cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5128735.v1
title: Supplementary Material for: Clinical Implication of Serine Metabolism-Associated Enzymes in Colon Cancer

description: <b><i>Purpose:</i></b> Recently, enzymes of the serine synthetic pathway (SSP) have been suggested as key player in the metabolic adaptation of oncogenesis. We assessed the expression of enzymes of the SSP in colonic tumor tissue (TT) and paired normal tissue (pNT) and the prognostic implications. <b><i>Methods:</i></b> From 2006 to 2010, we included 486 patients with colon cancer who underwent curative surgery at Kyungpook National University Hospital. Phosphoglycerate dehydrogenase (PHGDH), pyruvate dehydrogenase kinase (PDK) 1, PDK2, pyruvate kinase M2 (PKM2), and phosphoserine aminotransferase (PSAT) expression were investigated by immunohistochemical staining (IHC) in TT and pNT. The IHC values were calculated by multiplying intensity by proportion. The final score was classified as follows: 0-2 as negative and 3-12 as positive. <b><i>Results:</i></b> During the median follow-up duration of 55.5 months (37.4-90.6), 78 patients experienced recurrence. The expression of PHGDH, PDK1, and PSAT was significantly higher in TT than pNT (p &lt; 0.001 for each). The univariate analysis for relapse-free survival revealed that TT PDK2 positivity was the only positive prognostic factor (p = 0.023). However, the expression of TT PDK2 did not represent a prognostic value in multivariate analysis. <b><i>Conclusions:</i></b> In conclusion, PHGDH, PDK1, and PSAT were significantly increased in colonic TT compared with pNT. The prognostic implication of these enzymes needs to be further investigated.
DOI: 10.6084/m9.figshare.5128738.v1
title: Supplementary Material for: The Protective Effect of INH<sub>2</sub>BP, a Novel PARP Inhibitor 5-Iodo-6-Amino-1,2-Benzopyrone, Against Hydrogen Peroxide-Induced Apoptosis Through ERK and p38 MAPK in H9c2 Cells

description: INH<sub>2</sub>BP (5-iodo-6-amino-1,2-benzopyrone), a poly-ADP ribose polymerase inhibitor, has been shown to possess anti-cancer, anti-viral, and anti-inflammation properties. The aim of this study was to investigate the protective effect of INH<sub>2</sub>BP against oxidative stress-induced apoptosis in H9c2 cardiomyoblast cells. While the treatment of H9c2 cardiomyoblasts cells with hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) caused a loss of cell viability and an increase in the number of apoptotic cells, INH<sub>2</sub>BP significantly protected the cells against H<sub>2</sub>O<sub>2</sub>-induced cell death without any cytotoxicity. Our data also shows that INH<sub>2</sub>BP significantly scavenged intracellular reactive oxygen species (ROS), and markedly enhanced the expression of antioxidant enzymes such as Mn-SOD (superoxide) and Cu/Zn-SOD, and heme oxygenase-1, which was accompanied by the concomitant activation of extracellular regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) phosphorylation in H9c2 cells. The effects of INH<sub>2</sub>BP on ERK1/2 and p38 MAPK phosphorylation were abrogated by PD98059, an ERK1/2 inhibitor, and SB203580, a p38 inhibitor. In addition, inhibition of ERK1/2 and p38 MAPK by these inhibitors significantly attenuated INH<sub>2</sub>BP-mediated H9c2 viability as well as cleaved caspases-3, Bax, and Bcl-2 activation. Taken together, these results demonstrate that INH<sub>2</sub>BP prevents H<sub>2</sub>O<sub>2</sub>-induced apoptosis in H9c2 cells by reducing the production of intracellular ROS, regulating apoptotic-related proteins, and the activation of the ERK1/2 and p38 MAPK.
DOI: 10.6084/m9.figshare.5128723
title: Supplementary Material for: Variation of Meiotic Recombination Rates and MLH1 Foci Distribution in Spermatocytes of Cattle, Sheep and Goats

