bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methotrexate-gelonin conjugate – an inhibitor of MCF-7 cells expressing the dihydrofolate receptor
Authors: Badr Mohamed , Kopp Christian , Theison Sandra , Meyer Jennifer , Trommer Wolfgang E. 
Published: September 2014

Abstract
An immunotoxin composed of gelonin, a basic ribosome-inactivating protein, type I of 30 kDa, isolated from the seeds of the Indian plant Gelonium multiflorum and methotrexate (MTX) has been studied as a potential tool of gelonin delivery into the cytoplasm of MTX-responsive cells. On the average, about five molecules of methotrexate were chemically coupled to gelonin via an N-hydroxysuccinimide ester of the drug. The MTX-gelonin conjugate was able to reduce the viability of MCF-7 cells in a dose-dependent manner with ID50 of 10 nm, whereas gelonin or MTX alone showed none or very little effects. Besides its ribosome-inactivating activity, which is about ten-fold lower in an in vitro translation assay (IC50 of 50.5 ng/ml as compared to 4.6 ng/ml), the conjugate also significantly induced direct and oxidative DNA damage as shown by the alkaline comet assay. Hence, MTX-gelonin conjugates are promising candidates for the treatment of MTX-responsive cancers.
Genetic variation within transcriptional regulatory elements and its implications for human disease
Authors: Rada-Iglesias Alvaro 
Published: September 2014

Abstract
Common human pathologies have a complicated etiology involving both genetic and environmental risk factors. Moreover, the genetic basis of these disorders is also complex, with multiple and weak genetic variants contributing to disease susceptibility. In addition, most of these risk genetic variants occur outside genes, within the vast non-coding human genomic space. In this review I first illustrate how large-scale genomic studies aimed at mapping cis-regulatory elements in the human genome are facilitating the identification of disease-causative non-coding genetic variation. I then discuss some of the challenges that remain to be solved before the pathological consequences of non-coding genetic variation can be fully appreciated. Ultimately, revealing the genetics of human complex disease can be a critical step towards more personalized and effective diagnosis and treatments.
Titin: central player of hypertrophic signaling and sarcomeric protein quality control
Authors: Kötter Sebastian , Andresen Christian , Krüger Martina 
Published: September 2014

Abstract
The giant sarcomeric protein titin has multiple important functions in striated muscle cells. Due to its gigantic size, its central position in the sarcomere and its elastic I-band domains, titin is a scaffold protein that is important for sarcomere assembly, and serves as a molecular spring that defines myofilament distensibility. This review focuses on the emerging role of titin in mechanosensing and hypertrophic signaling, and further highlights recent evidence that links titin to sarcomeric protein turnover.
The epigenetic tracks of aging
Authors: Weidner Carola Ingrid , Wagner Wolfgang 
Published: September 2014

Abstract
Aging is associated with the deterioration of biological functions, which is either caused by accumulation of random defects or mediated by a controlled process. This article provides an overview of age-associated epigenetic alterations in the histone code, DNA-methylation (DNAm) pattern, and chromatin structure. In particular, age-related DNAm changes are highly reproducible at specific sites in the genome. The DNAm level at few CpGs facilitates estimation of chronological age and there is evidence that such predictions are indicative for biological age. Overall, aging appears to be associated with a tightly regulated epigenetic process, but the underlying mechanism remains to be elucidated.
The role of the Mpv17 protein mutations of which cause mitochondrial DNA depletion syndrome (MDDS): lessons from homologs in different species
Authors: Löllgen Stefanie , Weiher Hans 
Published: September 2014

