cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123269.v1
title: Supplementary Material for: Osteoporosis-Pseudoglioma Syndrome: Three Novel Mutations in the <i>LRP5 </i>Gene and Response to Bisphosphonate Treatment

description: <i>Background/Aims:</i> Osteoporosis-pseudoglioma (OPPG) syndrome is a rare disorder characterized by congenital or infancy-onset visual loss and severe juvenile osteoporosis. OPPG is caused by homozygous mutations in the low-density lipoprotein receptor-related protein 5 <i>(LRP5) </i>gene. We present three novel homozygous <i>LRP5 </i>mutations found in 3 unrelated Turkish children with consanguineous parents, along with clinical phenotypes and response to treatment with bisphosphonates (bisP). <i>Methods/Results:</i> The <i>LRP5 </i>gene was analyzed by direct sequencing after PCR amplification. Mutation screening for <i>LRP5</i> revealed homozygous nonsense R1002X mutation in the first patient and homozygous missense mutations V336M and G507S in the second and third patient, respectively. The parents were heterozygous for these mutations. The patients’ eye symptoms began during the first months of life but the OPPG diagnoses were made based on skeletal deformities and osteopenia after 4 years of age. The patients’ bone mineral density Z scores were very low and consistent with osteopenia. All patients were treated with bisP for 3.5–7 years. <i>Conclusion:</i> We report three novel <i>LRP5 </i>mutations in 3 Turkish patients with OPPG. We show that the response of bisP therapy has improved the lumbar spinal bone mineral density Z scores and the patients’ quality of life as the bone pains decreased.
DOI: 10.6084/m9.figshare.5123272
title: Supplementary Material for: Alternative Methods for H1 Simulations in Genome-Wide Association Studies

description: <i>Objective:</i> Assessing the statistical power to detect susceptibility variants plays a critical role in genome-wide association (GWA) studies both from the prospective and retrospective point of view. Power is empirically estimated by simulating phenotypes under a disease model H1. For this purpose, the gold standard consists in simulating genotypes given the phenotypes (e.g.Hapgen). We introduce here an alternative approach for simulating phenotypes under H1 that does not require generating new genotypes for each simulation. <i>Methods:</i> In order to simulate phenotypes with a fixed total number of cases and under a given disease model, we suggest 3 algorithms: (1) a simple rejection algorithm; (2) a numerical Markov chain Monte-Carlo (MCMC) approach, and (3) an exact and efficient backward sampling algorithm. In our study, we validated the 3 algorithms both on a simulated dataset and by comparing them with Hapgen on a more realistic dataset. For an application, we then conducted a simulation study on a 1000 Genomes Project dataset consisting of 629 individuals (314 cases) and 8,048 SNPs from chromosome X. We arbitrarily defined an additive disease model with two susceptibility SNPs and an epistatic effect. <i>Results:</i> The 3 algorithms are consistent, but backward sampling is dramatically faster than the other two. Our approach also gives consistent results with Hapgen. Using our application data, we showed that our limited design requires a biological a priori to limit the investigated region. We also proved that epistatic effects can play a significant role even when simple marker statistics (e.g. trend) are used. We finally showed that the overall performance of a GWA study strongly depends on the prevalence of the disease: the larger the prevalence, the better the power. <i>Conclusions:</i> Our approach is a valid alternative to Hapgen-type methods; it is not only dramatically faster but has 2 main advantages: (1) there is no need for sophisticated genotype models (e.g. haplotype frequencies, or recombination rates), and (2) the choice of the disease model is completely unconstrained (number of SNPs involved, gene-environment interactions, hybrid genetic models, etc.). Our 3 algorithms are available in an R package called ‘waffect’ (‘double-u affect’, for weighted affectations).
DOI: 10.6084/m9.figshare.5123281.v1
title: Supplementary Material for: Corpus Callosotomy with the CO<sub>2</sub> Laser Suction Device: A Technical Note

