To compare specific attention functions for school-age children with chronic kidney disease (CKD) to those of a typically developing control group.n = 30) in comparison to a typically developing control group (n = 41). The CKD group consisted of those receiving maintenance dialysis (n = 15) and those with mild/moderate CKD treated conservatively (n = 15). Measures aligning with Mirsky’s conceptual multidimensional model of attention were selected to compare groups across five dimensions of attention: Focus/Execute, Sustain, Stability, Shift, and Encode.A cross-sectional study examined attention dimensions for children and adolescents with CKD (Significant group differences were revealed, with the CKD group performing worse than controls on the Focus/Execute, Sustain, and Encode dimensions. The CKD group also had a larger proportion of children with scores one standard deviation or more below the mean on the Shift and Encode domains, suggesting an at-risk level of functioning in these dimensions. Secondary analyses showed disease severity to be correlated with worse attention functions for children with CKD.Children with CKD may be vulnerable to subtle, specific deficits in numerous attention dimensions relative to their typically developing peers, particularly for those with more severe disease. Chronic kidney disease (CKD) is a medical disorder that has been correlated with a number of neurodevelopmental concerns in childhood , even inMost studies that have studied attention in pediatric CKD have examined it as a unidimensional construct, although several studies have shown children and adolescents with CKD to be at risk for different types of attention-regulatory abilities  and typically developing controls (n = 41) from a single medical center in the southeastern United States. Fifty percent of the CKD group consisted of individuals with End-Stage Kidney Disease (ESKD) receiving dialysis therapy (n = 15) and the other 50% included those with mild/moderate CKD managed with conservative therapies (n = 15). Among the CKD participants with ESKD, nearly all (n = 14) were receiving hemodialysis as opposed to peritoneal dialysis (n = 1). Inclusion criteria comprised those participants with CKD (defined as GFR ≤ 75 mL/min/1.73 m2), calculated by the 40% of the CKD group had a history of grade retention, while 17% were receiving special education services. Exclusion criterion included a history of prior kidney transplantation or the presence of a co-existing condition associated with central nervous system anomalies . Control group participants (n = 41) were selected for participation if there was no prior history of chronic health conditions, head trauma, developmental disorder , neurological/psychiatric illness, or any current medication usage. All participants and their parent or legal guardian provided assent and consent prior to testing.Participants included children and adolescents with CKD  to control for any negative reactions that could invalidate results. Similarly, testing did not coincide with dialysis procedures as that procedure occurred on an entirely separate day in an effort to avoid confounding of the pre- or post-effects of dialysis. Participants in the control group only underwent neuropsychological testing and were not subjected to any medical procedures.Clinical variables included disease severity, as defined by GFR, duration of disease, age of onset, and co-morbid diagnoses , and were obtained for participants in the CKD group. Anemia was defined as a hemoglobin level < 10.7 mg/dl, and hypertension was defined as measured blood pressure above the 95th percentile or the presence of antihypertensive therapy. Socioeconomic status was defined by maternal education which was nominally coded .Measures were selected to align with the five-factor attention model posited by Prior to conducting statistical analyses, scores for each of the dimensions of attention were calculated. Age-based standard scores  were calculated from normative data for the following variables: TOL Total Moves, TOL Total Execution Time, GDS Total Correct, GDS Mean Response Time, GDS Correct Variability, ACPT Total Correct, WRAML Finger Windows, and WRAML Number/Letter. Means and standard deviations for the RFFT Perseverations and ACPT Correct Variability scores were generated from control group data for this age range so as to calculate standard scores for the entire sample. Scores were scaled such that higher standard scores indicated better performance for all variables. Once standard scores were generated for all variables, alpha coefficients were calculated as reliability indices to assess internal consistency within each attention dimension to determine if selected measures were at least moderately related to one another.T-tests were conducted to evaluate group differences between the CKD and control groups with respect to age and IQ. Pearson’s chi-square tests were run to compare groups on the variables of maternal education, and sex. If differences between the groups were evident, each variable was examined for its potential to confound results and whether to include it in subsequent multivariate analyses. Chronological age was chosen a priori as a covariate for all subsequent analyses given the wide age range in the entire sample and due to the conversion of RFFT and ACPT variables from raw scores to standard scores using all of the individuals in the control group.Preliminary analyses compared the CKD and control groups on the variables of age, sex, maternal education, and IQ to determine whether the groups differed systematically on any of these variables. For the primary analysis, scores on the five attention dimensions were compared between the CKD and control groups using MANCOVA and follow-up univariate procedures with a significant model. Estimates of effect sizes were calculated using partial eta squared  and stanGiven the small sample size, a secondary exploratory univariate ANCOVA and corresponding chi-square tests for the at-risk status also were calculated to compare the attention dimensions across severity groups . A Bonferroni correction was applied to adjust for the multiple comparisons. Additionally, correlations were obtained on CKD group data to examine the associations among the attention dimensions and selected disease-related variables including disease severity , age of CKD onset, and duration of CKD. Given the construction of several of the attention variables from sample-based data, chronological age was partialed out in the secondary correlation analysis.Internal reliability estimates using Cronbach’s alpha coefficient produced acceptable reliability for each of the five attention dimensions: Focus/Execute α = 0.56, Sustain α = 0.65, Stability α = 0.53, Shift α = 0.59, and Encode α = 0.67. Given this level of internal consistency, the attention dimensions were calculated as described above.t-test revealed no group differences on the mean age of participants, t(69) = 1.21, p = 0.23; nevertheless, as noted above, chronological age was used as a covariate in subsequent analyses given the wide age range of the sample and the use of the Control group to calculate standard scores for two attention variables. The CKD and Control groups differed significantly in their overall levels of intelligence based on the Full-Scale IQ from the WASI, t(69) = 6.99, p < 0.001, with the mean score for the CKD group falling at the lower end of the average range  = 2.48, p < 0.04. Follow-up univariate procedures indicated that the CKD group performed lower than the Control group on the dimensions of Focus/Execute, F = 4.41, p < 0.007, Sustain, F = 4.08, p < 0.01; and Encode, F = 11.81, p < 0.001. Effects sizes for these group differences were large in magnitude. The CKD and Control groups did not differ significantly on the Stability (p < 0.08) and Shift (p < 0.18) dimensions, although medium effect sizes were present for each variable.Descriptive statistics for both groups are presented in p < 0.004) and this variable was included as a covariate in the ANOVAs.Secondary exploratory univariate analyses of variance (ANOVAs) were used to compare the control versus the mild/moderate CKD versus the ESKD groups on the attention dimensions . Prelimip < 0.001), Sustain (p < 0.001), Stability (p < 0.01), and Encode (p < 0.001). The groups did not differ significantly on the Shift attention dimension (p < 0.29). Follow-up pairwise comparisons for the significant overall findings revealed that the ESKD group performed significantly more poorly than the other two groups, with all scores falling within the bottom quartile. The Control group and Mild/Moderate CKD group performed similarly across the five attention dimensions ESKD, suggesting a possible dose effect related to severity.Initial inspection of the mean scores across the five attention dimensions revealed the expected “stairstep” pattern (with the exception of the Mild/Moderate CKD Group being slightly higher than the Control Group on Focus/Execute), with the higher scores being demonstrated by the Control Group followed by the Mild/Moderate Group and then the ESKD Group. After adjusting for chronological age and maternal education, results of the univariate ANOVAs indicated that the groups differed significantly on four of the five attention dimensions: Focus/Execute (p < 0.04), indicated that the proportion of scores more than one standard deviation below the mean differed significantly between the CKD and Control groups on the attention dimensions of Shift, χ2(1) = 7.84, p < 0.005; and Encode, χ2(1) = 10.73, p < 0.001. The proportion of participants with attention dysfunction was similar between groups on the dimensions of Focus/Execute, χ2(1) = 1.52, p < 0.22; Sustain, χ2(1) = 2.46, p < 0.12; and Stability, χ2(1) = 1.75, p < 0.19.Results from chi-square tests for the two group comparison  with thep < 0.04) exploratory chi-square analyses revealed that the ESKD groups differed significantly in their proportions of cases deemed at-risk on all five dimensions, with the ESKD group having a significantly higher rate of individuals scoring in the at-risk range on each of these dimensions: Focus/Execute, χ2(2) = 9.85, p < 0.007; Sustain, χ2(2) = 12.23 p < 0.002; Stability, χ2(2) = 8.09, p < 0.02; Shift, χ2(2) = 7.84, p < 0.02; and Encode, χ2(2) = 15.30, p < 0.001. Consistent with the findings from the univariate ANOVAs, the ESKD group showed a significantly higher proportion of individuals falling in the at-risk range than either of the other two groups. The only attention dimension that deviated from that pattern somewhat was Shift, which showed similar rates of at-risk status for the CKD groups, and it was the only dimension where the Mild/Moderate group had a significantly higher proportion of individuals at-risk than the Control group.For the three-group comparison  with ther = 0.50). Similarly, the Sustain and Encode dimensions moderately and significantly correlated with GFR in the positive direction (r = 0.37 for both), indicating that better kidney functioning was associated with better attention in these three dimensions. Additionally, the Encode dimension moderately and significantly correlated with the duration of CKD, such that higher Encoding scores reflected a shorter disease duration (r = −0.35). The Focus-Execute Dimension did not significantly relate to age of onset or duration of CKD. The Stability and Shift dimensions of attention were not significantly related to any of the three disease-related variables. The co-morbidities of anemia and hypertension were not correlated with any of the attention dimensions, thus were not used in further analyses.The study was not powered to enter additional variables into the modeling, but it was important to determine the relationship of selected disease-related variables to the attention dimensions. After partialing out chronological age, correlations suggested significant associations between the Focus/Execute dimension and GFR. The magnitude of the relationship reached the moderate to strong range , stay vigilant for an extended period of time (Sustain), and actively hold information in mind (Encode). The abilities to move from one salient aspect of a stimulus to another in a flexible, efficient manner (Shift) and to maintain consistency in response patterns over time (Stability) were not different between groups. The CKD and control groups also differed with respect to the proportion of participants showing at-risk status for attentional impairments (≥1 standard deviation below the mean) on the Shift and Encode attention dimensions, indicating that there is a significantly large number of children with CKD who will struggle with these types of attention. The proportion of participants in the CKD group who were at-risk for attention impairments also was similar in frequency to findings in at least one previous study . SecondaThis finding implicating disease severity as impacting attention dimensions was further supported by the strong correlation between GFR and the attention dimensions of focus/execute, sustain, and encode. Interestingly, the stability and shift attention dimensions were not correlated with any of the CKD-related variables, perhaps secondary to the small sample sizes in the subgroups in this study and/or to some other unknown confounding factor. Other disease-related factors, such as duration of disease, may have small to moderate relationships with selected attention dimensions. While these associations warrant further investigation with a larger sample, the correlational findings were in the expected directions. For example, less disease severity related to better functioning in the Focus/Execute, Sustain, and Encode attention dimensions, while shorter disease duration related to higher scores on the Encode dimension. Identifying attention problems, in a more detailed fashion, may subsequently impact a child’s life course by guiding more specific types of educational and/or behavioral interventions , and futThe literature on attention in adults with CKD is broader, but has focused more on improvements in attention associated with the use of dialysis techniques or kidney transplant e.g., . OverallSeveral explanations exist for the group differences obtained in the current study. First, the effects of CKD on attention may be more prevalent in adolescence when academic demands in middle and high school require more sophisticated and intact attention. In this sense, task demands as a function of developmental stage may play a significant factor with encoding, focus/execute, and sustaining attention dimensions being most vulnerable early in the developmental process. A second explanation for the group differences relate to the effects of CKD severity. In this regard, children with the most severe forms of CKD who are more urgent candidates for a kidney transplant and receiving dialysis treatment may have even more significant attention difficulties, perhaps driven by both cognitive and emotional conditions. Although there were differences between the mild/moderate CKD and ESKD groups on selected attention dimensions, one might also suspect a higher potential for a more generalized impairment in cases of advanced kidney disease . Third, in all likelihood, there is a combination of developmental factors , including psychosocial factors, that contribute to differential attention disruption. For example, as the various worries and concerns in both the child and caregiver regarding the child’s health increase with worsening kidney function, it is entirely possible that specific attention problems may be seen in the focus/execute and sustain functions. Further, there may be additional non-kidney related biological mechanisms in action, such as genetic predispositions , that alAlthough this study examined a critically important avenue of assessment in pediatric CKD, the study did have a number of limitations that should be considered. First, the study included a small sample size, which precludes any broad generalization or interpretation of the results. Additionally, the small sample size reduced the power needed for inclusion of other covariates in the primary model, thus relegating key disease-related variables to secondary correlational analyses. Future research should endeavor to establish larger sample sizes through multisite collaboration to allow for inclusion of additional covariates , thus resulting in more extensive analysis of potential predictors of attention function/dysfunction. This would assist in developing a predictive model of attention outcomes in CKD, giving pediatric nephrologists and other care providers of this population a valuable tool to guide collaborative, interdisciplinary care. Second, the study included a single control group. While this represented an appropriate initial comparison, it is not clear how this pattern of attentional dysfunction would compare or contrast to another pediatric chronic illness group, thus limiting the specificity of the findings. Indeed, this study also provided a signal regarding the importance of disease severity to attention function and a larger comparative group—even within the CKD spectrum —could be enlightening. Third, this study leaned on the Mirsky model of attention, but it is possible that another model of attention , or even a different operationalization of the Mirsky model using different neurocognitive measures, might lead to a different set of findings. Relatedly, while our internal reliability estimates of the attention dimensions were adequate for an initial study, the minimally satisfactory reliability of the dimensions warrants the need for improved measurement models with increased reliability  of specific attention functions. Finally, this study was decidedly cross-sectional in its design and, as such, could not address the critical issue of neurocognitive development within the context of a chronic illness and, in this instance, in the context of examining increasing disease severity in a continuous fashion. Future studies should endeavor to conduct longitudinal follow-up so as to provide better insight into the onset and development of specific and general attention impairments in CKD. This would allow for more targeted educational supports in terms of recognizing specific learning, behavioral, or emotional needs, as well as developing plans for extended absenteeism or attention-related fatigue related to CKD.Although the sample size was small, results from the current study provide some of the most comprehensive findings to date on the differential attention functioning of children with CKD. Taken together, the results of this study suggest specific types of attention dysfunction, particularly in the focus/execute, sustain, and encoding, types of attention. This raises questions regarding the integrity of the underlying structure and function of frontal and prefrontal brain regions in the pediatric CKD population  in the dThe 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 Institutional Review Board, University of North Carolina at Chapel Hill. Written informed consent to participate in this study was provided by the participants or their legal guardian/next of kin.PD, DG, and SH contributed to the study design, collection of data, interpretation of the findings, manuscript preparation, and editing. PD and SH conducted the data analyses. 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.


