cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5128786
title: Supplementary Material for: Pretreatment Pokemon Level as a Predictor of Response to Cisplatin and Paclitaxel in Patients with Unresectable Non-Small Cell Lung Cancer

description: <b><i>Background:</i></b> We firstly investigated the expression of Pokemon in patients with non-small cell lung cancer (NSCLC), then characterized the role of Pokemon in evaluating the response to combined cisplatin and paclitaxel chemotherapy and prognosis. <b><i>Patients and Methods:</i></b> In this study, 61 patients with previously untreated locally advanced or metastatic NSCLC were treated with a combination chemotherapy comprising cisplatin and paclitaxel. The correlation between serum expression of Pokemon and effectiveness of chemotherapy was assessed. <b><i>Results:</i></b> The expression level of Pokemon in NSCLC patients was higher than that in healthy controls (p = 0.000), and was correlated with tumor size and TNM stage (p &lt; 0.05). Kaplan-Meier analysis and Cox proportional hazard model demonstrated a poor response and shorter survival time in patients with pretreatment Pokemon levels in excess of 135.09 ng/ml compared to those with Pokemon levels below 135.09 ng/ml (p = 0.013). Pokemon ≥ 135.09 ng/ml was an independent risk factor for survival time in NSCLC patients undergoing combination chemotherapy (p = 0.018). <b><i>Conclusion:</i></b> The serum level of Pokemon correlated with efficacy of cisplatin and paclitaxel combination chemotherapy and survival time, which indicated that Pokemon may be a potentially useful biomarker for predicting treatment effectiveness of first-line chemotherapy and prognosis in NSCLC.
DOI: 10.6084/m9.figshare.5128792.v1
title: Supplementary Material for: Oxidized Docosahexaenoic Acid Species and Lipid Peroxidation Products Increase Amyloidogenic Amyloid Precursor Protein Processing

description: One of the main characteristics of Alzheimer's disease (AD) is the β-amyloid peptide (Aβ) generated by β- and γ-secretase processing of the amyloid precursor protein (APP). Previously it has been demonstrated that polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are associated with a reduced risk of AD caused by decreased Aβ production. However, in epidemiological studies and nutritional approaches, the outcomes of DHA-dependent treatment were partially controversial. PUFAs are very susceptible to reactive oxygen species and lipid peroxidation, which are increased during disease pathology. In line with published results, lipid peroxidation was elevated in human postmortem AD brains; especially 4-hydroxy-nonenal (HNE) was increased. To investigate whether lipid peroxidation is only a consequence or might also influence the processes leading to AD, we analyzed 7 different oxidized lipid species including 5 oxidized DHA derivatives and the lipid peroxidation products of ω-3 and ω-6 PUFAs, HNE and 4-hydroxy-hexenal, in human neuroblastoma cells and mouse mixed cortical neurons. In the presence of oxidized lipids Aβ and soluble β-secreted APP levels were elevated, whereas soluble α-secreted APP was decreased, suggesting a shift from the nonamyloidogenic to the amyloidogenic pathway of APP processing. Furthermore, β- and γ-secretase activity was increased by oxidized lipids via increased gene expression and additionally by a direct effect on β-secretase activity. Importantly, only 1% oxidized DHA was sufficient to revert the protective effect of DHA and to significantly increase Aβ production. Therefore, our results emphasize the need to prevent DHA from oxidation in nutritional approaches and might help explain the divergent results of clinical DHA studies.
DOI: 10.6084/m9.figshare.5128783
title: Supplementary Material for: Autologous Internal Limiting Membrane Fragment Transplantation for Large, Chronic, and Refractory Macular Holes