Abstract
Mitochondrial DNA depletion syndromes (MDDS) are severe pediatric diseases with diverse clinical manifestations. Gene mutations that underlie MDDS have been associated with alterations in the mitochondrial DNA (mtDNA) replication machinery or in mitochondrial deoxyribonucleoside triphosphate pools. However, the nuclear gene MPV17, whose mutated forms are associated with hepatocerebral MDDS in humans, plays a so-far unknown role in mtDNA maintenance. A high degree of conservation has been determined between MPV17 and its mouse (Mpv17), zebrafish (tra) and yeast (SYM1) homologs, respectively, whereby mutants in these cause very different phenotypes. While dysfunction in this gene in humans causes fatal liver disease, kidney pathology is induced in mice. Moreover, in zebrafish inactivation of the Mpv17 homolog was detected as a viable dyscolouration mutant. Knock out of the yeast ortholog results in a temperature-sensitive metabolic growth phenotype. Detailed analyses on common denominators between these different phenotypes strengthen the hypothesis that the Mpv17 protein forms a channel in the inner mitochondrial membrane, allowing small molecules – in vertebrates probably nucleotides, and in yeast probably intermediates of the tricarboxylic acid cycle – to pass. Moreover, a function modifying the pathologic manifestations of MPV17-related disease in mice has been identified. This signaling pathway remarkably involves the non-mitochondrial catalytic subunit of DNA-dependent protein kinase (PRKDC), important in double-strand break repair resistance against reactive oxygen-induced genotoxic stress.
Trends in Hospitalizations and Resource Utilization for Pediatric Pertussis
Authors: Lopez Michelle A. , Cruz Andrea T. , Kowalkowski Marc A. , Raphael Jean L. 
Published: September 2014

Background and Objective:Pertussis is a serious and preventable childhood illness often necessitating hospitalization. The objective was to describe national trends in pediatric pertussis hospitalizations and resource utilization and factors associated with increased length of stay (LOS).Methods:This was a cross-sectional analysis of the 1997 to 2009 Healthcare Cost and Utilization Project Kids’ Inpatient Databases. We examined pediatric hospitalizations of children (0–18 years) with a diagnosis of pertussis. Primary outcomes were hospitalizations, LOS, and charges. Weighted linear regression was used to evaluate trends in resource utilization. Multivariate logistic regression was used to determine factors associated with prolonged LOS.Results:Infants 0 to 6 months old accounted for nearly 90% of pediatric pertussis hospitalizations. Hospitalizations in public payers increased from 50% in 1997 to 67.4% in 2009 (P &lt; .01). Among children with complex chronic conditions (CCCs), pertussis hospitalizations increased from 9.4% in 1997 to 16.8% in 2009 (P &lt; .01). Mean LOS for pediatric pertussis hospitalizations decreased from 5.40 days in 1997 to 5.28 days in 2009 (P &lt; .01), whereas those for children with CCCs increased from 8.86 days in 1997 to 9.25 days in 2009 (P &lt; .01). Mean adjusted charges for pediatric pertussis hospitalizations rose from $14 520 in 1997 to $22 278 in 2009 (P &lt; .01). For all study years, neonates and children with CCCs had greater odds of prolonged LOS.Conclusions:Young infants and publicly insured patients account for a disproportionate number of pertussis-related hospitalizations. Patients with CCCs are increasingly contributing to hospitalizations and resource utilization attributable to pertussis. As new vaccine recommendations are implemented, targeted interventions are warranted to increase preventive efforts in these vulnerable populations.
Factors Associated With Readmission in Late-Preterm Infants: A Matched Case-Control Study
Authors: Moyer Laurel B. , Goyal Neera K. , Meinzen-Derr Jareen , Ward Laura P. , Rust Christina L. , Wexelblatt Scott L. , Greenberg James M. 
Published: September 2014

Objective:
The goal of this study was to evaluate risk factors for readmission among late-preterm (34–36 weeks’ gestation) infants in clinical practice.

Methods:
This was a retrospective, matched case-control study of late-preterm infants receiving care across 8 regional hospitals in 2009 in the United States. Those readmitted within 28 days of birth were matched to non-readmitted infants at a ratio of 1:3 according to birth hospital, birth month, and gestational age. Step-wise modeling with likelihood ratio tests were used to develop a multivariable logistic regression model. A subgroup analysis of hyperbilirubinemia readmissions was also performed.

Results:
Of 1861 late-preterm infants delivered during the study period, 67 (3.6%) were readmitted within 28 days of birth. These were matched to 201 control infants, for a final sample of 268 infants. In multivariable regression, each additional day in length of stay was associated with a significantly reduced odds ratio (OR) for readmission (0.57, P = .004); however, for those infants delivered vaginally, there was no significant association between length of stay and readmission (adjusted OR: 1.08, P = .16). A stronger inverse relationship was observed in subgroup analysis for hyperbilirubinemia readmissions, with the adjusted OR associated with increased length of stay 0.40 (P = .002) for infants born by cesarean delivery but 1.14 (P = .27) for those delivered vaginally.

