bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of 12 weeks of basic military training on testosterone and cortisol responses
Authors: L Tait Jamie , M Bulmer S , M Drake J , R Drain J , C Main L
Published: October 2022

Introduction

Military personnel train and operate in challenging multistressor environments, which can affect hormonal levels, and subsequently compromise performance and recovery. The aims of this project were to evaluate concentrations of cortisol and testosterone and subjective perceptions of stress and recovery across basic military training (BMT).

Methods

32 male recruits undergoing BMT were tracked over a 12-week course. Saliva samples were collected weekly, on waking, 30 min postwaking and bedtime. Perceptions of stress and recovery were collected weekly. Daily physical activity (steps) were measured via wrist-mounted accelerometers across BMT. Physical fitness was assessed via the multistage fitness test and push-ups in weeks 2 and 8.

Results

Concentrations of testosterone and cortisol, and the testosterone:cortisol ratio changed significantly across BMT, with variations in responses concurrent with programmatic demands. Perceptions of stress and recovery also fluctuated according to training elements. Recruits averaged 17 027 steps per day between weeks 2 and 12, with week-to-week variations. On average, recruits significantly increased predicted VO2max(3.6 (95% CI 1.0 to 6.1) mL/kg/min) and push-ups (5. 5 (95% CI 1.4 to 9.7) repetitions) between weeks 2 and 8.

Conclusions

Recruit stress responses oscillated over BMT in line with programmatic demands indicating that BMT was, at a group level, well-tolerated with no signs of enduring physiological strain or overtraining. The sensitivity of cortisol, testosterone and the testosterone:cortisol ratio to the stressors of military training, suggest they may have a role in monitoring physiological strain in military personnel. Subjective measures may also have utility within a monitoring framework to help ensure adaptive, rather than maladaptive (eg, injury, attrition), outcomes in military recruits.
Medication burden in young adults with juvenile idiopathic arthritis: data from a multicentre observational study
Authors: Montag Laura J , Horneff Gerd , Hoff Paula , Klein Ariane , Kallinich Tilmann , Foeldvari Ivan , Seipelt Eva , Tatsis Stefanie , Peer Aries MD , Niewerth Martina , Klotsche Jens , Minden Kirsten
Published: October 2022

Objective

To assess the medication and disease burden of young adults with juvenile idiopathic arthritis (JIA).

Methods

Young adults with JIA prospectively followed in the Juvenile Arthritis Methotrexate/Biologics long-term Observation reported on their health status and medication use. All medications taken (disease-modifying antirheumatic drugs (DMARDs)/prescription/over-the-counter drugs, but excluding most local therapies) classified according to the Anatomical Therapeutic Chemical Classification System were included in this analysis. Medication use at last follow-up was evaluated by sex, JIA category and time from symptom onset to the first biological DMARD (bDMARD) start.

Results

A total of 1306 young adults (68% female) with JIA and a mean disease duration of 13.6±6 years were included in the study. Patients reported using on average 2.4±2.1 medicines and 1.5±1.7 non-DMARD medicines, respectively, at the last follow-up. Almost a quarter of the patients reported polypharmacy. The higher the number of medications used was, the higher the disease activity, pain and fatigue, and the lower the quality of life of patients. Medication usage differed significantly between sexes and JIA categories, being highest in patients with rheumatoid factor-positive polyarthritis and systemic JIA. The number of medications used was significantly associated with the time from symptom onset to bDMARD start. Patients taking opioids or antidepressants had a particularly high disease burden and had received bDMARDs an average of 2 years later than patients not taking these medications.

Conclusion

Medication use in adults with JIA varies depending on sex, JIA category, and the time between symptom onset and initiation of treatment with bDMARD.
On the quartic anharmonic oscillator and the Padé-approximant averaging method
Authors: Babenko V. A. , Petrov N. M.
Published: October 2022

For the quantum quartic anharmonic oscillator with the Hamiltonian [Formula: see text], which is one of the traditional quantum-mechanical and quantum-field-theory models, the summation of its factorially divergent perturbation series is studied on the basis of the proposed method of the averaging of the corresponding Padé approximants. Thus, applying proper averaging weight function, we are able for the first time to construct the Padé-type approximations that possess correct asymptotic behavior at infinity with a rise of the coupling constant [Formula: see text]. The approach gives very essential theoretical and applicatory-computational advantages in applications of the given method. The convergence of the utilized approximations is studied and the values for the ground state energy [Formula: see text] of the anharmonic oscillator are calculated by the proposed method for a wide range of variation of the coupling constant [Formula: see text]. In addition, we perform comparative analysis of the proposed method with the modern Weniger delta-transformation method and show insufficiency of the latter to sum the divergent perturbation series in the region of the superstrong coupling [Formula: see text].
"I Want To See How Smart This AI Really Is": Player Mental Model Development of an Adversarial AI Player
Authors: Villareale Jennifer , Harteveld Casper , Zhu Jichen
Published: October 2022

