bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review with meta‐analysis: the impact of Clostridium difficile infection on the short‐ and long‐term risks of colectomy in inflammatory bowel disease
Authors: Law C. C. Y. , Tariq R. , Khanna S. , Murthy S. , McCurdy J. D. 
Published: February 2017

SummaryBackgroundClostridium difficile infection (CDI) is associated with increased mortality in inflammatory bowel disease (IBD), but the risk of colectomy is variable and has not been adequately studied.AimTo perform a systematic review and meta‐analysis to assess the impact of CDI on colectomy risk in IBD.MethodsMultiple databases were searched systematically for observational studies reporting colectomy risk in IBD, stratified by the presence of CDI, and the duration of follow‐up (short term 3 months, and long term at least 1 year). Weighted summary estimates were calculated using generalised inverse variance with random‐effects model. Study quality was assessed using the Newcastle–Ottawa scale.ResultsTwelve observational studies were identified and included 35 057 IBD patients with CDI, and 929 259 without CDI. CDI did not increase the short‐term colectomy risk in IBD patients overall (10 studies) (OR: 1.35; 95% CI: 0.68–2.67), or in patients with ulcerative colitis (nine studies) (OR: 1.20; 95% CI: 0.39–3.76). In contrast, CDI was associated with higher long‐term colectomy risk in patients with IBD overall (five studies) (OR: 2.23; 95% CI: 1.18–4.21), and in patients with ulcerative colitis (four studies) (OR: 2.96; 95% CI: 1.19–7.34). The results were stable in subgroups stratified by recruitment period, hospitalisation status and geographical location. All studies were at least of moderate quality. The results were limited in the ability to compare IBD severity and the type of anti‐microbial therapy.ConclusionBased on 12 observational studies with at least moderate quality, Clostridium difficile infection appears to increase colectomy risk in IBD in the long‐ but not short‐ term.
Sarcoidosis extent relates to molecular variability
Authors: Monast C S , Li K , Judson M A , Baughman R P , Wadman E , Watt R , Silkoff P E , Barnathan E S , Brodmerkel C 
Published: February 2017

SummaryThe molecular basis of sarcoidosis phenotype heterogeneity and its relationship to effective treatment of sarcoidosis have not been elucidated. Peripheral samples from sarcoidosis subjects who participated in a Phase II study of golimumab [anti-tumour necrosis factor (TNF)-α] and ustekinumab [anti-interleukin (IL)−12p40] were used to measure the whole blood transcriptome and levels of serum proteins. Differential gene and protein expression analyses were used to explore the molecular differences between sarcoidosis phenotypes as defined by extent of organ involvement. The same data were also used in conjunction with an enrichment algorithm to identify gene expression changes associated with treatment with study drugs compared to placebo. Our analyses revealed marked heterogeneity among the three sarcoidosis phenotypes included in the study cohort, including striking differences in enrichment of the interferon pathway. Conversely, enrichments of multiple pathways, including T cell receptor signalling, were similar among phenotypes. We also identify differences between treatment with golimumab and ustekinumab that may explain the differences in trends for clinical efficacy observed in the trial. We find that molecular heterogeneity is associated with sarcoidosis in a manner that may be related to the extent of organ involvement. These findings may help to explain the difficulty in identifying clinically efficacious sarcoidosis treatments and suggest hypotheses for improved therapeutic strategies.
Effect of matrix stiffness on osteoblast functionalization
Authors: Zhang Tao , Lin Shiyu , Shao Xiaoru , Zhang Qi , Xue Changyue , Zhang Shu , Lin Yunfeng , Zhu Bofeng , Cai Xiaoxiao 
Published: February 2017

AbstractObjectivesStiffness of bone tissue differs response to its physiological or pathological status, such as osteoporosis or osteosclerosis. Consequently, the function of cells residing in bone tissue including osteoblasts (OBs), osteoclasts and osteocytes will be affected. However, to the best of our knowledge, the detailed mechanism of how extracellular matrix stiffness affects OB function remains unclear.Materials and methodsWe conducted a study that exposed rat primary OBs to polydimethylsiloxane substrates with varied stiffness to investigate the alterations of cell morphology, osteoblastic differentiation and its potential mechanism in mechanotransduction.ResultsDistinctive differences of cell shapes and vinculin expression in rat osteoblasts were detected on different PDMS substrates. As representatives for OB function, expression of alkaline phosphatase, Runx2 and osteocalcin were identified and showed a decrease trend as substrates become soft, which is associated with the Rho/ROCK signalling pathway.ConclusionsOur results indicated substrate elasticity as a potent regulator in OBs functionalization, which may pave a way for further understanding of bone diseases as well as a potential therapeutic alternative in tissue regeneration.
Lipid‐lowering efficacy and safety of alirocumab in patients with or without diabetes: A sub‐analysis of ODYSSEY COMBO II
Authors: Leiter Lawrence A. , Zamorano José Luis , Bujas‐Bobanovic Maja , Louie Michael J. , Lecorps Guillaume , Cannon Christopher P. , Handelsman Yehuda 
Published: February 2017

