bluuebunny/crossref_metadata_2025_split huggingface dataset:
Twelve years of low nutrient input stimulates growth of trees and dwarf shrubs in the treeline ecotone
Authors: Möhl Patrick , Mörsdorf Martin A. , Dawes Melissa A. , Hagedorn Frank , Bebi Peter , Viglietti Davide , Freppaz Michele , Wipf Sonja , Körner Christian , Thomas Frank M. , Rixen Christian 
Published: September 2018

AbstractAlmost all natural terrestrial ecosystems are nutrient limited in terms of growth, and we expect treeline vegetation to be no exception. However, direct constraints of low temperature on tissue formation may superimpose effects of low nutrient availability.We examined growth responses of two tree (Larix deciduaandPinus uncinata) and two dwarf shrub species (Vaccinium myrtillusandVaccinium gaultherioides) to 12 years of moderate fertilizer addition (NPK applied at a rate of 15 and 30 kg nitrogen ha−1 a−1) along an elevation gradient within the treeline ecotone in the Swiss Alps (2,083 to 2,225 m a.s.l.). We measured annual top‐ and side‐shoot increments as well as stem ring width in trees and shoot increments in dwarf shrubs.Fertilizer addition increased soil nutrient availability, indicated by enhanced soil extractable N, higher concentrations of N, P and K in leaves and higher foliar δ15N.Fertilizer addition stimulated annual growth of all four species: by 11%–20% forL. deciduaand 15%–36% forP. uncinata(depending on trait) and by 8%–16% for the two dwarf shrub species. Growth stimulation by the higher fertilizer dose was not significantly stronger than by the lower dose (except forV. gaultherioides), suggesting an overall low nutrient demand for growth and saturation at a rather low nutrient input.Synthesis. Even slightly enhanced nutrient availability can stimulate growth of trees and dwarf shrubs in an alpine treeline ecosystem. Ongoing atmospheric nutrient deposition, in conjunction with global warming, may accelerate plant growth at the treeline.
Beyond “bouncing back”: Towards an integral, capability‐based understanding of organizational resilience
Authors: Darkow Philipp M. 
Published: September 2018

AbstractAcademic debates surrounding the notion of resilience still face dissent about definitions, contexts, and managerial implications. By summarizing recent literature on resilience, this paper reveals two dominating paradigms, which I label the Plan to Resist Approach and the Containing Crisis Approach. By pinpointing and challenging the underlying assumptions of both approaches, I elucidate their potential shortcomings. To overcome these limitations, I develop an integral, capability‐based concept of organizational resilience, which builds on a temporal perspective on crises. Thereby it highlights the importance of enacting different yet specific capabilities at different phases of crises. This concept allows integrating the insights of the reviewed literature and sheds light on the recovery phase as being a so far neglected aspect in resilience research.
Influence of Physical Exercise on the Dialytic Adequacy Parameters of Patients on Hemodialysis
Authors: García Testal Alicia , García Maset Rafael , Hervás Marín David , Pérez‐Domínguez Borja , Royo Maicas Pilar , Rico Salvador Inmaculada Soledad , Meléndez‐Oliva Erika , Molina Aracil Javier , Murgui Chiva MªJosé , Del pozo Blanco Olga , Olagüe Díaz Pau , Fernández Najera Jose Enrique , Torregrosa De Juan Eduardo , Benedito Carrera Caterina , Segura‐Ortí Eva 
Published: September 2018

AbstractIt has been suggested that physical exercise in chronic hemodialysis could improve dialysis dose and reduce postdialysis rebound. A randomized controlled trial was performed to compare a group of patients doing physical exercise during the first 2 h of hemodialysis sessions and another group doing physical exercise at home. The descriptive variables, dialysis doses measured by KtV, and rebounds (urea, creatinine, potassium, phosphorus), were recorded. For 69 patients: the mean KtV was 1.84; the 30‐min rebound of creatinine was 32.37%, urea 24.39%, potassium 15.31%, and phosphorus 51.29%. For each patient, the basal measurement was compared with those determined when performing physical exercise; no statistically significant differences were observed between the changes determined to dose and rebound in the group with hemodialysis exercise compared to those of the home exercise group. In conclusion, performing physical exercise during the first 2 hours of hemodialysis sessions neither lowered postdialysis molecules rebound nor improved dialysis dose.
The emergence of human capital: Roles of social capital and coordination that drive unit performance
Authors: Harris Christopher M. , Wright Patrick M. , McMahan Gary C. 
Published: September 2018

