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In recent years, academic interest in new developments in Artificial Intelligence (AI) and its ethical challenges in higher education has increased. The new emerging technologies that have become popular among the university community in recent times require an exhaustive study to evaluate their impact on academic integrity and plagiarism. The main stakeholders in higher education (SoTL, educational authorities, and policymakers) must understand the new trends and the most relevant studies to have action guides that preserve academic integrity standards in deploying AI in the university. This research analyzes scientific articles published in high-impact journals indexed in the Journal Citation Reports (JCR) (n=254) and carries out a bibliometric study using VOSviewer 1.6.18 and WordStat 2023.1. The Normalized Impact per Document (NID) and per Year (NIY) are studied, and four thematic groups and twelve main themes are identified and discussed, allowing the internal research structure of this field of study to be determined. Based on the findings, a roadmap for implementing AI in higher education is proposed, preserving ethical standards and based on three levels (Micro, Meso, Macro). This study offers practical implications for SoTL, academic authorities, and policymakers. Furthermore, the evidence found allows editors of high-impact journals to advise on unclosed gaps and new research trends and new research trends in the area.

Educators of International Teaching Assistants (ITAs) have been overlooked, erroneously. As teacher educators, their work is exponentially important to North American universities. A multiple case study examined three ITA Educators' ideologies, involving data from two interviews -one being a stimulated recall using classroom observations fieldnotes, syllabi, assignments, and feedback left on students' work. Through qualitative content analysis, two incompatible ideologies were found being implemented in sections of one class: one orienting learners to undergraduate classrooms, and the other towards passing mandatory language testing. Cynicism was found to characterize two instructors' pedagogies. Findings highlight the ethical complexities of language teaching and assessment. ITA training programs must address foundational issues and examine how ITA Educators are supported. This novel study provides a baseline for future work on ITA Educators, and contributes to literature on language teachers' ideologies. Future work should elucidate how ITA Educators' identities and external ideologies impact ITAs' learning trajectories.

This study connects to an ongoing discussion about the limits and affordances of simulators as realistic and relevant contexts for professional learning, in this case in the development of visual expertise. Earlier studies of simulator-based maritime pilot training conclude that there are risks associated with so-called negative skills transfer due to a lack of photorealism in simulator environments. The aim of this study is to carefully examine how visual expertise develops in and through training in a simulated environment. Through a practice-based approach to the development of visual expertise, and by using qualitative interaction analysis of video recorded training sessions, the analytical focus is directed towards maritime pilot trainees' talk about imperfections and inconsistencies in the virtual environment during exercises in a high-fidelity bridge simulator. Considering the multi-layered nature of the maritime pilot's visual expertise, findings show that the maritime pilots in training noticed and adapted to the specific methodological and technological challenges when manoeuvring a simulated vessel. During such reflection-in-action, they also commented on and explored the differences between, navigating in a simulator, on the one hand, and, on the other hand, navigating on board a ship. Instead of concluding that there is a risk for negative skills transfer that follows from the differences between the two contexts of navigating, we argue that the challenges introduced by representations encountered when training in a virtual environment may add to the expertise of the trainees and lead to enriched conceptual, methodological, and technical knowledge regarding the specificities of visually demanding and ambiguous navigation situations. In this way, this study contributes to advance our understanding of learning in virtual environments to the frontline of learning research.

This paper presents a review of the literature pertaining to exam anxiety, highlighting findings from empirical studies, theoretical frameworks, and practical strategies. Exam anxiety is a pervasive issue affecting students worldwide, impacting academic performance and psychological well-being. This review explores the causes, manifestations, and consequences of exam anxiety, and evaluates existing interventions. By examining a diverse range of scholarly works, this paper seeks to contribute to a deeper understanding of exam anxiety and offers insights for educators as well as students. The paper also provides a brief list of alternative forms of summative assessment that have the potential to alleviate exam anxiety.

During the COVID-19 pandemic, numerous schools halted face-to-face teaching and instead resorted to online classes. The impact of online learning on students' academic worries, social relationships, and psychological well-being has received growing attention. Based on a sample of 1095 students aged 14-16 in 12 secondary schools in Hong Kong, structural equation modeling was used to investigate the association between online learning problems, academic worries and performance, social interaction, and psychosocial well-being during the pandemic. The path relationships among variables were compared by gender groups and socio-economic status (SES). Online learning problems were found to be negatively associated with psychosocial well-being through academic worries and social interaction as mediators. The effect of mediation among female students was larger than that of males, whereas the impact of academic worries on both psychosocial well-being and social interaction was stronger and significant only in the low SES group. As the COVID-19 pandemic significantly impacted the learning and well-being of students, attention should be given to gender and SES difference among students.

