Organisational learning through a charitable trust-initiated project focusing on end-of-life care.

PURPOSE: We identify lessons from a project sponsored by a large charitable trust, which sought to build capability for end-of-life (EOL) care in Hong Kong through interdisciplinary and multi-agency collaboration. DESIGN/METHODOLOGY/APPROACH: An in-depth case study drawing on 21 in-depth interviews with diverse stakeholders was conducted. Lyman et al.'s (2018) model of organisational learning (OL) in healthcare settings was applied to analyse the relative emphasis on particular contextual factors and mechanisms, and to identify outcomes perceived to have been achieved. FINDINGS: Infrastructure such as materials for assessment and education received the most emphasis among the contextual factors and deliberate learning such as training sessions received the greatest attention among the mechanisms. While perceptions indicated that desired outcomes were being achieved in terms of social impact, there were relatively few mentions of "soft" factors such as enhanced motivation, leadership or OL skills among staff. ORIGINALITY/VALUE: This study extends the literature on how to create valuable social impact through OL. While prior studies have examined social impact in terms of solutions for social and environmental problems, ours is one of the few that examines how improvements are made to organisations' capability to deliver such impacts in the context of healthcare.

Emerging Adults Mirror Infants' Emotions and Yawns.

Infants' nonverbal expressions-a broad smile or a sharp cry-are powerful at eliciting reactions. Although parents' reactions to their own infants' expressions are relatively well understood, here we studied whether adults more generally exhibit behavioral and physiological reactions to unfamiliar infants producing various expressions. We recruited U.S. emerging adults (N = 84) prior to parenthood, 18-25 years old, 68% women, ethnically (20% Hispanic/Latino) and racially (7% Asian, 13% Black, 1% Middle Eastern, 70% White, 8% multiracial) diverse. They observed four 80-s audio-video clips of unfamiliar 2- to 6-month-olds crying, smiling, yawning, and sitting calmly (emotionally neutral control). Each compilation video depicted 9 different infants (36 clips total). We found adults mirrored behaviorally and physiologically: more positive facial expressions to infants smiling, and more negative facial expressions and pupil dilation-indicating increases in arousal-to infants crying. Adults also yawned more and had more pupil dilation when observing infants yawning. Together, these findings suggest that even nonparent emerging adults are highly sensitive to unfamiliar infants' expressions, which they naturally "catch" (i.e., behaviorally and physiologically mirror), even without instructions. Such sensitivity may have-over the course of humans' evolutionary history-been selected for, to facilitate adults' processing of preverbal infants' expressions to meet their needs.

Gender and Geographical Representation on Editorial Board Members of Medical Informatics Journals.

Previous work has suggested that gender and geographical distribution (affiliation) of Editors-in-Chief (EiC) and Editorial Board (EB) members are inequitable in representation of scientific communities, and could benefit from increasing diversity of representation. Specifically, previous studies suggest that male and ethnically white (or non-minoritized groups) are overrepresented. Such differences in representation may potentially influence the scientific and scholarly record. This paper aims to build on pre-existing literature by examining the diversity of representation among EiCs and EB members in the top (Q1) journals in the "Medicine-Health Informatics" category (ranked by SCImago Journal and Country Rank, or SJR) in terms of gender as assessed by genderize.io) and geographical distribution of affiliations. Preliminary findings are consistent with those of previous work on the topic: only 25% (8/32) of the EiCs in the selected journals are female, while females only represent 32.7% (426/1303) of the EB members across journals. Furthermore, the US is highly represented in EBs, with more than half of the members, i.e., 52.2% (698/1337), being US-affiliated. Present results suggest the need for an intentional approach to diversifying representation on editorial boards of medical informatics journals. Such intention can be seen as part of a call to action from important stakeholders, including medical informatics leaders and programs, journal management and publishers, and the medical informatics and scientific community more generally.

A familial, telomere-to-telomere reference for human de novo mutation and recombination from a four-generation pedigree.