AbstractEmpirical work on human capital has tended to focus on the direct effects of human capital on performance, whereas little attention has been paid to behaviours through which human capital influences performance. This study uses the “human capital emergence” model to examine relationships among human capital, social capital, coordination, and performance over a 2‐year period of time. Findings indicate that human capital, social capital, and coordination each influence performance. Human capital and social capital also positively predict coordination. Lastly, coordination mediates the relationships between human capital and performance and social capital and performance.
Lactobacillus reuteri F‐9‐35 Prevents DSS‐Induced Colitis by Inhibiting Proinflammatory Gene Expression and Restoring the Gut Microbiota in Mice
Authors: Sun Mao‐cheng , Zhang Fu‐cheng , Yin Xue , Cheng Bi‐jun , Zhao Chang‐hui , Wang Yan‐ling , Zhang Zheng‐zhe , Hao Hong‐wei , Zhang Tie‐hua , Ye Hai‐qing 
Published: September 2018

AbstractProbiotics are considered to be a potential treatment for ulcerative colitis (UC). The aim of this study was to compare the preventive effect of a space flight‐induced mutant L. reuteri F‐9‐35 and its wild type on UC in vivo. Female mice were randomly assigned to five groups: one normal and four colitic. Mice from colitis groups were daily gavaged with 0.2 mL 12% (w/v) skim milk containing the mutant or wild type (1 × 1011 CFU/mL), skim milk alone or distilled water for the whole experiment period, starting 7 days before colitis induction. UC was induced by administrating mice with 3.5% (w/v) dextran sulfate sodium (DSS) in drinking water for 7 days, after which DSS was removed and maintained for 3 days as a recovery phase. The results showed that the mice fed with L. reuteri F‐9‐35 had less inflammatory phenotype according to macroscopic and histological analysis, reduced myeloperoxidase activity, and lower expression of proinflammatory genes (Tumor necrosis factor‐α, cyclooxygenase‐2 and interleukin‐6) in colonic tissue compared with control. Furthermore, L. reuteri F‐9‐35 protected the mice from gut microbiota dysbiosis from DDS induced colitis. Neither wild type nor the milk alone had such beneficial effects. From above we conclude that L. reuteri F‐9‐35 has great potential in the prevention of UC as a dietary supplement.Practical ApplicationUlcerative colitis (UC) is the most common inflammatory bowel diseases and there is still a lack of safe and effective treatments. Consumption of L. reuteri F‐9‐35 may effective in preventing human UC.
In Vitro Digestion of Lipids in Real Foods: Influence of Lipid Organization Within the Food Matrix and Interactions with Nonlipid Components
Authors: Calvo‐Lerma Joaquim , Fornés‐Ferrer Victoria , Heredia Ana , Andrés Ana 
Published: September 2018

AbstractIn vitro digestion research has scarcely addressed the assessment of the complexity of digestion in real food. The aim of the present study was to evaluate the influence of intestinal conditions, nonlipid components, and lipid organization within the food matrix on lipolysis extent. A selection of 52 foods was studied under different simulated intestinal conditions, including those related to patients with cystic fibrosis (pH6, bile salts 1 mM due to decreased pancreatic and biliary secretions) and to healthy subjects (pH7, bile salts 10 mM). Linear mixed regression models were applied to explain associations of food properties with lipolysis. Normal intestinal conditions allowed for optimal lipolysis in most of the foods in contrast to the altered intestinal scenario (30 compared with 1 food reaching > 90% lipolysis). Lipid‐protein and lipid‐starch interactions were evidenced to significantly affect lipolysis (P < 0.001) in all the digestion conditions, decreasing in those foods with low fat and high protein or high starch content. In addition, under decreased intestinal pH and bile concentration, lipolysis was lower in foods with complex solid structures and continuous lipid phase than in the oil‐in‐water continuous aqueous phase (global P < 0.01). However, in the normal conditions lipid organization within the food matrix did not show a significant effect on lipolysis (global P = 0.08). In conclusion, food properties play a crucial role in lipolysis, which should be considered when establishing dietary recommendations.Practical ApplicationFood composition, lipid organization within the food matrix, and gastrointestinal conditions are key factors affecting lipolysis. Knowledge on that can be used to modulate lipolysis performance after food ingestion. Different applications are foreseen, as food design and nutritional recommendations for the general populations and specific target groups. The most immediate application is related to the scope of the research project that frames this work (www.mycyfapp.eu). These results have contributed to the development of a mobile app for cystic fibrosis patients, which includes an algorithm for enzyme dose prediction based on food properties. The app is currently being tested in a clinical trial setting.
Targeting the ICOS/ICOS‐L pathway in a mouse model of established allergic asthma disrupts T follicular helper cell responses and ameliorates disease
Authors: Uwadiae Faith I. , Pyle Chloe J. , Walker Simone A. , Lloyd Clare M. , Harker James A. 
Published: September 2018

