Adults with substance use disorders (SUDs) often have co-occurring mental health problems. Emotion regulation may play a vital role in mental health problems. The Cognitive Emotion Regulation Questionnaire (CERQ) is a widely used measure for assessing cognitive emotion regulation. However, it has not been used in Pakistan on patients with co-occurring SUDs and mental health issues. The present study aims to translate and adapt the CERQ into the Urdu language and to determine its reliability and convergent validity in a sample of male patients with SUDs in Pakistan.Participants completed a demographic information form, the CERQ, the Depression, Anxiety, and Stress Scale Short Form [DASS-21)], and the Rosenberg Self-Esteem Scale [RSES)] in Urdu.N = 237) 18–50 years of age  were recruited from four substance use disorder treatment centers and hospitals in Karachi. The reliability of the Urdu version of the CERQ was based on an examination of its internal consistency reliability (Cronbach's α) and test–retest reliability for both the total scale and its subscales. Internal consistency for the CERQ total (α = 0.80) was adequate, as it was for subscales of self-blame, (0.76) acceptance (0.78), rumination (0.72), positive refocusing (0.79), focus on planning (0.89), positive reappraisal (0.81), putting into perspective (0.83), catastrophizing (0.73), and other blame (0.70). The 10–14 day test–retest reliability of the CERQ total score was 0.86. Higher CERQ scores were significantly (ps < 0.001) negatively associated with DASS-21depression (r = –0.24), anxiety (r = –0.23), and stress (r = –0.27) subscales, as well as the DASS-21 total score (r = –0.26) and positively associated with the RSES self-esteem score (r = 0.30).Male participants (The Urdu version of the CERQ is a reliable measure for investigating cognitive emotion regulation strategies related to mental health and SUDs in Pakistan. In the past two decades, research on the construct of emotion regulation (ER) has grown rapidly. ER is defined as strategies to maintain, increase, or suppress a current affective state and includes the ability to regulate emotions and physiological changes to respond to a situation adequately . ER aimsDisruptions in the ability to regulate emotions have been linked to various psychopathologies, including anxiety and depression . NumerouIndividuals using maladaptive cognitive emotion regulation strategies (CERs) are prone to risky behavior, including substance use disorder . ResearcSimilarly, previous findings have indicated a strong association between mental health issues like anxiety, depression, aggression, and psychological distress with low adaptive coping strategies and the excessive utilization of maladaptive strategies , 16. TheBased on the published literature, CER may have a significant role in mental health and SUDs. It is an essential constituent in assessing patients in clinical research and practice. Researchers have asserted that clinicians must have a reliable and valid tool that can be used in different languages and cultures . This goSince its development, the CERQ has been translated into several different languages, including Indonesian , Arabic Ethical approval for the study was granted by the Departmental Ethical Review Committee, Institute of Clinical Psychology, University of Karachi, Pakistan. The concerned authorities of substance use treatment and rehabilitation centers/hospitals  were approached and provided permission for the study to be conducted in their centers/hospitals. Data were collected from 01 June to 30 December 2019.The present study recruited only male patients with a SUD. Although reports of psychoactive substance use among females are also a growing concern in Pakistan, access to this population is challenging due to the extreme stigma and discrimination associated with substance use in females in Pakistan and the fear and shame associated with this problem among women.Adult male patients diagnosed with SUD were recruited using a purposive sampling technique. A total of 300 participants were initially approached to participate in this study: 5 refused to participate, and 58 did not meet the criteria to participate in the study, leaving a sample of 237 participants. Inclusion criteria were a SUD diagnosis, completion of a minimum of 3 weeks in treatment, detoxification completion, clinically stable, and ability to respond. Exclusion criteria included being unable to comprehend the instructions provided to complete the research questionnaires and being unable to read and write.The authors obtained permission to translate and adapt the CERQ via email from its copyright owners.Experts were selected according to the guidelines provided by the International Test Commission . These gThe instrument was first independently translated into Urdu by the two forward translators. To independently translate the original English CERQ into Urdu, the translators were provided detailed information about the scale's content and the study's objectives, and the sample to be recruited. After independent translation into Urdu, the directions, items, and format of the two different Urdu versions were compared with each other and with the original English version of the scale by the expert panel. The expert panel critically evaluated the translated version to resolve any contradictions and ambiguities in the items. Items of both translations that retained Pakistani culture's conceptual, linguistic, and cultural aspects were merged into a single draft. Substitutes recommended by the experts were also taken into consideration. All the items were retained, and no items were removed in the forward translation process.The final forward-translated version was then given to two expert translators for backward translation. These two individuals were not involved in the forward translation and were completely blind to the original version of the CERQ to minimize any bias in back-translation. These two translators independently translated the Urdu version back into English. Each item from the backward translations was analyzed and compared with the original English version of CERQ. Items after backward translation that did not retain the initial concepts were modified and rephrased by the translators. All comments given by the experts were transcribed. After a thorough evaluation of this preliminary version, a final version of the Urdu CERQ was prepared. It was then initially piloted on 30 individuals to determine feasibility. No further revisions were necessary, and the Urdu CERQ was determined to be ready to administer and test.Participants completed the Urdu translated version of CERQ, the Depression, Anxiety, and Stress Scale Short Form , and thThe CERQ has 36-items, including nine conceptually distinct subscales . The ninThe DASS-21 is a self-report short form of the 42-item DASS . It is cThe RSES was developed by Rosenberg . It contBefore enrollment in the study, potential participants were provided with an information sheet that shared the study and informed consent procedures. This sheet included the study's objective, voluntary participation, nature of confidentiality, risk, and benefits, and researcher contact details for possible contact after study completion. Data were only collected from those patients who were deemed stable. Participants completed a patient information form at the start of the study. Personal information was obtained regarding age, gender, number of siblings, education, residential area, family structure, number of family members, family income and number of earning members, drug of addiction, history, and the onset of the problem. Researchers ensured test conditions were similar for the instructions and administration of measures at their respective treatment and rehabilitation centers. Out of 237 participants, our Urdu version of the CERQ was re-administered to 47 participants, with a 10–14 days gap. The scores obtained from the same participants on the two different administrations of the test could then be compared be correlated to assess test–retest reliability.Cronbach's α was used to estimate the internal consistency reliability of the CERQ and its subscales. In contrast, simple Pearson product–moment correlations were used to assess test–retest reliability, calculated for the 47 participants who were re-administered the CERQ. Convergent validity of the CERQ was determined by examining the simple Pearson product-moment correlations of the CERQ total score and subscale scores with the DASS-21 total and subscale scores and with the RSES score. All statistical analyses were conducted with the Statistical Package for Social Sciences .N = 237) 18–50 years of age  were recruited from different substance use treatment centers and hospitals in Karachi, Pakistan. Regarding marital status, 57.4% reported they were single, 40.9% married, and 1.7% divorced. Their mean years of education completed was  with a monthly income in PKR . Regarding work status, 43% were employed, 22.4% were on daily wages and worked as laborers, 14.8% had their own business, and 19.8% were unemployed. In terms of living arrangements, 44.3% lived in a nuclear family setup, and 55.7% were in a joint family setup. Regarding the type of substance use, 44% reported using heroin, 15.6% used cannabis, and 32.9% reported using multiple psychoactive substances. Regarding using psychoactive substances, 32.1% reported such use due to family-related issues . A total of 27.8% reported started using psychoactive substances for experimentation, 27% reported use due to personal psychological issues, and 13.1% reported use due to friends using. Regarding substance use history in their family, 39.2% reported use by their immediate family members. When asked about family history of substance use, 39.2% reported that at least one immediate family member uses drugs.Male patients  and positively associated with self-esteem (p < 0.001). There was a clear pattern to the correlations of the CERQ subscale scores with the DASS-21 total and subscale scores and the RSES score, with the CERQ subscales that measure positive characteristics  showing significant negative associations with the DASS-21 total and subscale scores, and a positive association with the RSES score.The simple Pearson product-moment correlations of the CERQ total and subscales scores with