Health professions education (HPE) research in the General Practice domain (GP-HPE) is vital for high-quality healthcare. Collaboration among GP-HPE researchers is crucial but challenging. Formulating a research agenda, involving stakeholders, and fostering inter-institutional collaboration can address these challenges and connect educational research and practice. We used Q-methodology to explore perspectives on GP-HPE research of participants from all Dutch postgraduate GP training institutes. Participants individually sorted statements based on the relevance of future GP-HPE research for educational practice. Data analysis comprised inverted factor analysis, rotation, and qualitative interpretation of configurations of all statements. The National Meeting on Educational Research took a participatory approach. We included 73 participants with diverse involvement in GP-HPE research. We identified five distinct perspectives, each representing a research focus area for developing and innovating GP education: the clinician scientist, the socially engaged GP, the specific GP identity, the GP as an entrepreneur, and the GP engaged in lifelong learning. The resulting five perspectives align with General Practice hallmarks. Q-methodology and a participatory approach facilitated collaboration among stakeholders. Successful inter-institutional collaboration requires a common goal, neutral leadership, participant commitment, regular meetings, audit trail support, process transparency, and reflexivity. Future research should address evidence gaps within these perspectives. Using Q-methodology turned out to be valuable for compiling a national research agenda for GP-HPE research. The research process helped to cross boundaries between researchers in different institutions, thus putting inter-institutional collaborative advantage center stage. Our approach could provide a conceivable procedure for HPE researchers worldwide.

Purpose: Aging increases risk for hearing loss, cognitive decline, and social isolation; however, the nature of their interconnection remains unclear. This study examined the interplay between age-related hearing loss, cognitive decline, and social isolation in adults by testing the ability to understand speech in background noise, a challenge frequently reported by many older adults. Method: We analyzed data collected from 128 adults (20-79 years of age, M[subscript age] = 51 years) recruited as part of the Aging Brain Cohort at the University of South Carolina repository. The participants underwent testing for hearing, cognition, and social interaction, which included pure-tone audiometry, a words-in-noise (WIN) test, a hearing questionnaire (Speech, Spatial and Qualities of Hearing Scale [SSQ12]), a social questionnaire (Patient-Reported Outcomes Measurement Information System-57 Social), and the Montreal Cognitive Assessment. We used a single pure-tone average (PTA) threshold value and a single WIN threshold value for each participant because there were no differences on average between the left and right ears. Results: Poorer hearing was significantly associated with cognitive decline, through both PTA and WIN thresholds, with a stronger association observed for WIN threshold. Adults with poorer hearing also exhibited greater social isolation, as evidenced by their WIN threshold and SSQ12 score, although not through PTA. This connection was more pronounced with the WIN threshold than with the SSQ12 score. Cognition was not related to social isolation, suggesting that social isolation is affected more by the ability to understand words in noise than by cognition in a nondemented population. Conclusions: Understanding speech in challenging auditory environments rather than mere threshold detection is strongly linked to social isolation and cognitive decline. Thus, inclusion of a word-recognition-in-noise test and a social isolation survey in clinical settings is warranted.

In relational event networks, the tendency for actors to interact with each other depends greatly on the past interactions between the actors in a social network. Both the volume of past interactions and the time that has elapsed since the past interactions affect the actors' decision-making to interact with other actors in the network. Recently occurred events may have a stronger influence on current interaction behavior than past events that occurred a long time ago--a phenomenon known as "memory decay". Previous studies either predefined a short-run and long-run memory or fixed a parametric exponential memory decay using a predefined half-life period. In real-life relational event networks, however, it is generally unknown how the influence of past events fades as time goes by. For this reason, it is not recommendable to fix memory decay in an ad-hoc manner, but instead we should learn the shape of memory decay from the observed data. In this paper, a novel semi-parametric approach based on Bayesian Model Averaging is proposed for learning the shape of the memory decay without requiring any parametric assumptions. The method is applied to relational event history data among socio-political actors in India and a comparison with other relational event models based on predefined memory decays is provided.

