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Abstract In the future, large language models (LLMs) may enhance the delivery of healthcare, but there are risks of misuse. These methods may be trained to allocate resources via unjust criteria involving multimodal data - financial transactions, internet activity, social behaviors, and healthcare information. This study shows that LLMs may be biased in favor of collective/systemic benefit over the protection of individual rights and could facilitate AI-driven social credit systems.

Abstract Transarterial chemoembolization (TACE) is an image-guided minimally invasive treatment for liver cancer which involves delivery of chemotherapy and embolic material into tumor-supplying arteries to block blood flow to a liver tumor and to deliver chemotherapy directly to the tumor. However, the released drug diffuses only less than a millimeter away from the beads. To enhance the efficacy of TACE, the development of microbubbles electrostatically bound to the surface of drug-eluting beads loaded with different amounts of doxorubicin (0–37.5 mg of Dox/mL of beads) is reported. Up to 400 microbubbles were bound to Dox-loaded beads (70–150 microns). This facilitated ultrasound imaging of the beads and increased the release rate of Dox upon exposure to high intensity focused ultrasound (HIFU). Furthermore, ultrasound exposure (1 MPa peak negative pressure) increased the distance at which Dox could be detected from beads embedded in a tissue-mimicking phantom, compared with a no ultrasound control.

Abstract Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery.

Abstract Liver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution. Thus, drug delivery varies widely, highly-dependent upon technique. An X-ray imageable poloxamer 407 (POL)-based drug delivery gel was developed and characterized, enabling real-time feedback. Utilizing three needle devices, POL or a control iodinated contrast solution were injected into an ex vivo bovine liver. The 3D distribution was assessed with cone beam computed tomography (CBCT). The 3D distribution of POL gels demonstrated localized spherical morphologies regardless of the injection rate. In addition, the gel 3D conformal distribution could be intentionally altered, depending on the injection technique. When doxorubicin (DOX) was loaded into the POL and injected, DOX distribution on optical imaging matched iodine distribution on CBCT suggesting spatial alignment of DOX and iodine localization in tissue. The controllability and localized deposition of this formulation may ultimately reduce the dependence on operator technique, reduce systemic side effects, and facilitate reproducibility across treatments, through more predictable standardized delivery.

Large language models (LLM) (e.g., ChatGPT) have garnered massive attention due to their potential to serve as interactive partners for a wide range of teaching and learning activities. In instructed second language acquisition, one potential use of LLMs is for pragmatics instruction. The current study sought to assess ChatGPT’s suitability for this task by analyzing its output in response to 144 DCTs (discourse completion tasks), which test a language learner’s ability to create apologies, requests, and refusals over differential levels of social and power distance, and degrees of imposition. Quantitatively, ChatGPT produced significantly shorter apologies than the other two speech acts (p < .001, R2 = .49), utilizing fewer pragmatic strategies (p < .001, R2 = .38). Closer social distance and greater imposition also resulted in longer responses, with higher imposition also eliciting ChatGPT to use more pragmatic strategies. Qualitatively, human raters scored ChatGPT’s apologies significantly lower in terms of their appropriateness, politeness, and language use, despite there being no statistical differences in ratings for requests and refusals. The main pedagogical implications are that, while ChatGPT offers an attractive option for students looking for more language exposure and interaction outside of the classroom, some degree of skepticism is still required due to its quantitative and qualitative inconsistencies.

Abstract Background Individuals with a moderate-to-severe traumatic brain injury (m/sTBI), despite experiencing good locomotor recovery six months post-injury, face challenges in adapting their locomotion to the environment. They also present with altered cognitive functions, which may impact dual-task walking abilities. Whether they present collision avoidance strategies with moving pedestrians that are altered under dual-task conditions, however, remains unclear. This study aimed to compare between individuals with m/sTBI and age-matched control individuals: (1), the locomotor and cognitive costs associated with the concurrent performance of circumventing approaching virtual pedestrians (VRPs) while attending to an auditory-based cognitive task and; (2) gaze behaviour associated with the VRP circumvention task in single and dual-task conditions. Methodology Twelve individuals with m/sTBI (age = 43.3 ± 9.5 yrs; >6 mo. post injury) and 12 healthy controls (CTLs) (age = 41.8 ± 8.3 yrs) were assessed while walking in a virtual subway station viewed in a head-mounted display. They performed a collision avoidance task with VRPs, as well as auditory-based cognitive tasks (pitch discrimination and auditory Stroop), both under single and dual-task conditions. Dual-task cost (DTC) for onset distance of trajectory deviation, minimum distance from the VRP, maximum lateral deviation, walking speed, gaze fixations and cognitive task accuracy were contrasted between groups using generalized estimating equations. Results In contrast to CTLs who showed locomotor DTCs only, individuals with m/sTBI displayed both locomotor and cognitive DTCs. While both groups walked slower under dual-task conditions, only individuals with m/sTBI failed to modify their onset distance of trajectory deviation and maintained smaller minimum distances and smaller maximum lateral deviation compared to single-task walking. Both groups showed shorter gaze fixations on the approaching VRP under dual-task conditions, but this reduction was less pronounced in the individuals with m/sTBI. A reduction in cognitive task accuracy under dual-task conditions was found in the m/sTBI group only. Conclusion Individuals with m/sTBI present altered locomotor and gaze behaviours, as well as altered cognitive performances, when executing a collision avoidance task involving moving pedestrians in dual-task conditions. Potential mechanisms explaining those alterations are discussed. Present findings highlight the compromised complex walking abilities in individuals with m/sTBI who otherwise present a good locomotor recovery.

