bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeat robot‐assisted partial nephrectomy (RAPN): feasibility and early outcomes
Authors: Autorino Riccardo , Khalifeh Ali , Laydner Humberto , Samarasekera Dinesh , Rizkala Emad , Eyraud Remi , Haber Georges‐Pascal , Stein Robert J. , Kaouk Jihad H. 
Published: April 2013

Objective
To demonstrate the feasibility, and to report our single‐centre perioperative outcomes of repeat robot‐assisted partial nephrectomy (RAPN).
Patients and Methods
From June 2006 to June 2012, 490 patients underwent RAPN for a renal mass at our centre. Of these patients, nine who had undergone previous ipsilateral nephron‐sparing surgery (NSS) were included in the analysis.
Patient charts were reviewed to obtain demographic data, preoperative surgical history, operative details, and postoperative outcomes and follow‐up data.
Results
In all, 12 tumours were removed in nine patients (median age 69 years; six female). A third of the operations were performed on patients with a solitary kidney. The median (range) R.E.N.A.L. nephrometry score for the resected masses was 7 (4–8).
The warm ischaemia time was 17.5 min and in three of the nine patients an unclamped procedure was performed. No intraoperative complications were registered, whereas only two minor complications occurred postoperatively. There were no renal unit losses. All surgical margins were negative.
There was no significant difference between mean preoperative and latest postoperative mean estimated glomerular filtration rates (70.5 vs 63.5 mL/min/1.73m2, P > 0.05).
At a mean (sd) follow‐up of 8.3 (13) months, eight of the nine patients with a pathology diagnosis of malignant neoplasm were alive and free from disease at the latest follow‐up.
Conclusion
Although technically more demanding, repeat RAPN can be safely and effectively performed in patients presenting with local recurrence after primary NSS for kidney cancer.
A gene trap mutagenesis screen for genes underlying cellular response to the mood stabilizer lithium
Authors: Gow Matthew , Mirembe Dora , Longwe Zaomba , Pickard Benjamin S. 
Published: April 2013

AbstractIdentifying the biological pathways mediating the action of a therapeutic compound may help the development of more specific treatments while also increasing our understanding of the underlying disease pathology. Salts of the metal lithium are commonly used as a front‐line mood stabilizing treatment for bipolar disorder. Lithium's action has been variously linked to inositol phosphate metabolism and the WNT/Glycogen Synthase Kinase 3β (GSK3β)/β‐Catenin signalling cascade, but, to date, little is known about which of these provides the principal therapeutic benefit for patients and, more specifically, which constituent genes, through presumed sequence variation, determine differences in patient response to treatment. Here, we describe a functional screen in which SH‐SY5Y neuroblastoma cells were randomly mutated through genomic integration of the pMS1 poly A ‘gene trap’ plasmid vector. Lithium normally induces differentiation of neuroblastoma cells, but a small proportion of mutated cells continued to proliferate and formed colonies. Rapid amplification of cDNA ends (RACE)‐PCR was used to identify the ‘trapped’ gene in each of these lithium‐resistant colonies. Heterozygous, gene trap integrations were identified within ten genes, eight of which are likely to produce loss‐of‐function mutations including MED10, MSI2 and three long intergenic non‐coding (LINC) RNAs. Both MED10 and MSI2 have been previously linked with WNT/GSK3β/β‐Catenin pathway function suggesting that this is an important mediator of lithium action in this screen. The methodology applied here provides a rapid, objective and economic approach to define the genetic contribution to drug action, but could also be readily adapted to any desired in vitro functional selection/screening paradigm.
Iron storage disease in Asia‐Pacific populations: The importance of non‐HFE mutations
Authors: McDonald Cameron J , Wallace Daniel F , Crawford Darrell H G , Subramaniam V Nathan 
Published: April 2013

AbstractHereditary hemochromatosis (HH) is a widely recognized and well‐studied condition in European populations. This is largely due to the high prevalence of the C282Y mutation of HFE. Although less common than in Europe, HH cases have been reported in the Asia‐Pacific region because of mutations in both HFE and non‐HFE genes. Mutations in all of the currently known genes implicated in non‐HFE HH (hemojuvelin, hepcidin, transferrin receptor 2, and ferroportin) have been reported in patients from the Asia‐Pacific region. This review discusses the molecular basis of HH and the genes and mutations known to cause non‐HFE HH with particular reference to the Asia‐Pacific region. Challenges in the genetic diagnosis of non‐HFE HH are also discussed and how new technologies such as next generation sequencing may be informative in the future.
DID INEQUALITY CAUSE THE U.S. FINANCIAL CRISIS?
Authors: van Treeck Till 
Published: April 2013

