bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of a novel molecular method to age free‐living wild Bechstein's bats
Authors: Wright Patrick G. R. , Mathews Fiona , Schofield Henry , Morris Colin , Burrage Joe , Smith Adam , Dempster Emma L. , Hamilton Patrick B. 
Published: July 2018

AbstractThe age profile of populations fundamentally affects their conservation status. Yet, age is frequently difficult to assess in wild animals. Here, we assessed the use of DNA methylation of homologous genes to establish the age structure of a rare and elusive wild mammal: the Bechstein's bat (Myotis bechsteinii). We collected 62 wing punches from individuals whose ages were known as a result of a long‐term banding study. DNA methylation was measured at seven CpG sites from three genes, which have previously shown age‐associated changes in humans and laboratory mice. All CpG sites from the tested genes showed a significant relationship between DNA methylation and age, both individually and in combination (multiple linear regression R2 = 0.58, p < 0.001). Despite slight approximation around estimates, the approach is sufficiently precise to place animals into practically useful age cohorts. This method is of considerable practical benefit as it can reliably age individual bats. It is also much faster than traditional capture–mark–recapture techniques, with the potential to collect information on the age structure of an entire colony from a single sampling session to better inform conservation actions for Bechstein's bats. By identifying three genes where DNA methylation correlates with age across distantly related species, this study also suggests that the technique can potentially be applied across a wide range of mammals.
Quantifying vegetation and canopy structural complexity from terrestrial LiDARdata using theforestr rpackage
Authors: Atkins Jeff W. , Bohrer Gil , Fahey Robert T. , Hardiman Brady S. , Morin Timothy H. , Stovall Atticus E. L. , Zimmerman Naupaka , Gough Christopher M. 
Published: July 2018

AbstractTerrestrial LiDAR(light detection and ranging) technologies have created new means of quantifying forest canopy structure, allowing not only the estimation of biomass, but also descriptions of the position and variability in canopy elements in space. Such measures provide novel structural information broadly useful to ecologists.There is a growing need for both a detailed taxonomy of forest canopy structural complexity (CSC) and open, transparent, and flexible tools to quantify complexity in ways that will advance foundational ecological knowledge of structure‐function relationships.TheCSCtaxonomy we present groups structural descriptors into five categories: leaf area and density, canopy height, canopy arrangement, canopy openness, and canopy variability. This paper also introduces therpackageforestr, the first open‐sourcerpackage for the calculation ofCSCmetrics from terrestrial LiDARdata.Therpackageforestris an analysis toolbox that works with portable canopy LiDAR(PCL) data and other pixelated/voxelized point clouds derived from terrestrial LiDARscanning (TLS) data to calculateCSCmetrics of interest to ecologists, modellers, forest managers, and remote sensing scientists.
Quantification of the Leydig cell compartment in testicular biopsies and association with biochemical Leydig cell dysfunction in testicular cancer survivors
Authors: Tarsitano M. G. , Bandak M. , Jørgensen N. , Skakkebæk N. E. , Juul A. , Lenzi A. , Daugaard G. , Rajpert‐De Meyts E. 
Published: July 2018

SummaryA simple histological method to evaluate the Leydig cell compartment is lacking. We aimed to establish such a method and to investigate if Leydig cell hyperplasia of the biopsy contralateral to the tumour‐bearing testicle in patients with testicular germ cell cancer is associated with biochemical signs of Leydig cell dysfunction after long‐term follow‐up. A case group of 50 long‐term testicular germ cell cancer survivors without human chorionic gonadotropin elevation, 10 testicular germ cell cancer patients with elevated human chorionic gonadotropin and 10 controls without testicular malignancy were included. For each subject, 2–4 representative sections from their testicular biopsies were selected for analysis. Using the image processing program ImageJ (V.1.48, NIH), an area with a minimum of 50 tubules was selected and delineated (total selected area) and the total Leydig cell area was calculated by adding up every delineated Leydig cell group within the total selected area. Four different methods were tested for the ability to quantify the Leydig cell compartment. In the 50 testicular germ cell cancer survivors, associations between the area of the Leydig cell compartment and serum levels of testosterone and luteinising hormone were investigated using linear regression analysis. The Leydig cell compartment was best quantified by the total Leydig cell area/total selected area index, which was significantly larger in the human chorionic gonadotropin‐positive patients than in controls (P = 0.00001). In the 50 human chorionic gonadotropin‐negative testicular germ cell cancer survivors, increasing total Leydig cell area/total selected area was significantly associated with decreased levels of total testosterone and decreased total testosterone/luteinising hormone ratio after a median of 9‐year follow‐up. In conclusion, a new simple method, total Leydig cell area/total selected area, was established to estimate the Leydig cell compartment in testicular biopsies. The index identified Leydig cell hyperplasia in the contralateral biopsy in patients with testicular germ cell cancer, and it was associated with long‐term biochemical Leydig cell dysfunction. Although in testicular germ cell cancer survivors, the clinical value is limited because the contralateral biopsies are not commonly available, we propose a closer andrological follow‐up in any patient with an increased total Leydig cell area/total selected area index.
Association between leukocytospermia and semen interleukin‐6 and tumor necrosis factor‐alpha in infertile men
Authors: Eldamnhoury E. M. , Elatrash G. A. , Rashwan H. M. , El‐Sakka A. I. 
Published: July 2018

