bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disparities in childcare and breastfeeding rates among US children of single mothers
Authors: kim juhee 
Published: June 2021

ObjectivesThis study is to evaluate the characteristics and disparities in childcare and breastfeeding rates among children of single mothers compared to those of two parents using a nationally representative US children.MethodsThe study sample consisted of children aged 0 to 5 years enrolled in the National Study of Children's Health 2007 (children of single mothers ( n=3,803, 16.6%) and children of two‐parents (n=22,510, 83.4%). The primary caregiver of the study child responded the following outcome measures: 1) childcare type, 2) employment problems due to childcare, 3) last‐min change of childcare arrangement, 4) breastfeeding initiation, 5) exclusive breastfeeding for 6 months, 6) any breastfeeding for 6 months, and 7) started complementary foods before 6 months.ResultsThe profiles of race/ethnicity, birth weight, education, poverty, employment and nativity of mothers in children of single mothers may present higher risk for low breastfeeding rates. There were disparities in childcare use and problems among children of single mothers. Exclusive breastfeeding and early initiation of complementary foods were not significantly different by family structure; however, breastfeeding initiation (OR= 0.78: 95% CI=0.64–0.97) and any breastfeeding for 6 months (OR=0.76: 95% CI=0.61–0.95) were much lower among children of single mothers compared to those of two parents.ConclusionThis study documented disparities in childcare use and problems as well as breastfeeding rates among children of single mothers, raising a need for public health interventions targeting single mothers.This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government, (NRF‐2011‐330‐B00190).
B‐Lymphocyte Stimulator in neuroendocrine tumors: correlation with disease behaviour
Authors: Fabris Martina , Tonutti Elio , Pizzolitto Stefano , Isola Miriam , Curcio Francesco , Grimaldi Franco 
Published: June 2021

Aim of the studyTo test B‐Lymphocyte Stimulator (BLyS) as a new serological marker in the follow‐up of patients with neuroendocrine tumors (NET).MethodsEighty‐one consecutive NET patients and 56 controls were enrolled in the study. Patients were classified in 2 subgroups: persistent but stable disease or remission (n = 45) vs patients with recurrent disease (progressive patients, n = 36). BLyS and Chromogranin A (CgA) serum levels were analyzed by ELISA.ResultsBLyS levels were more elevated in NET patients than in controls (1153±529 pg/ml vs 655±158 pg/ml; p <0.0001) and correlated with tumor differentiation (1058±398 pg/ml in gastroenteric G1‐typical lungs vs 1325±640 pg/ml in gastroenteric G2–atypical lungs; p=0.026). Stable/remission patients displayed lower BLyS than progressive patients (889±251 pg/ml versus 1461±623 pg/ml; p <0.0001). BLyS did not change in patients who remained stable after 6.6±2.8 months (from 864± 283 pg/ml to 809±235 pg/ml), while further increased in patients with disease progression (from 1575±810 pg/ml to 1887±1163 pg/ml; p=0.045). Whereas, CgA showed contradictory changes. Metastatic patients displayed higher BLyS than non metastatic (1391±724 pg/ml vs 1079±422 pg/ml; p=0.022).ConclusionElevated BLyS serum levels characterize more aggressive NET patients. BLyS appears as a new potential prognostic marker in the follow‐up.
PEZH2 and H3K27me3 are associated with Mallory‐Denk body forming liver cell phenotype and HCC
Authors: French Barbara A. , Bardag-Gorce Fawzia , Oliva Joan , Li Jun , Zhong Jin , French Samuel W. 
Published: June 2021

BackgroundMallory‐Denk body (MDB) forming hepatocytes in chronic liver disease (CLD) and hepatocellular carcinoma (HCC) share phenotypic characteristics including altered expression of pEZH2 and H3K27me3.MethodLivers from DDC primed mice were induced to form MDBs by refeeding DDC with or without SAMe for 7 days after 1 month DDC withdrawal. These mice were used to test the role of pEZH2 and H3K27me3 using immunohistochemistry (IHC), Western blot and qRTPCR.ResultsLivers from mice refed DDC showed MDB forming hepatocytes and decreased staining for H3K27me3 in the nuclei compared to neighboring normal hepatocytes. The MDBs double stained for ubiquitin (Ub) and pEZH2 showed colocalization of Ub and pEZH2 in MDBs. Double stains of human livers with AH and HCC, showed colocalization of pEZH2 and Ub in the MDBs formed. Stains for H3K27 showed decreased staining of nuclei in liver cells forming MDBs. qRTPCR of EZH2 showed that DDC refeeding with SAMe reduced EZH2 levels significantly. Western blots of pEZH2 levels showed that pEZH2 was largely concentrated in the MDB band at the top of the gel. This correlated with the IHC results.ConclusionChanges in H3K27me3 and pEZH2 observed in MDB forming cells in AH, HCC and DDC fed mice indicated that MDBs are a phenotypic change related to loss of gene silencing, dedifferentiation and liver cell proliferation. Supported by NIH PA50‐011999.
Dietary supplementation with aromatic amino acids improves net protein synthesis in children with severe acute malnutrition during hospitalization
Authors: Hsu Jean W , Badaloo Asha , Taylor-Bryan Carolyn , Reid Marvin , Forrester Terrence , Jahoor Farook 
Published: June 2021