Understanding players' mental models are crucial for game designers who wish to successfully integrate player-AI interactions into their game. However, game designers face the difficult challenge of anticipating how players model these AI agents during gameplay and how they may change their mental models with experience. In this work, we conduct a qualitative study to examine how a pair of players develop mental models of an adversarial AI player during gameplay in the multiplayer drawing game iNNk. We conducted ten gameplay sessions in which two players (n = 20, 10 pairs) worked together to defeat an AI player. As a result of our analysis, we uncovered two dominant dimensions that describe players' mental model development (i.e., focus and style). The first dimension describes the focus of development which refers to what players pay attention to for the development of their mental model (i.e., top-down vs. bottom-up focus). The second dimension describes the differences in the style of development, which refers to how players integrate new information into their mental model (i.e., systematic vs. reactive style). In our preliminary framework, we further note how players process a change when a discrepancy occurs, which we observed occur through comparisons (i.e., compare to other systems, compare to gameplay, compare to self). We offer these results as a preliminary framework for player mental model development to help game designers anticipate how different players may model adversarial AI players during gameplay.
Alienated Serendipity and Reflective Failure: Exploring Queer Game Mechanics and Queerness in Games via Queer Temporality
Authors: Hantsbarger Matthew , Troiano Giovanni Maria , To Alexandra , Harteveld Casper
Published: October 2022

Queerness can help redefine interactive technologies and re-conceptualize their design beyond cisheteronormativity. Recently, games have emerged as promising avenues for exploring queerness. In this research-through-design (RtD) effort, we advance queer explorations in games by leveraging queer temporality to evoke and explore feelings of alienation and isolation in a horror game called You're Going To Be Late. We further engage with queer individuals who playtest our game and participate in focus groups to discuss how queer they felt our game was and what they regard as queer game mechanics. Participants had varying experiences while playing our game, ranging from serendipity and wonder to alienation and confusion. The focus groups described queer game mechanics as queer modes of play and often tapped into gender representation. Finally, we show how including and amplifying queer voices in discursive efforts around interactive technology design has implications for transformative and critical reflections that can broadly benefit game design and HCI research.
Cine-AI: Generating Video Game Cutscenes in the Style of Human Directors
Authors: Evin Inan , Hämäläinen Perttu , Guckelsberger Christian
Published: October 2022

Cutscenes form an integral part of many video games, but their creation is costly, time-consuming, and requires skills that many game developers lack. While AI has been leveraged to semi-automate cutscene production, the results typically lack the internal consistency and uniformity in style that is characteristic of professional human directors. We overcome this shortcoming with Cine-AI, an open-source procedural cinematography toolset capable of generating in-game cutscenes in the style of eminent human directors. Implemented in the popular game engine Unity, Cine-AI features a novel timeline and storyboard interface for design-time manipulation, combined with runtime cinematography automation. Via two user studies, each employing quantitative and qualitative measures, we demonstrate that Cine-AI generates cutscenes that people correctly associate with a target director, while providing above-average usability. Our director imitation dataset is publicly available, and can be extended by users and film enthusiasts.
Close but Not Too Close: Distance and Relevance in Designing Games for Reflection
Authors: Iacovides Ioanna , Cutting Joe , Beeston Jen , Cecchinato Marta E. , Mekler Elisa D. , Cairns Paul
Published: October 2022

Reflection is an important precursor to attitude and behavior change, but existing advice on designing for reflection in games is mixed and requires further empirical investigation. We report on the design and evaluation (n=32) of a game to prompt student reflection on work-life balance. Participants played as themselves or a third person character (Alex). An inductive qualitative analysis of post-play interviews, and a follow-up one week later, resulted in four themes relating to how gameplay facilitated reflection: making (sensible) consequences visible; it's like MY life; the space between Alex and I; and triggers in everyday life. A deductive qualitative analysis also indicated that while both games resulted in different forms of reflection for the majority of players, those who role-played as Alex appeared more likely to experience higher levels of reflection. Through exploring the ways in which the two versions of the game succeeded, and failed, to support reflection, we highlight the importance of providing a relevant context to players (so the game feels close to their experience), and allowing them to role-play as someone other than themselves (but not too close).
Do Hexad User Types Matter? Effects of (Non-) Personalized Gamification on Task Performance and User Experience in an Image Tagging Task
Authors: Altmeyer Maximilian , Zenuni Berina , Spelt Hanne , Jegen Thierry , Lessel Pascal , Krüger Antonio
Published: October 2022

The perception of gamification elements differs across users, which is why personalizing gamified systems is important. Past research showed that the Hexad user types model is particularly suitable for this purpose by demonstrating correlations between user types and gamification elements. However, previous studies were mostly survey-based, i.e. relied on participants' rating of gamification elements based on e.g. textual descriptions or storyboards. Thus, the question whether personalization based on Hexad user types provides benefits in implemented gameful systems was neglected. We contribute to this by investigating the effects of (contra-) tailoring the set of gamification elements to a user's Hexad type on performance and user experience, assessed with survey and physiological measures, in an image tagging context. In a lab study (N=29), we found that gamification increases performance and affects psychophysiological measures of arousal. Moreover, we demonstrate that personalization increases enjoyment, positively-valenced affective experiences and participants' absorption in the task at hand.
Feeling Good and In Control: In-game Tools to Support Targets of Toxicity
Authors: Reid Elizabeth , Mandryk Regan L. , Beres Nicole A. , Klarkowski Madison , Frommel Julian
Published: October 2022