description: <b><i>Objective:</i></b> To evaluate a technique of autologous internal limiting membrane (ILM) fragment transplantation for the treatment of large, chronic, and/or refractory macular holes (MH). <b><i>Design:</i></b> This was a 6-month prospective interventional case series. <b><i>Method:</i></b> Ten eyes of 10 patients with MH underwent pars plana vitretomy (PPV) and ILM peeling followed by transplantation of an autologous ILM fragment to the MH. Six patients had primary MH with an internal diameter greater than 500 µm and a duration of more than 18 months, including 1 patient with nonproliferative diabetic retinopathy previously treated with panretinal photocoagulation. Four eyes with MH had previously been submitted to PPV (i.e. 1 for retinal detachment and 3 to attempt to close large MH). One of the latter also displayed juxtapapillary choroidal neovascularization due to age-related macular degeneration. The primary and secondary outcomes were MH closure and improvement of the best corrected visual acuity (BCVA), respectively. <b><i>Results:</i></b> Complete MH closure was achieved in all cases. A statistically significant improvement in the average BCVA was observed after 6 months of follow-up (p = 0.018; paired t test). The BCVA improved in 8 eyes (80%), and in 6 of those eyes it improved by ≥15 letters. In 1 patient, the BCVA remained unchanged after the surgery, but the visual field reportedly improved. One patient experienced a slight worsening (0.16 logMAR). Two cases developed atrophy of the retinal pigment epithelium despite MH closure and BCVA improvement. <b><i>Conclusion:</i></b> Treatment with autologous ILM fragment transplantation seems to be an efficient alternative for large, chronic, and refractory MH.
DOI: 10.6084/m9.figshare.5128774
title: Supplementary Material for: Apolipoprotein E e4 and Cognitive Function: A Modifiable Association? Results from Two Independent Cohort Studies

description: <b><i>Background:</i></b> The apolipoprotein E <i>(APOE)</i> e4 genetic polymorphism is a major risk factor for Alzheimer' s disease, hence the possible prevention of its detrimental effects on cognition is of high relevance. <b><i>Methods:</i></b> We used linear regression models to assess associations of <i>APOE</i> e4 with cognitive performance in a population-based cohort study (n = 1,434) and in a cohort of patients with coronary heart disease (n = 366), and restricted cubic splines to explore dose-response relationships between serum cholesterol levels and cognition depending on <i>APOE</i> polymorphism. <b><i>Results:</i></b> The association of <i>APOE</i> e4 with cognitive function was strongly amplified in the presence of hypercholesterolemia and cardiovascular disease in both independent cohorts; hypercholesterolemia was associated with cognitive function only among <i>APOE</i> e4 carriers in the presence of cardiovascular disease. The interaction effect between <i>APOE</i> genotype and hypercholesterolemia was statistically significant in both cohorts. <b><i>Conclusions:</i></b> The detrimental effects of <i>APOE</i> e4 polymorphism on cognition may strongly depend on modifiable risk factors.
DOI: 10.6084/m9.figshare.5128777
title: Supplementary Material for: Gly388Arg FGFR4 Polymorphism Is Not Predictive of Everolimus Efficacy in Well-Differentiated Digestive Neuroendocrine Tumors

