cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5128339.v1
title: Supplementary Material for: Description of the SAGhE Cohort: A Large European Study of Mortality and Cancer Incidence Risks after Childhood Treatment with Recombinant Growth Hormone

description: <b><i>Background:</i></b> The long-term safety of growth hormone treatment is uncertain. Raised risks of death and certain cancers have been reported inconsistently, based on limited data or short-term follow-up by pharmaceutical companies. <b><i>Patients and Methods:</i></b> The SAGhE (Safety and Appropriateness of Growth Hormone Treatments in Europe) study assembled cohorts of patients treated in childhood with recombinant human growth hormone (r-hGH) in 8 European countries since the first use of this treatment in 1984 and followed them for cause-specific mortality and cancer incidence. Expected rates were obtained from national and local general population data. The cohort consisted of 24,232 patients, most commonly treated for isolated growth failure (53%), Turner syndrome (13%) and growth hormone deficiency linked to neoplasia (12%). This paper describes in detail the study design, methods and data collection and discusses the strengths, biases and weaknesses consequent on this. <b><i>Conclusion:</i></b> The SAGhE cohort is the largest and longest follow-up cohort study of growth hormone-treated patients with follow-up and analysis independent of industry. It forms a major resource for investigating cancer and mortality risks in r-hGH patients. The interpretation of SAGhE results, however, will need to take account of the methods of cohort assembly and follow-up in each country.
DOI: 10.6084/m9.figshare.5128324
title: Supplementary Material for: Development of the Avian Dorsal Thalamus: Patterns and Gradients of Neurogenesis

description: The dorsal thalamus is a region of the diencephalon that relays sensory and motor information between areas of the brain stem and the telencephalon. Although a dorsal thalamic region is recognized in all vertebrates and believed to be homologous, little is known about how the regions within it evolved and whether some or all regions within the dorsal thalamus are homologous among different vertebrate species. To characterize the gradients and patterns of neurogenesis of the avian dorsal thalamus, a single application of a low dose of bromodeoxyuridine (BrdU) was delivered to each chick between embryonic day (E)3 and E8 (stages 21 and 34), and chicks were followed up to E8 or E10 (stage 34 or 36). Comparisons of anti-BrdU labeling patterns across the different injection days suggest that nearly all dorsal thalamic neurons are born early in chick embryogenesis, between E3 and E8. Furthermore, neurons in the lateral, dorsal, and posterior parts of the dorsal thalamus are generally born earlier than those in the medial, ventral, and anterior parts. Analyses of the birth dates for nine regions show that the general pattern of neurogenesis in the avian dorsal thalamus resembles that of homologous regions within the rodent thalamus, with the exception of the auditory region, the nucleus ovoidalis, which is born later than the mammalian auditory medial geniculate nucleus. The similar pattern of neurogenesis in birds and mammals may represent a highly conserved developmental pattern that was present in the common ancestor of living birds and mammals, or may represent independently derived states. Additional studies in reptiles and amphibians are needed to distinguish between these evolutionary histories.
DOI: 10.6084/m9.figshare.5128327
title: Supplementary Material for: Cell and Tissue Damage after Skin Exposure to Ionizing Radiation: Short- and Long-Term Effects after a Single and Fractional Doses

description: Ionizing radiation is often used to treat progressive neoplasms. However, the consequences of long-term radiation exposure to healthy skin tissue are poorly understood. We aimed to evaluate the short- and long-term radiation damage to healthy skin of the same irradiation given either as single or fractional doses. C57BL/J6 mice were randomly assigned to one of three groups: a control and two exposure groups (5 Gy ×2 or 10 Gy ×1). The inguinal area was irradiated (6-MeV beam) 1 week after depilation in the treatment groups. Skin samples were evaluated macroscopically and histologically for up to 6 months after the final exposure. After anagen hair follicle injury by irradiation, hair cycling resumed in both groups, but hair graying was observed in the 10 Gy ×1 group but not in the 5 Gy ×2 group, suggesting the dose of each fractional exposure is more relevant to melanocyte stem cell damage than the total dose. On the other hand, in the long term, the fractional double exposures induced more severe atrophy and capillary reduction in the dermis and subcutis, suggesting fractional exposure may cause more depletion of tissue stem cells and endothelial cells in the tissue. Thus, our results indicated that there were differences between the degrees of damage that occurred as a result of a single exposure compared with fractional exposures to ionizing radiation: the former induces more severe acute injury to the skin with irreversible depigmentation of hairs, while the latter induces long-term damage to the dermis and subcutis.
DOI: 10.6084/m9.figshare.5128336.v1
title: Supplementary Material for: Rapid Diagnosis of Imprinting Disorders Involving Copy Number Variation and Uniparental Disomy Using Genome-Wide SNP Microarrays

