bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced therapeutic effects of human mesenchymal stem cells transduced with superoxide dismutase 3 in a murine atopic dermatitis‐like skin inflammation model
Authors: Sah Shyam Kishor , Agrahari Gaurav , Nguyen Cuong Thach , Kim Yeon‐Soo , Kang Kyung‐Sun , Kim Tae‐Yoon 
Published: August 2018

AbstractBackgroundThe use of mesenchymal stem cells (MSCs) has been proposed to treat various autoimmune diseases. However, effective strategies for treating atopic dermatitis (AD) are still lacking, and the mechanisms underlying stem cell therapy remain largely unknown. In this study, we sought to explore potential clinical application of superoxide dismutase 3‐transduced MSCs (SOD3‐MSCs) to experimental AD‐like skin inflammation in in vitro and in vivo and its underlying anti‐inflammatory mechanisms.MethodsSOD3‐MSCs were administered subcutaneously to mice with AD, and associated symptoms and biologic changes were evaluated. Human keratinocytes, mast cells, and murine T helper (Th) 2 cells were cocultured in vitro with SOD3‐MSCs to investigate potential therapeutic effects of SOD3‐MSCs.ResultsIn mice with AD, SOD3‐MSCs ameliorated AD pathology and enhanced the efficacy of MSC therapy by controlling activated immune cells, by reducing expression levels of proinflammatory mediators in the skin, and by inhibiting the histamine H4 receptor (H4R)‐mediated inflammatory cascade and activation of Janus kinase signal transducer and activator of transcription pathways. Similarly, coculture of SOD3‐MSCs with mast cells, keratinocytes, and Th2 cells effectively dampened H4R‐dependent persistent inflammatory responses by multiple mechanisms. Moreover, we also showed that SOD3 interacts with H4R and IL‐4 receptor α. The functional significance of this interaction could be a markedly reduced inflammatory response in keratinocytes and overall AD pathogenesis, representing a novel mechanism for SOD3's anti‐inflammatory effects.ConclusionSOD3‐MSCs can be potentially used as an effective and clinically relevant therapy for AD and other autoimmune disorders.
An analysis of retractions of papers authored by Scott Reuben, Joachim Boldt and Yoshitaka Fujii
Authors: McHugh U. M. , Yentis S. M. 
Published: August 2018

SummaryWe analysed how long it has taken for papers authored by Scott Reuben, Joachim Boldt and Yoshitaka Fujii to be retracted: investigations into these three anaesthetists have shown much of their research to be unethical or fraudulent. To date, 94% of their combined papers requiring retraction have been retracted; however, only 85% of the retraction notices were compliant with guidelines produced by the Committee on Publication Ethics. We contacted the Editors‐in‐Chief and/or publishers of all the journals containing articles that had been identified as requiring retraction but had not yet been retracted. In response to our enquiries, 16 articles have since been retracted; we have documented the journals’ responses regarding the remaining papers and await further retractions in the future. There is room for improvement in the way that unethical or fraudulent papers are handled by journals and publishers, beyond the identification of the authors’ misconduct.
Bilateral breast cancers in an Asian population, and a comparison between synchronous and metachronous tumours
Authors: Sim Yirong , Tan Veronique K. M. , Sidek Nur A. B. , Chia Daryl K. A. , Tan Benita K. T. , Madhukumar Preetha , Yong Wei Sean , Wong Chow Yin , Ong Kong Wee 
Published: August 2018