description: Despite similar genome sizes, a great variability in recombination rates is observed in mammals. We used antibodies against SYCP3, MLH1 and centromeres to compare crossover frequency, position along chromosome arms and the effect of crossover interference in spermatocytes of 4 species from the family Bovidae (<i>Bos taurus</i>, 2n = 60, tribe Bovini;<i> Ovis aries</i>, 2n = 54,<i> Capra hircus</i>, 2n = 60 and <i>Ammotragus lervia</i>, 2n = 58, tribe Caprini). Despite significant individual variability, our results also show significant differences in both recombination rates and the total length of autosomal synaptonemal complexes (SC) between cattle (47.53 MLH1 foci/cell, 244.59 µm) and members of the tribe Caprini (61.83 MLH1 foci, 296.19 µm) which can be explained by the length of time that has passed since their evolutionary divergence. Sheep displayed the highest number of MLH1 foci per cell and recombination density, although they have a lower diploid chromosome number caused by centric fusions corresponding to cattle chromosomes 1;3, 2;8 and 5;11. However, the proportion of MLH1 foci observed on the fused chromosomes in sheep (26.14%) was significantly lower than on the orthologous acrocentrics in cattle (27.6%) and goats (28.2%), and their distribution along the SC arms differed significantly. The reduced recombination rate in metacentrics is probably caused by interference acting across the centromere.
DOI: 10.6084/m9.figshare.5128726
title: Supplementary Material for: Patterns of Sensitization to Inhalant Allergens in Japanese Lower-Grade Schoolchildren and Related Factors

description: <b><i>Objective:</i></b> This study clarified sensitization patterns to house dust mite (HDM) and Japanese cedar pollen (JCP) in Japanese lower-grade schoolchildren. We also explored factors associated with allergic sensitization. <b><i>Methods:</i></b> This cross-sectional study used a database from the Study on Respiratory Disease and Automobile Exhaust (SORA), a Japanese health study project. The subjects comprised 8,815 pupils aged 6-9 years. We obtained the distribution of HDM- and JCP-specific IgE, respectively, as a marker of sensitization. To determine factors associated with sensitization, we used logistic regression and calculated adjusted odds ratios (AORs) for the relative prevalence of sensitization. The cut-off point for specific IgE levels was 0.35 kU/l. <b><i>Results:</i></b> Sensitization to HDM and JCP was detected in 51 and 39% of subjects, respectively, occurring more often in boys and at older ages. In addition, AORs of sensitization to HDM/JCP were higher in subjects with a history of bronchitis, parental asthma, parental atopic eczema and parental pollinosis. In contrast, AORs for sensitization were lower in those subjected to maternal passive smoking as well as among boys with pets. AORs of sensitization to JCP alone were lower in those with a history of otitis media, those who had been bottle milk fed, and those who were not the firstborn and who lived near a busy road. <b><i>Conclusion:</i></b> Sensitization to HDM and JCP was detected in 51 and 39% of lower-grade schoolchildren, respectively.
DOI: 10.6084/m9.figshare.5128729
title: Supplementary Material for: FGFR4 Is a Potential Predictive Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma

description: <b><i>Objective:</i></b> The aim of this study was to investigate whether fibroblast growth factor receptor 4 (FGFR4) could serve as a potential therapeutic target, prognostic biomarker or biomarker predicting radiotherapy sensitivity in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC). <b><i>Methods:</i></b> FGFR4 immunohistochemistry and <i>FGFR4</i>/<i>CEN5q</i> FISH were performed on tissue microarrays from 212 OSCC and 238 OPSCC patients. <i>FGFR4</i> genotypes were determined by PCR and DNA sequencing in 76 random OPSCC samples. The response to radiotherapy was evaluated 3 months after the last radiotherapy treatment session by a head and neck radiation oncologist and/or surgeon during clinic visits. The results were correlated to overall survival and response to radiotherapy. <b><i>Results:</i></b> The FGFR4 protein was overexpressed in 64% (153/238) of OPSCCs and 41% (87/212) of OSCCs. The <i>FGFR4 </i>gene was amplified in 0.47% (1/212) of OSCCs and 0.42% (1/238) of OPSCCs, and the <i>FGFR4</i> Gly388Arg polymorphism was detected in 62% (47/76) of OPSCCs. FGFR4 protein expression, <i>FGFR4 </i>gene copy numbers and <i>FGFR4 </i>genotypes were not related to overall survival or response to radiotherapy in OSCC or OPSCC. <b><i>Conclusion:</i></b> FGFR4 is frequently overexpressed in OSCC and OPSCC in the absence of gene amplification, and may serve as a potential predictive marker for FGFR4-directed targeted therapy in OSCC and OPSCC.
DOI: 10.6084/m9.figshare.5128717
title: Supplementary Material for: Reduction of Inflammatory and Noninflammatory Lesions with Topical Tyrothricin 0.1% in the Treatment of Mild to Severe Acne Papulopustulosa: A Randomized Controlled Clinical Trial

