While the use of social media and online-communication applications has become an integral part of everyday life, some individuals suffer from an excessive, uncontrolled use of social media despite experiencing negative consequences. In accordance with neuropsychological models of addiction, we assume the tendency of a social-networks-use disorder to be related to an interplay of predisposing personality traits , and reductions in cognitive functions . The current study makes first strides towards examining this interplay. In addition to a newly developed social-networks-specific auditory Go-NoGo paradigm, other neuropsychological paradigms were used. Impulsivity and social-networks-use-disorder symptoms were assessed by standardized questionnaires. The results show that the symptom severity of a social-networks-use disorder is mainly associated with attentional impulsivity. General executive functions and specific inhibitory control of social-networks-related cues have no direct effect on symptom severity. However, moderated regression analyses emphasize that increased symptom severity is associated with higher attentional impulsivity, especially if there are additionally reductions in executive functions or specific inhibitory control. The results complement previous findings and inform future research on social-networks-use disorder. The findings support the applicability of theoretical models of addictive behaviors to the social-networks-use disorder and point to social-networks-related specificities regarding attention-related facets. Such devices typically generate auditory cues (ringtones) to inform people about new messages; and these are generated many times per day, anytime and anywhere2. Such ringtones indicate incoming calls, messages, or other novel information provided by online applications; and are associated with an implicit or explicit demand of a specific action, i.e., interacting with the smartphone3. One of the most popular applications used on smartphones are social-media applications or online-communication applications 4, which allow users to interact with others, to stay connected, and to share pictures, videos, or personal information6. The repetitive use of social media via smartphones and the reinforcement of reward expectations, can lead to habitual usage and impulsive responses to social media cues8, and also to the emergence of addiction-like symptoms in cases of loss of control and repeated use, despite negative consequences8.In 2016, there were 2.16 billion smartphone users worldwide and experts expect the number to rise to over 3.01 billion users by the year 2021th revision of the International Classification of Diseases (ICD-11)9, only gambling disorder and gaming disorder are included as specific forms of disorders due to addictive behaviors. Both can be further subcategorized as occurring predominantly offline or online. The definitions of gambling disorder and gaming disorder include symptoms similar to those of disorders due to substance-use, i.e. impaired control over the behavior, increasing priority given to the behavior by neglecting other interests or activities, and continuation of the behavior despite negative consequences9. Even though social-networks-use disorder has not yet been officially classified, researchers already outline that this addiction-like behavior may be comparable to other behavioral addictions or substance-use disorders, at least along several dimensions12.A growing number of studies support the view that the uncontrolled use of the abovementioned online -communication applications can be a type of disorder. Yet, social-networks-use disorder , is not classified within respective classification manuals. In the 1115. The reflective system is associated with prefrontal cortex operations, such as executive functions and inhibitory control, which enable the control of impulsive responses19. According to Goldstein and Volkow14, dysfunctions in respective brain regions contribute to impairments in response inhibition. Situational factors (e.g. the presence of specific cues) and individual predisposing factors  are assumed to interactively influence the way impulsive and reflective processes influence the decision to perform (or not to perform) a specific behavior see also20.From a neuropsychological perspective, addictive behaviors  are assumed to result from an imbalance between two interacting neural systems. More specifically, it is assumed that a hyperactivity of an impulsive system, which enables quick and emotional responses towards immediately gratifying options, undermines cognitive control processes of a reflective system resulting in addictive behaviors; e.g.,23, the I-PACE (Interaction of Person-Affect-Cognition-Execution) model by Brand, et al.24 builds on empirical findings from behavioral and neuroimaging studies and summarizes the process of the development and maintenance of addictive behaviors. According to this model, individual predisposing variables, including trait impulsivity, affect the subjective perception of situational cues. Situational factors  are assumed to interact with individual coping styles and cognitive biases, leading to affective and cognitive responses, e.g. cue-reactivity, craving, and attentional bias25. Furthermore, inhibitory control and general executive functions, which encompass several cognitive processes such as retrieval and integration of information, cognitive flexibility, planning, monitoring, updating, strategy evaluation and application, as well as attention and inhibitory control27, buffer against addictive behavior enactment and the development of addiction symptoms. Reductions in general executive functions and inhibitory control intensify a specific behavior, e.g. the use of certain online applications, in a seemingly automatic way due to the anticipated experience of gratification and/or compensation. Brand, et al.24, therefore, positions general inhibitory control as a moderator in early stages of the addiction process, while in later stages, the so called “stimuli-specific reductions in inhibitory control” contribute to the maintenance of the respective addictive behavior. Such general and domain-specific cognitive control abilities can help social media users overcome tempting behaviors that are cued by the environment29. When such executive function and inhibition abilities are weak, conditioned learning and reinforcement mechanisms, such as stabilization and intensification, are augmented. This cycle could, over time, result in a loss of control over the behavior and thus in a continuous use of a specific online applications, despite negative consequences in everyday life.In accordance with such dual-process approaches and previous theoretical models35. For example, attentional impulsivity was shown to correlate with symptoms of gaming disorder36 and online pornography-use disorder37. General executive functions were found be reduced in individuals with gambling or gaming disorder42. Furthermore, a recent meta-analysis by Ioannidis, et al.43, demonstrated cognitive reductions  in individuals with unspecified Internet-use disorder.The special relevance of impulsivity and general executive functions is highlighted by empirical findings on gambling disorder, gaming disorder, and other addictive behaviors related to application-specific Internet-use disorders. High impulsivity has been consistently associated with symptoms of specific Internet-use disorders e.g.44, but not with social-networks use disorder45. Possible interactions between impulsivity, general executive functions, and specific inhibitory control, as emphasized by theoretical models25, have been scarcely investigated in the context of specific Internet-use disorders. In one of the first studies addressing this interplay, Antons and Brand37 investigated impulsivity, craving, and specific inhibitory control in online pornography-users by using a Stop-Signal Task with pornographic cues. The authors concluded that the interactions between the mentioned factors contribute to problematic online behavior, and that this interplay should be further examined with other online behaviors and in other online contexts37.Specific inhibitory control has been relatively under-studied in the context of specific Internet-use disorders. Results of empirical studies investigating inhibitory control effects on addiction-related cues demonstrate inhibition deficits to be associated with gaming disorder and problematic online pornography use e.g.,48; and that impairments in attentional control and inhibition abilities can be associated with problematic social media use behaviors51. Empirical studies on specific inhibitory control in social-networks-use disorder have also been rare. For example, Chung, et al.52 reported no significant associations between general inhibitory control assessed by a Go-NoGo paradigm (without addiction-related cues) and the symptom severity of a social-networks-use disorder. Moreover, Gao, et al.53 used a Go-NoGo paradigm with addiction-related cues in the context of social-networks-use disorder to show that individuals presenting social-networks-use disorder and healthy controls did not differ in Go-NoGo performance on a behavioral level. Lastly, brain regions involved in general and domain-specific self-control functions were not associated with social-networks-use disorder symptom severity56.In the context of social-networks use, only a few studies examined the effects of impulsivity and cognitive functions, albeit independently, on problematic use. They showed, for example, that impulsivity can be a risk factor for the development and maintenance of a social-networks-use disorderPossible interactions between impulsivity, general executive functions, and specific inhibitory control, indicating the interplay of impulsive and reflective processes have not yet been investigated experimentally in the context of social-networks-use disorder. Nevertheless, providing experimental data supporting the aforementioned interactions would have important implications for the current view of social-networks-use disorder. It can potentially more clearly indicating parallels to other addictive behaviors in terms of underlying psychological mechanisms. Looking at the interplay between such factors can also explain inconsistent and non-significant prior findings. For instance, it is possible that domain-specific inhibition was not significant in prior research because it is relevant only for people high in impulsivity trait. Overall, theoretical models and empirical findings allude to the idea that impulsivity, general executive functions, and specific inhibitory control can interact to influence the development and maintenance of addictive behaviors; and might therefore be involved in the problematic use of social networking sites. This study, therefore, addresses this gap and examines such interactions.Specifically, the current study aims at investigating the roles of attentional impulsivity, reduced general executive functions and diminished specific inhibitory control in explaining social-networks-use disorder symptom severity. Based on the I-PACE model, we hypothesize that  trait impulsivity interacts with general executive functions and specific inhibitory control in the prediction of social-networks-use disorder symptoms . Following the main aim of our study, we examined the effect of measures of reduced general executive functions  and reduced specific inhibitory control (auditory Go-NoGo paradigm) on the symptom severity of social-networks-use disorder (sIAT-SNS), both separately, as well as in interaction with trait impulsivity (BIS-15). Therefore, in a first step, we calculated bivariate correlations between the mentioned measures. In a second step, we analyzed how impulsivity interacts with general executive functions and specific inhibitory control in the prediction of social-networks-use-disorder symptoms. Therefore, we performed moderated regression analyses (see below) with three steps using mean-centered variables57.The sum score of the sIAT-SNS indicating social-networks-use disorder symptoms mean score of Correlation analysis indicated that the level of symptoms of social-networks-use disorder (s-IAT-SNS) is significantly positively associated with the attentional subscale of the BIS-15, but not with any other measure  as first predictor. Each analysis included another measure of general executive functions or specific inhibitory control as the second predictor, resulting in seven different analyses. The respective interaction terms were calculated using mean-centered values of the first and second predictors57.We next analyzed