AbstractIn his widely discussed book ‘Fault Lines’ (2010), Raghuram Rajan argues that many low and middle income consumers have reduced their saving and increased debt since income inequality started to soar in the United States in the early 1980s. This has temporarily kept private consumption and employment high, but it also contributed to the creation of a credit bubble. This surge in household indebtedness turned out to be unsustainable in the financial crisis starting in 2007. Although Rajan and others emphasize the role of government in promoting credit to those households with declining relative (permanent) incomes, other strands of the literature have focused more explicitly on the implications of rising inequality for aggregate demand and households’ demand for credit. These differences in emphasis may explain why the literature on the inequality‐crisis nexus appears somewhat disparate, even though the various strands are far from mutually exclusive but rather complement each other. We therefore place the ‘Rajan hypothesis’ in the context of competing theories of consumption, and survey the empirical literature on the effects of inequality on household behaviour. We conclude that the empirical evidence calls for a renaissance of the relative income hypothesis of consumption.
Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort
Authors: Fedorowski A. , Burri P. , Struck J. , Juul‐Möller S. , Melander O. 
Published: April 2013

ObjectivesThe aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.Design and settingAn observational study was conducted including 255 patients (mean age 60 years, range 15–93; 45% men) with unexplained syncopal attacks. Subjects underwent an expanded head‐up tilt test including carotid sinus massage, and nitroglycerin provocation if indicated. Using logistic regression, we explored the associations between specific diagnoses of syncope and resting levels of circulating biomarkers: C‐terminal pro‐arginine vasopressin (CT‐proAVP), C‐terminal endothelin‐1 precursor fragment (CT‐proET‐1), midregional fragments of pro‐atrial natriuretic peptide (MR‐proANP) and pro‐adrenomedullin (MR‐proADM).ResultsA total of 142 (56%) patients were diagnosed with vasovagal syncope (VVS), 85 (33%) with orthostatic hypotension (OH) and 47 (18%) with carotid sinus hypersensitivity (CSH); in addition, 74 (29%) patients had more than one diagnosis. Thirty‐five patients (14%) demonstrated a cardioinhibitory reflex. The probability of VVS was highest in the first quartile of MR‐proANP [Q1 vs. Q4: odds ratio (OR) 5.57, 95% confidence interval (CI) 1.86–16.74; P < 0.001] and CT‐proET‐1 (OR 7.17, 95% CI 2.43–21.13; P < 0.001). By contrast, the probability of OH was highest in the fourth quartile of CT‐proET‐1 (Q4 vs. Q1: OR 8.66, 95% CI 2.49–30.17; P < 0.001). Furthermore, CSH was most frequently observed in the first quartile of MR‐proANP (Q1 vs. Q4: OR 6.57, 95% CI 1.62–26.62; P = 0.008) among those over 60 years of age, whereas the cardioinhibitory reflex was strongly associated with low CT‐proET‐1 levels (Q1 vs. Q4: OR 69.7, 95% CI 6.97–696.6; P < 0.001). Moreover, in patients with VVS, a high concentration of CT‐proET‐1 was predictive of OH (OR per 1 SD 2.4, 95% CI 1.15–5.02; P = 0.02), whereas low CT‐proET‐1 suggested involvement of the cardioinhibitory reflex (OR per 1SD 0.42, 95% CI 0.25–0.70; P = 0.001).ConclusionsThe levels of MR‐proANP and CT‐proET‐1 are markedly changed in common forms of syncope, suggesting the involvement of novel neurohormonal mechanisms in syncopal attacks.
Circulating interleukin‐6 concentration and cognitive decline in old age: the PROSPER study
Authors: Mooijaart S. P. , Sattar N. , Trompet S. , Lucke J. , Stott D. J. , Ford I. , Jukema J. W. , Westendorp R. G. J. , de Craen A. J. M. 
Published: April 2013

