bluuebunny/crossref_metadata_2025_split huggingface dataset:
A majority of children in Los Angeles and New York City have elevated urine osmolality associated with not drinking water at the start of the school day
Authors: Stookey Jodi , Brass Bernie , Holliday Ava , Arieff Allen , Constant Florence 
Published: June 2021

This study determined the prevalence and dietary correlates of elevated urine osmolality, a possible risk factor for reduced cognitive performance, in children (9–11y) at the start of the school‐day in Los Angeles (LA) and New York City (NYC). Randomly selected children in LA (n=334) and NYC (n=208) recorded morning food and beverage intake and gave a urine sample on a school‐day between 8:30–9:30am. In LA and NYC, 63% and 66% of children had elevated urine osmolality (>800 mOsm/kg). In multivariable‐adjusted logistic regression models, children who did not drink water in the morning were 3 times more likely to have elevated urine osmolality than children who had no food or fluid, food but no drink, or a beverage other than water in the morning. The relative odds of elevated urine osmolality associated with milk or juice was the same as that associated with overnight fluid restriction. Urine osmolality below 800 mOsm/kg was associated with >500ml drinking water. A majority of children in LA and NYC have elevated urine osmolality associated with not drinking water in the morning.Funding source: Unrestricted grant from Nestle Waters
Barriers to Healthy Nutrition and Food Preparation Practices of Rural Families
Authors: McWhinney Sharon , McKyer Lisako , Outley Corliss , McDonald Andrea 
Published: June 2021

The increased incidence of obesity is a major concern and intervention efforts to thwart this trend in low income minority populations continue. Good nutritional habits and behavioral practices are important for healthy weight management and maintenance. This project was conducted to gain insight the personal and contextual factors, and barriers, impacting food preparation and consumption in rural families'. Focus groups were conducted with 100 low income parents from rural communities to collect cultural perspectives and to identify barriers to healthy eating and food preparation practices. Statements were extracted and categorized from the focus group transcripts. Analysis of the data resulted in themes including general food purchases, preparation practices, and barriers to good nutrition. Food preparation was based primarily on family history and tradition; example ‘fired fish Fridays’, and ‘family member preferences’. Advertising and children in charge were discussed by most of the participants as being significant barriers to healthy eating. Surprisingly, many of the families dining out decisions were determined by daily specials offered at local fast food restaurants with little thought given to the nutritional value of meals.Funding for this project was made possible by 1P20MD0002295 from the National Center on Minority Health and Health Disparities.
Beyond food insecurity: How context can help improve complementary feeding interventions
Authors: Paul Keriann H. , Khalfan Sabra S. , Muti Monica , Humphrey Jean H. , Stoltzfus Rebecca J. 
Published: June 2021

Context has not been elaborated in current recommendations for complementary feeding (CF) interventions apart from a categorization of food security. We compared 2 food insecure settings in Africa to explore how context affects CF practices and nutrient intakes and in turn a suitable intervention strategy. We conducted 24‐hr recalls and interviews with mothers of 6–12 mo‐olds in rural Zimbabwe (n=32) and Pemba Island, Tanzania (n=44). In both settings, many infants had suboptimal nutrient intakes, poor dietary diversity, and hygiene. Pemba had poor breastfeeding, and Zimbabwe had low energy density. Contextual determinants were indigenous knowledge, livelihoods, family foods, agriculture, and the ecosystem. Both settings require education targeting indigenous knowledge and family eating behaviors. A home‐based fortificant is enough for Pemba because the island's ecosystem provides sufficient sources of macronutrients. However, Zimbabwe needs a fortified food‐based supplement to overcome the poor agricultural and economic context. Assessing context was essential to intervention design. A framework for formative research is proposed. Supported in part by DFID and NIH grant T32 HD007331.Grant Funding Source: NIH grant T32 HD007331
Diets high in saturated fat increase intestinal inflammation associated with IBD via alterations in the microbiota
Authors: Devkota Suzanne , Wang Yunwei , Antonopoulos Dion , Chang Eugene 
Published: June 2021

