bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic utility of biopsy‐derived cell cycle progression score in patients with National Comprehensive Cancer Network low‐risk prostate cancer undergoing radical prostatectomy: implications for treatment guidance
Authors: Tosoian Jeffrey J. , Chappidi Meera R. , Bishoff Jay T. , Freedland Stephen J. , Reid Julia , Brawer Michael , Stone Steven , Schlomm Thorsten , Ross Ashley E. 
Published: May 2017

ObjectivesTo determine the prognostic utility of the cell cycle progression (CCP) score in men with National Comprehensive Cancer Network (NCCN)‐defined low‐risk prostate cancer (PCa) undergoing radical prostatectomy (RP).Patients and MethodsMen who underwent RP for Gleason score ≤6 PCa at three institutions (Martini Clinic [MC], Durham Veterans Affairs Medical Center [DVA] and Intermountain Healthcare [IH]) were identified. The CCP score was obtained from diagnostic (DVA, IH) or simulated biopsies (MC). The primary outcome was biochemical recurrence (BCR; prostate‐specific antigen ≥0.2 ng/mL) after RP. The prognostic utility of the CCP score was assessed using Kaplan–Meier analysis and multivariable Cox proportional hazards models in the subset of men meeting NCCN low‐risk criteria and in the overall cohort.ResultsAmong the 236 men identified, 80% (188/236) met the NCCN low‐risk criteria. Five‐year BCR‐free survival for the low (<0), intermediate (0–1) and high (>1) CCP score groups was 89.2%, 80.4%, 64.7%, respectively, in the low‐risk cohort (P = 0.03), and 85.9%, 79.1%, 63.1%, respectively, in the overall cohort (P = 0.041). In multivariable models adjusting for clinical and pathological variables with the Cancer of the Prostate Risk Assessment (CAPRA) score, the CCP score was an independent predictor of BCR in the low‐risk (hazard ratio [HR] 1.77 per unit score, 95% confidence interval [CI] 1.21, 2.58; P = 0.003) and overall cohorts (HR 1.41 per unit score, 95% CI 1.02, 1.96; P = 0.039).ConclusionIn a cohort of men with NCCN‐defined low‐risk PCa, the CCP score improved clinical risk stratification of men who were at increased risk of BCR, which suggests the CCP score could improve the assessment of candidacy for active surveillance and guide optimum treatment selection in these patients with otherwise similar clinical characteristics.
Persistent activation of α7 nicotinic ACh receptors associated with stable induction of different desensitized states
Authors: Papke Roger L , Stokes Clare , Damaj M Imad , Thakur Ganesh A , Manther Khan , Treinin Millet , Bagdas Deniz , Kulkarni Abhijit R , Horenstein Nicole A 
Published: May 2017

Background and PurposeGAT107 ((3aR,4S,9bS)‐4‐(4‐bromo‐phenyl)‐3a,4,5,9b‐tetrahydro‐3H‐cyclopenta‐[c]quinoline‐8‐sulfonamide) is a positive allosteric modulator (PAM) and agonist of α7 nicotinic acetylcholine receptors (nAChRs)that can cause a prolonged period of primed potentiation of acetylcholine responses after drug washout. NS6740 is a silent agonist of α7 nAChRs that has little or no efficacy for activating the ion channel but induces stable desensitization states, some of which can be converted into channel‐active states by PAMs. Although GAT107 and NS6740 appear to stably induce different non‐conducting states, both agents are effective treatment for inflammation and inflammatory pain models. We sought to better understand how both of these drugs that have opposite effects on channel activation could regulate signal transduction.Experimental ApproachVoltage‐clamp experiments were conducted with α7 nAChRs expressed in Xenopus oocytes.Key ResultsLong‐lived sensitivity to a PAM or to an agonist was produced by NS6740 or GAT107 respectively. With sequential applications, these two drugs induced varying levels of persistent activation, which is a unique condition for a receptor that is known for rapid desensitization. The non‐conducting states induced by NS6740 or GAT107 differ in their sensitivity to an α7 nAChR‐selective antagonist and in how effectively they promote current.Conclusions & ImplicationsOur data suggest that the persistent currents represent a dynamic interconversion between different stable desensitized states and the PAM‐inducible conducting states. However, the similarity of NS6740 and GAT107 effects on inflammation and pain suggests that the different stable non‐conducting states have common activity on signal transduction.Linked ArticlesThis article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc
Oxidized low‐density lipoprotein stimulates epithelial sodium channels in endothelial cells of mouse thoracic aorta
Authors: Liang Chen , Wang Qiu‐Shi , Yang Xu , Niu Na , Hu Qing‐Qing , Zhang Bao‐Long , Wu Ming‐Ming , Yu Chang‐Jiang , Chen Xiao , Song Bin‐Lin , Zhang Zhi‐Ren , Ma He‐Ping 
Published: May 2017

