bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta‐analysis examining the epidemiology of clozapine‐associated neutropenia
Authors: Myles N. , Myles H. , Xia S. , Large M. , Kisely S. , Galletly C. , Bird R. , Siskind D. 
Published: May 2018

BackgroundClozapine is associated with life‐threatening neutropenia. There are no previous meta‐analyses of the epidemiology of clozapine‐associated neutropenia.ObjectivesTo determine the cumulative incidence of mild, moderate and severe neutropenia, incidence of death related to severe neutropenia, case fatality rate of neutropenia and the longitudinal incidence of neutropenia following exposure to clozapine.Data sourcesA systematic search of Medline, EMBASE and PsycINFO using search terms [clozapine OR clopine OR zaponex OR clozaril] AND [neutropenia OR agranulocytosis].MethodsRandom effects meta‐analysis to determine event rates and longitudinal incidence of events per 100 person‐years of exposure.ResultsA total of 108 studies were included. The incidence of clozapine‐associated neutropenia was 3.8% (95% CI: 2.7–5.2%) and severe neutropenia 0.9% (95% CI: 0.7–1.1%). The incidence of death related to neutropenia following prescription of clozapine was 0.013% (95% CI: 0.01–0.017%). The case fatality rate of severe neutropenia was 2.1% (95% CI: 1.6–2.8%). The peak incidence of severe neutropenia occurred at one month of exposure and declined to negligible levels after one year of treatment.ConclusionSevere neutropenia associated with clozapine is a rare event and occurs early with a substantial decline in risk after one year of exposure. Death from clozapine‐associated neutropenia is extremely rare. Implications for haematological monitoring are discussed.
A novel thyroid function index associated with opposite therapeutic outcomes in advanced hepatocellular carcinoma patients receiving chemotherapy or sorafenib
Authors: Chu Yu‐De , Lin Kwang‐Huei , Huang Ya‐Hui , Lin Chen‐Chun , Hung Chien‐Fu , Yeh Ta‐Sen , Lee Wei‐Chen , Yeh Chau‐Ting 
Published: May 2018

AbstractAimA sustained proportion of advanced hepatocellular carcinoma (HCC) patients worldwide received either chemotherapy or sorafenib. However, to date, effective and convenient biomarkers to predict their therapeutic outcomes remained elusive. Hypothyroidism was associated with favorable anticancer treatment outcomes in several advanced cancers. Here, we aimed to investigate the potential of using thyroid‐stimulating hormone (TSH) and free T4 (FT4) levels as biomarkers to predict clinical outcomes in HCC patients receiving chemotherapy or sorafenib.MethodsTotal 123 advanced HCC patients at Barcelona Clinical Liver Cancer Stage C were included. They were separated into two cohorts, one treated by sorafenib (n = 62) and the other by chemotherapy (n = 61). Clinical data including TSH and FT4 were retrieved and correlated with treatment outcomes.ResultsBecause of restriction in local insurance policy, the baseline liver function reserve was better in patients receiving sorafenib. Therefore, the two cohorts were analyzed separately. The results showed that a higher (> median) TSH × FT4 value was independently associated with favorable time‐to‐tumor progression (P = 0.006) and overall survival (P = 0.002) if chemotherapy was provided; whereas it was associated with unfavorable time‐to‐tumor progression (P = 0.017) and overall survival (P = 0.001) if sorafenib was administrated. These opposite associations remained valid when patients with Child–Pugh class A liver function from either cohort were included for analysis.ConclusionA novel thyroid function index, TSH × FT4, significantly predicted opposite clinical outcomes in advanced HCC patients receiving sorafenib or chemotherapy treatment.
Comorbidity of viral hepatitis and chronic spontaneous urticaria: A systematic review
Authors: Kolkhir P. , Pereverzina N. , Olisova O. , Maurer M. 
Published: May 2018

