People sometimes persistently pursue hard-to-get targets. Why people pursue such targets is unclear. Here, we hypothesized that choice perseverance, which is the tendency to repeat the same choice independent of the obtained outcomes, leads individuals to repeatedly choose a hard-to-get target, which consequently increases their preference for the target. To investigate this hypothesis, we conducted an online experiment involving an avatar choice task in which the participants repeatedly selected one avatar, and the selected avatar expressed their valence reactions through facial expressions and voice. We defined “hard-to-get” and “easy-to-get” avatars by manipulating the outcome probability such that the hard-to-get avatars rarely provided a positive reaction when selected, while the easy-to-get avatars frequently did. We found that some participants repeatedly selected hard-to-get avatars (Pursuit group). Based on a simulation, we found that higher choice perseverance accounted for the pursuit of hard-to-get avatars and that the Pursuit group had significantly higher choice perseverance than the No-pursuit group. Model fitting to the choice data also supported that choice perseverance can account for the pursuit of hard-to-get avatars in the Pursuit group. Moreover, we found that although baseline attractiveness was comparable among all avatars used in the choice task, the attractiveness of the hard-to-get avatars was significantly increased only in the Pursuit group. Taken together, we conclude that people with high choice perseverance pursue hard-to-get targets, rendering such targets more attractive. The tolerance for negative outcomes might be an important factor for succeeding in our lives but sometimes triggers problematic behavior, such as stalking. The present findings may contribute to understanding the psychological mechanisms of passion and perseverance for one’s long-term goals, which are more general than the romantic context imitated in avatar choice. People sometimes persistently pursue “hard-to-get” targets that do not easily provide the desired outcomes. For instance, scientists passionately pursue specific hypotheses that are difficult to prove for a long time e.g., . Even inReinforcement learning has been widely used in a variety of areas to account for choice behavior in organisms . From a per se increases the preference for a chosen target , we established hard-to-get and easy-to-get avatars. The participants rated the attractiveness of the avatars again after the choice task, allowing us to examine whether attractiveness was altered by the choice task. All participants pursued the easy-to-get avatar, which frequently responded positively, whereas some participants pursued the hard-to-get avatar, which rarely responded positively. The simulation supported the hypothesis that the pursuit of the hard-to-get avatar was caused by higher choice perseverance. Subsequently, this hypothesis was empirically confirmed by fitting models to the experimental data.via CrowdWorks.1 Due to the nature of our task, we only recruited participants who were at least 18 years old and were romantically interested in women. At the time this study was designed, there was no information regarding the effect size of the difference between participants who pursued and did not pursue the hard-to-get avatar. Therefore, the power analysis was conducted assuming that the difference between the two groups had a moderate effect size (0.25) (α = 0.05 and β = 0.80) revealed that a minimum sample size of 64 participants per group was necessary. In addition, considering the possibility that the proportion of participants who pursued the hard-to-get avatar was relatively small, we decided to recruit 150 participants. The study was approved by the ethical research committee at Nagoya University and was carried out in accordance with relevant guidelines and regulations (NUPSY-200306-K-01).One hundred fifty participants were recruited e (0.25) . The powInformed consent was obtained from all participants when they clicked “I Agree” after reading information regarding the aims and procedures of this study. After they completed the survey collecting basic demographic information, including gender and age, they downloaded the Inquisit player  and started a series of behavioral tasks (see the details below). To protect the participants’ privacy, all data were anonymized. If the participants completed the entire task and survey without interruption, we paid them 550 yen (approximately $5).To exclude the effect of inappropriate choice behavior, the following exclusion criteria were applied: (i) the participants did not respond within the time limit  in more than 30% of the total trials in the choice task, (ii) the participants’ choice reaction time was too short (less than 300 ms) in more than 30% of trials in the task, and (iii) the participants demonstrated a task-irrelevant choice pattern, such as alternating between left and right or always selecting only one side (even though each avatar randomly appeared on both sides). Only two participants were excluded from the subsequent analyses based on criterion (i). No participants met criterion (ii) or (iii). Thus, the data of 148 participants  were analyzed.2). First, the participants performed an avatar evaluation task in which they investigated the baseline attractiveness of 48 avatars. In this task  and had the potential to become more attractive , avatars rated 6 or 7 points were selected.•Step 2: If fewer than eight avatars were rated 6 or 7 points, among the avatars that rated less than 5 points, the avatar with the highest rating was selected.•Step 3: If the total number of selected avatars was still less than eight, among the avatars rated more than 8 points, the avatar with the lowest rating selected. If there was more than one avatar with the highest rating among the avatars rated less than 5 points in Step 2 or with the lowest rating among the avatars rated more than 8 points in Step 3, an avatar was randomly selected from the avatars that fit the criteria. Then, Steps 2 and 3 were repeated in sequence until eight avatars were selected.The participants again rated the attractiveness of the 48 avatars presented in the initial evaluation task after they completed the avatar choice task, allowing us to investigate whether the attractiveness of the avatars was altered after the choice task.hard” and “neutraleasy”) in the first trial, the reaction probability was set at 0.5/0.5. These probabilities were fixed across the task. The participants were not informed in advance of the response probability of each avatar. Therefore, the participants were required to learn the response probability of each avatar . The trials of both pairs were presented in a random order for each participant and session. That is, in each session, pairs A and B were presented in a mixed manner. In each trial , the parh avatar . The fulhard), the participants were divided into the following two groups: the Pursuit group (CPhard was more than 0.5) and the No-pursuit group (CPhard was less than 0.5). Since there was no previous evidence regarding the pursuit of hard-to-get targets, the criteria for grouping were based on the chance level . To confirm the difference in the CP of the hard-to-get and easy-to-get avatars between groups, two-way mixed-design analysis of variance (ANOVA) with group (Pursuit vs. No-pursuit) and avatar (hard-to-get vs. easy-to-get) was conducted.We calculated the choice probability (hereafter CP) of avatars presented in the avatar choice task by dividing the number of choices by the number of trials (40 per avatar). Based on the CP of the hard-to-get avatar  and avatar  was performed. Additionally, to investigate whether attractiveness changed after the avatar choice task, we calculated the difference in the avatars’ attractiveness before and after the participants completed the avatar choice task. Then, two-way mixed-design ANOVA with group (Pursuit vs. No-pursuit) and avatar  was performed. To examine whether the attractiveness of each avatar changed, the degree of change in attractiveness was compared with zero using one-sample t-tests. The issue of multiple comparisons for one-sample t-tests was corrected with Bonferroni’s method. Moreover, to examine whether the choice per se increased the attractiveness of the chosen avatar, a general linear model analysis was performed. In this model, the change in attractiveness was a dependent variable. The changes in the attractiveness of the avatars used in the choice task were pooled across all participants. The number of choices, the number of positive reactions, and an interaction were independent variables.To examine whether the baseline attractiveness differed among the avatars, including hard-to-get, easy-to-get, neutral3 Mendoza’s multisample sphericity test was used to check the validity of the sphericity assumption in all ANOVAs. To correct for violation of the sphericity assumption, Greenhouse–Geisser’s adjustment of the degrees of freedom was used in all ANOVAs when appropriate. Post hoc pairwise comparisons for significant effects were conducted based on Shaffer’s correction for multiple comparisons. The statistical threshold for significance was set at 0.05 for all behavioral analyses.All analyses were executed using R version 4.0.2 statistical software.To investigate whether asymmetric value updating or choice perseveration better explains the pursuit of hard-to-get targets, we fit (i) asymmetric and (ii) perseveration models to the choice data. In addition, we previously demonstrated that a hybrid model including both asymmetric value updating and choice perseverance allows us to separately evaluate the contribution of these two cognitive processes to actual choice behavior . Thus, wi = 1 or 2). The model assigns each option i an expected outcome Qi(t), where t is the index of the trial. The initial Q-values are set to zero . The model updates the Q-values depending on the outcome of the choice . The actual outcome at trial t is denoted by R(t). We typically consider a binary outcome case whereby we set R(t) = 1 if a positive reaction is given and R(t) = 0 if a negative reaction is given. Learning rate α determines how much the model updates the action value depending on the reward prediction error, δ(t). Here, we denote the option that is chosen at trial t by act(t) (= 1 or 2). Based on the set of Q-values, the model assigns the probability of choosing option 1 using the softmax function:Throughout this article, we usually consider cases with only two options  is better than the expected outcome Q(t)); the changes with α– are vice versa  is defined to introduce the effect of past choice into the CP. The initial values of Ci(t) are set to zero . Indicator function I(⋅) takes a value of 1 if the statement is true and 0 if the statement is false. Decay rate τ is a free parameter that determines the number of preceding choices in the choice history influencing the current choice. When the choice is binary, the probability of choosing option 1 is implemented by the following:Choice trace φ) is a parameter that controls the tendency to repeat previous choices or avoid previously chosen options. A high positive value of this parameter indicates that the agent frequently repeats the previous choice.where the weight of choice history . A previous study demonstrated that this hybrid model allows separate evaluation