Puppy whines mediate maternal behavior in domestic dogs.

In mammals, offspring vocalizations typically encode information about identity and body condition, allowing parents to limit alloparenting and adjust care. But how do these vocalizations mediate parental behavior in species faced with the problem of rearing not one, but multiple offspring, such as domestic dogs? Comprehensive acoustic analyses of 4,400 whines recorded from 220 Beagle puppies in 40 litters revealed litter and individual (within litter) differences in call acoustic structure. By then playing resynthesized whines to mothers, we showed that they provided more care to their litters, and were more likely to carry the emitting loudspeaker to the nest, in response to whine variants derived from their own puppies than from strangers. Importantly, care provisioning was attenuated by experimentally moving the fundamental frequency (fo, perceived as pitch) of their own puppies' whines outside their litter-specific range. Within most litters, we found a negative relationship between puppies' whine fo and body weight. Consistent with this, playbacks showed that maternal care was stronger in response to high-pitched whine variants simulating relatively small offspring within their own litter's range compared to lower-pitched variants simulating larger offspring. We thus show that maternal care in a litter-rearing species relies on a dual assessment of offspring identity and condition, largely based on level-specific inter- and intra-litter variation in offspring call fo. This dual encoding system highlights how, even in a long-domesticated species, vocalizations reflect selective pressures to meet species-specific needs. Comparative work should now investigate whether similar communication systems have convergently evolved in other litter-rearing species.

Assessing Spontaneous Categorical Processing of Visual Shapes via Frequency-Tagging EEG.

Categorization is an essential cognitive and perceptual process, which happens spontaneously. However, earlier research often neglected the spontaneous nature of this process by mainly adopting explicit tasks in behavioral or neuroimaging paradigms. Here, we use frequency-tagging (FT) during electroencephalography (EEG) in 22 healthy human participants (both male and female) as a direct approach to pinpoint spontaneous visual categorical processing. Starting from schematic natural visual stimuli, we created morph sequences comprising 11 equal steps. Mirroring a behavioral categorical perception discrimination paradigm, we administered a FT-EEG oddball paradigm, assessing neural sensitivity for equally sized differences within and between stimulus categories. Likewise, mirroring a behavioral category classification paradigm, we administered a sweep FT-EEG oddball paradigm, sweeping from one end of the morph sequence to the other, thereby allowing us to objectively pinpoint the neural category boundary. We found that FT-EEG can implicitly measure categorical processing and discrimination. More specifically, we could derive an objective neural index of the required level to differentiate between the two categories, and this neural index showed the typical marker of categorical perception (i.e., stronger discrimination across as compared with within categories). The neural findings of the implicit paradigms were also validated using an explicit behavioral task. These results provide evidence that FT-EEG can be used as an objective tool to measure discrimination and categorization and that the human brain inherently and spontaneously (without any conscious or decisional processes) uses higher-level meaningful categorization information to interpret ambiguous (morph) shapes.

Structures of LIG1 provide a mechanistic basis for understanding a lack of sugar discrimination against a ribonucleotide at the 3'-end of nick DNA.

Human DNA ligase 1 (LIG1) is the main replicative ligase that seals Okazaki fragments during nuclear replication and finalizes DNA repair pathways by joining DNA ends of the broken strand breaks in the three steps of the ligation reaction. LIG1 can tolerate the RNA strand upstream of the nick, yet an atomic insight into the sugar discrimination mechanism by LIG1 against a ribonucleotide at the 3'-terminus of nick DNA is unknown. Here, we determined X-ray structures of LIG1/3'-RNA-DNA hybrids and captured the ligase during pre- and post-step 3 the ligation reaction. Furthermore, the overlays of 3'-rA:T and 3'-rG:C step 3 structures with step 2 structures of canonical 3'-dA:T and 3'-dG:C uncover a network of LIG1/DNA interactions through Asp570 and Arg871 side chains with 2'-OH of the ribose at nick showing a final phosphodiester bond formation and the other ligase active site residues surrounding the AMP site. Finally, we demonstrated that LIG1 can ligate the nick DNA substrates with pre-inserted 3'-ribonucleotides as efficiently as Watson-Crick base-paired ends in vitro. Together, our findings uncover a novel atomic insight into a lack of sugar discrimination by LIG1 and the impact of improper sugar on the nick sealing of ribonucleotides at the last step of DNA replication and repair.