AbstractChronic viral infections including those by hepatitis B (CHB) virus and hepatitis C (CHC) virus have been reported to be comorbidities of chronic spontaneous urticaria (CSU). Here, we performed the first comprehensive review of the peer‐reviewed literature (PubMed, Web of Science and Google Scholar) on the prevalence of CHB and CHC in patients with CSU and vice versa. The prevalence of CHB and CHC in CSU does not appear to be increased. Less than 5% and 2% of patients with CSU have markers of CHB and CHC, respectively, according to most of the 32 studies reviewed. Urticarial rash including CSU occurs in ≤3% of patients with CHC as reported by most of 20 studies analysed. Very few patients have been assessed for the effects of antiviral hepatitis treatment on their CSU, and two but not all reportedly showed improvement. Hepatitis B/C infections appear unlikely to be linked to CSU. We suggest that routine screening for these infections in patients with CSU is not relevant or cost‐effective and should not be performed unless liver function tests are abnormal, risk factors or symptoms of viral hepatitis are present, or urticarial vasculitis is suspected.
Temporal and long‐term gut microbiota variation in allergic disease: A prospective study from infancy to school age
Authors: Simonyté Sjödin K. , Hammarström M.‐L. , Rydén P. , Sjödin A. , Hernell O. , Engstrand L. , West C. E. 
Published: May 2018

AbstractBackgroundCompositional changes in the early‐life gut microbiota have been implicated in IgE‐associated allergic diseases, but there is lack of longitudinal studies. We examined gut microbiota development from infancy to school age in relation to onset of IgE‐associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T‐cell regulation, estimated as responses to polyclonal T‐cell activation.MethodsStool samples were collected from 93 children at 4, 6, 13 months, and 8 years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children, and mononuclear cells were polyclonally activated. Levels of IL‐10 and FOXP3 mRNA copies were determined using real‐time quantitative reverse transcriptase‐PCR.ResultsAt 8 years of age, 21 children were diagnosed with IgE‐associated allergic disease and 90% displayed allergic comorbidity. Seventy‐two children were nonallergic and nonsensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. The gut microbiota of the allergic 8‐year‐olds was enriched in Bifidobacterium and depleted of Lactobacillus, Enterococcus, and Lachnospira. In allergic 8‐year‐olds, Faecalibacterium correlated with IL‐10 mRNA levels (rs = 0.49, Padj = 0.02) with the same trend for FOXP3 (rs = 0.39, Padj = 0.08).ConclusionsWe identified both temporal and long‐term variation in the differential abundance of specific bacterial genera in children developing IgE‐associated allergic disease. Improved dietary interventions aiming at expanding immune‐modulatory taxa could be studied for prevention of allergic disease.
Outcomes of oesophageal self‐dilation for patients with refractory benign oesophageal strictures
Authors: Qin Y. , Sunjaya D. B. , Myburgh S. , Sawas T. , Katzka D. A. , Alexander J. A. , Halland M. 
Published: May 2018

SummaryBackgroundCurrent management of refractory benign oesophageal strictures with endoscopic dilations and stenting leads to resolution of dysphagia in only 30% of patients. Oesophageal self‐dilation may be an alternative.AimTo evaluate the efficacy and safety of oesophageal self‐dilation at a tertiary referral centre.MethodsWe conducted a retrospective review of patients with refractory benign oesophageal strictures who participated in oesophageal self‐dilation at Mayo Clinic (Rochester, MN, USA) between 2003 and 2017. Clinical data including stricture characteristics, Dakkak and Bennett Dysphagia Score, number and dates of endoscopies, and complications were collected. A two‐tailed paired Student's t test was used to compare the measures of efficacy, with differences considered significant at a 5% probability level.ResultsWe identified 52 patients with refractory strictures treated with self‐dilation. The median number of endoscopic interventions was reduced from 9.5 (range 5‐30) to 0 (range 0‐3) within 12 months before and after self‐dilation, respectively (P < 0.0001). A median intervention‐free interval of 417 days (IQR 256‐756 days) was observed. The mean dysphagia score at baseline was 2.5 (95% CI 2.2‐2.8) and 0.33 (95% CI 0.11‐0.53) after self‐dilation. 23 of 27 (85%) patients who received enteral nutrition prior to self‐dilation had their feeding tubes removed.ConclusionsOesophageal self‐dilation is an effective way of maintaining oesophageal patency in refractory benign oesophageal strictures, with safety comparable to current standard of care. Prospective studies are needed to further validate the role of self‐dilation in treatment of refractory benign oesophageal strictures.
Prospective evaluation of 68Ga‐DOTATATE PET/CT in limited disease neuroendocrine tumours and/or elevated serum neuroendocrine biomarkers
Authors: Gabriel Sophie , Garrigue Philippe , Dahan Laetitia , Castinetti Frédéric , Sebag Frédéric , Baumstark Karine , Archange Cendrine , Jha Abhishek , Pacak Karel , Guillet Benjamin , Taïeb David 
Published: May 2018

