bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superparamagnetic iron oxide nanoparticles for MR imaging of pancreatic cancer: Potential for early diagnosis through targeted strategies
Authors: Zhang Chongjie , Yan Yuzhong , Zou Qi , Chen Jie , Li Chunsheng 
Published: December 2015

AbstractSuperparamagnetic iron oxide nanoparticles (SPION)‐based magnetic resonance imaging is a powerful, noninvasive tool in biomedical imaging. The recent embedding of SPIO in nanoencapsulations that had different controllable surface properties has now made it possible to use SPIO in the imaging of metabolic processes. The two major issues to realize maximized and selective SPIO cancer targeting are the minimization of macrophage uptake and the preferential binding to cancerous cells over healthy neighbor cells. The utility of SPIO has been shown in clinical applications using a series of marketed SPION‐based contrast agents. Applications have ranged from detecting inflammatory diseases to the specific identification of cell surface markers expressed on tumors. This review focuses on iron‐oxide‐based nanoparticles, to include the physiochemical properties of SPION surface engineering and its synthetic methods as well as SPIO imaging applications and specifically targeted SPIO conjugates (e.g. targeted probes) for labeling cancerous, cell‐surface molecules. As a specific application of this technology, we discuss its use in the imaging of pancreatic duct adenocarcinoma in addition to its potential for use in early diagnosis through targeted strategies.
Exploratory analysis of early treatment discontinuation and clinical outcomes of patients with attention‐deficit/hyperactivity disorder
Authors: Wu Sheng Hu , Wang Ke , Chen Yun , Wang Wan Qi , Wang Fan , Montgomery William , Treuer Tamas 
Published: December 2015

AbstractIntroductionThis post‐hoc analysis was to investigate the impact of treatment discontinuation on clinical outcomes in patients with attention‐deficit/hyperactivity disorder (ADHD).MethodsData are from a 12‐month, observational, multinational study that included outpatients aged 6–17 years who were diagnosed with ADHD and treated with atomoxetine, methylphenidate, or nootropic agents. Treatment effectiveness and proportions of patients who discontinued treatment were compared between China and the other non‐Western countries/regions combined. Propensity score matching was used to further estimate the association between treatment discontinuation and effectiveness.ResultsOf the 546 patients who entered the study, 337 patients had complete data and were included in the analyses. Compared with the other countries/regions, China subgroup had a higher treatment discontinuation rate (odds ratio = 25.80; P < 0.0001) and poorer treatment effectiveness: least‐squares (LS) mean changes were 5.74 versus 8.56 (P = 0.0225) for the Child Health and Illness Profile‐Child Edition (CHIP‐CE) Achievement domain and −1.87 versus −2.13 (P = 0.0401) for Clinical Global Impressions‐ADHD‐Severity (CGI‐ADHD‐S). Further analyses of matched discontinuer–maintainer pairs showed that discontinuers demonstrated poorer effectiveness: LS mean changes for the CHIP‐CE Achievement domain and CGI‐ADHD‐S (discontinuer versus maintainer) were 5.36 versus 9.10 (P = 0.0255) and −1.32 versus −1.96 (P = 0.0179) for overall population, respectively, and 4.40 versus 10.17 (P = 0.0065) and −1.48 versus −2.45 (P = 0.0089), respectively, for China subgroup.DiscussionThis analysis found that early treatment discontinuation was associated with worse clinical outcomes for patients with ADHD. China subgroup had substantially higher discontinuation rates and poorer effectiveness outcomes. Strategies to improve medication persistence have the potential to improve outcomes for ADHD patients in China.
The Moral Reasoning of U.S. Evangelical and Mainline Protestant Children, Adolescents, and Adults: A Cultural–Developmental Study
Authors: Jensen Lene Arnett , McKenzie Jessica 
Published: December 2015

This cultural–developmental interview study examined moral reasoning in relation to religious culture (evangelical, mainline Protestants), age (children, adolescents, adults), and moral issue (public, private; N = 120). Compared to adolescents and adults, children used more Ethic of Autonomy and less Ethic of Community reasoning. With age, differences between religious cultures became pronounced. Mainline adults invoked an Ethic of Divinity for private issues. Evangelical adolescents and adults used this ethic frequently, but more for public than private issues. These and other findings indicate that evangelical and mainline Protestants diverge on what should be society's moral lingua franca, and cast new and nuanced light on America's “culture wars.” Results furthermore highlight comodulation of development and culture that requires life course research on moral reasoning.
What Could You Really Learn on Your Own?: Understanding the Epistemic Limitations of Knowledge Acquisition
Authors: Lockhart Kristi L. , Goddu Mariel K. , Smith Eric D. , Keil Frank C. 
Published: December 2015

