Several studies have shown that PPARγ/TZDs decrease IGF-1 levels and, thus, reduce cancer growth in carcinomas such as the pancreas, colon, liver, and prostate. However, other studies have shed light on the potential of the receptor as a biomarker for uroepithelial carcinomas, particularly due to its stimulatory effect on migration of bladder cancer cells. Furthermore, PPARγ may provide the tumor-promoting microenvironment by de novo synthesis of nutrients that are needed for bladder cancer development. In this review, we closely examine the TZD class of drugs and their effects on PPARγ in patient studies along with additional molecular factors that are positive modulators, such as protein phosphatase 5 (PP5), which may have considerable implications for bladder cancer therapy.The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPAR The predominant type of bladder cancer diagnosed among individuals in the United States is urothelial  carcinoma . Bladderγ) used in therapeutic treatments for patients diagnosed with type II diabetes mellitus [γ and play a role in metabolism through induction of genes that control glucose and lipid uptake [γ also activates adipogenesis, which is the process of transforming a preadipocyte stem cell into fully mature adipocyte [γ signaling in bladder cancer cells may provide a tumor microenvironment that allows for de novo lipogenesis for the use of increasing tumor mass and energy usage. However, the role of PPARγ in bladder cells is unknown.There has been increasing evidence showing that antidiabetic TZDs are linked to the risk of bladder cancer as well as other complications such as cardiovasculature (CVD) events. TZDs, such as pioglitazone and rosiglitazone, are synthetic ligands of peroxisome proliferator-activated receptors gamma  and adipocyte protein 2 (aP2) [γ has a major role in lipid and carbohydrate metabolism.PPARs are ligand-activated transcription factors that belong to the nuclear receptor superfamily . When a osanoids , PPARγ i 2 (aP2) , 26; theγ [γ activation affects lipid metabolism and ultimately enhances lipid storage and promotes insulin sensitivity in adipose tissue, liver, and muscle [γ and its ligands in cancer. Several cancers have shown reduced growth with PPARγ activation with the TZD troglitazone such as in carcinomas of the breast, kidney, liver, colon, pancreas, and prostate [TZDs have long been a common therapeutic method to treat patients with type II diabetes mellitus. TZDs are used to treat hyperglycemia and insulin resistance, lowering fasting blood glucose and insulin, as well as HbA1C levels . Previouγ , and PPAd muscle , 23. Desd muscle , which od muscle . Studiesd muscle , 32, 33.prostate –39 as weprostate  and ACTHprostate . Howeverprostate , thyroidprostate , and nonprostate . On the prostate , ovarianprostate , oral caprostate , kidney prostate , and thyprostate . Analysiγ affects the expression of IGF-1, IGFBP-3, or the IGF receptor (IGFR) in the bladder or differences among the TZD drug class. The use of pioglitazone, and not rosiglitazone, has been associated with an increased risk of bladder cancer in a population-based cohort study, suggesting the risk is TZD specific and not a particular class [Some TZDs have been shown to reduce levels of the insulin-like growth factor-1 (IGF-1) in the blood, which is a known growth factor that may induce cancer . Plasma ar class . InvestiAn interim longitudinal cohort study using the Kaiser Permanente Northern California Registry analyzed a sample size of 193,099 diabetic patients and observed a correlation between pioglitazone therapy and bladder cancer . The incPioglitazone may be the only TZD to enhance cases of bladder cancer, as results from the National Health Insurance Research Database (NHIRD) group also presented an association with uroepithelial carcinomas . Throughp = 0.12) but no association with rosiglitazone treatment . Interestingly, the odds ratio was associated with a large confidence interval, 0.84–5.02, which the authors attributed to a small sample size, three studies, due to potential bias from incomplete disclosure of negative results. In addition, the second meta-analysis conducted by Bosetti et al. showed only a modest increased risk of developing bladder cancer when treated with TZDs for less than two years  [There is some debate as to the association of TZDs with bladder cancer. Two meta-analyses show only moderate to no risk of developing bladder cancer. Monami et al. found that the overall risk of malignancies (regardless of location) was decreased by TZD treatments . However07–1.34) . There wγ on bladder cell progression, Yang et al. analyzed samples of both benign bladder and bladder cancer mucosal samples by fluorescence in situ hybridization (FISH) assay for expression of PPARγ, and the authors found 31% (8/21 samples) of the bladder cancer mucosal samples and 4.3% (1/23 samples) of benign bladder samples showed amplification [γ amplification were detected in non-muscle-invasive bladder cancer samples compared to muscle-invasive samples  [γ expression. The 5637 bladder cell line had a considerably higher mRNA and protein expression of PPARγ compared to other bladder cancer cell lines such as UMUC-3. Moreover, the 5637 cancer cell line displayed higher cell migration and invasion than the UMUC-3 cell line [γ and high levels of the nuclear receptor glucocorticoid receptor β (GRβ), which also showed higher migration rates than the UMUC-3 cells that have low PPARγ and GRβ expression [γ may be a potential biomarker of bladder cancer aggressiveness, where high levels of receptor expression correlate with higher rates of cancer cell migration and invasion.To provide a closer look at the impact of PPARfication . In addi, resp.) . Yang etell line . Anotherpression . These rγ expression between the two cancer cell lines may account for this observation, as the 5637 cell line has a considerably higher PPARγ expression than UMUC-3 cell line [γ expression in the presence of rosiglitazone treatment compared to those that were not treated. Furthermore, rats that were exposed to OH-BBN and treated with the highest dosage of rosiglitazone have the highest incidence of bladder cancer. Rats on rosiglitazone therapy had earlier cancer onsets and larger tumor sizes in the bladders, and a dose-dependent response existed between rosiglitazone and bladder cancer incidence. TZDs may not have an effect in the earlier stages but may promote cancer progression at the later stages of bladder cancer [γ expression may potentially alter bladder cancer migration and invasive abilities. Therefore, regulating levels of PPARγ expression in the urinary bladder may have implications for targeting bladder cancer, particularly regarding metastasis and cancer cell progression.Rosiglitazone treatments have been shown to have varying effects on 5637 and UMUC-3 cancer cells . The 563ell line . Lubet eell line . Interesr cancer . Howeverγ [γ in bladder tumor tissue consequently enhancing tumor growth and migration through angiogenesis. However, the specific TZDs that may enhance VEGF-A or if PPARγ induces VEGF-A in bladder are yet to be determined.In general, tumor development in the urinary bladder is dependent upon complex interactions with host molecular factors that are part of its surrounding microenvironment , 61. Furγ . The levγ . Additioγ . Potentiγ agonists [γ upon entering the nucleus to drive adipogenic activities [In order to continue to proliferate indefinitely, cancer cells require molecular factors that increase both glucose uptake and rates of glycolysis for energy. Elevated rates of glycolysis produce higher amounts of lactic acid, and this pathway enhances lipogenesis through fatty acid synthase (FAS). FAS is the key enzyme involved in de novo synthesis of fatty acids for lipid storage, and high expression levels are frequently limited in tissues with lipogenic activity, such as adipose tissue and liver . Howeveragonists . These ltivities . Unlike tivities . Evidenctivities . On the tivities . The difMetabolic changes may occur in nonadipose tissues when they receive fatty acids released by hypertrophic dysfunctional adipose tissue, commonly seen among obese and type II diabetic patients . Nonadipγ and enhances lipid uptake, similar to adipose tissue. Eventually, sufficient amounts of free fatty acids (FFAs) will be present in the bladder due to ectopic fat accumulation, and the bladder may no longer require A-FABP to import additional extracellular FFAs but will heavily utilize FAS for lipid production. FFAs bind PPARγ and other PPAR isoforms and activate transcriptional activity. Other dysregulated metabolic pathways, including those that involve glycolysis [γ activity may alter the microenvironment in a way that allows for the cells to autonomously synthesize nutrients within the bladder through lipid accumulation and angiogenesis. However, more studies need to be performed to understand the role of PPARγ in bladder cancer.It may be possible that, in bladder tissue, lipid accumulation modifies metabolic functions in a way that strongly upregulates PPARycolysis , can cauγ as the predominant PPAR in urinary bladder epithelium, PPARα has also been found to be expressed in both rabbit and human bladder epithelium. PPARα is activated by a class of synthetic ligands known as fibrates  and is predominantly expressed in the liver, heart, brain, skeletal muscle, and kidney. Also, endogenous ligands such as fatty acids can bind PPARα to increase transcriptional activity. Recently, bilirubin was also shown to function as an endogenous PPARα agonist by direct binding [γ. Once activated, PPARα regulates genes that encode for mitochondrial and peroxisomal β-oxidation, which reduces dyslipidemia. In addition, activated PPARα functions to hinder hepatic fatty acid synthesis through inhibition of FAS and SREBP1 and therefore lower lipid levels [α and PPARγ, thereby combating diabetes mellitus and the metabolic syndrome among patients diagnosed with both conditions [Despite evidence showing PPAR binding  and was d levels , 79, 80.nditions . Examplenditions .α and PPARγ synthetic dual-acting agonists may have a carcinogenic impact on rodents, especially targeting urinary bladder epithelium. In a recent study, Egerod et al. found that rat bladder epithelium expresses both PPARγ and PPARα through a crosstalk link that involves the early growth response-1 (Egr-1) factor [α and PPARγ by their respective synthetic ligands fenofibrate and rosiglitazone. Together, fenofibrate and rosiglitazone appear to exert a positive interaction in the bladder epithelium, upregulating high Egr-1 expression. However, this positive interaction is not observed in other tissues, such as the liver, where there are high expression levels of Egr-1 and the absence of carcinogenic effects of dual-acting agonists on rats [It is worth noting that certain combinations of PPAR) factor . Egr-1 i) factor . When ei) factor . High Eg on rats .