bluuebunny/crossref_metadata_2025_split huggingface dataset:
Folate intake post‐folic acid grain fortification and pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Oaks Brietta , Dodd Kevin W , Meinhold Cari L , Jiao Li , Church Timothy R , Stolzenberg‐Solomon Rachael Z 
Published: June 2021

Folate plays a critical role in DNA methylation, synthesis, and repair. Several epidemiologic studies suggest that higher folate intake is associated with reduced pancreatic cancer risk. We investigated the association between dietary folate intake and pancreatic cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. Dietary data were collected using a food frequency questionnaire (1998–2005). Among the 51,988 male and 57,187 female participants, aged 55–74 years at enrollment, 162 men and 104 women developed pancreatic cancer during follow‐up (median 6.5 years). We used Cox proportional hazard regression to calculate hazard ratios (HR) and 95% confidence intervals (CI). The highest compared to the lowest quartile of food folate was associated with a significantly reduced pancreatic cancer risk among women, (≥ 253.3 vs. ≤ 179.1 μg/day, HR = 0.47, 95% CI 0.23, 0.94, ptrend = 0.09) but not among men (≥ 229.6 μg/day vs. ≤ 158.0 μg/day, HR = 1.20, 95% CI, 0.70, 2.04, ptrend = 0.67, p‐interaction by sex = 0.03). There was also a significant inverse trend in risk of pancreatic cancer across increasing quartiles of total folate in women (ptrend = 0.04) but not men (ptrend = 0.65). Folic acid supplements were not associated with pancreatic cancer. These findings support an association between higher food and total folate intakes and reduced risk of pancreatic cancer in women but not men.Grant Funding Source: NIH Cancer Research Training Award
1. Maternal zinc supplementation during pregnancy: effects on offspring autonomic function at 4 ½ years of age
Authors: Caulfield Laura Elizabeth , Zavaleta Nelly , Chen Ping , Putnick Diane , Bornstein Marc H , DiPietro Janet 
Published: June 2021

ObjectiveTo evaluate the persistence of differences in autonomic function in Peruvian children at 4 ½ years of age, whose mothers had participated during pregnancy in a zinc supplementation trial.MethodsWe followed up 205 children from the original trial, and present data on 165 (80%) children, 79 who mothers took 25 mg/d zinc in addition to 60 mg iron and 250 ug folic acid (FA) during pregnancy, and 86 whose mothers took iron and FA only. We collected ECG data on the children at rest and while they undertook cognitive testing following a standardized protocol. Derived cardiac measures were heart period (HP), HP variability (HPV), respiratory sinus arrhythmia (RSA), mean standard deviation (MSD) and HP range.ResultsAt baseline, children in the zinc supplementation group had greater HP, RSA, HPV, MSD and range (P < 0.05). When analyzed across the tasks, prenatal zinc supplementation was estimated to result in 21.602 (9.491) greater HP, 0.310 (0.130) greater HPV, 4.723 (1.946) greater MSD (all P < 0.05), 0.327 (0.182) greater RSA (P =0.075), and 14.298 (8.273) greater range (P=0.086).ConclusionsDifferences in autonomic function associated with maternal prenatal zinc supplementation were detectable in the offspring at 4 ½ years of age. Supported by NICHD.
A single dose of quercetin lowers blood pressure in hypertensive but not prehypertensive males
Authors: Larson Abigail , Guo Yi , Black Kathryn S , Hayman Melissa A , Richardson Russell S , Bruno Richard S , Jalili Thunder , Symons J David 
Published: June 2021