Audio description (AD) plays a crucial role in making audiovisual media accessible to people with a visual impairment, enhancing their experience and understanding. This study employs an event segmentation task to examine how people without sight perceive and segment narrative events in films with AD, compared to sighted viewers without AD. Two AD versions were utilized, differing in the explicitness of conveyed event boundaries. Results reveal that the participants without sight generally perceived event boundaries similarly to their sighted peers, affirming AD's effectiveness in conveying event structures. However, when key event boundaries were more implicitly expressed, event boundary recognition diminished. Collectively, these findings offer valuable insights into event segmentation processes across sensory modalities. Additionally, they underscore the significance of how AD presents event boundaries, influencing the perception and interpretation of audiovisual media for people with a visual impairment and providing applied insights into event segmentation, multimodal processing, and audiovisual accessibility.

This study examines the embodied ways in which learners monitor their cognition while learning about exponential functions in an immersive virtual reality (VR) based game, "Pandemic" by Prisms of Reality. Traditionally, metacognitive monitoring has been assessed through behavioural traces and verbalised instances. When learning in VR, learners are fully immersed in the learning environment, actively manipulating it based on affordances designed to support learning, offering insights into the relationship between physical interaction and metacognition. The study collected multimodal data from 15 participants, including think-aloud audio, bird's-eye view video recordings and physiological data. Metacognitive monitoring was analysed through qualitative coding of the think-aloud protocol, while movement was measured via optical flow analysis and cognitive load was assessed through heart rate variability analysis. The results revealed embodied metacognition by aligning the data to identify learners' physical states alongside their verbalised metacognition. The findings demonstrated a temporal interplay among cognitive load, metacognitive monitoring, and motion during VR-based learning. Specifically, cognitive load, indicated by the low- and high-frequency heart rate variability index, predicted instances of metacognitive monitoring, and monitoring predicted learners' motion while interacting with the VR environment. This study further provides future directions in understanding self-regulated learning processes during VR learning by utilizing multimodal data to inform real-time adaptive personalised support within these environments.

Intelligent tutoring systems (ITSs) incorporate pedagogical agents (PAs) to scaffold learners' self-regulated learning (SRL) via prompts and feedback to promote learners' monitoring and regulation of their cognitive, affective, metacognitive and motivational processes to achieve their (sub)goals. This study examines PAs' effectiveness in scaffolding and teaching SRL during learning with MetaTutor, an ITS on the human circulatory system. Undergraduates (N = 118) were randomly assigned to a condition: "Control Condition" (i.e. learners could only self-initiate SRL strategies) and "Prompt and Feedback Condition" (i.e. PAs prompted learners to engage in SRL). Learners' log-file data captured when strategies were used, the initiator of the strategy (i.e. learner and PA), and the relevance of instructional content pages in relation to learner subgoals. While results showed that PAs were effective scaffolders of SRL in which they prompted learners to engage in SRL strategies more when content was relevant towards their subgoals and as time on page and task increased, there were mixed findings about the effectiveness of PAs as teachers of SRL. Findings show how production rules guiding PA prompts can improve their scaffolding and teaching of SRL across the learning task - through contextualizing SRL strategies to the instructional content and in relation to the relevance of the content to learners' subgoals.

Service-learning can produce timely paradigmatic shifts in the psychology curriculum and in teaching practices. This innovative pedagogy enhances students' academic learning, personal growth, civic development, and professional development. Service-learning pedagogy also has the potential of enhancing students' understanding of, and commitment to, "glocal" (global-local) issues as expressed in the United Nations' Sustainable Development Goals. Service-learning is defined and proffered to transform the undergraduate psychology curriculum by engaging the department faculty to align course outcomes and scaffold community-engaged activities from the introductory to capstone courses. This transformation is illustrated with a major contemporary challenge: climate change.

The adoption of genetically modified organisms (GMOs) in Ghana has raised a lot of public concerns and mixed feelings among some Ghanaians. Our present study, therefore, explored the current knowledge of the general public on GMOs, their perceptions, and factors that influence their understanding of GMOs. A total of 200 Ghanaians were interviewed using an online semi-structured questionnaire to solicit information on their knowledge of GMOs. The findings of the study showed that most Ghanaians (183 out of 200) are aware of GMOs. Age and level of education significantly influenced consumers' awareness of GMOs. The results also revealed that most of the participants have a medium to a high level of knowledge of GMOs; however, limited information about GMOs is available to the public. About 61% of the respondents are willing to consume GMOs when made available in Ghana. Also, the findings of the study showed that the respondents would prefer GM-labelled products. The educational level of the respondents significantly influenced their knowledge and understanding of GMOs. The study recommends that scientists and various media platforms provide a platform to address the concerns of the public on GMOs and occasionally engage them in GMO-related issues and their role in addressing food insecurity and malnutrition.