Distinct neural markers of evidence accumulation index metacognitive processing before and after simple visual decisions.

Perceptual decision-making is affected by uncertainty arising from the reliability of incoming sensory evidence (perceptual uncertainty) and the categorization of that evidence relative to a choice boundary (categorical uncertainty). Here, we investigated how these factors impact the temporal dynamics of evidence processing during decision-making and subsequent metacognitive judgments. Participants performed a motion discrimination task while electroencephalography was recorded. We manipulated perceptual uncertainty by varying motion coherence, and categorical uncertainty by varying the angular offset of motion signals relative to a criterion. After each trial, participants rated their desire to change their mind. High uncertainty impaired perceptual and metacognitive judgments and reduced the amplitude of the centro-parietal positivity, a neural marker of evidence accumulation. Coherence and offset affected the centro-parietal positivity at different time points, suggesting that perceptual and categorical uncertainty affect decision-making in sequential stages. Moreover, the centro-parietal positivity predicted participants' metacognitive judgments: larger predecisional centro-parietal positivity amplitude was associated with less desire to change one's mind, whereas larger postdecisional centro-parietal positivity amplitude was associated with greater desire to change one's mind, but only following errors. These findings reveal a dissociation between predecisional and postdecisional evidence processing, suggesting that the CPP tracks potentially distinct cognitive processes before and after a decision.

Toe stimulation improves tactile perception of the genitals.

The human body is represented in a topographic pattern in the primary somatosensory cortex (S1), and genital representation is displaced below the toe representation. However, the relationship between the representation of the genitals and toe in S1 remains unclear. In this study, tactile stimulation was applied to the big toe in healthy subjects to observe changes in tactile acuity in the unstimulated genital area, abdomen, and metacarpal dorsal. Then tactile stimulation was applied to the right abdomen and metacarpal dorsal to observe changes in tactile acuity in bilateral genitals. The results revealed that tactile stimulation of the big toe led to a reduction in the 2-point discrimination threshold (2PDT) not only in the stimulated big toe but also in the bilateral unstimulated genitals, whereas the bilateral abdomen and metacarpal dorsal threshold remained unchanged. On the other hand, tactile stimulation of the abdomen and metacarpal dorsal did not elicit 2-point discrimination threshold changes in the bilateral genitals. Cortical and subcortical mechanisms have been proposed to account for the findings. One explanation involves the intracortical interaction between 2 adjacent representations. Another possible explanation is that the information content of a specific body part is broadly distributed across the S1. Moreover, exploring the links between human behaviors and changes in the cerebral cortex is of significant importance.

A radiomics-based brain network in T1 images: construction, attributes, and applications.

T1 image is a widely collected imaging sequence in various neuroimaging datasets, but it is rarely used to construct an individual-level brain network. In this study, a novel individualized radiomics-based structural similarity network was proposed from T1 images. In detail, it used voxel-based morphometry to obtain the preprocessed gray matter images, and radiomic features were then extracted on each region of interest in Brainnetome atlas, and an individualized radiomics-based structural similarity network was finally built using the correlational values of radiomic features between any pair of regions of interest. After that, the network characteristics of individualized radiomics-based structural similarity network were assessed, including graph theory attributes, test-retest reliability, and individual identification ability (fingerprinting). At last, two representative applications for individualized radiomics-based structural similarity network, namely mild cognitive impairment subtype discrimination and fluid intelligence prediction, were exemplified and compared with some other networks on large open-source datasets. The results revealed that the individualized radiomics-based structural similarity network displays remarkable network characteristics and exhibits advantageous performances in mild cognitive impairment subtype discrimination and fluid intelligence prediction. In summary, the individualized radiomics-based structural similarity network provides a distinctive, reliable, and informative individualized structural brain network, which can be combined with other networks such as resting-state functional connectivity for various phenotypic and clinical applications.

