cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126452.v1
title: Supplementary Material for: Development of Normal Gestational Ranges for the Right Myocardial Performance Index in the Australian Population with Three Alternative Caliper Placements

description: <b><i>Objectives:</i></b> To construct gestational age-adjusted reference ranges for the right fetal modified myocardial performance index (RMPI) in an Australian population and to assess the influence of valve click caliper position on constituent time intervals and the RMPI. <b><i>Methods:</i></b> A prospective cross-sectional study of RMPI from 235 normal fetuses at 17-38 weeks of gestation was performed. Two Doppler waveforms were obtained: tricuspid and pulmonary valves for ‘a' and ‘b' readings, respectively. The ultrasound machine settings were: Doppler sweep velocity 15 cm/s, angle of insonation &lt;15°, minimal gain, and wall motion filter 300 Hz. The ‘a' and ‘b' intervals were measured at three different caliper positions in each fetus: at the beginning of the original valve clicks (‘original'), at the beginning of the reflected tricuspid and pulmonary closure clicks (‘reflected') and at the peak of valve clicks (‘peak'). RMPI was calculated as (a - b)/b. The three readings were obtained and averaged per examination, with intraobserver repeatability assessed by intraclass correlation coefficient (ICC) and 95% CI. <b><i>Results:</i></b> For ‘original', ‘reflected' and ‘peak' RMPI, mean ± SD, ICC (95% CI) were: 0.53 ± 0.10, 0.86 (0.83-0.89); 0.48 ± 0.10, 0.84 (0.81-0.87) and 0.48 ± 0.10, 0.89 (0.87-0.91), respectively. The RMPI increased by approximately 15% as gestation increased and decreased slightly with increasing heart rate. <b><i>Conclusion:</i></b> This is the first publication of reference ranges for RMPI based on caliper position. All methods showed good ICC, including the ‘peak' method which we have previously proposed for routine use based on its repeatability and ease of identification when measuring the myocardial performance index.
DOI: 10.6084/m9.figshare.5126458.v1
title: Supplementary Material for: Effect of Niacin on FGF23 Concentration in Chronic Kidney Disease

description: <b><i>Background:</i></b> Elevated serum phosphorus and FGF23 are independent cardiovascular risk factors in patients with chronic kidney disease. In a randomized controlled trial of patients with dyslipidemia assigned to either extended release niacin (ERN) alone, ERN combined with the selective prostaglandin D<sub>2</sub> receptor subtype 1 inhibitor laropiprant (ERN-L) or placebo, niacin lowered serum phosphorus; however, it is not known if it lowers FGF23 concentrations. <b><i>Methods:</i></b> This is an ancillary study to a multicenter, randomized, double-blind, placebo-controlled trial among patients with dyslipidemia and an estimated glomerular filtration rate (eGFR) of 30-74 ml/min/1.73 m<sup>2</sup>. Participants were randomized to ERN-L (n = 162), ERN (n = 97), or placebo (n = 68) in a 3:2:1 ratio for 24 weeks. The primary outcome was a change in serum FGF23 concentrations, and secondary outcomes were changes in other mineral metabolism parameters. <b><i>Results:</i></b> Both the ERN and ERN-L groups showed significant declines in serum phosphorus, calcium and calcium·phosphorus product at 24 weeks compared to placebo. A significant decline from baseline (10.9%, p &lt; 0.01) in the serum FGF23 concentration was observed in the ERN group compared to placebo, but not in the ERN-L group compared to placebo (p = 0.36 and 0.97 for ERN-L and placebo, respectively), despite equivalent declines in serum phosphorus. Similarly, the most marked declines in PTH occurred in the ERN-only group versus placebo; no change in PTH was observed in the ERN-L group. <b><i>Conclusions:</i></b> In this ancillary study of hyperlipidemic patients with an eGFR of 30-74 ml/min/1.73 m<sup>2</sup>, ERN alone but not in combination with laropiprant lowered FGF23 and PTH concentrations. If confirmed, niacin may provide a novel strategy to decrease phosphorus, FGF23, and PTH concentrations in patients with chronic kidney disease.
DOI: 10.6084/m9.figshare.5126443
title: Supplementary Material for: Medical Genetic Counseling for Breast Cancer in Primary Care: A Synthesis of Major Determinants of Physicians' Practices in Primary Care Settings

