bluuebunny/crossref_metadata_2025_split huggingface dataset:
The GnRH analogues affect novel neuropeptide SMIM20/phoenixin and GPR173 receptor expressions in the female rat hypothalamic–pituitary–gonadal (HPG) axis
Authors: Suszka‐Świtek Aleksandra , Pałasz Artur , Filipczyk Łukasz , Menezes Itiana Castro , Mordecka‐Chamera Kinga , Angelone Tommaso , Bogus Katarzyna , Bacopoulou Flora , Worthington John J. , Wiaderkiewicz Ryszard 
Published: January 2019

SummaryThe recently discovered peptide phoenixin (PNX) and its receptor GPR173 are novel factors that exhibit a large spectrum of regulatory activity, especially when considered as a central modulator of GnRH‐related hormonal control of reproductive processes. It has been already proven that GnRH agonists and antagonists can modulate peptidergic signalling in the HPG axis. Despite these findings, there is so far no information regarding the influence of treatment with GnRH analogues on SMIM20/phoenixin signalling in the hypothalamic–pituitary–gonadal axis. In the current study, SMIM20/phoenixin and GPR173 mRNA levels were measured in the hypothalamus, pituitary and ovaries of female rats in the dioestrus phase following treatment with GnRH‐R agonist (buserelin) and antagonist (cetrorelix) using quantitative real‐time PCR. The serum PNX concentrations were also estimated with ELISA technique. The hypothalamic, hypophyseal and especially ovarian levels of SMIM20 mRNA were increased after both buserelin and cetrorelix administration. The GPR173 expressions were in turn decreased in the hypothalamus and pituitary. Treatment with the GnRH analogues led to the modulation of SMIM20/phoenixin and GPR173 mRNA expression in the female rat hypothalamic–pituitary–gonadal axis. By identifying buserelin and cetrorelix as novel modulators of phoenixin signalling in the animal HPG axis, these results cast new light on the GnRH analogues mode of action and contribute to a better understanding of the mechanisms responsible for the hormonal control of reproduction.
Azithromycin inhibits muscarinic 2 receptor‐activated and voltage‐activated Ca2+ permeant ion channels and Ca2+ sensitization, relaxing airway smooth muscle contraction
Authors: Wang Qian , Yu Meng‐Fei , Zhang Wen‐Jing , Liu Bei‐Bei , Zhao Qing‐Yang , Luo Xi , Xu Hao , She Yu‐Shan , Zang Dun‐An , Qiu Jun‐Ying , Shen Jinhua , Peng Yong‐Bo , Zhao Ping , Xue Lu , Chen Weiwei , Ma Li‐Qun , Nie Xiaowei , Shen Chenyou , Chen Shu , Chen Shanshan , Liu Quan , Dai Jiapei , Qin Gangjian , Zheng Yun‐min , Wang Yong‐Xiao , ZhuGe Ronghua , Chen Jingyu , Liu Qing‐Hua 
Published: January 2019

SummaryAzithromycin (AZM) has been used for the treatment of asthma and chronic obstructive pulmonary disease (COPD); however, the effects and underlying mechanisms of AZM remain largely unknown. The effects of AZM on airway smooth muscles (ASMs) and the underlying mechanisms were studied using isometric muscle force measurements, the examination of lung slices, imaging, and patch‐clamp techniques. AZM completely inhibited acetylcholine (ACH)‐induced precontraction of ASMs in animals (mice, guinea pigs, and rabbits) and humans. Two other macrolide antibiotics, roxithromycin and Klaricid, displayed a decreased inhibitory activity, and the aminoglycoside antibiotics penicillin and streptomycin did not have an inhibitory effect. Precontractions were partially inhibited by nifedipine (selective inhibitor of L‐type voltage‐dependent Ca2+ channels (LVDCCs)), Pyr3 (selective inhibitor of TRPC3 and/or STIM/Orai channels, which are nonselective cation channels (NSCCs)), and Y‐27632 (selective inhibitor of Rho‐associated kinase (ROCK)). Moreover, LVDCC‐ and NSCC‐mediated currents were inhibited by AZM, and the latter were suppressed by the muscarinic (M) 2 receptor inhibitor methoctramine. AZM inhibited LVDCC Ca2+ permeant ion channels, M2 receptors, and TRPC3 and/or STIM/Orai, which decreased cytosolic Ca2+ concentrations and led to muscle relaxation. This relaxation was also enhanced by the inhibition of Ca2+ sensitization. Therefore, AZM has potential as a novel and potent bronchodilator. The findings of this study improve the understanding of the effects of AZM on asthma and COPD.
Multi‐observer contouring of male pelvic anatomy: Highly variable agreement across conventional and emerging structures of interest
Authors: Roach Dale , Holloway Lois C , Jameson Michael G , Dowling Jason A , Kennedy Angel , Greer Peter B , Krawiec Michele , Rai Robba , Denham Jim , De Leon Jeremiah , Lim Karen , Berry Megan E , White Rohen T , Bydder Sean A , Tan Hendrick T , Croker Jeremy D , McGrath Alycea , Matthews John , Smeenk Robert J , Ebert Martin A 
Published: January 2019