AbstractBackgroundAllergic asthma is characterized by chronic inflammation and remodelling of the airways, associated with dysregulated type 2 immune responses and allergen‐specific IgE. T follicular helper cells (TFH) are crucial in T‐dependent B‐cell responses and have been implicated in allergic airway disease (AAD). TFH, unlike other CD4+ T cells, are uniquely reliant on continuous ICOS signalling to maintain their phenotype after T‐cell priming; therefore, disrupting this signal can impair TFH responses. However, the contribution of TFH to disease during chronic aero‐allergen exposure and the therapeutic potential of targeting these cells have not been evaluated.MethodsTo establish AAD, female BALB/c mice were repeatedly exposed to house dust mite or Alternaria alternata three times a week for up to 5 weeks. To examine the impact of TFH on AAD, mice were allergen exposed for 5 weeks and co‐administered anti‐ICOS Ligand‐targeted antibodies, three times a week for the last 2 weeks.ResultsTFH were first observed in the lung‐draining lymph nodes and with further exposure were also found locally within the lungs. TFH accumulated with sustained allergen exposure, alongside germinal centre (GC) B cells. Blockade of ICOS signalling after AAD establishment successfully depleted TFH but did not affect the differentiation of other CD4+ T‐cell subsets. This reduced GC responses, allergen‐specific IgE, inflammation, pulmonary IL‐13 and airway hyper‐responsiveness.ConclusionsTFH are crucial in the regulation of AAD and the ICOS/ICOS‐L pathway could represent a novel therapeutic target in allergic asthma.
Increased Plasma‐Free Hemoglobin Levels Identify Hemolysis in Patients With Cardiogenic Shock and a Trans valvular Micro‐Axial Flow Pump
Authors: Esposito Michele L. , Morine Kevin J. , Annamalai Shiva K. , O’Kelly Ryan , Aghili Nima , Pedicini Robert , Breton Catalina , Mullin Andrew , Hamadeh Anas , Kiernan Michael S. , DeNofrio David , Kapur Navin K. 
Published: September 2018

AbstractHemolysis is a potential limitation of percutaneously delivered left‐sided mechanical circulatory support pumps, including trans valvular micro‐axial flow pumps (TVP). Hemolytic biomarkers among durable left ventricular assist devices include lactate dehydrogenase (LDH) >2.5 times the upper limit of normal (ULN) and plasma‐free hemoglobin (pf‐Hb) >20 mg/dL. We examined the predictive value of these markers among patients with cardiogenic shock (CS) receiving a TVP. We retrospectively studied records of 116 consecutive patients receiving an Impella TVP at our institution between 2012 and 2017 for CS. Twenty‐three met inclusion/exclusion criteria, and had sufficient pf‐Hb data for analysis. Area under receiver‐operator characteristic (ROC) curve for diagnosing hemolysis were calculated. Mean age was 62 ± 14 years and ejection fraction was 15 ± 5%. Mean duration of support was 5.4 ± 3.5 days. Pre‐device LDH levels were >2.5x ULN in 71% (n = 5/7) of 5.0 and 29% of CP patients, while pre‐device pf‐Hb levels were >20 mg/dL in 14% (n = 1/7) of 5.0 and 25% (n = 4/16) of CP patients. Given elevated baseline LDH and pf‐Hb levels, we defined hemolysis as a pf‐Hb level >40 mg/dL within 72 h post‐implant plus clinical evidence of device‐related hemolysis. We identified that 30% (n = 7/23) had device‐related hemolysis. Using ROC curve‐derived cut‐points, an increase in delta pf‐Hb by >27mg/dL, not delta LDH, within 24 h after TVP implant (delta pf‐Hb: C‐statistic = 0.79, sensitivity: 57%, specificity: 93%, p <0.05) was highly predictive of hemolysis. In conclusion, we identified a change in pf‐Hb, not LDH, levels is highly sensitive and specific for hemolysis in patients treated with a TVP for CS.
Neuropeptide Y treatment induces retinal vasoconstriction and causes functional and histological retinal damage in a porcine ischaemia model
Authors: Christiansen Anders T. , Sørensen Nina B. , Haanes Kristian A. , Blixt Frank W. , la Cour Morten , Warfvinge Karin , Klemp Kristian , Woldbye David P. D. , Kiilgaard Jens F. 
Published: September 2018

