bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of cutaneous squamous cell carcinoma in a New Zealand population of chronic lymphocytic leukaemia patients
Authors: Hock B. D. , McIntosh N. D. , McKenzie J. L. , Pearson J. F. , Simcock J. W. , MacPherson S. A. 
Published: September 2016

BackgroundChronic lymphocytic leukaemia (CLL) is associated with an increased incidence and aggressiveness of skin cancers, particularly cutaneous squamous cell carcinoma (cSCC), but little is known about cSCC incidence in Australasian CLL patients.AimIn this retrospective study, we analysed the incidence of cSCC in patients seen at a tertiary hospital in New Zealand (NZ).MethodsWe retrospectively assessed the clinical history and histology data of CLL patients (n = 371) who presented to the Haematology Department, Christchurch Hospital, NZ during the period 1996–2015. Baseline characteristics, incidence of second cancers, treatment details and overall survival were analysed.ResultsDuring follow‐up (median = 11.8 years), 221 second cancers were recorded in 88 patients. Of these cancers, 185 were cSCC, removed from 61 patients. In 56% of these patients, >1 cSCC was removed, and the majority of cSCC occurred following the treatment for CLL. The cumulative incidence of a first cSCC was 11% at 5 years, whereas the cumulative incidence of a subsequent cSCC was 88% at 5 years. The incidence of cSCC in male patients was threefold higher than that reported for the general NZ population.Conclusion
NZ CLL patients have a high incidence of cSCC relative to the levels observed in the general population, which are themselves among the highest in the world. The careful monitoring of CLL patients is warranted, particularly those who have a progressive disease or have had a first cSCC removed.
Donepezil promotes differentiation of neural stem cells into mature oligodendrocytes at the expense of astrogenesis
Authors: Imamura Osamu , Arai Masaaki , Dateki Minori , Takishima Kunio 
Published: September 2016

AbstractOligodendrocytes are the myelin‐forming cells of the central nervous system. Oligodendrocyte loss and failure of myelin development result in serious human disorders, including multiple sclerosis. Previously, using oligodendrocyte progenitor cells, we have shown that donepezil, which is an acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease, stimulates myelin gene expression and oligodendrocyte differentiation. Here, we aimed to analyze the effects of donepezil on primary mouse embryonic neural stem cells (NSCs). Donepezil treatment led to impaired self‐renewal ability and increased apoptosis. These effects appeared to be mediated through the Akt/Bad signaling pathway. Using neurosphere differentiation analysis, we observed that donepezil leads to reduced numbers of astrocytes and increased numbers of oligodendrocytes and neurons. Consistent with this finding, mRNA and protein levels for the oligodendrocyte markers myelin‐associated glycoprotein, 2′, 3′‐cyclic‐nucleotide 3′‐phosphodiesterase (CNPase), and myelin basic protein, as well as the neuronal marker β‐tubulin type III (Tuj1) were up‐regulated. In contrast, the expression of the astrocyte marker glial fibrillary acidic protein (GFAP) was down‐regulated by donepezil in a dose‐ and time‐dependent manner. Moreover, donepezil increased oligodendrocyte differentiation, resulting in a reduction in the differentiation of NSCs into astrocytes, by suppressing the activation of signal transducer and activator of transcription 3 (STAT3), SMAD1/5/9, and the downstream target gene GFAP, even under astrocyte‐inducing conditions. These results suggest that efficient differentiation of NSCs into oligodendrocytes by donepezil may indicate a novel therapeutic role for this drug in promoting repair in demyelinated lesions in addition to its role in preventing astrogenesis.
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Visualisation of Kiss1 Neurone Distribution Using a Kiss1‐CRE Transgenic Mouse
Authors: Yeo S.‐H. , Kyle V. , Morris P. G. , Jackman S. , Sinnett‐Smith L. C. , Schacker M. , Chen C. , Colledge W. H. 
Published: September 2016