Previously we reported that 730 mg/d quercetin (Q) for 28 d reduces blood pressure (BP) in hypertensive subjects without affecting systemic markers of oxidative stress. Q supplementation in hypertensive rodents lowers BP by decreasing ACE activity. We hypothesized that a single dose of Q would lower BP and ACE activity in hypertensive males. A preliminary study conducted in normotensive males (n=6) indicated that maximal plasma Q concentrations (2.33 ± 0.72 μM) occurred 10 h after ingesting 1095 mg Q and levels returned to baseline (0.45 ± 0.06 μM) by 24 h. Based on these data hypertensive (n = 6, 40 ± 11 y, BMI < 35) and prehypertensive (n = 5, 48 ± 10 y, BMI < 35) males consumed a low Q diet for 7 days. Participants then ingested placebo (P) or 1095 mg Q, with each treatment separated by >48 h. BP (mmHg), heart rate (HR), and blood samples to assess ACE activity (U/L) were obtained 10 h later after an overnight fast. In hypertensive males systolic BP (139 ± 3 vs. 149 ± 3) and mean BP (105 ± 3 vs. 112 ± 3) were decreased (p<0.05) by Q vs. P treatment, respectively. ACE activity was not different between the Q (16 ± 4 U/L) and P (18 ± 4 U/L) treatments. BP, HR, and ACE activity were similar 10 h following Q and P in prehypertensive subjects. Thus, a single Q dose decreases BP in hypertensive but not prehypertensive males.Grant Funding Source: PEAK Academy of the University of Utah
Antibodies to TNF‐α Soluble Receptors Exacerbate Airway Inflammation in a Mouse Model of Asthma
Authors: Kim Jiyoun , Vaickus Louis , Bouchard Jacqueline , Schuller Elizabeth , Remick Daniel G 
Published: June 2021

We investigated TNF soluble receptor (TNF‐SR) regulation of airway TNF‐α expression to determine mediators responsible for exacerbation of pulmonary inflammation and airway hyperresponsiveness (AHR).A house dust extract (HDE) containing cockroach allergens and endotoxin was used to immunize BALB/c mice on day 0 with 2 additional pulmonary challenges on d14 and d21. Groups of mice received a mixture of rat anti TNF‐α SR I and II antibodies (Abs), or rat IgG. Two hrs after the last HDE challenge AHR was measured and bronchoalveolar lavage (BAL) fluid collected.Abs to TNF‐α SR essentially depleted pulmonary TNF‐α SR I and II while the airway concentration of TNF‐α was significantly increased compared to control Abs. Total inflammatory cells were reduced, primarily due to fewer neutrophils despite increases in the CXC chemokines KC and MIP‐2. Blockade of TNF‐SRs increased AHR.

IgG
Anti TNF SR Abs
P value

TNF‐α (pg/ml)
5371 ±641
14498 ± 2988
0.007

TNF‐sRI
143 ±9
16 ± 2
<0.0001

TNF‐sRII
2829 ±204
7 ± 1
<0.0001

Total cells (x1000)
657 ± 215
960 ± 334
0.049

Neutrophils (x1000)
557 ± 200
868 ± 331
0.039

KC (pg/ml)
1227 ±415
1997±247
0.021

MIP‐2 (pg/ml)
2081 ±647
3704±670
0.023

AHR (% increase of Penh)
180±21
285±45
0.04

These results demonstrate that blocking both TNF‐α SR I and II significantly increases AHR and exacerbates the asthma‐like pulmonary inflammation via increased expression of TNF and CXC chemokines in a mouse model of asthma.This work was supported by NIH Grant R01 ES0135283‐03.
Avoiding Cardiovascular Complications in People Living With Systolic Hypertension, The ACCOMPLISH Trial
Authors: Jamerson Kenneth A 
Published: June 2021