the DASS-21 total and subscale scores and the RSES score are presented in the right-hand section of The aims and objectives of this study were: (1) to develop a culturally sound Urdu version of CERQ; and to investigate (2) the reliability of this Urdu version of the CERQ; and (3) its convergent validity in a sample of male patients with SUD. Convergent validity was examined regarding the relationship of the CERQ total and subscale scores with depression, anxiety, and stress and a measure of self-esteem. No normative data on these measures are available in Pakistan, but the examination of the means in relation to their respective range of scores, as well as their respective standard deviations, would suggest reasonable estimates of DASS-21 and RSES. The overall findings of this study support the strong psychometric properties of the Urdu translated version of CERQ.The reliability and convergent validity of the Urdu version of the CERQ in a sample of adult males with SUDs would suggest that this translated measure could be used to better understand the CER strategies in this population. This better understanding of cognitive and emotional regulation may then aid in designing and implementing interventions to improve people's coping strategies with substance use disorder. Better interventions for cognitive and emotional regulation may, in turn, help improve treatment adherence, maintain a drug-free status, and overall recovery. Psycho-education of patients with SUDs, their families, and significant others about substance use could also help reduce the stigma and discrimination that creates barriers to recovery.The present findings show an inverse relationship of CER strategies with depression, anxiety, and stress and a direct relationship with self-esteem. In the context of a substance use disorder, CER strategies, specifically maladaptive strategies, can significantly impair psychosocial functioning. So, it is vital to understand how and when these maladaptive strategies can be detrimental and intervene to overcome these problems. According to a model from Gross , emotionIndividuals use emotion regulation strategies to manage and reduce the consequences of the stressors , 44. SomThe present study has certain limitations related to the study design. The sample was one of convenience, and data were collected at a single time. However, the relationship of cognitive emotion regulation strategies with depression, anxiety, stress, and self-esteem could operate differently over time. Furthermore, the sample only included male patients receiving treatment for SUD. Thus, generalizability is limited to male patients without a SUD, female patients with or with a SUD, or the non-patient general population. Future research may wish to include a more diverse sample, including non-clinical samples, to understand the role of emotion regulation in improving well-being and mental health outcomes in males and females without a SUD. Future research may also attempt to disentangle the role of emotional regulation as a possible mediator between mental health issues and substance use disorder.Existing literature related to cognitive emotion regulation strategies indicates a strong link between cognitive emotion regulation with mental health problems and self-esteem. The present study showed that the Urdu version of the CERQ would be a reliable measure for patients with SUD. Using this measure may help us fill the gap in understanding the emotion regulation strategies and implementing evidence-based practices (EBPs) while linking it with the client's specific problems to improve treatment outcomes. In addition, the Urdu version of the CERQ may be helpful in the identification of adaptive and maladaptive strategies that may constitute the basis for preventive or treatment interventions specifically for patients with SUD aimed at enhancing their well-being.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The study involving human participants were reviewed and approved by Departmental Ethical Review Committee, Institute of Clinical Psychology, University of Karachi, Pakistan. The patients/participants provided their written informed consent to participate in this study.SS main researcher, design of the research, wrote part of the manuscript, and responsible for the sample selection, data collection, and data analysis. NBa wrote the introduction and discussion. NBe provided data collection, wrote part of the manuscript, and provided statistical analysis. HJ provided manuscript reviews, edits, corrections, and amendments. All authors participated and approved the study design, contributed to manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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The specific objectives of the study are to examine the mental health (depression and anxiety) of the first generation of post-Taliban government and compare these measures with its preceding generation, and to assess war experience of the first generation of post-Taliban government. We also wanted to assess the daily stressors and their contribution to the mental health, and to assess mental health as a result of war experiences and daily stressors with respect to demographic measures such as sex, marital status, age, mother's age, birth order, and ethnicities.In a cross-sectional design, 621 high school students, were randomly selected to participate in the study to assess war experience, daily stressors, and mental health among the first generation of young adults under post-Taliban government.P = 0.08). There was no association between war experiences and the age and ethnicity of our participants . Age differences were negligible for daily stressors too (P = 0.07). Daily stressors scores were higher for female than male students (P = 0.02). The majority of young adults surveyed, declared themselves in agreement with statements such as the security situation in Afghanistan makes me frustrated (56%), air pollution as a concern (41%), and not having anyone to talk about what is in their heart (28.8%). Gender differences were highly significant for mental health, as appraised by both The Hopkins Symptoms Checklist (HSCL) –depression and HSCL-anxiety. Girls presented higher rates of depression, anxiety, and daily stressors than boys, and boys presented higher rates of war experiences than girls.The participants had 17.37 ± 0.9 mean years of ages, 94.8% of them were unmarried. Poor mental health was significantly associated with higher exposure to war, but not with the age of participants (War experience, daily stressors, and mental health were irrelevant with age, ethnicity and marital status. Factor such as being the first-born child of the family, higher reported war experiences, and daily stressors all negatively impact mental health. Alongside war and its direct effects, the existing socio-cultural context must be considered as a potential factor mediating the mental health of girls in Afghanistan. Mental health is an integral and essential component of children's and adolescent's healthy development, but has been treated with low priority in Afghanistan . DespiteAccording to the World Health Organization (WHO), youth exposed to war and home displacement may develop mental disorders including depression, suicide ideation, Post-Traumatic Stress Disorders (PTSD), and substance abuse . Armed vAs of today, every child born and raised in Afghanistan has experienced war and conflict in the country . ApproxiFrom the 20th of January to March 30th, 2018, we employed a cross-sectional design, wherein participants were included randomly. Participants were high school students aged between 16 and 18 years old from Mazar-e-sharif. This is the center of Balkh province which is known to have one of the high attendance in school in Afghanistan. Mazar-e-Sharif province has 10 local districts. Three-stage school-based sampling was used in this survey . The firFor the third stage of sampling, a random sample of 28 classes was collected from grades 10–12 with a minimum of 50 participants from each school. At the beginning of our survey, we randomly selected students from the class attendance list, though all the students were willing to participate in the study. We surveyed the entire members of one or two classes. Before the distribution of questionnaires, we obtained oral consent from all the students. Almost all students agreed to take part in the study and answer the questionnaires because of the novelty of our research. Due to the literacy level of the participants, we were able to maintain the same environmental conditions thus preventing response biases in our study. Afghans are not normally comfortable to talk about their distressing emotions. In this study, everyone got their own questionnaire and completed answering by themselves without an interviewer reading it aloud or them answering it for the interviewer in an audible voice. Most of the participants were asked whether their participation would benefit them with regards to their mental health or not. They were told that their responses will be gathered for research purposes only and findings will be shared back to the school .The survey team had three staff that included two medical students and a driver. The two medical students were educated in Mazar-e-Sharif and were known by the students thus facilitating easy rapport with the students. The team moved sequentially from school to school which maximized efficiency in data collection and quality. The questionnaires were filled by students for ~15 min to complete. The protocol was approved by Shahid Beheshti University of Medical Science, Balkh education presidency and by all subsidiary school directors. As such, all ethical considerations were in order throughout the length of this study. One exclusion criteria for the study was not being part of the first generation young adults under the post-Taliban government.We used screening instruments for measuring mental health, which were chosen based on traumatic events considered, culturally specific attitudes and relevant psychometric properties for the war- affected population. Our study comprises three standard instruments: the Afghan Stressors Scale (ADSS), Afghan War Experiences Scale (AWES), and The Hopkins Symptom Checklist-25 (HSCL) , 17.Independent variables considered are:Socio-demographic characteristics