SummarySeminal cytokines were previously reported to adversely affect process of spermatogenesis and ultimately induce poor semen quality. However, association between both IL‐6 and TNF‐α and leukocytospermia was not yet settled. The aim of this study was to evaluate the association between leukocytospermia and levels of interleukin‐6 (IL‐6) and tumor necrosis factor‐alpha (TNF‐α) in semen of infertile men. This cross‐sectional study included 100 age‐matched (≥18–45 years.) men. Participants were divided into four groups with 25 patients in each group: Group (A) – infertile patients with leukocytospermia and normal other semen parameters; Group (B) – infertile patients with leukocytospermia and abnormal semen parameters; Group (C) – infertile patients with oligospermia and/or asthenospermia and/or teratospermia but with no leukocytospermia; Group (D) – fertile patients with normal semen parameters and without leukocytospermia. All patients were assessed by detailed medical, sexual, fertility history, and complete physical examination. Laboratory assessment included hormonal and semen analysis and assessment of IL‐6 and TNF‐α in semen plasma. There were significant differences among the study groups regarding total sperm count, sperm concentration, and progressive motility (p < 0.05 for each). There was significant increase in semen WBC counts in groups A and B vs. groups C and D (p = 0.003). There were significant associations between increase levels of WBCs ≥ 5/HPF and decrease levels of total sperm count (p = 0.023), sperm concentration (p = 0.001), and sperm progressive motility (p = 0.02). There were significant upregulations in mean level of IL‐6 (p = 0.001) and mean level of TNF‐α (p = 0.003) in groups A and B vs. groups C and D. Overall, leukocytospermia is associated with reduction in sperm count, progressive motility and further upregulation of seminal IL‐6 and TNF‐α. The effect of treatment of leukocytospermia on the level of seminal cytokines is important point of future research.
Allosteric and orthosteric pharmacology of cannabidiol and cannabidiol‐dimethylheptyl at the type 1 and type 2 cannabinoid receptors
Authors: Tham Mylyne , Yilmaz Orhan , Alaverdashvili Mariam , Kelly Melanie E M , Denovan‐Wright Eileen M , Laprairie Robert B 
Published: July 2018

