cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.9810674
title: Chilliness in Japanese middle-aged women is associated with anxiety and low n-3 fatty acid intake

description: <b>Objective:</b> This cross-sectional study investigated chilliness, which is the most prevalent sexual-vasomotor symptom in middle-aged Japanese women. <b>Methods:</b> First-visit records of 475 Japanese women (age 40–65 years) enrolled in the health and nutrition education program at a menopause clinic were analyzed. Chilliness was estimated based on responses to the Menopausal Symptom Scale. Effects of age, menopausal status, body composition, cardiovascular parameters, resting energy expenditure, physical fitness, menopausal symptoms, lifestyle, and estimated daily intake of nutrients were assessed using a multivariate logistic regression analysis. <b>Results:</b> Severe chilliness was found in 28.4% of women. It was not related to age, menopausal status, body mass index, or body fat percentage. The anxiety subscale score of the Hospital Anxiety and Depression Scale was the sole background characteristic independently associated with severe chilliness (adjusted odds ratio, 1.09; 95% confidence interval, 1.04–1.15 per point). Daily intakes of vitamin D and n-3 fatty acids were significantly lower in women with severe chilliness. Daily intake of n-3 fatty acids was negatively associated with severe chilliness after adjustment (odds ratio, 0.54; 95% confidence interval, 0.29–0.95 per g/1000 kcal intake). <b>Conclusions:</b> Chilliness is associated with anxiety and low intake of n-3 fatty acids.
DOI: 10.6084/m9.figshare.9810677.v1
title: HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

description: Cancer is a major cause of death worldwide. MET tyrosine kinase receptor [MET, c-MET, hepatocyte growth factor (HGF) receptor] pathway activation is associated with the appearance of several hallmarks of cancer. The HGF/MET pathway has emerged as an important actionable target across many solid tumors; therefore, biomarker discovery becomes essential in order to guide clinical intervention and patient stratification with the aim of moving towards personalized medicine. The focus of this review is on how the aberrant activation of the HGF/MET pathway in tumor tissue or the circulation can provide diagnostic and prognostic biomarkers and predictive biomarkers of drug response. Many meta-analyses have shown that aberrant activation of the MET pathway in tumor tissue, including <i>MET</i> gene overexpression, gene amplification, exon 14 skipping and other activating mutations, is almost invariably associated with shorter survival and poor prognosis. Most meta-analyses have been performed in non-small cell lung cancer (NSCLC), breast, head and neck cancers as well as colorectal, gastric, pancreatic and other gastrointestinal cancers. Furthermore, several studies have shown the predictive value of MET biomarkers in the identification of patients who gain the most benefit from HGF/MET targeted therapies administered as single or combination therapies. The highest predictive values have been observed for response to foretinib and savolitinib in renal cancer, as well as tivantinib in NSCLC and colorectal cancer. However, some studies, especially those based on MET expression, have failed to show much value in these stratifications. This may be rooted in lack of standardization of methodologies, in particular in scoring systems applied in immunohistochemistry determinations or absence of oncogenic addiction of cancer cells to the MET pathway, despite detection of overexpression. Measurements of amplification and mutation aberrations are less likely to suffer from these pitfalls. Increased levels of MET soluble ectodomain (sMET) in circulation have also been associated with poor prognosis; however, the evidence is not as strong as it is with tissue-based biomarkers. As a diagnostic biomarker, sMET has shown its value in distinguishing cancer patients from healthy individuals in prostate and bladder cancers and in melanoma. On the other hand, increased circulating HGF has also been presented as a valuable prognostic and diagnostic biomarker in many cancers; however, there is controversy on the predictive value of HGF as a biomarker. Other biomarkers such as circulating tumor DNA (ctDNA) and tumor HGF levels have also been briefly covered. In conclusion, HGF/MET aberrations can provide valuable diagnostic, prognostic and predictive biomarkers and represent vital assets for personalized cancer therapy.
DOI: 10.6084/m9.figshare.9810719.v1
title: A high-throughput drug combination screen of targeted small molecule inhibitors in cancer cell lines - supplementary table

