bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of intravitreal anti‐tumour necrosis factor drugs in adults with non‐infectious uveitis – a systematic review
Authors: Leal Inês , Rodrigues Filipe B , Sousa David Cordeiro , Romão Vasco C , Duarte Gonçalo S , Carreño Ester , Dick Andrew D , Marques‐Neves Carlos , Costa João , Fonseca João Eurico 
Published: March 2018

AbstractAnti‐tumour necrosis factor (TNF) drugs have been extensively used in non‐infectious uveitis (NIU), when corticosteroids or conventional immunosuppressive drugs cannot adequately control inflammation or intolerable side‐effects occur. However, systemic anti‐TNF therapies are also associated with a myriad of side‐effects. Therefore, intravitreal administration of anti‐TNF biologics has been employed to minimize patient morbidity and systemic adverse effects, while maintaining therapeutic effectivity. We undertook a systematic review to determine evidence of efficacy and safety of intravitreal administration of anti‐TNF drugs in adults with NIU. We conducted this systematic review according to the PRISMA guidelines. The protocol was registered with PROSPERO (CRD42016041946). We searched CENTRAL, MEDLINE and EMBASE, from inception to April 2017, as well as clinical trial registries and grey literature. The qualitative analysis included all studies of adult patients with a diagnosis of NIU and who received intravitreal anti‐TNF drugs with a 4‐week minimum follow‐up. A total of 4840 references were considered for title and abstract screening. Seven full texts were screened, and five studies were considered for analysis. All studies were open‐label, single‐centre, prospective, non‐randomized, interventional case series with a follow‐up between 4 and 26 weeks, employing either adalimumab in two studies and infliximab in three. Three studies showed a treatment effect of anti‐TNF intravitreal injections, while one study revealed short‐term improvement and one study revealed no efficacy of anti‐TNF intravitreal therapy. None of the studies reported ocular adverse effects but only two studies included electrophysiological assessment in the safety analysis and no study assessed systemic human anti‐drug antibodies. The available evidence is not sufficiently robust to conclude about the clinical effectivity of intravitreal anti‐TNF in NIU and so no recommendation can be made. In conclusion, intravitreal injection of anti‐TNF antibodies remains a possible treatment option to be explored through robust clinical investigation.
Safety and feasibility of laparoscopic gastrectomy accompanied by D1+ lymph node dissection for early gastric cancer in elderly patients
Authors: Yasukawa Daiki , Kadokawa Yoshio , Kato Shigeru , Aisu Yuki , Hori Tomohide 
Published: March 2018

AbstractIntroductionThe age of patients with gastric cancer has increased worldwide. The aim of this study was to investigate the safety and feasibility of laparoscopic gastrectomy (LG) for early gastric cancer in elderly patients.MethodsWe retrospectively investigated 221 consecutive patients who underwent LG for early gastric cancer during a 5‐year period (January 2010 to December 2014). We divided the patients into two groups: elderly patients (≥75 years old) and younger patients (<75 years old). We compared these two groups with respect to clinical characteristics, histopathological findings, intraoperative factors, and postoperative outcomes.ResultsThe preoperative characteristics were similar in both groups. Except for the number of harvested lymph nodes (42.0 vs 34.9; P = 0.0016), the short‐term operative outcomes, including postoperative complications and histopathological findings, were comparable between the two groups. Although significantly fewer lymph nodes were harvested in the elderly group, the overall survival and relapse‐free survival rates did not significantly differ between the groups. Postoperative complications, such as acute cholecystitis and internal hernia, occurred during the long‐term postoperative period after LG, and these unexpected complications were more frequently observed in elderly patients. All elderly patients required additional emergent surgeries for delayed complications.ConclusionThe outcomes of LG for early gastric cancer in elderly patients seem to be reasonable. Aggressive lymph node dissection may be omissible in elderly patients with acceptable results. LG can be a safe and feasible procedure in elderly patients. However, the higher rate of delayed but urgent complications during the long‐term postoperative period must be considered.
Carbon Monoxide‐Releasing Molecule Enhances Coagulation and Decreases Fibrinolysis in Normal Canine Plasma
Authors: Donaghy Dillon , Yoo Seung , Johnson Tyler , Nielsen Vance , Olver Christine 
Published: March 2018