The stress of infection in children with severe acute malnutrition (SAM) imposes a metabolic demand for increased synthesis of acute phase proteins which have a higher content of aromatic amino acids (AAA), phenylalanine (Phe), tyrosine and tryptophan. We investigated whether supplementation with an AAA cocktail (330 mg·kg−1·d−1
) compared with isonitrogenous amounts of alanine (ALA) would improve measures of protein kinetics in 22 (11 with AAA, 11 ALA) children with SAM (age 4–31 mo) during treatment for SAM. Protein kinetics were assessed by measuring Phe kinetics in the fed state using a primed‐continuous infusion of 13C‐Phe. Supplementation started after the baseline experiment at the end of maintenance period (Phase 1) and continued to recovery. The 2nd and 3rd experiments were done at mid‐catch up growth when the children had replaced 50% of their weight deficit (Phase 2) and at recovery (Phase 3).

Phase 1
Phase 2
Phase 3

AAA
ALA
AAA
ALA
AAA
ALA

Phe Kinetics
μmol·kg−1·h−1

Total Intake
18±1
18±0.4
81±2 a
42±2
74±3a
35±2

Flux
48±4
53±5
60±5
47±6
81±15
72±13

NOD
7.5±2
9.8±1
32±5a
12±1
35±10a
23±3

Balance
12±2
10±2
49±5a
31±2
37±8a
11±3

Mean±SEM; NOD = Non‐oxidative disposal
significantly different from ALA group in same phase, P < 0.05

We conclude that dietary supplementation with AAA improves net protein synthesis in children with SAM.Supported by NIH Grant # 5R01DK75018
Protein requirement of elderly women determined using the indicator amino acid oxidation technique
Authors: Tang Minghua , McCabe George P , Elango Rajavel , Pencharz Paul B , Ball Ronald O , Campbell Wayne W 
Published: June 2021

ObjectiveThis study was designed to determine the protein requirement of elderly women age 80 y and older using the indicator amino acid oxidation technique.DesignEight Caucasian women aged 80–87 y (83 ± 3 y and BMI 27 ± 4 kg/m2, mean ± SD) completed a 3‐day protocol 7 times. Each woman consumed an adaptation diet for 2 days and on day 3 consumed a crystalline amino acid mixture with one of 7 protein intakes (0.1, 0.3, 0.6, 0.9, 1.2, 1.5 or 1.8 g·kg‐1·day‐1) tested randomly. Group‐based protein requirement was assessed using a biphase linear regression model of protein intake and L‐[1–13C] phenylalanine oxidation. The break point, at which there was no further decline in the 13C rate of appearance in breath, represented the mean protein requirement.ResultsThe mean protein requirement was 1.06 g·kg‐1·day‐1 (standard error of the group mean estimate: 0.095). This requirement is 61 % higher than the current Estimated Average Requirement (EAR) for adults of 0.66 g·kg‐1·day‐1 based on nitrogen balance.ConclusionThis study is the first to assess the dietary protein requirement of women in their 80s and the first to use the indicator amino acid oxidation technique with elderly participants. These findings bring into question the accuracy and adequacy of the current nitrogen balance based EAR for elderly women.Support: NIH RR025761; Bilsland Fellowship from Purdue Univ.Grant Funding Source : NIH RR025761; Bilsland Fellowship from Purdue Univ
Maternal vitamin D supplementation to optimize the vitamin D status of breastfed infants
Authors: Oberhelman Sara Schwind , Meekins Michael , Fischer Phillip , Lee Bernard , Gardner Brian , Singh Ravinder , Cha Stephen , Pettifor John , Thacher Thomas 
Published: June 2021

