bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic value of the preoperative albumin to alkaline phosphatase ratio in patients with non‐small cell lung cancer after surgery
Authors: Zhang Lianmin , Zhang Hua , Yue Dongsheng , Wei Wei , Chen Yulong , Zhao Xiaoliang , Zhu Jianquan , Zhang Bin , Zhang Zhenfa , Wang Changli 
Published: June 2019

BackgroundTo assess the potential prognostic value of the albumin to alkaline phosphatase ratio (AAPR) in patients with non‐small cell lung cancer (NSCLC) after surgery.MethodsThe log‐rank and Kaplan‐Meier analyses were performed to detect differences in survival levels between different groups. A model of Cox proportional hazards was used to perform univariate and multivariate survival analyses. Comparisons of receiver operating characteristic (ROC) curves and the likelihood ratio test (LRT) were also utilized to compare the prognostic abilities of different systems for overall survival (OS) prediction.ResultsThe optimal cut‐off value of the preoperative AAPR was 0.64. A decreased AAPR was associated with several clinicopathological and clinicolaboratory variables related to cancer progression. The preoperative AAPR of patients was positively correlated with the poor prognosis of NSCLC. In multivariate analyses, the preoperative AAPR was identified as an independent prognostic factor for disease‐free survival (DFS; P = 0.001) and overall survival (OS; P = 0.003). The LRT showed that the AAPR tumor‐node‐metastasis (TNM) system presented a significantly larger χ2 value (112.4 vs. 89.2, respectively, P < 0.01) and a relatively smaller Akaike information criterion (AIC) value (2955 vs. 2977, respectively, P < 0.01) than the TNM staging system.ConclusionPreoperative AAPR was a potentially valuable prognostic factor in NSCLC patients who underwent surgery. Our results further showed that the AAPR‐TNM system was superior to the current TNM staging system.
The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake
Authors: Luján Miguel Ángel , Cantacorps Lídia , Valverde Olga 
Published: June 2019

AbstractThe administration of cannabidiol has shown promising evidence in the treatment of some neuropsychiatric disorders, including cocaine addiction. However, little information is available as to the mechanisms by which cannabidiol reduces drug use and compulsive seeking. We investigated the role of adult hippocampal neurogenesis in reducing cocaine voluntary intake produced by repeated cannabidiol treatment in mice. Cocaine intake was modelled using the intravenous cocaine self‐administration procedure in CD1 male mice. Cannabidiol (20 mg/kg) reduced cocaine self‐administration behaviour acquisition and total cocaine intake and enhanced adult hippocampal neurogenesis. Our results show that a 6‐day repeated temozolomide treatment (25 mg/kg/day), a chemotherapy drug that blocks hippocampal neurogenesis, prevented cannabidiol‐induced increment in the early stages of neuronal maturation and differentiation, without altering the basal levels of BrdU/NeuN and doublecortin immunostaining. The reduction of total cocaine intake and operant behaviour acquisition observed following cannabidiol exposure was attenuated by temozolomide treatment. Our results also show a similar effect of temozolamide on a cannabidiol‐induced improvement of novel object recognition memory, a task influenced by the proneurogenic effects of cannabidiol (10 and 20 mg/kg). The anxiolytic effects of cannabidiol (10 and 20 mg/kg), however, remained unaffected after its proneurogenic effects decreased. The present study confirms that adult hippocampal neurogenesis is one of the mechanisms by which cannabidiol lowers cocaine reinforcement and demonstrates the functional implication of adult hippocampal neurogenesis in cocaine voluntary consumption in mice. Such findings highlight the possible use of cannabidiol for developing new pharmacotherapies to manage cocaine use disorders.
Long‐term effects of repeated fuel‐reduction burning and logging on bats in south‐eastern Australia
Authors: Law Bradley , Kathuria Amrit , Chidel Mark , Brassil Traecey 
Published: June 2019