AbstractThe dog is an important companion animal and also purpose‐bred for research studies. Coagulopathies in dogs are common, although the availability of blood products for therapy is inconsistent throughout the profession. A pro‐coagulant therapeutic that is readily available and easily stored would be useful for the treatment of coagulopathies. Tricarbonyldichlororuthenium (II) dimer [Carbon monoxide‐releasing molecule‐2 (CORM‐2)] acts as a prothrombotic agent in plasma by increasing the velocity of clot formation and clot strength, and by decreasing the clot's vulnerability to fibrinolysis. We sought to test CORM‐2's effect on coagulation and fibrinolysis in vitro in canine plasma using thromboelastography. Measures of the rate of clot formation and clot strength in plasma without CORM‐2 were highly correlated with fibrinogen concentration. We found that CORM‐2 significantly enhanced the rate of clot formation and clot strength and significantly reduced the rate of fibrinolysis and the clot lysis time. The per cent change in rate of clot formation and clot strength was not significantly correlated with fibrinogen concentration, indicating that CORM‐2's pro‐coagulant effect is not dependent on fibrinogen concentration. This study corroborates studies in other species that show that CORM‐2 is pro‐coagulant in plasma, and lays the groundwork for developing CORM‐2 as a therapeutic agent for canine coagulopathies. Future studies will evaluate the effect of CORM‐2 on whole blood both in vitro and in vivo.
Bayesian Nonparametric Generative Models for Causal Inference with Missing at Random Covariates
Authors: Roy Jason , Lum Kirsten J. , Zeldow Bret , Dworkin Jordan D. , Re Vincent Lo , Daniels Michael J. 
Published: March 2018

SummaryWe propose a general Bayesian nonparametric (BNP) approach to causal inference in the point treatment setting. The joint distribution of the observed data (outcome, treatment, and confounders) is modeled using an enriched Dirichlet process. The combination of the observed data model and causal assumptions allows us to identify any type of causal effect—differences, ratios, or quantile effects, either marginally or for subpopulations of interest. The proposed BNP model is well-suited for causal inference problems, as it does not require parametric assumptions about the distribution of confounders and naturally leads to a computationally efficient Gibbs sampling algorithm. By flexibly modeling the joint distribution, we are also able to impute (via data augmentation) values for missing covariates within the algorithm under an assumption of ignorable missingness, obviating the need to create separate imputed data sets. This approach for imputing the missing covariates has the additional advantage of guaranteeing congeniality between the imputation model and the analysis model, and because we use a BNP approach, parametric models are avoided for imputation. The performance of the method is assessed using simulation studies. The method is applied to data from a cohort study of human immunodeficiency virus/hepatitis C virus co-infected patients.
Identification of potent and selective small molecule inhibitors of the cation channel TRPM4
Authors: Ozhathil Lijo Cherian , Delalande Clémence , Bianchi Beatrice , Nemeth Gabor , Kappel Sven , Thomet Urs , Ross‐Kaschitza Daniela , Simonin Céline , Rubin Matthias , Gertsch Jürg , Lochner Martin , Peinelt Christine , Reymond Jean‐Louis , Abriel Hugues 
Published: March 2018

Background and PurposeTRPM4 is a calcium‐activated non‐selective cation channel expressed in many tissues and implicated in several diseases, and has not yet been validated as a therapeutic target due to the lack of potent and selective inhibitors. We sought to discover a novel series of small‐molecule inhibitors by combining in silico methods and cell‐based screening assay, with sub‐micromolar potency and improved selectivity from previously reported TRPM4 inhibitors.Experimental ApproachHere, we developed a high throughput screening compatible assay to record TRPM4‐mediated Na+ influx in cells using a Na+‐sensitive dye and used this assay to screen a small set of compounds selected by ligand‐based virtual screening using previously known weakly active and non‐selective TRPM4 inhibitors as seed molecules. Conventional electrophysiological methods were used to validate the potency and selectivity of the hit compounds in HEK293 cells overexpressing TRPM4 and in endogenously expressing prostate cancer cell line LNCaP. Chemical chaperone property of compound 5 was studied using Western blots and electrophysiology experiments.Key ResultsA series of halogenated anthranilic amides were identified with TRPM4 inhibitory properties with sub‐micromolar potency and adequate selectivity. We also showed for the first time that a naturally occurring variant of TRPM4, which displays loss‐of‐expression and function, is rescued by the most promising compound 5 identified in this study.Conclusions and ImplicationsThe discovery of compound 5, a potent and selective inhibitor of TRPM4 with an additional chemical chaperone feature, revealed new opportunities for studying the role of TRPM4 in human diseases and developing clinical drug candidates.
Co‐expression of μ and δ opioid receptors by mouse colonic nociceptors
Authors: Guerrero‐Alba Raquel , Valdez‐Morales Eduardo Emmanuel , Jiménez‐Vargas Nestor Nivardo , Bron Romke , Poole Daniel , Reed David , Castro Joel , Campaniello Melissa , Hughes Patrick A , Brierley Stuart M , Bunnett Nigel , Lomax Alan E , Vanner Stephen 
Published: March 2018

