cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.30560975.v1
title: Integrating newborn genetic screening with traditional screening to improve newborn screening

description: Traditional newborn screening (tNBS) for inborn errors of metabolism (IEMs) and deafness has limitations, including the detection of few genetic disorders and variants, high false-positive rates, and long turnaround times. This study aimed to explore the clinical validity of newborn genetic screening (NBGS) in newborns screened for IEMs and deafness. We retrospectively enrolled 223 cases screened for IEMs using tandem mass spectrometry-next-generation sequencing (MS/MS-NGS), including 55 study-defined positive, 68 study-defined suspected positive, and 100 negative cases. Additionally, 196 cases screened for deafness were enrolled, including 96 variant-positive and 100 negative cases. Dried blood spot samples (DBSs) from newborns were used for NBGS. For IEM, NBGS detected 34 positives in 55 study-defined positive cases with a sensitivity of 61.8% (34/55), no variants were detected in 21 cases. Four additional positive cases were identified, including one at risk of glucose-6-phosphate dehydrogenase deficiency and three at risk of deafness. The turnaround time was significantly different between the two methods: 13 days for NBGS versus 35 days for MS/MS-NGS. For deafness, the consistency of the positive results between the two methods was 96.9% (93/96). Unexpectedly, three mitochondrial gene (MT-RNR1) heteroplasmy variants (m.1555A &gt; G and m.7445A &gt; G) were not detected by NBGS. We also detected nine variants in the 100 negative cases, including seven variants in GJB2 (c.109G &gt; A), one in GJB3 (c.547G &gt; A), and one in MYO15A (c.10250_10252delCCT), for a 9% (9/100) detection rate by NBGS. As an emerging screening method for newborns, NBGS offers the potential to detect a broader spectrum of pathogenic gene variants, reduce false-positive rates, and shorten the diagnostic cycle. However, current NBGS technology has limitations and cannot fully supplant traditional detection methods. Therefore, integrating both approaches can become a critical strategy for enhancing the accuracy and efficiency of newborn screening.
DOI: 10.6084/m9.figshare.28467585
title: Novel therapeutic targets uncovered by genome-wide integrative analysis in bronchopulmonary dysplasia

description: Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease in extremely premature infants. This study aims to identify gene expression dysregulation and explore various molecular pathways implicated in BPD. This study integrated BPD genome-wide association study (GWAS), single-cell transcriptomics (scRNA-seq), and Mendelian randomization (MR) analysis to investigate the causal relationship between gene expression and BPD. Cell annotation and ligand-receptor analysis highlighted myofibroblasts as the most interactive cell type. Key genes, including CDH4, ENC1, and PAM, were identified as protective factors against BPD, while GRB10 was associated with increased disease risk. Immune metabolism-related pathways showed elevated activity of PAM, GRB10, and ENC1 in epithelial-mesenchymal transition. The Drug-Gene Interaction Database (DGIdb) predicted three drugs—LM10, navoximod, and ziprasidone—that potentially interact with these key genes. This integrative genome-wide analysis provides valuable insights into the genetic mechanisms underlying BPD. The findings facilitate the identification of novel therapeutic targets and pave the way for personalized treatment strategies for affected neonates.
DOI: 10.6084/m9.figshare.28467585.v1
title: Novel therapeutic targets uncovered by genome-wide integrative analysis in bronchopulmonary dysplasia

description: Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease in extremely premature infants. This study aims to identify gene expression dysregulation and explore various molecular pathways implicated in BPD. This study integrated BPD genome-wide association study (GWAS), single-cell transcriptomics (scRNA-seq), and Mendelian randomization (MR) analysis to investigate the causal relationship between gene expression and BPD. Cell annotation and ligand-receptor analysis highlighted myofibroblasts as the most interactive cell type. Key genes, including CDH4, ENC1, and PAM, were identified as protective factors against BPD, while GRB10 was associated with increased disease risk. Immune metabolism-related pathways showed elevated activity of PAM, GRB10, and ENC1 in epithelial-mesenchymal transition. The Drug-Gene Interaction Database (DGIdb) predicted three drugs—LM10, navoximod, and ziprasidone—that potentially interact with these key genes. This integrative genome-wide analysis provides valuable insights into the genetic mechanisms underlying BPD. The findings facilitate the identification of novel therapeutic targets and pave the way for personalized treatment strategies for affected neonates.
DOI: 10.13130/rd_unimi/ui9ecn/ljh4ra
title: Gennaio_1880_Pagina_122.jpg