Vitamin D supplementation of breastfed infants is recommended because breast milk levels are low. We sought to determine if maternal supplementation would increase breast milk levels to achieve sufficiency in their infants. Forty mothers with exclusively breastfed infants were randomized to receive oral cholecalciferol (vitamin D3) 5000 IU/d for 28 days or 150,000 IU once. Maternal serum, breast milk and urine were collected on days 0, 1, 3, 7, 14 and 28 and infant serum on days 0 and 28. In mothers receiving daily vitamin D, serum and breast milk cholecalciferol attained steady levels of 18 and 8 ng/ml, respectively, from day 3 through 28. In mothers given the single dose, serum and breast milk cholecalciferol peaked at 160 and 40 ng/ml, respectively at day 1, before rapidly declining. Breast milk and maternal serum cholecalciferol were related (r=0.87). Infant serum 25OHD (mean±SD) increased from 17±13 to 39±6 ng/ml in the single dose group and from 16±12 to 39±12 ng/ml in the daily dose group (P= 0.88). All infants achieved sufficient 25OHD serum levels (≥20ng/mL). This study suggests that maternal supplementation can achieve sufficient infant serum levels of 25OHD via breastfeeding. A large single dose of vitamin D was equivalent to daily dosing for optimizing infant vitamin D status. This research was funded by the National Center for Research Resources and Mayo Clinic.Grant Funding Source: NCRR and Mayo Clinic
Visualizing homologous recombination and illustrating DNA repair pathway interaction in vivo via a bioengineered fluorescent reporter system
Authors: Sukup Jackson Michelle R. , Kiraly Orsolya , Rowaland Elizabeth , Schulte Kelly , Niedernhofer Laura J , Engelward Bevin P. 
Published: June 2021

Homologous recombination (HR) is a DNA repair process critical for maintaining genomic integrity. HR is generally beneficial, but over‐ or under‐utilization of HR can lead to can lead to deleterious rearrangements and cancer. To study HR, our laboratory previously developed the Fluorescent Yellow Direct Repeat (FYDR) mouse in which HR yields a fluorescent signal.We have utilized this mouse to study the interplay between HR and non‐homologous end‐joining (NHEJ) by knocking out the Ku86 protein. Both pathways are known to repair double strand breaks (DSB); preventing NHEJ in Ku86−/− mice resulted in an increase in HR. The newly proposed alternative end‐joining pathway was explored by knocking down the repair protein Ercc1. The Ercc1−/Δ mice showed an increase in HR in the pancreas, confirming in vivo an alternative DSB repair pathway and implicating ERCC1 in this pathway.While an excellent tool, the FYDR mouse is limited to study of HR in the pancreas and skin. We created the RADR (Recombination at a Direct Repeat) mouse, an improved model that has enabled our study of HR in a wide range of tissues including gut and liver. We can now study DNA damage and HR in multiple tissues in response to a treatment or exposure.Grant Funding Source : NIEHS Grant T32‐ES07020, NSF GRF, NIH Grant# P01‐CA026731‐31, R33‐CA112151‐01A2
Novel regulation of PDGFRα activation in Glioblastoma
Authors: Phillips Joanna J. , Huillard Emmanuelle , Robinson Aaron , Rosen Steven D. , Rowitch David H. , Werb Zena 
Published: June 2021

Glioblastoma (GBM) is characterized by abnormal activation of receptor tyrosine kinase (RTK) signaling pathways. We demonstrate that the extracellular sulfatase, SULF2, an enzyme that regulates multiple heparan sulfate proteoglycan‐dependent RTK signaling pathways, is a novel regulator of RTK‐signaling in GBM. In primary human GBM SULF2 protein is expressed in 29/57 (50%) tumors and using data from The Cancer Genome Atlas SULF2 transcript is increased in 197/424 (46%) tumors (http://cancergenome.nih.gov). To determine the functional role of SULF2 in GBM we knocked down SULF2 in GBM cell lines and generated murine malignant astrocytomas from Sulf2−/− tumorigenic neurospheres. These data demonstrated a striking SULF2‐dependence in activity of PDGFRα, a major signaling pathway in GBM. Ablation of SULF2 resulted in decreased PDGFRα phosphorylation and decreased downstream MAPK signaling activity. In addition, in vivo tumor growth was decreased. Interestingly, the proneural GBM subtype, characterized by aberrations in PDGFRα, demonstrated the strongest SULF2 expression. SULF2 may help identify a subset of GBMs that may be more dependent on exogenous growth factor‐mediated signaling.This work was supported by funds from the National Institutes of Health (K08 NS063456 to J.J.P.) and the Preuss Foundation.
The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7 in endothelial cells
Authors: CASTRONOVO Vincent , MATHEUS Nicolas , DUMONT Bruno , PEIXOTO Paul , HENNEQUIERE Vincent , DEROANNE Christophe , COLIGE Alain , DE PAUW Edwin , BELLAHCENE Akeila , MOTTET Denis , TURTOI Andrei 
Published: June 2021

