Effect of simulating parity-odd observables in high energy heavy ion collisions on Balance Functions of charged particles and elliptic flow of pions

At the early stage of heavy ion collisions, non-trivial topologies of the gauge fields can be created resulting in an imbalance of axial charge density and eventually separation of electric charges along the direction of the magnetic field produced in such collisions. This process is called the chiral magnetic effect (CME). In this work we implement such a charge separation at the partonic level in AMPT for Au+Au collisions at $\sqrt{s_{NN}}$ = 200 GeV to study its consequence on experimental observables. We present the effects on the pion elliptic flow ($v_2$) and the charged particle balance function (BF) for varying strengths of initial charge separation. We find that the shape of the balance function is sensitive to the increasing charge separation. $v_2$ of pion shows a strong decreasing trend at higher transverse momenta ($p_T$) with increasing charge separation. Charge balance functions show a peak at $\Delta\phi \sim 180$ with charge separation implemented in the partonic level as expected for the parity violation. We have also calculated parity observable $\gamma$ in the form of BF's moments. $\gamma$ shows a decreasing trend with charge separation. It has a negative value for charge separation produced by flipping more than 30 $\%$ of quarks in the parton level. We also notice that $<\gamma>$ for the same charge correlation and the opposite charge correlation shows negative and positive values, respectively

The genes with most frequent differential APA events.

<p>Number of experiments indicate the number of microarray experiments where the APA event shows differential expression. The biological conditions of the most relevant experiments were listed here.</p

The 10 selected RBPs showing the highest positive or negative associations with the global shift in APA.

<p>The median correlation coefficients between RBPs and gULIs across experiments are indicated within the parenthesises.</p

Description of our integrated mouse poly(A) site database.

<p>(A). Venn diagram shows the overlaps of three sources of our poly(A) site database including PolyA_DB2, polyA-seq, and 3′ ends of UCSC Known Genes. (B). Histogram shows the distribution of the number of poly(A) site per gene in comparison with UCSC annotation alone. The poly(A) sites based on UCSC Known Gene data alone are colored in grey and our integrated poly(A) database is colored in black. (C). Scheme for probeset customization of microarray probes for APA detection. The expression values of the probesets after quantification and normalization were used for differential APA expression analysis within each experiment.</p

Scheme of the workflow.

<p>We generated an integrated poly(A) database and analyzed differential expression of APAs and RBPs in publically available microarrays from GEO aiming to reveal RBP's functions in differential APA regulation. The results of our analysis were highlighted in blue color, which include APA differential expression detection and interpretation in the left panel, RBP-APA co-expression network in the middle panel, and RBP regulation models in APA by combining available CLIP data and microarray gene expression data in the right panel.</p

Examples of global shifts in APA.

<p>Six experiments were selected from the top list to represent global ULI shifts under different biological conditions. UTR shortening was preferred in certain tissues (GSE9441, GSE17478) as well as in carcinoma (GSE9012), developments (GSE20954), differentiations (GSE21749), and hypoxia (GSE15894). Box-whiskers indicate global UTR lengthening indices (gULI) across biological replicates within each condition. Y-axis: global UTR lengthening index; X-axis: experimental conditions. The descriptions for the biological conditions are listed below each boxplot. Grey color outlines the conditions with lengthening of UTRs while white color for the conditions with shortening of UTRs.</p

Differential expression of APA for <i>Cpsf6</i> and <i>Eif4e2</i> in various biological conditions.

<p>(A). Boxplots show the differential expression of <i>Cpsf6</i> APA isoforms (a tandem UTR event) in different tissues and cell lines, as well as different development stages. (B). Boxplots show the differential expression of <i>Eif4e2</i> APA isoforms (an alternative UTR event) in different tissues, development and spermatogenesis. Gene models of the APA isoforms are indicated on top, with microarray probes targeted regions on the 3′ UTRs marked with colors. Blue color represents the common or proximal UTR probeset while red color represents extended or distal UTR probeset. Box-whiskers indicate the expression of probesets across biological replicates within each condition. Y-axis: log2-transformed expression values from microarrays; X-axis: experimental conditions. The descriptions for the biological conditions are listed below each boxplot. <i>cor</i>: Pearson correlation coefficient; <i>p</i>: two-way ANOVA p value.</p

RBP and APA co-expression network.

<p>The arrow-headed edge pointing from an RBP indicates that the up-regulation of RBP is correlated with 3′ UTR lengthening of the target gene, while T-headed edge indicates that the up-regulation of RBP is correlated with 3′ UTR shortening. RBP gene is colored in blue and non-RBP gene in white. Gene with APA event is in the diamond shape and gene without APA event is in the round shape. Note that some RBP genes such as <i>Cpsf6</i> also contain APA events. The strength of correlation is indicated by thickness of the edges. <i>|r|</i>, absolute value of Pearson's correlation coefficient.</p

The list of biological conditions that most significantly perturb global APA usage.

<p>ΔgULI is the maximal shift of global UTR lengthening indices (gULIs).</p

DataSheet_1_Comparative efficacy and safety of targeted therapy and immunotherapy for HER2-positive breast cancer: a systematic review and network meta-analyses.pdf

BackgroundIn recent years, novel therapies targeting specific molecular pathways and immunotherapies have exhibited promising outcomes for treating human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Our work aimed to assess the effectiveness and safety of these emerging treatment regimens for this disease.Material and methodsWe systematically searched databases including PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials their inception to August 2023 to identify relevant randomized controlled trials (RCTs). The quality of eligible RCTs was evaluated with the Cochrane risk-of-bias tool, version 2 (RoB2). Investigated outcomes encompassed progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), pathologic complete remission (pCR), and adverse events (AEs). They were expressed as hazard ratio (HR) with 95% conference intervals (CI) or risk ratio (RR) with 95% CI.ResultsOur analysis identified a total of 28 RCTs suitable for inclusion in the NMA. Regarding the PFS, all these treatment regimens exhibited comparable effectiveness. In terms of OS, Capecitabine+Trastuzumab, Lapatinib+Trastuzumab and Pyrotinib+Capecitabine exhibited better effect compared to other treatments. Regarding pCR and AEs, all these treatment regimens exhibited comparable effectiveness, especially Lapatinib+Trastuzumab and Pyrotinib+Capecitabine.ConclusionOur study highlights the prominent role of targeted therapies and immunotherapies in treating HER2-positive breast cancer. The efficacy of trastuzumab-containing regimens was superior to other treatment options, while maintaining a comparable safety profile. Based on these findings, trastuzumab-containing regimens emerge as a preferable and recommended choice in clinical practice for managing HER2-positive breast cancer.Systematic Review RegistrationPROSPERO, identifier CRD42023414348.</p