cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123452.v1
title: Supplementary Material for: Dietary Phosphate Binding and Loading Alter Kidney Angiotensin-Converting Enzyme mRNA and Protein Content in 5/6 Nephrectomized Rats

description: <i>Background:</i> Vitamin D receptor activation with paricalcitol can modulate the transcription of renin-angiotensin system components in the surgical 5/6 nephrectomy rat model (5/6 NX) of chronic renal insufficiency. We tested the hypothesis whether dietary modification of phosphate influences kidney renin-angiotensin system gene expression at the mRNA level in 5/6 NX rats. <i>Methods:</i> Fifteen weeks after surgery, rats were given control diet (0.3% calcium, 0.5% phosphate), phosphate-lowering diet (3% calcium as carbonate) or high-phosphate diet (1.5%) for 12 weeks. Sham-operated rats were on control diet. <i>Results:</i> Blood pressure, plasma phosphate, parathyroid hormone, glomerulosclerosis, tubulointerstitial damage, and FGF-23 were increased in remnant kidney rats, whereas creatinine clearance was decreased. Phosphate, parathyroid hormone, glomerulosclerosis, tubulointerstitial damage, and FGF-23 were further elevated by the high-phosphate diet, but were reduced by the phosphate-lowering diet. Plasma calcium was increased with the phosphate-lowering diet and decreased with the high-phosphate diet. Remnant kidney rats on control diet showed upregulated kidney angiotensin-converting enzyme (ACE) and angiotensin (Ang) IV receptor (AT<sub>4</sub>) transcription, while ACE2, Ang II type 2 receptor and renin receptor transcription were downregulated in comparison with sham rats. Phosphate-lowering diet reduced whereas high-phosphate diet increased kidney ACE, and these effects were observed at both mRNA and protein levels. Dietary phosphate loading also resulted in lower AT<sub>1a</sub> gene transcription. <i>Conclusion:</i> Dietary phosphate loading was associated with elevated kidney ACE expression, increased tissue damage and lower AT<sub>1a</sub> transcription in 5/6 NX rats. Phosphate binding with 3% calcium carbonate had opposite effects on ACE and kidney damage.
DOI: 10.6084/m9.figshare.5123434
title: Supplementary Material for: Smoking Prevention and Cessation in the Africa and Middle East Region: A Consensus Draft Guideline for Healthcare Providers – Executive Summary

description: Despite the abundance of scientific evidence confirming the health consequences of smoking and other forms of tobacco use, the tobacco epidemic remains an important public health problem and by 2030 it is predicted that more than 80% of tobacco deaths will be in developing countries. In Africa and the Middle East, many local factors contribute to the initiation and maintenance of tobacco use. Although efforts to reduce the mortality and morbidity associated with smoking and tobacco dependence are underway, there is a need for guidance on how to utilize appropriate tobacco control policies and psychology- and pharmacology-based therapies to counter tobacco dependence as recommended by the Framework Convention on Tobacco Control (FCTC). A group of tobacco cessation experts from public health services and/or academic institutions in Africa and the Middle East participated in a series of four meetings held in Cairo, Cape Town, and Dubai between May 2008 and February 2011 to develop a draft guideline tailored to their region. This article provides the background to the development of this draft smoking cessation guideline and discusses how the recommendations can be implemented and progress monitored to promote both primary prevention and cessation of tobacco use within our countries. The draft guideline for Africa and the Middle East provides an important resource in combating the devastating effects of tobacco use in these regions which can be further localized through engagement with local stakeholders in the countries of the region.
DOI: 10.6084/m9.figshare.5123440.v1
title: Supplementary Material for: Minimal Homozygous Endothelial Deletion of Eng with VEGF Stimulation Is Sufficient to Cause Cerebrovascular Dysplasia in the Adult Mouse