Conclusions:
Infants born via cesarean delivery with longer length of hospital stay have a decreased risk for readmission. As hospitals implement protocols to standardize length of stay, mode of delivery may be a useful factor to identify late-preterm infants at higher risk for readmission.
Predictors of Long Length of Stay in Infants Hospitalized With Urinary Tract Infection
Authors: McMullen Janet A. , Mahant Sanjay , DeGroot Julie M. , Stephens Derek , Parkin Patricia C. 
Published: September 2014

Objective:
Urinary tract infection (UTI) is the most common serious bacterial infection in infants. To use resources optimally, factors contributing to costs through length of stay (LOS) must be identified. This study sought to identify clinical and health system factors associated with long LOS in infants with UTI.

Methods:
Using a case–control design, we included infants &lt;6 months old hospitalized with UTI. Cases had LOS ≥96 hours; controls had LOS &lt;96 hours. Clinical and health system variables were extracted from medical records. Cases and controls were compared by using comparative statistics and multiple logistic regression analysis.

Results:
Cases (n = 71) and controls (n = 71) did not differ by gender; cases were more likely to be younger (4.2 vs 7.1 weeks, P = .04), born preterm (13% vs 3%, P = .03), have known genitourinary disease (17% vs 4%, P = .01), an ultrasound (85% vs 68%, P = .02) or voiding cystourethrogram (VCUG) (61% vs 34%, P = .001) ordered, longer wait for VCUG (53 vs 27 hours, P = .002), consult requested (54% vs 10%, P &lt; .001), and longer duration of intravenous (IV) antibiotics (125 vs 62 hours, P &lt; .001). Multiple logistic regression demonstrated that cases were more likely to be premature (odds ratio [OR] 7.6), have known genitourinary disease (OR 7.3), and have VCUG ordered in the hospital (OR 4.5).

Conclusions:
Infants who are older, are born full term, have no genitourinary disease, receive shorter courses of IV antibiotics, and do not have a VCUG ordered have shorter stays and may be eligible for a short-stay unit. Earlier transition to oral antibiotics and delayed ordering of a VCUG may decrease LOS.
Improving Developmental Screening Documentation and Referral Completion
Authors: Talmi Ayelet , Bunik Maya , Asherin Ryan , Rannie Michael , Watlington Tyler , Beaty Brenda , Berman Stephen 
Published: September 2014

BACKGROUND AND OBJECTIVES:
Screening, early identification, and referral improves outcomes for young children at risk for developmental delays. Effective developmental screening processes should include efforts to ensure referral completion and documentation of evaluation results and service eligibility in the child’s medical record. Our objectives were to improve provider documentation of actions taken after an abnormal developmental screening result and increase Early Intervention (State Part C) referrals.

METHODS:
Various strategies including an electronic medical record template, monthly clinical informatics reporting, and a phone follow-up after an abnormal screening result were implemented to enhance provider documentation of screening results and improve referral actions and outcomes.

RESULTS:
Of the children eligible for screening (n = 3023), 2610 (86%) were screened, with 382 (15%) scoring in the abnormal range. With phone follow-up, 50% of the abnormal screenings were referred to community resources, including 43% to Early Intervention (EI), in contrast to 20% community referrals and 13% EI referrals with the screening template only (P &lt; .0001). Provider documentation of EI outcomes increased when screening templates and follow-up calls were implemented together (31%) as compared with using the screening template alone (15%).

CONCLUSIONS:
Enhanced documentation of developmental screening efforts using screening templates and clinical informatics reporting in combination with phone follow-up after an abnormal screening result improved developmental screening outcomes, including referral rates, completed evaluations, and provider documentation of EI services. Such strategies can be effectively used in pediatric primary care settings to improve screening processes and ensure that young children access appropriate services.
Immunologic Effects of Hydroxyurea in Sickle Cell Anemia
Authors: Lederman Howard M. , Connolly Margaret A. , Kalpatthi Ram , Ware Russell E. , Wang Winfred C. , Luchtman-Jones Lori , Waclawiw Myron , Goldsmith Jonathan C. , Swift Andrea , Casella James F. 
Published: September 2014

BACKGROUND AND OBJECTIVE:
Susceptibility to encapsulated bacteria is well known in sickle cell disease (SCD). Hydroxyurea use is common in adults and children with SCD, but little is known about hydroxyurea’s effects on immune function in SCD. Because hydroxyurea inhibits ribonucleotide reductase, causing cell cycle arrest at the G1–S interface, we postulated that hydroxyurea might delay transition from naive to memory T cells, with inhibition of immunologic maturation and vaccine responses.

