bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ricolinostat (ACY‐1215) induced inhibition of aggresome formation accelerates carfilzomib‐induced multiple myeloma cell death
Authors: Mishima Yuko , Santo Loredana , Eda Homare , Cirstea Diana , Nemani Neeharika , Yee Andrew J. , O'Donnell Elizabeth , Selig Martin Karl , Quayle Steven N. , Arastu‐Kapur Shirin , Kirk Christopher , Boise Lawrence H. , Jones Simon S. , Raje Noopur 
Published: February 2015

SummaryProteasome inhibition induces the accumulation of aggregated misfolded/ubiquitinated proteins in the aggresome; conversely, histone deacetylase 6 (HDAC6) inhibition blocks aggresome formation. Although this rationale has been the basis of proteasome inhibitor (PI) and HDAC6 inhibitor combination studies, the role of disruption of aggresome formation by HDAC6 inhibition has not yet been studied in multiple myeloma (MM). The present study aimed to evaluate the impact of carfilzomib (CFZ) in combination with a selective HDAC6 inhibitor (ricolinostat) in MM cells with respect to the aggresome‐proteolysis pathway. We observed that combination treatment of CFZ with ricolinostat triggered synergistic anti‐MM effects, even in bortezomib‐resistant cells. Immunofluorescent staining showed that CFZ increased the accumulation of ubiquitinated proteins and protein aggregates in the cytoplasm, as well as the engulfment of aggregated ubiquitinated proteins by autophagosomes, which was blocked by ricolinostat. Electron microscopy imaging showed increased autophagy triggered by CFZ, which was inhibited by the addition of ACY‐1215. Finally, an in vivo mouse xenograft study confirmed a decrease in tumour volume, associated with apoptosis, following treatment with CFZ in combination with ricolinostat. Our results suggest that ricolinostat inhibits aggresome formation, caused by CFZ‐induced inhibition of the proteasome pathway, resulting in enhanced apoptosis in MM cells.
Haematopoietic and immune defects associated with GATA2 mutation
Authors: Collin Matthew , Dickinson Rachel , Bigley Venetia 
Published: February 2015

SummaryHeterozygous familial or sporadic GATA2 mutations cause a multifaceted disorder, encompassing susceptibility to infection, pulmonary dysfunction, autoimmunity, lymphoedema and malignancy. Although often healthy in childhood, carriers of defective GATA2 alleles develop progressive loss of mononuclear cells (dendritic cells, monocytes, B and Natural Killer lymphocytes), elevated FLT3 ligand, and a 90% risk of clinical complications, including progression to myelodysplastic syndrome (MDS) by 60 years of age. Premature death may occur from childhood due to infection, pulmonary dysfunction, solid malignancy and MDS/acute myeloid leukaemia. GATA2 mutations include frameshifts, amino acid substitutions, insertions and deletions scattered throughout the gene but concentrated in the region encoding the two zinc finger domains. Mutations appear to cause haplo‐insufficiency, which is known to impair haematopoietic stem cell survival in animal models. Management includes genetic counselling, prevention of infection, cancer surveillance, haematopoietic monitoring and, ultimately, stem cell transplantation upon the development of MDS or another life‐threatening complication.
Salvage radical prostatectomy for recurrent prostate cancer: verification of European Association of Urology guideline criteria
Authors: Mandel Philipp , Steuber Thomas , Ahyai Sascha , Kriegmair Maximilian , Schiffmann Jonas , Boehm Katharina , Heinzer Hans , Michl Uwe , Schlomm Thorsten , Haese Alexander , Huland Hartwig , Graefen Markus , Tilki Derya 
Published: February 2015