AbstractFire regimes have a major influence on biodiversity in many ecosystems around the globe, yet our understanding of the longer‐term response of fauna is typically poor. We sampled bats with ultrasonic detectors in three different years in dry sclerophyll forests of south‐eastern Australia in a long‐term, management‐scale experiment. Frequent low‐intensity burning (every 2 or 4 years plus unburnt) and logging (with 33% retention of the original unlogged tree basal area) were manipulated to assess their effects on bats. We found that both the fire regime and regrowth after logging influenced the local bat community. The routine burning treatment (burnt every 4 years) in unlogged forest was consistently related to higher total bat activity (2–3 times) and species richness when compared to unburnt controls and logging treatments. Foraging activity was more variable, but it was typically lowest in Unlogged Unburnt Controls. These patterns were evident at both the detector site scale and the block scale and were probably due to a reduction in understorey stem density with burning, especially in unlogged forest. Bat activity was significantly lower across the entire study area (including controls) in 1 year, when sampling occurred within 6 months of burning. When pooled across burning treatments, unlogged forest supported higher bat activity (1.5 times) and species richness than logged forest (12‐ to 17‐year‐old regrowth), again most likely because of a negative association with high stem density in regrowth after logging. We conclude that low‐intensity burning had positive benefits for echolocating bats, most notably in unlogged forest. However, careful planning is required to generate heterogeneous vegetation patterns that are likely to be most suitable for a range of taxa.
Influences on general practitioner referral to allied health professionals for fall prevention in primary care
Authors: Liddle Jeannine , Clemson Lindy , Mackenzie Lynette , Lovarini Meryl , Tan Amy , Pit Sabrina W. , Roberts Chris , Tiedemann Anne , Sherrington Cathie , Willis Karen 
Published: June 2019

AbstractObjectiveTo explore influences on referral for fall prevention from general practitioners (GPs) to allied health professionals (AHPs) to better equip AHPs engage with GPs regarding fall prevention.MethodsQualitative, semi‐structured interviews with GPs (n = 24), practice nurses (n = 3) and AHPs (n = 15) and field notes were analysed inductively using constant comparative methods.ResultsThree main themes regarding influences on GP referral to AHPs for fall prevention were identified as follows: GPs' knowledge of AHPs; The “reliable and good” AHP; and Patient feedback‐Patient choice. Three‐way communication and trust between GP, patient and AHP underpinned each of these themes.ConclusionsStrategies for encouraging GP referral include AHPs personally contacting GPs to explain their services; writing to GPs about every patient seen; and being aware that interprofessional relationships are based on trust and take time to develop. GPs and AHPs are encouraged to communicate directly rather than relying on patients to convey verbal information.
Ranging behaviour of Uganda’s elephants
Authors: Grogan James , Plumptre Andrew , Mabonga Joshua , Nampindo Simon , Nsubuga Mustapha , Balmford Andrew 
Published: June 2019

AbstractElephant populations are in decline across the African continent, but recent aerial surveys show that populations in Uganda are increasing. However, threats such as poaching and habitat disturbance remain. Having a comprehensive knowledge of the ranging behaviour of Ugandan elephants is crucial to understanding where critical habitat for the species occurs. We investigated various aspects of ranging behaviour of 45 radio‐collared elephants (Loxodonta africana) in three areas—Queen Elizabeth Protected Area (QEPA), Murchison Falls (MFPA) Protected Area and Kidepo Valley (KVCA) Conservation Area. We also set Ugandan analyses in a continental context by comparison with home ranges reported in published literature. Elephants within KVCA had larger core ranges than elephants in QEPA or MFPA. Wet season ranges in KVCA were much larger than dry season ranges. The most important core areas in all three national parks were centred around water resources. Home range size was negatively correlated with net primary productivity (NPP) at Ugandan (N = 39 individuals) and continental (N = 17 sites) scales. This study indicates that, at a local scale, factors such as water source location are important in shaping elephant ranging behaviour. At larger scales, factors such as NPP are good predictors of elephant home range size.
The design and evaluation of a novel low‐cost portable ventilator
Authors: Darwood A. , McCanny J. , Kwasnicki R. , Martin B. , Jones P. 
Published: June 2019