description: Bulletin of 1880/01/31
DOI: 10.6084/m9.figshare.29984050
title: Early metabolic biomarkers in neonates of diabetic mothers: predictive insights from amino acid and acylcarnitine profiling

description: To investigate early metabolic biomarkers in neonates born to mothers with gestational diabetes mellitus (GDM), focusing on amino acid and acylcarnitine profiles to assess metabolic risk, including obesity and future metabolic syndrome. This retrospective study analyzed dried blood spot samples from 184 GDM and 167 control neonates. GDM was categorized as large-for-gestational-age (LGA) or appropriate-for-gestational-age (AGA). Amino acid and acylcarnitine concentrations at 24–48 h postnatal age were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Neonatal hypoglycemia was defined and managed according to standard guidelines. Principal component analysis (PCA) was performed to identify clustering patterns. Tyrosine concentrations were significantly lower in the GDM-LGA group compared to the control-AGA group (<i>p</i> = 0.018). Total carnitine levels were higher in GDM-LGA infants relative to controls (<i>p</i> &lt; 0.05), reflecting increased fatty acid mobilization in larger infants. Specific long-chain acylcarnitines, such as C18:1 and C18:2, were lower in GDM group. whereas stearoyl carnitine (C18:0) was elevated, indicating an altered fatty acid oxidation profile. PCA revealed distinct metabolic patterns, suggesting early metabolic heterogeneity in GDM. The study identifies distinctive early metabolic profiles in neonates of gestational diabetic mothers, including lower tyrosine and altered acylcarnitine patterns, which may signal a predisposition to metabolic disorders. These findings support early metabolic screening protocols and targeted follow-up for high-risk infants. Longitudinal studies are warranted to confirm the predictive value of these biomarkers and to clarify the long-term impacts of metabolic disturbances in GDMs.
DOI: 10.6084/m9.figshare.29984050.v1
title: Early metabolic biomarkers in neonates of diabetic mothers: predictive insights from amino acid and acylcarnitine profiling

description: To investigate early metabolic biomarkers in neonates born to mothers with gestational diabetes mellitus (GDM), focusing on amino acid and acylcarnitine profiles to assess metabolic risk, including obesity and future metabolic syndrome. This retrospective study analyzed dried blood spot samples from 184 GDM and 167 control neonates. GDM was categorized as large-for-gestational-age (LGA) or appropriate-for-gestational-age (AGA). Amino acid and acylcarnitine concentrations at 24–48 h postnatal age were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Neonatal hypoglycemia was defined and managed according to standard guidelines. Principal component analysis (PCA) was performed to identify clustering patterns. Tyrosine concentrations were significantly lower in the GDM-LGA group compared to the control-AGA group (<i>p</i> = 0.018). Total carnitine levels were higher in GDM-LGA infants relative to controls (<i>p</i> &lt; 0.05), reflecting increased fatty acid mobilization in larger infants. Specific long-chain acylcarnitines, such as C18:1 and C18:2, were lower in GDM group. whereas stearoyl carnitine (C18:0) was elevated, indicating an altered fatty acid oxidation profile. PCA revealed distinct metabolic patterns, suggesting early metabolic heterogeneity in GDM. The study identifies distinctive early metabolic profiles in neonates of gestational diabetic mothers, including lower tyrosine and altered acylcarnitine patterns, which may signal a predisposition to metabolic disorders. These findings support early metabolic screening protocols and targeted follow-up for high-risk infants. Longitudinal studies are warranted to confirm the predictive value of these biomarkers and to clarify the long-term impacts of metabolic disturbances in GDMs.
DOI: 10.6084/m9.figshare.30100865
title: Causal associations of mood swings with preterm birth: a Mendelian randomization analysis

description: Mood swings are associated with an elevated risk of preterm birth. However, the causal relationships between them still remain unclear. We performed a two-sample Mendelian randomization (MR) analysis to clarify the association between mood swings and preterm birth. To investigate the proportion mediated by recognized risk factors, we applied two-step MR mediation analyses. Three regression methods were used in MR analyses and using inverse-variance weighted (IVW) as main method. The MR analysis included 373,733 individuals with data on mood swings and 204,913 participants with data on preterm birth. The results demonstrated significant causal effects of mood swings on preterm birth (OR = 1.761, 95% confidence interval (CI): 1.151, 2.692). Further mediation analysis indicated hypertension (7.283%, 95% CI: 0.387–15.394%) and high cholesterol (5.012%, 95% CI: 1.302–8.613%) may mediate the causal pathways from mood swings to preterm. Mood swings have a notable causal impact on preterm birth, partly mediated by hypertension and high cholesterol.
DOI: 10.6084/m9.figshare.30100865.v1
title: Causal associations of mood swings with preterm birth: a Mendelian randomization analysis

