A digital score of peri‐epithelial lymphocytic activity predicts malignant transformation in oral epithelial dysplasia

Oral squamous cell carcinoma (OSCC) is amongst the most common cancers, with more than 377,000 new cases worldwide each year. OSCC prognosis remains poor, related to cancer presentation at a late stage, indicating the need for early detection to improve patient prognosis. OSCC is often preceded by a premalignant state known as oral epithelial dysplasia (OED), which is diagnosed and graded using subjective histological criteria leading to variability and prognostic unreliability. In this work, we propose a deep learning approach for the development of prognostic models for malignant transformation and their association with clinical outcomes in histology whole slide images (WSIs) of OED tissue sections. We train a weakly supervised method on OED cases (n = 137) with malignant transformation (n = 50) and mean malignant transformation time of 6.51 years (±5.35 SD). Stratified five-fold cross-validation achieved an average area under the receiver-operator characteristic curve (AUROC) of 0.78 for predicting malignant transformation in OED. Hotspot analysis revealed various features of nuclei in the epithelium and peri-epithelial tissue to be significant prognostic factors for malignant transformation, including the count of peri-epithelial lymphocytes (PELs) (p < 0.05), epithelial layer nuclei count (NC) (p < 0.05), and basal layer NC (p < 0.05). Progression-free survival (PFS) using the epithelial layer NC (p < 0.05, C-index = 0.73), basal layer NC (p < 0.05, C-index = 0.70), and PELs count (p < 0.05, C-index = 0.73) all showed association of these features with a high risk of malignant transformation in our univariate analysis. Our work shows the application of deep learning for the prognostication and prediction of PFS of OED for the first time and offers potential to aid patient management. Further evaluation and testing on multi-centre data is required for validation and translation to clinical practice. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Search for Exotic Mesons in pi- P Interactions at 18 GeV/c

The recent search for non $q \bar{q}$ mesons in $\pi^{-}p$ interactions at Brookhaven National Laboratory is summarized. Many final states such as $\eta \pi$, $\eta' \pi^{-}$, $a_{0} \pi$, $f_{1} \pi$, $a_{2} \pi$, $b_{1} \pi$, which are favored decay modes of exotics, are under investigation.Comment: 9 pages, PostScript, Presented at the International School of Nuclear Physics, Erice, Sicily, Italy, September 199

Confirmation of a pi_1^0 Exotic Meson in the \eta \pi^0 System

The exclusive reaction $\pi^- p \to \eta \pi^0 n$, $\eta \to \pi^+ \pi^- \pi^0$ at 18 GeV$/c$ has been studied with a partial wave analysis on a sample of 23~492 $\eta \pi^0 n$ events from BNL experiment E852. A mass-dependent fit is consistent with a resonant hypothesis for the $P_+$ wave, thus providing evidence for a neutral exotic meson with $J^{PC} = 1^{-+}$, a mass of $1257 \pm 20 \pm 25$ MeV$/c^2$, and a width of $354 \pm 64 \pm 60$ MeV$/c^2$. New interpretations of the meson exotics in neutral $\eta \pi^0$ system observed in E852 and Crystal Barrel experiments are discussed.Comment: p3, rewording the paragraph (at the bottom) about the phase variations. p4, rewording paragrath "The second method ..." . p4, at the bottom of paragrath "The third method ..." added consistent with the results of methods 1 and 2

Exotic Meson Production in the f1(1285)π−f_{1}(1285)\pi^{-} System observed in the Reaction π−p→ηπ+π−π−p\pi^{-} p \to \eta\pi^{+}\pi^{-}\pi^{-} p at 18 GeV/c

This letter reports results from the partial wave analysis of the $\pi^{-}\pi^{-}\pi^{+}\eta$ final state in $\pi^{-}p$ collisions at 18GeV/c. Strong evidence is observed for production of two mesons with exotic quantum numbers of spin, parity and charge conjugation, $J^{PC} = 1^{-+}$ in the decay channel $f_{1}(1285)\pi^{-}$. The mass $M = 1709 \pm 24 \pm 41$ MeV/c^2 and width $\Gamma = 403 \pm 80 \pm 115$ MeV/c^2 of the first state are consistent with the parameters of the previously observed $\pi_{1}(1600)$. The second resonance with mass $M = 2001 \pm 30 \pm 92$ MeV/c^2 and width $\Gamma = 333 \pm 52 \pm 49$ MeV/c^2 agrees very well with predictions from theoretical models. In addition, the presence of $\pi_{2}(1900)$ is confirmed with mass $M = 2003 \pm 88 \pm 148$ MeV/c^2 and width $\Gamma = 306 \pm 132 \pm 121$ MeV/c^2 and a new state, $a_{1}(2096)$, is observed with mass $M = 2096 \pm 17 \pm 121$ MeV/c^2 and width $\Gamma = 451 \pm 41 \pm 81$ MeV/c^2. The decay properties of these last two states are consistent with flux tube model predictions for hybrid mesons with non-exotic quantum numbers

