bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of length for age Z scores among children aged 6–23 months in Central Java, Indonesia: a path analysis
Authors: Kartasurya Martha Irene , Syauqy Ahmad , Suyatno Suyatno , Dewantiningrum Julian , Nuryanto Nuryanto , Sunarto Sunarto , Isnawati Muflihah , Nurcahyani Yusi Dwi , Wati Erna Kusuma , Hapsari Pramesthi Widya , Samsudin Mohamad , Fuada Noviati 
Published: April 2023

IntroductionLength for Age Z (LAZ) score determinants are complex and vary among different areas, but it is important for designing effective and efficient strategies to decrease stunting prevalence among children under 2 years. This study aimed to investigate the determinants of LAZ scores among children under 2 years in Central Java, Indonesia.MethodsThis study was conducted on the 2021 Indonesian Nutritional Status Study (INSS) dataset, which was a cross-sectional survey. Data on 3,430 children aged 6–23 months from Central Java province were derived from the 2021 INSS data. After missing data elimination, 3,238 subjects were included in the analysis. Determinant factors included direct and indirect factors. Direct factors were the mother's age, birth weight Z score (BWZ), birth length Z score (BLZ), exclusively breastfed history, dietary diversity scores (DDS), empty calorie drink consumption, unhealthy snacks consumption, and infections. Indirect factors were early initiation of breastfeeding (EIBF) and posyandu (integrated health post) utilization. Underlying factors were socioeconomic status (SES) and the mother's education. Bivariate analyses and multiple linear regressions were conducted. A path analysis with a hypothesized model based on the UNICEF conceptual framework was also performed.ResultsStunting, wasting and underweight proportions among the subjects were 19.1%, 7.6% and 12.3%, respectively. The mean LAZ scores were −0.95 ± 1.22; the mother's age was 29.7 ± 5.95 years; BWZ was −0.47 ± 0.97; BLZ was −0.55 ± 1.05; and DDS was 4.45 ± 1.51. The infection proportion among the subjects was 28%. BWZ and BLZ were positively correlated to LAZ scores, with r = 0.267 (p &lt; 0.01) and r = 0.260 (p &lt; 0.01), respectively. The mother's age was negatively correlated to LAZ scores with r = −0.041 (p &lt; 0.05). Maternal education was positively correlated to SES but had no direct effect on LAZ scores. LAZ score determinants of BLZ (p &lt; 0.001) and SES (p &lt; 0.001) showed positive direct associations with LAZ scores, but the mother's age (p = 0.039), exclusively breastfed history (p &lt; 0.001), and empty calorie drinks consumption (p &lt; 0.001) had negative associations with LAZ scores.ConclusionTo prevent stunting among children aged 6–23 months in Central Java, Indonesia, intervention programs to increase the nutritional status of women at child-bearing age and nutrition education on child feeding practices should be conducted more efficiently and effectively.
Preoperative levels of folate receptor-positive circulating tumor cells in different subtypes of early-stage lung adenocarcinoma: Predictive value for determining extent of surgical resection
Authors: Zhou Chao , Zhao Ran , Zhao Ruiying , Wang Ansheng , Li Wentao 
Published: April 2023

BackgroundThe objective was to measure the correlations of preoperative levels of folate receptor-positive circulating tumor cells (FR+CTCs) with clinical characteristics and histologic subtype in early-stage lung adenocarcinoma, and to determine the predictive value of FR+CTC level in preoperative determination of the extent of surgical resection.Patients and methodsIn this retrospective, single-institution, observational study, preoperative FR+CTC levels were measured via ligand-targeted enzyme-linked polymerization in patients with early-stage lung adenocarcinoma. Receiver operating characteristic (ROC) analysis was used to identify the optimal cutoff value of FR+CTC level for prediction of various clinical characteristics and histologic subtypes.ResultsNo significant difference in FR+CTC level was observed among patients with adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) (P = 0.813). Within the non-mucinous adenocarcinoma group, no difference was observed among patients with tumors whose predominant growth patterns were lepidic, acinar, papillary, micropapillary, solid, and complex gland (P = 0.053). However, significant differences in FR+CTC level were observed between patients with and without the micropapillary subtype [11.21 (8.22-13.61) vs. 9.85 (7.43-12.63), P = 0.017], between those with and without the solid subtype [12.16 (8.27-14.90) vs. 9.87 (7.50-12.49), P = 0.022], and between those with any of the advanced subtypes (micropapillary, solid, or complex glands) vs. none of these [10.48 (7.83-13.67) vs. 9.76 (7.42-12.42), P = 0.032]. FR+CTC level was also correlated with degree of differentiation of lung adenocarcinoma (P = 0.033), presence of visceral pleural invasion (VPI) of lung carcinoma (P = 0.003), and lymph node metastasis of lung carcinoma (P = 0.035).ConclusionFR+CTC level is of potential predictive value in determining the presence of aggressive histologic patterns (micropapillary, solid, and advanced subtypes), degree of differentiation, and occurrence of VPI and lymph node metastasis in IAC. Measurement of FR+CTC level combined with intraoperative frozen sections may represent a more effective method of guiding resection strategy in cases of cT1N0M0 IAC with high-risk factors.
Validation of attenuation imaging coefficient, shear wave elastography, and dispersion as emerging tools for non-invasive evaluation of liver tissue in children
Authors: Cetiner Metin , Schiepek Felix , Finkelberg Ilja , Hirtz Raphael , Büscher Anja K. 
Published: April 2023

