bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment
Authors: Kosten Thomas R. , Baxter Louis E. 
Published: January 2019

Background and ObjectivesThe opioid crisis has taken an immense toll in the United States. On average, five lives are lost to an opioid overdose every hour of the day; estimated costs associated with opioid misuse exceed $500 billion annually. Illicit opioid discontinuation is the first step in the treatment of opioid use disorder (OUD), and transition to an opioid agonist may initiate treatment. However, discontinuation to abstinence from either OUD directly or following agonist treatment results in severely distressing opioid withdrawal symptoms (OWS).MethodsThis review evaluated studies on the etiology, burden, and management of OWS.ResultsNoradrenergic hyperactivity generates many OWS. These OWS can cause patients to relapse during early opioid discontinuation. While agonist therapies are generally first‐line for moderate or severe OUD and reduce OWS, prescribing restrictions can limit their availability.Discussion and ConclusionsNon‐opioid medications to treat OWS provides a gateway into long‐term treatment with naltrexone or psychosocial therapies. For opioid dependent patients without OUD, non‐opioid treatments like α‐2 adrenergic agonists can facilitate opioid tapering.Scientific SignificanceFor the millions who are physically dependent on opioids, new treatments for OWS can enhance recovery from OUD and prevent relapse. (© 2019 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc.;XX:1–8)
Preclinical efficacy of an anti‐methamphetamine vaccine using E6020 adjuvant
Authors: Arora Reetakshi , Haile Colin N. , Kosten Therese A. , Wu Yan , Ramakrishnan Muthu , Hawkins Lynn D. , Orson Frank M. , Kosten Thomas R. 
Published: January 2019

Background and ObjectiveMethamphetamine (MA) substance use disorder (SUD) does not have an efficacious pharmacotherapy. We developed a MA vaccine and investigated its potential to attenuate MA induced responses.MethodsWe examined a novel adjuvant, E6020, a Toll‐like receptor‐4 (TLR‐4) agonist combined with tetanus‐toxoid conjugated to succinyl‐methamphetamine (TT‐SMA) adsorbed on aluminum hydroxide (alum). Adult BALB/c female mice received the vaccine and booster injections at weeks 0, 3, and 6. The efficacy of the vaccine was assessed by the level and affinity of anti‐MA antibodies elicited, its ability to attenuate MA induced locomotor activation and its reduction in the amount of MA entering the brains of vaccinated mice.ResultsThe TT‐SMA vaccine containing alum and E6020 adjuvant produced anti‐MA antibodies with nanomolar affinities and showed threefold greater peak titer levels than without E6020 (700 vs 250 μg/ml). These antibodies significantly decreased MA‐induced locomotor activation (p < .05), and reduced the brain (p < .005) MA levels following MA administration in actively immunized mice.ConclusionsThus, this anti‐MA vaccine formulated with E6020 demonstrated effective functional protection against behavioral disruptions induced by MA.Scientific SignificanceTogether, anti‐MA vaccine showing a promising improvement in the efficacy of the vaccine that could be an effective candidate vaccine for methamphetamine use disorder (MUD). Furthermore, combinations of adjuvants may be a tool to design vaccines for MA dependence in humans. (Am J Addict 2019;XX:1–8)
Timing of brain metastases development in metastatic renal cell cancer patients treated with targeted therapies and survival outcomes: An Australian multicenter study
Authors: Ha Francis J. , Spain Lavinia , Dowling Anthony , Kwan Edmond M. , Pezaro Carmel , Day Daphne , Chia Puey Ling , Tran Ben , Pook David , Weickhardt Andrew J. 
Published: January 2019

