bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docosahexaenoic acid‐thyroid hormone combined protocol as a novel approach to metabolic stress disorders: Relation to mitochondrial adaptation via liver PGC‐1α and sirtuin1 activation
Authors: Vargas Romina , Riquelme Bárbara , Fernández Javier , Álvarez Daniela , Pérez Ignacio F. , Cornejo Pamela , Fernández Virginia , Videla Luis A. 
Published: December 2018

AbstractDocosahexaenoic acid (DHA) and 3,3′,5‐triiodothyronine (T3) combined protocol affords protection against liver injury via AMPK signaling supporting energy requirements. The aim of this work was to test the hypothesis that a DHA + T3 accomplish mitochondrial adaptation through downstream upregulation of PPAR‐γ coactivator 1α (PGC‐1α). Male Sprague–Dawley rats were given daily oral doses of 300 mg DHA/kg or saline (controls) for three consecutive days, followed by 0.05 mg T3/kg (or hormone vehicle) ip at the fourth day, or single dose of 0.1 mg T3/kg alone. Liver mRNA levels were assayed by qPCR, NAD+/NADH ratios, hepatic proteins, histone 3 acetylation and serum T3 and β‐hydroxybutyrate levels were determined by specific ELISA kits. Combined DHA + T3 protocol led to increased liver AMPK, PGC‐1α, NRF‐2, COX‐IV, and β‐ATP synthase mRNAs, with concomitant higher protein levels of COX‐IV and NRF‐2, 369% enhancement in the NAD+/NADH ratio, 47% decrease in histone 3 acetylation and 162% increase in serum levels of β‐hydroxybutyrate over control values. These changes were reproduced by the higher dose of T3 without major alterations by DHA or T3 alone. In conclusion, liver mitochondrial adaptation by DHA + T3 is associated with PGC‐1α upregulation involving enhanced transcription of the coactivator, which may be contributed by PGC‐1α deacetylation and phosphorylation by SIRT1 and AMPK activation, respectively. This contention is supported by NRF‐2‐dependent enhancement in COX‐1 and β‐ATP synthase induction with higher fatty acid oxidation resulting in a significant ketogenic response, which may represent a suitable strategy for hepatic steatosis with future clinical applications. © 2018 BioFactors, 45(2):271–278, 2019
Spatial modulation and cofactor engineering of key pathway enzymes for fumarate production in Candida glabrata
Authors: Chen Xiulai , Li Yang , Tong Tian , Liu Liming 
Published: December 2018

AbstractFumarate is a naturally occurring organic acid that is an intermediate of the tricarboxylic acid (TCA) cycle and has numerous applications in food, pharmaceutical, and chemical industries. However, microbial fumarate production from renewable feedstock is limited by the intrinsic inefficiency of its synthetic pathway caused by week metabolites transportation and cofactor imbalance. In this study, spatial modulation and cofactor engineering of key pathway enzymes in the reductive TCA pathway were performed for the development of a Candida glabrata strain capable of efficiently producing fumarate. Specifically, DNA‐guided scaffold system was first constructed and optimized to modulate pyruvate carboxylase, malate dehydrogenase, and fumarase, increasing the fumarate titer from 0.18 to 11.3 g/L. Then, combinatorially tuning cofactor balance by controlling the expression strengths of adenosine diphosphate‐dependent phosphoenolpyruvate carboxykinase and NAD+‐dependent formate dehydrogenase led to a large increase in fumarate production up to 18.5 g/L. Finally, the engineered strain T.G‐4G‐S(1:1:2)‐P(M)‐F(H) was able to produce 21.6 g/L fumarate in a 5‐L batch bioreactor. This strategy described here, paves the way to develop efficient cell factories for the production of the other industrially useful chemicals.
Simultaneous determination of amitraz, chlordimeform, formetanate and metabolites in human blood by liquid chromatography tandem mass spectrometry with phospholipid‐removal pretreatment
Authors: Gao Xue , Sun Yongbin , You Haidan , Dai Yannan , Guo Hao , Zhao Qingbiao 
Published: December 2018