METHODS:
T-cell subsets, naive and memory T cells, and antibody responses to pneumococcal and measles, mumps, and rubella vaccines were measured among participants in a multicenter, randomized, double-blind, placebo-controlled trial of hydroxyurea in infants and young children with SCD (BABY HUG).

RESULTS:
Compared with placebo, hydroxyurea treatment resulted in significantly lower total lymphocyte, CD4, and memory T-cell counts; however, these numbers were still within the range of historical healthy controls. Antibody responses to pneumococcal vaccination were not affected, but a delay in achieving protective measles antibody levels occurred in the hydroxyurea group. Antibody levels to measles, mumps, and rubella showed no differences between groups at exit, indicating that effective immunization can be achieved despite hydroxyurea use.

CONCLUSIONS:
Hydroxyurea does not appear to have significant deleterious effects on the immune function of infants and children with SCD. Additional assessments of lymphocyte parameters of hydroxyurea-treated children may be warranted. No changes in current immunization schedules are recommended; however, for endemic disease or epidemics, adherence to accelerated immunization schedules for the measles, mumps, and rubella vaccine should be reinforced.
Infant Feeding Practices and Reported Food Allergies at 6 Years of Age
Authors: Luccioli Stefano , Zhang Yuanting , Verrill Linda , Ramos-Valle Moraima , Kwegyir-Afful Ernest 
Published: September 2014

OBJECTIVE:
The goal of this study was to identify the frequency of physician-diagnosed food allergies among 6-year-old US children and study the impact of exclusive breastfeeding and complementary food introduction on this frequency.

METHODS:
Data were analyzed from children who participated in the Infant Feeding Practices Study II Year 6 Follow-Up Study (Y6FU). Children with probable food allergy (pFA) were defined as children with report of physician-diagnosed food allergy at age 6 years. Subgroups of pFA included children who were not diagnosed before 1 year of age (new pFA) and those with atopic risk factors (high risk).

RESULTS:
Prevalence of total pFA in the Y6FU was 6.34%. The majority of these children had new pFA and high-risk factors. Higher maternal education, higher family income, family history of food allergy, and reported eczema before 1 year of age were significantly associated with higher odds of total or new pFA. Exclusive breastfeeding duration and timing of complementary food introduction were not significantly associated with total pFA. However, exclusive breastfeeding of ≥4 months compared with no breastfeeding was marginally associated with lower odds of new pFA (adjusted odds ratio: 0.51; P = .07); this effect was not observed with high-risk children.

CONCLUSIONS:
Analysis of infant and maternal variables in the Y6FU cohort of US children revealed that socioeconomic and atopic factors were the main predictors of pFA at age 6 years. Exclusive breastfeeding of ≥4 months may have a preventive effect on development of pFA after 1 year of age in non high-risk children.
Adherence to Breastfeeding Guidelines and Maternal Weight 6 Years After Delivery
Authors: Sharma Andrea J. , Dee Deborah L. , Harden Samantha M. 
Published: September 2014

OBJECTIVES:
There is a dearth of information on the long-term maternal effects of breastfeeding. The objective of this study was to examine adherence to breastfeeding recommendations of exclusive breastfeeding for ≥4 months and continuation of breastfeeding for ≥1 year and maternal weight retention 6 years after delivery.

METHODS:
Using data from the Infant Feeding Practices Study II (IFPS II), we categorized women by the degree to which they met breastfeeding recommendations. Mothers’ self-reported weight 6 years after delivery (IFPS Year 6 Follow-Up) was compared with self-reported prepregnancy weight from IFPS II. Using linear regression models, adjusting for covariates, we examined associations between breastfeeding recommendation adherence and weight retention.