SummaryModern mechanical ventilator technologies broadly consist of digitally‐controlled electronic devices and analogue systems driven by compressed gas sources. Drawbacks such as high cost, complex maintenance and the need for cumbersome sources of compressed driving gas hinder adoption in pre‐hospital and low‐resource environments. We describe the evaluation and testing of a simple, low‐cost alternative ventilator that uses a novel pressure‐sensing approach and control algorithm. This is designed to provide portable positive‐pressure mechanical ventilation at a reduced cost, while autonomously monitoring patient condition and important safety parameters. A prototype ventilator was constructed and evaluated using an anaesthetic test‐lung as a patient surrogate. Using a modifiable test‐lung and digital pressure sensor, we investigated ventilation pressure waveform circuit leak detection, and compliance and resistance change detection. During intermittent positive‐pressure ventilation to the test‐lung, the prototype system showed acceptable pressure waveform parameters: all simulated circuit leaks ≥ 6 mm2 in size were detected; compliance changes were detected between 10 ml.cmH2O−1, 20 ml.cmH2O−1 and 50 ml.cmH2O−1; and resistance changes were detected across the available simulated range. These results show this prototype technology has the potential to provide safe emergency ventilation without the use of any complex digital sensors or software while its construction and design enables significant reductions in cost and complexity. The study suggests further work is now justified in progressing the technology to clinical trials.
Proteins adsorbed to a polysulfone hemodialysis membrane under heparin and citrate anticoagulation regimens
Authors: Mares Jan , Tuma Zdenek , Moravec Jiri , Pavlina Richtrova , Matejovic Martin 
Published: June 2019

AbstractThe study aim was to compare molecular‐level effects (blood‐dialyzer interactions) of heparin and citrate anticoagulation using proteome‐wide analysis of biofilm adsorbed to dialysis membrane. Ten patients receiving maintenance hemodialysis were examined in a crossover design under three different anticoagulation regimens, namely citrate, heparin, and anticoagulation‐free (control). Following a regular hemodialysis session (4 hours, polysulfone membrane), dialyzers were flushed and the surface biofilm eluted by acetic acid. Protein composition of the eluates was determined by 2‐dimensional gel electrophoresis and resulting patterns compared between regimens. Proteins responsible for the difference were identified by mass spectrometry. Citrate anticoagulation was associated with significantly less protein adsorption to the membrane than heparin (2.2 [1.1‐2.9] mg vs. 6.5 [2.9‐11.6] mg, P = 0.009). Among the proteins identified as major discriminators between citrate and the other regimens, fibrin α‐chain fragments of molecular weight below 40 kDa prevailed. In these fragments, an analysis of the amino acid sequence has been performed by comparison with the UniProt database. It showed missing α‐chain cross‐links. On the contrary, heparin prevented adsorption and cleavage of several heparin‐binding proteins; especially complement factor H‐related protein 3, insulin‐like growth factor binding proteins (2, 4, and 5), and chemerin. Compared to heparin, citrate is associated with less protein adsorption and imperfectly crosslinked fibrin clot formation. Membrane adsorptive properties are significantly modified by the anticoagulation regimen.
Inhibition of polycomb repressor complex 2 ameliorates neointimal hyperplasia by suppressing trimethylation of H3K27 in vascular smooth muscle cells
Authors: Liang Jing , Li Qi , Cai Wenbin , Zhang Xuejiao , Yang Bing , Li Xin , Jiang Shuai , Tian Shanshan , Zhang Kai , Song Hao , Ai Ding , Zhang Xu , Wang Chunjiong , Zhu Yi 
Published: June 2019

Background and PurposeThe increased proliferation and migration of vascular smooth muscle cells (VSMCs) after arterial injury contributes greatly to the pathogenesis of neointimal hyperplasia. As a major component of epigenetics, histone methylation plays an important role in several cardiovascular diseases. However, its role in restenosis is still unclear.Experimental ApproachHuman aortic VSMCs were challenged with PDGF‐BB, and total histones were extracted and analysed by HPLC/MS. For the in vivo study, rats were subjected to wire‐guided common carotid injury.Key ResultsPDGF‐BB markedly increased the H3K27me3 level, as demonstrated by use of HPLC/MS and confirmed by western blot analysis. Enhancer of zeste homologue 2 (EZH2), the histone H3K27 methyltransferase component of polycomb repressive complex 2, was also up‐regulated by PDGF‐BB in VSMCs, and in the neointimal hyperplasia induced by wire injury of the rat carotid artery. Furthermore, inhibiting H3K27me3 by treatment with 3‐μM UNC1999, an EZH2/1 inhibitor, significantly suppressed PDGF‐BB‐induced VSMC proliferation compared with the PDGF‐BB‐treated group. Consistently, neointimal formation was significantly attenuated by oral or perivascular administration of UNC1999 compared with the sham group. Mechanistically, the increase in H3K27me3 inhibited the transcription of the cyclin‐dependent kinase inhibitor p16INK4A and thus promoted VSMC proliferation.Conclusions and ImplicationsVascular injury elevated the expression of EZH2 and the downstream target H3K27me3, which suppressed p16INK4A expression in VSMCs and promoted VSMC proliferation and neointimal hyperplasia. EZH2 inhibition might be a potential therapeutic target for restenosis.
Comparison of the ligand‐binding properties of fluorescent VEGF‐A isoforms to VEGF receptor 2 in living cells and membrane preparations using NanoBRET
Authors: Peach Chloe J. , Kilpatrick Laura E. , Woolard Jeanette , Hill Stephen J. 
Published: June 2019