such as age , gender, marital status, ethnicity, past educational gap, birth order, past exam failed, and house location.War experiences such as exposure to war-related violence and loss was measured by the Afghan War Experiences Scale (AWES). This scale contains 17 war-related items; responses are rated on a 3-point Likert scale, (1) Never, (2) once, and (3) more than once. The sum of scores, yielding within a range of 17–51, with excellent reliability across gender  .Daily stressors measured by the Afghan Daily Stressors Scale (ADSS). The ADSS was developed by Professor Miller with Dr. Omidian and other Afghani colleagues, using a multi-step process in Kabul. This culturally-grounded questionnaire contains 26 items which ask respondents to indicate how stressful they have found each item during the past month, the responses are rated on a 3-point Likert scale, (1) not stressful, (2) somewhat stressful, and (3) very stressful. The sum of scores, yielding a total score of 26–79. The ADSS is useful in assessing a wide range of daily stressors such as financial hardships, health problems, social isolation, family conflicts and environmental concerns. The reliability of ADSS varied by gender . ADSS was also validated as a screening tool in a community setting in Pakistan .Dependent variables considered are:Mental health which measured depression and anxiety using the Hopkins Symptom Checklist (HSCL-25) . The HSCt-test, and Pearson‘s correlations were applied where appropriate. All the data were screened for linearity and normality with p < 0.05 considered as statistically significant for this study. The major number of analyses were conducted separately for each gender.All statistical analyses were conducted using SPSS version 16 for Windows. All numerical data were expressed as mean ± SD and percentage values for analysis, responses to Likert scale questionnaires were summed across constituent items, to yield total scores for each participant. Both categorical and continuous variables were subjected to bivariate test to examine association with ASCL scores using one-way ANOVAs, independent sample A total of 621 participants with 17.37 ± 0.9 mean years of age, completed the three questionnaires. Their father's and mother's mean of ages were 50.12 and 43, respectively. 62.9%  of our participants were females and 37.1% males, most were unmarried (94.8%). Nine percent of our participants had past educational deprivation and 29% reported failure in some school exams. The participants were predominantly Tajik (68.1%), Hazara (12.5%) and Pashtun (10.2%), which reflect the predominance of Tajik in Mazar-e-Sharif. Almost all (99.9%) participants had both parents still alive. Most of the students (67%) were the fourth eldest descendants (according to the birth-order) of their families .P < 0.001). For assessing war experience of the first generation of post-Taliban government, the AWE-17 scores ranged from 17 to 51 with an average score of 19.32 ± 3.72. The mean score of ADSS-26 was 42 ± 10  of the first generation under the post-Taliban government and to compare these measures with its preceding generation. Positive correlation were obtained between HSCL-Depression and HSCL-anxiety ( 42 ± 10 . The maj 42 ± 10 . Five pe 42 ± 10 .p < 0.001). Most of our participants had no experience of being injured, jailed or tortured during war. However, poor mental health status was significantly associated with higher exposure to war experience irrespective of gender and marital status (P < 0.001). High level of war experiences was significant among men (P = 0.01), with mean scores of 19.83 for males and 19.01 for females. Poor mental health was significantly associated with higher exposure to war, but not with the age of participants (P = 0.08). There was no association between war experiences and the age and ethnicity of our participants . Age differences were negligible for daily stressors too (P = 0.07).Gender differences were highly significant for differences in reported mental health, as appraised by both HSCL –depression and HSCL-anxiety. In our study, HSCL –depression and anxiety scores were higher for females than males (P = 0.02), and six items were significantly more stressful for females than males in this study, including “Not being able to find work,” “Not feeling happy with my family,” “Problems with my teeth,” “My family member being sick,” “Air pollution,” “Feeling like people don't give me enough support.” Furthermore, higher HSCL scores were significantly associated with high daily stressors (P = 0.01). Headache, feeling fearful, crying easily and feeling lonely among girl students and heart pounding or racing and loss of sexual interest or pleasure among boys' students were chosen extremely on four Likert scales. Compared to the first four family members, last family members experienced higher daily stressors (P = 0.04) (P = 0.04).Daily stressors scores were higher for female than male students ( = 0.04) . Also, nDespite the fall of the Taliban, every child born and raised in Afghanistan has experienced war and conflict , 14, 15.On a design level, our study shows that schools are a valuable source of ascertaining mental health and mental health related factors among school-age young adults due to their feasibility, high national-diversity  and the student's willingness and pleasure to answer questions about their feelings and emotions. Our participants reported that they had never been asked about their feelings, emotional status and daily stressors, as has been reported in previous studies , 26. ThiWe found that daily stressors are stronger predictors of mental health than war experiences. These stressors were reported significantly higher in girls than in boys, in congruence with the study by Miller et al. , but notOur work contributes to the broader corpus of literature on youth mental health and resilience amid conflict and war in Afghanistan. Afghanistan's conflict setting is both rural and urban in nature, with an estimated 9.4 million people in need of humanitarian assistance . MoreoveThe first systematic, longitudinal study of measures of mental health and resilience in Afghanistan found that poor mental health was driven predominantly by gender, trauma exposure, caregiver wellbeing, and geographical area . The resIn turn, we position the present work as building off this base by investigating the daily stressors that are present in the lives of young adults attending the schools of Mazar-e-Sharif. Previous literature also points to the need for public health researchers and scientists not to focus solely on the macrolevel effects of war and conflict. This is because a focus on the macrolevel alone leads to the erasure of the direct daily lived experiences of the individuals afflicted with the effects of the conflict. Ventevogel et al.  articulaMoreover, research on resilience in humanitarian contexts has emphasized the use of multilayered psychosocial care that addresses health, familial status and dynamics, economic situation, and other layered factors contributing to one's mental health . This isp < 0.05), this result is the same as that found by Miller et al. . The mean participant score for HSCL-A and HSCL-D obtained was 19.39 and 28.45 and mean Miller's study scores were 27.66 and 36.76 for HSCL-A and HSCL-D, respectively. This shows a significantly lower prevalence of mental health problems among young adult school goers in Mazar-e-Sharif. These findings are in contrast to older studies that observed a higher prevalence of mental problems among Afghans (The mean score of war experiences obtained 12 scores lesser than the AWES mean showing a dramatic decrease in war experiences; and the majority of our participants had no experience of bad injury, imprisonment, or torture ( Afghans , 18. In  Afghans .In the HSCL questionnaire, headache, feeling fearful, crying easily and feeling lonely among girl students and heart pounding or racing and loss of sexual interest or pleasure between boy students were chosen extremely, on four Likert scale. According to the most recent survey of women between 20 and 24 years old, 34.8% of them were married by age of 18 , 36, meaOur finding suggests that adolescents in Mazar-e-Sharif present good mental health status, low war experiences and low level of daily stressors than previous studies have shown. However, in this present study females reported higher rates of depression, anxiety and daily stressors than boys, and boys presented higher rates of war experiences than girls. All three items were not associated significantly with age, ethnicity and marital status. Being the first child of the family, higher reported war experiences, and daily stressors, negatively impact mental health. Past educational deprivation and underage marriage were seen at low frequencies. Alongside the direct implications of war, existing socio-cultural contexts must be considered as a potential factor influencing the mental health of girls in Afghanistan.We observed a number of limitations in the study. First, we failed to clarify a relative contribution of war experience and daily stressor on mental health of the considered students. This limited an implication of this study to develop potential countermeasures for the students' mental health problems. Second, although, both questionnaires of AWES and ADSS have high consistency in our study, they were created in a Kabul setting which may have some differences to the Mazar-e-Sharif context in this study. Some of the psychometric questionnaire items may not apply to Mazar-e-Sharif. For example, traffic has never been a significant stressor for Mazar-e-Sharif residents. Moreover, this study was carried out by school attendees, the mental health state of non-young school goers remains unknown. Future public health researchers may find it fruitful to expand on these findings by broadening the study sample to include young-school aged children. Among these students, we also do not know the existing mental health status, or if student participants were on medication for psychiatric disorders. We did not obtain information on socio-economic status of the participants. However, a large percentage of Afghans including Mazar-Sharif have low socio-economic status.We have found schools as a viable source of collecting information and potential point of intervention. There is no existing school-based mental health intervention in Mazar-e-Sharif. It could be a novel and helpful mode of therapy for all students.