bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of non‐visualization following dynamic sentinel lymph node biopsy for squamous cell carcinoma of the penis
Authors: Sahdev Varun , Albersen Maarten , Christodoulidou Michelle , Parnham Arie , Malone Peter , Nigam Raj , Bomanji Jamshed , Muneer Asif 
Published: October 2016

ObjectivesTo review the management and clinical outcomes of uni‐ or bilateral non‐visualization of inguinal lymph nodes during dynamic sentinel lymph node biopsy (DSNB) in patients diagnosed with penile cancer and clinically impalpable inguinal lymph nodes (cN0), and to develop an algorithm for the management of patients in which non‐visualization occurs.Patients and MethodsThis is a retrospective observational study over a period of 4 years, comprising 166 patients with penile squamous cell carcinoma undergoing DSNB and followed up for a minimum of 6 months. All cases diagnosed with uni‐ or bilateral non‐visualization of sentinel nodes in this cohort were identified from a penile cancer database. The management of the inguinal lymph nodes after non‐visualization and the oncological outcomes including local and regional recurrence rates were documented.ResultsOut of 166 consecutive patients undergoing DSNB, 20 patients (12%) had unilateral non‐visualization after injection of intradermal 99mTc. Of these 20 patients, seven underwent repeat DSNB at a later date, with six having successful visualization. One patient had persistent non‐visualization and proceeded to a superficial modified inguinal lymphadenectomy (SML). None of these patients experienced recurrence at follow‐up. A further seven patients underwent modified SML with on‐table frozen‐section analysis of the lymph node packet; none of these patients were found to have micrometastatic disease in the inguinal lymph nodes, although one patient developed metastatic inguinal node disease at a later date. Six patients elected to undergo clinical surveillance and have remained disease‐free.ConclusionPatients with impalpable inguinal lymph nodes undergoing DSNB with ≥G2 T1 disease should ideally have bilateral visualization of the sentinel lymph nodes, reflecting the drainage pattern from the primary tumour. In the present series, 12% of patients were found to have unilateral non‐visualization after DSNB. Among patients offered a repeat DSNB at a later date, localizing the sentinel node was successful in 86% of cases. Patients with favourable histological characteristics can be placed on clinical surveillance. Those with high‐risk disease can be offered a repeat DSNB procedure on the proviso that SML may be carried out if there is repeated non‐visualization. Larger cohorts are required to validate this proposed algorithm.
Additive effects of the Rho kinase inhibitor Y‐27632 and vardenafil on relaxation of the corpus cavernosum tissue of patients with erectile dysfunction and clinical phosphodiesterase type 5 inhibitor failure
Authors: Uvin Pieter , Albersen Maarten , Bollen Ine , Falter Maarten , Weyne Emmanuel , Linsen Loes , Tinel Hanna , Sandner Peter , Bivalacqua Trinity J. , De Ridder Dirk J. M. K. , Van der Aa Frank , Brône Bert , Van Renterghem Koenraad 
Published: October 2016

ObjectivesTo evaluate the expression of the Rho/Rho‐associated protein kinase (ROCK) pathway in the corpus cavernosum of patients with severe erectile dysfunction (ED) compared with healthy human corpus cavernosum, and to test the functional effects of two Rho kinase inhibitors (RKIs) on erectile tissue of patients with severe ED, which did not respond to phosphodiesterase type 5 inhibitors (PDE5Is).Patients and MethodsHuman corpus cavernosum samples were obtained after consent from men undergoing penile prosthesis implantation (n = 7 for organ bath experiments, n = 17 for quantitative PCR [qPCR]). Potent control subjects (n = 5) underwent penile needle biopsy. qPCR was performed for the expression of RhoA and ROCK subtypes 1 and 2. Immunohistochemistry staining against ROCK and α smooth muscle actin (αSMA) was performed on the corpus cavernosum of patients with ED. Tissue strips were precontracted with phenylephrine and incubated with 1 μm of the PDE5I vardenafil or with DMSO (control). Subsequently, increasing concentrations of the RKIs azaindole or Y‐27632 were added, and relaxation of tissue was quantified.ResultsThe expression of ROCK1 was unchanged (P > 0.05), while ROCK2 (P < 0.05) was significantly upregulated in patients with ED compared with controls. ROCK1 and ROCK2 protein colocalized with αSMA, confirming the presence of this kinase in cavernous smooth muscle cells and/or myofibroblasts. After incubation with DMSO, 10 μm azaindole and 10 μm Y‐27632 relaxed precontracted tissues with 49.5 ± 7.42% (P = 0.1470 when compared with vehicle) and 85.9 ± 10.3% (P = 0.0016 when compared with vehicle), respectively. Additive effects on relaxation of human corpus cavernosum were seen after preincubation with 1 μm vardenafil.ConclusionThe RKI Y‐27632 causes a significant relaxation of corpus cavernosum in tissue strips of patients with severe ED. The additive effect of vardenafil and Y‐27632 shows that a combined inhibition of Rho‐kinase and phosphodiesterase type 5 could be a promising orally administered treatment for severe ED.
The role of perivascular adipose tissue in obesity‐induced vascular dysfunction
Authors: Xia Ning , Li Huige 
Published: October 2016