Background and PurposeThe epithelial sodium channel (ENaC) is expressed in endothelial cells and acts as a negative modulator of vasodilatation. Oxidized LDL (ox‐LDL) is a key pathological factor in endothelial dysfunction. In the present study we examined the role of ENaC in ox‐LDL‐induced endothelial dysfunction and its associated signal transduction pathway.Experimental ApproachPatch clamp techniques combined with pharmacological approaches were used to examine ENaC activity in the endothelial cells of a split‐open mouse thoracic aorta. Western blot analysis was used to determine ENaC expression in the aorta. The aorta relaxation was measured using a wire myograph assay.Key ResultsOx‐LDL, but not LDL, significantly increased ENaC activity in the endothelial cells attached to split‐open thoracic aortas, and the increase was inhibited by a lectin‐like ox‐LDL receptor‐1 (LOX‐1) antagonist (κ‐carrageenan), an NADPH oxidase inhibitor (apocynin), and a scavenger of ROS (TEMPOL). Sodium nitroprusside, an NO donor, diminished the ox‐LDL‐mediated activation of ENaC, and this effect was abolished by inhibiting soluble guanylate cyclase (sGC) and PKG. Ox‐LDL reduced the endothelium‐dependent vasodilatation of the aorta pectoralis induced by ACh, and this reduction was partially restored by blocking ENaC.Conclusion and ImplicationsOx‐LDL stimulates ENaC in endothelial cells through LOX‐1 receptor‐mediated activation of NADPH oxidase and accumulation of intracellular ROS. Since the stimulation of ENaC can be reversed by elevating NO, we suggest that both inhibition of ENaC and an elevation of NO may protect the endothelium from ox‐LDL‐induced dysfunction.Linked ArticlesThis article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc
Beyond chemoreception: diverse tasks of soluble olfactory proteins in insects
Authors: Pelosi Paolo , Iovinella Immacolata , Zhu Jiao , Wang Guirong , Dani Francesca R. 
Published: May 2017