description: <b><i>Objectives:</i></b> This paper aims to identify relevant potential predictors of medical genetic counseling for breast cancer (MGC-BC) in primary care and to develop a comprehensive questionnaire to study MGC-BC. <b><i>Methods:</i></b> A scoping review was conducted to identify the predictors of MGC-BC among primary care physicians. Relevant articles were identified in selected databases (PubMed, Embase, CINAHL, ISI Web of Science, PsycINFO, and Cochrane CENTRAL) and 4 selected relevant electronic journals. <b><i>Results:</i></b> An inductive analysis of the 193 quantitatively tested variables, conducted by 3 researchers, showed that 6 conceptual categories of determinants, namely (1) demographic, (2) organizational, (3) experiential, (4) professional, (5) psychological, and (6) cognitive, influence MGC-BC practices. <b><i>Conclusion:</i></b> There is a scarcity of literature addressing the medical behavior determinants of MGC-BC. Future research is needed to identify effective strategies put into action to support the integration of MGC-BC in primary care medical practices and routines. However, our results shed light on 2 levels of actions that could improve genetic counseling services in primary care: (1) medical training and educational efforts emphasizing family history collection (individual level), and (2) clarification of roles and responsibilities in ordering and referral practices in genetic counseling and genetic testing for better healthcare management (organizational level).
DOI: 10.6084/m9.figshare.5126446
title: Supplementary Material for: Desmosterol in Brain Is Elevated because <b><i>DHCR24</i></b> Needs REST for Robust Expression but <b><i>REST</i></b> Is Poorly Expressed

description: Cholesterol synthesis in the fetal brain is inhibited because activity of DHCR24 (24-dehydrocholesterol reductase) is insufficient, causing concentrations of the precursor desmosterol to increase temporarily to 15-25% of total sterols at birth. We demonstrate that failure of <i>DHCR24</i> to be adequately upregulated during periods of elevated cholesterol synthesis in the brain results from the presence in its promoter of the repressor element 1 (RE1) nucleotide sequence that binds the RE1-silencing transcription factor (REST) and that REST, generally reduced in neural tissues, uncharacteristically but not without precedent, enhances <i>DHCR24</i> transcription. <i>DHCR24</i> and <i>REST</i> mRNA levels are reduced 3- to 4-fold in fetal mouse brain compared to liver (p &lt; 0.001). Chromatin immunoprecipitation assays suggested that REST binds to the human <i>DHCR24</i> promoter in the vicinity of the predicted human RE1 sequence. Luminescent emission from a human <i>DHCR24</i> promoter construct with a mutated RE1 sequence was reduced 2-fold compared to output from a reporter with wild-type RE1 (p &lt; 0.005). Silencing <i>REST</i> in HeLa cells resulted in significant reductions of <i>DHCR24</i> mRNA (2-fold) and DHCR24 protein (4-fold). As expected, relative concentrations of Δ<sup>24</sup>-cholesterol precursor sterols increased 3- to 4-fold, reflecting the inhibition of DHCR24 enzyme activity. In contrast, mRNA levels of <i>DHCR7</i> (sterol 7-dehydrocholesterol reductase), a gene essential for cholesterol synthesis lacking an RE1 sequence, and concentrations of HMGR (3-hydroxy-3-methyl-glutaryl-CoA reductase) enzyme protein were both unaffected. Surprisingly, a dominant negative fragment of REST consisting of just the DNA binding domain (about 20% of the protein) and full-length REST enhanced <i>DHCR24</i> expression equally well. Furthermore, RE1 and the sterol response element (SRE), the respective binding sites for REST and the SRE binding protein (SREBP), are contiguous. These observations led us to hypothesize that REST acts because it is bound in close proximity to SREBP, thus amplifying its ability to upregulate <i>DHCR24</i>. It is likely that modulation of <i>DHCR24</i> expression by REST persisted in the mammalian genome either because it does no harm or because suppressing metabolically active DHCR24 while providing abundant quantities of the multifunctional sterol desmosterol during neural development proved useful.
DOI: 10.6084/m9.figshare.5126440
title: Supplementary Material for: The Developmental Mismatch in Structural Brain Maturation during Adolescence

