Deciphering the Belle II data on B→KννˉB\to K \nu \bar\nu decay in the (dark) SMEFT with minimal flavour violation

Recently, the Belle II collaboration announced the first measurement of $\mathcal B(B^+\to K^+\nu\bar\nu)$, which is found to be about $2.7\sigma$ higher than the SM prediction. We decipher the data with two new physics scenarios: the underlying $b\to s \nu\bar\nu$ transition is, besides the SM contribution, further affected by heavy new mediators that are much heavier than the EW scale, or amended by an additional decay channel with undetected light final states like dark matter or axion-like particles. These two scenarios can be most conveniently analyzed in the SMEFT and the dark SMEFT (DSMEFT) framework, respectively. We consider the flavour structures of the resulting effective operators to be either generic or satisfy the minimal flavour violation (MFV) hypothesis, both for the quark and lepton sectors. In the first scenario, once the MFV is assumed, only one SM-like low-energy effective operator induced by the SMEFT dim-6 operators can account for the Belle II excess, the parameter space of which is, however, excluded by the Belle upper bound on $\mathcal B(B^0\to K^{*0}\nu\bar\nu)$. In the second scenario, it is found that the Belle II excess can be accommodated by 22 of the DSMEFT operators involving one or two scalar, fermionic, or vector dark matters as well as ALPs. These operators also receive dominant constraints from the $B^0\to K^{*0}+$inv and $B_s\to$inv decays. In the MFV hypothesis, the number of viable operators is reduced to 14, and the $B^+\to\pi^+ +$inv and $K^+\to\pi^++$inv decays start to put further constraints. Within the parameter space allowed by all the current experimental data, the $q^2$ distributions (and $F_L$) of the $B\to K^{(*)}+$inv decays are studied for each viable operator. In addition, we, for the first time, calculate systematically the longitudinal polarization fraction $F_L$ of $K^*$ in the $B\to K^*+$inv decays within the DLEFT.Comment: 51 pages, 13 figures, comments welcome; v2: discussions on $F_L$ of the $B \to K^* + \text{inv}$ decay in the DSMEFT added, errors in the $B \to V + \text{inv}$ decays for some operators involving two scalar or vector DM fields fixed, the related discussions and figures 2, 6, 7, 11 and 12 corrected, main conclusion unchanged, a few comments and refs adde

FedFTN: Personalized Federated Learning with Deep Feature Transformation Network for Multi-institutional Low-count PET Denoising

Low-count PET is an efficient way to reduce radiation exposure and acquisition time, but the reconstructed images often suffer from low signal-to-noise ratio (SNR), thus affecting diagnosis and other downstream tasks. Recent advances in deep learning have shown great potential in improving low-count PET image quality, but acquiring a large, centralized, and diverse dataset from multiple institutions for training a robust model is difficult due to privacy and security concerns of patient data. Moreover, low-count PET data at different institutions may have different data distribution, thus requiring personalized models. While previous federated learning (FL) algorithms enable multi-institution collaborative training without the need of aggregating local data, addressing the large domain shift in the application of multi-institutional low-count PET denoising remains a challenge and is still highly under-explored. In this work, we propose FedFTN, a personalized federated learning strategy that addresses these challenges. FedFTN uses a local deep feature transformation network (FTN) to modulate the feature outputs of a globally shared denoising network, enabling personalized low-count PET denoising for each institution. During the federated learning process, only the denoising network's weights are communicated and aggregated, while the FTN remains at the local institutions for feature transformation. We evaluated our method using a large-scale dataset of multi-institutional low-count PET imaging data from three medical centers located across three continents, and showed that FedFTN provides high-quality low-count PET images, outperforming previous baseline FL reconstruction methods across all low-count levels at all three institutions.Comment: 13 pages, 6 figures, Accepted at Medical Image Analysis Journal (MedIA

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

TLR7 Activation of Macrophages by Imiquimod Inhibits HIV Infection through Modulation of Viral Entry Cellular Factors

The Toll-like receptor (TLR) 7 is a viral sensor for detecting single-stranded ribonucleic acid (ssRNA), the activation of which can induce intracellular innate immunity against viral infections. Imiquimod, a synthetic ligand for TLR7, has been successfully used for the topical treatment of genital/perianal warts in immunocompetent individuals. We studied the effect of imiquimod on the human immunodeficiency virus (HIV) infection of primary human macrophages and demonstrated that the treatment of cells with imiquimod effectively inhibited infection with multiple strains (Bal, YU2, and Jago) of HIV. This anti-HIV activity of imiquimod was the most potent when macrophages were treated prior to infection. Infection of macrophages with pseudotyped HIV NL4-3-ΔEnv-eGFP-Bal showed that imiquimod could block the viral entry. Further mechanistic studies revealed that while imiquimod had little effect on the interferons (IFNs) expression, its treatment of macrophages resulted in the increased production of the CC chemokines (human macrophage inflammatory protein-1 alpha (MIP-1α), MIP-1β, and upon activation regulated normal T cells expressed and secreted (RANTES)), the natural ligands of HIV entry co-receptor CCR5, and decreased the expression of CD4 and CCR5. The addition of the antibodies against the CC chemokines to macrophage cultures could block imiquimod-mediated HIV inhibition. These findings provide experimental evidence to support the notion that TLR7 participates in the intracellular immunity against HIV in macrophages, suggesting the further clinical evaluation of imiquimod for its additional benefit of treating genital/perianal warts in people infected with HIV

Reproduction and In-Depth Evaluation of Genome-Wide Association Studies and Genome-Wide Meta-analyses Using Summary Statistics

In line with open-source genetics, we report a novel linear regression technique for genome-wide association studies (GWAS), called Open GWAS algoriTHm (OATH). When individual-level data are not available, OATH can not only completely reproduce reported results from an experimental model, but also recover underreported results from other alternative models with a different combination of nuisance parameters using naïve summary statistics (NSS). OATH can also reliably evaluate all reported results in-depth (e.g., p-value variance analysis), as demonstrated for 42 Arabidopsis phenotypes under three magnesium (Mg) conditions. In addition, OATH can be used for consortium-driven genome-wide association meta-analyses (GWAMA), and can greatly improve the flexibility of GWAMA. A prototype of OATH is available in the Genetic Analysis Repository (https://github.com/gc5k/GEAR)

Bowman‒Birk Inhibitor Suppresses Herpes Simplex Virus Type 2 Infection of Human Cervical Epithelial Cells

The Bowman‒Birk inhibitor (BBI), a protease inhibitor derived from soybeans, has been extensively studied in anti-tumor and anti-inflammation research. We recently reported that BBI has an anti-HIV-1 property in primary human macrophages. Because HSV-2 infection plays a role in facilitating HIV-1 sexual transmission, we thus examined whether BBI has the ability to inhibit HSV-2 infection. We demonstrated that BBI could potently inhibit HSV-2 replication in human cervical epithelial cells (End1/E6E7). This BBI-mediated HSV-2 inhibition was partially through blocking HSV-2-mediated activation of NF-&kappa;B and p38 MAPK pathways. In addition, BBI could activate the JAK/STAT pathway and enhance the expression of several antiviral interferon-stimulated genes (ISGs). Furthermore, BBI treatment of End1/E6E7 cells upregulated the expression of tight junction proteins and reduced HSV-2-mediated cellular ubiquitinated proteins&rsquo; degradation through suppressing the ubiquitin‒proteasome system. These observations indicate that BBI may have therapeutic potential for the prevention and treatment of HSV-2 infections