cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126500.v1
title: Supplementary Material for: The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD): Rationale, Study Design, and Cohort Description

description: <b><i>Background:</i></b> Accumulating epidemiological evidence from several populations supports the important role of the Mediterranean-type diet (MeDi) in reducing the risk for age-related diseases such as Alzheimer's disease (AD). However, the relevant literature is clearly deficient for most Mediterranean countries that more closely adhere to the originally described MeDi. Greece resides in the Mediterranean basin, and older generations traditionally adhere to a MeDi. <b><i>Methods:</i></b> We here present the design and the preliminary baseline characteristics of the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). The HELIAD is a population-based, multidisciplinary, collaborative study designed to estimate the prevalence and incidence of AD, other dementias, mild cognitive impairment, and other neuropsychiatric conditions of aging in the Greek population and to investigate associations between nutrition and cognitive dysfunction/age-related neuropsychiatric diseases in this Mediterranean population. The study also ascertains several demographic, medical, social, environmental, clinical, nutritional, and neuropsychological determinants and lifestyle activities. <b><i>Results:</i></b> In total, 1,050 participants of a random sample have already completed the initial evaluation. The subjects were, on average, 73.4 (SD = 6.0) years old, 60% of the sample were female, and most of the participants were poorly educated with an average of 5.41 (SD = 3.5) years of education. The performance on the neuropsychological tests was equivalent to the average scores of previous normative Greek samples. More than one third of the population under investigation was considered to be at high risk for malnutrition. <b><i>Conclusions:</i></b> The HELIAD may provide important data for expanding our knowledge regarding the prevalence, incidence, and risk factors of AD and several other neuropsychiatric diseases in the Mediterranean region.
DOI: 10.6084/m9.figshare.5126503.v1
title: Supplementary Material for: Effects of Psychotherapy on DNA Strand Break Accumulation Originating from Traumatic Stress

description: <b><i>Background:</i></b> Previous research reveals an association between traumatic stress and an increased risk for numerous diseases, including cancer. At the molecular level, stress may increase carcinogenesis via increased DNA damage and impaired DNA repair mechanisms. We assessed DNA breakage in peripheral blood mononuclear cells from individuals with post-traumatic stress disorder (PTSD) and measured the cellular capacity to repair single-strand breaks after exposure to ionizing X-radiation. We also investigated the effect of psychotherapy on both DNA breakage and DNA repair. <b><i>Methods:</i></b> In a first study we investigated DNA breakage and repair in 34 individuals with PTSD and 31 controls. Controls were subdivided into 11 trauma-exposed subjects and 20 individuals without trauma exposure. In a second study, we analysed the effect of psychotherapy (Narrative Exposure Therapy) on DNA breakage and repair. Thirty-eight individuals with PTSD were randomly assigned to either a treatment or a waitlist control condition. Follow-up was performed 4 months and 1 year after therapy. <b><i>Results:</i></b> In study 1 we found higher levels of basal DNA breakage in individuals with PTSD and trauma-exposed subjects than in controls, indicating that traumatic stress is associated with DNA breakage. However, single-strand break repair was unimpaired in individuals with PTSD. In study 2, we found that psychotherapy reversed not only PTSD symptoms, but also DNA strand break accumulation. <b><i>Conclusion:</i></b> Our results show - for the first time in vivo - an association between traumatic stress and DNA breakage; they also demonstrate changes at the molecular level, i.e., the integrity of DNA, after psychotherapeutic interventions.
DOI: 10.6084/m9.figshare.5126491
title: Supplementary Material for: The Transcription Factor Nuclear Factor of Activated T Cells c3 Modulates the Function of Macrophages in Sepsis

description: The role of the transcription factor nuclear factor of activated T cells (NFAT) was initially identified in T and B cell gene expression, but its role in regulating gene expression in macrophages during sepsis is not known. Our data show that NFATc3 regulates expression of inducible nitric oxide synthase (iNOS) in macrophages stimulated with lipopolysaccharide. Selective inhibition of NFAT by cyclosporine A and a competitive peptide inhibitor 11R-VIVIT inhibited endotoxin-induced expression of iNOS and nitric oxide (NO) release. Macrophages from NFATc3 knockout (KO) mice show reduced iNOS expression and NO release and attenuated bactericidal activity. Gel shift and chromatin immunoprecipitation assays show that endotoxin challenge increases NFATc3 binding to the iNOS promoter, resulting in transcriptional activation of iNOS. The binding of NFATc3 to the iNOS promoter is abolished by NFAT inhibitors. NFATc3 KO mice subjected to sepsis show that NFATc3 is necessary for bacterial clearance in mouse lungs during sepsis. Our study demonstrates for the first time that NFATc3 is necessary for macrophage iNOS expression during sepsis, which is essential for containment of bacterial infections.
DOI: 10.6084/m9.figshare.5126485
title: Supplementary Material for: Consensus on the Prevention, Screening, Early Diagnosis and Treatment of Colorectal Tumors in China: Chinese Society of Gastroenterology, October 14-15, 2011, Shanghai, China