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.KR, FQ, PQ, SQ, and HF conceived and designed the study and wrote the manuscript. JS, AA, and FQ helped collect data. MP, AS, and SM performed the statistical analysis and wrote the manuscript. DL-P and YK confirmed the eligibility of the participants' for the study. SQ, FN, and AO supervised the whole study and approved the final version of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Repetitive transcranial magnetic stimulation (rTMS) has a positive effect on patients with depressive disorder, while the underpinning molecular mechanism is unknown. Here, we aimed to investigate the effect of rTMS on serum levels of serum amyloid A (SAA) and testosterone in a real-world setting.n = 52) and testosterone (n = 37) were measured before and after 2 weeks of treatment, and the treatment effect was evaluated by Hamilton Rating Scale for Depression (HAMD).In total, ninety-seven patients with depressive disorder were treated with medicine and rTMS (the rTMS group) while 122 patients were treated using the medicine only (the control group). Plasma levels of SAA  in the second week was significantly correlated with the percentage of decrease in HAMD score in the rTMS group, but not in the control group.The treatment effect revealed by the percentage of decrease in HAMD in the second week was significantly greater in the rTMS group compared with the control group. No significant difference was found in SAA or testosterone levels between the two groups. However, the percentage of changes in SAA (Patients with depression benefit more from combined rTMS and medication treatment in this naturalistic study. Changes in SAA level, but not testosterone level, were related to depressive remission after 2 weeks’ combined treatment. Depression is a common psychiatric disorder with high lifetime prevalence, affecting up to 15% of the world’s population . DepressRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique with broad clinical applications. A significant positive effect of rTMS on adult MDD patients has been demonstrated in several studies . In currSeveral inflammatory markers, namely interleukin-1β (IL-1β), IL-6, and C-reactive protein (CRP), are associated with depression . Serum aOn the other hand, the association between testosterone and depression has been extensively debated because testosterone is a neuroactive steroid hormone influencing mood . A populIn the present study, we aimed to verify the effectiveness of combined rTMS and medication depression therapy in real-world clinical settings, and investigate the effect of rTMS on serum levels of SAA and testosterone in depression patients.This study included inpatients from the Affiliated Mental Health Center and the Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine. All the data were acquired from the Integration Platform for Clinical and Scientific Research on Mental Disorders. In total, 3,091 patients aged between 18 and 65 years, were diagnosed with depressive disorder by two treating psychiatrists according to the international classification of diseases, tenth (ICD-10) revision. Those who completed more than six sessions of rTMS (except for the control group) and finished clinical assessment of the Hamilton Rating Scale for Depression (HAMD) three times would be included in this study. Exclusion criteria were: received other electromagnetic stimulations such as electroconvulsive therapy; depression caused by other severe psychiatric disorders; history of severe somatic diseases and organic diseases of the brain; and having medication other than antidepressants, benzodiazepines/non-benzodiazepines, or low-dose of olanzapine/quetiapine. The flow chart of the study design is shown in All the rTMS treatment was administered by trained medical doctors. All the patients were seated in a comfortable chair while TMS stimuli were delivered to the left prefrontal cortex (using the 5-cm rule) with a figure-of-eight coil and an OSF-6 magnetic stimulator . The patients received 5 sessions of rTMS treatment per week and the stimulation frequency was 10 Hz with power (intensity) level of 90% of motor threshold (MT). Each session contained 60 rTMS trains with 40 pulses per train and the intertrain interval was 15 s.The primary outcome of the study was the percentage of decrease in scores on the 24-item version of the HAMD. The outcome measure of HAMD was assessed at baseline (before rTMS treatment), first week (5 sessions), and second week (10 sessions). Response to treatment was defined as an over 50% decrease in HAMD. Remission was defined as a HAMD score of less than 8 in the second week.The blood sample was collected between 7:00 and 9:00 a.m. in a fasting state. Analyses of SAA and testosterone were performed on fresh biospecimens on the day of sample collecting. The SAA was analyzed using a particle-enhanced turbidimetric immunoassay (PETIA) and testosterone was analyzed using chemiluminescence analysis (CLIA).n = 122) included patients with medical treatment while the rTMS group (n = 97) included those with joint medicine and rTMS treatments. Chi-square tests were used to investigate differences in men/women between groups. Repeated two-way ANOVA (group * time) was conducted to investigate the HAMD score/percentage of decrease in HAMD/SAA level/testosterone level difference between groups across 2 weeks of measures. Student’s t-test were used to investigate differences between groups in the percentage of changes in HAMD score, SAA, and testosterone level. Pearson correlation was used to investigate the relationship between the percentage of changes in SAA, testosterone levels, and HAMD score.Data were analyzed using standard descriptive statistics in PASW Statistics 18.0  statistical software. The control group  = 1431.734, p < 0.001] but not in the group  and interaction   = 5.799, p = 0.017] and time , but not in interaction , suggesting the effectiveness of rTMS treatment along the time. Further t-test showed that the percentage of decrease in HAMD in the rTMS group was significantly greater than in the control group in the first  and second week . However, the response rate or remission rate of the rTMS group did not differ from the control group in the second week.When conducting the two-way ANOVA statistic with group factors (rTMS/Control) and time factors  within HAMD score, there was a significant effect in time [= 0.175] . When coF = 0.696, p = 0.408], time effect , or interaction effect  (t(50) = 1.550, p = 0.128] did not differ between control and the rTMS group.When conducting the two-way ANOVA statistic with group factors (rTMS/Control) and time factors (baseline and second week) within SAA level of 52 patients, there was no significant group effect [= 0.625] . The perF = 0.001, p = 0.979], time effect , or interaction effect  (t(35) = 0.671, p = 0.507] did not differ between control and the rTMS group.When conducting the two-way ANOVA statistic with group factors (rTMS/Control) and time factors (baseline and second week) within testosterone level of 37 patients, there was no significant group effect [= 0.260] . The perr = −0.492, p = 0.017) , or among all patients .The significant relationship was found between percentage of decrease in SAA level and the percentage of decrease in HAMD score in the rTMS group at second week (= 0.017) , rather r = −0.071, p = 0.675) nor in separate groups .Notably, no relationship was found between the percentage of change in testosterone level at second week and the percentage of decrease in HAMD score, neither in all patients (In this study, we found a greater percentage of decrease in HAMD score in the second week when combined with rTMS treatment than medical treatment only in depression patients, and the percentage of decrease in HAMD score was associated with the percentage of changes in SAA level in the second week.The rTMS could accelerate the onset time of beneficial treatment effects and improve clinical symptoms of depression . In a stAlthough no significant result was found on the SAA level during the 2 weeks of combined rTMS treatment, the percentage of decrease in SAA level was related to the percentage of decrease in HAMD score. Changes in inflammatory mediators such as SAA were related to insomnia , which iIt should be pointed out that no significant difference was found in testosterone levels between the two groups. Besides, no relationship was found between therapeutic effects and changes in testosterone levels either. Although lower testosterone level was associated with depression in men , the resThe limitations of this study are intrinsic to those of retrospective research conducted in a naturalistic setting. A sham rTMS group was not used to control for placebo effects. In addition, the present study used an atypical rTMS treatment protocol and did not control for concurrent medications or psychotherapy. The sample size of patients who completed baseline and second-week serological examinations was small, which limited our further analysis. At last, the follow-up time was only 2 weeks, which helped to understand the early onset but not the long-term effectiveness of rTMS therapy.In conclusion, patients with depression benefit more from combined rTMS treatment with medicine in a naturalistic study. Changes in SAA but not testosterone level were related to depressive remission after 2 weeks of combined treatment. Future research is needed in the form of double-blind, randomized control trials that examines the relationship between SAA level and rTMS depression outcome.yuzhcoo@sina.com.The datasets generated and analyzed during the current study are not publicly available because permission is needed to access the database of the hospital, but they are available from the corresponding author on reasonable request. Requests to access these datasets should be directed to ZY, The studies involving human participants were reviewed and approved by Ethics Committee of Affiliated Mental Health Center and Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine. The patients/participants provided their written informed consent to participate in this study.All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.