This outcome did not suffer any publication bias. However, after removing an outlier study, the recalculated OR was 1.88. In conclusion, the presence of sarcopenia in knee OA patients was high, affecting one person in every two persons and was higher than in the control groups included.An association between knee osteoarthritis (OA) and sarcopenia has been proposed, but the evidence is controversial, with the recent literature showing disparate results. Therefore, we aimed to perform a systematic review and meta-analysis to evaluate the prevalence of sarcopenia in knee OA patients compared to people not affected by this condition. We searched several databases until 22 February 2022. The data regarding prevalence were summarized using odds ratios (ORs) with their 95% confidence intervals (CIs). Among the 504 papers initially screened, 4 were included for a total of 7495 participants with a mean age of 68.4 years, who were mainly females (72.4%). The prevalence of sarcopenia in people with knee OA was 45.2%, whilst, in the controls, it was 31.2%. Pooling the data of the studies included that the prevalence of sarcopenia in knee OA was more than two times higher than in the control group (OR = 2.07; 95%CI: 1.43–3.00; I Sarcopenia remains one of the most widespread geriatric syndromes and the major leading cause of mortality . The priOsteoarthritis (OA), by its turn, is the most common articular disorder, rising as the population ages and affecting up to a fifth of people worldwide, thus being the most prevalent cause of joint disease globally . AlthougBeing that OA and sarcopenia are very frequent conditions, it is not unexpected that they often co-exist, raising the possibility of them interacting with one another. The biomechanical effect resulting from an altered bone and periarticular muscle cross-talk could be responsible for the atrophy or weakness of the muscles themselves, thus leading to the development, progression and severity of OA . The intDespite the multiple interconnections postulated to explain a possible modulating effect of OA on sarcopenia, data demonstrating a relationship between the two diseases remains elusive and, at times, conflicting. Taking these considerations into account, we aimed to perform a systematic review and meta-analysis to evaluate the prevalence of sarcopenia in knee OA patients, compared to people not affected by this condition, and whether it could be demonstrated as significant evidence concerning an association between sarcopenia and knee OA in terms of the latter to OA development, progression and severity.This systematic review adhered to the PRISMA statement  and follTwo investigators independently conducted a literature search using PubMed/Medline, Scopus and Web of Science from their database inception until 22 February 2022 and included observational studies investigating the presence of sarcopenia in patients affected by knee OA. In PubMed/Medline, the following search strategy was used: (Osteoarthriti* OR osteo arthritis OA or osteo-arthriti* OR osteoarthros* OR osteo-arthros* OR osteoarthros* OR arthrosis) AND (sarcopenia)”, adapting the search for Scopus and Web of Science. Any inconsistencies during the title, abstract and, finally, full-text screening were resolved by consensus with a third senior author (NV). The inclusion criteria for this meta-analysis were as follows: (i) an observational study; (ii) reporting a diagnosis of knee OA, using radiological and/or medical information; (iii) reporting data on sarcopenia, independently from the definition used ; (iv) reporting data regarding the controls defined as people without any evidence of knee OA. Studies were excluded if: (i) they did not include humans; (ii) they did not include a control group, i.e., without knee OA.Two independent investigators extracted key data from the included articles on a standardized Excel spreadsheet, with a third independent investigator (NV) checking the data. For each article, we extracted data on the authors’ names, year of publication, country, sample size, age and percentage of females, and the mean body mass index (BMI) diagnostic criteria used for the definition of knee OA and sarcopenia.The primary outcome was the prevalence of sarcopenia in knee OA versus the controls.Two independent authors  carried out the assessment of the studies’ quality using the Newcastle–Ottawa Scale (NOS) . The NOSThe primary analysis compared the cumulative prevalence of sarcopenia between participants with knee OA and participants without this condition. We calculated the odds ratio (OR) with their 95% confidence intervals (CIs), applying a random-effect model .2 metric and χ2 statistics. Given the significant heterogeneity , we conducted a series of meta-regression analyses [Heterogeneity across studies was assessed by the Ianalyses , using aanalyses .p-value less than 0.05 was considered statistically significant. All analyses were performed using STATA, version 14.0 , and RevMan 5.4 .For all analyses, a As shown in 2. Three studies were conducted in Asia, whilst the other one was in Europe. Three studies used a definition of knee OA with only radiological information and with a moderate severity according to the Kellgren–Lawrence scale. The diagnosis of sarcopenia was made in two studies using only low muscle mass, whilst the other two used a combination of low muscle mass and physical performance. Finally, the quality of the studies was, in general, very good, without any study presenting a high risk of bias. As shown in p = 0.0001; I2 = 85%). This outcome did not suffer from any publication bias according to the funnel plot inspection and Egger’s test . As shown in 2 = 20%, with a recalculated OR of 1.88 (95%CI: 1.53–2.30). On the contrary, the age (p = 0.59), percentage of females (p = 0.48) or BMI (p = 0.06) did not moderate our findings. Since the outcome of our interest was characterized by high heterogeneity, we used a sensitivity analysis, removing one study at each step. After removing the cohort of females of Sung et al., the heterogeneity significantly decreased to an IThis systematic review with the meta-analysis represents a step forward in the thus far investigated interplay between two major geriatric clinical entities that, when associated, could progressively lead to devastating consequences. When pooling the data of four selected studies, evaluating a sample of 7495 subjects, we clearly identified that the prevalence of sarcopenia in people with knee OA (45.2%) resulted more than two times higher than in the control group (31.2%) since the OR was 2.07. A complex interaction of multiple factors contributes to the development and progression of OA, making physiopathology harder to define. Initially, biomechanics and macroscopic structural factors regulating bone alignment and cartilage kinetics were the main focus. Moreover, in the latter years, researchers focused the lens on biomechanics, interpreting the factors that contribute to cartilage destruction and the remodeling of subchondral bone . Upper eFurthermore, even confronting weight-bearing joints, such as the knee, the recognition of inflammatory damage patterns activating the complement cascade as pathogenetic factors highlights the concept that OA may not actually be a single disease . In paraIn our systematic review, knee OA was diagnosed and classified according to the radiographic criteria of the Kellgren and Lawrence classification as moderate severity, and in one study, the clinical information was integrated. Furthermore, sarcopenia was defined as low muscle mass and/or physical performance, as suggested by the EWGSOP criteria. In line with both these considerations and the previous scientific literature postulating that OA and sarcopenia may be co-existing conditions—an entity usually called osteosarcopenia —our workIn knee OA, quadriceps weakness is an issue of paramount importance. The previous literature describes subjects with OA of the knee who are unable to effect a maximal voluntary contraction of the quadriceps . This phA large longitudinal cohort study found that, in 1653 subjects without radiographic knee OA at baseline, an increased risk of radiographic OA was not associated with sarcopenia alone but rather with sarcopenic and body composition-based obesity . In our 2 = 20%, with a recalculated OR of 1.88 (95%CI: 1.53–2.30), maybe indicating a different role of gender in the association between sarcopenia and knee OA.Since the outcome of our interest was characterized by high heterogeneity, we used a sensitivity analysis, removing one study at each step. After removing the cohort of females of Sung et al., the heterogeneity significantly decreased to an IThe findings of our systematic review must be interpreted within its limitations. First, the studies that were included were observational and cross-sectional/case-control: therefore, a high probability of reverse causation, i.e., people with sarcopenia have a higher prevalence of knee OA, is possible. Second, the outcomes of our interest are characterized by high heterogeneity, even though it is mainly driven by one study. Third, different definitions of sarcopenia were used in this systematic review, including definitions using only muscle mass assessment. In this regard, several societies indicated that low muscle mass identifies only a stage of pre-sarcopenia than sarcopenia itself, for which other measurements are needed, such as physical performance or muscle strength. ,30 In ouThe presence of sarcopenia in knee OA in patients was high, affecting one person on two and was higher than in the control groups included. Future studies with a longitudinal design are required to confirm whether the incidence of sarcopenia will be higher in people affected by knee OA and the role of some important mediators, such as obesity, in this association.


