cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123254.v1
title: Supplementary Material for: Curcumin Requires Tumor Necrosis Factor α Signaling to Alleviate Cognitive Impairment Elicited by Lipopolysaccharide

description: A decline in cognitive ability is a typical feature of the normal aging process, and of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. Although their etiologies differ, all of these disorders involve local activation of innate immune pathways and associated inflammatory cytokines. However, clinical trials of anti-inflammatory agents in neurodegenerative disorders have been disappointing, and it is therefore necessary to better understand the complex roles of the inflammatory process in neurological dysfunction. The dietary phytochemical curcumin can exert anti-inflammatory, antioxidant and neuroprotective actions. Here we provide evidence that curcumin ameliorates cognitive deficits associated with activation of the innate immune response by mechanisms requiring functional tumor necrosis factor α receptor 2 (TNFR2) signaling. In vivo, the ability of curcumin to counteract hippocampus-dependent spatial memory deficits, to stimulate neuroprotective mechanisms such as upregulation of BDNF, to decrease glutaminase levels, and to modulate N-methyl-D-aspartate receptor levels was absent in mice lacking functional TNFRs. Curcumin treatment protected cultured neurons against glutamate-induced excitotoxicity by a mechanism requiring TNFR2 activation. Our results suggest the possibility that therapeutic approaches against cognitive decline designed to selectively enhance TNFR2 signaling are likely to be more beneficial than the use of anti-inflammatory drugs per se.
DOI: 10.6084/m9.figshare.5123257.v1
title: Supplementary Material for: Liver Proteome Changes Induced by a Short-Term High-Fat Sucrose Diet in Wistar Rats

description: <i>Background/Aims:</i> The aim of this study was to gain insight into those proteins that might be involved in the early stages of liver fat accumulation as a consequence of a different fat versus simple sugar dietary intake. <i>Methods:</i> Forty-five male Wistar rats were randomly distributed into four dietary groups: a starch-rich control diet (CD; n = 10), a high-fat diet (n = 12), a high-sucrose diet (n = 11), and a high-fat sucrose diet (HFSD; n = 12) for 5 weeks. A comparative analysis by 2D-DIGE and LC-ESI-MS/MS was performed to characterize the liver protein expression profiles due to the three obesogenic diets. <i>Results:</i> Ten out of 17 proteins whose expression levels were altered by &gt;1.25-fold were identified. Four proteins (Hspa8, Hspa9, Ca3, and Cat) were differentially expressed after the HFSD period compared to CD. The heat shock proteins (Hspa8 and Hspa9) resulted significantly downregulated in liver from rats fed HFSD versus CD (p &lt; 0.05). The results were confirmed by Western blot. <i>Conclusions:</i> This descriptive study might be useful for further studies aiming at understanding the mechanisms by which diets rich in both fat and sugar affect the initiation of hepatic steatosis.
DOI: 10.6084/m9.figshare.5123239
title: Supplementary Material for: Influence of Minimal Changes in Preoperative Renal Function on Outcomes of Cardiac Surgery

description: <b><i>Background/Aims:</i></b> Cardiovascular morbidity and mortality are high in patients with chronic kidney disease. We evaluated the influence of small differences in preoperative kidney function on mortality and complications following cardiac surgery. <b><i>Methods:</i></b> This is an observational study that included adult patients undergoing cardiac surgery. Preoperative estimated glomerular filtration rate (eGFR) was estimated by the 4-component Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on preoperative creatinine levels. For analysis, patients were divided into groups according to their preoperative creatinine (0.2 mg/dl increments) and eGFR levels (15–30 ml/min/1.73 m<sup>2</sup> decrements). <b><i>Results:</i></b> Data on 5,340 patients were analyzed. A significant increase in postoperative mortality was demonstrated with preoperative creatinine at high-normal versus low-normal values (OR 1.7, 95% CI: 1–2.5; p = 0.02). For preoperative creatinine &gt;1.2 mg/dl, adjusted OR for in-hospital mortality increased stepwise with every 0.2-mg/dl increment of creatinine. In addition, a statistically significant increment of mortality was detected with every 15-ml/min/1.73 m<sup>2</sup> decrement in preoperative eGFR. <b><i>Conclusions:</i></b> Minimal changes of preoperative kidney function are associated with a substantial increase in the risk of mortality and morbidity following cardiac surgery. Even within the ‘normal’ range, minimal increases in serum creatinine levels are associated with increased risk of adverse events postoperatively.
DOI: 10.6084/m9.figshare.5123236
title: Supplementary Material for: Not All Inflammatory Markers Are Linked to Kidney Function: Results from a Population-Based Study