possible interaction effects using multiple hierarchical regression analysesF = 16.44, p < 0.001. The addition of any of the general executive function measures, in the second steps, did not lead to further variance explanation . However, the interactions between BIS-15 attentional × TMT-B  and BIS-15 attentional × MCST  were significant in explaining additional ~3% of the variance in sIAT-SNS. Both overall models were significant in explaining variance of the sIAT-SNS  = 7.16, p < 0.001, MCST as moderator: R² = 0.173, F = 7.55, p < 0.001). Looking at the simple slopes revealed a similar picture for both interactions: sIAT-SNS was the highest in individuals with high attentional impulsivity  and low general executive functions . Individuals with high attentional impulsivity had significantly higher levels of symptoms of social-networks-use disorder only if, additionally, general executive functions were low. The significant interaction effects are illustrated in Fig. As measures of general executive functions, the performance scores in the Stroop test (seconds needed in part 3), the TMT-B (seconds needed), and the MCST (perseverative errors) were each included within a separate analysis. The results revealed that attentional impulsivity, in the first steps, significantly explained 13% of the variance sIAT-SNS, The variables of the new auditory Go-NoGo paradigm modified for SNS served as measures of specific inhibitory control. Following the above-described procedure, attentional impulsivity  was included as the first predictor and, in separate analyses, each of the Go-NoGo scores  were included as the second predictor, respectively. The dependent variable was again sIAT-SNS, capturing symptom severity of social-networks-use disorder.R² < 0.007, all p’s > 0.05). However, there was a significant interaction between false-Go-SNS with BIS-15 attentional on sIAT-SNS, ΔR² = 0.034, ΔF = 4.47, p = 0.037. The overall model was significant in explaining 16.9% of the variance in sIAT-SNS, F = 7.31, p < 0.001. The simple slopes analysis illustrated that individuals with high attentional impulsivity  had a significantly higher sIAT-SNS scores than those with low attentional impulsivity but particularly if accompanied by high false-Go-SNS, t = 4.45, p < 0.001, rather than low false-Go-SNS, t = 1.32, p = 0.189. Accordingly, social-networks-use-disorder symptoms are the highest in individuals with weaknesses in both attentional impulsivity and Go-reactions on SNS cues. Figure The results showed that, beyond the already reported effect of attentional impulsivity, none of the Go-NoGo variables had an additional effect  = 0.16, p> 0.05. The interactions with false reactions on neutral trials also did not contribute to additional variance explanation, neither for Go trials , ΔR² = 0.012, ΔF = 1.51, p > 0.05, nor for NoGo trials , ΔR² < 0.001, ΔF = 0.05, p > 0.05.In contrast, the interaction between BIS-15 attentional and false-NoGo-SNS had no additional effect, ΔThe current study investigated the importance of considering impulsivity, general executive functions, and specific inhibitory control in tandem, for understanding and explaining the development and maintenance of a social-networks-use disorder. The results suggest that attentional impulsivity is related to a higher symptom severity of social-networks-use disorder. At the same time, we found no direct associations of general executive functions and specific inhibitory control with symptom severity of social-networks-use disorder. However, there were several interaction effects emphasizing that individuals with higher attentional impulsivity are especially predisposed to develop stronger symptoms of a social-networks-use disorder if they additionally show reductions in general executive functions and social-networks-specific inhibitory control.48 and of other specific Internet-use disorders e.g.,59. For example, the reward system in the brain , which creates states of motivation for impulsive behaviors, and that has been implicated across various impulsive behaviors, has been found to be hyper-active45, structurally pruned and more efficient55 in people with stronger social-networks-use disorder symptoms. Indeed, in their review, Mitchell and Potenza60 summarized the critical role of impulsivity by highlighting that personality traits associated with more impulsive behavior are related to several forms of substance-use disorders. They further mention interactions between different facets of impulsive behavior (i.e. interactions between impulsivity and sensation-seeking) to be associated with substance use. In that sense, our findings are in line with prior research that highlights the importance of impulsivity in promoting risky social-networks-use behaviors48 and addictive social-networks use61. These effects are rooted in part in dual-system theories62 as also applied to social networking sites23; according to which impulsivity is a manifestation of the hyperactivity of the brain system that govern reward expectation and processing (system 1)63.The results are consistent with former research illustrating associations between impulsivity and symptoms of social-networks-use disorderet al.24 extends and contextualizes such dual system models of addictive behaviors to the case of Internet applications. Based on this model, we hypothesized that the interactions between personality traits and general executive functions, as well as with specific inhibitory control can result in a diminished control over the behavior. Our results confirmed this hypothesis. If impulsivity appears together with either reduced general executive functions or impaired specific inhibitory control of social-networks related cues, then individuals have higher symptom severity of social-networks-use disorder compared to those without impairments in general executive functions or specific inhibitory control. Antons and Brand37 showed similar interaction effects between impulsivity and specific inhibitory control for male participants with problematic online pornography use. Results of a later study64 showed that the attentional domain of impulsivity differentiates recreational from unregulated pornography use. Our current results indicate that attentional impulsivity is an especially relevant facet in the context of social-networks-use disorder as well. This points to a similar role of impulsivity across various problematic online behaviors, and to the generalizability of the core dual-system and I-PACE ideas across various problematic online behaviors. Together, the findings emphasize that the presentation of specific Internet-related stimuli affects attentional processes, which could result in diminished control over the use of Internet/social-networks, if accompanied by high attentional impulsivity as a predisposing variable. This view has also been supported from a neuroscientific standpoint, by studies showing that activation and morphology of centers of impulsivity and diminished ability to overcome impulsions are associated with social-networks-use disorder symptom severity56.The I-PACE model by Brand, 65. However, there was no significant interaction between impulsivity and general executive functions measured by the Stroop test, which is often used as a measure of general inhibition capability. This may indicate that “higher-level” executive functions (as mainly measured by the MCST), such as updating and set-shifting, and “lower-level” executive functions (as mainly measured by the Stroop test), such as inhibition ability e.g.,67, are differentially involved in mediating addictive behaviors online. We call for future research to delve deeper into such distinctions.The current findings illustrate that especially those variables that are associated with deficits in attention and information processing interact with higher attentional impulsivity, which ultimately results in higher levels of social-networks-use disorder symptoms. The special relevance of attention-related facets of inhibitory control is indicated by the fact that interactions only occurred with false “Go” (and not “NoGo”) reactions on online-communication-related cues. Interestingly, general executive functions assessed by the MCST  show similar interaction patterns with attentional impulsivity, which supports theoretical assumptions on addictive Internet use69. A dominance of the impulsive system is assumed to induce approach tendencies towards potentially gratifying options while neglecting long-term risks, which may result in risky behavior such as drug consumption e.g.,70. These approach tendencies could be triggered and/or reinforced by facing specific cues related to the expected gratification. In the context of smartphone use, a ringtone or auditory signal associated with an online-communication application can be one such cue. Smartphones, and especially certain cues associated with new incoming information or messages, have an explicit demanding character and are able to induce craving to use online-communication applications71. Auditory smartphone notifications were shown to attract attention and affect task performance, especially in individuals with a tendency towards an excessive use72. Cognitive control processes are necessary in order to inhibit or ignore impulsive responses on demanding cues in situations, when responding to the auditory signals is not appropriate. The current findings support the assumption that individuals with reductions in both attention and general executive functions are especially prone to develop stronger social-networks-use disorder symptoms when they are impulsive. The observed interaction effects are in line with prior research on impulsive alcohol consumption73 and social media use29; such studies showed that cognitive-emotional preoccupation with the behavior (akin to and/or associated with impulsivity) increases problematic behaviors, and that this effect is augmented by weak cognitive behavioral control (akin to and/or associated with executive functions). We hence call for future research to integrate these perspectives and provide a more fine-grained explanation of the interactions we observed here.The reported interactions between the different components further fit dual-process perspectives, which suggest that addictive behaviors result from an imbalance between impulsive and reflective processes24, facing a demanding cue could be described as an additional reinforcement mechanism, resulting in that exercising control over the behavior becomes increasingly difficult over time. It is possible that cue activation strength alone can lead to social-networks-use disorder symptoms, even if executive control is intact; the hyper-sensitization of the cue processing system in the brain can create a strong motivation state that even a healthy prefrontal cortex may not be able to handle45. Further research should address the demanding character of smartphones and online-communication applications as well as their effect on the individual’s attention more systematically. The investigation of possible long-term effects, such as attentional deficits, when cognitive control is additionally reduced or distracted is important for better understanding the impact of the use of social media on human  behavior. For example, attention deficits have been linked to risky online behavior, such as checking social media while driving; and such risky behaviors have immense adverse societal implications48. Our findings allude to the idea that, besides the investigation of mechanisms for the development and maintenance of an addictive behavior, examining the interplay of mobile phone cues , impulsivity, general executive function and domain specific inhibition abilities may be relevant for the investigation of a broader set of emotional-cognitive deficits and their associated behaviors.Following the I-PACE model45 and we show here that auditory cues on social media can also trigger automatic responses and addictive behaviors. Furthermore, our findings can inform the debate about the concept of “smartphone addiction” or disordered smartphone use. While some argue that people can develop addiction-like symptoms in relation to smartphone use77, others suggest that people develop such symptoms in relation to specific applications, that are mediated, in part  via the smartphone78 and that such symptoms rarely meet addiction criteria79. While we do not resolve this debate here, we show that common features of smartphone, such as auditory cues, can underlie the development and maintenance of strong motivation states that may manifest in addiction-like symptoms in relation to social media use via the smartphone. That