bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dogs choose 23% of their calories as protein which is associated with body composition and circulating metabolites
Authors: Jewell Dennis Edward , Vondran Jodi C. , Vanchina Melissa A. 
Published: November 2023

As in other mammals, domestic dogs have specific taste preferences that can be influenced by macronutrient composition and physical characteristics of food as well as the presence or absence of specific taste imparting compounds (palatability enhancers). This study investigated the relationship of body composition and food choice and that choice on subsequent metabolomic shifts. Experimental foods were prepared with similar palatability for a population (as evaluated by the ratio of the test food to the total daily food consumed [grams test/(grams test+grams control)] through manipulations of factors independent of macronutrients. These foods with similar palatability preference for the population as a whole were then investigated for intake choice with 20 dogs with varying body fat (mean 3.9 kg, Std. Dev. 0.9) as well as subsequent effect of food choice on serum metabolites. Four completely balanced foods were available to the dogs at all times. The four foods had: a) 33% of calories from protein, b) 54% calories from fat, c) 56% calories from carbohydrate and d) intermediate level of calories from protein, fat and carbohydrate. Dogs chose to consume 23.0% calories from protein (Std. Dev. 1.5%, min 20% max 26%). Body composition influenced the choice of percent calories as protein; There was a positive relationship between body fat and percent calories as protein (r=0.56 p=0.02) while there was no relationship between body lean and percent calories as protein (r=0.06; p=0.82). Overall, dogs with high body fat showed the highest preference for dietary calories from protein. There was a positive association between the percent of calories as protein and ornithine and homocitrulline suggesting increased urea cycle metabolism. Increasing calories from protein were also negatively associated with specific metabolites in the TCA cycle (citrate, alpha ketoglutarate). There was an association with increased protein intake and decreasing endocannobionods (N‐oleoyltaurine, palmitoyl ethanolamide N‐palmitoyltaurine). In summary, when given the opportunity to choose between foods which had similar palatability dogs chose to consume 23.0% of their calories as protein and had an increased preference for protein as adiposity increased. These intake preferences were associated with metabolic changes reflecting metabolic shifts.Support or Funding InformationHill's Pet Nutrition, Inc.
BRAIN DEVELOPMENT AFTER PRETERM BIRTH IS ENANCED BY INCLUDING PHOSPHATIDYLSERINE IN FORMULA: EVIDENCE FROM PRETERM PIGS
Authors: Buddington Randal K , Chizhikov Victor V , Sable Jeffrey J , Sable Helen J , Iskusnykh Igor Y , Steshina E Y , Holloway Zade R , Buddington Karyl K , Lifshitz Yael 
Published: November 2023

Brain development is compromised in 40–50% of preterm infants. This is evident from the decreased cerebellar size from MRI imaging, delays in sensory processing and neural development, and an increased risk of hearing loss after preterm birth. In light of the importance of nutrition support for brain development of preterm infants, we tested if development of the brain of pigs delivered prematurely at a stage of development relevant to 32 week preterm infants (92% term; day 105 of 115 d of gestation would benefit from feeding a formula supplemented with phosphatidylserine (1.9 g/L; InCogTM; Enzymotec, Israel). Controls included siblings fed formula without InCogTM and newborn vaginally delivered term pigs. Event‐related brain potentials (ERP) were recorded the day of delivery and postnatal days 2, 5, and 10 in response to pairs of 50‐ms tones (500‐ms inter‐tone interval) with randomized inter‐pair intervals (IPI) of 1 or 5 seconds during a 30 minute period with randomized inter‐pair intervals (IPI) of 1 or 5 seconds. ERPs (specifically the negative (N1) and positive (P2) deflection components ~100 ms and 200 ms after a stimulus, respectively) were not detected the day of delivery, were discernable at day 2, and at day 10 (term equivalent) were significantly larger and earlier than at days 2 and 5 emergence. The pigs were euthanized at day 10 and the cerebella were removed, weighed and evaluated by immunohistochemistry. The formula with InCogTM resulted in increased cerebellar weight and numbers of granule cells compared with control formula. These findings suggest InCogTM is a promising ingredient for preterm formula that will improve cerebellar growth and maturation after preterm birth.Support or Funding InformationThis study was partially funded by Enzymotec
Probiotics (Lactobacillus gasseri KS‐13, Bifidobacterium bifidum G9‐1, and Bifidobacterium longum MM‐2) and Health‐Related Quality of Life in Individuals with Seasonal Allergies
Authors: Dennis Jennifer C. , Culpepper Tyler , Nieves Carmelo , Ukhanova Maria , Mai Volker , Christman Mary C. , Langkamp‐Henken Bobbi 
Published: November 2023