AbstractBackgroundInflammation is involved in the pathogenesis of cardiovascular disease and cognitive decline. Interleukin‐6 (IL‐6) has a role in cardiovascular disease, but the association of IL‐6 concentration and the functional IL‐6 ‐174 polymorphism with cognitive decline has not been demonstrated unequivocally. The objective of this study was to investigate the associations between both high concentration of IL‐6 and the ‐174 promoter polymorphism, and increased cognitive decline in old age.MethodsOver 5000 participants of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) with a mean age of 75 years and a history of cardiovascular disease or its risk factors were included in this study. We determined baseline concentrations of IL‐6 and genotype of the IL‐6 ‐174 polymorphism, of which the C allele was previously shown to be associated with higher circulating concentrations of IL‐6. A cognitive test battery was administered at baseline and repeatedly during follow‐up (mean 39 months).ResultsIn the cross‐sectional analysis of 5653 participants, higher IL‐6 concentration was associated with worse executive cognitive function (P < 0.001), independent of cardiovascular disease status and risk factors. No association was found between IL‐6 concentration and memory function (P > 0.14). In the prospective analysis, higher IL‐6 concentration was associated with an increased rate of cognitive decline in both executive function (P = 0.002) and memory function (P = 0.002), again independent of cardiovascular disease status and risk factors. Although not associated with IL‐6 concentrations, the IL‐6 ‐174 CC genotype was associated with worse performance on the Stroop test (P = 0.045).ConclusionsHigher circulating levels of IL‐6 were associated with worse cognitive function and steeper cognitive decline and provide preliminary genetic evidence for a potential causal association. The findings support the importance of the need for further investigation of the IL‐6 pathway in cognitive decline.
Soluble urokinase plasminogen activator receptor is compartmentally regulated in decompensated cirrhosis and indicates immune activation and short‐term mortality
Authors: Zimmermann H. W. , Reuken P. A. , Koch A. , Bartneck M. , Adams D. H. , Trautwein C. , Stallmach A. , Tacke F. , Bruns T. 
Published: April 2013

AbstractObjectivePatients with decompensated cirrhosis are susceptible to bacterial infections, which are associated with organ failure and a high mortality rate. Reliable biomarkers are needed to identify patients who require intensified treatment. Our objective was to study the regulation and prognostic relevance of elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) in patients with advanced cirrhosis.Design, setting and participantsWe examined the associations between serum and ascitic fluid (AF) suPAR and liver function, bacterial infection, and short‐term mortality in 162 consecutive patients with decompensated cirrhosis undergoing diagnostic paracentesis in a tertiary health care centre in Germany.Main outcome measureTwenty‐eight‐day mortality.ResultsCirculating suPAR levels were increased in patients with decompensated cirrhosis and correlated with the severity of liver dysfunction and systemic inflammation but were not indicative of bacterial infection. Circulating suPAR levels >14.4 ng mL−1 predicted 28‐day mortality, even after adjustment for liver function and confounders [HR = 3.05 (1.35–6.90); P = 0.0076] equal to the MELD score (AUC = 0.71; 95% CI = 0.61–0.81; P < 0.001). Cut‐off levels derived from cohorts without liver disease were not applicable due to the low specificity. AF suPAR levels were elevated during spontaneous bacterial peritonitis (SBP), but not during episodes in which bacteria or bacterial DNA was translocated into the ascites. AF suPAR levels correlated poorly with systemic suPAR but were associated with a more severe course of SBP and a worse outcome. In vitro experiments revealed that monocytes, and to a lesser extent neutrophils, secrete suPAR after Toll‐like‐receptor ligation, which led to rapid urokinase plasminogen activator receptor cleavage followed by increased synthesis.ConclusionBlood and ascitic suPAR levels provide distinct, but relevant prognostic information on the severity of complications in patients with end‐stage liver disease.
Individualized therapy for metastatic colorectal cancer
Authors: Silvestri A. , Pin E. , Huijbers A. , Pellicani R. , Parasido E. M. , Pierobon M. , Petricoin E. , Liotta L. , Belluco C. 
Published: April 2013

AbstractSystemic therapeutic efficacy is central to determining the outcome of patients with metastatic colorectal cancer (CRC). In these patients, there is a critical need for predictive biomarkers to optimize efficacy whilst minimizing toxicity. The integration of a new generation of molecularly targeted drugs into the treatment of CRC, coupled with the development of sophisticated technologies for individual tumours as well as patient molecular profiling, underlines the potential for personalized medicine. In this review, we focus on the latest progress made within the genomic and proteomic fields, concerning predictive biomarkers for individualized therapy in metastatic CRC.
Impact of oral silymarin on virus‐ and non‐virus‐specific T‐cell responses in chronic hepatitis C infection
Authors: Adeyemo O. , Doi H. , Rajender Reddy K. , Kaplan D. E. 
Published: April 2013