of asymmetric learning rates and choice perseverance .hard and CPeasy based on the simulated choice data. The task structure used in the simulation was identical to that in the online experiment.To investigate what computational process contributes to the pursuit of the hard-to-get avatar, we simulated agents’ choices with the hybrid model. In particular, we systematically varied the free parameters of the hybrid model and evaluated CPα+, α–), inverse temperature (β), decay rate (τ), and weight of choice history (φ). Because we were interested in the degree of asymmetric learning rates, the difference in learning rates (αbias = α+ – α–) was calculated as the learning rate bias. In case 1, to examine the parameters related to the impact of past outcomes, the learning rate bias  and inverse temperature  were varied, but the decay rate (τ = 0.5) and the weight of choice history (φ = 1) were fixed. In case 2, to examine the parameters related to the impact of past choice, the decay rate  and the weight of choice history  were varied, but the learning rate bias (αbias = 0) and inverse temperature (β = 2) were fixed. We hypothesized that the increased CPhard would be accounted for by the higher choice perseverance, which was represented as the greater weight of choice history. Thus, we further examined the interaction between the weight of choice history and parameters related to the impact of past outcomes on the CP. In case 3, the learning rate bias  and the weight of choice history  were varied, while the inverse temperature (β = 2) and the decay rate (τ = 0.5) were fixed. In case 4, the inverse temperature  and the weight of choice history  were varied, while the learning rate bias (αbias = 0) and the decay rate (τ = 0.5) was fixed. In the simulation, 100 virtual datasets were simulated for each parameter setting.The hybrid model had five parameters: learning rates for positive and negative reward prediction error  prior distribution. The inverse temperature was constrained to the range of β ≥ 0 with a gamma  distribution. In the perseverance model, the decay rate was constrained to the range of 0 ≤ τ ≤ 1 with a beta  distribution , and the choice trace weight was constrained to the range of −10 ≤ φ ≤ 10 with a norm  distribution.We fit the four models mentioned above  to the choice data derived from the avatar choice task. The standard RL model was also included as a benchmark for model fitting. Using the R function “solnp” in the Rsolnp package , we fit Post hoc pairwise comparisons were performed based on Shaffer’s correction for multiple comparisons. For the bias of learning rates, inverse temperature, decay rate, and weight of choice history, the group difference was evaluated using a two-sample t-test. All analyses were executed using R version 4.0.2 statistical software (see text footnote 3). The statistical threshold for significance was set at 0.05 for all comparisons of model fit and estimated model parameters.For the model comparisons, two-way mixed-design ANOVA with group (Pursuit and No-pursuit) and model  was conducted to compare the log marginal likelihoods. Additionally, we compared the estimated model parameters. For the learning rates  were analyzed in the following steps. First, by calculating the CP in the avatar choice task, we investigated whether some participants pursued the hard-to-get avatars. Second, based on the subjective ratings of the attractiveness of the avatars, we tested the hypothesis that the pursuit of a specific avatar consequently increased the attractiveness of the pursued avatar. Third, to determine which cognitive processes  accounted for the pursuit of the hard-to-get avatar, we simulated hypothetical choice rates by varying the parameters of the hybrid model including the two cognitive processes . Finallyhard) in the avatar choice task. For 68 of 148 participants, CPhard was greater than 0.5 . Thus, we divided the participants into two different groups based on CPhard. The participants with a CPhard value greater than 0.5 were assigned to the Pursuit group , while the participants with a CPhard value lower than 0.5 were assigned to the No-pursuit group . The CP exhibited significant group differences between the hard-to-get and easy-to-get avatars . CPhard in the Pursuit group was significantly higher than that in the No-pursuit group , confirming that the participants were grouped as intended. Meanwhile, CPeasy was comparable between groups . These results confirmed that the participants in the Pursuit group behaved differently only toward the hard-to-get avatar, whereas the participants in both groups repeatedly chose the easy-to-get avatar.To characterize the participants who pursued the hard-to-get avatar despite frequent negative reactions, we focused on the choice probability of the hard-to-get avatar  was not significantly different between groups . On the other hand, baseline attractiveness was significantly different among avatars . The avatars used in the choice task were rated as more attractive than the unused avatars . In addition, the avatars in pair B, including easy-to-get and neutraleasy avatars, had significantly higher attractiveness scores than the avatars in pair A, including hard-to-get and neutralhard avatars , with the exception of the comparison between hard-to-get and neutraleasy avatars . However, the paired avatars had comparable attractiveness in the two groups .If the baseline attractiveness of the initially chosen avatar was higher than that of the unchosen avatar, this difference in baseline attractiveness might have affected whether the participant pursued the hard-to-get avatar. However, our results indicated that the attractiveness of the avatars used in the choice task was not different between groups and that the paired avatars were rated at the same level of attractiveness in both groups. We compared the attractiveness rated before the choice task between avatars and groups. The baseline attractiveness for any type of avatar  = 14.61, p < 0.001, η2G = 0.058]. The attractiveness of the unused avatars was not changed after the choice task in either group . The change in the attractiveness of the easy-to-get and neutraleasy avatars did not differ between groups . In both groups, the easy-to-get avatar was rated as more attractive , while the neutraleasy avatar was rated as less attractive after the choice task . On the other hand, the attractiveness of the hard-to-get avatar increased in the Pursuit group , while it did not change in the No-pursuit group . In contrast, the attractiveness of the neutralhard avatar, which was paired with the hard-to-get avatar, decreased in the Pursuit group  but did not change in the No-pursuit group . These results indicated that both hard-to-get and easy-to-get avatars were more attractive after the choice task in the Pursuit group, while only easy-to-get avatars were more attractive in the No-pursuit group.We investigated how the attractiveness of the avatars changed through the choice task. The change in avatar attractiveness was calculated by subtracting the score before the choice task from the score after the choice task . The intβ = 0.28, p < 0.001, d = 0.021). The main effect of the number of positive reactions  and the interaction between the number of positive reactions and the number of choices were not significant . Thus, the changes in attractiveness depended on the choice per se rather than reactions in the choice task.The increased attractiveness of the hard-to-get and easy-to-get avatars in the Pursuit group raised the question of what events occurred in the choice task to increase the attractiveness of avatars. To answer this question, we conducted a general linear model analysis with the number of choices, the number of positive reactions, and an interaction with these numbers as independent variables and the changes in attractiveness as the dependent variable . The number of choices had a significant effect only on the change in attractiveness observed after the choice task (α+ and α–), inverse temperature (β), decay rate of choice history (τ), and choice trace weight (φ) . The degree of asymmetric value updating is denoted by the difference in the two learning rates . Thus, we simulated an agent’s choice behavior by manipulating these four parameters  under the same task structure as the online experiment .We found that some participants  pursued the hard-to-get avatar despite receiving very few positive reactions. This behavioral phenomenon raised the question of which cognitive process led these participants to pursue the hard-to-get avatar. To answer this question, we used several variants of reinforcement learning models to determine what accounted for this choice behavior. As mentioned in the Introduction, asymmetric value updating  and choiαbias and β were varied, while τ (= 0.5) and φ (= 1.0) were fixed. The asymmetric learning rates quadratically decreased CPhard (easy (αbias = 0.4) induced the smallest CPhard, while moderate negativity (αbias = −0.6) bias induced the largest CPeasy. The inverse temperature produced a linear decrease in CPhard and a linear increase in CPeasy. In any combination, CPhard was less than 0.5, indicating that these parameters did not account for the behavioral pattern observed in the Pursuit group (CPhard > 0.5).In case 1, d CPhard  but quadrd  and β (= 2.0) were fixed. For the hard-to-get avatar, CPhard values in the condition with a moderate decay rate (τ > 0.2) and higher perseverance factor (φ > 6.0) reached over 0.7 , we covaried either αbias (case 3) or β (case 4) with φ. In case 3, although CPhard was modulated by the asymmetric learning rates (αbias) in the condition with lower perseverance (φ < 6.0), the condition with higher perseverance (φ > 6.0) showed higher CPhard (easy (φ > 6.0), CPhard  = 52.39, p < 0.001, η2G = 0.011]. There were no significant differences among the models in the No-pursuit group , but there were differences in the Pursuit group . For the Pursuit group, there was no significant difference between the perseveration and hybrid models . However, the RL and asymmetric models, which did not include the choice history process, were much worse than the perseveration and hybrid models, which did include the choice history process .To further investigate the mechanisms driving the pursuit of the hard-to-get avatar, we fit computational models to the choice data derived from the experiment. We used four variants of RL models to examine the benchmark of model fit: (1) a standard Q-learning model , (2) the asymmetric model, (3) the perseveration model, and (4) the hybrid model . The results revealed that the perseveration model was the best for the Pursuit group, while the asymmetric model was the best for the No-pursuit group . Mixed-dF = 41.58, p < 0.001, η2G = 0.037] but not in pair B . Although the simple main effect of model in pair A was significant in both groups , post hoc pairwise comparisons did not show any differences among models in the No-pursuit group . In contrast, there was a significant difference between all models in the Pursuit group  with the exception of the comparison between the perseveration and hybrid models .Furthermore, to examine whether the group difference in the underlying cognitive process was manifested in both pair A (including the hard-to-get avatar) and pair B (including the easy-to-get avatar), we separated the choice data of pairs A and B and then fit four models into