SummaryContextThe 68Ga‐labelled somatostatin analogues (68Ga‐DOTA‐SSAs) is becoming popular as an important diagnostic tool in neuroendocrine tumours as evidenced by a growing number of reports detailing institutional experience with various DOTA peptides. However, only few prospective studies have compared 68Ga‐DOTA‐SSAs and somatostatin receptor scintigraphy (SRS) in gastroenteropancreatic neuroendocrine tumours (GEP‐NETs) and pulmonary neuroendocrine tumours.ObjectiveThe aim of our prospective study was to perform head‐to‐head comparison between 68 Ga‐DOTATATE PET/CT and standard imaging work‐up (SI) that included multiphasic CT, liver MRI and SRS using single photon emission computed tomography.DesignIn this prospective study, the patients were enrolled only if they met any of the following inclusion criteria: (i) initial staging of a NETs without distant metastases on SI or neuroendocrine tumour with unknown primary on SI; (ii) restaging of NETs that could be treated by focused therapeutic interventions; (iii) elevated serum neuroendocrine hormones or peptides. The exclusion criteria was grade 3 GEP‐NETs.ResultsThirty‐two patients were enrolled in the study. Eleven patients (6 pancreas, 4 ileum, 1 duodenal) were included for initial evaluation and staging of NETs, 8 patients (5 pancreas, 1 ileal, 1 lung, 1 duodenal gastrinoma) for restaging, and 13 patients for elevated serum neuroendocrine biomarkers (5 ectopic Cushing's syndrome, 5 organic hypoglycaemia, 1 patient each with elevated vasoactive inhibitory peptide, chromogranin A and neuron‐specific enolase). 68Ga‐DOTATATE PET/CT detected more primary tumours than SRS (15/18 vs 10/18: P = .074). The missed tumours on 68Ga‐DOTATATE PET/CT were located in the lung in two cases and duodenum in one case. For other anatomical regions (nodal and distant metastasis), no statistical difference was observed between imaging modalities using 68Ga‐DOTATATE PET/CT and SRS. Overall, 68Ga‐DOTATATE PET/CT+CT+MRI detected 31/33 of the involved regions (including primaries) (29 and 22 for 68Ga‐DOTATATE and SRS, respectively).ConclusionOur study shows that 68Ga‐DOTATATE PET/CT detected similar number of sites than combination of SRS, liver MRI and thoraco‐abdominopelvic CT on region‐based analysis. 68Ga‐DOTATATE PET/CT missed half of primary lung carcinoids with ectopic Cushing's syndrome.
Peri‐implant soft tissue status and crestal bone levels around adjacent implants placed in patients with and without type‐2 diabetes mellitus: 6 years follow‐up results
Authors: Alasqah Mohammed N. , Alrabiah Mohammed , Al‐Aali Khulud Abdulrahman , Mokeem Sameer A. , Binmahfooz Abdulelah M. , ArRejaie Aws S. , Abduljabbar Tariq 
Published: May 2018

AbstractBackgroundThe long‐term success and survival of dental implants type‐2 diabetic subjects is debatable.PurposeThe present 6 years' follow‐up prospective clinical study compared the peri‐implant soft tissue status and crestal bone loss (CBL) around adjacent implants placed among type‐2 diabetic and nondiabetic subjects.Materials and MethodsType‐2 diabetic (Group‐1) and nondiabetic individuals (Group‐2) with adjacent dental implants were included. Hemoglobin A1c (HbA1c) levels were recorded; and a questionnaire was used to collect demographic information. Information regarding implant dimensions, duration in function, loading protocol, and type of restoration was recorded. Peri‐implant bleeding‐on‐probing (BOP), plaque index (PI), probing depth (PD), and mesial and distal CBL were measured. P < .05 were considered statistically significant.ResultsEighty‐six male participants (44 in Group‐1 and 42 in Group‐2) were included. The mean age of individuals in groups 1 and 2 were 57.6 ± 5.5 and 61.6 ± 4.3 years, respectively. In Group‐1, the mean duration of type‐2 diabetes was 10.1 ± 3.5 years. A family history of diabetes was more often reported by individuals in Group‐1 than Group‐2. In groups 1 and 2, 44 and 42 pairs of adjacent implants, respectively were placed in the regions of missing premolars and molars in both arches. All implants were delayed loaded and were fixed with non‐splinted screw‐retained restorations. In groups 1 and 2, tooth‐brushing twice daily was reported by 79.5% and 85.7% individuals, respectively. There was no difference in peri‐implant PI, BOP, PD, mesial and distal CBL and HbA1c levels among individuals in groups 1 and 2.ConclusionAdjacent implants can remain esthetically and functionally stable in type 2 diabetic patients in a manner similar to healthy individuals provided glycemic levels are strictly controlled and maintained.
Elevated levels of 8‐OHdG and PARK7/DJ‐1 in peri‐implantitis mucosa
Authors: Kasnak Gökhan , Firatli Erhan , Könönen Eija , Olgac Vakur , Zeidán‐Chuliá Fares , Gursoy Ulvi Kahraman 
Published: May 2018

