Relationship between the Plasma Proteome and Changes in Inflammatory Markers after Bariatric Surgery

Severe obesity is a disease associated with multiple adverse effects on health. Metabolic bariatric surgery (MBS) can have significant effects on multiple body systems and was shown to improve inflammatory markers in previous short-term follow-up studies. We evaluated associations between changes in inflammatory markers (CRP, IL6 and TNFα) and circulating proteins after MBS. Methods: Sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics was performed on plasma samples taken at baseline (pre-surgery) and 6 and 12 months after MBS, and concurrent analyses of inflammatory/metabolic parameters were carried out. The change in absolute abundances of those proteins, showing significant change at both 6 and 12 months, was tested for correlation with the absolute and percentage (%) change in inflammatory markers. Results: We found the following results: at 6 months, there was a correlation between %change in IL-6 and fold change in HSPA4 (rho = −0.659; p = 0.038) and in SERPINF1 (rho = 0.714, p = 0.020); at 12 months, there was a positive correlation between %change in IL-6 and fold change in the following proteins—LGALS3BP (rho = 0.700, p = 0.036), HSP90B1 (rho = 0.667; p = 0.05) and ACE (rho = 0.667, p = 0.05). We found significant inverse correlations at 12 months between %change in TNFα and the following proteins: EPHX2 and ACE (for both rho = −0.783, p = 0.013). We also found significant inverse correlations between %change in CRP at 12 months and SHBG (rho = −0.759, p = 0.029), L1CAM (rho = −0.904, p = 0.002) and AMBP (rho = −0.684, p = 0.042). Conclusion: Using SWATH-MS, we identified several proteins that are involved in the inflammatory response whose levels change in patients who achieve remission of T2DM after bariatric surgery in tandem with changes in IL6, TNFα and/or CRP. Future studies are needed to clarify the underlying mechanisms in how MBS decreases low-grade inflammation

Quantitative SWATH-based proteomic profiling of urine for the identification of endometrial cancer biomarkers in symptomatic women

BackgroundA non-invasive endometrial cancer detection tool that can accurately triage symptomatic women for definitive testing would improve patient care. Urine is an attractive biofluid for cancer detection due to its simplicity and ease of collection. The aim of this study was to identify urine-based proteomic signatures that can discriminate endometrial cancer patients from symptomatic controls.MethodsThis was a prospective case–control study of symptomatic post-menopausal women (50 cancers, 54 controls). Voided self-collected urine samples were processed for mass spectrometry and run using sequential window acquisition of all theoretical mass spectra (SWATH-MS). Machine learning techniques were used to identify important discriminatory proteins, which were subsequently combined in multi-marker panels using logistic regression.ResultsThe top discriminatory proteins individually showed moderate accuracy (AUC > 0.70) for endometrial cancer detection. However, algorithms combining the most discriminatory proteins performed well with AUCs > 0.90. The best performing diagnostic model was a 10-marker panel combining SPRR1B, CRNN, CALML3, TXN, FABP5, C1RL, MMP9, ECM1, S100A7 and CFI and predicted endometrial cancer with an AUC of 0.92 (0.96–0.97). Urine-based protein signatures showed good accuracy for the detection of early-stage cancers (AUC 0.92 (0.86–0.9)).ConclusionA patient-friendly, urine-based test could offer a non-invasive endometrial cancer detection tool in symptomatic women. Validation in a larger independent cohort is warranted

All-sky Search for Transient Astrophysical Neutrino Emission with 10 Years of IceCube Cascade Events

Neutrino flares in the sky are searched for in data collected by IceCube between 2011 and 2021 May. This data set contains cascade-like events originating from charged-current electron neutrino and tau neutrino interactions and all-flavor neutral-current interactions. IceCube’s previous all-sky searches for neutrino flares used data sets consisting of track-like events originating from charged-current muon neutrino interactions. The cascade data set is statistically independent of the track data sets, and while inferior in angular resolution, the low-background nature makes it competitive and complementary to previous searches. No statistically significant flare of neutrino emission was observed in an all-sky scan. Upper limits are calculated on neutrino flares of varying duration from 1 hr to 100 days. Furthermore, constraints on the contribution of these flares to the diffuse astrophysical neutrino flux are presented, showing that multiple unresolved transient sources may contribute to the diffuse astrophysical neutrino flux

Citizen science for IceCube: Name that Neutrino

Name that Neutrino is a citizen science project where volunteers aid in classification of events for the IceCube Neutrino Observatory, an immense particle detector at the geographic South Pole. From March 2023 to September 2023, volunteers did classifications of videos produced from simulated data of both neutrino signal and background interactions. Name that Neutrino obtained more than 128,000 classifications by over 1800 registered volunteers that were compared to results obtained by a deep neural network machine-learning algorithm. Possible improvements for both Name that Neutrino and the deep neural network are discussed

A Search for Coincident Neutrino Emission from Fast Radio Bursts with Seven Years of IceCube Cascade Events