Dynamically Reconfigurable on-Chip Polarimeters Based on Nanoantenna Enabled Polarization Dependent Optoelectronic Computing.

On-chip polarization detectors have attracted extensive research interest due to their filterless and ultracompact architecture. However, their polarization-dependent photoresponses cannot be dynamically adjusted, hindering the development toward intelligence. Here, we propose dynamically reconfigurable polarimetry based on in-sensor differentiation of two self-powered photoresponses with orthogonal polarization dependences and tunable responsivities. Such a device can be electrostatically configured in an ultrahigh polarization extinction ratio (PER) mode, where the PER tends to infinity, a Stokes parameter direct sensing mode, where the photoresponse is proportional to S1 or S2 with high accuracy (RMSES1 = 1.5%, RMSES2 = 2.0%), or a background suppressing mode, where the target-background polarization contrast is singularly enhanced. Moreover, the device achieves a polarization angle sensitivity of 0.51 mA·W-1·degree-1 and a specific polarization angle detectivity of 2.8 × 105 cm·Hz1/2·W·degree-1. This scheme is demonstrated throughout the near-to-long-wavelength infrared range, and it will bring a leap for next-generation on-chip polarimeters.

Neocortical cholinergic pathology after neonatal brain injury is increased by Alzheimer's disease-related genes in mice.

Hypoxic-ischemic encephalopathy (HIE) in neonates causes mortality and neurologic morbidity, including poor cognition with a complex neuropathology. Injury to the cholinergic basal forebrain and its rich innervation of cerebral cortex may also drive cognitive pathology. It is uncertain whether genes associated with adult cognition-related neurodegeneration worsen outcomes after neonatal HIE. We hypothesized that neocortical damage caused by neonatal HI in mice is ushered by persistent cholinergic innervation and interneuron (IN) pathology that correlates with cognitive outcome and is exacerbated by genes linked to Alzheimer's disease. We subjected non-transgenic (nTg) C57Bl6 mice and mice transgenically (Tg) expressing human mutant amyloid precursor protein (APP-Swedish variant) and mutant presenilin (PS1-ΔE9) to the Rice-Vannucci HI model on postnatal day 10 (P10). nTg and Tg mice with sham procedure were controls. Visual discrimination (VD) was tested for cognition. Cortical and hippocampal cholinergic axonal and IN pathology and Aß plaques, identified by immunohistochemistry for choline acetyltransferase (ChAT) and 6E10 antibody respectively, were counted at P210. Simple ChAT+ axonal swellings were present in all sham and HI groups; Tg mice had more than their nTg counterparts, but HI did not affect the number of axonal swellings in APP/PS1 Tg mice. In contrast, complex ChAT+ neuritic clusters (NC) occurred only in Tg mice; HI increased that burden. The abundance of ChAT+ clusters in specific regions correlated with decreased VD. The frequency of attritional ChAT+ INs in the entorhinal cortex (EC) was increased in Tg shams relative to their nTg counterparts, but HI obviated this difference. Cholinergic IN pathology in EC correlated with NC number. The Aß deposition in APP/PS1 Tg mice was not exacerbated by HI, nor did it correlate with other metrics. Adult APP/PS1 Tg mice have significant cortical cholinergic axon and EC ChAT+ IN pathologies; some pathology was exacerbated by neonatal HI and correlated with VD. Mechanisms of neonatal HI induced cognitive deficits and cortical neuropathology may be modulated by genetic risk, perhaps accounting for some of the variability in outcomes.

Impaired perceptual discrimination of complex objects in older adults at risk for dementia.