AbstractIn this study, a reliable ultra‐performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method coupled with an easy, fast and effective sample pretreatment procedure was developed for simultaneous determination of amitraz, chlordimeform, formetanate and their metabolites in human blood. With the procedures of protein precipitation and a phospholipid‐removal step, the endogenous compound interference was significantly reduced, and matrix effects were significantly reduced. The linear ranges of matrix‐matched standard curves were from 0.5 to 1000 ng/mL with coefficients of determination >0.996. Very low limits of detection (0.05–0.12 ng/mL) and limits of quantitation (0.15–0.4 ng/mL) were achieved. Reasonable recoveries ranging from 88.1 to 103.5% were obtained. The intra‐day RSDs ranging from 3.2 to 8.6% and inter‐day RSDs ranging from 4.8 to 9.2% indicated good precision. With the introduction of a phospholipid‐removal step, the ME ranged from 90.1 to 98.5%. The established method was successfully applied to the analysis of a blood sample from a formetanate poisoning case. This method possesses the advantages of high sensitivity, reduced matrix effects and rapidity.
Case‐control study of heart rate abnormalities across the breast cancer survivorship continuum
Authors: Groarke John D. , Mahmood Syed S. , Payne David , Ganatra Sarju , Hainer Jon , Neilan Tomas G. , Partridge Ann H. , Di Carli Marcelo F. , Jones Lee W. , Mehra Mandeep R. , Nohria Anju 
Published: December 2018

AbstractBackgroundMechanisms underlying impaired exercise capacity and increased cardiovascular mortality observed in breast cancer (BC) patients remain unclear. The prevalence, functional, and prognostic significance of elevated resting heart rate (HR) and abnormal heart rate recovery (HRR) in breast cancer (BC) requires evaluation.MethodsIn a single‐center, retrospective, case‐control study of women referred for exercise treadmill testing (ETT), 448 BC patients (62.6 ± 10.0 years) were compared to 448 cancer‐free, age‐matched controls. Elevated resting HR was defined as HR ≥80 bpm at rest. Abnormal HRR at 1‐minute following exercise was defined as ≤12 bpm if active recovery or ≤18 bpm if passive recovery. Association of these parameters with exercise capacity and all‐cause mortality was evaluated.ResultsElevated resting HR (23.7% vs 17.0%, P = 0.013) and abnormal HRR (25.9% vs 20.3%, P = 0.048) were more prevalent in BC cohort than controls. In adjusted analyses, BC patients with elevated resting HR (−0.9 METs (SE 0.3); P = 0.0003) or abnormal HRR (−1.3 METs (SE 0.3); P < 0.0001) had significant reductions in metabolic equivalents (METs) achieved during exercise. Elevated resting HR was not associated with mortality. There was a trend toward increased mortality in BC cohort with abnormal HRR (adjusted hazard ratio 2.06 (95% CI 0.95‐4.44, P = 0.07)).ConclusionsWomen across the BC survivorship continuum, referred for ETT, have an increased prevalence of elevated resting HR and abnormal HRR relative to cancer‐free, age‐matched female controls. These parameters were associated with decreased exercise capacity. Strategies to modulate these abnormalities may help improve functional capacity in this cohort.
Physicochemical properties of hammer‐milled yellow split pea (Pisum Sativum L.)
Authors: Kaiser Amber C. , Barber Natsuki , Manthey Frank , Hall Clifford 
Published: December 2018

AbstractBackground and objectivesIncorporating pulse flours into cereal‐based foods is of interest due to demand for healthful convenience foods. Hammer milling was investigated as a method of pulse flour production. Yellow split pea at 9% and 11% moisture was hammer‐milled at two rotor speeds (34 and 102 m/s) and with nine mill screen apertures (0.84–9.53 mm).FindingsAlthough reduction in flour moisture and protein was observed during milling, flour composition differences appeared to be due to the drying process rather than to milling. Median particle size was lowest (98 µm) when milling at 102 m/s rotor speed with 0.84 mm screen aperture. Flour particle size was negatively correlated with bulk density, redness, and yellowness and positively correlated with brightness. Damaged starch ranged from 0.1% to 1.4% and was lower at 102 m/s than at 34 m/s for small screen apertures. Peak and final viscosities were negatively correlated with particle size and were highest when milling at 102 m/s with 0.84 mm screen aperture.ConclusionsAlthough seed moisture had some impact on flour quality, hammer mill settings were the most important factors in particle size reduction of yellow split pea. Particle size is a predictor of flour quality.Significance and noveltyThese relationships among hammer mill parameters, seed moisture, and flour quality are not extensively reported in the literature. Results can be used to provide processing guidance for pulse hammer milling.
Astrocytic changes with aging and Alzheimer's disease‐type pathology in chimpanzees
Authors: Munger Emily L. , Edler Melissa K. , Hopkins William D. , Ely John J. , Erwin Joseph M. , Perl Daniel P. , Mufson Elliott J. , Hof Patrick R. , Sherwood Chet C. , Raghanti Mary Ann 
Published: December 2018