description: Imprinting disorders, such as Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS) and Angelman syndrome (AS), can be detected via methylation analysis, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), or other methods. In this study, we applied single nucleotide polymorphism (SNP)-based chromosomal microarray analysis to detect copy number variations (CNVs) and uniparental disomy (UPD) events in patients with suspected imprinting disorders. Of 4 patients, 2 had a 5.25-Mb microdeletion in the 15q11.2q13.2 region, 1 had a 38.4-Mb mosaic UPD in the 11p15.4 region, and 1 had a 60-Mb detectable UPD between regions 14q13.2 and 14q32.13. Although the 14q32.2 region was classified as normal by SNP array for the 14q13 UPD patient, it turned out to be a heterodisomic UPD by short tandem repeat marker analysis. MS-MLPA analysis was performed to validate the variations. In conclusion, SNP-based microarray is an efficient alternative method for quickly and precisely diagnosing PWS, AS, BWS, and other imprinted gene-associated disorders when considering aberrations due to CNVs and most types of UPD.
DOI: 10.6084/m9.figshare.5128321
title: Supplementary Material for: Declining Estimated Glomerular Filtration Rate and Its Association with Mortality and Comorbidity Over 10 Years in Elderly Women

description: <b><i>Background/Aims:</i></b> Renal function deteriorates with age, but a few studies have addressed this longitudinally in elderly women. Our objective was, using 5 estimated glomerular filtration rates (eGFR)-equations, to evaluate changes in renal function and association with adverse outcomes for a decade in 75-year-old women. <b><i>Methods:</i></b> Plasma creatinine was measured at ages 75 (n = 1,011), 78 (n = 827), 80 (n = 689) and 85 (n = 363). Glomerular filtration rates were estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI); Modification of Diet in Renal Disease (MDRD); revised Lund-Malmö (LM-rev); Berlin Initiative Study 1 (BIS1) and Cockcroft-Gault/body surface area (CG/BSA) equations. Mortality and comorbidity were investigated in women with chronic kidney disease (CKD) stage 3A and 3B-5. <b><i>Results:</i></b> Approximately, 95% of women had eGFR indicating CKD stage 2-3 and progression towards stage 3 was continuous. The women lost 22% of their eGFR during follow-up and loss accelerated between 80 and 85. Mean loss per decade was 16.6 ml/min/1.73 m<sup>2</sup>. Women in CKD stage 3B-5 had an adjusted hazard ratio for death of 3.5 (95% CI 2.1-5.8) compared to stage 1-2 during follow-up and increased risk of diabetes, heart failure and hypertension. The CG/BSA, BIS1 and LM-rev equations continuously predicted lower eGFR than the MDRD and CKD-EPI equations. <b><i>Conclusion:</i></b> eGFR in women aged 75-85 ranges from 30 to 89 ml/min/1.73 m<sup>2</sup> (stage 2-3). Decline was 16.6 ml/min/1.73 m<sup>2</sup> per decade; accelerated with age and appeared nonlinear. Women with CKD 3B-5 demonstrate an over 3-fold risk of death. eGFR &lt;45 ml/min/1.73 m<sup>2</sup> was associated with mortality, confirming the new KDIGO classification 3A and 3B, as clinically applicable in the elderly.
DOI: 10.6084/m9.figshare.5128315
title: Supplementary Material for: Relationships between Cognitive Performance, Neuroimaging and Vascular Disease: The DHS-MIND Study

