bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disrupted copper availability in sporadic ALS: Implications for CuII(atsm) as a treatment option
Authors: Hilton James BW , Kysenius Kai , Liddell Jeffrey R , Rautengarten Carsten , Mercer Stephen W. , Paul Bence , Beckman Joseph S , McLean Catriona A. , White Anthony R , Donnelly Paul S , Bush Ashley I , Hare Dominic J , Roberts Blaine R , Crouch Peter J 
Published: April 2020

ABSTRACTObjectiveThe copper compound CuII(atsm) is in phase 2/3 testing for treatment of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). CuII(atsm) consistently and reproducibly ameliorates neurodegeneration in mutant SOD1 mouse models of ALS where its neuroprotective activity has been ascribed in part to improving availability of copper to essential cuproenzymes. However, SOD1 mutations cause only ~2% of ALS cases with most cases being of unknown aetiology. Therapeutic pertinence of CuII(atsm) to sporadic ALS is therefore unclear.MethodsWe assayed post-mortem spinal cord tissue from sporadic cases of ALS for the anatomical and biochemical distribution of copper, the expression of genes involved in copper handling, and the activities of cuproenzymes.ResultsThe natural distribution of copper is disrupted in sporadic ALS. The ALS-affected tissue has a molecular signature consistent with an unsatiated requirement for copper and cuproenzyme activity is affected. Copper levels are decreased in the ventral grey matter, the primary anatomical site of neuronal loss in ALS.InterpretationMice expressing mutant SOD1 recapitulate salient features of ALS. The unsatiated requirement for copper that is evident in these mice is a biochemical target for CuII(atsm). Evidences provided here for disrupted copper bioavailability in human cases of sporadic ALS indicate that a therapeutic mechanism for CuII(atsm) involving copper bioavailability is pertinent to sporadic cases of ALS, and not just those involving mutant SOD1.
Identifying contextually relevant improvement measures, illustrated by a case of executive walkrounds
Authors: Reed Nick J. , Wilson Natalie , Hayes Kathryn J. 
Published: April 2020

PurposeA method to engage salient organisational stakeholders in identifying and ranking measures of healthcare improvement programs is described. The method is illustrated using Executive WalkRounds (EWRs) in a multi-site Australian Health District.Design/methodology/approachSubject matter experts (SMEs) conducted document analysis, identified potential EWRs measures, created driver diagrams and then eliminated weak measures. Next, a panel of executives skilled in EWRs ranked and ratified the potential measures using a modified Delphi technique.FindingsEWRs measurement selection demonstrated the feasibility of the method. Of the total time to complete the method 79% was contributed by SMEs, 14% by administration personnel and 7% by executives. Document analysis revealed three main EWRs aims. Ten of 28 potential measures were eliminated by the SME review. After repeated Delphi rounds the executive panel achieved consensus (75% cut-off) on seven measures. One outcome, one process and one implementation fidelity metric were selected to measure and monitor the impact of EWRs in the health district.Practical implicationsPerceptions of weak relationships between measures and intended improvements can lead to practitioner scepticism. This work offers a structured method to combine the technical expertise of SMEs with the practical knowledge of healthcare staff in selecting improvement measures.Originality/valueThis research describes and demonstrates a novel method to systematically leverage formal and practical types of expertise to select measures that are strongly linked to local quality improvement goals. The method can be applied in diverse healthcare settings.
Evidence for altered insulin signalling in the brains of genetic absence epilepsy rats from Strasbourg
Authors: Sekar Sathiya , Marks Wendie N. , Gopalakrishnan Venkat , Greba Quentin , Snutch Terrance P. , Howland John G. , Taghibiglou Changiz 
Published: April 2020