IntroductionThe number of children with acute and chronic liver disease is rising. Moreover, liver involvement may be limited to subtle changes in organ texture especially in early childhood and some syndromic conditions, such as ciliopathies. Attenuation imaging coefficient (ATI), shear wave elastography (SWE), and dispersion (SWD) are emerging ultrasound technologies providing data about attenuation, elasticity, and viscosity of liver tissue. This additional and qualitative information has been correlated with certain liver pathologies. However, limited data are available for healthy controls and have mainly been raised in adults.MethodsThis prospective monocentric study was conducted at a university hospital with a specialization in pediatric liver disease and transplantation. Between February and July 2021, 129 children aged 0-17.92 years were recruited. Study participants attended outpatient clinics due to minor illnesses excluding liver or cardiac diseases, acute (febrile) infections or other conditions affecting liver tissue and function. ATI, SWE, and SWD measurements were performed on an Aplio i800 (Canon Medical Systems) with an i8CX1 curved transducer by two different investigators with long-standing experience in pediatric ultrasound according to a standardized protocol.ResultsConsidering multiple potential covariates, we derived percentile charts for all 3 devices relying on the Lambda-Mu-Sigma (LMS) approach. 112 children were considered for further analysis, excluding those with abnormal liver function and under-/overweight (BMI SDS&lt;-1.96/&gt; 1.96, respectively). Age range was 0-17.92 years (mean 6.89±0.50SD), 58% were male. The mean duration of the ultrasound examination (basic ultrasound plus SWE, SWD, and ATI) was 6.67±0.22 minutes and it was well tolerated in 83% (n=92) of cases. While ATI was related to age, SWD was found to depend on BMI SDS, and SWE on abdominal wall thickness and sex. ATI correlated with neither SWE nor SWD, but SWE was correlated with SWD.ConclusionsOur study provides norm values and reference charts for ATI, SWE, and SWD considering important covariates including age, sex and, BMI. This may help to implement these promising tools into imaging diagnostics of liver disease and to improve the diagnostic relevance of liver ultrasound. In addition, these noninvasive techniques proved to be time-effective and highly reliable, which make them ideal for application in children.
25-hydroxyvitamin D levels in children of different ages and with varying degrees of Helicobacter pylori infection and immunological features
Authors: Ma Peng-fei , Dai Qun , Chu Jing , Zhuo Lin , Chen Yi , Cheng Rong , Wu Cheng , Yuan Li-Ping 
Published: April 2023

