cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5124433
title: Supplementary Material for: Neuropathology of Partial PGC-1α Deficiency Recapitulates Features of Mitochondrial Encephalopathies but Not of Neurodegenerative Diseases

description: <b><i>Background:</i></b> Deficient peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) function is one component of mitochondrial dysfunction in neurodegenerative diseases. Current molecular classification of such diseases is based on the predominant protein accumulating as intra- or extracellular aggregates. Experimental evidence suggests that mitochondrial dysfunction and impaired protein processing are closely interrelated. In vitro findings further indicate that PGC-1α dysfunction may contribute to protein misfolding in neurodegeneration. <b><i>Objective:</i></b> To systematically evaluate the neuropathological alterations of mice lacking the expression of the full-length PGC-1α protein (FL-PGC-1α) but expressing an N-truncated fragment. <b><i>Methods:</i></b> To assess the pattern of neurodegeneration-related proteins, we performed immunostaining for Tau, pTau, α-synuclein, amyloid-β, amyloid precursor protein, prion protein, FUS, TDP-43 and ubiquitin. Using hematoxylin and eosin, Klüver-Barrera and Bielschowsky silver stainings and anti-GFAP immunohistochemistry, we performed an anatomical mapping to provide a lesion profile. <b><i>Results:</i></b> The immunohistochemical pattern of neurodegeneration-related proteins did not differ between FL-PGC-1α knockout and wild-type animals, and there was a complete lack of protein deposits or ubiquitin-positive inclusions. The analysis of neuropathological alterations revealed widespread vacuolation predominating in the cerebral white matter, caudate-putamen, thalamus and brainstem, and reactive astrogliosis in the brainstem and cerebellar nuclei. This morphological phenotype was thus reminiscent of human mitochondrial encephalopathies, especially the Kearns-Sayre syndrome. <b><i>Conclusion:</i></b> We conclude that the lack of FL-PGC-1α per se is insufficient to recapitulate major features of neurodegenerative diseases, but evokes a pathology seen in mitochondrial encephalopathies, which makes PGC-1α-deficient mice a valuable model for this yet incurable group of diseases.
DOI: 10.6084/m9.figshare.5124442.v1
title: Supplementary Material for: Stereotypic Movements in Case of Sporadic Creutzfeldt-Jakob Disease: Possible Role of Anti-NMDA Receptor Antibodies

description: Sporadic Creutzfeldt-Jakob disease (sCJD) and anti-NMDA receptor antibody encephalitis (NMDAE) can both produce a rapidly progressive dementia with resulting state of catatonia or akinetic mutism. Both are associated with movement disorders. In published case series, myoclonus appears to be the most frequent movement disorder in sCJD, while stereotypic, synchronized, one-cycle-per-second movements such as arm or leg elevation, jaw opening, grimacing, head turning, and eye deviation are seen in NMDAE. We report a case of a 59-year-old woman with rapidly worsening cognitive disturbance leading to a nearly catatonic state interrupted by stereotypic movements. sCJD was diagnosed via periodic sharp wave complexes on EEG as well as cerebrospinal fluid (CSF) 14-3-3 and tau protein elevation. Characteristic movement disorder of NMDAE was present in absence of ovarian mass or CSF pleiocytosis. Given prior case reports of presence of anti-NMDA receptor antibodies in sCJD, we propose that the movement disorder in this case was caused by anti-NMDA receptor antibodies whose formation was secondary to neuronal damage from prion disease. It is important to consider sCJD even in cases that have some clinical features suggestive of NMDAE.
DOI: 10.6084/m9.figshare.5124424
title: Supplementary Material for: Patterns of Subarachnoid Hemorrhage Admissions in England, 2008–2011