description: <i>Introduction:</i> Patients with symptomatic generalized epilepsy who are not candidates for resections may be considered for corpus callosotomy. <i>Methods:</i> The two patients who were followed in this series underwent resection of the corpus callosum utilizing the OmniGuide CO<sub>2</sub> Laser System. <i>Surgical Technique:</i> The OmniGuide CO<sub>2</sub> Laser Systemcan be used in place of the bipolar electrocautery in a corpus callosotomy to improve midline dissection, decrease the likelihood of entering the ventricle, and improve visualization in the dissection. <i>Conclusion:</i> The OmniGuide CO<sub>2</sub> Laser System is a valuable option when performing a corpus callosotomy.
DOI: 10.6084/m9.figshare.5123263
title: Supplementary Material for: Irinotecan-Induced Dysarthria

description: Colorectal carcinomas are among the most common tumor types and are generally treated with palliative chemotherapy in case of metastatic disease. Here, we describe the case of a 46-year-old patient with metastatic rectal carcinoma who received second-line therapy with irinotecan and developed isolated transient dysarthria (with normal MR imaging of the brain) following each administration of irinotecan. Neurological and logopedical evaluation revealed that the dysarthria predominantly resulted from a reduced capacity in fine-tuning of motor functions of the tip of the tongue and a minimal reduction in the power of speech at labiodental contact. As hypoglossal nerve activity has been reported to be especially susceptible to cholinergic stimulation and irinotecan can cause cholinergic side effects by binding to and inactivating acetylcholinesterase, we suspect this mechanism to be responsible for irinotecan-induced dysarthria.
DOI: 10.6084/m9.figshare.5123266
title: Supplementary Material for: Cerebral Embolism Associated with Left Atrial Myxoma That Was Treated with Thrombolytic Therapy

description: We present a case of cerebral embolism associated with a left atrial myxoma that was treated with intravenous thrombolytic therapy. A 79-year-old right-handed man with no history of neurological or psychiatric illnesses was referred to our hospital because of confusion. He had been self-supported in the activity of daily living and could enjoy gardening until just before his admission. He had aphasia, left conjugate deviation, right hemiparesis, and right pathological reflexes. His NIHSS score was 24. Cranial DWI showed hyperintense lesions in the left middle cerebral artery territory, and MRA revealed left middle cerebral artery occlusion. We started treatment with the recombinant tissue plasminogen activator alteplase intravenously 3 h after the onset. However, the therapy was ineffective, and the NIHSS score was 25 on the second day. A transthoracic echocardiogram and heart MRI showed a left atrial myxoma. However, surgery was contraindicated because of the patient’s poor general condition. Although intravenous recombinant tissue plasminogen activator is a reasonable treatment for stroke patients, even with a cardiac myxoma, we cannot always expect good effects, especially if the emboli are parts of the tumor itself. In this case, we could not perform an endovascular mechanical embolectomy; however, we speculate that mechanical embolus retrieval in cerebral ischemia might be effective in such cases.
DOI: 10.6084/m9.figshare.5123275.v1
title: Supplementary Material for: Elevated Temperature Applied during Gonadal Transformation Leads to Male Bias in Zebrafish <b><i>(Danio rerio)</i></b>

description: Temperature effects on sex determination or differentiation exist in many fish species, with high temperatures predominantly producing more males. The present study aimed at elucidating the genetic background of temperature effects on sex differentiation in zebrafish. Experimental fish were generated by matings between 4 or 6 golden females and a normal or a mitotic gynogenetic male, respectively. All the larvae were reared at 28.5°C until they were divided into 3 groups per full-sib family, a control group raised at 28.5°C and 2 treatment groups reared at 35°C from 20 to 30 dpf or 25 to 35 dpf, respectively. Backcross progenies, reared at 28.5°C, were derived from F1 temperature-treated sons (35°C, 25–35 dpf) that were sired by a mitotic gynogenetic male and their corresponding mothers. No significant differences were observed regarding the survival rate between the control and treatment groups. Significant differences in the phenotypic male proportions from the controls were observed in groups treated at 35°C. The sex ratio in zebrafish was influenced by the male spawner, the female spawner, and a significant interaction of genotype by temperature. Backcross experiments point to a continuum of major genetic, minor genetic, and environmental factors in the expression of the phenotypic sex in zebrafish.
DOI: 10.6084/m9.figshare.5123260
title: Supplementary Material for: A Population-Based Prospective 24-Month Study of Stroke: Incidence and 30-Day Case-Fatality Rates of First-Ever Strokes in Croatia