BackgroundHelicobacter pylori (HP) is a major cause of upper digestive tract diseases. However, the relationship between HP infection and 25-hydroxyvitamin D [25(OH)D] levels in children has not been fully elucidated. This study investigated the levels of 25(OH)D in children of different ages and with varying degrees of HP infection and immunological features as well as the correlations between 25(OH)D levels in children infected with HP and their ages and degrees of infection.Materials and methodsNinety-four children who underwent upper digestive endoscopy were divided into an HP-positive group without peptic ulcers (Group A), an HP-positive group with peptic ulcers (Group B) and an HP-negative control group (Group C). The serum levels of 25(OH)D and immunoglobulin and the percentages of lymphocyte subsets were determined. HP colonization, the degree of inflammation, and the degree of activity were further evaluated by HE staining and immunohistochemical staining in gastric mucosal biopsy.ResultsThe 25(OH)D level of the HP-positive groups (50.93 ± 16.51 nmol/L) was significantly lower than that of the HP-negative group (62.89 ± 19.18 nmol/L). The 25(OH)D level of Group B (47.79 ± 14.79 nmol/L) was lower than that of Group A (51.53 ± 17.05 nmol/L) and was significantly lower than that of Group C (62.89 ± 19.18 nmol/L). The 25(OH)D level decreased with increasing age, and there was a significant difference between Group C subjects who were ≤5 years old and those who were aged 6–9 years and ≥10 years. The 25(OH)D level was negatively correlated with HP colonization (r = −0.411, P &lt; 0.01) and the degree of inflammation (r = −0.456, P &lt; 0.01). The percentages of lymphocyte subsets and immunoglobulin levels among Groups A, B and C were not significantly different.ConclusionsThe 25(OH)D level was negatively correlated with HP colonization and the degree of inflammation. As the age of the children increased, the level of 25(OH)D decreased, and the susceptibility to HP infection increased.
Anti-hyperuricemia effect of hesperetin is mediated by inhibiting the activity of xanthine oxidase and promoting excretion of uric acid
Authors: An Meng-Fei , Shen Chang , Zhang Shao-Shi , Wang Ming-Yue , Sun Ze-Rui , Fan Mao-Si , Zhang Li-Juan , Zhao Yun-Li , Sheng Jun , Wang Xuan-Jun 
Published: April 2023

Graphical AbstractBoth in vivo and in vitro experiments suggested that HSE may effectively lower uric acid. The mechanism might be the inhibition of XOD activity, down-regulation of TLR4-NLRP3 inflammasome and up-regulation expression of OAT1, OAT3, OCT1, OCT2 proteins.
The value of cuproptosis-related differential genes in guiding prognosis and immune status in patients with skin cutaneous melanoma
Authors: Sun Yuming , Lei Shaorong , Luo Xiangyue , Jiang Chufeng , Li Zhexuan 
Published: April 2023

Background: Skin cutaneous melanoma (SKCM) is one of the most common cutaneous malignancies, which incidence is increasing. Cuproptosis is a new type of programming cell death recently reported, which may affect the progression of SKCM.Method: The mRNA expression data of melanoma were obtained from the Gene Expression Omnibus and the Cancer Genome Atlas databases. We constructed a prognostic model according to the cuproptosis-related differential genes in SKCM. Finally, real-time quantitative PCR was performed to verify the expression of cuproptosis-related differential genes in patients with different stages of cutaneous melanoma.Results: We detected 767 cuproptosis-related differential genes based on 19 cuproptosis-related genes, and screened out 7 differential genes to construct a prognostic model, which including three high-risk differential genes (SNAI2, RAP1GAP, BCHE), and four low-risk differential genes (JSRP1, HAPLN3, HHEX, ERAP2). Kaplan-Meier analysis indicated that SKCM patients with low-risk differential genes signals had better prognosis. The Encyclopedia of Genomes results manifested that cuproptosis-related differential genes are not only involved in T cell receptor signaling channel, natural killer cell mediated cytotoxicity, but also chemokine signaling pathway and B cell receptor signaling pathway. In our risk scoring model, the receiver operating characteristic (ROC) values of the three-time nodes are 0.669 (1-year), 0.669 (3-year) and 0.685 (5-year), respectively. Moreover, the tumor burden mutational and immunology function, cell stemness characteristics and drug sensitivity have significant differences between low-risk group and high-risk group. The mRNA level of SNAI2, RAP1GAP and BCHE in stage Ⅲ+Ⅳ SKCM patients was significantly higher than that in stage Ⅰ+Ⅱ patients, while the level of JSRP1, HAPLN3, HHEX and ERAP2 in stage Ⅰ+Ⅱ SKCM patients was more remarkable higher than that in stage Ⅲ+Ⅳ SKCM patients.Conclusion: In summary, we suggest that cuproptosis can not only regulate the tumor immune microenvironment but also affect the prognosis of SKCM patients, and may offer a basic theory for SKCM patients survival studies and clinical decision-making with potentially therapeutic drugs.
High-fat diets enhance and delay ursodeoxycholic acid absorption but elevate circulating hydrophobic bile salts
Authors: Huang Liang , Wei Wei , Huang Xiaomei , Li Xuejing , Liu Haisha , Gui Lanlan , Jiang Jinping , Wan Linfei , Zhou Xiangxiang , Ding Jingsong , Jiang Xuehua , Zhang Bikui , Lan Ke 
Published: April 2023