the separated datasets . The resThese results indicate that the choice behaviors in the Pursuit group depended on the choice history, while the choice behaviors in the No-pursuit group did not show such a clear difference in history dependence. Furthermore, this group difference in the impact of choice history was observed only in the specific context involving avatars with relatively few positive reactions.To directly examine what computational process elicited the difference in choice behavior between the two groups, we compared the model parameters estimated from the hybrid model between groups. Although the hybrid model was not the best for the Pursuit and No-pursuit groups , our preα+, α−) than the No-pursuit group . Positive learning rates were higher than negative learning rates in both groups . The interaction was not significant . Furthermore, the difference between the positive learning rate minus the negative learning rate was calculated as the learning rate bias. There was no significant difference in the learning rate bias between groups . The inverse temperature (β) was significantly lower in the Pursuit group than in the No-pursuit group . While the decay rate (τ) was not significantly different between groups , the choice trace weight (φ) was significantly higher in the Pursuit group than in the No-pursuit group . These results indicated that the Pursuit group placed greater weight on past choices than the No-pursuit group, while past outcomes had a greater influence on choice in the No-pursuit group than in the Pursuit group.The Pursuit group had higher learning rates  = 78.36, p < 0.001, η2G = 0.222; pair B: F = 42.88, p < 0.001, η2G = 0.128], whereas the interaction was not significant . While the Pursuit group had a higher learning rate than the No-pursuit group with pair A , no significant difference was shown with pair B . The learning rate bias was not significantly different with either pair . The inverse temperature was significantly lower in the Pursuit group than in the No-pursuit group with both pairs . The decay rate was not significantly different between groups  with both pairs. Importantly, while the choice trace weight was significantly higher in the Pursuit group than in the No-pursuit group with pair A , there was no significant difference with pair B . The increased weighting for past choices shown in the Pursuit group was noticeable only in the context that included the hard-to-get avatar. The results suggested that an increased weight of past choices  may lead to the pursuit of the hard-to-get avatar.To examine whether this group difference in choice perseverance was observed in a specific context, we compared the model parameters in each separate dataset. Regarding the learning rates with both pair A  and pairper se. The attractiveness of the avatars after the choice task changed in accordance with the number of choices. Subsequently, following the choice task, the Pursuit group rated the hard-to-get avatar as more attractive, while the No-pursuit group rated this avatar as less attractive. Then, we used a computational modeling approach to reveal the cognitive process mediating the pursuit of the hard-to-get avatar. In a simulation, we demonstrated that a higher weight for choice history  led to repetitive selection of not only the easy-to-get avatar but also the hard-to-get avatar. To confirm this finding in the empirical data, we fitted the hybrid model proposed in a previous study  frequently chose hard-to-get avatars that seldom had positive reactions and easy-to-get avatars. Thus, we confirmed that some people pursue hard-to-get targets. The participants also performed an avatar evaluation task to investigate increased attractiveness dependent on the choice us study  to the cThe primary finding of this study is that a part of participants pursued the hard-to-get avatar, which rarely provided positive outcomes. The pursuit of hard-to-get avatars in the Pursuit group was not explained by traditional reinforcement learning theory, which argues that the action probability is increased if the action is associated with positive outcomes , even thAnother important finding is that the increase in attractiveness depended on the number of choices rather than the number of positive reactions. This choice-dependent reevaluation has been reported . Brehm . In thisφ) was observed only in the choice context including hard-to-get avatars but not in the context including easy-to-get avatars. This finding suggests that the choice context modulated choice perseverance even among the participants who pursued hard-to-get avatars. The choice-dependent reevaluation mentioned above could be a potential source of choice perseverance. As discussed above, the choice-induced increase in the attractiveness of the chosen avatar might be mediated by value updating based on the pleasure derived from imagination during the decision process . On the other hand, our previous study used an instrumental learning task with non-meaning simple symbols . Even inWe are able to evaluate the attractiveness of targets in various aspects such as physical, sexual, emotional, or aesthetic. Participants in this study were not instructed to rate attractiveness in terms of a specific aspect. It is possible that the aspects from which they rated attractiveness differed among participants. Nevertheless, the choice-dependent reevaluation of the avatar’s attractiveness was consistently found in both Pursuit and No-pursuit groups. We believe that individual differences in the aspect from which the attractiveness was rated did not have a significant effect on the present findings. Furthermore, in the present study, the apparent features such as hair and eyes were varied across avatars. Although the avatars used in the avatar choice task were selected based on the participant’s ratings preceding the choice task, it is possible that the differences in the apparent features between avatars might affect the choices if there was a bias in the apparent features. Indeed, numerous evidences show that avatars’ apparent features such as age, face shape, ethnicity, and eye/hair colors affect our perceptual responses . The impThe present study has at least three limitations. The first issue is that statistical bias resulting from the free-choice paradigm might affect the choice-dependent attractiveness change observed in this study . Althougvia the choice-induced reevaluation mechanism. The tendency to pursue hard-to-get targets can be interpreted as tolerance for negative outcomes, contributing to grit . The patients/participants provided their written informed consent to participate in this study.MS conceived the study, performed the experiment, analyzed the data, and wrote the manuscript. MS and KK designed the experiment and interpreted the results. KK revised the manuscript. Both authors contributed to the article and approved the submitted version.


In the crystal structure of the title compound, the copper(I) cations are each tetrahedrally coordinated by two 2-chloropyrazine ligands and two iodide anions and linked into binuclear complexes by pairs of μ-1,1-bridging iodide anions. 2I2(C4H3ClN2)4] or (CuI)2(2-chloropyrazine)4, which was characterized by single-crystal X-ray diffraction. In its crystal structure, the CuI cations are each tetrahedrally coordinated by two iodide anions and two 2-chloropyrazine ligands and are linked into binuclear complexes consisting of (CuI)2 rings located on centers of inversion. PXRD investigations of a few crystals obtained from the suspension indicate that the title compound is contaminated with a small amount of the 2-chloropyrazine-deficient compound CuI(2-chloropyrazine) already reported in the literature. PXRD investigations prove that the title compound immediately decomposes at room temperature into CuI(2-chloropyrazine) and this might be the reason why no pure samples can be obtained. TDA–TG–MS investigations shows two mass losses, the first of which corresponds to the formation of CuI(2-chloropyrazine), whereas in the second mass loss CuI is formed.Reaction of copper(I) iodide in pure 2-chloropyrazine leads to the formation of a few crystals of the title compound, [Cu In general, it is observed that with decreasing amounts of the coligand, the synthesis leads to the formation of compounds with more condensed CuX substructures. In this context, it is noted that upon heating, the most coligand-rich compounds usually lose their coligands stepwise and transform into coligand-deficient phases and that this is not limited to CuI, but can also be expanded to CdII and ZnII compounds  and 2-chloropyrazine as ligands with the general composition CuX(2-chloropyrazine) . In contrast, in CuI(2-chloropyrazine), each copper cation is tetrahedrally coordinated by three iodide anions and only one terminal N-bonding 2-chloropyrazine ligand that is coordinated to the copper center by the N atom that is not adjacent to the chloro substituent. The cations are linked into double chains via bridging iodide anions . If the chloride and the bromide compounds are heated, all 2-chloropyrazine ligands are removed in a single step, leading to the formation of CuX . In contrast, the iodide compound decomposes in two discrete steps, where in the first step only half of the coligands are removed, leading to the formation of (CuI)2(2-chloropyrazine), which decomposes into CuI upon further heating 2 might exist, in which, according to simple chemical considerations, each two copper cations would be tetrahedrally coordinated by two halide anions and two N-terminal 2-chloropyrazine ligands and linked into binuclear complexes by pairs of μ-1,1-bridging halide anions. One might argue that this arrangement is less stable compared to that with bridging 2-chloropyrazine ligands, but one should keep in mind that both N atoms of this ligand are not equivalent, because coordination to the N atom that is adjacent to the chloro substituent is sterically hindered. That this coordination exists is obvious from the crystal structure of (CuI)(2-chloropyrazine) mentioned above, even if this CuX substructure is different. Moreover, a few compounds with such a structure have already been reported in the literature, including, for example, (CuI)2(2-cyanopyrazine)4 4 4   with X = Cl, Br are obtained. Single-crystal structure analysis proved that a new compound with the composition (CuI)2(2-chloropyrazine)4 has been obtained.To check if such a compound can be synthesized, all three copper(I) halides were reacted in different solvents with a very large excess of 2-chloropyrazine, but no new crystalline phases were observed. On the contrary, if CuI is reacted as a suspension in pure 2-chloropyrazine, yellow-colored crystals of a new crystalline phase are obtained. In contrast, with CuCl or CuBr only the known compounds Cu2.2(2-chloropyrazine)4 consists of one copper(I) cation, one iodide anion and two 2-chloropyrazine ligands that are located in general positions. The copper(I) cations are tetrahedrally coordinated by two symmetry-related iodide anions and two crystallographically independent 2-chloropyrazine ligands  Å (Table 1The asymmetric unit of the title compound (CuI)ds Fig. 1. Each twÅ Table 1. Bond leÅ Table 1.2(2-cyanopyrazine)4 4 4  3.a-axis direction . Careful inspection of the powder pattern indicates that this sample is contaminated at least with CuI(2-chloropyrazine) reported in the literature . These