AbstractIntroductionThis study quantified inter‐observer contouring variations for multiple male pelvic structures, many of which are of emerging relevance for prostate cancer radiotherapy progression and toxicity response studies.MethodsFive prostate cancer patient datasets (CT and T2‐weighted MR) were distributed to 13 observers for contouring. CT structures contoured included the clinical target volume (CTV), seminal vesicles, rectum, colon, bowel bag, bladder and peri‐rectal space (PRS). MR contours included CTV, trigone, membranous urethra, penile bulb, neurovascular bundle and multiple pelvic floor muscles. Contouring variations were assessed using the intraclass correlation coefficient (ICC), Dice similarity coefficient (DSC), and multiple additional metrics.ResultsClinical target volume (CT and MR), bladder, rectum and PRS contours showed excellent inter‐observer agreement (median ICC = 0.97; 0.99; 1.00; 0.95; 0.90, DSC = 0.83 ± 0.05; 0.88 ± 0.05; 0.93 ± 0.03; 0.81 ± 0.07; 0.80 ± 0.06, respectively). Seminal vesicle contours were more variable (ICC = 0.75, DSC = 0.73 ± 0.14), while colon and bowel bag contoured volumes were consistent (ICC = 0.97; 0.97), but displayed poor overlap (DSC = 0.58 ± 0.22; 0.67 ± 0.21). Smaller MR structures showed significant inter‐observer variations, with poor overlap for trigone, membranous urethra, penile bulb, and left and right neurovascular bundles (DSC = 0.44 ± 0.22; 0.41 ± 0.21; 0.66 ± 0.21; 0.16 ± 0.17; 0.15 ± 0.15). Pelvic floor muscles recorded moderate to strong inter‐observer agreement (ICC = 0.50–0.97), although large outlier variations were observed.ConclusionsInter‐observer contouring variation was significant for multiple pelvic structures contoured on MR.
sFRP3 inhibition improves age‐related cellular changes in BubR1 progeroid mice
Authors: Cho Chang Hoon , Yoo Ki Hyun , Oliveros Alfredo , Paulson Summer , Hussaini Syed Mohammed Qasim , van Deursen Jan M. , Jang Mi‐Hyeon 
Published: January 2019

AbstractWnt signaling is a well‐known molecular pathway in age‐related pathogenesis and therapy of disease. While prior studies have mainly focused on Wnt ligands or Wnt activators, the in vivo functions of naturally secreted Wnt inhibitors are not clear, especially in brain aging. Using BubR1H/H mice as a novel mouse model of accelerated aging, we report that genetic inhibition of sFRP3 restores the reduced body and brain size observed in BubR1H/H mice. Furthermore, sFRP3 inhibition ameliorates hypomyelination in the corpus callosum and rescues neural progenitor proliferation in the hippocampal dentate gyrus of BubR1H/H mice. Taken together, our study identifies sFRP3 as a new molecular factor that cooperates with BubR1 function to regulate brain development, myelination, and hippocampal neurogenesis.
Dying under pressure: cellular characterisation and in vivo functions of cell death induced by compaction
Authors: Valon Léo , Levayer Romain 
Published: January 2019