Under physiological conditions, perivascular adipose tissue (PVAT) attenuates agonist‐induced vasoconstriction by releasing vasoactive molecules including hydrogen peroxide, angiotensin 1–7, adiponectin, methyl palmitate, hydrogen sulfide, NO and leptin. This anticontractile effect of PVAT is lost under conditions of obesity. The central mechanism underlying this PVAT dysfunction in obesity is likely to be an ‘obesity triad’ (consisting of PVAT hypoxia, inflammation and oxidative stress) that leads to the impairment of PVAT‐derived vasoregulators. The production of hydrogen sulfide, NO and adiponectin by PVAT is reduced in obesity, whereas the vasodilator response to leptin is impaired (vascular leptin resistance). Strikingly, the vasodilator response to acetylcholine is reduced only in PVAT‐containing, but not in PVAT‐free thoracic aorta isolated from diet‐induced obese mice, indicating a unique role for PVAT in obesity‐induced vascular dysfunction. Furthermore, PVAT dysfunction has also been observed in small arteries isolated from the gluteal/visceral fat biopsy samples of obese individuals. Therefore, PVAT may represent a new therapeutic target for vascular complications in obesity. A number of approaches are currently being tested under experimental conditions. Potential therapeutic strategies improving PVAT function include body weight reduction, enhancing PVAT hydrogen sulfide release (e.g. rosiglitazone, atorvastatin and cannabinoid CB1 receptor agonists) and NO production (e.g. arginase inhibitors), inhibition of the renin–angiotensin–aldosterone system, inhibition of inflammation with melatonin or cytokine antagonists, activators of AMP‐activated kinase (e.g. metformin, resveratrol and diosgenin) and adiponectin releasers or expression enhancers.Linked ArticlesThis article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue – Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc
Survival of dental implants placed in sites of previously failed implants
Authors: Chrcanovic Bruno R. , Kisch Jenö , Albrektsson Tomas , Wennerberg Ann 
Published: October 2016

AbstractObjectivesTo assess the survival of dental implants placed in sites of previously failed implants and to explore the possible factors that might affect the outcome of this reimplantation procedure.Materials and methodsPatients that had failed dental implants, which were replaced with the same implant type at the same site, were included. Descriptive statistics were used to describe the patients and implants; survival analysis was also performed. The effect of systemic, environmental, and local factors on the survival of the reoperated implants was evaluated.Results175 of 10,096 implants in 98 patients were replaced by another implant at the same location (159, 14, and 2 implants at second, third, and fourth surgeries, respectively). Newly replaced implants were generally of similar diameter but of shorter length compared to the previously placed fixtures. A statistically significant greater percentage of lost implants were placed in sites with low bone quantity. There was a statistically significant difference (P = 0.032) in the survival rates between implants that were inserted for the first time (94%) and implants that replaced the ones lost (73%). There was a statistically higher failure rate of the reoperated implants for patients taking antidepressants and antithrombotic agents.ConclusionsDental implants replacing failed implants had lower survival rates than the rates reported for the previous attempts of implant placement. It is suggested that a site‐specific negative effect may possibly be associated with this phenomenon, as well as the intake of antidepressants and antithrombotic agents.
Methamphetamine Induces Anhedonic‐Like Behavior and Impairs Frontal Cortical Energetics in Mice
Authors: Fonseca Raquel , Carvalho Rui A. , Lemos Cristina , Sequeira Ana C. , Pita Inês R. , Carvalho Fábio , Silva Carlos D. , Prediger Rui D. S. , Jarak Ivana , Cunha Rodrigo A. , Fontes Ribeiro Carlos A. , Köfalvi Attila , Pereira Frederico C. 
Published: October 2016