description: <b><i>Background:</i></b> Brain arteriovenous malformations (bAVMs) represent a high risk for hemorrhagic stroke, leading to significant neurological morbidity and mortality in young adults. The etiopathogenesis of bAVM remains unclear. Research progress has been hampered by the lack of animal models. Hereditary Hemorrhagic Telangiectasia (HHT) patients with haploinsufficiency of endoglin (<i>ENG, </i>HHT1) or activin receptor-like kinase 1 (<i>ALK1, </i>HHT2) have a higher incidence of bAVM than the general population. We previously induced cerebrovascular dysplasia in the adult mouse that resembles human bAVM through <i>Alk1</i> deletion plus vascular endothelial growth factor (VEGF) stimulation. We hypothesized that <i>Eng</i> deletion plus VEGF stimulation would induce a similar degree of cerebrovascular dysplasia as the <i>Alk1</i>-deleted brain. <b><i>Methods:</i></b> Ad-Cre (an adenoviral vector expressing Cre recombinase) and AAV-VEGF (an adeno-associated viral vector expressing VEGF) were co-injected into the basal ganglia of 8- to 10-week-old <i>Eng</i><sup>2f/2f</sup> (exons 5 and 6 flanked by loxP sequences), <i>Alk1</i><sup>2f/2f</sup> (exons 4–6 flanked by loxP sequences) and wild-type (WT) mice. Vascular density, dysplasia index, and gene deletion efficiency were analyzed 8 weeks later. <b><i>Results:</i></b> AAV-VEGF induced a similar degree of angiogenesis in the brain with or without <i>Alk1</i>- or <i>Eng</i>-deletion. Abnormally patterned and dilated dysplastic vessels were found in the viral vector-injected region of <i>Alk1</i><sup>2f/2f</sup> and <i>Eng</i><sup>2f/2f</sup> brain sections, but not in WT. <i>Alk1</i><sup>2f/2f</sup> mice had about 1.8-fold higher dysplasia index than <i>Eng</i><sup>2f/2f</sup> mice (4.6 ± 1.9 vs. 2.5 ± 1.1, p &lt; 0.05). However, after normalization of the dysplasia index with the gene deletion efficiency (<i>Alk1</i><sup>2f/2f</sup>: 16% and <i>Eng</i><sup>2f/2f</sup>: 1%), we found that about 8-fold higher dysplasia was induced per copy of <i>Eng</i> deletion (2.5) than that of <i>Alk1</i> deletion (0.3). ENG-negative endothelial cells were detected in the Ad-Cre-treated brain of <i>Eng</i><sup>2f/2f</sup> mice, suggesting homozygous deletion of <i>Eng</i> in the cells. VEGF induced more severe vascular dysplasia in the Ad-Cre-treated brain of <i>Eng</i><sup>2f/2f</sup> mice than that of <i>Eng</i><sup>+/–</sup> mice. <b><i>Conclusions:</i></b> (1) Deletion of <i>Eng</i> induces more severe cerebrovascular dysplasia per copy than that of <i>Alk1</i> upon VEGF stimulation. (2) Homozygous deletion of <i>Eng</i> with angiogenic stimulation may be a promising strategy for development of a bAVM mouse model. (3) The endothelial cells that have homozygous causal gene deletion in AVM could be crucial for lesion development.
DOI: 10.6084/m9.figshare.5123443
title: Supplementary Material for: Culture-Proven Neonatal Sepsis in Japanese Neonatal Care Units in 2006–2008

description: <b><i>Background:</i></b> Recent Japanese epidemiology of neonatal sepsis and its predominant pathogens has not been reported. It is also unknown whether there are center differences in the incidence of neonatal sepsis, including early-onset sepsis (EOS) and late-onset sepsis (LOS) in Japan. <b><i>Objectives:</i></b> To investigate the morbidity and characteristics of neonatal sepsis in recent years and the differences in the incidence of sepsis among Japanese neonatal care units. <b><i>Methods:</i></b> We retrospectively collected the data of newborn infants with culture-proven sepsis that occurred in five Japanese centers of perinatal care from 2006 to 2008. The incidence of sepsis was calculated, including EOS and LOS, and compared among centers. <b><i>Results:</i></b> Morbidity from sepsis occurred in 51/6,894 (0.74%) infants. The incidence of EOS and LOS was 0.13 and 0.61%, respectively. The incidence of total sepsis and LOS in infants &lt;1,000 g of birth weight was significantly higher than that in infants who weighed &gt;1,000 g at birth, whereas there were no significant differences in the incidence of EOS between the different birth weights. Methicillin-resistant <i>Staphylococcus aureus</i> was the most common pathogen involved in morbidity and mortality of neonatal sepsis. Significant center differences were observed in the incidence of LOS, but not EOS. <b><i>Conclusions:</i></b> The majority of culture-proven neonatal sepsis is LOS, which differs among centers, especially in infants who weigh &lt;1,000 g at birth in Japan. We consider that it is important to control nosocomial infection in newborn care units to further reduce the morbidity of neonatal sepsis in Japan.
DOI: 10.6084/m9.figshare.5123428
title: Supplementary Material for: How Can We Better Classify NSAID Hypersensitivity Reactions? – Validation from a Large Database

