bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Double‐Blind, Phase I, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of BOS161721 in Healthy Subjects
Authors: Hussaini Azra , Mukherjee Rajat , Berdieva Dina M. , Glogowski Christen , Mountfield Richard , Ho Peter T.C. 
Published: October 2019

The purpose of this study was to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of BOS161721, a humanized immunoglobulin G1 triple mutation (M252Y/S254T/T256E) monoclonal antibody that inhibits interleukin‐21 (IL‐21) bioactivity. This randomized, single‐center, double‐blind, placebo‐controlled study randomized healthy volunteers 3:1 to single ascending intravenous and subcutaneous doses of BOS161721 (range 1–240 mg) or placebo. BOS161721 and placebo groups had similar rates of adverse events, mostly mild; none led to study discontinuation. There were no clinically significant findings in physical examination, vital signs, or laboratory assessment. In the pooled BOS161721 population, four subjects (8.5%) tested antidrug antibody‐positive predose, and seven (14.9%) postdose. Absolute CD4+ lymphocyte count remained normal throughout follow‐up. BOS161721 administered subcutaneously was absorbed slowly, with a median time to maximum concentration (Tmax) of 144 hours across doses (range 1–15 days) and a mean apparent terminal elimination half‐life of 80–87 days for doses ≥ 30 mg. Area under the concentration‐time curve from time zero to infinity (AUC0‐inf) and maximum observed concentration (Cmax) were linear across doses > 10 mg. Subcutaneous bioavailability was 64%. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) decreased dose‐dependently with threshold characteristics at doses of ≥ 10 mg. Downregulation in BATF, IL6, LAG3, and SOCS3 genes caused by IL‐21 stimulation was reversed dose‐dependently. BOS161721 was well‐tolerated across doses, suppressed IL‐21‐induced pSTAT3 dose‐dependently, and reversed downregulation of genes critical to tolerance induction and T‐cell exhaustion induced by IL‐21. Further clinical studies are ongoing in patients with systemic lupus erythematosus, in which IL‐21 has a pathogenetic role.
Itraconazole Increases Ibrutinib Exposure 10‐Fold and Reduces Interindividual Variation—A Potentially Beneficial Drug‐Drug Interaction
Authors: Tapaninen Tuija , Olkkola Aleksi M. , Tornio Aleksi , Neuvonen Mikko , Elonen Erkki , Neuvonen Pertti J. , Niemi Mikko , Backman Janne T. 
Published: October 2019

The oral bioavailability of ibrutinib is low and variable, mainly due to extensive first‐pass metabolism by cytochrome P450 (CYP) 3A4. The unpredictable exposure can compromise its safe and effective dosing. We examined the impact of itraconazole on ibrutinib pharmacokinetics. In a randomized crossover study, 11 healthy subjects were administered itraconazole 200 mg or placebo twice on day 1, and once on days 2–4. On day 3, 1 hour after itraconazole (placebo) and breakfast, ibrutinib (140 mg during placebo; 15 mg during itraconazole) was administered. Itraconazole increased the dose‐adjusted geometric mean area under the concentration‐time curve from zero to infinity (AUC0–∞) of ibrutinib 10.0‐fold (90% confidence interval (CI) 7.2–13.9; P < 0.001) and peak plasma concentration (Cmax) 8.8‐fold (90% CI 6.3–12.1; P < 0.001). During itraconazole, the intersubject variation for the AUC0–∞ (55%) and Cmax (53%) was around half of that during placebo (104%; 99%). In conclusion, itraconazole markedly increases ibrutinib bioavailability and decreases its interindividual variability, offering a possibility to improved dosing accuracy and cost savings.
Natural compulsive‐like behaviour in the deer mouse (Peromyscus maniculatus bairdii) is associated with altered gut microbiota composition
Authors: Scheepers Isabella M. , Cryan John F. , Bastiaanssen Thomaz F. S. , Rea Kieran , Clarke Gerard , Jaspan Heather B. , Harvey Brian H. , Hemmings Sian M. J. , Santana Leonard , van der Sluis Rencia , Malan‐Müller Stefanie , Wolmarans De Wet 
Published: October 2019