Three studies explored the abilities of 205 children (5–11 years) and 74 adults (18–72 years) to distinguish directly versus indirectly acquired information in a scenario where an individual grew up in isolation from human culture. Directly acquired information is knowledge acquired through firsthand experience. Indirectly acquired information is knowledge that requires input from others. All children distinguished directly from indirectly acquired knowledge (Studies 1–3), even when the indirectly acquired knowledge was highly familiar (Study 2). All children also distinguished difficult‐to‐acquire direct knowledge from simple‐to‐acquire direct knowledge (Study 3). The major developmental change was the increasing ability to completely rule out indirect knowledge as possible for an isolated individual to acquire.
Relationship between sputum clusterin levels and childhood asthma
Authors: Sol I. S. , Kim Y. H. , Park Y. A. , Lee K. E. , Hong J. Y. , Kim M. N. , Kim Y. S. , Oh M. S. , Yoon S. H. , Kim M. J. , Kim K. W. , Sohn M. H. , Kim K. E. 
Published: December 2015

SummaryBackgroundClusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammation‐associated diseases. Clusterin levels in childhood asthma have not been evaluated.Objectives(1) To evaluate sputum clusterin levels in children with asthma compared to a control group. (2) To assess the relationships between sputum clusterin levels and airway inflammation, pulmonary function, and bronchial hyperresponsiveness.MethodsThis study included 170 children aged 5–18 years with stable asthma (n = 91), asthma exacerbation (n = 29), or no asthma (healthy controls; n = 50). Induced sputum, pulmonary function, and methacholine challenge tests were performed. Stable asthma was classified into two groups according to the severity. Clusterin levels in sputum were measured using an enzyme‐linked immunosorbent assay.ResultsChildren with stable asthma had a higher clusterin level than healthy controls [4540 (3872–5651) pg/mL vs. 3857 (1054–4369) pg/mL, P < 0.001]. The clusterin level was also more elevated in eosinophil‐dominant sputum than in non‐eosinophilic sputum in stable asthma [5094 (4243–6257) pg/mL vs. 4110 (1871–4839) pg/mL, P = 0.0017]. Clusterin levels were associated with asthma severity. Paradoxically, clusterin levels were lower during asthma exacerbation than in stable asthma [1838 (350–4790] pg/mL vs. 4540 (3872–5651) pg/mL, P < 0.001]. Clusterin levels were strongly correlated with the methacholine concentration that caused a 20% decrease in the forced expiratory volume in 1 s (r = −0.617, P < 0.001); there was no significant correlation between clusterin levels and other pulmonary function parameters.Conclusions and Clinical RelevanceClusterin levels were altered in children with stable asthma and asthma exacerbation because of its antioxidant and anti‐inflammatory effects. Clusterin may be a marker that reflects airway inflammation and severity of symptoms, and it can be used in the assessment and management of childhood asthma.
The role of IgE recognition in allergic reactions to amoxicillin and clavulanic acid
Authors: Torres M. J. , Montañez M. I. , Ariza A. , Salas M. , Fernandez T. D. , Barbero N. , Mayorga C. , Blanca M. 
Published: December 2015

SummaryBetalactam (BL) antibiotics are the drugs most frequently involved in IgE‐mediated reactions. The culprit BL varies according to consumption patterns, with amoxicillin (AX) more prevalent in Southern Europe and penicillin V in Scandinavian countries. Nowadays, the combination of AX and clavulanic acid (CLV) is the most highly consumed BL containing medicine worldwide. Both BLs, AX and CLV, can independently be involved in reactions, which poses a diagnostic challenge. In patients with immediate allergic reactions to AX, two patterns of responses have been described, those responding to benzylpenicillin (cross‐reactors) and those selective to AX. In addition, selective reactions to CLV account for around 30% of allergic reactions to the combination AX‐CLV. These patterns of IgE recognition could be related to differences in the haptenation process, in the immunological response, or in the BL involved in the first sensitization. In this regard, patients with selective responses to CLV are generally younger than those allergic to AX or benzylpenicillin. So far, no evidence of cross‐reactivity between CLV and other BLs has been reported. This shows the importance of an accurate diagnosis of CLV allergy, as patients with selective reactions to CLV could take other BLs including AX. Diagnosis can be performed in vivo and in vitro, although no immunoassay currently exists. Research regarding the CLV antigenic determinants and protein conjugates is essential to improve diagnosis. BLs need to covalently bind to a carrier protein to be immunogenic. The antigenic determinant of AX is the amoxicilloyl amide, but CLV leads to unstable structures, many of which are unknown. Moreover, the nature of the BL–protein conjugates plays an important role in IgE recognition. This review aims to summarize current knowledge on the immunochemistry, diagnostic approaches as well as chemical and proteomic studies for both AX and CLV.
Preclinical Assessment of Inflammatory Pain
Authors: Muley Milind M. , Krustev Eugene , McDougall Jason J. 
Published: December 2015