description: <b><i>Background:</i></b> Colorectal cancer (CRC) is steadily increasing in China. Colorectal adenoma (CRA) is the most important precancerous disease of CRC. Screening for colorectal tumors can aid early diagnosis. Advances in endoscopic mucosal resection and endoscopic submucosal dissection can aid the early treatment of colorectal tumors. Furthermore, because of high risk of recurrence after removal of adenomas under endoscopy, factors contributing to recurrence, the follow-up mode and the interval established, and the feasibility of application and the time of various chemical preventions should be concerned. However, a relevant consensus on the screening, early diagnosis and treatment, and prevention of colorectal tumors in China is lacking. <b><i>Summary:</i></b> The consensus recommendations include epidemiology, pathology, screening, early diagnosis, endoscopic treatment, monitoring and follow-up, and chemoprevention of colorectal tumors in China. <b><i>Key Message:</i></b> This is the first consensus on the prevention, screening, early diagnosis and treatment of CRA and CRC in China based on evidence in the literature and on local data. <b><i>Practical Implications:</i></b> Through reviewing the literature, regional data and passing the consensus by an anonymous vote, gastroenterology experts from all over China launch the consensus recommendations in Shanghai. The incidence and mortality of CRC in China has increased, and the incidence or detection rate of CRA has increased rapidly. Screening for colorectal tumors should be performed at age 50-74 years. Preliminary screening should be undertaken to find persons at high risk, followed by colonoscopy. A screening cycle of 3 years is recommended for persistent interventions. Opportunistic screening is a mode suitable for the current healthcare system and national situation. Colonoscopy combined with pathological examination is the standard method for the diagnosis of colorectal tumors. CRA removal under endoscopy can prevent CRC to some extent, but CRA has an obvious recurrence trend. The follow-up interval after the removal or surgery of colorectal tumors should be different with lesions. Primary prevention of CRA includes improved diet with more fiber, supplements containing calcium and vitamin D, supplements containing folic acid for those with low hemoglobin levels, and cessation of tobacco smoking. Non-steroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors have been recognized to prevent recurrence after adenoma removal.
DOI: 10.6084/m9.figshare.5126488
title: Supplementary Material for: Cerebral Microbleeds Are Associated with the Progression of Ischemic Vascular Lesions

description: <b><i>Background:</i></b> Despite their different appearance on imaging, hemorrhagic and ischemic vascular lesions frequently co-occur in the brain and are hypothesized to progress concurrently. Although silent hemorrhagic and ischemic vascular brain lesions are highly prevalent in the general population, the concomitant progression of these lesions has only been studied to a limited extent in this population. We therefore aimed to investigate whether pre-existing and incident cerebral microbleeds (CMBs) are related to the progression of ischemic lesions in the general population. <b><i>Methods:</i></b> In the prospective population-based Rotterdam Scan Study, 803 individuals aged ≥60 years underwent magnetic resonance imaging at baseline and after an average interval of 3.4 years. The presence of microbleeds and lacunes was visually rated by trained research physicians, and white matter lesions (WMLs) were automatically segmented at both time points. Logistic regression was used to investigate the association of microbleeds with incident lacunes, and linear regression was used to investigate the relation between microbleeds and progression of WML volume. All analyses were adjusted for age, sex and the time interval between baseline and follow-up scanning. The analyses were repeated after additional adjustments for cardiovascular risk factors: blood pressures; total and high-density lipoprotein cholesterol; smoking; diabetes mellitus; lipid lowering, antihypertensive and antiplatelet medications, and <i>apolipoprotein E</i> ε4. The analyses involving WMLs were also adjusted for intracranial volume. <b><i>Results:</i></b> We found that pre-existing microbleeds in any location of the brain were related to a higher incidence of lacunes (odds ratio [OR] adjusted for age, sex and scan interval: 4.67; 95% confidence interval [CI]: 1.84-11.85). Pre-existing microbleeds were not related to progression of WML volume (mean difference in WML volume increase: -0.03; 95% CI: -0.15 to 0.09). Additional adjustments for cardiovascular risk factors did not change the results considerably. Incident microbleeds in any location of the brain were associated with a higher incidence of lacunes (OR: 9.18; 95% CI: 3.61-23.35), whereas only incident microbleeds located in cortico-subcortical regions were related to progression of WML volume (mean difference in WML volume increase: 0.41; 95% CI: 0.21-0.62). Again, adjustments for cardiovascular risk factors did not change the results significantly. <b><i>Conclusions:</i></b> Our findings suggest that in the general population, CMBs serve as a predictor of ischemic brain lesions and may represent an imaging marker of active vasculopathy. These results support the hypothesis of a common underlying pathway in the development of ischemic and hemorrhagic brain lesions.
DOI: 10.6084/m9.figshare.5126494.v1
title: Supplementary Material for: Food Intake and Overweight in School-Aged Children in Germany: Results of the GINIplus and LISAplus Studies