ObjectiveTo analyse oncological and functional outcomes of salvage radical prostatectomy (SRP) in patients with recurrent prostate cancer and to compare outcomes of patients within and outside the European Association of Urology (EAU) guideline criteria (organ‐confined prostate cancer ≤T2b, Gleason score ≤7 and preoperative PSA level <10 ng/mL) for SRP.Patients and MethodsIn all, 55 patients who underwent SRP from January 2007 to December 2012 were retrospectively analysed. Kaplan–Meier curves assessed time to biochemical recurrence (BCR), metastasis‐free survival (MFS) and cancer‐specific survival. Cox regressions addressed factors influencing BCR and MFS. BCR was defined as a PSA level of >0.2 ng/mL and rising, continence as the use of 0–1 safety pad/day, and potency as a five‐item version of the International Index of Erectile Function score of ≥18.ResultsThe median follow‐up was 36 months. After SRP, 42.0% of the patients experienced BCR, 15.9% developed metastasis, and 5.5% died from prostate cancer. Patients fulfilling the EAU guideline criteria were less likely to have positive lymph nodes (LNs) and had significantly better BCR‐free survival (5‐year BCR‐free survival 73.9% vs 11.6%; P = 0.001). In multivariate analysis, low‐dose‐rate brachytherapy as primary treatment (P = 0.03) and presence of positive LNs at SRP (P = 0.02) were significantly associated with worse BCR‐free survival. The presence of positive LNs or Gleason score >7 at SRP were independently associated with metastasis. The urinary continence rate at 1 year after SRP was 74%. Seven patients (12.7%) had complications ≥III (Clavien grade).ConclusionSRP is a safe procedure providing good cancer control and reasonable urinary continence. Oncological outcomes are significantly better in patients who met the EAU guideline recommendations.
Quantitative relationship between liver fat content and metabolic syndrome in obese children and adolescents
Authors: Zhang Hongxi , Yang Huiping , Lai Can , Xu Xiaoqin , Huang Ke , Fu Junfen 
Published: February 2015

SummaryObjectivePrevious studies have shown a significant association between quantified liver fat content (LFC) and metabolic syndrome (MetS) in adults, but the nature of this association in obese paediatric populations is unclear. The aim of this study was to investigate the quantitative relationship of LFC to MetS and its individual components in obese children and adolescents.DesignA population‐based cross‐sectional study.Patients and measurementsOne hundred and eighty‐nine Chinese obese paediatric subjects aged 5–16 years were enrolled. Measurements included MetS components, as defined by the Chinese‐specific version of the International Diabetes Foundation MetS criteria (MetS‐CHN2012), and LFC using proton magnetic resonance spectroscopy.ResultsLFC was significantly higher in subjects with MetS [median 9·7% (interquartile range 4·5–19·9%)] than without MetS [5·7% (2·0–12·8%)] (P < 0·01). LFC was also positively associated with the total number of MetS components (P for trend <0·01). In analyses adjusted for traditional risk factors, increasing levels of LFC were associated with a greater risk of MetS, hypertriglyceridaemia and low high‐density lipoprotein cholesterol (P < 0·05 for all associations), but were not associated with risk of hyperglycaemia or hypertension.ConclusionsIn obese Chinese paediatric patients, quantitative measures of LFC are positively associated with the risk of MetS, hypertriglyceridaemia and low high‐density lipoprotein cholesterol, independent of traditional risk factors. These findings suggest that quantitatively measured LFC may be a clinically useful marker for identifying obese paediatric who are at increased risk of developing MetS and its components.
Plasma zinc α2‐glycoprotein levels are elevated in smokers and correlated with metabolic syndrome
Authors: Tsai Jaw‐Shiun , Chen Su‐Chiu , Huang Kuo‐Chin , Lue Bee‐Horng , Lee Long‐Teng , Chiu Tai‐Yuan , Chen Ching‐Yu , Guo Fei‐Ran , Chuang Lee‐Ming 
Published: February 2015

AbstractBackgroundSmoking is a strong risk factor of metabolic syndrome. Zinc α2‐glycoprotein (ZAG) is a protein involved in metabolic syndrome. This study aims to investigate the effect of smoking on plasma ZAG levels and its relations to metabolic syndrome.Materials and methodsA group of 41 cigarette smokers and 47 non‐smokers were enrolled. ZAG levels were measured to correlate to participants’ demographic and metabolic parameters.ResultsPlasma ZAG levels of smokers were higher than those of controls (P < 0·0001). Plasma ZAG levels were positively correlated with male gender (P = 0·0002), number of cigarettes smoked per day (P < 0·0001), smoking duration in years (P < 0·0001), smoking index (P < 0·0001) and nicotine dependence score (P < 0·0001). In the multiple regression analysis, smoking was a strong independent factor affecting plasma ZAG levels (P = 0·0034). Plasma ZAG levels elevated progressively with the number of metabolic syndrome components (P = 0·0143). In the multiple regression analysis, plasma ZAG was an independent factor for metabolic syndrome.ConclusionsPlasma ZAG levels are high in smokers and correlate with metabolic syndrome. Our results indicate ZAG is an independent risk factor, but also interacted with smoking, for the metabolic syndrome.
Cocaine self‐administration enhances excitatory responses of pyramidal neurons in the rat medial prefrontal cortex to human immunodeficiency virus‐1 Tat
Authors: Wayman Wesley N. , Chen Lihua , Napier T. Celeste , Hu Xiu‐Ti 
Published: February 2015