Fetal Autonomic Nervous sysTem Evaluation (FANTE) is a non-invasive tool that evaluates the autonomic nervous system activity in a fetus. Autonomic nervous system maturation and development during prenatal life are pivotal for the survival and neuropsychiatric development of the baby.Aim of the study is to evaluate the effect of music stimulation on fetal heart rate and specific parameters linked to ANS activity, in particular fetal heart rate variability.Thirty-two women between the 32nd and 38th week with a singleton uncomplicated pregnancy were recruited. All FANTE data collections were acquired using a 10-derivation electrocardiograph placed on the maternal abdomen. In each session , FANTE was registered. The music stimulus was “Clair de lune” Debussy, played through headphones on the mother’s abdomen (CTR: 31927).p = 0.037, ANNsd p = 0.039, SD2 p = 0.019) during music stimulation in comparison to the basal phase. Heart rate variability increase depends mainly on the activation of parasympathetic branches (CVI p = 0.013), meanwhile, no significant changes from basal to stimulation phase were observed for indices of sympathetic activity. All the parameters of heart rate variability and parasympathetic activity remained activated in the post-stimulus phase compared to the stimulus phase. In the post-stimulus phase, sympathetic activity resulted in a significant reduction (LFn p = 0.037).Music does not change the mean value of fetal heart rate. However, indices of total fetal heart rate variability statistically increase (RRsd Music can influence the basal activity of the fetal autonomic nervous system, enhancing heart rate variability, without changing fetal heart rate mean value. Music is enabled to induce a relaxation state in a near-to-term fetus, mediated by parasympathetic activation and by a parallel sympathetic inhibition. The autonomic nervous system (ANS) is a key homeostatic regulator both in prenatal and post-natal life . The maiFetal and neonatal wellbeing, as like fetal outcomes at birth, is strongly linked with ANS function. During fetal adaptation to postnatal life, ANS acts as the main regulator of the new-born cardiovascular and respiratory systems . At birtFor these reasons, it is important to identify markers and tools useful to evaluate and activate fetal ANS activity, to assess the neural maturity of a fetus, and to project clinical intervention about abnormal maturation of ANS management.Several techniques have been studied to asset the quality of ANS activity in fetal life. Since the autonomic capacity is mirrored in cardiovascular regulation, a marker widely used for evaluating ANS activity is Heart Rate Variability (HRV) , 13, 14.The evaluation of HRV is used as a predictor in a wide variety of disorders, like stroke, multiple sclerosis, end-stage renal disease, diabetes mellitus, ischemic heart disease, particularly myocardial infarction, cardiomyopathy, patients awaiting cardiac transplantation, valvular heart disease, and congestive heart failure –20.Recently, some authors proposed fetal cardiomagnetography (fCMG) for the study of fetal ANS activity. The fMCG analysis allows obtaining time-domain and frequencies-domain parameters that reflect general maturation, adaptation, and organization of fetal ANS. Although, this method is quite expensive, not very usable in maternity care, and potentially dangerous if used routinely , 24–26.Our research group developed a non-invasive method of data collection of the fetal heart activity which could be considered equal to fCMG in providing useful data on ANS activity, called Fetal Autonomic Nervous sysTem Evaluation (FANTE) , 28. Thiin utero  suitably modified. We used ten standard electrodes. The peripheral electrodes  were placed on the maternal abdomen in a triangle around the navel (orange) with lower apex, while the precordial ones  were put on an external circle . The NeuConsistently with previous studies, the effect of the auditory stimulus on fetuses and newborns was verified using classic music –46. For In our study, we decided to apply a music stimulus with a sound intensity under the level consider detrimental (85 dB) to avoid any possible harmful effect on the fetuses .Moreover, in a previous study by Gagnon et al. , the autTo all patients, FANTE multiple data collections were proposed. The data collections were performed in the same room, in supine position, without other acoustic interference.In every session, we obtain a basal FANTE data collection (5 min), a stimulus FANTE data collection (10 min), and a subsequent post-stimulus FANTE data collection (5 min).Fetal ECG extraction and subsequent analysis from FANTE were achieved with a dedicated analysis software based on an algorithm developed and tested by the group of IFC-CNR , 48, 49.From the initial sample of 32 mothers, 19 were excluded because their FANTE data collections were too noisy, and our method was unable to extract the fetal ECG and the obtained fetal RR series was meaningless. To exclude these cases from the analysis, we define a quality index. The Bad Index (BI) consider:-the trimmed mean of the absolute successive differences of RR.-the trimmed mean of the absolute successive second differences of RR.-the ratio between the number of matched positions  and the total number of QRS.-a non-linear correction factor that takes accounts for the probability distribution of the mean fetal RR.For this analysis, we consider FANTE data collection suitable for the analysis with a BI < 0.1 . It is worth explaining that, at this gestational age, the execution of FANTE is achievable in 100% of cases. However, given the limited number of patients recruited, to obtain the best possible data quality, we included only FANTE data collection session in which BI < 0.1 in all three phases. This preliminary assessment led to the final sample of 13 mothers. Some of these mothers had multiple data collections in different gestational ages, leading to a sample of 20 signals.The selected RR series was first screened for artifacts, uterine contractions, arrhythmias and then processed to compute temporal and frequency indices.The following indices were extracted from the RR series:-Time-domain features of HRV:•fHRm: fetal HR mean.•RRsd (ms): standard deviation of RR intervals, index of total HRV;•ANNsd (ms): standard deviation of the Average NN intervals for each 5 min segment of a 24 h HRV registration, index of total HRV;•SD1 (ms): standard deviation perpendicular to the line of the identity of Poincairè Plot; short term variability, mainly controlled by parasympathetic tone;•SD2 (ms): standard deviation along the line of the identity of Poincairè Plot; long term variability, index of total HRV;•2): log10 (SD2xSD1); Cardiac Vagal Index, the contribution of the parasympathetic nervous system to cardiac regulation.CVI (ms-Frequency-domain features of HRV:•2): total power of fetal RR series, index of total HRV, mainly controlled by sympathetic tone;Ptot  normalized for the total power; low-frequency band mainly controlled by sympathetic tone;•HFn: spectral power in the low-frequency band (0.15–0.4 Hz) normalized for the total power; low-frequency band mainly controlled by parasympathetic tone.GraphPad Prism 7  program was used for data analysis and graphic presentations.The parameters assessed in women have been included in the table. Category variables have been represented as frequencies and percentages, while continuous variables were represented as averages, standard deviations (SD), and interquartile ranges.The normality of the variables was determined using the Shapiro–Wilk normality test. In accordance, ordinary or repeated measures (RM) one-way ANOVA, followed by paired sample Tukey’s multiple comparisons test, was performed when comparing features extracted from fetal RR series in every session for each patient.p < 0.05 were considered statistically significant.For all comparisons, the values of This study was carried out in agreement with the recommendations of the Good Clinical Practice (ICH/GCP), Ministerial Decree of 1997. The protocol was approved by the Regional Ethics Committee for Clinical Trials, Tuscan North West Wide Area. All subjects gave written informed consent by the Declaration of Helsinki .The demographic and clinical characteristics of the population are summarized in All women had a full-term delivery. No newborn needed neonatal resuscitation.Music presents different effects on fetuses. The value of fHRm does not change during the stimulus phase and in the post-stimulus. However, fetal HRV statistically increases during the stimulus phase and this modification persists in the post-stimulus FANTE data collection ; Table 2F = 6.71, p = 0.037, R2 = 0.26) , SD2 , Ptot    , ANNsd ( = 0.25) . CVI, ma = 0.29)  while ot = 0.29) .F = 5.16, p = 0.88, R2 = 0.21)  .p = 0.99) (p = 0.832), SD2 (p = 0.997), Ptot (p = 0.346) (p = 0.037) (p = 0.695)  , ANNsd (= 0.346) , but LFn= 0.037) . CVI, co= 0.695) .Considering ANS signaling before and after music stimulation, we can note an important role of music as a stimulus of ANS activation. When the music stops, ANS modification persists in the following 5 min. Comparing ANS activity in the basal phase and the post-stimulus phase, the parameters showed a significant increase of the HRV  , 4A–C moIn this paper, we presented the effects of a short musical stimulus (10 min) on the activity of the fetal ANS, through the modulation of sympathetic and parasympathetic signaling. We registered this modulation through external sensors placed on the maternal abdomen as already shown in a previous work .Music induces a modification of the parameters which regulate HRV , without a significant change in fetal heart rate.This modulation persists as a short-term effect even after the music stops, for the entire length of the post-stimulus FANTE data collection (about 5 min). In our opinion, this demonstrates that music, at the intensity we used (mean 50.8 dB), determinates the activation of ANS without inducing a fight-or-flight reaction, sympathetically mediated, as a simple sound stimulus does. The music-dependent relaxation-state of the fetus is achieved by the increase of CVI through the activation parasympathetic system , 3.It has been widely demonstrated that acoustic stimulation can influence HR activity –32, 36. Defense response is typically elicited by high-intensity stimulus and it determinates a sympathetic activation, meanwhile orienting response is activated by low-intensity stimulus and it reflexes a parasympathetic activation. Based on Sokolov’s model, those two responses were related to cardiac change .In our study, the application of a music stimulus did not change the value of fetal heart rate. In accord with our results, D’Elia et al.  did not In the study conducted by Lecanuet et al. , the autFrom a translational point of view, the demonstration of the efficacy of an external stimulus in modulating the ANS signal is innovative and very promising, especially in those cases of incomplete development of the ANS.ad hoc stimulation, could help the activation of the ANS and therefore its development.For the first time, we demonstrated that, with music, it is possible to modulate fetal ANS activity in the short term, opening potentially significant scenarios from a therapeutic point of view. For example, in pregnant women with threatened preterm labor (where it is expected the birth of infants with delayed development of the ANS) rather than in term fetuses with potential risks of associated diseases , the use of music in the prenatal period, through On the other hand, we demonstrated music determines an early modulation of the whole autonomic activity, although, with our data, it is still not possible to verify if these modulating effects determine a long-term modification of fetal ANS basal activity.The missing data about the possible long-term effect of music on the fetus is the real point of the weakness of our study. We were not able to demonstrate if this stimulus could have a real and positive effect on fetal ANS. This needs further investigation to clarify if we can long-term modulate fetal development and wellness with acoustic stimulus, perhaps repeated several times, at different time points of the pregnancy.Another limitation of the study is the small sample size. In our previous article, we have been able to retrieve fetal ECG signals in the 62.5% of data collections. In the present study, the efficiency of the FANTE data collection was a little bit lower, since from 32 weeks of gestation to term, the presence of vernix caseosa can limit the possibility of fetal ECG signal extraction . MoreoveThis study concludes that music can modulate fetal ANS basal tone in the short term, enhancing HRV, without changing fHRm. In particular, music enables to induce a relaxation state in a near-to-term fetus, mostly mediated by parasympathetic activation.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 Regional Ethics Committee for Clinical Trials, Tuscan North West Wide Area. The patients/participants provided their written informed consent to participate in this study.PM, LB, and MV conceived and designed the study and coordinated the project. FM, AC, and GI performed the study and collected the data. LB and MV were responsible for the formal analysis. FM and MM-G were responsible for the data curation and provided the support in data analysis and visualization of results. PM, LB, and FM were involved in the interpretation of the data. FM prepared the first draft of the manuscript. PM, LB, MV, and TS revised it critically. All authors have given their approval for this version to be published.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.