AbstractCells and tissues are exposed to multiple mechanical stresses during development, tissue homoeostasis and diseases. While we start to have an extensive understanding of the influence of mechanics on cell differentiation and proliferation, how excessive mechanical stresses can also lead to cell death and may be associated with pathologies has been much less explored so far. Recently, the development of new perturbative approaches allowing modulation of pressure and deformation of tissues has demonstrated that compaction (the reduction of tissue size or volume) can lead to cell elimination. Here, we discuss the relevant type of stress and the parameters that could be causal to cell death from single cell to multicellular systems. We then compare the pathways and mechanisms that have been proposed to influence cell survival upon compaction. We eventually describe the relevance of compaction‐induced death in vivo, and its functions in morphogenesis, tissue size regulation, tissue homoeostasis and cancer progression.
Neuronal sub‐compartmentalization: a strategy to optimize neuronal function
Authors: Donato Alessandra , Kagias Konstantinos , Zhang Yun , Hilliard Massimo A. 
Published: January 2019

ABSTRACTNeurons are highly polarized cells that consist of three main structural and functional domains: a cell body or soma, an axon, and dendrites. These domains contain smaller compartments with essential roles for proper neuronal function, such as the axonal presynaptic boutons and the dendritic postsynaptic spines. The structure and function of these compartments have now been characterized in great detail. Intriguingly, however, in the last decade additional levels of compartmentalization within the axon and the dendrites have been identified, revealing that these structures are much more complex than previously thought. Herein we examine several types of structural and functional sub‐compartmentalization found in neurons of both vertebrates and invertebrates. For example, in mammalian neurons the axonal initial segment functions as a sub‐compartment to initiate the action potential, to select molecules passing into the axon, and to maintain neuronal polarization. Moreover, work in Drosophila melanogaster has shown that two distinct axonal guidance receptors are precisely clustered in adjacent segments of the commissural axons both in vivo and in vitro, suggesting a cell‐intrinsic mechanism underlying the compartmentalized receptor localization. In Caenorhabditis elegans, a subset of interneurons exhibits calcium dynamics that are localized to specific sections of the axon and control the gait of navigation, demonstrating a regulatory role of compartmentalized neuronal activity in behaviour. These findings have led to a number of new questions, which are important for our understanding of neuronal development and function. How are these sub‐compartments established and maintained? What molecular machinery and cellular events are involved? What is their functional significance for the neuron? Here, we reflect on these and other key questions that remain to be addressed in this expanding field of biology.
Towards a ‘Sea‐Level Sensitive’ dynamic model: impact of island ontogeny and glacio‐eustasy on global patterns of marine island biogeography
Authors: Ávila Sérgio P. , Melo Carlos , Berning Björn , Sá Nuno , Quartau Rui , Rijsdijk Kenneth F. , Ramalho Ricardo S. , Cordeiro Ricardo , De Sá Nuno C. , Pimentel Adriano , Baptista Lara , Medeiros António , Gil Artur , Johnson Markes E. 
Published: January 2019

ABSTRACTA synthetic model is presented to enlarge the evolutionary framework of the General Dynamic Model (GDM) and the Glacial Sensitive Model (GSM) of oceanic island biogeography from the terrestrial to the marine realm. The proposed ‘Sea‐Level Sensitive’ dynamic model (SLS) of marine island biogeography integrates historical and ecological biogeography with patterns of glacio‐eustasy, merging concepts from areas as diverse as taxonomy, biogeography, marine biology, volcanology, sedimentology, stratigraphy, palaeontology, geochronology and geomorphology. Fundamental to the SLS model is the dynamic variation of the littoral area of volcanic oceanic islands (defined as the area between the intertidal and the 50‐m isobath) in response to sea‐level oscillations driven by glacial–interglacial cycles. The following questions are considered by means of this revision: (i) what was the impact of (global) glacio‐eustatic sea‐level oscillations, particularly those of the Pleistocene glacial–interglacial episodes, on the littoral marine fauna and flora of volcanic oceanic islands? (ii) What are the main factors that explain the present littoral marine biodiversity on volcanic oceanic islands? (iii) How can differences in historical and ecological biogeography be reconciled, from a marine point of view? These questions are addressed by compiling the bathymetry of 11 Atlantic archipelagos/islands to obtain quantitative data regarding changes in the littoral area based on Pleistocene sea‐level oscillations, from 150 thousand years ago (ka) to the present. Within the framework of a model sensitive to changing sea levels, we discuss the principal factors affecting the geographical range of marine species; the relationships between modes of larval development, dispersal strategies and geographical range; the relationships between times of speciation, modes of larval development, ecological zonation and geographical range; the influence of sea‐surface temperatures and latitude on littoral marine species diversity; the effect of eustatic sea‐level changes and their impact on the littoral marine biota; island marine species–area relationships; and finally, the physical effects of island ontogeny and its associated submarine topography and marine substrate on littoral biota. Based on the SLS dynamic model, we offer a number of predictions for tropical, subtropical and temperate volcanic oceanic islands on how rates of immigration, colonization, in‐situ speciation, local disappearance, and extinction interact and affect the marine biodiversity around islands during glacials and interglacials, thus allowing future testing of the theory.
Parvovirus infection and its treatment
Authors: Young N S 
Published: January 2019

