Spatial Proximity and Relative Distribution of Tumor-Infiltrating Lymphocytes and Macrophages Predict Survival in Melanoma

Tumor microenvironment plays a crucial role in primary cutaneous melanoma (CM) progression. Although the role of tumor-infiltrating lymphocyte (TIL) density has been known for a long time, its spatial distribution and impact with or without tumor-associated macrophages (TAMs) remain controversial. Herein, we investigated spatial proximity between tumor cells and immune cells in 113 primary CM and its correlation with disease-free (DFS) and overall survival (OS). The study cohort included clinical stage II (n 1⁄4 79) and stage III (n 1⁄4 34) primary CM with a Breslow thickness of >2 mm (with a median age of 64 years, including 72 men and 41 women). In univariate models, patients with SOX10þ melanoma cells with high proximity to CD8þ TILs in a 20 mm radius showed longer DFS (hazard ratio [HR], 0.58; 95% CI, 0.36e0.93; P 1⁄4 .025) and OS (HR, 0.55; 95% CI, 0.32e0.92; P 1⁄4 .023). Furthermore, at multivariate combined analysis, patients with SOX10þ melanoma cells with high proximity to CD8þ TILs or low proximity to CD163þ TAMs in a 20 mm radius showed an increased OS (aHR, 0.37; 95% CI, 0.14e0.96; P 1⁄4 .04) compared with melanoma patients with low proximity to CD8þ TILs or high proximity to CD163þ TAMs. In a subgroup analysis including 92 patients, a significant negative impact on DFS (aHR, 4.49; 95% CI, 1.73e11.64; P 1⁄4 .002) and OS (aHR, 3.97; 95% CI, 1.37e11.49; P 1⁄4 .01) was observed in sentinel lymph node (SLN)-negative patients with a high proximity of CD163þ TAMs to CD8þ TILs. These findings could help identify high-risk patients in the context of thick melanoma and a negative SLN. Our study suggests the importance of quantifying not only the density of immune cells but also the individual and combined relative spatial distributions of tumor cells and immune cells for clinical outcomes in SLN-negative primary CM patients

Test of the photon detection system for the LHCb RICH Upgrade in a charged particle beam

The LHCb detector will be upgraded to make more efficient use of the available luminosity at the LHC in Run III and extend its potential for discovery. The Ring Imaging Cherenkov detectors are key components of the LHCb detector for particle identification. In this paper we describe the setup and the results of tests in a charged particle beam, carried out to assess prototypes of the upgraded opto-electronic chain from the Multi-Anode PMT photosensor to the readout and data acquisition system.Comment: 25 pages, 22 figure

Tumor-Infiltrating Lymphocyte Recognition in Primary Melanoma by Deep Learning Convolutional Neural Network

The presence of tumor-infiltrating lymphocytes (TILs) is associated with a favorable prognosis of pri-mary melanoma (PM). Recently, artificial intelligence (AI)-based approach in digital pathology was proposed for the standardized assessment of TILs on hematoxylin and eosin-stained whole slide images (WSIs). Herein, the study applied a new convolution neural network (CNN) analysis of PM WSIs to automatically assess the infiltration of TILs and extract a TIL score. A CNN was trained and validated in a retrospective cohort of 307 PMs including a training set (237 WSIs, 57,758 patches) and an inde-pendent testing set (70 WSIs, 29,533 patches). An AI-based TIL density index (AI-TIL) was identified after the classification of tumor patches by the presence or absence of TILs. The proposed CNN showed high performance in recognizing TILs in PM WSIs, showing 100% specificity and sensitivity on the testing set. The AI-based TIL index correlated with conventional TIL evaluation and clinical outcome. The AI-TIL index was an independent prognostic marker associated directly with a favorable prognosis. A fully automated and standardized AI-TIL appeared to be superior to conventional methods at differentiating the PM clinical outcome. Further studies are required to develop an easy-to-use tool to assist pathologists to assess TILs in the clinical evaluation of solid tumors. (Am J Pathol 2023, 193: 2099-2110; https://doi.org/10.1016/j.ajpath.2023.08.013