SummaryWhile acute inflammation is a natural physiological response to tissue injury or infection, chronic inflammation is maladaptive and engenders a considerable amount of adverse pain. The chemical mediators responsible for tissue inflammation act on nociceptive nerve endings to lower neuronal excitation threshold and sensitize afferent firing rate leading to the development of allodynia and hyperalgesia, respectively. Animal models have aided in our understanding of the pathophysiological mechanisms responsible for the generation of chronic inflammatory pain and allowed us to identify and validate numerous analgesic drug candidates. Here we review some of the commonly used models of skin, joint, and gut inflammatory pain along with their relative benefits and limitations. In addition, we describe and discuss several behavioral and electrophysiological approaches used to assess the inflammatory pain in these preclinical models. Despite significant advances having been made in this area, a gap still exists between fundamental research and the implementation of these findings into a clinical setting. As such we need to characterize inherent pathophysiological pathways and develop new endpoints in these animal models to improve their predictive value of human inflammatory diseases in order to design safer and more effective analgesics.
NS383 Selectively Inhibits Acid‐Sensing Ion Channels Containing 1a and 3 Subunits to Reverse Inflammatory and Neuropathic Hyperalgesia in Rats
Authors: Munro Gordon , Christensen Jeppe K. , Erichsen Helle K. , Dyhring Tino , Demnitz Joachim , Dam Eva , Ahring Philip K. 
Published: December 2015

SummaryAimsHere, we investigate the pharmacology of NS383, a novel small molecule inhibitor of acid‐sensing ion channels (ASICs).MethodsASIC inhibition by NS383 was characterized in patch‐clamp electrophysiological studies. Analgesic properties were evaluated in four rat behavioral models of pain.ResultsNS383 inhibited H+‐activated currents recorded from rat homomeric ASIC1a, ASIC3, and heteromeric ASIC1a+3 with IC50 values ranging from 0.61 to 2.2 μM. However, NS383 was completely inactive at homomeric ASIC2a. Heteromeric receptors containing AISC2a, such as ASIC1a+2a and ASIC2a+3, were only partially inhibited, presumably as a result of stoichiometry‐dependent binding. NS383 (10–60 mg/kg, i.p.), amiloride (50–200 mg/kg, i.p.), acetaminophen (100–400 mg/kg, i.p.), and morphine (3–10 mg/kg, i.p.) all dose‐dependently attenuated nocifensive behaviors in the rat formalin test, reversed pathological inflammatory hyperalgesia in complete Freund's adjuvant‐inflamed rats, and reversed mechanical hypersensitivity in the chronic constriction injury model of neuropathic pain. However, in contrast to acetaminophen and morphine, motor function was unaffected by NS383 at doses at least 8‐fold greater than those that were effective in pain models, whilst analgesic doses of amiloride were deemed to be toxic.ConclusionsNS383 is a potent and uniquely selective inhibitor of rat ASICs containing 1a and/or 3 subunits. It is well tolerated and capable of reversing pathological painlike behaviors, presumably via peripheral actions, but possibly also via actions within central pain circuits.
Stress and the Microbiota–Gut–Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome
Authors: Moloney Rachel D. , Johnson Anthony C. , O'Mahony Siobhain M. , Dinan Timothy G. , Greenwood‐Van Meerveld Beverley , Cryan John F. 
Published: December 2015