α agonists have not been shown to induce bladder cancer. PPARα agonists with a different structure, the clofibrates [γ. Furthermore, it is rather a unique characteristic of bladder epithelium to express high levels of both PPARα and PPARγ. While the exact mechanism behind the interactions of PPAR agonists and bladder cancer remains unknown, these studies provide further insight into the relevance of PPAR activation, particularly in bladder cancer development.It has also been demonstrated that ragaglitazar treatment has a carcinogenic impact on rat bladder epithelium and involves the induction of Egr-1 , 84. Impfibrates , have befibrates . Howeverfibrates . The difγ activity is inhibited by the phosphorylation of serine 112, and, currently, only one phosphatase, protein phosphatase 5 (PP5), has been shown to bind directly to the receptor [γ in the presence of proadipogenic activity, with PP5 described as a “prolipogenic phosphatase” [γ by dephosphorylating PPARγ at serine-112 residue [γ becomes active and regulates genes in metabolic processes, such as adipogenesis. Not only is PP5 a potential target in the treatment of obesity [γ in the bladder epithelium similar to adipose, as high levels of PPARγ are also associated with bladder cancer. If PP5 is a positive modulator of PPARγ in the bladder epithelium, then reducing PP5 expression may serve as an alternative therapeutic target to hinder bladder cancer progression. However, these studies are yet to be conducted.PPARreceptor . PP5 belreceptor , 89. Evireceptor , 89 (Figphatase” . Upon ac residue , 90. Onc obesity , but it  obesity . Also, i obesity . It is uγ activity levels are associated with higher incidences of bladder cancer, potentially due to the downstream effects of PPARγ-mediated metabolism. In addition to incidence rates, PPARγ activity is associated with increased bladder cancer cell migration and invasion. Further understanding of the roles of the PPARs and their agonists in the bladder may uncover additional strategies in bladder cancer therapy. Previously, there have not been studies examining the interaction of PP5 with PPARγ in bladder epithelium and cancer development. It will be of therapeutic importance to determine if the same relationship exists between PP5 and PPARγ in the bladder epithelium as for adipose tissue in the presence of TZD therapy. Bilirubin may offer a therapeutic potential because it activates PPARα and suppresses PPARγ, and fenofibrate has not been associated with bladder cancer. In the future, therapies that target PPARγ, or possibly PP5, may prove to be useful in bladder cancer treatment, particularly among diabetic patients that require long-term health management.Long-term TZD therapy may increase the risk of developing bladder cancer, especially pioglitazone. Rosiglitazone does not appear to have the long-term effects on the bladder. Prolonged and higher PPAR


S and its complement, a new S-type upper bound for the largest singular value of nonnegative rectangular tensors is given and proved to be better than some existing ones. Numerical examples are given to verify the theoretical results.By breaking  Singular value problems of rectangular tensors have become an important topic in applied mathematics and numerical multilinear algebra, and it has a wide range of practical applications, such as the strong ellipticity condition problem in solid mechanics , 2 and tLet α, let m dimension real vector whose ith component isn dimension real vector whose jth component isλ is a singular value of x and y are a left and a right eigenvectors of λ. If λ is an H-singular value of x and y are a left and a right H-eigenvectors of λ l is evenS of N, we denoteRecently, many people focus on bounding the largest singular value for nonnegative rectangular tensors , 9, 10. In , Yang an, TheoremLetbe ath orderdimensional nonnegative rectangular tensor. Thenwhereet al. [When mentclass2pt{minim, TheoremLetbe ath orderdimensional nonnegative rectangular tensor. ThenwhereS and its complement S̄, Zhao and Sang [S-type upper bound for the largest singular value of nonnegative rectangular tensors.Similarly, under the condition of and Sang  provided, TheoremLetbe ath orderdimensional nonnegative rectangular tensor, Sbe a nonempty proper subset ofN, S̄be the complement ofSinN. ThenwhereS-type upper bound for the largest singular value of nonnegative rectangular tensors. It is proved that the new upper bound is better than those in Theorems In this paper, we continue this research, and give a new Letbe ath orderdimensional nonnegative rectangular tensor, Sbe a nonempty proper subset ofN, S̄be the complement ofSinN. ThenwhereBecause Case I: If i.e.,(i) If m 2.2 in , we havementclass2pt{minimN}. From  of Theor(ii) If Case II: Assume that Case III: Assume that Case IV: Assume that The conclusion follows from Cases I, II, III and IV. □We next give the following comparison theorem for these upper bounds in Theorems Letbe ath orderdimensional nonnegative rectangular tensor, S be a nonempty proper subset ofN, S̄be the complement ofSinN. ThenI. By Remark 2.2 in , \documeII. Next, we prove (i) Suppose thatm 2.2 in , we can (ii) Suppose thatIII. Finally, we prove that Let i.e., (i) Suppose that atisfies , then \di.e., i.e.,i.e., If A). From , we can atisfies , then \d(ii) Suppose that dividing  by \documentclasspt{minimamentclasspt{minimaatisfies , then \d≤1, then  holds, w≤1, then  from 9)\documentatisfies , then \dLet mentclass2pt{minimmentclass2pt{minimLet S-type upper bound N into disjoint subsets S and its complement. It is proved that the bound In this paper, a new those in .S to make n is large. We will research this problem in the future.Note here that when


Drosophila, specific effects can be discriminated in vivo. Here, we show that in the adult neuromuscular junction (NMJ), presynaptic expression of Aβ40 hinders the synaptic addition that normally occurs in adults, yielding NMJs with an invariable number of active zones at all ages tested. A similar trend is observed for Aβ42 at young ages, but net synaptic loss occurs at older ages in NMJs expressing this amyloid species. In contrast, Aβ42arc produces net synaptic loss at all ages tested, although age-dependent synaptic variations are maintained. Inhibition of the PI3K synaptogenic pathway may mediate some of these effects, because western analyses show that Aβ peptides block activation of this pathway, and Aβ species-specific synaptotoxic effects persists in NMJs overgrown by over-expression of PI3K. Finally, individual Aβ effects are also observed when toxicity is examined by quantifying neurodegeneration and survival. Our results suggest a physiological effect of Aβ40 in synaptic plasticity, and imply different toxic mechanisms for each peptide species.Complexity in the processing of the Amyloid Precursor Protein, which generates a mixture of βamyloid peptides, lies beneath the difficulty in understanding the etiology of Alzheimer’s disease. Moreover, whether Aβ peptides have any physiological role in neurons is an unresolved question. By expressing single, defined Aβ peptides in  For genotypes expressing only Aβ peptides, Aβ-induced synaptic reduction was calculated relative to UAS controls, which showed a slightly lower synaptic count than Gal4 controls, and thus provided a conservative measure. For flies expressing Aβ and PI3K, synaptic reduction was calculated with respect to age-matched PI3K-expressing NMJs. To control for possible GAL4 titration effects that could reduce the levels of PI3K when expressed in conjunction with Aβ, nlsGFP instead of Aβ was co-expressed with PI3K  was used throughout. Data are presented as average ± SEM, and statistical functions are reported as Fg,N-1 for the ANOVA analysis and Hg,N for the Kruskal-Wallis test, where N refers to the number of samples and g to the degrees of freedom. For regression analysis, we used the Real Statistics Resource Pack software  Charles Zaiontz; www.real-statistics.com) on Excel (Microsoft).For NMJ parameters and neurodegeneration, we tested for the normality of all variables and their usual logarithmic transformation. Statistical significance was calculated for the normally distributed variables with a two-way ANOVA test followed by Bonferroni Differences in survival were analyzed using the Kaplan-Meier survival plots and log-rank analysis with the online survival analysis package OASIS . StatistDrosophila adult abdominal ventral NMJ  = 17.807, p<0.001; 4,91 = 36.178, p<0.001; boutons: F4,91 = 14.833, p<0.001; branches: H = 1.343, p = 0.854;). Synapses continuously increased from 3 to 15 days after eclosion (dae), decreased from 15 to 30 dae and stabilized until at least 45-days of age .The three parameters showed segmental differences , age, and their interaction, were statistically analyzed Figs .Drosophila synapses  and age on synapses , denotinpost hoc analyses identified Aβ40 as the only genotype in which the number of active zones did not differ between ages, while all other genotypes showed age dependent variations . Second, as with normal PI3K levels, Aβ42arc exerted the strongest effect on branch and boutons in conditions of elevated PI3K .In general, specific Aβ effects on active zones in NMJs overexpressing PI3K followed a similar tendency to that observed with normal PI3K levels, providing further support for the specific effects uncovered in this study , while D42-Gal4 control males had slightly reduced survival when compared to the other control genotypes . Life span of flies overexpressing PI3K alone was undistinguishable from the Gal4 control , but lower than the other control genotypes (p<0.001).We next tested if PI3K positively affected life span in males expressing each of the Aβ peptides. Although most controls showed undistinguishable cumulative survival curves , there wvs. Experiment Aβ40+PI3K: χ2 = 0.22, p = 1) and flies expressing PI3K alone , which points to a possible neuroprotective effect of this peptide. In contrast, Aβ42 significantly reduced survival rate . Furtherenotypes), as has enotypes), indicatenotypes). Thus, oDrosophila adult glutamaergic neuromuscular junction (NMJ) would provide an ideal system in which to address these issues, because its stereotypic morphology would allow uncovering subtle albeit relevant changes. Moreover, our work has revealed a temporal biphasic process of synaptic remodeling at the adult NMJ. An early phase of net synapse addition takes place during the first two weeks of adult life, a critical time period in which several areas of the young fly brain have been shown to undergo experience-dependent structural plasticity [Synapse dysfunction and loss are key to dementia in Alzheimer’s disease (AD). It is currently established that amyloid-β peptides are important contributors to these synaptic alterations, but the precise identity of the Aβ species involved is not well defined ,49. Likeasticity ,50,51. Tasticity ,32,50,52Drosophila had shown early memory defects induced by expression of both Aβ40 and Aβ42-derived peptides [Studies in peptides ,20,22,23peptides ,20,25,26Drosophila. Interestingly, early defects in ocular dominance plasticity in APPswe transgenic mice, which generate elevated levels of wild type amyloid species, are associated with reduced strengthening and expansion of non-deprived eye cortical representations, while deprived eye weakening