Supplementary Material for: Association Between Hypoxia-Inducible Factor-2α (HIF-2α) Expression and Colorectal Cancer and Its Prognostic Role: a Systematic Analysis

<b><i>Background/Aims:</i></b> Although some studies showed that HIF-2α expression was correlated with an unfavorable prognosis in colorectal cancer (CRC), the prognostic results remain conflicting in CRC. The present study was performed to evaluate the association between HIF-2α expression and the clinicopathological features of this disease and to examine the potential prognostic role of HIF-2α expression in CRC. <b><i>Methods:</i></b> Pooled odds ratios (ORs) or hazard ratios (HRs) were calculated from available publications, The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. Trial sequential analysis (TSA) was used to estimate the required sample information. <b><i>Results:</i></b> HIF-2α protein expression was more frequent in CRC than in normal colonic tissues (OR = 150.49, <i>P</i> < 0.001), higher in male than female CRC patients (OR = 1.47, <i>P</i> = 0.008), and lower in high-grade than low-grade CRC (OR = 0.49, <i>P</i> = 0.029). TSA verified the reliability of the above results. HIF-2α expression was not linked to the prognosis of CRC in overall survival (OS), disease-specific survival (DSS), metastasis-free survival, and relapse-free survival, and no significant correlation was found between HIF-2α alteration and OS or disease-free survival (DFS) of CRC. Expression of both HIF-2α and vascular endothelial growth factor (VEGFA, VEGFB, or VEGFC) was associated with a poor metastasis-free survival of CRC (HR = 6.95, HR = 113.51, and HR = 8.11, respectively). No association was observed between HIF-2α expression and DFS in other cancers, but HIF-2α expression was correlated with a worse DFS of CRC (HR = 1.23, <i>P</i> = 0.037). Moreover, HIF-2α expression was linked to a good survival benefit in some cancers (B-cell lymphoma and lung adenocarcinoma: OS, multiple myeloma: DSS, breast cancer: distant metastasis-free survival, liposarcoma: distant recurrence-free survival) (all HRs < 1, <i>Ps</i> < 0.05). <b><i>Conclusions:</i></b> HIF-2α expression may be associated with the carcinogenesis of CRC, which is higher in males than in females, negatively linked to tumor differentiation, and correlated with a worse DFS of CRC. Additional prospective studies are needed

Supplementary Material for: Association of serum activin levels with allograft outcomes in patients with kidney transplant: Results from the KNOW-KT

Introduction: Serum activin A has been reported to contribute to vascular calcification and kidney fibrosis in chronic kidney disease. We aimed to investigate whether higher serum activin levels were associated with poor allograft outcomes in patients with kidney transplants (KT). Methods: A total of 860 KT patients from KNOW-KT (KoreaN cohort study for Outcome in patients With Kidney Transplantation) were analyzed. We measured serum activin levels at pre-KT and 1 year after KT. The primary outcome was the composite of a ≥ 50% decline in eGFR and graft failure. Multivariable cause-specific hazard model was used to analyze association of 1-year activin levels with the primary outcome. The secondary outcome was coronary artery calcification score (CACS) at 5 years after KT. Results: During the median follow-up of 6.7 years, the primary outcome occurred in 109 (12.7%) patients. The serum activin levels at 1 year were significantly lower than those at pre-KT (488.2 ± 247.3 vs. 704.0 ± 349.6). When patients were grouped based on the median activin level at 1 year, the high-activin group had a 1.91-fold higher risk (95% CI, 1.25-2.91) for the primary outcome compared to the low-activin group. A one standard deviation increase in activin levels as a continuous variable was associated with a 1.36-fold higher risk (95% CI, 1.16-1.60) for the primary outcome. Moreover, high activin levels were significantly associated with 1.56-fold higher CACS (95% CI, 1.12-2.18). Conclusion: Post-transplant activin levels were independently associated with allograft functions as well as coronary artery calcification in kidney transplant patients

Supplementary Material for: Functional Genetic Variants of PPARγ and PPARα Encoding Peroxisome Proliferator-Activated Receptors and Susceptibility to Ischemic Stroke in Chinese Han Population