is, smartphones can serve as efficient channels that afford and facilitate impulsive behaviors on communication applications by affording the provision of auditory cues. Future research can examine whether and how other smartphone features, such as “waking up” when a new message arrives, contribute to addiction symptom formation and maintenance, and whether these effects are unique to smartphones, or can accrue also in other technologies that mediate communication applications .The use of auditory tones as cues is also noteworthy. First, it extends prior insights on dual-system deficits that underlie automatic responses and addictive behaviors; such studies typically used visual cues80. The recent meta-analysis by Ioannidis, et al.43 illustrates cognitive reductions in individuals showing addictive unspecified Internet use. However, in contrast to the current study that focused on relatively normal users , the meta-analysis findings focused on differences between addicted individuals (those who meet common addiction criteria) and healthy controls. Impairments in general executive functions and especially specific inhibitory control are assumed to occur in later stages of the addiction process24, which may explain the missing direct associations in the current sample including individuals who are at most in an early stage or at risk of developing social-networks-use disorder. This is in line with neuroscientific evidence that disordered social media use symptoms in non-clinical samples are typically not associated with prefrontal brain impairments, which would manifest in reduced executive function and inhibition81. Future research should examine when and how prefrontal brain impairment, reduced executive function, and inhibition abilities contribute to the transition of impulsive non-clinical populations into significant impairments to normal functioning that can be classified as social-networks-use disorder cases.Importantly, the results of the current study revealed no direct relationships between reduced general executive functions, specific inhibitory control, and social-networks-use disorder symptoms. This is in contrast to studies reporting diminished inhibitory control (Stroop and Go-NoGo tasks) in addictive behaviors82. Given our findings (the moderation effects), the strengthening of general executive functions could be an important preventive mechanism for individuals suffering from attention-deficit/hyperactivity disorder or general higher attentional impulsivity. Furthermore, improving specific inhibitory control when confronted with certain cues might be a promising avenue for treatment and for maintaining abstinence60. In addition, because auditory cues can create strong motivation states, removing such cues  can help people prevent and reduce impulsive use of communication applications. Additionally, interactions between impulsivity and general executive functions as well as specific inhibitory control should be kept in mind in the context of clinical treatment83. Neuropsychological training could support the reflective system and respective cognitive resources in suppressing impulsive responses. Future research should also look into stress reduction techniques (e.g. meditation) and executive function enhancement  as a means to improve people’s inhibition abilities in relation to social-networks use.The findings have implications for prevention and treatment programs. It seems that individuals with high attentional impulsivity are at a higher risk for developing social-networks-use disorder symptoms. This is consistent with prior research demonstrating attention-deficit/hyperactivity disorder as a comorbidity of social-networks-use disorder e.g.,60, it can be assumed that impulsive tendencies are associated with a specific neurobiological constitution, which serves as a predisposing factor increasing the susceptibility for developing an addictive behavior , but that this association might be altered with progression in the addiction process. Thus, future research can employ longitudinal designs to examine how the associations we observed here change overtime as the disorder symptoms develop. Second, the auditory Go-NoGo paradigm with addiction-related cues is a newly developed instrument that needs further validation. Future studies could use the paradigm for assessing specific inhibitory control in other behavioral addictions, e.g., the effect of the auditory signal of a slot machine in individuals with gambling disorder. However, the current results illustrate correlations between the auditory Go-NoGo paradigm and the instruments for measuring general executive functions comparable to the study by Wegmann, et al.84, which provides initial evidence regarding the validity and reliability of the paradigm (see Supplementary Information). A further limitation is the low reliability of the subscale “attentional impulsivity” of the Barratt Impulsiveness Scale85. Given that the subscale has five items only, which represent different facets of attentional impulsivity, the internal consistency may not be the best measure for reliability. Since the internal consistency of the subscale in our sample is comparable to previous studies investigating the validity and reliability of the questionnaire e.g.,87, we think that this low reliability is not specific for the current sample and does not indicate a sample-specific systematic measurement error. However, the relatively low internal consistency of this subscale should be taken into account when generalizing the results of our study. Although the questionnaire has been used globally in hundreds of studies, it may be worth considering the psychometric properties of the scale in future studies including a large and representative sample.Several limitations of this study are noteworthy. First, we cannot infer causal relations from the results. Like in the case of substance-use disordersTo conclude, the current findings add to studies emphasizing the relevance of facets of state and trait impulsivity for the development of addictive behaviors (online and offline) by showing respective associations in the context of social-networks-use disorder. They further extend the range of cues that motivate social media use from visual to auditory. However, even if the results emphasize the relevance of investigating the interaction between impulsivity, and general executive functions as well as specific inhibitory control, we have to keep in mind that the effect size of the interaction effect is relatively low, explaining approximately 3% of the variance in a non-clinical sample. We argue, however, that this effect is meaningful, given that typically effects in a clinical sample with a larger variance of symptom severity are stronger compared to effects found in non-clinical samples. Theoretical assumptions about the interactions between personality traits, general executive functions, and specific inhibitory control, and their effects on tendencies towards specific Internet-use disorders are supported in the case of use of online-communication applications.M = 22.76, SD = 7.11). Most of the participants were apprentices or students (83.9%), 49.2% lived in a romantic relationship, and 6.3% had children. The majority (72.3%) reported to have a general qualification for university entrance, and the rest either graduated university (10.8%) or post-high-school institution (16.1%), or provided no information (0.9%). The majority (93 participants) scored non-problematic, 15 participants scored problematic, and 4 participants reached the cutoff for a pathological use on the social-networks-use disorder scale. This non-clinical, convenient sample was recruited by mailing lists and contact lists of the University of Duisburg-Essen. The study was conducted in a laboratory, individual stetting. The procedure was approved by the local ethics committee of the division of Computer Science and Applied Cognitive Sciences at the Faculty of Engineering of the University of Duisburg-Essen in accordance with the Declaration of Helsinki. All participants gave written informed consent by signing a declaration of consent. Germany allows self-reliant participation from the age of 14 onwards in case the content is not morally harmful to youth, which has been approved by the local ethics committee as well. In Germany, university students from the age of 16 are allowed to participate in studies without the confirmation by the parents, since for participation they receive credits for university courses. The current study included participants at the age of 17 and older.In the current study, we investigated 112 participants  aged between 17 and 53 years old (88) and a sample size of N = 112. The respective estimation revealed that a sample size of at least N = 77 would have been necessary to detect a medium-sized effect size with a power of 0.8088.A power analysis using G*Power (version 3.1.9.2) revealed a power of 0.93 given a medium effect size for multiple regression analyses  to 5 (=very often). The sum score can range from 12 to 60, whereby scores > 30 indicate problematic and scores > 37 indicate pathological use90. We use these classifications for descriptive purposes, which are in line with recent studies90, and not in the analysis, given the embryonic stage of classification systems and that there is still no agreed upon cut-offs. Cronbach’s α was 0.859.The severity of symptoms of social-networks-use disorder was measured with the short Internet Addiction Test modified for social-networking sites (sIAT-SNS)85. The BIS-15 consists of 15 items  rated on a four-point Likert scale . The sum scores of the three subscales serve as measures of non-planning , motor , and attentional impulsivity , respectively.Trait impulsivity was assessed with the German short version of the Barratt Impulsiveness Scale named BIS-1591 measuring information processing and resistance to cognitive interference, (2) part A and B of the Trail Making Test93 measuring visual attention and switching, and (3) a computerized version of Nelson’s94 Modified Card Sorting Test (MCST) as a measure of cognitive functions such as rule detection, feedback processing, and cognitive flexibility. In the MCST, errors due to perseveration in the previous rule despite explicit information that the rule has changed are summed as perseverative errors. Other incorrect sorting are summed as non-perseverative errors. We used these different measures, since each of them is assumed to cover slightly different aspects of executive functions see also96.Three instruments for measuring general executive function were used: (1) the Stroop Color-Word-Interference Testet al.84 and the concepts of the visual version by Verdejo-García and Pérez-García97. As auditory cues, we used four different kinds of ringtones of comparable length. The cues included digital  and analog  ringtones, which in part overlap semantically in a systematic manner  by pressing a specific key or not-react  to different auditory cues. Second, each of the four different cues was introduced along with a pictorial presentation of the source of the respective tone . This introductory step aimed to ensure that the cues are recognized correctly as digital or analog ringtones, respectively. In the actual Go-NoGo task, the cues were presented only auditory. Third, participants performed 20 practice trials  in order to become familiar with the task procedure.84. Presentation ® software was used to perform the task .The actual task consisted of four rounds of 20 trials each, resulting in a total of 80 trails. In each round, every cue was presented five times without direct repetition. Before each round, participants were instructed on which two tones they should react by button press , and on which two tones they should not react . Go trials occurred no more than twice in succession. After each round, the associations between the Go and NoGo tones reversed. Performance was measured as the sum of false reactions in Go and independently, in NoGo trials. Both sum scores were additionally separated by type of cue, namely digital and analog ringtones . False reactions in Go trials served as an indicator of deficits in attention and information processing, and false reactions in NoGo trials indicated reduced inhibitory controlThe different reaction patterns and correlations with other tests are similar to those reported for the original auditory Go-NoGo task . Pearson correlation coefficients were calculated to test the bivariate correlations between two variables, with r ≥ 0.01 indicating a small, r ≥ 0.03 indicating a medium, and r ≥ 0.05 indicating a high effect sizeSupplementary Information.


