cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5124022
title: Supplementary Material for: Clopidogrel Two Doses Comparative 1-Year Assessment of Safety and Efficacy (COMPASS) Study in Japanese Patients with Ischemic Stroke

description: <b><i>Background:</i></b> Clopidogrel 75 mg once daily is licensed in Japan for the prevention of recurrent ischemic cerebrovascular events in adults as the usual dosage. However, a lower dose (50 mg) is an option in patients at an increased risk of bleeding depending on age, body weight and symptoms. This study compared the safety of both 75- and 50-mg doses of clopidogrel in patients with noncardioembolic ischemic stroke. <b><i>Methods:</i></b> This was a double-blind, double-dummy postmarketing clinical trial carried out across 118 Japanese institutions. Patients with an episode of noncardioembolic ischemic stroke at least 8 days prior to randomization, who were aged &lt;75 years or had a body weight &gt;50 kg were randomized to 50 or 75 mg clopidogrel once daily for 52 weeks. The primary endpoint was the incidence of bleeding adverse events. The secondary safety endpoints included the incidence of serious adverse events, serious bleeding adverse events and other prespecified adverse events. The secondary efficacy endpoint was the incidence of vascular events, including ischemic stroke, myocardial infarction, and peripheral artery disease. <b><i>Results:</i></b> A total of 1,110 patients were randomized to clopidogrel 50 mg (n = 558) or 75 mg (n = 552). No significant difference between the groups was detected in the incidence of bleeding adverse events, which was 14.0 and 16.5% in the clopidogrel 50- and 75-mg groups, respectively (hazard ratio = 0.831, 95% CI = 0.615–1.124, p = 0.2274). Additionally, there was no statistical difference with respect to any of the secondary safety endpoints. No significant difference between the groups was detected in the incidence of serious adverse events, which was 8.6 and 9.5% in the clopidogrel 50- and 75-mg groups, respectively (hazard ratio = 0.877, 95% CI = 0.597–1.289, p = 0.5035), and there was no significant difference between the groups in the incidence of serious bleeding events, which was 1.7 and 1.5% in the clopidogrel 50- and 75-mg groups, respectively (hazard ratio = 1.240, 95% CI = 0.489–3.142, p = 0.6496). The percentages of intracranial hemorrhage in the 50- and 75-mg groups were 0.18% (1/558) and 0.18% (1/552), respectively. The cumulative incidence of vascular events was somewhat lower in the 75-mg group, but was not statistically different (2.6 vs. 3.8%; p = 0.4118). <b><i>Conclusions:</i></b> Clopidogrel 75 mg provides a clinically acceptable safety profile and suggests better clinical benefit as compared to clopidogrel 50 mg for the secondary prevention of ischemic stroke in Japanese patients who are &lt;75 years old with a body weight &gt;50 kg, considering the balance of safety and efficacy on this trial.
DOI: 10.6084/m9.figshare.5124028.v1
title: Supplementary Material for: Using Ecological Niche Modelling to Predict Spatial and Temporal Distribution Patterns in Chinese Gibbons: Lessons from the Present and the Past

description: Ecological niche modelling (ENM) is used to predict species’ tolerance to changing environmental conditions. Understanding changes in the spatial distribution of species across time is essential in order to develop effective conservation strategies. Here we map the past and present distribution of gibbons across China, a country experiencing extensive anthropogenic habitat destruction and ongoing biodiversity loss. The distribution of gibbons across three time intervals is described based on fossil, historical and modern-day data, and ENM, implemented using DIVA-GIS, is used to predict how modern-day gibbon distributions might respond to future climate change. Predictions based on modern-day data alone fail to reveal patterns of environmental tolerance and geographical distribution shown by gibbons in the relatively recent historical period, emphasizing the need to incorporate past as well as present data in conservation analyses.
DOI: 10.6084/m9.figshare.5123998
title: Supplementary Material for: Genotype and Phenotype Predictors of Relapse of Graves’ Disease after Antithyroid Drug Withdrawal