description: <i>Background:</i> Several studies have reported increased levels of inflammatory biomarkers in chronic kidney disease (CKD), but data from the general population are sparse. In this study, we assessed levels of the inflammatory markers C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 across all ranges of renal function. <i>Methods:</i> We conducted a cross-sectional study in a random sample of 6,184 Caucasian subjects aged 35–75 years in Lausanne, Switzerland. Serum levels of hsCRP, TNF-α, IL-6, and IL-1β were measured in 6,067 participants (98.1%); serum creatinine-based estimated glomerular filtration rate (eGFR<sub>creat</sub>, CKD-EPI formula) was used to assess renal function, and albumin/creatinine ratio on spot morning urine to assess microalbuminuria (MAU). <i>Results:</i> Higher serum levels of IL-6, TNF-α and hsCRP and lower levels of IL-1β were associated with a lower renal function, CKD (eGFR<sub>creat</sub> &lt;60 ml/min/1.73 m<sup>2</sup>; n = 283), and MAU (n = 583). In multivariate linear regression analysis adjusted for age, sex, hypertension, smoking, diabetes, body mass index, lipids, antihypertensive and hypolipemic therapy, only log-transformed TNF-α remained independently associated with lower renal function (β –0.54 ±0.19). In multivariate logistic regression analysis, higher TNF-α levels were associated with CKD (OR 1.17; 95% CI 1.01–1.35), whereas higher levels of IL-6 (OR 1.09; 95% CI 1.02–1.16) and hsCRP (OR 1.21; 95% CI 1.10–1.32) were associated with MAU. <i>Conclusion:</i> We did not confirm a significant association between renal function and IL-6, IL-1β and hsCRP in the general population. However, our results demonstrate a significant association between TNF-α and renal function, suggesting a potential link between inflammation and the development of CKD. These data also confirm the association between MAU and inflammation.
DOI: 10.6084/m9.figshare.5123242
title: Supplementary Material for: Pharmacoeconomic Impact of Different Regimens to Prevent Cytomegalovirus Infection in Renal Transplant Recipients

description: <b><i>Background:</i></b> The aim of this study was to determine the cost impact of four different strategies for prevention of cytomegalovirus (CMV) disease after renal transplantation. <b><i>Methods:</i></b> Hospitalization data and medical resource utilization data were prospectively collected alongside two randomized trials. In the first trial, the patients were randomized to 3-month prophylaxis with either oral ganciclovir (1 g t.i.d., n = 36) or valacyclovir (2 g q.i.d., n = 35), and to the control group (n = 12) managed by deferred therapy. In the second trial, the patients were randomly assigned to 3-month valacyclovir prophylaxis (n = 34) or preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n = 36) for significant CMV DNAemia. The cost analysis involved all real costs directly related to CMV during the first year after renal transplantation. <b><i>Results:</i></b> The mean CMV-associated costs per patient were EUR 4,581, 2,577, 4,968, and 8,050 in patients in the ganciclovir, valacyclovir, preemptive, and deferred therapy groups, respectively (p &lt; 0.001). Valacyclovir prophylaxis was significantly less expensive than any other regimen. The cost of one episode of CMV disease was EUR 7,510 per patient. Due to excessive incidence of CMV disease, deferred therapy was the most expensive strategy (p &lt; 0.001). <b><i>Conclusions:</i></b> Valacyclovir prophylaxis is less expensive strategy compared with any other regimen.
DOI: 10.6084/m9.figshare.5123245.v1
title: Supplementary Material for: Efficacy of Bevacizumab plus Erlotinib for Advanced Hepatocellular Carcinoma and Predictors of Outcome: Final Results of a Phase II Trial