AbstractAimTargeted therapy (TT) has improved survival for metastatic renal cell carcinoma (mRCC). However, survival is usually limited if brain metastases (BMs) develop. We aimed to evaluate survival outcomes in mRCC patients based on timing of BM diagnosis.MethodsWe conducted a multicenter, retrospective study of mRCC patients with BM who received TT at any point between 2005 and 2014. We determined overall survival (OS) from stage IV diagnosis, TT initiation and BM diagnosis, and prognostic factors. Patients were grouped into three categories: synchronous‐BM, metachronous‐BM diagnosed while conservatively managed (metachronous‐BM before TT) and metachronous‐BM diagnosed during TT. Survival was calculated by Kaplan–Meier method and predictors were calculated using Cox hazards regression.ResultsIncidence of BM was 17% in mRCC patients treated with TT (two centers). Fifty‐four mRCC‐BM patients were identified from five tertiary centers. Twenty‐eight percentage (15/54) had synchronous‐BM, 28% (15/54) had metachranous‐BM before TT and 44% (24/54) had metachronous‐BM during TT. Most had central nervous system (CNS) symptoms at BM diagnosis (78%; 42/54). Median OS from stage IV diagnosis, TT commencement and BM diagnosis was 28 months (95% confidence interval [CI] 16–43), 19 months (95% CI 9–26) and 9 months (95% CI 5–16), respectively. Synchronous‐BM group trended toward poorer survival from TT commencement (P = 0.06). Metachronous‐BM during TT group had lower survival from BM diagnosis than synchronous‐BM and metachronous‐BM before TT group (P < 0.001). Eight of 50 deaths (16%) were from neurological complications. The presence of CNS symptoms did not predict worse survival from stage IV diagnosis (P = 0.73).ConclusionIn patients with mRCC, the development of BM while on TT portends shorter prognosis compared with synchronous diagnosis of BM at stage IV disease or metachronous BM developed prior to commencing TT. The presence of CNS symptoms does not predict worse survival.
The Sensible Life of Return: Collaborative Experiments in Art and Anthropology in Palestine/Israel
Authors: Strohm Kiven 
Published: January 2019

ABSTRACTAs a younger generation of Palestinians have started to return to the lands and villages of their parents and grandparents over the last decade, they have come to acknowledge a sensible world for which they have no immediate experience. The smell of wild za'atar, the sound of the breeze roaming the land, and the stories of trees and rocks are all experiences handed down by their parents and grandparents, heretofore unavailable to their own sensible life. This article is about a project‐to‐come that attends to these returns and the sensible/material worlds being invented. It is about the making of a collaboration between an anthropologist and an artist to create an experimental laboratory for Palestinians returning to their former lands and villages for speculating about their futures or what is yet to come. [Landscape, Sensible Colonialism, Materiality, Participatory Art, Palestine/Israel]
Suprachoroidally injected pharmacological agents for the treatment of chorio‐retinal diseases: a targeted approach
Authors: Habot‐Wilner Zohar , Noronha Glenn , Wykoff Charles C. 
Published: January 2019

AbstractDelivery of pharmaceuticals to the posterior segment presents challenges that arise from the anatomy and clearance pharmacokinetics of the eye. Systemic and several local administration options [topical, periocular, intravitreal (IVT) and subretinal] are in clinical use, each with a unique benefit to risk profile shaped by factors including the administered agent, frequency of dosing, achievable pharmaceutical concentrations within posterior segment structures versus elsewhere in the eye or the body, invasiveness of the procedure and the inherent challenges with some administration methods. The use of the suprachoroidal space (SCS), which is the region between the sclera and the choroid, is being explored as a potential approach to target pharmacotherapies to the posterior segment via a minimally invasive injection procedure. Preclinical data on agents such as vascular endothelial growth factor inhibitors and triamcinolone acetonide (TA) indicate that administration via suprachoroidal injection results in more posterior distribution of the pharmacologic agent, with higher exposure to the sclera, choroid, retinal pigment epithelium cells and retina, and lesser exposure to the anterior segment, than observed with IVT administration. Based in part on these findings, clinical trials have explored the efficacy and safety of suprachoroidal administration of pharmacologic therapies in conditions affecting the posterior segment. Data on a proprietary formulation of TA administered by suprachoroidal injection show improvement in anatomic and visual outcomes in subjects with noninfectious uveitis, with the potential to mitigate the known risks of cataract and increased intraocular pressure (IOP) associated with the use of intraocular corticosteroids. Suprachoroidal administration appears to be a promising treatment modality and is also in the early stages of investigation for other possible applications, such as injection of antiglaucoma agents into the anterior SCS for long‐lasting control of elevated IOP, and as a mode of delivery for gene‐ or cell‐based therapies for retinal disorders.
Adequacy of scoring systems in diagnosing paediatric autoimmune hepatitis: retrospective study using a control group children with Hepatitis B infection
Authors: Niţă Andreia Florina , Păcurar Daniela 
Published: January 2019