AimThis sub‐analysis of the ODYSSEY COMBO II study compared the effects of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in high cardiovascular risk patients with or without diabetes mellitus (DM) receiving maximally tolerated statin therapy.MethodsCOMBO II was a 104‐week, double‐blind study (n = 720) enrolling patients with documented atherosclerotic cardiovascular disease (ASCVD) and baseline LDL‐C ≥70 mg/dL (1.8 mmol/L), and patients without documented ASCVD at high cardiovascular risk with LDL‐C ≥100 mg/dL (2.6 mmol/L). Patients receiving maximally tolerated statin therapy were randomized (2:1) to alirocumab 75 mg every 2 weeks (Q2W; 1 mL subcutaneous injection) or oral ezetimibe 10 mg daily. Alirocumab dose was increased to 150 mg Q2W (also 1 mL) at Week 12 if Week 8 LDL‐C was ≥70 mg/dL.ResultsHistory of DM was reported in 31% (n = 148) of patients on alirocumab and 32% (n = 77) of patients on ezetimibe. At Week 24, alirocumab consistently reduced LDL‐C from baseline in patients with (−49.1%) or without DM (−51.2%) to a significantly greater extent than ezetimibe (−18.4% and −21.8%, respectively). Occurrence of treatment‐emergent adverse events was similar between groups. Efficacy results at 104 weeks were similar to those at 24 weeks.ConclusionsOver a 104‐week double‐blind study period, alirocumab provided consistently greater LDL‐C reductions than ezetimibe, with similar LDL‐C results in patients with or without DM. Safety of alirocumab was similar regardless of baseline DM status.
Adhesives based on butyl‐cyanoacrylate for fixation of autologous bone graft: Pilot study in rabbits
Authors: Hochuli‐Vieira Eduardo , Engler Pinto Ana Carolina Basso , Pereira‐Filho Valfrido Antonio , Saska Sybele , Monnazzi Marcelo Silva 
Published: February 2017

AbstractBackground/AimInjuries to bone during trauma may require bone grafts and/or fixation to ensure optimal healing. Autologous bone grafts are still very common, but little data exist regarding the most effective means of fixation of such grafts. The aim of this study was to compare the fixation of autologous bone grafts with titanium screws and adhesives based on n‐butyl‐cyanoacrylate.Material and MethodsTwenty adult rabbits were used. In group I, the graft was fixed with titanium screws (in one side of the animal head), while in groups II and III (in other spots in the same animal head), the graft was fixed with adhesive Tissuacryl® and Histoacryl®, respectively. The animals were sacrificed on post‐operative days 7, 15, 30, 60, and 120. Histological and histomorphometric analyses were performed.ResultsInflammatory reactions were observed in all groups at 7 days. At 15 days, group I showed no inflammatory reaction. There was new bone formation in group I at 30 days and at 60 days in groups II and III. After 120 days, the grafts were completely incorporated in group I and partially incorporated in groups II and III. Groups II and III presented less graft resorption at the final evaluation: 32.58 (±10.22) and 34.75 (±8.25), compared to 26.58 (±6.48) for group I (P=.001).ConclusionsThe adhesives were compatible when they were in contact with bone structures, and they were effective in fixing the grafts. Groups II and III had less graft resorption.
Characterization of mouthguards: Impact performance
Authors: Guérard Sandra , Barou Jean‐Luc , Petit Julien , Poisson Philippe 
Published: February 2017