observations indicate that CuI(2-chloropyrazine) with a bridging coordination of the 2-chloropyrazine ligand is more stable than the title compound, in which the 2-chloropyrazine acts as a terminal ligand. Additional DTA–TG–MS investigations reveal that the title compound loses two 2-chloropyrazine ligands in two subsequent steps, in which 2-chloropyrazine is always removed  is much larger than that expected for the removal of all of the 2-chloropyrazine ligands from the title compound , which originates from the fact that the 2-chloropyrazine coating the crystals cannot be removed. However, PXRD of the residue obtained after the first mass loss confirms that CuI(2-chloropyrazine) is formed as an intermediate , because this event would happen at a much lower temperature, whereas our measurements indicate an excess of 2-chloropyrazine is still present in the gas phase. Finally, the product formed after the second mass loss was also investigated py PXRD, which proves that CuI .Further investigations prove that the unreacted 2-chloropyrazine cannot be removed by filtration and washing because immediate decomposition is observed. Nevertheless, XRPD investigations reveal that most of the sample consists of crystals of the title compound, even if all of the powder patterns are of very low quality, which can be traced back to the instability of this compound and to the fact that only very small amounts of crystals were obtained and these were embedded in pure 2-chloropyrazine and that grinding of such samples leads to the formation of an amorphous phase 4 4 4   with X = Cl, Br, I mentioned above 2 with X = Cl, Br that contain CuII cations  with X = Cl, Br  . Moreover, both the 2-methylpyrazine and the 2-chloropyrazine compounds crystallize in the monoclinic space group P21/c with very similar lengths of the unit-cell axes, but with a significantly different β angle. In this context it is noted that with 2-methylpyrazine, two coligand-deficient compounds with the composition (CuX)2(2-methylpyrazine) with X = Br, I 2(2-methylpyrazine)(triphenylphosphine)2 acetonitrile solvate with X = Br, I [Refcodes: AKOPOI 2(2-methylpyrazine)2-2-methylpyrazine solvate (triphenylphosphine)2 with X = Cl, I [Refcodes: KAMKER  of CuI and 2 mL of 2-chloropyrazine. No stoichiometric ratios can be used as an excess of 2-chloropyrazine is needed because it acts as reactant and solvent. The additional 2-chloropyrazine cannot be removed by filtration and washing, because this leads immediately to the transformation of the title compound into CuI(2-chloropyrazine).Experimental detailsKα radiation.The data collection for single crystal structure analysis was performed using an Imaging Plate Diffraction System (IPDS-1) from Stoe with Mo Kα1 radiation (λ = 1.540598 Å) using a Stoe Transmission Powder Diffraction System (STADI P) equipped with a MYTHEN 1K detector and a Johansson-type Ge(111) monochromator.The PXRD measurements were performed with Cu 2O3 crucibles with a heating rate of 4°C min−1. The instrument was calibrated using standard reference materials.Differential thermoanalysis and thermogravimetry coupled to mass spectrometry (DTA–TG–MS) investigations were performed with a STA-429 thermobalance from Netzsch with skimmer coupling to a quadrupole mass spectrometer from Balzers. The measurements were performed in a dynamic nitrogen atmosphere in Al7.iUso(H) = 1.2Ueq(C).Crystal data, data collection and structure refinement details are summarized in Table 310.1107/S2056989023001238/jq2025sup1.cifCrystal structure: contains datablock(s) I. DOI: 10.1107/S2056989023001238/jq2025Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2056989023001238/jq2025sup3.jpgFig. S1. Crystal structure of CuX(2-chloropyrazine)  with the CuBr compound as representative (left) and of CuI(2-chloropyrazine) (right) drawn based on the data given in reference Nather et al., 2002. DOI: Click here for additional data file.10.1107/S2056989023001238/jq2025sup4.jpgFig. S2. Experimental PXRD pattern of freshly prepared crystals of the title compound (top), together with the calculated powder pattern for the title compound (mid) and CuI(2-chloropyrazine) (bottom) retrieved from literature . DOI: Click here for additional data file.10.1107/S2056989023001238/jq2025sup5.jpgFig. S3. Experimental PXRD pattern of the residue obtained by storing freshly prepared crystals of the title compound for 1 d at room-temperature (top) and calculated powder pattern for CuI(2-chloropyrazine) (bottom) retrieved from literature . DOI: Click here for additional data file.10.1107/S2056989023001238/jq2025sup6.jpgFig. S4. Experimental PXRD pattern of the residue obtained at 200C in a TG-DTA-MS measurement of the title compound (top) and calculated pattern for CuI retrieved from literature . DOI: 2241117CCDC reference:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


Literature suggests that immigrant adolescents receive limited sexual and reproductive health (SRH) education and rarely utilize SRH services in Canada. This study sought to explore the SRH information needs of immigrant adolescents in the province of Alberta.A qualitative descriptive methodology was undertaken to conduct 21 individual interviews with immigrant adolescents in Alberta.A total of four themes emerged from the interviews: (1) Barriers to SRH; (2) needs of adolescents regarding SRH; (3) sources of knowledge; and (4) strategies to improve SRH. Our findings document the conflicting needs and preferences between adolescents and their parents regarding access to SRH resources and services.Adolescents often felt unprepared to deal with their SRH issues due to socio-cultural barriers and conflicts with their parents' conservative attitude toward SRH concerns. Structural barriers to accessing SRH resources and services were also reported, including the location and cost of services. As a result, the majority of adolescents relied on digital methods to receive SRH information.This study highlights that future research and SRH service provider efforts need to remain cognizant of the positionality of immigrant adolescents and explore innovative ways to deliver SRH resources and services that meet their unique needs. Inclusion and diversity are celebrated as pillars within Canadian society. As a welcoming place, Canada is home to a large immigrant population, with over 300,000 immigrants that arrived in 2016, the largest number since 1971 –6. ImporFor immigrant adolescents, specific needs are warranted to achieve healthy behaviors that adequately navigate their cultural identities, migration contexts, family expectations, and emerging attitudes developed within the Canadian context . For exaThe right to sexual health and well-being exists for every individual; this can be achieved by providing accessible and comprehensive sexual education and services, educating about the risks involved, and educating about the adverse consequences of unprotected sexual activity . AccordiTo attain Canadian promises of inclusion and diversity, developing SRH resources and services specific to the adolescent immigrant population is paramount. In the absence of SRH resources and services that are inclusive of immigrant adolescents' needs, the young immigrant population in Canada may adopt unhealthy SRH attitudes and behaviors or experience exclusion and discrimination within SRH care . DespiteWhat are the SRH information needs of adolescent immigrants in Canada?What are the strategies that can improve access to SRH services among adolescents immigrant in Canada?The current study was part of a larger community-based research study examining the sexual and reproductive health needs and rights (SRHR) of immigrant adolescents in Canada consisting of four phases: (1) development of an adolescent advisory group; (2) scoping review of the literature; (3) qualitative interviews; (4) adolescent advisory group engagement evaluation. This paper reports phase 3 of the larger study utilizing qualitative descriptive methodology .The data was collected from 21 adolescent immigrants through interviews in 2021. SLP and SK followed up with interested participants by email to schedule a virtual interview at a mutually agreed-upon date and time.Purposive sampling was employed for participant recruitment using two strategies , 20. FirParticipants were recruited in the study by following the eligibility criteria: (a) immigrant adolescent; (b) aged 14 and 19 years; (c) fluent in English; and (d) living in Alberta, Canada.Data collection and analysis occurred iteratively until data saturation was achieved . After wAll interviews were digitally recorded, professionally transcribed verbatim, and cleaned for accuracy and completeness. Transcripts were uploaded to NVivo data management system. Inductive thematic data analysis was performed by two research team members  trained in qualitative data analysis methods . First, Ethics approval was obtained from the University of Alberta Health Research Ethics Board (Pro00097730).A total of 21 adolescents participated in the study. The demographic data of the participants are reported in A total of four themes were identified; (1) barriers toward SRH, (2) needs of adolescents regarding SRH, (3) sources of knowledge, (4) strategies to improve SRH. These themes emerged from the nine sub-themes as presented in The first theme of the study focused on the barriers for adolescents in accessing products and services related to SRH. The most commonly reported types of barriers include cultural, structural, and financial.The participants shared that they had challenges due to cultural influence and conflicts with their parents' preferences and their choices in dealing with their SRH. For example, one participant said that, “my mom and all of our relatives don't use tampons, but I really wanted to get into that and start using them” (P. 1). Likewise, one participant shared that, “...sometimes I have concerns about myself, so I want to go and visit a doctor, but my parents are immigrants, it's been a little bit tough because they feel uncomfortable with the topic” (P. 1).Other participants shared that if they prefer to go to a physician or a consultant, they keep it a secret from their parents. As one participant shared, “like if I have to go to a doctor about something, but I don't want to tell my parents” (P.2). Most of the participants expressed that they often found it challenging to openly communicate with their parents regarding their SRH needs and preferences. For example, one of the participants said;it's sometimes hard to talk about this stuff, I have to talk about it with friends if I need to. It makes me a little uncomfortable if I talk about it with my family and my parents. Like it just feels weird (P. 1).Another participant shared the similar concerns;Oh. I cannot really talk about it with my dad [Laughs], because I guess there are like two sides to this rejection to talk to him about it. Because on my side, it's apparently because I'm embarrassed. I'm not saying I don't trust him, but I just – honestly, I think he might have some irrelevant views on the subject, based on how he behaves and talks. I– and apparently, he's of the opposite gender, and when it's – and talking to the opposite gender on such delicate subjects can be very hard (P. 17).