural transitions between different characters. First, we conducted a scoping review to identify existing multiprotagonist VR games (N=18) and grouped their used transition techniques into four categories. Based on these findings and prior research, we designed two transition techniques (Static Map vs. Rebodying) and conducted a between-participants (N=36) study to explore their effect on user experience. Our results show that Rebodying outperforms Static Map regarding the perceived realism, acceptance, and spatial understanding of the character transitions. Both conditions do not differ significantly in terms of cybersickness. Finally, we provide future directions for developing, improving, and exploring of multiprotagonist transition techniques in VR games.
Counterplay: Circumventing the Belgian Ban on Loot Boxes by Adolescents
Authors: Denoo Maarten , Dupont Bruno , Grosemans Eva , Zaman Bieke , De Cock Rozane
Published: October 2023

In 2018, Belgium made the world news for being the first country to ban loot boxes in games for all its inhabitants. As players’ freedom to purchase loot boxes was restricted, however, methods of circumventing the ban came into practice. Departing from counterplay theory, we drew from an online survey among Belgian adolescents aged 11 18 with two questions in mind: what counterplay practices are used to circumvent the Belgian ban on loot boxes, and how do counterplayers (N = 124) compare to non counterplayers (N = 329) in terms of their engagement with loot boxes and games more broadly? Our findings suggest that counterplayers resist current regulatory arrangements in a myriad of ways, delineating the boundaries of a national ban in a global game ecology. Counterplayers appeared to differentiate themselves from non counterplayers both in terms of depth characteristics (sense of belonging to an online community, perceived gaming ability, gaming disorder, and risky loot box use) and breadth characteristics (frequency of skin betting, selling loot box rewards, and (re)watching loot box opening livestreams). Ultimately, our study may tease out debate on how to regulate games successfully in the face of players’ technical abilities and motivation to gain access.
“An Adapt-or-Die Type of Situation”: Perception, Adoption, and Use of Text-to-Image-Generation AI by Game Industry Professionals
Authors: Vimpari Veera , Kultima Annakaisa , Hämäläinen Perttu , Guckelsberger Christian
Published: October 2023

Text-to-image generation (TTIG) models, a recent addition to creative AI, can generate images based on a text description. These models have begun to rival the work of professional creatives, and sparked discussions on the future of creative work, loss of jobs, and copyright issues, amongst other important implications. To support the sustainable adoption of TTIG, we must provide rich, reliable and transparent insights into how professionals perceive, adopt and use TTIG. Crucially though, the public debate is shallow, narrow and lacking transparency, while academic work has focused on studying the use of TTIG in a general artist population, but not on the perceptions and attitudes of professionals in a specific industry. In this paper, we contribute a qualitative, exploratory interview study on TTIG in the Finnish videogame industry. Through a Template Analysis on semi-structured interviews with 14 game professionals, we reveal 12 overarching themes, structured into 39 sub-themes on professionals' perception, adoption and use of TTIG in games industry practice. Experiencing (yet another) change of roles and creative processes, our participants' reflections can inform discussions within the industry, be used by policymakers to inform urgently needed legislation, and support researchers in games, HCI and AI to support the sustainable, professional use of TTIG, and foster games as cultural artefacts.
Why Should Red and Green Never Be Seen? Exploring Color Blindness Simulations as Tools to Create Chromatically Accessible Games
Authors: Pinheiro Mateus , Viana Windson , de Gois Ribeiro Darin Ticianne
Published: October 2023

Video games have become an important aspect of modern culture, especially with the widespread use of mobile devices. Thus, it is important that video games are accessible to all people, but colorblind players are still affected by the use of colors in game interfaces. Some challenges of developing chromatically accessible games are the limited availability of colorblind test subjects and the importance of identifying and considering accessibility threats even in the early stages of development. Thus, digital simulations emerge as possible tools to increase accessibility and awareness. In this paper, we conducted three empirical studies that seek to verify the relationship between the identification of color accessibility problems by people with typical color vision using simulations and people with color blindness, in the context of mobile games. Results indicate concrete uses in which color blindness simulations give advantages to developers with typical vision in identifying chromatic accessibility issues in their games. Additionally, we discuss different possibilities for incorporating simulation tools, accessibility guidelines, and colorblind user participation into a realistic game design life cycle. We also discuss how the incorporation of simulation tools could be beneficial to foment the discussion of accessibility in game design studios.
Analyzing Trans (Mis)Representation in Video Games to Remediate Gender Dysphoria Triggers
Authors: Liang Shano , Cormier Michelle V. , Toups Dugas Phoebe O. , Bohrer Rose
Published: October 2023