ABSTRACTOdorant‐binding proteins (OBPs) and chemosensory proteins (CSPs) are regarded as carriers of pheromones and odorants in insect chemoreception. These proteins are typically located in antennae, mouth organs and other chemosensory structures; however, members of both classes of proteins have been detected recently in other parts of the body and various functions have been proposed. The best studied of these non‐sensory tasks is performed in pheromone glands, where OBPs and CSPs solubilise hydrophobic semiochemicals and assist their controlled release into the environment. In some cases the same proteins are expressed in antennae and pheromone glands, thus performing a dual role in receiving and broadcasting the same chemical message. Several reports have described OBPs and CSPs in reproductive organs. Some of these proteins are male specific and are transferred to females during mating. They likely carry semiochemicals with different proposed roles, from inhibiting other males from approaching mated females, to marking fertilized eggs, but further experimental evidence is still needed. Before being discovered in insects, the presence of binding proteins in pheromone glands and reproductive organs was widely reported in mammals, where vertebrate OBPs, structurally different from OBPs of insects and belonging to the lipocalin superfamily, are abundant in rodent urine, pig saliva and vaginal discharge of the hamster, as well as in the seminal fluid of rabbits. In at least four cases CSPs have been reported to promote development and regeneration: in embryo maturation in the honeybee, limb regeneration in the cockroach, ecdysis in larvae of fire ants and in promoting phase shift in locusts. Both OBPs and CSPs are also important in nutrition as solubilisers of lipids and other essential components of the diet. Particularly interesting is the affinity for carotenoids of CSPs abundantly secreted in the proboscis of moths and butterflies and the occurrence of the same (or very similar CSPs) in the eyes of the same insects. A role as a carrier of visual pigments for these proteins in insects parallels that of retinol‐binding protein in vertebrates, a lipocalin structurally related to OBPs of vertebrates. Other functions of OBPs and CSPs include anti‐inflammatory action in haematophagous insects, resistance to insecticides and eggshell formation. Such multiplicity of roles and the high success of both classes of proteins in being adapted to different situations is likely related to their stable scaffolding determining excellent stability to temperature, proteolysis and denaturing agents. The wide versatility of both OBPs and CSPs in nature has suggested several different uses for these proteins in biotechnological applications, from biosensors for odours to scavengers for pollutants and controlled releasers of chemicals in the environment.
ASQ‐3 scores are sensitive to small differences in age in a Peruvian infant population
Authors: Chong K. C. , Zhou V. L. , Tarazona D. , Tuesta H. , Velásquez‐Hurtado J. E. , Sadeghi R. , Llanos F. 
Published: May 2017

AbstractObjectiveThe Ages and Stages Questionnaires Edition 3 (ASQ‐3) are a well‐validated international screen for developmental delays in young children. However, previous studies demonstrate variable scores between children eligible to take the same ASQ‐3 interval. This study aimed to determine a relationship between age and ASQ‐3 score for each screening interval.MethodsThis was a baseline exploratory cross‐sectional study of infants under 2 years old evaluated for the Peruvian social programme Cuna Más. Participants were included in Cuna Más if they lived in districts with fewer than 2000 inhabitants or 400 homes, indicating a predominantly rural population. The appropriate ASQ‐3 screening interval was administered to each subject. Subjects were divided into four 2‐week chronological subgroups based on age within each 2‐month screening window and aggregated across all 12 screening intervals. Fisher's exact test, analysis of variance and Bonferonni post hoc test were used to compare differences between age subgroups. Linear regression was performed to assess the relationship between ASQ‐3 score and both aggregated and disaggregated age subgroup.ResultsA total of 5850 Peruvian infants were evaluated in 2013. Mean age was 13 ± 6.6 months, 50.7% were male and mean maternal education was 6.6 ± 4.0 years; 34.8% infants were stunted, 7.8% were underweight, 0.9% were wasted and 2% had age adjusted greater than 35 days for prematurity for ASQ‐3 interval assignment. Mean total ASQ‐3 was 42.2 ± 8.2. The ASQ‐3 allocated 49.6% with suspected delay in one or more developmental areas.Before and after adjusting for wealth quintile, maternal education level, infant nutritional status and prematurity adjustment, age subgroup remained significantly associated with total ASQ‐3 score (β = 1.8, CI: 1.7–2.0, P < 0.001), sectional ASQ‐3 score (all P < 0.001) and inversely associated with one or more scores indicating suspected developmental delay (P < 0.001).ConclusionsThe ASQ‐3 may underestimate the sensitivity of child development to small differences in age in this population.
Sacral nerve stimulation can be an effective treatment for low anterior resection syndrome
Authors: Eftaiha S. M. , Balachandran B. , Marecik S. J. , Mellgren A. , Nordenstam J. , Melich G. , Prasad L. M. , Park J. J. 
Published: May 2017