AbstractObsessive–compulsive disorder (OCD) is a psychiatric illness that significantly impacts affected patients and available treatments yield suboptimal therapeutic response. Recently, the role of the gut–brain axis (GBA) in psychiatric illness has emerged as a potential target for therapeutic exploration. However, studies concerning the role of the GBA in OCD are limited. To investigate whether a naturally occurring obsessive–compulsive‐like phenotype in a rodent model, that is large nest building in deer mice, is associated with perturbations in the gut microbiome, we investigated and characterised the gut microbiota in specific‐pathogen‐free bred and housed large (LNB) and normal (NNB) nest‐building deer mice of both sexes (n = 11 per group, including three males and eight females). Following baseline characterisation of nest‐building behaviour, a single faecal sample was collected from each animal and the gut microbiota analysed. Our results reveal the overall microbial composition of LNB animals to be distinctly different compared to controls (PERMANOVA p < .05). While no genera were found to be significantly differentially abundant after correcting for multiple comparisons, the normal phenotype showed a higher loading of Prevotella and Anaeroplasma, while the OC phenotype demonstrated a higher loading of Desulfovermiculus, Aestuariispira, Peptococcus and Holdemanella (cut‐off threshold for loading at 0.2 in either the first or second component of the PCA). These findings not only provide proof‐of‐concept for continued investigation of the GBA in OCD, but also highlight a potential underlying aetiological association between alterations in the gut microbiota and the natural development of obsessive–compulsive‐like behaviours.
Exploring the Role of Practical Wisdom in Addressing Adolescent Childrearing Dilemmas
Authors: Small Stephen A. , Metler David Charles 
Published: October 2019

ObjectiveTo explore whether practical wisdom may provide a useful lens for understanding how mothers can address difficult childrearing problems more effectively when raising adolescents.BackgroundOne of the major difficulties of raising adolescents is that there are no clear‐cut responses or universal solutions to many of the problems that regularly arise. Parents are expected to make responsible decisions about complex, indefinite problems even though they may lack a thorough understanding of the situation and have little formal training in childrearing. Practical wisdom—the ability to make sound, ethical judgments and decisions about difficult and uncertain problems—may be a valuable asset for addressing such challenges.MethodThirty mothers of adolescents (12–17 years of age) were asked to reason aloud about how they would respond to a series of hypothetical childrearing dilemmas.ResultsGuided by prior work on practical wisdom, our qualitative analysis identified a complex combination of eight interrelated parenting wisdom strategies: Compassion for Self and Child, Integrative Thinking, Parenting Knowledge, Perspective‐Taking, Problem‐Framing, Purpose Identification, Reflection, and Socioemotional Awareness.ConclusionThe findings provide evidence that mothers sometimes use a process that has been historically conceptualized as practical wisdom and offer insight into what some of these practices entail.ImplicationsThe identification of these wise problem‐solving strategies highlight an important overlooked aspect of childrearing and hold promise as a valuable asset for helping mothers address difficult parenting problems.
Bovine milk transcriptome analysis reveals microRNAs and RNU2 involved in mastitis
Authors: Lai Yu‐Chang , Lai Yu‐Ting , Rahman Md Mahfuzur , Chen Hui‐Wen , Husna Al Asmaul , Fujikawa Takuro , Ando Takaaki , Kitahara Go , Koiwa Masateru , Kubota Chikara , Miura Naoki 
Published: October 2019

Mastitis is a common inflammatory infectious disease in dairy cows. To understand the microRNA (miRNA) expression profile changes during bovine mastitis, we undertook a genome‐wide miRNA study of normal milk and milk that tested positive on the California mastitis test for bovine mastitis (CMT+). Twenty‐five miRNAs were differentially expressed (23 miRNAs upregulated and two downregulated) during bovine mastitis relative to their expression in normal milk. Upregulated mature miR‐1246 probably derived from a U2 small nuclear RNA rather than an miR‐1246 precursor. The significantly upregulated miRNA precursors and RNU2 were significantly enriched on bovine chromosome 19, which is homologous to human chromosome 17. A gene ontology analysis of the putative mRNA targets of the significantly upregulated miRNAs showed that these miRNAs were involved in binding target mRNA transcripts and regulating target gene expression, and a Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the upregulated miRNAs were predominantly related to cancer and immune system pathways. Three novel miRNAs were associated with bovine mastitis and were relatively highly expressed in milk. We confirmed that one of the novel mastitis‐related miRNAs was significantly upregulated using a digital PCR system. The differentially expressed miRNAs were involved in human cancers, infections, and immune‐related diseases. The genome‐wide analysis of miRNA profiles in this study provides insight into bovine mastitis and inflammatory diseases.DatabasesThe miRNAseq generated for this study can be found in the Sequence Read Archive (SRA) under BioProject Number PRJNA421075 and SRA Study Number SRP126134 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA421075).
Effects of two centuries of global environmental variation on phenology and physiology of Arabidopsis thaliana
Authors: DeLeo Victoria L. , Menge Duncan N. L. , Hanks Ephraim M. , Juenger Thomas E. , Lasky Jesse R. 
Published: October 2019