description: <b><i>Background/Aims:</i></b> Antibiotic-induced drug resistance requires new approaches in topical acne treatment. Tyrothricin is known to produce no resistance. In this study, it was tested for the first time in topical acne treatment. The efficacy and tolerability of topical tyrothricin 0.1% was evaluated. <b><i>Methods:</i></b> A<b> </b>randomized, active comparator-controlled, exploratory, observer-blind clinical study was conducted in 24 patients with acne papulopustulosa. Randomization on a split-face was either tyrothricin versus clindamycin + benzoyl peroxide (BPO) (n = 12) or tyrothricin versus BPO 5% (n = 12). The main outcome was change in inflammatory and noninflammatory lesion counts. <b><i>Results:</i></b> The mean differences in inflammatory lesion counts from baseline were -12.3 (95% CI: -20.5 to -4.1) in clindamycin + BPO, -10.2 (95% CI: -15.3 to -5.0) in BPO 5%, and -7.7 (95% CI: -11.7 to -3.7) in tyrothricin. Tyrothricin reduced noninflammatory lesions (mean difference: -6.5 (95% CI: -11.6 to -1.4) and caused less product-related adverse events (n = 31) compared to BPO (n = 37) and clindamycin + BPO (n = 20). <b><i>Conclusion:</i></b> The results indicate that tyrothricin might be a candidate for treating acne and it seems to be more tolerable than both comparator treatments.
DOI: 10.6084/m9.figshare.5128720
title: Supplementary Material for: Re-Sequencing of the <b><i>APOL1</i></b>-<b><i>APOL4</i></b> and <b><i>MYH9</i></b> Gene Regions in African Americans Does Not Identify Additional Risks for CKD Progression

description: <b><i>Background:</i></b> In African Americans (AAs), <i>APOL1</i> G1 and G2 nephropathy risk variants are associated with non-diabetic end-stage kidney disease (ESKD) in an autosomal recessive pattern. Additional risk and protective genetic variants may be present near the <i>APOL1</i> loci, since earlier age ESKD is observed in some AAs with one <i>APOL1</i> renal-risk variant, and because the adjacent gene <i>MYH9</i> is associated with nephropathy in populations lacking G1 and G2 variants. <b><i>Methods:</i></b> Re-sequencing was performed across a ∼275 kb region encompassing the <i>APOL1-APOL4</i> and <i>MYH9</i> genes in 154 AA cases with non-diabetic ESKD and 38 controls without nephropathy who were heterozygous for a single <i>APOL1</i> G1 or G2 risk variant. <b><i>Results:</i></b> Sequencing identified 3,246 non-coding single nucleotide polymorphisms (SNPs), 55 coding SNPs, and 246 insertion/deletions. No new coding variations were identified. Eleven variants, including a rare <i>APOL3</i> Gln<sup>58</sup>Ter null variant (rs11089781), were genotyped in a replication panel of 1,571 AA ESKD cases and 1,334 controls. After adjusting for <i>APOL1</i> G1 and G2 risk effects, these variations were not significantly associated with ESKD. In subjects with &lt;2 <i>APOL1</i> G1 and/or G2 alleles (849 cases; 1,139 controls), the <i>APOL3</i> null variant was nominally associated with ESKD (recessive model, OR 1.81; p = 0.026); however, analysis in 807 AA cases and 634 controls from the Family Investigation of Nephropathy and Diabetes did not replicate this association. <b><i>Conclusion:</i></b> Additional common variants in the <i>APOL1-APOL4</i>-<i>MYH9</i> region do not contribute significantly to ESKD risk beyond the <i>APOL1</i> G1 and G2 alleles.
DOI: 10.6084/m9.figshare.5128717.v1
title: Supplementary Material for: Reduction of Inflammatory and Noninflammatory Lesions with Topical Tyrothricin 0.1% in the Treatment of Mild to Severe Acne Papulopustulosa: A Randomized Controlled Clinical Trial