Summary
B19 parvovirus is an important pathogen in man. Acute infection produces fifth disease (erythema infectiosum) in normal individuals, transient aplastic crisis in the patient with haemolysis, and pure red cell aplasia in the immunologically incompetent host. Fetal infection can lead to hydrops fetalis. The target cell of the virus is the marrow erythroid progenitor. The immune response to the virus is largely humoral and directed against limited numbers of epitopes. Persistent infection is due to failure to produce neutralizing antibodies. Because viral infection is prevalent in the population, therapeutic immune globulin preparations arc a good source of anti-B19 antibodies. IgG administration can lead to cure of anaemia in the congenitally immunodeficient patient and to its amelioration in AIDS patients with persistent parvovirus infection.
Intravenous immune globulin in multiple sclerosis: clinical and neuroradiological results and implications for possible mechanisms of action
Authors: Achiron A , Barak Y , Goren M , Gabbay U , Miron S , Rotstein Z , Noy S , Sarova-Pinhas I 
Published: January 2019

SummaryExtensive evidence exists indicating that immunoregulatory mechanisms are involved in the pathogenesis of Multiple Sclerosis (MS). Several possible mechanisms by which intravenous immune globulin (IVIG) modulates the course of the disease are related to limiting the inflammatory process and repairing the damage by enhancing remyelination. Presently, the evidence for the effect of IVIG in MS is based on the results of small open trials, some of which have been encouraging. In the current study, the positive impact of IVIG treatment on arresting disease progression was evident by decreased brain Magnetic Resonance Imaging (MRI) scores of the lesion area. In an effort to extend these findings, the authors initiated a multicentre, prospective, randomized, double-blind, placebo-controlled study. The trial was designed to compare the ellicacy of IVIG treatment with placebo in relapsing-remitting patients (ages 20–55 years) with definite MS, disease duration of 210 years and frequency of exacerbations 1–3/year during the 2 years prior to the study. Patients were examined monthly and brain MRI studies scheduled at entry, and after the first and second years of the trial. The primary endpoints included the number of acute exacerbations and neurological disability. The secondary endpoints included change in the MRI lesion burden, evaluated by the number and area of lesions. The trial ended in June 1995.
Supplemental immune globulins in sepsis: a critical appraisal
Authors: Werdan K , Pilz G 
Published: January 2019

Summary
For ‘the total population of patients with sepsis, sepsis syndrome or SIRS’, the question of whether intravenous immune globulin (IVIG) reduces mortality is neither proved nor disproved. For the sepsis subgroups ‘postoperative sepsis with a sepsis score &gt; 19’ and ‘endotoxaemic, early septic shock’, a significant reduction in mortality by IVIG has been documented in a single, placebo-controlled, small trial of each subgroup; subsequent studies are needed for confirmation. The incidence of some severe infections in defined 'patients at risk’ and ‘operations at risk’ is lowered by IVIG prophylaxis. Postoperative APACHE II-score identification of high-risk cardiac surgery patients prone to sepsis and severe SIRS may represent one approach to optimize individual, early therapy. Applying this concept to immune globulin treatment in a pilot study, the administration of IgG-IVIG and IgGMA-IVIG yielded similar results.
Implant health and factors affecting peri‐implant marginal bone alteration for implants placed in staged maxillary sinus augmentation: A 5‐year prospective study
Authors: Krennmair Stefan , Hunger Stefan , Forstner Thomas , Malek Michael , Krennmair Gerald , Stimmelmayr Michael 
Published: January 2019