AbstractBackground/AimIt is difficult to characterize the impact behavior of mouthguards on the basis of their components. Impact behavior tests should be performed on mouthguard formed to simulate their intra‐oral performance. The aim of this study was to compare the impact behavior of six models of mouthguards using a standardized experimental protocol.Material and methodsFour commercially available mouth‐formed mouthguards (SDI™, Gel Nano™, Opro Shield Gold™ and Kipsta R300™), one mouth‐formed mouthguard prototype and one custom‐made mouthguard were tested. The procedures recommended by the manufacturers (injecting procedure for custom‐made mouthguard and “boil‐and‐bite” procedures for mouth‐formed mouthguards) were used to adapt five samples per model on steel jaws. Impact performances were assessed according to labial aspect thickness and maximum contact load (FMax) during impact using a drop tower.ResultsSDI™ and Opro Shield Gold™ had the thinnest labial aspect thickness (P<.01), followed by the Gel Nano™ and the Kipsta R300™ (P<.01) with a thickness of about 3 mm. The prototype and custom‐made mouthguard were thicker (almost 4 mm). The custom‐made mouthguard, the Kipsta R300™ and the prototype had the best impact performances, but the labial aspect thickness of the Kipsta R300™ was significantly lower than that of the custom‐made mouthguard and the prototype. Analysis of force curves and position of the mouthguard on the impacted zone showed that the Kipsta R300™ was less well adapted.ConclusionThickness and impact performance are not sufficient criteria to characterize performance of mouthguards.
Seasonal patterns of downstream movement in partially migratory stream‐dwelling Dolly Varden
Authors: Ayer Christopher G. , Katahira Hirotaka , Fukui Sho , Koizumi Itsuro 
Published: February 2017

AbstractMigration is a common behaviour among salmonids, but not all individuals within a population migrate, instead becoming residents and remaining in their natal streams. This phenomenon, known as “partial migration,” is well studied among sea‐run and lake‐run populations; however, the lower migratory benefits and costs for mainstem‐run individuals question whether the same mechanisms can be applied for stream‐dwelling salmonids. In this study, we investigated main stem‐run timing and body condition of partially migratory stream‐dwelling Dolly Varden charr (Salvelinus malma) in the Shiisorapuchi River in central Hokkaido, Japan. Based on commonly observed patterns in sea‐run and lake‐run salmonids, we predicted that migration would occur during spring and consist predominantly of age 1 + females with some small subordinate males. Traps were placed at the mouths of two small tributaries along the Shiisorapuchi River periodically from May to December 2015. Adipose fin samples were taken forDNAto sex the individuals. Consistent to initial predictions, downstream movement occurs only once in the spring, dominated by age‐1 + females. Trapped fishes (presumed migrants) were slightly longer but slimmer compared to the fish caught in the tributaries (presumed resident), which may be equivalent to smolts in anadromous populations. Regardless of migratory habitat, mechanisms driving partial migration in salmonids may be the same as long as production between natal stream and feeding habitats is significantly different.
Characterization of focal cortical dysplasia with balloon cells by layer‐specific markers: Evidence for differential vulnerability of interneurons
Authors: Nakagawa Julia M. , Donkels Catharina , Fauser Susanne , Schulze‐Bonhage Andreas , Prinz Marco , Zentner Josef , Haas Carola A. 
Published: February 2017

SummaryObjectiveFocal cortical dysplasia (FCD) is a major cause of pharmacoresistant focal epilepsy. Little is known about the pathomechanisms underlying the characteristic cytoarchitectural abnormalities associated with FCD. In the present study, a broad panel of markers identifying layer‐specific neuron subpopulations was applied to characterize dyslamination and structural alterations in FCD with balloon cells (FCD 2b).MethodsPan‐neuronal neuronal nuclei (NeuN) and layer‐specific protein expression (Reelin, Calbindin, Calretinin, SMI32 (nonphosphorylated neurofilament H), Parvalbumin, transducin‐like enhancer protein 4 (TLE4), and Vimentin) was studied by immunohistochemistry on paraffin sections of FCD2b cases (n = 22) and was compared to two control groups with (n = 7) or without epilepsy (n = 4 postmortem cases). Total and layer‐specific neuron densities were systematically quantified by cell counting considering age at surgery and brain region.ResultsWe show that in FCD2b total neuron densities across all six cortical layers were not significantly different from controls. In addition, we present evidence that a basic laminar arrangement of layer‐specific neuron subtypes was preserved despite the severe disturbance of cortical structure. SMI32‐positive pyramidal neurons showed no significant difference in total numbers, but a reduction in layers III and V. The densities of supragranular Calbindin‐ and Calretinin‐positive interneurons in layers II and III were not different from controls, whereas Parvalbumin‐expressing interneurons, primarily located in layer IV, were significantly reduced in numbers when compared to control cases without epilepsy. In layer VI, the density of TLE4‐positive projection neurons was significantly increased. Altogether, these data show that changes in cellular composition mainly affect deep cortical layers in FCD2b.SignificanceThe application of a broad panel of markers defining layer‐specific neuronal subpopulations revealed that in FCD2b neuronal diversity and a basic laminar arrangement are maintained despite the severe disturbance of cytoarchitecture. Moreover, it showed that Parvalbumin‐positive, inhibitory interneurons are highly vulnerable in contrast to other interneuron subtypes, possibly related to the epileptic condition.
Multiplex ligation‐dependent probe amplification as first mutation screening for large deletions and duplications in haemophilia
Authors: Belvini D. , Salviato R. , Radossi P. , Tagariello G. 
Published: February 2017