AbstractThe medial prefrontal cortex (mPFC) plays a critical role in reward‐motivated behaviors. Repeated cocaine exposure dysregulates the dorsal mPFC, and this is thought to contribute to cocaine‐seeking and relapse of abstinent abusers. Neuropathology of the mPFC also occurs in human immunodeficiency virus (HIV)‐positive individuals, and this is exaggerated in those who also abuse cocaine. The impact of the comorbid condition on mPFC neuronal function is unknown. To fill this knowledge gap, we performed a behavioral and electrophysiological study utilising adult male rats that self‐administered cocaine by pressing a lever for 14 once‐daily operant sessions. Saline‐yoked (SAL‐yoked) rats served as controls. Cue reactivity (CR) was used to indicate drug‐seeking, assessed by re‐exposing the rats to cocaine‐paired cues wherein non‐reinforced lever pressing was quantified 1 day (CR1) and 18–21 days (CR2) after the 14th operant session. Only cocaine self‐administration (COC‐SA) rats showed CR. One day after CR2, brain slices were prepared for electrophysiological assessment. Whole‐cell patch‐clamp recordings of dorsal (prelimbic) mPFC pyramidal neurons from COC‐SA rats showed a significant increase in firing evoked by depolarizing currents as compared with those from SAL‐yoked control rats. Bath application of the toxic HIV‐1 protein transactivator of transcription (Tat) also depolarized neuronal membranes and increased evoked firing. The Tat‐induced excitation was greater in the neurons from withdrawn COC‐SA rats than in controls. Tat also reduced spike amplitude, and this co‐varied with cocaine‐seeking during CR2. Taken together, these novel findings provide support at the neuronal level for the concept that the increased excitability of mPFC pyramidal neurons following cocaine self‐administration drives drug‐seeking and augments the neuropathophysiology caused by HIV‐1 Tat.
Different cerebrospinal fluid levels of Alzheimer‐type biomarker Aβ42 between general paresis and asymptomatic neurosyphilis
Authors: Luo X. , Shi H. , Hou L. , Zhong X. , Chen X. , Zhang Y. , Zheng D. , Tan Y. , Hu G. , Mu N. , Chen J. , Fang Y. , He H. , Ning Y. 
Published: February 2015

Background and purposeNeurosyphilis is a neurological disease that involves infection of the central nervous system with Treponema pallidum. With increases in unsafe sexual behaviour, syphilis has re‐emerged worldwide. To explore the amyloid and tau metabolism in neurosyphilis patients in different stages, the levels of Alzheimer‐type biomarkers in general paresis (GP) and asymptomatic neurosyphilis (ANS) patients in comparison to patients with Alzheimer's disease (AD) and normal controls (NCs) were investigated.Methodsβ‐amyloid peptide 1‐42 (Aβ42) and Aβ 1‐40 (Aβ40), tau hyperphosphorylated at threonine 181 (p‐tau181) and total tau (t‐tau) in cerebrospinal fluid (CSF) were measured by enzyme‐linked immunosorbent assay kits in 44 patients with GP, 10 patients with ANS, 45 patients with AD and 39 NCs.ResultsAlzheimer's disease patients had lower CSF Aβ42 levels combined with higher CSF t‐tau and p‐tau181 levels than other groups (all P < 0.001). The CSF Aβ42 levels decreased in GP compared to ANS and NCs (P < 0.001). CSF Aβ40, t‐tau and p‐tau181 levels were not different between the GP, ANS or NC groups.ConclusionsOur research has demonstrated that GP, ANS and AD patients are characterized by distinct patterns of the CSF biomarkers Aβ and tau. The distinct CSF Aβ pattern in GP suggests the existence of abnormal Aβ metabolism. Furthermore, different levels of CSF Aβ will be helpful for the differentiation between different stages of neurosyphilis.
Losses of soil carbon by converting tropical forest to plantations: erosion and decomposition estimated by δ13C
Authors: Guillaume Thomas , Damris Muhammad , Kuzyakov Yakov 
Published: February 2015

