cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123470.v1
title: Supplementary Material for: Hypothalamic Deep Brain Stimulation Influences Autonomic and Limbic Circuitry Involved in the Regulation of Aggression and Cardiocerebrovascular Control in the Göttingen Minipig

description: <b><i>Background:</i></b> Deep brain stimulation (DBS) in the ventral tuberal hypothalamus (VTH) is currently under investigation for the treatment of severe obesity. Stimulation impact on a number of closely related hypothalamic neural systems could potentially influence normal hypothalamic function and thereby generate adverse side effects. <b><i>Objective:</i></b> To assess the feasibility and safety of VTH DBS in a non-primate large animal model. <b><i>Methods:</i></b> In the VTH of 6 Göttingen minipigs, quadropolar leads were implanted bilaterally (n = 2) or unilaterally (n = 4), using optimized MRI sequences allowing identification of major diencephalic landmarks. Heart rate, weight, behavior and nighttime locomotor activity were recorded throughout the study period. Two of the unilaterally implanted minipigs were examined with [<sup>15</sup>O]H<sub>2</sub>O positron emission tomography (PET) scans performed in DBS-off and DBS-on mode. <b><i>Results:</i></b> VTH DBS elicited an amplitude-dependent increase in heart rate and transient aggressive behavior. PET demonstrated that VTH DBS caused a global increase in cerebral blood flow velocities and decreased mean transit time. <b><i>Conclusions:</i></b> VTH DBS results in behavioral and physiological changes, which may derive from activation of closely related limbic and autonomic networks. Caution and further studies of longer length should be requested before this procedure is used more widely in humans.
DOI: 10.6084/m9.figshare.5123464.v1
title: Supplementary Material for: Differential Sirtuin Expression Patterns in Amyotrophic Lateral Sclerosis (ALS) Postmortem Tissue: Neuroprotective or Neurotoxic Properties of Sirtuins in ALS?

description: <b><i>Background/Aims:</i></b> Sirtuins (SIRT1–7; class III histone deactylases) modulate fundamental mechanisms in age-related neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We assessed the expression levels of sirtuins in human postmortem ALS and control brain and spinal cord. <b><i>Methods and Results:</i></b> By quantitative real-time PCR, a significant reduction of SIRT1 and SIRT2 was detected in homogenates of the primary motor cortex (white and gray matter), while there were no differences in spinal cord homogenates. When specifically analyzing mRNA and protein expression in the gray matter (cortical layers I–VI of the precentral gyrus, ventral/dorsal horn of the spinal cord) by in situ hybridization histochemistry and immunohistochemistry, we found increased levels of SIRT1, SIRT2 and SIRT5 in ALS which were significant for SIRT1 and SIRT5 mRNA in the spinal cord. <b><i>Conclusion:</i></b> Our results indicate a general reduction of SIRT1 and SIRT2 in ALS primary motor cortex, while in situ hybridization histochemistry and immunohistochemistry showed neuron-specific upregulation of SIRT1, SIRT2 and SIRT5, particularly in the spinal cord. Opposed effects have been described for SIRT1 and SIRT2: while SIRT1 activation is mainly associated with neuroprotection, SIRT2 upregulation is toxic to neuronal cells. Novel therapeutic approaches in ALS could therefore target SIRT1 activation or SIRT2 inhibition.
DOI: 10.6084/m9.figshare.5123455
title: Supplementary Material for: When Do Short Children Realize They Are Short? Prepubertal Short Children’s Perception of Height during 24 Months of Catch-Up Growth Hormone Treatment

description: <b><i>Aim:</i></b> To examine perceived height during the first 24 months of growth hormone (GH) treatment in short prepubertal children. <b><i>Methods:</i></b> Ninety-nine 3- to 11-year-old short prepubertal children with either isolated GH deficiency (n = 32) or idiopathic short stature (n = 67) participated in a 24-month randomized trial of individualized or fixed-dose GH treatment. Children’s and parents’ responses to three perceived height measures: relative height (Silhouette Apperception Test), sense of height (VAS short/tall), and judgment of appropriate height (yes/no) were compared to measured height. <b><i>Results:</i></b> Children and parents overestimated height at start (72%, 54%) and at 24 months (52%, 30%). Short children described themselves as tall until 8.2 years (girls) and 9 years (boys). Prior to treatment, 38% of children described their height as appropriate and at 3 months, 63%. Mother’s height, parental sense of the child’s tallness and age explained more variance in children’s sense of tallness (34%) than measured height (0%). <b><i>Conclusion:</i></b> Short children and parents overestimate height; a pivotal age exists for comparative height judgments. Even a small gain in height may be enough for the child to feel an appropriate age-related height has been reached and to no longer feel short.
DOI: 10.6084/m9.figshare.5123458
title: Supplementary Material for: Sensitization of Glioma Cells by X-Linked Inhibitor of Apoptosis Protein Knockdown