Game developers, researchers, and players recognize the harm of toxic behaviour in online games-yet toxicity persists. Players' coping strategies are limited to tools that focus on punishing toxic players (e.g., muting, blocking, reporting), which are inadequate and often misused. To address the needs of players experiencing toxicity, we took inspiration from research in other online spaces that provide support tools for targets of harassment. We iteratively designed and evaluated in-game tools to support targets of toxicity. While we found that most players prefer tools that explicitly address toxicity and increase feelings of control, we also found that tools that solely provide social or emotional support also decrease stress, increase feelings of control, and increase positive affect. Our findings suggest that players may benefit from variety in toxicity support tools that both explicitly address toxicity in the moment and help players cope after it has occurred.
Learning by Doing: Intrinsic Integration Directs Attention to Increase Learning In Games
Authors: Cutting Joe , Iacovides Ioanna
Published: October 2022

Educational games have long been seen as having great potential, but evidence for their effectiveness is mixed, suggesting deficiencies in our theoretical understanding of learning in games and associated design principles. The principle of "Intrinsic integration" of learning content with game mechanics (Habgood and Ainsworth, 2011) increases learning in educational games, but the theoretical mechanisms behind the principle are unclear, leading to implementation issues. In response, we performed a pre-registered study (n=210) to test possible motivational, cognitive load or attentional mechanisms for moderating learning at an abstract learning task within an educational game similar to Pacman. Learning was higher in the intrinsically integrated version with no significant effects of motivation or cognitive load leading to the conclusion that intrinsic integration increased learning via an attentional mechanism where players only pay attention to features needed for the game task and ignore task-irrelevant information. We discuss theoretical implications for game learning as well as insights for designers of educational games.
LightPlay: Using an External Ambient Lighting Strip for Video Game Indicators
Authors: Fung Kin Pong , Rogers Katja , Hallifax Stuart , Woodside Gabrielle S. , Vogel Daniel , Nacke Lennart E.
Published: October 2022

Visual indicators provide important in-game information, but displaying them on screen consumes space and increases clutter. In addition, the option to increase indicator brightness above levels possible in standard monitors can substantially improve accessibility. To address both aspects, we developed an ambient lighting system for video game indicators using an LED strip attached around the back border of a monitor. A controlled study compares the speed, error rate, and perceived workload of this approach with an on-screen baseline method. Results show that ambient lights can capture attention 17.5% faster compared to on-screen indicators, and ambient lights performed at least as well as on-screen across all other metrics. Our work provides empirical evidence that ambient lights can be an adequate replacement for on-screen methods when displaying indicators in games, allowing people to reclaim screen real estate and adjust brightness for accessibility, without sacrificing performance.
Live Feedback for Training Through Real-Time Data Visualizations: A Study with League of Legends
Authors: Rijnders Frans , Wallner Günter , Bernhaupt Regina
Published: October 2022

With competitive gaming on the rise, players have developed an increased interest in data-driven feedback of their in-game performance. In many cases, this feedback is presented visually post-play but live companions that provide real-time analytics are gaining more and more attention. However, the design of such systems poses different requirements which have been little explored from a scholarly point of view.

In this paper, we report on a study of two visualizations - a physical and digital one - providing live feedback to League of Legends players designed based on a community survey (N= 175) and expert input. We further discuss results of a qualitative evaluation with 13 players and an expert, touch upon potential benefits and drawbacks of physical and digital implementations, and present derived design considerations and challenges for such real-time data visualizations, revolving around issues of information density, contextualization, representation, and a diverse range of user needs.
Streamer's Hell - Investigating Audience Influence in Live-Streams Beyond the Game
Authors: Lessel Pascal , Altmeyer Maximilian , Sahner Julian , Krüger Antonio
Published: October 2022

In the context of game live-streams, we focus on whether audience influence options can be extended beyond the game, e.g., to the streamers' environment (e.g., controlling their room lighting), the streamers themselves (e.g., activating vibration feedback on their forearms) and the streamers' hardware and peripheral devices (e.g., switching key bindings). An online study (n=81) showed that viewers have mixed feelings and that the context matters, as only a few game genres are assessed as suitable for such an experience. In a lab-study six streamers experienced the idea while playing a horror game. They saw appeal in extending the influence space, but also again highlighted that context matters and customization options are necessary. The studies hint that although this interactivity is from a technical perspective independent of the content streamed, in practice it is not, as the perception is moderated by e.g., the game and why the streamer is playing it.
The Effect of Auditory-Motor Synchronization in Exergames on the Example of the VR Rhythm Game BeatSaber
Authors: Albert Iannis , Burkard Nicole , Queck Dirk , Herrlich Marc
Published: October 2022