description: <b><i>Background:</i></b> Type 2 diabetes mellitus increases the risk of cognitive decline and dementia, and elevated burdens of vascular disease are hypothesized to contribute to this risk. These relationships were examined in the Diabetes Heart Study-MIND using a battery of cognitive tests, neuroimaging measures and subclinical cardiovascular disease (CVD) burden assessed by coronary artery calcified (CAC) plaque. We hypothesized that CAC would attenuate the association between neuroimaging measures and cognition performance. <b><i>Methods:</i></b> Associations were examined using marginal models in this family-based cohort of 572 European Americans from 263 families. All models were adjusted for age, gender, education, type 2 diabetes and hypertension, with some neuroimaging measures additionally adjusted for intracranial volume. <b><i>Results:</i></b> Higher total brain volume was associated with better performance on the Digit Symbol Substitution Task and Semantic Fluency (both p ≤ 7.0 × 10<sup>-4</sup>). Higher gray matter volume was associated with better performance on the Modified Mini-Mental State Examination and Semantic Fluency (both p ≤ 9.0 × 10<sup>-4</sup>). Adjusting for CAC caused minimal changes to the results. <b><i>Conclusions:</i></b> Relationships exist between neuroimaging measures and cognitive performance in a type 2 diabetes-enriched European American cohort. Associations were minimally attenuated after adjusting for subclinical CVD. Additional work is needed to understand how subclinical CVD burden interacts with other factors and impacts relationships between neuroimaging and cognitive testing measures.
DOI: 10.6084/m9.figshare.5128309
title: Supplementary Material for: Prognostic Significance of AMP-Dependent Kinase Alpha Expression in Cervical Cancer

description: <b><i>Objectives:</i></b> Cervical cancer is one of the most common gynecological malignancies worldwide, and its association with the AMP-activated protein kinase (AMPK) is still unknown. We aimed to investigate the clinical correlation between AMPK expression and cervical cancer. <b><i>Methods:</i></b> The expression of AMPKα1, AMPKα2 and phosphorylated AMPKα (p-AMPKα) was determined immunohistochemically in 524 formalin-fixed, paraffin-embedded malignant and premalignant cervical tissues. Subsequently, associations with clinicopathological characteristics and patient survival were assessed. <b><i>Results:</i></b> AMPKα2 expression was observed in the cytoplasm and nucleus, while expression of AMPKα1 and p-AMPKα was mainly observed in the cytoplasm. p-AMPKα expression increased during the normal-to-tumor transition of cervical carcinoma (p &lt; 0.001), but, once cancer developed, the expression of AMPKα2 and p-AMPKα decreased in large-sized tumors when compared to smaller tumors (36 vs. 68%, p = 0.004 and 39 vs. 64%, p = 0.029, respectively). Notably, AMPKα2 expression was significantly associated with better disease-free survival (HR 0.29, 95% CI 0.10-0.86, p = 0.026). <b><i>Conclusion:</i></b> The AMPKα2 isoform showed potential as a favorable prognostic marker in cervical cancer. Therefore, additional studies are necessary to further clarify the complex contribution of AMPK isoforms and of phosphorylation status to cervical cancer progression and prognosis.
DOI: 10.6084/m9.figshare.5128315.v1
title: Supplementary Material for: Relationships between Cognitive Performance, Neuroimaging and Vascular Disease: The DHS-MIND Study

description: <b><i>Background:</i></b> Type 2 diabetes mellitus increases the risk of cognitive decline and dementia, and elevated burdens of vascular disease are hypothesized to contribute to this risk. These relationships were examined in the Diabetes Heart Study-MIND using a battery of cognitive tests, neuroimaging measures and subclinical cardiovascular disease (CVD) burden assessed by coronary artery calcified (CAC) plaque. We hypothesized that CAC would attenuate the association between neuroimaging measures and cognition performance. <b><i>Methods:</i></b> Associations were examined using marginal models in this family-based cohort of 572 European Americans from 263 families. All models were adjusted for age, gender, education, type 2 diabetes and hypertension, with some neuroimaging measures additionally adjusted for intracranial volume. <b><i>Results:</i></b> Higher total brain volume was associated with better performance on the Digit Symbol Substitution Task and Semantic Fluency (both p ≤ 7.0 × 10<sup>-4</sup>). Higher gray matter volume was associated with better performance on the Modified Mini-Mental State Examination and Semantic Fluency (both p ≤ 9.0 × 10<sup>-4</sup>). Adjusting for CAC caused minimal changes to the results. <b><i>Conclusions:</i></b> Relationships exist between neuroimaging measures and cognitive performance in a type 2 diabetes-enriched European American cohort. Associations were minimally attenuated after adjusting for subclinical CVD. Additional work is needed to understand how subclinical CVD burden interacts with other factors and impacts relationships between neuroimaging and cognitive testing measures.
DOI: 10.6084/m9.figshare.5128318
title: Supplementary Material for: The Relation between Obesity and Hospital Length of Stay after Elective Lateral Skull Base Surgery: An Analysis of the American College of Surgeons National Surgical Quality Improvement Program