description: <b><i>Objective:</i></b> Glioblastomas are a kind of cancer with high resistance to treatments, requiring more efficient alternatives of treatment. X-linked inhibitor of apoptosis (XIAP) is highly expressed in gliomas and, due to its inhibition of caspases, can participate in resistance to therapy. Here we test the sensitization of glioma cells with XIAP gene knockdown (KD) to drugs used in chemotherapy. <b><i>Methods:</i></b> We silenced XIAP expression in U87MG glioblastoma using stable shRNA, and cells were treated with taxol, BCNU, temozolomide, cisplatin, etoposide, resveratrol (Rsv), vincristine and doxorubicin. We analyzed cell viability, cell cycle, apoptosis and senescence. <b><i>Results:</i></b> XIAP KD cells were more sensitive to etoposide, Rsv, vincristine and doxorubicin compared to wild-type (WT) cells. Doxorubicin 1 µ<i>M</i> and vincristine 100 n<i>M</i> induced higher activation of caspases after 24 h and doxorubicin induced a higher degree of senescence induction in XIAP KD cells in relation to WT cells. Phospho-p53 and phospho-H2Ax Western blot indicate subsequent DNA damage as an important effector of doxorubicin-induced death. <b><i>Conclusions:</i></b> This study suggests that XIAP inhibitors may sensitize gliomas to certain drugs and induce death and that the mechanisms of sensitization involve apoptosis, senescence and p53 signaling.
DOI: 10.6084/m9.figshare.5123446
title: Supplementary Material for: Comparative Safety and Efficiency of Five Percutaneous Kidney Biopsy Approaches of Native Kidneys: A Multicenter Study

description: <i>Background:</i> Renal biopsy (RB) is necessary for the diagnosis, prognosis, and therapy guidance of native kidney diseases. Few studies have compared outcomes of RB procedures. We retrospectively compared the safety and efficiency of five biopsy procedures. <i>Methods:</i> The number of glomeruli on light microscopy (LM) and on immunofluorescence (IF) and serious adverse events following RB performed in five nephrology units (C1–C5) were collected. C1 performed ultrasound (US) assessment before RB and used a 14-gauge core-cutting needle biopsy gun, C2 US guidance and a 14-gauge needle, C3 tomodensitometry guidance and a 14-gauge needle, C4 US guidance and a 16-gauge needle, and C5 tomodensitometry guidance and a 16-gauge needle. <i>Results:</i> RB was performed in 943 adults between January 2006 and July 2010. Serious adverse events occurred in 1.5% of biopsies. The complication rate was not different between nephrology units. The mean number of glomeruli on biopsy was 14.2 ± 8.6 with LM and 4.4 ± 3.3 on IF. It was different according to the nephrology unit for LM (p = 0.01) and for IF (p &lt; 0.001). The number of failed biopsies was influenced by the nephrology unit and radiological guidance technique, favoring real-time US guidance. Failed biopsies using US or tomodensitometry assessment before RB was certainly due to kidney imprecise localization since it was often non-renal tissue sampling. At least 10 glomeruli were found in 69% of biopsies on LM. This rate varied according to the nephrology unit (p = 0.004) and was higher when 14-gauge needles were used in comparison with 16-gauge needles. <i>Conclusion:</i> RB is safe regardless of the technical procedure, but radiological guidance and needle size influence the efficiency of biopsies.
DOI: 10.6084/m9.figshare.5123449
title: Supplementary Material for: An Information Theory Analysis of Gene-Environmental Interactions in Count/Rate Data