SummaryIntroductionWe recently showed that a single high dose of methamphetamine (METH) induces a persistent frontal cortical monoamine depletion that is accompanied by helpless‐like behavior in mice. However, brain metabolic alterations underlying both neurochemical and mood alterations remain unknown.AimsHerein, we aimed at characterizing frontal cortical metabolic alterations associated with early negative mood behavior triggered by METH. Adult C57BL/6 mice were injected with METH (30 mg/kg, i.p.), and their frontal cortical metabolic status was characterized after probing their mood and anxiety‐related phenotypes 3 days postinjection.ResultsMethamphetamine induced depressive‐like behavior, as indicated by the decreased grooming time in the splash test and by a transient decrease in sucrose preference. At this time, METH did not alter anxiety‐like behavior or motor functions. Depolarization‐induced glucose uptake was reduced in frontocortical slices from METH‐treated mice compared to controls. Consistently, astrocytic glucose transporter (GluT1) density was lower in the METH group. A proton high rotation magic angle spinning (HRMAS) spectroscopic approach revealed that METH induced a significant decrease in N‐acetyl aspartate (NAA) and glutamate levels, suggesting that METH decreased neuronal glutamatergic function in frontal cortex.ConclusionsWe report, for the first time, that a single METH injection triggers early self‐care and hedonic deficits and impairs frontal cortical energetics in mice.
Immunohistochemical studies and fluorodeoxyglucose uptake on positron emission tomography in pharyngeal cancer for predicting radiotherapy‐based treatment outcomes
Authors: Lin Y.‐C. , Chen R.‐Y. , Chen S.‐W. , Hsieh T.‐C. , Yen K.‐Y. , Liang J.‐A. , Yang S.‐N. , Wang Y.‐C. , Chen Y.‐H. , Chow N.‐H. , Kao C.‐H. 
Published: October 2016

ObjectivesThis study correlated immunohistochemical studies with fluorodeoxyglucose (FDG) uptake on positron emission tomography–computed tomography (PET–CT) and identified prognostic factors for radiotherapy (RT)‐based treatment outcomes in patients with squamous cell carcinoma of the oropharynx and hypopharynx.MethodsGenomic data from pre‐treatment biopsy specimens (Glut1, CAIX, VEGF, HIF‐1α, EGFR, Ki‐67, Bcl‐2, CLAUDIN‐4, YAP‐1, c‐Met and p16) of 76 patients were analysed using tissue microarrays. FDG uptake was evaluated using the maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG).ResultsThe overexpression of Glut1 positively associated with increased values of the SUVmax, MTV and TLG, whereas VEGF and HIF‐1α expression with the MTV and TLG, respectively. A VEGF immunoreactive score (IRS) >2 (P = 0.001, hazard ratio [HR] = 3.94) and an MTV defined by an SUV of 2.5 (MTV2.5) >14.5 mL (P = 0.004, HR = 3.31) were prognostic factors for low cause‐specific survival, whereas a VEGF IRS >2 (P = 0.02, HR = 2.83) for low primary relapse‐free survival.ConclusionThe overexpression of Glut1, VEGF and HIF‐1α associated with increased FDG uptake. For patients with pharyngeal cancer requiring RT, the treatment outcome can be stratified by VEGF and MTV2.5.
Acute resistance exercise using free weights on aortic wave reflection characteristics
Authors: Tai Yu Lun , Gerhart Hayden , Mayo Xián , Kingsley J. Derek 
Published: October 2016