Clinical evidence suggests the chronic inflammation seen in inflammatory bowel diseases (IBD) results from a combination of environmental/microbial factors on a background of genetic susceptibility. This study evaluates the environmental factor of dietary fat composition on the incidence of IBD via alterations in gut microbiota. Male C57bl/6j mice (6 w/o) were fed a high saturated fat (SF; 47% energy from carbohydrates, 16% energy from protein, 37% energy from fat), high polyunsaturated fat (PF; 47:16:37), or a low fat control diet (C; 70:16:14) for 3 wks (n=10/diet). Cecal contents were collected for microbial pyrosequencing of 16s rDNA and revealed a “bloom” of b.wadsworthia, a cytotoxic proteobacteria, only in the SF diet. Body weight was greater on SF diet than PF and LF despite no significant difference in kcals consumed, suggesting an increased microbial capacity for energy harvest on SF, a contributing factor to local inflammation. Next, male IL‐10−/− mice (4 w/o), a model of spontaneous colitis, were fed LF or SF (n=5/diet) for 12 wks. Only 20% of these mice developed colitis on LF vs. 100% on SF accompanied by a 4‐fold increase in pro‐inflammatory IL‐6 and IL‐12 and a microbial profile like that of the C57bl/6j mice fed SF. These data indicate that SF diets create an environment favorable for the growth of harmful bacteria contributing to incidence to IBD.Supported by the National Institutes of Health R01 and T32Grant Funding Source: National Institutes of Health
A Reduced Carbohydrate Diet Results in Loss in Lean Mass in Peripubertal African American Girls
Authors: Casazza Krista 
Published: June 2021

Pharmacologic lowering of insulin has been shown to improve insulin dynamics, delay reproductive maturation and result in less body fat accumulation over time in early maturing girls. Modification of the diet may result in comparable outcomes. The main objective of the project was to examine the effectiveness of a diet low in carbohydrate on improving metabolic profile and promoting weight loss in overweight African American (AA) females aged 9–14 years. The study included two phases utilizing a eucaloric (weight‐stable) in the first phase and a hypocaloric diet (weight‐loss; 1000kcal deficit) in the second phase. Twenty‐four girls were randomized to one of two diets, a reduced carbohydrate diet (redCHO;42% CHO, 40% fat) or standard (STAN; 60% CHO, 22% fat). Energy requirements were determined by indirect calorimetry and all meals were provided to the participants. Fasting blood samples were collected for metabolic analysis and body composition was assessed by DXA. During the eucaloric phase, subjects on the redCHO diet had a greater reduction in triglycerides (p<0.05), with no other differences in metabolic profile observed. In addition, participants on the redCHO diet had greater weight loss (p<0.05); however, the weight loss was due to loss of muscle mass, not fat or bone mass. During the hypocaloric phase, there were no differences in weight loss or body composition between the diet groups.Grant Funding Source: APS
Epigenetic Modifications Cause Transcriptional Repression of p21 Gene in Mammary Gland in the Offspring of Protein‐Restricted Rats
Authors: Zheng Shasha , Pan Yuan‐Xiang 
Published: June 2021

Maternal nutrition during pregnancy is an important intrauterine environmental factor resulting in persistent alteration of the offspring epigenome and is associated with developmental susceptibility as well as the health outcome in later life. This study examined the effect of maternal low protein diet on the regulation of p21 gene expression in offspring mammary gland in rat. Timed‐pregnant Sprague‐Dawley rats were fed one of the two isocaloric diets, control (18% casein) or low protein diet (LP, 9% casein) during gestation period. Compared to control, offspring rats from LP group showed 38% decrease in p21 mRNA level in mammary gland. Western blot analysis confirmed the down‐regulation of p21 at protein level. Chromatin immunoprecipitation (ChIP) assay demonstrated that the down‐regulation of p21 transcription in LP offspring was associated with histone code changes within the p21 promoter region, including reduced acetylation of histone H3 and H4. These results supported the hypothesis that maternal protein restriction during pregnancy programs p21 expression and histone code in offspring mammary gland.Grant Funding Source: NIH
Wnt/β‐catenin signaling, but not AKT/β‐catenin signaling is required for epithelial restitution following colitis
Authors: Koch Stefan , Nava Porfirio , Parkos Charles A , Nusrat Asma 
Published: June 2021