SummarySilymarin displays anti‐inflammatory effects on T lymphocytes in vitro. The immunomodulatory properties of oral silymarin in vivo in humans with chronic hepatitis C have not previously been characterized. We hypothesized that silymarin would suppress T‐cell proliferation and pro‐inflammatory cytokine production of virus‐ and non‐virus‐specific T cells while increasing anti‐inflammatory IL‐10 production in vivo. Patients from one site of the SyNCH‐HCV double‐masked, placebo‐controlled study of oral silymarin in prior interferon nonresponders with chronic hepatitis C provided blood samples at baseline and treatment week 20. Mononuclear cells were stimulated with recombinant HCV proteins and controls in 3H‐thymidine proliferation assays, IFNγ ELISPOT and IL‐10 ELISPOT. The frequency of CD4+CD25hi and CD4+foxp3+ regulatory T cells, serum cytokine levels, serum IP‐10 and lymphocyte interferon‐stimulated gene expression were also quantified at baseline and week 20. Thirty‐two patients were recruited (10; placebo, 11; 420 mg three times a day, 11; 700 mg three times a day). Serum ALT and HCV RNA titres did not change in any group. HCV‐specific CD4+ T‐cell proliferation and the frequency of IFNγ‐ and IL‐10‐producing T cells were not significantly changed in silymarin‐treated subjects. However, C. albicans‐induced T‐cell IFNγ and phytohaemagglutinin‐induced T‐cell proliferation were suppressed by silymarin therapy. A trend towards augmentation of interferon‐induced ISG15 expression was present in the high‐dose silymarin group. While no effect on HCV‐specific T cells was identified, these data confirm that high‐dose oral silymarin exerts modest nonspecific immunomodulatory effects in vivo. The impact of this anti‐inflammatory effect on long‐term liver health in chronic hepatitis C merits future clinical investigation.
Does Economic Freedom Foster Tolerance?
Authors: Berggren Niclas , Nilsson Therese 
Published: April 2013

SummaryTolerance has the potential to affect both economic growth and wellbeing. It is therefore important to discern its determinants. We contribute to the literature by investigating whether the degree to which economic institutions and policies are market‐oriented is related to different measures of tolerance. Cross‐sectional and first‐difference regression analysis of up to 69 countries reveals that economic freedom is positively related to tolerance towards homosexuals, especially in the longer run, while tolerance towards people of a different race and a willingness to teach kids tolerance are not strongly affected by how free markets are. Stable monetary policy and outcomes is the area of economic freedom most consistently associated with greater tolerance, but the quality of the legal system seems to matter as well. Through instrumental variables and first‐difference results we find indications of a causal relationship.
Interaction of Mycobacterium tuberculosis Cell Wall Components with the Human Natural Killer Cell Receptors NKp44 and Toll‐Like Receptor 2
Authors: Esin S. , Counoupas C. , Aulicino A. , Brancatisano F. L. , Maisetta G. , Bottai D. , Di Luca M. , Florio W. , Campa M. , Batoni G. 
Published: April 2013

AbstractWe have previously demonstrated that a soluble form of the human NK cell natural cytotoxicity receptor NKp44, binds to the surface of Mycobacterium tuberculosis (MTB). Herein, we investigated the interaction of MTB cell wall components (CWC) with NKp44 or with Toll‐like receptor 2 (TLR2) and the role of NKp44 and TLR2 in the direct activation of NK cells upon stimulation with MTB CWC. By using several purified bacterial CWC in an ELISA, we demonstrated that NKp44 was able to bind to the MTB cell wall core mycolyl‐arabinogalactan‐peptidoglycan (mAGP) as well as to mycolic acids (MA) and arabinogalactan (AG), while soluble TLR2 bound to MTB peptidoglycan (PG), but not to MA or AG. The mAGP complex induced NK cell expression of CD25, CD69, NKp44 and IFN‐γ production at levels comparable to M. bovis Bacillus Calmette–Guérin‐stimulated (BCG) cells. While AG and MA used alone failed to induce NK cell activation, mycobacterial PG‐exhibited NK cell stimulatory capacity. Activation of resting NK cells by mAGP and IFN‐γ production were inhibited by anti‐TLR2 MAb, but not by anti‐NKp44 MAb. Differently, anti‐NKp44 MAb partially inhibited CD69 expression on NK cells pre‐activated with IL‐2 and then stimulated with mAGP or whole BCG. Overall, these results provide evidence that components abundant in mycobacterial cell wall are able to interact with NKp44 (AG, MA) and TLR‐2 (PG), respectively. While interaction of TLR2 with mycobacterial cell wall promotes activation of resting NK cells and IFN‐γ production, NKp44 interaction with its putative ligands could play a secondary role in maintaining cell activation.
Levels of Interleukin‐(IL)‐12p40 are Markedly Increased in Brucellosis Among Patients with Specific IL‐12B Genotypes
Authors: Eskandari‐Nasab E. , Moghadampour M. , Asadi‐Saghandi A. , Kharazi‐nejad E. , Rezaeifar A. , Pourmasoumi H. 
Published: April 2013