remains intact [Drosophila larval NMJ, the transition from immature to mature synapse involves changes in the relative contribution of specific glutamate receptors in postsynaptic receptor fields opposed to presynaptic active zones [In general, exposure to Aβ is associated with weakening of synapses, which is consistent with a postulated Aβ function in promoting activity-dependent synaptic elimination during mammalian postnatal development . Our dats intact . These dve zones . In mammve zones , a proceve zones ,56–58. TAlthough we cannot provide a mechanistic basis for the specific synaptotoxic activities of each Aβ species, the data on NMJs overexpressing PI3K suggest the direct implication of this pathway. First, despite its strong synaptogenic activity, PI3K over expression was not able to block Aβ-induced synaptic reduction. Second, western quantification showed that the activity of the pathway is reduced by Aβ expression, which is consistent with data from mammalian systems that suggest that amyloid peptides block Akt activation downstream of the PI3K enzyme ,45, and The risk of AD increases with age, but the link between aging and Aβ toxicity is not fully understood. We have shown that after a stage of synaptic growth, synaptic elimination commences in the fly NMJ sometime between 15 and 20 days after eclosion. This age also represents a point of transition from growth to retraction for the abdominal longitudinal NMJ  and the in vitro and in vivo studies have demonstrated different aggregation kinetics for the three Aβ species, which result in higher effective concentrations of specific aggregation forms with diverse toxic activities. Specifically, a recent in vivo study expressing tandem dimeric Aβ peptides in Drosophila has shown that the aggregation kinetics of Aβ42 favors a relatively high population of toxic oligomeric species, while this population is undetectable for Aβ40, which seems to more rapidly transit from monomeric to insoluble inert forms [Drosophila adult NMJ would provide invaluable data to test this hypothesis.Several rt forms . The E22rt forms ,61. Thusrt forms  on the DDrosophila, and in other models, suggest that the mechanisms underlying Aβ synaptotoxicity, cytotoxicity, and reduction of life span are different [in vivo data demonstrate that manipulations that alter aggregation propensity can induce qualitative, rather than quantitative, shifts in the pathology induced [Multiple studies in ifferent ,23,46,47 induced . Our datThe differential effect of PI3K hyperactivation on Aβ-related phenotypic outcomes is intriguing. PI3K is an essential signaling pathway with multiple developmental and physiological functions; these include widespread functions such as regulation of cell proliferation and metabolism, or control of cellular remodeling and migration, but also cell-type specific roles such as synapse plasticity in neurons . Moreovein vivo model we demonstrate that (1) different amyloid species disturb synapses by differentially influencing synapse addition or synapse elimination, (2) age-dependent changes in their synaptotoxicity are species-specific, and (3) the toxic actions of each Aβ peptide differ in different contexts. Furthermore, our work demonstrates the value of the Drosophila adult NMJ as an ideal in vivo model for understanding specific effects of amyloid peptides on synaptic plasticity.In summary, using an


In this paper, symmetries and symmetry reduction of two higher-dimensional nonlinear evolution equations (NLEEs) are obtained by Lie group method. These NLEEs play an important role in nonlinear sciences. We derive exact solutions to these NLEEs via the  Equan method , 24, and [et al. –27 introP is a polynomial of an unknown function Suppose that a nonlinear partial differential equation (PDE) is given byF is a polynomial of Step 1. Substituting the traveling wave transformequation  convertsStep 2. Assume that equation  has the δ, μ are constants that will be determined later and c is an arbitrary constant. We take the homogeneous balance between nonlinear terms and highest order derivatives of equation mth-order BBEq, we have the following lemma.In 2009, Eremenko et al.  studied , 30, 31), 3130, 3Letand amth-order BBEqsatisfies the weakcondition, then the meromorphic solutionsSupposing for some values of the parameters the solutionwexists, then any other meromorphic solutions will be one parameter familyIn addition, every elliptic solutionwwith a pole atis expressed aswhereare determined by  distinct poles of multiplicityq.Every simply periodic solutionis a rational function ofand is expressed aswhich hash (≤p) distinct poles of multiplicityq.By the above definitions and lemma, we now present the complex method.Step 1. Insert the transformation Step 2. Insert  into theStep 3. Insert the indeterminate solutions introduced in Lemma Step 4. Obtain meromorphic solutions Step 5. Inserting the inverse transformation u is the solution of equation (a, b, c, d, e, f are unknown functions of real variables x, y, s, t. According to Lie group analysis [σ satisfiesIn order to find the symmetry equation , we setequation , a, b, canalysis , σ satisu is the solution of equation (a, b, c, d, e, f are unknown functions of real variables x, y, s, t. According to Lie group analysis, σ satisfiest. Substituting equations (In order to find the symmetry equation , we setequation , a, b, cσBy solving the characteristic equation  of σ31\Setting Setting σBy solving the characteristic equation  of σ35\Setting Setting z, we obtainγ is the integration constant which can be determined later.Substituting the traveling wave transformequation , then inδ and μ are arbitrary constants.Taking the homogeneous balance between equation  yields4w, μ and δ are arbitrary constants.Substitute equation  and equaSubstituting equations  into equequation  into equWhen When When When When Inserting  into equW. We will show meromorphic solutions of equation (Therefore, equation  is a secequation  in the fBy , we infeSubstituting equation , we haveSo the rational solutions of equation  are\docTo obtain simply periodic solutions, let equation , then43Substitutingequation , we obtaInserting equation  and equaequation , we can equation  with a pSo simply periodic solutions of equation  are\docFrom , we haveE and Thus, the elliptic function solutions of equation  are\docz, we obtainγ is the integration constant which can be determine later.Substituting the traveling wave transformequation , then inSetting equation  becomesδ and μ are arbitrary constants.Taking the homogeneous balance between equation  yields4w, Substitute equation  and equaμ and δ are arbitrary constants.Solving the above algebraic equations, we obtainSubstituting equations  into equequation  into equWhen When When When When Inserting  into equW. We will show meromorphic solutions of equation (Therefore, equation  is a secequation  in the fBy , we deduSubstituting equation , we get So the rational solutions of equation  are\docTo obtain simply periodic solutions, let equation , then weequation ,\documeTherefore the simply periodic solutions of equation  are\docFrom , we can Substituting equation , we obtaTherefore, the elliptic solutions of equation  are\docImplementing the By employing the complex method, we are capable to obtain simply periodic solutions mentclass2pt{minimmentclass2pt{minimBy using the complex method, we achieve to obtain simply periodic solutions entclass1pt{minimaIn this section, we illustrate some results by the computer simulations. We carry out further analysis to the properties of simply periodic solutions mentclass2pt{minimIn this article, we utilize Lie group analysis to obtain symmetries and symmetry reduction for two higher-dimensional NLEEs. In this way, we can reduce the dimension of the NLEEs, which is relevant in the fields of mathematical physics and engineering. Five types of explicit function solutions are constructed by the


Teredinibacter turnerae. After ∼3,025 generations, base-pair substitutions (BPSs) and insertion–deletion (indel) events were characterized by whole-genome sequencing analysis of 47 independent MA lines, yielding a BPS rate of 1.14 × 10−9 per site per generation and indel rate of 1.55 × 10−10 events per site per generation, which are among the highest within free-living and facultative intracellular bacteria. As in other endosymbionts, a significant bias of BPSs toward A/T and an excess of deletion mutations over insertion mutations are observed for these MA lines. However, even with a deletion bias, the genome remains relatively large (∼5.2 Mb) for an endosymbiotic bacterium. The estimate of the effective population size (Ne) in T. turnerae is quite high and comparable to free-living bacteria (∼4.5 × 107), suggesting that the heavy bottlenecking associated with many endosymbiotic relationships is not prevalent during the life of this endosymbiont. The efficiency of selection scales with increasing Ne and such strong selection may have been operating against the deletion bias, preventing genome erosion. The observed mutation rate in this endosymbiont is of the same order of magnitude of those with similar Ne, consistent with the idea that population size is a primary determinant of mutation-rate evolution within endosymbionts, and that not all endosymbionts have low Ne.Mutations contribute to genetic variation in all living systems. Thus, precise estimates of mutation rates and spectra across a diversity of organisms are required for a full comprehension of evolution. Here, a mutation-accumulation (MA) assay was carried out on the endosymbiotic bacterium  Ne, reduces the efficiency of selection on spontaneous mutations, allowing for the accumulation of all but the most deleterious mutations. Genome-wide sequencing of multiple MA lines has generated unbiased estimates of the rate and spectrum of spontaneous mutations across eukaryotes and bacteria (−7–10−10 mutations per site per generation) and the evolution of mutation rate has been linked to the population size of the organisms . Under this view, the increased power of genetic drift (which is inversely related to Ne) reduces the efficiency of purifying selection at removing slightly deleterious mutations, leading to a deleterious pattern of genome evolution . Teredinibacter turnerae supplies cellulolytic enzymes and nitrogen compounds  was isolated from Neoteredo reynei (Teredinidae) sampled in a Mangrove in Rio de Janeiro, Brazil  was ∼175 bp. The paired-end reads from each MA line were individually mapped against the reference genome T. turnerae T7901 (https://www.ncbi.nlm.nih.gov) using two different mappers: BWA v0.7.4 (www.novocraft.com). The generated pileup files were converted to SAM format using SAMTOOLS v0.1.18 (101-bp paired-end Illumina (Illumina Hi-Seq platform) sequencing was applied to randomly selected 47 A v0.7.4  and NOVO v0.1.18 . We usedBase-pair substitutions (BPSs) identification was carried out as previously described  using a bs) for each MA line is estimated as m is the number of observed base substitutions, n is the number of nucleotide sites analyzed, and T is the total number of generations in the MA assay. The standard error for each MA line was calculated using The base-substitution (BPS) mutation rate per site per generation  as described  divided by the genome size (5.19 6), and by the number of MA lines (47), and multiplied the corresponding window sizes . The chance of occurrence of one MNM in at least one window in a single MA line is then  within window sizes of 20, 50, or 100 nt in the genome of  is then :(4)1−cdT. turnerae strain CS30 used in this work was originally isolated from a N. reynei  host sampled in a mangrove in Rio de Janeiro, Brazil  at 30 °C (T. turnerae MA lines were subjected to 101-bp paired-end high-throughput whole-genomic sequencing (Illumina Hi-Seq platform); the resulting reads were mapped against the T. turnerae T7901 (NC_012997) reference genome; and mutations were identified as previously described  and the expected ratio of nonsynonymous to synonymous mutations  are not significantly different from random expectations. Because a large proportion of nonsynonymous mutations are expected to be removed by natural selection if effective, a random distribution of nonsynonymous and synonymous mutations indicates that selection played a minimal role on the mutation process during this MA experiment.The , Brazil . 