Predicting and controlling the reactivity of immune cell populations against cancer

Heterogeneous cell populations form an interconnected network that determine their collective output. One example of such a heterogeneous immune population is tumor-infiltrating lymphocytes (TILs), whose output can be measured in terms of its reactivity against tumors. While the degree of reactivity varies considerably between different TILs, ranging from null to a potent response, the underlying network that governs the reactivity is poorly understood. Here, we asked whether one can predict and even control this reactivity. To address this we measured the subpopulation compositions of 91 TILs surgically removed from 27 metastatic melanoma patients. Despite the large number of subpopulations compositions, we were able to computationally extract a simple set of subpopulation-based rules that accurately predict the degree of reactivity. This raised the conjecture of whether one could control reactivity of TILs by manipulating their subpopulation composition. Remarkably, by rationally enriching and depleting selected subsets of subpopulations, we were able to restore anti-tumor reactivity to nonreactive TILs. Altogether, this work describes a general framework for predicting and controlling the output of a cell mixture

The GJ1214 Super-Earth System: Stellar Variability, New Transits, and a Search for Additional Planets

The super-Earth GJ1214b transits a nearby M dwarf that exhibits 1% intrinsic variability in the near-infrared. Here, we analyze new observations to refine the physical properties of both the star and planet. We present three years of out-of-transit photometric monitoring of the stellar host GJ1214 from the MEarth Observatory and find the rotation period to be long, mostly likely an integer multiple of 53 days, suggesting low levels of magnetic activity and an old age for the system. We show such variability will not pose significant problems to ongoing studies of the planet's atmosphere with transmission spectroscopy. We analyze 2 high-precision transit light curves from ESO's Very Large Telescope along with 7 others from the MEarth and FLWO 1.2 meter telescopes, finding physical parameters for the planet that are consistent with previous work. The VLT light curves show tentative evidence for spot occultations during transit. Using two years of MEarth light curves, we place limits on additional transiting planets around GJ1214 with periods out to the habitable zone of the system. We also improve upon the previous photographic V -band estimate for the star, finding V = 14.71 \pm 0.03.Comment: 16 pages, 10 figures, 6 tables, in emulateapj format. Published in ApJ. Replaced a missing reference in section 6.

Single-Spin Addressing in an Atomic Mott Insulator

Ultracold atoms in optical lattices are a versatile tool to investigate fundamental properties of quantum many body systems. In particular, the high degree of control of experimental parameters has allowed the study of many interesting phenomena such as quantum phase transitions and quantum spin dynamics. Here we demonstrate how such control can be extended down to the most fundamental level of a single spin at a specific site of an optical lattice. Using a tightly focussed laser beam together with a microwave field, we were able to flip the spin of individual atoms in a Mott insulator with sub-diffraction-limited resolution, well below the lattice spacing. The Mott insulator provided us with a large two-dimensional array of perfectly arranged atoms, in which we created arbitrary spin patterns by sequentially addressing selected lattice sites after freezing out the atom distribution. We directly monitored the tunnelling quantum dynamics of single atoms in the lattice prepared along a single line and observed that our addressing scheme leaves the atoms in the motional ground state. Our results open the path to a wide range of novel applications from quantum dynamics of spin impurities, entropy transport, implementation of novel cooling schemes, and engineering of quantum many-body phases to quantum information processing.Comment: 8 pages, 5 figure

Burden of Disease Caused by Otitis Media: Systematic Review and Global Estimates

<div><h3>Background</h3><p>Otitis media (OM) is a leading cause of health care visits and drugs prescription. Its complications and sequelae are important causes of preventable hearing loss, particularly in developing countries. Within the Global Burden of Diseases, Injuries, and Risk Factors Study, for the year 2005 we estimated the incidence of acute OM, chronic suppurative OM, and related hearing loss and mortality for all ages and the 21 WHO regional areas.</p> <h3>Methods</h3><p>We identified risk factors, complications and sequelae of OM. We carried out an extensive literature review (Medline, Embase, Lilacs and Wholis) which lead to the selection of 114 papers comprising relevant data. Data were available from 15 of the 21 WHO regions. To estimate incidence and prevalence for all countries we adopted a two stage approach based on risk factors formulas and regression modelling.</p> <h3>Results</h3><p>Acute OM incidence rate is 10.85% i.e. 709million cases each year with 51% of these occurring in under-fives. Chronic suppurative OM incidence rate is 4.76‰ i.e. 31million cases, with 22.6% of cases occurring annually in under-fives. OM-related hearing impairment has a prevalence of 30.82 per ten-thousand. Each year 21thousand people die due to complications of OM.</p> <h3>Conclusions</h3><p>Our study is the first attempt to systematically review the available information and provide global estimates for OM and related conditions. The overall burden deriving from AOM, CSOM and their sequelae is considerable, particularly in the first five years of life and in the poorest countries. The findings call for incorporating OM-focused action within preventive and case management strategies, with emphasis on the more affected.</p> </div

Flight of the Bumblebee: the Early Excess Flux of Type Ia Supernova 2023bee revealed by TESSTESS, SwiftSwift and Young Supernova Experiment Observations

We present high-cadence ultraviolet through near-infrared observations of the Type Ia supernova (SN Ia) 2023bee in NGC~2708 ($D = 32 \pm 3$ Mpc), finding excess flux in the first days after explosion relative to the expected power-law rise from an expanding fireball. This deviation from typical behavior for SNe Ia is particularly obvious in our 10-minute cadence $TESS$ light curve and $Swift$ UV data. Compared to a few other normal SNe Ia with detected early excess flux, the excess flux in SN 2023bee is redder in the UV and less luminous. We present optical spectra of SN 2023bee, including two spectra during the period where the flux excess is dominant. At this time, the spectra are similar to those of other SNe Ia but with weaker Si II, C II and Ca II absorption lines, perhaps because the excess flux creates a stronger continuum. We compare the data to several theoretical models that have been proposed to explain the early flux excess in SNe Ia. Interaction with either a nearby companion star or close-in circumstellar material is expected to produce a faster evolution than seen in the data. Radioactive material in the outer layers of the ejecta, either from a double detonation explosion or simply an explosion with a $^{56}$Ni clump near the surface, can not fully reproduce the evolution either, likely due to the sensitivity of early UV observable to the treatment of the outer part of ejecta in simulation. We conclude that no current model can adequately explain the full set of observations. We find that a relatively large fraction of nearby, bright SNe Ia with high-cadence observations have some amount of excess flux within a few days of explosion. Considering potential asymmetric emission, the physical cause of this excess flux may be ubiquitous in normal SNe Ia.Comment: 21 pages, 12 figures. Accepted by the astrophysical journa

Federated learning enables big data for rare cancer boundary detection.

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Author Correction: Federated learning enables big data for rare cancer boundary detection.

10.1038/s41467-023-36188-7NATURE COMMUNICATIONS14