Background and PurposeTo better understand opioid signalling in visceral nociceptors, we examined the expression and selective activation of μ and δ opioid receptors by dorsal root ganglia (DRG) neurons innervating the mouse colon.Experimental ApproachDRG neurons projecting to the colon were identified by retrograde tracing. δ receptor‐GFP reporter mice, in situ hybridization, single‐cell RT‐PCR and μ receptor‐specific antibodies were used to characterize expression of μ and δ receptors. Voltage‐gated Ca2+ currents and neuronal excitability were recorded in small diameter nociceptive neurons (capacitance <30 pF) by patch clamp and ex vivo single‐unit afferent recordings were obtained from the colon.Key ResultsIn situ hybridization of oprm1 expression in Fast Blue‐labelled DRG neurons was observed in 61% of neurons. μ and δ receptors were expressed by 36–46% of colon DRG neurons, and co‐expressed by ~25% of neurons. μ and δ receptor agonists inhibited Ca2+ currents in DRG, effects blocked by opioid antagonists. One or both agonists inhibited action potential firing by colonic afferent endings. Incubation of neurons with supernatants from inflamed colon segments inhibited Ca2+ currents and neuronal excitability. Antagonists of μ, but not δ receptors, inhibited the effects of these supernatant on Ca2+ currents, whereas both antagonists inhibited their actions on neuronal excitability.Conclusions and ImplicationsA significant number of small diameter colonic nociceptors co‐express μ and δ receptors and are inhibited by agonists and endogenous opioids in inflamed tissues. Thus, opioids that act at μ or δ receptors, or their heterodimers may be effective in treating visceral pain.
Upregulation of CXCR4 through promoter demethylation contributes to inflammatory hyperalgesia in rats
Authors: Li Feng , Xue Zhou‐Ya , Yuan Yuan , Huang Sai‐Sai , Fan Yi‐Hui , Zhu Xiang , Wei Lei 
Published: March 2018

SummaryAim and methodsChronic pain associated with inflammation is a common clinical problem, and the underlying mechanisms yet are incompletely defined. DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under inflammatory pain condition remain largely unknown. Here, we investigated how chemokine receptor CXCR4 expression is regulated by DNA methylation and how it contributes to inflammatory pain induced by complete Freund's adjuvant (CFA) in rats.ResultsIntraplantar injection of CFA could not only induce significant hyperalgesia in rats, but also significantly increase the expression of CXCR4 mRNA and protein in the dorsal root ganglion (DRG). Intrathecal injection of CXCR4 antagonist AMD3100 significantly relieved hyperalgesia in inflammatory rats in a time‐ and dose‐dependent manner. Bisulfite sequencing and methylation‐specific PCR demonstrate that CFA injection led to a significant demethylation of CpG island at CXCR4 gene promoter. Consistently, the expression of DNMT3b was significantly downregulated after CFA injection. Online software prediction reveals three binding sites of p65 in the CpG island of CXCR4 gene promoter, which has confirmed by the chromatin immunoprecipitation assay, CFA treatment significantly increases the recruitment of p65 to CXCR4 gene promoter. Inhibition of NF‐kB signaling using p65 inhibitor pyrrolidine dithiocarbamate significantly prevented the increases of the CXCR4 expression.ConclusionUpregulation of CXCR4 expression due to promoter demethylation followed by increased recruitment of p65 to promoter of CXCR4 gene contributes to inflammatory hyperalgesia. These findings provide a theoretical basis for the treatment of chronic pain from an epigenetic perspective.
Patient‘s perspective on long‐term complications after superficial parotidectomy for benign lesions: Prospective analysis of a 2‐year follow‐up
Authors: Wolber P. , Volk G.F. , Horstmann L. , Finkensieper M. , Shabli S. , Wittekindt C. , Klussmann J.P. , Guntinas‐Lichius O. , Beutner D. , Grosheva M. 
Published: March 2018