47 MA lat 30 °C . By the at 30 °C . The T. escribed . Spontanescribed  online. escribed , the numT. turnerae MA lines, of which 779 (88.1%) are BPSs and 106 (11.9%) are indels (−9 (standard error of the mean [SEM] = 0.55) per site per generation, or 5.59 × 10−3 (SEM = 1.61) mutations per genome per generation, and the indel rate 1.55 × 10−10 (SEM = 0.16) events per site per generation are among the highest within free living and facultative intracellular bacteria . Yet, MNMs are observed in over a third (34.0%) of the MA lines. Most clustered mutations are found as pairs, with a single instance of three closely neighboring mutations in MA line 29 , with deletion accounting for a loss of 9.89 × 10−2 nucleotides per generation per MA line (175.93-fold higher than the gain by insertions). These data are consistent with a general deletion bias observed in bacteria  are transitions  online, bacteria .Ne) is inversely proportional to the power of random genetic drift, which has been suggested to have an influence on the evolution of mutation rate  according to bs (1.14 × 10−9 per site per generation) in the formula, we estimate Ne to be ∼4.5 × 107. As shown in Ne is slightly lower than comparable measures in most free-living bacteria . Moreov 108 [Ne , reinfor [Ne  higher than those observed in most free-living and facultative intracellular pathogenic bacteria and of the same order of magnitude of other nonfree-living bacteria such as Buchnera aphidicola  is also one of the highest among bacteria , with 2.2× more spontaneous deletion events than insertion events, resulting in a loss of 9.83 × 10−2 nucleotides per generation per MA line. This observation suggests that genome erosion might be strong and have a role in T. turnerae evolution.In MA lines of the endosymbiont T. turnerae exhibits mutational properties that are similar to other endosymbionts (higher mutation rate and strong deletion bias), T. turnerae retains a relatively large genome (∼5.2 Mb), comparable in size to many free-living bacteria such as E. coli (Pseudomonas aeruginosa (Bacillus subtilis (B. aphidicola that has a genome size of 0.6 Mb (T. turnerae (∼4.5 × 107) lies between the Ne measured in the free-living bacteria B. subtilis (107) and E. coli (108)  , suggestymbionts . Thus, aTeredinibacter turneae is an intracellular bacterium that can be cultivated under in vitro conditions. Moreover, based on morphological data and the high sequence identity of the 16S rDNA from T. turnerae isolated from many Teredinidae species from unrelated geographical regions, this bacterium might be subject to horizontal transfer across hosts (P. aeruginosa (Ne during their life cycles. Thus, we propose that the endosymbiont T. turnerae is maintained in large enough populations when transferred from one generation to another, with selection acting efficiently enough to counteract a deletion bias and to maintain mutation rates at levels that lie between those of free-living bacteria and endosymbiotic bacteria that undergo frequent bottlenecking.ss hosts . In factss hosts , and somruginosa  are capaGenome Biology and Evolution online.Supplementary DataClick here for additional data file.


The effect of intravitreal bevacizumab in a rare case of retinal dystrophy with secondary cystoid macular edema"", authors Macovei Mioara-Laura, Nica Maria-Alexandra, was published in Romanian Journal of Ophthalmology, 2017; 61(2): 123-127. The authors would like to change the text “oral acetazolamide 500 mg daily and aspacardin 100 mg daily” into “Acetazolamida Arena oral 250mg x 2/ daily, Aspacardin Terapia oral 39mg/ 12mg x2/ daily”.The article The above-mentioned change should be made at all the levels, starting with the journal’s web page – www.rjo.ro and ending with the database the journal is indexed in (PubMed). The publishers regret any inconvenience caused by this change.


RARβ hypermethylation on the incidence of NSCLC and clinicopathological characteristics in human NSCLC patients. Final valuation and analysis of 1780 cancer patients from 16 eligible studies was performed. RARβ hypermethylation was found to be significantly higher in NSCLC than in normal lung tissue, the pooled OR from 7 studies including 646 NSCLC and 580 normal lung tissues, OR = 6.05, 95% CI = 3.56-10.25, p<0.00001. RARβ hypermethylation was significantly higher in adenocarcinoma (AC) compared to squamous cell carcinoma (SCC), pooled OR is 0.68 . RARβ hypermethylation was also found to occur significantly higher in smoker (n = 232) than non-smoker (n = 213) . Our results indicate that RARβ hypermethylation correlates well with an increased risk in NSCLC patients. RARβ geneinactivation caused by RARβ methylation contributes the NSCLC tumorigenesis and may serve as a potential risk factor, diagnostic marker and drug target of NSCLC.Emerging evidence indicates that Retinoic acid receptor-β (RARβ) is a tumor suppressor in many types of tumor. However, whether or not RARβ is a risk factor and is correlated to clinicopathological characteristics of non-small cell lung cancer (NSCLC) remains unclear. In this report, we performed a meta-analysis to determine the effects of  Non-small cell lung carcinoma (NSCLC) consists of squamous cell carcinoma (SCC), adenocarcinoma (AC), large cell carcinoma and others. There are approximately 80% of NSCLC cases in later stage where the treatment and prognosis is far from satisfactory . Thus, iRetinoic acid (RA) and its derivative, retinoid can bind its three retinoic acid receptors (RAR), RARα, RARβ and RARγ, are required for normal lung development –9. PreviSixteen publications which fitted into the inclusion criteria were collected into in this study. One hundred and ninety one publications were not included for the reasons such as in vivo animal work or in vitro cell culture model, non-original articles , or irrelevant publications. Figure By determine the RARβ promoter hypermethylation using lung tissues, the NSCLC patients showed significantly higher RARβ promter hypermethylation frequency than those of normal individuals. That is the RARβ conveyed the positive association for promoter hypermethylation when comparing NSCLC tumors to normal controls, with the pooled OR of 6.05  from 7 studies having both NSCLC tissues (n = 646) and normal lung tissues (n = 580)  RARβ hypermethylation was determined in the lung tissues of primary NSCLC patients, (2) RARβ promoter hypermethylation was detected by polymerase chain reaction (PCR), (3) the data provided the information on both status of RARβ hypermethylation as well as clinicopathological indexes of the NSCLC patients (4) the statistic information was given such as individual hazard ratio (HR) of overall survival (OS) and 95 % confidence interval (CI). However, the Letters, reviews, case reports, conference abstracts, editorials, expert opinion, and all research which are involved in vitro/ex vivo studies were not included.We reviewed the following information in each eligible study, authorship, time of publication, sample collection, case numbers, clinicopathological information, the techniques used to calculate gene promoter methylation, methylation frequences and/or gene product expression, and the process of follow-up. Disagreements between the analyzers were fully discussed until come to an agreement. Demographic data and clinical responses were formatted into a table. Heterogeneity of study was calculated to determine if the dataset were suitable for a meta-analysis.The methodology of each study was evaluated and scored based on the REMARK and ELCWP guidelines –44.Analysis was performed by the softwares of STATA 12.0  and Review Manager 5.2 . The pooled ratios of RARβ promoter hypermethylation and 95% confidence intervals (95% CI) were calculated. The frequency of RARβ hypermethylation was analyzed and correlated to various tumor phenotypes. Heterogeneity among studies was calculated by Cochran's Q test  which shPublication bias was assessed by using a method reported by Egger et al . We also


The purpose of this paper is to assess the usefulness of nutritionlabels in Thailand during nutrition transition from traditional to moderndiets that increase salt, sugar, and calorie intake and to notesocio-demographic interactions and associations with consumption oftransitional processed foods.The authors studied 42,750 distance learning Open University adultsaged 23-96 years in 2013 residing nationwide and participating in an ongoingcommunity-based prospective cohort study. The authors used multivariablelogistic regression to relate nutrition label experiences, socio-demographic factors, and consumption of fourtransitional foods. These foods included “unhealthy” instantfoods, carbonated soft drinks, and sweet drinks, or “healthy”milk.Overall, two-thirds reported good understanding and frequent use ofnutrition labels. Unhealthy transition-indicator processed foods werefrequently consumed: instant foods (7 per cent), (carbonated) soft drinks(15 per cent), and sweet drinks (41 per cent). Frequent users of nutritionlabels  were less likely toconsume unhealthy indicator foods. Those with the most positive overallnutrition label experience (“read” + “goodunderstanding” + “frequent use”) had the best indicatorfood profiles: instant foods (odds ratio (OR) 0.63; 95%CI, 0.56-0.70); softdrinks ; sweet drinks ; milk .Knowledge protected – those with most nutrition labelexperience were least likely to consume unhealthy foods. Results supportgovernment regulated nutrition labels, expanding to include sweet drinks.The study is remarkable for its large size and nationwide footprint. Studysubjects were educated, represent Thais of the future, and show highawareness of transition-indicator foods. Rapidly modernizing traditional societies have diets that are changing from low fat cereal-based agrarian foods to industrial processed foods, high in sodium and sugar . This “nIn Thailand, a leading South