description: <b><i>Background:</i></b> To investigate hospital admissions for subarachnoid hemorrhage (SAH) across regions in England in recent years, with the hypothesis that deprived areas have higher admissions. <b><i>Methods:</i></b> Hospital episode statistics between July 2008 and June 2011 were retrieved. Hospital admissions by geographic and seasonal variations were examined. Data on prevalence of deprivation were extracted from the English Indices of Deprivation. Comparisons were made by using linear regression models to test associations between deprivation and classical risk contributors and SAH admissions at the area level. <b><i>Results:</i></b> SAH admissions were observed to be higher in warm months and lower in cold months. There was not much variation in SAH admissions across regions. Areas with higher prevalence of risk contributors had higher SAH admissions (all p &lt; 0.05), but no relation with deprivation was found. Additionally, over the last 13 years, SAH admissions have decreased (beta: –0.011, 95% CI: –0.015 to –0.008, p &lt; 0.001) annually, but the proportion of male patient admissions has increased (beta: 0.022, 95% CI: 0.008–0.036, p = 0.005). <b><i>Conclusion:</i></b> SAH admissions varied across seasons but not geographically. Additionally, they were correlated with known risk contributors. Policies attending to lifestyle change are suggested in reducing this disease.
DOI: 10.6084/m9.figshare.5124427
title: Supplementary Material for: Idiopathic Intraventricular Aneurysm Presenting with Intraventricular Hemorrhage: Case Report and Review of the Literature

description: Intraventricular hemorrhage (IVH) is a relatively commonly encountered problem in neurosurgical practice. The underlying causes could include hypertension, arteriovenous malformations (AVM), angiomas, trauma, tumors, aneurysms and moyamoya disease. Truly idiopathic intraventricular aneurysms (IVA) are rare. A high index of suspicion needs to be maintained since, with the appropriate treatment, the outcome is generally good.<b> </b>We report the case of a 14-year-old boy who presented with sudden onset headache and vomiting. CT angiogram pointed to the possibility of an IVA. This was confirmed by MRI with three-dimensional constructive interference in steady state (CISS-3D) sequences and digital subtraction angiography. The patient underwent microsurgical excision of the aneurysm and is doing well on follow-up.<b> </b>Idiopathic IVA can present with IVH at any age. MRI with CISS-3D and MR angiography would be the imaging modality of choice since it can also rule out other causes of intraventricular bleeding such as tumors and AVM. These lesions could be managed effectively by microsurgical excision/clipping. The necessity of investigating every patient who presents with IVH is debatable.
DOI: 10.6084/m9.figshare.5124421
title: Supplementary Material for: Secreted Expression of a Hyperthermophilic α-Amylase Gene from <b><i>Thermococcus</i></b> sp. HJ21 in <b><i>Bacillus subtilis</i></b>

description: The hyperthermophilic α-amylase from <i>Thermococcus</i> sp. HJ21 possesses unique traits (Ca<sup>2+</sup>-independent thermostability and optimal temperature of 95°C) that make it a great potential candidate for use in the food industry. However, this Archaea isolated from a deep-sea thermal vent requires strict control of culture conditions and produces only small amounts of α-amylase. To solve these problems, the α-amylase gene was cloned and expressed in <i>Bacillus subtilis</i>, which is an ideal food-grade host for heterologous protein expression. To express high levels of this α-amylase in <i>B. subtilis</i>, the promoters P<sub><i>grac</i></sub>, P<sub><i>xylA</i></sub>, P43, and P<sub><i>hag</i></sub> were used to construct four different expression vectors for testing. The vector containing the P<sub><i>xylA</i></sub> promoter was found to have the highest transcriptional activity and produce the highest amylase activity (19.6 U/ml). To test the secretion efficiency of signal peptides in <i>B. subtilis</i>, three signal peptides were cloned and fused to the α-amylase gene (lacking its native signal peptide). The optimal signal peptide was S<sub><i>amyQ</i></sub>, with a secretion efficiency of approximately 90%. These results indicate that the promoter P<sub><i>xylA</i></sub> and signal peptide S<sub><i>amyQ</i></sub> tested in this study may be useful for the expression and secretion of archaeal proteins in <i>B. subtilis</i>.
DOI: 10.6084/m9.figshare.5124433.v1
title: Supplementary Material for: Neuropathology of Partial PGC-1α Deficiency Recapitulates Features of Mitochondrial Encephalopathies but Not of Neurodegenerative Diseases