AbstractAimSacral nerve stimulation has become a preferred method for the treatment of faecal incontinence in patients who fail conservative (non‐operative) therapy. In previous small studies, sacral nerve stimulation has demonstrated improvement of faecal incontinence and quality of life in a majority of patients with low anterior resection syndrome. We evaluated the efficacy of sacral nerve stimulation in the treatment of low anterior resection syndrome using a recently developed and validated low anterior resection syndrome instrument to quantify symptoms.MethodA retrospective review of consecutive patients undergoing sacral nerve stimulation for the treatment of low anterior resection syndrome was performed. Procedures took place in the Division of Colon and Rectal Surgery at two academic tertiary medical centres. Pre‐ and post‐treatment Cleveland Clinic Incontinence Scores and Low Anterior Resection Syndrome scores were assessed.ResultsTwelve patients (50% men) suffering from low anterior resection syndrome with a mean age of 67.8 (±10.8) years underwent sacral nerve test stimulation. Ten patients (83%) proceeded to permanent implantation. Median time from anterior resection to stimulator implant was 16 (range 5–108) months. At a median follow‐up of 19.5 (range 4–42) months, there were significant improvements in Cleveland Clinic Incontinence Scores and Low Anterior Resection Syndrome scores (P < 0.001).ConclusionSacral nerve stimulation improved symptoms in patients suffering from low anterior resection syndrome and may therefore be a viable treatment option.
Laparoscopic abdominoperineal excision with trans‐abdominal individualized levator transection: interim analysis of a randomized controlled trial
Authors: Feng B. , Lu J. , Zhang S. , Yan X. , Li J. , Xue P. , Wang M. , Lu A. , Ma J. , Zang L. , Dong F. , He Z. , Yue F. , Sun J. , Hong X. , Zheng M. 
Published: May 2017

AbstractAimExtralevator abdominoperineal excision (ELAPR) is challenging ‘conventional’ abdominoperineal excision (APR), yet the safety and efficacy of ELAPR is still under debate. We therefore developed a laparoscopic APR with trans‐abdominal individualized levator transection (LAPR‐TILT) approach and compared the outcome with a conventional laparoscopic APR (CLAPR).MethodAll eligible patients were entered a single‐centre randomized controlled trial to compare CLAPR and LAPR‐TILT. We assessed the first 185 patients, including operative findings, complications, histopathology and urogenital function.ResultsNinety‐three patients in the CLAPR group and 92 patients in the APR‐TILT group were included for analysis. The APR‐TILT procedure took less time [137 (101–175) min vs 146 (102–187) min; P = 0.03], mainly owing to faster perineal dissection. APR‐TILT resulted in a reduced rate of bowel perforation (1.1% vs 8.6%; P = 0.04), circumferential resection margin positivity (1.1% vs 10.8%; P = 0.01) and postoperative wound complications (5.4% vs 16.2%; P = 0.02) compared with the CLAPR procedure. At a median follow‐up of 19 months after surgery, three patients (3.2%) in the CLAPR group had tumour recurrence while no tumour recurrence occurred in the LAPR‐TILT group. Patients who underwent LAPR‐TILT reported fewer urinary or sexual problems (LAPR‐TILT vs CLAPR, 10.9% vs 24.7% and 17.4% vs 38.7%, respectively).ConclusionCompared with CLAPR, LAPR‐TILT achieved better pathological results for factors that are surrogate parameters for local recurrence. LAPR‐TILT could also reduce the risk of urogenital dysfunction.
Effect of diltiazem on exercise capacity after heart transplantation
Authors: Varnado Sara , Peled‐Potashnik Yael , Huntsberry Ashley , Lowes Brian D. , Zolty Ronald , Burdorf Adam , Lyden Elizabeth R. , Moulton Michael J. , Um John Y. , Raichlin Eugenia 
Published: May 2017