Using five complementary short- and long-read sequencing technologies, we phased and assembled >95% of each diploid human genome in a four-generation, 28-member family (CEPH 1463) allowing us to systematically assess de novo mutations (DNMs) and recombination. From this family, we estimate an average of 192 DNMs per generation, including 75.5 de novo single-nucleotide variants (SNVs), 7.4 non-tandem repeat indels, 79.6 de novo indels or structural variants (SVs) originating from tandem repeats, 7.7 centromeric de novo SVs and SNVs, and 12.4 de novo Y chromosome events per generation. STRs and VNTRs are the most mutable with 32 loci exhibiting recurrent mutation through the generations. We accurately assemble 288 centromeres and six Y chromosomes across the generations, documenting de novo SVs, and demonstrate that the DNM rate varies by an order of magnitude depending on repeat content, length, and sequence identity. We show a strong paternal bias (75-81%) for all forms of germline DNM, yet we estimate that 17% of de novo SNVs are postzygotic in origin with no paternal bias. We place all this variation in the context of a high-resolution recombination map (~3.5 kbp breakpoint resolution). We observe a strong maternal recombination bias (1.36 maternal:paternal ratio) with a consistent reduction in the number of crossovers with increasing paternal (r=0.85) and maternal (r=0.65) age. However, we observe no correlation between meiotic crossover locations and de novo SVs, arguing against non-allelic homologous recombination as a predominant mechanism. The use of multiple orthogonal technologies, near-telomere-to-telomere phased genome assemblies, and a multi-generation family to assess transmission has created the most comprehensive, publicly available "truth set" of all classes of genomic variants. The resource can be used to test and benchmark new algorithms and technologies to understand the most fundamental processes underlying human genetic variation.

Corrigendum to: COVID-19 Vaccine Hesitancy: Umbrella Review of Systematic Reviews and Meta-Analysis.

[This corrects the article DOI: 10.2196/54769.].

Recommendations to promote fairness and inclusion in biomedical AI research and clinical use.

OBJECTIVE: Understanding and quantifying biases when designing and implementing actionable approaches to increase fairness and inclusion is critical for artificial intelligence (AI) in biomedical applications. METHODS: In this Special Communication, we discuss how bias is introduced at different stages of the development and use of AI applications in biomedical sciences and health care. We describe various AI applications and their implications for fairness and inclusion in sections on 1) Bias in Data Source Landscapes, 2) Algorithmic Fairness, 3) Uncertainty in AI Predictions, 4) Explainable AI for Fairness and Equity, and 5) Sociological/Ethnographic Issues in Data and Results Representation. RESULTS: We provide recommendations to address biases when developing and using AI in clinical applications. CONCLUSION: These recommendations can be applied to informatics research and practice to foster more equitable and inclusive health care systems and research discoveries.

Infants' salivary oxytocin and positive affective reactions to people.

Oxytocin is a neuropeptide positively associated with prosociality in adults. Here, we studied whether infants' salivary oxytocin can be reliably measured, is developmentally stable, and is linked to social behavior. We longitudinally collected saliva from 62 U.S. infants (44 % female, 56 % Hispanic/Latino, 24 % Black, 18 % non-Hispanic White, 11 % multiracial) at 4, 8, and 14 months of age and offline-video-coded the valence of their facial affect in response to a video of a smiling woman. We also captured infants' affective reactions in terms of excitement/joyfulness during a live, structured interaction with a singing woman in the Early Social Communication Scales at 14 months. We detected stable individual differences in infants' oxytocin levels over time (over minutes and months) and in infants' positive affect over months and across contexts (video-based and in live interactions). We detected no statistically significant changes in oxytocin levels between 4 and 8 months but found an increase from 8 to 14 months. Infants with higher oxytocin levels showed more positive facial affect to a smiling person video at 4 months; however, this association disappeared at 8 months, and reversed at 14 months (i.e., higher oxytocin was associated with less positive facial affect). Infant salivary oxytocin may be a reliable physiological measure of individual differences related to socio-emotional development.

Newborn auditory brainstem response and sudden infant death syndrome.