description: <b><i>Objective:</i></b> To investigate the cross-sectional association between food intake and overweight in children. <b><i>Methods:</i></b> Height and weight were measured in 2,565 school-aged children. Intakes of 11 food groups were categorized (low, medium and high) using specific tertile cutoffs. Multivariate energy partition models were applied. Adjustment included energy intake from other food groups, city, family income, parental education and ‘screen' time. Possible underreporters were identified and used in sensitivity analyses. <b><i>Results:</i></b> Compared to low intake, high intakes of meat, fish, beverages and bakery products were associated with greater BMI z-scores [β (95% CI) = 0.32 (0.21, 0.42), 0.13 (0.03, 0.24), 0.23 (0.11, 0.35) and 0.10 (-0.01, 0.20)] and increased risk of being overweight [odds ratio (OR) (95% CI) = 2.08 (1.58, 2.73), 1.39 (1.08, 1.80), 1.36 (1.01, 1.84) and 1.62 (1.24, 2.11)]. Conversely, medium and high intakes of confectionery were associated with smaller BMI z-scores [β = -0.18 (-0.28, -0.07) and -0.22 (-0.33, -0.12)] and decreased risk of being overweight [OR = 0.64 (0.50, 0.83) and 0.53 (0.40, 0.68)]. These associations were robust to sensitivity analyses. <b><i>Conclusions:</i></b> Intakes of meat, fish, beverages and bakery products correlate with body weight status.
DOI: 10.6084/m9.figshare.5126479
title: Supplementary Material for: Pharmacological Characterization of a Highly Selective and Potent Partial Agonist of the MT<sub>2</sub> Melatonin Receptor

description: <b><i>Background/Aims:</i></b> The MT<sub>2</sub> melatonin receptor is a potential target for treating circadian rhythm sleep disorders. This study aims to characterize the recently identified MT<sub>2</sub> melatonin receptor agonist. <b><i>Methods:</i></b> The pharmacological properties of the MT<sub>2</sub> melatonin receptor-selective agonist as exemplified by compound 1 [N-(2-[7-benzyl-1,6-dihydro-2H-indeno(5,4-b)furan-8-yl]ethyl)acetamide] were evaluated by use of cell-free binding and cell-based functional assays. <b><i>Results:</i></b> Competition binding assays using 2-[<sup>125</sup>I]iodomelatonin revealed rapid, reversible, and high-affinity binding of compound 1 to human, mouse, and rat MT<sub>2</sub> melatonin receptors. cAMP, ERK1/2, and PathHunter β-arrestin recruitment assays revealed partial agonist activities. However, compound 1 induced a more intense internalization of human MT<sub>2</sub> melatonin receptor than melatonin. Based on studies using structurally related analogs of compound 1, we further demonstrated that the extent of internalization is independent of the intrinsic efficacy of agonists. <b><i>Conclusion:</i></b> These findings provide novel insights into the relationship between intrinsic agonist efficacy and agonist-induced internalization and demonstrate that compound 1 could serve as a pharmacological tool for future studies to elucidate the detailed molecular mechanism of MT<sub>2</sub> receptor internalization.
DOI: 10.6084/m9.figshare.5126482
title: Supplementary Material for: Carpal Tunnel Surgery as Proxy for Dialysis-Related Amyloidosis: Results from the Japanese Society for Dialysis Therapy