RESULTS:
Of the 726 women in our study, 17.9% never breastfed. Among those who initiated breastfeeding, 29.0% breastfed exclusively for ≥4 months, and 20.3% breastfed exclusively for ≥4 months and continued breastfeeding for ≥12 months. Prepregnancy BMI modified the association between breastfeeding recommendation adherence and weight retention. Adjusting for covariates, we found no association between breastfeeding recommendations adherence and weight retention among normal and overweight mothers. Among obese mothers, there was a significant linear trend (P = .03), suggesting that those who fully adhered to breastfeeding recommendations retained less weight (−8.0 kg) than obese women who never breastfed.

CONCLUSIONS:
This study suggests that improving adherence to breastfeeding recommendations may help reduce long-term maternal weight retention among obese mothers. Larger studies, with diverse populations and similar longitudinal designs, are needed to explore this relationship.
The Association of Sugar-Sweetened Beverage Intake During Infancy With Sugar-Sweetened Beverage Intake at 6 Years of Age
Authors: Park Sohyun , Pan Liping , Sherry Bettylou , Li Ruowei 
Published: September 2014

OBJECTIVES:
To examine whether sugar-sweetened beverage (SSB) intake during infancy predicts SSB intake at 6 years of age.

METHODS:
A longitudinal cohort analysis of 1333 US children was conducted by using data from the 2005–2007 Infant Feeding Practices Study II and the 2012 Follow-Up Study at 6 years of age. The exposure variables were maternal-reported SSB intakes during infancy. The outcome variable was maternal-reported SSB intake at age 6 years. Multivariable logistic regression analyses were used to calculate adjusted odds ratios (aOR) for associations of SSB intake during infancy with consuming SSBs ≥1 time/day at 6 years old after controlling for baseline child’s and parent’s characteristics.

RESULTS:
Based on maternal recall, approximately one-fifth of children consumed SSBs at least 1 time/day at age 6 years. Adjusted odds of consuming SSBs at age 6 years ≥1 time/day was significantly associated with any SSB intake during infancy (aOR, 2.22 vs none), age at SSB introduction (aOR, 2.33 for age ≥6 months and 2.01 for age &lt;6 months vs never), and mean SSB intake during age 10 to 12 months (aOR, 2.72 for 1 to &lt;2 times/week and 2.57 for ≥3 times/week vs none).

CONCLUSIONS:
SSB intake during infancy significantly increased the likelihood of consuming SSBs ≥1 time/day at 6 years of age. Our findings suggest that infancy may be an important time for mothers to establish healthy beverage practices for their children and these findings can be used to inform intervention efforts to reduce SSB intake among children.
Bottle-Feeding Practices During Early Infancy and Eating Behaviors at 6 Years of Age
Authors: Li Ruowei , Scanlon Kelley S. , May Ashleigh , Rose Chelsea , Birch Leann 
Published: September 2014

BACKGROUND:Evidence suggests an association of breastfeeding with a maternal feeding style (MFS) that is less controlling than formula feeding, which, in turn, may improve a child’s self-regulation of eating. This study examines associations of bottle-feeding practices during infancy with MFS and children’s eating behavior (CEB) at 6 years old.METHODS:We linked data from the Infant Feeding Practices Study II to the Year 6 Follow-Up, which include 8 MFS and CEB measures adapted from previous validated instruments. Bottle-feeding practices during the first 6 months estimated by using the Infant Feeding Practices Study II were bottle-feeding intensity (BFI), mother’s encouragement of infant to finish milk in the bottle, and infant finishing all milk in the bottle. Adjusted odds ratios (aORs) for associations of bottle-feeding practices with MFS and CEB at 6 years old were calculated by using multivariable logistic regressions controlling for sociodemographic characteristics and other feeding practices (N = 1117).RESULTS:Frequent bottle emptying encouraged by mothers during infancy increased odds of mothers encouraging their child to eat all the food on their plate (aOR: 2.37; 95% confidence interval [CI]: 1.65–3.41] and making sure their child eats enough (aOR: 1.62; 95% CI: 1.14–2.31) and of children eating all the food on their plate at 6 years old (aOR: 2.01; 95% CI: 1.05–3.83). High BFI during early infancy also increased the odds of mothers being especially careful to ensure their 6-year-old eats enough.CONCLUSIONS:Bottle-feeding practices during infancy may have long-term effects on MFS and CEB. Frequent bottle emptying encouraged by mothers and/or high BFI during early infancy increased the likelihood of mothers pressuring their 6-year-old child to eat and children’s low satiety responsiveness.