BackgroundQuality of life (QOL) is often reduced during seasonal allergies due to troubles from nose and eye symptoms. Probiotics modulate immune function and may improve QOL for some individuals during allergy season. Induction of tolerance by regulatory T cells (Tregs) may be involved in this processMethodsIn this double‐blind, placebo‐controlled, randomized clinical trial, 173 participants (26.0±1.2 y [mean±SEM] and 62.8% females, probiotic group; 27.6±1.4 y and 74.7% females, placebo group) who self‐identified as having seasonal allergies received either a probiotic (2 capsules/day, 1.5 billion cells/capsule) or placebo capsule during spring allergy season for 6 weeks. QOL was assessed throughout the study using the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MRQLQ), which reports the average score for 14 symptoms rated from 0 (not troubled) to six (extremely troubled). Intestinal microbial profiles were determined via 16S rRNA sequencing from stool samples collected at baseline and at final (week 6). Fasting blood samples were taken from a subgroup (n=72) at baseline and final to determine immune parameters; serum total IgE and Tregs were quantified via ELISA and flow cytometry, respectively.ResultsTotal IgE increased from baseline to final regardless of group (data were log transformed for analysis; untransformed: 547±62.5 vs. 595±66.6 ng/mL, p=0.033), indicating a sustained response to allergens. Both groups reported decreases in MRQLQ scores from baseline to final, indicating a possible placebo effect or induction of tolerance; however, the negative change in global MRQLQ scores from baseline to final was significantly larger in magnitude in the probiotic group (−0.66±0.13 vs. −0.23±0.16, p=0.039), indicating higher QOL. Several domain scores from the MRQLQ also differed significantly between groups (−0.55±0.15 vs. −0.05±0.16, p=0.017 for activities; −0.71±0.18 vs. −0.09±0.19, p=0.016 for nose symptoms; −0.90±0.18 vs. −0.37±0.18, p=0.008 for other symptoms). Alpha and beta diversity indices to measure representative intestinal bacterial phyla did not differ between groups. The percentage of Tregs increased from baseline to final in all participants, but changes were not different between groups.ConclusionsThis combination of probiotics resulted in a higher self‐reported QOL during allergy season for healthy individuals who experience seasonal allergies. However, further research is needed to elucidate the mechanism by which probiotics influence allergy‐related QOL and to establish the clinical relevance for the change in the MRQLQ scores.Support or Funding InformationWakunaga of America Co., Ltd.
Homeostatic model assessment index 1 and 2 are associated with serum 25‐hydroxyvitamin D among Haitians and African‐Americans living in South Florida
Authors: Ajabshir Sahar , Exebio Joel , Zarini Gustavo , Voccaro Joan , Huffman Fatma 
Published: November 2023