Many trans people experience gender dysphoria -- distress caused by mismatches in internal and external experiences of gender.
Video games engage intimately with the self, creating intense experiences involving identities, bodies, and social interaction.
This combination of factors renders trans players vulnerable to gender dysphoria triggers: failures of interaction design that result in gender dysphoria.
The present research undertakes a thematic analysis of four popular games, drawn from an initial corpus of 31.
It contributes a definition of gender dysphoria triggers, case studies of triggering games, an initial gender dysphoria categorization to provide a useful design language, and examples of alternative designs for extant triggers.
The analysis combines the authors' positionality as trans gamers; critical cultural studies methodologies, including textual analysis; a critical discourse analysis of production-side statements and interviews and player-side comments about diversity in those games; and close readings of the games themselves.
The paper concludes with a call for trans inclusivity in game design, which we structure around the necropolitical concept of the relation of care.
The Aesthetics of Disharmony: Harnessing Sounds and Images for Dynamic Soundscapes Generation
Authors: Escarce Junior Mário , Rossmann Martins Georgia , Soriano Marcolino Leandro , Rubegni Elisa
Published: October 2023

This work presents an autonomous approach that explores the dynamic generation of relaxing soundscapes for games and artistic installations. Differently from past works, this system can generate music and images simultaneously, preserving human intent and coherency. We present our algorithm for the generation of audiovisual instances and also a system based on this approach, verifying the quality of the outcomes it can produce in light of current approaches for the generation of images and music. We also instigate the discussion around the new paradigm in arts, where the creative process is delegated to autonomous systems, with limited human participation. Our user study (N=74) shows that our approach overcomes current deep learning models in terms of quality, being recognized as human production, as if the outcome were being generated out of an endless musical improvisation performance.
Fused Spectatorship: Designing Bodily Experiences Where Spectators Become Players
Authors: Patibanda Rakesh , Saini Aryan , Overdevest Nathalie , Montoya Maria F. , Li Xiang , Chen Yuzheng , Nisal Shreyas , Andres Josh , Knibbe Jarrod , van den Hoven Elise , Mueller Florian ‘Floyd’
Published: October 2023

Spectating digital games can be exciting. However, due to its vicarious nature, spectators often wish to engage in the gameplay beyond just watching and cheering. To blur the boundaries between spectators and players, we propose a novel approach called "Fused Spectatorship", where spectators watch their hands play games by loaning bodily control to a computational Electrical Muscle Stimulation (EMS) system. To showcase this concept, we designed three games where spectators loan control over both their hands to the EMS system and watch them play these competitive and collaborative games. A study with 12 participants suggested that participants could not distinguish if they were watching their hands play, or if they were playing the games themselves. We used our results to articulate four spectator experience themes and four fused spectator types, the behaviours they elicited and offer one design consideration to support each of these behaviours. We also discuss the ethical design considerations of our approach to help game designers create future fused spectatorship experiences.
Creative Console: A Player-Driven Game Based on a Modular Fast-Evolving-and-Verifying Framework
Authors: Fang Ke , Jiang Jinsheng , Sun Xing , Chen Yuqing , He Jiajia , Huang Lei
Published: October 2023

We present Creative Console, a player-driven game in which a player, without prior knowledge of game programming, can design and realize a game within 15 minutes. Players design a game by selecting, adding, or changing a game component and then playtesting the game immediately. We refer to this central process as the Fast-Evolving-And-Verifying (FEAV) module. Players play successive FEAV modules, each taking around 3 minutes, and progressively complete a game design. We conducted an exploratory study of Creative Console. Within 48 hours, all 21 participants developed 527 game levels, covering 10 genres of games. The study demonstrates that Creative Console is enjoyable to play and effectively empowers creative and diversified game design. We furthermore conducted a grounded theory analysis of their design process. Our analysis concludes that modular FEAV, serendipity, and social communication are the three pillars of Creative Console, which casts light on future player-driven creative design systems.
Auto-Paizo Games: Towards Understanding the Design of Games That Aim to Unify a Player’s Physical Body and the Virtual World
Authors: Patibanda Rakesh , Hill Chris , Saini Aryan , Li Xiang , Chen Yuzheng , Matviienko Andrii , Knibbe Jarrod , van den Hoven Elise , Mueller Florian ‘Floyd’
Published: October 2023

Most digital bodily games focus on the body as they use movement as input. However, they also draw the player’s focus away from the body as the output occurs on visual displays, creating a divide between the physical body and the virtual world. We propose a novel approach – the "Body as a Play Material" – where a player uses their body as both input and output to unify the physical body and the virtual world. To showcase this approach, we designed three games where a player uses one of their hands (input) to play against the other hand (output) by loaning control over its movements to an Electrical Muscle Stimulation (EMS) system. We conducted a thematic analysis on the data obtained from a field study with 12 participants to articulate four player experience themes. We discuss our results about how participants appreciated the engagement with the variety of bodily movements for play and the ambiguity of using their body as a play material. Ultimately, our work aims to unify the physical body and the virtual world.
How Gamified Are Sustainable Food Apps? Applying the Gameful Design Heuristics to Evaluate Sustainable Food Apps
Authors: Grüger Diana , Weiblen Julian , Weber Philip , Ludwig Thomas
Published: October 2023