“... I think coming from an immigrant family, they don't really like to talk about this kind of stuff, so I had most of my education from school” (P.11). Another shared the same feelings;Additionally, adolescents also expressed that they felt embarrassed when they were asked by the school to get the form signed by their parents at home. Participants shared; “They didn't really teach much at my school because usually my parents don't really like to sign [consent] forms, since they're really strict about it” (P.19). Another participant echoed the same experiences; It's not culturally relevant…it's not common in my culture, like to do this kind of stuff… Like people who came to university straight from another country, they see all this kind of stuff happening, and they're just not sure about what's going on, and like so it's kind of confusing for them (P. 1).Some of the adolescents shared that talking about their SRH with their families was a cultural shock for them and for their families.I feel like that [SRH] would be a huge culture shock… But it might be different if you came to Canada when you're a young child, like in kindergarten. I feel like they wouldn't have as much culture shock and cultural difference. So I feel like that's one of the main issues (P. 3).In terms of SRH services and resources, the adolescents explained that because of the centers' remote location, they were unable to access them. One participant said, “I was thinking that I wanted to contact a doctor, but I don't know who will drive me, or what will happen, right?” (P. 6). Adolescents added that in addition to their hesitancy for open communication regarding their sexual health, the far location and cost of transportation were another hindrance to accessing sexual health services. “Besides the hesitancy, if there – if I had to go somewhere physically, that's another barrier that would add onto it and strengthen the hesitancy” (P. 9). Another participant added, “there are transportation costs. There's like kind of – you know, again, it's the whole uncomfortable thing that I mentioned before” (P. 3). Likewise, a participant shared the same challenge, “– maybe it should be more affordable, so it doesn't scare them off …, so like if there is something, that's a cheaper alternative, I think they [adolescents] would go for it” (P. 19). Other participants shared the same experience, by sharing ‘that [finance] would be a challenge (P. 14) and that “the transportation of getting there would also be kind of [challenging] especially if you don't have your own car. It's like making time for that” (P. 5). Another participant added that changing their house address affected their access to SRH services and centers. “we used to live closer to the downtown area, or like the heart of the city, and that's kind of where it's located. But we've moved out to like the suburbs, I guess, so it's quite a bit of a drive. But yeah, it's nothing too restrictive”.This theme highlights the significance of specific needs reported by adolescents regarding their SRH. The needs as follows include access to SRH services and products and a support system.Almost all the participants reported that SRH knowledge, services, and products should be accessible to adolescents.This information should I think compulsory to be available to like adolescents, so they don't have to keep guessing, probably because they don't know, or who haven't been exposed to things like this (P.11).All participants reported that a digital platform would be convenient and the most preferred method of accessing SRH. This is because physically going out to seek SRH services and knowledge is cumbersome.It's convenient because… it's online and everyone is able to like access through it…. If you have to ask your family doctor you have to first book an appointment, and then you have to go there and talk to him and then come back, so it's quite time consuming. But when it's like online, you can just call them and then just wait, and then you'll be done in pretty much 30 minutes… it's very convenient (P. 9).Several participants suggested that the knowledge about SRH services and products should be understandable to adolescents to increase accessibility; “I guess I would say being able to access it, making sure that it's easily readable… legible to younger people, because they have a harder time taking in information” (P. 1).Various participants reported that holistic SRH knowledge should be accessible and to increase accessibility, sources need to be trustworthy and anonymity and confidentiality should be ensured.Apparently that's Internet, but also, one must be careful when trusting sources….World Health Organization, or like this organization out there that operates like on a high level, and actually proves their points, like cites their resources, like and those resources are also reliable, like only then, I think, people like can actually trust the sites. Because like to be completely honest, I don't trust like information when it comes from… a journal, like Elle, or stuff like that (P. 23).I prefer online resources, just because of the anonymity. So if people – like if I feel uncomfortable about the topic, or if I'm too shy or something, I can just search it up. And that feels more comfortable… There's no pressure or anything. Nobody's going to judge you. (P. 20).Participants stated that schools can also contribute to the accessibility of SRH needs for immigrant adolescents; “I don't know if that's even possible, but if there were check-ups like at school so they wouldn't have to go through their parents and everyone would kind of have to go through it” (P. 16).Several participants highlighted the accessibility of menstrual products. Specifically, participants described that menstrual products should be cost-free as “access to stuff like pads, tampons, and all of that, is just something that I still think is very important… whether that's having a dispenser in all the like university washrooms” (P. 22).Many participants reported immigrant adolescents need a person to talk to as a support system.I think they're expecting just someone to guide them, and so that they don't feel so alone and lost… You go through puberty, and it's just a lot to take in at once. …someone to almost like hold their hand through it would be nice, so like support would be probably one (P. 20).Participants prefer friends, family, or even a stranger as a support system for them to access services related to SRH. One of the participants stated:I would say it's like a healthy support system, like with my family… I do appreciate the advice of people that I'm close with…I think like just talking it over with other people, I quite like to keep that connection… especially if they have already had that experience, I tend to trust them a lot (P. 21).Several participants stated that having a support system was influential in the decisions-making of SRH; “also getting that kind of support within the household to like make independent decisions” (P. 6).Whoever the support person may be, several participants placed importance on feeling safe and comfortable in their support systems.Going back to my point about making sure that whoever is there is comfortable is really important, because I feel like that's the only way that the person who's going to be using them will like open up… and like talk about what they need it. So like comfort level… Not necessarily like a instructor, but open space (P. 13).Several participants spoke about how de-stigmatizing conversations about SRH can increase support systems as immigrant adolescents will approach more strangers or professionals if there was less judgment.I'd really also like to see… more openness about that kind of stuff, even if it's not just like outright resources. I just think that people should be a lot more comfortable talking about those things, and I feel like that would just be a general resource that I could make use of (P. 21).taught to create support systems.Other participants mentioned de-stigmatized behavior needs to be I would also say just in general, trying to teach more about how to be open in that way, with your parents, or how you can approach those topics with other people that you might not feel comfortable with, more maturely, and with the partners (P. 13).This theme highlights the significance of sources of knowledge related to SRH among adolescents. The major sources of information were the internet, peers, and family as presented below in detail.“from the Internet, I get it from there, … that I don't know or I'm not aware of, so the Internet is what I look at” (P. 22) Additionally, some participants specifically utilized YouTube as their source of SRH information: “I watched it like a YouTube video. YouTube has been super helpful, like seeing people actually experience stuff and do stuff” (P. 13). “YouTube was very helpful” (P. 16). “I had to do the research all by myself and again, go on YouTube and watch girls' stories, see how they did it” (P. 5).The participants were asked to share about the source of knowledge on SRH. Most of the participants expressed that the most common source of information was the internet and they mainly rely on YouTube videos to gain knowledge related to their SRH needs.. Another participant added that, “Yeah, basically Google, just Google about it, and the Internet has all the information, so it's a good resource” (P. 4). Similarly, other participants highlighted that the internet was generally useful for obtaining their SRH needs: “It's all Internet, I would say” (P. 6); “I would probably say like the Internet is a big one” (P. 11); “And mainly, like for me, it's the Internet” (P.12); One participant explained that, “Because I feel like a lot of people are maybe embarrassed to talk about these issues, and so Internet has been really helpful for making decisions about sexual and reproductive health” (P. 6). Another added that, “I just had to Google like what was it. I thought that things were called puberty. Like I didn't even know period was like a term” (P. 2). Likewise, one more adolescent shared that:So yeah, I had to Google a lot and figure out what it was, and then, yeah, I think that's how I learned. And then asking older friends as well”. those popular YouTubers that talk about periods and everything, so I got some education from there as well (P.15).The second most common source of information reported by the adolescents was friends. One participant said, “some of my friends were telling me about the IUD” (P. 1). Another added that, “I'd say probably from my friends. I don't think school really covered that” (P. 22). One another participant shared that;I had a couple of friends that were on birth control, so I asked them about it, and they gave me the pros and cons of it, so that's kind of what helped me make my decision. I'd probably say my friends (P.3).Some adolescents found that the school was not a helpful source of information for them and they had to mainly rely on their friends for getting information. One participant shared that,really happens, and that's when you know (P.7).I thought that in schools they seem to dance around the topic of sex, and sexual intercourse in particular. Like they would give us the biological names of what happened, but as kids, we don't know what any of that means. So, you go into it blindly, and then by the time you get to junior high, some of your friends tell you what Similarly, another adolescent added that,I think I'd say mostly just experiences that I've heard from friends, both negative and good experiences that contributed to a lot of my