Temporal seeing is a mode of visual perception that interrupts the spatial bias we bring to visual literacy practices. Although an image only captures one moment in time, there are multiple spatioanalytical tools we can use to consider any image. Spatial literacy, which is the practice of analyzing objects through their properties in space, tends to be the default analytical mode for making sense of imagery. For people to bring a commensurate temporal richness to their articulated visual readings, we first highlight the perspectival richness of time and temporality. We next present five precepts that can guide enriched temporal seeing: contextual histories; relational chronologies; internal rhymicity; desequenced and resequenced narrative; and critique and meaning-making. Finally, we suggest that temporal seeing holds a series of educative possibilities for expanding the interpretive frames and perceptual apparatuses of literacy researchers and practitioners.

Musical instrument training has been linked to improved academic and cognitive abilities in children, but it remains unclear why this occurs. Moreover, access to instrument training is not always feasible, thereby leaving less fortunate children without opportunity to benefit from such training. Although music-based video games may be more accessible to a broader population, research is lacking regarding their benefits on academic and cognitive performance. To address this gap, we assessed a custom-designed, digital rhythm training game as a proxy for instrument training to evaluate its ability to engender benefits in math and reading abilities. Furthermore, we tested for changes in core cognitive functions related to math and reading to inform how rhythm training may facilitate improved academic abilities. Classrooms of 8-9 year old children were randomized to receive either 6 weeks of rhythm training (N = 32) or classroom instruction as usual (control; N = 21). Compared to the control group, results showed that rhythm training improved reading, but not math, fluency. Assessments of cognition showed that rhythm training also led to improved rhythmic timing and language-based executive function (Stroop task), but not sustained attention, inhibitory control, or working memory. Interestingly, only the improvements in rhythmic timing correlated with improvements in reading ability. Together, these results provide novel evidence that a digital platform may serve as a proxy for musical instrument training to facilitate reading fluency in children, and that such reading improvements are related to enhanced rhythmic timing ability and not other cognitive functions associated with reading performance.

Successful implementation of school-wide interventions (i.e., delivered to all students by a wide array of school personnel) is key to promoting students' academic achievement and psychosocial development. Yet, the implementation of school-wide interventions is complex and can be psychologically taxing for implementing personnel. If evidence-based practice and program (EBP) implementation goes unsupported, implementation challenges might result in chronic stress among school personnel that leads to burnout. While generally effective leadership tends to decrease educator burnout, implementation-specific leadership may also decrease burnout through its strategic supports for EBP implementation. A series of linear regression and path models were used to examine the concurrent association between transformational (e.g., general) and implementation (e.g., strategic) leadership and burnout and its component parts (i.e., emotional exhaustion, depersonalization, personal accomplishment). In a sample of 338 school personnel, we found transformational and implementation leadership were each significantly associated with decreased burnout. However, transformational leadership was not significantly associated with any of the three burnout components, whereas implementation leadership was significantly associated with increased personal accomplishment. These results suggest both general and strategic forms of leadership are key supports for school personnel burnout and as such, leaders may benefit from training to improve each. Additional implications for schools and future directions to understand how best to support school personnel are discussed.

The performance of superconducting qubits is degraded by a poorly characterized set of energy sources breaking the Cooper pairs responsible for superconductivity, creating a condition often called quasiparticle poisoning. Both superconducting qubits and low threshold dark matter calorimeters have observed excess bursts of quasiparticles or phonons that decrease in rate with time. Here, we show that a silicon crystal glued to its holder exhibits a rate of low-energy phonon events that is more than two orders of magnitude larger than in a functionally identical crystal suspended from its holder in a low-stress state. The excess phonon event rate in the glued crystal decreases with time since cooldown, consistent with a source of phonon bursts which contributes to quasiparticle poisoning in quantum circuits and the low-energy events observed in cryogenic calorimeters. We argue that relaxation of thermally induced stress between the glue and crystal is the source of these events.

BACKGROUND: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. METHODS: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. DISCUSSION: In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.