description: Regions of the human brain develop at different rates across the first two decades of life, with some maturing before others. It has been hypothesized that a mismatch in the timing of maturation between subcortical regions (involved in affect and reward processing) and prefrontal regions (involved in cognitive control) underlies the increase in risk-taking and sensation-seeking behaviors observed during adolescence. Most support for this ‘dual systems' hypothesis relies on cross-sectional data, and it is not known whether this pattern is present at an individual level. The current study utilizes longitudinal structural magnetic resonance imaging (MRI) data to describe the developmental trajectories of regions associated with risk-taking and sensation-seeking behaviors, namely, the amygdala, nucleus accumbens (NAcc) and prefrontal cortex (PFC). Structural trajectories of gray matter volumes were analyzed using FreeSurfer in 33 participants aged 7-30 years, each of whom had at least three high-quality MRI scans spanning three developmental periods: late childhood, adolescence and early adulthood (total 152 scans). The majority of individuals in our sample showed relatively earlier maturation in the amygdala and/or NAcc compared to the PFC, providing evidence for a mismatch in the timing of structural maturation between these structures. We then related individual developmental trajectories to retrospectively assessed self-reported risk-taking and sensation-seeking behaviors during adolescence in a subsample of 24 participants. Analysis of this smaller sample failed to find a relationship between the presence of a mismatch in brain maturation and risk-taking and sensation-seeking behaviors during adolescence. Taken together, it appears that the developmental mismatch in structural brain maturation is present in neurotypically developing individuals. This pattern of development did not directly relate to self-reported behaviors at an individual level in our sample, highlighting the need for prospective studies combining anatomical and behavioral measures.
DOI: 10.6084/m9.figshare.5126437
title: Supplementary Material for: Dose of Hemodialysis and Survival: A Marginal Structural Model Analysis

description: <b><i>Background:</i></b> Observational studies have consistently demonstrated the survival benefits of a greater dialysis dose in maintenance hemodialysis (MHD) patients, whereas randomized controlled trials have shown conflicting results. The possible causal impact of dialysis dose on mortality needs to be investigated using rich cohort data analyzed with novel statistical methods such as marginal structural models (MSMs) that account for time-varying confounding and exposure. <b><i>Methods:</i></b> We quantified the effect of delivered dose of hemodialysis (HD) [single-pool Kt/V (spKt/V)] on mortality risk in a contemporary cohort of 68,110 patients undergoing HD 3 times weekly (7/2001-9/2005). We compared conventional Cox proportional hazard and MSM survival analyses, accounting for time-varying confounding by applying longitudinally modeled inverse-probability-of-dialysis-dose weights to each observation. <b><i>Results:</i></b> In conventional Cox models, baseline spKt/V showed a weak negative association with mortality, while higher time-averaged spKt/V was strongly associated with lower mortality risk. In MSM analyses, compared to a spKt/V range of 1.2-&lt;1.4, a spKt/V range of &lt;1.2 was associated with a higher risk of mortality [HR (95% CI) 1.67 (1.54-1.80)], whereas mortality risks were significantly lower with higher spKt/V [HRs (95% CI): 0.74 (0.70-0.78), 0.63 (0.59-0.66), 0.56 (0.52-0.60), and 0.56 (0.52-0.61) for spKt/V ranges of 1.4-&lt;1.6, 1.6-&lt;1.8, 1.8-&lt;2.0, and ≥2.0, respectively]. Thus, MSM analyses showed that the greatest survival advantage of a higher dialysis dose was observed for a spKt/V range of 1.8-&lt;2.0, and the dialysis dose-mortality relationship was robust in almost all subgroups of patients. <b><i>Conclusions:</i></b> Higher HD doses were robustly associated with greater survival in MSM analyses that more fully and appropriately accounted for time-varying confounding.
DOI: 10.6084/m9.figshare.5126446.v1
title: Supplementary Material for: Desmosterol in Brain Is Elevated because <b><i>DHCR24</i></b> Needs REST for Robust Expression but <b><i>REST</i></b> Is Poorly Expressed