AbstractIntraspecific trait variation is caused by genetic and plastic responses to environment. This intraspecific diversity is captured in immense natural history collections, giving us a window into trait variation across continents and through centuries of environmental shifts. Here we tested if hypotheses based on life history and the leaf economics spectrum explain intraspecific trait changes across global spatiotemporal environmental gradients. We measured phenotypes on a 216‐year time series of Arabidopsis thaliana accessions from across its native range and applied spatially varying coefficient models to quantify region‐specific trends in trait coordination and trait responses to climate gradients. All traits exhibited significant change across space or through time. For example, δ15N decreased over time across much of the range and leaf C:N increased, consistent with predictions based on anthropogenic changes in land use and atmosphere. Plants were collected later in the growing season in more recent years in many regions, possibly because populations shifted toward more spring germination and summer flowering as opposed to fall germination and spring flowering. When climate variables were considered, collection dates were earlier in warmer years, while summer rainfall had opposing associations with collection date depending on regions. There was only a modest correlation among traits, indicating a lack of a single life history/physiology axis. Nevertheless, leaf C:N was low for summer‐ versus spring‐collected plants, consistent with a life history–physiology axis from slow‐growing winter annuals to fast‐growing spring/summer annuals. Regional heterogeneity in phenotype trends indicates complex responses to spatiotemporal environmental gradients potentially due to geographic genetic variation and climate interactions with other aspects of environment. Our study demonstrates how natural history collections can be used to broadly characterize trait responses to environment, revealing heterogeneity in response to anthropogenic change.
Global change biology: A primer
Authors: Sage Rowan F. 
Published: October 2019

AbstractBecause of human action, the Earth has entered an era where profound changes in the global environment are creating novel conditions that will be discernable far into the future. One consequence may be a large reduction of the Earth's biodiversity, potentially representing a sixth mass extinction. With effective stewardship, the global change drivers that threaten the Earth's biota could be alleviated, but this requires clear understanding of the drivers, their interactions, and how they impact ecological communities. This review identifies 10 anthropogenic global change drivers and discusses how six of the drivers (atmospheric CO2 enrichment, climate change, land transformation, species exploitation, exotic species invasions, eutrophication) impact Earth's biodiversity. Driver impacts on a particular species could be positive or negative. In either case, they initiate secondary responses that cascade along ecological lines of connection and in doing so magnify the initial impact. The unique nature of the threat to the Earth's biodiversity is not simply due to the magnitude of each driver, but due to the speed of change, the novelty of the drivers, and their interactions. Emphasizing one driver, notably climate change, is problematic because the other global change drivers also degrade biodiversity and together threaten the stability of the biosphere. As the main academic journal addressing global change effects on living systems, GCB is well positioned to provide leadership in solving the global change challenge. If humanity cannot meet the challenge, then GCB is positioned to serve as a leading chronicle of the sixth mass extinction to occur on planet Earth.
A meta‐analysis examining lactic acid bacteria inoculants for maize silage: Effects on fermentation, aerobic stability, nutritive value and livestock production
Authors: Bernardi Alexandre , Härter Carla J. , Silva Antonio W. L. , Reis Ricardo A. , Rabelo Carlos H. S. 
Published: October 2019