ObjectiveEvaluation of patients′ perspective on long‐term complications after superficial parotidectomy for benign lesions.DesignA prospective nonrandomized controlled multicenter study.SettingThree university‐based tertiary referral centers (Departments of Otorhinolaryngology of Cologne, Jena and Giessen; all in Germany).Participants130 adult patients, who underwent a primary superficial parotidectomy for benign tumors of the parotid gland, were consecutively included from 09/2010 to 05/2012. 61 patients completed every follow‐up examination.Main outcome measuresComplications were evaluated using the validated German‐language questionnaire Parotidectomy Outcome Inventory 8 at six, 12 and 24 months after surgery. Pain intensity was assessed on a numeric rating scale (NRS) at each follow‐up visit.ResultsAt 6 months after surgery, 90% characterized hypoesthesia as the most disturbing problem, followed by fear of revision surgery (57%) and scar (56%). Facial palsy (14%) posed the minor problem. Hypoesthesia improved significantly during the follow‐up period (all P < .05), but still posed a problem for 78% of the patients after 2 years. Pain, which initially bothered 53% of the patients, significantly decreased, whereas impairment due to Frey′s syndrome significantly increased during the follow‐up (6 vs 24 months; P = .002 and P = .001, respectively). Scar, substance loss, xerostomia, facial palsy, and anxiety affected patients with unvarying severity during the 2 years (all P > .05).ConclusionsFrom patients′ perspective, sensation loss posed the major subjective problem after superficial parotidectomy. Appearance of the scar, and fear of revision surgery impaired more than 50% of the patients in their daily life without significant improvement during the 2 years postoperatively. Although superficial parotidectomy is a highly standardized and safe procedure, limited parotidectomy for proven benign parotid salivary gland neoplasms is more likely to result in patients with minimal or no displeasing complications.
Prognostic value of inferior mesenteric artery lymph node metastasis in cancer of the descending colon, sigmoid colon and rectum
Authors: Rao X. , Zhang J. , Liu T. , Wu Y. , Jiang Y. , Wang P. , Chen G. , Pan Y. , Wu T. , Liu Y. , Wan Y. , Huang S. , Wang X. 
Published: March 2018

AbstractAimThis study aimed to analyse the potential significance of metastasis to the inferior mesenteric artery lymph node (IMA‐LN) in patients with malignancy of the left colon and rectum.MethodA retrospective analysis of a cohort of 890 patients collected prospectively who underwent radical resection of a primary tumour of the descending colon, sigmoid colon and rectum in our department from 1 January 2009 to 31 December 2015 was performed. Patients were divided into an IMA‐LN metastasis (IMA‐LN (+)) group (n = 51) and a non IMA‐LN metastasis (IMA‐LN (‐)) group (n = 839). A total of 801 patients were followed by a designated member of the study staff. Clinical features, pathological characteristics, recurrence patterns and survival rates were compared between the two groups.ResultsIn the IMA‐LN (+) group, the risk ratio of overall recurrence and tumour related death was 7.786 (95% CI 4.142–14.637) and 7.756 (95% CI 4.142–14.525) respectively. Significant differences were found in overall survival (log‐rank: χ2 = 69.06, P < 0.0001) and disease‐free survival (log‐rank: χ2 = 69.06, P < 0.0001) between the two groups. Furthermore, there were significant differences in overall survival (log‐rank: χ2 = 18.47, P < 0.0001) and disease‐free survival (log‐rank: χ2 = 16.99, P < 0.0001) between the IMA‐LN (−) and IMA‐LN (+) subgroups of patients with Stage N2 disease. Multivariate survival analysis indicated that IMA‐LN (+) was an independent risk factor of poor prognosis. There was no difference in the prognosis between high tie and low tie with IMA‐LN dissection.ConclusionInferior mesenteric artery lymph node metastasis was an independent predictive factor for high systemic recurrence. Low ligation of the IMA with IMA‐LN dissection was not inferior to high ligation.
Corporate governance of audit firms: Assessing the usefulness of transparency reports in a Europe‐wide analysis
Authors: La Rosa Fabio , Caserio Carlo , Bernini Francesca 
Published: March 2018