Individuals at ultra-high risk for psychosis (UHR) present with subtle alterations in cerebral white matter (WM), which appear to be associated with clinical and functional outcome. The effect of cognitive remediation on WM organization in UHR individuals has not been investigated previously.In a randomized, clinical trial, UHR individuals aged 18 to 40 years were assigned to treatment as usual (TAU) or TAU plus cognitive remediation for 20 weeks. Cognitive remediation comprised 20 x 2-h sessions of neurocognitive and social-cognitive training. Primary outcome was whole brain fractional anisotropy derived from diffusion weighted imaging, statistically tested as an interaction between timepoint and treatment group. Secondary outcomes were restricted to five predefined region of interest (ROI) analyses on fractional anisotropy, axial diffusivity, radial diffusivity and mean diffusivity. For significant timepoint and treatment group interactions within these five ROIs, we explored associations between longitudinal changes in WM and cognitive functions/clinical symptoms. Finally, we explored dose-response effects of cognitive remediation on WM.A total of 111 UHR individuals were included. Attrition-rate was 26%. The cognitive remediation group completed on average 12 h of neurocognitive training, which was considerably lower than per protocol. We found no effect of cognitive remediation on whole-brain FA when compared to treatment as usual. Secondary ROI analyses revealed a nominal significant interaction between timepoint*treatment of AD in left medial lemniscus (P=0.016) which did not survive control for multiple comparisons. The exploratory test showed that this change in AD correlated to improvements of mental flexibility in the cognitive remediation group (p=0.001). We found no dose-response effect of neurocognitive training on WM.Cognitive remediation comprising 12 h of neurocognitive training on average did not improve global or regional WM organization in UHR individuals. Further investigations of duration and intensity of cognitive training as necessary prerequisites of neuroplasticity-based changes are warranted.ClinicalTrials.gov, identifier NCT02098408. Individuals at ultra-high risk (UHR) for psychosis present with cognitive impairments , intermeMoreover, magnetic resonance imaging studies have revealed widespread, but subtle alterations in WM organization in UHR individuals, typically measured as lower fractional anisotropy . FractioStudies on patients with psychotic disorders have indicated that the relationship between WM-integrity and cognitive functions are altered by severe mental illness , 14. ThiCognitive remediation is a structured method of cognitive training, which is defined as “a behavioral training-based intervention that aims at improving cognitive processes  with the goal of durability and generalisation” . Thus, ca priori ROIs. The regions were selected as the five regions our previous study had shown differentially associated to cognitive functions in UHR individuals. Next, we planned exploratory correlation-analyses between changes in WM-measures in the predefined regions, which showed significant interaction-effects on time*group and changes in clinical symptoms and cognitive functions. We expected correlations between changes in regional WM and changes in clinical symptoms/cognitive functions to be different, when comparing UHR individuals receiving cognitive remediation versus TAU. Finally, we explored a dose-response effect of cognitive remediation on WM.In this randomized clinical trial , we aimed to evaluate the effect of comprehensive neurocognitive and social cognitive remediation in UHR individuals on cerebral WM organization, as assessed by fractional anisotropy. We hypothesized, that 20 weeks of cognitive remediation in addition to treatment as usual (TAU) would increase whole-brain fractional anisotropy in UHR individuals allocated to the intervention, when compared to UHR individuals allocated to TAU. Second, we investigated the effects of cognitive remediation on FA and additional WM-measures in The current study is a sub study of a randomized, assessor-blinded, parallel-group, superiority clinical trial comparing TAU plus 20 weeks of intensive cognitive remediation with TAU . The main trial protocol has been published , and theFollowing baseline assessments, participants were randomly assigned to TAU or TAU plus cognitive remediation for 20 weeks. The randomisation was centralised and computerised with a concealed randomisation sequence carried out by the Copenhagen Trial Unit (CTU). Randomisation was stratified by current use of antipsychotic medication (yes/no) and IQ score (≤100/>100). Block size was blinded. Group allocation was concealed until the statistical analyses of the data had been completed. Investigators blinded to group allocation conducted assessments at 26-weeks (post-treatment) at a site remote from the intervention. Participants were instructed not to disclose their allocation prior to assessments. In case of failure of concealment, the assessment would be conducted by another research assessor. Assessors were psychologists and medical doctors with extensive training in the assessment instruments. Efficacy-analyses on WM were conducted by a blinded researcher.UHR individuals were recruited from psychiatric in-and outpatient facilities in the catchment area of Copenhagen. Individuals were help-seeking individuals aged 18 to 40 years, who fulfilled one or more of the UHR criteria as assessed by the Comprehensive Assessment of At-Risk Mental State (CAARMS) : attenuaThe CAARMS interview and The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and part of the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II) , 30 wereThe third version of the Danish Weschler Adult Intelligence Scale (WAIS-III)  providedwww.mrtrix.org) were used for image processing. Motion parameters were extracted to correct for head motion. Maps of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were calculated. Tract-based spatial statistics (TBSS) . Diffusion-weighted images (DWIs) were acquired using single shot spin-echo echoplanar imaging (EPI) sequence with 30 noncollinear diffusion-weighted  directis (TBSS)  was useds (TBSS) , we compsciculus . MRI quasciculus   . ExercisT-manual . AdherenT-manual  by an exBoth the cognitive remediation group and the control group received TAU, which consisted of the treatment offered by the psychiatric services. TAU involved monitoring of medication, regular contact to primary practitioner delivering supportive counselling, and frequently a more regular psychotherapeutic intervention, such as social skills training, psycho-education, family-groups, supportive group-therapy, or individual therapeutic sessions with a psychologist, but not targeted cognitive remediation.The primary outcome was whole brain fractional anisotropy (FA) as an effect of interaction between timepoint and treatment-group (‘cognitive remediation versus TAU’).Secondary outcomes were measures of white matter: FA, axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) in the five ROIs fornix, medial lemniscus bilaterally, left superior cerebellar peduncle, and left uncinate fasciculus, as an effect of interaction between timepoint and treatment-group (‘cognitive remediation versus TAU’).Planned explorative tests were correlation analyses between WM-changes in the predefined ROIs, which showed significant between-group difference on secondary outcomes, and clinical and cognitive changes as compared between treatment-groups (‘cognitive remediation versus TAU’). Moreover, as motivated by the potential dose-dependent effect of cognitive remediation on WM , we postThe main trial planned to enroll 126 UHR individuals. Power-calculation estimating sample-size was based on cognitive outcomes for the main trial  was tested for normality, and group differences were tested using general linear modelling (GLM) co-varied for age and gender. Group differences in ordinal data  were tested using the Mann–Whitney U test or Fisher’s exact test. Nominal data were tested using Pearson’s χ2 test. Group differences on baseline whole brain and regional FA were tested using univariate GLM and co-varied for age, gender, and relative and absolute head motion in the scanner.Main analyses of treatment effect of cognitive remediation on primary and secondary outcomes were conducted using linear mixed models with repeated measurements and an unstructured covariance matrix as recommended for RCTs , assessiPlanned exploratory correlation analyses between changes in WM-measures on secondary outcomes and changes in clinical symptoms and cognitive functions, respectively, were conducted with bivariate correlation analyses using Pearson’s r or Spearmans rho as appropriate. In order to examine correlations specifically related to a potential treatment effect, testing was conducted on the predefined ROIs, which had shown an interaction-effect on time*group. Change-scores were calculated as: [numerical follow-up score – numerical baseline score]. Testing was performed with and without extreme outliers. If the main results remained unaffected, outliers were included in the analyses. Results were corrected for multiple comparisons using Bonferroni correction, and the significance threshold was set at P ≤ 0.001 (0.05/(1 ROI x 6 cognitive tests x 4 WM-measures x 2 treatment-groups)).Exploratory post-hoc analyses to test potential dose-response effect of cognitive remediation at the follow-up were conducted with linear mixed models with repeated measurements and an unstructured covariance matrix, with covarying for number of attended neurocognitive training-hours. All analyses were covaried for age, gender, IQ, antipsychotic medication, and head motion in scanner (relative/absolute).All analyses were performed using IBM SPSS Statistics for Windows, Version 25.0, Armonk, NY, and the significance level was set to 0.05 (two-sided).The main trial results have been described elsewhere  . In shorCognitive remediation and TAU-groups did not differ significantly on sociodemographic variables  in left medial lemniscus, and changes in CANTAB IED   for the cognitive remediation group, but not for TAU  did not survive adjustment for multiple comparisons. The lack of global and regional WM-changes as a result of cognitive remediation we found are in line with the results from the main trial , which dThe result could, beyond the conclusion of no effect of cognitive remediation on WM, be explained by the low number of neurocognitive training sessions. The average of 12 h of neurocognitive training is considerably lower than the recommended dosage (25–30 h) assumed necessary for driving cognitive improvements . A contrExploratory analyses revealed mental flexibility to be correlated with a change of left medial lemniscus AD in the cognitive remediation group, but not in the TAU-group. Although our observation is marginal and should be interpreted very cautiously, medial lemniscus is part of the cerebello-thalamocortical connections [CTC ], which A strength of this study is that it was undertaken as part of a high quality randomized, assessor-blinded clinical trial. Limiting the study is the moderate attrition-rate, along with the low number of mean neurocognitive training hours, which impede reaching firm conclusions about the effect of cognitive remediation delivered per the trial-protocol. Furthermore, sample-size was calculated on different outcomes from the main trial, which is a weakness in our study-design. However, this study presents a large sample-size compared to previous studies examining neuroplastic effects of cognitive interventions.Cognitive remediation comprising 12 h of neurocognitive training on average did not improve global or regional WM organization in UHR individuals. Further investigations of the duration and intensity of neuroplasticity-based cognitive training as necessary prerequisites of WM-changes are warranted.tina.dam.kristensen@regionh.dk.The data sets presented in this article are not readily available because: Not allowed by the Danish Data Protection Agency. Requests to access the datasets should be directed to TK, The studies involving human participants were reviewed and approved by The study protocol was approved by the Committee on Health Research Ethics of the Capital Region Denmark (study: H-6-2013-015) and the Danish Data Protection Agency (RHP-2014-009-02670). The patients/participants provided their written informed consent to participate in this study.MN, LG, and BF conceived and designed the trial protocol. MN, BG, LG, CH, TK, and CW raised the funding. JJ and BF supervised the data collection. BE, RM, and CP supervised the study. JR processed MRI-data. TK conducted the analyses supervised by CH. TK wrote the initial draft. All authors contributed to the article and approved the submitted version.The study was funded by The Danish Council for Independent Research (DFF-4004-00314); TrygFoundation (108119); the Mental Health Services in the Capital Region of Denmark; the research fund of the Capital Region of Denmark; the Lundbeck Foundation Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS (R155-2013-16337). CP was supported by a NHMRC Senior Principal Research Fellowship (1105825) and by a grant from Lundbeck Foundation (R246-2016-3237).BE is part of the Advisory Board of Eli Lilly Denmark A/S, Janssen-Cilag, and Takeda Pharmaceutical Company Ltd; and has received lecture fees from Bristol-Myers Squibb, Otsuka Pharma Scandinavia AB, Eli Lilly Company, and Lundbeck Pharma A/S. BG is the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), which is partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. Her group has also received a research grant from Lundbeck A/S for another independent investigator-initiated study. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. She has no other conflicts to disclose.The remaining 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.