description: <b><i>Introduction:</i></b> Preclinical data suggest that the single nucleotide polymorphism substituting a glycine for an arginine in codon 388 of the FGFR4 transmembrane domain may increase the proliferation of xenografted neuroendocrine cell lines and decrease their sensitivity to everolimus by modulating STAT3 signaling and the mTOR pathway. <b><i>Aim:</i></b> To evaluate the prognostic and predictive values of this polymorphism on everolimus efficacy in patients treated for digestive neuroendocrine tumor (NET). <b><i>Patients and Methods:</i></b> This monocentric retrospective cohort included patients with small bowel NET (SBNET) and pancreatic NET (PNET) treated with everolimus (2006-2013). The patients were genotyped by classical sequencing, and mTOR pathway activity was assessed by immunochemistry on formalin-fixed paraffin-embedded samples (PTEN/pPTEN/pAKT/pmTOR/pS6/p4EBP1). <b><i>Results:</i></b> Forty-one patients (21 males, median age 57 years) with PNET (n = 28), SBNET (n = 12) or NET of unknown origin (n = 1), grade 1 (n = 8), 2 (n = 27), 3 (n = 3) or unknown grade (n = 3), were studied. At least one 388Arg allele was found in 14/23 PNET and 10/11 SBNET. Progression-free survival in the whole population and the PNET subgroup was not influenced by the presence of one or two 388Arg alleles [HR = 1.31 (0.58-2.99), p = 0.52 and HR = 1.11 (0.45-2.73), p = 0.82, respectively]. Similarly, overall survival was not influenced. Finally, mTOR pathway molecule expression was not modified by the presence of at least one 388Arg allele. <b><i>Conclusion:</i></b> The Gly388Arg FGFR4 polymorphism does not seem to have a prognostic value in digestive NET. In addition, it neither predicts the response to everolimus nor modifies the activation of the mTOR pathway.
DOI: 10.6084/m9.figshare.5128780
title: Supplementary Material for: A Case Report of Nystagmus with Acute Comitant Esotropia Secondary to Heroin Withdrawal: A Novel Presentation

description: <b><i>Background:</i></b> Acute comitant esotropia secondary to heroin withdrawal is a rarely reported phenomenon that has never been described with nystagmus. Adverse effects of heroin on eye alignment were first reported in soldiers returning from Vietnam, yet no theory is generally accepted as the cause of these abnormalities. <b><i>Method:</i></b> We present a case of a 22-year-old female who developed 40 prism diopters of alternating comitant esotropia with nystagmus 8 days after abrupt heroin cessation, review the existing literature, and propose a novel hypothesis for this phenomenon. <b><i>Results:</i></b> After 76 days, her esotropia resolved, and she was left with 7 prism diopters of esophoria. <b><i>Conclusion:</i></b> This case demonstrates that acquired nystagmus can present in addition to acute-onset esotropia after abrupt heroin cessation. We compare and contrast the theories of this mechanism and review the literature.
DOI: 10.6084/m9.figshare.5128783.v1
title: Supplementary Material for: Autologous Internal Limiting Membrane Fragment Transplantation for Large, Chronic, and Refractory Macular Holes

description: <b><i>Objective:</i></b> To evaluate a technique of autologous internal limiting membrane (ILM) fragment transplantation for the treatment of large, chronic, and/or refractory macular holes (MH). <b><i>Design:</i></b> This was a 6-month prospective interventional case series. <b><i>Method:</i></b> Ten eyes of 10 patients with MH underwent pars plana vitretomy (PPV) and ILM peeling followed by transplantation of an autologous ILM fragment to the MH. Six patients had primary MH with an internal diameter greater than 500 µm and a duration of more than 18 months, including 1 patient with nonproliferative diabetic retinopathy previously treated with panretinal photocoagulation. Four eyes with MH had previously been submitted to PPV (i.e. 1 for retinal detachment and 3 to attempt to close large MH). One of the latter also displayed juxtapapillary choroidal neovascularization due to age-related macular degeneration. The primary and secondary outcomes were MH closure and improvement of the best corrected visual acuity (BCVA), respectively. <b><i>Results:</i></b> Complete MH closure was achieved in all cases. A statistically significant improvement in the average BCVA was observed after 6 months of follow-up (p = 0.018; paired t test). The BCVA improved in 8 eyes (80%), and in 6 of those eyes it improved by ≥15 letters. In 1 patient, the BCVA remained unchanged after the surgery, but the visual field reportedly improved. One patient experienced a slight worsening (0.16 logMAR). Two cases developed atrophy of the retinal pigment epithelium despite MH closure and BCVA improvement. <b><i>Conclusion:</i></b> Treatment with autologous ILM fragment transplantation seems to be an efficient alternative for large, chronic, and refractory MH.
DOI: 10.6084/m9.figshare.5128768
title: Supplementary Material for: Impact of Non-Adherence on Renal and Cardiovascular Outcomes in US Veterans