Background and PurposeVascular endothelial growth factor A (VEGF‐A) is a key mediator of angiogenesis. A striking feature of the binding of a fluorescent analogue of VEGF165a to nanoluciferase‐tagged VEGF receptor 2 (VEGFR2) in living cells is that the BRET signal is not sustained and declines over time. This may be secondary to receptor internalisation. Here, we have compared the binding of three fluorescent VEGF‐A isoforms to VEGFR2 in cells and isolated membrane preparations.Experimental ApproachLigand‐binding kinetics were monitored in both intact HEK293T cells and membranes (expressing nanoluciferase‐tagged VEGFR2) using BRET between tagged receptor and fluorescent analogues of VEGF165a, VEGF165b, and VEGF121a. VEGFR2 endocytosis in intact cells expressing VEGFR2 was monitored by following the appearance of fluorescent ligand‐associated receptors in intracellular endosomes using automated quantitative imaging.Key ResultsQuantitative analysis of the effect of fluorescent VEGF‐A isoforms on VEGFR2 endocytosis in cells demonstrated that they produce a rapid and potent translocation of ligand‐bound VEGFR2 into intracellular endosomes. NanoBRET can be used to monitor the kinetics of the binding of fluorescent VEGF‐A isoforms to VEGFR2. In isolated membrane preparations, ligand‐binding association curves were maintained for the duration of the 90‐min experiment. Measurement of the koff at pH 6.0 in membrane preparations indicated shorter ligand residence times than those obtained at pH 7.4.Conclusions and ImplicationsThese studies suggest that rapid VEGF‐A isoform‐induced receptor endocytosis shortens agonist residence times on the receptor (1/koff) as VEGFR2 moves from the plasma membrane to the intracellular endosomes.
Acquired resistance mechanisms to afatinib in HER2‐amplified gastric cancer cells
Authors: Yoshioka Takahiro , Shien Kazuhiko , Takeda Tatsuaki , Takahashi Yuta , Kurihara Eisuke , Ogoshi Yusuke , Namba Kei , Torigoe Hidejiro , Sato Hiroki , Tomida Shuta , Yamamoto Hiromasa , Soh Junichi , Fujiwara Toshiyoshi , Toyooka Shinichi 
Published: June 2019

AbstractCancer treatment, especially that for breast and lung cancer, has entered a new era and continues to evolve, with the development of genome analysis technology and the advent of molecular targeted drugs including tyrosine kinase inhibitors. Nevertheless, acquired drug resistance to molecular targeted drugs is unavoidable, creating a clinically challenging problem. We recently reported the antitumor effect of a pan‐HER inhibitor, afatinib, against human epidermal growth factor receptor 2 (HER2)‐amplified gastric cancer cells. The purpose of the present study was to identify the mechanisms of acquired afatinib resistance and to investigate the treatment strategies for HER2‐amplified gastric cancer cells. Two afatinib‐resistant gastric cancer cell lines were established from 2 HER2‐amplified cell lines, N87 and SNU216. Subsequently, we investigated the molecular profiles of resistant cells. The activation of the HER2 pathway was downregulated in N87‐derived resistant cells, whereas it was upregulated in SNU216‐derived resistant cells. In the N87‐derived cell line, both MET and AXL were activated, and combination treatment with afatinib and cabozantinib, a multikinase inhibitor that inhibits MET and AXL, suppressed the cell growth of cells with acquired resistance both in vitro and in vivo. In the SNU216‐derived cell line, YES1, which is a member of the Src family, was remarkably activated, and dasatinib, a Src inhibitor, exerted a strong antitumor effect in these cells. In conclusion, we identified MET and AXL activation in addition to YES1 activation as novel mechanisms of afatinib resistance in HER2‐driven gastric cancer. Our results also indicated that treatment strategies targeting individual mechanisms of resistance are key to overcoming such resistance.
Impact of number of registration points on the positional accuracy of a prosthetic treatment plan incorporated into a cone beam computed tomography scan by surface scan registration: An in vitro study
Authors: Jamjoom Faris Z. , Yilmaz Burak , Johnston William M. 
Published: June 2019