It has been widely reported that isoprene emissions from the Arctic ecosystem have a strong temperature response. Here we identify sedges (Carex spp. and Eriophorum spp.) as key contributors to this high sensitivity using plant chamber experiments. We observe that sedges exhibit a markedly stronger temperature response compared to that of other isoprene emitters and predictions by the widely accepted isoprene emission model, the Model of Emissions of Gases and Aerosols from Nature (MEGAN). MEGAN is able to reproduce eddy-covariance flux observations at three high-latitude sites by integrating our findings. Furthermore, the omission of the strong temperature responses of Arctic isoprene emitters causes a 20% underestimation of isoprene emissions for the high-latitude regions of the Northern Hemisphere during 2000-2009 in the Community Land Model with the MEGAN scheme. We also find that the existing model had underestimated the long-term trend of isoprene emissions from 1960 to 2009 by 55% for the high-latitude regions.

The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

OBJECTIVE: Emerging research suggests that rheumatoid arthritis (RA) is associated with intestinal dysbiosis. This prospective pilot study evaluates changes in intestinal microbial composition in patients with RA initiating treatment with either methotrexate (MTX) or a tumor necrosis factor inhibitor (TNFi). METHODS: Consecutive patients, fulfilling the 2010 American College of Rheumatology/EULAR classification criteria for RA, who started treatment with either MTX or TNFi delivered a stool sample upon initiation of immunosuppression and 3 months later. A 16S ribosomal RNA gene-based validated microbiota test (GA-map Dysbiosis Index Score [DIS], Genetic Analysis, Oslo, Norway) was used to evaluate for the presence and degree of dysbiosis. Fecal levels of Prevotella copri (P. copri) were analyzed by custom-made quantitative polymerase chain reaction. Changes in microbial composition were analyzed in relation to changes in disease activity, as measured by the disease activity score based on 28-joint counts, using C-reactive protein. RESULTS: At baseline, dysbiosis was present in 33 of 50 (66%) participants and more common in participants with more than 2 years of disease duration (P = 0.019). At the 3-month follow-up, 27 of 50 (54%) were good treatment responders and the DIS had improved in 14 of 50 (28%). Participants initiating TNFi more often exhibited improvement in the DIS compared with those initiating MTX (P = 0.031). P. copri was identified in 32 of 50 (64%) at baseline. An improvement in disease activity score based on 28-joint counts, using C-reactive protein was associated with a simultaneous decrease in P. copri abundance (rs = 0.30, P = 0.036). CONCLUSION: This study affirms that dysbiosis is a feature of RA. Although patients were not randomized to MTX or TNFi, the findings suggest that specific therapies may differentially modulate the gastrointestinal microbiota in RA. The association between P. copri and treatment response requires further study.

A major limitation of gene therapy for sickle cell disease (SCD) is the availability and access to a potentially curative one-time treatment, due to high treatment costs. We have developed a high-titer bifunctional lentiviral vector (LVV) in a vector backbone that has reduced size, high vector yields, and efficient gene transfer to human CD34+ hematopoietic stem and progenitor cells (HSPCs). This LVV contains locus control region cores expressing an anti-sickling βAS3-globin gene and two microRNA-adapted short hairpin RNA simultaneously targeting BCL11A and ZNF410 transcripts to maximally induce fetal hemoglobin (HbF) expression. This LVV induces high levels of anti-sickling hemoglobins (HbAAS3 + HbF), while concurrently decreasing sickle hemoglobin (HbS). The decrease in HbS and increased anti-sickling hemoglobin impedes deoxygenated HbS polymerization and red blood cell sickling at low vector copy per cell in transduced SCD patient CD34+ cells differentiated into erythrocytes. The dual alterations in red cell hemoglobins ameliorated the SCD phenotype in the SCD Berkeley mouse model in vivo. With high titer and enhanced transduction of HSPC at a low multiplicity of infection, this LVV will increase the number of patient doses of vector from production lots to decrease costs and help improve accessibility to gene therapy for SCD.

Collaborative quantitative scientists, including biostatisticians, epidemiologists, bio-informaticists, and data-related professionals, play vital roles in research, from study design to data analysis and dissemination. It is imperative that academic health care centers (AHCs) establish an environment that provides opportunities for the quantitative scientists who are hired as staff to develop and advance their careers. With the rapid growth of clinical and translational research, AHCs are charged with establishing organizational methods, training tools, best practices, and guidelines to accelerate and support hiring, training, and retaining this staff workforce. This paper describes three essential elements for building and maintaining a successful unit of collaborative staff quantitative scientists in academic health care centers: (1) organizational infrastructure and management, (2) recruitment, and (3) career development and retention. Specific strategies are provided as examples of how AHCs can excel in these areas.