IntroductionMolecular characterization has shown a wide mutational spectrum underlying haemophilia A (HA) and haemophilia B (HB). Different molecular assays have allowed laboratories to perform genetic testing for F8 and F9 mutations.AimRecently, multiplex ligation‐dependent probe amplification (MLPA), a simple technique for relative quantitation of targeted genomic regions, has been introduced in HA and HB for detection of large deletions and duplications. We want to verify if MLPA might be used at the beginning of the molecular investigation.MethodsWe used it to test 22 patients with suspected large deletions, nine patients negative for mutation detection by other methods and finally, 45 new patients as their first screening test.ResultsCarrier status was also established in 28 related females and gross rearrangements were also searched for by MLPA in 19 females with reduced FVIII or FIX levels. All suspected deletions were confirmed apart from two patients. In patients with a negative screening test, MLPA revealed one large duplication, while in two patients where MLPA was used as the first screening step, an exon duplication was detected. In females with reduced FVIII or FIX, no large deletions or duplications were found.ConclusionsOwing to its simplicity, MLPA seems useful at the beginning of the molecular investigation, saving all the following steps, where positive. Single exon deletion diagnosis requires caution due to the risk of misdiagnosis, but benefits of MLPA appear to overcome the pitfalls.
Comparison of clinical and pathological features of lung lesions of systemic IgG4‐related disease and idiopathic multicentric Castleman's disease
Authors: Terasaki Yasuhiro , Ikushima Soichiro , Matsui Shoko , Hebisawa Akira , Ichimura Yasunori , Izumi Shinyu , Ujita Masuo , Arita Machiko , Tomii Keisuke , Komase Yuko , Owan Isoko , Kawamura Tetsuji , Matsuzawa Yasuo , Murakami Miho , Ishimoto Hiroshi , Kimura Hiroshi , Bando Masashi , Nishimoto Norihiro , Kawabata Yoshinori , Fukuda Yuh , Ogura Takashi ,   the Tokyo Diffuse Lung Diseases Study Group
Published: February 2017

AimsThe lung lesion [immunoglobulin (Ig)G4‐L] of IgG4‐related disease (IgG4‐RD) is a condition that occurs together with IgG4‐RD and often mimics the lung lesion [idiopathic multicentric Castleman's disease (iMCD‐L)] of idiopathic multicentric Castleman's disease (iMCD). Because no clinical and pathological studies had previously compared features of these diseases, we undertook this comparison with clinical and histological data.Methods and resultsNine patients had IgG4‐L (high levels of serum IgG4 and of IgG4+ cells in lung specimens; typical extrapulmonary manifestations). Fifteen patients had iMCD‐L (polyclonal hyperimmunoglobulinaemia, elevated serum interleukin‐6 levels and polylymphadenopathy with typical lymphadenopathic lesions). Mean values for age, serum haemoglobin levels and IgG4/IgG ratios were higher in the IgG4‐L group and C‐reactive protein levels were higher in the iMCD‐L group. All IgG4‐RD lung lesions showed myxomatous granulation‐like fibrosis (active fibrosis), with infiltration of lymphoplasmacytes and scattered eosinophils within the perilymphatic stromal area, such as interlobular septa and pleura with obstructive vasculitis. All 15 lung lesions of iMCD, however, had marked accumulation of polyclonal lymphoplasmacytes in lesions with lymphoid follicles and dense fibrosis, mainly in the alveolar area adjacent to interlobular septa and pleura without obstructive vasculitis.ConclusionsAlthough both lesions had lymphoplasmacytic infiltration, lung lesions of IgG4‐RD were characterized by active fibrosis with eosinophilic infiltration within the perilymphatic stromal area with obstructive vasculitis, whereas lung lesions of iMCD had lymphoplasmacyte proliferating lesions mainly in the alveolar area adjacent to the perilymphatic stromal area. These clinicopathological features may help to differentiate the two diseases.
Resilient practices of consumption in times of crisis—Biographical interviews with members of vulnerable households in Germany
Authors: Boost Marie , Meier Lars 
Published: February 2017