Background: Ursodeoxycholic acid (UDCA) is a natural drug essential for the treatment of cholestatic liver diseases. The food effects on the absorption of UDCA and the disposition of circulating bile salts remain unclear despite its widespread global uses. This study aims to investigate the effects of high-fat (HF) diets on the pharmacokinetics of UDCA and disclose how the circulated bile salts were simultaneously perturbed.Methods: After an overnight fast, a cohort of 36 healthy subjects received a single oral dose (500 mg) of UDCA capsules, and another cohort of 31 healthy subjects received the same dose after consuming a 900 kcal HF meal. Blood samples were collected from 48 h pre-dose up to 72 h post-dose for pharmacokinetic assessment and bile acid profiling analysis.Results: The HF diets significantly delayed the absorption of UDCA, with the Tmax of UDCA and its major metabolite, glycoursodeoxycholic acid (GUDCA), changing from 3.3 h and 8.0 h in the fasting study to 4.5 h and 10.0 h in the fed study, respectively. The HF diets did not alter the Cmax of UDCA and GUDCA but immediately led to a sharp increase in the plasma levels of endogenous bile salts including those hydrophobic ones. The AUC0–72h of UDCA significantly increased from 25.4 μg h/mL in the fasting study to 30.8 μg h/mL in the fed study, while the AUC0–72h of GUDCA showed no difference in both studies. As a result, the Cmax of total UDCA (the sum of UDCA, GUDCA, and TUDCA) showed a significant elevation, while the AUC0–72h of total UDCA showed a slight increase without significance in the fed study compared to the fasting study.Conclusion: The HF diets delay UDCA absorption due to the extension of gastric empty time. Although UDCA absorption was slightly enhanced by the HF diets, the beneficial effect may be limited in consideration of the simultaneous elevation of circulating hydrophobic bile salts.
Reducing anxiety and improving self-acceptance in children and adolescents with osteosarcoma through group drawing art therapy
Authors: Liu Xin , Sun Lihong , Du Xinhui , Zhang Chang , Zhang Yijia , Xu Xiaoxia 
Published: April 2023

PurposeThis study explored the effect of group drawing art therapy (GDAT) on anxiety and self-acceptance in children and adolescents with osteosarcoma.MethodsUsing a randomized experimental study design, 40 children and adolescents with osteosarcoma who were treated in our hospital from December 2021 to December 2022 were selected as the research objects, including 20 in the intervention group and 20 in the control group. The control group received routine care for osteosarcoma, while the intervention group participated in eight sessions of GDAT, twice a week, 90–100 min each, in addition to routine care for osteosarcoma. A screening for children’s anxiety disorders (SCARED) and a self-acceptance questionnaire (SAQ) were used to evaluate the patients before and after the intervention.ResultsAfter 8 weeks of GDAT, the SCARED total score in the intervention group was 11.30 ± 8.603, and that in the control group was 22.10 ± 11.534. The difference between the two groups was statistically significant (t = -3.357, P &lt; 0.05). In the intervention group, the SAQ total score was 48.25 ± 4.204, with self-acceptance and self-evaluation factor scores of 24.40 ± 2.521 and 23.85 ± 2.434, respectively. In the control group, the SAQ total score was 42.20 ± 4.047; the self-acceptance factor score was 21.20 ± 3.350 and that of the self-evaluation factor was 21.00 ± 2.224. The differences between the two groups were statistically significant (t = 4.637, P &lt; 0.001; t = 3.413, P &lt; 0.05; t = 3.866, P &lt; 0.001, respectively).ConclusionGroup drawing art therapy can reduce anxiety and improve the levels of self-acceptance and self-evaluation in children and adolescents with osteosarcoma.
Sex Modulates the Pathological Aging Effect on Caudate Functional Connectivity in Mild Cognitive Impairment
Authors: Yang Zhengshi , Caldwell Jessica Z. K. , Cummings Jeffrey L. , Ritter Aaron , Kinney Jefferson W. , Cordes Dietmar ,   The Alzheimer's Disease Neuroimaging Initiative (ADNI)
Published: April 2023