description: Cholesterol synthesis in the fetal brain is inhibited because activity of DHCR24 (24-dehydrocholesterol reductase) is insufficient, causing concentrations of the precursor desmosterol to increase temporarily to 15-25% of total sterols at birth. We demonstrate that failure of <i>DHCR24</i> to be adequately upregulated during periods of elevated cholesterol synthesis in the brain results from the presence in its promoter of the repressor element 1 (RE1) nucleotide sequence that binds the RE1-silencing transcription factor (REST) and that REST, generally reduced in neural tissues, uncharacteristically but not without precedent, enhances <i>DHCR24</i> transcription. <i>DHCR24</i> and <i>REST</i> mRNA levels are reduced 3- to 4-fold in fetal mouse brain compared to liver (p &lt; 0.001). Chromatin immunoprecipitation assays suggested that REST binds to the human <i>DHCR24</i> promoter in the vicinity of the predicted human RE1 sequence. Luminescent emission from a human <i>DHCR24</i> promoter construct with a mutated RE1 sequence was reduced 2-fold compared to output from a reporter with wild-type RE1 (p &lt; 0.005). Silencing <i>REST</i> in HeLa cells resulted in significant reductions of <i>DHCR24</i> mRNA (2-fold) and DHCR24 protein (4-fold). As expected, relative concentrations of Δ<sup>24</sup>-cholesterol precursor sterols increased 3- to 4-fold, reflecting the inhibition of DHCR24 enzyme activity. In contrast, mRNA levels of <i>DHCR7</i> (sterol 7-dehydrocholesterol reductase), a gene essential for cholesterol synthesis lacking an RE1 sequence, and concentrations of HMGR (3-hydroxy-3-methyl-glutaryl-CoA reductase) enzyme protein were both unaffected. Surprisingly, a dominant negative fragment of REST consisting of just the DNA binding domain (about 20% of the protein) and full-length REST enhanced <i>DHCR24</i> expression equally well. Furthermore, RE1 and the sterol response element (SRE), the respective binding sites for REST and the SRE binding protein (SREBP), are contiguous. These observations led us to hypothesize that REST acts because it is bound in close proximity to SREBP, thus amplifying its ability to upregulate <i>DHCR24</i>. It is likely that modulation of <i>DHCR24</i> expression by REST persisted in the mammalian genome either because it does no harm or because suppressing metabolically active DHCR24 while providing abundant quantities of the multifunctional sterol desmosterol during neural development proved useful.
DOI: 10.6084/m9.figshare.5126425
title: Supplementary Material for: Left Ventricular Mass Progression despite Stable Blood Pressure and Kidney Function in Stage 3 Chronic Kidney Disease

description: <b><i>Background/Aims:</i></b> Progressive chronic kidney disease (CKD) is associated with worsening cardiovascular (CV) risk not explained by traditional risk factors. Left ventricular (LV) hypertrophy (LVH) is an important CV risk factor, but its progression has not been documented in early CKD. We explored whether progression of LVH in early CKD would occur despite stable kidney function. <b><i>Methods:</i></b> We conducted a post hoc analysis of a 12-month study of lanthanum carbonate in stage 3 CKD, which included longitudinal assessments of CV biomarkers. Primary outcome for the analysis was the change in LV mass (LVM) indexed to height in meters<sup>2.7</sup> (LVM/Ht<sup>2.7</sup>). Secondary outcomes were changes in blood pressure (BP), pulse-wave velocity, LV systolic/diastolic function, fibroblast growth factor 23 (FGF23), klotho, and estimated glomerular filtration rate (eGFR). <b><i>Results:</i></b> Thirty-one of 38 original subjects had sufficient data for analysis. LVM/Ht<sup>2.7</sup> increased (47 ± 13 vs. 53 ± 13 g/m<sup>2.7</sup>, p = 0.006) over 12 months despite stable BP, stable eGFR and normal LV systolic function. Vascular stiffness and LV diastolic dysfunction persisted throughout the study. Klotho levels decreased (748 ± 289 to 536 ± 410 pg/ml, p = 0.03) but were unrelated to changes in LVM/Ht<sup>2.7</sup>. The change in FGF23/klotho ratio was strongly correlated with changes in LVM/Ht<sup>2.7</sup> (r<sup>2</sup> = 0.582, p = 0.03). <b><i>Conclusion:</i></b> Subjects with stage 3 CKD exhibited increasing LVM, persistent LV diastolic dysfunction and vascular stiffness despite stable kidney function, BP and LV systolic function. Abnormal FGF23 signaling due to reduced klotho expression may be associated with increasing LVM. These findings deserve further evaluation in a larger population given the adverse prognostic value of these CV biomarkers.
DOI: 10.6084/m9.figshare.5126428
title: Supplementary Material for: The Metabolic Syndrome and Cognitive Decline in the Atherosclerosis Risk in Communities Study (ARIC)