AbstractAimTo evaluate how correct is made the diagnosis of autoimmune hepatitis (AIH) in children, comparing the adults scoring systems – the 1999 revised scoring system by International Autoimmune Hepatitis Group and the 2007 Simplified Scoring System. The inaccuracies in diagnosis have been analysed.MethodsThe two scoring systems have been applied for 28 children with AIH pre‐treatment and 28 with Hepatitis B infection – matched by sex and age, all diagnosed between 2010 and 2017 in an emergency children's hospital in Bucharest, Romania. They were retrospectively followed throughout the period assessed.ResultsAutoimmune hepatitis was present in 85.7% cases according to the 1999 revised score, respectively, 57.0% as per the 2007 simplified score. The 2007 simplified score led to false negative results when AIH was associated with another autoimmune disease (p = 0.009). Patients who did not undergo liver biopsy were associated with a downgraded diagnosis by the 2007 simplified score (p = 0.001).ConclusionThere is a need for a scoring system tailored to children's characteristics. Two compulsory components of the future score might be liver biopsy and associated autoimmune disorders. The existing scores could be used in children with consideration, preferably both at once and together with liver biopsy for increased accuracy.
The interplay of corporate social responsibility and corporate political activity in emerging markets: The role of strategic flexibility in non‐market strategies
Authors: Kamasak Rifat , James Simon R. , Yavuz Meltem 
Published: January 2019

AbstractCorporate social responsibility (CSR) and corporate political activities are complementary, and the coordinated management of corporate social responsibility and corporate political activities may lead to better firm performance. However, corporate social responsibility and corporate political activities should be aligned carefully to utilize this complementarity. Strategic flexibility, which is the ability of a firm to adapt to changes in the external environment and make necessary organizational modifications quickly, can help firms to align their corporate social responsibility and corporate political activities. This paper empirically investigates the political dimension and the interactive dimension which describes interactions between corporate social responsibility and corporate political activities together with strategic flexibility and their effects on firm performance through a study of 142 firms in Turkey using moderated multiple regression methods. The results show that, while the political dimension had an inverted U‐shaped effect on firm performance, indicating that only a moderate level of corporate political activities may improve financial performance, the interactive dimension had positive but limited implications for performance. Finally, it was found strategic flexibility plays a positive moderating role on the relationships between the interactive dimension and firm performance. It is concluded that complementarity between corporate social responsibility and corporate political activities which may result in better performance is contingent on strategic flexibility.
AMPK signalling: Implications for podocyte biology in diabetic nephropathy
Authors: Szrejder Maria , Piwkowska Agnieszka 
Published: January 2019

AbstractDiabetic nephropathy is a major long‐term complication of diabetes mellitus and one of the most common causes of end‐stage renal disease. Thickening of the glomerular basement membrane, glomerular cell hypertrophy and podocyte loss are among the main pathological changes that occur during diabetic nephropathy, resulting in proteinuria. Injury to podocytes, which are a crucial component of the glomerular filtration barrier, seems to play a key role in the development of diabetic nephropathy. Recent studies have suggested that dysregulation of AMP‐activated kinase protein, which is an essential cellular energy sensor, may play a fundamental role in this process. The purpose of this review is to highlight the molecular mechanisms associated with AMP‐activated protein kinase (AMPK) in podocytes that are involved in the pathogenesis of diabetic nephropathy.
Nuclear envelope dynamics during mammalian spermatogenesis: new insights on male fertility
Authors: Pereira Cátia D. , Serrano Joana B. , Martins Filipa , da Cruz e Silva Odete A. B. , Rebelo Sandra 
Published: January 2019