description: <b><i>Background:</i></b> Deficient peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) function is one component of mitochondrial dysfunction in neurodegenerative diseases. Current molecular classification of such diseases is based on the predominant protein accumulating as intra- or extracellular aggregates. Experimental evidence suggests that mitochondrial dysfunction and impaired protein processing are closely interrelated. In vitro findings further indicate that PGC-1α dysfunction may contribute to protein misfolding in neurodegeneration. <b><i>Objective:</i></b> To systematically evaluate the neuropathological alterations of mice lacking the expression of the full-length PGC-1α protein (FL-PGC-1α) but expressing an N-truncated fragment. <b><i>Methods:</i></b> To assess the pattern of neurodegeneration-related proteins, we performed immunostaining for Tau, pTau, α-synuclein, amyloid-β, amyloid precursor protein, prion protein, FUS, TDP-43 and ubiquitin. Using hematoxylin and eosin, Klüver-Barrera and Bielschowsky silver stainings and anti-GFAP immunohistochemistry, we performed an anatomical mapping to provide a lesion profile. <b><i>Results:</i></b> The immunohistochemical pattern of neurodegeneration-related proteins did not differ between FL-PGC-1α knockout and wild-type animals, and there was a complete lack of protein deposits or ubiquitin-positive inclusions. The analysis of neuropathological alterations revealed widespread vacuolation predominating in the cerebral white matter, caudate-putamen, thalamus and brainstem, and reactive astrogliosis in the brainstem and cerebellar nuclei. This morphological phenotype was thus reminiscent of human mitochondrial encephalopathies, especially the Kearns-Sayre syndrome. <b><i>Conclusion:</i></b> We conclude that the lack of FL-PGC-1α per se is insufficient to recapitulate major features of neurodegenerative diseases, but evokes a pathology seen in mitochondrial encephalopathies, which makes PGC-1α-deficient mice a valuable model for this yet incurable group of diseases.
DOI: 10.6084/m9.figshare.5124418
title: Supplementary Material for: Genetic Variation at NCAN Locus Is Associated with Inflammation and Fibrosis in Non-Alcoholic Fatty Liver Disease in Morbid Obesity

description: <b><i>Objective:</i></b> Obesity-associated non-alcoholic fatty liver disease (NAFLD) may cause liver dysfunction and failure. In a previously reported genome-wide association meta-analysis, single nucleotide polymorphisms (SNPs) near <i>PNPLA3</i>, <i>NCAN</i>, <i>GCKR</i>, <i>LYPLAL1</i> and <i>PPP1R3B</i> were associated with NAFLD and with distinctive serum lipid profiles. The present study examined the relevance of these variants to NAFLD in extreme obesity. <b><i>Methods:</i></b> In 1,092 bariatric surgery patients, the candidate SNPs were genotyped and association analyses with liver histology and serum lipids were performed. <b><i>Results:</i></b> We replicated the association of hepatosteatosis with <i>PNPLA3</i> rs738409[G] and with <i>NCAN</i> rs2228603[T]. We also replicated the association of rs2228603[T] with hepatic inflammation and fibrosis. rs2228603[T] was associated with lower serum low-density lipoprotein, total cholesterol and triglycerides. After stratification by the presence or absence of NAFLD, these associations were present predominantly in the subgroup with NAFLD. <b><i>Conclusion:</i></b><i>NCAN</i> rs2228603[T] is a risk factor for liver inflammation and fibrosis, suggesting that this locus is responsible for progression from steatosis to steatohepatitis. In this bariatric cohort, rs2228603[T] was associated with low serum lipids only in patients with NAFLD. This supports a NAFLD model in which the liver may sequester triglycerides as a result of either increased triglyceride uptake and/or decreased lipolysis.
DOI: 10.6084/m9.figshare.5124427.v1
title: Supplementary Material for: Idiopathic Intraventricular Aneurysm Presenting with Intraventricular Hemorrhage: Case Report and Review of the Literature

description: Intraventricular hemorrhage (IVH) is a relatively commonly encountered problem in neurosurgical practice. The underlying causes could include hypertension, arteriovenous malformations (AVM), angiomas, trauma, tumors, aneurysms and moyamoya disease. Truly idiopathic intraventricular aneurysms (IVA) are rare. A high index of suspicion needs to be maintained since, with the appropriate treatment, the outcome is generally good.<b> </b>We report the case of a 14-year-old boy who presented with sudden onset headache and vomiting. CT angiogram pointed to the possibility of an IVA. This was confirmed by MRI with three-dimensional constructive interference in steady state (CISS-3D) sequences and digital subtraction angiography. The patient underwent microsurgical excision of the aneurysm and is doing well on follow-up.<b> </b>Idiopathic IVA can present with IVH at any age. MRI with CISS-3D and MR angiography would be the imaging modality of choice since it can also rule out other causes of intraventricular bleeding such as tumors and AVM. These lesions could be managed effectively by microsurgical excision/clipping. The necessity of investigating every patient who presents with IVH is debatable.
DOI: 10.6084/m9.figshare.5124412
title: Supplementary Material for: Differentiation Patterns of Embryonic Stem Cells in Two- versus Three-Dimensional Culture