AbstractA database containing 140 articles published in journals (731 treatment means evaluated) was used to examine the effect of different lactic acid bacteria (LAB) on fermentation, chemical composition and aerobic stability of maize (corn) silage. Compared with the control, dry matter (DM) loss increased by 8% and 50% (p < .01) due to inoculation of maize silage with either homolactic LAB (hoLAB) or heterolactic LAB (heLAB). In vitro DM digestibility of maize silage increased only with hoLAB inoculation (+2.22%; p < .01). The heLAB inoculation increased (p < .01) the aerobic stability of maize silage by 71.3 hr. To investigate the effect of silage inoculation on livestock production, a second database comprising 35 articles [99 treatment means evaluated based on results from 648 cattle (429 beef cattle and 219 dairy cows) and 298 sheep] was used. Inoculation of maize silage with either hoLAB or heLAB did not affect milk yield (p > .05), but their combination (mixLAB) depressed milk yield (–2.5 kg/day; p < .01). Inoculation with hoLAB increased DM intake in sheep (+0.15 kg/day; p = .02), but decreased it in beef cattle (–0.26 kg/day; p = .01) without affecting average daily gain for both sheep and beef cattle (p ≥ .06). In conclusion, fermentative loss increased regardless of the bacterial inoculant used, while aerobic stability increased mainly by using heLAB. Benefits from hoLAB inoculation on animal performance were noted only for feed intake in sheep, while productive performances of dairy cows and beef cattle were not improved.
IL‐17 and its role in inflammatory, autoimmune, and oncological skin diseases: state of art
Authors: Bernardini Nicoletta , Skroza Nevena , Tolino Ersilia , Mambrin Alessandra , Anzalone Alessia , Balduzzi Veronica , Colapietra Daniela , Marchesiello Anna , Michelini Simone , Proietti Ilaria , Potenza Concetta 
Published: October 2019

AbstractRecent data support the theory of the involvement of IL‐17 in the pathogenesis of several chronic inflammatory skin diseases (psoriasis, atopic dermatitis, acne, hidradenitis suppurativa) and autoimmune skin diseases (alopecia areata, vitiligo, bullous diseases). Even if the role of IL‐17 in inflammatory and autoimmune diseases has been reported extensively, its role in tumor is still controversial. Some reports show that Th17 cells eradicate tumors, while others reveal that they promote the initiation and early growth of tumors. Herein, we review the role of IL‐17 in the involvement of some common dermatologic diseases: psoriasis, atopic dermatitis, hidradenitis suppurativa, acne, vitiligo, melanoma, and nonmelanoma skin cancers.
Polycystic ovary syndrome in adolescent girls
Authors: Ibáñez Lourdes , de Zegher Francis 
Published: October 2019

SummaryPCOS is already a prevalent endocrinopathy in adolescent girls, and its prevalence is rising further since, in essence, it is the result of a mismatch between an energy‐sparing (epi)genetic background and a (relatively) obesogenic environment. This mismatch results in an excess of fat storage in ectopic depots, notably in the liver and viscera (= hepato‐visceral, or central fat). There is still no FDA‐approved treatment for adolescent PCOS. The prime aim should be a preferential loss of central fat, through lifestyle measures. Failure to sustain these measures is frequent, and the standard approach is to add an estroprogestagen contraceptive, even for girls who do not need contraception. Treatment with SPIOMET, a low‐dose combination of spironolactone (to antagonize androgen and mineralocorticoid effects, and to activate BAT thereby raising energy expenditure), pioglitazone (to raise circulating HMW adiponectin concentrations) and metformin, is an alternative approach that holds the potential to revert the PCOS phenotype.
Using a collaborative decision-making approach to identify, prioritise and respond to issues influencing Good Pharmacy Practice across countries of the Western Pacific Region
Authors: Jackson John , Caliph Suzanne , Chui Wai Keung , Ocampo Leonila 
Published: October 2019

Abstract

Objectives
The Western Pacific Pharmaceutical Forum aims to foster Good Pharmacy Practice (GPP) in the Western Pacific Region (WPR). Our objective in this work was to develop and implement a process that equitably and constructively engaged pharmacy associations from the diverse cultures, languages and models of pharmacy practice in the WPR to identify common issues influencing the implementation of GPP.

Methods
The World Café concept was incorporated into a modified Tuckman's model for group development to conduct a workshop of leaders from the major pharmacy associations of the WPR. Facilitated discussion groups and collaborative decision-making were used to gather opinions and achieve agreement between the regional leaders.

Key findings
Participants reported the method to be open, systematic and enabled full contribution. Two major issues were identified in relation to each of the four key pharmacist roles associated with GPP. The regional pharmacy leaders agreed the common priority issue for implementing GPP as: ‘National competency standards should be established to enable the formulation of professional development framework that lead to enhanced pharmacy practice and patient care’ and developed a strategy and work plan to address this issue.

