cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5128618
title: Supplementary Material for: A Deletion of More than 800 kb Is the Most Recurrent Mutation in Chilean Patients with <b><i>SHOX</i></b> Gene Defects

description: <b><i>Background:</i></b> Deletions in the <i>SHOX</i> gene are the most frequent genetic cause of Leri-Weill syndrome and Langer mesomelic dysplasia, which are also present in idiopathic short stature. <b><i>Aim:</i></b> To describe the molecular and clinical findings observed in 23 of 45 non-consanguineous Chilean patients with different phenotypes related to <i>SHOX</i> deficiency. <b><i>Methods:</i></b> Multiplex ligation-dependent probe amplification was used to detect the deletions; the <i>SHOX</i> coding region and deletion-flanking areas were sequenced to identify point mutations and single-nucleotide polymorphisms (SNPs). <b><i>Results:</i></b> The main genetic defects identified in 21 patients consisted of deletions; one of them, a large deletion of &gt;800 kb, was found in 8 patients. Also, a smaller deletion of &gt;350 kb was observed in 4 patients. Although we could not precisely determine the deletion breakpoint, we were able to identify a common haplotype in 7 of the 8 patients with the larger deletion based on 22 informative SNPs. <b><i>Conclusion:</i></b> These results suggest that the large deletion-bearing allele has a common ancestor and was either introduced by European immigrants or had originated in our Amerindian population. This study allowed us to identify one recurrent deletion in Chilean patients; also, it contributed to expanding our knowledge about the genetic background of our population.
DOI: 10.6084/m9.figshare.5128621
title: Supplementary Material for: Molecular Genetic and Crystal Structural Analysis of 1-(4-Hydroxyphenyl)-Ethanol Dehydrogenase from <b><i>‘Aromatoleum aromaticum'</i></b> EbN1

description: The dehydrogenation of 1-(4-hydroxyphenyl)-ethanol to 4-hydroxyacetophenone represents the second reaction step during anaerobic degradation of <i>p</i>-ethylphenol in the denitrifying bacterium ‘<i>Aromatoleum aromaticum</i>' EbN1. Previous proteogenomic studies identified two different proteins (ChnA and EbA309) as possible candidates for catalyzing this reaction [Wöhlbrand et al: J Bacteriol 2008;190:5699-5709]. Physiological-molecular characterization of newly generated unmarked <i>in-frame</i> deletion and complementation mutants allowed defining ChnA (renamed here as Hped) as the enzyme responsible for 1-(4-hydroxyphenyl)-ethanol oxidation. Hped [1-(4-hydroxyphenyl)-ethanol dehydrogenase] belongs to the ‘classical' family within the short-chain alcohol dehydrogenase/reductase (SDR) superfamily. Hped was overproduced in <i>Escherichia coli</i>, purified and crystallized. The X-ray structures of the apo- and NAD<sup>+</sup>-soaked form were resolved at 1.5 and 1.1 Å, respectively, and revealed Hped as a typical homotetrameric SDR. Modeling of the substrate 4-hydroxyacetophenone (reductive direction of Hped) into the active site revealed the structural determinants of the strict <i>(R)</i>-specificity of Hped (Phe<sup>187</sup>), contrasting the <i>(S)</i>-specificity of previously reported 1-phenylethanol dehydrogenase (Ped; Tyr<sup>93</sup>) from strain EbN1 [Höffken et al: Biochemistry 2006;45:82-93].
DOI: 10.6084/m9.figshare.5128627.v1
title: Supplementary Material for: Surgical Videos with Synchronised Vertical 2-Split Screens Recording the Surgeons' Hand Movement

description: <b><i>Purpose:</i></b> To improve the state-of-the-art teaching system by creating surgical videos with synchronised vertical 2-split screens. <b><i>Methods:</i></b> An ultra-compact, wide-angle point-of-view camcorder (HX-A1, Panasonic) was mounted on the surgical microscope focusing mostly on the surgeons' hand movements. In combination with the regular surgical videos obtained from the CCD camera in the surgical microscope, synchronised vertical 2-split-screen surgical videos were generated with the video-editing software. <b><i>Results:</i></b> Using synchronised vertical 2-split-screen videos, residents of the ophthalmology department could watch and learn how assistant surgeons controlled the eyeball, while the main surgeons performed scleral buckling surgery. In vitrectomy, the synchronised vertical 2-split-screen videos showed the surgeons' hands holding the instruments and moving roughly and boldly, in contrast to the very delicate movements of the vitrectomy instruments inside the eye. <b><i>Conclusions:</i></b> Synchronised vertical 2-split-screen surgical videos are beneficial for the education of young surgical trainees when learning surgical skills including the surgeons' hand movements.
DOI: 10.6084/m9.figshare.5128633.v1
title: Supplementary Material for: Isolated Posterior Inferior Cerebellar Artery Dissection as a Cause of Ischemic Stroke: Clinical Features and Prognosis