description: <i>Objective:</i> A phase II study was performed to evaluate the efficacy and tolerability of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) patients, and to investigate clinical and molecular predictors of outcome. <i>Methods:</i> 59 patients with advanced HCC received 10 mg/kg i.v. of bevacizumab every 14 days and 150 mg p.o. of erlotinib daily. The primary endpoint was progression-free survival (PFS) at 16 weeks. Clinical characteristics and plasma biomarkers expression levels were analyzed. <i>Results:</i> PFS at 16 weeks was 64% (95% CI 51–76): 14 patients achieved partial response (24%), 33 had stable disease (56%), 6 progressed (10%), and 6 were not evaluable (10%). Median overall survival was 13.7 months (95% CI 9.6–19.7), and median PFS was 7.2 months (95% CI 5.6–8.3). Grade 3–4 adverse events included fatigue (30%), diarrhea (17%), hypertension (14%), elevated transaminases (12%), and gastrointestinal hemorrhage (10%). High plasma angiopoietin-2, epidermal growth factor receptor, and endothelin-1, and lack of acneiform rash were associated with poor outcome. <i>Conclusions:</i> The combination of bevacizumab with erlotinib achieved encouraging results in patients with advanced HCC. Current correlatives may help to guide future HCC studies.
DOI: 10.6084/m9.figshare.5123233
title: Supplementary Material for: Airway Hyperresponsiveness Is Negatively Associated with Obesity or Overweight Status in Patients with Asthma

description: <b><i>Background:</i></b> Obesity is a risk factor for asthma in the general population, but the effect of obesity on airway hyperresponsiveness (AFHR) or airway inflammation in asthma is not clear. This study evaluated the relationship between obesity and asthma, assessing aspects of symptoms, AHR, and severity. <b><i>Methods:</i></b> In total, 852 patients with asthma diagnosed by asthma specialists based on AHR as confirmed by a methacholine bronchial provocation test, were enrolled from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA) adult asthma cohort. The intensity of AHR was assessed by the concentration of methacholine needed to cause a 20% decrease in FEV<sub>1</sub> (PC<sub>20</sub>). Patients were classified into four categories based on body mass index (BMI): underweight (&lt;18.5), normal weight (18.5–24.9), overweight (25.0–29.9), and obese (≥30). <b><i>Results:</i></b> BMI was negatively correlated with FEV<sub>1</sub> (l), FVC (l), and FEV<sub>1</sub>/FVC (%) in lung function tests. The prevalence of wheezing increased with higher BMI after adjustment for age, sex, smoking, medication history, and PC<sub>20</sub> (p &lt; 0.0001). logPC<sub>20</sub> was lower in the normal weight group compared with the overweight group (p = 0.003). The risk of moderate or severe AHR (PC<sub>20</sub> ≤ 4 mg/ml) decreased with increased BMI after adjustment for age, sex, smoking, and medication history (p <i>= </i>0.035). <b><i>Conclusions:</i></b> Obesity is a risk factor for asthma in the general population, but obesity in asthmatic patients is negatively correlated with the intensity of AHR and is not related to asthma severity. Obesity is positively related with the prevalence of wheezing but negatively related to AHR in asthmatic patients.
DOI: 10.6084/m9.figshare.5123239.v1
title: Supplementary Material for: Influence of Minimal Changes in Preoperative Renal Function on Outcomes of Cardiac Surgery

description: <b><i>Background/Aims:</i></b> Cardiovascular morbidity and mortality are high in patients with chronic kidney disease. We evaluated the influence of small differences in preoperative kidney function on mortality and complications following cardiac surgery. <b><i>Methods:</i></b> This is an observational study that included adult patients undergoing cardiac surgery. Preoperative estimated glomerular filtration rate (eGFR) was estimated by the 4-component Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on preoperative creatinine levels. For analysis, patients were divided into groups according to their preoperative creatinine (0.2 mg/dl increments) and eGFR levels (15–30 ml/min/1.73 m<sup>2</sup> decrements). <b><i>Results:</i></b> Data on 5,340 patients were analyzed. A significant increase in postoperative mortality was demonstrated with preoperative creatinine at high-normal versus low-normal values (OR 1.7, 95% CI: 1–2.5; p = 0.02). For preoperative creatinine &gt;1.2 mg/dl, adjusted OR for in-hospital mortality increased stepwise with every 0.2-mg/dl increment of creatinine. In addition, a statistically significant increment of mortality was detected with every 15-ml/min/1.73 m<sup>2</sup> decrement in preoperative eGFR. <b><i>Conclusions:</i></b> Minimal changes of preoperative kidney function are associated with a substantial increase in the risk of mortality and morbidity following cardiac surgery. Even within the ‘normal’ range, minimal increases in serum creatinine levels are associated with increased risk of adverse events postoperatively.
DOI: 10.6084/m9.figshare.5123230
title: Supplementary Material for: Signaling Pathways Mediating Chemokine Induction in Keratinocytes by Cathelicidin LL-37 and Flagellin