A quarter of humanity is estimated to have been exposed to Mycobacterium tuberculosis (Mtb) with a 5-10% risk of developing tuberculosis (TB) disease. Variability in responses to Mtb infection could be due to host or pathogen heterogeneity. Here, we focused on host genetic variation in a Peruvian population and its associations with gene regulation in monocyte-derived macrophages and dendritic cells (DCs). We recruited former household contacts of TB patients who previously progressed to TB (cases, n = 63) or did not progress to TB (controls, n = 63). Transcriptomic profiling of monocyte-derived DCs and macrophages measured the impact of genetic variants on gene expression by identifying expression quantitative trait loci (eQTL). We identified 330 and 257 eQTL genes in DCs and macrophages (False Discovery Rate (FDR) < 0.05), respectively. Four genes in DCs showed interaction between eQTL variants and TB progression status. The top eQTL interaction for a protein-coding gene was with FAH, the gene encoding fumarylacetoacetate hydrolase, which mediates the last step in mammalian tyrosine catabolism. FAH expression was associated with genetic regulatory variation in cases but not controls. Using public transcriptomic and epigenomic data of Mtb-infected monocyte-derived dendritic cells, we found that Mtb infection results in FAH downregulation and DNA methylation changes in the locus. Overall, this study demonstrates effects of genetic variation on gene expression levels that are dependent on history of infectious disease and highlights a candidate pathogenic mechanism through pathogen-response genes. Furthermore, our results point to tyrosine metabolism and related candidate TB progression pathways for further investigation.

BackgroundLow grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited.AimWe examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors.MethodsParticipants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index).ResultsMean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed.ConclusionsGrip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

Playing two-dimensional video games has been shown to result in improvements in a range of visual and cognitive tasks, and these improvements appear to generalize widely1,2,3,4,5,6. Here we report that young adults with healthy vision, surprisingly, showed a dramatic improvement in stereo vision after playing three-dimensional, but not two-dimensional, video games for a relatively short period of time. Intriguingly, neither group showed any significant improvement in binocular contrast sensitivity. This dissociation suggests that the visual enhancement was specific to genuine stereoscopic processing, not indirectly resulting from enhanced contrast processing, and required engaging in a disparity cue-rich three-dimensional environment.

Antibodies are critical tools for research into extracellular vesicles (EVs) and other extracellular nanoparticles (ENPs), where they can be used for their identification, characterization, and isolation. However, the lack of a centralized antibody platform where researchers can share validation results thus minimizing wasted personnel time and reagents, has been a significant obstacle. Moreover, because the performance of antibodies varies among assay types and conditions, detailed information on assay variables and protocols is also of value. To facilitate sharing of results on antibodies that are relevant to EV/ENP research, the EV Antibody Database has been developed by the investigators of the Extracellular RNA Communication Consortium (ERCC). Hosted by the ExRNA Portal (https://exrna.org/resources/evabdb/), this interactive database aggregates and shares results from antibodies that have been tested by research groups in the EV/ENP field. Currently, the EV Antibody Database includes modules for antibodies tested for western Blot, EV Flow Cytometry, and EV Sandwich Assays, and holds 110 records contributed by 6 laboratories from the ERCC. Detailed information on antibody sources, assay conditions, and results is provided, including negative results. We encourage ongoing expert input and community feedback to enhance the databases utility, making it a valuable resource for comprehensive validation data on antibodies and protocols in EV biology.

OBJECTIVE: Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). We assessed the association between regular aspirin use and ASCVD mortality among individuals with versus without elevated Lp(a) in a nationally representative US cohort. METHODS: Eligible participants were aged 40-70 years without clinical ASCVD, reported on aspirin use, and had Lp(a) measurements from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), the only cycle of this nationally representative US cohort to measure Lp(a). Regular aspirin use was defined as taking aspirin ≥30 times in the previous month. Using NHANES III linked mortality records and weighted Cox proportional hazards regression, the association between regular aspirin use and ASCVD mortality was observed in those with and without elevated Lp(a) (≥50 versus