We and others have previously shown that inflammatory cytokine induce the production of the secreted Wnt signaling antagonist Dkk1. Since elevated cytokine levels in the intestinal mucosa are a hallmark of inflammatory disorders of the intestine, we evaluated the contribution of this Wnt inhibitor to the pathogenesis of chronic colitis using Dkk1 hypomorphic doubleridge mice, and anti‐Dkk1 antibody treatment in vivo and in vitro. Dkk1 hypomorphic animals showed a significantly faster recovery from experimental colitis as assessed by a combined disease activity score and histological examination, which coincided with increased LRP6 levels in intestinal epithelial cells and increased PI3K activity. Conversely, AKT protein levels and activity, and subsequent AKT‐mediated β‐catenin phosphorylation were decreased in doubleridge mice during acute colitis. Downregulation of AKT in the absence of Dkk1 was confirmed by extended treatment of model intestinal epithelial cell lines with anti‐Dkk1 antibody. These results suggest that Wnt/β‐catenin, but not AKT/β‐catenin signaling is required for the recovery from inflammatory epithelial injury.Supported by grants from the National Institutes of Health (DK72564, DK61379 and DK79392 to C.A.P., DK53202, DK55679, DK59888 to A.N.), and the Crohn's & Colitis Foundation of America (to S.K. and P.N.).
Leukocyte recruitment to the cremaster muscle exhibits circadian oscillations
Authors: Scheiermann Christoph , Kunisaki Yuya , Chow Andrew , Lucas Daniel , Frenette Paul 
Published: June 2021

Circulating leukocyte numbers exhibit circadian oscillations with peak values in mice during the day [Zeitgeber time, ZT 5 (hours after the onset of light)], and trough at night [ZT 13]. Here, we report that leukocyte recruitment to the cremaster muscle oscillates in antiphase with blood count patterns, with numbers of adherent and extravasated leukocytes peaking at night and exhibiting a nadir during the day (ZT5/ZT13: 5.3 ± 0.3/7.3 ± 0.3 cells per 100 × 50 μm2 extravascular vessel segment, P<0.001) as assessed by in vivo and ex vivo imaging of the cremasteric microvasculature. Circadian differences depended on ICAM‐1 expression and local innervation, as ICAM‐1 deficiency and surgical denervation of the genitofemoral nerve ablated oscillations. Systemic stimulation of mice with fMLP resulted in increased recruitment of granulocytes during the day compared to night (ZT5/ZT13: 1.3 ± 0.3/0.6 ± 0.3 cells per 100 × 50 μm2 extravascular vessel segment, P<0.05). On the other hand, mice subjected to a 12h jetlag did not exhibit circadian oscillations in leukocyte recruitment and failed to show inflammatory leukocyte infiltration after fMLP treatment. These data show that leukocyte trafficking to the cremaster exhibits circadian oscillations and suggest that circadian time can influence the recruitment of leukocytes during inflammation.Funded by the German Academic Exchange Service (DAAD) and the NIH.
Requirement of a4b1 and a5b1 Integrin Expression in Bone‐Marrow Derived Progenitor Cells in Preventing Endotoxin‐Induced Lung Vascular Injury and Edema in Mice
Authors: Wary Kishore K , Malik Asrar B 
Published: June 2021

The goal of this study was to address the hypothesis that integrin‐mediated cell adhesion is a critical requirement for the endothelial barrier protection induced by bone marrow derived progenitor cells (BMPCs). Bone marrow (BM)‐derived mononuclear cells (MNCs) from donor C57BL mice were used as a source for BMPCs and characterized for BMPCs marker and integrin expression. To test the efficacy of BMPCs treatment and to address the mechanisms of the benefit, we used a mouse model of endotoxin‐induced ALI. We noted robust expression of α4 and α5 integrins in donor BMPCs. The adhesion of BMPCs onto purified extracellular matrix not only induced Fak phosphorylation, but also the formation of branching point structures in an α4 and α5 integrin‐dependent manner. BMPCs expressing red fluorescent protein (RFP) were administered via the retro‐orbital venous route in mice treated intraperitonially with LPS. These mice received either control endothelial cells (ECs) or BMPC or BMPCs incubated with specific anti‐integrin monoclonal antibodies, or BMPCs tranduced with a specific shRNA integrin construct. BMPCs afforded a 50% survival and reduced extravascular fluid content. Blocking or silencing the α4 and α5 integrins in donor BMPCs failed to protect these mice from injury or to reduce extravascular fluid content. In these mice, we also noted an increased retention of RFP+, Flk1+ and CD34+ BMPCs (20%) for the next 8 weeks, as well as overall improved lung architecture. Collectively, our data showed that BMPCs play a critical role in mounting lung microvessel repair through the expression of α4β1 and α5β1 integrins, causing restoration of lung fluid balance and increased survival rates in a mouse model of ALI.This study was supported by NIH‐RO1, HL079356 and R01HL090152.
The Scientists' Perspective on Kennewick Man
Authors: Owsley Douglas W. 
Published: June 2021