East Asian country with a middle income economy, the nutrition transition is quite advanced and NCDs are now the largest cause (71 per cent) of Thai mortality . AccompaIn other countries, the impact of nutrition labels on consumers has been related to socio-demographic factors including sex, age, and education . But in Some foods associated with the nutrition transition have become a focus of labelling because they are vectors of excess salt and sugar . For exaTo address this knowledge gap we studied nutrition labels and transitional foods in a large nationwide cohort that is part of our ongoing health-risk (and nutrition) transition research in Thailand. That research is focussed on emerging NCD as incomes rise, mother-child mortality falls, and nutrition transition proceeds (This research on nutrition label experience is a sub-study within an overarching Thai cohort study (TCS) that has been described elsewhere  students residing all over Thailand. Generally cohort members displayed considerable variation of socio-economic status, lifestyle, personal behaviours, and were similar to the profile of their community. In 2005, they responded to the baseline questionnaire, representing well the Thai population for sex ratio, median age, religion, ethnicity, regional distribution, and median income  responded at the four year follow up in 2009 and 42,785 (71 per cent) at the eight year follow up in 2013. For each survey  a questionnaire was developed and pretested with small groups of on-campus STOU students. Whenever possible, standard validated questions were used. The baseline questionnaire (20-pages) collected socio-demographic, cultural, environmental, behavioural, dietary, and health information; the four and eight year questionnaires were shorter (ten pages) and made repeat observations on changeable variables and added new questions according to current research topics.n = 35), who cannot go shopping, 42,750 TCS members remained for analysis.In 2013, the eight year follow-up was conducted and included new questions on nutrition labelling as well as diet indicators see  section.In 2013, respondents fell into three age groups: 23-34, 35-49, and ≥;50years. We noted location of residence , region (sixcategories), the number of people in the household, and income categories.Participants were studying at university in 2005 and had completed years9-12 of high school. Occupation was elicited by the question “Whichof the following best describes your primary occupation?” Most ofthose not responding to this question were not in paid employment or hadretired. Information on religion  was obtained from the baseline survey in 2005.Four questions on nutrition labels were included in the 2013 follow-up questionnaire. The first three questions focussed on key label experiences . In the fourth question we asked “Would you like to see additional nutrition labels on food products?” (yes/no).Read “Have you ever seen nutrition labels on food products?” Responses were “seen and read”, “seen not read”, and “unaware”. Responses were dichotomized, contrasting the first experience category (“read”) with the last two experience categories (combined as “not read”).Understand “How well do you understand the information presented on nutrition labels?” Possible responses included “understand fully”, “understand most information”, “understand some information”, “do not understand information but I know it has potential”, and “do not understand information or its potential”. The first two responses were collapsed into “good understanding” and the other three responses into “not good understanding”.Use “How often do you use information from nutrition labels on food products to assist your food purchasing decision?” Possible responses included “every time I shop”, “often”, “sometimes”, “seldom”, and “never”. The responses were combined so that “every time” and “often” became “frequent use” and other responses as “infrequent use”.For analysis, responses to the questions on read, understand, and use were dichotomized into coherent binary variables. This balanced cell numbers and facilitated interpretation of the results. It also enabled use of logistic regressions which were easily adjusted for covariants.Focussed on the nutrition transition, diet was assessed using a simplified food frequency instrument developed (in Thai) for four indicator foods – “instant foods”, “soft drinks”, “sweet drinks”, and “milk”. Examples given for instant foods were instant noodles, for soft drinks were coke and pepsi, for sweet drinks were green tea, iced coffee, and herbal drinks, and for milk were fresh, UHT, or powder milk. These four indicator foods were adapted from food items investigated in recent Thai national food consumption surveys  . They alN = 42,785) were scanned and digitized using Thai Scandevet software. Further editing used SQL and SPSS software. For analysis we used Stata v14. Individuals with missing data were excluded from analyses. We also excluded respondents from households with more than 15 people, as they may have been living in institutions . We classified occupations into six groups: professional, managers, office assistants, workers, not working or retired, and unidentified occupation.Completed questionnaires returned by mail  and the Australian National University Human research Ethics Committee (protocols 2004/344 and 2009/570). Informed written consent was obtained from all participants.Overall, responses of 42,750 cohort members were analysed for the eight year survey, including 19,295 men (45.1 per cent) and 23,455 women (54.9 per cent). The mean ± SD age was 40.5 ± 8.5 years, 6.0 per cent lived alone, 55.3 per cent lived in an urban environment, and the most frequent household size was 2-4 persons. Participants resided all over Thailand with the largest groups located in the central-east (30.7 per cent) or Bangkok (15.8 per cent). Most of the cohort (79.8 per cent) was university educated and the most frequent occupations were “professional” (26.4 per cent), or “office assistant” (30.8 per cent). Monthly incomes were modest, with nearly 60 per cent reporting 20,000 baht (approximately USD$550) or less per month. Responses to the nutrition label questions indicated 89.0 per cent had “read”, 69.5 per cent had a “good understanding”, and 64.4 per cent had “frequent use”. Almost everyone (96.4 per cent) “wanted to see additional nutrition labels”. The participants also reported frequent consumption of indicator foods – instant foods (7.0 per cent), soft drinks (14.6 per cent), other sweet drinks (40.7 per cent), and milk (45.5 per cent) .p < 0.05) with at least one label outcome. When explored further, associations for age, sex, location, region, and occupation were found to be strongly connected (p < 0.001) to at least two of the outcomes.Socio-demographic characteristics were examined for bivariate associations with nutrition label outcomes . Overall, age, sex, location, region, religion, household size, education, occupation, and income were all significantly associated . As well, these groups had less frequent consumption of unhealthy indicator foods  and more frequent consumption of  milk. These relationships persisted after adjusting for many covariates.p < 0.01) than younger persons  study of nutrition label use among Thai consumers, we found other label attributes could mediate education effects including readability, technical jargon, unobtrusive location, and suspected truthfulness  . Our repSome limitations and strengths of our study should be noted. First, participants were educated so for outcomes related to education level it was not possible to generalize results. Otherwise, cohort members were socio-demographically similar to the Thai population. Second, data are based on self-administered responses to mailed questionnaires but cohort members are used to complex information received by mail. Questionnaires were quite long (10-20-pages) so special interest in one or two questions would have little influence on overall responses  strongly associated with nutrition label experiences  and frequent intake of indicator foods typical of the nutrition transition . Nutrition label experiences were strongly and significantly associated with consumption of transition-indicator foods. These results arise in a South East Asian country that recently defeated malnutrition but now confronts an equally important new community nutrition challenge . Overall


Perinatal management and prognostic value of clinical evaluation and diagnostic tools have changed with the generalization of therapeutic hypothermia (TH) in infants with hypoxic-ischemic encephalopathy (HIE)to ascertain the prognostic value of amplitude integrated electroencephalogram (aEEG) in neonates with HIE considering hours of life and treatment with TH.A systematic review was performed. Inclusion criteria were studies including data of neonates with HIE, treated or not with TH, monitored with aEEG and with neurodevelopmental follow-up of at least 12 months. The period of bibliographic search was until February 2016. No language restrictions were initially applied. Consulted databases were MEDLINE, Scopus, CINHAL and the Spanish language databases GuiaSalud and Bravo. Article selection was performed by two independent reviewers. Quality for each individual paper selected was evaluated using QUADAS-2. Review Manager (RevMan) version 5.3 software was used. Forest plots were constructed to graphically show sensitivity and specificity for all included studies, separating patients treated or not with hypothermia. Summary statistics were estimated using bivariate models and random effects approaches with the R package MADA from summary ROC curves. Meta-regression was used to estimate heterogeneity and trends.not treated with hypothermia the maximum reliability of an abnormal aEEG background to predict death or moderate/severe disability was at 36 hours of life, when a positive post-test probability of 97.90% was achieved (95%CI 88.40 to 99.40%). Positive likelihood ratio (+LR) at these hours of life was 26.60 (95%CI 4.40 to 94.90) and negative likelihood ratio (-LR) was 0.23 (95%CI 0.10 to 0.44). A high predictive value was already present at 6 hours of life in this group of patients, with a positive post-test probability of 88.20% (95%CI 79.80 to 93%) and a +LR of 4.34 (95%CI 2.31 to 7.73). In patients treated with TH the maximum predictive reliability was achieved at 72 hours of life . +LR at this age was 24.30 (95%CI 5.89 to 71.30) and–LR was 0.40 (95%CI 0.25 to 0.57). Predictive value of aEEG at 6 hours of life was low in these patients .from the 403 articles initially identified, 17 were finally included and critically reviewed. In infants This study confirms that aEEG´s background activity, as recorded during the first 72 hours after birth, has a strong predictive value in infants with HIE treated or not with TH. Predictive values of traces throughout the following 72 hours are a helpful guide when considering and counselling parents about the foreseeable long-term neurological outcome Perinatal hypoxic ischemic encephalopathy (HIE) is an important cause of early