AbstractBrucellosis remains a major zoonosis worldwide. Brucella antigens induce the production of T‐helper 1 (Th1) cytokines such as interleukin‐12 (IL‐12) in humans. We aimed to investigate the association of two single nucleotide polymorphisms (SNPs) in the gene encoding the IL‐12p40 cytokine (IL‐12B) with brucellosis and to examine the functionality of these SNPs through measuring serum levels of IL‐12p40. We genotyped IL‐12B gene rs3212227, A>C; rs6887695 G>C polymorphisms in a case‐control study on a total of 281 subjects including 153 patients with active brucellosis and 128 healthy controls, using RFLP and serum IL‐12p40 levels, were assessed by ELISA. The rs3212227 minor allele (C) and homozygote genotype (CC) were more frequent in controls compared with patients with brucellosis (P = 0.006, OR = 0.608, 95%CI = 0.429–0.861 for the C allele; P = 0.024, OR = 0.443, 95% CI: 0.218–0.900 for the CC genotype). Comparison of IL‐12B genotypes and serum levels of the IL‐12p40 revealed that rs3212227 AA genotype, with higher frequency in patients than in controls, was associated with increased levels of the cytokine (P = 0.0001). Furthermore, the distribution of haplotype and genotype combinations in our study suggested that rs3212227C/rs6887695C haplotype or CC/GC or CC/CC genotype combinations may protect controls against Brucella infection by contributing to a functional downregulation of the serum IL‐12p40 production in vivo, as shown by ELISA (P < 0.05). Overall, our study demonstrated that rs3212227 A variant was associated with higher levels of serum IL‐12p40 and could possibly contribute to an inherited predisposition to brucellosis.
Molecular phylogeny of the beetle tribe Oxypodini (Coleoptera: Staphylinidae: Aleocharinae)
Authors: OSSWALD JUDITH , BACHMANN LUTZ , GUSAROV VLADIMIR I. 
Published: April 2013

AbstractThis is the first study to comprehensively address the phylogeny of the tribe Oxypodini Thomson and its phylogenetic relationships to other tribes within the staphylinid subfamily Aleocharinae. Using the hitherto largest molecular dataset of Aleocharinae comprising of 4599 bp for representatives of 22 tribes, the Oxypodini are recovered as non‐monophyletic. Members of the tribe belong to three distantly related lineages within the Aleocharinae: (i) the Amarochara group as sister clade to the tribe Aleocharini, (ii) the subtribe Tachyusina within a clade that also includes the tribes Athetini and Hygronomini, (iii) all other Oxypodini in a clade that also includes the tribes Placusini, Hoplandriini and Liparocephalini. Based on the inferred phylogeny, five subtribes of the Oxypodini are recognized: Dinardina Mulsant & Rey, Meoticina Seevers, Microglottina Fenyes, Oxypodina Thomson and Phloeoporina Thomson. The following changes in the classification of the Aleocharinae are proposed: (i) Amarochara Thomson is removed from the Oxypodini and placed in the tribe Aleocharini; (ii) the subtribe Taxicerina Lohse of the Athetini is reinstated as tribe Taxicerini to include Discerota Mulsant & Rey, Halobrecta Thomson (both removed from the Oxypodini) and Taxicera Mulsant & Rey; (iii) the subtribe Tachyusina Thomson is excluded from the Oxypodini and provisionally treated as tribe Tachyusini; (iv) the oxypodine subtribe name Blepharhymenina Klimaszewski & Peck is placed in synonymy with the subtribe name Dinardina Mulsant & Rey.
Discovery of the natural anti‐Gal antibody and its past and future relevance to medicine
Authors: Galili Uri 
Published: April 2013

AbstractThis is a personal account of the discovery of the natural anti‐Gal antibody, the most abundant natural antibody in humans, the reciprocal distribution of this antibody and its ligand the α‐gal epitope in mammals and the immunological barrier this antibody has formed in porcine to human xenotransplantation. This barrier has been overcome in the recent decade with the generation of α1,3‐galactosyltransferase gene‐knockout pigs. However, anti‐Gal continues to be relevant in medicine as it can be harnessed for various therapeutic effects. Anti‐Gal converts tumor lesions injected with α‐gal glycolipids into vaccines that elicit a protective anti‐tumor immune response by in situ targeting of tumor cells for uptake by antigen‐presenting cells. This antibody further accelerates wound and burn healing by interaction with α‐gal nanoparticles applied to injured areas and induction of rapid recruitment and activation of macrophages. Anti‐Gal/α‐gal nanoparticle immune complexes may further induce rapid recruitment and activation of macrophages in ischemic myocardium and injured nerves, thereby inducing tissue regeneration and prevention of fibrosis.