Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: a report of the international immuno‐oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer (BC) has been well established, and tumor-infiltrating lymphocytes (TILs) have emerged as a predictive and prognostic biomarker for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer (TNBC) and HER2-positive breast cancer. How computational assessment of TILs can complement manual TIL-assessment in trial- and daily practices is currently debated and still unclear. Recent efforts to use machine learning (ML) for the automated evaluation of TILs show promising results. We review state-of-the-art approaches and identify pitfalls and challenges by studying the root cause of ML discordances in comparison to manual TILs quantification. We categorize our findings into four main topics; (i) technical slide issues, (ii) ML and image analysis aspects, (iii) data challenges, and (iv) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns, or design choices in the computational implementation. To aid the adoption of ML in TILs assessment, we provide an in-depth discussion of ML and image analysis including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial- and routine clinical management of patients with TNBC

Observation of Cabibbo-suppressed two-body hadronic decays and precision mass measurement of the Ωc0\Omega_{c}^{0} baryon

The first observation of the singly Cabibbo-suppressed $\Omega_{c}^{0}\to\Omega^{-}K^{+}$ and $\Omega_{c}^{0}\to\Xi^{-}\pi^{+}$ decays is reported, using proton-proton collision data at a centre-of-mass energy of $13\,{\rm TeV}$, corresponding to an integrated luminosity of $5.4\,{\rm fb}^{-1}$, collected with the LHCb detector between 2016 and 2018. The branching fraction ratios are measured to be $\frac{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}K^{+})}{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}\pi^{+})}=0.0608\pm0.0051({\rm stat})\pm 0.0040({\rm syst})$, $\frac{\mathcal{B}(\Omega_{c}^{0}\to\Xi^{-}\pi^{+})}{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}\pi^{+})}=0.1581\pm0.0087({\rm stat})\pm0.0043({\rm syst})\pm0.0016({\rm ext})$. In addition, using the $\Omega_{c}^{0}\to\Omega^{-}\pi^{+}$ decay channel, the $\Omega_{c}^{0}$ baryon mass is measured to be $M(\Omega_{c}^{0})=2695.28\pm0.07({\rm stat})\pm0.27({\rm syst})\pm0.30({\rm ext})\,{\rm MeV}/c^{2}$, improving the precision of the previous world average by a factor of four.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-011.html (LHCb public pages

Measurement of ZZ boson production cross-section in pppp collisions at s=5.02\sqrt{s} = 5.02 TeV

The first measurement of the $Z$ boson production cross-section at centre-of-mass energy $\sqrt{s} = 5.02\,$TeV in the forward region is reported, using $pp$ collision data collected by the LHCb experiment in year 2017, corresponding to an integrated luminosity of $100 \pm 2\,\rm{pb^{-1}}$. The production cross-section is measured for final-state muons in the pseudorapidity range $2.0 20\,\rm{GeV/}\it{c}$. The integrated cross-section is determined to be $$\sigma_{Z \rightarrow \mu^{+}\mu^{-}} = 39.6 \pm 0.7\,(\rm{stat}) \pm 0.6\,(\rm{syst}) \pm 0.8\,(\rm{lumi}) \ \rm{pb}$$ for the di-muon invariant mass in the range $60<M_{\mu\mu}<120\,\rm{GeV/}\it{c^{2}}$. This result and the differential cross-section results are in good agreement with theoretical predictions at next-to-next-to-leading order in the strong coupling. Based on a previous LHCb measurement of the $Z$ boson production cross-section in $p$Pb collisions at $\sqrt{s_{NN}}=5.02$ TeV, the nuclear modification factor $R_{p\rm{Pb}}$ is measured for the first time at this energy. The measured values are $1.2^{+0.5}_{-0.3}\,(\rm{stat}) \pm 0.1\,(\rm{syst})$ in the forward region ($1.53<y^*_{\mu}<4.03$) and $3.6^{+1.6}_{-0.9}\,(\rm{stat}) \pm 0.2\,(\rm{syst})$ in the backward region ($-4.97<y^*_{\mu}<-2.47$), where $y^*_{\mu}$ represents the muon rapidity in the centre-of-mass frame.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-010.html (LHCb public pages