Physical inactivity and an increasingly sedentary lifestyle constitute a significant public health concern. Exergames try to tackle this problem by combining exercising with motivational gameplay. Another approach in sports science is the use of auditory-motor synchronization, the entrainment of movements to the rhythm of music. There are already commercially successful games making use of the combination of both, such as the popular VR rhythm game BeatSaber. However, unlike traditional exercise settings often relying on periodic movements that can be easily entrained to a rhythmic pulse, exergames typically offer an additional cognitive challenge through their gameplay and might be based more on reaction or memorization. That poses the question as to what extent the effects of auditory-motor synchronization can be transferred to exergames, and if the synchronization of music and gameplay facilitates the playing experience. We conducted a user study (N = 54) to investigate the effects of different degrees of synchronization between music and gameplay using the VR rhythm game BeatSaber. Results show significant effects on performance, perceived workload, and player experience between the synchronized and non-synchronized conditions, but the results seem to be strongly mediated by the ability of the participants to consciously perceive the synchronization differences.
Using fNIRS to Assess Cognitive Activity During Gameplay
Authors: Klarkowski Madison , Causse Mickaël , Duprès Alban , del Campo Natalia , Vella Kellie , Johnson Daniel
Published: October 2022

This work explores the use of functional Near Infrared Spectroscopy (fNIRS) to assess cognitive activity during videogame play, and compare it to cognitive activity during cognitive tasks that assess executive control. To this end, we assessed haemodynamic response to videogame and cognitive tasks in the prefrontal cortex, each manipulated on a spectrum of difficulty. In our study (n = 37), we find that mental effort expended during videogame play did not differ from mental effort expended during cognitive tasks---and speculate that regional cognitive activity during gameplay is indicative of functions pertaining to memory encoding and retrieval, planning, and sustainment of attention. Our findings suggest the utility of fNIRS as a means to understand challenge as part of the player experience, and contest the popular conception of videogame play as cognitively undemanding entertainment. Further, we were successful in distinguishing between difficulty levels in the gameplay tasks, situating fNIRS as broadly useful for granular assessment of gameplay difficulty. As such, we contend that fNIRS is an effective and useful tool for generating high-resolution insights regarding cognition (and particularly the experience of difficulty) during gameplay.
Proving hypersafety compositionally
Authors: D’Osualdo Emanuele , Farzan Azadeh , Dreyer Derek
Published: October 2022

Hypersafety properties of arity
n
are program properties that relate
n
traces of a program (or, more generally, traces of
n
programs).
Classic examples include determinism, idempotence, and associativity.
A number of
relational program logics
have been introduced to target this class of properties. Their aim is to construct simpler proofs by capitalizing on structural similarities between the
n
related programs.
We propose an unexplored, complementary proof principle that establishes hyper-triples (i.e. hypersafety judgments) as a unifying compositional building block for proofs, and we use it to develop a
Logic for Hyper-triple Composition
(LHC), which supports forms of proof compositionality that were not achievable in previous logics.
We prove LHC sound and apply it to a number of challenging examples.
Model checking for a multi-execution memory model
Authors: Moiseenko Evgenii , Kokologiannakis Michalis , Vafeiadis Viktor
Published: October 2022

Multi-execution memory models, such as Promising and Weakestmo, are an advanced class of weak memory
consistency models that justify certain outcomes of a concurrent program by considering multiple candidate executions collectively. While this key characteristic allows them to support effective compilation to hardware models and a wide range of compiler optimizations, it makes reasoning about them substantially more difficult. In particular, we observe that Promising and Weakestmo inhibit effective model checking because they allow some suprisingly weak behaviors that cannot be generated by examining one execution at a time.

We therefore introduce Weakestmo2, a strengthening of Weakestmo by constraining its multi-execution
nature, while preserving the important properties of Weakestmo: DRF theorems, compilation to hardware models, and correctness of local program transformations. Our strengthening rules out a class of surprisingly weak program behaviors, which we attempt to characterize with the help of two novel properties: load buffering race freedom and certification locality. In addition, we develop WMC, a model checker for Weakestmo2 with performance close to that of the best tools for per-execution models.
Necessity
specifications for robustness
Authors: Mackay Julian , Eisenbach Susan , Noble James , Drossopoulou Sophia
Published: October 2022

Robust modules guarantee to do only what they are supposed to do – even in the presence of untrusted malicious clients, and considering not just the direct behaviour of individual methods, but also the emergent behaviour from calls to more than one method. Necessity is a language for specifying robustness, based on novel necessity operators capturing temporal implication, and a proof logic that derives explicit robustness specifications from functional specifications. Soundness and an exemplar proof are mechanised in Coq.
UniRec: a unimodular-like framework for nested recursions and loops
Authors: Sundararajah Kirshanthan , Saumya Charitha , Kulkarni Milind
Published: October 2022