worldview, and how I approach that subject, as well as how my parents talked about it, or how comfortable they were about those things. Mostly that. Yeah, mostly just friends (P.12).There were very few participants who reported that they learned SRH from their parents or someone from their family. For example, one participant said that, “Well, the information I use is basically from either again, my sister, or the Internet” (P.12). “And like if, you know, or sexual reproductive needs, I would like to go to my family for that, because I do again, like have a lot of women in my family” (P. 11). Another participant also shared the same experience of learning; “I know because of my older siblings, there's like counseling” (P. 3). Those participants who had their elder siblings were helpful for them to learn from them: “I have an older sister, so I knew about things like tampons and pads, and then later I learned about menstrual cups and things like that. So, there's that. I don't know what else, what other stuff to say, to be honest” (P. 1).Adolescents reported strategies that could help them in improving their SRH. These include making a digital story or platform and maintaining confidentiality.Almost all participants reported that a digital strategy is quick, confidential, and convenient. Specifically, a participant explained that “If it's digitally, I can access it quickly. Or if I have a spare minute and I just see it on my phone, I'll check it. And it's quiet too. Yeah, it's convenient” (P.18).Several participants reported that YouTube is a great digital platform as it showcases shared experiences.Either go on like a website or go on like YouTube channels. Because sometimes people will make these informative videos about like sexual reproductive health, and then I won't like just trust what they say… I will go through the comment section and see like, “Oh, yeah, I had the same problem, and I did this, and it worked” (P.9).Participants stated that digital strategies should be trustworthy. Many participants regard resources that are certificated or supported by professionals as trustworthy; “Maybe like a peer-reviewed journal. Or like sometimes WikiHealth when it's like a certified author and you can see their credentials” (P.19).Numerous participants stated that they would like to have resources or contact information for professional services for various SRH-related issues on a digital platform. A participant reported that resources on violence or emergency help should be on the digital platform. Additionally, the costs of such services should also be disclosed. This participant also mentioned that these links would aid adolescents with mental health issues as well.Like information about the place, where you could go to, and like how they work. So, if anyone has anxiety or anything like that, they would know ahead of time. As well as like cost … as well as like where you could go to report violence (P.16).Many participants reported that they would like holistic information on menstruation in the digital platform; “Female reproductive health needs, like discharge and periods, and learning about that” (P.3).Almost all participants mentioned that confidentiality is extremely crucial for immigrant adolescents in accessing SRH services, especially confidentiality from their parents; “everything stays confidential, and they won't inform your parents if – if like you don't want them to” (P.1) To increase confidentiality, a participant reported that confidentiality should be legalized with a document. This would make SRH services assuring and comfortable for immigrant adolescents.A doctor would like to show them some documents that they cannot and will not like – and they are legally obligated to not disclose any information that a teen provides, like with anyone else but the teen… because from what I know from psychology classes, adolescents are like they tend to think conventionally. Like that's actually the name of the stage, when they think based on the standards of society and the law… the most reassuring thing for them would be if a professional is legally obligated to be quiet (P.23).Another participant added that they would rather seek SRH services from strangers for the sake of confidentiality.know they can trust, and who was professional (P. 4).It might be nice to have, I guess, a stranger, who you connected with yourself to help you. Just because in terms of a family doctor, it could be your whole family that is taking treatment from this doctor, so you're scared that your information is not kept private, or I know it probably will be, but a lot of people will have a lot of fear surrounding the subject, so it would be good for them to be able to reach out to a certain person who they The current study documents the experiences of immigrant adolescents regarding their SRH concerns and needs in Alberta, Canada. This study highlighted the barriers, information needs, and strategies to improve SRH resources and services from the perspective of immigrant adolescents. Importantly, this study illuminates barriers to accessing resources and services related to SRH health among immigrant adolescents in Canada. Immigrant adolescents in Canada find health centers offering SRH services inaccessible. Despite the vast availability of SRH resources and services, the location and financial cost associated with accessing such services created significant barriers for immigrant adolescents. Our findings reporting the inaccessibility of SRH resources and services are complemented by previous research examining the SRH needs of adolescents . The inaNonetheless, simply developing SRH resources and services that are practical and financially accessible insufficiently meets the SRH needs among immigrant adolescents in Canada. Past evidence reports that immigrant adolescents are at risk of unintended pregnancies due to poor access to SRH resources and services such as contraceptive methods , 12. TheAs such, participants felt the structural barriers of SRH services are further complicated by means of their parents' cultural expectations. For example, immigrant adolescents reported that they were unable to access general practitioners to receive birth control measures given the requirement of parental consent to obtain such services. These findings are critically important as they highlight the need for future Canadian SRH resources and services to further account for the unique socio-cultural context of this population. The conflicting needs and preferences between adolescents and their parents regarding accessing SRH resources is a critical barrier in meeting the SRH needs of immigrant adolescents. Despite the availability of SRH resources and services, immigrant adolescents felt unprepared to deal with their SRH issues due to cultural conflicts with their parents' conservative attitude toward SRH. Specifically, the participants in this study describe the immense challenges of openly discussing their SRH needs with their parents given the element of shame within their family's cultural practices. Such findings are aligned with previous research on immigrant adolescents' challenges when navigating cultural nuances to meet their SRH needs , 23–25. In addition to accessing SRH resources and services, socio-cultural contexts also determined immigrant adolescents' level and sources of SRH knowledge. Given the aforementioned barrier to accessing formal SRH resources and services, the majority of immigrant adolescents relied on the internet and media sources for obtaining information related to their SRH needs. Immigrant adolescents reported that digital access to SRH information provides an opportunity to gain knowledge on SRH topics and address their concerns. Specifically, participants described that digital methods protected their anonymity and confidentiality, and were feasible within their socio-cultural contexts. However, participants in this study often relied on informal digital venues such as Youtube and Google search engine. Access to reliable and evidence-based digital SRH information was lacking despite immigrant adolescents' reporting their interest in such resources. These insights suggest that there is a critical opportunity for SRH research and services providers to close the gap in immigrant adolescents unmet SRH needs. Developing and implementing evidence-based digital SRH resources and services may address immigrant adolescents' SRH needs to adequately navigate their distinct structural barriers and socio-cultural contexts.This study expands on the existing literature base by offering unique perspectives from adolescent immigrants regarding inclusive strategies to improve sexual and reproductive health (SRH) services. Specifically, developing digital SRH resources and services offers a unique avenue for immigrant adolescents to navigate their distinct structural and socio-cultural barriers. Despite the strengths of our study, three limitations were present. First, our study explored a topic among a population that may deem SRH as sensitive or stigmatized. Accordingly, some of the interviews ranged from 10 to 15 min in duration given the nature of the topic and the possible limited SRH knowledge and experiences of participants. The short interview length may have limited the depth of data obtained. Second, the interviews were conducted virtually. Given the sensitive nature of the topic, participants may have felt uncomfortable discussing interview content within their context . The virtual interview context may have limited the types of responses provided to the interviewer, in addition to the interviewer unable to fully capture nonverbal communication. Third, this study did not include a diverse range of genders (majority identifying as girls), which may have influenced the perspectives portrayed in our findings. Future studies may seek to gain perspectives from diverse gender identities.The study results suggest inclusive sexual and reproductive health services for adolescent immigrants in Canada. It is highly recommended that digital SRH resources and services should be offered to adolescent immigrants to meet their unique cultural preferences.The present study explored the SRH experiences and information needs of immigrant adolescents living in Alberta, Canada. Given the structural and cultural barriers immigrant adolescents face, the future direction in SRH research and services requires the development of inclusive digital methods to access SRH information and resources. Future areas of research inquiry and SRH service provider efforts need to remain cognizant of the unique positionality of immigrant adolescents and explore innovative ways to deliver SRH resources and services that meet the needs of this population.The raw data supporting the conclusions of this article will be made available by the authors upon request.The authors obtained ethical approval from the University of Alberta Ethics Review Board (Pro00097730). Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.SM conceived and co-designed this study. SM, SK, and SL-P conducted interviews. SM, SK, SL-P, and SI led the analysis and drafted the manuscript. All authors commented on all drafts of the article and approved the final draft.This project was supported by Women and Children's Health Research Institute (Grant Number: RES0047403).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