Kennewick Man is one of the oldest and most complete skeletons ever found in North America. Findings from this 9,300 year old skeleton are providing new insights into the ongoing mystery of who colonized the New World, a process more complicated than previously envisioned. Recent evidence suggests multiple migrations by different peoples entering the Americas from different homelands at a time earlier than originally thought. Securing the right to study important discoveries found on federal lands, such as was the case with Kennewick Man, has helped us learn more about what life was like for the earliest Americans. It helps secure the right to ask questions of the past, and to challenge long held assumptions about a time period for which we have much to learn.The Kennewick skeleton was discovered after it had eroded out of the south bank of the Columbia River in the state of Washington. Although not found in situ, analysis by a team of scientists has determined the original stratigraphic placement and positioning of the remains in the bank. Other observations provide detailed information about his body size and shape, health, injuries, habitual activities, diet, and origin.Investigation of the skeleton was enhanced by the use of computer aided high technology systems. In order to reconstruct the skull and right os coxa, industrial computed tomography imaging and replication was necessary. This work produced dimensionally accurate copies of the broken and separated bones, which could be reassembled for study and measurement. CT visualization and rapid prototyping also made it possible to digitally remove for examination a projectile point embedded in the right os coxa. This presentation will highlight what has been revealed through careful scientific analysis.
Detection of vascular oxidative stress in atherosclerotic lesions by electrochemical impedance spectroscopy
Authors: YU FEI , Ai Lisong , Edington Collin David , Kim Eun Sok , Hsiai Tzung 
Published: June 2021

Rupture of atherosclerotic plaques leads to acute coronary syndromes and stroke. However, detecting mechanically unstable plaque remains an unmet clinical need. We proposed that arterial walls harboring oxidative stress exhibit distinct electrochemical properties as measured by electrochemical impedance spectroscopy (EIS). Using concentric microelectrodes, we developed an EIS sensor to assess vascular oxidative stress (defined as foam cells and oxizided low density lipoprotein [oxLDL]) in explants of New Zealand White rabbit aortas. EIS sensor was made in contact with the endoluminal surface of aortas isolated from rabbits fed on a high‐fat diet for 8 weeks. Statistical correlation between EIS and oxidative stress was established by immunohistochemical analysis for oxLDL and foam cell infiltration. The increase in impedance measurements were statistically significant in atherosclerotic lesions harboring oxidative stress at 100kHz (lesions: 26.7kΩ±2.7kΩ; control: 15.8kΩ±2.4kΩ, n=10, P<0.001) and at 10kHz (lesions: 49.2kΩ±7.3kΩ; control: 27.6 kΩ±2.7kΩ, n=10, P<0.001). Characterization of 2mm × 2mm lesions harboring 10% endoluminal stenosis was reproducible. Hence, our data provides a basis to further develop intravascular oxidative stress sensors for the assessment of mechanically unstable plaque. Research supported by NHLB 083015 and NHLBI 068689.Grant Funding Source: NHLBI
Epigenetic Lineage Barriers ensure normal Trophoblast Differentiation in Early Development
Authors: Hemberger Myriam C 
Published: June 2021

Cells that give rise to the trophoblast lineage are set aside in the earliest differentiation event after fertilization to mediate implantation, placenta formation and fetal nutrition. We are interested in genetic and epigenetic factors that contribute to normal trophoblast differentiation and formation of a functional placenta. Correlating with the global asymmetry in DNA methylation levels between cells of the embryonic and trophoblast lineage, we have found that DNA methylation is critical to ensure the stability of early cell lineage determination. In a genome‐wide screen for promoter DNA methylation differences, we have identified a gatekeeper gene, Elf5, that is unmethylated and expressed in the trophoblast lineage, but methylated and stably repressed in the embryonic lineage. We show that this gatekeeper acts downstream of initial lineage determination to either reinforce commitment to the trophoblast lineage, or to abort this pathway in the embryonic lineage. This finding is the first example of a major epigenetic restriction of cell lineage fate and provides a molecular mechanism for the concept of canalization of developmental pathways during embryogenesis.This work was supported by the MRC, BBSRC and the Centre for Trophoblast Research.
Dysregulation of Multiple MicroRNAs Accompanies DNMT3b Overexpression and Expression of a Hypermethylation Defect in Breast Cancer Cell Lines
Authors: Sandhu Rupninder , Coleman William B 
Published: June 2021