BackgroundWomen with unilateral breast cancer have an increased risk of developing bilateral breast cancer (BBC). Patients with metachronous BBC (mBBC) usually have an earlier age of onset, and their prognoses have been shown to be either similar or poorer than those with synchronous BBC (sBBC). Given the differing presentation and characteristics of breast cancers in the Asian population and the West, this study aims to characterize Asian patients with BBC.MethodsAll patients who had oncological breast surgery between 2001 and 2010 at the Singapore General Hospital and National Cancer Centre Singapore were reviewed. Patients with BBC were identified and studied.ResultsA total of 5520 Singaporean women had oncological breast surgery, 155 women (2.8%) had BBC. Of those with BBC, 47.1% (n = 73) were synchronous and 52.9% (n = 82) metachronous (mean interval of 39.4 months), and there was no difference in median age in both groups (54 years of age). Patients with sBBC were more likely to have a positive family history and had asymptomatic contralateral tumours. Although patients with sBBCs were more likely to have ER/PR positive and Her2 negative tumours, they had a lower 5‐year overall survival than those with mBBC (P = 0.022).ConclusionOur study shows that Asian women with BBC have different characteristics to their Western counterparts. In particular, women with sBBC tended to have a lower 5‐year overall survival compared to those with mBBC, despite having seemingly biologically favourable tumours, which suggest that there may be more underlying their tumour biology and genetics.
Hypertension in childhood obesity
Authors: Wühl Elke 
Published: August 2018

AbstractAimThe prevalence of childhood hypertension is rising in parallel with global increases in the prevalence of overweight and obesity. We looked at key papers and documents covering three decades.MethodsThis mini review examined a wide range of material published in English, with the main focus on 1993–2018, including clinical trials, meta‐analyses, guidelines and data produced by the World Health Organization and the World Obesity Federation.ResultsThe literature showed that body weight and blood pressure are closely correlated and obesity‐related hypertension contributes further to the clustering of cardiovascular risk factors in obesity. Because the duration of hypertension affects the risk of end‐organ damage, timely diagnosis and initiation of treatment are important. First‐line interventions should aim for blood pressure control and weight reduction. However, lifestyle modifications are often not successful with regard to attaining and maintaining long‐term blood pressure and weight control, despite a multidisciplinary approach. Antihypertensive treatment is recommended for all hypertensive children with failure of nonpharmacological treatment, diabetes, secondary hypertension, stage 2 hypertension or target organ damage.ConclusionWe found that obesity‐related hypertension was associated with a significantly increased cardiovascular morbidity and mortality, and early diagnosis and treatment for blood pressure control and weight reduction is essential.
Combined hydroxyurea and ETA receptor blockade reduces renal injury in the humanized sickle cell mouse
Authors: Taylor Crystal , Kasztan Malgorzata , Tao Binli , Pollock Jennifer S. , Pollock David M. 
Published: August 2018

AbstractAimThe objective of this study is to determine if ambrisentan (ETA selective antagonist) and hydroxyurea (HU) treatment has a synergistic effect on renal injury in sickle cell nephropathy when compared to HU treatment alone. The premise of the study is based on recent studies showing that endothelin‐1 (ET‐1) contributes to the pathophysiology of nephropathy in sickle cell disease (SCD) and that ETA receptor blockade improves renal function and protects against renal injury. Hydroxyurea (HU) is commonly prescribed for the treatment of SCD and has been shown to reduce renal injury in patients with SCD.MethodsMale 12‐week‐old humanized sickle mice (HbSS) and their genetic controls (HbAA) were treated with vehicle, HU, ambrisentan, or HU with ambrisentan for 2 weeks and renal structure and function were assessed.ResultsVehicle treated HbSS mice exhibited significant proteinuria compared to vehicle treated HbAA mice. HbSS mice also displayed significantly elevated plasma ET‐1 concentrations and decreased urine osmolality compared to HbAA controls. Proteinuria was significantly lower in both HU and ambrisentan treated animals compared to vehicle treated HbSS mice; however, there was no additional improvement in HbSS mice treated with combined ambrisentan and HU. The combination of HU and ambrisentan resulted in significantly lower KIM‐1 excretion, glomerular injury, and interstitial inflammation than HU alone.ConclusionThese findings indicate that HU and ETA receptor blockade produce similar reductions in renal injury in the humanized sickle mouse suggesting that both treatments may converge on the same mechanistic pathway.
Distinct patterns of skeletal muscle mitochondria fusion, fission and mitophagy upon duration of exercise training
Authors: Arribat Yoan , Broskey Nicholas T. , Greggio Chiara , Boutant Marie , Conde Alonso Sonia , Kulkarni Sameer S. , Lagarrigue Sylviane , Carnero Elvis A. , Besson Cyril , Cantó Carles , Amati Francesca 
Published: August 2018