SummaryAortic wave reflection characteristics such as the augmentation index (AIx), wasted left ventricular pressure energy (ΔEw) and aortic haemodynamics, such as aortic systolic blood pressure (ASBP), strongly predict cardiovascular events. The effects of acute resistance exercise (ARE) using free‐weight exercises on these characteristics are unknown. Therefore, we sought to determine the effects of acute free‐weight resistance exercise on aortic wave reflection characteristics and aortic haemodynamics in resistance‐trained individuals. Fifteen young, healthy resistance‐trained (9 ± 3 years) individuals performed two randomized sessions consisting of an acute bout of free‐weight resistance exercise (ARE) or a quiet control (CON). The ARE consisted of three sets of 10 repetitions at 75% one repetition maximum for squat, bench press and deadlift. In CON, the participants rested in the supine position for 30 min. Measurements were made at baseline before sessions and 10 min after sessions. A two‐way ANOVA was used to compare the effects of condition across time. There were no significant interactions for aortic or brachial blood pressures. Compared to rest, there were significant increases in augmentation pressure (rest: 5·7 ± 3·0 mmHg; recovery: 10·4 ± 5·7 mmHg, P = 0·002), AIx (rest: 116·8 ± 4·2%; recovery: 123·2 ± 8·4%, P = 0·002), AIx normalized at 75 bpm (rest: 5·2 ± 7·6%; recovery: 27·3 ± 13·2%, P<0·0001), ΔEw (rest: 1215 ± 674 dynes s cm−2; recovery: 2096 ± 1182 dynes s cm−2, P = 0·008), and there was a significant decrease in transit time of the reflected wave (rest: 150·7 ± 5·8 ms; recovery 145·5 ± 5·6 ms, P<0·001) during recovery from ARE compared to CON. These data suggest that ARE using free‐weight exercises may have no effect on aortic and brachial blood pressure but may significantly alter aortic wave reflection characteristics.
Beneficial effect of lixisenatide after 76 weeks of treatment in patients with type 2 diabetes mellitus: A meta‐analysis from the GetGoal programme
Authors: Broglio Fabio , Mannucci Edoardo , Napoli Raffaele , Nicolucci Antonio , Purrello Francesco , Nikonova Elena , Stager William , Trevisan Roberto 
Published: October 2016

AimsTo evaluate the long‐term efficacy and safety of lixisenatide, a short‐acting, prandial glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) as add‐on therapy in type 2 diabetes mellitus.MethodsA meta‐analysis of 76‐week results of 5 placebo‐controlled clinical trials from the GetGoal programme was performed, including 3000 inadequately controlled adult diabetic patients where lixisenatide 20 µg once‐daily was administered in combination with metformin (GetGoal‐M and GetGoal‐F1), sulphonylurea ± metformin (GetGoal‐S), basal insulin ± metformin (GetGoal‐L) or pioglitazone ± metformin (GetGoal‐P).ResultsA significant reduction in HbA1c at 76 weeks was observed in the intervention arm compared to placebo (LSM difference: −0.41%, 95%CI: −0.51, −0.32,
P
< .00001). Compared to placebo, lixisenatide induced a larger decrease in fasting plasma glucose (LSM difference −0.49 mmol/L, 95% CI −0.71, −0.27,
P
< .0001) and postprandial glucose excursion after a standard test meal (LSM difference −3.29 mmol/L, 95% CI −4.17, −2.42,
P
< .00001). A bodyweight reduction was observed in the lixisenatide arm (LSM difference −0.40 kg, 95%CI: −0.8, −0.01,
P
= .05). The risk of hypoglycaemia was slightly higher with lixisenatide vs placebo (risk difference +0.02, 95% CI: 0, 0.04,
P
= .04). The most commonly observed non‐severe adverse events were nausea and vomiting, which after week 16 and week 8, were steadily <4% and <1% in the lixisenatide arm, respectively.ConclusionsLixisenatide, a once‐daily prandial GLP‐1 RA, provides long‐term glycaemic control, a sustained beneficial effect on weight and with a good safety profile.
Melanoma risk alleles are associated with downregulation of the MTAP gene and hypermethylation of a CpG island upstream of the gene in dermal fibroblasts
Authors: Sangalli Antonella , Malerba Giovanni , Tessari Gianpaolo , Rodolfo Monica , Gomez‐Lira Macarena 
Published: October 2016

AbstractSeveral association studies and GWAS on melanoma skin cancer risk have reported statistically significant signals on 9p21.3 region, where MTAP gene maps. None of the associated SNPs identified in these studies lie in the coding region of the gene and the causative relation of risk alleles with melanoma predisposition has not been elucidated. MTAP has a tumor suppressor activity and epigenetic silencing has been described in melanoma cell lines. In the present study, we show that melanoma risk alleles correlate with a MTAP allele‐specific hyper‐methylation and down‐regulation of gene expression.
Using expert elicitation to estimate the potential impact of improved diagnostic performance of laboratory tests: a case study on rapid discharge of suspected non–ST elevation myocardial infarction patients
Authors: Kip Michelle MA , Steuten Lotte MG , Koffijberg Hendrik , IJzerman Maarten J , Kusters Ron 
Published: October 2016