Retinitis pigmentosa (RP) is the most frequent retinal hereditary dystrophy and result in blindness if progresses. Several case reports have revealed the possible association between RP and primary angle-closure glaucoma (PACG). We conducted a population-based study to explore whether RP significantly increased the risk of PACG development.Using the Taiwan National Health Insurance Research Database, we enrolled patients with RP into the RP group from 2001 to 2013 and included a comparison group of 1:4 age- and sex-matched individuals without RP. We performed a Cox regression analysis to estimate the crude and adjusted hazard ratios (HRs) of RP for PACG after adjustment for hypertension, diabetes, hyperlipidaemia, chronic kidney disease, and lens subluxation.We enrolled 6223 subjects with RP and 24892 subjects for comparison. The mean age of the cohort was 49.0 ± 18.1 years. The RP group had significantly higher percentages of diabetes mellitus, hypertension, and hyperlipidaemia. The cumulative incidence of PACG in patients with RP was 1.61%, which was significantly higher than that in the comparison group . According to the univariate Cox regression analysis, the hazard of PACG development was significantly greater in the RP group, with an unadjusted HR of 2.09 . The increased risk persisted after adjusting for confounders .This nationwide population-based cohort study showed that people with RP are at a significantly greater risk of developing PACG than individuals without RP. Retinitis pigmentosa (RP) is a genetic disorder that involves the breakdown and loss of photoreceptor cells. Patients may experience night vision loss at first, followed by peripheral vision loss, optic nerve dysfunction, and blindness. Several studies have reported the possible association between RP and primary angle-closure glaucoma (PACG) –4. The pSince RP is a rare disease with a worldwide prevalence that varies from 0.014% to 0.04% , a populThe importance of understanding the relationship between RP and PACG is based on two factors. First, an increase in intraocular pressure due to angle-closure may aggravate the visual impairment of RP patients. Second, an appropriate examination should be performed to prevent PACG  if RP dehttps://dep.mohw.gov.tw/dos/cp-5283-63826-113.html).This retrospective population-based cohort study was approved by the ethics committee of Taichung Veterans General Hospital (CE21351B). The Taiwan NHIRD is maintained by the Ministry of Health and Welfare and includes all health care records. Diagnoses are registered according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. To ensure confidentiality, all the data were deidentified by the Ministry of Health and Welfare and written informed consent was exempt according to the rules of the Institutional Review Board. The database is legal to be used on-site for research purposes after applying for the permission. Application procedures are described online (We selected patients with RP (ICD-9-CM codes 362.74) from the NHIRD from January 1, 2001, to December 31, 2013. RP was confirmed by ophthalmologists through a well-acknowledged, standard diagnostic protocol which included retinal bone-spiculae pigments, arteriolar attenuation, and waxy pallor of the optic disk under indirect ophthalmoscopy . Visual Thereafter, we randomly selected individuals who were never diagnosed with RP and allocated them to the comparison group, which was 1:4 matched with the RP group on age, sex, and index year (year of enrolment).The two groups were followed until the end of 2013 to determine whether they subsequently developed PACG (ICD-9-CM code 365.2). Patients diagnosed with PACG should show glaucomatous visual field defects or glaucomatous optic neuropathy with primary angle closure .We identified comorbidities that were confounders  to be adThe differences in the demographic/clinical characteristics between the RP and comparison cohorts were analysed by the two-sample t test for continuous variables and the chi-square test for categorical variables. The cumulative incidence of PACG during the follow-up period was also assessed and compared between the two groups.A Cox proportional hazard model was utilized to estimate the hazard ratio (HR) for the occurrence of PACG according to each variable in the univariate analysis. Two sets of multivariate Cox regression were performed. Covariates adjusted in Model 1 were age, sex, and comorbidities . In Model 2, in order to reduce the possibility of over-adjustment, only diabetes mellitus, hypertension, hyperlipidaemia, chronic kidney disease, and lens subluxation were adjusted as covariates. Comorbidities were considered time-dependent variables to avoid immortal time bias . All anaIn the study, a total of 6223 RP patients and 24892 matched comparisons were enrolled. p < 0.0001].p < 0.0001). Furthermore, both age and female sex were significant risk factors for PACG in the Model 1 multivariate analysis. The adjusted HR for PACG in patients over 60 years of age reached 12.51  compared to those younger than 40 years of age. Of all comorbidities, diabetes and cataracts were the only two statistically significant risk factors for PACG after adjustment for confounders .In Model 1 of the multivariate Cox regression adjusted for all the covariates , RP remained significantly associated with incident PACG . Additionally, diabetes remained a significant risk factor for PACG .In order to avoid over-adjustment, we assessed Model 2 which did not include age, sex, and cataract as covariates. In Model 2, RP still had a significant association with incident PACG  and the outcome (PACG), it is not appropriate to be adjusted. Therefore, in Model 2, we did not adjust cataract. Additionally, the study and the comparison cohorts were matched on age and sex. Therefore, we did not adjust age and sex In Model 2 in order to avoid over-adjustment. We still keep Model 1 adjusted for age and sex because in cohort study, even individuals matched on age and sex have different follow-up period; therefore, age and sex might play a role in the Cox regression analysis.One limitation of our study is, at present, we only have access to NHIRD which is before the year 2013. However, our research still can be regarded as a preliminary study, revealing the association between RP and PACG. Afterwards, we will request the access of recent dataset to see if there are any different statistical results.Another limitation of our study is the lack of genetic sequencing or laboratory data. Despite of the inherent drawback of database, our large-scale epidemiologic study has revealed the possible relationship between RP and PACG. Based on the findings of our study, laboratory research and further genetic studies will have a role in investigating the underlying mechanisms. Although combining Taiwan biobank with NHIRD is still not allowed now, the proposed legislation for permission is on the way. Otherwise, we can apply international biobank such as UK biobank to elucidate whether specific genes or biochemical profiles may explain the relationship between RP and PACG.Our study found that patients with RP have an increased risk of developing PACG. As a result, ophthalmologists should be aware of the risk of PACG when treating patients with RP. Because PACG can result in irreversible optic nerve damage and further deteriorate diminished visual function in RP patients, an appropriate clinical examination is crucial, especially for those who have high risks of PACG , to achieve early diagnosis and prompt intervention.