Measurement of the CKM angle γ\gamma in the B0→DK∗0B^0 \to DK^{*0} channel using self-conjugate D→KS0h+h−D \to K_S^0 h^+ h^- decays

A model-independent study of CP violation in $B^0 \to DK^{*0}$ decays is presented using data corresponding to an integrated luminosity of 9fb$^{-1}$ collected by the LHCb experiment at centre-of-mass energies of $\sqrt{s}=7, \, 8$ and $13$TeV. The CKM angle $\gamma$ is determined by examining the distributions of signal decays in phase-space bins of the self-conjugate $D \to K_S^0 h^+ h^-$ decays, where $h = \pi, K$. Observables related to CP violation are measured and the angle $\gamma$ is determined to be $\gamma=(49^{+ 23}_{-18})^\circ$. Measurements of the amplitude ratio and strong-phase difference between the favoured and suppressed $B^0$ decays are also presented.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-009.html (LHCb public pages

Observation of strangeness enhancement with charmed mesons in high-multiplicity pPbp\mathrm{Pb} collisions at sNN=8.16 \sqrt {s_{\mathrm{NN}}}=8.16\,TeV

The production of prompt $D^+_{s}$ and $D^+$ mesons is measured by the LHCb experiment in proton-lead ($p\mathrm{Pb}$) collisions in both the forward ($1.5<y^*<4.0$) and backward ($-5.0<y^*<-2.5$) rapidity regions at a nucleon-nucleon center-of-mass energy of $\sqrt {s_{\mathrm{NN}}}=8.16\,$TeV. The nuclear modification factors of both $D^+_{s}$ and $D^+$ mesons are determined as a function of transverse momentum, $p_{\mathrm{T}}$, and rapidity. In addition, the $D^+_{s}$ to $D^+$ cross-section ratio is measured as a function of the charged particle multiplicity in the event. An enhanced $D^+_{s}$ to $D^+$ production in high-multiplicity events is observed for the whole measured $p_{\mathrm{T}}$ range, in particular at low $p_{\mathrm{T}}$ and backward rapidity, where the significance exceeds six standard deviations. This constitutes the first observation of strangeness enhancement in charm quark hadronization in high-multiplicity $p\mathrm{Pb}$ collisions. The results are also qualitatively consistent with the presence of quark coalescence as an additional charm quark hadronization mechanism in high-multiplicity proton-lead collisions.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-021.html (LHCb public pages

Search for CP\textit{CP} violation in the phase space of D0→KS0K±π∓D^{0} \rightarrow K_{S}^{0} K^{\pm} \pi^{\mp} decays with the energy test

A search for $\textit{CP}$ violation in $D^{0} \rightarrow K_{S}^{0} K^{+} \pi^{-}$ and $D^{0} \rightarrow K_{S}^{0} K^{-} \pi^{+}$ decays is reported. The search is performed using an unbinned model-independent method known as the energy test that probes local $\textit{CP}$ violation in the phase space of the decays. The data analysed correspond to an integrated luminosity of $5.4~$fb$^{-1}$ collected in proton-proton collisions by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=13$~TeV, amounting to approximately 950000 and 620000 signal candidates for the $D^{0} \rightarrow K_{S}^{0} K^{-} \pi^{+}$ and $D^{0} \rightarrow K_{S}^{0} K^{+} \pi^{-}$ modes, respectively. The method is validated using $D^{0} \rightarrow K^{-} \pi^{+} \pi^{-} \pi^{+}$ and $D^{0} \rightarrow K_{S}^{0} \pi^{+} \pi^{-}$ decays, where $\textit{CP}$-violating effects are expected to be negligible, and using background-enhanced regions of the signal decays. The results are consistent with $\textit{CP}$ symmetry in both the $D^{0} \rightarrow K_{S}^{0} K^{-} \pi^{+}$ and the $D^{0} \rightarrow K_{S}^{0} K^{+} \pi^{-}$ decays, with $p$-values for the hypothesis of no $\textit{CP}$ violation of 70% and 66%, respectively.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-019.html (LHCb public pages