Tau pathology accumulates in the perirhinal cortex (PRC) of the medial temporal lobe (MTL) during the earliest stages of the Alzheimer's disease (AD), appearing decades before clinical diagnosis. Here, we leveraged perceptual discrimination tasks that target PRC function to detect subtle cognitive impairment even in nominally healthy older adults. Older adults who did not have a clinical diagnosis or subjective memory complaints were categorized into "at-risk" (score <26; n = 15) and "healthy" (score ≥26; n = 23) groups based on their performance on the Montreal Cognitive Assessment. The task included two conditions known to recruit the PRC: faces and complex objects (greebles). A scene condition, known to recruit the hippocampus, and a size control condition that does not rely on the MTL were also included. Individuals in the at-risk group were less accurate than those in the healthy group for discriminating greebles. Performance on either the face or size control condition did not predict group status above and beyond that of the greeble condition. Visual discrimination tasks that are sensitive to PRC function may detect early cognitive decline associated with AD.

Systematic Review of Scales for Measuring Infectious Disease-Related Stigma.

Infectious disease outbreaks are associated with substantial stigma, which can have negative effects on affected persons and communities and on outbreak control. Thus, measuring stigma in a standardized and validated manner early in an outbreak is critical to disease control. We reviewed existing scales used to assess stigma during outbreaks. Our findings show that many different scales have been developed, but few have been used more than once, have been adequately validated, or have been tested in different disease and geographic contexts. We found that scales were usually developed too slowly to be informative early during an outbreak and were published a median of 2 years after the first case of an outbreak. A rigorously developed, transferable stigma scale is needed to assess and direct responses to stigma during infectious disease outbreaks.

Isolation, discrimination, and feeling "constant Guilt": A mixed-methods analysis of female physicians' experience with fertility, family planning, and oncology careers.

INTRODUCTION: Family planning among female physicians is harmed by high risks of infertility, workload burden, poor family leave policies, and gender discrimination. Many women report feeling unsupported in the workplace, despite national policies to protect against unfair treatment. METHODS: This secondary analysis applied a modified version of the rigorous and accelerated data reduction technique to conduct a thematic analysis of comments to an open-ended prompt. Comments were coded by multiple trained researchers then grouped and merged into illustrative themes via qualitative techniques. RESULTS: Of 1004 responses to the quantitative survey, 162 physicians completed the open-ended prompt. Initial codes (n = 16) were combined into eight groups including, from which three overarching themes were identified. Institutional barriers were highlighted with comments discussing the increased need for parental leave, part-time options and the concern for academic or professional punishment for being pregnant and/or having children. Departmental barriers were explored with comments grouped around codes of discrimination/negative culture and challenges with breastfeeding/pumping and childcare. Personal barriers were discussed in themes highlighting the difficulties that female physicians faced around the timing of family planning, challenges with reproductive health and assistance, and alternative circumstances and/or decisions against family planning. CONCLUSION: Barriers to family planning in oncology exist across career domains from dysfunctional maternity leave to poor education on infertility risk. Solutions include improving institutional support, expanding parental leave, and general cultural change to improve awareness and promotion of family and career balance.

Learning to discriminate the eye-of-origin during continuous flash suppression.

Helmholtz asked whether one could discriminate which eye is the origin of one's perception merely based on the retinal signals. Studies to date showed that participants' ability to tell the eye-of-origin most likely depends on contextual cues. Nevertheless, it has been shown that exogenous attention can enhance performance for monocularly presented stimuli. We questioned whether adults can be trained to discriminate the eye-of-origin of their perceptions and if this ability depends on the strength of the monocular channels. We used attentional feed-forward training to improve the subject's eye-of-origin discrimination performance with voluntary attention. During training, participants received a binocular cue to inform them of the eye-of-origin of an upcoming target. Using continuous flash suppression, we also measured the signal strength of the monocular targets to see any possible modulations related to the cues. We collected confidence ratings from the participants about their eye-of-origin judgements to study in further detail whether metacognition has access to this information. Our results show that, even though voluntary attention did not alter the strength of the monocular channels, eye-of-origin discrimination performance improved following the training. A similar pattern was observed for confidence. The results from the feedforward attentional training and the increase in subjective confidence point towards a high-level decisional mechanism being responsible for the eye-of-origin judgements. We propose that this high-level process is informed by subtle sensory cues such as the differences in luminance or contrast in the two monocular channels.