OBJECTIVE: Many studies support the notion that polygenic risk scores (PRS) improve risk prediction for coronary heart disease (CHD) beyond conventional risk factors. However, PRS are not yet considered risk-enhancing factor in guidelines. Our objective was to determine the predictive performance of a commercially available PRS (CARDIO inCode-Score®) compared with the Pooled Cohorts Equations (PCE) in a contemporary, multi-ethnic cohort. METHODS: Participants (n = 63,070; 67 % female; 18 % non-European) without prior CHD were followed from 2007 through 12/31/2022. The association between the PRS and incident CHD was assessed using Cox regression adjusting for genetic ancestry and risk factors. Event rates were estimated by categories of PCE and by low/intermediate/high genetic risk within PCE categories; risk discrimination and net reclassification improvement (NRI) were also assessed. RESULTS: There were 3,289 incident CHD events during 14 years of follow-up. Adjusted hazard ratio (aHR) for incident CHD per 1 SD increase in PRS was 1.18 (95 % CI:1.14-1.22), and the aHR for the upper vs lower quintile of the PRS was 1.66 (95 % CI:1.49-1.86). The association was consistent in both sexes, in European participants compared with all minority groups combined and was strongest in the first 5 years of follow-up. The increase in the C-statistic was 0.004 (0.747 vs. 0.751; p < 0.0001); the NRI was 2.4 (0.9-3.8) for the entire cohort and 9.7 (7.5-12.0) for intermediate PCE risk individuals. After incorporating high genetic risk, a further 10 percent of participants at borderline/intermediate PCE risk would be candidates for statin therapy. CONCLUSION: Inclusion of polygenic risk improved identification of primary prevention individuals who may benefit from more intensive risk factor modification.

ObjectiveBlockchain has emerged as a potential data-sharing structure in healthcare because of its decentralization, immutability, and traceability. However, its use in the biomedical domain is yet to be investigated comprehensively, especially from the aspects of implementation and evaluation, by existing blockchain literature reviews. To address this, our review assesses blockchain applications implemented in practice and evaluated with quantitative metrics.Materials and methodsThis systematic review adapts the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework to review biomedical blockchain papers published by August 2023 from 3 databases. Blockchain application, implementation, and evaluation metrics were collected and summarized.ResultsFollowing screening, 11 articles were included in this review. Articles spanned a range of biomedical applications including COVID-19 medical data sharing, decentralized internet of things (IoT) data storage, clinical trial management, biomedical certificate storage, electronic health record (EHR) data sharing, and distributed predictive model generation. Only one article demonstrated blockchain deployment at a medical facility.DiscussionEthereum was the most common blockchain platform. All but one implementation was developed with private network permissions. Also, 8 articles contained storage speed metrics and 6 contained query speed metrics. However, inconsistencies in presented metrics and the small number of articles included limit technological comparisons with each other.ConclusionWhile blockchain demonstrates feasibility for adoption in healthcare, it is not as popular as currently existing technologies for biomedical data management. Addressing implementation and evaluation factors will better showcase blockchain's practical benefits, enabling blockchain to have a significant impact on the health sector.

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood1-3. Here, the Molecular Transducers of Physical Activity Consortium4 profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository ( https://motrpac-data.org/ ).

Electrification to reduce or eliminate greenhouse gas emissions is essential to mitigate climate change. However, a substantial portion of our manufacturing and transportation infrastructure will be difficult to electrify and/or will continue to use carbon as a key component, including areas in aviation, heavy-duty and marine transportation, and the chemical industry. In this Roadmap, we explore how multidisciplinary approaches will enable us to close the carbon cycle and create a circular economy by defossilizing these difficult-to-electrify areas and those that will continue to need carbon. We discuss two approaches for this: developing carbon alternatives and improving our ability to reuse carbon, enabled by separations. Furthermore, we posit that co-design and use-driven fundamental science are essential to reach aggressive greenhouse gas reduction targets.

Chronic graft-versus-host-disease (cGVHD) is divided into two subtypes: classic (absence of acute GVHD features) and overlap cGVHD (ocGVHD), in which both chronic and acute GVHD clinical features are present simultaneously. While worse outcomes with ocGVHD have been reported, there are few recent analyses. We performed a secondary analysis of data from the ABA2 trial (N = 185), in which detailed GVHD data were collected prospectively and systematically adjudicated. Analyses included cumulative incidence of classic versus ocGVHD, their specific organ manifestations, global disease severity scores, non-relapse mortality (NRM), disease-free survival (DFS) and overall survival (OS) in these two cGVHD subtypes. Of 92 patients who developed cGVHD, 35 were classified as ocGVHD. The 1-year cumulative incidence, organ involvement, and global severity of classic and ocGVHD were similar between ABA2 patients receiving CNI/MTX+placebo and CNI/MTX+abatacept; thus, cohorts were combined for ocGVHD evaluation. This analysis identified ocGVHD as having significantly higher severity at presentation and at maximum global severity compared to classic cGVHD. OS and DFS were significantly lower for ocGVHD versus classic cGVHD. OcGVHD is associated with increased cGVHD severity scores, and is associated with decreased OS and DFS compared to classic cGVHD, underscoring the high risks with this cGVHD subtype.