Observation of Pseudoscalar and Axial Vector Resonances in pi- p -> K+ K- pi0 n at 18 GeV

A new measurement of the reaction pi- p -> K+ K- pi0 n has been made at a beam energy of 18 GeV. A partial wave analysis of the K+ K- pi0 system shows evidence for three pseudoscalar resonances, eta(1295), eta(1416), and eta(1485), as well as two axial vectors, f1(1285), and f1(1420). Their observed masses, widths and decay properties are reported. No signal was observed for C(1480), an IG J{PC} = 1+ 1{--} state previously reported in phi pi0 decay.Comment: 7 pages, 6 figs, to be submitted to Phys. Let

Observation of a New J(PC)=1(+-) Isoscalar State in the Reaction Pi- Proton -> Omega Eta Neutron at 18 GeV/c

Results are presented on a partial wave analysis of the Omega Eta final state produced in Pi- Proton interactions at 18 GeVc where Omega -> Pi+ Pi- Pi0, Pi0 -> 2 Gammas, and Eta -> 2 Gammas. We observe the previously unreported decay mode Omega(1650) -> Omega Eta and a new 1(+-) meson state h1(1595) with a mass M=1594(15)(+10)(-60) MeV/c^2 and a width Gamma=384(60)(+70)(-100) MeV/c^2. The h1(1595) state exhibits resonant-like phase motion relative to the Omega(1650).Comment: Submitted to Physics Letters B Eight total pages including 11 figures and 1 tabl

Evidence for a narrow dip structure at 1.9 GeV/c2^2 in 3π+3π−3\pi^+ 3\pi^- diffractive photoproduction

A narrow dip structure has been observed at 1.9 GeV/c$^2$ in a study of diffractive photoproduction of the $~3\pi^+3\pi^-$ final state performed by the Fermilab experiment E687.Comment: The data of Figure 6 can be obtained by downloading the raw data file e687_6pi.txt. v5 (2nov2018): added Fig. 7, the 6 pion energy distribution as requested by a reade

Development and validation of a multivariable model for prediction of malignant transformation and recurrence of oral epithelial dysplasia

Background Oral epithelial dysplasia (OED) is the precursor to oral squamous cell carcinoma which is amongst the top ten cancers worldwide. Prognostic significance of conventional histological features in OED is not well established. Many additional histological abnormalities are seen in OED, but are insufficiently investigated, and have not been correlated to clinical outcomes. Methods A digital quantitative analysis of epithelial cellularity, nuclear geometry, cytoplasm staining intensity and epithelial architecture/thickness is conducted on 75 OED whole-slide images (252 regions of interest) with feature-specific comparisons between grades and against non-dysplastic/control cases. Multivariable models were developed to evaluate prediction of OED recurrence and malignant transformation. The best performing models were externally validated on unseen cases pooled from four different centres (n = 121), of which 32% progressed to cancer, with an average transformation time of 45 months. Results Grade-based differences were seen for cytoplasmic eosin, nuclear eccentricity, and circularity in basal epithelial cells of OED (p < 0.05). Nucleus circularity was associated with OED recurrence (p = 0.018) and epithelial perimeter associated with malignant transformation (p = 0.03). The developed model demonstrated superior predictive potential for malignant transformation (AUROC 0.77) and OED recurrence (AUROC 0.74) as compared with conventional WHO grading (AUROC 0.68 and 0.71, respectively). External validation supported the prognostic strength of this model. Conclusions This study supports a novel prognostic model which outperforms existing grading systems. Further studies are warranted to evaluate its significance for OED prognostication

A study of the reaction pim p --> omega pim p at 18 GeV/c: The D and S decay amplitudes for b1(1235) --> omega pi

The reaction pim p --> omega pim p, omega --> pip pim pi0 has been studied at 18 GeV/c. The omega pim mass spectrum is found to be dominated by the b1(1235). Partial Wave Analysis shows that b1 production is dominated by natural parity exchange. The S-wave and D-wave amplitudes for b1(1235) --> omega pi have been determined, and it is found that the amplitude ratio, |D/S| = 0.269 +/- (0.009)stat +/- (0.01)sys and the phase difference, phi(D-S) = 10.54 deg +/- (2.4)stat +/- (3.9)sys.Comment: 7 pages, 9 figures, revtex4 format, to be published in Physics Letters

The origins and spread of domestic horses from the Western Eurasian steppes

Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region.Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).Descriptive and Comparative Linguistic