description: Raw and processed data accompanying the Nature Scientific Data article titled "A high-throughput drug combination screen of targeted small molecule inhibitors in cancer cell lines"
DOI: 10.6084/m9.figshare.9810674.v1
title: Chilliness in Japanese middle-aged women is associated with anxiety and low n-3 fatty acid intake

description: <b>Objective:</b> This cross-sectional study investigated chilliness, which is the most prevalent sexual-vasomotor symptom in middle-aged Japanese women. <b>Methods:</b> First-visit records of 475 Japanese women (age 40–65 years) enrolled in the health and nutrition education program at a menopause clinic were analyzed. Chilliness was estimated based on responses to the Menopausal Symptom Scale. Effects of age, menopausal status, body composition, cardiovascular parameters, resting energy expenditure, physical fitness, menopausal symptoms, lifestyle, and estimated daily intake of nutrients were assessed using a multivariate logistic regression analysis. <b>Results:</b> Severe chilliness was found in 28.4% of women. It was not related to age, menopausal status, body mass index, or body fat percentage. The anxiety subscale score of the Hospital Anxiety and Depression Scale was the sole background characteristic independently associated with severe chilliness (adjusted odds ratio, 1.09; 95% confidence interval, 1.04–1.15 per point). Daily intakes of vitamin D and n-3 fatty acids were significantly lower in women with severe chilliness. Daily intake of n-3 fatty acids was negatively associated with severe chilliness after adjustment (odds ratio, 0.54; 95% confidence interval, 0.29–0.95 per g/1000 kcal intake). <b>Conclusions:</b> Chilliness is associated with anxiety and low intake of n-3 fatty acids.
DOI: 10.6084/m9.figshare.9810629
title: Dataset for: Serotonin is essential for eye regeneration in planaria Schmidtea mediterranea

description: Planaria is an ideal system to study factors involved in regeneration and tissue homeostasis. Little is known about the role of metabolites and small molecules, in stem cell maintenance and lineage specification in planarians. Using LC-MS-based quantitative metabolomics, we determined the relative levels of metabolites in stem cells, progenitors, and differentiated cells of planarian S.mediterranea. Tryptophan and its metabolic product serotonin are significantly enriched in stem cells and progenitor population. Serotonin biosynthesis in these cells is brought about by a non-canonical enzyme phenylalanine hydroxylase (PAH). Knockdown of Smed-pah leads to complete disappearance of eyes in regenerating planaria while exogenous supply of serotonin and its precursor rescued the eyeless phenotype. Our results demonstrate a key role for serotonin in eye regeneration.
DOI: 10.6084/m9.figshare.9810632
title: networks and gender - Díaz-Faes et al.

description: Data from a questionnaire, administered to biomedical scientists and technicians in Spain, which enquired into multiple aspects of personal research networks
DOI: 10.6084/m9.figshare.9810629.v1
title: Dataset for: Serotonin is essential for eye regeneration in planaria Schmidtea mediterranea

description: Planaria is an ideal system to study factors involved in regeneration and tissue homeostasis. Little is known about the role of metabolites and small molecules, in stem cell maintenance and lineage specification in planarians. Using LC-MS-based quantitative metabolomics, we determined the relative levels of metabolites in stem cells, progenitors, and differentiated cells of planarian S.mediterranea. Tryptophan and its metabolic product serotonin are significantly enriched in stem cells and progenitor population. Serotonin biosynthesis in these cells is brought about by a non-canonical enzyme phenylalanine hydroxylase (PAH). Knockdown of Smed-pah leads to complete disappearance of eyes in regenerating planaria while exogenous supply of serotonin and its precursor rescued the eyeless phenotype. Our results demonstrate a key role for serotonin in eye regeneration.
DOI: 10.6084/m9.figshare.9810620
title: TNNT1, a prognostic indicator in colon adenocarcinoma, regulates cell behaviors and mediates EMT process