mortality and permanent major disability in full term infants ,2. TheraAmplitude-integrated electroencephalography (aEEG) is a simplified bedside neurophysiology tool that is nowadays widely used in neonatal units today  In term Prior to the use of TH for neonates with HIE, abnormal aEEG background pattern during the first 3–6 postnatal hours was reported to be highly predictive of adverse outcome, with the combination of aEEG pattern and clinical examination being more predictive than either of these parameters independently ,15–16. WA systematic review of the medical literature was performed to ascertain the prognostic value of aEEG in newborns with HIE considering hours of life and treatment with hypothermia. This review was part of the Spanish National Health System Clinical Practice Guideline (CPG) on HIE .We conducted a systematic review and performed a meta-analysis (MA). Inclusion criteria were studies including newborns with HIE, treated or not with hypothermia, monitored with aEEG and with neurodevelopmental follow-up of at least 12 months.Librarians and the CPG´s panel group performed the electronic literature research. Consulted databases were MEDLINE, Scopus, CINHAL and the Spanish language databases GuiaSalud and Bravo. Clinical trials registers were checked for on-going studies. The period of bibliographic search was until February 2016. No language restrictions were initially applied. Bibliographic references of selected papers were tracked if pertinent. A combination of the following subject headings and keywords was adapted for each electronic database: “Hypoxic ischemic encephalopathy”, “hypoxia-ischemia”, “brain”, “anoxia”, “brain injuries”, “hypoxia brain”, “brain ischemia”, “asphyxia”, “newborn”, “developmental disabilities”, “neurodevelopment”, “cerebral palsy”, “infant mortality”, “hypothermia”, “hypothermia induced”, “neurological morbidity”, “cerebral damage”, “severe hypoxia”, “asphyxia neonatorum”, “oxygen inhalation therapy”, “resuscitation”, “fatal outcome”, “treatment outcome”, “seizures” and “electroencephalography”. Initial search strategy used in Pubmed is shown in Article selection was performed by two independent reviewers (DB and RR) and in case of discordance a third author intervened (AGA). Only studies including: 1) human infants with a gestational age of 35 weeks or more, 2) neonatal encephalopathy caused by perinatal asphyxia and 3) neurodevelopmental outcome data available at a postnatal age of at least 12 months were eligible. Review articles, opinion articles, and editorials were excluded as well as abstracts and conference proceedings. A standardized extraction form was used to record the characteristics of each study. For each paper aEEG background pattern at 6, 24, 26, 48 and 72 hours of life was analysed and neurodevelopmental outcome after follow up was recorded. Rates of true positive, true negative, false positive and false negative were recorded. aEEG background trace was considered abnormal according to the pattern classification if the trace was flat, low voltage or burst suppression . Using tQuality for each individual paper selected was evaluated using QUADAS-2 . QualityUsing Review Manager (RevMan) version 5.3 software, forest plots were constructed to graphically show sensitivity and specificity for all included studies, separating patients receving TH from patients not receiving this therapy. Summary statistics  were estimated using bivariate models and random effects approaches with the R package MADA, from the summary receiver operative operating characteristic curve (SROC). MADA uses a linear mixed model with known variances of the random effects, similar to the computational approach by Reitsma et al . HeterogFour hundred and three articles were identified. Fifty-seven publications were initially preselected on the basis of the article´s title and abstract. Finally, only 17 articles met the inclusion and exclusion criteria  and werenot treated with hypothermia thirteen studies including 671 patients were included [treated with hypothermia [Forest plot of sensitivity and specificity with 95% confidence intervals is shown in included –28,31,34othermia ,29–34.not treated with hypothermia the maximum reliability of an abnormal aEEG background to predict death or moderate/severe disability was at 36 hours of life, when a positive post-test probability of 97.90% (95%CI 88.40 to 99.40%) was achieved . Positive likelihood ratio at this age was 24.30 (95%CI 5.89 to 71.30) and negative likelihood ratio 0.40 (95%CI 0.25 to 0.57). Compared with newborns not treated with TH, the predictive value of aEEG at 6 hours of life Click here for additional data file.S2 Fig(DOC)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


Sarcomas represent a heterogeneous group of malignancies of mesenchymal origin with more than 70 histological types. Sarcomas are genetically highly heterogeneous, but they can be classified into two broad groups, one with simple karyotypes  and the other with complex genomic alterations and high chromosomal instability . One of Integrin-α10 belongs to the collagen-binding integrin subfamily, consisting of α1, α2, α10, and α11, all of which form heterodimers with β1 . Unlike Canonical “outside-in” integrin signaling activates FAK and SRC family kinases. Integrin-α10 in myxofibrosarcoma, however, activates RAC/PAK and AKT upon the collagen binding, and not FAK or SRC. Integrin-α10 is essential for AKT and PAK activities in tumor cells but not in normal mesenchymal stem cells. Some pro-oncogenic integrins are known to cooperate with oncogenic receptor tyrosine kinases, including ERBB2 and MET . Even thTRIO and RICTOR . TR. TRTRIO d RICTOR . First, Selective inhibitors of RAC (EHop-016), PAK IPA3), and mTORC (INK128) exerted anti-tumor effects in vitro and in mice, the latter in both xenograft tumors and metastatic growth in the lung. The RAC and mTORC inhibitors had highest efficacy when combined, demonstrating that integrin-α10 downstream signaling is targetable [, and mTO


Our “diabetogenic diet” composition  was indeRegarding the wheat utilized in the study, whole wheat grains were used for all wheat sources tested including conventional wheat bread grains. As mentioned , “harvesRegarding the diagnosis of diabetes, as stated , none ofAs stated in the “Experimental design”, 10 animals were used for each diet. All analyses including glucose, insulin, cholesterol, interferon-γ (IFN-γ), and IL-10 levels utilized all of the animals. No subsamples were used in this research. We hope we have clarified all of the issues raised.


Catecholamine agents are commonly used to support circulation; however, they may cause unexpected hypotension in a special situation. Here we describe the first unexpected case of hypotension in response to catecholamine agents.A 29-year-old Japanese man with schizophrenia was transferred to our emergency department. He was in shock and in coma. After fluid resuscitation, we induced catecholamine agents; however, his blood pressure decreased to 59/40 mmHg in response to catecholamine infusion. On the other hand, after we started vasopressin, his blood pressure markedly improved, and he finally became stable. On day 2, he admitted to ingesting a large amount of risperidone, and we diagnosed risperidone overdose. We believe that this unexpected hypotension in response to catecholamine infusion was caused by an α-adrenergic blockade effect of risperidone. Animal experiments proved that the simultaneous administration of adrenaline with an α-adrenergic blockade provoked a fall in blood pressure; this phenomenon is called “adrenaline reversal.” In our case, catecholamine infusion under the α-adrenergic blockade effect of risperidone might have caused a fall in blood pressure in the same mechanism; we call this phenomenon “catecholamine reversal.” In such a situation, because the mechanism of vasopressin is different from that of catecholamine, we recommend vasopressin for maintaining the blood pressure.We described the first clinical case of “catecholamine reversal” and highlighted that if unexpected hypotension occurs in response to catecholamine infusion, we should suspect the use of α-adrenergic antagonists. In such situations, we should consider the administration of vasopressin instead. Thus, we suspected unknown distributive shock refractory to a large amount of catecholamine infusion. Therefore, in addition to catecholamine infusion, we initiated vasopressin at 3 U/hour 150 minutes after arrival. Subsequently, his BP markedly improved to 135/45 mmHg. Three hours after arrival, we transferred him to our intensive care unit. We performed continuous hemodiafiltration because of the presence of metabolic acidosis , 73.8 mmHg; partial pressure of carbon dioxide in arterial blood (PaCO2), 39.3 mmHg; bicarbonate (HCO3-), − 1.2 mmol/l; lactate (Lac), 1.5 mmol/l; and fraction of inspired oxygen (FiO2), 0.3. On day 2, we terminated vasopressin infusion. After extubation, his condition was stable: BP, 123/75 mmHg; HR, 100 bpm; and Glasgow Coma Scale score (E4V5M6), 15. He was transferred to our general ward. He admitted to ingesting approximately 150 mg risperidone to attempt suicide. The risperidone concentration in his blood sample on admission was very high  was 57/29 mmHg, heart rate (HR) was 135 beats per minute (bpm), respiratory rate was 40/minute, and his body temperature was 35.6 °C. His Glasgow Coma Scale score was (E1V1M1) 3. We immediately performed intubation because of his shock and coma. Fluid resuscitation of 3000 ml crystalloid temporarily increased his BP to 73/28 mmHg, but his shock still persisted. Before a central venous line was inserted, we tentatively initiated dopamine infusion at 5 μg/kg per minute, which was increased to 10 μg/kg per minute; however, his hypotension gradually worsened to 66/37 mmHg (Fig. 2-adrenergic effects are predominantly enhanced (Fig. We experienced unexpected hypotension in response to catecholamine infusion, and we believe that this unexpected hypotension was caused by a pharmacological phenomenon: the catecholamine effect under the α-adrenergic blockade effect of risperidone. In animal experiments, if adrenaline is simultaneously administered with α-adrenergic receptor blockers such as phentolamine, the α-adrenergic effects are masked and the βced Fig.  3]. Con. Con2-adDopamine and dobutamine also have both α-adrenergic and β-adrenergic effects ; we thinOn the other hand, vasopressin is a type of vasoactive agent that increases peripheral vasoconstriction via V1 receptors  and is cThis is the first clinical case to describe unexpected hypotension as “catecholamine reversal.” Most antipsychotic agents have α-adrenergic blockade; thus, this educational case highlights that we should determine which vasoactive agent should be selected for the patient who uses these medicines.We described the first clinical case of “catecholamine reversal” and highlighted that if unexpected hypotension occurs in response to catecholamine infusion, we should suspect that the patient has used α-adrenergic antagonists. In such a situation, we should consider administration of vasopressin instead.