The world is currently facing a serious health burden of waterborne diseases, including diarrhea, gastrointestinal diseases, and systemic illnesses. The control of these infectious diseases ultimately depends on the access to safe drinking water, properly managed sanitation, and hygiene practices. Therefore, ultrasensitive, rapid, and specific monitoring platforms for bacterial pathogens in ambient waters at the point of sample collection are urgently needed. We conducted a literature review on state-of-the-art research of rapid in-field aquatic bacteria detection methods, including cell-based methods, nucleic acid amplification detection methods, and biosensors. The detection performance, the advantages, and the disadvantages of the technologies are critically discussed. We envision that promising monitoring approaches should be automated, real-time, and target-multiplexed, thus allowing comprehensive evaluation of exposure risks attributable to waterborne pathogens and even emerging microbial contaminants such as antibiotic resistance genes, which leads to better protection of public health. Access to adequate water, sanitation, and hygiene (WASH) has long been a significant public health concern and an international development policy. According to the World Health Organization, global mortality attributable to waterborne diseases is estimated to be > 2.2 million per year, among which about 1.4 million are children, resulting in nearly $12 billion per year of economic loss worldwide [Microbial detection techniques are usually classified into phenotypic methods and molecular methods. Culture-based methods as the mainstream of phenotyping have the advantages of cost-effectiveness and simplicity, and remain the gold standard for bacterial monitoring and identification. However, it requires days for culture-based methods to provide conclusive results, which greatly hampers their applications in water quality monitoring . MoleculSalmonella enterica serovar Typhi (S. typhi) in water. Here, we review representative technologies categorized into cell-based methods, nucleic acid amplification methods, and biosensors. We also further discuss the needs of future developments on microbial monitoring platforms in the underdeveloped parts of the world.Overall, microbial pathogen detection is urged to be ultrasensitive, rapid, simple, low-cost, field-deployable, and easily operable by undertrained individuals for applications in environmental surveillance. Over the past years, numerous research advances have been made in such integrated platform for detection and identification of bacterial pathogens including but not limited to Compared to molecular-based detection platforms that target specific nucleic acids or proteins, cell-based detection methods offer direct identification and measurement with relative simple workflows . Utiliza2)–dependent cells in nonpreferable growing environment with limited CO2, humidity and a non-37°C temperature. Even for uncultivatable microbial species in various environments, an isolation chip with miniature diffusion chambers was developed to achieve parallel cultivation and isolation [Miniaturized cell cultivation techniques based on microfluidic devices and Lab-on-a-Chip technologies consume less fluid, take less volume, and usually have higher tolerance toward ambient conditions, thus reducing the total cost and time for bacterial analysis . One exasolation . HoweverCompared to cell culture, flow cytometers (FCMs) for direct cell counting enable fast quantification of the total bacterial community in the environment with high reproducibility and relatively small standard deviation. More importantly, many commercial FCMs are available for adaptations and the setup of FCM is suitable for automation, making FCM a great candidate for online routine bacterial monitoring . Besmer Escherichia coli was back-calculated [Besides miniature cell cultivation and FCM, other online cell-based sensing methods have also been developed. A real-time sensor using multiangle light scattering (MALS) technology was developed by Sherchan et al. By comparing the light scattering patterns after using a laser beam to strike particulates in water  with light scattering patterns in the computerized database, data obtained was characterized and the load of injected lculated . Due to lculated . Furtherlculated . Tables Many methods mentioned in the section have been successfully implanted for days or even months with full automation, and can be constructed easily with commercial instruments. However, the sensitivity of these methods can be easily influenced by different environmental factors and the detection limit is relatively high. Moreover, it is challenging to identify specific pathogens solely based on cell-level analysis, not to mention their genetic information. Therefore, further molecular level detections are needed to secure higher sensitivity and specificity.Compared to phenotyping methods, molecular methods typically based on the quantification and identification of specific genomic segments of the pathogen’s genomes allow rapid, highly specific, and more sensitive detection, which better fit the expectations of timely monitoring and effective surveillance of aquatic pathogens in a range of water environmental settings. In this section, advances in monitoring methods based on PCR and loop-mediated isothermal amplification (LAMP) are respectively discussed.E. coli in milk matrix [Flavobacterium psychrophilum in filtered water samples [The major drawback of PCR-related methods usually lies in their long response time and limited portability, since they rely on fussy thermal cycling and require additional equipment to detect the amplification products . Anotherk matrix . Detaile samples . The stuEscherichia coli, Proteus hauseri, Vibrio parahemolyticus, and Salmonella subspecies were simultaneously detected with high selectivity and sensitivity, as shown in E. coli, Salmonella species, and Vibrio cholerae in chicken meat were successfully detected with the sample-to-response time of < 1 hour [E. coli, Enterococcus faecalis, and S. Typhi [E. coli and S. Typhi spiked in unprocessed pond water and seawater could be completed within 1 hour with the sensitivity down to single cell [E. coli and S. Typhi) and viruses (bacteriophage MS2) were immobilized with LAMP reagents in polyethylene glycol hydrogel matrix and were then amplified [E. coli and S. Typhi, relevant detection limits were not reported, which needs further validation. More detailed information about all of the above-mentioned LAMP-based systems can be found in LAMP is one of the most commonly used isothermal amplification methods , 38 and < 1 hour . Moreove< 1 hour . Lin et S. Typhi . Lin et gle cell . Huang emplified . AlthougBiosensors are analytical devices that consist of target recognition molecules and signal transducers to detect the interaction between the recognition molecules and the specific target. Innovations in recognition molecules and signal transduction methods, as summarized in Staphylococcus aureus [2-MIL-53(Fe), functioned as a water-dispersible and stable matrix, and also as an optical transducer whose reduction in photoluminescence was proportional to target bacterial concentration. This type of stable and economical biosensor with notable quantification performance could be an attractive solution to scale up for point-of-sample-collection detection. However, it should be noted that such target-specific bacteriophage is not available for every bacterial pathogen. As an alternative class of recognition molecules, aptamers (synthetic single-stranded oligonucleotides) can fold into designed 3D structure to bind specific targets. The sequence of the aptamers can be selected in vitro through systematic evolution of ligands by exponential enrichment, and the easily synthesized aptamers have high stability, specificity, and affinity to the targets [The novel combination of target recognition molecules and new substrates for their immobilization has been demonstrated to boost the sensitivity of biosensors and the applicability in-field applicability. For example, Bhardwaj et al conjugated bacteriophage onto metal-organic framework (MOF) for specific quantification of s aureus . The MOF targets .E. coli and Salmonella Typhimurium. However, these commercial kits mainly use colorimetric detection based on nanoparticle aggregation caused by antibody–antigen reaction, which takes hours to give qualitative results [Salmonella coated Dynabeads and paper-based sandwich immunoassay using the detection enzyme β-galactosidase, which forms a red-violet product with chlorophenol red galactopyranoside for colorimetric detection. The immunomagnetic separation enabled species-specific capture and enrichment from a 1-mL sample [Integration of nanomaterials with paper microfluidics has led to development of convenient portable biosensor devices. Commercial test strips, such as RapidCheK and Watersafe, are available for environmental detection of  results . Using a results . HoweverL sample . AlthougE. coli–specific immunoassay on a microfluidic chip [E. coli followed by qPCR detection of total bacterial DNA [E. coli and microfluidic chip-based LAMP detection [For automated and low-cost bacterial pathogen monitoring, immunoassay-based electrochemical biosensors are approaching commercialization, owing to the consistent assay performance and easily automated instrumentation . For exadic chip . The insrial DNA . Li et aetection . The latetection , 34. MorPortable systems for rapid, ultrasensitive, and specific environmental pathogen monitoring are essential in risk assessment, outbreak prevention, and vaccine distribution for low-resource settings. Recent advances in cell-based, nucleic acid–based, and biosensor-based platforms are reviewed here, with a focus on promising solutions for bacterial pathogen detection in ambient waters at the point of sample collection. Among the reviewed technologies, miniaturized PCR instruments is the most well-developed and commercialized method that is readily deployable in field for sensitive and specific pathogenic bacterial detection, as summarized in