description: <b><i>Background/Aims:</i></b> This study aims to identify current risk factors for developing dialysis-related amyloidosis using carpal tunnel syndrome (CTS) as proxy for general amyloidosis. <b><i>Methods:</i></b> The cohort consisted of 166,237 patients on dialysis (mean age 66.1 ± 12.4 years; mean dialysis vintage 7.2 ± 6.4 years) who could be followed for a year between 2010 and 2011. Of these, 2,157 (1.30%) needed first-time CTS surgery during the study period. Odds ratios (ORs) for CTS were calculated at a 95% confidence interval (95% CI) after adjusting for age, gender, primary kidney disease, history of smoking, history of hypertension vintage, dialysis modality, use of high-flux membrane, body mass index, serum albumin, Kt/V, normalized protein catabolic rate, C-reactive protein, pretreatment β<sub>2</sub>-microglobulin (β<sub>2</sub>MG), and β<sub>2</sub>MG clearance. <b><i>Results:</i></b> Adjusted ORs of first-time CTS for vintages 10-15, 15-20, 20-25 (referent), 25-30, and &gt;30 years were, respectively, 0.18 (0.12-0.26), 0.43 (0.31-0.62), 1.00, 2.37 (1.64-3.40), and 3.87 (2.52-5.93). Adjusted ORs for ages 40-50, 50-60 (referent), 60-70, 70-80, and &gt;80 were 0.53 (0.30-0.94), 1.00, 1.89 (1.41-2.52), 1.52 (1.08-2.14), and 1.04 (0.60-1.80). Female gender, low serum albumin, and diabetic nephropathy were also associated with CTS. Pretreatment serum β<sub>2</sub>MG and β<sub>2</sub>MG clearance &lt;80% were not significant, although β<sub>2</sub>MG clearance &gt;80% was negatively associated with CTS [OR 0.34 (0.13-0.90)]. <b><i>Conclusion:</i></b> ORs of first-time CTS almost doubled with every 5-year increase in dialysis vintage. ORs of CTS were highest for patients aged 60-70. Other factors associated with CTS were gender, serum albumin, and diabetic nephropathy. β<sub>2</sub>MG clearance &gt;80% may decrease the incidence of CTS.
DOI: 10.6084/m9.figshare.5126491.v1
title: Supplementary Material for: The Transcription Factor Nuclear Factor of Activated T Cells c3 Modulates the Function of Macrophages in Sepsis

description: The role of the transcription factor nuclear factor of activated T cells (NFAT) was initially identified in T and B cell gene expression, but its role in regulating gene expression in macrophages during sepsis is not known. Our data show that NFATc3 regulates expression of inducible nitric oxide synthase (iNOS) in macrophages stimulated with lipopolysaccharide. Selective inhibition of NFAT by cyclosporine A and a competitive peptide inhibitor 11R-VIVIT inhibited endotoxin-induced expression of iNOS and nitric oxide (NO) release. Macrophages from NFATc3 knockout (KO) mice show reduced iNOS expression and NO release and attenuated bactericidal activity. Gel shift and chromatin immunoprecipitation assays show that endotoxin challenge increases NFATc3 binding to the iNOS promoter, resulting in transcriptional activation of iNOS. The binding of NFATc3 to the iNOS promoter is abolished by NFAT inhibitors. NFATc3 KO mice subjected to sepsis show that NFATc3 is necessary for bacterial clearance in mouse lungs during sepsis. Our study demonstrates for the first time that NFATc3 is necessary for macrophage iNOS expression during sepsis, which is essential for containment of bacterial infections.
DOI: 10.6084/m9.figshare.5126485.v1
title: Supplementary Material for: Consensus on the Prevention, Screening, Early Diagnosis and Treatment of Colorectal Tumors in China: Chinese Society of Gastroenterology, October 14-15, 2011, Shanghai, China