Success in the social world requires the ability to perceive not just individuals and their actions, but pairs of people and the interactions between them. Despite the complexity of social interactions, humans are adept at interpreting those interactions they observe. Although the brain basis of this remarkable ability has remained relatively unexplored, converging functional MRI evidence suggests the posterior superior temporal sulcus (pSTS) is centrally involved. Here, we sought to determine whether this region is sensitive to both the presence of interactive information, as well as to the content of qualitatively different interactions (i.e. competition vs. cooperation). Using point-light human figure stimuli, we demonstrate that the right pSTS is maximally activated when contrasting dyadic interactions vs. dyads performing independent, non-interactive actions. We then used this task to localize the same pSTS region in an independent participant group, and tested responses to non-human moving shape stimuli (i.e. two circles’ movements conveying either interactive or non-interactive behaviour). We observed significant support vector machine classification for both the presence and type of interaction  in the pSTS, as well as neighbouring temporo-parietal junction (TPJ). These findings demonstrate the important role that these regions play in perceiving and understanding social interactions, and lay the foundations for further research to fully characterize interaction responses in these areas. •The pSTS is sensitive to visual dynamic social interactions.•We show that the pSTS is sensitive to both the presence & contents of interactions.•This effect is independent of face & body information. From an early age, people use the social interactions they observe to decide who to trust, who to learn from and who is in charge. Despite the importance of our ability to parse social interactions in building our knowledge of others and the relationships between them, relatively few studies have investigated the brain's response to observed social interactions between multiple actors. Instead, the bulk of the current ‘social vision’ literature has focused on the perception and appraisal of individual agents. One aspect of such work has greatly increased our understanding of the social brain and has implicated a core set of regions in perceiving and evaluating individual social objects e.g. . What isA likely candidate in which to find such a region is the posterior superior temporal sulcus (pSTS). The pSTS has been described in the literature as the ‘hub’ of the social brain  and is ohuman actors in these scenarios. Indeed, similar responses have been demonstrated with simple moving shape stimuli  when contrasting interactions with other forms of shape motion; for example, greater pSTS activation is observed when viewing two shapes engaged in a complex interaction relative to shapes moving in an aimless, non-intentional manner  judgements such as rating how ‘intentional’ shapes’ movements appeared to be , pSTS activation is observed when individuals make explicit intentional inferences, that is, deliberative thinking or reasoning about the contents of an individual's mind. The following extreme case demonstrates the influence of explicit inferences in the absence of socially meaningful behaviour: presence and contents of the social interaction itself , or if previously reported responses in the pSTS are driven by differences in animate motion or the task of making explicit social judgements.Importantly, however, most such paradigms have not sought to directly investigate social interaction ed to be . Whilst content of an interaction rather than simply sensitive to the presence of an interaction, a multivariate approach may be required. Exploring content sensitivity in this fashion will provide clues to the functional role(s) of the pSTS in perceiving and understanding other people in interaction.Whilst the preceding evidence demonstrates that the pSTS is sensitive to visual interactive behaviour, much remains to be learned about what this region computes about such behaviour, especially qualitatively different interactions; for example, how might interactions in which two agents compete with each other be differentiated from those in which they cooperate with each other? Previous studies have found pSTS modulation when comparing qualitatively different interactions: In experiment 1, we used point-light human stimuli across a large group of participants to demonstrate that the right pSTS is the most strongly activated region when contrasting interactions > visually matched non-interactions. In a separate group of participants, we then used the same contrast to localize human interaction-sensitive cortex within the pSTS before using a multivariate approach – that would afford greater sensitivity – to test whether this area would also contain information about the presence and qualitative content of abstract moving shape interactions. The task and stimuli were designed to focus on the role of pSTS in interaction perception while tightly controlling many ‘low-level’ visual cues and also attempting to reduce the influence of other social features known to engage this broad region. Specifically, these dynamic displays depicted highly-controlled moving shape stimuli that did not contain face or body information. Further, we used an orthogonal response task that did not require reporting interaction content, to minimize, as much as possible, explicit ToM inferences.This approach allowed us to test two main hypotheses within the pSTS: Firstly, that above-chance classification of interactions vs. non-interactions would be observed. Secondly, we predicted that above-chance classification of different kinds of interactions. Specifically, we contrasted competitive vs. cooperative scenarios, as these types of interactions do not convey strongly differential emotional valence, which could confound interaction classification. A further practical advantage of testing these scenarios is that they are easily represented with moving shape animations. In the present study, for example, we conveyed cooperation via two shapes pushing the same side of an object together, and competition via two shapes pushing opposite sides of an object.anatomically specific such a pattern of results might be by comparing pattern classification performance in the localized interaction region to a neighbouring ToM-localized region in the temporo-parietal junction (TPJ). In addition, we also included a control region in the right lateral occipito-temporal cortex (LOTC) – an area centrally involved in action perception  participated in the study. One participant's data was omitted from further analyses due to excessive head motion. The MIT Committee on the Use of Humans as Experimental Subjects reviewed and approved the experimental protocol and participants completed informed consent forms before taking part.Fifty participants  or engaged in two independent actions . The independence of the two actions was further underscored by having the two figures face away from each other, and a line was placed down the center to form a ‘wall’ between the characters. The source of the interacting dyads was from Imaging data was acquired on a Siemens 3 T MAGNETOM Tim Trio Scanner at the Athinoula A. Martinos Imaging Center at MIT using a 32-channel head coil. Functional data were collected using a T2 * -weighted echo planar imaging (EPI) pulse sequence . In addition, a high resolution T1-weighted anatomical image (multi-echo MPRAGE) was collected , echo spacing = 9.3 ms. TI = 1400 ms, flip angle = 7°, FOV = 220 × 220 mm, matrix size = 220 × 220 mm, slice thickness = 1 mm, 176 near axial slices, acceleration factor = 3, 32 reference lines).2.3All preprocessing steps and general linear modeling (GLM) was performed using Freesurfer version 5.3 (freesurfer.net). Preprocessing consisted of standard motion correction and then the alignment of each functional run to that participant's anatomical volume. Functional data were then smoothed using a 5 mm full width at half maximum (FWHM) Gaussian kernel. Smoothed data were used when defining regions of interest (ROIs), but percent signal-change data was extracted from unsmoothed data. For group-level analyses, data were normalized to the Freesurfer FSAverage template and a surface-based random effects group analysis was run across all participants, weighted by the amount of data contributed by each participant . All ROI analyses were performed in each participant's native anatomical space.2.4p < .005 uncorrected. Of the 40 participants entered in the ROI analysis, we could not localize an ROI for five participants, leaving 35 participants in the final ROI analysis.Subject-specific pSTS ROIs were created using a leave-one-out method . This process was iterated until percent signal change had been calculated from all runs. The nine participants who had only two runs of data to work with were not included in the percent signal change analysis. ROIs were defined by intersecting an 8 mm-radius sphere with the cluster peak  in the right pSTS/STG where the contrast maps were thresholded at 3p < .001 uncorrected, this activation remains primarily in the STS, spreading more anteriorly on the right, and showing a small and much weaker response on the left  = 8.20, p < .001; see The group analysis showed a region within the right pSTS that responded much more strongly to social interaction than to independent actions. Indeed, when false discovery rate (FDR) corrected for multiple comparisons (at 5%), only two clusters remain – both in the STS  were recruited from the Bangor University student population. Data from two participants were removed from all analyses due to consistently low behavioral response accuracy . The study was authorized by the School of Psychology ethics committee, and participants gave informed consent and received monetary compensation for the session.23 right-handed participants  and interaction type (competition and cooperation). Interaction variants of competition and cooperation, respectively, depicted the shapes either working together, or against each other to achieve their respective or shared goals. To ensure that the outcome of each video was not confounded with the type of interaction, half of both interaction types resulted in successful object action (e.g. a door was successfully opened), and half resulted in unsuccessful action. Because successful and unsuccessful object actions had qualitatively different meanings for competition and cooperation , we did not analyze successful vs. unsuccessful object actions. To minimize the visual familiarity of individual videos, each video was presented at four 90° rotations. In total, there were 256 novel stimuli (i.e. 4 conditions x 2 outcomes x 8 scenarios x 4 video rotations), of which 240 were randomly selected for the experiment.The stimuli depicted eight different scenes from an aerial perspective .ps > .462; see To ensure that stimulus motion energy did not differ between conditions, we used the same approach adopted in previous studies by computing differences in pixel intensity between video frames e.g. . SpecifiA blocked-design was used in which 10 runs