description: <i>Background:</i> In Central/Eastern European countries, cerebrovascular diseases are among the leading causes of mortality. We aimed to determine the incidence of first-ever stroke (FES) in the north-western part of Croatia. <i>Methods:</i> A population-based prospective incidence study was conducted between July 1, 2007, and June 30, 2009. Cases were sought from multiple overlapping sources. Incidence rates by stroke type and gender were calculated. <i>Results:</i> A total of 1,487 events were recorded, 1,017 of which were FESs. European age-adjusted incidence rates (per 100,000 population) were: total FESs 223.6 [women/men rate ratio (w/m RR) = 0.65 (95% CI 0.57–0.73)]; ischemic stroke 162.4 (w/m RR = 0.65, 0.56–0.76); intracerebral hemorrhage 28.4 (w/m RR = 0.44, 0.30–0.63); subarachnoid hemorrhage 7.2 (w/m RR = 1.18, 0.55–2.54); unknown etiology 25.5 (w/m RR = 0.78, 0.54–1.14). Adjusted incidence rates of ischemic strokes by subtype were: cardioembolic 52.9 (w/m RR = 0.77, 0.59–0.99); large-artery atherosclerosis 14.4 (w/m RR = 0.22, 0.13–0.38); small-artery occlusion 24.5 (w/m RR = 0.53, 0.37–0.77) and ‘other or uncertain causes’ 70.6 (w/m RR = 0.77, 0.62–0.97). Thirty-day case-fatality rate was 23.5% overall and 17.1% for ischemic stroke. <i>Conclusions:</i> The incidence of FES and 30-day mortality of patients with ischemic strokes in the studied population is higher than in Western European countries.
DOI: 10.6084/m9.figshare.5123263.v1
title: Supplementary Material for: Irinotecan-Induced Dysarthria

description: Colorectal carcinomas are among the most common tumor types and are generally treated with palliative chemotherapy in case of metastatic disease. Here, we describe the case of a 46-year-old patient with metastatic rectal carcinoma who received second-line therapy with irinotecan and developed isolated transient dysarthria (with normal MR imaging of the brain) following each administration of irinotecan. Neurological and logopedical evaluation revealed that the dysarthria predominantly resulted from a reduced capacity in fine-tuning of motor functions of the tip of the tongue and a minimal reduction in the power of speech at labiodental contact. As hypoglossal nerve activity has been reported to be especially susceptible to cholinergic stimulation and irinotecan can cause cholinergic side effects by binding to and inactivating acetylcholinesterase, we suspect this mechanism to be responsible for irinotecan-induced dysarthria.
DOI: 10.6084/m9.figshare.5123266.v1
title: Supplementary Material for: Cerebral Embolism Associated with Left Atrial Myxoma That Was Treated with Thrombolytic Therapy

description: We present a case of cerebral embolism associated with a left atrial myxoma that was treated with intravenous thrombolytic therapy. A 79-year-old right-handed man with no history of neurological or psychiatric illnesses was referred to our hospital because of confusion. He had been self-supported in the activity of daily living and could enjoy gardening until just before his admission. He had aphasia, left conjugate deviation, right hemiparesis, and right pathological reflexes. His NIHSS score was 24. Cranial DWI showed hyperintense lesions in the left middle cerebral artery territory, and MRA revealed left middle cerebral artery occlusion. We started treatment with the recombinant tissue plasminogen activator alteplase intravenously 3 h after the onset. However, the therapy was ineffective, and the NIHSS score was 25 on the second day. A transthoracic echocardiogram and heart MRI showed a left atrial myxoma. However, surgery was contraindicated because of the patient’s poor general condition. Although intravenous recombinant tissue plasminogen activator is a reasonable treatment for stroke patients, even with a cardiac myxoma, we cannot always expect good effects, especially if the emboli are parts of the tumor itself. In this case, we could not perform an endovascular mechanical embolectomy; however, we speculate that mechanical embolus retrieval in cerebral ischemia might be effective in such cases.
DOI: 10.6084/m9.figshare.5123251
title: Supplementary Material for: Smoking Is Not a Risk Factor for Sporadic Amyotrophic Lateral Sclerosis in an Australian Population