description: Cathelicidin LL-37 is a multifunctional immunomodulatory and antimicrobial host defense peptide that has an important role in the immune defenses of the skin and other epithelial barriers. We have previously demonstrated that at physiological concentrations LL-37 synergistically augments the production of immune mediators in response to microbial compounds in human primary keratinocytes. Here we define the signaling mechanisms responsible for this activity. We demonstrate that inhibition of Src family kinases (SFKs) strongly inhibited the synergistic chemokine production in response to LL-37 and flagellin in keratinocytes. SFK activation was induced by LL-37 stimulation and was required for the downstream activation of Akt (protein kinase B) and the transcription factors CREB and ATF1. In cells stimulated with LL-37 and flagellin together, Akt activation was primarily induced by LL-37, while both flagellin and LL-37 contributed to the activation of CREB and ATF1 and consequently chemokine induction. The purinergic receptor P2X<sub>7</sub> was identified as the receptor upstream of SFK activation in LL-37-stimulated keratinocytes. Overall, these findings established the P2X<sub>7</sub>–SFK–Akt–CREB/ATF1 signaling pathway activated by LL-37 in primary keratinocytes. These signaling mechanisms mediated the synergistic effects of LL-37 on chemokine production in flagellin-stimulated keratinocytes, and thus might have a role in the immune defenses of the skin and possibly other epithelial barriers.
DOI: 10.6084/m9.figshare.5123233.v1
title: Supplementary Material for: Airway Hyperresponsiveness Is Negatively Associated with Obesity or Overweight Status in Patients with Asthma

description: <b><i>Background:</i></b> Obesity is a risk factor for asthma in the general population, but the effect of obesity on airway hyperresponsiveness (AFHR) or airway inflammation in asthma is not clear. This study evaluated the relationship between obesity and asthma, assessing aspects of symptoms, AHR, and severity. <b><i>Methods:</i></b> In total, 852 patients with asthma diagnosed by asthma specialists based on AHR as confirmed by a methacholine bronchial provocation test, were enrolled from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA) adult asthma cohort. The intensity of AHR was assessed by the concentration of methacholine needed to cause a 20% decrease in FEV<sub>1</sub> (PC<sub>20</sub>). Patients were classified into four categories based on body mass index (BMI): underweight (&lt;18.5), normal weight (18.5–24.9), overweight (25.0–29.9), and obese (≥30). <b><i>Results:</i></b> BMI was negatively correlated with FEV<sub>1</sub> (l), FVC (l), and FEV<sub>1</sub>/FVC (%) in lung function tests. The prevalence of wheezing increased with higher BMI after adjustment for age, sex, smoking, medication history, and PC<sub>20</sub> (p &lt; 0.0001). logPC<sub>20</sub> was lower in the normal weight group compared with the overweight group (p = 0.003). The risk of moderate or severe AHR (PC<sub>20</sub> ≤ 4 mg/ml) decreased with increased BMI after adjustment for age, sex, smoking, and medication history (p <i>= </i>0.035). <b><i>Conclusions:</i></b> Obesity is a risk factor for asthma in the general population, but obesity in asthmatic patients is negatively correlated with the intensity of AHR and is not related to asthma severity. Obesity is positively related with the prevalence of wheezing but negatively related to AHR in asthmatic patients.
DOI: 10.6084/m9.figshare.5123242.v1
title: Supplementary Material for: Pharmacoeconomic Impact of Different Regimens to Prevent Cytomegalovirus Infection in Renal Transplant Recipients