SummaryVisceral pain is a global term used to describe pain originating from the internal organs of the body, which affects a significant proportion of the population and is a common feature of functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). While IBS is multifactorial, with no single etiology to completely explain the disorder, many patients also experience comorbid behavioral disorders, such as anxiety or depression; thus, IBS is described as a disorder of the gut–brain axis. Stress is implicated in the development and exacerbation of visceral pain disorders. Chronic stress can modify central pain circuitry, as well as change motility and permeability throughout the gastrointestinal (GI) tract. More recently, the role of the gut microbiota in the bidirectional communication along the gut–brain axis, and subsequent changes in behavior, has emerged. Thus, stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviors. This review will highlight the evidence by which stress and the gut microbiota interact in the regulation of visceral nociception. We will focus on the influence of stress on the microbiota and the mechanisms by which microbiota can affect the stress response and behavioral outcomes with an emphasis on visceral pain.
Hearing in school‐aged children with trisomy 21 – results of a longitudinal cohort study in children identified at birth
Authors: Yaneza M.M.C. , Hunter K. , Irwin S. , Kubba H. 
Published: December 2015

ObjectivesTo report the prevalence of hearing problems and the hearing sequelae in school‐aged children with trisomy 21 in a longitudinal study.DesignAll children with trisomy 21 were identified via schools, community‐based child development centres, general practitioners, or the universal newborn hearing screen. Audiological data and otorhinolaryngological problems were prospectively entered in to the Audiological Surveillance Programme database from each visit.SettingRetrospective review of the Audiological Surveillance Programme database in the Glasgow area (United Kingdom) of all children reviewed between 2004 and 2012.ParticipantsAll pre‐teenaged children with trisomy 21 of school age (aged 5–12 years old).Main outcome measuresHearing thresholds, aetiology of hearing loss and management of hearing loss was determined for the cohort of children.ResultsA total of 102 children were included. Fifty‐four had normal hearing. Twenty‐six had fluctuating otitis media with effusion; five had hearing in normal limits, six were managed with hearing aids, fourteen were managed conservatively, and one had ventilation tube insertion. Fifteen had persistent otitis media with effusion; four had ventilation tube insertion; and nine were managed with hearing aids. Seven had mixed hearing loss with four required hearing aids.ConclusionsOtitis media with effusion was the commonest cause of hearing impairment; effusions may fluctuate through the pre‐teenaged years, and thus, hearing aids are beneficial. Ventilation tube insertion and bone‐conducting hearing aids were useful when ear‐level hearing aids were not tolerated. Mixed hearing loss occurred in later years as sensorineural hearing loss developed on a background of otitis media with effusion.
IgG subclass profile among anti‐Glutathione S‐transferase T1 antibodies in post‐transplant de novo immune hepatitis
Authors: Aguilera Isabel , Martinez‐Bravo Maria José , Sousa Jose Manuel , Pozo‐Borrego Antonio Jesús , Núñez‐Roldán Antonio 
Published: December 2015

AbstractAlthough the pathogenic pathways leading to de novo immune hepatitis (IH) are not completely understood, we have shown strong evidences of an antidonor response against Glutathione S‐transferase T1 (GSTT1), an antigen exclusively expressed in the donor liver. The first sign of this process is the production of GSTT1 antibodies that, in 25% of the cases, will precede de novo IH. Because the presence of the antibodies is not sufficient to trigger the disease, we aimed to study GSTT1 IgG subclasses in a group of 18 liver transplant patients, 12 that developed de novo IH and 6 that remained free of disease. Surprisingly, the predominant subclasses were IgG1‐GSTT1 and IgG4‐GSTT1. The presence of IgG4‐expressing plasma cells was also investigated in 10 available liver biopsies. Six biopsies coinciding with diagnosis showed a mean value of 32.8 IgG4+ plasma cells/hpf vs. 5.55 in patients without the disease. We have not found a distinctive GSTT1‐IgG profile in patients with de novo IH, but the ratio IgG1‐GSTT1/IgG4‐GSTT1 in samples from close to the time of diagnosis seemed to be important. The novel finding of abundant IgG4‐GSTT1 in liver transplantation is intriguing, but their possible role in pathogenesis of de novo IH remains unknown.
EMMPRIN expression is involved in the development of interstitial fibrosis and tubular atrophy in human kidney allografts
Authors: Kemmner Stephan , Schulte Christian , Hann von Weyhern Claus , Schmidt Roland , Baumann Marcus , Heemann Uwe , Renders Lutz , Schmaderer Christoph 
Published: December 2015