Since the emergence of the COVID-19 pandemic, variable measures have been implemented to control the invasion of SARS-CoV-19 worldwide. Some of these measures included lockdowns for several months in some countries. In Jordan, various protocols have been implemented to deal with the epidemic, such as border closures, closures and local protocols for open days until we reach the partial opening in mid-2021. These measures and protocols have affected all sectors in the country, including the education system and the economy. In addition, lifestyle is one of the measurement issues that have been affected by government regulations during the COVID-19 pandemic. In this study, we aimed to investigate the impact of the COVID-19 pandemic on the eating and nutrition habits of the Jordanian population. An online sectional survey was built using Google Forms from Google. Responses were collected from November 12, 2020, through November 24, 2020. Researchers submitted a total of 2,511 responses. The results showed that there was a significant decrease in sugar intake (P = <0.005) with no critical fat and oil intake (P = 0.12). There was a significant change in daily consumption of fruits, vegetables, garlic, onions, and ginger, and downloads of health-related applications and supplements (P < 0.005). In addition, there was an increase in appetite, weight and number of daily meals. These changes are attributed to the extra free time due to lockdown and studying or working from home has significant impacts. However, 31.4% of respondents reported that the limited economic availability of food products and the closure of restaurants and cafes lead to a healthier lifestyle. Only 26.2% have been influenced by family members, friends, doctors, or social media to change their eating habits during the pandemic.  COVID-19; SARs-Cov-19; Health; Life style; Nutrition. DFull or partial lockdown measures resulted in more people adopting inactive behaviors , 7, 8, 9Moreover, many people have decided to strengthen their immune system to fight infection, by making healthier diet choices and taking dietary supplements , 15, 16.This study aims to examine whether and how the people of Jordan have changed some of their health-related behaviors during the COVID-19 pandemic. The measures we seek to monitor include diets, dietary supplement use, and weight changes.2In the wake of the COVID19 pandemic, people around the world have witnessed a major change in how they go about their daily lives. An essential aspect of human well-being is diet. In light of this, we conducted an online survey to study the eating behaviors of the Jordanian population during the national lockdown that Jordan underwent in the first months of 2020. The aim was to discover whether and how people's eating habits changed under the newly imposed restrictions. The study wanted to reveal patterns of pro-health versus unhealthy food choices and see if the pandemic is making people eat more.2.1The current study is an online cross-sectional survey built using Google's Google Forms service. It consists of three main question sets containing all the multiple-choice questions. At the beginning of the survey, we mentioned that the data collected will only be used for this study. No personal information was obtained through any questions in the survey, and participants voluntarily filled out the survey and had the option to leave the link at any time.The survey was primarily distributed via social media platforms, including WhatsApp, Facebook, Instagram, and via the Yarmouk University email portal to all students in the university. The researchers relied on their family members and friends to pass on the survey link to get as many respondents as possible.The target population was Jordanians that have been residing in Jordan since the start of the pandemic. The survey is a self-administered questionnaire. It was written in the Arabic language, the mother tongue of Jordanians. Responses were collected starting from November 12, 2020, until November 24, 2020. The researchers yielded a total of 2511 responses.Inclusion and exclusion criteria: All participants who live in Jordan since the start of the pandemic can complete the questionnaire in the Arabic language and give online consent participants were included in this study.2.22.2.1Participants were asked to specify their age, gender, educational level, and occupation. The story of education was sub-classified into "High school diploma or still in school," "Diploma or bachelor's degree in a health-related major," "Diploma or bachelor's degree in non-health-related major," and "Master's degree or Ph.D." As for occupation, we divided participants into those working in a health-related field, those working in a non-health-related field, and those who did not work.2.2.2The consumption patterns of four food groups were studied. These were junk food, sugar, fats, oils, fruits and vegetables. Participants were asked to indicate the frequency of their intake of these nutrients before and after the pandemic began to see if and how it had changed during the newly emerging conditions. They had to choose four frequency classes; in sequential order were: "almost daily", "three to four times a week", "once a week", "once a month or less".The number of daily consumed meals, the number of meals eaten during nighttime, and how the pandemic affected these numbers were assessed. Questions regarding changes observed by participants in their weight and appetite were posed. Participants were also asked about their use of social media platforms to access dietary and nutrition-related content both before and after the start of the pandemic.We wanted to determine the attitude of the study sample toward taking dietary supplements and whether the general population has changed their views about taking them. We also asked participants about adding well-known natural remedies such as onions, garlic and ginger to their diets.33.1A total of 2511 respondents from all governorates in Jordan completed the questionnaire. 3.1.1The survey was designed to explore the consumption patterns of four food groups: fast food, sugar, fat and oils, and fruits and vegetables. Respondents were asked to indicate the frequency of their intake of these foodstuffs both before and after the start of the pandemic to see if and how it changed throughout the newly arising circumstances. They had to choose four frequency categories; these in consecutive order were: "Almost daily," "Three to four times a week," "Once a week," and "Once a month or less."For instance, when the respondents were asked about the frequency of their fast-food intake, 483 (19.2%) stated that they consumed fast food three to four times or almost daily before the pandemic, and this consumption significantly decreased by 1.6-fold after the pandemic to be 295 (11.7%) . However, there is a significant reduction in the sugar intake  on an almost daily basis from 885 (35.2%) before the pandemic to 798 (31.8%) following it. Also, the number of respondents who stated that they consumed sugar once monthly rose from 176 (7.0%) before the pandemic to 252 (10.0%) after the pandemic . Correspondingly for fat and oil intake, there is a statistical association in reduction of daily consumption of fat and oil , which decreased from 863 (34.4%) before the pandemic to 797 (31.7%) after the start of the pandemic. On the other hand, the number of respondents who consumed fat and oil once monthly slightly rose from 202 (8.0%) before the pandemic to 242 (9.6%) after the start of the pandemic . There is a significant change in daily intake of fruits and vegetables  which was 1299 (51.8%) before and 1445 (57.6%) after the pandemic .Figure 2Notwithstanding, the change in fast food consumption, sugar, fat, oil, fresh fruit, and vegetable before and after the pandemic was significantly associated with demographic factors like age, gender, social status, educational level, and occupation  Tables .Respondents who consumed almost daily fast food since the start of the pandemic were significantly associated with young age less than 18 years, male gender, single social status, increased number of daily meals, nighttime meals, increased appetite , gain weight , free of chronic disease , and having 3 or fewer household members . However, there was no association with educational level , occupation , performing physical activity , and downloading any applications or starting to follow any social media accounts concerning healthy lifestyle and nutrition  . AlsoWe also found it appropriate to ask participants about any changes in their appetite that coincide with the generality of religion. Nearly half of the participants (46%) said they saw no change in their appetite. On the other hand, 37.6% reported an increase in their appetite, while the remaining percentage experienced a decrease in appetite. Another study that was interested in examining people's appetite during the COVID-19 lockdown was an Italian study by Laura Di Renzo et al., and they found that the feeling of hunger and satiety changed in more than half of the population: 17.8% of the respondents had a decrease in appetite, while 34.4% of the respondents experienced an increased appetite .In the present study, when cross-tabulating between changes in weight of respondents and changes in their appetites' it was found that of the 1154 individuals that experienced no alterations to their appetite, 623 didn't notice any difference in their weight either. The same pattern applied to the 945 persons who reported a growing appetite during the pandemic, 618 of them had detected a more significant number on the scale. This comes to show that in most cases, weight and appetite go hand in hand. On the contrary, Al-Domi H et al found an increased appetite among 44.3% of their Jordanian sample, 32.0% with no change, and the rest (23.6%) said “maybe” increase in their appetite. They found a significant association between increasing appetite and being obese or overweight compared to normal-weight participants  . In our Studies show that the use of ginger, garlic and onion extract can have beneficial effects on individuals with lung problems such as acute respiratory distress syndrome, lung injury, pulmonary fibrosis, and pneumonia, as well as those with inflammatory conditions such as sepsis, all of which are symptoms seen in patients with COVID-19 .In light of the alternative medicine recommendations circulating on social media here in Jordan, such as adding ingredients such as garlic, onions, and ginger to one's daily diet. We found that there was a significant relationship  between those who increased the intake of the above components and those who ate a large number of fresh fruits and vegetables since the beginning of the epidemic. In our study, 65.5% of participants added at least one type of garlic, onion, and ginger to help them cope with the epidemic. On the other hand, Zhang J et al found that only 9.8% of Chinese participants added ginger to deal with the epidemic .Since the start of the pandemic, there has been a constant public debate about the role of nutritional supplements in boosting the immune response against emerging diseases. Mayasari, N. et al. found a significantly increased Google search using nutritional supplements keywords especially vitamins, herbs, and zinc during the COVID-19 pandemic . In systRespondents in our study were asked about their interest in taking dietary supplements such as zinc and iron before the pandemic compared to after its onset. 