Scheduling transformations reorder operations in a program to improve locality and/or parallelism. There are mature loop transformation frameworks such as the polyhedral model for composing and applying instance-wise scheduling transformations for loop nests.In recent years, there have been efforts to build frameworks for composing and applying scheduling transformations for nested recursion and loops, but these frameworks cannot employ the full power of transformations for loop nests since they have overly-restrictive representations. This paper describes a new framework, UniRec, that not only generalizes prior frameworks for reasoning about transformations on recursion, but also generalizes the unimodular framework, and hence unifies reasoning about perfectly-nested loops and recursion.
Monadic and comonadic aspects of dependency analysis
Authors: Choudhury Pritam
Published: October 2022

Dependency analysis is vital to several applications in computer science. It lies at the essence of secure information flow analysis, binding-time analysis, etc. Various calculi have been proposed in the literature for analysing individual dependencies. Abadi et. al., by extending Moggi’s monadic metalanguage, unified several of these calculi into the Dependency Core Calculus (DCC). DCC has served as a foundational framework for dependency analysis for the last two decades. However, in spite of its success, DCC has its limitations. First, the monadic bind rule of the calculus is nonstandard and relies upon an auxiliary protection judgement. Second, being of a monadic nature, the calculus cannot capture dependency analyses that possess a comonadic nature, for example, the binding-time calculus, λ
∘
, of Davies. In this paper, we address these limitations by designing an alternative dependency calculus that is inspired by standard ideas from category theory. Our calculus is both monadic and comonadic in nature and subsumes both DCC and λ
∘
. Our construction explains the nonstandard bind rule and the protection judgement of DCC in terms of standard categorical concepts. It also leads to a novel technique for proving correctness of dependency analysis. We use this technique to present alternative proofs of correctness for DCC and λ
∘
.
A concurrent program logic with a future and history
Authors: Meyer Roland , Wies Thomas , Wolff Sebastian
Published: October 2022

Verifying fine-grained optimistic concurrent programs remains an open problem. Modern program logics provide abstraction mechanisms and compositional reasoning principles to deal with the inherent complexity. However, their use is mostly confined to pencil-and-paper or mechanized proofs. We devise a new separation logic geared towards the lacking automation. While local reasoning is known to be crucial for automation, we are the first to show how to retain this locality for (i) reasoning about inductive properties without the need for ghost code, and (ii) reasoning about computation histories in hindsight. We implemented our new logic in a tool and used it to automatically verify challenging concurrent search structures that require inductive properties and hindsight reasoning, such as the Harris set.
Indexing the extended Dyck-CFL reachability for context-sensitive program analysis
Authors: Shi Qingkai , Wang Yongchao , Yao Peisen , Zhang Charles
Published: October 2022

Many context-sensitive dataflow analyses can be formulated as an extended Dyck-CFL reachability problem, where function calls and returns are modeled as partially matched parentheses. Unfortunately, despite many works on the standard Dyck-CFL reachability problem, solving the extended version is still of quadratic space complexity and nearly cubic time complexity, significantly limiting the scalability of program analyses. This paper, for the first time to the best of our knowledge, presents a cheap approach to transforming the extended Dyck-CFL reachability problem to conventional graph reachability, a much easier and well-studied problem. This transformation allows us to benefit from recent advances in reachability indexing schemes, making it possible to answer any reachability query in a context-sensitive dataflow analysis within almost constant time plus only a few extra spaces. We have implemented our approach in two common context-sensitive dataflow analyses, one determines pointer alias relations and the other tracks information flows. Experimental results demonstrate that, compared to their original analyses, we can achieve orders of magnitude (10
2
× to 10
5
×) speedup at the cost of only a moderate space overhead. Our implementation is publicly available.
BFF: foundational and automated verification of bitfield-manipulating programs
Authors: Zhu Fengmin , Sammler Michael , Lepigre Rodolphe , Dreyer Derek , Garg Deepak
Published: October 2022

Low-level systems code often needs to interact with data, such as page table entries or network packet headers, in which multiple pieces of information are packaged together as bitfield components of a single machine integer and accessed via bitfield manipulations (e.g., shifts and masking). Most existing approaches to verifying such code employ SMT solvers, instantiated with theories for bit vector reasoning: these provide a powerful hammer, but also significantly increase the trusted computing base of the verification toolchain.

In this work, we propose an alternative approach to the verification of bitfield-manipulating systems code, which we call BFF. Building on the RefinedC framework, BFF is not only highly automated (as SMT-based approaches are) but also foundational---i.e., it produces a machine-checked proof of program correctness against a formal semantics for C programs, fully mechanized in Coq. Unlike SMT-based approaches, we do not try to solve the general problem of arbitrary bit vector reasoning, but rather observe that real systems code typically accesses bitfields using simple, well-understood programming patterns: the layout of a bit vector is known up front, and its bitfields are accessed in predictable ways through a handful of bitwise operations involving bit masks. Correspondingly, we center our approach around the concept of a structured bit vector---i.e., a bit vector with a known bitfield layout---which we use to drive simple and predictable automation. We validate the BFF approach by verifying a range of bitfield-manipulating C functions drawn from real systems code, including page table manipulation code from the Linux kernel and the pKVM hypervisor.
Introduction to the Special Issue on Understanding the Spread of COVID-19, Part 1
Authors: Züfle Andreas , Anderson Taylor , Gao Song
Published: October 2022