description: <b><i>Background:</i></b> For patients with Graves’ disease (GD), the primary goal of antithyroid drug therapy is to temporarily restore the patient to the euthyroid state and wait for a subsequent remission of the disease. This study sought to identify the predictive markers for the relapse of disease. <b><i>Methods:</i></b> To do this, we studied 262 GD patients with long enough follow-up after drug withdrawal to determine treatment outcome. The patients were divided into three groups by time of relapse: early relapse group (n = 91) had an early relapse within 9 months, late relapse group (n = 65) had a relapse between 10 and 36 months, and long-term remission group (n = 106) were either still in remission after at least 3 years or relapsed after 3 years of drug withdrawal. We assessed the treatment outcome of 23 SNPs of costimulatory genes, phenotype and smoking habits. We used permutation to obtain p values for each SNP as an adjustment for multiple testing. Cox proportional hazards models was performed to assess the strength of association between the treatment outcome and clinical and laboratory variables. <b><i>Results:</i></b> Four SNPs were significantly associated with disease relapse: rs231775 (OR 1.96, 95% CI 1.18–3.26) at CTLA-4 and rs745307 (OR 7.97, 95% CI 1.01–62.7), rs11569309 (OR 8.09, 95% CI 1.03–63.7), and rs3765457 (OR 2.60, 95% CI 1.08–6.28) at CD40. Combining risk alleles at CTLA-4 and CD40 improved the predictability of relapse. Using 3 years as the cutoff point for multivariate analysis, we found several independent predictors of disease relapse: number of risk alleles (HR 1.30, 95% CI 1.09–1.56), a large goiter size at the end of the treatment (HR 1.30, 95% CI 1.05–1.61), persistent TSH-binding inhibitory Ig (HR 1.64, 95% CI 1.15–2.35), and smoking habit (HR 1.60, 95% CI 1.05–2.42). <b><i>Conclusion:</i></b> Genetic polymorphism of costimulatory genes, smoking status, persistent goiter, and TSH-binding inhibitory Ig predict disease relapse.
DOI: 10.6084/m9.figshare.5124022.v1
title: Supplementary Material for: Clopidogrel Two Doses Comparative 1-Year Assessment of Safety and Efficacy (COMPASS) Study in Japanese Patients with Ischemic Stroke

description: <b><i>Background:</i></b> Clopidogrel 75 mg once daily is licensed in Japan for the prevention of recurrent ischemic cerebrovascular events in adults as the usual dosage. However, a lower dose (50 mg) is an option in patients at an increased risk of bleeding depending on age, body weight and symptoms. This study compared the safety of both 75- and 50-mg doses of clopidogrel in patients with noncardioembolic ischemic stroke. <b><i>Methods:</i></b> This was a double-blind, double-dummy postmarketing clinical trial carried out across 118 Japanese institutions. Patients with an episode of noncardioembolic ischemic stroke at least 8 days prior to randomization, who were aged &lt;75 years or had a body weight &gt;50 kg were randomized to 50 or 75 mg clopidogrel once daily for 52 weeks. The primary endpoint was the incidence of bleeding adverse events. The secondary safety endpoints included the incidence of serious adverse events, serious bleeding adverse events and other prespecified adverse events. The secondary efficacy endpoint was the incidence of vascular events, including ischemic stroke, myocardial infarction, and peripheral artery disease. <b><i>Results:</i></b> A total of 1,110 patients were randomized to clopidogrel 50 mg (n = 558) or 75 mg (n = 552). No significant difference between the groups was detected in the incidence of bleeding adverse events, which was 14.0 and 16.5% in the clopidogrel 50- and 75-mg groups, respectively (hazard ratio = 0.831, 95% CI = 0.615–1.124, p = 0.2274). Additionally, there was no statistical difference with respect to any of the secondary safety endpoints. No significant difference between the groups was detected in the incidence of serious adverse events, which was 8.6 and 9.5% in the clopidogrel 50- and 75-mg groups, respectively (hazard ratio = 0.877, 95% CI = 0.597–1.289, p = 0.5035), and there was no significant difference between the groups in the incidence of serious bleeding events, which was 1.7 and 1.5% in the clopidogrel 50- and 75-mg groups, respectively (hazard ratio = 1.240, 95% CI = 0.489–3.142, p = 0.6496). The percentages of intracranial hemorrhage in the 50- and 75-mg groups were 0.18% (1/558) and 0.18% (1/552), respectively. The cumulative incidence of vascular events was somewhat lower in the 75-mg group, but was not statistically different (2.6 vs. 3.8%; p = 0.4118). <b><i>Conclusions:</i></b> Clopidogrel 75 mg provides a clinically acceptable safety profile and suggests better clinical benefit as compared to clopidogrel 50 mg for the secondary prevention of ischemic stroke in Japanese patients who are &lt;75 years old with a body weight &gt;50 kg, considering the balance of safety and efficacy on this trial.
DOI: 10.6084/m9.figshare.5123983
title: Supplementary Material for: Simultaneous and Sequential Concurrent Myeloproliferative and Lymphoproliferative Neoplasms