Based on the postanesthesia recovery procedure for elderly patients with colorectal cancer, a care bundle program was conducted to validate its effectiveness.  According to the characteristics of elderly patients with colorectal cancer, five measures including respiratory management, circulatory stability, pain assessment, body temperature monitoring, and internal environment stability were integrated into one bundle. Postanesthesia care unit (PACU) care bundle program for elderly patients was developed and used to improve recovery care. The monitoring data of the pre-PACB group given care bundles were collected and compared with the data of the post-PACB group who were given conventional recovery care. P < 0.05). The length of stay in PACU was longer in pre-PACB group . More adverse events were found in the post-PACB group than in the pre-PACB group (72.1% vs. 34.0%).  222 patients in post-PACB group had shorter intubation time than 291 patients in pre-PACB group (37.7 ± 24.4 min vs. 42.1 ± 23.3 min,  After general anesthesia of patients with colorectal cancer, the application of the care bundles can improve the quality of recovery, shorten the intubation time and the length of stay in PACU, and reduce the complications caused by anesthesia. Colorectal cancer is the second leading cause of cancer-related mortality worldwide , and surCare bundles are a set of safe and effective care interventions provided by medical workers when patients are treated under unavoidable risks . It was This was a single-center retrospective study conducted at a tertiary hospital . The study subjects were elderly patients undergoing colorectal cancer surgery between March 2020 and February 2021. Two periods were defined, based on the history of the postanesthetic care bundle (PACB): pre-PACB stage (March 2020-August 2020) and post-PACB stage (September 2020-February 2021). This study was approved by the ethics committee of the Second Affiliated Hospital of Zhejiang University (2021-0937). The categories of colorectal cancer surgery included laparoscopic, laparoscopic robot-assisted, and open resection for colorectal cancer. Data were collected from patients who met the following eligibility criteria. The inclusion criteria were (1) age 65 years or older, (2) a diagnosis of colorectal cancer, (3) treatment by colorectal cancer surgery under endotracheal general anesthesia, and (4) admission to postanesthesia care unit (PACU) postoperatively. The exclusion criteria were (1) presence of pulmonary infection, (2) presence of renal insufficiency, and (3) plan of recovery in the operating room or admission to intensive care unit (ICU) following surgery.2 were found, they were instructed to take deep breaths and cough properly. After they met the requirements to be transferred out of PACU, they would be sent to the ward after assessment by anesthesiologists. The nursing methods of pre-PACB group and post-PACB group are shown in The patients in the pre-PACB group were treated with conventional recovery caring methods. After transferred to PACU, these patients were given assist control ventilation and synchronized intermittent mandatory ventilation, ECG monitoring, symptomatic treatment, and body temperature measurement. If body temperature is lower than 36°C, active warming was provided. Besides, after muscle strength was restored, the tracheal catheter was removed according to the doctor's advice. After extubation, the condition of the patients was continuously observed. If signs of respiratory depression or decrease in SPOThe PACB was developed from the evidence obtained from a few guidelines and expert consensus in the United States and China –15. ThesThe PACB team consists of twelve PACU nurses and one anesthesiologist. The anesthesiologist is responsible for the evaluation of perioperative anesthesia and the management of multimodal analgesia. PACU nurses are responsible for the care of all patients and the recording of related monitoring data. Prior to implementation of the PACB, the head nurse gave the PACU nurses a train of three 30-minute courses on temperature monitoring, early extubation procedure, mechanical ventilation setting, assessment of respiratory function, clinical assessment of muscle strength recovery, monitoring of circulatory function, and pain assessment. We used the verbal rating scale (VRS) for pain assessment: grade 0: no pain; grade 1: mild pain. Although there is pain, it can be tolerated and can live normally. Sleep is not disturbed. Grade 2: moderate pain, obvious pain, intolerable, required to take analgesics, and sleep disturbed. Grade 3: severe pain, severe and intolerable pain, requiring analgesics, severely disturbed sleep, and may be accompanied by autonomic nerve dysfunction, showing passive posture.Data will be collected from the anesthesia information system. Data to be collected includes patient demographics , procedural data , and patient outcomes (any complications and adverse events in PACU). Data on the time of hospital admission and discharge were obtained from the hospital information system (HIS). The conditions of the patients, the decisions made by doctors and nurses, and the issues that needed to be or not to be addressed can be found in the PACU-related documents.x ± s) and compared with a 2-sample t test. The dichotomous data were expressed in frequency and percentage and were compared using χ2 test. If the P value for a two-tailed test is less than 0.05 (P < 0.05), it is a statistically significant result.The data were input into Microsoft Excel®2010 and analyzed after being imported into SPSS Windows . The continuous variable values were expressed as mean ± standard deviation (P < 0.05)  .P < 0.05); the length of PACU stay in the pre-PACB group was 81.6 ± 31.1 min, shorter than in the post-PACB group ; the delayed PACU stay event rate significantly decreased from (15.3%) to (9.3%) in the pre-PACB group and the post-PACB group, respectively (P < 0.05). But the postoperative duration of hospital stay did not significantly change over time . Adverse events in the pre-PACB group were fewer than the post-PACB group . Although the rate of patients being unexpectedly transferred to ICU in the pre-PACB group was lower than that in the post-PACB group , there was no significant difference between the two groups (P > 0.05)  .P < 0.01), hypothermy , agitation , and respiratory complications  were the main adverse events with significant difference between the two groups. But the incidence of cardiovascular complications and nausea and vomiting was not significantly different between the two groups (P > 0.05)  .It has been reported that the quality of recovery from anesthesia can be improved by optimizing the extubation process , improviWhen the elderly patients with colorectal cancer are extubated at the early stage of recovery from anesthesia, respiratory complications, like hypersomnia, glossocoma, insufficient ventilation, respiratory depression, impaired airway protective reflex, cough with sputum, weakness, and atelectasis, are likely to occur due to delayed and residual effects of neuromuscular-blocking drug caused by the residues of anesthesia drugs and analgesics . In addiPain assessment of elderly patients with colorectal cancer is an integral part of medical care under this management program. Individualized pain assessment should be performed immediately after patients are admitted to PACU. Early pain intervention can greatly reduce the occurrence of moderate and severe pain and postoperative agitation after extubation. Also, the effective analgesia helps the deep breath and the cough of patients and reduces the occurrence of pulmonary complications. An effective pain assessment is the first step in improving pain management. Before nurses in PACU perform pain assessment, they should be aware that anesthesia method, the use of sedatives and analgesics, and unfamiliar environments can affect the cognitive ability of patients, in addition to letting patients know about the details of the assessment before surgery. So, it is necessary to select a proper pain assessment method to relieve their pain effectively. Besides, patients should be warned of breakthrough pain, especially in the beginning of regaining consciousness.Elderly patients with colorectal cancer have a high risk of perioperative hypothermia due to over 2 hours of operative time under anesthesia and intravenous infusion of crystalloid fluid of more than 1500 mL . HypotheThe management programming of the care bundles involves many systems and people, so it is very important to manage the implementation process well. To this end, a quality management team needs to be built to ensure the program is implemented by following the steps and following the results. Besides, a complete and recognized feedback and evaluation system should be created by monitoring the movement of the patients out of bed, time of feeding, length of stay in the hospital, unexpected being transferred to ICU, and postoperative mortality.There are several limitations to this study. First, results from this study are retrospective and observational in nature; we are unable to identify a true causal effect of PACB on clinical outcomes. We acknowledge that during the time period of this study, some advances have been made in PACU, including increase of equipment and employees. These developments would have led to decreased length of PACU stay, thus potentially confounding our results. In addition, it is uncommon to extubate in PACU like our hospital, since extubation is often done in OR. The difference in anesthesia management may limit the external validity of the results.The findings in the current study demonstrate a substantial shorten in PACU stay, along with higher event rates after implementing a PACB program. The care we describe as the PACB was the most common morbidity in PACU. The findings support our hypothesis that enhanced patients' recovery through a PACB program. They also provide additional guidance in support of PACB for elderly patients with colorectal cancer.In China, elderly patients with colorectal cancer undergo radical surgery increasingly, and targeted measures are needed to ensure that these patients recover well after anesthesia. The care in PACU under this program will incorporate many measures targeting the characteristics of the elderly patients into one bundle, which can provide procedure-based medical care. These measures can shorten the recovery time and improve the recovery quality after surgery. This could make the health care system more efficient, reduce unnecessary medical costs, and improve the operation efficiency of medical institutions.