AbstractAstrocytes are the main homeostatic cell of the central nervous system. In addition, astrocytes mediate an inflammatory response when reactive to injury or disease known as astrogliosis. Astrogliosis is marked by an increased expression of glial fibrillary acidic protein (GFAP) and cellular hypertrophy. Some degree of astrogliosis is associated with normal aging and degenerative conditions such as Alzheimer's disease (AD) and other dementing illnesses in humans. The recent observation of pathological markers of AD (amyloid plaques and neurofibrillary tangles) in aged chimpanzee brains provided an opportunity to examine the relationships among aging, AD‐type pathology, and astrocyte activation in our closest living relatives. Stereologic methods were used to quantify GFAP‐immunoreactive astrocyte density and soma volume in layers I, III, and V of the prefrontal and middle temporal cortex, as well as in hippocampal fields CA1 and CA3. We found that the patterns of astrocyte activation in the aged chimpanzee brain are distinct from humans. GFAP expression does not increase with age in chimpanzees, possibly indicative of lower oxidative stress loads. Similar to humans, chimpanzee layer I astrocytes in the prefrontal cortex are susceptible to AD‐like changes. Both prefrontal cortex layer I and hippocampal astrocytes exhibit a high degree of astrogliosis that is positively correlated with accumulation of amyloid beta and tau proteins. However, unlike humans, chimpanzees do not display astrogliosis in other cortical layers. These results demonstrate a unique pattern of cortical aging in chimpanzees and suggest that inflammatory processes may differ between humans and chimpanzees in response to pathology.
Quantitative Isoperimetry à la Levy‐Gromov
Authors: Cavalletti F. , Maggi F. , Mondino A. 
Published: December 2018

AbstractOn a Riemannian manifold with a positive lower bound on the Ricci tensor, the distance of isoperimetric sets from geodesic balls is quantitatively controlled in terms of the gap between the isoperimetric profile of the manifold and that of a round sphere of suitable radius. The deficit between the diameters of the manifold and of the corresponding sphere is likewise bounded. These results are actually obtained in the more general context of (possibly nonsmooth) metric measure spaces with curvature‐dimension conditions through a quantitative analysis of the transport rays decompositions obtained by the localization method. © 2018 Wiley Periodicals, Inc.
Assessment of cell block technique in head and neck pathology diagnoses: A preliminary study
Authors: Desai Karishma M. , Angadi Punnya V. , Kale Alka D. , Hallikerimath Seema 
Published: December 2018

ObjectiveThe head and neck region is a composite site made of multiple tissue components. These tissues when affected by disease or pathology present with an array of changes in the tissue architecture and pattern. It is essential to visualize the cellular details and tissue patterns for accurate diagnosis and treatment planning. Aspiration cytology primarily makes use of the cellular details for diagnosing lesions of the head and neck. Despite the promising results, its use is still limited in certain cases of the head and neck. The reason implicated could be the indiscernible appearance of cells in the absence of tissue integrity. In this regard, cell blocks are known to facilitate the visualization of the cytomorphological as well as the tissue arrangement patterns. Thus, the present study was designed to evaluate the role of cell block cytology in the diagnosis of various lesions of the head and neck.MethodsOdontogenic lesions, epithelial carcinomas and connective tissue pathology of the head and neck origin were included in the study (n = 45). Aspiration cytology smears and cell block diagnosis were compared with tissue biopsy diagnosis for determining their sensitivity (%) and diagnostic efficacy.ResultsCell blocks showed distinct preservation of the architectural pattern. In case of fluid‐filled lesions, the contents were preserved and correlated with the tissue biopsy results. The results of cell blocks were similar to that of tissue biopsy in majority of the cases (95.56%).ConclusionWe recommend using cell blocks as a part of routine laboratory practice for all head‐neck cases.
Higher pulse pressure predicts initiation of dialysis in Japanese patients with diabetes
Authors: Osawa Taeko , Fujihara Kazuya , Harada Mayuko , Yamamoto Masahiko , Ishizawa Masahiro , Suzuki Hiroshi , Ishiguro Hajime , Matsubayashi Yasuhiro , Seida Hiroyasu , Yamanaka Nauta , Tanaka Shiro , Shimano Hitoshi , Kodama Satoru , Sone Hirohito 
Published: December 2018