Background and PurposeWe sought to understand why (−)‐cannabidiol (CBD) and (−)‐cannabidiol‐dimethylheptyl (CBD‐DMH) exhibit distinct pharmacology, despite near identical structures.Experimental ApproachHEK293A cells expressing either human type 1 cannabinoid (CB1) receptors or CB2 receptors were treated with CBD or CBD‐DMH with or without the CB1 and CB2 receptor agonist CP55,940, CB1 receptor allosteric modulator Org27569 or CB2 receptor inverse agonist SR144528. Ligand binding, cAMP levels and βarrestin1 recruitment were measured. CBD and CBD‐DMH binding was simulated with models of human CB1 or CB2 receptors, based on the recently published crystal structures of agonist‐bound (5XRA) or antagonist‐bound (5TGZ) human CB1 receptors.Key ResultsAt CB1 receptors, CBD was a negative allosteric modulator (NAM), and CBD‐DMH was a mixed agonist/positive allosteric modulator. CBD and Org27569 shared multiple interacting residues in the antagonist‐bound model of CB1 receptors (5TGZ) but shared a binding site with CP55,940 in the agonist‐bound model of CB1 receptors (5XRA). The binding site for CBD‐DMH in the CB1 receptor models overlapped with CP55,940 and Org27569. At CB2 receptors, CBD was a partial agonist, and CBD‐DMH was a positive allosteric modulator of cAMP modulation but a NAM of βarrestin1 recruitment. CBD, CP55,940 and SR144528 shared a binding site in the CB2 receptor models that was separate from CBD‐DMH.Conclusion and ImplicationsThe pharmacological activity of CBD and CBD‐DMH in HEK293A cells and their modelled binding sites at CB1 and CB2 receptors may explain their in vivo effects and illuminates the difficulties associated with the development of allosteric modulators for CB1 and CB2 receptors.Linked ArticlesThis article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc
Branched rolling circle amplification method for measuring serum circulating microRNA levels for early breast cancer detection
Authors: Fan Tingting , Mao Yu , Sun Qinsheng , Liu Feng , Lin Jin‐Shun , Liu Yajie , Cui Junwei , Jiang Yuyang 
Published: July 2018

AbstractSerum circulating microRNAs (c‐miRNAs) are serving as useful biomarkers for cancer diagnosis. Here, we describe the development of a one‐step branched rolling circle amplification (BRCA) method to measure serum c‐miRNAs levels for early diagnosis of breast cancer. Four c‐miRNAs, c‐miRNA16 (c‐miR‐16), c‐miRNA21 (c‐miR‐21), c‐miRNA155 (c‐miR‐155), and c‐miRNA195 (c‐miR‐195) were isolated from the serum of 49 breast cancer patients (stages I‐IV) and 19 healthy controls, and analyzed using one‐step BRCA. The serum levels of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 were higher (P < 0.0001) in stage I breast cancer patients than healthy controls. These levels were also higher in several breast cancer molecular subtypes (HER‐2 over‐expression, Luminal A, Luminal B, and triple negative breast cancer) than in healthy control subjects. The diagnostic accuracy of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 for early diagnosis of breast cancer was confirmed by receiver operating characteristic (ROC) curve assay. These results show that the BRCA method can be used to measure serum c‐miRNAs levels, and that this method has high accuracy, sensitivity, and specificity. Moreover, both BRCA approach and quantitative real‐time PCR (qRT‐PCR) method show that the serum levels of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 could be used as biomarkers to improve the early diagnosis of breast cancer, and distinguish different breast cancer molecular subtypes.
Canakinumab treatment in kidney transplant recipients with AA amyloidosis due to familial Mediterranean fever
Authors: Trabulus Sinan , Korkmaz Merve , Kaya Eda , Seyahi Nurhan 
Published: July 2018

AbstractBackgroundFamilial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent serosal inflammation with fever, which can result in amyloid deposition. Anti‐interleukin‐1 drugs emerge as a therapeutic option for colchicine‐resistant patients. In this study, we aimed to document our experience with canakinumab use in kidney transplant recipients who developed AA amyloidosis due to FMF.MethodsA total of nine patients with FMF amyloidosis treated with canakinumab were enrolled. Laboratory and clinical data were collected from the patient files, electronic database of the hospital and with interviews.ResultsFive of the patients were male and four were female (median age: 33, range: 27‐62 years). All of the patients had rapid or gradual disappearance of FMF attacks. The following changes in the laboratory parameters were observed before and after the treatment: C‐reactive protein: 18.31 ± 13.58 mg/L vs 9.98 ± 11.66 mg/L, creatinine clearance: 45.27 ± 21.5 mL/min vs 50.71 ± 22.48 mL/min, and 24‐hour proteinuria: 2381.8 ± 3910.4 mg vs 710.0 ± 1117.5 mg; there were no statistically significant differences on those parameters. One patient developed a reaction to injection while another showed symptoms of Cytomegalovirus pneumonia.ConclusionCanakinumab can be considered as a safe and efficient drug in preventing the FMF attacks in kidney transplant recipients.
Impact of pharyngeal endoscopic tip placement and water flushing interval on upper respiratory tract disorders in horses undergoing overground endoscopy
Authors: McGivney C. L. , Sweeney J. , Gough K. F. , Hill E. W. , Katz L. M. 
Published: July 2018