Dark matter search in a Beam-Dump eXperiment (BDX) at Jefferson Lab

MeV-GeV dark matter (DM) is theoretically well motivated but remarkably unexplored. This Letter of Intent presents the MeV-GeV DM discovery potential for a 1 m$^3$ segmented plastic scintillator detector placed downstream of the beam-dump at one of the high intensity JLab experimental Halls, receiving up to 10$^{22}$ electrons-on-target (EOT) in a one-year period. This experiment (Beam-Dump eXperiment or BDX) is sensitive to DM-nucleon elastic scattering at the level of a thousand counts per year, with very low threshold recoil energies ($\sim$1 MeV), and limited only by reducible cosmogenic backgrounds. Sensitivity to DM-electron elastic scattering and/or inelastic DM would be below 10 counts per year after requiring all electromagnetic showers in the detector to exceed a few-hundred MeV, which dramatically reduces or altogether eliminates all backgrounds. Detailed Monte Carlo simulations are in progress to finalize the detector design and experimental set up. An existing 0.036 m$^3$ prototype based on the same technology will be used to validate simulations with background rate estimates, driving the necessary R$\&$D towards an optimized detector. The final detector design and experimental set up will be presented in a full proposal to be submitted to the next JLab PAC. A fully realized experiment would be sensitive to large regions of DM parameter space, exceeding the discovery potential of existing and planned experiments by two orders of magnitude in the MeV-GeV DM mass range.Comment: 28 pages, 17 figures, submitted to JLab PAC 4

Biological options for crop health (Nutrition, pest and disease) management-sanguine to sustainable agriculture

Interest in biological control of plant insect pests and pathogens has been stimulated in recent years by trends in agriculture towards greater sustainability and public concern about the use of hazardous pesticides. Microorganisms have the capability to synthesize many different biologically active secondary metabolites such as antibiotics, herbicides, pesticides, antiparasitic and enzymes like cellulase, chitinase and xylanase. Microbial collection at ICRISAT, Patancheru, India has over 2000 accessions of bacteria and actinomycetes isolated from various sources and/or niches of composts, rhizosphere and rhizoplane soil samples of sorghum and rice. These accessions possess at least one of six agriculturally beneficial traits studied viz. phosphate solublization, siderophore production, cellulose degradation, nitrogen fixation, antagonism to disease causing fungi and fluorescent Pseudomonas. In addition to that ICRISAT has also identified 28 entomopathogenic bacteria and actinomycetes capable of managing the mos

First Observation of CP Violation in B0->D(*)CP h0 Decays by a Combined Time-Dependent Analysis of BaBar and Belle Data

We report a measurement of the time-dependent CP asymmetry of B0->D(*)CP h0 decays, where the light neutral hadron h0 is a pi0, eta or omega meson, and the neutral D meson is reconstructed in the CP eigenstates K+ K-, K0S pi0 or K0S omega. The measurement is performed combining the final data samples collected at the Y(4S) resonance by the BaBar and Belle experiments at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain ( 471 +/- 3 ) x 10^6 BB pairs recorded by the BaBar detector and ( 772 +/- 11 ) x 10^6, BB pairs recorded by the Belle detector. We measure the CP asymmetry parameters -eta_f S = +0.66 +/- 0.10 (stat.) +/- 0.06 (syst.) and C = -0.02 +/- 0.07 (stat.) +/- 0.03 (syst.). These results correspond to the first observation of CP violation in B0->D(*)CP h0 decays. The hypothesis of no mixing-induced CP violation is excluded in these decays at the level of 5.4 standard deviations.Comment: 9 pages, 2 figures, submitted to Physical Review Letter

Measurement of ISR-FSR interference in the processes e+ e- --> mu+ mu- gamma and e+ e- --> pi+ pi- gamma