description: <b><i>Objective:</i></b> To develop and critically evaluate an information theory method for identifying gene-gene and gene-environment interactions in count and rate data. <b><i>Methods:</i></b> The entropy-based metric <i>k</i>-way interaction information (KWII) was critically assessed for utility in detecting interactions with count data and over-dispersed count data in three simulation studies of increasing complexity and in datasets from animal models of depression and colitis. The results were compared to Poisson regression. The power and effect size dependence of the KWII for detecting interactions was also assessed. <b><i>Results:</i></b> The KWII was capable of effectively identifying the genetic and environmental predictors and their interactions in all three simulated datasets. The results indicate that the KWII approach may produce more parsimonious results than regression. In a rat model of depression, we successfully identified a prominent gender effect as well as other published associations. Analysis of severity scores from an animal model of colitis identified markers from chromosome 3, as well as unique first- and second-order associations for the individual sections of the colon and cecum. <b><i>Conclusions:</i></b> The results demonstrate the utility and versatility of our entropy-based method for gene-environment interaction analysis of count and rate data with Poisson and over-dispersed distributions.
DOI: 10.6084/m9.figshare.5123449.v1
title: Supplementary Material for: An Information Theory Analysis of Gene-Environmental Interactions in Count/Rate Data

description: <b><i>Objective:</i></b> To develop and critically evaluate an information theory method for identifying gene-gene and gene-environment interactions in count and rate data. <b><i>Methods:</i></b> The entropy-based metric <i>k</i>-way interaction information (KWII) was critically assessed for utility in detecting interactions with count data and over-dispersed count data in three simulation studies of increasing complexity and in datasets from animal models of depression and colitis. The results were compared to Poisson regression. The power and effect size dependence of the KWII for detecting interactions was also assessed. <b><i>Results:</i></b> The KWII was capable of effectively identifying the genetic and environmental predictors and their interactions in all three simulated datasets. The results indicate that the KWII approach may produce more parsimonious results than regression. In a rat model of depression, we successfully identified a prominent gender effect as well as other published associations. Analysis of severity scores from an animal model of colitis identified markers from chromosome 3, as well as unique first- and second-order associations for the individual sections of the colon and cecum. <b><i>Conclusions:</i></b> The results demonstrate the utility and versatility of our entropy-based method for gene-environment interaction analysis of count and rate data with Poisson and over-dispersed distributions.
DOI: 10.6084/m9.figshare.5123452
title: Supplementary Material for: Dietary Phosphate Binding and Loading Alter Kidney Angiotensin-Converting Enzyme mRNA and Protein Content in 5/6 Nephrectomized Rats

description: <i>Background:</i> Vitamin D receptor activation with paricalcitol can modulate the transcription of renin-angiotensin system components in the surgical 5/6 nephrectomy rat model (5/6 NX) of chronic renal insufficiency. We tested the hypothesis whether dietary modification of phosphate influences kidney renin-angiotensin system gene expression at the mRNA level in 5/6 NX rats. <i>Methods:</i> Fifteen weeks after surgery, rats were given control diet (0.3% calcium, 0.5% phosphate), phosphate-lowering diet (3% calcium as carbonate) or high-phosphate diet (1.5%) for 12 weeks. Sham-operated rats were on control diet. <i>Results:</i> Blood pressure, plasma phosphate, parathyroid hormone, glomerulosclerosis, tubulointerstitial damage, and FGF-23 were increased in remnant kidney rats, whereas creatinine clearance was decreased. Phosphate, parathyroid hormone, glomerulosclerosis, tubulointerstitial damage, and FGF-23 were further elevated by the high-phosphate diet, but were reduced by the phosphate-lowering diet. Plasma calcium was increased with the phosphate-lowering diet and decreased with the high-phosphate diet. Remnant kidney rats on control diet showed upregulated kidney angiotensin-converting enzyme (ACE) and angiotensin (Ang) IV receptor (AT<sub>4</sub>) transcription, while ACE2, Ang II type 2 receptor and renin receptor transcription were downregulated in comparison with sham rats. Phosphate-lowering diet reduced whereas high-phosphate diet increased kidney ACE, and these effects were observed at both mRNA and protein levels. Dietary phosphate loading also resulted in lower AT<sub>1a</sub> gene transcription. <i>Conclusion:</i> Dietary phosphate loading was associated with elevated kidney ACE expression, increased tissue damage and lower AT<sub>1a</sub> transcription in 5/6 NX rats. Phosphate binding with 3% calcium carbonate had opposite effects on ACE and kidney damage.
DOI: 10.6084/m9.figshare.5123455.v1
title: Supplementary Material for: When Do Short Children Realize They Are Short? Prepubertal Short Children’s Perception of Height during 24 Months of Catch-Up Growth Hormone Treatment