description: <b><i>Background/Aims:</i></b> Antibiotic-induced drug resistance requires new approaches in topical acne treatment. Tyrothricin is known to produce no resistance. In this study, it was tested for the first time in topical acne treatment. The efficacy and tolerability of topical tyrothricin 0.1% was evaluated. <b><i>Methods:</i></b> A<b> </b>randomized, active comparator-controlled, exploratory, observer-blind clinical study was conducted in 24 patients with acne papulopustulosa. Randomization on a split-face was either tyrothricin versus clindamycin + benzoyl peroxide (BPO) (n = 12) or tyrothricin versus BPO 5% (n = 12). The main outcome was change in inflammatory and noninflammatory lesion counts. <b><i>Results:</i></b> The mean differences in inflammatory lesion counts from baseline were -12.3 (95% CI: -20.5 to -4.1) in clindamycin + BPO, -10.2 (95% CI: -15.3 to -5.0) in BPO 5%, and -7.7 (95% CI: -11.7 to -3.7) in tyrothricin. Tyrothricin reduced noninflammatory lesions (mean difference: -6.5 (95% CI: -11.6 to -1.4) and caused less product-related adverse events (n = 31) compared to BPO (n = 37) and clindamycin + BPO (n = 20). <b><i>Conclusion:</i></b> The results indicate that tyrothricin might be a candidate for treating acne and it seems to be more tolerable than both comparator treatments.
DOI: 10.6084/m9.figshare.5128720.v1
title: Supplementary Material for: Re-Sequencing of the <b><i>APOL1</i></b>-<b><i>APOL4</i></b> and <b><i>MYH9</i></b> Gene Regions in African Americans Does Not Identify Additional Risks for CKD Progression

description: <b><i>Background:</i></b> In African Americans (AAs), <i>APOL1</i> G1 and G2 nephropathy risk variants are associated with non-diabetic end-stage kidney disease (ESKD) in an autosomal recessive pattern. Additional risk and protective genetic variants may be present near the <i>APOL1</i> loci, since earlier age ESKD is observed in some AAs with one <i>APOL1</i> renal-risk variant, and because the adjacent gene <i>MYH9</i> is associated with nephropathy in populations lacking G1 and G2 variants. <b><i>Methods:</i></b> Re-sequencing was performed across a ∼275 kb region encompassing the <i>APOL1-APOL4</i> and <i>MYH9</i> genes in 154 AA cases with non-diabetic ESKD and 38 controls without nephropathy who were heterozygous for a single <i>APOL1</i> G1 or G2 risk variant. <b><i>Results:</i></b> Sequencing identified 3,246 non-coding single nucleotide polymorphisms (SNPs), 55 coding SNPs, and 246 insertion/deletions. No new coding variations were identified. Eleven variants, including a rare <i>APOL3</i> Gln<sup>58</sup>Ter null variant (rs11089781), were genotyped in a replication panel of 1,571 AA ESKD cases and 1,334 controls. After adjusting for <i>APOL1</i> G1 and G2 risk effects, these variations were not significantly associated with ESKD. In subjects with &lt;2 <i>APOL1</i> G1 and/or G2 alleles (849 cases; 1,139 controls), the <i>APOL3</i> null variant was nominally associated with ESKD (recessive model, OR 1.81; p = 0.026); however, analysis in 807 AA cases and 634 controls from the Family Investigation of Nephropathy and Diabetes did not replicate this association. <b><i>Conclusion:</i></b> Additional common variants in the <i>APOL1-APOL4</i>-<i>MYH9</i> region do not contribute significantly to ESKD risk beyond the <i>APOL1</i> G1 and G2 alleles.
DOI: 10.6084/m9.figshare.5128729.v1
title: Supplementary Material for: FGFR4 Is a Potential Predictive Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma

description: <b><i>Objective:</i></b> The aim of this study was to investigate whether fibroblast growth factor receptor 4 (FGFR4) could serve as a potential therapeutic target, prognostic biomarker or biomarker predicting radiotherapy sensitivity in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC). <b><i>Methods:</i></b> FGFR4 immunohistochemistry and <i>FGFR4</i>/<i>CEN5q</i> FISH were performed on tissue microarrays from 212 OSCC and 238 OPSCC patients. <i>FGFR4</i> genotypes were determined by PCR and DNA sequencing in 76 random OPSCC samples. The response to radiotherapy was evaluated 3 months after the last radiotherapy treatment session by a head and neck radiation oncologist and/or surgeon during clinic visits. The results were correlated to overall survival and response to radiotherapy. <b><i>Results:</i></b> The FGFR4 protein was overexpressed in 64% (153/238) of OPSCCs and 41% (87/212) of OSCCs. The <i>FGFR4 </i>gene was amplified in 0.47% (1/212) of OSCCs and 0.42% (1/238) of OPSCCs, and the <i>FGFR4</i> Gly388Arg polymorphism was detected in 62% (47/76) of OPSCCs. FGFR4 protein expression, <i>FGFR4 </i>gene copy numbers and <i>FGFR4 </i>genotypes were not related to overall survival or response to radiotherapy in OSCC or OPSCC. <b><i>Conclusion:</i></b> FGFR4 is frequently overexpressed in OSCC and OPSCC in the absence of gene amplification, and may serve as a potential predictive marker for FGFR4-directed targeted therapy in OSCC and OPSCC.
DOI: 10.6084/m9.figshare.5128711
title: Supplementary Material for: Effects of Recombinant Human Leptin (Metreleptin) on Nocturnal Luteinizing Hormone Secretion in Lipodystrophy Patients

description: <b><i>Background:</i></b> Leptin replacement in patients with leptin gene mutations improves hypogonadotropic hypogonadism. The effects of leptin replacement on luteinizing hormone (LH) secretion in patients with lipodystrophy are unknown. <b><i>Aim:</i></b> We examined nocturnal LH secretory dynamics on and off exogenous leptin therapy using a 2-period, nonrandomized study that included leptin-naïve and leptin-treated subjects with lipodystrophy. <b><i>Methods:</i></b> In period 1 (5 days) the leptin-treated group (n = 4) continued leptin; leptin was then withdrawn for the next 14 days (period 2). Leptin-naïve subjects (n = 8) were studied without leptin in period 1 and with leptin replacement in period 2. LH secretory dynamics were assessed (23:00-07:00 h, sampling every 10 min, analyzed by multiparameter deconvolution algorithm) at the end of each period. <b><i>Results:</i></b> Mean (on vs. off: 5.0 ± 3.1 vs. 3.2 ± 1.3 IU/l, p = 0.04) and integrated LH concentrations (2,403 ± 1,495 vs. 1,534 ± 642 IU × l<sup>-1</sup> × min<sup>-1</sup>, p = 0.04) were higher on leptin therapy. Leptin treatment increased burst mass (9.7± 15.4 vs. 7.0 ± 11.2 IU/l, p = 0.03) and tended to nonsignificantly increase LH burst frequency (0.77 ± 0.26 vs. 0.67 ± 0.24 h<sup>-1</sup>, p = 0.08). Consequently, leptin therapy increased the pulsatile production rate (64 ± 101 vs. 57 ± 73 IU × l<sup>-1</sup> × 8 h<sup>-1</sup>, p = 0.01). On leptin, testosterone (507 ± 286 vs. 360 ± 174 ng/dl, p = 0.09) and estradiol levels (74 ± 36 vs. 29 ± 24 pg/ml, p = 0.01) were higher in males and females, respectively. <b><i>Conclusions:</i></b> Leptin increases spontaneous nocturnal LH secretion in patients with lipodystrophy. This is consistent with rodent and in vitro studies showing a direct stimulatory effect (hypothalamic, pituitary or both) of leptin on LH secretion. These novel findings may explicate some of the salutary effects of leptin therapy on the hypothalamic-pituitary-gonadal axis in lipodystrophy.
DOI: 10.6084/m9.figshare.5128714
title: Supplementary Material for: Grade Increases in Gastroenteropancreatic Neuroendocrine Tumor Metastases Compared to the Primary Tumor