AbstractPurposeTo investigate the effects of intravitreal neuropeptide Y (NPY) treatment following acute retinal ischaemia in an in vivo porcine model. In addition, we evaluated the vasoconstrictive potential of NPY on porcine retinal arteries ex vivo.MethodsTwelve pigs underwent induced retinal ischaemia by elevated intraocular pressure clamping the ocular perfusion pressure at 5 mmHg for 2 hr followed by intravitreal injection of NPY or vehicle. After 4 weeks, retinas were evaluated functionally by standard and global‐flash multifocal electroretinogram (mfERG) and histologically by thickness of retinal layers and number of ganglion cells. Additionally, the vasoconstrictive effects of NPY and its involved receptors were tested using wire myographs and NPY receptor antagonists on porcine retinal arteries.ResultsIntravitreal injection of NPY after induced ischaemia caused a significant reduction in the mean induced component (IC) amplitude ratio (treated/normal eye) compared to vehicle‐treated eyes. This reduction was accompanied by histological damage, where NPY treatment reduced the mean thickness of inner retinal layers and number of ganglion cells. In retinal arteries, NPY‐induced vasoconstriction to a plateau of approximately 65% of potassium‐induced constriction. This effect appeared to be mediated via Y1 and Y2, but not Y5.ConclusionIn seeming contrast to previous in vitro studies, intravitreal NPY treatment caused functional and histological damage compared to vehicle after a retinal ischaemic insult. Furthermore, we showed for the first time that NPY induces Y1‐ and Y2‐ but not Y5‐mediated vasoconstriction in retinal arteries. This constriction could explain the worsening in vivo effect induced by NPY treatment following an ischaemic insult and suggests that future studies on exploring the neuroprotective effects of NPY might focus on other receptors than Y1 and Y2.
Increased tacrolimus blood concentration by Beni‐Madonna – a new hybrid citrus cultivar categorized as ‘Tangor’, in a liver transplant patient: likely furanocoumarin‐mediated inhibition of CYP3A4 or P‐glycoprotein
Authors: Ushijima Kentaro , Mizuta Koichi , Otomo Shinya , Ogaki Keiko , Sanada Yukihiro , Hirata Yuta , Ihara Yoshiyuki , Urahashi Taizen , Imai Yasushi , Fujimura Akio 
Published: September 2018

Adverse eventA drug interaction leading to greater exposure to tacrolimus.Drug implicatedTacrolimus and Beni‐Madonna (a new cultivar citrus categorized as ‘Tangor’).The patientA 9‐month‐old girl with biliary atresia (body weight, 7.5 kg) taking tacrolimus after liver transplantation.Evidence that links the drug to the eventThe time course was consistent with the appearance of the interaction, which was confirmed by an increase in the blood concentration of tacrolimus. Dihydroxybergamottin was detected in peel of Beni‐Madonna and in peel and fruit pulp of grapefruit.ManagementAvoiding Beni‐Madonna intake.MechanismInhibition of activity of CYP3A4, P‐glycoprotein, or both, by Beni‐Madonna.Implication for therapyClinicians should be aware of this potential interaction, and patients taking drugs such as tacrolimus (the kinetics of which are affected by grapefruit juice) should avoid Beni‐Madonna intake.Hypothesis to be testedFurther study is required to determine if other Citrus species categorized as Tangor contain furanocoumarins.
Oral fluoroquinolones and risk of fibromyalgia
Authors: Ganjizadeh‐Zavareh Saeed , Sodhi Mohit , Spangehl Tori , Carleton Bruce , Etminan Mahyar 
Published: September 2018

AbstractThe Food and Drug Administration (FDA) has recently included a black box warning on fibromyalgia‐like symptoms with fluoroquinolones (FQs) but no large epidemiologic study is to date available. We undertook a case–control study using a random sample of 9 053 240 subjects obtained from the PharMetrics Plus health claims database in the United States. Cases received at least two fibromyalgia diagnoses coded by a rheumatologist matched to ten randomly selected controls. After identifying 5148 cases of fibromyalgia and 51 480 controls, the adjusted rate ratio (RR) of fibromyalgia for use of any fluoroquinolones, amoxicillin and azithromycin were 1.63 (95% CI: 1.41–1.87), 1.64 (95% CI: 1.46–1.85) and 1.68 (95% CI, 1.49–1.89), respectively. The adjusted RR for any use of FQ compared to any use of amoxicillin or azithromycin was 0.99 (95% CI: 0.83–1.18) and azithromycin is 0.97 (95%CI: 0.82–1.16), respectively. The risk of fibromyalgia with FQs is similar to that with amoxicillin and azithromycin.
Osteoanabolic and dual action drugs
Authors: Tabacco Gaia , Bilezikian John P. 
Published: September 2018