Previous studies have shown that inhibition of HDAC7 blocks angiogenesis both in vitro and in vivo, however the underlying molecular mechanisms are not fully understood. The goal of the present study was to further the understanding of HDAC7 epigenetic control of angiogenesis in human endothelial cells.We performed siRNA‐mediated gene expression silencing of HDAC7 in human umbilical vein endothelial cells (HUVECs) followed by proteomic analysis. A‐kinase anchor protein 12 (AKAP12) was the most reproducibly up‐regulated protein and its overexpression was responsible for the inhibition of migration and tube formation in HDAC7‐depleted HUVEC. Mechanistically, H3 histones associated with AKAP12 promoter are acetylated following the removal of HDAC7, leading to an increase in its mRNA and protein levels. AKAP12 is responsible for protein kinase C‐β‐mediated phosphorylation of signal transducer and activator of transcription 3 (STAT3). Phosphorylated STAT3 increasingly binds to the chromatin and is necessary for maintaining the elevated levels of AKAP12 following HDAC7 knockdown.We demonstrated that AKAP12 is an angiogenesis suppressor gene, an epigenetic target of HDAC7 and a negative regulator of HUVEC migration and tube‐like structures formation.This work is supported by Walloon Region (NEO‐ANGIO), the University of Liège and the National Fund for Scientific Research, Belgium.
FRONTIERS IN BIOMEDICAL EDUCATION: INTEGRATIVE TEACHING/LEARNING OF PATHOPHYSIOLOGY AND CONCEPT OF ETIOPATHOGENETIC CLUSTERS
Authors: Kovac Zdenko 
Published: June 2021

Pathophysiology education has been following many pathways, including concepts of general principles, nosology and organ‐related pathophysiology. During the studies adults construct the knowledge in self‐directed, autonomous and previous experience‐related manner. They try to apply new knowledge directly to a problem solving. Evaluation and active resynthesis of data seem to facilitate a gain and retain of knowledge. In postgenomic era, students of medicine are faced with various levels of cognitive certainty of knowledge (from a clear cause‐effect to a fuzzy‐logic relation), complexity, variability and endless quantities of data.We developed educational method that contains four elements: 1. exposition of problem 2. repetition of relevant knowledge 3. algorhythmic resynthesis, and 4. feedback integration of the problem. Four reiterative steps are an efficient way to deal with complexities. The method is 2.3 times more efficient in comparison to classical teaching. It nurtures vertical, horizontal and longitudinal conceptualization of the problem. Etiopathogenetic pathways tend to form the clusters in which branching and integration take place. Therapeutical corrections of such cluster values lead to a clinical improvement. There are 91 principal clusters within the 30000 diseases. The concept of clusters helps to grasp a nonlinearity and complexity of pathobiology within the real study‐time framework.
Comparative Neuronutritive Protection of Citrus sinensis & Vitamin C on Differential Gene Expression in Brain Tissues of Female Sprague Dawley Rats
Authors: Ogunleye Olorunwa Olufunmilayo , James Ayorinde Babatunde , Ebuehi Osaretin Albert , Iwalokun Bamidele , Saibu Gbemisola Morounke , Odesanmi Selina Omolola , Magbagbeola Olubunmi , Omilabu Sunday Aremu 
Published: June 2021

Citrus sinensis (Orange), a popular fruit has been known to contain various antioxidant compounds in which vitamin C is one of them. These antioxidants scavenge free radicals that may cause neurodegenerative diseases. In this study, we investigated the comparative effects of orange juice and vitamin C on the differential gene expression of tumor necrosis factor receptor (Tnfr), p53, superoxide dismutase (Sod), and estrogen receptor genes in female rats.Minerals and vitamin C composition was determined from extracted orange juice. 5ml/kg of the extracted orange juice and 20mg/kg Vit C were administered to the animals which were divided into control, Vit C and orange groups. On the 7th day, rat brain tissues were collected in liquid nitrogen and total RNA was extracted and cDNAs were made from 100ng normalized RNA samples. Gene expression was assayed using SyBR green relative quantification. Data was analyzed using Applied Biosystems SDS software and Graphpad Prism 5.Our findings show that orange juice caused higher levels (46 Fold) of gene expression in antioxidant gene (Sod), anti‐tumour p53 gene (36 Fold) and estrogen receptor gene (3.5 Fold) which explains the promising neuro‐protective effect of orange juice.Grant Funding Source: AAA
Understanding the regulation of AMPA and NMDA iGluRs through the binding of sulfated neurosteroids
Authors: Bartle Emily Irene , Fanelli David , Roark Ryan , Young Amber , Gentile Lisa 
Published: June 2021