A large number of mobile apps support the sustainable use of food. These apps often use playful elements to enhance the user experience and promote their long-term use. However, we know little about which conceptual aspects of gamification and which gamified elements are actually used in the context of sustainable food apps. Therefore, in this paper, we analyse 76 mobile apps from the Google Play Store found with the term ‘sustainable food’ of which we analyse 27 apps in detail using the Gameful Design Heuristics. Our analysis uncovers a low average heuristics score and an unbalanced usage of subheuristics and heuristic categories. Additionally, gamification is unevenly distributed among food themes and sustainability categories. This study’s results contribute to the research on commercial gamified apps related to sustainability and food. Thus, this paper contributes to gamification design by identifying design opportunities that serve as interesting starting points for future work.
Fluito: Towards Understanding the Design of Playful Water Experiences through an Extended Reality Floatation Tank System
Authors: Montoya Maria F. , Ji YuYang , Wee Ryan , Overdevest Nathalie , Patibanda Rakesh , Saini Aryan , Pell Sarah Jane , Mueller Florian ‘Floyd’
Published: October 2023

Water's pleasant nature and associated health benefits have captivated the interest of HCI researchers. Prior WaterHCI work mainly focused on advancing instrumental applications, such as improving swimming performance, and less on designing systems that support interacting with technology in water in more playful contexts. In this regard, we propose floatation tanks as research vehicles to investigate the design of playful interactive water experiences. Employing somaesthetic design, we developed a playful extended reality floatation tank experience: "Fluito". We conducted a 13-participant study to understand how specific design features amplified participants' water experiences. We used a postphenomenological lens to articulate eight strategies useful for designers aiming to develop digital playful experiences in water, such as designing to call attention to the water and designing to encourage breathing and body awareness in water experiences. Ultimately, we hope that our work supports people to be playful and benefit from the many advantages of being in water.
Visualizing the Spatio-Temporal Evolution of Gameplay using Storyline Visualization: A Study with League of Legends
Authors: Wallner Günter , Wang Letian , Dormann Claire
Published: October 2023

Players increasingly adopt a data-driven approach to review and improve their gaming skills. In the wake of this, spatio-temporal visualizations gained popularity but remain challenging to design. Storyline visualizations are unique in the way they integrate time and location information into a single view to show how entity relationships develop over time. We adopt the storyline visualization technique to summarize gameplay for the purpose of post-play review. We demonstrate the method by applying it to League of Legends matches and evaluated it with 39 players of the game in a task-based online study using the triad framework for spatio-temporal queries by Peuquet. Results indicate that players responded positively to the approach and could, by and large, solve tasks well but that time-based tasks proved most challenging and least efficient to solve. Based on our findings, we reflect on possibilities for enhancing the design of storyline visualizations for game-related data analysis.
Tiles to Move: Investigating Tile-Based Locomotion for Virtual Reality
Authors: Funke Jana Franceska , Schikorr Anja , Karaosmanoglu Sukran , Hirzle Teresa , Steinicke Frank , Rukzio Enrico
Published: October 2023

Tile-based locomotion (TBL) is a popular locomotion technique for computer, console, and board games.
However, despite its simplicity and unconventional movement, the transfer of TBL to virtual reality (VR)
as a game platform remains unexplored. To fill this gap, we introduce TBL for VR on the example of two
techniques: a controller and a feet-based one. In a first user study, we evaluated the usability and acceptance
of the techniques compared to teleportation and touchpad locomotion. In a second exploratory user study, we
evaluated the user experience of both TBL techniques in a maze and a museum scenario. The findings show that
both techniques provide enjoyment and acceptable usability by creating either a relaxing (controller-based) or
a physically active (feet-based) solution. Finally, our results highlight that TBL techniques work particularly
well for small, constrained spaces that allow users to focus on exploring details in the nearby environment
(important for games) in contrast to large open spaces that require faster locomotion, like teleportation.
Privacy Is the Price: Player Views and Technical Evaluation of Data Practices in Online Games
Authors: Bourdoucen Amel , Nurgalieva Leysan , Lindqvist Janne
Published: October 2023

Online games engage players in sharing their personal data with the games themselves and other players, which can pose security, privacy, and integrity risks to players. This paper presents an analysis of data practices in 21 online games and a qualitative interview study (N=20) that explores players' views on sharing their data in online games. Our results show that players' willingness to share personal information is contextual and related to game settings and game design elements. Our findings also highlight players' misconceptions and concerns surrounding data collection in games, and approaches to mitigate these concerns. Finally, this work identifies questionable design practices with online games and suggests design implications that will increase transparency and player control over data sharing.
Objective Difficulty-Skill Balance Impacts Perceived Balance but Not Behaviour: A Test of Flow and Self-Determination Theory Predictions
Authors: Deterding Sebastian , Cutting Joe
Published: October 2023