description: Slow skeletal muscle troponin T (TNNT1) has been reported to be correlated with several cancers, but there are no evidences proving that TNNT1 is required in colon adenocarcinoma (COAD). TNNT1 expression in COAD tissues and its prognostic significance were acquired from TCGA database. The proliferative, migratory, and invasive abilities of COAD cells were detected by CCK-8 and transwell assays, respectively. Correlations between TNNT1 and epithelial–mesenchymal transition (EMT)-related markers were determined using western blotting and Pearson’s analysis. Our results stated that TNNT1 expression was high-regulated in COAD tissues, which was related with unfavorable prognosis of COAD patients. Functional analyses suggested that TNNT1 promoted the cellular behaviors. Moreover, aberrant expression of TNNT1 affected the expression level of EMT-related proteins. And TNNT1 was negatively linked with E-cadherin. In conclusion, our findings indicated that TNNT1 may promote the progression of COAD, mediating EMT process, and thus shed a novel light on COAD therapeutic treatments. TNNT1 regulated cancer-related cellular behaviors following the elements of EMT process alteration and correlated with prognosis of colon adenocarcinoma patients.
DOI: 10.6084/m9.figshare.9810620.v1
title: TNNT1, a prognostic indicator in colon adenocarcinoma, regulates cell behaviors and mediates EMT process

description: Slow skeletal muscle troponin T (TNNT1) has been reported to be correlated with several cancers, but there are no evidences proving that TNNT1 is required in colon adenocarcinoma (COAD). TNNT1 expression in COAD tissues and its prognostic significance were acquired from TCGA database. The proliferative, migratory, and invasive abilities of COAD cells were detected by CCK-8 and transwell assays, respectively. Correlations between TNNT1 and epithelial–mesenchymal transition (EMT)-related markers were determined using western blotting and Pearson’s analysis. Our results stated that TNNT1 expression was high-regulated in COAD tissues, which was related with unfavorable prognosis of COAD patients. Functional analyses suggested that TNNT1 promoted the cellular behaviors. Moreover, aberrant expression of TNNT1 affected the expression level of EMT-related proteins. And TNNT1 was negatively linked with E-cadherin. In conclusion, our findings indicated that TNNT1 may promote the progression of COAD, mediating EMT process, and thus shed a novel light on COAD therapeutic treatments. TNNT1 regulated cancer-related cellular behaviors following the elements of EMT process alteration and correlated with prognosis of colon adenocarcinoma patients.
DOI: 10.6084/m9.figshare.9810602
title: Experiment data

description: These data includes task completion time, accuracy of x, y, and exocentric positions for direct-pointing and indirect-cursor techniques. The input of spss software to calculate the ANOVA is also included
DOI: 10.6084/m9.figshare.9810602.v1
title: Experiment data

description: These data includes task completion time, accuracy of x, y, and exocentric positions for direct-pointing and indirect-cursor techniques. The input of spss software to calculate the ANOVA is also included
DOI: 10.6084/m9.figshare.9810548
title: Supplementary Material for: Effect of the Tryptophan Hydroxylase Inhibitor Telotristat on Growth and Serotonin Secretion in 2D and 3D Cultured Pancreatic Neuroendocrine Tumor Cells