AbstractObjectivesTo evaluate the accuracy of a prosthetic treatment plan incorporation into a cone beam computed tomography (CBCT) scan using point‐based registration with three registration points selected and to evaluate the impact of number of registration points on prosthetic plan accuracy.Material and MethodsA CBCT scan of a completely dentate master model with removable teeth was exposed after removing the mandibular left first premolar, second premolar, and first molar. A digital scan of the master model with all teeth present was made by scanning a stone replica using a laboratory scanner. The digital model was registered onto the three‐dimensional (3D) volume rendering of the CBCT scan using implant planning software. The point‐based registration was repeated using three, four, five, six, seven, eight, nine, and 10 reference points. Metrology software was used to measure the 3D deviation of the registered models for each reference point group on standard tessellation language (STL) files obtained from the CBCT scans. An STL file of the master model with all teeth present obtained from another CBCT scan was used as reference.ResultsUsing three registration points, the registered prosthetic plan had a mean absolute deviation of 17.63 µm from the reference. Increasing the number of registration points failed to demonstrate statistically significant effects on the deviation (p > 0.05).ConclusionsFor this clinical scenario, three registration points provided adequate accuracy for prosthetic plan incorporation into CBCT scans. Increasing the number of registration points had no significant impact on the prosthetic plan accuracy in this study.
Eruptive ulcerative follicular spicules heralding progression of smoldering multiple myeloma
Authors: Tomasini Carlo , Michelerio Andrea , Brazzelli Valeria 
Published: June 2019

AbstractHerein, we describe a patient with immunoglobulin G (IgG)‐lambda smoldering multiple myeloma with translocation t(4:14) who developed widespread ulcerative horny‐like spicules, heralding rapid progression to overt myeloma requiring aggressive chemotherapy and autologous stem cell transplantation. The serum abnormal immunoglobulin in the blood was cryoglobulin, which typically precipitates in the tissues at low temperatures causing inflammation and tissue damage. Histopathological changes, observed in lesions at different evolutionary stages, evidenced columns of horny‐like eosinophilic homogeneous material, immunoreactive for IgG lambda, protruding from the dilated and/or distorted follicular openings or acrosyringia and small vessel thrombotic vasculopathy and vasculitis in concert with an inflammatory neutrophilic and lymphocytic reaction. Biochemical investigations on material from a spicule and ulcero‐necrotic lesion revealed cryoprecipitates containing IgG‐lambda with electrophoretic characteristics identical to those of the serum dysprotein. Our findings suggest that the formation of spicules and development of ulcerative lesions are a part of the same clinical spectrum where the cold‐dependent precipitation of the immunogenic dysprotein, both in the skin vessels and hair follicle infundibula, play a major pathogenetic role. Whether this highly characteristic paraneoplastic dermatosis can identify patients with high‐risk cytogenetic abnormalities and be incorporated into prognostic models, applicable early on in the course of myeloma, warrants further investigation.
A Stochastic Joint Replenishment Problem with Dissimilar Items
Authors: Li Linda , Schmidt Charles P. 
Published: June 2019

ABSTRACTThe classical stochastic joint replenishment problem (SJRP) often assumes uncapacitated batch size, and identical items. However, real problems encountered relate to the truck , or the container which has limited capacity. When the shipping capacity is limited, and the items are dissimilar in size, the problem becomes more challenging. By defining a class of order‐up‐to policies, we formulate the SJRP of this kind as a combinatorial optimization problem. To solve the problem, a data structure and an algorithm are developed. Based on the algorithm, we also suggest several heuristics including the (U, S) policy—a generalization of the well‐known (Q, S) policy for dissimilar items. The numerical study shows the (U, S) policy is robust and efficient. It performs well, especially when the items become more dissimilar, in terms of shipping size and inventory velocity.