description: Concurrent manifestation of two chronic-stage myeloid and lymphoid/plasmacytoid neoplasms in one patient is rare and occurs in ≤1% of patients. There has been no systematic analysis of which combinations are frequent/infrequent and whether two concurrent diseases in one patient are clonally related or represent independent diseases. We therefore characterised a series of cases from our own archive (n = 65) and collected a large number of previously reported cases of patients in whom myeloid and lymphoid/plasmacytoid neoplasms co-occurred (n = 185). The most frequent combination was Philadelphia chromosome-negative myeloproliferative neoplasm with concurrent B cell chronic lymphocytic leukaemia, accounting for approximately 50% of double-disease patients. We compared the quantity of unsorted bone marrow cell-derived JAK2<sup>V617F</sup> and KIT<sup>D816V</sup> alleles with the quantity of the lymphoid/plasmacytoid compartment and analysed a subfraction of cases with fluorescence in situ hybridisation. Although a common aberrant progenitor has been reported in some cases in the literature, we found evidence of two independent chronic-stage myeloid and lymphoid/plasmacytoid neoplasms.
DOI: 10.6084/m9.figshare.5123989
title: Supplementary Material for: Pathways of Infusate Loss during Convection-Enhanced Delivery into the Putamen Nucleus

description: <b><i>Background:</i></b> New strategies aiming to treat Parkinson’s disease, such as delivery of trophic factors via protein infusion or gene transfer, depend upon localized intracerebral infusion, mainly into the putamen nucleus. Convection-enhanced delivery (CED) has been proposed as a method to improve intracerebral distribution of therapies. Yet analysis of controversial results during the clinical translation of these strategies suggests that intracerebral misdistribution of infusate may have affected the outcomes by limiting the amount of treatment into the target region. <b><i>Objectives:</i></b> This study aimed to identify possible pathways of infusate loss and their relative impact in the success of targeted CED into the postcommissural ventral putamen nucleus. <b><i>Methods:</i></b> Thirteen adult macaque monkeys received intraputaminal CED infusions of 100 µl of 2.0 mM gadoteridol and bromophenol blue (0.16 mg/ml) solution at a rate of 1.0 µl/min under intraoperative magnetic resonance imaging (MRI) guidance. Quantitative maps of infusate concentration were computed at 10-min intervals throughout the procedure in a 3-Tesla MRI scanner. The fraction of tracer lost from the putamen as well as the path of loss were evaluated and quantified for each infusion. <b><i>Results:</i></b> All injections (total 22) were successfully placed in the ventral postcommissural putamen nucleus. Four major paths of infusate loss from the putamen were observed: <i>overflow</i> across putamen boundaries, <i>perivascular flow</i> along large blood vessels, <i>backflow</i> along the inserted catheter and <i>catheter tract leakage</i> into the vacated catheter tract upon catheter removal. Overflow loss was observed within the first 30 µl of infusion in all cases. Measurable tracer loss following the path of an artery out of the putamen was observed in 15 cases, and in 8 of these cases, the loss was greater than 10% of infusate. Backflow that exited the putamen was observed in 4 cases and led to large loss of infusate (80% in 1 case) into the corona radiata. Loss into the vacated catheter tract amounted only to a few microliters. <b><i>Conclusions:</i></b> Our analysis demonstrates that after controlling for targeting, catheter type, infusion rate and infusate, the main issues during surgical planning are the identification of appropriate infusate volume that matches the target area, as well as mapping the regional vasculature as it may become a pathway for infusate loss. Most importantly, these results underscore the significance of presurgical planning for catheter placement and infusion, and the value of imaging guidance to ensure targeting accuracy.
DOI: 10.6084/m9.figshare.5123992
title: Supplementary Material for: Surfactant Protein A Associated with Respiratory Distress Syndrome in Korean Preterm Infants: Evidence of Ethnic Difference