SummaryBackgroundEndoscopic tip placement in the pharynx and water flushing interval (FI) may affect exercising upper respiratory tract (URT) endoscopic results.ObjectivesTo determine associations between the endoscopic tip position in the pharynx and automatedFIwith overground endoscopic (OGE) results.Study designRandomised balanced 2X5 factorial design.MethodsA total of n = 200 horses undergoingOGEwere randomly assigned into 10 groups (n = 20/group) of different automated endoscopicFIs (no flushing, 60, 120, 180, 240 s) with the endoscope tip positioned either rostrally (position A) or caudally (position B) in the pharynx. Endoscopic videos were analysed and allURTabnormalities graded using published scales. Disorders with ≤10% prevalence were excluded from the final analysis with only arytenoid asymmetry at exercise (AAex), vocal fold collapse (VFC), palatal dysfunction (PD) and medial deviation of the aryepiglottic folds (MDAF) included. The association of endoscope position andFIwithURTdisorders was assessed using ordinal regression models with P≤0.05 significant.ResultsEndoscope tip positioning was significantly associated withPDgrading (P = 0.002), with 63/100 horses diagnosed withPDin position A and 45/100 in position B. No other significant direct associations betweenURTdisease and endoscope tip position were identified, although interactions between exercise velocity and endoscope position affectedMDAFgrade.FIwas not directly associated with alterations in disorder grading, although interactions between exercise velocity andFIappeared to affectMDAFgrade.Main limitationsThe same horse was not evaluated under each test condition potentially resulting in sample bias. Interactions between disorders were not evaluated. The sample size was insufficient to conclusively explore relationships between all factors and disorder grading.ConclusionsPosition of the endoscope tip within the pharynx appears to affect grading ofPDduringOGEexamination. Exercise velocity may affectMDAFgrade through interactions with endoscope position andFI.
Characterizing a pH‐switch anti‐C5 antibody as a tool for human and mouse complement C5 purification and cross‐species inhibition of classical and reactive lysis
Authors: Zelek Wioleta M. , Stott Matthew , Walters David , Harris Claire L. , Morgan B. Paul 
Published: July 2018

SummaryC5 plays a major role in complement activation; C5 convertase cleaves C5 into the pro‐inflammatory C5a, and C5b, the nidus for the formation of the lytic membrane attack complex. C5 is a major target for anti‐complement drugs, necessitating better methods for the study of C5 function. Purification of C5 is complicated; classical methods involve precipitation or pH shifts that result in functional loss and low yield. We here present a method for C5 purification using a novel anti‐C5 monoclonal antibody (mAb); RO7112689 (C5i mAb, SKY59), pH‐switch engineered to induce antibody–antigen dissociation in the acidic endosome (~ pH 5·5). RO7112689 was bound on an affinity column; applied serum was completely depleted of C5. Elution at pH 5 produced fully active C5 at 98% yield. The mAb also bound C5b in the C5b6 complex, preventing C5b6 binding to target membranes and enabling purification of C5b6 from activated serum. RO7112689 inhibited C5 in mouse serum and efficiently purified mouse C5. Used as capture, RO7112689 produced sensitive and specific assays for human and mouse C5. This novel antibody enables efficient production of intact, fully active, pure human and mouse C5, and quantification of C5 in these species. The demonstration that RO7112689 binds C5b6 adds an additional mechanism of membrane attack complex inhibition by this mAb.
Low gallium‐content, dysprosium III‐doped, Ge–As–Ga–Se chalcogenide glasses for active mid‐infrared fiber optics
Authors: Tang Zhuoqi , Furniss David , Neate Nigel C. , Benson Trevor M. , Seddon Angela B. 
Published: July 2018