Developing and validating clinical prediction models in hepatology - An overview for clinicians.

Prediction models are everywhere in clinical medicine. We use them to assign a diagnosis or a prognosis, and there have been continuous efforts to develop better prediction models. It is important to understand the fundamentals of prediction modelling, thus, we herein describe nine steps to develop and validate a clinical prediction model with the intention of implementing it in clinical practice: Determine if there is a need for a new prediction model; define the purpose and intended use of the model; assess the quality and quantity of the data you wish to develop the model on; develop the model using sound statistical methods; generate risk predictions on the probability scale (0-100%); evaluate the performance of the model in terms of discrimination, calibration, and clinical utility; validate the model using bootstrapping to correct for the apparent optimism in performance; validate the model on external datasets to assess the generalisability and transportability of the model; and finally publish the model so that it can be implemented or validated by others.

A New Theranostic Platform Against Gram-Positive Bacteria Based on Near-Infrared-Emissive Aggregation-Induced Emission Nanoparticles.

Infections induced by Gram-positive bacteria pose a great threat to public health. Antibiotic therapy, as the first chosen strategy against Gram-positive bacteria, is inevitably associated with antibiotic resistance selection. Novel therapeutic strategies for the discrimination and inactivation of Gram-positive bacteria are thus needed. Here, a specific type of aggregation-induced emission luminogen (AIEgen) with near-infrared fluorescence emission as a novel antibiotic-free therapeutic strategy against Gram-positive bacteria is proposed. With the combination of a positively charged group into a highly twisted architecture, self-assembled AIEgens (AIE nanoparticles (NPs)) at a relatively low concentration (5 µm) exhibited specific binding and photothermal effect against living Gram-positive bacteria both in vitro and in vivo. Moreover, toxicity assays demonstrated excellent biocompatibility of AIE NPs at this concentration. All these properties make the AIE NPs as a novel generation of theranostic platform for combating Gram-positive bacteria and highlight their promising potential for in vivo tracing of such bacteria.

Novel Benzofuran Derivatives Induce Monoamine Release and Substitute for the Discriminative Stimulus Effects of 3,4-Methylenedioxymethamphetamine.

3,4-Methylenedioxymethamphetamine (MDMA) has shown efficacy as a medication adjunct for treating post-traumatic stress disorder (PTSD). However, MDMA is also used in non-medical contexts that pose risk for cardiovascular and neurological complications. It is well established that MDMA exerts its effects by stimulating transporter-mediated release of the monoamines, 5­hydroxytryptamine (5-HT), norepinephrine, and dopamine. Current research efforts are aimed at developing MDMA-like monoamine releasers with better efficacy and safety profiles. To this end, we investigated neurochemical and behavioral effects of novel analogs of the designer drug, 5-(2-methylaminopropyl)benzofuran (5-MAPB). We used in vitro transporter assays in rat brain synaptosomes to examine transmitter uptake inhibition and releasing properties for enantiomers of 5-(2-methylaminobutyl)benzofuran (5-MABB) and 6-(2-methylaminobutyl)benzofuran (6-MABB) as compared to MDMA. We then tested these same compounds in male Sprague-Dawley rats trained to discriminate MDMA (1.5 mg/kg) from saline. In vitro results revealed that S isomers of 5- and 6-MABB are efficacious releasing agents at transporters for 5-HT (SERT), norepinephrine (NET), and dopamine (DAT). By contrast, R isomers are efficacious releasers at SERT, partial releasers at NET, but lack releasing activity at DAT. In vivo results showed that all compounds produce dose-dependent increases in MDMA-lever responding and full substitution at the highest dose tested. The diminished NET and DAT releasing activities for R isomers of 5- and 6-MABB are associated with reduced potency for inducing behavioral effects. Collectively, these findings indicate that the aminoalkyl benzofuran scaffold may be a viable template for developing compounds with MDMA-like properties. Significance Statement Despite the clinical utility of MDMA, the drug is associated with certain cardiovascular risks and metabolic side effects. Developing a therapeutic alternative with MDMA-like monoamine releasing activity is of interest. Our in vitro and in vivo findings indicate that the aminoalkyl benzofuran scaffold may be useful for developing compounds with MDMA-like properties.