BackgroundACCOMPLISH is the first trial to use combination therapy for the initial treatment of high‐risk hypertensive patients. The single hypothesis, the combination of amlodipine/benazapril will be superior to hydrochlorothiazide/benazapril in reducing CV morbidity and mortality challenges two standards of care in treating hypertensive patients (monotherapy and diuretic based therapy).Methods11,442 patients were recruited in the US and Scandinavia after meeting inclusion criteria for higher CV risk. Subjects began study medication after randomization without washout or run in periods. Randomization procedures were centralized and double blinded. The planned mean observation of 36 months had 90% power to detect a 15% reduction in the composite end point (CV mortality, stroke, MI, coronary revascularization, unstable angina, and resuscitation from death).ResultsThe Data Safety and Monitoring Committee observed that with 60% of the expected information for the trial, that an efficacy boundary for the primary end point had been crossed and recommended termination of the trial.Hypertension remains a leading cause of morbidity and mortality globally. While lowering blood pressure with any effective therapy reduces cardiovascular risk, the ACCOMPLISH trial found additional benefit attributable to a specific combination of antihypertensive medications. In particular, the combination of benazepril plus amlodipine was superior to the combination of benazepril plus hydrochlorothiazide in reducing cardiovascular disease events in high‐risk hypertensive subjects.ConclusionThe results of the ACCOMPLISH trial provide evidence for a paradigm shift in the management of patients with hypertension.
Variations in cord 25‐hydroxyvitamin D levels in Hispanic and Caucasian infants are not related to neonatal bone mineral status
Authors: Hicks Penni Davila , Hawthorne Keli M. , Rogers Stefanie P. , Carpenter Thomas O. , Abrams Steven A. 
Published: June 2021

BackgroundAt birth, an infant's vitamin D status, as assessed by 25‐hydroxyvitamin D level (25‐OHD) is dependent on the 25‐OHD status of the mother. There are few data regarding 25‐OHD in Hispanic infants and the relationship between 25‐OHD and bone mineral outcomes.ObjectivesTo evaluate the range of 25‐OHD in Hispanic newborn infants (HNI) compared to Caucasian newborn infants (CNI) in a southern US setting and to determine if cord blood 25‐OHD is related to bone mineral status in the first week of life.MethodsAt birth, umbilical cord blood was analyzed using the Diasorin RIA (Diasorin Inc, Stillwater, MN) for 25‐OHD. Approximately 1 week after birth, infants' received a whole body dual‐energy x‐ray absorptiometry measurement to assess bone mineral content/density (BMC/BMD).ResultsData are Mean ± SD. The 25‐OHD levels were significantly lower in HNI (n=20) versus CNI (n=18) (17.2 ± 5.7 ng/mL vs 24.1 ± 6.8 ng/mL, p = 0.002). There was no difference in whole body BMC or BMD between HNI and CNI (BMD: 0.197 ±0.013 g/cm2 vs 0.196 ± 0.011 g/cm2, p = 0.9). Using a value of 20 ng/mL to indicate possible vitamin D insufficiency there was no difference in BMC or BMD of 19 infants with 25‐OHD levels < 20 ng/mL vs 19 infants with 25‐OHD levels ≥ 20 ng/mL (BMD: 0.195 ± 0.015 g/cm2 vs 0.197 ± 0.011 g/cm2, p = 0.8).ConclusionHispanic newborns in a southern US setting have lower 25‐OHD than Caucasians but this is not related to newborn bone mineral status.Supported in part by the Marshall Klaus Award of the American Academy of Pediatrics
Impairment of maintenance and function of influenza‐specific T cell memory in diet‐induced obese mice
Authors: Karlsson Erik A , Sheridan Patricia A , Beck Melinda A 
Published: June 2021

Memory T cells generated during a primary influenza infection are important for protection against subsequent influenza exposures. Previously, we have demonstrated that diet‐induced obese mice have increased morbidity and mortality following secondary influenza infection compared with lean mice. To determine if the problem resided in a failure to generate and/or maintain memory T cells and/or a failure in T cell memory function, obese and lean mice were infected with influenza X‐31. At day 31 post infection, obese memory T cells had a >50% decrease in response to stimulation by influenza PR8‐pulsed dendritic cells from lean mice. This defect was specific to memory T cells, as dendritic cells from obese mice present antigen normally to memory T cells from lean mice. At 80 days post infection, obese mice had a 10% reduction in memory T cell numbers. This reduction may be due to significantly reduced memory T cell expression of IL‐2Rβ (CD122), but not IL‐7Rα (CD127), which are both required for memory cell maintenance. Since leptin has been associated with both IL‐15 and CD122, peripheral leptin resistance in the obese mice may be a contributing factor to the impairment. It is imperative to understand how the obese state alters ability of memory T cells to function and be maintained. Moreover, impairment in maintenance of functional memory responses has significant implications for vaccine efficacy in an obese population.Grant Funding Source: DK56350
Associations between eating patterns, dietary intakes and eating behaviours in premenopausal overweight women
Authors: Leblanc Vicky , Provencher Véronique , Bégin Catherine , Corneau Louise , Tremblay Angelo , Lemieux Simone 
Published: June 2021