A subset of breast cancer cell lines express a hypermethylation defect associated with DNMT hyperactivity and DNMT3b overexpression. To determine the mechanism of DNMT3b overexpression in breast cancer cell lines, we examined the role of regulatory microRNAs (miRs) that have been implicated in the regulation of DNMT3b (miR‐29a, 29b, 29c, 148a, 148b) and miRs that are predicted to regulate DNMT3b (26a, 26b, 203, 222). miR expression levels were determined by qPCR (normalized to RNU66) in non‐neoplastic MCF12A cells and a panel of 16 breast cancer cell lines previously characterized as hypermethylators (n=10) or non‐hypermethylators (n=6). 90% of hypermethylator cell lines express low levels of ≥4 miRs and 100% of non‐hypermethylator cell lines express ≥4 miRs at normal levels. Average expression of miRs 29c, 148a, 148b, 26a, 26b, and 203 in hypermethylator cell lines was reduced 60%–85% compared to non‐hypermethylator cell lines. Further, miR expression correlated with methylation‐sensitive gene expression (R=0.68, p=0.0035) and with gene promoter methylation status (R=0.55, p=0.026) among these cell lines. These findings suggest that post‐transcriptional regulation of DNMT3b involves multiple miR species and that loss of regulation of miR expression contributes to the DNMT3b overexpression in hypermethylator cell lines.UNC University Cancer Research Fund
Lung‐kidney interactions during pneumonia and acute kidney injury
Authors: Singbartl Kai , Bishop Jeffrey , Kellum John 
Published: June 2021

Sepsis is a major contributor to organ failure in critically‐ill patients. Mortality drastically increases with the number of failing organs. Both lung and kidney injury are very common in severe sepsis. The aim of this study was to investigate kidney‐lung interactions during pneumonia‐induced sepsis and acute kidney injury (AKI).We have sequentially combined murine models of folic‐acid (FA)‐induced AKI and P. aeruginosa‐induced pneumonia (PNA). A subgroup of mice received a neutrophil (PMN)‐depleting antibody or respective control before induction of PNA. 24h after induction of PNA, we measured oxygen saturation (SpO2), plasma creatinine (pCrea), and P. aeruginosa colony‐forming units (CFUs) in lung homogenates. Statistical analysis included one‐way ANOVA, Kruskal‐Wallis one‐way analysis of variance, post‐hoc Student‐Newman‐Keuls test, and t‐test. All data is given as median (inter‐quartile range).PNA leads to severe AKI in mice, which seems to be independent of PMNs. In a PMN‐dependent model of PNA, AKI worsens PNA. As AKI is known to impair pulmonary recruitment of PMNs [1], one can hypothesize that the effects of AKI on pneumonia are mediated by PMNs. In summary, we show functionally relevant kidney‐lung interactions during PNA and AKI, which are partially PMN‐dependent.
Synthetic education in pathophysiology. Role of etiopathogenetic clusters.
Authors: Kovac Zdenko 
Published: June 2021

In order to make pathophysiology teaching/learning, both, teacher‐workable and student‐friendly, we developed educational model with four steps. 1. Exposition of problem gives short presentation of “raw data” derived from patient records, selected publications with experimental data, etc. 2. Repetition of relevant knowledge is a multiple choice test, whose statements is related to the exposition and referred teaching materials. 3. Algorhythmic workout of the pathogenesis is task in which students, out of given 25–30 units of etiopathogenesis, build‐up the cause‐consequence sequence of events, with positive and negative feedback loops, and parallel and contextual events. 4. Feedback integration of the problem deals with additional relations, systematization and quantitative aspects of the same problem.This four‐step matrix‐like approach clearly outlines etiopathogenetic pathways and networks of interconnected elements within the hierarchy of the system. Along with data analysis, students are asked to design a synthetic view of the problem. They use both exact and fuzzy logic in such integration. Some interconnecting nodes (e.g., processes, structural alterations, concentration abnormalities, etc) form clusters, with multiple entries and outputs. Focusing to such clustering points seems to be a reliable approach to master complexities in medicine and bridging the basic and clinical knowledge.