Charge asymmetry in processes e+ e- --> mu+ mu- gamma and e+ e- --> pi+ pi- gamma is measured using 232 fb-1 of data collected with the BABAR detector at center-of-mass energies near 10.58 GeV. An observable is introduced and shown to be very robust against detector asymmetries while keeping a large sensitivity to the physical charge asymmetry that results from the interference between initial and final state radiation. The asymmetry is determined as afunction of the invariant mass of the final-state tracks from production threshold to a few GeV/c2. It is compared to the expectation from QED for e+ e- --> mu+ mu- gamma and from theoretical models for e+ e- --> pi+ pi- gamma. A clear interference pattern is observed in e+ e- --> pi+ pi- gamma, particularly in the vicinity of the f_2(1270) resonance. The inferred rate of lowest order FSR production is consistent with the QED expectation for e+ e- --> mu+ mu- gamma, and is negligibly small for e+ e- --> pi+ pi- gamma.Comment: 32 pages,29 figures, to be submitted to Phys. Rev.

Measurement of B(B-->X_s {\gamma}), the B-->X_s {\gamma} photon energy spectrum, and the direct CP asymmetry in B-->X_{s+d} {\gamma} decays

The photon spectrum in B --> X_s {\gamma} decay, where X_s is any strange hadronic state, is studied using a data sample of (382.8\pm 4.2) \times 10^6 e^+ e^- --> \Upsilon(4S) --> BBbar events collected by the BABAR experiment at the PEP-II collider. The spectrum is used to measure the branching fraction B(B --> X_s \gamma) = (3.21 \pm 0.15 \pm 0.29 \pm 0.08)\times 10^{-4} and the first, second, and third moments = 2.267 \pm 0.019 \pm 0.032 \pm 0.003 GeV,, )^2> = 0.0484 \pm 0.0053 \pm 0.0077 \pm 0.0005 GeV^2, and )^3> = -0.0048 \pm 0.0011 \pm 0.0011 \pm 0.0004 GeV^3, for the range E_\gamma > 1.8 GeV, where E_{\gamma} is the photon energy in the B-meson rest frame. Results are also presented for narrower E_{\gamma} ranges. In addition, the direct CP asymmetry A_{CP}(B --> X_{s+d} \gamma) is measured to be 0.057 \pm 0.063. The spectrum itself is also unfolded to the B-meson rest frame; that is the frame in which theoretical predictions for its shape are made.Comment: 37 pages, 19 postscript figures, submitted to Phys. Rev. D. No analysis or results have changed from previous version. Some changes to improve clarity based on interactions with Phys. Rev. D referees, including one new Figure (Fig. 13), and some minor wording/punctuation/spelling mistakes fixe

A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)

We present a measurement of time-dependent CP-violating asymmetries in neutral B meson decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data sample consists of 29.7 ${\rm fb}^{-1}$ recorded at the $\Upsilon(4S)$ resonance and 3.9 ${\rm fb}^{-1}$ off-resonance. One of the neutral B mesons, which are produced in pairs at the $\Upsilon(4S)$, is fully reconstructed in the CP decay modes $J/\psi K^0_S$, $\psi(2S) K^0_S$, $\chi_{c1} K^0_S$, $J/\psi K^{*0}$ ($K^{*0}\to K^0_S\pi^0$) and $J/\psi K^0_L$, or in flavor-eigenstate modes involving $D^{(*)}\pi/\rho/a_1$ and $J/\psi K^{*0}$ ($K^{*0}\to K^+\pi^-$). The flavor of the other neutral B meson is tagged at the time of its decay, mainly with the charge of identified leptons and kaons. The proper time elapsed between the decays is determined by measuring the distance between the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample finds $\Delta m_d = 0.516\pm 0.016 {\rm (stat)} \pm 0.010 {\rm (syst)} {\rm ps}^{-1}$. The value of the asymmetry amplitude $\sin2\beta$ is determined from a simultaneous maximum-likelihood fit to the time-difference distribution of the flavor-eigenstate sample and about 642 tagged $B^0$ decays in the CP-eigenstate modes. We find $\sin2\beta=0.59\pm 0.14 {\rm (stat)} \pm 0.05 {\rm (syst)}$, demonstrating that CP violation exists in the neutral B meson system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review