AbstractBackgroundSinus tachycardia (ST) is common after heart transplantation (HTx). The aim of the study was to evaluate the effect of diltiazem treatment during the first year after HTx on heart rate (HR), cardiac allograft function, and exercise capacity.MethodsFrom the total cohort, 25 HTx recipients started diltiazem treatment 4±2 weeks after HTx and continued it for at least 1 year (diltiazem group). Each study case was matched to a control. All patients underwent hemodynamic assessment and cardiopulmonary exercise test (CPET) at 1 year after HTx.ResultsHR decreased in the diltiazem group from 99±11 bpm to 94±7 bpm (P=.03) and did not change in the controls (98±11 bpm vs 100±13 bpm, P=.14). The difference between the groups at 1 year after HTx was significant (P=.04). In the diltiazem group left ventricular (LV), stroke volume and ejection fraction increased (48±16 vs 55±17 mL, P=.02, and 60%±10% vs 62%±12% P=.03, respectively) but did not differ from controls. E/E' decreased (10.7±2.7 vs 7.3±1.9, P=.003) while cardiac index was higher (3.5±0.8 vs 3.1±0.5; P=.05) in the diltiazem group at 1‐year follow‐up. The absolute peak VO2 (21±4 vs 18±6 mL/kg/min; P=.05) and normalized peak VO2 (73%±17% vs 58%±14%; P=.004) were significantly higher in the diltiazem group.ConclusionsThis study showed that diltiazem treatment reduces ST, may improve cardiac allograft function and exercise tolerance during the first year after HTx.
Farmer producer organizations as farmer collectives: A case study from India
Authors: Bikkina Nalini , Turaga Rama Mohana R. , Bhamoriya Vaibhav 
Published: May 2017

AbstractSmall and marginal farmers in India have been vulnerable to risks in agricultural production. Several organizational prototypes are emerging to integrate them into the value chain with the objective of enhancing incomes and reducing transaction costs. Among these are Farmer Producer Organizations (FPOs). We explore the potential of FPOs as collective institutions through a case study of Avirat, one of the first FPOs in Gujarat. Our analysis suggests that FPOs have the potential to provide benefits through effective collective action. The main challenge, however, is to raise sufficient capital to maximize these benefits. We discuss the implications of our findings to policy.
What encourages community health workers to use mobile technologies for health interventions? Emerging lessons from rural Rwanda
Authors: Mwendwa Purity 
Published: May 2017

AbstractThis article explores the determinants of using mobile phone technologies for public health (mHealth) through a quantitative study with community health workers (CHWs) in rural Rwanda. A total of 72 CHWs from two districts in Rwanda who were using the mHealth tool, RapidSMS, were surveyed in June 2014. Using a socio‐technical approach, user, programme and technical characteristics were tested and deemed influential in determining use. Technical characteristics (reminders and alerts) were by far the strongest predicting factors of use. The user characteristic, age, had no influence on utilization, while supports though training and supervision (programme characteristics) revealed mixed findings. These findings illustrate the uniqueness of each context and reiterate the need to consider social and technical factors when implementing mHealth projects.
Quantitation of valve regurgitation severity by three‐dimensional vena contracta area is superior to flow convergence method of quantitation on transesophageal echocardiography
Authors: Abudiab Muaz M. , Chao Chieh‐Ju , Liu Shuang , Naqvi Tasneem Z. 
Published: May 2017