description: <b><i>Background:</i></b> Colorectal cancer (CRC) is steadily increasing in China. Colorectal adenoma (CRA) is the most important precancerous disease of CRC. Screening for colorectal tumors can aid early diagnosis. Advances in endoscopic mucosal resection and endoscopic submucosal dissection can aid the early treatment of colorectal tumors. Furthermore, because of high risk of recurrence after removal of adenomas under endoscopy, factors contributing to recurrence, the follow-up mode and the interval established, and the feasibility of application and the time of various chemical preventions should be concerned. However, a relevant consensus on the screening, early diagnosis and treatment, and prevention of colorectal tumors in China is lacking. <b><i>Summary:</i></b> The consensus recommendations include epidemiology, pathology, screening, early diagnosis, endoscopic treatment, monitoring and follow-up, and chemoprevention of colorectal tumors in China. <b><i>Key Message:</i></b> This is the first consensus on the prevention, screening, early diagnosis and treatment of CRA and CRC in China based on evidence in the literature and on local data. <b><i>Practical Implications:</i></b> Through reviewing the literature, regional data and passing the consensus by an anonymous vote, gastroenterology experts from all over China launch the consensus recommendations in Shanghai. The incidence and mortality of CRC in China has increased, and the incidence or detection rate of CRA has increased rapidly. Screening for colorectal tumors should be performed at age 50-74 years. Preliminary screening should be undertaken to find persons at high risk, followed by colonoscopy. A screening cycle of 3 years is recommended for persistent interventions. Opportunistic screening is a mode suitable for the current healthcare system and national situation. Colonoscopy combined with pathological examination is the standard method for the diagnosis of colorectal tumors. CRA removal under endoscopy can prevent CRC to some extent, but CRA has an obvious recurrence trend. The follow-up interval after the removal or surgery of colorectal tumors should be different with lesions. Primary prevention of CRA includes improved diet with more fiber, supplements containing calcium and vitamin D, supplements containing folic acid for those with low hemoglobin levels, and cessation of tobacco smoking. Non-steroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors have been recognized to prevent recurrence after adenoma removal.
DOI: 10.6084/m9.figshare.5126488.v1
title: Supplementary Material for: Cerebral Microbleeds Are Associated with the Progression of Ischemic Vascular Lesions

description: <b><i>Background:</i></b> Despite their different appearance on imaging, hemorrhagic and ischemic vascular lesions frequently co-occur in the brain and are hypothesized to progress concurrently. Although silent hemorrhagic and ischemic vascular brain lesions are highly prevalent in the general population, the concomitant progression of these lesions has only been studied to a limited extent in this population. We therefore aimed to investigate whether pre-existing and incident cerebral microbleeds (CMBs) are related to the progression of ischemic lesions in the general population. <b><i>Methods:</i></b> In the prospective population-based Rotterdam Scan Study, 803 individuals aged ≥60 years underwent magnetic resonance imaging at baseline and after an average interval of 3.4 years. The presence of microbleeds and lacunes was visually rated by trained research physicians, and white matter lesions (WMLs) were automatically segmented at both time points. Logistic regression was used to investigate the association of microbleeds with incident lacunes, and linear regression was used to investigate the relation between microbleeds and progression of WML volume. All analyses were adjusted for age, sex and the time interval between baseline and follow-up scanning. The analyses were repeated after additional adjustments for cardiovascular risk factors: blood pressures; total and high-density lipoprotein cholesterol; smoking; diabetes mellitus; lipid lowering, antihypertensive and antiplatelet medications, and <i>apolipoprotein E</i> ε4. The analyses involving WMLs were also adjusted for intracranial volume. <b><i>Results:</i></b> We found that pre-existing microbleeds in any location of the brain were related to a higher incidence of lacunes (odds ratio [OR] adjusted for age, sex and scan interval: 4.67; 95% confidence interval [CI]: 1.84-11.85). Pre-existing microbleeds were not related to progression of WML volume (mean difference in WML volume increase: -0.03; 95% CI: -0.15 to 0.09). Additional adjustments for cardiovascular risk factors did not change the results considerably. Incident microbleeds in any location of the brain were associated with a higher incidence of lacunes (OR: 9.18; 95% CI: 3.61-23.35), whereas only incident microbleeds located in cortico-subcortical regions were related to progression of WML volume (mean difference in WML volume increase: 0.41; 95% CI: 0.21-0.62). Again, adjustments for cardiovascular risk factors did not change the results significantly. <b><i>Conclusions:</i></b> Our findings suggest that in the general population, CMBs serve as a predictor of ischemic brain lesions and may represent an imaging marker of active vasculopathy. These results support the hypothesis of a common underlying pathway in the development of ischemic and hemorrhagic brain lesions.