AbstractInsulin‐mediated signalling in the brain is critical for neuronal functioning. Insulin resistance is implicated in the development of some neurological diseases, although changes associated with absence epilepsy have not been established yet. Therefore, we examined the major components of PI3K/Akt‐mediated insulin signalling in cortical, thalamic, and hippocampal tissues collected from Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and Non‐Epileptic Control (NEC) rats. Insulin levels were also measured in plasma and cerebrospinal fluid (CSF). For the brain samples, the nuclear fraction (NF) and total homogenate (TH) were isolated and investigated for insulin signalling markers including insulin receptor beta (IRβ), IR substrate‐1 and 2 (IRS1 & 2), phosphatase and tensin homologue (PTEN), phosphoinositide 3‐kinase phospho‐85 alpha (PI3K p85α), phosphatidylinositol 4,5‐bisphosphate, phosphatidylinositol (3,4,5)‐trisphosphate, protein kinase B (PKB/Akt1/2/3), glucose transporter‐1 and 4 (GLUT1 & 4) and glycogen synthase kinase‐3β (GSK3β) using western blotting. A significant increase in PTEN and GSK3β levels and decreased PI3K p85α and pAkt1/2/3 levels were observed in NF of GAERS cortical and hippocampal tissues. IRβ, IRS1, GLUT1, and GLUT4 levels were significantly decreased in hippocampal TH of GAERS compared to NEC. A non‐significant increase in insulin levels was observed in plasma and CSF of GAERS rats. An insulin sensitivity assay showed decreased p‐Akt level in cortical and hippocampal tissues. Together, altered hippocampal insulin signalling was more prominent in NF and TH compared to cortical and thalamic regions in GAERS. Restoring insulin signalling may improve the pathophysiology displayed by GAERS, including the spike‐and‐wave discharges that relate to absence seizures in patients.
Home range variability, spatial aggregation, and excursions of Akodon azarae and Oligoryzomys flavescens in Pampean agroecosystems
Authors: GOROSITO Irene , BENÍTEZ Ailén , BUSCH Maria 
Published: April 2020

AbstractRodents are reservoirs of various types of hantavirus, some of which are agents of hantavirus pulmonary syndrome in humans. Each hantavirus is associated with a single rodent host species but successive spill‐over events may eventually lead to host‐switching and new species’ becoming host of a given pathogen. This study aims to gain an understanding of the spatial ecology of two hantavirus‐host species, Akodon azarae, and Oligoryzomys flavescens, by identifying factors modulating their home range sizes and stability, and by evaluating intra‐ and interspecific spatial aggregation for these species and a third one—Oxymycterus rufus—living in sympatry. For this, eleven capture‐mark‐recapture surveys were carried out, spanning 22 months.We found that A. azarae males have larger and more mobile home ranges than females, independently of the season. Consequently, males could likely have a more relevant role in the transmission of hantavirus because of their greater exposure both to a higher number of contacts between individuals and viral contamination of the environment. Contrasting, O. flavescens individuals showed negligible displacements of their home range through time, which could limit the range of hantavirus spread in host populations. Since O. flavescens is host to Lechiguanas hantavirus (pathogenic to humans) this result encompasses epidemiological relevance, for it may imply the existence of local foci of infection. Additionally, individuals of both species performed excursions outside their home ranges. These events could enable hantavirus spread over distances beyond the normal range of movements and lead to new hantavirus outbreaks in formerly non‐infected rodent populations, favoring the persistence of the virus in nature.
Amoxicillin‐induced gut dysbiosis influences estrous cycle in mice and cytokine expression in the ovary and the caecum
Authors: Silva Evandro Neves , Martins Thaís Viana Fialho , Miyauchi‐Tavares Tatimara Maria , Miranda Bianca Aparecida Expedito , dos Santos Gabriela de Assis , Rosa Caio Pupin , Santos Jeferson Antônio , Novaes Rômulo Dias , de Almeida Leonardo Augusto , Corsetti Patrícia Paiva 
Published: April 2020

AbstractProblemGut dysbiosis is caused by several factors, including the use of antibiotics. Since intestinal dysbiosis is associated with a wide range of immunopathological and reproductive conditions, the main goal of this study was to evaluate amoxicillin‐induced gut dysbiosis and its influence on the oestrous cycle in mice.Method of studyMice were treated with amoxicillin or PBS, and faecal microbiota was evaluated by 16S rDNA metagenomic sequencing. The oestrous cycle was evaluated by vaginal cytology, vaginal opening and flow cytometry. After the induction of gut dysbiosis, the ovaries and the caecum were analysed to differential expression of IL‐1β and IL‐10 genes and histological analysis.ResultsAmoxicillin‐treated mice presented differing bacterial groups in the faecal microbiota when compared to the PBS‐treated group indicating that amoxicillin treatment‐induced gut dysbiosis and they gained weight. The vaginal cytology analysis showed that amoxicillin‐induced gut dysbiosis decreased the number of cells but increased the relative number of leucocytes and altered the oestrous cycle. IL‐1β was shown to be upregulated in the caecum and in the ovary of the dysbiotic mice. On the other hand, IL‐10 expression was shown to be diminished in both organs of the dysbiotic mice. The oocyte area from dysbiotic group presented lower than non‐dysbiotic mice with increasing thickness of the pellucid zone. The follicular teak from dysbiotic mice showed lower thickness than non‐dysbiotic mice.ConclusionThe results indicate that amoxicillin induces gut dysbiosis and influences the oestrous cycle and the inflammatory status of the ovary and the caecum.
Sex of the first‐born and obstetric complications in the subsequent birth. A study of 2.3 million second births from Denmark, Finland, Norway, and Sweden
Authors: Mortensen Laust H. , Cnattingius Sven , Gissler Mika , Klungsøyr Kari , Skjærven Rolv , Nybo Andersen Anne‐Marie , Nielsen Henriette S. 
Published: April 2020