Flow and self-determination theory predict that game difficulty in balance with player skill maximises enjoyment and engagement, mediated by attentive absorption or competence. Yet recent evidence and methodological concerns are challenging this view, and key theoretical predictions have remained untested, importantly which objective difficulty-skill ratio is perceived as most balanced. To test these, we ran a preregistered study (n=309) using a Go-like 2-player game with an AI opponent, randomly assigning players to one of three objective difficulty-skill ratios (AI plays to win, draw, or lose) over five matches. The AI successfully manipulated objective balance, with the draw condition perceived as most balanced. However, balance did not impact play behaviour, nor did we find the predicted uniform 'inverted-U' between balance and positive play experiences. Importantly, we found both theories too underspecified to severely test. We conclude that balance and competence likely matter less for behavioural engagement than commonly held. We propose alternative factors such as player appraisals, novelty, and progress, and debate the value and challenges of theory-testing work in games HCI.
Method of Electrical Muscle Stimulation for Training FPS Game Players in the Timing of Shots
Authors: Zhou Shuo , Segawa Norihisa
Published: October 2023

In first-person shooter (FPS) games, players often need to calculate the timing of their shots for moving targets in advance based on the speed and relative position of those targets. For most players, the accurate timing of shots requires extended gaming experience and training. Unlike professional players, hobby players have less time to compete and train, do not receive professional game guidance, and cannot afford expensive gaming devices. According to previous studies, wearable devices with electrical stimulation can effectively control the muscles with rapid reactions. Here, we provide a method for training the timing of gaming shooters using electrical muscle stimulation (EMS). We believe that training with EMS is feasible and effective, allowing players to quickly learn and improve their gaming experience. To test the feasibility and effectiveness of our approach, we first tested the player's reaction time when using the EMS device to ensure that it did not have a negative impact on the player. Participants were then trained in a custom FPS game with three methods: EMS, non-EMS and EMS-only. The results showed a more significant increase in the average hit rate of EMS-trained participants compared to those trained using the other two methods. Thus, our study shows the possibility of using EMS devices as a training medium for a custom FPS game.
Spatio-temporal Contrastive Learning-enhanced GNNs for Session-based Recommendation
Authors: Wan Zhongwei , Liu Xin , Wang Benyou , Qiu Jiezhong , Li Boyu , Guo Ting , Chen Guangyong , Wang Yang
Published: October 2023

Session-based recommendation (SBR) systems aim to utilize the user’s short-term behavior sequence to predict the next item without the detailed user profile.Most recent works try to model the user preference by treating the sessions as between-item transition graphs and utilize various graph neural networks (GNNs) to encode the representations of pair-wise relations among items and their neighbors. Some of the existing GNN-based models mainly focus on aggregating information from the view of spatial graph structure, which ignores the temporal relations within neighbors of an item during message passing and the information loss results in a sub-optimal problem. Other works embrace this challenge by incorporating additional temporal information but lack sufficient interaction between the spatial and temporal patterns. To address this issue, inspired by the uniformity and alignment properties of contrastive learning techniques, we propose a novel framework called Session-based Recommendation with Spatio-temporal Contrastive Learning-enhanced GNNs (RESTC). The idea is to supplement the GNN-based main supervised recommendation task with the temporal representation via an auxiliary cross-view contrastive learning mechanism. Furthermore, a novel global collaborative filtering graph embedding is leveraged to enhance the spatial view in the main task.Extensive experiments demonstrate the significant performance of RESTC compared with the state-of-the-art baselines. We release our source code athttps://github.com/SUSTechBruce/RESTC-Source-code.
Survey of Information Encoding Techniques for DNA
Authors: Heinis Thomas , Sokolovskii Roman , Alnasir Jamie J.
Published: October 2023

The yearly global production of data is growing exponentially, outpacing the capacity of existing storage media, such as tape and disk, and surpassing our ability to store it. DNA storage—the representation of arbitrary information as sequences of nucleotides—offers a promising storage medium. DNA is nature’s information-storage molecule of choice and has a number of key properties: It is extremely dense, offering the theoretical possibility of storing 455 EB/g; it is durable, with a half-life of approximately 520 years that can be increased to thousands of years when DNA is chilled and stored dry; and it is amenable to automated synthesis and sequencing. Furthermore, biochemical processes that act on DNA potentially enable highly parallel data manipulation.

While biological information is encoded in DNA via a specific mapping from triplet sequences of nucleotides to amino acids, DNA storage is not limited to a single encoding scheme, and there are many possible ways to map data to chemical sequences of nucleotides for synthesis, storage, retrieval, and data manipulation. However, there are several biological, error-tolerance, and information-retrieval considerations that an encoding scheme needs to address to be viable.