description: <i>Background:</i> Controversy persists as to whether smoking is a risk factor for sporadic amyotrophic lateral sclerosis (SALS), the most common form of sporadic motor neuron disease (SMND). We therefore undertook a large case-control study of smoking and SALS in Australia. <i>Methods:</i> Cases and controls were recruited Australia-wide over a 10-year period. SALS and the other subgroups of SMND were categorised on the basis of neurologists’ reports. Controls were partners or friends of SMND patients or community volunteers. Individuals filled in a questionnaire regarding smoking habits. A total of 809 patients with SMND (631 with SALS) and 779 controls were included in the study. SALS males and females were analysed separately. <i>Results:</i> No differences between SALS patients and control groups were found with regard to (1) the odds ratios of ever-smokers, ex-smokers or current smokers compared to never-smokers, (2) the means of numbers of cigarettes per day, years of smoking, pack years or age smoking began or (3) the proportions of their parents who had ever smoked. The proportion of ever-smokers and mean pack years did not differ between the clinical subgroups of SMND or between different sites of SALS onset. Partner smoking did not increase the risk of SMND. <i>Conclusion:</i> This Australian case-control study does not support a link between cigarette smoking and any form of SMND.
DOI: 10.6084/m9.figshare.5123254
title: Supplementary Material for: Curcumin Requires Tumor Necrosis Factor α Signaling to Alleviate Cognitive Impairment Elicited by Lipopolysaccharide

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

description: <i>Background/Aims:</i> The aim of this study was to gain insight into those proteins that might be involved in the early stages of liver fat accumulation as a consequence of a different fat versus simple sugar dietary intake. <i>Methods:</i> Forty-five male Wistar rats were randomly distributed into four dietary groups: a starch-rich control diet (CD; n = 10), a high-fat diet (n = 12), a high-sucrose diet (n = 11), and a high-fat sucrose diet (HFSD; n = 12) for 5 weeks. A comparative analysis by 2D-DIGE and LC-ESI-MS/MS was performed to characterize the liver protein expression profiles due to the three obesogenic diets. <i>Results:</i> Ten out of 17 proteins whose expression levels were altered by &gt;1.25-fold were identified. Four proteins (Hspa8, Hspa9, Ca3, and Cat) were differentially expressed after the HFSD period compared to CD. The heat shock proteins (Hspa8 and Hspa9) resulted significantly downregulated in liver from rats fed HFSD versus CD (p &lt; 0.05). The results were confirmed by Western blot. <i>Conclusions:</i> This descriptive study might be useful for further studies aiming at understanding the mechanisms by which diets rich in both fat and sugar affect the initiation of hepatic steatosis.
DOI: 10.6084/m9.figshare.5123260.v1
title: Supplementary Material for: A Population-Based Prospective 24-Month Study of Stroke: Incidence and 30-Day Case-Fatality Rates of First-Ever Strokes in Croatia