PurposeTo assess the pathological aging effect on caudate functional connectivity among mild cognitive impairment (MCI) participants and examine whether and how sex and amyloid contribute to this process.Materials and MethodsTwo hundred and seventy-seven functional magnetic resonance imaging (fMRI) sessions from 163 cognitive normal (CN) older adults and 309 sessions from 139 participants with MCI were included as the main sample in our analysis. Pearson's correlation was used to characterize the functional connectivity (FC) between caudate nuclei and each brain region, then caudate nodal strength was computed to quantify the overall caudate FC strength. Association analysis between caudate nodal strength and age was carried out in MCI and CN separately using linear mixed effect (LME) model with covariates (education, handedness, sex, Apolipoprotein E4, and intra-subject effect). Analysis of covariance was conducted to investigate sex, amyloid status, and their interaction effects on aging with the fMRI data subset having amyloid status available. LME model was applied to women and men separately within MCI group to evaluate aging effects on caudate nodal strength and each region's connectivity with caudate nuclei. We then evaluated the roles of sex and amyloid status in the associations of neuropsychological scores with age or caudate nodal strength. An independent cohort was used to validate the sex-dependent aging effects in MCI.ResultsThe MCI group had significantly stronger age-related increase of caudate nodal strength compared to the CN group. Analyzing women and men separately revealed that the aging effect on caudate nodal strength among MCI participants was significant only for women (left: P = 6.23 × 10−7, right: P = 3.37 × 10−8), but not for men (P &gt; 0.3 for bilateral caudate nuclei). The aging effects on caudate nodal strength were not significantly mediated by brain amyloid burden. Caudate connectivity with ventral prefrontal cortex substantially contributed to the aging effect on caudate nodal strength in women with MCI. Higher caudate nodal strength is significantly related to worse cognitive performance in women but not in men with MCI.ConclusionSex modulates the pathological aging effects on caudate nodal strength in MCI regardless of amyloid status. Caudate nodal strength may be a sensitive biomarker of pathological aging in women with MCI.
A pilot investigation of differential hydroxymethylation levels in patient-derived neural stem cells implicates altered cortical development in bipolar disorder
Authors: Kumar Ashish , Kos Mark Z. , Roybal Donna , Carless Melanie A. 
Published: April 2023

IntroductionBipolar disorder (BD) is a chronic mental illness characterized by recurrent episodes of mania and depression and associated with social and cognitive disturbances. Environmental factors, such as maternal smoking and childhood trauma, are believed to modulate risk genotypes and contribute to the pathogenesis of BD, suggesting a key role in epigenetic regulation during neurodevelopment. 5-hydroxymethylcytosine (5hmC) is an epigenetic variant of particular interest, as it is highly expressed in the brain and is implicated in neurodevelopment, and psychiatric and neurological disorders.MethodsInduced pluripotent stem cells (iPSCs) were generated from the white blood cells of two adolescent patients with bipolar disorder and their same-sex age-matched unaffected siblings (n = 4). Further, iPSCs were differentiated into neuronal stem cells (NSCs) and characterized for purity using immuno-fluorescence. We used reduced representation hydroxymethylation profiling (RRHP) to perform genome-wide 5hmC profiling of iPSCs and NSCs, to model 5hmC changes during neuronal differentiation and assess their impact on BD risk. Functional annotation and enrichment testing of genes harboring differentiated 5hmC loci were performed with the online tool DAVID.ResultsApproximately 2 million sites were mapped and quantified, with the majority (68.8%) located in genic regions, with elevated 5hmC levels per site observed for 3’ UTRs, exons, and 2-kb shorelines of CpG islands. Paired t-tests of normalized 5hmC counts between iPSC and NSC cell lines revealed global hypo-hydroxymethylation in NSCs and enrichment of differentially hydroxymethylated sites within genes associated with plasma membrane (FDR = 9.1 × 10−12) and axon guidance (FDR = 2.1 × 10−6), among other neuronal processes. The most significant difference was observed for a transcription factor binding site for the KCNK9 gene (p = 8.8 × 10−6), encoding a potassium channel protein involved in neuronal activity and migration. Protein–protein-interaction (PPI) networking showed significant connectivity (p = 3.2 × 10−10) between proteins encoded by genes harboring highly differentiated 5hmC sites, with genes involved in axon guidance and ion transmembrane transport forming distinct sub-clusters. Comparison of NSCs of BD cases and unaffected siblings revealed additional patterns of differentiation in hydroxymethylation levels, including sites in genes with functions related to synapse formation and regulation, such as CUX2 (p = 2.4 × 10−5) and DOK-7 (p = 3.6 × 10−3), as well as an enrichment of genes involved in the extracellular matrix (FDR = 1.0 × 10−8).DiscussionTogether, these preliminary results lend evidence toward a potential role for 5hmC in both early neuronal differentiation and BD risk, with validation and more comprehensive characterization to be achieved through follow-up study.