This comprehensive review focuses on comparing existing work done in encoding arbitrary data within DNA in terms of their encoding schemes, methods to address biological constraints, and measures to provide error correction. We compare encoding approaches on the overall information density and coverage they achieve, as well as the data-retrieval method they use (i.e., sequential or random access). We also discuss the background and evolution of the encoding schemes.
N-Heterocyclic Carbene Organic Dyes Derived from 2,4,5,6-tetra(9H-Carbazol-9-yl)isophthalonitrile (4CzIPN) Bonded to TiO2 Surfaces
Authors: Martinez-Perez Octavio , Amiri Mona , Rasu Loorthuraja , Bergens Steven H.
Published: October 2023

A high-yield route to N-heterocyclic carbene (NHC) derivatives of 2,4,5,6-tetra(9H-carbazol-9-yl)benzene-1,3-dicarbonitrile (4CzIPN) is reported. The NHC-dye was studied in solution by NMR, infrared- and UV–vis spectroscopy, cyclic voltammetry, and photoluminescence. The NHC group bonds to the surface of TiO2 forming a semiconductor/chromophore system that was characterized by cyclic voltammetry, XPS, infrared and UV–vis spectroscopy as well as photoluminescence. The bonding between the NHC group and TiO2 is quite stable towards the photooxidation of sacrificial electron donors under alkaline conditions without applying any protective layers.
The Distribution Properties of Consecutive Quadratic Residue Sequences
Authors: Wang Xiao , Fang Hao
Published: October 2023

We consider any prime number

p

. Let

k
,
s

be two positive integers. We are interested in the arithmetic progressions (sequences) with the common difference

s

and length

k

, where the sequence entries are from the set of quadratic residue modulo

p

or the set of quadratic nonresidue modulo

p

. The numbers of such sequences are denoted as

N

p

k
,
s

and

N

p

′

k
,
s

, respectively. In this paper, we apply analytic number theory methods, in particular, properties of Legendre’s symbol modulo

p

and character sums, to study the numbers

N

p

k
,
s

and

N

p

′

k
,
s

. Exact formulas are given for certain values of

k

and

s

under some restrictions. In addition, estimation formulas in other cases are given.
XRCC1 R194W and R399Q Polymorphisms and Colorectal Cancer Risk in a Northeastern Mexican Population
Authors: Meza-Espinoza Juan Pablo , Peralta-Leal Valeria , Durán-González Jorge , Macías-Gómez Nelly , Bocanegra-Alonso Anabel , Leal-Ugarte Evelia
Published: October 2023

Colorectal cancer (CRC) is one of the most common cancers worldwide. Its etiopathogenesis is complex, mainly influenced by genetic instability caused by the accumulation of mutations. The XRCC1 gene, which is involved in DNA repair, has been associated with CRC through the R194W (C194T) and R399Q (G399A) polymorphisms, but the results are inconsistent. Here, we analyzed the association of these polymorphisms with sporadic CRC in a northeastern Mexican population, including 155 male CRC patients and 155 male controls. Genotyping was performed using the RFLP method. An association with CRC was found for the 399A allele (G vs A; OR = 1.48 (1.03–2.13),

P
=
0.034

) and for the 399AA genotype in a codominant model (AA vs GG; OR = 3.11 (1.06–9.10),

P
=
0.031

). In contrast, there were no significant differences between CRC patients and controls for the C194T polymorphism (C vs T; OR = 0.82 (0.52–1.31),

P
=
0.41

). These results are consistent with many similar studies, but further research is needed to verify whether the XRCC1 R194W and R399Q polymorphisms play a role in CRC etiology. The functional significance of these polymorphisms is unclear, but some studies suggest that they influence DNA repair capacity and, thus, cancer risk.
Comparative Direct Compression Property of a Novel Pregelatinized Starch in Paracetamol Tablets
Authors: Balcha Balla Tamrat , Mary Joseph Nisha , Belete Anteneh
Published: October 2023

Background. Among all the pharmaceutical dosage forms, tablets are still the most preferred and the most commonly used option because of their advantages. The direct compression method of tablet preparation exempts several steps needed in the granulation method. Therefore, the pursuit of better direct compression tablet excipients is evident in contemporary research endeavors. Pregelatinized Taro Boloso-I starch has comparable flow properties and higher compressibility and compactibility than Starch 1500®. However, there is no evidence in the literature regarding the lubricant sensitivity and dilution potential of pregelatinized Taro Boloso-I starch. This study was aimed at performing the in vitro evaluation of paracetamol tablets prepared using pregelatinized Taro Boloso-I starch as a direct compression excipient using paracetamol as a model drug. Methods. Taro Boloso-I starch was pregelatinized, and its properties including amylose to amylopectin ratio, densities, flow properties, swelling power, water solubility index, particle morphology, moisture content, and moisture sorption profile were evaluated. Furthermore, the lubricant sensitivity test, dilution potential study, and compatibility test with the paracetamol drug using ATR spectroscopy were performed. The properties of the directly compressed tablets prepared accordingly were evaluated. The majority of evaluations were performed in comparison with Starch 1500®. Results and Discussion. PGTBIS had a significantly lower amount of amylose than Starch 1500®. In the ATR-IR spectra of the mixture of the paracetamol and pregelatinized PGTBIS, all the major absorbance peaks of the drug were maintained indicating the absence of chemical modifications. PGTBIS showed better flow properties than Starch 1500®. The modified starch was shown to withstand magnesium stearate up to 0.5% concentration. Conclusion. PGTBIS could accommodate higher drug cargo than Starch 1500® with acceptable tablet properties. Accordingly, PGTBIS starch could be taken as a potential direct compression excipient.
Allelic and Genotypic Analysis of LncRNA ANRIL rs4977574 A/G Mutations in Oral Squamous Cell Carcinoma Patients: Insights into Tumor Characteristics and Genotypic Correlations
Authors: Amiri Mohammad Amin , Amiri Delara , Mokhtari Mohammad Javad , Lavaee Fatemeh , Fattahi Mohammad Javad , Ghaderi Abbas , Khademi Bijan
Published: October 2023