Conclusions
Identification of GPP issues and the common major priority occurred with shared knowledge of the current state of practice across the WPR. The adopted methodology overcame cultural and practice differences to ensure full and equal participation of all delegates. The approach ensured ownership by all participants of the strategy and work plan developed to address competency and professional development in the WPR.
Travail et normes comptables internationales: une question de justice sociale
Authors: JUBÉ Samuel 
Published: October 2019

RésuméEn tant que garante internationale de la justice sociale, l'OIT se trouve confrontée à une révolution comptable mondiale, parachevée par les normes comptables internationales (IAS‐IFRS). La comptabilité mesurait autrefois l'économie en rapport avec les capacités et les responsabilités des travailleurs et de ceux qui en disposent. C'est aujourd'hui l'exact opposé: les normes IAS‐IFRS ont perdu le sens de la mesure du travail et de l'entreprise en se référant au concept abstrait d'une entité cybernétique capable d'incessantes réorganisations, au prix d'inégalités sans limites. L'auteur en dénonce les incohérences et démontre la nécessité de redonner au travail toute sa valeur comptable.
Highly oxidized low‐density lipoprotein mediates activation of monocytes but does not confer interleukin‐1β secretion nor interleukin‐15 transpresentation function
Authors: Sieg Scott F. , Bazdar Douglas A. , Zidar David , Freeman Michael , Lederman Michael M. , Funderburg Nicholas T. 
Published: October 2019

SummaryOxidized low‐density lipoprotein (LDL) contributes to cardiovascular disease in part by mediating activation and maturation of monocytes and macrophages. Furthermore, co‐localization studies using histochemical approaches have implicated a potential role for oxidized LDL as a mediator of interleukin‐15 (IL‐15) expression in myeloid cells of atherosclerotic plaque. The latter activity could be an important pro‐inflammatory mechanism that mediates myeloid cell/T‐cell crosstalk. Here, we examined the responses of primary human monocytes to highly oxidized LDL molecules. Oxidized LDL readily induced secretion of chemokines MCP‐1 (CCL2) and GRO‐α (CXCL1) but unlike lipopolysaccharide (LPS), has limited capacity to induce a variety of other cytokines including tumor necrosis factor‐α, IL‐6, IL‐1β and interferon‐γ‐induced protein‐10 and also displayed a poor capacity to induce p‐Akt or P‐S6 signaling. Failure of oxidized LDL to induce IL‐1β secretion was associated with limited induction of caspase‐1 activation. Furthermore, despite finding evidence that oxidized LDL could enhance the expression of IL‐15 and IL‐15 receptor expression in monocytes, we found no evidence that it could confer IL‐15 transpresentation capability to these cells. This observation contrasted with induction of IL‐15 transpresentation in lipopolysaccharide‐stimulated monocytes. Overall, our data suggest that highly oxidized LDL is a selective inducer of monocyte activation. Sterile inflammatory mediators, particularly those implicated in Toll‐like receptor 4 signaling, may play a role in vascular pathology but the activities of these agents are not uniform.
Mental health nurses’ experience of physical health care and health promotion initiatives for people with severe mental illness
Authors: Lundström Sofie , Jormfeldt Henrika , Hedman Ahlström Britt , Skärsäter Ingela 
Published: October 2019

AbstractHealth care for people with severe mental illness is often divided into physical health care and mental health care despite the importance of a holistic approach to caring for the whole person. Mental health nurses have an important role not only in preventing ill health, but also in promoting health, to improve the overall health among people with severe mental illness and to develop a more person‐centred, integrated physical and mental health care. Thus, the aim of this study was to describe mental health nurses’ experiences of facilitating aspects that promote physical health and support a healthy lifestyle for people with severe mental illness. Interviews were conducted with mental health nurses (n = 15), and a qualitative content analysis was used to capture the nurse’s experiences. Analysis of the interviews generated three categories: (i) to have a health promotion focus in every encounter, (ii) to support with each person’s unique prerequisites in mind and (iii) to take responsibility for health promotion in every level of the organization. The results show the importance of a health promotion focus that permeates the entire organization of mental health care. Shared responsibility for health and health promotion activities should exist at all levels: in the person‐centred care in the relation with the patient, embedded in a joint vision within the working unit, and in decisions at management level.