Kisspeptin neuropeptides are encoded by the Kiss1 gene and play a critical role in the regulation of the mammalian reproductive axis. Kiss1 neurones are found in two locations in the rodent hypothalamus: one in the arcuate nucleus (ARC) and another in the RP3V region, which includes the anteroventral periventricular nucleus (AVPV). Detailed mapping of the fibre distribution of Kiss1 neurones will help with our understanding of the action of these neurones in other regions of the brain. We have generated a transgenic mouse in which the Kiss1 coding region is disrupted by a CRE‐GFP transgene so that expression of the CRE recombinase protein is driven from the Kiss1 promoter. As expected, mutant mice of both sexes are sterile with hypogonadotrophic hypogonadism and do not show the normal rise in luteinising hormone after gonadectomy. Mutant female mice do not develop mature Graafian follicles or form corpora lutea consistent with ovulatory failure. Mutant male mice have low blood testosterone levels and impaired spermatogenesis beyond the meiosis stage. Breeding Kiss‐CRE heterozygous mice with CRE‐activated tdTomato reporter mice allows fluorescence visualisation of Kiss1 neurones in brain slices. Approximately 80‐90% of tdTomato positive neurones in the ARC were co‐labelled with kisspeptin and expression of tdTomato in the AVPV region was sexually dimorphic, with higher expression in females than males. A small number of tdTomato‐labelled neurones was also found in other locations, including the lateral septum, the anterodorsal preoptic nucleus, the amygdala, the dorsomedial and ventromedial hypothalamic nuclei, the periaquaductal grey, and the mammillary nucleus. Three dimensional visualisation of Kiss1 neurones and fibres by CLARITY processing of whole brains showed an increase in ARC expression during puberty and higher numbers of Kiss1 neurones in the caudal region of the ARC compared to the rostral region. ARC Kiss1 neurones sent fibre projections to several hypothalamic regions, including rostrally to the periventricular and pre‐optic areas and to the lateral hypothalamus.
Interleukin‐12 modulates the immunomodulatory properties of human periodontal ligament cells
Authors: Issaranggun Na Ayuthaya B. , Satravaha P. , Pavasant P. 
Published: September 2016

Background and ObjectiveThe cytokine interleukin 12 (IL‐12) has been implicated as a potent stimulator of tissue degradation in the pathogenesis of several inflammatory diseases, including periodontitis. In patients with periodontitis, an increased level of IL‐12 is found in serum and gingival crevicular fluid. As inflammatory cytokines have been demonstrated to induce activation of the immunomodulatory properties of mesenchymal stem cells (MSCs), this study aimed to investigate the influence of IL‐12 on these properties in human periodontal ligament (hPDL) cells.Material and MethodsHuman PDL cells were isolated from periodontal tissue and incubated with 0–10 ng/mL of IL‐12 for 24 h. The levels of expression of interferon gamma (IFN‐γ), indoleamine 2,3‐dioxygenase (IDO) and human leukocyte antigen G (HLA‐G), as well as of the stem cell markers, CD73, CD90 and CD105, were assessed by quantitative PCR. The level of IFN‐γ protein was measured by ELISA, and IDO activity was measured by activity assay. The participation of IFN‐γ in the expression of IDO and HLA‐G was analyzed using neutralizing antibody against IFN‐γ.ResultsIL‐12 upregulated the expression of IFN‐γ in a dose‐dependent manner. Moreover, IL‐12 induced the expression of the immunomodulatory proteins IDO and HLA‐G via an IFN‐γ‐dependent pathway, as indicated by experiments using an IFN‐γ neutralizing antibody. Addition of exogenous IFN‐γ upregulated the expression of HLA‐G and IDO. Expression of the stem cell markers CD73, CD90 and CD105, as well as the pluripotent markers Nanog homeobox, octamer‐binding transcription factor 4 and SRY‐box 2, were also upregulated in IL‐12‐treated hPDL cells. Finally, IL‐12 inhibited osteogenic differentiation of the hPDL cells and preserved the self‐clonal expansion property of these cells, as assessed by Alizarin Red S staining and the colony‐forming unit assay.ConclusionExpression of IL‐12 during periodontitis may play an important role in the control of the inflammatory response via the induction of immunosuppressive molecules by hPDL cells. We hypothesize that this immunomodulatory property of IL‐12 will serve as a protective mechanism to preserve a population of stem cells under inflammatory conditions.
Matrix metalloproteinase‐8 activity in gingival crevicular fluid: development of a novel assay
Authors: Mc Crudden M. T. C. , Irwin C. R. , El karim I. , Linden G. J. , Lundy F. T. 
Published: September 2016