<b><i>Background:</i></b> PPARγ and PPARα belong to a receptor family of ligand-activated transcription factors involved in the regulation of inflammation, cellular glucose uptake, protection against atherosclerosis and endothelial cell function. Through these effects, they might be involved with the ischemic stroke (IS). <b><i>Methods:</i></b> One thousand two hundred ninety-six subjects from the Chinese Han Population were chosen to assess the nature of the functional polymorphisms of PPARs and any links with IS. Multivariate logistic regression analysis was used to examine the association between PPARγ and PPARα genotypes and a diagnosis of IS. <b><i>Results:</i></b> Pro/Ala carriage may be associated with the decreased risk of IS in Hans (OR 0.542, 95% CI 0.346-0.850). The 162Val allele frequency at the DNA-binding region of PPARα was extremely rare in Chinese Han population. <b><i>Conclusions:</i></b> PPARγ 12Pro/Ala resulting in an amino acid exchange in N-terminal sequence may be an independent protective factor for IS in the Chinese Han population. However, more populations are warranted to validate our findings

Supplementary Material for: Once-Weekly Administration of Sustained-Release Growth Hormone in Korean Prepubertal Children with Idiopathic Short Stature: A Randomized, Controlled Phase II Study

<b><i>Background/Aims:</i></b> To determine the optimal dose of LB03002, a sustained-release, once-weekly formulation of recombinant human growth hormone (rhGH), and to compare its efficacy and safety with daily rhGH in children with idiopathic short stature (ISS). <b><i>Methods:</i></b> This multicenter, randomized, open-label, phase II study included<b><i></i></b> GH-naïve, prepubertal children with ISS, randomized to receive daily rhGH 0.37 mg/kg/week (control, <i>n</i> = 16), LB03002 0.5 mg/kg/week (<i>n</i> = 14), or LB03002 0.7 mg/kg/week (<i>n</i> = 16). The primary endpoint was height velocity (HV) change at week 26. <b><i>Results:</i></b> At week 26, the least square (LS) means for HV change (cm/year) with control, LB03002 0.5 mg/kg/week, and LB03002 0.7 mg/kg/week were 5.08, 3.65, and 4.38, and the LS means for the change in height standard deviation score were 0.65, 0.49, and 0.58, respectively. The lower bound of the 90% confidence interval for the difference between LB03002 0.7 mg/kg/week and the control in the LS mean for HV change (–1.72) satisfied the noninferiority margin (–1.75). Adverse events were generally mild and short-lived. <b><i>Conclusion:</i></b> A once-weekly regimen of LB03002 0.7 mg/kg demonstrated noninferiority to the daily regimen of rhGH 0.37 mg/kg/week in terms of HV increments. LB03002 was well tolerated and its safety profile was comparable with that of daily rhGH

Supplementary Material for: Karyotypes and Distribution of Tandem Repeat Sequences in Brassica nigra Determined by Fluorescence in situ Hybridization

<p>Whole-genome shotgun reads were analyzed to determine the repeat sequence composition in the genome of black mustard, <i>Brassica nigra</i> (L.) Koch. The analysis showed that satellite DNA sequences are very abundant in the black mustard genome. The distribution pattern of 7 new tandem repeats (BnSAT13, BnSAT28, BnSAT68, BnSAT76, BnSAT114, BnSAT180, and BnSAT200) on black mustard chromosomes was visualized using fluorescence in situ hybridization (FISH). The FISH signals of BnSAT13 and BnSAT76 provided useful cytogenetic markers; their position and fluorescence intensity allowed for unambiguous identification of all 8 somatic metaphase chromosomes. A karyotype showing the location and fluorescence intensity of these tandem repeat sequences together with the position of rDNAs and centromeric retrotransposons of <i>Brassica</i> (CRB) was constructed. The establishment of the FISH-based karyotype in <i>B. nigra</i> provides valuable information that can be used in detailed analyses of <i>B. nigra</i> accessions and derived allopolyploid <i>Brassica</i> species containing the B genome.</p