However, the significance of m6A-modified circular RNAs (circRNAs) has not been elucidated in HGSOC peritoneal metastasis. Here, we aimed to investigate the participation and potential functions of m6A-modified circRNAs in HGSCO peritoneal metastasis.High-grade serous ovarian cancer (HGSOC) remains the most lethal female cancer due to metastasis. CircRNAs are recently identified to be modified by N6-methyladenosine . Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of the m6A-modified circRNAs.Cancerous tissues were collected from the 6A-modified circRNAs, 259 were upregulated and 227 were downregulated in the peritoneal metastasis than in the situ lesions of HGSCO patients. For the m6A peaks, 1541 were upregulated and 1293 were downregulated in the peritoneal metastasis than in the in situ lesions of HGSCO patients. For the differential expressed circRNAs, 1911(19.6%) were upregulated and 2883(29.6%) were downregulated in the peritoneal metastasis than in the in situ lesions of HGSCO patients. The upregulated m6A-modified circRNAs were associated with the HIF-1 signaling. The downregulated m6A-modified circRNAs were associated with the MAPK signaling.For the m6A-modified circRNAs in peritoneal metastasis of HGSCO. Our findings provided novel evidences about the participation of m6A-modified circRNAs via HIF-1 and MAPK signaling and a new insight in molecular target of HGSCO peritoneal metastasis.This work firstly identified the transcriptome-wide map of m In 2 cancers , 4. OC c cancers , 4. High cancers , 2, and HGSOC is typically diagnosed at advanced stages owing to the deficiency of specific symptoms at early stages, which is characterized by the involvement of bilateral ovaries, aggressive behavior and low survival without effective molecular targeted therapy. To date, regardless of the continuous improvement and development of surgical and systematic management, the mortality of these patients has not been improved under the standard regimens with approximately 70% of patients having relapse and metastasis after treatment. Consequently, identifying the mechanisms that drive HGSOC metastasis will translate into clinical managements that would improve their outcomes , 5–8.Currently, significant efforts have been made for personalized treatment to improve prognosis of HGSOC patients, including application of genomic technologies to identify the expression profile, copy-number changes, mutations, and epigenetic modifications of the genes. RNA sequencing (RNA-seq) is one of the key genomic technologies applied to reveal molecular pathogenesis in HGSOC –8.Circular RNA (circRNA) is one type of noncoding RNA (ncRNAs) with a closed loop structure without 5′-3′polarity and poly A tail, which were firstly identified abundant in viruses by RNA-seq, and predominantly regulates the gene expressions at the transcriptional and post-transcriptional levels –12. More6A), methylated at the N6 position of adenosine, is identified as the most universal epigenetic modification on ncRNAs in eukaryotes and affects the circRNA expressions  such as METTL3/14/16, removed by demethylases (“erasers”) FTO or ALKBH5, and interacts with the m6A binding proteins (“readers”), such as YTHDF1/2/3 and IGF2BP1/2/3  antibody and Rnase R were purchased from Merck Millipore-Sigma-Aldrich .TRIzol Reagent was bought from Invitrogen-Gibco . NEBNext rRNA Depletion Kit and NEBNext Ultra II Directional RNA Library Prep Kit New England Biolabs, Inc. .GenSeqTM m6A-MeRIP Kit was bought from GenSeq Inc. . Anti-N6-methyladenosine   , 23.Total RNA (10 mg) was obtained from the cancerous tissues by using the TRIzol Reagent following the manufacturer’s protocols. The extracted RNAs were purified with Rnase R  digestion to remove linear transcripts.NEBNext rRNA Depletion Kit was used to remove rRNAs from the total RNAs. The RNA concentration was measured at 260/280 nm (1.8 to 2.1) by using NanoDrop ND-2000. Total RNA quality was evaluated with the band intensity ratio of 18S/28S ribosomal after electrophoresis in an ethidium bromide-containing 1% agarose gel , 23.After quality filtering, paired-end reads were collected from Illumina Hiseq Sequence. The reads were aligned to the reference genome (UCSC RN5) with STAR software. The CIRI software was applied to detect and annotate circRNAs. Raw junction reads were normalized against per million reads mapped to the genome by using log2 scaled .6A-methylated RNAs, the anti-N6-methyladenosine (m6A) antibody was cultured with the fragmented total RNAs extracted from the cancerous tissues of HGSCO patients after rRNA depletion with the GenSeqTM m6A-MeRIP Kit following the manufacturer’s instructions. The bound RNAs were eluted from the protein A/G magnetic beads after incubation.To immunoprecipitate the m6A-immunoprecipitated (m6A-IP) RNAs were reverse-transcribed to cDNA for the construction of the RNA-seq library by using NEBNext Ultra II Directional RNA Library Prep Kit. The library quality was weighed by using a BioAnalyzer 2100 system . Then the qualified m6A-IP and input samples were subjected to 150 bp paired-end deep sequencing on Illumina HiSeq sequencer to obtain the high-resolution reads of m6A-methylated RNAs.The input RNAs and m6A RNA-Seq were carried out by the Cloud-seq Biotech Inc. .The RNA-seq of circRNAs and the mPaired-end reads were collected from Illumina HiSeq sequencer with the quality control of Q30. After 3’ adaptor-trimming, the low-quality reads were removed with the cutadapt software (v1.9.3). First, the clean reads of input libraries were aligned to the reference genome (UCSC HG38) by using the STAR software. Based on the STAR alignment results, the circRNAs were identified by using the DCC software. Then, the clean reads of all libraries were aligned to the reference genome with the Hisat2 software (v2.0.4). The MACS software was applied to identify the methylated sites on circRNAs (peaks) and the diffReps was further used to identify the differentially methylated sites. The overlapping sites between the peaks, identified by both software based on the circRNA exons, were selected by the home-made scripts.6A methylated circRNAs were achieved by Gene Ontology (GO), as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses based on the online software DAVID.The comprehensive function annotations of the source genes of differentially mp < 0.05 was considered statistically significant  and GraphPad Prism software 7.0 . The single factor ANOVA was used for statistical analyses, nificant .6A-modified circRNAs was performed in cancerous specimens of three biological replicates from the in situ lesions (n = 3) and the peritoneal metastasis lesions (n = 3) from HGSCO patients. Patient information is presented in 6A abundance in the peritoneal metastasis lesions (1070 + 259 for the m6A-modified circRNAs and 2089 + 1541 for the m6A peaks) was found to be slightly increased than the in situ lesions (1070 + 227 for the m6A-modified circRNAs and 2089 + 1293 for the m6A peaks) of the HGSCO patients, which were further visualized by the Heatmap  overlapping circRNAs were identified. CircRNA expression was decreased in the peritoneal metastasis lesions than in the situ lesions. These findings suggest that m6A may downregulate the circRNA expressions in peritoneal metastasis lesions of HGSCO patients  analysis. The parent genes of circRNAs with upregulated m6A peaks were enriched in the intracellular, organelle and cytoplasm, while downregulated m6A peaks were enriched in the intracellular, organelle, cytoplasm and membrane-bounded organelle in the cellular component (CC) analysis. The parent genes of circRNAs with upregulated m6A peaks were enriched in the adenyl ribonucleotide binding and the adenyl nucleotide binding, while downregulated m6A peaks were enriched in the catalytic activity in the molecular functions (MF) analysis.In the GO analysis Figure 46A-modified circRNAs, while MAPK signaling pathway was associated with the downregulated m6A-modified circRNAs  can be found in the article/supplementary material.All animal procedures were approved by the Research Ethics Committee of the Second Hospital of Hebei Medical University.Conceptualization, methodology, design, and writing: LG, NX, DQ, XY, and SZ. Supervision: HZ. All authors contributed to the article and approved the submitted version.This research has been supported by Health Research Funding of Shaanxi Province Grant (Number: 2022D063); Innovation Project of Tangdu Hospital (Grant Number: 2018QYTS009).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Blue spaces is associated with self-rated health (SRH), but little is known about the pathways underlying this association among Chinese urban elderly individuals. Based on neighborhood effect theory, this study examined the relationship between neighborhood blue spaces and SRH among elderly individuals using data from a questionnaire survey conducted in Guangzhou, remote sensing images, street views, and environmental information in the context of a Chinese megacity. In addition, multilevel linear model and mediating effect model empirical analyses were performed. Results showed that first, the SRH of the elderly was associated with individual- and neighborhood-level factors. Second, the multilevel mediation model revealed that multiple biopsychosocial pathways existed between neighborhood blue spaces and the SRH of the elderly, specifically, the blue space characteristics related to the SRH of the elderly via the mediating effect of stress. Third, owing to demographic characteristics and socioeconomic status, the stratified analyses also indicated a strong association between neighborhood blue spaces and SRH outcomes in the older and low-income groups. The mediating effect of stress in the age and income groups was also observed, and the mediation pathways and group differences were confirmed in the context of Chinese cities. This research enriches the empirical literature on blue spaces and elderly health from a multidisciplinary perspective and suggests the need for “healthy neighborhood” and “health-aging” planning in Chinese settings. Population aging and urbanization are two prominent characteristics that comprise the major force shaping the 21st century, especially in developing countries. According to the World Health Organization, the proportion of the world’s population over the age of 60 years will reach 22% in 2050, and 80% of the elderly population will be living in low- and middle-income countries  and was coded as E1) to the buffer zone (1 km buffer zone of the neighborhood’s boundary). We assessed the quality of blue space landscapes with reference to the concept of “landscape fragmentation/isolation” in landscape ecology. Landscape fragmentation may lead to a lack of habitat ecological function . FurtherProximity: We used proximity as an indicator to assess the nearby blue spaces. The distance to the nearest water body was the Euclidean distance between the centroid of the residential neighborhood and nearest river (second-order rivers or higher), lake, or wetland.Hydrophilicity: Hydrophilicity accounted for the blue space activities and uses. Hydrophilicity can be used to determine whether a respondent had a view of or came in contact with a nearby body of water. According to our in-depth interviews, the elderly with poor mobility were likely to stay in nearby blue spaces for a relatively long period of time. Elderly residents around hydrophilic areas can engage in hydrophilic activities, such as