Observation of the decays B(s)0→Ds1(2536)∓K±B_{(s)}^{0}\to D_{s1}(2536)^{\mp}K^{\pm}

This paper reports the observation of the decays $B_{(s)}^{0}\to D_{s1}(2536)^{\mp}K^{\pm}$ using proton-proton collision data collected by the LHCb experiment, corresponding to an integrated luminosity of $9\,\mathrm{fb}^{-1}$. The branching fractions of these decays are measured relative to the normalisation channel $B^{0}\to \overline{D}^{0}K^{+}K^{-}$. The $D_{s1}(2536)^{-}$ meson is reconstructed in the $\overline{D}^{*}(2007)^{0}K^{-}$ decay channel and the products of branching fractions are measured to be $$\mathcal{B}(B_{s}^{0}\to D_{s1}(2536)^{\mp}K^{\pm})\times\mathcal{B}(D_{s1}(2536)^{-}\to\overline{D}^{*}(2007)^{0}K^{-})=(2.49\pm0.11\pm0.12\pm0.25\pm0.06)\times 10^{-5},$$ $$\mathcal{B}(B^{0}\to D_{s1}(2536)^{\mp}K^{\pm})\times\mathcal{B}(D_{s1}(2536)^{-}\to\overline{D}^{*}(2007)^{0}K^{-}) = (0.510\pm0.021\pm0.036\pm0.050)\times 10^{-5}.$$ The first uncertainty is statistical, the second systematic, and the third arises from the uncertainty of the branching fraction of the $B^{0}\to \overline{D}^{0}K^{+}K^{-}$ normalisation channel. The last uncertainty in the $B_{s}^{0}$ result is due to the limited knowledge of the fragmentation fraction ratio, $f_{s}/f_{d}$. The significance for the $B_{s}^{0}$ and $B^{0}$ signals is larger than $10\,\sigma$. The ratio of the helicity amplitudes which governs the angular distribution of the $D_{s1}(2536)^{-}\to\overline{D}^{*}(2007)^{0}K^{-}$ decay is determined from the data. The ratio of the $S$- and $D$-wave amplitudes is found to be $1.11\pm0.15\pm 0.06$ and its phase $0.70\pm0.09\pm 0.04$ rad, where the first uncertainty is statistical and the second systematic.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-014.html (LHCb public pages

Studies of η\eta and η′\eta' production in pppp and ppPb collisions

The production of $\eta$ and $\eta'$ mesons is studied in proton-proton and proton-lead collisions collected with the LHCb detector. Proton-proton collisions are studied at center-of-mass energies of $5.02$ and $13~{\rm TeV}$, and proton-lead collisions are studied at a center-of-mass energy per nucleon of $8.16~{\rm TeV}$. The studies are performed in center-of-mass rapidity regions $2.5<y_{\rm c.m.}<3.5$ (forward rapidity) and $-4.0<y_{\rm c.m.}<-3.0$ (backward rapidity) defined relative to the proton beam direction. The $\eta$ and $\eta'$ production cross sections are measured differentially as a function of transverse momentum for $1.5<p_{\rm T}<10~{\rm GeV}$ and $3<p_{\rm T}<10~{\rm GeV}$, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for $\eta$ and $\eta'$ mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of $\eta$ mesons are also used to calculate $\eta/\pi^0$ cross section ratios, which show evidence of a deviation from the world average. These studies offer new constraints on mass-dependent nuclear effects in heavy-ion collisions, as well as $\eta$ and $\eta'$ meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb public pages

Amplitude analysis of the Λb0→pK−γ decay

The resonant structure of the radiative decay Λb0→pK−γ in the region of proton-kaon invariant-mass up to 2.5 GeV/c2 is studied using proton-proton collision data recorded at centre-of-mass energies of 7, 8, and 13 TeV collected with the LHCb detector, corresponding to a total integrated luminosity of 9 fb−1. Results are given in terms of fit and interference fractions between the different components contributing to this final state. Only Λ resonances decaying to pK− are found to be relevant, where the largest contributions stem from the Λ(1520), Λ(1600), Λ(1800), and Λ(1890) states