Teriparatide (TPTD) and abaloparatide (ABL) are the only osteoanabolic drugs available, at this time, for treatment of osteoporosis. TPTD is a 34‐amino acid fragment that is identical in its primary sequence to the 34 amino acids of full‐length human parathyroid hormone [hPTH(1‐84)]. ABL is identical to parathyroid hormone‐related peptide (PTHrP) through the first 22 residues with significantly different amino acids inserted thereafter, between residues 22 and 34. The osteoanabolic actions of PTH are due directly to its effects on cells of the osteoblast lineage and indirectly by stimulating IGF‐I synthesis and suppressing sclerostin and associated enhancement of Wnt signalling. Both TPTD and ABL are ligands that bind to and activate the PTH receptor type 1 (PTHR1) receptor but they appear to do so differently: ABL favours the transient, more anabolic configuration of the receptor. Both TPTD and ABL reduce the risk of vertebral fractures and non‐vertebral fractures. Both drugs are administered for a maximum of 24 months, and should be followed by an antiresorptive agent to maintain gains in bone mineral density (BMD). Romosozumab, a monoclonal antibody that binds to and inhibits sclerostin, appears to have dual actions by stimulating bone formation and reducing bone resorption. In the pivotal clinical trial, romosozumab, administered as a 210 mg monthly subcutaneous dose, significantly reduced new vertebral fractures and in a subsequent study reduced both vertebral and non‐vertebral fractures.
Lack of ethnic differences in the pharmacokinetics and pharmacodynamics of evolocumab between Caucasian and Asian populations
Authors: Wang Chen , Zheng Qingshan , Zhang Mingqiang , Lu Hong 
Published: September 2018

AimsTo evaluate the potential ethnic differences in the pharmacokinetics (PK) and pharmacodynamics (PD) of evolocumab in Caucasian and Asian populations using population PK/PD modelling analysis.MethodsData from different ethnic groups in 5 Phase I clinical trials, including two American studies, one Japanese study and two Chinese studies, were chosen for model building and evaluation. A target‐mediated drug disposition model together with an indirect response model best captured evolocumab binding and the removal of unbound proprotein convertase subtilisin/kexin type 9 (PCSK9) as well as a reduction in circulating low‐density lipoprotein cholesterol (LDL‐C). Ethnicity and other related factors (body weight, target expression level etc.) were analysed as potential covariates.ResultsThe estimated linear clearance and volume of evolocumab were 0.24 l day–1 and 2.75 l, respectively, which was consistent with the previous modelling results from the American trials. The time course of the LDL‐C reduction was described by an indirect response model with the elimination rate of LDL‐C being modulated by unbound PCSK9. The concentration of unbound PCSK9 associated with the half‐maximal inhibition of LDL‐C elimination was 1.28 nmol l–1. Both the PK and PD characteristics were consistent between the Caucasian and Asian populations.ConclusionThe target‐mediated drug disposition model successfully described the PK and PD characteristics of evolocumab, and this analysis found no significant differences in the PK/PD relationship for its LDL‐C lowering effects between Caucasians and Asians.
In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5‐HT2 and α1 receptors
Authors: Heng Hui Li , Chee Chin Fei , Thy Chun Keng , Tee Jia Ti , Chin Sek Peng , Herr Deron R. , Buckle Michael J. C. , Paterson Ian C. , Doughty Stephen W. , Abd. Rahman Noorsaadah , Chung Lip Yong 
Published: September 2018

AbstractCompounds with activity at serotonin (5‐hydroxytryptamine) 5‐HT2 and α1 adrenergic receptors have potential for the treatment of central nervous system disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in vitro functional activities at human 5‐HT2 and adrenergic α1 receptor subtypes were evaluated. The enantiomers of isolaureline and dicentrine acted as antagonists at 5‐HT2 and α1 receptors with (R)‐isolaureline showing the greatest potency (pKb = 8.14 at the 5‐HT2C receptor). Both (R)‐ and (S)‐glaucine also antagonized α1 receptors, but they behaved very differently to the other compounds at 5‐HT2 receptors: (S)‐glaucine acted as a partial agonist at all three 5‐HT2 receptor subtypes, whereas (R)‐glaucine appeared to act as a positive allosteric modulator at the 5‐HT2A receptor.