Greater mesophyll conductance and leaf photosynthesis in the field through modified cell wall porosity and thickness via AtCGR3 expression in tobacco.

Mesophyll conductance (gm) describes the ease with which CO2 passes from the sub-stomatal cavities of the leaf to the primary carboxylase of photosynthesis, Rubisco. Increasing gm is suggested as a means to engineer increases in photosynthesis by increasing [CO2] at Rubisco, inhibiting oxygenation and accelerating carboxylation. Here, tobacco was transgenically up-regulated with Arabidopsis Cotton Golgi-related 3 (CGR3), a gene controlling methylesterification of pectin, as a strategy to increase CO2 diffusion across the cell wall and thereby increase gm. Across three independent events in tobacco strongly expressing AtCGR3, mesophyll cell wall thickness was decreased by 7%-13%, wall porosity increased by 75% and gm measured by carbon isotope discrimination increased by 28%. Importantly, field-grown plants showed an average 8% increase in leaf photosynthetic CO2 uptake. Up-regulating CGR3 provides a new strategy for increasing gm in dicotyledonous crops, leading to higher CO2 assimilation and a potential means to sustainable crop yield improvement.

'Humility, Concern, Respect': A Qualitative Study Exploring Parent Perspectives on a Pediatrician's Role in Addressing Racism.

OBJECTIVE: To explore racially minoritized families' perceptions on how, and if, physicians should address children's racial identity and concepts of racism within clinical settings. STUDY DESIGN: Parents of racially minoritized children, ages 5 through 18, were interviewed to explore experiences with racial identity formation, discrimination, and the extent to which they wanted pediatricians to address these topics. Children were included at the discretion of their parents. Interviews were transcribed, coded, and analyzed through a critical race theory lens based in constructivist grounded theory. RESULTS: Parents encouraged their children to embrace their racial identities but also wanted to shield them from negative experiences of racism to preserve identity safety. Parents felt pediatricians should address racial issues in a manner specific to their child's situation. Thoughtful inclusion of race-related questions, whether in discussion or on questionnaires, is essential to prevent tension in a therapeutic relationship. There was no consensus on the use of preclinical screening. Instead, families highlighted the importance of embracing humility, trust, and respect. CONCLUSIONS: Participant families have preferences for approaches to address the effects of racism on their children's health. Pediatricians should understand the importance of identity safety and approach their discussions with cultural humility, which includes self-reflection, empathy, active listening, and flexible negotiation. Above all, pediatricians need to create a safe environment for appropriate discussion of these issues.

Harnessing photosynthetic C18O16O discrimination dynamics under leaf water nonsteady state to estimate mesophyll conductance: a new, regression-based method.

Mesophyll conductance (gm) is a crucial plant trait that can significantly limit photosynthesis. Measurement of photosynthetic C18O16O discrimination (Δ18O) has proved to be the only viable means of resolving gm in both C3 and C4 plants. However, the currently available methods to exploit Δ18O for gm estimation are error prone due to their inadequacy in constraining the degree of oxygen isotope exchange (θ) during mesophyll CO2 hydration. Here, we capitalized on experimental manipulation of leaf water isotopic dynamics to establish a novel, nonsteady state, regression-based approach for simultaneous determination of gm and θ from online Δ18O measurements. We demonstrated the methodological and theoretical robustness of this new Δ18O-gm estimation approach and showed through measurements on several C3 and C4 species that this approach can serve as a benchmark method against which to identify previously-unrecognized biases of the existing Δ18O-gm methods. Our results highlight the unique value of this nonsteady state-based approach for contributing to ongoing efforts toward quantitative understanding of mesophyll conductance for crop yield improvement and carbon cycle modeling.

