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.

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.

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.

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.

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.

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.

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.

New reporting items and recommendations for randomized trials impacted by COVID-19 and force majeure events: a targeted approach.

Background: Appropriate analyses and reporting are essential to the reproducibility and interpretation of clinical trials. However, the coronavirus disease 19 (COVID-19) pandemic and other force majeure events, like the war in Ukraine, have impacted the conduct of clinical trials. Methods: The number of clinical trials potentially impacted were estimated from clinicaltrials.gov. To identify reporting items considered vital for assessing the impact of COVID-19, we reviewed 35 randomized phase III trials from three top oncology journals published between July and December 2020. For validation, we reviewed 29 phase III trials published between January and December 2021. Results: Our results show that the number of clinical trials being potentially impacted in cancer, cardiovascular diseases, and diabetes is at least 1,484, 535, and 145, respectively. The magnitude of disruption is most significant in oncology trials. Based on the review of 35 trials, a modified checklist with ten new and four modified items covering pandemic's impact on trial conduct, protocol changes, delays, data capture, analysis and interpretation was developed to ensure comprehensive and transparent reporting. Our validation shows that six out of seven applicable reporting items were reported in less than 21% of the articles. Conclusions: Our recommendations were proposed to improve the reporting of randomized clinical trials impacted by COVID-19 and force majeure events that are broadly applicable to different areas of medical research.

A personal history of trauma and experience of secondary traumatic stress, vicarious trauma, and burnout in mental health workers: A systematic literature review.

OBJECTIVE: Secondary traumatic stress (STS), vicarious trauma (VT), and burnout (BO) are work-related outcomes commonly ascribed to mental health workers, given their exposure to clients' traumatic experiences. It is theorized that a worker's own history of trauma increases the occurrence of these outcomes, through retraumatization/activation of threat cues during client interactions and overinvolvement with a client's progress. Given the inconsistencies in the literature and the ubiquity of trauma among workers, a systematic review was conducted to examine the association of personal trauma and the 3 related, but separate, work outcomes. METHOD: A systematic search strategy was used across relevant research databases (Cochrane, JSTOR, PsycINFO, PubMed) for empirical studies conducted from 2000-2021. In accordance with PRISMA guidelines, a four-phase selection process was used, resulting in 39 studies identified meeting the inclusion criteria. RESULTS: A clear (positive) association between personal trauma history and STS and VT were identified, whereas mostly null findings were observed in regard to BO. The majority of studies were conducted in Western countries, adopted questionnaires as the primary means of data collection, and all but one were cross-sectional in design. CONCLUSION: In addition to a lack of diversity in study design, there were conceptual limitations to the research conducted (e.g., treating victims as a unitary group, neglecting the inclusion of mechanisms). To assist in moving the field forward, five research recommendations are outlined with the goal of creating greater clarity in the work-outcomes literature and increased nuance in how personal trauma is understood. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Infant temperamental fear, pupil dilation, and gaze aversion from smiling strangers.

In childhood, higher levels of temperamental fear-an early-emerging proclivity to distress in the face of novelty-are associated with lower social responsivity and greater social anxiety. While the early emergence of temperamental fear in infancy is poorly understood, it is theorized to be driven by individual differences in reactivity and self-regulation to novel stimuli. The current study used eye tracking to capture infants' (N = 124) reactions to a video of a smiling stranger-a common social encounter-including infant gaze aversions from the stranger's face (indexing arousal regulation) and pupil dilation (indexing physiological reactivity), longitudinally at 2, 4, 6, and 8 months of age. Multilevel mixed-effects models indicated that more fearful infants took more time to look away from a smiling stranger's face than less fearful infants, suggesting that high-fear infants may have slower arousal regulation. At 2 and 4 months, more fearful infants also exhibited greater and faster pupil dilation before gaze aversions, consistent with greater physiological reactivity. Together, these findings suggest that individual differences in infants' gaze aversions and pupil dilation can index the development of fearful temperament in early infancy, facilitating the identification of, and interventions for, risk factors to social disruptions.

A Socio-Ecological Approach to Addressing Digital Redlining in the United States: A Call to Action for Health Equity.

Physical distancing requirements due to the coronavirus (COVID-19) pandemic has increased the need for broadband internet access. The World Health Organization defines social determinants of health as non-medical factors that impact health outcomes by affecting the conditions in which people are born, grow, work, live, and age. By this definition broadband internet access is a social determinant of health. Digital redlining-the systematic process by which specific groups are deprived of equal access to digital tools such as the internet-creates inequities in access to educational and employment opportunities, as well as healthcare and health information. Although it is known that internet service providers systematically exclude low-income communities from broadband service, little has been done to stop this discriminatory practice. In this paper, we seek to amplify the call to action against the practice of digital redlining in the United States, describe how it contributes to health disparities broadly and within the context of the COVID-19 pandemic, and use a socio-ecological framework to propose short- and long-term actions to address this inequity.