AbstractIndonesia lost more tropical forest than all of Brazil in 2012, mainly driven by the rubber, oil palm, and timber industries. Nonetheless, the effects of converting forest to oil palm and rubber plantations on soil organic carbon (SOC) stocks remain unclear. We analyzed SOC losses after lowland rainforest conversion to oil palm, intensive rubber, and extensive rubber plantations in Jambi Province on Sumatra Island. The focus was on two processes: (1) erosion and (2) decomposition of soil organic matter. Carbon contents in the Ah horizon under oil palm and rubber plantations were strongly reduced up to 70% and 62%, respectively. The decrease was lower under extensive rubber plantations (41%). On average, converting forest to plantations led to a loss of 10 Mg C ha−1 after about 15 years of conversion. The C content in the subsoil was similar under the forest and the plantations. We therefore assumed that a shift to higher δ13C values in plantation subsoil corresponds to the losses from the upper soil layer by erosion. Erosion was estimated by comparing the δ13C profiles in the soils under forest and under plantations. The estimated erosion was the strongest in oil palm (35 ± 8 cm) and rubber (33 ± 10 cm) plantations. The 13C enrichment of SOC used as a proxy of its turnover indicates a decrease of SOC decomposition rate in the Ah horizon under oil palm plantations after forest conversion. Nonetheless, based on the lack of C input from litter, we expect further losses of SOC in oil palm plantations, which are a less sustainable land use compared to rubber plantations. We conclude that δ13C depth profiles may be a powerful tool to disentangle soil erosion and SOC mineralization after the conversion of natural ecosystems conversion to intensive plantations when soils show gradual increase of δ13C values with depth.
The many faces of information technology interruptions: a taxonomy and preliminary investigation of their performance effects
Authors: Addas Shamel , Pinsonneault Alain 
Published: February 2015

AbstractDespite the growing importance of information technology (IT) interruptions for individual work, very little is known about their nature and consequences. This paper develops a taxonomy that classifies interruptions based on the relevance and structure of their content, and propositions that relate different interruption types to individual performance. A qualitative approach combining the use of log diaries of professional workers and semi‐structured interviews with product development workers provide a preliminary validation of the taxonomy and propositions and allow for the discovery of a continuum of interruption events that fall in‐between the extreme types in the taxonomy. The results show that some IT interruptions have positive effects on individual performance, whilst others have negative effects, or both. The taxonomy developed in the paper allows for a better understanding of the nature of different types of IT interruption and their consequences on individual work. By showing that different types of interruptions have different effects, the paper helps to explain and shed light on the inconsistent results of past research.
Antibacterial, antifungal and in vitro antileukaemia activity of metal complexes with thiosemicarbazones
Authors: Pahontu Elena , Julea Felicia , Rosu Tudor , Purcarea Victor , Chumakov Yurie , Petrenco Petru , Gulea Aurelian 
Published: February 2015

Abstract1‐phenyl‐3‐methyl‐4‐benzoyl‐5‐pyrazolone 4‐ethyl‐thiosemicarbazone (HL) and its copper(II), vanadium(V) and nickel(II) complexes: [Cu(L)(Cl)]·C2H5OH·(1), [Cu(L)2]·H2O (2), [Cu(L)(Br)]·H2O·CH3OH (3), [Cu(L)(NO3)]·2C2H5OH (4), [VO2(L)]·2H2O (5), [Ni(L)2]·H2O (6), were synthesized and characterized. The ligand has been characterized by elemental analyses, IR, 1H NMR and 13C NMR spectroscopy. The tridentate nature of the ligand is evident from the IR spectra. The copper(II), vanadium(V) and nickel(II) complexes have been characterized by different physico‐chemical techniques such as molar conductivity, magnetic susceptibility measurements and electronic, infrared and electron paramagnetic resonance spectral studies. The structures of the ligand and its copper(II) (2, 4), and vanadium(V) (5) complexes have been determined by single‐crystal X‐ray diffraction. The composition of the coordination polyhedron of the central atom in 2, 4 and 5 is different. The tetrahedral coordination geometry of Cu was found in complex 2 while in complex 4, it is square planar, in complex 5 the coordination polyhedron of the central ion is distorted square pyramid. The in vitro antibacterial activity of the complexes against Escherichia coli, Salmonella abony, Staphylococcus aureus, Bacillus cereus and the antifungal activity against Candida albicans strains was higher for the metal complexes than for free ligand. The effect of the free ligand and its metal complexes on the proliferation of HL‐60 cells was tested.
Prediction of risk for hepatocellular carcinoma by response of serum α‐fetoprotein to entecavir therapy
Authors: Yang Sung Wook , Kim Gi Hyun , Chung Jung Wha , Sohn Hyung Rae , Lee Sang Soo , Hong Sukho , Chung Seong Min , Jang Eun Sun , Jeong Sook‐Hyang , Kim Jin‐Wook 
Published: February 2015