Background and ObjectiveThe matrix metalloproteinases (MMPs) play a role in regulating turnover and metabolism of connective tissues in health but they have also been implicated in a wide variety of pathological conditions, including periodontal disease. MMP‐8 has been extensively studied in periodontal health and disease using ELISA, although this technique is limited by its inability to determine enzyme activity. The aim was to develop an assay specifically to measure MMP‐8 activity and to demonstrate its use in the analysis of gingival crevicular fluid samples.Material and MethodsA specific antibody was used to coat black 96‐well microtitre plates to capture MMP‐8 selectively. The activity of bound MMP‐8 was measured using a fluorogenic substrate. Gingival crevicular fluid samples, from healthy and periodontally diseased sites, were collected using PerioPaper strips and tested for MMP‐8 activity.ResultsSignificantly higher MMP‐8 activity was demonstrated in gingival crevicular fluid from periodontally diseased sites compared with healthy sites that exhibited basal or no MMP‐8 activity. No cross‐reactivity with other MMPs was noted.ConclusionWe show, for the first time, that MMP‐8 activity can be specifically detected and quantified in gingival crevicular fluid samples. Measurement of MMP‐8 activity could prove to be useful in monitoring periodontal disease progression.
Retracted: Glucose deprivation induced upregulation of phosphoenolpyruvate carboxykinase modulates virulence in Leishmania donovani
Authors: Saini Savita , Kumar Ghosh Ayan , Singh Ruby , Das Sushmita , Abhishek Kumar , Kumar Ajay , Verma Sudha , Mandal Abhishek , Hasan Sardar Abul , Purkait Bidyut , Kumar Ashish , Kumar Sinha Kislay , Das Pradeep 
Published: September 2016

SummaryVarious physiological stimuli trigger the conversion of noninfective Leishmania donovani promastigotes to the infective form. Here, we present the first evidence of the effect of glucose starvation, on virulence and survival of these parasites. Glucose starvation resulted in a decrease in metabolically active parasites and their proliferation. However, this was reversed by supplementation of gluconeogenic amino acids. Glucose starvation induced metacyclogenesis and enhanced virulence through protein kinase A regulatory subunit (LdPKAR1) mediated autophagy. Glucose starvation driven oxidative stress upregulated the antioxidant machinery, culminating in increased infectivity and greater parasitic load in primary macrophages. Interestingly, phosphoenolpyruvate carboxykinase (LdPEPCK), a gluconeogenic enzyme, exhibited the highest activity under glucose starvation to regulate growth of L. donovani by alternatively utilising amino acids. Deletion of LdPEPCK (Δpepck) decreased virulent traits and parasitic load in primary macrophages but increased autophagosome formation in the mutant parasites. Furthermore, Δpepck parasites failed to activate the Pentose Phosphate Pathway shunt, abrogating NADPH/NADP+ homoeostasis, conferring increased susceptibility towards oxidants following glucose starvation. In conclusion, this study showed that L. donovani undertakes metabolic rearrangements via gluconeogenesis under glucose starvation for acquiring virulence and its survival in the hostile environment.
The bacteriophage‐derived transcriptional regulator, LscR, activates the expression of levansucrase genes in Pseudomonas syringae
Authors: Abdallah Khaled , Hartman Katharina , Pletzer Daniel , Zhurina Daria , Ullrich Matthias S. 
Published: September 2016