AbstractEarly health technology assessment can provide insight in the potential cost‐effectiveness of new tests to guide further development decisions. This can increase their potential benefit but often requires evidence which is lacking in early test development stages. Then, expert elicitation may be used to generate evidence on the impact of tests on patient management. This is illustrated in a case study on a new triple biomarker test (copeptin, heart‐type fatty acid binding protein, and high‐sensitivity troponin [HsTn]) at hospital admission. The elicited evidence enables estimation of the impact of using the triple biomarker on time to exclusion of non–ST elevation myocardial infarction compared with current serial HsTn measurement (performed 0, 2, and 6 h after admission). Cardiologists were asked to estimate the effect of the triple biomarker on patient's discharge rates and interventions performed, depending on its diagnostic performance. This elicited evidence was combined with Dutch reimbursement data and published evidence into a decision analytic model. Direct hospital costs and patients' discharge rates were assessed for 3 testing strategies including this triple biomarker (ie, only at admission or combined with HsTn measurements after 2 and 6 h). Direct hospital costs of suspected non–ST elevation myocardial infarction patients using serial HsTn measurements are estimated at €1825 per patient. Combining this triple biomarker with HsTn measurements after 2 and 6 hours is expected to be the most cost‐effective strategy. Depending on the diagnostic performance of the triple biomarker, this strategy is estimated to reduce costs with €66 to €205 per patient (ie, 3.6%‐11.3% reduction). Expert elicitation can be a valuable tool for early health technology assessment to provide an initial estimate of the cost‐effectiveness of new tests prior to their implementation in clinical practice. As demonstrated in our case study, improved diagnostic performance of the triple biomarker may have benefits that should be further explored.
Analyst Herding and Stock Price Crash Risk: Evidence from China
Authors: Xu Nianhang , Jiang Xuanyu , Chan Kam C. , Wu Shinong 
Published: October 2016

AbstractWe examine the proposition that firms with disproportionately more analysts herding in their coverage, as measured by a larger herding index value, have higher crash risk. Our findings are consistent with the main proposition. The results suggest that information production, rather than monitoring, is the primary mechanism behind the positive relation between herding and crash risk. Our conclusion is robust to different measures of crash risk, crash risk windows, herding measures, subsamples, and instrumental estimation. In addition, using post‐earnings announcement drift, we report that analyst herding slows down bad news transmission in the market. Our findings extend the literature by documenting that analyst herding plays a role in enhancing crash risk. Analyst herding has economic consequences on the covered firms. We offer support for the concern in the literature regarding analyst herding and market fluctuations.
Immunoglobulin M indirect‐fluorescent antibody test for the diagnosis of acute toxoplasmosis during pregnancy in the avidity era: A 14‐year experience at the Tuscany Reference Center for Infectious Diseases in Pregnancy, Florence, Italy
Authors: Trotta Michele , Borchi Beatrice , Zammarchi Lorenzo , Sterrantino Gaetana , Brogi Michela , Kiros Seble Tekle , Lorini Chiara , Bonaccorsi Guglielmo , Colao Maria Grazia , Bartoloni Alessandro 
Published: October 2016

AbstractAimThe aim of this study was to evaluate immunoglobulin M indirect‐fluorescent antibody test (IgM IFAT) for the diagnosis of acute or chronic Toxoplasma infection in pregnancy.MethodsPregnant women with suspected acute toxoplasmosis referred to the Tuscany Reference Center for Infectious Diseases in Pregnancy during the period 1998–2012 were retrospectively enrolled. All women were tested with a panel of serological tests, including enzyme‐linked immunosorbent assay for IgG avidity and IgM IFAT. On the basis of anamnestic, clinical, and serological criteria, pregnant women were classified into three groups: recently infected (RI), latently infected (LI), and doubtful latently infected (DLI). Patients classified as DLI were excluded from the analysis. The association between IgM IFAT (positive or negative) and the diagnosis of infection (acute or chronic) was assessed. Positive predictive value and negative predictive value of the IgM IFAT were calculated.ResultsA total of 810 pregnant women were enrolled in the study: 302 in the RI group and 508 in the LI group. Fifty‐two women classified as DLI were excluded. IgM IFAT was positive in 172 out of 302 (56.9%) pregnant women in the RI group and in 29 out of 508 (5.7%) in the LI group. The positive predictive value and negative predictive value of IgM IFAT in predicting RI was 85.6% and 78.6%, respectively.ConclusionIgM IFAT has reasonable sensitivity and specificity in diagnosing recent infection and, mostly in case of borderline avidity test, could be considered as a further aid for an accurate diagnosis of acute toxoplasmosis in pregnancy.