description: <b><i>Background:</i></b> Adherence is paramount in treating hypertension; however, no gold standard method is available for non-adherence screening, delineating high-risk patients. An International Classification of Diseases 9th Edition non-adherence diagnostic code (V15.81) has been available for decades; but, its utility is poorly studied. We examined the association between the V15.81 code assigned prior to the initiation of anti-hypertensive drugs (AHDs) and renal and cardiovascular outcomes. <b><i>Methods:</i></b> This was a historical prospective cohort study involving 312,489 newly treated hypertensive individuals (mean age 53.8 years, 90.9% males, 20.3% black, median follow-up 8.0 years). We used crude and Cox models adjusted for baseline socio-demographic characteristics, estimated glomerular filtration rate (eGFR), body mass index, blood pressure, comorbidities, and prospective AHD adherence (measured as proportion of days covered, PDC). <b><i>Results:</i></b> In the unadjusted analysis, the V15.81 code was associated with higher risks for faster eGFR decline (hazard ratio, HR 1.22, 95% CI 1.11-1.33), incident CKD (HR 1.17, 95% CI 1.09-1.27), end-stage renal disease (ESRD) (HR 2.53, 95% CI 1.72-3.72), incident coronary artery disease (CAD) (HR 1.26, 95% CI 1.15-1.38), and stroke (HR 1.55, 95% CI 1.38-1.73). In the adjusted model, the V15.81 code remained predictive of increased risk of CKD (HR 1.33, 95% CI 1.22-1.45), ESRD (HR 1.81, 95% CI 1.18-2.78), incident CAD (HR 1.26, 95% CI 1.14-1.40), and stroke (HR 1.46, 95% CI 1.29-1.65). Additional adjustment for PDC did not alter adverse associations between V15.81 code and studied outcomes. <b><i>Conclusions:</i></b> Assignment of V15.81 code prior to AHD therapy was associated with higher risks of renal and cardiovascular outcomes in incident hypertensive US veterans. Previous history of non-adherence is a poor prognostic marker in hypertensive individuals; therefore, patients with V15.81 code may require close monitoring. The observational nature of this study limits our ability to make firm recommendations for clinical practice.
DOI: 10.6084/m9.figshare.5128771
title: Supplementary Material for: National Analysis of Short-Term Outcomes and Volume-Outcome Relationships for Transcatheter Aortic Valve Replacement in the Era of Commercialization

description: <b><i>Objectives:</i></b> We queried the 2012 National Inpatient Sample in order to (1) further describe the short-term outcomes for transcatheter aortic valve replacement (TAVR) and (2) characterize possible volume-outcome relationships and other prognostic factors for this procedure. <b><i>Methods:</i></b> Demographics and inhospital outcomes were tabulated for all patients, as were hospital characteristics and procedural-volume data for all centers at which patients underwent TAVR. Logistic regression analyses were performed to identify independent risk factors for mortality or morbidity. <b><i>Results:</i></b> 7,635 patients aged ≥18 years received TAVR during the study period; 84.5% (n = 6,450) underwent transfemoral TAVR and the rest were treated transapically. The median age was 83 years (IQR 77-88 years) and cardiovascular comorbidities were widespread. Overall inhospital mortality was 5.0% (n = 380), and 1.4% (n = 105) of the patients experienced a stroke. All-cause procedure-related morbidity was 24.7% (n = 1,885). Annual hospital TAVR volume did not predict inhospital mortality or morbidity (OR 1.00, 95% CI 0.99-1.00, p = 0.111 and OR 1.00, 95% CI 0.99-1.00, p = 0.947, respectively). <b><i>Conclusions:</i></b> Our analysis helps to confirm the short-term safety profile of TAVR and further demonstrates that inhospital outcomes have remained acceptable as this procedure has become commercialized.
DOI: 10.6084/m9.figshare.5128774.v1
title: Supplementary Material for: Apolipoprotein E e4 and Cognitive Function: A Modifiable Association? Results from Two Independent Cohort Studies