31.5% (791) of the total sample said that they had already been taking supplements before the pandemic; this figure rose to 1511 respondents (45.8%) taking supplements after it started. This 1.9-fold increase indicates the pandemic reinforces this dietary choice. In the Polish survey by Błaszczyk-Bebenek et al., no significant differences were noted in using dietary supplements between two-time points in the study group (p = 0.3057). Before lockdown, just over a third of the participants had used supplements, and 33.7% used them during the lockdown. The most frequently used supplement among participants was vitamin D . Magnesium was used the least frequently  .5In conclusion, our study showed a significant reduction in sugar intake, increased appetite, weight and intake of multiple meals, fruits and vegetables per day during the COVID-19 pandemic. Moreover, the study showed some health behaviors in specific population groups related to educational level, age, and the influence of family members and friends. Some other factors related to the COVID-19 epidemic, such as smoking and drinking habits, can be investigated.6The main limitation of this study is that it is based on a self-reported electronic questionnaire, which can lead to the possibility of reporting bias. Although this is a known problem for any online survey, we try to overcome it with a large representative sample and using the appropriate statistical tools mentioned in the methodology part. The lower number of males in our sample compared to females is another limitation.Almu'atasim Khamees: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.Sajeda Awadi: Conceived and designed the experiments; Performed the experiments; Wrote the paper.Shireen Rawashdeh, Muna Talafha, Jamal Bani-Issa: Performed the experiments; Wrote the paper.Mohammad Ali S. Alkadiri, Mazhar Salim Al Zoubi, Emad Hussein, Fadi Abdel Fattah, Ibrahim H. Bashayreh, Mohannad Al-Saghir: Performed the experiments; Analyzed and interpreted the data; 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.Data included in article/supplementary material/referenced in article.The authors declare no conflict of interest.No additional information is available for this paper.


The study aimed at examining the combined association of socioeconomic status (SES) and diet diversity (DD) with health-related quality of life (HRQoL) and exploring whether DD played a mediating role in the relationship between varied SES and HRQoL among Chinese older persons.A multi-stage random sampling method was conducted in Shanxi Province of China, with 3,250 older adults participating in this cross-sectional survey. SES was divided into groups by quartiles and DD by means, and these variable groups were combined in pairs to generate a total of eight combinations. The PROCESS macro developed by Hayes was employed for the simple mediation analysis.OR = 1.65, 95% CI 1.41–2.92); low SES/ high DD ; middle low SES/ low DD ; middle low SES/ high DD ; upper high SES/ low DD ; and high SES/ low DD . The mediation analysis revealed that DD mediated the relationship between SES and HRQoL , with its indirect effects accounting for 39.29% of the total effects.Compared with the reference group (those with both high SES and high DD), older adults who were classified to have lower SES or DD had elevated odds of having worse HRQoL: low SES/ low DD (These findings highlighted the role of DD as a mediator of the relationship between SES and HRQoL. As DD could be protective, modifiable, and easy for older adults to understand and implement, village clinics and community health stations should work collaboratively to design proper DD intervention measures for better HRQoL. With increasing average life expectancy, populations are now living longer but longevity does not necessarily mean that people have a better life quality . Health-People's behaviors and observable attributes could be affected by SES, and these behaviors could also insert an impact on people's health . As a maIn terms of the association between DD and HRQoL, it has also been confirmed by previous research. According to a 20-year longitudinal study of 91,993 Chinese citizens over the age of 65, poor DD was significantly associated with a poor quality of life after being adjusted for potential confounders . Other cTo contribute to a deeper understanding of the underlying mechanisms, the aim of the study was to examine the combined association of SES and DD with HRQoL. It also sought to explore whether DD played a mediating role in the relationship between different SES and HRQoL. We hypothesized that higher levels of DD could attenuate the impact of SES on HRQoL in Chinese older adults.A questionnaire-based cross-sectional study was undertaken in all 11 cities of Shanxi Province  using a multistage stratified sampling method. First, according to the order of districts (counties) on the government's website, each district (county) in every city was numbered. Second, two (districts) counties in each city were selected using the random number table, and then, two communities (administrative villages) were drawn from each district (county) in the same way. Third, considering the different scales of each community (administrative village), once again, we select 1 to 2 residential communities  from each community (administrative village) by the random number table. Finally, we obtained older people's name lists and numbered them in each community or natural village. A random number table was also applied to select older adults who meet the inclusion criteria in this session.The inclusion criteria for this study were as follows: (1) being aged 60 and above and (2) having clear awareness and barrier-free communication skills. Those who had difficulty communicating were excluded.Before our formal survey, a pre-study had been conducted to ensure the accuracy, validity, and understandability of the questionnaires. The pre-study was conducted in Taiyuan, Shanxi Province, with 137 questionnaires distributed and 135 returned. The pre-study data were not included in the formal study. Additionally, the results demonstrated that the questionnaire had good reliability and validity and could be well understood by older adults.All participants were interviewed face-to-face using a structured questionnaire by trained interviewers with medical knowledge in Shanxi Province, China. We used face-to-face interviews instead of self-complete questionnaires because some older adults were illiterate, and some of them could not read or write due to poor vision, hand tremors, or other reasons. The study involved 3,266 older adults, of whom 3,250 completed the questionnaire effectively, with an effective response rate of 99.51%.In our study, occupation before retirement , educational level  and personal monthly income  were selected to measure the older adults' SES . As a geIn our study, DD was accessed by diet diversity score. According to the Chinese dietary guidelines for Chinese populations , we inveIn this study, HRQoL was estimated by the European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ-5D-5L), which was translated into Chinese in 2002 by Luo et al. . The EQ-We identified potential confounders for HRQoL based on the existing studies , 33. Pot2). According to the Chinese criteria, participants' BMI was classified as underweight (<18.50 kg/m2), normal (18.50–23.99 kg/m2), overweight (24.00–27.99 kg/m2), and obese (≥28.00 kg/m2) (Demographic information was collected by self-report. The family size information was measured based on the question “How many people live with you now (including yourself)?” The answers were grouped as live alone; 2 people; 3–4 people; 5 people; and above. Physical activity level was measured by the International Physical Activity Questionnaire long-form (IPAQ), which consists of 27 questions reflecting on the last 7 days' activities . Based o0 kg/m2) . InformaData were analyzed using SPSS version 24.0 . Categorical variables are presented as the number of participants and compared across SES quartiles by the chi-square tests. Continuous variables are presented as means and standard deviations, compared across SES quartiles by Kruskal–Wallis test because of the non-normal distribution of both the DD score and EQ-5D utility score. The association between the continuous variables was examined using Pearson's correlation.To examine the combined association of SES and DD on HRQoL, DD scores were grouped into two groups by the mean score of 5 . DD groups were combined in pairs with SES divided by quartiles and generated a total of eight combinations as follows: low SES/ low DD; low SES/ high DD; middle low SES/ low DD; middle low SES/ high DD; upper high SES/ low DD; upper high SES/ high DD; high SES/ low DD; and high SES/ high DD. A generalized linear model (GLM) with a Gamma distribution and a log link was applied to investigate the combined association of SES and DD on HRQoL. As the GLM required none-negative values, EQ-5D disutility score (disutility score = 1-utility score) was generated and entered as the dependent variable in this study .A common method bias test was performed using Harman's single factor test to control for common method bias effects. If there is a problem with the common method variance, the