AbstractAimsTo determine incidence and predictors of starting dialysis in patients with diabetes emphasizing blood pressure variables.MethodsA nationwide database with claim data on 18 935 people (15 789 men and 3146 women) with diabetes mellitus aged 19 to 72 years in Japan was used to elucidate predictors for starting dialysis. Initiation of dialysis was determined from claims using ICD‐10 codes and medical procedures. Using multivariate Cox modelling, interactions between glycaemic and blood pressure values were determined.ResultsDuring a median follow‐up of 5.3 years, incidence of dialysis was 0.81 per 1000 person‐years. Multivariate analysis of a model involving systolic and diastolic blood pressure (SBP and DBP) simultaneously as covariates showed that hazard ratios (HRs) for starting dialysis for each 1‐SD elevation in SBP and DBP were 2.05 (95% confidence interval 1.58‐2.64) and 0.66 (0.50‐0.88), respectively, implying that pulse pressure (PP) was a promising predictor. For confirmation, a model involving SBP and PP simultaneously as covariates demonstrated that HRs for each 1‐SD elevation in SBP and PP were 1.09 (0.81‐1.48) and 1.54 (1.14‐2.08), respectively, with PP the more potent predictor. Compared with HbA1c <8% and PP <60 mmHg, the HR for those with HbA1c ≥8% and PP ≥60 mmHg was 6.32 (3.42‐11.7).ConclusionsIn our historical cohort analysis, SBP and PP were independent predictors for starting dialysis. PP was the more potent, suggesting the contribution of increased arterial stiffness to the incidence of dialysis. Future studies are needed to conclude the independent influence of PP and HbA1c on dialysis considering other risk factors.
Roflumilast analogs with improved metabolic stability, plasma protein binding, and pharmacokinetic profile
Authors: Moussa Bahia A. , El‐Zaher Asmaa A. , El‐Ashrey Mohamed K. , Fouad Marwa A. 
Published: December 2018

AbstractWith the aim of studying their in vitro and in vivo pharmacokinetics, new chromatographic methods were developed for the determination of three new roflumilast synthetic analogs (I−III) as PDE‐4B inhibitors in rat liver S9 fraction, phosphate buffered saline, pH 7.4, and human and rat plasma. The developed high performance liquid chromatography−ultra violet (HPLC−UV) methods were performed on a Zorbax Eclipse C8 column and UV detection was carried out at 215 nm. The three compounds were tested for their metabolic stability and were found to be metabolically more stable than roflumilast especially the 2‐mercaptobenzothiazol‐6‐yl analog (III) which displayed an in vitro half‐life time (247.55 minutes) higher than that of roflumilast (12.29 minutes) and a low in vitro clearance of 5.67 mL/min./kg. Possible phase I metabolites were investigated using ultra‐performance liquid chromatography−tandem mass spectrometry (UPLC–MS/MS) showing hydroxylation of the unsubstituted benzothiazol‐2‐yl (I) and benzothiazole‐6‐yl (II) analogs and a cleaved benzothiazole metabolite of the 2‐mercaptobenzothiazol‐6‐yl analog (III). Plasma protein binding affinity was tested using equilibrium membrane dialysis method showing a very high percentage (more than 95%) of plasma protein binding of compounds I and II where compound III exhibited lower percentage (53.71%) demonstrating its accessibility for tissue distribution. Also, a UPLC–MS/MS method was developed using an Acquity UPLC BEH shield RP C18 column to be applied to an in vivo pharmacokinetic study in rats following a subcutaneous dose (1 mg/kg). Compounds I−III showed improved in vivo pharmacokinetic parameters especially compound III which displayed a half‐life 3‐fold greater than roflumilast (21 hours) and a Cmax value of 113.958 ng/mL. Accordingly, this new chemical entity should be subjected to further investigation as it can be a good drug candidate for treating chronic obstructive pulmonary disease.
Nutrient export and elemental stoichiometry in an urban tropical river
Authors: McDowell William H. , McDowell William G. , Potter Jody D. , Ramírez Alonso 
Published: December 2018