AbstractPurposeEvaluating the extent of and the factors affecting marginal bone level (MBL) alterations and consecutively implant success and implant health for implants placed in staged maxillary sinus floor (SF) augmentation.Materials and MethodsA 5‐year prospective, cohort study was conducted on 85 patients with 124 maxillary sinus augmentation procedure and 295 implants placed. Peri‐implant MBL alterations (reductions) were evaluated radiographically at the first year, third year, and fifth year postloading follow‐ups and were considered to patient‐related risk factors (age, gender, diabetes mellitus, smoking, rheumatic disorders, and history of periodontal disease [PD]), to clinican/surgically related risk factors (membrane perforations, sinus site, and residual ridge height), to implant/prosthesis‐related features (implant length, diameter, location, keratinized gingiva, and restoration gap), and to the plaque score. Additionally, implant and prostheses survival/success rate and peri‐implant health (mucositis/peri‐implantitis) were assessed.ResultsAbout 267/295 implants (drop‐out:n9 pat; 28 implants: 9%) were followed for 5 years (survival/success: 99.3%/96.5%), presenting significant (P < .001) differences of MBL alterations (−1.45 ± 0.38 mm) over time. The univariate analysis demonstrated differences of MBL alterations for smokers versus nonsmokers (P = .005), for patients with versus without history of PD (P = .001), and presence versus absence of plaque (P = .041). In the 5‐year multivariate analysis, MBL alteration was influenced by time (P = .001) and was related to risk factors as smoking (P = .001; odds ratio [OR] = 6.563) and history of PD (P = .015; OR = 4.450). Significant ORs for MBL alterations were also found for a restoration gap used for a full‐arch dentures (P = .001; OR = 8.275) associated with reduced (≤3 mm) residual ridge height (P = .015; OR = 1.365). The overall 5 year incidence of peri‐implant mucositis and peri‐implantitis was 25.3% and 3.7% at implant level and 30.3% and 6.6% at patient level, respectively.ConclusionsApart from the high success rate and healthy status of implant placed in staged SF seen, MBL alteration increased over time and was negatively affected predominately by patient‐specific risk factors such as smoking status and previous history of periodontitis.
Double‐blind, randomized clinical trial assessing the efficacy and safety of early initiation of sitagliptin during metformin uptitration in the treatment of patients with type 2 diabetes: The CompoSIT‐M study
Authors: Frias Juan P. , Zimmer Zachary , Lam Raymond L.H. , Amorin Guillermo , Ntabadde Catherine , Iredale Carol , O'Neill Edward A. , Engel Samuel S. , Kaufman Keith D. , Makimura Hideo , Crutchlow Michael F. 
Published: January 2019

AimsTo characterize the glycaemic efficacy and safety of initiation of the dipeptidyl peptidase‐4 inhibitor sitagliptin during metformin dose escalation in people with type 2 diabetes (T2D) not at glycated haemoglobin (HbA1c) goal on a sub‐maximal dose of metformin.Materials and methodsStudy participants with HbA1c ≥58 mmol/mol and ≤97 mmol/mol (≥7.5% and ≤11.0%) while on 1000 mg/d metformin were randomized to sitagliptin 100 mg once daily or placebo. All were to uptitrate metformin to 2000 mg/d. A longitudinal data analysis model was used to test the primary hypothesis that sitagliptin is superior to placebo when initiated during uptitration of metformin in reducing HbA1c at week 20. [ClinicalTrials.gov Identifier: NCT02791490, EudraCT: 2015‐004224‐59]ResultsA total of 458 participants (mean HbA1c 71.1 mmol/mol [8.7%], T2D duration 6.3 years) were treated. After 20 weeks, the least squares (LS) mean changes from baseline in HbA1c were −12.1 mmol/mol (−14.0, −10.1) (−1.10% [−1.28, −0.93]) and −7.6 mmol/mol (−9.6, −5.6) (−0.69% [−0.88, −0.51]) with sitagliptin and placebo, respectively; the between‐group difference in LS mean changes from baseline HbA1c was −4.5 mmol/mol (−6.5, −2.5) (−0.41% [−0.59, −0.23]); P < 0.001. The likelihood of having HbA1c <53 mmol/mol (<7.0%) at week 20 was higher in the sitagliptin group than in the placebo group in the overall population (relative risk 1.7, P = 0.002) and in those with a baseline HbA1c ≥69 mmol/mol (≥8.5%) (relative risk 2.4, P = 0.026). There were no notable differences between groups with regard to adverse events overall, hypoglycaemia events, changes in body weight or other safety variables.ConclusionIn participants not at HbA1c goal on a sub‐maximal dose of metformin, addition of sitagliptin at the time of metformin dose uptitration improved glycaemic response and HbA1c goal attainment, with similar safety and tolerability, compared to metformin uptitration alone.