AbstractA systematic investigation is presented, for the first time, of a 1000 ppmw (parts per million, by weight) Dy3+‐doped Ge–As–Ga–Se chalcogenide glass series, with a fixed low Ga content of 1 atomic% (at. %), suitable for active mid‐infrared fiber optics. Seven glasses constitute the series, which have increasing average coordination number from 2.49 to 2.61, in steps of 0.02, with the GeSe2, As2Se3, and Ga2Se3 stoichiometries kept. Glass formation is confirmed using X‐ray diffraction and differential scanning calorimetry. Fourier transform infrared spectroscopy is reported for the series. Parallel plate viscometry enables prediction of fiber‐drawing temperatures and, with differential thermal analysis, determines the potential for fiber fabrication. X‐ray diffraction of samples after parallel‐plate viscometry shows that Ge25As9Ga1Se65 (at. %) alone, in the glass‐series, devitrifies to form the single‐crystalline phase: monoclinic‐GeSe2; scanning electron microscope imaging suggests that this phase is both surface and bulk grown. Overall, the recommended host glass at. % compositions for doping with rare‐earth ions and drawing to active mid‐infrared fiber are: Ge17.5As18Ga1Se63.5, Ge15As21Ga1Se63, and Ge12.5As24Ga1Se62.5.
Impact of hepatocellular carcinoma aetiology and liver function on the benefit of surveillance: A novel approach for the adjustment of lead‐time bias
Authors: Toyoda Hidenori , Kumada Takashi , Tada Toshifumi , Mizuno Kazuyuki , Hiraoka Atsushi , Tsuji Kunihiko , Ishikawa Toru , Akita Tomoyuki , Tanaka Junko 
Published: July 2018

AbstractBackground & AimsSurveillance reportedly has benefit on survival in patients with hepatocellular carcinoma (HCC), even after adjustment for lead‐time bias. However, previous adjustment for lead‐time bias using tumour volume doubling time (TVDT) had inherent problem in accuracy. We evaluated survival benefit of HCC surveillance with newly developed approach for adjusting lead‐time bias. In addition, survival benefit was evaluated according to HCC aetiology and liver function.MethodsA total of 3899 patients were studied. TVDT was calculated in 255 study patients with ≥2 tumour size measurements before the diagnosis of HCC. Adjusted survival time was calculated based on TVDT, as the time from when HCC was assumed to be 5 mm to death or last follow‐up. Survival rates based on this adjusted survival time were compared between the surveillance and nonsurveillance groups and categorized by HCC aetiology and liver function.ResultsCalculated TVDT varied widely by study patients (median 141.9, IQR, 73.1‐261.7 days). Survival rates based on adjusted survival time were higher in the surveillance group overall and by patients HCC aetiology. Whereas adjusted survival rates were higher in the surveillance group in Child‐Pugh class A patients, the survival benefit was smaller in Child‐Pugh class B patients and not statistically significant in Child‐Pugh class C patients.ConclusionsThe survival benefit of surveillance for patients with HCC was demonstrated after adjustment for lead‐time bias with novel, more accurate methodology. However, the benefits differed based on liver function and may vary largely by patients because of wide variation in TVDT.
Risk factors and impact of allergic bronchopulmonary aspergillosis in Pseudomonas aeruginosa‐negative CF patients
Authors: De Baets Frans , De Keyzer Linde , Van daele Sabine , Schelstraete Petra , Van Biervliet Stephanie , Van Braeckel Eva , Thomas Muriel , Wanyama Simeon S. 
Published: July 2018

AbstractBackgroundAllergic bronchopulmonary aspergillosis (ABPA) is a major complication in cystic fibrosis (CF) patients. Risk factors for ABPA and clinical deterioration in CF patients, negative for Pseudomonas aeruginosa (Pa), were explored.MethodsWe performed a retrospective case‐control study in 73 Pa‐negative patients. Each patient was matched with 2 controls for age, gender, pancreas sufficiency, DeltaF508 mutation (homozygous or heterozygous), and Pa colonization.ResultsMedian FEV1 at the year of diagnosis (index year) was significantly lower in patients with ABPA. The median of cumulative values of FEV1 and FVC before the index year was not significantly different. After the index year, the median of cumulative data for FEV1 and FVC was significantly lower; there were significantly more hospitalization days and more IV antibiotic days compared to controls. Comparing pre‐ and post‐index year data in patients with ABPA, significantly more hospitalization days and more IV antibiotic days were observed after the index year. During the period preceding the index year, significantly more ABPA patients were treated with rhDNase and inhaled corticosteroids.ConclusionsBronchial damage cannot be considered as a facilitating factor for ABPA. ABPA causes a significant increase in bronchial damage. In patients with ABPA, further bronchial damage can be controlled by an increase in hospitalization days and use of IV antibiotics. rhDNase and inhaled corticosteroids were associated with the development of ABPA.