It has been suggested that consuming a large proportion of energy in the morning is associated with a lower daily energy intake. To our knowledge, no study has yet investigated how the distribution of energy consumed at different times of the day is associated with eating behaviours.ObjectiveTo examine associations between eating patterns, energy intakes and eating behaviours in 144 overweight premenopausal women.MethodsWomen completed a 3‐day food record. The Three‐Factor‐Eating‐Questionnaire was used to assess eating behaviours (dietary restraint, disinhibition, hunger).ResultsProportion of energy consumed at breakfast was negatively associated with total daily energy intake (r= −0.22; p< 0.01) and energy density (r= −0.17; p< 0.05) while proportion of energy from snacks was associated with total daily energy intake (r= 0.27; p< 0.01). Proportion of energy consumed at breakfast was associated with flexible restraint (r= 0.24; p< 0.01) while it was negatively correlated with situational susceptibility to disinhibition (r= −0.21; p< 0.05). Finally, proportion of energy consumed in the evening was correlated with hunger (r= 0.23; p< 0.01).ConclusionThese results suggest that eating behaviours could be important factors to further consider in order to explain the association observed between a higher proportion of energy consumed earlier in the day and lower total energy intake.Supported by CIHR.
Incubation of C2C12 myotubes with the phopholipase D (PLD) inhibitor 1‐butanol ablates contraction‐induced but not leucine‐induced signaling to p70 S6 kinase (S6K1) via phosphatidic acid (PA)
Authors: Atherton Philip James , Loughna Paul , Hill Derek Samuel , Rankin Debbie , Rennie Michael 
Published: June 2021

Signaling through mammalian target of rapamycin complex 1 (mTORC1) regulates muscle protein synthesis (MPS) responses to amino acids (AA) (particularly leucine, (Leu)) and contraction via mechanisms independent of upstream insulin signaling (e.g. phosphoinositide 3‐kinase). Recently, it was shown that PLD‐dependent production of the lipid 2nd‐messenger PA (which binds and relieves inhibition of mTORC1 by FK506‐binding protein 12, thus activating mTORC1) is necessary for signaling to S6K1 after eccentric contractions. We hypothesized that, similarly, Leu‐induced increases in S6K1 signaling might also be PA‐dependent. Murine C2C12 myotubes were contracted for 30 min (1 or 4 Hz, 20 V, 24 ms pulses) or incubated with 1 mM Leu (n=6) in the presence/absence of 0.25 % 1‐butanol, a potent inhibitor of PA production by PLD. Phosphorylation of S6K1Thr389 was measured by immunoblotting. Increased phosphorylation of S6K1 with 4 Hz stimulation exceeded that with 1 Hz (+53 vs. +33%; P<0.05), but was ablated by 1‐butanol at both 1 and 4 Hz. Conversely, the increase in S6K1 phosphorylation caused by Leu (+33%; P<0.01) was unaffected by 1‐butanol (+31%; P<0.01), which also did not alter basal S6K1 phosphorylation. Thus, whereas contraction requires PA for signaling to S6K1, Leu regulates mTORC1 signaling separately, perhaps explaining why AA and contraction synergistically stimulate MPS. Support: BBSRC, RCUK, EXGENESISGrant Funding Source: Physiology (APS)
Situational analysis of infant and young child nutrition (IYCN) activities in six countries of the African Sahel demonstrates that most IYCN policies, and related training materials & programs, are consistent with international guidelines, but substantial gaps exist in program coverage and effective monitoring & evaluation (M&E)
Authors: Wuehler Sara E , Hess Sonja Y , Brown Kenneth H 
Published: June 2021