description: <b><i>Aim:</i></b> To examine perceived height during the first 24 months of growth hormone (GH) treatment in short prepubertal children. <b><i>Methods:</i></b> Ninety-nine 3- to 11-year-old short prepubertal children with either isolated GH deficiency (n = 32) or idiopathic short stature (n = 67) participated in a 24-month randomized trial of individualized or fixed-dose GH treatment. Children’s and parents’ responses to three perceived height measures: relative height (Silhouette Apperception Test), sense of height (VAS short/tall), and judgment of appropriate height (yes/no) were compared to measured height. <b><i>Results:</i></b> Children and parents overestimated height at start (72%, 54%) and at 24 months (52%, 30%). Short children described themselves as tall until 8.2 years (girls) and 9 years (boys). Prior to treatment, 38% of children described their height as appropriate and at 3 months, 63%. Mother’s height, parental sense of the child’s tallness and age explained more variance in children’s sense of tallness (34%) than measured height (0%). <b><i>Conclusion:</i></b> Short children and parents overestimate height; a pivotal age exists for comparative height judgments. Even a small gain in height may be enough for the child to feel an appropriate age-related height has been reached and to no longer feel short.
DOI: 10.6084/m9.figshare.5123437
title: Supplementary Material for: The Association between Physical Morbidity and Subtypes of Severe Depression

description: <b><i>Background:</i></b> Physical illness and depression are related, but the association between specific physical diseases and diagnostic subtypes of depression remains poorly understood. This study aimed to clarify the relationship between a number of physical diseases and the nonpsychotic and psychotic subtype of severe depression. <b><i>Methods:</i></b> This is a historical prospective cohort study. The study population consisted of all patients diagnosed with ICD-10 severe depression, either nonpsychotic or psychotic subtype, in Danish psychiatric hospitals between 1994 and 2008. The patients’ history of physical disease was assessed using the Danish National Patient Register. Using logistic regression it was investigated whether specific physical diseases were associated with relative increased risk for subsequent development of either the nonpsychotic or psychotic depressive subtype. <b><i>Results:</i></b> A total of 24,173 patients with severe depression were included in the study. Of those, 8,260 (34%) were of the psychotic subtype. A history of the following physical diseases, as opposed to their absence, increased the relative risk for subsequent development of the nonpsychotic compared to the psychotic depressive subtype [adjusted incidence odds ratio (AIOR) nonpsychotic vs. psychotic]: ischemic heart disease (AIOR = 1.3, p &lt; 0.001), hypertension (AIOR = 1.2, p = 0.008), stroke (AIOR = 1.2, p = 0.042) and chronic lower pulmonary disease (AIOR = 1.2, p = 0.005). The total load of physical disease also increased the relative risk of nonpsychotic depression [AIOR = 1.05 (per disease), p = 0.001]. <b><i>Conclusions:</i></b> This study revealed that, in severe depression, a history of physical disease increased the relative risk of the nonpsychotic rather than the psychotic subtype.
DOI: 10.6084/m9.figshare.5123440
title: Supplementary Material for: Minimal Homozygous Endothelial Deletion of Eng with VEGF Stimulation Is Sufficient to Cause Cerebrovascular Dysplasia in the Adult Mouse