description: Pluripotent stem cells are attractive candidates as a cell source for regenerative medicine and tissue engineering therapies. Current methods of differentiation result in low yields and impure populations of target phenotypes, with attempts for improved efficiency often comparing protocols that vary multiple parameters. This basic science study focused on a single variable to understand the effects of two-dimensional (2D) versus three-dimensional (3D) culture on directed differentiation. We compared mouse embryonic stem cells (ESCs) differentiated on collagen type I-coated surfaces (SLIDEs), embedded in collagen type I gels (GELs), and in suspension as embryoid bodies (EBs). For a systematic analysis in these studies, key parameters were kept identical to allow for direct comparison across culture configurations. We determined that all three configurations supported differentiation of ESCs and that the kinetics of differentiation differed greatly for cells cultured in 2D versus 3D. SLIDE cultures induced overall differentiation more quickly than 3D configurations, with earlier expression of cytoskeletal and extracellular matrix proteins. For 3D culture as GELs or EBs, cells clustered similarly, formed complex structures and promoted differentiation towards cardiovascular phenotypes. GEL culture, however, also allowed for contraction of the collagen matrix. For differentiation towards fibroblasts and smooth muscle cells which actively remodel their environment, GEL culture may be particularly beneficial. Overall, this study determined the effects of dimensionality on differentiation and helps in the rational design of protocols to generate phenotypes needed for tissue engineering and regenerative medicine.
DOI: 10.6084/m9.figshare.5124424.v1
title: Supplementary Material for: Patterns of Subarachnoid Hemorrhage Admissions in England, 2008–2011

description: <b><i>Background:</i></b> To investigate hospital admissions for subarachnoid hemorrhage (SAH) across regions in England in recent years, with the hypothesis that deprived areas have higher admissions. <b><i>Methods:</i></b> Hospital episode statistics between July 2008 and June 2011 were retrieved. Hospital admissions by geographic and seasonal variations were examined. Data on prevalence of deprivation were extracted from the English Indices of Deprivation. Comparisons were made by using linear regression models to test associations between deprivation and classical risk contributors and SAH admissions at the area level. <b><i>Results:</i></b> SAH admissions were observed to be higher in warm months and lower in cold months. There was not much variation in SAH admissions across regions. Areas with higher prevalence of risk contributors had higher SAH admissions (all p &lt; 0.05), but no relation with deprivation was found. Additionally, over the last 13 years, SAH admissions have decreased (beta: –0.011, 95% CI: –0.015 to –0.008, p &lt; 0.001) annually, but the proportion of male patient admissions has increased (beta: 0.022, 95% CI: 0.008–0.036, p = 0.005). <b><i>Conclusion:</i></b> SAH admissions varied across seasons but not geographically. Additionally, they were correlated with known risk contributors. Policies attending to lifestyle change are suggested in reducing this disease.
DOI: 10.6084/m9.figshare.5124409
title: Supplementary Material for: Systematic Review of Blinding Assessment in Randomized Controlled Trials in Schizophrenia and Affective Disorders 2000-2010