SummarySynthesis of the exopolysaccharide levan occurs in the bacterial blight pathogen of soybean, Pseudomonas syringae pv. glycinea PG4180, when this bacterium encounters moderate to high concentrations of sucrose inside its host plant. The process is mediated by the temperature‐dependent expression and secretion of two levansucrases, LscB and LscC. Previous studies showed the importance of a prophage‐associated promoter element in driving the expression of levansucrase genes. Herein, heterologous screening for transcriptional activators revealed that the prophage‐borne transcriptional regulator, LscR, from P. syringae mediates expression of levansucrase. A lscR‐deficient mutant was generated and exhibited a levan‐negative phenotype when grown on a sucrose‐rich medium. This phenotype was confirmed by zymographic analysis and Western blots which demonstrated absence of levansucrase in the supernatant and total cell lysates. Transcriptional analysis showed a down‐regulation of expression levels of levansucrase and glycosyl hydrolase genes in the lscR‐deficient mutant. Ultimately, a direct binding of LscR to the promoter region of levansucrase was demonstrated using electrophoretic mobility shift assays allowing to conclude that a bacteriophage‐derived regulator dictates expression of bacterial genes involved in in planta fitness.
Mainstream capnography system for nonintubated children in the postanesthesia care unit: Performance with changing flow rates, and a comparison to side stream capnography
Authors: Nagoshi Makoto , Morzov Rica , Hotz Justin , Belson Paula , Matar Marla , Ross Patrick , Wetzel Randall 
Published: September 2016

AbstractIntroductionMonitoring of exhaled carbon dioxide (CO2) in nonintubated patients is challenging. We compared the precision of a mainstream mask capnography to side stream sampling nasal cannula capnography. In addition, we compared the effect of gas flow rates on the measured exhaled CO2 between mainstream mask and side stream nasal cannula capnography.MethodsA mainstream mask capnography system (cap‐ONE) was tested. Children (weight of 7–40 kg, ASA 1–2) following anesthesia for minor procedures were assigned randomly to side stream or mainstream sampling groups. The side stream group wore a nasal cannula with CO2 side port (NC). In the postanesthesia care unit, O2 flow was started at 5 l·min−1, reduced to 2 and then 0.25 l·min−1 every 3 min. Capnogram analysis measuring heights of all the waveforms was performed for continuous 120 s from the end of recording at each O2 flow rate for each group.ResultsFifty‐eight children were enrolled and 39 were analyzed (18 side stream NC and 21 mainstream mask). There were two mouth breathing children excluded from study in side stream NC group due to failure to capture measurable CO2 waveforms. Peak CO2 values measured by mainstream mask system were normally (Gaussian) distributed with smaller standard deviation (sd) at each O2 flow than were those measured by side stream NC system which demonstrated irregular distributions with larger sd. Peak CO2 values measurement was less affected by a change in flow rate in mainstream mask group than in side stream NC group (P = 0.04 in 5–0.25 l·min−1 O2 flow change).ConclusionA new mainstream mask system (cap‐ONE) performed with greater precision than side stream NC monitoring regardless of mouth breathing. Measurement of peak CO2 values by mainstream mask system showed normal distribution with smaller standard deviation (sd) and was less affected by O2 flow change in predictable fashion.
Risk factors of infant anemia in the perinatal period
Authors: Hirata Michio , Kusakawa Isao , Ohde Sachiko , Yamanaka Michiko , Yoda Hitoshi 
Published: September 2016

AbstractBackgroundInfants are at particular risk of iron‐deficiency anemia. We investigated changes in the blood count of the mother and infant as well as the relationship between them and the relationship between infant nutrition method and infant anemia.MethodsThis retrospective cohort study included healthy neonates born between August 2011 and July 2014 at St Luke's International Hospital, Tokyo, Japan. Data from maternal blood samples obtained during late pregnancy and those of infants obtained at birth and at the age of 3, 6, and 9 months were analyzed. Using multivariate logistic regression, we investigated nutrition methods, maternal anemia, and other clinically relevant parameters that were potential risk factors for infant anemia.ResultsIn total, data for 3472 infants and their mothers were analyzed. Nutrition method was the most significant risk factor for infant anemia, with risk of future anemia decreasing in the following order: exclusive breast‐feeding, partial breast‐feeding, and formula feeding. Furthermore, low umbilical cord blood hemoglobin led to a tendency toward anemia in the child.ConclusionInfant nutrition method was the most significant factor related to anemia in late infancy. Infants with low umbilical cord blood hemoglobin are more likely to develop anemia in late infancy.
Willingness of human immunodeficiency virus‐positive patients to donate their organs for transplantation in Taiwan: a cross‐sectional questionnaire survey
Authors: Lee Yi‐Chieh , Hung Chien‐Ching , Cheng Aristine , Liu Wen‐Chun , Wu Pei‐Ying , Yang Shang‐Ping , Zhang Jun‐Yu , Luo Yu‐Zhen , Chang Hsi‐Yen , Sun Hsin‐Yun , Chang Shan‐Chwen 
Published: September 2016