description: <b><i>Background:</i></b> Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) is one of the most common drug hypersensitivities. Several clinical subtypes have been distinguished depending on symptomatology (respiratory, cutaneous, anaphylaxis), timing (immediate, delayed), underlying chronic disease (asthma, chronic urticaria) or putative mechanism of the reaction (allergic, nonallergic mediated). The aim of the present study was to better classify the many hypersensitivity reactions to NSAIDs. <b><i>Methods:</i></b> In the present retrospective study, during<b> </b>an 11-year study period, we collected data from all patients with a proven NSAID hypersensitivity. Reactions were classified according to clinical patterns, chronology, underlying diseases and the results of oral provocation tests into 5 and 7 groups in line with two published classifications, respectively. <b><i>Results:</i></b> Forty-nine and 88 out of 307 reactions (in 122 patients) could not be classified on the basis of the two previously published classifications. We created a new classification which could include all patient reactions. <b><i>Conclusions:</i></b> Our new classification is more suitable for clinical expression of NSAID hypersensitivity. It allows clinicians to identify patients at a high risk, based on the clinical history and clinical manifestations. Moreover, it is helpful for a better understanding and teaching of these reactions.
DOI: 10.6084/m9.figshare.5123431
title: Supplementary Material for: Identification and Analysis of Two Novel Sites of Rat GnRH Receptor Gene Promoter Activity: The Pineal Gland and Retina

description: <b><i>Background and Aims:</i></b> In mammals, activation of pituitary GnRH receptor (GnRHR) by hypothalamic GnRH increases the synthesis and secretion of LH and FSH, which, in turn, regulate gonadal functions. However, GnRHR gene <i>(Gnrhr)</i> expression is not restricted to the pituitary. <b><i>Methods:</i></b> To gain insight into the extrapituitary expression of <i>Gnrhr</i>, a transgenic mouse model that expresses the human placental alkaline phosphatase reporter gene driven by the rat <i>Gnrhr</i> promoter was created. <b><i>Results:</i></b> This study shows that the rat <i>Gnrhr</i> promoter is operative in two functionally related organs, the pineal gland, as early as embryonic day (E) 13.5, and the retina where activity was only detected at E17.5. Accordingly, <i>Gnrhr</i> mRNA were present in both tissues. Transcription factors known to regulate <i>Gnrhr</i> promoter activity such as the LIM homeodomain factors LHX3 and ISL1 were also detected in the retina. Furthermore, transient transfection studies in CHO and gonadotrope cells revealed that OTX2, a major transcription factor in both pineal and retina cell differentiation, is able to activate the <i>Gnrhr</i> promoter together with either CREB or PROP1, depending on the cell context. <b><i>Conclusion:</i></b> Rather than using alternate promoters, <i>Gnrhr</i> expression is directed to diverse cell lineages through specific associations of transcription factors acting on distinct response elements along the same promoter. These data open new avenues regarding GnRH-mediated control of seasonal and circadian rhythms in reproductive physiology.
DOI: 10.6084/m9.figshare.5123434.v1
title: Supplementary Material for: Smoking Prevention and Cessation in the Africa and Middle East Region: A Consensus Draft Guideline for Healthcare Providers – Executive Summary

description: Despite the abundance of scientific evidence confirming the health consequences of smoking and other forms of tobacco use, the tobacco epidemic remains an important public health problem and by 2030 it is predicted that more than 80% of tobacco deaths will be in developing countries. In Africa and the Middle East, many local factors contribute to the initiation and maintenance of tobacco use. Although efforts to reduce the mortality and morbidity associated with smoking and tobacco dependence are underway, there is a need for guidance on how to utilize appropriate tobacco control policies and psychology- and pharmacology-based therapies to counter tobacco dependence as recommended by the Framework Convention on Tobacco Control (FCTC). A group of tobacco cessation experts from public health services and/or academic institutions in Africa and the Middle East participated in a series of four meetings held in Cairo, Cape Town, and Dubai between May 2008 and February 2011 to develop a draft guideline tailored to their region. This article provides the background to the development of this draft smoking cessation guideline and discusses how the recommendations can be implemented and progress monitored to promote both primary prevention and cessation of tobacco use within our countries. The draft guideline for Africa and the Middle East provides an important resource in combating the devastating effects of tobacco use in these regions which can be further localized through engagement with local stakeholders in the countries of the region.
DOI: 10.6084/m9.figshare.5123422
title: Supplementary Material for: Expression of the Sodium/Calcium/Potassium Exchanger, NCKX4, in Ameloblasts