description: <b><i>Background:</i></b> The apolipoprotein E <i>(APOE)</i> e4 genetic polymorphism is a major risk factor for Alzheimer' s disease, hence the possible prevention of its detrimental effects on cognition is of high relevance. <b><i>Methods:</i></b> We used linear regression models to assess associations of <i>APOE</i> e4 with cognitive performance in a population-based cohort study (n = 1,434) and in a cohort of patients with coronary heart disease (n = 366), and restricted cubic splines to explore dose-response relationships between serum cholesterol levels and cognition depending on <i>APOE</i> polymorphism. <b><i>Results:</i></b> The association of <i>APOE</i> e4 with cognitive function was strongly amplified in the presence of hypercholesterolemia and cardiovascular disease in both independent cohorts; hypercholesterolemia was associated with cognitive function only among <i>APOE</i> e4 carriers in the presence of cardiovascular disease. The interaction effect between <i>APOE</i> genotype and hypercholesterolemia was statistically significant in both cohorts. <b><i>Conclusions:</i></b> The detrimental effects of <i>APOE</i> e4 polymorphism on cognition may strongly depend on modifiable risk factors.
DOI: 10.6084/m9.figshare.5128768.v1
title: Supplementary Material for: Impact of Non-Adherence on Renal and Cardiovascular Outcomes in US Veterans

description: <b><i>Background:</i></b> Adherence is paramount in treating hypertension; however, no gold standard method is available for non-adherence screening, delineating high-risk patients. An International Classification of Diseases 9th Edition non-adherence diagnostic code (V15.81) has been available for decades; but, its utility is poorly studied. We examined the association between the V15.81 code assigned prior to the initiation of anti-hypertensive drugs (AHDs) and renal and cardiovascular outcomes. <b><i>Methods:</i></b> This was a historical prospective cohort study involving 312,489 newly treated hypertensive individuals (mean age 53.8 years, 90.9% males, 20.3% black, median follow-up 8.0 years). We used crude and Cox models adjusted for baseline socio-demographic characteristics, estimated glomerular filtration rate (eGFR), body mass index, blood pressure, comorbidities, and prospective AHD adherence (measured as proportion of days covered, PDC). <b><i>Results:</i></b> In the unadjusted analysis, the V15.81 code was associated with higher risks for faster eGFR decline (hazard ratio, HR 1.22, 95% CI 1.11-1.33), incident CKD (HR 1.17, 95% CI 1.09-1.27), end-stage renal disease (ESRD) (HR 2.53, 95% CI 1.72-3.72), incident coronary artery disease (CAD) (HR 1.26, 95% CI 1.15-1.38), and stroke (HR 1.55, 95% CI 1.38-1.73). In the adjusted model, the V15.81 code remained predictive of increased risk of CKD (HR 1.33, 95% CI 1.22-1.45), ESRD (HR 1.81, 95% CI 1.18-2.78), incident CAD (HR 1.26, 95% CI 1.14-1.40), and stroke (HR 1.46, 95% CI 1.29-1.65). Additional adjustment for PDC did not alter adverse associations between V15.81 code and studied outcomes. <b><i>Conclusions:</i></b> Assignment of V15.81 code prior to AHD therapy was associated with higher risks of renal and cardiovascular outcomes in incident hypertensive US veterans. Previous history of non-adherence is a poor prognostic marker in hypertensive individuals; therefore, patients with V15.81 code may require close monitoring. The observational nature of this study limits our ability to make firm recommendations for clinical practice.
DOI: 10.6084/m9.figshare.5128777.v1
title: Supplementary Material for: Gly388Arg FGFR4 Polymorphism Is Not Predictive of Everolimus Efficacy in Well-Differentiated Digestive Neuroendocrine Tumors