Sudden infant death syndrome (SIDS)-the sudden and unexplained death of a seemingly healthy infant, <1 year old-may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep. While post-mortem studies suggest abnormalities in SIDS infants' brainstems, there are no studies of these infants' brainstem function before death. One way to assess the function of the brainstem is with auditory brainstem response (ABR), a routine hearing-screening method that noninvasively measures the brainstem's response to sound. We hypothesize that anomalies in newborns' ABR measures may predict SIDS. Indeed, previous studies identified abnormalities in ABR characteristics in small samples of near-miss SIDS infants hospitalized for infant apnea syndrome. However, there is a need to examine the ABRs of infants who died of SIDS. Therefore, in the current study, we propose integrating two secondary datasets to examine newborns' ABRs (N = 156,972), including those who later died of SIDS (n = ~42; .27 out of every 1000 infants), using existing archived records of neonatal ABR results from a sample of newborns born in Florida. We hypothesize that infants who die from SIDS are more likely than non-SIDS infants to have abnormal ABRs as newborns. Understanding the association between SIDS and ABR may facilitate more accurate identification of an infant's risk for SIDS at birth, enabling increased monitoring, which may facilitate interventions and improve survivorship.

Consolidated Reporting Guidelines for Prognostic and Diagnostic Machine Learning Models (CREMLS).

The number of papers presenting machine learning (ML) models that are being submitted to and published in the Journal of Medical Internet Research and other JMIR Publications journals has steadily increased. Editors and peer reviewers involved in the review process for such manuscripts often go through multiple review cycles to enhance the quality and completeness of reporting. The use of reporting guidelines or checklists can help ensure consistency in the quality of submitted (and published) scientific manuscripts and, for example, avoid instances of missing information. In this Editorial, the editors of JMIR Publications journals discuss the general JMIR Publications policy regarding authors' application of reporting guidelines and specifically focus on the reporting of ML studies in JMIR Publications journals, using the Consolidated Reporting of Machine Learning Studies (CREMLS) guidelines, with an example of how authors and other journals could use the CREMLS checklist to ensure transparency and rigor in reporting.

The impact of lowering the study design significance threshold to 0.005 on sample size in randomized cancer clinical trials.

The proposal of improving reproducibility by lowering the significance threshold to 0.005 has been discussed, but the impact on conducting clinical trials has yet to be examined from a study design perspective. The impact on sample size and study duration was investigated using design setups from 125 phase II studies published between 2015 and 2022. The impact was assessed using percent increase in sample size and additional years of accrual with the medians being 110.97% higher and 2.65 years longer respectively. The results indicated that this proposal causes additional financial burdens that reduce the efficiency of conducting clinical trials.

Infection detection in faces: Children's development of pathogen avoidance.

This study examined the development of children's avoidance and recognition of sickness using face photos from people with natural, acute, contagious illness. In a U.S. sample of fifty-seven 4- to 5-year-olds (46% male, 70% White), fifty-two 8- to 9-year-olds (26% male, 62% White), and 51 adults (59% male, 61% White), children and adults avoided and recognized sick faces (ds ranged from 0.38 to 2.26). Both avoidance and recognition improved with age. Interestingly, 4- to 5-year-olds' avoidance of sick faces positively correlated with their recognition, suggesting stable individual differences in these emerging skills. Together, these findings are consistent with a hypothesized immature but functioning and flexible behavioral immune system emerging early in development. Characterizing children's sickness perception may help design interventions to improve health.

Trends and age, sex, and race disparities in time to second primary cancer from 1990 to 2019.

BACKGROUND: Despite the growth in primary cancer (PC) survivors, the trends and disparities in this population have yet to be comprehensively examined using competing risk analysis. The objective is to examine trends in time to second primary cancer (SPC) and to characterize age, sex, and racial disparities in time-to-SPC. METHODS: A retrospective analysis was conducted based on Surveillance, Epidemiology, and End Results (SEER). Two datasets for this study are (1) the discovery dataset with patients from SEER-8 (1990-2019) and (2) the validation dataset with patients from SEER-17 (2000-2019), excluding those in the discovery dataset. Patients were survivors of lung, colorectal, breast (female only), and prostate PCs. RESULTS: The 5-year SPC cumulative incidences of lung PC increased from 1990 to 2019, with the cumulative incidence ratio being 1.73 (95% confidence intervals [CI], 1.64-1.82; p < 0.001). Age disparities among all PCs remained from 2010 to 2019, and the adjusted HRs (aHRs) of all PCs were above 1.43 when those below 65 were compared with those 65 and above. Sex disparity exists among colorectal and lung PC survivors. Racial disparities existed among non-Hispanic (NH) Black breast PC survivors (aHR: 1.11; 95% CI: 1.07-1.17; p < 0.001). The types of SPC vary according to PC and sex. CONCLUSIONS: Over the past three decades, there has been a noticeably shortened time-to-SPC among lung PC survivors. This is likely attributed to the reduced number of lung cancer deaths due to advancements in effective treatments. However, disparities in age, sex, and race still exist, indicating that further effort is needed to close the gap.