touching the water, walking, and talking with neighbors. Hydrophilic areas mean that the blue spaces are publicly accessible. The European Commission recommends open public spaces to be within 300 m of a residence. In our field research, we found few roadside obstacles and many paths leading to parks or rivers within 500 m around the neighborhood, so we considered using the Euclidean distance to express. Moreover, considering the investigation and neighborhood life circle in Guangzhou, we adopted 500 m as the standard for deeming a water body accessible. The hydrophilicity index was a binary variable, where 0 represented a non-hydrophilic area, and 1 represented a hydrophilic area.We obtained four potential mediators  from the subjective and objective data, as suggested in the literature, and treated them as continuous variables in this study. First, we assessed the pollution data  in each neighborhood using the air quality index obtained from annual data comprising 62 national monitoring points in Guangzhou in 2018 and calculated the information via spatial interpolation. In this study, because spatial interpolation made an estimate within the range of the known data, we used the inverse distance weighted (IDW) method, which has the advantages of having a simple algorithm, being able to overcome estimation bias, and being easy to implement, for spatial interpolation to obtain an accurate estimation . Second,We incorporated a series of individual-level variables based on previous studies and our theoretical framework. We controlled for socioeconomic and demographic covariates, including age, gender, educational attainment, marital status, hukou status, monthly household income, and employment information. The summary statistics of all the variables are shown in Multilevel linear model: Multilevel models are specifically geared toward the analysis of data with a hierarchical structure, which can accurately distinguish and calculate the contribution of different geographical levels of elements. Considering the data nesting, in which individuals are nested in neighborhoods, we fitted a multilevel linear model using a random intercept model to assess the association between neighborhood blue spaces (neighborhood level) and the elderly’s SRH , which was necessary owing to the hierarchical structure of the data .Multistep mediation analysis: To determine whether the mediators could partially or fully explain the association between neighborhood blue space and an elderly individual’s SRH, we conducted multistep mediation analysis to decompose the effect of neighborhood blue space on SRH into a direct and mediating component as well as a total effect . The medIn this study, we used Stata 14.0  to conduct all the data analyses, which involved several steps. First, to identify the direct association, we regressed SRH (a continuous variable) on neighborhood blue space  and assessed the model performance using the Akaike information criterion. Second, we regressed each of the four mediators on the neighborhood blue space indicators and covariates (Models 2a–2d) to identify the effect of the mediators on the independent variable. Third, to identify the mediating effect, we regressed SRH outcomes on the four mediators and neighborhood blue space (Models 2a’–2d’). Fourth, to test the statistical significance of the mediating effect, we conducted bootstrap tests. The test statistic assessed whether including a mediator in the regression with neighborhood blue space reduced the health effect while the mediator remained significantly correlated. Fifth, we conducted stratified analyses to further explore the heterogeneous effect of socioeconomic status on the association between neighborhood blue space and SRH using multilevel and mediation models.To deal with the selection bias due to the observables and check whether the relationship was robust, we used linear regressions, along with propensity score matching (PSM) , for the2, SD ± 9592.703), dispersed water patch , distance to a river , and hydrophilicity . The respondents reported relatively low stress , average physical activity duration , and a neutral social interaction score .All the characteristics variables are shown in With a neighborhood-level intraclass correlation of 0.1203 in the null model (without any variables), the application of the multilevel model was justifiable, meaning that neighborhood blue space indicators effectively explained the heterogeneity of the elderly’s SRH at the neighborhood level.p < 0.05), age , and monthly income  were significantly related to SRH outcomes. As for the neighborhood characteristics, the NDWI  was negatively associated with the elderly’s SRH, and the patch separation index  and hydrophilicity index  were positively associated with the elderly’s SRH.Model 1 shows the results of the total effect of neighborhood blue space on SRH . In termp < 0.1) was negatively related to stress. In Model 2d, the patch separation index  was positively linked with social contact, whereas the hydrophilicity index  was negatively related to social contact.p < 0.1) and per capita water area  were negatively related to the elderly’s SRH, whereas pollution  was negatively related to SRH. In Model 2b’, the NDWI  was negatively related to SRH, whereas stress  was negatively related to SRH. In Model 2c’, the NDWI  and per capita water area  were negatively related to the elderly’s SRH, whereas physical activity duration  was positively related to SRH. In Model 2d’, the NDWI  was negatively related to SRH, whereas the mediating effect of social contact was not significant. The results of the bootstrap tests showed that only stress was a significant mediator in the effect of the NDWI , thereby indicating that stress had a significant partial mediating effect.We further examined whether the four mediators had a mediating effect (Models 2a’–2d’). p < 0.1), radius matching , and kernel matching . Regardless of the employed matching method, the effect of neighborhood blue space on the elderly’s SRH remained robust after we partially controlled for the selection bias.We further employed PSM to control for the selection bias in Model 1 owing to the observed characteristics. The value of the NDWI ATT was significant in the three methods of k-nearest neighbor matching  and the hydrophilicity index  were associated with SRH outcomes only among the participants older than 75 years. In the gender-stratified analysis (p < 0.05) was positively associated with SRH outcomes only in the group of female participants. In the monthly income-stratified analysis (p < 0.1) and middle–high-income group .In the age-stratified analysis , no neiganalysis , no neiganalysis ., per caAs for the mediating effect presented in A small but growing body of evidence demonstrates the potential health effect of engaging with blue spaces in the elderly’s later life. Our results are in line with previous studies that suggested a significant association between neighborhood blue space and the elderly’s general health ,27,37,38Our study suggested that the blue space characteristics (NDWI) were negatively associated with the elderly’s SRH. According to certain research frameworks from previous studies and in-depth field interviews, our research results can be potentially explained by the water quality of the Pearl River in Guangzhou (blue space features modifier). We used the water quality index (WQI) to evaluate the water quality and its impact on human health, and a low WQI value poses a potential threat to human health . In lineConsistent with previous evidence obtained for adults, some of the functions of neighborhood blue space, such as stress relief , were reTo the best of our knowledge, the elderly’s SRH was patterned by socioeconomic and other demographic factors. In this study, we found that the relationship between neighborhood blue space and SRH varied significantly by age and income. We observed that the neighborhood blue space–SRH association was significant in the older group. These results are inconsistent with those of previous work that determined that the older elderly group benefits more from neighborhood blue spaces than the younger elderly group. For example, a study showed that high freshwater coverage in the wide neighborhood is associated with low antidepressant prevalence only among 50–64 year olds, with no significant association observed for the >65 year olds . ElderlyAs for the mediating effect, we observed some indications that neighborhood blue space, SRH status, and stress, as a mediator, may be highly relevant to the older and low-income groups. This result is partially consistent with that of a New Zealand study on significant associations between personal income and psychological distress . A possiOur research has three particular strengths. (1) In this study, we paid special attention to the health of the elderly. Based on the neighborhood effect, our study extended the findings of previous studies on the association between neighborhood blue spaces and the elderly’s health. (2) In the Chinese context of aging and dense populations, our empirical research explored multiple biopsychosocial pathways linking neighborhood blue space with the elderly’s SRH through the mediating effect of stress. With reference to the salutogenic effect, our study confirmed the “biophilia hypothesis”  and “heaOur research also has some limitations. First, the cross-sectional study had a limited ability in making causal inferences regarding our evaluated associations and mediation roles. Second, we used a self-reported questionnaire to obtain the subjective SRH data and mediators in the analysis. Third, we were unable to consider the participants’ frequency or duration of using blue spaces owing to the lack of data, which may have affected our assessment.This study examined the relationship between neighborhood blue spaces and SRH among elderly individuals in Guangzhou using a questionnaire and other data in the Chinese megacity context. Our results showed that the elderly’s SRH was associated with individual- and neighborhood-level factors. Among the individual-level factors, the indicators of age, gender, and monthly income were significantly associated with the elderly’s SRH. At the neighborhood level, the characteristics of blue spaces were significantly associated with the elderly’s SRH. The multilevel mediation model showed that multiple biopsychosocial pathways existed between neighborhood blue spaces and the elderly’s SRH. Specifically, the blue space characteristics were related to the elderly’s SRH through the mediating effect of stress. The stratified analyses identified potentially susceptible groups owing to their demographic characteristics and socioeconomic status, that is, the strong association between neighborhood blue spaces and SRH outcomes in the older and low-income groups. We also observed the full mediating effect of stress in the age and income groups.However, no evidence supported the mediating role of pollution, physical activity duration, and social contact. Hence, further research is necessary to address the remaining questions and limitations of our study, including influencing indicators and underlying mechanisms, such as the mediating effect of water pollution. Furthermore, objective data, such as health or environmental data, can be collected for the analysis, such as water samples around the neighborhood to be tested by a testing agency.