Natriuretic peptides, brain natriuretic peptide (BNP), and N-terminal probrain natriuretic peptide (NT-proBNP) are mainly known as diagnostic markers for heart failure with high diagnostic and prognostic values in the general population. In patients who are undergoing hemodialysis (HD), changes in NT-proBNP can be related to noncardiac problems such as fluid overload, inflammation, or malnutrition and can also be influenced by the dialysis characteristics. The current review aimed to summarize findings from studies on the association between NT-proBNP and malnutrition in HD patients. Articles published after 2009 and over a ten-year period were considered for inclusion. We first briefly discuss the traditional functions of NT-proBNP, and after, we describe the functions of this prohormone by focusing on its relation with protein energy wasting (PEW) in HD patients. Mechanisms that could explain these relationships were also discussed. Overall, 7 studies in which the investigation of the relations between NT-proBNP and nutritional status in HD patients were among the main objects were taken into account. NT-proBNP levels correlated with several factors described in the 4 categories of markers indicative of PEW  and/or were associated with PEW. Interactions between several parameters could be involved in the association between NT-proBNP and malnutrition with a strong role of weight status. NT-proBNP is elevated in HD patients and is associated with malnutrition. Nevertheless, the prognostic value of NT-proBNP on nutritional status should be evaluated. Uremic malnutrition, also called malnutrition inflammation complex syndrome or protein energy wasting, corresponding to a decrease in energy and body protein, is a common problem in patients with end-stage renal disease (ESRD) undergoing HD and has been consistently associated with mortality in different populations –5.Brain natriuretic peptide (BNP) is synthesized mainly in the heart as a proBNP that is further cleaved into bioactive BNP and biologically inactive NT-proBNP . Both BNThe current review aimed to summarize findings from studies on the association between NT-proBNP and malnutrition in HD patients.For this review, we reviewed the literature using PubMed, Medline, and Scopus with the following search terms: N-terminal probrain natriuretic peptide (NT-proBNP), nutritional status, malnutrition, and hemodialysis (HD) in humans. We also searched in the selected articles and took into account some of the relevant references cited by the authors. Mechanisms that could explain these relationships were also discussed while also taking the results of some animal studies into account.Articles published after 2009 and over a ten-year period, in adults (>18 year of age), were considered for inclusion.We first briefly discuss the characteristics and traditional functions of NT-proBNP, and after, we describe the functions of this prohormone by focusing on its relation with protein energy wasting (PEW) in patients undergoing maintenance HD.During the period taken into account in this review, we found 7 studies in which the investigation of the relations between NT-proBNP and nutritional status in HD patients were among the main objects –17. ThesThe levels of the prohormone vary according to the population studied. NT-proBNP is cleared by the kidney and, in patients with CKD, especially those on HD, levels of NT-proBNP are usually increased as a consequence of increasing secretion and decreasing renal clearance .Thus, elevated levels of the prohormone are often observed in HD patients without clinical evidence of cardiovascular disease. These high NT-proBNP levels in patients with renal dysfunction , 18–20 wThe influences of age, gender, body mass index (BMI), time of the dialysis session during the week, time of measurement of NT-proBNP before or after a hemodialysis session, dialysis characteristics, and membrane type have been reported –24.In some studies, blood concentrations of NT-ProBNP were associated with hypervolemia or fluid overload , 25–28. Inflammation also influences NT-proBNP levels , 17, 29.Studies on maintenance of HD patients have reported the association between NT-proBNP levels and malnutrition by subjective global assessment (SGA), malnutrition-inflammation score (MIS), or markers defined in the International Society of Renal Nutrition and Metabolism (ISRNM) nomenclature –17.Globally, SGA is a tool that uses 5 components of a medical history  and 3 components of a brief physical examination  to assess nutritional status . The MISThe practice guidelines and criteria for evaluating nutritional status in ESRD patients recommend the use of nomenclatures for PEW , 33. In To study these relationships, we first focused on the relation between the main parameters described in the 4 categories of factors for PEW identification according to the ISRNM nomenclature, and after, we considered the relation with malnutrition status in each of the studies.Lower BMI, body fat, and unintentional weight loss over time are included in this category of nutritional markers in the ISRNM nomenclature.(1) Body Weight-BMI. Inverse relationships between BMI and circulating levels of NT-proBNP have been demonstrated, and lower BMI has been associated with higher NT-proBNP levels in subjects with and without heart failure [ failure , 34–38 a failure , 27, 39.(2) Weight Loss. Weight loss is known to increase natriuretic peptide levels [e levels –43. In He levels . NT-proBe levels , and pose levels .(3) Body Fat. In HD patients, fat tissue index decreased across NT-proBNP quartiles [uartiles , and lowuartiles . These auartiles .Assessment of nutritional status and especially evaluation of muscle mass is essential for the identification of patients at risk for the development of PEW . IndirecSome biochemical indicators have been proposed for the diagnosis of PEW, and serum albumin, serum prealbumin (transthyretin), and cholesterol have been studied as nutritional markers in CKD patients . NegativIn the ISRNM nomenclature, low dietary intake was considered in the presence of unintentional low dietary protein intake <0.8 g/kg/day for at least 2 months for dialysis patients or unintentional low dietary energy intake <25 kcal/kg/day for at least 2 months . The norThe 7 studies in which the investigation of the relations between NT-proBNP and nutritional status in HD patients were among the main objects are summarized in In 222 HD patients, the association between NT-proBNP, PEW, and inflammation was evaluated. NT-proBNP was analyzed in plasma by an immunometric assay. Patients presenting with an SGA score of 2–4 were defined as malnourished. A NT-proBNP level above 9,761 pg/ml was associated with PEW even following adjustment for age, dialysis vintage, inflammation, and Davies score .In 97 HD patients, the relationship between serum level of NT-proBNP and nutritional status, inflammation, and hydration was investigated. NT-proBNP was measured by an immunoassay. The nutritional status was evaluated with specific markers including BMI, albumin, and nPCR. NT-proBNP was only moderately associated directly with hydration status but was extremely elevated in patients with intensive catabolism .In 44 HD patients, nutritional status was assessed using subjective SGA and MIS. NT-proBNP was measured by immunoassay, malnutrition was accompanied by volume overload and associated with increased log NT-proBNP, and these levels were independently associated with increased left ventricular mass index . The autA prospective study was performed in 211 HD patients to analyze NT-proBNP variability and the factors predicting this variability. Malnutrition was one of the studied factors. NT-proBNP was measured by an immunometric assay. Longitudinal changes in NT-proBNP were associated with changes in nutritional status. Patients with wasting and patients with congestive heart failure had significantly higher NT-proBNP levels than patients without these conditions .P = 0.006). The TC level was the lowest in Q4 . But, although the data showed a relation of NT-proBNP with nutritional status, this link was less conspicuous than the link between NT-proBNP and hydratation [A study aiming to establish the usefulness of NT-proBNP for hydration assessment and the relation of NT-proBNP with the nutritional state and prognosis of survival was conducted in 321 HD patients. NT-proBNP was measured by immunoassay. Bioimpedance analysis was used. Patients were classified according to quartiles of NT-proBNP. NT-proBNP correlated negatively with practically all nutritional indices including serum albumin, cholesterol, and BMI. The highest albumin level was present in Q1 , NT-proBNP levels were measured by fully automated electrochemiluminescence. Nutritional status and changes in muscle mass were evaluated by subjective global assessment, %CGR, and creatinine index. NT-proBNP was significantly higher in HD patients with PEW. Prevalent HD patients with higher NT-proBNP  showed a high prevalence of malnutrition , decreased levels of creatinine, and decreased creatinine index. The authors suggested that compared with serum albumin, measurement of NT-proBNP could be a superior predictor of muscle loss in patients on HD. Patients with the highest NT-proBNP also showed a high prevalence of cardiac events and malnutrition [In a prospective observational study with one-year follow-up in a cohort of prevalent HD patients , and nPCR < 0.8 g/kg/day. NT-proBNP was assessed using a chemiluminescence immunoassay. The frequency of individuals with low serum albumin level was higher in those with NT-proBNP ≥6,243 pg/mL than in the others . A negative correlation between log NT-proBNP and nPCR was also found . High levels of NT-proBNP  were independently associated with PEW. NT-proBNP concentrations increased with PEW component number (on the basis of 1 in each of the 4 listed categories of PEW markers) [The association between PEW and NT-proBNP was evaluated in a cross-sectional study performed in 207 Afro-Caribbean HD patients. One component in each of the 4 categories for the wasting syndrome (according to the ISRNM nomenclature) was retained: serum albumin <38 g/L, BMI < 23 kg/mmarkers) .In some other studies, authors found associations between NT-proBNP and signs of wasting, but the investigation of these relations was not the main objects in these studies , 48.A direct effect of PEW on the level of NT-proBNP by affecting ventricular remodeling in HD patients has been suggested .Complex interactions between NT-proBNP, malnutrition, inflammation, and fluid overload have been reported in HD patients , 49, 50.Several parameters among 4 established categories  for the definition of PEW according to ISRNM are separately associated with NT-proBNP. Interaction between some of these parameters could be involved in the association between NT-proBNP and malnutrition with a strong role of weight status . In factOther hypothesis, suggested in patients without CKD, might be involved in HD patients.Several hypotheses have been proposed concerning the association between high NT-proBNP and PEW.Adipose tissue could also play an important role. It has been shown that NP display a lipolytic effect in adipose tissue , 54 and In summary, the data suggest that NT-proBNP correlates with the indices of protein energy wasting and malnutrition. Therefore, this marker seems to be useful in the evaluation of nutritional status in hemodialysis. However, limitations in most of the above studies include the small sample size, the isolated measurements of the biomarker, the lack of precision regarding the time of NT-proBNP measurement in some studies, and the potential biases related to the methods used for PEW assessment. Factors indicating the presence of PEW can also be induced by inflammatory processes. Thus, the clinical context should be taken into account for the interpretation of elevated NT-proBNP levels. Since high NT-proBNP is primarily a marker of cardiac dysfunction, the increased levels of the prohormone must draw attention to cardiac function but also to nutritional status. Nevertheless, we must highlight the need to evaluate the prognostic value of NT-proBNP for malnutrition in hemodialysis in further studies.