AbstractBackgroundMatrix metalloproteinases (MMP) are involved in the development of interstitial fibrosis and tubular atrophy (IF/TA) in renal disease. The synthesis of MMP is activated by the extracellular matrix metalloproteinases inducer protein (EMMPRIN). To analyze the role of EMMPRIN in IF/TA, we retrospectively detected EMMPRIN expression in specimens of human renal allografts with various levels of IF/TA.MethodsImmunohistochemistry was performed to detect EMMPRIN expression. In a retrospective analysis, a total cohort of 50 specimens were divided according to BANFF‐classification into four subgroups (0–3): no, mild (≤25%), moderate (26–50%), or severe (>50%) IF/TA. Among other parameters, renal function was analyzed and compared to EMMPRIN expression.ResultsIn 24 of 38 biopsies, we detected positive EMMPRIN staining. All nephrectomy (n = 12) samples were negative for EMMPRIN. Positive staining in the biopsy samples was detectable on the basolateral side of tubular epithelial cells. EMMPRIN staining was negatively correlated with IF/TA (p < 0.001). We found significant differences between the mean EMMPRIN expression in IF/TA groups 0 and 3 (p = 0.021) and groups 1 and 3 (p = 0.004). Furthermore, we found significant correlations between EMMPRIN staining and renal function.ConclusionOur data suggest that EMMPRIN is involved in the pathophysiology of IF/TA.
A comparative outcome analysis of incisional hernia repair in patients who underwent liver transplantation vs. those that underwent hepatopancreaticobiliary surgery using the EHS guidelines as a means of comparison
Authors: Lam Hwai‐Ding , Vanlander Aude , Berrevoet Frederik 
Published: December 2015

AbstractAimWe retrospectively analyzed incisional hernia (IH) outcomes of liver transplant (LT) vs. hepatopancreaticobiliary (HPB) cases sharing the same incision.MethodsIH repair patients with a history of LT were compared with those with HPB surgical history sharing the same type of incision and using the European Hernia Society classification and nomenclature for reporting outcome.ResultsEighty‐two patients (27 HPB and 55 LT) between February 2001 and February 2014 were analyzed. Baseline demographics showed that the LT group had more diabetes and steroid use, but were less physical active. Outcomes showed no differences in wound complication, SSI rate, and recurrence rate (recurrence rate of 11.1% and 16.4% for HPB and LT, respectively). Multivariate analysis showed longer operating time to be a risk factor for both wound complication and SSI. M‐tor inhibitor use was an additional risk factor for SSI. Interval to recurrence was significant longer in the LT group (35 vs. 61 months). Cox analysis showed steroid use, immunosuppression and not using a synthetic mesh as risk factors for recurrence.ConclusionIncisional hernia repair with synthetic mesh after liver transplantation does not result in more wound complications, SSI, and recurrences, when compared to patients without immunosuppression.
MicroRNA‐21 (miR‐21) expression in hypothermic machine perfusate may be predictive of early outcomes in kidney transplantation
Authors: Khalid Usman , Ablorsu Elijah , Szabo Laszlo , Jenkins Robert H. , Bowen Timothy , Chavez Rafael , Fraser Donald J. 
Published: December 2015

AbstractHypothermic machine perfusion is effective in improving outcome following kidney transplantation. Molecular analyses of hypothermic machine perfusate (HMP) have the potential to identify biomarkers of organ viability prior to transplantation, offering significant advantages to the transplant surgeon, and leading to a potential increase in the organ donor pool. MicroRNAs are emerging as important biomarkers in the context of kidney injury and transplantation. Recent data demonstrate increased microRNA‐21 (miR‐21) expression in the kidney following acute kidney injury. This study investigated the potential of miR‐21 detected in HMP to act as a sentinel for early kidney transplant outcomes. MiR‐21 was found to be readily detectable in HMP by RT‐qPCR. Eleven ECD kidneys were maintained on a hypothermic machine perfusion system for a median 627 (range 117–1027) minutes, and evaluation of flow and resistance characteristics suggested stability on the machine from 60 min post‐perfusion. MiR‐21 quantification at 60 min post‐perfusion correlated with eGFR at 6 and 12 months post‐transplantation. These data suggest that miR‐21 expression in HMP may be predictive of early outcomes following kidney transplantation. In the era of ECD kidneys, a reliable measure of organ quality is urgently needed, and this study suggests miR‐21 may be such a marker.