BackgroundQuantitation of regurgitation severity using the proximal isovelocity acceleration (PISA) method to calculate effective regurgitant orifice (ERO) area has limitations. Measurement of three‐dimensional (3D) vena contracta area (VCA) accurately grades mitral regurgitation (MR) severity on transthoracic echocardiography (TTE).MethodsWe evaluated 3D VCA quantitation of regurgitant jet severity using 3D transesophageal echocardiography (TEE) in 110 native mitral, aortic, and tricuspid valves and six prosthetic valves in patients with at least mild valvular regurgitation. The ASE‐recommended integrative method comprising semiquantitative and quantitative assessment of valvular regurgitation was used as a reference method, including ERO area by 2D PISA for assigning severity of regurgitation grade.ResultsMean age was 62.2±14.4 years; 3D VCA quantitation was feasible in 91% regurgitant valves compared to 78% by the PISA method. When both methods were feasible and in the presence of a single regurgitant jet, 3D VCA and 2D PISA were similar in differentiating assigned severity (ANOVAP<.001). In valves with multiple jets, however, 3D VCA had a better correlation to assigned severity (ANOVAP<.0001). The agreement of 2D PISA and 3D VCA with the integrative method was 47% and 58% for moderate and 65% and 88% for severe regurgitation, respectively.ConclusionMeasurement of 3D VCA by TEE is superior to the 2D PISA method in determination of regurgitation severity in multiple native and prosthetic valves.
Phenotypic and molecular differences between giant‐cell tumour of soft tissue and its bone counterpart
Authors: Mancini Irene , Righi Alberto , Gambarotti Marco , Picci Piero , Dei Tos Angelo P , Billings Steven D , Simi Lisa , Franchi Alessandro 
Published: May 2017

AimsGiant‐cell tumour (GCT) of soft tissue (GCT‐ST) is a primary soft tissue neoplasm that is histologically similar to GCT of bone (GCT‐B). Recently, it has been reported that >90% of GCT‐Bs have a driver mutation in the H3F3A gene. As the relationship between GCT‐ST and GCT‐B is unclear, the aim of this study was to compare a series of GCT‐STs and GCT‐Bs with regard to the presence of H3F3A mutations and several immunophenotypic markers.Methods and resultsEight GCT‐STs were retrieved from our institutional archives. Fifteen GCT‐Bs served as controls. Direct sequencing for H3F3A mutations in coding regions between codons 1 and 42, including the hotspot codons (28, 35, and 37), was performed on DNA extracted from formalin‐fixed paraffin‐embedded tissue. Tumours were studied immunohistochemically for the expression of CD14, CD33, RANKL, RANK, p63, and the osteoblastic markers SATB2 and RUNX2. None of the seven GCT‐STs that could be analysed showed H3F3A mutations, whereas 14 GCT‐Bs (93.3%) were mutated. All eight GCT‐STs were positive for RANK and RUNX2, whereas RANKL and SATB2 were detected in only two cases (25%). CD14 was detected only in mononuclear elements, whereas multinucleated giant cells and a proportion of the mononuclear population expressed CD33. Few mononuclear cells of GCT‐STs expressed p63. In comparison, GCT‐Bs showed higher expression of p63 (14 of 15 cases with >50% of positive mononuclear cells), RANKL, and SATB2, whereas CD14, CD33, RANK and RUNX2 were similarly expressed.ConclusionsAlthough GCT‐ST and GCT‐B are similar in histological appearance, our results indicate that they are immunophenotypically and genetically distinct.
Corrosion behavior and microstructural evolution of BN–ZrO2–SiC composites in molten steel
Authors: Chen Lei , Zhen Li , Wang Yujin , Duan Xiaoming , Ouyang Jia‐Hu , Zhou Yu 
Published: May 2017

AbstractThe influence of SiC content on corrosion resistance and microstructural evolution of BN–ZrO2–SiC composites after corrosion in molten steel at 1600°C has been investigated. The corrosion resistance of BN–ZrO2–SiC composite decreases with increasing the SiC content. When the SiC content is more than 15 vol%, the corrosion rate begins to accelerate sharply. A resintered ZrO2 bilayer structure with a distinctly reduced porosity in the corrosion layer contributes significantly to the enhanced corrosion resistance. Thus, optimizing the SiC content and tailoring the microstructural feature of residual corrosion layer are effective ways to improve the corrosion resistance of BN–ZrO2–SiC composite.