Infectious diseases are transmitted between human hosts when in close contact over space and time. Recently, an unprecedented amount of spatial and spatiotemporal data have been made available that can be used to improve our understanding of the spread of COVID-19 and other infectious diseases. This understanding will be paramount to prepare for future pandemics through spatial algorithms and systems to collect, capture, curate, and analyze complex, multi-scale human movement data to solve problems such as infectious diseases prediction, contact tracing, and risk assessment. In exploring and deepening the conversation around this topic, the eight articles included in the first volume of this special issue employ diverse theoretical perspectives, methodologies, and frameworks, including but not limited to infectious diseases simulation, risk prediction, response policy design, mobility analysis, and case diagnosis. Rather than focusing on a narrow set of problems, these articles provide a glimpse into the diverse possibilities of leveraging spatial and spatiotemporal data for pandemic preparedness.
Puppeteer: A Random Forest Based Manager for Hardware Prefetchers Across the Memory Hierarchy
Authors: Eris Furkan , Louis Marcia , Eris Kubra , Abellán José , Joshi Ajay
Published: October 2022

Over the years, processor throughput has steadily increased. However, the memory throughput has not increased at the same rate, which has led to the memory wall problem in turn increasing the gap between effective and theoretical peak processor performance. To cope with this, there has been an abundance of work in the area of data/instruction prefetcher designs. Broadly, prefetchers predict future data/instruction address accesses and proactively fetch data/instructions in the memory hierarchy with the goal of lowering data/instruction access latency. To this end, one or more prefetchers are deployed at each level of the memory hierarchy, but typically, each prefetcher gets designed in isolation without comprehensively accounting for other prefetchers in the system. As a result, individual prefetchers do not always complement each other, and that leads to lower average performance gains and/or many negative outliers. In this work, we propose Puppeteer, which is a hardware prefetcher manager that uses a suite of random forest regressors to determine at runtime which prefetcher should be ON at each level in the memory hierarchy, such that the prefetchers complement each other and we reduce the data/instruction access latency. Compared to a design with no prefetchers, using Puppeteer  we improve IPC by 46.0% in 1 one-core, 25.8% in four-core, and 11.9% in eight-core processors on average across traces generated from SPEC2017, SPEC2006, and Cloud suites with ~11-KB overhead. Moreover, we also reduce the number of negative outliers by more than 89%, and the performance loss of the worst-case negative outlier from 25% to only 5% compared to the state of the art.
Interrogating the Roles of Mutation–Selection Balance, Heterozygote Advantage, and Linked Selection in Maintaining Recessive Lethal Variation in Natural Populations
Authors: Marion Sarah B. , Noor Mohamed A.F.
Published: October 2022

For nearly a century, evolutionary biologists have observed chromosomes that cause lethality when made homozygous persisting at surprisingly high frequencies (>25%) in natural populations of many species. The evolutionary forces responsible for the maintenance of such detrimental mutations have been heavily debated—are some lethal mutations under balancing selection? We suggest that mutation–selection balance alone cannot explain lethal variation in nature and the possibility that other forces play a role. We review the potential that linked selection in particular may drive maintenance of lethal alleles through associative overdominance or linkage to beneficial mutations or by reducing effective population size. Over the past five decades, investigation into this mystery has tapered. During this time, key scientific advances have provided the ability to collect more accurate data and analyze them in new ways, making the underlying genetic bases and evolutionary forces of lethal alleles timely for study once more.
Innovations in Sampling: Improving the Appropriateness and Quality of Samples in Organizational Research
Authors: Zickar Michael J. , Keith Melissa G.
Published: October 2022

Technology has changed the way that organizational researchers obtain participants for their research studies. Although technology has facilitated the collection of large quantities of data through online platforms, it has also highlighted potential data quality issues for many of our samples. In this article, we review different sampling techniques, including convenience, purposive, probability-based, and snowball sampling. We highlight strengths and weaknesses of each approach to help organizational researchers choose the most appropriate sampling techniques for their research questions. We identify best practices that researchers can use to improve the quality of their samples, including reviewing screening techniques to increase the quality of online sampling. Finally, as part of our review we examined the sampling procedures of all empirical research articles published in the Journal of Applied Psychology in the past 5 years, and we use observations from these results to make conclusions about the lack of methodological and sample diversity in organizational research, the overreliance on a few sampling techniques, the need to report key aspects of sampling, and concerns about participant quality.
Extent and Resistance Patterns of ESKAPE Pathogens Isolated in Pus Swabs from Hospitalized Patients
Authors: Masoud Salim S. , Kovacevich Anna , Gangji Raidah , Nyawale Helmut , Nyange Mary , Ntukula Albert
Published: October 2022