description: <b><i>Background:</i></b> Brain arteriovenous malformations (bAVMs) represent a high risk for hemorrhagic stroke, leading to significant neurological morbidity and mortality in young adults. The etiopathogenesis of bAVM remains unclear. Research progress has been hampered by the lack of animal models. Hereditary Hemorrhagic Telangiectasia (HHT) patients with haploinsufficiency of endoglin (<i>ENG, </i>HHT1) or activin receptor-like kinase 1 (<i>ALK1, </i>HHT2) have a higher incidence of bAVM than the general population. We previously induced cerebrovascular dysplasia in the adult mouse that resembles human bAVM through <i>Alk1</i> deletion plus vascular endothelial growth factor (VEGF) stimulation. We hypothesized that <i>Eng</i> deletion plus VEGF stimulation would induce a similar degree of cerebrovascular dysplasia as the <i>Alk1</i>-deleted brain. <b><i>Methods:</i></b> Ad-Cre (an adenoviral vector expressing Cre recombinase) and AAV-VEGF (an adeno-associated viral vector expressing VEGF) were co-injected into the basal ganglia of 8- to 10-week-old <i>Eng</i><sup>2f/2f</sup> (exons 5 and 6 flanked by loxP sequences), <i>Alk1</i><sup>2f/2f</sup> (exons 4–6 flanked by loxP sequences) and wild-type (WT) mice. Vascular density, dysplasia index, and gene deletion efficiency were analyzed 8 weeks later. <b><i>Results:</i></b> AAV-VEGF induced a similar degree of angiogenesis in the brain with or without <i>Alk1</i>- or <i>Eng</i>-deletion. Abnormally patterned and dilated dysplastic vessels were found in the viral vector-injected region of <i>Alk1</i><sup>2f/2f</sup> and <i>Eng</i><sup>2f/2f</sup> brain sections, but not in WT. <i>Alk1</i><sup>2f/2f</sup> mice had about 1.8-fold higher dysplasia index than <i>Eng</i><sup>2f/2f</sup> mice (4.6 ± 1.9 vs. 2.5 ± 1.1, p &lt; 0.05). However, after normalization of the dysplasia index with the gene deletion efficiency (<i>Alk1</i><sup>2f/2f</sup>: 16% and <i>Eng</i><sup>2f/2f</sup>: 1%), we found that about 8-fold higher dysplasia was induced per copy of <i>Eng</i> deletion (2.5) than that of <i>Alk1</i> deletion (0.3). ENG-negative endothelial cells were detected in the Ad-Cre-treated brain of <i>Eng</i><sup>2f/2f</sup> mice, suggesting homozygous deletion of <i>Eng</i> in the cells. VEGF induced more severe vascular dysplasia in the Ad-Cre-treated brain of <i>Eng</i><sup>2f/2f</sup> mice than that of <i>Eng</i><sup>+/–</sup> mice. <b><i>Conclusions:</i></b> (1) Deletion of <i>Eng</i> induces more severe cerebrovascular dysplasia per copy than that of <i>Alk1</i> upon VEGF stimulation. (2) Homozygous deletion of <i>Eng</i> with angiogenic stimulation may be a promising strategy for development of a bAVM mouse model. (3) The endothelial cells that have homozygous causal gene deletion in AVM could be crucial for lesion development.
DOI: 10.6084/m9.figshare.5123446.v1
title: Supplementary Material for: Comparative Safety and Efficiency of Five Percutaneous Kidney Biopsy Approaches of Native Kidneys: A Multicenter Study

description: <i>Background:</i> Renal biopsy (RB) is necessary for the diagnosis, prognosis, and therapy guidance of native kidney diseases. Few studies have compared outcomes of RB procedures. We retrospectively compared the safety and efficiency of five biopsy procedures. <i>Methods:</i> The number of glomeruli on light microscopy (LM) and on immunofluorescence (IF) and serious adverse events following RB performed in five nephrology units (C1–C5) were collected. C1 performed ultrasound (US) assessment before RB and used a 14-gauge core-cutting needle biopsy gun, C2 US guidance and a 14-gauge needle, C3 tomodensitometry guidance and a 14-gauge needle, C4 US guidance and a 16-gauge needle, and C5 tomodensitometry guidance and a 16-gauge needle. <i>Results:</i> RB was performed in 943 adults between January 2006 and July 2010. Serious adverse events occurred in 1.5% of biopsies. The complication rate was not different between nephrology units. The mean number of glomeruli on biopsy was 14.2 ± 8.6 with LM and 4.4 ± 3.3 on IF. It was different according to the nephrology unit for LM (p = 0.01) and for IF (p &lt; 0.001). The number of failed biopsies was influenced by the nephrology unit and radiological guidance technique, favoring real-time US guidance. Failed biopsies using US or tomodensitometry assessment before RB was certainly due to kidney imprecise localization since it was often non-renal tissue sampling. At least 10 glomeruli were found in 69% of biopsies on LM. This rate varied according to the nephrology unit (p = 0.004) and was higher when 14-gauge needles were used in comparison with 16-gauge needles. <i>Conclusion:</i> RB is safe regardless of the technical procedure, but radiological guidance and needle size influence the efficiency of biopsies.