ABSTRACTThe production of highly specialized spermatozoa from undifferentiated spermatogonia is a strictly organized and programmed process requiring extensive restructuring of the entire cell. One of the most remarkable cellular transformations accompanying the various phases of spermatogenesis is the profound remodelling of the nuclear architecture, in which the nuclear envelope (NE) seems to be crucially involved. In recent years, several proteins from the distinct layers forming the NE (i.e. the inner and outer nuclear membranes as well as the nuclear lamina) have been associated with meiosis and/or spermiogenesis in different mammalian species. Among these are A‐ and B‐type lamins, Dpy‐19‐like protein 2 (DPY19L2), lamin B receptor (LBR), lamina‐associated polypeptide 1 (LAP1), LAP2/emerin/MAN1 (LEM) domain‐containing proteins, spermatogenesis‐associated 46 (SPATA46) and diverse elements of the linker of nucleoskeleton and cytoskeleton (LINC) complex, namely Sad‐1/UNC‐84 homology (SUN) and Klarsicht/ANC‐1/Syne‐1 homology (KASH) domain‐containing proteins. Herein, we summarize the current state of the art on the cellular and subcellular distribution of NE proteins expressed during mammalian spermatogenesis, and discuss the latest research developments regarding their testis‐specific functions. This review provides a comprehensive and innovative overview of the NE network as a regulatory platform and as an essential determinant of efficient meiotic chromosome recombination as well as spermiogenesis‐associated nuclear remodelling and differentiation in mammalian male germline cells. Thus, this review provides important novel insights on the biological relevance of NE proteins for male fertility.
Spectrophotometric versus spectrofluorometric assessment in the study of the relationships between lipid peroxidation and metabolic dysregulation
Authors: Ungurianu Anca , Șeremet Oana , Grădinaru Daniela , Ionescu‐Tîrgoviște Constantin , Margină Denisa , Dănciulescu Miulescu Rucsandra 
Published: January 2019

AbstractReactive oxygen species are crucial to normal cell function, but are also part of the pathogenesis of multiple modern maladies. As such, sensitive, fast, and reliable methods of appreciating redox status are needed. We aimed to optimize the Amplex Red (AR) and ferric–xylenol orange (FOX) methods using human serum samples, rat tissue homogenates, and mitochondrial preparations. For AR, we intended to reduce probe concentration, maintaining method sensitivity, as well as extending its use from isolated lipoproteins samples, and readjust it for a high‐throughput application. Also, we evaluated the usefulness of a modified xylenol orange‐based spectrophotometric protocol, comparing and contrasting these methods in terms of clinical relevance and suitability for their further use in assessing redox status of various biological samples in different pathological conditions. Our results show that these optimized protocols are suitable for complex in vivo studies, as they require low quantities of sample and reagents, and are sensitive, rapid, and economical, with the option of adapting them for high‐throughput analysis. For a better assessment of oxidative status of serum‐derived samples, the two methods can be used concurrently, while for tissue‐derived ones, either can be employed for the measurement of a global redox status.
Etiology and classification of food impaction around implants and implant‐retained prosthesis
Authors: Chopra Aditi , Sivaraman Karthik , Narayan Aparna I , Balakrishnan Dhanasekar 
Published: January 2019

AbstractBackgroundFood impaction is a common risk factor for the initiation of peri‐implant inflammation and failure of the osseointegrated implant. Although clinicians do acknowledge the presence of food impaction around implants and implant‐retained prosthesis, no classification system has yet classified the food impaction around the implant and implant‐retained prosthesis.PurposeThe present paper aims to identify and classify the plausible etiology of food impaction around implants and implant‐related prosthesis.Materials and MethodsThe following search terms were utilized for data search: “Food Impaction” AND “Implants” AND “Food Impaction” AND “Perimplantitis” AND “Food Impaction” AND “Classification.” Articles that were written in the English language in PubMed and Cochrane Library database from 1930 till September 2018 were scrutinized. A total of 24 articles were scrutinized, out of which only 15 articles were selected.ResultsFood impaction around implants is broadly classified into five categories based on the number of implants, nature of implants prosthesis involved for replacement and relation of the implant prosthesis to the adjacent tooth, restoration, or prosthesis.ConclusionThis is the first classification designed to classify food impaction around dental implants and implant‐retained prosthesis. The classification can be used by clinicians for optimal diagnosis, interpretation, and treatment plan for patients.
PASOS: a method for the phylogenetic analysis of shape ontogenies
Authors: Catalano Santiago A. , Segura Valentina , Vera Candioti Florencia 
Published: January 2019