AbstractAimHealthy ageing interventions encompass regular exercise to prevent mitochondrial dysfunction, key player in sarcopenia pathogenesis. Mitochondrial biogenesis has been well documented, but mitochondrial remodelling in response to exercise training is poorly understood. Here we investigated fusion, fission and mitophagy before and after an exercise intervention in older adults.MethodsSkeletal muscle biopsies were collected from 22 healthy sedentary men and women before and after 4 months of supervised training. Eight lifelong trained age‐ and gender‐matched volunteers served as positive controls. Transmission electron microscopy was used to estimate mitochondrial content. Western blotting and qRT‐PCR were used to detect changes in specific proteins and transcripts.ResultsAfter intervention, mitochondrial content increased to levels of controls. While enhancement of fusion was prevalent after intervention, inhibition of fission and increased mitophagy were dominant in controls. Similarly to PARKIN, BCL2L13 content was higher in controls. The observed molecular adaptations paralleled long‐term effects of training on physical fitness, exercise efficiency and oxidative capacity.ConclusionsThis study describes distinct patterns of molecular adaptations in human skeletal muscle under chronic exercise training. After 16 weeks of exercise, the pattern was dominated by fusion to increase mitochondrial content to the metabolic demands of exercise. In lifelong exercise, the pattern was dominated by mitophagy synchronized with increased fusion and decreased fission, indicating an increased mitochondrial turnover. In addition to these temporally distinct adaptive mechanisms, this study suggests for the first time a specific role of BCL2L13 in chronic exercise that requires constant maintenance of mitochondrial quality.
The Influence of Integrated Reporting on Business Model and Strategy Disclosures
Authors: Sukhari Aneetha , de Villiers Charl 
Published: August 2018

AbstractBusiness model (BM) and strategy disclosures could provide investors with relevant information. This study offers a platform for future research on BM and strategy disclosure and is the first to analyse the change in BM and strategy disclosures after the introduction of an integrated reporting (IR) requirement, to propose a framework for disclosure quality analyses, and to analyse how companies disclose the relationship between their BM and strategy. The findings show that BMs and strategy were not disclosed before the requirement to publish an integrated report in South Africa, but were disclosed thereafter. By 2014, companies used diagrams, flow charts, and informative narratives of business plans and value chains. Companies now disclose their strategic goals more transparently, but still do not link these goals to BMs, key performance indicators, risks or opportunities. The findings provide insight into disclosures that improved since the IR requirement and matters that are still not fully disclosed, which would be of interest to regulators tasked with investor protection.
Epithelial‐mesenchymal transition is activated in CD44‐positive malignant ascites tumor cells of gastrointestinal cancer
Authors: Nakano Michitaka , Ito Mamoru , Tanaka Risa , Ariyama Hiroshi , Mitsugi Kenji , Makiyama Akitaka , Uchino Keita , Esaki Taito , Tsuruta Nobuhiro , Hanamura Fumiyasu , Yamaguchi Kyoko , Okumura Yuta , Sagara Kosuke , Takayoshi Kotoe , Nio Kenta , Tsuchihashi Kenji , Tamura Shingo , Shimokawa Hozumi , Arita Shuji , Miyawaki Kohta , Kusaba Hitoshi , Akashi Koichi , Baba Eishi 
Published: August 2018

Disseminated cancer cells in malignant ascites possess unique properties that differ from primary tumors. However, the biological features of ascites tumor cells (ATC) have not been fully investigated. By analyzing ascites fluid from 65 gastrointestinal cancer patients, the distinguishing characteristics of ATC were identified. High frequency of CD44+ cells was observed in ATC using flow cytometry (n = 48). Multiplex quantitative PCR (n = 15) showed higher gene expression of epithelial‐mesenchymal transition (EMT)‐related genes and transforming growth factor beta (TGF‐beta)‐related genes in ATC than in the primary tissues. Immunohistochemistry (n = 10) showed that ATC also had much higher expression of phosphorylated SMAD2 than that in the corresponding primary tissues. TGF‐beta 1 was detected in all cases of malignant ascites by enzyme‐linked immunoassay (n = 38), suggesting the possible interaction of ATC and the ascites microenvironment. In vitro experiments revealed that these ATC properties were maintained by TGF‐beta 1 in cultured ATC(n = 3). Here, we showed that ATCrevealed high frequencies of CD44 and possessed distinct EMT features from primary tissues that were mainly maintained by TGF‐beta 1 in the ascites.
Clinical pharmacology of alemtuzumab, an anti-CD52 immunomodulator, in multiple sclerosis
Authors: Li Z , Richards S , Surks H K , Jacobs A , Panzara M A 
Published: August 2018