Hypertension associated with the increased risk of severe illness, which was not modified by other demographic factors, such as age, sex, hospital geological location and blood pressure levels on admission. More attention and treatment should be offered to patients with underlying hypertension, who usually are older, have more comorbidities and more susceptible to cardiac complications.Hypertension represents one of the most common pre-existing conditions and comorbidities in Coronavirus disease 2019 (COVID-19) patients. To explore whether hypertension serves as a risk factor for disease severity, a multi-centre, retrospective study was conducted in COVID-19 patients. A total of 498 consecutively hospitalised patients with lab-confirmed COVID-19 in China were enrolled in this cohort. Using logistic regression, we assessed the association between hypertension and the likelihood of severe illness with adjustment for confounders. We observed that more than 16% of the enrolled patients exhibited pre-existing hypertension on admission. More severe COVID-19 cases occurred in individuals with hypertension than those without hypertension (21%  Coronavirus disease 2019 (COVID-19) emerged in December 2019 and has triggered a health crisis in the world . The cruvs. 26.2% in those younger .This study had several limitations. Firstly, given the retrospective nature of this study, some parameters were not available in all patients. For example, we did not monitor dynamic changes in blood pressure during hospitalisation. Instead, we analysed the control rate of hypertension patients relying on blood pressure records on admission. Secondly, we defined underlying hypertension mainly based on the medical record, and we did not take the underestimation of hypertension into account under the COVID-19 emergency. So, the underlying hypertension of some patients might not be diagnosed and was grouped into the non-hypertension cohort. Thirdly, the sample size of this cohort is relatively small and restricted in China, with a low rate of outcome events and comorbid hypertension. Thus, the conclusion should be further confirmed by large-scale prospective cohort studies in ethnically diverse cohorts.In this multi-centre observational study involving 498 patients hospitalised due to COVID-19 outside Wuhan city, we confirmed previous observations suggesting that COVID-19 patients with underlying hypertension have a poorer prognosis than those without hypertension. We identified no harmful association of pre-existing hypertension with COVID-19 severity, after adjusted for confounders.


Shape-memory alloys such as nitinol are gaining popularity as advanced materials in the aerospace, medical, and automobile sectors. However, nitinol is a difficult-to-cut material because of its versatile specific properties such as the shape-memory effect, superelasticity, high specific strength, high wear and corrosion resistance, and severe strain hardening. Anunconventional machining process like wire-electrical-discharge-machining (WEDM) can be effectively and efficiently used for the machining of such alloys, although the WEDM-induced surface integrity of nitinol hassignificant impact on material performance. Therefore, this work investigated the surface integrity of WEDM-processed nitinol samples using digital microscopy imaging, scanning electron microscopy (SEM), and energy-dispersive X-ray (EDX) analysis. Three-dimensional analysis of the surfaces was carried out in two different patterns  andrevealed that surface roughness was maximalat the point where the surface was largely exposed to the WEDM dielectric fluid. To attain the desired surface roughness, appropriate discharge energy is required that, in turn, requires the appropriate parameter settings of the WEDM process. Different SEM image analyses showed a reduction in microcracks and pores, and in globule-density size at optimized parameters. EDX analysis revealed the absence of wire material on the machined surface In another study, Chaudhari et al. [on, Toff, and current are the main influencing factors for the response variables of the material-removal rate(MRR), surface roughness (SR), and microhardness for the WEDMof nickel-based alloys. Soni et al. [on, while both values decreased with increasing Toff and servo voltage. Researchers used brass and copper wires as electrodes, and studied their effect on the surface integrity of amachinedSMA surface [Shape-memory alloys (SMAs) have been extensively used in the biomedical, aerospace, automobile, robotics fields, and in some other important industrial applications  because of their shape-memory effect, high wear resistance, superelasticity, high corrosion resistance, biocompatibility, and high actuation strain ,2,3. SMAi et al.  concludei et al.  explored surface ,20. To tRecently, we demonstrated aparametric optimization study ofWEDM process parameters for the machining of nitinol shape-memory alloys using a heat-transfer-search algorithm . Pulse-oon, Toff, and current were the three most important process parameters that were chosen for machining. The experiment was conducted on a Concord WEDM machine DK7732 with dielectric fluid as EDM oil. Reusable molybdenum wire with a diameter of 0.8 mm was used as a tool electrode. A side-flushing mechanism (from top) was used in the current study during the WEDM process, as shown in In the current study, the surface integrity of the machined surface of anitinol shape-memory alloy was carried out by using the WEDM process. 3 + 4 mL HF + 82 mL H2O). A VEGA TESCAN-make scanning electron microscope  was used for surface morphology. The working distance between electron gun and workpiece surface was kept at 26.89 mm with measuring energy of 20 KV. Energy dispersive X-ray analysis  was carried out by connecting the instrument with Oxford software with anSEM machine. Thethree-dimensional (3D) superdepth digital microscope is an accurate and precise instrument that has a noncontact-type probe. Hence, a 3D superdepth digital microscope  wasused to measure the surface morphology of the WEDM-machined sample at various locations. A similar kind of the 3D analysis of a friction-stir-process Mg alloy wasrecently reported . The ariThe top surface of the WEDM processed sample along with SR values in µm is shown in The surface morphology of the WEDM surfaces of themachinednitinol sample is presented in The parameter settings for the sample, as shown in The present study focused on analyzing the surface integrity of a WEDM sample obtained at optimized parameter settings. Resultsindicated that, during the WEDM of nitinol SMA, appropriate discharge energy is required to achieve optimalSR. Greater discharge energy at the surface in contact with the wire showed increased surface roughness in areas where EDM oil was used in a good amount during machining. The selected parametersat optimized conditions  indicated a defectfree surface, along with a decrease inthe size and number of globules. The selected parameters were able to machine the alloy without wire erosion, which was formulated from EDX analyses. EDX analysis shows the presence of nickel and titanium elements of workpiece and little amount of oxygen. Work surface has been observed without the deposition of wire material. This result showed the suitability of the parameters and wire material (molybdenum) for the machining of nickel–titanium shape-memory alloys.