Background & objectivesDue to limited or no progress toward reducing <5 mortality and malnutrition, an alliance of international agencies joined to “Reposition children's right to adequate nutrition in the Sahel”, starting with an analysis of IYCN activities: national policies, training materials, programs, and M&E, compared with international recommendations.MethodsKey informants conducting IYCN‐related activities in Burkina Faso, Chad, Mali, Mauritania, Niger & Senegal were interviewed, and >500 documents were reviewed & compared with internationally recommended policies on: optimal breastfeeding & complementary feeding (CF) practices, prevention of micronutrient deficiencies, prevention of mother‐to‐child transmission of HIV (PMTCT), management of acute malnutrition (AM), & food security.ResultsMost IYCN policies & related training materials are consistent with international guidelines. Neglected topics include specific CF recommendations, zinc in diarrhea management, PMTCT & screening for AM. Programs target high‐risk populations, but few reach national coverage or are adapted to research into local barriers & beliefs. Most M&E activities do not permit identification of effective program components.ConclusionsThe IYCN foundation is set, but greater resources & capacity building are needed to enhance & expand program activities and M&E.Support: FAO, HKI, MI, UNICEF, WFP
Influence of garlic and ginger compared to aspirin on diabetic indicators in STZ‐induced diabetic rats
Authors: Thomson Martha , Al‐Qattan Khaled , Al‐Houli Mouna , Divya J.S. , Al‐Hassan Jassim , Al‐Sawan Shorooq , Ali Muslim 
Published: June 2021

The hypoglycemic effects of aqueous extracts of raw ginger (Zingiber officinale) and garlic (Allium savitum) in comparison to aspirin were studied in diabetic rats. Diabetes was induced by IP injection of streptozotocin and a fasting blood sugar >300 mg/dl indicated diabetes. Diabetic rats were divided into 4 groups: control, garlic‐treated, ginger‐treated and aspirin‐treated. Garlic and ginger extracts and aspirin were administered daily for 8 weeks. Blood glucose and serum creatinine, cholesterol and triglycerides were significantly elevated in diabetic control rats, and significantly lowered by both ginger and garlic treatments. Aspirin treatment of diabetic rats significantly decreased serum triglyceride and cholesterol levels but not blood glucose levels. Serum protein decreased significantly in diabetic compared to normal rats, with ginger and garlic treatment resulting in nearly normal serum protein levels. Urine creatinine and protein were elevated in diabetic rats, and significantly decreased by garlic and ginger but not aspirin. Diabetic rats lost weight, and increased water and food intake as well as urine output compared to normal. Ginger‐treated rats had a modest weight gain and decreased food and water intake and urine output, while garlic‐treated rats had a slight weight gain and decreased urine output. Aspirin treatment resulted in no change in urine protein and creatinine, body weight, water and food intake and urine output. Thus, garlic and ginger treatments were useful in ameliorating the negative progress of diabetes in STZ‐induced diabetic rats, while aspirin had limited effects.The study was supported by KFAS grant # 2007‐1302‐04.
Effects of protein intake on energy‐restriction‐induced changes in lipid‐lipoprotein profile, glycemic control, resting energy expenditure, and appetite in overweight men
Authors: Tang Minghua , Armstrong Cheryl LH , Mattes Richard D , Leidy Heather J , Campbell Wayne W 
Published: June 2021