description: <b><i>Purpose:</i></b> Length of stay is a marker of quality and efficiency of health care delivery. The objective of this study was to identify preoperative, intraoperative, and postoperative variables that impact length of stay after lateral skull base surgery. <b><i>Methods/Procedures:</i></b> The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) databases from 2009-2012 were analyzed, and patients undergoing elective lateral skull base surgery for benign lesions of cranial nerves were identified. The primary outcome measure of interest was length of hospital stay. Protracted length of stay was defined as ≥75th percentile of length of stay for all patients. The impact of demographic factors, intraoperative variables, and postoperative complications on length of stay was assessed. <b><i>Results:</i></b> In total, 252 patients were included. Almost half of the patients (41.2%) were classified as obese (body mass index ≥30). Patients who were obese had significantly longer lengths of stay (5.6 ± 3.9 days) when compared to patients who were not obese (4.6 ± 3.4 days, p = 0.006). Multivariate regression analysis demonstrated that operative time, reoperation within 30 days of initial surgery, and obesity were independent predictors for protracted length of stay. <b><i>Conclusion:</i></b> National multi-institutional data from the ACS-NSQIP suggest that operative time, reoperation, and obesity are predictors of longer hospital stays after lateral skull base approaches for benign cranial nerve neoplasms.
DOI: 10.6084/m9.figshare.5128321.v1
title: Supplementary Material for: Declining Estimated Glomerular Filtration Rate and Its Association with Mortality and Comorbidity Over 10 Years in Elderly Women

description: <b><i>Background/Aims:</i></b> Renal function deteriorates with age, but a few studies have addressed this longitudinally in elderly women. Our objective was, using 5 estimated glomerular filtration rates (eGFR)-equations, to evaluate changes in renal function and association with adverse outcomes for a decade in 75-year-old women. <b><i>Methods:</i></b> Plasma creatinine was measured at ages 75 (n = 1,011), 78 (n = 827), 80 (n = 689) and 85 (n = 363). Glomerular filtration rates were estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI); Modification of Diet in Renal Disease (MDRD); revised Lund-Malmö (LM-rev); Berlin Initiative Study 1 (BIS1) and Cockcroft-Gault/body surface area (CG/BSA) equations. Mortality and comorbidity were investigated in women with chronic kidney disease (CKD) stage 3A and 3B-5. <b><i>Results:</i></b> Approximately, 95% of women had eGFR indicating CKD stage 2-3 and progression towards stage 3 was continuous. The women lost 22% of their eGFR during follow-up and loss accelerated between 80 and 85. Mean loss per decade was 16.6 ml/min/1.73 m<sup>2</sup>. Women in CKD stage 3B-5 had an adjusted hazard ratio for death of 3.5 (95% CI 2.1-5.8) compared to stage 1-2 during follow-up and increased risk of diabetes, heart failure and hypertension. The CG/BSA, BIS1 and LM-rev equations continuously predicted lower eGFR than the MDRD and CKD-EPI equations. <b><i>Conclusion:</i></b> eGFR in women aged 75-85 ranges from 30 to 89 ml/min/1.73 m<sup>2</sup> (stage 2-3). Decline was 16.6 ml/min/1.73 m<sup>2</sup> per decade; accelerated with age and appeared nonlinear. Women with CKD 3B-5 demonstrate an over 3-fold risk of death. eGFR &lt;45 ml/min/1.73 m<sup>2</sup> was associated with mortality, confirming the new KDIGO classification 3A and 3B, as clinically applicable in the elderly.
DOI: 10.6084/m9.figshare.5128306
title: Supplementary Material for: Melatonin Reduces Hypoglycemia-Induced Neuronal Death in Rats

description: Melatonin, N-aceyl-5-methoxytryptamine, is the main secretory product of the pineal gland and has neuroprotective effects on several brain injuries, including ischemic stroke. In the present study, we hypothesized that exogenous melatonin may decrease hypoglycemia-induced neuronal death through the prevention of superoxide generation. To test our hypothesis, hypoglycemia was induced by injecting human insulin (10 U/kg, i.p.) in rats. Melatonin injection was started immediately after hypoglycemia (10 mg/kg, i.p.). The first melatonin injection was performed at the end of a 30-min isoelectric EEG period. The second and third injections were administered at 1 and 3 h after the first injection. Reactive oxygen species generation, as detected by dihydroethidium staining, was significantly reduced by melatonin treatment. Neuronal injury was reduced by the treatment of melatonin in the hippocampal CA1 and dentate granule cells. Microglia activation was robust in the hippocampus after hypoglycemia, which was almost completely prevented by melatonin treatment. Hypoglycemia-induced cognitive impairment was also significantly prevented by melatonin treatment. The present study suggests that melatonin has therapeutic potential to prevent hypoglycemia-induced brain injury.
DOI: 10.6084/m9.figshare.5128312
title: Supplementary Material for: 25-Gauge Pars Plana Vitrectomy for Retained Lens Fragments in Complicated Cataract Surgery