Summary
Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for treatment of relapsing multiple sclerosis (MS). In the Phase II/III trials, patients received 12 or 24 mg/day of alemtuzumab in two treatment courses (5 days for course 1 and 3 days for course 2), 12 months apart. Serum concentrations of alemtuzumab peaked on the last day of dosing in each course and mostly fell below the limit of quantitation by day 30. Alemtuzumab rapidly depleted circulating T and B lymphocytes, with the lowest observed values occurring within days. Lymphocytes repopulated over time, with B cell recovery usually complete within 6 months. T lymphocytes recovered more slowly and generally did not return to baseline by 12 months post-treatment. Approximately 40 and 80% of patients had total lymphocyte counts, reaching the lower limit of normal by 6 and 12 months after each course, respectively. The clearance of alemtuzumab is dependent on circulating lymphocyte count. A majority of treated patients tested positive for anti-alemtuzumab antibodies, including inhibitory antibodies, during the 2-year studies, and a higher proportion of patients tested positive in course 2 than in course 1. The presence of anti-alemtuzumab antibody appeared to be associated with slower clearance of alemtuzumab from the circulation but had no impact on the pharmacodynamics. No effects of age, race or gender on the pharmacokinetics or pharmacodynamics were observed. Together, the pharmacokinetics, pharmacodynamics and immunogenicity results support the continued development and use of alemtuzumab for the treatment of MS, and probably explain its sustained effects beyond the dosing interval.
Long‐term results of osseointegrated implant‐based dental rehabilitation in oncology patients reconstructed with a fibula free flap
Authors: Pellegrino Gerardo , Tarsitano Achille , Ferri Agnese , Corinaldesi Giuseppe , Bianchi Alberto , Marchetti Claudio 
Published: August 2018

BackgroundDental rehabilitation with conventional prostheses after microvascular jaw reconstruction is often unsuccessful because of the altered oral anatomy and the lack of adequate dentition for fixation.PurposeThis retrospective study evaluated the long‐term outcomes of patients who underwent jaws reconstruction with a fibula free flap and subsequent rehabilitation with implant‐supported prostheses.Materials and MethodsIn total, 21 patients were enrolled; 108 osseointegrated dental implants, positioned on 21 fibular free flaps were assessed. Follow‐up examinations were performed according to a standardized protocol, including clinical and radiological evaluations. The mean follow‐up after implant insertion was 90.2 (range, 20‐204) months.ResultsThe overall implant survival rate was 97.2% at the 12‐month follow‐up, 86.5% at 60 months, and 79.3% at 120 months. The rate of overall implant success was 95.4% at the 12‐month follow‐up, 73.5% at 60 months, and 64.7% at 120 months. Implant failure was more common in patients that had implants placed after they underwent radiation therapy.Peri‐implantitis and mucositis were identified in 14.8% and 20.3% of surviving implants, respectively, at the 5‐ and 10‐year follow‐up. The risk of developing peri‐implantitis was estimated to be higher (odds ratio = 1.5) for patients without connective tissue or skin grafts versus patients with one of them (18.2% vs 9.5%).ConclusionsLong‐term implant‐related outcomes show that the survival rate of implants placed into the fibula is acceptable. Radiotherapy negatively impacts survival and success, in particular in the short and medium‐term follow‐up. Moreover, a relevant peri‐implant bone resorption does occur over time and ultimately influences implants success, and it is mainly related to peri‐implant gingival mucositis. In this regard skin or connective tissue grafts seem to offer an aid to manage this problem.
Toddlers, teenagers, and terminal heights: the importance of puberty for male adult stature, Flanders, 1800–76
Authors: Depauw Ewout , Oxley Deborah 
Published: August 2018