AbstractIntroductionStudies have shown associations between a first‐born boy and increased risks of pregnancy loss, stillbirth, decreased birthweight, and preterm birth in subsequent pregnancies, but with limited precision.Material and MethodsWe examined associations between sex of the first‐born and obstetric complications in second births. We calculated the relative risks (RR)s of preeclampsia/eclampsia, placental abruption, stillbirth, and preterm birth in approximately 2.3 million second births comparing women with a preceding first‐born boy to those with a first‐born girl using the Medical Birth Registries of Denmark, Finland, Norway, and Sweden 1980‐2008.ResultsIn second births following a first‐born boy rather than a girl, the RR was 4% higher for preeclampsia/eclampsia (RR = 1.04, 95% CI 1.02‐1.06), 9% higher for placental abruption (RR = 1.09, 95% CI 1.05‐1.13), 9% higher for stillbirth (RR = 1.09, 95% CI 1.04‐1.14), and 8% higher for preterm birth (RR = 1.08, 95% CI 1.07‐1.09). The population attributable risks ranged from 2% to 4.5%.ConclusionsMale sex of the first‐born is associated with small increases in risks of obstetric complications in the second birth. Exploration of the underlying mechanisms is needed to increase our knowledge and treatment options for these serious obstetric complications.
Identity Continuity Protects Academic Performance, Retention, and Life Satisfaction among International Students
Authors: Cruwys Tegan , Ng Nikole W.K. , Haslam S. Alexander , Haslam Catherine 
Published: April 2020

International students transitioning to university undergo dramatic changes in social identity, with a need to adapt to a new culture, language, environment, and way of living. This paper explores the impact of this social identity change on academic performance, academic retention, mental health, and life satisfaction. The Social Identity Model of Identity Change (SIMIC) predicts that during life transitions of this form, an individual’s group memberships and associated social identities can protect them from the negative effects of life change. This longitudinal study tested SIMIC among international students (N = 210) transitioning to study overseas, with data collected at three time points across a Foundation Year programme in a large Australian university. Consistent with SIMIC, continuity of social identities predicted higher academic performance and better life satisfaction, and indirectly predicted student retention over time.
Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions
Authors: Rizaner Nahit , Uzun Sercan , Fraser Scott P. , Djamgoz Mustafa B. A. , Altun Seyhan 
Published: April 2020

AbstractAnti‐invasive effects of riluzole and ranolazine, a neuro‐protectant and an anti‐anginal drug, respectively, on Mat‐LyLu rat prostate cancer (PCa) cells were tested in vitro (a) at non‐toxic doses and (b) under both normoxic and hypoxic conditions, the latter common to growing tumours. Tetrodotoxin (TTX) was used as a positive control. Hypoxia had no effect on cell viability but reduced growth at 48 hours. Riluzole (5 μmol/L) or ranolazine (20 μmol/L) had no effect on cell viability or growth under normoxia or hypoxia over 24 hours. Matrigel invasion was not affected by hypoxia but inhibited by TTX, ranolazine and riluzole under a range of conditions. The expression of Nav1.7 mRNA, the prevailing, pro‐invasive voltage‐gated sodium channel α‐subunit (VGSCα), was up‐regulated by hypoxia. Riluzole had no effect on Nav1.7 mRNA expression in normoxia but significantly reduced it in hypoxia. VGSCα protein expression in plasma membrane was reduced in hypoxia; riluzole increased it but only under hypoxia. It was concluded (a) that riluzole and ranolazine have anti‐invasive effects on rat PCa cells and (b) that Nav1.7 mRNA and protein expression can be modulated by riluzole under hypoxia. Overall, therefore, riluzole and ranolazine may ultimately be “repurposed” as anti‐metastatic drugs against PCa.
Abemaciclib induces atypical cell death in cancer cells characterized by formation of cytoplasmic vacuoles derived from lysosomes
Authors: Hino Hirotsugu , Iriyama Noriyoshi , Kokuba Hiroko , Kazama Hiromi , Moriya Shota , Takano Naoharu , Hiramoto Masaki , Aizawa Shin , Miyazawa Keisuke 
Published: April 2020