Aim. Long noncoding RNAs (lncRNA) ANRIL and its genetic polymorphisms are shown to be associated with the risk of several cancers. However, the single nucleotide polymorphisms (SNPs) of lncRNA ANRIL are not thoroughly assessed in oral squamous cell carcinoma (OSCC) which is the most prevalent cancer in the head and neck area. Thus, this study aimed to assess the association of SNP of lncRNA ANRIL rs4977574 in patients with OSCC. Methods and Materials. 106 blood samples from the patients with OSCC were obtained with a gender- and age-matched control group to evaluate the SNP of rs4977574 of lncRNA ANRIL. The DNA was extracted using the salt-out technique and DNA genotyping was undertaken using specific primer pairs in the tetra-primer ARMS-PCR technique. Eventually, the frequency of wild-type (A) and the mutated allele (G), as well as the genotypes were estimated between the groups of patients with OSCC and healthy individuals. Results. The results of our study indicated no statistically significant difference in the frequency of rs4977574 A/G of lncRNA ANRIL among the patients with OSCC and healthy individuals (

p
>
0.05

). Likewise, no significant difference was found in the genotypes’ frequencies (

p
>
0.05

). Nevertheless, the marked association of GG with smaller tumor size and the high level of differentiation of OSCC cells in the presence of AA or AG genotypes were interesting outcomes of this study (

p
<
0.05

). Similarly, all the genotypes AA, AG, and GG were correlated with the site of the occurrence of OSCC. Furthermore, the association of the genotypes with the lymph node metastasis and the tumors stage was not found to be significant (

p
>
0.05

). Conclusions. The results of our study indicate that rs4977574 A/G and its genotypes do not have any direct correlation with the presence of OSCC; however, its association with the smaller tumor size and the level of the cancer cells differentiation could imply its possible indirect role.
The Impact of Heat Exposure, Obesity, and Physical Activity on Sperm Quality: An Observational Study
Authors: Melinawati Eriana , Prakosa Teguh , Budihastuti Uki Retno , Pangestu Mulyoto , Ratnasari Affi Angelia , Rismawan Puji Aris
Published: October 2023

In Indonesia, 12% or 3 million married couples suffer from infertility, with 36% of cases caused by male factors. Heat exposure, obesity, and lack of physical activity can decrease sperm quality by inducing oxidative stress and inflammation and altering the hypothalamic–pituitary–gonadal axis mechanisms. This study investigated the impact of heat exposure, obesity, and physical activity on sperm quality. This study employed an analytical observational design with a cross-sectional approach, conducted at the Sekar Fertility Clinic, Dr. Moewardi General Hospital. Sixty samples were analyzed using bivariate, multivariate, and χ2 tests or Fisher exact test with a 95% confidence interval and

p
<
0.05

. Exposure to heat was found to increase the risk of low-sperm concentration by 74.09 times (

p
=
0.001

), obesity increased the risk of low-sperm concentration by 16.74 times (

p
=
0.013

), and low-sperm motility by 6.12 times (

p
=
0.014

), and lack of physical activity increased the risk of low-sperm concentration by 27.23 times (

p
=
0.033

). Heat exposure, obesity, and physical inactivity are associated with low-sperm concentration, and obesity is also associated with low-sperm motility.
Figure S4 from Multimeric Anti-DR5 IgM Agonist Antibody IGM-8444 Is a Potent Inducer of Cancer Cell Apoptosis and Synergizes with Chemotherapy and BCL-2 Inhibitor ABT-199
Authors: Wang Beatrice T. , Kothambawala Tasnim , Wang Ling , Matthew Thomas J. , Calhoun Susan E. , Saini Avneesh K. , Kotturi Maya F. , Hernandez Genevive , Humke Eric W. , Peterson Marvin S. , Sinclair Angus M. , Keyt Bruce A.
Published: October 2023

Figure S4 shows DR5 expression in tumor xenografts and comparison of IGM-8444 and anti-DR5 IgG in vivo
NKG2A Is a Therapeutic Vulnerability in Immunotherapy Resistant MHC-I Heterogeneous Triple-Negative Breast Cancer
Authors: Taylor Brandie C. , Sun Xiaopeng , Gonzalez-Ericsson Paula I. , Sanchez Violeta , Sanders Melinda E. , Wescott Elizabeth C. , Opalenik Susan R. , Hanna Ann , Chou Shu-Ting , Van Kaer Luc , Gomez Henry , Isaacs Claudine , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Pietenpol Jennifer A. , Balko Justin M.
Published: October 2023