description: <b><i>Background:</i></b> The purpose of this study was to clarify the incidence, clinical and radiological features and outcomes of isolated posterior inferior cerebellar artery (PICA) dissection in isolated PICA territory infarctions. <b><i>Methods:</i></b> We retrospectively reviewed consecutive inpatients with ischemic stroke secondary to isolated PICA dissection from our stroke database between January 2004 and December 2013 and reviewed the literature with regard to those patients. <b><i>Results:</i></b> Of 167 consecutive patients with an isolated PICA territory infarction, a total of 10 patients (6.0%, 3 women, 48.1 ± 7.1 years) were diagnosed as having an isolated PICA dissection. Patients with PICA dissection were younger (p &lt; 0.001), more commonly experienced headache at onset (p = 0.008), less commonly had hyperlipidemia (p = 0.044) and showed a lower modified Rankin Scale score at discharge (p = 0.002) when compared with patients without arterial dissection. In 6 of these 10 patients, PICA dissections had not been suspected on initial magnetic resonance angiography (MRA) and were confirmed by follow-up MRA or digital subtraction angiography. In the follow-up period (median 1.5 years, interquartile range 0.5-6.3 years), there were no recurrent ischemic or hemorrhagic stroke events. <b><i>Conclusions:</i></b> Isolated PICA dissection as an etiological mechanism in isolated PICA territory infarctions may be more common than was previously recognized to be. The diagnosis of PICA dissection is often difficult and requires close and repeated morphological evaluation. We should carefully identify PICA dissections as a possible cause of PICA territory infarctions.
DOI: 10.6084/m9.figshare.5128615
title: Supplementary Material for: Plasma Copeptin and Decline in Renal Function in a Cohort from the Community: The Prospective D.E.S.I.R. Study

description: <b><i>Background/Aims:</i></b> In recent days, chronic kidney disease (CKD) is becoming an increasing public health problem. Identification of factors contributing to its progression is crucial for designing preventive interventions. Previous studies suggested that chronically high vasopressin is deleterious to the renal function. We evaluated plasma copeptin, a surrogate of vasopressin, as a predictor for renal function decline in a community cohort. <b><i>Methods:</i></b> Plasma copeptin was measured at baseline in 1,234 participants from the D.E.S.I.R. study, a prospective cohort from the French general population. All participants were followed for 9 years. Progression towards CKD during follow-up was defined as an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m<sup>2</sup> on at least one follow-up visit. We have also considered the criterion ‘Certain Drop in eGFR' proposed by the Kidney Disease Improving Global Outcomes (KDIGO) group. <b><i>Results:</i></b> Progression towards CKD was observed in 86 (7.0%) participants. Factors like age, female gender, plasma copeptin and use of angiotensin converting enzyme inhibitor or angiotensin 2 receptor blocker at baseline were positively associated, and eGFR inversely associated with CKD progression during follow-up. The hazard ratio per unit of log<sub>10</sub>-transformed plasma copeptin was 1.65 (95% CI 1.06-2.54) and p = 0.02. Copeptin was similarly associated with CKD and this was observed when we considered the KDIGO criterion: OR 3.03 (95% CI 1.21-7.57), p = 0.02. <b><i>Conclusion:</i></b> The plasma copeptin level was independently and positively associated with progression towards CKD in a community-based cohort. Our results add to the available evidence for a deleterious effect of high vasopressin on renal health not only in selected groups of patients with CKD but also in the general population.
DOI: 10.6084/m9.figshare.5128624.v1
title: Supplementary Material for: External Validation for Acute Kidney Injury Severity Scores: A Multicenter Retrospective Study in 14 Japanese ICUs