AMPA, NMDA, and kainate receptors belong to the ionotropic glutamate (iGluR) family of receptors located in the post‐synaptic neural membrane. Upon binding to glutamate, a major fast excitatory neurotransmitter, these channels activate and play an important role in synaptic plasticity, learning and memory. Mis‐regulation of these receptors has been linked to neurodegenerative diseases such as Alzheimer's and Parkinson's.Our research is aimed at understanding the regulation of AMPA and NMDA receptors by the endogenous neurosteroids pregnenolone sulfate (PS) and 3α‐hydroxy‐5β‐pregnan‐20‐one sulfate (Pregas) for potential disease state applications. PS potentiates NMDA receptors containing NR2A or NR2B subunits, while inhibiting NMDA receptors containing NR2C or NR2D subunits and all other iGluRs. Likewise, Pregas negatively regulates all iGluRs. Our findings show that both neurosteroids bind to the amino terminal domain (ATD) and S1S2 domain of the NMDA NR2B and AMPA GluR2 subunits, but only bind to the ATD of the NDMA NR2D subunit. Intrinsic fluorescence studies confirm the binding of PS and Pregas to the subunit domains. Data from additional studies, including KD and Stern‐Volmer analysis, will be presented to further elucidate and differentiate binding.
Dietary Bovine Lactoferrin Stimulates Intestinal Proliferation in Piglets
Authors: Reznikov Elizabeth Alexandra , Comstock Sarah S , Contractor Nikhat , Donovan Sharon M 
Published: June 2021

Human milk contains factors, such as lactoferrin(LF), that stimulate gastrointestinal growth and maturation. Herein, proliferative properties of bovine LF(bLF) were explored through 5‐ethynyl‐2′‐deoxyuridine(EdU) incorporation in vivo. Colostrum‐deprived pigs were fed formula containing 0.4(CON), 1(LF1) or 3.6(LF3) g bLF/L. On d7 or 14, pigs were intraperitoneally injected with 10mM EdU(1ml/kg body weight) 2h prior to euthanasia. Proliferation was assessed ex vivo in formalin‐fixed jejunal sections using Click‐iT EdU Alexa Fluor 555 Kit. Sections were imaged with a confocal microscope. Staining was quantified with AxioVision, where area positive for EdU(proliferation) was normalized by the area positive for DAPI(total nuclei). Formalin‐fixed jejunum sections were stained with haematoxylin and eosin for villus and crypt measurements. bLF did not affect body weight gain or intestinal weight or length. LF1 and LF3 pigs had a 1.5‐ fold increase in crypt cell proliferation compared to CON pigs. In LF3 pigs, crypt depth and area were greater(1.5‐fold on d7, 1.3‐ fold on d14) than in CON pigs. This study supports in vitro studies that showed LF could stimulate proliferation and is the first to show that physiologically‐relevant concentrations of milk‐borne bLF stimulate crypt cell proliferation in pigs suggesting LF plays a role in healthy GI development.(Funded by Pfizer Nutrition)Grant Funding Source : Pfizer Nutrition
Hi‐5 Way: A multidisciplinary approach to secondary prevention of obesity in children 5 and under from underserved areas
Authors: Gorman Kathy A. , Lim-Miller Aimee , Oliver Lauren , Lenders Carine 
Published: June 2021

There is evidence that most excess weight gained at puberty occurs before age 5. Rapid weight gain in infancy and early childhood is associated with obesity related complications later in life. Prevention of excess weight gain should begin in infancy and early childhood.The Nutrition and Fitness for Life (NFL) program is a multidisciplinary pediatric weight management clinic that targets underserved populations. In 2009, NFL began a secondary prevention intervention for children ages 5 and under who are obese or rapidly gaining weight: Hi5‐Way. Our team includes a medical doctor, registered dietitian, and mental health provider. After an in‐depth assessment, we help children achieve healthier weight gain through a variety of family interventions.Topics addressed include: role modeling, “table talk”, sleep/bedtime routines, meal/snack patterns, increasing active play, infant feeding, menu ideas, and picky eating. Material is modeled after Ellyn Satter's feeding principles and the WIC “Touching Hearts Touching Minds” program. Patients are referred to the BMC food pantry and community programs to promote health via increased access to resources. Frequency of clinic visits is tailored based on individual needs.ConclusionSecondary prevention of chronic diseases related to nutrition among underserved populations with young children is feasible. Support from the New Balance Foundation.