description: Mood swings are associated with an elevated risk of preterm birth. However, the causal relationships between them still remain unclear. We performed a two-sample Mendelian randomization (MR) analysis to clarify the association between mood swings and preterm birth. To investigate the proportion mediated by recognized risk factors, we applied two-step MR mediation analyses. Three regression methods were used in MR analyses and using inverse-variance weighted (IVW) as main method. The MR analysis included 373,733 individuals with data on mood swings and 204,913 participants with data on preterm birth. The results demonstrated significant causal effects of mood swings on preterm birth (OR = 1.761, 95% confidence interval (CI): 1.151, 2.692). Further mediation analysis indicated hypertension (7.283%, 95% CI: 0.387–15.394%) and high cholesterol (5.012%, 95% CI: 1.302–8.613%) may mediate the causal pathways from mood swings to preterm. Mood swings have a notable causal impact on preterm birth, partly mediated by hypertension and high cholesterol.
DOI: 10.13130/rd_unimi/ui9ecn/mcmfjv
title: Gennaio_1880_Pagina_123.jpg

description: Bulletin of 1880/01/31
DOI: 10.13130/rd_unimi/ui9ecn/jkm5i5
title: Gennaio_1880_Pagina_124.jpg

description: Bulletin of 1880/01/31
DOI: 10.13130/rd_unimi/ui9ecn/wwkhiw
title: Giugno_1880_Pagina_001.jpg

description: Bulletin of 1880/06/01
DOI: 10.13130/rd_unimi/ui9ecn/psgwfn
title: Giugno_1880_Pagina_002.jpg

description: Bulletin of 1880/06/01
DOI: 10.13130/rd_unimi/ui9ecn/mz5xij
title: Giugno_1880_Pagina_003.jpg

description: Bulletin of 1880/06/01
DOI: 10.6084/m9.figshare.28127852
title: An integrative approach to identifying <i>NPC1</i> as a susceptibility gene for gestational diabetes mellitus

description: The objective of this study was to identify a novel gene and its potential mechanisms associated with susceptibility to gestational diabetes mellitus (GDM) through an integrative approach. We analyzed data from genome-wide association studies (GWAS) of GDM in the FinnGen R11 dataset (16,802 GDM cases and 237,816 controls) and Genotype Tissue Expression v8 expression quantitative trait locus data. We used summary-data-based Mendelian randomization to determine associations between transcript levels and phenotypes, transcriptome-wide association studies to provide insights into gene-trait associations, multi-marker analysis of genomic annotation to perform gene-based analysis, genome-wide complex trait analysis–multivariate set-based association test–combo to determine gene prioritization, and polygenic priority scores to prioritize the causal genes to screen candidate genes. Subsequent Mendelian randomization analysis was performed to infer causality between the candidate genes and GDM and phenome-wide association study (PheWAS) analysis was used to explore the associations between selected genes and other characteristics. Furthermore, to gain a deeper understanding of the functional implications of these susceptibility genes, GeneMANIA analysis was used to determine the fundamental biological functions of the therapeutic targets and protein-protein interaction network analysis was performed to identify intracellular protein interactions. We identified two novel susceptibility genes associated with GDM: <i>NPC1</i> and <i>KIAA1191</i>. Magnetic resonance imaging revealed a strong correlation between <i>NPC1</i> expression levels and a lower incidence of GDM (odds ratio: 0.922, 95% confidence interval: 0.866–0.981, <i>p</i> = 0.011). PheWAS at the gene level indicated that <i>NPC1</i> was not associated with any other trait. The biological significance of this gene was evidenced by its strong association with sterol metabolism. Our study identified <i>NPC1</i> as a novel gene whose predicted expression level is linked to a reduced risk of GDM, providing new insights into the genetic framework of this disease.
DOI: 10.6084/m9.figshare.28127852.v1
title: An integrative approach to identifying <i>NPC1</i> as a susceptibility gene for gestational diabetes mellitus