AbstractIn the cell cycle, the G1/S transition is controlled by the cyclin‐dependent kinase (CDK) 4/6‐cyclin D complex. Constitutive activation of CDK4/6 dysregulates G1/S transition, leading to oncogenic transformation. We found that 3 CDK4/6 inhibitors, abemaciclib, ribociclib, and palbociclib, exerted a cytocidal effect as well as a cytostatic effect at the G1 phase in cancer cell lines, including A549 human non–small cell lung cancer cells. Among these inhibitors, abemaciclib exhibited the most potent cytotoxic effect. The cell‐death phenotype induced by abemaciclib, which entailed formation of multiple cytoplasmic vacuoles, was not consistent with apoptosis or necroptosis. Abemaciclib blocked autophagic flux, resulting in accumulation of autophagosomes, however vacuole formation and cell death induced by abemaciclib were independent of autophagy. In addition, methuosis, a cell‐death phenotype characterized by vacuole formation induced by excessive macropinocytosis, was excluded because the vacuoles did not incorporate fluorescent dextran. Of note, both formation of vacuoles and induction of cell death in response to abemaciclib were inhibited by vacuolar‐type ATPase (V‐ATPase) inhibitors such as bafilomycin A1 and concanamycin A. Live‐cell imaging revealed that the abemaciclib‐induced vacuoles were derived from lysosomes that expanded following acidification. Transmission electron microscopy revealed that these vacuoles contained undigested debris and remnants of organelles. Cycloheximide chase assay revealed that lysosomal turnover was blocked by abemaciclib. Furthermore, mTORC1 inhibition along with partial lysosomal membrane permeabilization occurred after abemaciclib treatment. Together, these results indicate that, in cancer cells, abemaciclib induces a unique form of cell death accompanied by swollen and dysfunctional lysosomes.
COVID‐19 impact on fruit and vegetable markets
Authors: Richards Timothy J. , Rickard Bradley 
Published: April 2020

AbstractCanadian fruit and vegetable markets were significantly impacted by the spread of the novel coronavirus SARS‐CoV‐2 (and COVID‐19 disease), beginning in March 2020. Due to the closure of restaurants, bars, and schools, produce growers and distributors were forced to shift supplies almost entirely from the foodservice to the retail channel. Shippers reported labor and logistical constraints in making the change, but the fresh produce supply chain remained robust. In the long term, we expect lasting changes in consumers’ online food‐purchasing habits, heightened constraints on immigrant labor markets, and tighter concentration in fresh produce distribution and perhaps retailing.
The teleological stance: Past, present, and future
Authors: Juvrud Joshua , Gredebäck Gustaf 
Published: April 2020

AbstractWe review the support for, and criticisms of, the teleological stance theory, often described as a foundation for goal‐directed action understanding early in life. A major point of contention in the literature has been how teleological processes and assumptions of rationality are represented and understood in infancy, and this debate has been largely centered on three paradigms. Visual habituation studies assess infant's abilities to retrospectively assess teleological processes; the presence of such processes is supported by the literature. Rational imitation is a phenomenon that has been questioned both theoretically and empirically, and there is currently little support for this concept in the literature. The involvement of teleological processes in action prediction is unclear. To date, the ontology of teleological processes remains unspecified. To remedy this, we present a new action‐based theory of teleological processes (here referred to as the embodied account of teleological processes), based on the development of goal‐directed reaching with its origin during the fetal period and continuous development over the first few months of life.
Multicenter evaluation of analytical performances of platelet counts and platelet parameters: Carryover, precision, and stability
Authors: Gioia Maria , Da Rin Giorgio , Manenti Barbara , Birindelli Sarah , Ciardelli Maria Laura , Gentile Roberto , Beretta Gianluca , Lorusso Giuseppe , Avino Daniela , Di Fabio Anna Maria , Dima Francesco , Fanelli Alessandra , Lorubbio Maria , Francione Sara , Marincheva Galina , Marini Alessandra , Papa Angela , Giannelli Elena , Pajola Rachele , Panzeri Andrea , Pipitone Silvia , Benegiamo Anna , Rolla Roberta , Vidali Matteo , Buoro Sabrina 
Published: April 2020