PurposeTo assess the effects of dietary protein (pro) on diet‐induced changes in indices of metabolic health.MethodsFor 12 wk, overweight men (BMI 25.0–39.9 kg/m2), aged 24–75 y, consumed a 750 kcal/d energy deficit diet with 25% energy as fat, and either 15% pro (normal pro, NP, n = 21) and 60% CHO, or 25% pro (higher pro, HP, n = 22) and 50% CHO. The NP diet excluded striated tissue and eggs; the HP diet had 15% pro from eggs and 25% pro from lean pork. Pre and post‐study, fasting blood was taken; body composition, blood pressure (BP), and resting energy expenditure (REE) were measured; and daily appetite was assessed.ResultsReductions over time (p<0.05) in the NP and HP groups included: weight 10 and 9%; fat mass 21 and 20%; lean body mass (LBM) 5 and 3%; cholesterol 18 and 22%; HDL 9 and 9%; LDL 19 and 20%; triacylglycerol 30 and 42%; insulin 3.7 ± 1.4 and 5.4 ± 1.2 μU/mL; HOMA 0.9 ± 0.2 and 1.4 ± 0.2; systolic:diastolic BP 8:6 and 7:8%; and REE 260 ± 112 and 97 ± 78 kcal/d. Diet did not influence these responses, except ΔLBM was greater in NP vs. HP (time × group, p<0.05). ΔREE was predicted by ΔLBM (R2 = 0.21). Daily desire to eat ratings decreased in both groups, but hunger decreased in HP only.ConclusionOverweight men can successfully improve indices of metabolic health after weight loss when consuming a normal protein vegetarian or higher protein omnivorous diet.Support: Natl Pork Brd; Am Egg Brd‐Egg Nutr Ctr; Purdue Ingest Behav Res Ctr.Grant Funding Source: American Egg Board, National Pork Board
Curcumin Inhibits IFN‐γ Signaling in Colonic Epithelial Cells
Authors: Midura‐Kiela Monica T , Larmonier Claire B , Laubitz Daniel , Ghishan Fayez K , Kiela Pawel R 
Published: June 2021

IFN‐γ is a proinflammatory cytokine with profound effects on colonic epithelial cells. Elevated IFN‐γ disrupts the epithelial barrier function, prevents epithelial cell migration and wound healing, and primes IEC cells to express MHC class II molecules and to serve as non‐professional antigen presenting cells (APC). In this report we demonstrate that curcumin inhibits IFN‐γ signaling in colonic epithelial T‐84 and YAMC cells. Curcumin significantly inhibited IFN‐γ induced GAS element‐driven luciferase activity. IFN‐γ dramatically stimulated expression of MHCII genes, HLA‐DRα and HLA‐DPα1, while curcumin dose‐dependently prevented this increase. Curcumin inhibited IFN‐γ stimulated expression of CII TA, a master regulator of MHCII class genes. EMSA analysis showed curcumin‐mediated inhibition of STAT‐1 binding to both GAS and ISRE cis‐elements. Immunofluorescence studies demonstrated that curcumin inhibited IFN‐γ‐stimulated nuclear translocation of Stat‐1. IFN‐γ induced and JAK‐dependent phosphorylation of Stat‐1 at Tyr701, a residue critical in Stat‐1 dimerization and nuclear translocation, was also inhibited. In summary, curcumin acts as a potent inhibitor of Jak‐Stat signaling pathway in the colonic epithelial cells, a phenomenon which may partially account for the beneficial effects of curcumin in experimental colitis as well as in human IBD.Grant support: 5R01DK067286 (P.R.K.)
Ubiquitin and Autophagy Networks
Authors: Dikic Ivan 
Published: June 2021

Ubiquitin is a small modifier that labels proteins in a highly specific manner. Initially, ubiquitination was described as the process of tagging proteins for degradation in the proteasome, a giant protein complex responsible for the breakdown of the majority of intracellular proteins. We have recently described Rpn13 as a novel ubiquitin receptor at the proteasome, which recruits ubiquitinated substrates and deubiquitinating enzyme Uch37 to the proteasome, thus co‐ordinating balance between recognition and disassembly of ubiquitinated substrates at the proteasome.Removal of harmful protein aggregates, damaged organelles and microbes is mediated by autophagy, a process by which the cell sequesters cytosolic cargo and delivers it for degradation by the lysosome. The involvement of ubiquitin in selective autophagy is becoming more evident. Identification of autophagy receptors, e.g. p62 and NBR1, which simultaneously bind both ubiquitin and autophagy‐specific ubiquitin‐like modifiers, LC3/GABARAP, has provided a molecular link between ubiquitination and autophagy. The molecular details of selective autophagy suitable for clearance of various cargoes, ranging from ubiquitinated protein aggregates to membrane‐bound organelles and microbes will be discussed.