Despite the success of immune checkpoint inhibition (ICI) in treating cancer, patients with triple-negative breast cancer (TNBC) often develop resistance to therapy, and the underlying mechanisms are unclear. MHC-I expression is essential for antigen presentation and T-cell–directed immunotherapy responses. This study demonstrates that TNBC patients display intratumor heterogeneity in regional MHC-I expression. In murine models, loss of MHC-I negates antitumor immunity and ICI response, whereas intratumor MHC-I heterogeneity leads to increased infiltration of natural killer (NK) cells in an IFNγ-dependent manner. Using spatial technologies, MHC-I heterogeneity is associated with clinical resistance to anti-programmed death (PD) L1 therapy and increased NK:T-cell ratios in human breast tumors. MHC-I heterogeneous tumors require NKG2A to suppress NK-cell function. Combining anti-NKG2A and anti–PD-L1 therapies restores complete response in heterogeneous MHC-I murine models, dependent on the presence of activated, tumor-infiltrating NK and CD8+ T cells. These results suggest that similar strategies may enhance patient benefit in clinical trials.

Significance:

Clinical resistance to immunotherapy is common in breast cancer, and many patients will likely require combination therapy to maximize immunotherapeutic benefit. This study demonstrates that heterogeneous MHC-I expression drives resistance to anti–PD-L1 therapy and exposes NKG2A on NK cells as a target to overcome resistance.

This article is featured in Selected Articles from This Issue, p. 201
Figure 6 from Tumor Cell–Intrinsic c-Myb Upregulation Stimulates Antitumor Immunity in a Murine Colorectal Cancer Model
Authors: van Gogh Merel , Glaus Garzon Jesus F. , Sahin Dilara , Knopfova Lucia , Benes Petr , Boyman Onur , Jurisica Igor , Borsig Lubor
Published: October 2023

c-Myb upregulation regulates intrinsic changes in MC38 tumor cells that control tumor growth by CD8+ T cells. A, qRT-PCR data for B2m, antigen peptide transporter 2 (Tap2), CD137 ligand (Cd137L), Ccr2, Ifnβ, and Il6 is normalized to Gapdh expression and relative to the Ctrl group (n = 4 mice per group). B, Killing assay of cultured MC38T/O cells; untreated (− Dox, grey) or treated with Dox for 24 hours (+ Dox, blue) prior to coculture. Twenty-four hours after the addition of enriched CD8+ T cells (tumor cell: CD8+ T cell ratio 1:2 / 1:5) from a spleen of a subcutaneous MC38T/O tumor-bearing C57BL/6J mouse (Ctrl- or Dox-mouse), early (AnnexinV+7-AAD−) and late (AnnexinV+7-AAD+) apoptotic tumor cells were assessed by flow cytometry. Data are presented as percentage of total MC38T/O cells. w/o: tumor cells cultured without CD8+ T cells. All data are presented from three independent experiments C,Batf3−/− mice were subcutaneously injected with MC38T/O cells and were fed Ctrl or Dox containing chow for the duration of the experiment. n = 5 mice per group. Tumor growth is shown. Data are presented as mean values ± SEM. Mann–Whitney test was used for statistical analysis (A). One-way ANOVA with Kruskal–Wallis posttest was used for statistical analysis of apoptosis (B). Two-way ANOVA was used for comparing tumor growth curves (C). *, P < 0.05, **, P < 0.01, ***, P < 0.001, ****, P < 0.0001.
Figure 4 from Tumor Cell–Intrinsic c-Myb Upregulation Stimulates Antitumor Immunity in a Murine Colorectal Cancer Model
Authors: van Gogh Merel , Glaus Garzon Jesus F. , Sahin Dilara , Knopfova Lucia , Benes Petr , Boyman Onur , Jurisica Igor , Borsig Lubor
Published: October 2023

Early c-Myb upregulation is crucial for control of tumor growth. A, Experimental setup. C57BL/6J mice were subcutaneously injected with MC38T/O cells and fed Ctrl or Dox chow. For two groups, chow is switched at day 14 for the rest of the experiment, Dox→Ctrl (D→C) or Ctrl→Dox (C→D). B–D, Tumor growth curves, final tumor weight, representative pictures (B); flow cytometry analysis (C); and Bio-plex analysis (D) of indicated groups are shown. Heat maps are shown of representative samples. E, Flow cytometry analysis of subcutaneous MC38T/O tumors at day 14. Flow cytometry analysis for CD8+ T cells (CD45+CD11b−CD3e+CD8+) are represented as number of cells per gram of tumor tissue (C, E). CD8+PD1+/perforin+/granzymeB+ populations are represented as percentage of total CD8+ T cells (C, E). F, Long-term tumor growth was assessed in C57BL/6J mice subcutaneously injected with MC38T/O cells and fed Ctrl or Dox chow for the duration of the experiment; or Dox chow for the first 14 days and subsequently switched to Ctrl chow for the rest of the experiment (D → C). n = 5–6 (B), n = 4 (C), n = 3–4 (D), n = 8–10 (E), n = 7–8 (F) mice per group. Data are presented as mean values ± SEM. Two-way ANOVA was used for comparing tumor growth curves (B, F). One-way ANOVA with Kruskal–Wallis posttest was used (C–E) for statistical analysis. *, P < 0.05; **, P < 0.01.
Mitochondria Dictate Function and Fate of HSCs and T Cells
Authors: Xu Yingxi , Chiang Yi-Hsuan , Ho Ping-Chih , Vannini Nicola
Published: October 2023