AbstractThis article analyzes the impact of different consumption patterns that are used to counteract economic hardship and to mitigate the effects of such hardship in times of crisis in Germany. We focus on resilient socioeconomic practices, such as the development of formal or informal practices of consumption, production, and saving. We develop a critical approach of social resilience that is combined with the idea of a bricolage (Levi‐Strauss, 1962) of “mixed economy” practices (Malcolmson, 1988). This is done by demonstrating the relevance of preconditions for resilient practices. Based on an analysis of in‐depth biographical interviews, two main types of resilient consumption practices and strategies of those who experience economic hardship are identified. First, saving, as the predominant practice, includes buying low‐priced items at discount stores, taking advantage of the offerings of charity organisations, and reducing expenditures overall. Second, home production consists of subsistence farming or do‐it‐yourself activities for personal use or bartering. In this context, particular attention is paid to the reactivation of traditional noncommodified practices, such as the nonmonetary (mutual) exchange of goods and services within social networks, and the reactivation of previously undervalued knowledge that results in new spheres of production. We conclude by discussing the relevance of preconditions and consequences—as well as the demands and personal costs—of the resilient practices used.
Inflammatory stress of pancreatic beta cells drives release of extracellular heat‐shock protein 90α
Authors: Ocaña Gail J. , Pérez Liliana , Guindon Lynette , Deffit Sarah N. , Evans‐Molina Carmella , Thurmond Debbie C. , Blum Janice S. 
Published: February 2017

SummaryA major obstacle in predicting and preventing the development of autoimmune type 1 diabetes (T1D) in at‐risk individuals is the lack of well‐established early biomarkers indicative of ongoing beta cell stress during the pre‐clinical phase of disease. Recently, serum levels of the α cytoplasmic isoform of heat‐shock protein 90 (hsp90) were shown to be elevated in individuals with new‐onset T1D. We therefore hypothesized that hsp90α could be released from beta cells in response to cellular stress and inflammation associated with the earliest stages of T1D. Here, human beta cell lines and cadaveric islets released hsp90α in response to stress induced by treatment with a combination of pro‐inflammatory cytokines including interleukin‐1β, tumour necrosis factor‐α and interferon‐γ. Mechanistically, hsp90α release was found to be driven by cytokine‐induced endoplasmic reticulum stress mediated by c‐Jun N‐terminal kinase (JNK), a pathway that can eventually lead to beta cell apoptosis. Cytokine‐induced beta cell hsp90α release and JNK activation were significantly reduced by pre‐treating cells with the endoplasmic reticulum stress‐mitigating chemical chaperone tauroursodeoxycholic acid. The hsp90α release by cells may therefore be a sensitive indicator of stress during inflammation and a useful tool in assessing therapeutic mitigation of cytokine‐induced cell damage linked to autoimmunity.
CD21intCD23+ follicular B cells express antigen‐specific secretory IgM mRNA as primary and memory responses
Authors: Meng Qing‐Hai , White Harry N. 
Published: February 2017

SummaryCD21int CD23+ IgM+ mouse follicular B cells comprise the bulk of the mature B‐cell compartment, but it is not known whether these cells contribute to the humoral antibody response. We show using a direct RT‐PCR method for antigen‐specific VH, that FACS‐sorted mouse CD21int CD23+ B cells express specific secretory IgM VH transcripts in response to immunization and also exhibit a memory response. The secretory IgM expressed is distinct from the IgG expressed by cells of this phenotype, which we also analyse here, having a distinct broader distribution of CDR‐H3 sequences and zero or low levels of somatic mutation in the region analysed. These results imply that cells of the CD21int CD23+ phenotype have distinct IgM+ and IgG+ populations that contribute directly to the humoral antibody and memory responses by expressing antigen‐specific secretory immunoglobulin. We also argue that the more diverse CDR‐H3 sequences expressed by antigen‐experienced IgM+ CD21int CD23+ follicular B cells would place them at the bottom of a recently hypothesized memory B‐cell hierarchy.