The Influence of Memory on Visual Perception in Infants, Children, and Adults.

Perception is not an independent, in-the-moment event. Instead, perceiving involves integrating prior expectations with current observations. How does this ability develop from infancy through adulthood? We examined how prior visual experience shapes visual perception in infants, children, and adults. Using an identical task across age groups, we exposed participants to pairs of colorful stimuli and implicitly measured their ability to discriminate relative saturation levels. Results showed that adult participants were biased by previously experienced exemplars, and exhibited weakened in-the-moment discrimination between different levels of saturation. In contrast, infants and children showed less influence of memory in their perception, and they actually outperformed adults in discriminating between current levels of saturation. Our findings suggest that as humans develop, their perception relies more on prior experience and less on current observation.

Assessing surrogacy using restricted mean survival time ratio for overall survival in liver cancer: a narrative review.

BACKGROUND AND OBJECTIVE: The application of immunotherapy in cancers, including liver cancer, has been increasing. However, non-proportional hazard (NPH) is often observed in cancer immunotherapy trials. In presence of violation of proportional hazard (PH) assumption, restricted mean survival time (RMST) ratio was proposed as an alternative to hazard ratio (HR) for evaluating the treatment effects of such trials. To shorten the total study duration, an intermediate endpoint with shorter follow-up such as progression-free survival (PFS) is used as the primary endpoint. Our aim is to evaluate the applicability of RMST ratio in addition to the HR in assessing the level of PFS serving as a surrogacy of overall survival (OS). METHODS: Phase II or phase III hepatocellular carcinoma (HCC) immunotherapy studies that were published between January 2013 and August 2022 were identified via the search in PubMed. Weighted least-square regression (WLSR) was applied to analyze the trial level data with the sample size of study being set as the weight. The evaluation was conducted twice with RMST ratio and HR being applied in respective evaluation to examine the level of PFS as a surrogacy for OS. KEY CONTENT AND FINDINGS: Based on the results of eight included trials, the R-square values of WLSR with either HR or RMST ratio being applied were 0.31 and 0.16 separately, indicating a moderate and low correlation between PFS and OS respectively. CONCLUSIONS: In this study, our results demonstrated the potential of RMST ratio in addition to HR for evaluating the level of surrogacy in immunotherapy trials. Furthermore, including more large scale and homogeneous studies into the research may help better understand the level of surrogacy in liver cancer.

Best Practices for Using AI Tools as an Author, Peer Reviewer, or Editor.

The ethics of generative artificial intelligence (AI) use in scientific manuscript content creation has become a serious matter of concern in the scientific publishing community. Generative AI has computationally become capable of elaborating research questions; refining programming code; generating text in scientific language; and generating images, graphics, or figures. However, this technology should be used with caution. In this editorial, we outline the current state of editorial policies on generative AI or chatbot use in authorship, peer review, and editorial processing of scientific and scholarly manuscripts. Additionally, we provide JMIR Publications' editorial policies on these issues. We further detail JMIR Publications' approach to the applications of AI in the editorial process for manuscripts in review in a JMIR Publications journal.

Can AI Mitigate Bias in Writing Letters of Recommendation?

Letters of recommendation play a significant role in higher education and career progression, particularly for women and underrepresented groups in medicine and science. Already, there is evidence to suggest that written letters of recommendation contain language that expresses implicit biases, or unconscious biases, and that these biases occur for all recommenders regardless of the recommender's sex. Given that all individuals have implicit biases that may influence language use, there may be opportunities to apply contemporary technologies, such as large language models or other forms of generative artificial intelligence (AI), to augment and potentially reduce implicit biases in the written language of letters of recommendation. In this editorial, we provide a brief overview of existing literature on the manifestations of implicit bias in letters of recommendation, with a focus on academia and medical education. We then highlight potential opportunities and drawbacks of applying this emerging technology in augmenting the focused, professional task of writing letters of recommendation. We also offer best practices for integrating their use into the routine writing of letters of recommendation and conclude with our outlook for the future of generative AI applications in supporting this task.