Hematopoietic stem cells (HSC) and T cells are intimately related, lineage-dependent cell populations that are extensively used as therapeutic products for the treatment of hematologic malignancies and certain types of solid tumors. These cellular therapies can be life-saving treatments; however, their efficacies are often limited by factors influencing their activity and cellular properties. Among these factors is mitochondrial metabolism, which influences the function and fate commitment of both HSCs and T cells. Mitochondria, besides being the “cellular powerhouse,” provide metabolic intermediates that are used as substrates for epigenetic modifications and chromatin remodeling, thus, driving cell fate decisions during differentiation. Moreover, mitochondrial fitness and mitochondrial quality control mechanisms are closely related to cellular function, and impairment of these mitochondrial properties associates with cellular dysfunction due to factors such as T-cell exhaustion and aging. Here, we give an overview of the role of mitochondria in shaping the behavior of these lineage-related cell populations. Moreover, we discuss the potential of novel mitochondria-targeting strategies for enhancing HSC- and T cell–based cancer immunotherapies and highlight how design and application of such approaches requires consideration of the metabolic similarities and differences between HSCs and T cells.

See related article on p. 1302.
Health service quality of human immunodeficiency virus voluntaries’ counselling and testing
Authors: Sudirman Sudirman , Purwiningsih Sri , Darmin Darmin , Susianawati Desak Eka , Arni Fitri , Fajrah Sitti
Published: October 2023

United Nations & AIDS (UNAIDS) in 2019 stated that 38 million individuals in the world were suffering from human immunodeficiency virus or HIV. Since it was discovered in 1987, the number of HIV cases in Indonesia until mid-2020 was 436,948 cases, of which 64,990 people have died. This study aims to assess the quality of health services with the service quality (SERVQUAL) analysis model on voluntary HIV counseling and testing. A quantitative study was conducted with a descriptive observational analytic approach and a cross-sectional design on 120 respondents. The variables were measured using a service quality questionnaire and Likert scale. The results showed a difference between the expectations and perceptions of respondents on the service quality of voluntary HIV counseling and testing. The statistical analysis (p=0.000) shows that the health services for voluntary HIV counseling and testing have poor quality. However, the respondents gave good scores on responsiveness and assurance of the services. Managers and relevant authorities need to plan and pay special attention to other yet optimal variables.
COVID-19 surveillance in educational institution as an early detection in subpopulation
Authors: Hargono Arief , Martini Santi , Hidajah Atik Choirul , Astutik Erni
Published: October 2023

Since the first time it was discovered in 2019, COVID-19 has been the major threat to public health. Surveillance is considered to be one of the main pillars in dealing with the pandemic as it enhances the efforts of prevention and control of COVID-19. This study aimed to develop COVID-19 surveillance system at Universitas Airlangga that play a great importance in detecting and monitoring of COVID-19 status among its academias. This study refers to system approach which include system analysis and system design. System analysis was conducted by describing it into its components, namely input, process, and output. The results from system analysis are then utilized to the system design. The surveillance system collects and analyzes data which resulted to epidemiological information and recommendation. The result from the monitoring then utilized as an effort to enhance the coordination for epidemic preparedness in the institution. This study concludes that the COVID-19 surveillance system model in this institution monitors the COVID-19 status and associated risk factors of the sub-population within the institution. The information generated is used by decision-makers for early detection and monitoring of COVID-19 status.
Cope children's anxious behavior and pain with virtual reality during venipuncture procedure in emergency department
Authors: Permaida Permaida , Rustina Yeni , Effendi Defi , Nurlaelah Siti
Published: October 2023

Venipuncture procedures undeniably increase anxiety behavior and pain while children are in the emergency department. This study aimed to analyze the effectiveness of virtual reality (VR) on anxiety behavior and pain with the Dorothy-behavior theory during the venipuncture procedures procedure in the emergency department. The research used a quasi-experimental two-group pretest-posttest design with a control group design with 42 respondents in the yellow zone of the emergency department of RSPUN Cipto Mangunkusumo. Data analysis used the Wilcoxon test, Mann-Whitney, and ordinal regression. There were significant differences and comparisons between anxiety behavior (p-value <0.001) and pain (p-value <0.001) when the venipuncture procedure was performed in the experimental group. School-age children (p-value 0.026; OR=4.958) affect pain. This study recommends that nurses in emergency departments provide VR during venipuncture procedures to address anxiety and pain behaviors. In addition, Dorothy's behavioral theory in the vein puncture procedure has become an innovation in nursing care. Provide aspects of protection based on the age, gender, and experience of the child; maintenance aspects by looking at VR effects; and aspects of stimulation as reference materials or recommendations for further research on VR to overcome anxiety and painful behavior in children during venipuncture procedures.