AbstractManuscript TypeEmpiricalResearch Question/IssueBased on both institutionalized agency theory and meso‐level theory, this study examines corporate governance disclosure in an audit firm's transparency report (TR) and whether more disclosure is associated with (a) the audit function of the country in which it is disclosed; (b) high levels of investor confidence in public interest entities (PIEs) shown in the portfolio of the audit firm; and (c) increased competition within the audit market.Research Findings/InsightsOn the basis of content analysis, different measures of a corporate governance disclosure index (CGDI) are calculated for a sample of 122 auditing firms from 10 European countries over the period 2010–2012. Despite attempts at harmonizing audit practice across the EU, results confirm the role of institutional context in explaining differences among European countries. Moreover, while the CGDI reveals that the TR does improve investor confidence, no evidence was found that the new disclosure requirement unsettled audit market concentration.Theoretical/Academic ImplicationsResults support arguments of the institutionalized agency theory that audit firms’ corporate governance disclosures depend on both firm‐ and country‐level factors. Moreover, the interplay between these macro and meso factors explains the information asymmetry reduction that exists between auditors and shareholders, thus improving micro‐level investor confidence.Practitioner/Policy ImplicationsThe study provides an analysis of audit firm transparency based on the information disclosed in mandatory TRs. Policymakers and practitioners may benefit from the knowledge of items included in the TRs expected to impact on investor confidence. It also proposes the use of the TR for achieving market competition strategies, although it may be inefficient.
Specificity of the Association between Marital Discord and Longitudinal Changes in Symptoms of Depression and Generalized Anxiety Disorder in the Irish Longitudinal Study on Ageing
Authors: Whisman Mark A. , Robustelli Briana L. , Labrecque Lindsay T. 
Published: March 2018

This longitudinal study was conducted to evaluate actor and partner effects of marital discord on changes in symptoms of depression and generalized anxiety disorder (GAD) in a large population sample of Irish adults (N = 1,445 couples), adjusting for the potential confounds of quality of other social relationships and other psychopathology symptoms. The Actor–Partner Interdependence Model was used to examine actor and partner effects of marital discord on changes in symptoms of depression and GAD at a 2‐year follow‐up. Additional models examined these associations adjusting for family and friend discord and symptoms of the other type of psychopathology (depressive or GAD symptoms). Actor effects of marital discord on depressive and anxiety symptoms were greater for men than for women. There were significant, positive actor effects of marital discord on depressive symptoms for husbands and wives, which remained significant when adjusting for family and friend discord and GAD symptoms. There were significant, positive actor effects of marital discord on GAD symptoms for husbands, which remained significant when adjusting for family and friend discord and depressive symptoms. Results demonstrate that longitudinal associations between marital discord and depressive symptoms (for wives and husbands) and GAD symptoms (for husbands) are incremental to other rival explanations (family and friend discord and the other set of symptoms). Findings provide evidence for a potential causal association leading from marital discord to symptoms of depression and GAD.
Associations of Army Fathers’ PTSD Symptoms and Child Functioning: Within‐ and Between‐Family Effects
Authors: Parsons Aleja , Knopp Kayla , Rhoades Galena K. , Allen Elizabeth S. , Markman Howard J. , Stanley Scott M. 
Published: March 2018

This study examined the within‐family and between‐family associations between fathers’ military‐related PTSD symptoms and parent ratings of children's behavioral and emotional problems. The sample included married couples (N = 419) with children composed of a civilian wife and an active‐duty husband serving in the U.S. Army. Results indicate that changes in fathers’ PTSD symptoms over time were associated with corresponding changes in both mothers’ and fathers’ reports of child behavioral and emotional problems. These within‐family findings were independent from between‐family effects, which showed that higher average PTSD symptomatology was associated with more overall behavioral and emotional problems for children. This study uses advances in statistical methodologies to increase knowledge about how PTSD symptoms and child problems are related, both across different families and over time within families.