description: <b><i>Introduction:</i></b> Preclinical data suggest that the single nucleotide polymorphism substituting a glycine for an arginine in codon 388 of the FGFR4 transmembrane domain may increase the proliferation of xenografted neuroendocrine cell lines and decrease their sensitivity to everolimus by modulating STAT3 signaling and the mTOR pathway. <b><i>Aim:</i></b> To evaluate the prognostic and predictive values of this polymorphism on everolimus efficacy in patients treated for digestive neuroendocrine tumor (NET). <b><i>Patients and Methods:</i></b> This monocentric retrospective cohort included patients with small bowel NET (SBNET) and pancreatic NET (PNET) treated with everolimus (2006-2013). The patients were genotyped by classical sequencing, and mTOR pathway activity was assessed by immunochemistry on formalin-fixed paraffin-embedded samples (PTEN/pPTEN/pAKT/pmTOR/pS6/p4EBP1). <b><i>Results:</i></b> Forty-one patients (21 males, median age 57 years) with PNET (n = 28), SBNET (n = 12) or NET of unknown origin (n = 1), grade 1 (n = 8), 2 (n = 27), 3 (n = 3) or unknown grade (n = 3), were studied. At least one 388Arg allele was found in 14/23 PNET and 10/11 SBNET. Progression-free survival in the whole population and the PNET subgroup was not influenced by the presence of one or two 388Arg alleles [HR = 1.31 (0.58-2.99), p = 0.52 and HR = 1.11 (0.45-2.73), p = 0.82, respectively]. Similarly, overall survival was not influenced. Finally, mTOR pathway molecule expression was not modified by the presence of at least one 388Arg allele. <b><i>Conclusion:</i></b> The Gly388Arg FGFR4 polymorphism does not seem to have a prognostic value in digestive NET. In addition, it neither predicts the response to everolimus nor modifies the activation of the mTOR pathway.
DOI: 10.6084/m9.figshare.5128762
title: Supplementary Material for: Characterisation of the Oxygenation Response to Inspired Oxygen Adjustments in Preterm Infants

description: <b><i>Background:</i></b> Oxygen saturation (SpO<sub>2</sub>) targeting in the preterm infant may be improved with a better understanding of the SpO<sub>2</sub> responses to changes in inspired oxygen (FiO<sub>2</sub>). <b><i>Objective:</i></b> We investigated the first-order FiO<sub>2</sub>-SpO<sub>2</sub> relationship, aiming to quantify the parameters governing that relationship, the influences on these parameters and their variability. <b><i>Methods:</i></b> In recordings of FiO<sub>2</sub> and SpO<sub>2</sub> from preterm infants on continuous positive airway pressure and supplemental oxygen, we identified unique FiO<sub>2</sub> adjustments and mapped the subsequent SpO<sub>2</sub> responses. For responses identified as first-order, the delay, time constant and gain parameters were determined. Clinical and physiological predictors of these parameters were sought in regression analysis, and intra- and inter-subject variability was evaluated. <b><i>Results:</i></b> In 3,788 h of available data from 47 infants at 31 (28-33) post-menstrual weeks [median (interquartile range)], we identified 993 unique FiO<sub>2</sub> adjustments followed by a first-order SpO<sub>2</sub> response. All response parameters differed between FiO<sub>2</sub> increments and decrements, with increments having a shorter delay, longer time constant and higher gain [2.9 (1.7-4.8) vs. 1.3 (0.58-2.6), p &lt; 0.05]. Gain was also higher in less mature infants and in the setting of recent SpO<sub>2</sub> instability, and was diminished with increasing severity of lung dysfunction. Intra-subject variability in all parameters was prominent. <b><i>Conclusions:</i></b> First-order SpO<sub>2</sub> responses show variable gain, influenced by the direction of FiO<sub>2</sub> adjustment and the severity of lung disease, as well as substantial intra-subject parameter variability. These findings should be taken into account in adjustment of FiO<sub>2</sub> for SpO<sub>2</sub> targeting in preterm infants.