AbstractBackgroundWith the introduction of combination antiretroviral therapy (cART) that has significantly improved survival, human immunodeficiency virus (HIV)‐positive patients may be potential organ donors to HIV‐positive recipients in a few countries. Organ shortage remains a challenge for organ transplantation in Taiwan, where organ donation by HIV‐positive patients remains prohibited by law.MethodsWe assessed the willingness of organ donation (should they be pronounced brain dead, and the ban on HIV‐positive organ donation be lifted) among HIV‐positive patients who received regular HIV care at a university hospital in a cross‐sectional survey between May and August 2015 with the use of an anonymous, self‐administered questionnaire interview.ResultsOf the 1010 participants, 93.7% were receiving cART with the latest mean CD4 count and plasma HIV RNA load of 587 cells/mm3 and 2.73 log10 copies/mL, respectively. Overall, 71.9% were willing to donate organs. In multivariate analysis, factors associated with willingness to donate organs included college or graduate school diploma (odds ratio [OR] 1.571, 95% confidence interval [CI] 1.166‐2.191), registered willingness to donate in the National Health Insurance system (OR 9.430, 95% CI 1.269‐70.051), and knowledge of the information on HIV‐positive deceased donors (HIVDD) (OR 1.673, 95% CI 1.073‐2.608).ConclusionsWe concluded that a significant proportion (71.9%) of HIV‐positive Taiwanese patients were willing to donate their organs. The willingness was associated with a higher education level, prior registered willingness to donate organs, and awareness of HIVDD.
Innovative Use of Palladium Compounds To Selectively Detect Live Enterobacteriaceae in Milk by PCR
Authors: Soejima Takashi , Iwatsuki Kei-ji 
Published: September 2016

ABSTRACT

Ethidium monoazide and propidium monoazide (EMA and PMA) have been used in combination with PCR for more than a decade to facilitate the discrimination of live and dead bacteria (LD discrimination). These methods, however, require many laborious procedures, including the use of a darkroom. Here, we demonstrate an innovative use of palladium compounds involving lower limits of detection and quantification of targeted live cells, fewer laborious procedures, lower costs, and potentially higher-throughput analysis than the use of EMA and PMA. We have also recently reported platinum compounds for LD discrimination, but platinum compounds carry costs that are 3 times higher because of the requirement for much larger amounts for LD discrimination than palladium compounds. Palladium compounds can penetrate dead (compromised) but not live bacteria and can be chelated primarily by chromosomal DNA and cell wall transmembrane proteins, with small amounts of DNA-binding proteins
in vivo
. The new mechanism for palladium compounds is obviously different from that of platinum compounds, which primarily target DNA. Combining palladium compounds with PCR (Pd-PCR) in water resulted in discrimination between live and dead
Enterobacteriaceae
bacteria that was much clearer than that seen with the PMA method. Pd-PCR correlated with reference plating or with the currently used PMA-PCR method for pasteurized milk, based on EN ISO 16140:2003 validation. Pd-PCR enabled us to specifically detect and assay viable
Enterobacteriaceae
cells at concentrations of 5 to 10 CFU/ml in milk while following U.S./EU regulations after a 4.5-h process in a typical laboratory exposed to natural or electric light, as specified by U.S./EU regulations.

IMPORTANCE
Ethidium monoazide and propidium monoazide (EMA and PMA) facilitate the discrimination of live and dead bacteria (LD discrimination). These methods, however, require many laborious procedures, including the use of a darkroom. Here, we demonstrate an innovative use of palladium compounds involving fewer laborious procedures, lower costs, and potentially higher-throughput analysis than the use of EMA and PMA. We have also recently reported platinum compounds for LD discrimination, but platinum compounds carry costs that are 3 times higher because of the requirement for much larger amounts for LD discrimination than palladium compounds, which have also a novel reaction mechanism different from that of platinum compounds. In view of testing cost, palladium compounds are also very useful here compared with platinum compounds. Ultimately, the innovative Pd-PCR method may be also substituted for the currently used reference plating methods.