description: <b><i>Background/Aim:</i></b> The neuroendocrine tumor (NET) proliferation-based grading system (ENETS/WHO) for gastroenteropancreatic (GEP) tumors has proved reliable for prognostic stratification. To date, concerns exist regarding Ki-67 heterogeneity within the tumor and little is known on whether grade varies between primary and secondary sites. As tumor heterogeneity may have a significant impact on clinical management, our aim was to retrospectively evaluate Ki-67 on a series of GEP NETs in order to establish whether there is variability in different samples of the same lesion or between primary and metastatic disease (local/distant, synchronous/metachronous). <b><i>Methods:</i></b> Sixty patients with multiple samples of tumor were accrued from a total of 338 GEP NETs; 44 of them also had tissue from local/distant metastases and a further 5 had multiple metastatic foci from unknown primary tumors. Immunohistochemistry for Ki-67 was performed on all paraffin blocks from both primary and metastatic tumors. <b><i>Results:</i></b> Intratumor Ki-67 heterogeneity sufficient to change grade at first diagnosis was seen in 3/60 cases (5%). Out of 49 patients with primary NETs and/or multiple metastases, discrepancy in grade between sites was identified in 19 (39%) cases and in particular in 11/47 (23%) and in 10/12 (83%) patients with synchronous and metachronous metastases, respectively (p = 0.0002). Change in grade was more frequent in distant compared to locoregional metastases (p = 0.024) and in particular in distant sites other than the liver (p = 0.006). <b><i>Conclusions:</i></b> NETs show frequent differences in grade between primary sites and their synchronous/metachronous metastases; assessment of Ki-67 at all sites may prove to be significant for patient management.
DOI: 10.6084/m9.figshare.5128726.v1
title: Supplementary Material for: Patterns of Sensitization to Inhalant Allergens in Japanese Lower-Grade Schoolchildren and Related Factors

description: <b><i>Objective:</i></b> This study clarified sensitization patterns to house dust mite (HDM) and Japanese cedar pollen (JCP) in Japanese lower-grade schoolchildren. We also explored factors associated with allergic sensitization. <b><i>Methods:</i></b> This cross-sectional study used a database from the Study on Respiratory Disease and Automobile Exhaust (SORA), a Japanese health study project. The subjects comprised 8,815 pupils aged 6-9 years. We obtained the distribution of HDM- and JCP-specific IgE, respectively, as a marker of sensitization. To determine factors associated with sensitization, we used logistic regression and calculated adjusted odds ratios (AORs) for the relative prevalence of sensitization. The cut-off point for specific IgE levels was 0.35 kU/l. <b><i>Results:</i></b> Sensitization to HDM and JCP was detected in 51 and 39% of subjects, respectively, occurring more often in boys and at older ages. In addition, AORs of sensitization to HDM/JCP were higher in subjects with a history of bronchitis, parental asthma, parental atopic eczema and parental pollinosis. In contrast, AORs for sensitization were lower in those subjected to maternal passive smoking as well as among boys with pets. AORs of sensitization to JCP alone were lower in those with a history of otitis media, those who had been bottle milk fed, and those who were not the firstborn and who lived near a busy road. <b><i>Conclusion:</i></b> Sensitization to HDM and JCP was detected in 51 and 39% of lower-grade schoolchildren, respectively.