description: The objective of this study was to identify a novel gene and its potential mechanisms associated with susceptibility to gestational diabetes mellitus (GDM) through an integrative approach. We analyzed data from genome-wide association studies (GWAS) of GDM in the FinnGen R11 dataset (16,802 GDM cases and 237,816 controls) and Genotype Tissue Expression v8 expression quantitative trait locus data. We used summary-data-based Mendelian randomization to determine associations between transcript levels and phenotypes, transcriptome-wide association studies to provide insights into gene-trait associations, multi-marker analysis of genomic annotation to perform gene-based analysis, genome-wide complex trait analysis–multivariate set-based association test–combo to determine gene prioritization, and polygenic priority scores to prioritize the causal genes to screen candidate genes. Subsequent Mendelian randomization analysis was performed to infer causality between the candidate genes and GDM and phenome-wide association study (PheWAS) analysis was used to explore the associations between selected genes and other characteristics. Furthermore, to gain a deeper understanding of the functional implications of these susceptibility genes, GeneMANIA analysis was used to determine the fundamental biological functions of the therapeutic targets and protein-protein interaction network analysis was performed to identify intracellular protein interactions. We identified two novel susceptibility genes associated with GDM: <i>NPC1</i> and <i>KIAA1191</i>. Magnetic resonance imaging revealed a strong correlation between <i>NPC1</i> expression levels and a lower incidence of GDM (odds ratio: 0.922, 95% confidence interval: 0.866–0.981, <i>p</i> = 0.011). PheWAS at the gene level indicated that <i>NPC1</i> was not associated with any other trait. The biological significance of this gene was evidenced by its strong association with sterol metabolism. Our study identified <i>NPC1</i> as a novel gene whose predicted expression level is linked to a reduced risk of GDM, providing new insights into the genetic framework of this disease.
DOI: 10.13130/rd_unimi/ui9ecn/tum0k6
title: Giugno_1880_Pagina_004.jpg

description: Bulletin of 1880/06/01
DOI: 10.6084/m9.figshare.28147988
title: Comparison of the value of transvaginal ultrasonography and MRI in the diagnosis of cesarean scar pregnancy: a meta-analysis

description: To compare the diagnostic value of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) in cesarean scar pregnancy (CSP) by a method of meta-analysis. Studies on TVS and MRI for CSP were collected from PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang data, and Chinese Scientific Journal Database (VIP database) until April 1, 2024. Stata 15.0 software was used for data analysis. Mann–Whitney U-test was applied to compare the diagnostic efficiency of the TVS and MRI groups. Nine articles with 713 subjects were involved in this review. The pooled sensitivity (0.96, 95%CI: 0.94–0.97), specificity (0.90, 95%CI: 0.84–0.94), and DOR (197.28, 95%CI: 99.71–390.31) in the MRI group were higher than those (Sensitivity = 0.83, 95%CI: 0.77–0.87; Specificity= 0.74, 95%CI: 0.63–0.83; DOR = 13.66, 95%CI: 7.84–23.79) in the TVS group. The positive likelihood ratio and negative likelihood ratio of the MRI group were 9.56 (95%CI: 8.82–15.72) and 0.05 (95%CI: 0.03–0.07), while those of the TVS group were 3.21 (95%CI:2.18–4.74) and 0.24 (95%CI: 0.18–0.31), respectively. In the MRI and TVS groups, the area under the curve (AUC) of the summary receiver operating characteristic was 0.9497 and 0.86, respectively. The results of Mann–Whitney U-tests of the two groups showed significant differences in the pooled sensitivity (Z= −3.311, <i>p</i> &lt; 0.001), specificity (Z= −2.123, <i>p</i> = 0.034), and DOR (Z= −3.272, <i>p</i> = 0.001). Both MRI and TVS can effectively diagnose CSP. However, compared with TVS, MRI has better diagnostic accuracy for CSP, with higher sensitivity and specificity. Considering the good diagnostic accuracy of ultrasound, patients with ultrasound suspicion of CSP should be sent to a reference center where MRI can express its full diagnostic potential regarding depth, topography of invasion and myometral residue, which is useful for subsequent management.
DOI: 10.6084/m9.figshare.28147988.v1
title: Comparison of the value of transvaginal ultrasonography and MRI in the diagnosis of cesarean scar pregnancy: a meta-analysis