AbstractBackgroundReactive oxygen species contribute to periodontal tissue homeostasis under control of anti‐oxidative responses. Disruption in this balance induces severe inflammation and extended tissue degradation.PurposeAim of this study was to identify the expression levels of nuclear factor, erythroid 2 like 2 (NFE2L2/NRF2), Parkinsonism associated deglycase (PARK7/DJ‐1), kelch‐like ECH associated protein 1 (KEAP1), and 8‐hydroxy‐deoxyguanosine (8‐OHdG) in peri‐implant mucosal tissues affected by peri‐implantitis, and to compare the levels to those of periodontally diseased and healthy tissue samples.MethodsTissue biopsies were collected from systemically healthy, non‐smoking 12 peri‐implantitis patients, 13 periodontitis patients, and 13 periodontally healthy controls. Expression levels of NFE2L2/NRF2, PARK7/DJ‐1, KEAP1, and 8‐OHdG in tissue samples were analyzed immunohistochemically. Statistical analysis was performed by one‐way ANOVA with Tukey's HSD test.ResultsInflammatory cell infiltration in the connective tissue and loss of architecture in the spinous layer of the epithelium were prominent in peri‐implantitis. Proportions of 8‐OHdG and PARK7/DJ‐1 expressing cells were elevated in both peri‐implantitis (P = .025 for 8‐OHdG and P = .014 for PARK7/DJ‐1) and periodontitis (P = .038 for 8‐OHdG and P = .012 for PARK7/DJ‐1) groups in comparison with controls. Staining intensities of 8‐OHdG and PARK7/DJ‐1 were higher in the periodontitis and peri‐implantitis groups than in the control (P < .01) groups. There was no difference in the expression levels of NFE2L2/NRF2 between the groups. KEAP1 was not observed in any tissue sample.ConclusionsPeri‐implantitis is characterized by severe inflammation and architectural changes in the epithelium and connective tissue. The expressions of 8‐OHdG and PARK7/DJ‐1 are elevated in both peri‐implantitis and periodontitis.
Effect of implant therapy on oral health‐related quality of life (OHIP‐49), health status (SF‐36), and satisfaction of patients with several agenetic teeth: Prospective cohort study
Authors: Filius Marieke A.P. , Vissink Arjan , Cune Marco S. , Raghoebar Gerry M. , Visser Anita 
Published: May 2018

AbstractBackgroundEffect of fixed prosthodontics on patients with several agenetic teeth is not well understood.PurposeTo assess the effect of implant‐based fixed prosthodontics on oral health‐related quality of life (OHRQoL), general health status, and satisfaction regarding dental appearance, ability to chew and speech in patients with several agenetic teeth.Materials and MethodsFor this prospective cohort study, all patients (≥18 years) with several agenetic teeth who were scheduled for treatment with fixed dental implants between September 2013 and July 2015 at our department were approached. Participants received a set of questionnaires before and 1 year after implant placement to assess OHRQoL (OHIP‐NL49), general health status (SF‐36), and satisfaction regarding dental appearance, ability to chew and speech.ResultsAbout 25 out of 31 eligible patients (10 male, 15 female; median age: 20 [19;23] years; agenetic teeth: 7 [5;10]) were willing to participate. Pre‐ and post‐treatment OHIP‐NL49 sum‐scores were 38 [28;56] and 17 [7;29], respectively (P < .001). Scores of all OHIP‐NL49 subdomains decreased tool, representing an improved OHRQoL (P < .05) as well as that satisfaction regarding dental appearance, ability to chew and speech increased (P < .001). General health status did not change with implant treatment (P > .05).ConclusionsTreatment with implant‐based fixed prosthodontics improves OHRQoL and satisfaction with dental appearance, ability to chew and speech, while not affecting general health status.
Predicting the ecological impacts of large‐dam removals on a river network based on habitat‐network structure and flow regimes
Authors: Ishiyama Nobuo , Ryo Masahiro , Kataoka Taiga , Nagayama Shigeya , Sueyoshi Masanao , Terui Akira , Mori Terutaka , Akasaka Takumi , Nakamura Futoshi 
Published: May 2018