description: <b><i>Background/Aims:</i></b> Acute kidney injury (AKI) is associated with high mortality. Multiple AKI severity scores have been derived to predict patient outcome. We externally validated new AKI severity scores using the Japanese Society for Physicians and Trainees in Intensive Care (JSEPTIC) database. <b><i>Methods:</i></b> New AKI severity scores published in the 21st century (Mehta, Stuivenberg Hospital Acute Renal Failure (SHARF) II, Program to Improve Care in Acute Renal Disease (PICARD), Vellore and Demirjian), Liano, Simplified Acute Physiology Score (SAPS) II and lactate were compared using the JSEPTIC database that collected retrospectively 343 patients with AKI who required continuous renal replacement therapy (CRRT) in 14 intensive care units. Accuracy of the severity scores was assessed by the area under the receiver-operator characteristic curve (AUROC, discrimination) and Hosmer-Lemeshow test (H-L test, calibration). <b><i>Results:</i></b> The median age was 69 years and 65.8% were male. The median SAPS II score was 53 and the hospital mortality was 58.6%. The AUROC curves revealed low discrimination ability of the new AKI severity scores (Mehta 0.65, SHARF II 0.64, PICARD 0.64, Vellore 0.64, Demirjian 0.69), similar to Liano 0.67, SAPS II 0.67 and lactate 0.64. The H-L test also demonstrated that all assessed scores except for Liano had significantly low calibration ability. <b><i>Conclusions:</i></b> Using a multicenter database of AKI patients requiring CRRT, this study externally validated new AKI severity scores. While the Demirjian's score and Liano's score showed a better performance, further research will be required to confirm these findings.
DOI: 10.6084/m9.figshare.5128609
title: Supplementary Material for: Glucocorticoid-Induced Leucine Zipper Is Expressed in Human Neutrophils and Promotes Apoptosis through Mcl-1 Down-Regulation

description: Glucocorticoid-induced leucine zipper (GILZ) is a potent anti-inflammatory protein, the expression of which is mainly induced by glucocorticoids (GCs) in haematopoietic cells. GILZ regulates signal transduction pathways of inflammation and plays a role in cell survival. The objective of this study was to evaluate the expression and mechanisms of action of GILZ in the apoptosis of human neutrophils. GILZ expression was induced by GCs in human neutrophils, enhanced upon phosphatidylinositol 3-kinase inhibition and resulted in apoptosis amplification. We then stably transfected PLB-985 cells with the human <i>gilz</i> gene and differentiated both control and GILZ-overexpressing clones in neutrophil-like cells. GILZ overexpression in PLB-985 cells led to an exacerbated apoptosis, associated with caspase-3, caspase-9 and caspase-8 activations, and a loss of mitochondrial potential, suggesting that GILZ-induced apoptosis used the mitochondrial pathway. The expression of BH3 interacting domain death agonist, Bcl-2 interacting mediator of cell death, annexin-A1 and Bcl-2-associated X was not affected in PLB-985-GILZ clones, but phosphorylation and subsequent proteasomal degradation of myeloid cell leukemia-1 (Mcl-1) were observed. Noteworthy, Mcl-1 phosphorylation was related to a significant and sustained activation of c-Jun N-terminal kinase (JNK) in PLB-985-GILZ clones. These results reveal GILZ to be a new actor in apoptosis regulation in neutrophil-like cells involving JNK and Mcl-1.
DOI: 10.6084/m9.figshare.5128612
title: Supplementary Material for: Statement on Exercise Testing in Cystic Fibrosis

description: This statement summarizes the information available on specific exercise test protocols and outcome parameters used in patients with cystic fibrosis (CF) and provides expert consensus recommendations for protocol and performance of exercise tests and basic interpretation of results for clinicians. The conclusions were reached employing consensus meetings and a wide-band Delphi process. Although data on utility are currently limited, standardized exercise testing provides detailed information on physiological health, allows screening for exercise-related adverse reactions and enables exercise counselling. The Godfrey Cycle Ergometer Protocol with monitoring of oxygen saturation and ventilatory gas exchange is recommended for exercise testing in people 10 years and older. Cycle ergometry only with pulse oximetry using the Godfrey protocol or treadmill exercise with pulse oximetry - preferably with measurement of gas exchange - are second best options. Peak oxygen uptake, if assessed, and maximal work rate should be reported as the primary measure of exercise capacity. The final statement was reviewed by the European Cystic Fibrosis society and revised based on the comments received. The document was endorsed by the European Respiratory Society.
DOI: 10.6084/m9.figshare.5128618.v1
title: Supplementary Material for: A Deletion of More than 800 kb Is the Most Recurrent Mutation in Chilean Patients with <b><i>SHOX</i></b> Gene Defects