description: <b><i>Background:</i></b> Midlife metabolic syndrome (MetS) may impact cognitive health as a construct independently of hypertension, hyperlipidemia and other components. <b><i>Methods:</i></b> 10,866 participants aged 45-64 years at baseline were assessed for MetS and completed cognitive testing at two later time points (3 and 9 years from the baseline visit). <b><i>Results:</i></b> MetS is associated with increased odds of low cognitive performance in the domains of executive function and word fluency, but not with 6-year cognitive decline. Individual MetS components explained this association (hypertension, diabetes, low HDL, elevated triglycerides and increased waist circumference). <b><i>Conclusions:</i></b> A focus on the individual risk factors as opposed to MetS during midlife is important to reduce the incidence of cognitive impairment in later life.
DOI: 10.6084/m9.figshare.5126431
title: Supplementary Material for: Gene Expression Profiling of Cecropin B-Resistant Haemophilus parasuis

description: Synthetically designed antimicrobial peptides (AMPs) present the potential of replacing antibiotics in the treatment of bacterial infections. However, microbial resistance to AMPs has been reported and little is known regarding the underlying mechanism of such resistance. The naturally occurring AMP cecropin B (CB) disrupts the anionic cell membranes of Gram-negative bacteria. In this study, CB resistance (CBR) was induced in <i>Haemophilus</i><i>parasuis</i> SH0165 by exposing it to a series of CB concentrations. The CB-resistant <i>H.</i><i>parasuis</i> strains CBR30 and CBR30-50 were obtained. The growth curves of SH0165 and CBR30 showed that CBR30 displayed lower growth rates than SH0165. The result of transmission electron microscopy showed cell membranes of the CB-resistant CBR30 and CBR30-50 were smoother than SH0165. Microarrays detected 257 upregulated and 254 downregulated genes covering 20 clusters of orthologous groups (COGs) of the CB-resistant CBR30 compared with SH0165 (&gt;1.5-fold change, p &lt; 0.05). Sixty genes were affected in CBR30-50 covering 18 COGs, with 28 upregulated and 32 downregulated genes. Under the COG function classification, the majority of affected genes in the CB-resistant CBR30 and CBR30-50 belong to the category of inorganic ion transport, amino acid transport, and metabolism. The microarray results were validated by real-time quantitative reverse transcription PCR. This study may provide useful guidance for understanding the molecular mechanism underlying <i>H.</i><i>parasuis</i> resistance to CB.
DOI: 10.6084/m9.figshare.5126434
title: Supplementary Material for: An Alternative Transcription Start Site Yields Estrogen-Unresponsive <b><i>Kiss1</i></b> mRNA Transcripts in the Hypothalamus of Prepubertal Female Rats

description: The importance of the <i>Kiss1</i> gene in the control of reproductive development is well documented. However, much less is known about the transcriptional regulation of <i>Kiss1</i> expression in the hypothalamus. Critical for these studies is an accurate identification of the site(s) where <i>Kiss1</i> transcription is initiated. Employing 5′-RACE PCR, we detected a transcription start site (TSS1) used by the hypothalamus of rats, mice, nonhuman primates and humans to initiate <i>Kiss1</i> transcription. In rodents, an exon 1 encoding 5′-untranslated sequences is followed by an alternatively spliced second exon, which encodes 5′-untranslated regions of two different lengths and contains the translation initiation codon (ATG). In nonhuman primates and humans, exon 2 is not alternatively spliced. Surprisingly, in rat mediobasal hypothalamus (MBH), but not preoptic area (POA), an additional TSS (TSS2) located upstream from TSS1 generates an exon 1 longer (377 bp) than the TSS1-derived exon 1 (98 bp). The content of TSS1-derived transcripts increased at puberty in the POA and MBH of female rats. It also increased in the MBH after ovariectomy, and this change was prevented by estrogen. In contrast, no such changes in TSS2-derived transcript abundance were detected. Promoter assays showed that the proximal TSS1 promoter is much more active than the putative TSS2 promoter, and that only the TSS1 promoter is regulated by estrogen<i>. </i>These differences appear to be related to the presence of a TATA box and binding sites for transcription factors activating transcription and interacting with estrogen receptor-α in the TSS1, but not TSS2, promoter.