Antimicrobial resistance has persisted as a global threat with increasing associated numbers of morbidity and mortality. ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) were termed by the Infectious Diseases Society of America as a group of bacteria with rapid antibiotic resistance development. The aim of the study was to describe the extent and resistance patterns of ESKAPE pathogens isolated in pus swabs from patients admitted at Muhimbili National Hospital, Tanzania. A retrospective cross-sectional study was performed in August 2019. A total of 75 admitted patients with open wounds and surgical site infections were recruited. Files were analyzed to collect microbiology laboratory data and relevant patient data. A total of 76 clinically significant bacteria were isolated of which 52 bacteria were categorized as ESKAPE pathogens. The most common bacteria isolated were 25% (n = 19/76) P. aeruginosa and 17.1% S. aureus. A high level of antibiotic resistance was shown in all ESKAPE and non-ESKAPE pathogens. The Gram-negative bacteria of ESKAPE pathogens were further analyzed comparing 3rd generation cephalosporin and carbapenems resistance patterns. A. baumannii showed the highest resistance towards 3rd generation cephalosporin and carbapenems. In addition, P. aeruginosa showed high resistance to 3rd generation cephalosporins with 89.5% resistance, with E. coli showing high resistance to carbapenems with 50.0% resistance. The burden of ESKAPE pathogens is high in pus swabs obtained from admitted patients at Muhimbili National Hospital. The results showed high antibiotic resistance within ESKAPE and non-ESKAPE pathogens including the “last resort” antibiotics: 3rd generation cephalosporin and carbapenems.
Efficacy of Intrapleural or Intrapericardial Injection of Single Bevacizumab in the Treatment of Lung Cancer-Mediated Malignant Effusion
Authors: He Dongyun , Guo Zhihua , Xie Zixian , Zhang Yalei , Deng Qiuhua , Yang Haihong
Published: October 2022

The usage of bevacizumab for malignant pleural effusion (MPE) or malignant pericardial effusion (MPCE) has attracted increasing interest from researchers, but the precise ways of bevacizumab administration remain unknown. Patients with histologically or cytologically confirmed non-small-cell lung cancer (NSCLC) with MPE or MPCE were enrolled in the study and treated with a low dose of single bevacizumab (100 mg) intrapleurally or intrapericardially injected after the drainage of the effusions. The Lung Cancer Symptom Scale (LCSS), efficacy, and safety of drug administration were used as evaluation parameters in this study. The results indicated that lung cancer-related symptoms were significantly improved following treatment, compared with symptoms before the treatment (LCSS, score 494 ± 78 vs. score 377 ± 77, mean ± SD) (

P
<
0.001

). Malignant effusions were well controlled, and the median time to progression (TTP) was 91 days and 111 days in MPE and MPCE, respectively. In addition, no severe side effects were observed, except in one patient with mild dizziness. In summary, the low dose of single bevacizumab (100 mg) with intrapleural or intrapericardial injection is effective and safe in the treatment of lung cancer-mediated malignant effusion, rapidly improving the malignant effusion-related symptoms and quality of life in patients with NSCLC.
Adaptive Auricular Point Acupressure for Sleep Disturbance in Women with Breast Cancer: A Randomized Controlled Trial
Authors: Wang Yuyan , Li Xinyu , Ji Xiaopeng , Wu Jing , Li Junxin , Zheng Wei , Wu Caiqin , Huang Lan , Geng Zhaohui , Zhou Jie
Published: October 2022

Objectives. The study aimed to evaluate the preliminary effect and efficacy of auricular point acupressure (APA) on the quality of sleep in women with breast cancer who were undergoing chemotherapy. Sample & Setting. We conducted a randomized controlled trial on 68 patients with breast cancer who reported poor sleep quality based on the Pittsburgh Sleep Quality Index (PSQI) scores (>7). Methods & Variables. Participants were randomly assigned to an APA treatment group or a control group. Patients in the APA group had magnetic pellets attached to selected auricular points and were instructed to apply pressure to these points 4×/day for three consecutive weeks. We objectively measured sleep quality using the Actiwatch Spectrum and the PSQI at the baseline and postintervention. Statistical analyses of changes in sleep data were performed using the t-test, a rank-sum test, and analyses of covariance. Results. In patients treated with APA, the PSQI total score and sleep onset latency had significantly decreased, while the total sleep time and sleep efficiency had significantly increased. Although the total PSQI score differed between groups at the baseline, ANCOVA results showed that the APA group had a significantly lower total PSQI score. Conclusion. APA could be an inexpensive and effective approach to improving sleep quality and reducing sleep disturbance in patients with breast cancer. Further research needs a larger sample size to verify our findings.
Too Much Fuel on the Fire? Linking Obesity, Metabolism, and Melanoma Outcomes
Authors: Smalley Keiran S.M.
Published: October 2022

Patients with metastatic melanoma who are overweight or obese have improved outcomes when treated with immunotherapies or targeted therapies. A recent study provides the first evidence that the host metabolic state influences the tumor metabolic phenotype, with implications for tumor progression and therapeutic response.