Refining the genomic determinants underlying escape from X-chromosome inactivation.

X-chromosome inactivation (XCI) epigenetically silences one X chromosome in every cell in female mammals. Although the majority of X-linked genes are silenced, in humans 20% or more are able to escape inactivation and continue to be expressed. Such escape genes are important contributors to sex differences in gene expression, and may impact the phenotypes of X aneuploidies; yet the mechanisms regulating escape from XCI are not understood. We have performed an enrichment analysis of transcription factor binding on the X chromosome, providing new evidence for enriched factors at the transcription start sites of escape genes. The top escape-enriched transcription factors were detected at the RPS4X promoter, a well-described human escape gene previously demonstrated to escape from XCI in a transgenic mouse model. Using a cell line model system that allows for targeted integration and inactivation of transgenes on the mouse X chromosome, we further assessed combinations of RPS4X promoter and genic elements for their ability to drive escape from XCI. We identified a small transgenic construct of only 6 kb capable of robust escape from XCI, establishing that gene-proximal elements are sufficient to permit escape, and highlighting the additive effect of multiple elements that work together in a context-specific fashion.

Social motivation predicts gaze following between 6 and 14 months.

Infants vary in their ability to follow others' gazes, but it is unclear how these individual differences emerge. We tested whether social motivation levels in early infancy predict later gaze following skills. We longitudinally tracked infants' (N = 82) gazes and pupil dilation while they observed videos of a woman looking into the camera simulating eye contact (i.e., mutual gaze) and then gazing toward one of two objects, at 2, 4, 6, 8, and 14 months of age. To improve measurement validity, we used confirmatory factor analysis to combine multiple observed measures to index the underlying constructs of social motivation and gaze following. Infants' social motivation-indexed by their speed of social orienting, duration of mutual gaze, and degree of pupil dilation during mutual gaze-was developmentally stable and positively predicted the development of gaze following-indexed by their proportion of time looking to the target object, first object look difference scores, and first face-to-object saccade difference scores-from 6 to 14 months of age. These findings suggest that infants' social motivation likely plays a role in the development of gaze following and highlight the use of a multi-measure approach to improve measurement sensitivity and validity in infancy research.

Behavioral and physiological sensitivity to natural sick faces.

The capacity to rapidly detect and avoid sick people may be adaptive. Given that faces are reliably available, as well as rapidly detected and processed, they may provide health information that influences social interaction. Prior studies used faces that were manipulated to appear sick (e.g., editing photos, inducing inflammatory response); however, responses to naturally sick faces remain largely unexplored. We tested whether adults detected subtle cues of genuine, acute, potentially contagious illness in face photos compared to the same individuals when healthy. We tracked illness symptoms and severity with the Sickness Questionnaire and Common Cold Questionnaire. We also checked that sick and healthy photos were matched on low-level features. We found that participants (N = 109) rated sick faces, compared to healthy faces, as sicker, more dangerous, and eliciting more unpleasant feelings. Participants (N = 90) rated sick faces as more likely to be avoided, more tired, and more negative in expression than healthy faces. In a passive-viewing eye-tracking task, participants (N = 50) looked longer at healthy than sick faces, especially the eye region, suggesting people may be more drawn to healthy conspecifics. When making approach-avoidance decisions, participants (N = 112) had greater pupil dilation to sick than healthy faces, and more pupil dilation was associated with greater avoidance, suggesting elevated arousal to threat. Across all experiments, participants' behaviors correlated with the degree of sickness, as reported by the face donors, suggesting a nuanced, fine-tuned sensitivity. Together, these findings suggest that humans may detect subtle threats of contagion from sick faces, which may facilitate illness avoidance. By better understanding how humans naturally avoid illness in conspecifics, we may identify what information is used and ultimately improve public health.