PurposeThe purpose of this study was to investigate the association between insulin resistance calculated by homeostatic model assessment index 1 (HOMA1‐IR), homeostatic model assessment index 2 (HOMA2‐IR) and serum 25‐hydroxyvitamin D [25(OH)D] among a group of Haitian‐Americans and African‐Americans living in South Florida.SignificanceLow serum vitamin D level is associated with a wide range of health concerns such as diabetes, osteomalacia, auto‐immune disorders and certain cancers. Several studies indicated higher insulin resistance is associated with increased risk of developing metabolic syndrome and type 2 diabetes. There are currently no studies investigating the relationship between vitamin D and insulin resistance among Haitian‐Americans and African‐Americans.ParticipantsThe sample for this study included 241 participants without type 2 diabetes, Haitian Americans (n= 124) and African‐Americans (n= 117), ages 35–82 years.Design and methodologyIn a cross‐sectional study participants were recruited from Miami‐Dade and Broward counties, Florida. Serum 25(OH)D, total cholesterol, triglycerides and C‐reactive protein were measured by ELISA method. HOMA1‐IR was calculated by the formula HOMA1‐IR=[fasting plasma insulin (μU/ml) × fasting plasma glucose (mmol/L)]/22.5 and HOMA2‐IR values were determined by an online calculator. Vitamin D and calorie intakes were calculated from a validated food frequency questionnaire. Multi‐linear regression models were run, adjusting for age, gender, ethnicity, serum total cholesterol, triglycerides, C‐reactive protein, systolic blood pressure, vitamin D and daily calorie intakes, smoking and alcohol consumption. HOMA1‐IR and HOMA2‐IR were the dependent variables.Data analysis and resultsThe mean age was 52.37±9.96 years. The mean serum 25(OH)D, HOMA1‐IR and HOMA2‐IR were 22.91±8.55 ng/ml, 2.88±2.09 and 1.51±1.02, respectively. Serum 25(OH)D was negatively correlated with HOMA1‐IR (r=−.147, P=.023) and HOMA2‐IR (r=−.143, P=.027). Multi‐linear regression analyses controlling for the covariates indicated a significant negative association between serum 25(OH)D and HOMA1‐IR (B=−.038, P=0.012) as well as HOMA2‐IR (B=−.019, P=0.009). These models explained 20.2% of the variation in HOMA1‐IR and 18% of the variation in HOMA2‐IR.ConclusionLower serum 25(OH)D is associated with higher insulin resistance calculated by both HOMA1‐IR and HOMA2‐IR methods. Presence of insulin resistance may be predictive of vitamin D insufficiency.Support or Funding InformationFunding source: Funding for this research was provided through a grant from NIH/NIDDK.
3D Printed Anatomical Teaching Material ‐ A Genuine Alternative?
Authors: McMenamin Paul G 
Published: November 2023

Whilst many medical schools, universities and teaching institutions charged with the task of teaching anatomy to medical students and allied health professionals have access to human cadaver material some cannot access this resource for a number of reasons. Use of human cadavers in teaching involves special ethical and legal considerations as well as resources or facilities that have an inherent, often hidden cost. In many countries cultural and religious factors also act as an impediment to cadaver‐based anatomy teaching. At Monash University, faced with ever expanding student loads, we were faced with a need for large numbers of anatomy prosections however problems of cost and the lack of our own donor bequest program meant that alternatives had to be considered. To address this issue we developed several methods of capturing surface topography and internal structural features from existing cadaver prosections and converting them into 3D printable files with high fidelity colour and resolution. The ‘Monash 3D Printed Human Anatomy Series’ now consists of over fifty 3D prints that display normal human anatomy ranging from orbital dissections to full dissected torsos. The 3D prints can be scaled up or down in size to suit specific needs. The 3D prints have been successfully integrated into our teaching programs and a double blind randomized controlled trial has shown their effectiveness against cadaveric materials for learning cardiac anatomy. One of the principle motivations for the creation of the 3D printed series was to give institutions that do not have cadaver access an alternative teaching resource beyond the currently available stylized plastic anatomical models and the expensive plastinated cadaver material that had none of the ethical issues associated with the latter. An example of the use of the 3D printed series in a medical school in The Republic of Liberia, West Africa, will be shown to illustrate how laboratory style anatomy teaching can be achieved in a country where exposure to cadavers has very specific health risks for staff and students. Recent research on the use of multicolour/multimaterial 3D printing of anatomical preparations will be illustrated as will preliminary data on the use of 3D printing to reproduce rare human pathological specimens.Support or Funding InformationMonash University and Eric Glasgow Memorial Fund
Effect of the Exposure to Progesterone Analogues in the Proliferation and Production of TNF‐alpha and IL‐10 by Circulating Leukocytes
Authors: Contreras Irazu , Ochoa‐Arriaga Fany Guadalupe , Erazo‐Muñoz Maria Carolina , Alvarado‐Guadarrama Michelle , Estrada Jose Antonio 
Published: November 2023