See related article by Hahn et al., p. 154
A Novel Engineered AAV-Based Neoantigen Vaccine in Combination with Radiotherapy Eradicates Tumors
Authors: Huang Kevin Chih-Yang , Lai Chia-Ying , Hung Wei-Ze , Chang Hsin-Yu , Lin Pei-Chun , Chiang Shu-Fen , Ke Tao-Wei , Liang Ji-An , Shiau An-Cheng , Yang Pei-Chen , Chen William Tzu-Liang , Chao K.S. Clifford
Published: October 2022

The potency of tumor-specific antigen (TSA) vaccines, such as neoantigen (neoAg)-based cancer vaccines, can be compromised by host immune checkpoint inhibitory mechanisms, such as programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1), that attenuate neoAg presentation on dendritic cells (DC) and hinder T cell–mediated cytotoxicity. To overcome PD-1/PD-L1 inhibition in DCs, we developed a novel adeno-associated virus (meAAV) neoAg vaccine, modified with TLR9 inhibitory fragments, PD-1 trap, and PD-L1 miRNA, which extend the persistence of meAAV and activate neoAg-specific T-cell responses in immune-competent colorectal and breast cancer murine models. Moreover, we found that in combination with radiotherapy, the meAAV-based neoAg cancer vaccine not only elicited higher antigen presentation ability, but also maintained neoAg-specific cytotoxic T lymphocyte (CTL) responses. These functional PD-1 traps and PD-L1 miRNAs overcome host PD-1/PD-L1 inhibitory mechanisms and boost the therapeutic efficacy of radiotherapy. More importantly, combined radiotherapy and meAAV neoAg cancer vaccines significantly enhanced neoAg-specific CTL responses, increased CTL infiltration in tumor microenvironment, and decreased tumor-associated immunosuppression. This process led to the complete elimination of colorectal cancer and delayed tumor growth of breast cancer in tumor-bearing mice. Taken together, our results demonstrated a novel strategy that combines neoAg cancer vaccine and radiotherapy to increase the therapeutic efficacy against colorectal and breast cancers.
The Microvascular-Lymphatic Interface and Tissue Homeostasis: Critical Questions That Challenge Current Understanding
Authors: Lampejo Arinola O. , Jo Michiko , Murfee Walter L. , Breslin Jerome W.
Published: October 2022

Lymphatic and blood microvascular networks play critical roles in the clearance of excess fluid from local tissue spaces. Given the importance of these dynamics in inflammation, tumor metastasis, and lymphedema, understanding the coordinated function and remodeling between lymphatic and blood vessels in adult tissues is necessary. Knowledge gaps exist because the functions of these two systems are typically considered separately. The objective of this review was to highlight the coordinated functional relationships between blood and lymphatic vessels in adult microvascular networks. Structural, functional, temporal, and spatial relationships will be framed in the context of maintaining tissue homeostasis, vessel permeability, and system remodeling. The integration across systems will emphasize the influence of the local environment on cellular and molecular dynamics involved in fluid flow from blood capillaries to initial lymphatic vessels in microvascular networks.
SIS3 Alleviates Cisplatin-Induced Acute Kidney Injury by Regulating the LncRNA Arid2-IR-Transferrin Receptor Pathway
Authors: Huang Jiayan , Lai Weiyan , Li Ming , Li Canming , Lou Tanqi , Peng Hui , Ye Zengchun
Published: October 2022

Introduction: TGF-β/Smad3 may be involved in the pathogenesis of acute kidney injury (AKI), but its functional role and mechanism of action in cisplatin-induced AKI are unclear. Here, we established a cisplatin-induced AKI mouse model to demonstrate that Smad3 may have roles in cisplatin nephropathy because of its potential effects on tubular epithelial cell (TEC) death and regeneration. Methods: Using a cisplatin-induced AKI model, the expression levels of lncRNA Arid2-IR were measured by qRT-PCR and the location detected by FISH. Transfected with overexpression of lncRNA Arid2-IR by lentiviral vector in TECs, and the expression of cleaved caspase 3, Bax, Bcl-2, PCNA, p21, p27, transferrin receptor (TFRC), FTH, and FTL were measured by Western blot. Protein molecules bound to lncRNA Arid2-IR were identified by RIP, RNA pull-down assay, mass spectrometry. Results: LncRNA Arid2-IR was significantly downregulated in vivo and in vitro. SIS3 decreased cell apoptosis and promoted cell regeneration by upregulating lncRNA Arid2-IR expression. LncRNA Arid2-IR regulated the cell cycle by decreasing expression of the cyclin-dependent kinase inhibitors p21 and p27. Finally, lncRNA Arid2-IR interacted with the TFRC, and overexpression of lncRNA Arid2-IR increased TFRC expression and decreased FTH and FTL. Conclusion: Smad3 regulated lncRNA Arid2-IR via TFRC, thereby regulating the cell cycle, protecting against cell apoptosis, and promoting cell regeneration.