description: Serotonin, a biologically active amine, is related to carcinoid syndrome in functioning neuroendocrine tumors (NETs). Telotristat ethyl is a novel inhibitor of the tryptophan hydroxylase (TPH), a key enzyme in the production of serotonin. While its use in patients with carcinoid syndrome and uncontrolled diarrhea under somatostatin analogs (SSAs) has been recently approved, in vitro data evaluating its effectiveness are lacking. For this reason, we aimed to evaluate the effect of telotristat as monotherapy, and in combination with SSAs, on proliferation and secretion in a NET cell line model. The human pancreatic NET cell lines BON-1/QGP-1 were used as 2D and 3D cultured models; somatostatin receptor and TPH mRNA expression, as well as the potential autocrine effect of serotonin on tumor cell proliferation using a 3D culture system were evaluated. Telotristat decreased serotonin production in a dose-dependent manner at a clinically feasible concentration, without affecting cell proliferation. Its combination with pasireotide, but not with octreotide, had an additive inhibitory effect on serotonin secretion. The effect of telotristat was slightly less potent, when BON-1 cells were co-treated with octreotide. Octreotide and pasireotide had no effect on the expression of TPH. Telotristat did not have an effect on mRNA expression of somatostatin receptor subtypes. Finally, we showed that serotonin did not have an autocrine effect on NET cell proliferation on the 3D cell model. These results suggest that telotristat is an effective drug for serotonin inhibition, but the effectiveness of its combination with SST<sub>2</sub> (somatostatin receptor subtype 2)-preferring SSA should be evaluated in more detail.
DOI: 10.6084/m9.figshare.9810533
title: Supplementary Material for: Salt and Water Retention Is Associated with Microinflammation and Endothelial Injury in Chronic Kidney Disease

description: <b><i>Background:</i></b> Progressive chronic kidney disease (CKD) inevitably leads to salt and water retention and disturbances in the macro-and microcirculation. <b><i>Objectives:</i></b> We hypothesize that salt and water dysregulation in advanced CKD may be linked to inflammation and microvascular injury pathways. <b><i>Methods:</i></b> We studied 23 CKD stage 5 patients and 11 healthy controls (HC). Tissue sodium concentration was assessed using <sup>23</sup>Sodium magnetic resonance (MR) imaging. Hydration status was evaluated using bioimpedance spectroscopy. A panel of inflammatory and endothelial biomarkers was also measured. <b><i>Results:</i></b> CKD patients had fluid overload (FO) when compared to HC (overhydration index: CKD = 0.5 ± 1.9 L vs. HC = –0.5 ± 1.0 L; <i>p</i> = 0.03). MR-derived tissue sodium concentrations were predominantly higher in the subcutaneous (SC) compartment (median [interquartile range] CKD = 22.4 mmol/L [19.4–31.3] vs. HC = 18.4 mmol/L [16.6–21.3]; <i>p</i> = 0.03), but not the muscle (CKD = 24.9 ± 5.5 mmol/L vs. HC = 22.8 ± 2.5 mmol/L; <i>p</i> = 0.26). Tissue sodium in both compartments correlated to FO (muscle: <i>r</i> = 0.63, <i>p</i> &lt; 0.01; SC: <i>r</i><sub>s</sub> = 0.63, <i>p</i> &lt; 0.01). CKD subjects had elevated levels of vascular cell adhesion molecule (<i>p</i> &lt; 0.05), tumor necrosis factor-alpha (<i>p</i> &lt; 0.01), and interleukin (IL)-6 (<i>p</i> = 0.01) and lower levels of vascular endothelial growth factor-C (<i>p</i> = 0.04). FO in CKD was linked to higher IL-8 (<i>r</i> = 0.51, <i>p</i> &lt; 0.05) and inversely associated to E-selectin (<i>r</i> = –0.52, <i>p</i> = 0.01). Higher SC sodium was linked to higher intracellular adhesion molecule (ICAM; <i>r</i><sub>s</sub> = 0.54, <i>p</i> = 0.02). <b><i>Conclusion:</i></b> Salt and water accumulation in CKD appears to be linked with inflammation and endothelial activation pathways. Specifically IL-8, E-Selectin (in FO), and ICAM (in salt accumulation) may be implicated in the pathophysiology of FO and merit further investigation.
DOI: 10.6084/m9.figshare.9810548.v1
title: Supplementary Material for: Effect of the Tryptophan Hydroxylase Inhibitor Telotristat on Growth and Serotonin Secretion in 2D and 3D Cultured Pancreatic Neuroendocrine Tumor Cells