description: <b><i>Purpose:</i></b> To verify the efficacy of 25-gauge pars plana vitrectomy (PPV) for the management of posteriorly dislocated lens material after complicated cataract extraction and to determine in what patients this approach offers the optimal benefit in terms of efficacy and safety, considering the amount of retained nuclear material and the duration of surgery. <b><i>Methods:</i></b> Forty eyes of 40 patients with retained lens fragments undergoing early (within 1 week) or late (within &gt;1 week) 25-gauge PPV were retrospectively reviewed. The amount of dislocated nuclear material was graded by the surgeon intraoperatively, and the patients were divided into two groups according to the nuclear grading: group A (≤50% dropped nucleus) and group B (&gt;50% dropped nucleus). The presence of brunescent nuclear pieces was considered. The outcomes measured included best-corrected visual acuity (BCVA) and postoperative complications such as retinal detachment, cystoid macular edema (CME) and postoperative ocular hypertension or hypotonia. <b><i>Results:</i></b> The patients had a mean age of 78 years. The mean preoperative logarithm of the minimum angle of resolution (logMAR) BCVA was 0.57 ± 0.24 (20/80). A significant positive correlation was found between nuclear material grade and PPV duration (R<sup>2</sup> = 0.81, p &lt; 0.0001). None of the patients had dislocation of brunescent nuclear pieces. On postoperative day 1, the mean postoperative intraocular pressure was 16.75 ± 2.7 mm Hg, with no case of ocular hypotonia. At 6 months of follow-up, the mean logMAR BCVA improved to 0.23 ± 0.3 (20/32). Retinal detachment developed in 4 patients (10%), occurring only in patients of group B (p &lt; 0.002). Four patients with late PPV developed postoperative CME, with no case of CME among patients with early vitrectomy (p = 0.014). <b><i>Conclusion:</i></b> Removal of dislocated lens fragments after complicated cataract surgery can be effectively managed with 25-gauge PPV, although it appears to be most efficient for cases with a limited amount of dislocated lens material. In consideration of the higher rate of retinal detachment observed in cases of prolonged PPV time, the expected duration of surgery should be taken into account when choosing the best surgical approach. Visual outcomes are not affected by the timing of PPV, whereas early vitrectomy seems to prevent the onset of inflammatory macular edema.
DOI: 10.6084/m9.figshare.5128318.v1
title: Supplementary Material for: The Relation between Obesity and Hospital Length of Stay after Elective Lateral Skull Base Surgery: An Analysis of the American College of Surgeons National Surgical Quality Improvement Program

description: <b><i>Purpose:</i></b> Length of stay is a marker of quality and efficiency of health care delivery. The objective of this study was to identify preoperative, intraoperative, and postoperative variables that impact length of stay after lateral skull base surgery. <b><i>Methods/Procedures:</i></b> The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) databases from 2009-2012 were analyzed, and patients undergoing elective lateral skull base surgery for benign lesions of cranial nerves were identified. The primary outcome measure of interest was length of hospital stay. Protracted length of stay was defined as ≥75th percentile of length of stay for all patients. The impact of demographic factors, intraoperative variables, and postoperative complications on length of stay was assessed. <b><i>Results:</i></b> In total, 252 patients were included. Almost half of the patients (41.2%) were classified as obese (body mass index ≥30). Patients who were obese had significantly longer lengths of stay (5.6 ± 3.9 days) when compared to patients who were not obese (4.6 ± 3.4 days, p = 0.006). Multivariate regression analysis demonstrated that operative time, reoperation within 30 days of initial surgery, and obesity were independent predictors for protracted length of stay. <b><i>Conclusion:</i></b> National multi-institutional data from the ACS-NSQIP suggest that operative time, reoperation, and obesity are predictors of longer hospital stays after lateral skull base approaches for benign cranial nerve neoplasms.