COVID-19 vaccine mistrust, health literacy, conspiracy theories, and racial discrimination among a representative ethnically diverse sample in Canada: The vulnerability of Arab, Asian, Black, and Indigenous peoples.

Despite increased risk of severe acute respiratory syndrome coronavirus 2 infections and higher rates of COVID-19-related complications, racialized and Indigenous communities in Canada have lower immunization uptake compared to White individuals. However, there is woeful lack of data on predictors of COVID-19 vaccine mistrust (VM) that accounts for diverse social and cultural contexts within specific racialized and Indigenous communities. Therefore, we sought to characterize COVID-19 VM among Arab, Asian, Black, and Indigenous communities in Canada. An online survey was administered to a nationally representative, ethnically diverse panel of participants in October 2023. Arabic, Asian, Indigenous, and Black respondents were enriched in the sampling panel. Data were collected on demographics, COVID-19 VM, experience of racial discrimination, health literacy, and conspiracy beliefs. We used descriptive and regression analyses to determine the extent and predictors of COVID-19 VM among racialized and Indigenous individuals. All racialized respondents had higher VM score compared to White participants. Among 4220 respondents, we observed highest VM among Black individuals (12.18; ±4.24), followed by Arabic (12.12; ±4.60), Indigenous (11.84; ±5.18), Asian (10.61; ±4.28), and White (9.58; ±5.00) participants. In the hierarchical linear regression analyses, Black participants, women, everyday racial discrimination, and major experience of discrimination were positively associated with COVID-19 VM. Effects of racial discrimination were mediated by addition of conspiracy beliefs to the model. Racialized and Indigenous communities experience varying levels of COVID-19 VM and carry specific predictors and mediators to development of VM. This underscores the intricate interaction between race, gender, discrimination, and VM that need to be considered in future vaccination campaigns.

COVID-19 vaccine uptake, conspiracy theories, and health literacy among Black individuals in Canada: Racial discrimination, confidence in health, and COVID-19 stress as mediators.

Factors influencing vaccine uptake in Black individuals remain insufficiently documented. Understanding the role of COVID-19 related stress, conspiracy theories, health literacy, racial discrimination experiences, and confidence in health authorities can inform programs to increase vaccination coverage. We sought to analyze these factors and vaccine uptake among Black individuals in Canada. A representative sample of 2002 Black individuals from Ontario, Quebec, Alberta, Nova Scotia, New Brunswick, British Columbia, and Manitoba, aged 14 years or older completed questionnaires assessing vaccine uptake, health literacy, conspiracy theories, racial discrimination experiences, COVID-19-related stress, and confidence in health authorities. Mediation analyses were conducted to assess (1) the effect of health literacy on COVID-19 vaccination uptake through confidence and need, COVID-19 related traumatic stress, and racial discrimination, and (2) the effect of conspiracy beliefs on COVID-19 vaccination uptake through the same factors. Overall, 69.57% (95% confidence interval, 67.55%-71.59%) of the participants were vaccinated and 83.48% of them received two or more doses. Those aged 55 years and older were less likely to be vaccinated, as well as those residing in British Columbia and Manitoba. Mediation models showed that the association between health literacy and COVID-19 vaccine uptake was mediated by confidence in health authorities (B = 0.02, p < 0.001), COVID-19-related stress (B = -0.02, p < 0.001), and racial discrimination (B = -0.01, p = 0.032), but both direct and total effects were nonsignificant. Lastly, conspiracy beliefs were found to have a partial mediation effect through the same mediators (B = 0.02, p < 0.001, B = -0.02, p < 0.001, B = -0.01, p = 0.011, respectively). These findings highlight the need for targeted interventions to address vaccine hesitancy and inform approaches to improve access to vaccinations among Black communities.