description: Transcellular calcium transport is an essential activity in mineralized tissue formation, including dental hard tissues. In many organ systems, this activity is regulated by membrane-bound sodium/calcium (Na<sup>+</sup>/Ca<sup>2+</sup>) exchangers, which include the NCX and NCKX [sodium/calcium-potassium (Na<sup>+</sup>/Ca<sup>2+</sup>-K<sup>+</sup>) exchanger] proteins. During enamel maturation, when crystals expand in thickness, Ca<sup>2+</sup> requirements vastly increase but exactly how Ca<sup>2+</sup> traffics through ameloblasts remains uncertain. Previous studies have shown that several NCX proteins are expressed in ameloblasts, although no significant shifts in expression were observed during maturation which pointed to the possible identification of other Ca<sup>2+</sup> membrane transporters. NCKX proteins are encoded by members of the solute carrier gene family, Slc24a, which include 6 different proteins (NCKX1–6). NCKX are bidirectional electrogenic transporters regulating Ca<sup>2+</sup> transport in and out of cells dependent on the transmembrane ion gradient. In this study we show that all NCKX mRNAs are expressed in dental tissues. Real-time PCR indicates that of all the members of the NCKX group, NCKX4 is the most highly expressed gene transcript during the late stages of amelogenesis. In situ hybridization and immunolocalization analyses clearly establish that in the enamel organ, NCKX4 is expressed primarily by ameloblasts during the maturation stage. Further, during the mid-late maturation stages of amelogenesis, the expression of NCKX4 in ameloblasts is most prominent at the apical poles and at the lateral membranes proximal to the apical ends. These data suggest that NCKX4 might be an important regulator of Ca<sup>2+</sup> transport during amelogenesis.
DOI: 10.6084/m9.figshare.5123428.v1
title: Supplementary Material for: How Can We Better Classify NSAID Hypersensitivity Reactions? – Validation from a Large Database

description: <b><i>Background:</i></b> Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) is one of the most common drug hypersensitivities. Several clinical subtypes have been distinguished depending on symptomatology (respiratory, cutaneous, anaphylaxis), timing (immediate, delayed), underlying chronic disease (asthma, chronic urticaria) or putative mechanism of the reaction (allergic, nonallergic mediated). The aim of the present study was to better classify the many hypersensitivity reactions to NSAIDs. <b><i>Methods:</i></b> In the present retrospective study, during<b> </b>an 11-year study period, we collected data from all patients with a proven NSAID hypersensitivity. Reactions were classified according to clinical patterns, chronology, underlying diseases and the results of oral provocation tests into 5 and 7 groups in line with two published classifications, respectively. <b><i>Results:</i></b> Forty-nine and 88 out of 307 reactions (in 122 patients) could not be classified on the basis of the two previously published classifications. We created a new classification which could include all patient reactions. <b><i>Conclusions:</i></b> Our new classification is more suitable for clinical expression of NSAID hypersensitivity. It allows clinicians to identify patients at a high risk, based on the clinical history and clinical manifestations. Moreover, it is helpful for a better understanding and teaching of these reactions.
DOI: 10.6084/m9.figshare.5123443.v1
title: Supplementary Material for: Culture-Proven Neonatal Sepsis in Japanese Neonatal Care Units in 2006–2008