description: Serotonin, a biologically active amine, is related to carcinoid syndrome in functioning neuroendocrine tumors (NETs). Telotristat ethyl is a novel inhibitor of the tryptophan hydroxylase (TPH), a key enzyme in the production of serotonin. While its use in patients with carcinoid syndrome and uncontrolled diarrhea under somatostatin analogs (SSAs) has been recently approved, in vitro data evaluating its effectiveness are lacking. For this reason, we aimed to evaluate the effect of telotristat as monotherapy, and in combination with SSAs, on proliferation and secretion in a NET cell line model. The human pancreatic NET cell lines BON-1/QGP-1 were used as 2D and 3D cultured models; somatostatin receptor and TPH mRNA expression, as well as the potential autocrine effect of serotonin on tumor cell proliferation using a 3D culture system were evaluated. Telotristat decreased serotonin production in a dose-dependent manner at a clinically feasible concentration, without affecting cell proliferation. Its combination with pasireotide, but not with octreotide, had an additive inhibitory effect on serotonin secretion. The effect of telotristat was slightly less potent, when BON-1 cells were co-treated with octreotide. Octreotide and pasireotide had no effect on the expression of TPH. Telotristat did not have an effect on mRNA expression of somatostatin receptor subtypes. Finally, we showed that serotonin did not have an autocrine effect on NET cell proliferation on the 3D cell model. These results suggest that telotristat is an effective drug for serotonin inhibition, but the effectiveness of its combination with SST<sub>2</sub> (somatostatin receptor subtype 2)-preferring SSA should be evaluated in more detail.
DOI: 10.6084/m9.figshare.9810527
title: Supplementary Material for: Systematic Review and Meta-Analysis of ­New-Generation Tyrosine Kinase Inhibitors versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia

description: <b><i>Backgrounds:</i></b> We performed this systematic review and meta-analysis to compare the efficacy of new-generation tyrosine kinase inhibitors (NG-TKIs; including dasatinib, nilotinib, bosutinib, radotinib, and ponatinib) versus imatinib for patients with newly diagnosed chronic myeloid leukemia (CML). <b><i>Summary:</i></b> We identified randomized controlled trials comparing the efficacy of NG-TKIs versus imatinib as the first-line treatment for CML patients by searching the PubMed, Cochrane library, and EMBASE databases. Two reviewers independently extracted data and assessed study quality. A meta-analysis was performed to calculate risk ratios and 95% CIs using a fixed-effects model.<b><i></i></b>Our study included 10 trials. Overall, treatment with NG-TKIs significantly improved the major molecular response and MR4.5 at all time points, and early molecular response at 3 months. Importantly, overall survival (OS) was significantly higher with the NG-TKIs at 12 months. Besides, NG-TKI-treated patients showed a significantly lower CML-related death and progression to the accelerated phase/blast crisis. <b><i>Key Messages:</i></b> In first-line treatment, NG-TKIs are superior to imatinib regarding OS at 12 months, and because molecular response rates were higher with the NG-TKIs at all time points, the NG-TKIs favor treatment-free remission.
DOI: 10.6084/m9.figshare.9810533.v1
title: Supplementary Material for: Salt and Water Retention Is Associated with Microinflammation and Endothelial Injury in Chronic Kidney Disease