BACKGROUND: MEDI7247 is a first-in-class antibody-drug conjugate (ADC) consisting of an anti-sodium-dependent alanine-serine-cysteine transporter 2 antibody-conjugated to a pyrrolobenzodiazepine dimer. OBJECTIVE: This first-in-human phase 1 trial evaluated MEDI7247 in patients with hematological malignancies. PATIENTS AND METHODS: Adults with acute myeloid leukemia (AML), multiple myeloma (MM), or diffuse large B-cell lymphoma (DLBCL) relapsed or refractory (R/R) to standard therapies, or for whom no standard therapy exists, were eligible. Primary endpoints were safety and determination of the maximum tolerated dose (MTD). Secondary endpoints included assessments of antitumor activity, pharmacokinetics (PK), and immunogenicity. RESULTS: As of 26 March 2020, 67 patients were treated (AML: n = 27; MM: n = 18; DLBCL: n = 22). The most common MEDI7247-related adverse events (AEs) were thrombocytopenia (41.8%), neutropenia (35.8%), and anemia (28.4%). The most common treatment-related grade 3/4 AEs were thrombocytopenia (38.8%), neutropenia (34.3%), and anemia (22.4%). Anticancer activity (number of responders/total patients evaluated) was observed in 11/67 (16.4%) patients. No correlation was observed between ASCT2 expression and clinical response. Between-patient variability of systemic exposure of MEDI7247 ADC and total antibody were high (AUCinf geometric CV%: 62.3-134.2, and 74.8-126.1, respectively). SG3199 (PBD dimer) plasma concentrations were below the limit of quantification for all patients after Study Day 8. Anti-drug antibody (ADA) prevalence was 7.7%, ADA incidence was 1.9%, and persistent-positive ADA was 5.8%. CONCLUSIONS: Thrombocytopenia and neutropenia limited repeat dosing. Although limited clinical activity was detected, the dose-escalation phase was stopped early without establishing an MTD. The study was registered with ClinicalTrials.gov (NCT03106428).

Imaging scaffolds composed of designed protein cages fused to designed ankyrin repeat proteins (DARPins) have enabled the structure determination of small proteins by cryogenic electron microscopy (cryo-EM). One particularly well characterized scaffold type is a symmetric tetrahedral assembly composed of 24 subunits, 12 A and 12 B, which has three cargo-binding DARPins positioned on each vertex. Here, the X-ray crystal structure of a representative tetrahedral scaffold in the apo state is reported at 3.8 Å resolution. The X-ray crystal structure complements recent cryo-EM findings on a closely related scaffold, while also suggesting potential utility for crystallographic investigations. As observed in this crystal structure, one of the three DARPins, which serve as modular adaptors for binding diverse `cargo proteins, present on each of the vertices is oriented towards a large solvent channel. The crystal lattice is unusually porous, suggesting that it may be possible to soak crystals of the scaffold with small (≤30 kDa) protein cargo ligands and subsequently determine cage-cargo structures via X-ray crystallography. The results suggest the possibility that cryo-EM scaffolds may be repurposed for structure determination by X-ray crystallography, thus extending the utility of electron-microscopy scaffold designs for alternative structural biology applications.

Earning industry certifications helps people prepare for jobs in a range of careers. Doing so in high school may help students prepare for college as well. Using administrative data on two cohorts of first-time 9th graders in Florida, we examined whether earning a certification was associated with postsecondary enrollment and degree attainment and whether the timing of the certification influenced that relationship. Earning a certification in high school prepared students for success in both 2-year and 4-year colleges. However, the patterns of certifications and college enrollment and degree attainment differed based on when students earned the certification. For early earners the certification was more closely associated with enrollment and attainment at 4-year colleges; for later earners, the certification was closely associated with enrollment and attainment in 2-year colleges.