Exposure to progesterone analogues is related to physiological alterations, including changes in body weight, behavior and estrous cycles. Use of these drugs for contraceptive purposes is statistically associated with the appearance of gynecologic pathologies, such as breast, uterine, ovarian and endometrial cancer. The main objective of this study was to analyze the effect of the exposure to progesterone analogues contained in oral contraceptives on the proliferation and cytokine production in circulating mononuclear leukocytes.We sampled 20 clinically healthy women who had not been previously exposed to oral contraceptives. Routine clinical data were collected and a 10 mL blood sample by venipuncture was obtained. Mononuclear leukocytes were isolated by Hypaque‐Ficoll density gradient. 1 X 106 cells were plated in 12 well plates in AIM‐V‐medium and exposed to the oral contraceptive at an equivalent dose to that found in serum (5 mg/mL), as well as a lower and higher dose (2.5 and 10 mg/mL). Cells were cultured for 3 and 24 hrs. Cell supernatants were used to measure TNF‐α and IL‐10 concentrations by ELISA and the remaining cells were harvested and used to estimate cell proliferation by propidium iodide incorporation by flow cytometry.We observed that administration of progesterone analogs from oral contraceptives increases the concentration of IL‐10 and decreases TNF‐α in cell supernatants after 24 hrs of exposure at a dose of 10 mg/mL, although the only statistical difference was observed with TNF‐α. Regarding cellular proliferation, we found that the same concentration reduced leukocyte proliferation, since we observed decreased incorporation of propidium iodide. Our preliminary data suggests that high concentrations of progesterone analogs may impair the pro‐inflammatory capacity and proliferation of mononuclear cells in circulation, and may increase the susceptibility to infection and cancer.Support or Funding InformationConsejo Mexiquense de Ciencia y Tecnología
CD36‐Myeloperoxidase Connection and the Activation of Intestinal Fibroblasts
Authors: Anderson‐Thomas Meghan , Nillas Andrea , Reaves Titus A. 
Published: November 2023

Intestinal fibroblasts are mesenchymal cells that express CD36, which is a scavenger and membrane‐bound receptor with several functions including an indicator of inflammation, interacts with TLR‐2, 4, 6 and is a receptor for collagen. Recent evidence emphasizes the important role of CD36 in intestinal detection of fatty acids under physiologic conditions. Myeloperoxidase (MPO) is a heme protease predominantly released by leukocytes and functions to destroy pathogens, marks tissue for removal, and can bind high density lipoprotein (HDL). Given that HDL removes very low density lipoprotein (VLDL‐ “bad” cholesterol), having high levels of HDL is beneficial. Thus, we investigate the role of MPO (expressed by fibroblasts) and CD36 in intestinal fibroblasts. Both CD36‐deficient fibroblasts and CD36‐deficient mice appear to display less inflammation. Using immunopurification, MPO and CD36 appear to be connected on the surface of fibroblasts. There is a hereditary MPO deficiency that results in an increased susceptibility to infections (candida albicans). Thus, MPO‐deficient fibroblasts were examined for differences in expression and function of CD36; activity of CD36 is also connected to the activity of MPO. These results highlight the importance and impact of the connection of nutrition and immune function.Support or Funding InformationNational Science Foundation RII
Maturation of intestinal barrier function by Glial cell line‐derived neurotrophic factor (GDNF) is mediated by inactivation of p38 MAPK
Authors: Meir Michael , Flemming Sven , Burkard Natalie , Germer Christoph‐Thomas , Schlegel Nicolas 
Published: November 2023

Recent data demonstrate that the glial cell line‐derived neurotrophic factor (GDNF) is involved in intestinal epithelial barrier differentiation. In the present study we analysed the mechanism underlying GDNF‐induced intestinal epithelial barrier maturation.As demonstrated previously application of recombinant GDNF on immature intestinal epithelial monolayers (Caco2 and HT29B6 cells) for 24h resulted in increased transepithelial electric resistance (TER) and a reduced permeability of 4 kDa FITC‐Dextran in a transwell filter system. This confirmed that GDNF contributes to intestinal epithelial barrier maturation. Barrier differentiation by GDNF was associated with a significant reduction of phosphorylated p38MAP kinase. Inactivation of p38 MAP kinase by incubation of immature Caco2 and HT29B6 monolayers with SB‐202190 mimicked GDNF‐induced barrier maturation. Vice versa, activation of p38 MAPK by Anisomycin led to augmented epithelial permeability. Furthermore, p38 MAPK activation by Anisomycin blocked GDNF‐induced barrier maturation. As revealed by immunostaining GDNF‐induced barrier maturation was paralleled by augmented staining patterns of tight junction proteins claudin‐1, claudin‐5, occludin and ZO‐1. In preliminary experiments the desmosomal protein Desmoglein2, which is regulated by p38 MAPK was upregulated in Western Blot analysis. Accordingly, in immunostaining Dsg2 was distributed to the cell borders following GDNF application indicating a maturation of desmosomal adhesion.In summary our present data show that GDNF contributes to epithelial barrier maturation by inactivation of p38 MAPK signaling which appears to affect Dsg2 integrity and thereby may stabilize tight junction stability.
Aberrant Modulation of the BRCA1 and G1/S Cell Cycle Pathways in Alcoholic Hepatitis Patients with Mallory Denk Bodies Present Revealed by RNA Sequencing
Authors: LIU HUI 
Published: November 2023