AbstractDoes adult stature capture conditions at birth or at some other stage in the growth cycle? Anthropometrics is lauded as a method for capturing net nutritional status over all the growing years. However, it is frequently assumed that conditions at birth were most influential. Was this true for historical populations? This article examines the heights of Flemish men born between 1800 and 1876 to tease apart which moments of growth were most sensitive to disruption and reflected in final heights. It exploits two proximate crises in 1846–9 and 1853–6 as shocks that permit age effects to be revealed. These are affirmed through a study of food prices and death rates. Both approaches suggest a shift of the critical moment away from the first few years of life and towards the adolescent growth spurt as the most influential on terminal stature. Furthermore, just as height is accumulated over the growing years, conditions influencing growth need to be understood cumulatively. Economic conditions at the time of birth were not explanatory, but their collective effects from ages 11 to 18 years were strongly influential. At these ages, both health and nutrition mattered, to varying degrees. Teenagers, rather than toddlers, should be our guides to the past.
Effect of the phase of force production on corticomuscular coherence with agonist and antagonist muscles
Authors: Desmyttere Gauthier , Mathieu Emilie , Begon Mickael , Simoneau‐Buessinger Emilie , Cremoux Sylvain 
Published: August 2018

AbstractDuring isometric contractions, the net joint torque stability is modulated with the force production phases, i.e., increasing (IFP), holding (HFP), and decreasing force (DFP) phases. It was hypothesized that this modulation results from an altered cortical control of agonist and antagonist muscle activations. Eleven healthy participants performed 50 submaximal isometric ankle plantar flexion contractions. The force production phase effect (IFP, HFP and DFP) was assessed on the net joint torque stability, agonist and antagonist muscles activations, cortical activation, and corticomuscular coherence (CMC) with agonist and antagonist muscles. In comparison to HFP, the net joint torque stability, the agonist muscles activation and the CMC with agonist muscles were lower during IFP and even more during DFP. Antagonist muscle activations, cortical activations and CMC with antagonist muscles were higher during HFP than during IFP only. Increased CMC with agonist and antagonist muscles appeared to enhance the fine motor control. At a cortical level, agonist and antagonist muscle activations seemed to be controlled independently according to their muscle function and the phase of force production. Results revealed that CMC was an adequate measure to investigate the cortical regulation of agonist and antagonist muscle activations. This may have potential applications for patients with altered muscle activations.
Modulating auditory selective attention by non‐invasive brain stimulation: Differential effects of transcutaneous vagal nerve stimulation and transcranial random noise stimulation
Authors: Rufener Katharina S. , Geyer Ulrike , Janitzky Kathrin , Heinze Hans‐Jochen , Zaehle Tino 
Published: August 2018

AbstractSelective attention is a basic process required to maintain goal‐directed behavior by appropriately responding to target stimuli and suppressing reactions to non‐target stimuli. It has been proposed that auditory selective attention is linked to the activity of the locus coeruleus‐norepinergic (LC‐NE) system and a large‐scale fronto‐parietal cortical network, but there is still sparse causal evidence for these assumptions. By applying transcutaneous vagal nerve stimulation (tVNS) and transcranial random noise stimulation (tRNS) over the frontal cortex, we systematically assessed the involvement of these subcortical and cortical components in the regulation of auditory selective attention. Using a single‐blinded, sham‐controlled, within‐subject design we analyzed online effects of tVNS and tRNS in 20 healthy participants during an auditory oddball paradigm. We show significant stimulation‐dependent modulations of auditory selective attention on the behavioral and electrophysiological level. Compared to sham, tVNS increased the P3 amplitude, while tRNS reduced the reaction time to target stimuli. Moreover, both techniques reduced the P3 latency. Our data provide evidence for the functional relevance of the subcortical NE system in the regulation of neural resources that allows a phasic response to incoming target stimuli. They indicate that frontal cortex structures are crucially involved in the successful evaluation of the respective information. Moreover, our results are in favor of the LC‐P3 hypothesis claiming the vital role of the NE system in auditory selective attention and in the generation of the P3. Of note, the effects of tVNS on auditory selective attention are comparable with those evoked by pharmacological interventions and invasive vagal nerve stimulation.