AbstractNutrient inputs to surface waters are particularly varied in urban areas, due to multiple nutrient sources and complex hydrologic pathways. Because of their close proximity to coastal waters, nutrient delivery from many urban areas can have profound impacts on coastal ecology. Relatively little is known about the temporal and spatial variability in stoichiometry of inorganic nutrients such as dissolved silica, nitrogen, and phosphorus (Si, N, and P) and dissolved organic matter in tropical urban environments. We examined nutrient stoichiometry of both inorganic nutrients and organic matter in an urban watershed in Puerto Rico served by municipal sanitary sewers and compared it to two nearby forested catchments using samples collected weekly from each river for 6 yr. Urbanization caused large increases in the concentration and flux of nitrogen and phosphorus (2‐ to 50‐fold), but surprisingly little change in N:P ratio. Concentrations of almost all major ions and dissolved silica were also significantly higher in the urban river than the wildland rivers. Yield of dissolved organic carbon (DOC) was not increased dramatically by urbanization, but the composition of dissolved organic matter shifted toward N‐rich material, with a larger increase in dissolved organic nitrogen (DON) than DOC. The molar ratio of DOC:DON was about 40 in rivers draining forested catchments but was only 10 in the urban river. Inclusion of Si in the assessment of urbanization's impacts reveals a large shift in the stoichiometry (Si:N and Si:P) of nutrient inputs. Because both Si concentrations and watershed exports are high in streams and rivers from many humid tropical catchments with siliceous bedrock, even the large increases in N and P exported from urban catchments result in delivery of Si, N, and P to coastal waters in stoichiometric ratios that are well in excess of the Si requirements of marine diatoms. Our data suggest that dissolved Si, often neglected in watershed biogeochemistry, should be included in studies of urban as well as less developed watersheds due to its potential significance for marine and lacustrine productivity.
An experimental investigation into the use of eye‐contact in social interactions in women in the acute and recovered stages of anorexia nervosa
Authors: Harrison Amy , Watterson Stephanie V. , Bennett Samuel D. 
Published: December 2018

AbstractObjectivePeople with anorexia nervosa (AN) report significant difficulties in social functioning and a growing literature is beginning to explain some of the differences in social skills that might underlie the social challenges experienced by patients. One vital area of social functioning that has been largely neglected to date is how eye‐contact is used in the context of social stimuli and in social situations.MethodsThis cross‐sectional, experimental study used eye‐tracking to measure the frequency and duration of eye‐contact made with the eye region of interest (ROI) of (1) static social stimuli (man and woman Ekman faces displaying basic emotions); (2) moving social stimuli (a video of two actors conversing); and (3) during a real‐life social interaction in 75 women (25 with AN, 25 recovered from AN, and 25 non‐AN controls; mean age = 27.18, SD = 6.19).ResultsParticipants showed greater eye‐contact during a real‐life social interaction than when viewing static social stimuli. Those with AN made contact with the eye ROI of the static and moving social stimuli and during a real‐life social interaction significantly less often and for significantly less time than non‐AN controls. Those recovered from AN showed greater eye‐contact than the acute group but significantly less eye‐contact with the eye ROI across the static and moving social stimuli and during the real‐life social interaction than non‐AN controls.DiscussionThese findings contribute new knowledge regarding the types of social skills that people with AN may need additional support with to allow them to make greater use of social support in their recovery.
Applying family‐based treatment (FBT) to three clinical presentations of avoidant/restrictive food intake disorder: Similarities and differences from FBT for anorexia nervosa
Authors: Lock James , Robinson Athena , Sadeh‐Sharvit Shiri , Rosania Kimberly , Osipov Lilya , Kirz Nina , Derenne Jennifer , Utzinger Linsey 
Published: December 2018

AbstractObjectiveThis article uses three brief case reports to illustrate how family‐based treatment (FBT) can be used to treat pre‐adolescents with avoidant/restrictive food intake disorder (ARFID).MethodWe present case material illustrating how FBT can be used in three different clinical presentations of ARFID: (1) low appetite and lack of interest; (2) sensory sensitive eaters; and (3) fear of aversive consequences eaters—all without shape or weight concerns.ResultsThis case material illustrates that the main principles of FBT—agnosticism as to the cause of the illness, externalization, emphasizing the seriousness of ARFID, parental empowerment, behavioral consultation, and practical behavioral focus—are applicable for a range of ARFID clinical presentations. Common challenges in this patient group include (1) promoting urgency; (2) challenging long term behavioral accommodation; (3) lack of parental alignment, parental fatigue, (4) and co‐morbid psychiatric problems in the patients. Strategies to address these problems are described.ConclusionFBT can be adapted for children with ARFID using the main principles of the approach.