description: <b><i>Background:</i></b> The aim of this study was to determine the cost impact of four different strategies for prevention of cytomegalovirus (CMV) disease after renal transplantation. <b><i>Methods:</i></b> Hospitalization data and medical resource utilization data were prospectively collected alongside two randomized trials. In the first trial, the patients were randomized to 3-month prophylaxis with either oral ganciclovir (1 g t.i.d., n = 36) or valacyclovir (2 g q.i.d., n = 35), and to the control group (n = 12) managed by deferred therapy. In the second trial, the patients were randomly assigned to 3-month valacyclovir prophylaxis (n = 34) or preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n = 36) for significant CMV DNAemia. The cost analysis involved all real costs directly related to CMV during the first year after renal transplantation. <b><i>Results:</i></b> The mean CMV-associated costs per patient were EUR 4,581, 2,577, 4,968, and 8,050 in patients in the ganciclovir, valacyclovir, preemptive, and deferred therapy groups, respectively (p &lt; 0.001). Valacyclovir prophylaxis was significantly less expensive than any other regimen. The cost of one episode of CMV disease was EUR 7,510 per patient. Due to excessive incidence of CMV disease, deferred therapy was the most expensive strategy (p &lt; 0.001). <b><i>Conclusions:</i></b> Valacyclovir prophylaxis is less expensive strategy compared with any other regimen.
DOI: 10.6084/m9.figshare.5123230.v1
title: Supplementary Material for: Signaling Pathways Mediating Chemokine Induction in Keratinocytes by Cathelicidin LL-37 and Flagellin

description: Cathelicidin LL-37 is a multifunctional immunomodulatory and antimicrobial host defense peptide that has an important role in the immune defenses of the skin and other epithelial barriers. We have previously demonstrated that at physiological concentrations LL-37 synergistically augments the production of immune mediators in response to microbial compounds in human primary keratinocytes. Here we define the signaling mechanisms responsible for this activity. We demonstrate that inhibition of Src family kinases (SFKs) strongly inhibited the synergistic chemokine production in response to LL-37 and flagellin in keratinocytes. SFK activation was induced by LL-37 stimulation and was required for the downstream activation of Akt (protein kinase B) and the transcription factors CREB and ATF1. In cells stimulated with LL-37 and flagellin together, Akt activation was primarily induced by LL-37, while both flagellin and LL-37 contributed to the activation of CREB and ATF1 and consequently chemokine induction. The purinergic receptor P2X<sub>7</sub> was identified as the receptor upstream of SFK activation in LL-37-stimulated keratinocytes. Overall, these findings established the P2X<sub>7</sub>–SFK–Akt–CREB/ATF1 signaling pathway activated by LL-37 in primary keratinocytes. These signaling mechanisms mediated the synergistic effects of LL-37 on chemokine production in flagellin-stimulated keratinocytes, and thus might have a role in the immune defenses of the skin and possibly other epithelial barriers.
DOI: 10.6084/m9.figshare.5123221
title: Supplementary Material for: Gamma Knife Radiosurgery in the Treatment of Tumor-Related Facial Pain

description: <i>Background:</i> Intracranial neoplasms can cause pain similar to trigeminal neuralgia. Literature regarding radiosurgery for this is limited. We present a retrospective review of patients with tumor-related facial pain from benign lesions treated with gamma knife radiosurgery (GKRS) at Wake Forest University. <i>Objectives: </i>The primary objectives were to determine long-term pain relief and predictive factors for pain alleviation. <i>Methods:</i> We reviewed 515 patients treated with GKRS for benign meningioma, vestibular schwannoma or trigeminal schwannoma between August 1999 and August 2010. Twenty-one eligible patients had tumor-related facial pain prior to GKRS. The median marginal tumor dose was 12 Gy. Long-term pain relief data were obtained by chart review and telephone interview. <i>Results:</i> The median follow-up for symptom evaluation was 3.8 years. Seventeen of 21 patients (81%) experienced a Barrow Neurological Institute (BNI) score of I–III at 6 months following GKRS. Kaplan-Meier estimates of freedom from BNI IV–V relapse were 66% at 1 year and 53% at 2 years. No pain relapses occurred after 2 years. <i>Conclusion:</i> GKRS of benign lesions is a noninvasive option for patients with tumor-related facial pain. Pain relief is modest, with the majority of pain relapses occurring within 2 years and approximately one half of patients maintaining relief beyond 2 years.