first unrotated factor extracted from the factor analysis would account for a large proportion of the total variance. The threshold was 40% according to the former study .The mediation analysis was conducted to establish a mediating model of three variables with adjustment for the above-mentioned control variables by the PROCESS macro developed by Hayes. In the mediation model, SES was determined to be the independent variable (IV), and HRQoL was the dependent variable (DV). DD (MV) was used as the pathway from SES to HRQoL. The total, direct, and indirect effects were estimated by the SPSS PROCESS macro (model 4). A total effect (c) refers to the relationship between the IV and DV without controlling for the MV. A direct effect (c') refers to the relationship between the IV and DV after controlling for the MV (DD) and other control variables. The indirect effects of the mediation analysis were the effects of the IV on the DV through the MV. To test the mediation role of DD between SES and HRQoL, a bootstrap estimation procedure was conducted with 5,000 bootstrap samples. According to the bootstrap test, the effect was significant when the path coefficient of a 95% CI did not overlap 0 . All thep < 0.05).OR = 1.65, [95% CI 1.41 to 2.92], p < 0.001); low SES/ high DD ; middle low SES/ low DD ; middle low SES/ high DD ; upper high SES/ low DD ; and high SES/ low DD , except for the dyad of upper high SES/ high DD (p > 0.05).r = 0.333, p < 0.01; for HRQoL, r = 0.182, p < 0.01). HRQoL was also significantly and positively correlated with DD . In addition, the results of the common method biases showed that the eigenvalues of seven factors were greater than one in the unrotated factors, implying that the data are explained by more than one factor. In addition, the first factor explained 28.14% of the variance, less than the threshold of 40%. As a result, the problem of common method bias in this study is not serious.In terms of the correlation between key variables, prominently, DD score and HRQoL were positively correlated with SES, respectively . The significance of the direct effect of SES on HRQoL  remained significant when the mediator of DD was included in the model, indicating that the mediating effect was partial. Moreover, the total indirect effects through the pathway of SES → DD → HRQoL were 0.011, which accounted for 39.29% of the total effect.This mediation analysis provided the estimates of path coefficients and significance tests for specified mediational models, as well as the estimates of indirect effects. All paths for the adjusted model are presented in B = 0.028, p < 0.001) remained significant when the mediator of DD was included in the model. In addition, SES was significantly associated with DD , with DD also significantly associated with HRQoL .The regression coefficients in the mediation analysis between SES on HRQoL with DD as a mediator are presented in In the present cross-sectional study, we explored the combined association of SES and DD with HRQoL among older adults, finding people who have lower SES and DD have higher odds of lower HRQoL. Through the bootstrapping analysis, the current study also confirmed that DD mediated the association between SES and HRQoL, which is in accordance with our theoretical assumption. As DD explained more than one-third of this relationship, the results may further suggest the value and importance of promoting DD for attenuating the negative impact of SES and HRQoL.The positive association of SES with HRQoL in the current study was consistent with the social causation theory and earlier studies , 9, 40. Our findings suggest that SES had a major influence on participants' DD echoed with a recent study in China that higher SES, including more education, family income, and perceived income status, was associated with higher DD . AnotherAccording to our findings, maintaining a diverse diet was positively associated with better HRQoL, which was in line with the former study in China that a higher DD score was associated with better health, such as being less likely to experience higher-level psychological stress , having The findings of the present study suggest that in comparison with the individuals with both high SES and high DD, another relatively low SES either in combination with high or low DD was found to be associated with decreased HRQoL except for the combination of upper high SES and high DD. Although sub-average SES was significantly associated with higher odds of lower HRQoL, the protective role of high DD was still evident in ameliorating the negative impact of relatively low SES. It is worth noting that even for older adults with more advanced SES, lower DD was also associated with decreased HRQoL. Considering the fact that when people get older, they are more likely to consume a monotonous diet , and it There are some limitations to this study that should be addressed. First, given the cross-sectional design of the present study, it is not possible to make causal inferences. Second, participants' consumption of food groups was collected through only self-reported, which may exist recall bias as well as social desirability bias. There was also unintentional bias as the participants who have difficulties in communication were excluded from our research without having proxy interviews. Third, the study participants were recruited locally from Shanxi Province, which does not represent other areas in China.Based on the study of 3,250 older adults in Shanxi province, China, the results not only presented the combined association of SES and DD on HRQoL but also suggested that the association between SES and HRQoL was partly mediated by DD. The findings had some implications for HRQoL enhancement as it is crucial to ensure that older populations from various socioeconomic backgrounds could equally enjoy their quality twilight years. Given the findings that higher DD could attenuate the negative impact of SES and HRQoL in Chinese older adults, village clinics and community health stations should work together on intervention programs encouraging older adults to adopt a diverse diet for improving or maintaining HRQoL.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by Shanxi Medical University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.CZ designed this study and served as the lead writer. JZ did the data interpretation and drafted the manuscript. SX and LS were involved in the study design and gave many valuable comments on the draft. YX and XZ participated in data analysis and critically revised the article. YK and XB helped with the language and format editing of this manuscript. XL, YC, YL, and GZ participated in data collection and post-works. All authors have read and approved the manuscript.


Uterine cervical neoplasms is widely concerned due to its high incidence rate. Early diagnosis is extremely important for prognosis. The purpose of this article is evaluating the efficacy of Raman spectroscopy in the diagnosis of suspected uterine cervical neoplasms.We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of science up to September 1, 2021. By analyzing the true positive (TP), false positive (FP), true negative (TN) and false negative (FN) of six included study, we evaluated the pooled and grouping sensitivity, specificity, positive, and negative likelihood ratios (LR), and diagnostic odds ratio (DOR), with 95% confidence intervals (CI), based on random effects models. The overall diagnostic accuracy of Raman spectrum was evaluated by SROC curve analysis and AUC.After screening with inclusion and exclusion criteria, a total of six study were included in the study. The pooled sensitivity and specificity was 0.98  and 0.95 . The total PLR and NLR were 21.05  and 0.03 , respectively. And the AUC of the SROC curve which show the overall diagnostic accuracy was 0.99 (0.98–1.00).Through analysis, we confirmed the role of Raman spectroscopy (RS) in the diagnosis of suspected uterine cervical tumors.https://www.crd.york.ac.uk/prospero/], identifier [CRD42021284966].[ The incidence rate of uterine cervical tumors is the fourth of female cancer. According to statistics, there were about 570,000 uterine cervical tumors patients and 310,000 deaths worldwide in 2018. Among them, China and India are the hardest hit areas of uterine cervical tumors, accounting for nearly two-thirds of the cases  released in 2010 pointed out that the false positive rate of cytology is high, which will bring excessive medical treatment and additional economic losses . TherefoRaman spectroscopy is a new and reliable technology, which can analyze the molecular structure of substances and the chemical composition of human tissues . In mediThis meta-analysis searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of science to ensure that all potentially eligible articles are included . We combined all the relevant medical subject heading (MeSH) terms of uterine cervical tumors and Raman spectrum: [ OR  OR  OR  OR  OR  OR  OR  OR  OR  OR  OR (Cervix Neoplasms) OR (Cervix Neoplasm) OR  OR (Cancer of the Uterine Cervix) OR (Cancer of the Cervix) OR  OR  OR  OR  OR  OR  OR  OR (Cancer of Cervix) OR (Cervix Cancer) OR  OR ] AND [ OR  OR (Raman Spectroscopy) OR  OR  OR  OR (Raman Scattering) OR ]. All potential studies were included with no other limitation. The meta-analysis has been registered in PROSPERO (CRD42021284966).Articles like review articles, comments, report, letters will be eliminated from the study. Criteria as follows: (I) without animal tissues in the experiments; (II) reported the use of RS in uterine cervical tumors; (III) used histopathology to confirm the diagnosis; (V) reported the true positive (TP), false positive (FP), true negative (TN) and false negative (FN), based on which the sensitivity and specificity values can be calculated. After screening, a total of six study were included in the study.Two independent investigators extracted a range of data from each study using a standardized data-collecting form: article title, first author, publication year, nationality. All relevant data is contained within the 6 included articles –17. ThenWe calculated the primary data of TP, FP, TN, FN from articles included, then calculated sensitivity, specificity, positive and negative likelihood ratios (LR), based on random effects models. We used Review Man 5.3 and Stata/SE 15.1 to generate the forest plots in