description: <i>Background:</i> In Central/Eastern European countries, cerebrovascular diseases are among the leading causes of mortality. We aimed to determine the incidence of first-ever stroke (FES) in the north-western part of Croatia. <i>Methods:</i> A population-based prospective incidence study was conducted between July 1, 2007, and June 30, 2009. Cases were sought from multiple overlapping sources. Incidence rates by stroke type and gender were calculated. <i>Results:</i> A total of 1,487 events were recorded, 1,017 of which were FESs. European age-adjusted incidence rates (per 100,000 population) were: total FESs 223.6 [women/men rate ratio (w/m RR) = 0.65 (95% CI 0.57–0.73)]; ischemic stroke 162.4 (w/m RR = 0.65, 0.56–0.76); intracerebral hemorrhage 28.4 (w/m RR = 0.44, 0.30–0.63); subarachnoid hemorrhage 7.2 (w/m RR = 1.18, 0.55–2.54); unknown etiology 25.5 (w/m RR = 0.78, 0.54–1.14). Adjusted incidence rates of ischemic strokes by subtype were: cardioembolic 52.9 (w/m RR = 0.77, 0.59–0.99); large-artery atherosclerosis 14.4 (w/m RR = 0.22, 0.13–0.38); small-artery occlusion 24.5 (w/m RR = 0.53, 0.37–0.77) and ‘other or uncertain causes’ 70.6 (w/m RR = 0.77, 0.62–0.97). Thirty-day case-fatality rate was 23.5% overall and 17.1% for ischemic stroke. <i>Conclusions:</i> The incidence of FES and 30-day mortality of patients with ischemic strokes in the studied population is higher than in Western European countries.
DOI: 10.6084/m9.figshare.5123245
title: Supplementary Material for: Efficacy of Bevacizumab plus Erlotinib for Advanced Hepatocellular Carcinoma and Predictors of Outcome: Final Results of a Phase II Trial

description: <i>Objective:</i> A phase II study was performed to evaluate the efficacy and tolerability of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) patients, and to investigate clinical and molecular predictors of outcome. <i>Methods:</i> 59 patients with advanced HCC received 10 mg/kg i.v. of bevacizumab every 14 days and 150 mg p.o. of erlotinib daily. The primary endpoint was progression-free survival (PFS) at 16 weeks. Clinical characteristics and plasma biomarkers expression levels were analyzed. <i>Results:</i> PFS at 16 weeks was 64% (95% CI 51–76): 14 patients achieved partial response (24%), 33 had stable disease (56%), 6 progressed (10%), and 6 were not evaluable (10%). Median overall survival was 13.7 months (95% CI 9.6–19.7), and median PFS was 7.2 months (95% CI 5.6–8.3). Grade 3–4 adverse events included fatigue (30%), diarrhea (17%), hypertension (14%), elevated transaminases (12%), and gastrointestinal hemorrhage (10%). High plasma angiopoietin-2, epidermal growth factor receptor, and endothelin-1, and lack of acneiform rash were associated with poor outcome. <i>Conclusions:</i> The combination of bevacizumab with erlotinib achieved encouraging results in patients with advanced HCC. Current correlatives may help to guide future HCC studies.
DOI: 10.6084/m9.figshare.5123251.v1
title: Supplementary Material for: Smoking Is Not a Risk Factor for Sporadic Amyotrophic Lateral Sclerosis in an Australian Population

description: <i>Background:</i> Controversy persists as to whether smoking is a risk factor for sporadic amyotrophic lateral sclerosis (SALS), the most common form of sporadic motor neuron disease (SMND). We therefore undertook a large case-control study of smoking and SALS in Australia. <i>Methods:</i> Cases and controls were recruited Australia-wide over a 10-year period. SALS and the other subgroups of SMND were categorised on the basis of neurologists’ reports. Controls were partners or friends of SMND patients or community volunteers. Individuals filled in a questionnaire regarding smoking habits. A total of 809 patients with SMND (631 with SALS) and 779 controls were included in the study. SALS males and females were analysed separately. <i>Results:</i> No differences between SALS patients and control groups were found with regard to (1) the odds ratios of ever-smokers, ex-smokers or current smokers compared to never-smokers, (2) the means of numbers of cigarettes per day, years of smoking, pack years or age smoking began or (3) the proportions of their parents who had ever smoked. The proportion of ever-smokers and mean pack years did not differ between the clinical subgroups of SMND or between different sites of SALS onset. Partner smoking did not increase the risk of SMND. <i>Conclusion:</i> This Australian case-control study does not support a link between cigarette smoking and any form of SMND.