AbstractLarge dams provide vital protection and services to humans. However, an increasing number of large dams worldwide are old and not operating properly. The removal of large dams has excellent potential to restore habitat connectivity and flow regimes; therefore, projecting the related ecological consequences is an emerging need for water resource and ecosystem management. However, no modeling methods are currently available for such projections at the basin scale. We devised a scheme that integrates changes in flow regimes and habitat network structure into a basin‐scale impact assessment of removal of large dams and applied it to the Nagara‐Ibi Basin, Japan. We used a graph‐theoretical approach and a hydrological model, to quantify changes in habitat availability for 11 freshwater fishes at the basin scale under multiple removal scenarios. We compared these results with the change predicted using a conventional scheme that considered only changes to the habitat network due to dam removal. Our proposed scheme revealed that an increase in flow variability associated with dam removal projected both positive and negative effects on basin‐scale habitat availability, depending on the focal species, endangered species had a negative response to dam removal. In contrast, the conventional approach projected only positive effects for all species. This difference in the outcomes indicates that large‐dam removal can have negative and positive effects on watershed restoration due to changes in flow regimes. Our results also suggest the effect of removal of large dams may depend on the dams and their locations. Our study is the first step in projecting ecological trade‐offs associated with the removal of large dams on riverscapes at the basin scale and provides a foundation for future process‐based watershed restoration.
Glomalin‐related soil protein in the rhizosphere of Robinia pseudoacacia L. seedlings under higher air temperature combined with Cd‐contaminated soil
Authors: Jia X. , Zhao Y. , He Y. , Chang Y. 
Published: May 2018

SummaryGlomalin‐related soil protein (GRSP) can bind heavy metals and plays an important role in soil carbon sequestration. The GRSP contains glycoproteins produced by arbuscular mycorrhizal fungi (AMF), as well as lipids, humic materials and non‐mycorrhizal‐related heat‐stable proteins, which might be affected by environmental conditions. Current and predicted changes in global climate make it important to understand how GRSP might be affected by higher atmospheric temperatures and heavy metal contamination of soil. Here, we investigated the response of GRSP to higher temperature in the rhizosphere of Robinia pseudoacacia L. seedlings in cadmium (Cd)‐contaminated soil. Easily extractable (EE) and total (T) GRSP concentrations increased significantly (P < 0.05) under Cd pollution alone. Compared with ambient temperature, a higher temperature (2.7°C) alone significantly (P < 0.05) increased EE‐ and T‐GRSP concentrations, the EE‐GRSP:T‐GRSP ratio and the GRSP:soil organic carbon (SOC) ratio, but significantly (P < 0.05) decreased SOC content in the rhizosphere. Higher temperature significantly (P < 0.05) increased EE‐ and T‐GRSP concentrations, the EE‐GRSP:T‐GRSP ratio and the GRSP:SOC ratio, but decreased SOC content under Cd pollution. Under higher temperature, the amount of Cd bound to GRSP increased significantly (P < 0.05), and available Cd content decreased significantly (P < 0.05). Glomalin‐related soil protein contributed more carbon to the rhizosphere SOC pool under higher temperature + Cd than under Cd alone, and the higher temperature led to a significant (P < 0.05) decrease in available Cd. Under the higher temperature, T‐GRSP contributed more to the decrease in available Cd than did EE‐GRSP. Increases in GRSP resulting from higher temperatures could increase Cd binding in contaminated soil.HighlightsHigher temperature increased GRSP in the rhizosphere of R. pseudoacacia seedlings.
The amount of Cd bound to GRSP increased under higher temperature.
Available Cd in rhizosphere soil decreased under higher temperature.
Higher temperature could contribute to chelation of Cd‐contaminated soil.