AbstractIntroductionThe correctness of the results of automated platelet analysis is still highly debated. The aim of this multicenter study, conducted according to international guidelines, was to verify the analytical performance of nine different types of hematology analyzers (HAs) in the automated platelet analysis.MethodsFour hundred eighty‐six peripheral blood samples (PB), collected in K3EDTA tubes, were analyzed by ABX Pentra, ADVIA2120i, BC‐6800, BC‐6800 Plus, Cell‐DYN Sapphire, DxH800, XE‐2100, XE‐5000, XN‐20 with PLT‐F App. Within‐run imprecision and between‐run imprecision were carried out using PB and material control, respectively. The carryover, low limit of quantification (LoQ), and the PB stability were evaluated.ResultsThe carryover was absent for all HAs. The LoQ of PLT ranged between 2.0 (Cell‐Dyn Sapphire) and 25.0 × 109/L (ADVIA 2120i), while immature platelet fraction (IPF) ranged between 1.0 (XN‐20) and 12.0 × 109/L (XE‐5000). The imprecision (%CV) increases as the platelet count decreases. No HAs showed desirable CVAPS for PLT counts less than 50.0 × 109/L, with the exception of Cell‐DYN Sapphire (CV 3.0% with PLT‐O mean value of 26.7 × 109/L), XN‐20 (CV 2.4% with PLT‐F mean value of 21.5 × 109/L), and BC‐6800 Plus (CV 1.9% with PLT‐O mean value of 26.5 × 109/L). The sample stability ranged between under two hours for MPV by ADVIA2120i and 8 hours for other PLT parameters and HAs.ConclusionThe findings of this study may provide useful information regarding carryover, precision, and stability of platelet counts and parameters, especially in thrombocytopenic samples. Moreover, the stability of sample for platelet analysis is conditioned by the HA and by temperature and storage time.
Positioning immobile critically ill patients who are at risk of pressure injuries using a purpose‐designed positioning device and usual care equipment: An observational feasibility study
Authors: Sousa Ines , Kapp Suzanne , Santamaria Nick 
Published: April 2020

AbstractThe prevalence of pressure injuries in the intensive care unit (ICU) setting is high with rates ranging from 13.1% to 45.5%. Evaluation of interventions to prevent pressure injuries should be informed by preliminary research to identify factors that should be considered during the design of future trials. The study objectives were to evaluate the process of participant recruitment and monitoring in the ICU; measure the maintenance of body angle (in the side‐lying lateral tilt position) and head and neck alignment angle (in the supine position) among immobile critically ill patients when using a purpose‐designed positioning device and usual care equipment, and; ascertain the time required to position patients with the purpose‐designed positioning device and the usual care equipment. A prospective, observational, feasibility study was conducted in an ICU in Victoria, Australia. The sample was immobile critically ill adults at high‐risk of developing pressure injuries. The usual care interventions were pillows, foam wedges, and rolled towels, and the intervention device was the Z‐Flo Fluidized Positioner. The body angle and head and neck alignment were measured on six occasions (at baseline, 1 hour, and 2 hours). The time required for positioning was also measured. The sample was predominately male (n = 5, 62%) with a mean age of 59 years. The majority of patients (n = 106, 92.2%) were not immobile and therefore were ineligible to participate. A total of 48 turning and positioning interventions were observed. For the side‐lying lateral tilt position, the degree of difference from baseline to 2 hours was no more than three degrees for all the devices (the Fluidized Positioner 25°‐26°, the foam wedge 29°‐27°, and the pillow 23°‐21°). For the head and neck position, the degree of difference from baseline to 2 hours was the greatest for the pillow and rolled towel (78°‐71°, a difference of 7°) and the pillow alone (79°‐74°, a difference of 5°). The degree of difference was the lowest for the Fluidized Positioner (84°‐86°, a difference of 2°). Future research to evaluate positioning equipment in the ICU should consider patient eligibility characteristics, particularly immobility. The conduct of preliminary studies to inform the design of larger pressure injury prevention trials is recommended.