description: <b><i>Background:</i></b> Insufficiency of the pulmonary surfactant system is the primary cause of respiratory distress syndrome (RDS) in preterm infants. Genetic factors, including specific single-nucleotide polymorphisms in the genetic components of surfactant protein A (SP-A1 and SP-A2), affect protein structure and function, as well as risk of RDS. <b><i>Objective:</i></b> We investigated the association between variations in SP-A genotypes and RDS within the genetically homogeneous Korean population. <b><i>Methods:</i></b> We used TaqMan® real-time polymerase chain reaction technology to assess nine single-nucleotide polymorphisms of SP-A in 261 full-term and 152 preterm infants. Among the preterm infants, 76 infants with RDS were matched with 76 control infants with respect to gestation, use of antenatal steroids and gender. <b><i>Results:</i></b> The SP-A2 1A⁰ variant and the homozygous 1A⁰/1A⁰ genotype were associated with protection from RDS (OR 0.31, 95% CI 0.13–0.78). In addition, the 1A<sup>1</sup> carrier genotype (containing one copy of the 1A<sup>1</sup> variant) was associated with increased risk of RDS (OR 2.42, 95% CI 1.06–5.52). The significance of these results is that the association of patterns with RDS was opposite to the findings of previous research with Finnish and North American study populations. <b><i>Conclusions:</i></b> We have identified associations between specific variants of the SP-A genes and RDS risk in the Korean preterm study population. Our data strongly support SP-A as a candidate gene for susceptibility to RDS, and reveal the dissimilarity of the associated risk/protective genetic variants between different ethnic study populations.
DOI: 10.6084/m9.figshare.5123986
title: Supplementary Material for: Spinal Transection Induces Widespread Proliferation of Cells along the Length of the Spinal Cord in a Weakly Electric Fish

description: The ability to regenerate spinal cord tissue after tail amputation has been well studied in several species of teleost fish. The present study examined the proliferation and survival of cells following complete spinal cord transection rather than tail amputation in the weakly electric fish <i>Apteronotus leptorhynchus</i>. To quantify cell proliferation along the length of the spinal cord, fish were given a single bromodeoxyuridine (BrdU) injection immediately after spinal transection or sham surgery. Spinal transection significantly increased the density of BrdU<sup>+</sup> cells along the entire length of the spinal cord at 1 day posttransection (dpt), and most newly generated cells survived up to 14 dpt. To examine longer-term survival of the newly proliferated cells, BrdU was injected for 5 days after the surgery, and fish were sacrificed at 14 or 30 dpt. Spinal transection significantly increased cell proliferation and/or survival, as indicated by an elevated density of BrdU<sup>+</sup> cells in the spinal cords of spinally transected compared to sham-operated and intact fish. At 14 dpt, BrdU<sup>+</sup> cells were abundant at all levels of the spinal cord. By 30 dpt, the density of BrdU<sup>+</sup> cells had decreased at all levels of the spinal cord except at the tip of the tail. Thus, newly generated cells in the caudal-most segment of the spinal cord survived longer than those in more rostral segments. Our findings indicate that spinal cord transection stimulates widespread cellular proliferation; however, there were regional differences in the survival of the newly generated cells.
DOI: 10.6084/m9.figshare.5123989.v1
title: Supplementary Material for: Pathways of Infusate Loss during Convection-Enhanced Delivery into the Putamen Nucleus

description: <b><i>Background:</i></b> New strategies aiming to treat Parkinson’s disease, such as delivery of trophic factors via protein infusion or gene transfer, depend upon localized intracerebral infusion, mainly into the putamen nucleus. Convection-enhanced delivery (CED) has been proposed as a method to improve intracerebral distribution of therapies. Yet analysis of controversial results during the clinical translation of these strategies suggests that intracerebral misdistribution of infusate may have affected the outcomes by limiting the amount of treatment into the target region. <b><i>Objectives:</i></b> This study aimed to identify possible pathways of infusate loss and their relative impact in the success of targeted CED into the postcommissural ventral putamen nucleus. <b><i>Methods:</i></b> Thirteen adult macaque monkeys received intraputaminal CED infusions of 100 µl of 2.0 mM gadoteridol and bromophenol blue (0.16 mg/ml) solution at a rate of 1.0 µl/min under intraoperative magnetic resonance imaging (MRI) guidance. Quantitative maps of infusate concentration were computed at 10-min intervals throughout the procedure in a 3-Tesla MRI scanner. The fraction of tracer lost from the putamen as well as the path of loss were evaluated and quantified for each infusion. <b><i>Results:</i></b> All injections (total 22) were successfully placed in the ventral postcommissural putamen nucleus. Four major paths of infusate loss from the putamen were observed: <i>overflow</i> across putamen boundaries, <i>perivascular flow</i> along large blood vessels, <i>backflow</i> along the inserted catheter and <i>catheter tract leakage</i> into the vacated catheter tract upon catheter removal. Overflow loss was observed within the first 30 µl of infusion in all cases. Measurable tracer loss following the path of an artery out of the putamen was observed in 15 cases, and in 8 of these cases, the loss was greater than 10% of infusate. Backflow that exited the putamen was observed in 4 cases and led to large loss of infusate (80% in 1 case) into the corona radiata. Loss into the vacated catheter tract amounted only to a few microliters. <b><i>Conclusions:</i></b> Our analysis demonstrates that after controlling for targeting, catheter type, infusion rate and infusate, the main issues during surgical planning are the identification of appropriate infusate volume that matches the target area, as well as mapping the regional vasculature as it may become a pathway for infusate loss. Most importantly, these results underscore the significance of presurgical planning for catheter placement and infusion, and the value of imaging guidance to ensure targeting accuracy.
DOI: 10.6084/m9.figshare.5123992.v1
title: Supplementary Material for: Surfactant Protein A Associated with Respiratory Distress Syndrome in Korean Preterm Infants: Evidence of Ethnic Difference