As time plays a fundamental role in our social activities, scholars have studied temporal perception since the earliest days of experimental psychology. Since the 1960s, the ubiquity of color has been driving research on the potential effects of the colors red and blue on temporal perception and on its underlying mechanism. However, the results have been inconsistent, which could be attributed to the difficulty of controlling physical properties such as hue and luminance within and between studies. Therefore, we conducted a two-interval duration-discrimination task to evaluate the perceived duration of color stimuli under different equiluminant conditions: subjective or pupillary light reflex (PLR)-based equiluminance. The results, based on psychometric functional analyses and simultaneous pupillary recordings, showed that the perceived duration of red was overestimated compared with blue even when the intensity of the stimulus was controlled based on subjective equiluminance (Experiment 1). However, since blue is known to induce a larger PLR than red despite equiluminance, we conducted a controlled study to distinguish the indirect effect of pupillary response to temporal perception. Interestingly, the effect observed in Experiment 1 faded when the luminance levels of the two stimuli were matched based on PLR response (Experiment 2). These results indicate that duration judgement can be affected not only by the hue but also by different equiluminance methods. Furthermore, this causality between the equiluminance method and temporal perception can be explained by the fluctuations in incident light entering the pupil. As color is indispensable to individuals’ perceptual experiences of the world, its effect has been the subject of research since the early history of psychology. Studies show that colors surrounding us in our daily lives profoundly affect bodily functions, including mood and behavior , 2. The e.g., red is often associated with danger, such as stop signs and warnings) [Although that study prompted much controversy, people have cognitive associations with specific colors. For instance, long-wavelength colors such as red are often considered dangerous and compelling, whereas short-wavelength colors such as blue are perceived as relaxing. Furthermore, red explicitly captures our attention and is associated with biological danger , 5, wherarnings) . TherefoUnsurprisingly, the growing interest in colors’ psychological effects on cognitive functions includes the pursuit of their effect on temporal perception was no exception. We also know from experience that perceptual time is not isomorphic to physical time, and our subjective experience of the passage of time is significantly influenced by non-temporal aspects, such as emotions, experiences, and our internal states. The fundamental role of time in social activities has led to temporal perception studies since the earliest days of experimental psychology , 13. PsyUnlike earlier investigations using a tachistoscope, recent studies use displays for stimulus presentation, enabling control of the stimuli’s physical properties, such as brightness and saturation. Gorn et al. reported that temporal perception was shorter with a blue background than with red or yellow backgrounds; warm colors were perceived for a longer time than blue . Shibasae.g., [The abovementioned studies show an inconsistency in the potential effects of color on temporal perception and indicate a lack of clarity regarding the probable mechanism of temporal perception modulation. Arousal is known to play an essential role in the distortion of perceived time, as suggested by the conspicuous internal-clock model (synonymous to the pacemaker–accumulator model) , 21, 22.e.g., , 24), ane.g., . Hence, e.g., [e.g., [To overcome these limitations, we conducted a two-interval duration-discrimination task to assess the effect of equiluminant colors on temporal perception. Specifically, we colorimetrically controlled the saturation of the presented red/blue stimuli and matched the luminance with subjective equiluminant to segregate the former’s effect on temporal perception (Experiment 1). Additionally, since short-wavelength light (blue) is more effective than long-wavelength light (red) in evoking a pupillary light reflex (PLR) even at identical physical luminance e.g., –28), the, thee.g., [e.g., , 30); ho, [e.g., ), which All experimental procedures and methods were approved by the Ethics Committee for Human Research at the Toyohashi University of Technology. Informed written consent was obtained after all procedural details were provided. The experiment involved 26 students  at the Toyohashi University of Technology. Eye movement data from two participants were excluded from pupillary analyses because the number of artifacts detected in the trials exceeded the 60% threshold, which could not be interpolated in the preprocessing phase. In the behavioral data analysis, trials with a reaction time > 10 s were also removed from the analysis, assuming poor task performance. This criterion rejected only a 0.18% of the trials. None of the participants reported color vision deficiency, and all had normal or corrected-to-normal vision.The experiment was conducted in a dimly lit room. MATLAB 2016a  and the MATLAB toolbox, Psychtoolbox 3 –33, wereIn the temporal discrimination task (main task), we used two-color disk stimuli with a 10-degree visual angle diameter. We individually adjusted the luminance of the red stimulus in the adjustment task to match the subjective luminance of the blue stimuli, and saturation was controlled despite the difference in hues. In the adjustment task, we used a square stimulus  instead. In both tasks, we displayed all experimental stimuli at the center of the screen.xy coordinates of the blue stimulus and the initial coordinates of red in the CIE1931 color space were  and , respectively. The background luminance remained constant at 37.83 cd/m2 for achromatic luminance . During the stimulus presentation, the fixation cross was located at the center of the screen for pupil diameter recording.The The experiment was divided into two tasks: an adjustment task and a duration-discrimination task. The adjustment task consisted of eight trials based on the heterochromatic flicker photometry method . The proEach trial in the adjustment task  recorded binocular pupillary responses at a sampling rate of 500 Hz. We did not instruct the participants when to blink during eye movement measurements since we placed importance on the temporal task; hence, we interpolated blinks before the main analysis using cubic-spline interpolation  in MATLAη  or CI , in the two-interval duration-discrimination task. To estimate the psychometric functions, the participants’ responses (proportion of CI stimuli judged longer) were modeled by fitting the logistic psychometric function using the Palamedes toolbox in MATLAB  and comp R, JASP  was used10 of 0.427 and a BF01 of 2.34, which can be interpreted as anecdotal evidence to support H0 over H1 [In the adjustment task, the participants conducted a luminance-matching task based on heterochromatic flicker photometry to determine subjectively equiluminant Y-value for the red stimulus. The mean average of the adjusted Y-value was 0.308, almost identical to the Y-value of blue (0.300). Therefore, we conducted a one-sample Bayesian t-test with a test value of 0.300 on the adjusted Y-values to statistically support this hypothesis. The analysis indicated a Bayes factor BF over H1 . The meaIn the duration-discrimination task, the participants indicated whether the RI  or CI  stimulus was perceived to have a longer duration. The order of the presented CI was not predetermined, and the CI was presented first (CI position: CI–RI) or second (RI–CI) with equal probability. Each CI-longer probability was used for psychometric function fitting for each duration step of the CI to compute the PSE and JND. The mean psychometric function shown in e.g., R–B represents the RI stimulus being red and the CI stimulus being blue). The dashed vertical lines represent the PSEs under each condition, proportional to the 50% probability of the function; the PSE denotes a specific duration of the CI judged equivalent to the RI, which is presented for 2,000 ms. A relative shift in the fitted function was observed in the incongruent stimulus comparison, whereas no shift emerged in the congruent stimulus comparison. Each solid line in p = 0.0006, t-test was also conducted. The post-hoc analysis showed that the two incongruent color sequences, R–B and B–R, differed significantly, as the PSEs were smaller when the CI color was red rather than blue (t[p = 0.0146), whereas no other color sequence combination showed significant differences. Additionally, the Bayesian repeated-measures ANOVA indicated BF10 = 36.5 and BF10 = 1.027 for PSE and JND, respectively. The PSE shift suggests a temporal overestimation of red stimuli compared with blue stimuli. Contrary to the PSE, the effect of color sequence on JND did not reach statistical significance  = 6.5613, n blue , und, unde.g.e.g., , with the.g., . Based oThe participants performed a two-interval duration-discrimination task at supra-second range intervals. According to the psychometric function analysis, the shift in the fitted function indicated that the duration of red stimuli was perceived as longer than that of blue stimuli .Moreover, we must emphasize that this effect was observed even when the colors of the two stimuli were controlled for saturation (colorimetric adjustments in terms of the CIE1931 color space) and luminance differences . Our results suggest that the temporal distortion effect of red and blue is primarily driven by hue and that the effects of luminance and saturation are partially limited. Moreover, notwithstanding the adoption of the heterochromatic flicker photometry method to satisfy subjective equiluminance conditions, the mean average of the adjusted Y-value was almost identical, and the red and blue stimuli were also closely physically equiluminant in mean.Furthermore, when we examined the pupillary responses, the PLR profile differed considerably, especially in amplitude. At the PLR peak for the blue stimulus, the pupil diameter was 1.66 times larger than that for the red stimulus . Since tBombeke et al. reported that differences in pupil diameter could modulate the magnitude of the initial feedforward response in the primary visual cortex and could, therefore, represent a confounding variable in studies investigating the neural influence of psychological factors . Suzuki As with Experiment 1, all procedures were approved by the Committee for Human Research at the Toyohashi University of Technology. Informed written consent was obtained after all procedural details were explained. Sixteen students  at the University of Oslo took part in the experiment. Two participants’ eye movement data were excluded from pupil analyses, and 2% of the trials were rejected based on excessive reaction time. The rejection criteria for both eye movement data and behavioral data were identical to those in Experiment 1.2 to match the display specifications in Experiment 1. The apparatus