Mallory‐Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. Liver injury from alcohol administration causes balloon hepatocytes and MDB formation impeding liver regeneration. By comparing AH livers where MDBs had formed with normal liver transcriptomes obtained by RNA sequencing (RNA‐Seq), there was significant up regulation of BRCA1‐mediated signaling and G1/S cell cycle checkpoint pathways. The transcriptional architecture of differentially expressed genes from AH patients reflected step‐wise transcriptional changes progressing to AH. Key molecules such as BRCA1, p15 and p21 involved in BRCA1 signaling and G1/S cell cycle checkpoints were significantly up regulated both in patients’ livers and in the livers of the DDC re‐fed mice model where MDBs had formed. MiR‐483‐3p was down regulated in AH livers. The down regulation of miR‐483‐3p may be the mechanism for the up regulation of BRCA1 since miR‐483‐3p is an inhibitor of BRCA1 expression. The hyperactivation of G1/S cell cycle checkpoint inhibitors p15 and p21 results in cell cycle arrest and liver regeneration inhibition.ConclusionsProvided here for the first time is the RNA‐Seq data that represents the fully annotated catalogue of the expression of mRNAs. The most prominent alterations observed were the changes in BRCA1‐mediated signaling and G1/S cell cycle checkpoint pathways. These new findings expand previous and related knowledge in the search for gene changes that might be critical in the understanding of the underlying progression to the development of AH.Support or Funding InformationNIH (AAU01021898‐04).
DNA Damage Response Plays Critical Role In Liver Regeneration After Acetaminophen Overdose
Authors: Borude Prachi C. , Bhushan Bharat , Apte Udayan 
Published: November 2023

Acetaminophen (APAP) overdose is a leading cause of Acute Liver Failure (ALF). Previous studies have shown that liver regeneration followed by APAP overdose plays a critical role in survival. Here we show that significant DNA double strand break leading to inhibited DNA repair results in prolonged activation of cell cycle checkpoint delaying liver regeneration. We used a novel incremental dose model developed in our laboratory using a regenerating (300 mg/kg, APAP300) and a non‐regenerating (600 mg/kg, APAP600) dose of APAP to identify pathways involved in regeneration after APAP overdose. Marker of liver injury, regeneration and microarray‐based global gene expression changes were studied in male C57BL6 mice over time course of 0 to 72 hr following treatment with either APAP300 or APAP600. The ingenuity pathway analysis of microarray data revealed significant differences in DNA damage, replication and checkpoint related pathways between both doses of APAP. Western blot and immunofluorescence staining of pH2AX Ser139, a hallmark of DNA double strand break, showed prolonged phosphorylation of histone H2AX in mice treated with APAP600 than APAP300. DNA repair proteins involved in Non Homologous End Joining (NHEJ) pathway showed a rapid induction in APAP300 but were significantly suppressed in APAP600, indicating delay or lack of DNA repair. Further, extensive stabilization and activation of p53, the DNA damage Response (DDR) effector protein, was observed in APAP600 as compared to APAP300. p53 stabilization was accompanied by significantly higher and prolonged activation of several p53 target genes such as GADD45α,PAI1, BAX, p21 in APAP600 treated mice as compared to APAP300 treated mice. Furthermore, studies in p53KO mice showed significantly higher injury than WT mice after APAP300 treatment at initial time points. Interestingly, despite the higher injury, p53KO mice recovered similarly as the WT mice due to faster cell cycle resulting in much higher liver regeneration. These data illustrate that lack of prompt DSB repair response after APAP overdose leads to p53‐mediated prolonged growth arrest and replicative senescence. These results suggest that improving DNA repair process to rapidly decrease cell cycle checkpoint alert resulting in faster initiation of liver regeneration following APAP overdose may have therapeutic benefit.Support or Funding InformationThese studies were supported by NIH‐COBRE (P20 RR021940‐03), NIEHS Toxicology Training Grant (T32ES007079‐34) and NIDDK R0198414