Abstract Pre-injured lungs are prone to injury progression in response to mechanical ventilation. Heterogeneous ventilation due to (micro)atelectases imparts injurious strains on open alveoli (known as volutrauma). Hence, recruitment of (micro)atelectases by positive end-expiratory pressure (PEEP) is necessary to interrupt this vicious circle of injury but needs to be balanced against acinar overdistension. In this study, the lung-protective potential of alveolar recruitment was investigated and balanced against overdistension in pre-injured lungs. Mice, treated with empty vector (AdCl) or adenoviral active TGF-β1 (AdTGF-β1) were subjected to lung mechanical measurements during descending PEEP ventilation from 12 to 0 cmH2O. At each PEEP level, recruitability tests consisting of two recruitment maneuvers followed by repetitive forced oscillation perturbations to determine tissue elastance (H) and damping (G) were performed. Finally, lungs were fixed by vascular perfusion at end-expiratory airway opening pressures (Pao) of 20, 10, 5 and 2 cmH2O after a recruitment maneuver, and processed for design-based stereology to quantify derecruitment and distension. H and G were significantly elevated in AdTGF-β1 compared to AdCl across PEEP levels. H was minimized at PEEP = 5–8 cmH2O and increased at lower and higher PEEP in both groups. These findings correlated with increasing septal wall folding (= derecruitment) and reduced density of alveolar number and surface area (= distension), respectively. In AdTGF-β1 exposed mice, 27% of alveoli remained derecruited at Pao = 20 cmH2O. A further decrease in Pao down to 2 cmH2O showed derecruitment of an additional 1.1 million alveoli (48%), which was linked with an increase in alveolar size heterogeneity at Pao = 2–5 cmH2O. In AdCl, decreased Pao resulted in septal folding with virtually no alveolar collapse. In essence, in healthy mice alveoli do not derecruit at low PEEP ventilation. The potential of alveolar recruitability in AdTGF-β1 exposed mice is high. H is optimized at PEEP 5–8 cmH2O. Lower PEEP folds and larger PEEP stretches septa which results in higher H and is more pronounced in AdTGF-β1 than in AdCl. The increased alveolar size heterogeneity at Pao = 5 cmH2O argues for the use of PEEP = 8 cmH2O for lung protective mechanical ventilation in this animal model.

Background and objective: Focal therapy (FT) is increasingly recognized as a promising approach for managing localized prostate cancer (PCa), notably reducing treatment-related morbidities. However, post-treatment anatomical changes present significant challenges for surveillance using current imaging techniques. This study aimed to evaluate the inter-reader agreement and efficacy of the Prostate Imaging after Focal Ablation (PI-FAB) scoring system in detecting clinically significant prostate cancer (csPCa) on post-FT multiparametric magnetic resonance imaging (mpMRI). Methods: A retrospective cohort study was conducted involving patients who underwent primary FT for localized csPCa between 2013 and 2023, followed by post-FT mpMRI and a prostate biopsy. Two expert genitourinary radiologists retrospectively evaluated post-FT mpMRI using PI-FAB. The key measures included inter-reader agreement of PI-FAB scores, assessed by quadratic weighted Cohen’s kappa (κ), and the system’s efficacy in predicting in-field recurrence of csPCa, with a PI-FAB score cutoff of 3. Additional diagnostic metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were also evaluated. Key findings and limitations: Scans from 38 patients were analyzed, revealing a moderate level of agreement in PI-FAB scoring (κ = 0.56). Both radiologists achieved sensitivity of 93% in detecting csPCa, although specificity, PPVs, NPVs, and accuracy varied. Conclusions and clinical implications: The PI-FAB scoring system exhibited high sensitivity with moderate inter-reader agreement in detecting in-field recurrence of csPCa. Despite promising results, its low specificity and PPV necessitate further refinement. These findings underscore the need for larger studies to validate the clinical utility of PI-FAB, potentially aiding in standardizing post-treatment surveillance. Patient summary: Focal therapy has emerged as a promising approach for managing localized prostate cancer, but limitations in current imaging techniques present significant challenges for post-treatment surveillance. The Prostate Imaging after Focal Ablation (PI-FAB) scoring system showed high sensitivity for detecting in-field recurrence of clinically significant prostate cancer. However, its low specificity and positive predictive value necessitate further refinement. Larger, more comprehensive studies are needed to fully validate its clinical utility.