N = 1,113) were recruited from eight Universities in Shenyang, China. Of them, 146 did not effectively respond to the questionnaires. Thus, 967 participants were eligible for the final analysis. The mediating or moderating role of self-efficacy in the anxiety-PSU relationship was explored using hierarchical multiple regression. Then the mediation model was further verified using the SPSS macros program (PROCESS v3.0). Our results showed that anxiety symptoms was positively correlated with PSU , while self-efficacy was negatively correlated with anxiety symptoms and PSU . Self-efficacy partly mediated the relationship between anxiety symptoms and PSU, which accounted for ~17.5% of the total effect that anxiety symptoms have on PSU. However, the moderating effect of self-efficacy on the anxiety-PSU relationship was insignificant. In summary, our findings suggested that self-efficacy partly mediates but not moderates the link between anxiety symptoms and PSU among Chinese University students. Therefore, multicomponent interventions should be made to restrict the frequency of smartphone usage, enhance the level of self-efficacy, and thus promote the mental health status of University students.Problematic smartphone use (PSU) is a novel manifestation of addictive behaviors. It is frequently reported to be correlated with anxiety symptoms among University students. However, the underlying mechanism has not yet been thoroughly studied. Whether the association between anxiety symptoms and PSU is mediated or moderated by self-efficacy remains unclarified. A cluster sampling cross-sectional study was thus conducted to explore the potential mediating or moderating effect of self-efficacy in Chinese University students. Participants ( A smartphone is no longer simply considered a “mobile phone” but rather a portable and omnipotent pocket computer. Owning smartphones enables us to keep in touch with our friends anywhere at any time, helps us to stay organized, guarantee stress-free travel through navigation apps, helps us to cope with emergencies, offers easy access to information and technology, and even promotes health through health-related apps . Given tHowever, smartphone usage is a double-edged sword, as it helps to facilitate our daily lives but might also cause a series of worrisome problems due to problematic smartphone use (PSU). PSU has been previously defined as excessive use of a smartphone that is accompanied by functional impairments in daily living, and substance addiction-like symptoms . Youths,Anxiety is one of the most commonly investigated mental health variables related to PSU –17. A reSelf-efficacy refers to individuals' beliefs in their own capabilities to execute behaviors necessary to produce specific performances . Belief Our primary aim was to clarify the role of self-efficacy in explaining the relationship between anxiety symptoms and the severity of PSU based on a sample of Chinese University students. We were particularly interested in the mediating and moderating effect of self-efficacy.The most widely accepted theoretical framework underlying the PIU or PSU is the I-PACE model , 26–30. Anxiety symptoms severity should be positively correlated with the severity of PSU. The association between anxiety symptoms and PSU severity has been previously confirmed by many studies . Finally, a total of 1,113 undergraduate students were then randomly recruited. Of them, 146 were excluded due to incomplete responses, with at least 10% of the items not answered. Thus, only 967 subjects were eligible for the final analysis, resulting in an effective response rate of 86.9%. The current study was a school-based cross-sectional study using a cluster random sampling strategy. From November 2018 to March 2019, students from eight universities were randomly selected from Shenyang city located in northeastern China. Participants came from medical universities, normal universities, and other majors. Their participation in our survey was voluntary, and they were free to withdraw at any time without being forced to complete the tasks. Electronic informed consent was obtained from each participant before the investigation, and then all participants were asked to answer self-rating questionnaires using the Wenjuanxing Online Survey System  developed by Zung was employed to assess the level of anxiety symptoms among University students during the past week . The SASThe Smartphone Addiction Scale-Short Version (SAS-SV)  was emplSelf-efficacy was assessed using the General Self-Efficacy Scale (GSES) designed by Schwarzer et al. . The selP < 0.05 considered statistically significant. The group differences of continuous variables were tested by t-test or ANOVA as appropriate. The post-hoc analysis for multiple comparisons was conducted using Dunnett's t-test. A correlation matrix was examined using Pearson's correlation analysis among PSU, self-efficacy, and anxiety symptoms. Missing values were imputed by multiple imputation method.All statistical analyses were performed using IBM SPSS Statistics for Windows . All tests were single-tailed, with The mediating or moderating role of self-efficacy in the anxiety-PSU relationship was explored using hierarchical multiple regression. All demographic variables that were significantly associated with PSU by univariate linear regression analysis served as control covariates. Category variables were transformed into dummy variables. Furthermore, continuous independent variables and mediator/moderator (self-efficacy) were centralized before hierarchical multiple regression. The covariates, independent variables, and mediator/moderator were sequentially included in the regression models in three steps. To explore the potential mediating role of self-efficacy, the covariates were added in step 1; anxiety symptoms was added as the independent variable in step 2; self-efficacy was added as a mediator in step 3. Similarly, to explore the potential moderating role of self-efficacy, the covariates were added 1 in step 1. However, in step 2, both anxiety symptoms and self-efficacy were included. The product of anxiety symptoms and self-efficacy was added in step 3. Multicollinearity was examined by the variance inflation factor (VIF). A VIF value>10 indicated the existence of a serious multicollinear problem.*b) were checked. The bias-corrected and accelerated 95% confidence interval (BCa 95%CI) for the indirect effect was also calculated. The mediating effect is considered statistically significant if the 95%CI of indirect effect (path a*c) does not contain zero.The potential mediating role of self-efficacy was further verified using the SPSS macros program (PROCESS v3.0 by Andrew F. Hayes) with 5,000 bootstrap sampling . The conThe demographic characteristics of the study participants and group differences are shown in P < 0.01; anxiety symptoms: 53.89 vs. 52.37, P < 0.05), but no sex difference was found regards to self-efficacy. The levels of PSU, self-efficacy, and anxiety symptoms significantly varied across the different grades of University students (P < 0.01). Monthly living expenses higher than 1,000 yuan were associated with elevated levels of PSU and self-efficacy, but not with anxiety symptoms. The PSU scores were significantly different between students from urban and rural areas . Finally, University students who had no siblings tended to have higher levels of anxiety disorders than those who had siblings .Female University students had higher PSU and anxiety symptoms than male University students . In contrast, self-efficacy was negatively associated with both anxiety symptoms and PSU .The mean values and bivariate correlations between continuous variables are shown in R2 = 0.113, ΔR2 = 0.120, P < 0.01). Among them, age, sex, grade, and monthly living expense were significantly related to PSU severity. In step 2, after adjusting for control covariates, anxiety symptoms was positively associated with PSU . Anxiety symptoms explained additional 8.3% of the variance of PSU. In step 3, self-efficacy was negatively associated with PSU , which accounted for additional 2.9% of the variance. When self-efficacy was added to the model, the absolute value of the regression coefficient of anxiety symptoms on PSU was decreased from 0.292 to 0.241. Therefore, self-efficacy might probably serve as a mediator in the association between anxiety symptoms and PSU among University students.As shown in c = 0.292, P < 0.01). Second, the indirect effect of anxiety symptoms on PSU via self-efficacy was found statistically significant . Since the confidence interval for indirect effect did not include the null value, then we could conclude that self-efficacy played a mediating role between anxiety symptoms and PSU. Finally, when self-efficacy was included in the model as a mediator, the direct effect of anxiety symptoms on PSU (path c′) remained statistically significant . Therefore, self-efficacy had a partial mediating effect on the association between anxiety symptoms and PSU for University students. The mediation of self-efficacy accounted for ~17.5% (a*b/c) of the total effect. The visualization of the model was demonstrated in Regarding the implications of hierarchical multiple regression, the mediation of self-efficacy in the anxiety-PSU relationship was further validated using PROCESS v 3.0. P < 0.01), while self-efficacy was negatively associated with PSU . The model fits were significantly improved by anxiety symptoms and self-efficacy . In step 3, the interaction term of anxiety symptoms and self-efficacy was not statistically significant . Thus, self-efficacy could not moderate the relationship between anxiety symptoms and PSU among University students.As shown in The main findings of this study were as follows. A higher level of anxiety symptoms was significantly correlated with more severe PSU. There was a significantly negative association between self-efficacy and anxiety symptoms. Furthermore, self-efficacy can mediate the association between anxiety symptoms and PSU. Nevertheless, the moderating effect of self-efficacy on the association between anxiety symptoms and PSU was insignificant. To the best of our knowledge, this was the first study to explore the mediating/moderating effect of self-efficacy on the relationship between anxiety symptoms and excessive smartphone use in University students.Our study reported a small to moderate positive correlation between anxiety symptoms and PSU among University students, which was consistent with findings from previous empirical studies , 17. MorAs expected, we found a negative correlation between self-efficacy and anxiety symptoms in our study. Self-efficacy, as one of the most important positive psychological qualities, has become a plastic internal psychological resource and can serve as a buffer against mental disorders –43. CL LOur findings suggested that self-efficacy could act as a mediator between anxiety symptoms and PSU among University students. The mediating effect of self-efficacy could explain ~17.5% of the total effect that anxiety symptoms have on PSU. Nevertheless, the moderating effect of self-efficacy on the anxiety-PSU relationship was insignificant. As mentioned in the Introduction section, self-efficacy can be treated as one of the affective and cognitive response variables of the I-PACE model , 21. TheHowever, no studies have investigated the mediating or moderating role of self-efficacy in the anxiety-PSU relationship. We believe that students who perceive a higher level of self-efficacy usually possess more confidence and perseverance to cope with interpersonal troubles and have a higher level of self-control over their impulsivity to pursue pleasure through smartphones, resulting in decreased exposure to PSU compared to those with a lower level of self-efficacy . MeanwhiSeveral limitations should be taken into account in this study. First, data were collected at just one timepoint instead of longitudinally which limited the ability to establish the causal inferences or determine the direction of the causal relationships. Future prospective studies with a large sample size are warranted to validate our findings. Second, the survey was conducted using self-report questionnaires, which might not objectively reflect the actual smartphone usage and psychological exposures. Third, other psychiatric disorders such as depression personality disorders and medications for psychiatric reasons were not investigated, which would prevent us from fully understanding the mechanisms between various psychological factors and problematic smartphone use. Fourth, a sample of adolescent Chinese students may disable the external generalization of our findings. More representative samples of general smartphone users are needed. Finally, as an observational study, the mediating effect of self-efficacy on the relationship between anxiety and PSU should be confirmed by randomized controlled trials. Future research on interventions should be extensively conducted to verify our hypothetical models and radically prevent addictive behaviors among college students.PSU can cause many detrimental psychological disorders such as anxiety symptoms. It has become a mental health threat to University students. The current study is the first to provide evidence that self-efficacy can partly mediate the association between PSU and anxiety symptoms in Chinese University students. Considering the increasing prevalence of PSU among University students, multicomponent interventions, from the joint efforts of school-family-students, should be made to restrict the frequency of smartphone usage and increase the level of self-efficacy to thus promote the mental health of University students.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of China Medical University. The patients/participants provided their electronic informed consent to participate in this study.YL and M-LY contributed to data collection, statistical analysis, and revision of the manuscript. YL drafted the manuscript. Y-TQ and C-LL contributed to organizing the survey and interpretation of the data. HW and G-XL contributed to the study design, data collection, and revision of the manuscript. All authors read and approved the final version of the manuscript for submission.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.