description: <b><i>Background:</i></b> Deletions in the <i>SHOX</i> gene are the most frequent genetic cause of Leri-Weill syndrome and Langer mesomelic dysplasia, which are also present in idiopathic short stature. <b><i>Aim:</i></b> To describe the molecular and clinical findings observed in 23 of 45 non-consanguineous Chilean patients with different phenotypes related to <i>SHOX</i> deficiency. <b><i>Methods:</i></b> Multiplex ligation-dependent probe amplification was used to detect the deletions; the <i>SHOX</i> coding region and deletion-flanking areas were sequenced to identify point mutations and single-nucleotide polymorphisms (SNPs). <b><i>Results:</i></b> The main genetic defects identified in 21 patients consisted of deletions; one of them, a large deletion of &gt;800 kb, was found in 8 patients. Also, a smaller deletion of &gt;350 kb was observed in 4 patients. Although we could not precisely determine the deletion breakpoint, we were able to identify a common haplotype in 7 of the 8 patients with the larger deletion based on 22 informative SNPs. <b><i>Conclusion:</i></b> These results suggest that the large deletion-bearing allele has a common ancestor and was either introduced by European immigrants or had originated in our Amerindian population. This study allowed us to identify one recurrent deletion in Chilean patients; also, it contributed to expanding our knowledge about the genetic background of our population.
DOI: 10.6084/m9.figshare.5128621.v1
title: Supplementary Material for: Molecular Genetic and Crystal Structural Analysis of 1-(4-Hydroxyphenyl)-Ethanol Dehydrogenase from <b><i>‘Aromatoleum aromaticum'</i></b> EbN1

description: The dehydrogenation of 1-(4-hydroxyphenyl)-ethanol to 4-hydroxyacetophenone represents the second reaction step during anaerobic degradation of <i>p</i>-ethylphenol in the denitrifying bacterium ‘<i>Aromatoleum aromaticum</i>' EbN1. Previous proteogenomic studies identified two different proteins (ChnA and EbA309) as possible candidates for catalyzing this reaction [Wöhlbrand et al: J Bacteriol 2008;190:5699-5709]. Physiological-molecular characterization of newly generated unmarked <i>in-frame</i> deletion and complementation mutants allowed defining ChnA (renamed here as Hped) as the enzyme responsible for 1-(4-hydroxyphenyl)-ethanol oxidation. Hped [1-(4-hydroxyphenyl)-ethanol dehydrogenase] belongs to the ‘classical' family within the short-chain alcohol dehydrogenase/reductase (SDR) superfamily. Hped was overproduced in <i>Escherichia coli</i>, purified and crystallized. The X-ray structures of the apo- and NAD<sup>+</sup>-soaked form were resolved at 1.5 and 1.1 Å, respectively, and revealed Hped as a typical homotetrameric SDR. Modeling of the substrate 4-hydroxyacetophenone (reductive direction of Hped) into the active site revealed the structural determinants of the strict <i>(R)</i>-specificity of Hped (Phe<sup>187</sup>), contrasting the <i>(S)</i>-specificity of previously reported 1-phenylethanol dehydrogenase (Ped; Tyr<sup>93</sup>) from strain EbN1 [Höffken et al: Biochemistry 2006;45:82-93].
DOI: 10.6084/m9.figshare.5128615.v1
title: Supplementary Material for: Plasma Copeptin and Decline in Renal Function in a Cohort from the Community: The Prospective D.E.S.I.R. Study