description: <b><i>Background:</i></b> Blinding is an integral part of many randomized controlled trials (RCTs). However, both blinding and blinding assessment seem to be rarely documented in trial reports. <b><i>Method:</i></b> Systematic review of articles on RCTs in schizophrenia and affective disorders research during 2000-2010. <b><i>Results:</i></b> Among 2,467 publications, 61 (2.5%; 95% confidence interval: 1.9-3.1%) reported assessing participant, rater, or clinician blinding: 5/672 reports on schizophrenia (0.7%; 0.3-1.6%) and 33/1,079 (3.1%; 2.1-4.2%) on affective disorders, without significant trends across the decade. Rarely was blinding assessed at the beginning, in most studies assessment was at the end. Proportion of patients' and raters' correct guesses of study arm averaged 54.4 and 62.0% per study, with slightly more correct guesses in treatment arms than in placebo arms. Three fourths of responders correctly guessed that they received the active agent. Blinding assessment was more frequently reported in papers on psychotherapy and brain stimulation than on drug trials (5.1%, 1.7-11.9%, vs. 8.3%, 4.3-14.4%, vs. 2.1%, 1.5-2.8%). Lack of assessment of blinding was associated with: (a) positive findings, (b) full industrial sponsorship, and (c) diagnosis of schizophrenia. There was a moderate association of treatment success and blinding status of both trial participants (r = 0.51, p = 0.002) and raters (r = 0.55, p = 0.067). Many RCT reports did not meet CONSORT standards regarding documentation of persons blinded (60%) or of efforts to match interventions (50%). <b><i>Conclusions:</i></b> Recent treatment trials in major psychiatric disorders rarely reported on or evaluated blinding. We recommend routine documentation of blinding strategies in reports.
DOI: 10.6084/m9.figshare.5124415
title: Supplementary Material for: Differences in the Receptor Status between Primary and Recurrent Breast Cancer - The Frequency of and the Reasons for Discordance

description: <b><i>Objective:</i></b> Receptor discordances between primary and recurrent breast cancer have been described for years, but only a few analyses have elucidated the factors that influence receptor changes. <b><i>Methods:</i></b> Explorative analyses of prospective data from a breast cancer database of a tertiary breast cancer unit. <b><i>Results:</i></b> Recurrent tumours that had expressed oestrogen (ER) and progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) as primary tumours were negative for the respective receptor in 22.8, 41.4 and 40.8% of cases. ER, PR and HER2 expression was found in 19.8, 16.7 and 11.5% of recurrent tumours, although no expression had been observed in primary tumours. Receptor discordances in recurrent disease leading to different therapeutic approaches were noted in 126 of 411 patients (30.7%). In patients with tumours expressing primary ER and HER2, independent factors associated with discordance were endocrine therapy and treatment with trastuzumab. <b><i>Conclusion:</i></b> High rates of receptor discordance were found. The impact of factors that influence receptor changes is small so that no subgroup of patients with recurrent breast cancer should be excluded from biopsy. Whenever possible, a biopsy should be taken to confirm the diagnosis of a possible relapse as well as the receptor status of patients with breast cancer.
DOI: 10.6084/m9.figshare.5124403
title: Supplementary Material for: Longitudinal Measurements of Oxygen Consumption in Growing Infants during the First Weeks after Birth: Old Data Revisited

description: <b><i>Background:</i></b> In a study conducted in 1966–1969, longitudinal measurements were made of the metabolic rate in growing infants. Statistical methods for analyzing longitudinal data weren’t readily accessible at that time. <b><i>Objectives:</i></b> To measure minimal rates of oxygen consumption (V·O<sub>2</sub>, ml/min) in growing infants during the first postnatal weeks and to determine the relationships between postnatal increases in V·O<sub>2</sub>, body size and postnatal age. <b><i>Methods:</i></b> We studied 61 infants of any birth weight or gestational age, including 19 of very low birth weight. The infants, nursed in incubators, were clinically well and without need of oxygen supplementation or respiratory assistance. Serial measures of V·O<sub>2</sub> using a closed-circuit method were obtained at approximately weekly intervals. V·O<sub>2</sub> was measured under thermoneutral conditions with the infant asleep or resting quietly. Data were analyzed using mixed-effects models. <b><i>Results:</i></b> During early postnatal growth, V·O<sub>2</sub> rises as surface area (m<sup>2</sup>)<sup>1.94</sup> (standard error, SE 0.054) or body weight (kg)<sup>1.24</sup> (SE 0.033). Multivariate analyses show statistically significant effects of both size and age. Reference intervals (RIs) for V·O<sub>2</sub> for fixed values of body weight and postnatal age are presented. As V·O<sub>2</sub> rises with increasing size and age, there is an increase in the skin-operative environmental temperature gradient (T skin-op) required for heat loss. Required T skin-op can be predicted from surface area and heat loss (heat production minus heat storage). <b><i>Conclusions:</i></b> Generation of RIs for minimal rates of V·O<sub>2</sub> in growing infants from the 1960s was enabled by application of mixed-effects statistical models for analyses of longitudinal data. Results apply to the precaffeine era of neonatal care.