description: <b><i>Background:</i></b> Progressive chronic kidney disease (CKD) inevitably leads to salt and water retention and disturbances in the macro-and microcirculation. <b><i>Objectives:</i></b> We hypothesize that salt and water dysregulation in advanced CKD may be linked to inflammation and microvascular injury pathways. <b><i>Methods:</i></b> We studied 23 CKD stage 5 patients and 11 healthy controls (HC). Tissue sodium concentration was assessed using <sup>23</sup>Sodium magnetic resonance (MR) imaging. Hydration status was evaluated using bioimpedance spectroscopy. A panel of inflammatory and endothelial biomarkers was also measured. <b><i>Results:</i></b> CKD patients had fluid overload (FO) when compared to HC (overhydration index: CKD = 0.5 ± 1.9 L vs. HC = –0.5 ± 1.0 L; <i>p</i> = 0.03). MR-derived tissue sodium concentrations were predominantly higher in the subcutaneous (SC) compartment (median [interquartile range] CKD = 22.4 mmol/L [19.4–31.3] vs. HC = 18.4 mmol/L [16.6–21.3]; <i>p</i> = 0.03), but not the muscle (CKD = 24.9 ± 5.5 mmol/L vs. HC = 22.8 ± 2.5 mmol/L; <i>p</i> = 0.26). Tissue sodium in both compartments correlated to FO (muscle: <i>r</i> = 0.63, <i>p</i> &lt; 0.01; SC: <i>r</i><sub>s</sub> = 0.63, <i>p</i> &lt; 0.01). CKD subjects had elevated levels of vascular cell adhesion molecule (<i>p</i> &lt; 0.05), tumor necrosis factor-alpha (<i>p</i> &lt; 0.01), and interleukin (IL)-6 (<i>p</i> = 0.01) and lower levels of vascular endothelial growth factor-C (<i>p</i> = 0.04). FO in CKD was linked to higher IL-8 (<i>r</i> = 0.51, <i>p</i> &lt; 0.05) and inversely associated to E-selectin (<i>r</i> = –0.52, <i>p</i> = 0.01). Higher SC sodium was linked to higher intracellular adhesion molecule (ICAM; <i>r</i><sub>s</sub> = 0.54, <i>p</i> = 0.02). <b><i>Conclusion:</i></b> Salt and water accumulation in CKD appears to be linked with inflammation and endothelial activation pathways. Specifically IL-8, E-Selectin (in FO), and ICAM (in salt accumulation) may be implicated in the pathophysiology of FO and merit further investigation.
DOI: 10.6084/m9.figshare.9810527.v1
title: Supplementary Material for: Systematic Review and Meta-Analysis of ­New-Generation Tyrosine Kinase Inhibitors versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia

description: <b><i>Backgrounds:</i></b> We performed this systematic review and meta-analysis to compare the efficacy of new-generation tyrosine kinase inhibitors (NG-TKIs; including dasatinib, nilotinib, bosutinib, radotinib, and ponatinib) versus imatinib for patients with newly diagnosed chronic myeloid leukemia (CML). <b><i>Summary:</i></b> We identified randomized controlled trials comparing the efficacy of NG-TKIs versus imatinib as the first-line treatment for CML patients by searching the PubMed, Cochrane library, and EMBASE databases. Two reviewers independently extracted data and assessed study quality. A meta-analysis was performed to calculate risk ratios and 95% CIs using a fixed-effects model.<b><i></i></b>Our study included 10 trials. Overall, treatment with NG-TKIs significantly improved the major molecular response and MR4.5 at all time points, and early molecular response at 3 months. Importantly, overall survival (OS) was significantly higher with the NG-TKIs at 12 months. Besides, NG-TKI-treated patients showed a significantly lower CML-related death and progression to the accelerated phase/blast crisis. <b><i>Key Messages:</i></b> In first-line treatment, NG-TKIs are superior to imatinib regarding OS at 12 months, and because molecular response rates were higher with the NG-TKIs at all time points, the NG-TKIs favor treatment-free remission.
DOI: 10.6084/m9.figshare.9810500
title: Thermodynamic analysis in silico of missense variants in MEN1

description: Dataset for thermodynamic analysis in silico of 338 previously-reported missense variants in MEN1
DOI: 10.6084/m9.figshare.9810455
title: A high-throughput drug combination screen of targeted small molecule inhibitors in cancer cell lines

description: Dataset, code and supplementary information for the Nature Scientific Data publication titled "A high-throughput drug combination screen of targeted small molecule inhibitors in cancer cell lines"