description: <b><i>Background/Aims:</i></b> In recent days, chronic kidney disease (CKD) is becoming an increasing public health problem. Identification of factors contributing to its progression is crucial for designing preventive interventions. Previous studies suggested that chronically high vasopressin is deleterious to the renal function. We evaluated plasma copeptin, a surrogate of vasopressin, as a predictor for renal function decline in a community cohort. <b><i>Methods:</i></b> Plasma copeptin was measured at baseline in 1,234 participants from the D.E.S.I.R. study, a prospective cohort from the French general population. All participants were followed for 9 years. Progression towards CKD during follow-up was defined as an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m<sup>2</sup> on at least one follow-up visit. We have also considered the criterion ‘Certain Drop in eGFR' proposed by the Kidney Disease Improving Global Outcomes (KDIGO) group. <b><i>Results:</i></b> Progression towards CKD was observed in 86 (7.0%) participants. Factors like age, female gender, plasma copeptin and use of angiotensin converting enzyme inhibitor or angiotensin 2 receptor blocker at baseline were positively associated, and eGFR inversely associated with CKD progression during follow-up. The hazard ratio per unit of log<sub>10</sub>-transformed plasma copeptin was 1.65 (95% CI 1.06-2.54) and p = 0.02. Copeptin was similarly associated with CKD and this was observed when we considered the KDIGO criterion: OR 3.03 (95% CI 1.21-7.57), p = 0.02. <b><i>Conclusion:</i></b> The plasma copeptin level was independently and positively associated with progression towards CKD in a community-based cohort. Our results add to the available evidence for a deleterious effect of high vasopressin on renal health not only in selected groups of patients with CKD but also in the general population.
DOI: 10.6084/m9.figshare.5128606
title: Supplementary Material for: Repeated Intravenous Treatment with Recombinant Tissue-Type Plasminogen Activator in Patients with Acute Ischemic Stroke

description: <b><i>Objective:</i></b> Increased use of systemic thrombolysis, demographic changes, and higher chances of surviving first-ever strokes all lead to an increasing number of patients with recurrent stroke. However, data on repeated thrombolysis are limited. Here, we report on the safety and clinical effects of repeated intravenous recombinant tissue-type plasminogen activator (rt-PA) treatment in a large consecutive cohort of stroke patients. <b><i>Methods:</i></b> We identified all stroke patients who received repeated thrombolysis. We determined safety and 3-month clinical outcome after the first and second thrombolysis. All patients received follow-up brain imaging. Good clinical outcome was defined as a modified Rankin Scale of 0-2 or recovery to the prestroke status. <b><i>Results:</i></b> In total, 24 patients were included (i.e. 1.5% of all stroke patients treated with rt-PA at our center who survived the first treatment; male 45.8%; median age at first event: 74.5 years). No allergic or anaphylactic reactions were recorded after the first time of treatment, but oral angioedema developed once during the second treatment. No symptomatic intracerebral hemorrhage was observed. Clinical outcome was good in 75.0% after the first, but in only 41.7% after the second treatment (p = 0.021). <b><i>Conclusions:</i></b> Repeated thrombolysis was not associated with a higher rate of complications. However, the clinical outcome appears to be less satisfactory than after the first treatment.
DOI: 10.6084/m9.figshare.5128609.v1
title: Supplementary Material for: Glucocorticoid-Induced Leucine Zipper Is Expressed in Human Neutrophils and Promotes Apoptosis through Mcl-1 Down-Regulation

description: Glucocorticoid-induced leucine zipper (GILZ) is a potent anti-inflammatory protein, the expression of which is mainly induced by glucocorticoids (GCs) in haematopoietic cells. GILZ regulates signal transduction pathways of inflammation and plays a role in cell survival. The objective of this study was to evaluate the expression and mechanisms of action of GILZ in the apoptosis of human neutrophils. GILZ expression was induced by GCs in human neutrophils, enhanced upon phosphatidylinositol 3-kinase inhibition and resulted in apoptosis amplification. We then stably transfected PLB-985 cells with the human <i>gilz</i> gene and differentiated both control and GILZ-overexpressing clones in neutrophil-like cells. GILZ overexpression in PLB-985 cells led to an exacerbated apoptosis, associated with caspase-3, caspase-9 and caspase-8 activations, and a loss of mitochondrial potential, suggesting that GILZ-induced apoptosis used the mitochondrial pathway. The expression of BH3 interacting domain death agonist, Bcl-2 interacting mediator of cell death, annexin-A1 and Bcl-2-associated X was not affected in PLB-985-GILZ clones, but phosphorylation and subsequent proteasomal degradation of myeloid cell leukemia-1 (Mcl-1) were observed. Noteworthy, Mcl-1 phosphorylation was related to a significant and sustained activation of c-Jun N-terminal kinase (JNK) in PLB-985-GILZ clones. These results reveal GILZ to be a new actor in apoptosis regulation in neutrophil-like cells involving JNK and Mcl-1.