description: To compare the diagnostic value of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) in cesarean scar pregnancy (CSP) by a method of meta-analysis. Studies on TVS and MRI for CSP were collected from PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang data, and Chinese Scientific Journal Database (VIP database) until April 1, 2024. Stata 15.0 software was used for data analysis. Mann–Whitney U-test was applied to compare the diagnostic efficiency of the TVS and MRI groups. Nine articles with 713 subjects were involved in this review. The pooled sensitivity (0.96, 95%CI: 0.94–0.97), specificity (0.90, 95%CI: 0.84–0.94), and DOR (197.28, 95%CI: 99.71–390.31) in the MRI group were higher than those (Sensitivity = 0.83, 95%CI: 0.77–0.87; Specificity= 0.74, 95%CI: 0.63–0.83; DOR = 13.66, 95%CI: 7.84–23.79) in the TVS group. The positive likelihood ratio and negative likelihood ratio of the MRI group were 9.56 (95%CI: 8.82–15.72) and 0.05 (95%CI: 0.03–0.07), while those of the TVS group were 3.21 (95%CI:2.18–4.74) and 0.24 (95%CI: 0.18–0.31), respectively. In the MRI and TVS groups, the area under the curve (AUC) of the summary receiver operating characteristic was 0.9497 and 0.86, respectively. The results of Mann–Whitney U-tests of the two groups showed significant differences in the pooled sensitivity (Z= −3.311, <i>p</i> &lt; 0.001), specificity (Z= −2.123, <i>p</i> = 0.034), and DOR (Z= −3.272, <i>p</i> = 0.001). Both MRI and TVS can effectively diagnose CSP. However, compared with TVS, MRI has better diagnostic accuracy for CSP, with higher sensitivity and specificity. Considering the good diagnostic accuracy of ultrasound, patients with ultrasound suspicion of CSP should be sent to a reference center where MRI can express its full diagnostic potential regarding depth, topography of invasion and myometral residue, which is useful for subsequent management.
DOI: 10.13130/rd_unimi/ui9ecn/h1bf5z
title: Giugno_1880_Pagina_005.jpg

description: Bulletin of 1880/06/02
DOI: 10.13130/rd_unimi/ui9ecn/dyalir
title: Giugno_1880_Pagina_006.jpg

description: Bulletin of 1880/06/02
DOI: 10.6084/m9.figshare.30183966
title: The effect of preterm premature rupture of membranes on neonatal outcomes in low-birth-weight infants: a retrospective study

description: This study evaluated the effect of preterm premature rupture of membranes (PPROM) on neonatal outcomes in low-birth-weight infants. We included premature infants born in our hospital and divided them into PPROM group and non-PPROM group. Maternal and neonatal data were collected, and follow-up assessments were performed at 3, 6, and 9 months of corrected age. The PPROM group had significantly lower birth weights, gestational ages, higher maternal infection rates, longer hospital stays, and higher complication rate (<i>p</i> &lt; 0.001). PPROM, 5-minute Apgar score &lt;7, and birth weight &lt;1500 g was significant risk factors for complications (<i>p</i> &lt; 0.001). Birth weight &lt;1500 g, sepsis, premature encephalopathy, asphyxia and necrotizing enterocolitis (<i>p</i> &lt; 0.01) were significant predictors of death. Infants with PPROM duration &gt;7 days had the highest mortality rate and lower mental development index scores at 3 months (<i>p</i> &lt; 0.05). PPROM significantly impacts neonatal outcomes in low-birth-weight infants, leading to higher complication rates and longer hospital stays, which is associated with high risk of neonatal complication.
DOI: 10.6084/m9.figshare.30183966.v1
title: The effect of preterm premature rupture of membranes on neonatal outcomes in low-birth-weight infants: a retrospective study

description: This study evaluated the effect of preterm premature rupture of membranes (PPROM) on neonatal outcomes in low-birth-weight infants. We included premature infants born in our hospital and divided them into PPROM group and non-PPROM group. Maternal and neonatal data were collected, and follow-up assessments were performed at 3, 6, and 9 months of corrected age. The PPROM group had significantly lower birth weights, gestational ages, higher maternal infection rates, longer hospital stays, and higher complication rate (<i>p</i> &lt; 0.001). PPROM, 5-minute Apgar score &lt;7, and birth weight &lt;1500 g was significant risk factors for complications (<i>p</i> &lt; 0.001). Birth weight &lt;1500 g, sepsis, premature encephalopathy, asphyxia and necrotizing enterocolitis (<i>p</i> &lt; 0.01) were significant predictors of death. Infants with PPROM duration &gt;7 days had the highest mortality rate and lower mental development index scores at 3 months (<i>p</i> &lt; 0.05). PPROM significantly impacts neonatal outcomes in low-birth-weight infants, leading to higher complication rates and longer hospital stays, which is associated with high risk of neonatal complication.
DOI: 10.13130/rd_unimi/ui9ecn/8476nu
title: Giugno_1880_Pagina_007.jpg

description: Bulletin of 1880/06/02