description: <b><i>Background:</i></b> Insufficiency of the pulmonary surfactant system is the primary cause of respiratory distress syndrome (RDS) in preterm infants. Genetic factors, including specific single-nucleotide polymorphisms in the genetic components of surfactant protein A (SP-A1 and SP-A2), affect protein structure and function, as well as risk of RDS. <b><i>Objective:</i></b> We investigated the association between variations in SP-A genotypes and RDS within the genetically homogeneous Korean population. <b><i>Methods:</i></b> We used TaqMan® real-time polymerase chain reaction technology to assess nine single-nucleotide polymorphisms of SP-A in 261 full-term and 152 preterm infants. Among the preterm infants, 76 infants with RDS were matched with 76 control infants with respect to gestation, use of antenatal steroids and gender. <b><i>Results:</i></b> The SP-A2 1A⁰ variant and the homozygous 1A⁰/1A⁰ genotype were associated with protection from RDS (OR 0.31, 95% CI 0.13–0.78). In addition, the 1A<sup>1</sup> carrier genotype (containing one copy of the 1A<sup>1</sup> variant) was associated with increased risk of RDS (OR 2.42, 95% CI 1.06–5.52). The significance of these results is that the association of patterns with RDS was opposite to the findings of previous research with Finnish and North American study populations. <b><i>Conclusions:</i></b> We have identified associations between specific variants of the SP-A genes and RDS risk in the Korean preterm study population. Our data strongly support SP-A as a candidate gene for susceptibility to RDS, and reveal the dissimilarity of the associated risk/protective genetic variants between different ethnic study populations.
DOI: 10.6084/m9.figshare.5123998.v1
title: Supplementary Material for: Genotype and Phenotype Predictors of Relapse of Graves’ Disease after Antithyroid Drug Withdrawal

description: <b><i>Background:</i></b> For patients with Graves’ disease (GD), the primary goal of antithyroid drug therapy is to temporarily restore the patient to the euthyroid state and wait for a subsequent remission of the disease. This study sought to identify the predictive markers for the relapse of disease. <b><i>Methods:</i></b> To do this, we studied 262 GD patients with long enough follow-up after drug withdrawal to determine treatment outcome. The patients were divided into three groups by time of relapse: early relapse group (n = 91) had an early relapse within 9 months, late relapse group (n = 65) had a relapse between 10 and 36 months, and long-term remission group (n = 106) were either still in remission after at least 3 years or relapsed after 3 years of drug withdrawal. We assessed the treatment outcome of 23 SNPs of costimulatory genes, phenotype and smoking habits. We used permutation to obtain p values for each SNP as an adjustment for multiple testing. Cox proportional hazards models was performed to assess the strength of association between the treatment outcome and clinical and laboratory variables. <b><i>Results:</i></b> Four SNPs were significantly associated with disease relapse: rs231775 (OR 1.96, 95% CI 1.18–3.26) at CTLA-4 and rs745307 (OR 7.97, 95% CI 1.01–62.7), rs11569309 (OR 8.09, 95% CI 1.03–63.7), and rs3765457 (OR 2.60, 95% CI 1.08–6.28) at CD40. Combining risk alleles at CTLA-4 and CD40 improved the predictability of relapse. Using 3 years as the cutoff point for multivariate analysis, we found several independent predictors of disease relapse: number of risk alleles (HR 1.30, 95% CI 1.09–1.56), a large goiter size at the end of the treatment (HR 1.30, 95% CI 1.05–1.61), persistent TSH-binding inhibitory Ig (HR 1.64, 95% CI 1.15–2.35), and smoking habit (HR 1.60, 95% CI 1.05–2.42). <b><i>Conclusion:</i></b> Genetic polymorphism of costimulatory genes, smoking status, persistent goiter, and TSH-binding inhibitory Ig predict disease relapse.