description: <b><i>Background:</i></b> Recent Japanese epidemiology of neonatal sepsis and its predominant pathogens has not been reported. It is also unknown whether there are center differences in the incidence of neonatal sepsis, including early-onset sepsis (EOS) and late-onset sepsis (LOS) in Japan. <b><i>Objectives:</i></b> To investigate the morbidity and characteristics of neonatal sepsis in recent years and the differences in the incidence of sepsis among Japanese neonatal care units. <b><i>Methods:</i></b> We retrospectively collected the data of newborn infants with culture-proven sepsis that occurred in five Japanese centers of perinatal care from 2006 to 2008. The incidence of sepsis was calculated, including EOS and LOS, and compared among centers. <b><i>Results:</i></b> Morbidity from sepsis occurred in 51/6,894 (0.74%) infants. The incidence of EOS and LOS was 0.13 and 0.61%, respectively. The incidence of total sepsis and LOS in infants &lt;1,000 g of birth weight was significantly higher than that in infants who weighed &gt;1,000 g at birth, whereas there were no significant differences in the incidence of EOS between the different birth weights. Methicillin-resistant <i>Staphylococcus aureus</i> was the most common pathogen involved in morbidity and mortality of neonatal sepsis. Significant center differences were observed in the incidence of LOS, but not EOS. <b><i>Conclusions:</i></b> The majority of culture-proven neonatal sepsis is LOS, which differs among centers, especially in infants who weigh &lt;1,000 g at birth in Japan. We consider that it is important to control nosocomial infection in newborn care units to further reduce the morbidity of neonatal sepsis in Japan.
DOI: 10.6084/m9.figshare.5123419
title: Supplementary Material for: Acute Kidney Injury and Mortality in Hospitalized Patients

description: <i>Background:</i> The objective of this study was to determine the incidence of acute kidney injury (AKI) and its relation with mortality among hospitalized patients. <i>Methods:</i> Analysis of hospital discharge and laboratory data from an urban academic medical center over a 1-year period. We included hospitalized adult patients receiving two or more serum creatinine (sCr) measurements. We excluded prisoners, psychiatry, labor and delivery, and transferred patients, ‘bedded outpatients’ as well as individuals with a history of kidney transplant or chronic dialysis. We defined AKI as (a) an increase in sCr of ≥0.3 mg/dl; (b) an increase in sCr to ≥150% of baseline, or (c) the initiation of dialysis in a patient with no known history of prior dialysis. We identified factors associated with AKI as well as the relationships between AKI and in-hospital mortality. <i>Results:</i> Among the 19,249 hospitalizations included in the analysis, the incidence of AKI was 22.7%. Older persons, Blacks, and patients with reduced baseline kidney function were more likely to develop AKI (all p &lt; 0.001). Among AKI cases, the most common primary admitting diagnosis groups were circulatory diseases (25.4%) and infection (16.4%). After adjustment for age, sex, race, admitting sCr concentration, and the severity of illness index, AKI was independently associated with in-hospital mortality (adjusted odds ratio 4.43, 95% confidence interval 3.68–5.35). <i>Conclusions:</i> AKI occurred in over 1 of 5 hospitalizations and was associated with a more than fourfold increased likelihood of death. These observations highlight the importance of AKI recognition as well as the association of AKI with mortality in hospitalized patients.
DOI: 10.6084/m9.figshare.5123425
title: Supplementary Material for: Usefulness of the Preoperative Administration of Tegafur Suppositories as Alternative Adjuvant Chemotherapy for Patients with Resectable Stage II or III Colorectal Cancer: A KODK4 Multicenter Randomized Control Trial

description: <b><i>Objective:</i></b> The aim of this study was to evaluate the feasibility and conferred protection against recurrence of preoperatively administered tegafur suppositories following the intravenous and oral administration of fluoropyrimidine in a multicenter randomized control trial. <b><i>Methods:</i></b> Patients with clinical T3/4 colorectal cancer were randomly assigned to receive the preoperative administration of tegafur suppositories (group A) or no preoperative treatment (group B). The primary end points were disease-free survival (DFS) and overall survival (OS). <b><i>Results:</i></b> The mean follow-up periods were 80.9 ± 31.0 months in group A and 64.5 ± 28.8 months in group B. The 5-year DFS rates were 89.3% in group A and 70.3% in group B (p = 0.045), whereas the 5-year OS rates were 91.4% in group A and 73.2% in group B (p = 0.051). Furthermore, a significant difference in the cumulative distant metastatic rate was observed (group A, 7.4% vs. group B, 23.4%; p = 0.03). However, no significant difference in the cumulative local recurrence rate was seen (group A, 4.6% vs. group B, 8.2%; p = 0.68). <b><i>Conclusion: </i></b>Despite a relatively small sample size, preoperative tegafur suppositories might protect recurrences and improve survival rates, mainly by preventing distant metastasis. These findings suggest the utility of tegafur suppositories as an alternative neoadjuvant treatment in modern chemotherapy for colorectal cancer.