arrangements also followed those in Experiment 1, except that the viewing distance was set to 66 cm from the screen. All behavioral responses were delivered via a numeric keypad with unnecessary keys removed.The task was conducted in a different dimly lit room using MATLAB 2019a  and MATLAB’s Psychtoolbox, as mentioned in Experiment 1. The experimental stimuli were presented on an LCD monitor  with a resolution of 1,680 × 1,050 pixels and a refresh rate of 60 Hz. Colorimetric calibrations were conducted in advance for linear light output, and maximum luminance was corrected to 120 cd/mThe chromatic properties of the stimuli presented in the temporal discrimination task (main task) were identical to those in Experiment 1. However, the luminance of the stimuli was computed individually in the PLR-matching task. In this task, the luminance of the colored disks  varied at Y = 0.22, 0.25, 0.28, 0.31, and 0.34.The procedure of the temporal discrimination task was nearly identical to that in Experiment 1. However, instead of the heterochromatic flicker photometry method, a PLR-based method was used in Experiment 2  = 10 combinations) and randomly presented in a total of 50 trials per participant over two sessions. After stimulus presentation, the pupillary response was analyzed offline to determine a specific Y-value of blue. After preprocessing the pupillary data, the average PLR peak of all ten conditions was computed, and a linear regression analysis was performed to fit the discrete data points of luminance and PLR amplitude for both red and blue. Finally, luminance was evaluated via a fitted polynomial at the point where the PLR amplitude of red became equivalent. Simply put, the Y-value of blue that matched the PLR amplitude of red (Y = 0.300), was calculated. This calculated value was used to generate the blue stimulus in the following duration-discrimination task.Followed by a sufficient break, the participants performed the two-interval duration-discrimination task  eye-tracking system at a sampling rate of 250 Hz. A nine-point calibration was performed before each session in the PLR-matching and duration-discrimination tasks. In both phases, participants were not instructed when to blink, and, thus, blinks and artifacts were interpolated before analysis using the same method as in Experiment 1 . Trials Pupil size was measured in SI units (mm) by the eye tracker. Because of the specifications of the eye-tracking system, the units varied from those in Experiment 1. Measurements in terms of absolute units may not be entirely invariant to factors such as viewing distance and are, thus, somewhat arbitrary . TherefoRaw pupil data were preprocessed, as explained in the Methods section. −4 to 104 cd/m2) [e.g., approximately 26.4–39.6 cd/m2 in achromatic luminance). Hence, we concluded that linear regression provided adequate fitting accuracy, as indicated by the dashed lines in The typical PLR profile was observed from the responses in hue and luminance conditions; that is, a tendency for (1) PLR amplitude (constriction amount) to increase with luminance and (2) blue to induce a prominent PLR. The first finding can be explained by pupil constriction in response to brightness, a function of retinal illuminance control of physical inputs from the ambient environment . Second,4 cd/m2) , the intAs previously conducted, we tracked pupil diameter changes induced by the presentation of color stimuli in CI positions and all CI durations. F[p = 0.1370, F[p = 0.1083, Two-way repeated-measures ANOVA (color condition × stimulus-type condition) on the effect of peak PLR amplitude showed no significant main effect on color condition  were calculated by fitting a cumulative normal function and determining the 50% point. p = 0.3565, p = 0.0369, 10 = 3.012 and BF10 = 1.718 for the PSE and JND, respectively. The Bayes factor of the JND analysis  reaching statistical significance in the classical ANOVA, indicated anecdotal evidence to support H1 over H0 [From the estimated psychometric function, no significant shift was observed in congruent- or incongruent stimulus comparisons. The computed PSEs and JND were used for statistical testing. A one-way repeated-measures ANOVA was conducted on each color sequence; the effect for the PSE was not significant  previous studies investigating the temporal distortion effect on hue show inconsistent results, which may be due to the failure of stimulus intensity matching; and (2) pupil diameter differs depending on the hue, which can play a role in temporal distortions, in addition to the arousal level induced by the hue. To the best of our knowledge, this study is the first attempt to investigate the relationship between the PLR response, temporal perception, and stimulus color.Regarding PLR matching, e.g., [Statistical analysis suggested no significant temporal distortion via the hue condition, even though arousing stimuli are typically reported to be perceived longer. Many researchers have reported that observing emotional expressions can cause temporal distortion by increasing perceivers’ arousal levels . MoreovThis study investigated whether the color of a visual stimulus affects its perceived duration in different equiluminant conditions, to uniformly explain inconsistent research findings . This interaction supports the fact that different equiluminance methods can result in differences in temporal perception.In Experiment 1, the red/blue stimuli were matched by subjective luminance using heterochromatic flicker photometry. From the behavioral results, a shift in the PSE was observed in incongruent color conditions, indicating an overestimation of red stimuli compared to blue stimuli. In contrast, our analysis suggests no JND modulation in temporal judgments. These behavioral results aligned with those of previous studies e.g., , 16, 18), 18e.g.,e.g., , 45. More.g., [e.g., [Although the physiological models suggesting a differential effect of different PLR amplitudes on temporal perception are currently lacking, our newly found causality between the equiluminance method and temporal perception can be explained by neural intensity fluctuations based on the amount of incident light entering the pupil. The PLR generally controls pupil diameter to assist in vision adaptation via pupil constriction against intense ambient luminance and dilation in a dark environment. Therefore, the physical constriction of the pupil reduces the number and probability of photons captured by the retina. Notably, recent studies suggest that the PLR is not merely a reflex to brightness, but also affected by higher-order factors . As a mae.g., –28, 43),, [e.g., –54). Fur, [e.g., , resulti, [e.g., , 56. In , [e.g., . Moreovee.g., [Furthermore, Katsuura et al., who examined the effect of red and blue colors on temporal perception, reported that the cortical activity level in the visual pathway  might influence the temporal modulation effect, as mentioned earlier . Since oe.g., , 58). Dee.g., difficulties in the duration-discrimination task) and pupil near response  might affect the pupil diameter during the task [Here, we will note few limitations to the study. First, temporal processing mechanisms may vary between sub-second (milliseconds) and supra-second (seconds to minutes) interval ranges , 60. Addthe task . These eIn our analyses of psychometric functions and pupil diameter, our results showed that the perceived duration of red was overestimated compared to blue, even when the physical aspects of the stimuli were strictly controlled in subjectively  equiluminant conditions. However, this overestimation faded when the luminances of the two stimuli were matched based on the PLR amplitude. This causality between the equiluminance method and temporal perception may be due to the amount of incident light entering the pupil, leading to the modulation of different degrees of neural activation in visual-related regions. These results suggest another possible mechanism of temporal distortion by hue, in addition to the previously discussed hue-arousing effect. In addition, our results suggests that the pupillary somehow plays a role in temporal perception from a phenomenological perspective. Although these links remain speculative at present and require further consideration, incorporating neuroscientific approaches and discussion on theoretical frameworks, we believe that discovering this causal role may help clarify the inconsistent results of previous studies and further elucidate the underlying mechanisms of temporal perception.


The viscosity of the nanofluid was examined in different conditions. Lab data were used to model dynamic viscosity of HNF using the Response Surface Methodology (RSM), and first, second, third, fourth and fifth-order models were created. An analysis of the statistical parameters concluded that with a correlation coefficient of 0.9999, the fifth-order model is the best performer. The trend of alterations in viscosity shows that an increase in temperature has great effects on viscosity, and its influence is also more important than that of changes in shear rate (SR) and SVF. Optimal viscosity was also calculated and was equal to 158.1 mPa.sec at SVF = 0.05 %, SR = 11,997 s−1 and T = 14.97 °C.The science of nanofluids is still fairly new and due to this, the properties of many nanofluids are yet to be explored. Therefore, equations for precise calculations in this field are not available yet. For this reason, as a thermophysical property of an MWCNT (40%)/TiO Optimal modeling; Dynamic viscosity; Hybrid nanofluids; Response surface methodology (RSM). This noticeable effect is due to the increased mobility of the particles, weakened intermolecular forces and easier sliding of the nanofluids layers on each other, as the temperature rises. A optimal nanofluid for cold seasons is one that has lower viscosity at low temperatures, so proper lubrication is ensured. For the selected model, at SVF = 0.050%, SR = 11,996 (1/s) and T = 14.97 °C, the optimal viscosity is 158.1 mPa.s. Since the science of nanofluids is still very much new, many opportunities for activity and research are available in the field. HNF consisting of MWCNT-TiO2 nanoparticles was investigated in this research, but many more are yet to be explored, and experimental research, modelling and simulations for these nanofluids can be considered for future studies. Comparing different nanofluids and choosing the best one is also another research idea. Using the RSM to model process costs and thermophysical properties such as thermal conductivity, density etc., are also among the subjects that require further research.Dynamic viscosity of a 10W40 oil-based MWCNT (40%)/TiOMohammad Hemmat Esfe: Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.Sayyid Majid Motallebi: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data.Davood Toghraie: Conceived and designed the experiments; Performed the experiments; Contributed reagents, materials, analysis tools or data; Wrote the paper.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.No data was used for the research described in the article.The authors declare no conflict of interest.No additional information is available for this paper.