AbstractWe present a novel phylogenetic approach to infer ancestral ontogenies of shape characters described as landmark configurations. The method is rooted in previously published theoretical developments to analyse landmark data in a phylogenetic context with parsimony as the optimality criterion, in this case using the minimization of differences in landmark position to define not only ancestral shapes but also the changes in developmental timing between ancestor–descendant shape ontogenies. Evolutionary changes along the tree represent changes in relative developmental timing between ontogenetic trajectories (possible heterochronic events) and changes in shape within each stage. The method requires the user to determine the shape of the specimens between two standard events, for instance birth and onset of sexual maturity. Once the ontogenetic trajectory is discretized into a series of consecutive stages, the method enables the user to identify changes in developmental timing associated with changes in the offset and/or onset of the shape ontogenetic trajectories. The method is implemented in a C language program called SPASOS. The analysis of two empirical examples (anurans and felids) using this novel method yielded results in agreement with previous hypotheses about shape evolution in these groups based on non‐phylogenetic analyses.
Short‐ and long‐term outcomes of laser haemorrhoidoplasty for grade II–III haemorrhoidal disease
Authors: Faes S. , Pratsinis M. , Hasler‐Gehrer S. , Keerl A. , Nocito A. 
Published: January 2019

AbstractAimLaser haemorrhoidoplasty is associated with minimal postoperative pain and good symptom improvement in the short‐term. However, less is known about its long‐term efficacy. This study aims to determine the short‐ and long‐term outcomes of laser haemorrhoidoplasty.MethodBetween October 2010 and May 2012, 50 consecutive patients with grade II–III haemorrhoids were treated with laser haemorrhoidoplasty. Short‐term follow‐up was assessed on days 1, 30 and 60 and long‐term follow‐up was at 5 years (haemorrhoidal stage reduction, pain, patient satisfaction, symptom improvement, incapacity for work, continence, complications, recurrence).ResultsShort‐term follow‐up was achieved for all patients and long‐term follow‐up for 44/50 patients (88%). At short‐term follow‐up, haemorrhoidal stage reduction was documented in 49 (98%) patients. Complete or good symptom improvement was reported by 36/50 (72%) and 10/50 patients (20%) at 60 days. Postoperative complications occurred in 9/50 patients (18%) with three Clavien–Dindo grade IIIb complications (two fistulas, one incontinence), one grade IIIa (perianal thrombosis) and five grade I (one perianal thrombosis, two perianal eczema, one local bleeding, one anal fissure). Postoperative pain was low (visual analogue scale 0–1) at day 1 in 37/50 (74%), at day 30 in 47/50 (94%) and at day 60 in 50/50 patients (100%). After a mean follow‐up of 5.4 years (SD 5.4 months) the recurrence rate was 34% (15/44 patients) with a median time to recurrence of 21 months (range 0.2–6 years).ConclusionAlthough laser haemorrhoidoplasty achieves a high short‐term success rate with respect to stage reduction and symptom improvement, it is associated with a high rate of minor postoperative complications and long‐term recurrence. Therefore, laser haemorrhoidoplasty should be used with caution.
The “green nail” phenomenon in ICG‐enhanced fluorescence optical imaging – a potential tool for the differential diagnosis of psoriatic arthritis
Authors: Wiemann Oliver , Werner Stephanie G. , Langer Hans‐Eckhard , Backhaus Marina , Chatelain René 
Published: January 2019

SummaryBackground and objectivesEarly diagnosis of psoriatic arthritis poses a particular challenge. A novel fluorescence optical imaging technique, the Xiralite® system is very useful in this regard as it allows for visualization of microvasculature and perfusion. The present study is the first to systematically examine fluorescence optical signals in a large psoriatic arthritis cohort.Patients and methodsIn the primary study, we reviewed and analyzed extra‐articular fluorescence optical signal patterns in 241 imaging sequences obtained from 187 psoriatic arthritis patients; 36 fluorescence optical sequences from 31 patients with rheumatoid arthritis served as controls. In a follow‐up study, 203 consecutive fluorescence optical sequences from 54 psoriatic arthritis patients and 149 control subjects with various inflammatory rheumatic disorders were retrospectively evaluated in order to validate the primary study results in terms of the patterns previously identified.ResultsPsoriatic arthritis patients exhibited three different fluorescence optical signal patterns in projection of the nails that have not been previously described. One of these patterns was the “green nail” sign, which was highly specific (97 %) for psoriatic arthritis. In the follow‐up study, the specificity of this phenomenon in psoriatic arthritis was 87 % in comparison to the control cohort.ConclusionsIn the present study, fluorescence optical signals in the nail region proved to be highly specific for psoriatic arthritis. The “green nail” phenomenon seems to be of particular diagnostic interest as a potential sign of impaired microcirculation of the nail bed.