order to show sensitivity and specificity.in vivo and in vitro studies. Therefor we conducted a subgroup analysis according to these studies.Meanwhile, Summary Receiver Operator Characteristics (SROC) curves was generated to assess the combination of sensitivity and specificity by Stata/SE 15.1. To assess publication bias, we generated funnel plot using Stata/SE 15.1. In the meantime, we found that articles in uterine cervical tumors include P = 0.420, less than 0.05, and Egger’s regression test indicates that there is no publication bias.Two independent investigators used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines by Review Manager 5.3 to evaluate the quality of included studies. And the risk of bias of included studies was shown in And we conducted a sensitivity analysis. In n = 106, Web of science, n = 186, Embase, n = 111), in which included 198 duplicate records. Among the rest of 205 articles, 38 articles excluded due to: they were review, meeting or letters. Go a step further by browsing the 167 potentially relevant studies, 126 records excluded due to they were cytological study (n = 79), serological research (n = 28), medicine efficacy study (n = 11), animals research (n = 8). By reading the rest of 41 articles, 24 reports excluded due to they were biochemical assessment (n = 12), failed to give concrete date (n = 6) and irrelevant to the subject (n = 6). After careful perusing, 5 articles excluded due to failed to mention TN, FN, TP, FP and 6 excluded because of cervical precancer. Ultimately, 6 studies included in this review.The process of included articles screening was presented in in vivo, therefor their samples were cervix in vivo, and the other four studies were in vitro, so their samples were ex vivo tissues. Three of four studies in vitro obtained fresh tissue slices, the rest of one study obtained Formalin-fixed paraffin preserved tissue.The sensitivity and specificity were calculated to assess diagnostic accuracy of all the six studies. And the forest plot of pooled sensitivity and specificity was shown in The total PLR and NLR were 21.05  and 0.03 , respectively. And the AUC of the SROC curve which show the overall diagnostic accuracy was 0.99 (0.98–1.00). The plots were shown in in vivo which had a total of 87 samples and 300 tested spectra. The sensitivity of two studies was 1.00  and 0.91 , respectively, and the specificity was 0.95  and 0.96 , respectively. Since the number of study included in this group is less than 4, data analysis cannot be done in STATA. All of the data and grouping situation were shown in Two studies , 16 showin vitro which had a total of 322 samples and 420 tested spectra (two articles didn’t provide the number of spectra). The sensitivity of four studies ranged from 0.92  to 1.00 , and the pooled sensitivity was 0.98 . The specificity ranged from 0.75  to 0.99 , and the pooled specificity was 0.97 . Total PLR and NLR were 33.38  and 0.02 , respectively. The SROC curve was described and the AUC was 0.99 (0.98–1.00). All of the plots of vitro group were shown in Four studies –14, 17 sin vivo and in vitro by RS in 1998  were also more than 90%. In the subgroup analysis, the sensitivity and specificity also achieved high standard, that meant whether RS analyze uterine cervical tumors tissues RS also was used in researching uterine cervical tumors by cervical cells and blood serum except fresh cervical tissue. Sitarz et al.  studied With the prevalence of TCT and HPV examination, pathological biopsy is widely used in clinic and is considered as the gold standard of cervical cancer, what are the outstanding advantages of Raman technology? In other words, how should Raman technology position itself in clinical application?After reading a lot of literature, people generally believe that the outstanding advantage of Raman microscope lies in its timeliness, such as real-time images, convenience and rapidity, reducing the demand and burden of pathologists and so on. According to the current research progress, Raman technology does not seem to be enough to make us think that it can replace postoperative pathology. However, with the rapid development of modern science and technology, there is an emerging technology called handheld Raman spectrometer, which can quickly and quantitatively detect the anti-cancer drug 5-fluorouracil (5-FU) in serum . We haveP-values are greater than 0.05, it means no great significance (in vivo subgroup analysis. Too few may not directly indicate the effectiveness of Raman technology, which needs more sample size and literature research.There are some limitations in this article. First and foremost, the heterogeneity was high. In order to explore the reasons for this result, we conducted a sensitivity analysis, and the results have been analyzed in ificance . We beliDue to the high cost and expense of RS, there are not many related studies at present. But in the existing research, it is believed that RS does play an important role in the diagnosis of uterine cervical tumors. This is a satisfactory result which predicts the emergence of a new and efficient diagnostic technology.Through this meta-analysis, we can confidently believe that Raman spectroscopy has high specificity and sensitivity in the diagnosis of uterine cervical tumors, and we have reason to believe that Raman spectroscopy will become an efficient diagnostic method of uterine cervical tumors in the future. However, more research and evidence are needed to fully demonstrate the role of Raman spectroscopy in the diagnosis of uterine cervical tumors before it is used in clinic. We are also looking forward to more samples and more researches.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.Z-WS, L-JZ, Z-YS, XZ, Z-FZ, and FX wrote the manuscript together and made great contributions to the article. This article has taken place under the guidance of two experienced tutors, ZX and RL. All authors agreed to be responsible for the content of this article and 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.


N = 595 university students. We analyzed the fit between the demands of the study program and the abilities of the student, using the algebraic, squared and absolute difference score, response surface analysis (RSA), and direct fit as measurement approaches. Our results indicate that RSA explains the most variance for objective outcomes, and that direct fit explains the most variance for subjective outcomes. We hope that this contribution will help researchers distinguish the different measurement approaches of demands-abilities fit (and ultimately person-environment fit) and use them accordingly.Researchers studying person-environment fit can choose between various measurement approaches. Even though these measures are distinctly different, they often get used interchangeably, which makes interpreting the results of person-environment fit studies difficult. In the present article, we contrast the most commonly used measurement approaches for person-environment fit in higher education and compare them in terms of explained variance. We obtained data on the fit as well as subjective and objective study-related outcomes of  Person-environment fit (P-E fit) theory  suggestsThe present study contrasts the most commonly used measurement approaches for P-E fit and compares them in terms of their explained variance. We focus on P-E fit in higher education, a context with many applications of P-E fit theory in recent years , and anaex post (Most measurement approaches can be put into one of two dominant research streams: (1) The indirect assessment of fit as the interaction between personal and environmental factors, or (2) the direct assessment of fit as an internal feeling . When fiex post . This isex post  or by caex post . We willX-Y), squared (X-Y)2, and absolute | X-Y| difference score , only students with a university e-mail address were eligible for the lottery. Participants were from heterogeneous study disciplines including teacher education, economics, psychology, mathematics, medicine, and sociology. Mean age was M = 22.89 years (SD = 3.53). The majority of the participants were female . On average, students were in their 5.21th semester (SD = 4.00).We collected data of k = 132). For the RSA, missing values were dealt with using Full Information Maximum Likelihood estimates. For the correlation tests, missing values were omitted using pairwise deletions.The data contained only few missing values, mostly for grades  the ability level required for their studies, and (b) their own ability level on a five-point Likert scale ranging from “very low” (1) to “very high” 5; see . These iReliability analyses yielded acceptable to very good values for Cronbach’s alpha (between α = 0.65 and α = 0.89). Individual items and their descriptive statistics can be found in R2 (and adjusted R2 for RSA), the fit scores of the algebraic, squared and absolute difference scores were then correlated with study satisfaction, intent to leave, and grades.All calculations were done in R . Comparing the measurement approaches in terms of additional criteria, such as reliability and practicality, could be a worthwhile project and further enhance our understanding of the different measurement approaches.When interpreting our results, a few limitations have to be considered. First, our results and recommendations are limited to the higher education context, and do not allow us to draw direct conclusions for other research areas. However, as we specifically chose outcomes  that are frequently used in the organizational context, we consider it likely that our results are transferable. Second, we focus on demands-abilities fit to the exclusion of other types of fit . Demands-abilities fit is frequently studied in the higher education context  and provDespite these limitations, our study can contribute to the literature on P-E fit by distinguishing the commonly used measurement approaches and by giving insights on how they influence different outcomes. These results can help researchers interpret studies using the different measurement approaches.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study.CB and TR conceived and planned the study. TR conducted the data collection, reviewed and revised the manuscript, and prepared it for publication. CB and JB analyzed the data and prepared a first draft 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.