Abstract Heat-based local ablation techniques are effective treatments for specific oligometastatic and localized cancers and are being studied for their potential to induce immunogenic cell death and augment systemic immune responses to immunotherapies. The diverse technologies associated with thermal therapy have an unmet need for method development to enable device-specific experimentation, optimization, calibration and refinement of the parameter space to optimize therapeutic intent while minimizing side effects or risk to the patient. Quality assurance, training, or comparing thermal dose among different modalities or techniques using animal models is time and resource intensive. Therefore, the application and use of tissue mimicking thermosensitive, thermochromic liquid crystal and thermochromic paint phantom models may reduce costs and hurdles associated with animal use. Further, their homogenous composition may enable more precise assessment of ablative techniques. This review utilized SciFinder, Web of Science, PubMed and EMBASE to systematically evaluate the literature describing the background and applications of thermochromic liquid crystal, thermochromic paint and tissue-mimicking thermochromic phantoms used to characterize the thermal effects of ablation devices with a focus on facilitating their use across the medical device development life cycle. Graphical Abstract

While listeners tend to downgrade speakers' accent and comprehensibility when they perceive them to be from a different language community--a process known as reverse linguistic stereotyping (RLS)--research has generally relied solely on quantitative data such as Likert scale ratings. The current study sought to extend the analysis further by investigating the reasons which informed raters' decisions. A sample of 210 Japanese university students (six groups of n = 35) were asked to listen to recorded speeches by native Japanese speakers. In a matched-guise design, the groups were either shown photos of a Japanese, Caucasian, or Southeast Asian male, and asked to provide ratings of accentedness, comprehensibility, and intelligibility. They were then asked to report what factors influenced their comprehensibility ratings. In line with previous research, listeners rated non-Japanese guises as significantly more accented than the Japanese one, though differences in intelligibility were non-significant. A key finding was that while comprehensibility ratings were statistically comparable, the rationales given were qualitatively different. Groups who viewed the Caucasian or Southeast Asian photographs cited pronunciation issues significantly more than the Japanese group which reported grammatical and lexical factors as the reasons behind their downgraded ratings.

Mobile-learning (m-learning), or mobile-assisted language learning (MALL), has been the object of a great deal of research over the last twenty years. However, empirical work in this area has largely failed to produce generalizable conclusions due to variation in methodology, target feature, and task-type (Burston, 2014, 2015). As schools in Japan begin to join the growing number of classrooms worldwide using mobile-based assignments, this study examined how Japanese EFL students' writing task production differed depending on writing medium (i.e., handwritten on paper vs. tapped on a smartphone). Writing samples were collected from N = 1,449 participants, divided into smartphone- or paper-based groups, across a spectrum of English proficiencies. Handwritten submissions were found to be significantly longer than those composed on a smartphone (p < 0.001, d = 0.54), with differences being more pronounced for learners of higher proficiency than lower ones. Significance and effect sizes steadily dropped from p < 0.001, d = 0.66 for advanced learners to p = 0.168, d = 0.38 for beginners. These results indicate that care must be taken in designing m-learning activities, and that students must be given adequate training in smartphone-input skills (i.e., tapping) and time to acclimate before using such tasks for high-stakes assessments.

Research has suggested that the type and frequency of learning strategies employed by successful listeners is greater than their less successful counterparts. Based on evidence that metacognitive strategies (e.g. listening-for-gist; inferring meaning) are more effective than cognitive ones (e.g. word-for-word translation), this study sought to measure the effect that rhymical training had on the listening comprehension acuity of 313 Japanese university students. The theoretical basis was that rhythmical priming assists learners parse the input based on prosody and identify salient words by stress. Small but significant increases were observed among students who were rhythmically trained, compared to a comparison group that received explicit instruction but no rhythm training, and a "true" control group that received no treatment. These results extend the feasibility of input enhancement, rhythmic priming, and perception-based instruction beyond the traditional grammar and pronunciation instruction domains.