AbstractBackground and AimsSerum α‐fetoprotein (AFP) is frequently elevated in patients with chronic hepatitis B (CHB) who do not have hepatocellular carcinoma (HCC). Entecavir (ETV) treatment reduces AFP levels in these patients, but the clinical significance of AFP response to ETV has not been fully studied. The aims of this study were to elucidate the temporal response of AFP to ETV therapy and to determine the relationship between AFP response and the subsequent development of HCC.MethodsAll consecutive nucleos(t)ide‐naïve CHB patients who started ETV therapy between March 2007 and February 2009 were selected from an electronic medical record database at a tertiary referral center (BESTCare). Clinical, biochemical, and virologic parameters were evaluated in relation to the serial AFP levels tested during ETV treatment.ResultsAmong the 244 enrolled patients, 66 had elevated AFP levels before ETV therapy. Low serum albumin was a significant predictor for elevated AFP. During 12 months of ETV therapy, AFP levels normalized in approximately three fourths of these patients. The decrease in AFP was delayed in patients with high baseline hepatitis B virus titers and in patients who subsequently developed HCC during ETV therapy. Incidence of HCC was similar regardless of baseline AFP levels. Among patients with elevated AFP, however, HCC developed exclusively in the subgroup where elevated AFP persisted for more than 6 months of ETV therapy.ConclusionsDelayed AFP response to ETV may serve as an indicator of high HCC risk.
Recycling Construction and Demolition Wastes as Building Materials: A Life Cycle Assessment
Authors: Guignot Sylvain , Touzé Solène , Von der Weid Frédéric , Ménard Yannick , Villeneuve Jacques 
Published: February 2015

SummaryThe present study addresses the topic of recycling materials from construction and demolition (C&D) wastes by proposing an environmental comparison between two recycling schemes for gravel wastes. The first scheme is the baseline process, and leads to direct most of the gravel to road construction. The second scheme relies on an innovative technology for the processing of gravel, based on electrical fragmentation, which leads to a clear separation between the aggregate contained in the gravel and the cement paste. The purity of the obtained materials opens new recycling outlets—as part of high‐quality structural concrete for the aggregate and as a substitute to natural minerals in clinker kilns for the cement paste. This shift towards more‐specific outlets for the materials found in reclaimed gravel carries significant modifications in the overall handling of C&D wastes and in the supply of natural and non‐natural materials for road construction and concrete formulation. The environmental implications of these modifications are evaluated according to a life cycle assessment methodology, which specifically addresses the influence of the distances and modalities of transportation of wastes to the crushing processes, as well as of natural and recycled aggregate to construction and demolition sites. The results point out significant environmental gains for the alternative recycling scheme, in all the considered impact categories and whatever the implemented scenarios. These gains are modulated by the various transport distances of the heavy materials heeded in the global system.
Mathematics interventions for children and adolescents with Down syndrome: a research synthesis
Authors: Lemons C. J. , Powell S. R. , King S. A. , Davidson K. A. 
Published: February 2015

AbstractBackgroundMany children and adolescents with Down syndrome fail to achieve proficiency in mathematics. Researchers have suggested that tailoring interventions based on the behavioural phenotype may enhance efficacy.MethodThe research questions that guided this review were (1) what types of mathematics interventions have been empirically evaluated with children and adolescents with Down syndrome?; (2) do the studies demonstrate sufficient methodological rigor?; (3) is there evidence of efficacy for the evaluated mathematics interventions?; and (4) to what extent have researchers considered aspects of the behavioural phenotype in selecting, designing and/or implementing mathematics interventions for children and adolescents with Down syndrome? Nine studies published between 1989 and 2012 were identified for inclusion.ResultsInterventions predominantly focused on early mathematics skills and reported positive outcomes. However, no study met criteria for methodological rigor. Further, no authors explicitly considered the behavioural phenotype.ConclusionsAdditional research using rigorous experimental designs is needed to evaluate the efficacy of mathematics interventions for children and adolescents with Down syndrome. Suggestions for considering the behavioural phenotype in future research are provided.
From service quality in organisations to self‐determination at home
Authors: Martínez‐Tur V. , Moliner C. , Peñarroja V. , Gracia E. , Peiró J. M. 
Published: February 2015

AbstractBackgroundIn our proposed model, family members' perceptions of service quality in organisations improve communication about self‐determination. In turn, family perceptions of communication openness have a positive relationship with self‐determination attitudes of family members. Finally, these attitudes predict self‐determination behaviours of individuals with intellectual disability, as reported by family members.MethodWe tested this model with a sample of 625 family members (196 using ‘day care services’ and 429 using ‘occupational services’).ResultsMulti‐sample structural equation modelling (SEM) supported the model. Communication and attitudes fully mediated the link from service quality to self‐determination behaviours.ConclusionsImproving family members' perceptions of service quality and opening channels of communication between professionals and family members are useful strategies to facilitate parents' positive attitudes and increase the frequency of self‐determination behaviours at home.