were completed, each lasting 242 s and consisted of eight experimental blocks, two per condition, 20 s each (3 × 6 s videos + 2 s fixation epoch at the end of the block), along with three 20 s rest blocks at the beginning, middle, and end of each run. A total of 80 experimental blocks were completed . Block ordering was randomized across runs, and runs were randomized across participants.Participants performed an orthogonal response task whilst viewing stimuli that was intended to minimize the tendency to make explicit ToM attributions; participants pressed a button whenever one of the agents momentarily changed color (i.e. from blue to pink). This change lasted for one animation frame (i.e. 41.67 ms) and always occurred 5.5 s after trial onset. To minimize the predictability of these trials, only one trial per block contained a color-change, with presentation order randomized across blocks. The brevity of the color-change also served to encourage active attending to both agents, as this change could easily be missed if a participant's attention momentarily drifted away from the agents. While not cognitively demanding, this was a relatively difficult task; it required consistent attention to both agents in order to catch the very brief change.4.3To localize interaction-sensitive regions of the pSTS, we used a shortened version of the task used in experiment 1 (i.e. contrasting two interacting point-light figures with two figures performing independent actions). Participants completed two blocked runs , with blocks presented in a randomized order across runs. In order to localize ToM-sensitive cortex in the TPJ, participants also completed two runs of a written story false-belief localizer task . The sti4.4p < .05. ROIs were defined by intersecting a 6 mm-radius sphere with the cluster peak  in the right pSTS. As before, we chose to localize pSTS only in the right hemisphere due to observed stronger right lateralization in the group data in experiment 1, as well as in prior interaction studies .Scanning was performed with a Philips 3T scanner at Bangor University. Functional images were acquired with the following parameters: a T2*-weighted gradient-echo single-shot EPI pulse sequence; TR = 2000 ms, TE = 30 ms, flip angle = 90°, FOV = 230 × 230 × 132 mm, acquisition matrix = 76 × 74 (reconstruction matrix = 128 × 128); 35 ascending slices , acquired voxel size (mm) = 3.03 × 3.11 × 3.0 (reconstructed voxel size (mm) = 1.8 × 1.8 × 3.0). Four dummy scans were discarded prior to image acquisition for each run. Structural images were obtained with the following parameters: T1-weighted image acquisition using a gradient echo, multi-shot turbo field echo pulse sequence, with a five echo average; TR = 12 ms, TE = 3.5 ms − 10.2 ms, in 1.6 ms steps, acquisition time = 329 s, FA = 8°, FOV = 250 × 250 × 170, acquisition matrix = 252 × 224 (reconstruction matrix = 256 × 256); 170 contiguous slices, acquired voxel size = .99 × 1.12 × 2.0 mm (reconstructed voxel size = 1 mm) to assess excessive scan-to-scan head-motion. As head motion can reduce classification accuracy  analyses. Four separate regressors  were generated for each run. For the interaction vs. non-interaction contrasts, the corresponding regressors were modelled together, that is, interaction = [competition + cooperation], non-interaction = [non-interaction competition + non-interaction cooperation].t-tests against chance (i.e. 100% / 2 classes = 50% chance). An FDR-correction threshold of p ≤ .01, was determined based on 5 t-tests yielding one-sided p-values ≤ .05 (i.e. .05 / 5 = .01). FDR corrected p-values of ≤ .025 were determined for significant t-tests that followed PSC ANOVAs, (i.e. .05 / 2 = .025).The Decoding Toolbox  was usedResponse accuracy (%) was calculated for each participant (i.e. a button-press response occurring < 1.5 s after color-change onset). Runs containing > 2 inaccurate responses (i.e. < 75% accuracy) were omitted from further analysis (i.e. 1 run from 2 separate participants) to ensure that only actively attended runs were included.55.1M = 95.02, SD = 2.87; non-interaction: M = 91.70, SD = 7.03; F = 6.36, p = .020), demonstrating that participants were more accurate in the interaction than non-interaction conditions. Neither the main effect between competition and cooperation  = .38, p = .543), nor the interaction term was significant  = 1.40, p = .251).A 2 × 2 ANOVA was performed on response accuracy scores with interaction and non-interaction as levels of the first factor and competition and cooperation as levels of the second factor. Unexpectedly, a main effect between interaction and non-interaction was observed (interaction: ps < .001), showing that interactions were perceived as more interactive, goal-directed, and animate than non-interactions. No other term was significant across any of the three ANOVAs , indicating no perceived differences in interactivity, goal-directedness, or animacy between competition and cooperation (or the respective non-interaction variants of these conditions).Additionally, we obtained stimulus ratings from a separate group of participants (N = 20) outside of the scanner. This served to aid our interpretation of what might drive greater response accuracy for interactions than non-interactions. Participants viewed a randomly selected subset of the original stimuli . Participants gave Likert-scale ratings  of the videos, for the following three statements: ‘The agents interacted with each other’ (interactivity); ‘The agents were goal-directed’ ; ‘The agents were alive/animate’ (animacy). Along with interactivity, we included ratings of goal-directedness and animacy as these constructs are shown to drive pSTS responses in moving shape displays e.g. . We then5.2M = 65.20%, SD = 11.15, t(18) = 5.94, p < .001; competition vs. cooperation: M = 56.97%, SD = 11.15, t(18) = 2.53, p = .010). For the TPJ, we also observed above-chance classification for both contrasts, but at the uncorrected (p ≤ .05) level only  = 1.90, p = .038; competition vs. cooperation: M = 57.35%, SD = 13.80; t(15) = 2.13, p = .025). Therefore, above-chance classification for both contrasts was observed in the pSTS and also to a weaker extent in the TPJ.To test our main hypotheses – that the pSTS would significantly differentiate interactions from non-interactions, and competition from cooperation – we performed SVM classification within subjects’ pSTS ROIs see . For botM = 69.29%, SD = 11.77, t(19) = 7.32, p < .001) but not for competition vs. cooperation . These results are consistent with recent studies that demonstrate robust classification between a variety of actions, such as pushing and pulling .We then compared these results to a control region in the LOTC; we observed above-chance classification in the interaction vs. non-interaction contrast .Although we found no difference in motion energy between any contrasted pair of conditions see  we sough5.3In addition to classification analyses, we also sought to determine whether univariate responses differed between pSTS and TPJ, for both main contrasts. Based on the univariate contrast from experiment 1, we expected greater activation for shape interactions than non-interactions. For the competition vs. cooperation contrast however, we had no clear expectation as to whether competition or cooperation should evoke greater activation, or whether such differentiation could be captured with univariate analysis. However, a similar contrast in a recent study  demonstrM = .43, SD = .42; TPJ: M = .05, SD = .30; F = 12.74, p = .003), a marginal main effect of contrast  = 4.26, p = .058), but no interaction between the two factors  = 1.88, p = .192). Paired t-tests (2-tailed) revealed a significant difference between interaction and non-interaction in the TPJ (t(15) = 2.53, p = .023), but unexpectedly, the same trend was not significant in the pSTS (t(18) = 1.59, p = .129).To this end, we extracted subjects’ PSC values for each condition and ROI, and ran two 2 × 2 ANOVAs – one for each of the contrasts . For interaction vs. non-interaction see , we obseM = .49, SD = .41; TPJ: M = .12, SD = .32; F = 9.71, p = .008), along with a marginal main effect of contrast  = 3.61, p = .078), and marginal interaction  = 3.94, p = .067). Follow-up t-tests (2-tailed) revealed greater activation for competition than cooperation in the pSTS at the uncorrected level (p ≤ .05) only (t(18) = 2.22, p = .040), but not in the TPJ (t(15) = 1.68, p = .113).For the competition vs. cooperation contrast see , a main 6The results from experiment 1 reveal that a region in the right pSTS is strongly responsive to dyadic social interactions; it is one of only a few regions that shows such a response in a whole-brain group analysis in a relatively large sample, and it responds about twice as strongly to such interactions when compared to visually similar depictions of two individuals performing non-interactive actions. The identification of the pSTS as being uniquely responsive to human interactions is replicable in an independent set of data from our own lab . Although there is mixed evidence as to whether the pSTS reliably differentiated the interaction > non-interaction contrast across our two stimulus sets, our univariate and classification results give direct evidence that the pSTS differentiates between qualitatively different interactions and suggest that the pSTS might play a central role in the perception and understanding of social interactions. Whilst further evidence is undoubtedly required to fully support this possibility , the present findings align closely with a very recent paper investigating a similar research question and using conceptually similar stimuli . Togethedid reach significance in the pSTS. Conversely, for the competition vs. cooperation contrast, similar differentiation of conditions was observed in both regions, but only reached (uncorrected) significance for the pSTS. Therefore, similarities in classification performance and mixed univariate results prevent a clear functional separation of the two regions.We also found that the pSTS was not the only region to differentiate between our conditions; similar classification responses were observed in neighbouring ToM-task localized TPJ, although these responses were somewhat weaker. In addition, their relative responses to the univariate interaction > non-interaction contrast are similar, although the difference was only significant in the TPJ. It is, however, worth noting that in a similar contrast in In some ways, the similarity between the two regions is not surprising. They occupy neighbouring cortex, and functional and structural distinctions between the TPJ and pSTS are not always clear in the literature e.g. . In termHowever, a purely visual account the pSTS seems unlikely given top-down modulation of the pSTS when viewing moving shapes  and appathird-person interactions, yet these findings may inform other lines of interaction research: For example, social cognition and do not require person-perception (e.g. playing a computer game against an unseen opponent) typically recruit fronto-parietal regions  (ERC-2016-StG-716974) under the European Union's Horizon 2020 research and innovation programme .This work has received funding from the