This paper presents the results of a search for neutrinos that are spatially and temporally coincident with 22 unique, nonrepeating fast radio bursts (FRBs) and one repeating FRB (FRB 121102). FRBs are a rapidly growing class of Galactic and extragalactic astrophysical objects that are considered a potential source of high-energy neutrinos. The IceCube Neutrino Observatory\u27s previous FRB analyses have solely used track events. This search utilizes seven years of IceCube cascade events which are statistically independent of track events. This event selection allows probing of a longer range of extended timescales due to the low background rate. No statistically significant clustering of neutrinos was observed. Upper limits are set on the time-integrated neutrino flux emitted by FRBs for a range of extended time windows

Constraining High-energy Neutrino Emission from Supernovae with IceCube

Core-collapse supernovae are a promising potential high-energy neutrino source class. We test for correlation between seven years of IceCube neutrino data and a catalog containing more than 1000 core-collapse supernovae of types IIn and IIP and a sample of stripped-envelope supernovae. We search both for neutrino emission from individual supernovae as well as for combined emission from the whole supernova sample, through a stacking analysis. No significant spatial or temporal correlation of neutrinos with the cataloged supernovae was found. All scenarios were tested against the background expectation and together yield an overall p-value of 93%; therefore, they show consistency with the background only. The derived upper limits on the total energy emitted in neutrinos are 1.7 × 1048 erg for stripped-envelope supernovae, 2.8 × 1048 erg for type IIP, and 1.3 × 1049 erg for type IIn SNe, the latter disfavoring models with optimistic assumptions for neutrino production in interacting supernovae. We conclude that stripped-envelope supernovae and supernovae of type IIn do not contribute more than 14.6% and 33.9%, respectively, to the diffuse neutrino flux in the energy range of about [ 103-105] GeV, assuming that the neutrino energy spectrum follows a power-law with an index of −2.5. Under the same assumption, we can only constrain the contribution of type IIP SNe to no more than 59.9%. Thus, core-collapse supernovae of types IIn and stripped-envelope supernovae can both be ruled out as the dominant source of the diffuse neutrino flux under the given assumptions

IceCat-1: The IceCube Event Catalog of Alert Tracks

We present a catalog of likely astrophysical neutrino track-like events from the IceCube Neutrino Observatory. IceCube began reporting likely astrophysical neutrinos in 2016, and this system was updated in 2019. The catalog presented here includes events that were reported in real time since 2019, as well as events identified in archival data samples starting from 2011. We report 275 neutrino events from two selection channels as the first entries in the catalog, the IceCube Event Catalog of Alert Tracks, which will see ongoing extensions with additional alerts. The Gold and Bronze alert channels respectively provide neutrino candidates with a 50% and 30% probability of being astrophysical, on average assuming an astrophysical neutrino power-law energy spectral index of 2.19. For each neutrino alert, we provide the reconstructed energy, direction, false-alarm rate, probability of being astrophysical in origin, and likelihood contours describing the spatial uncertainty in the alert's reconstructed location. We also investigate a directional correlation of these neutrino events with gamma-ray and X-ray catalogs, including 4FGL, 3HWC, TeVCat, and Swift-BAT

Searches for Neutrinos from Large High Altitude Air Shower Observatory Ultra-high-energy γ-Ray Sources Using the IceCube Neutrino Observatory

Galactic PeV cosmic-ray accelerators (PeVatrons) are Galactic sources theorized to accelerate cosmic rays up to PeV in energy. The accelerated cosmic rays are expected to interact hadronically with nearby ambient gas or the interstellar medium, resulting in γ-rays and neutrinos. Recently, the Large High Altitude Air Shower Observatory (LHAASO) identified 12 γ-ray sources with emissions above 100 TeV, making them candidates for PeVatrons. While at these high energies the Klein-Nishina effect exponentially suppresses leptonic emission from Galactic sources, evidence for neutrino emission would unequivocally confirm hadronic acceleration. Here, we present the results of a search for neutrinos from these γ-ray sources and stacking searches testing for excess neutrino emission from all 12 sources as well as their subcatalogs of supernova remnants and pulsar wind nebulae with 11 yr of track events from the IceCube Neutrino Observatory. No significant emissions were found. Based on the resulting limits, we place constraints on the fraction of γ-ray flux originating from the hadronic processes in the Crab Nebula and LHAASO J2226+6057

Limits on Neutrino Emission from GRB 221009A from MeV to PeV Using the IceCube Neutrino Observatory

Gamma-ray bursts (GRBs) have long been considered a possible source of high-energy neutrinos. While no correlations have yet been detected between high-energy neutrinos and GRBs, the recent observation of GRB 221009A—the brightest GRB observed by Fermi-GBM to date and the first one to be observed above an energy of 10 TeV—provides a unique opportunity to test for hadronic emission. In this paper, we leverage the wide energy range of the IceCube Neutrino Observatory to search for neutrinos from GRB 221009A. We find no significant deviation from background expectation across event samples ranging from MeV to PeV energies, placing stringent upper limits on the neutrino emission from this source

Constraints on Populations of Neutrino Sources from Searches in the Directions of IceCube Neutrino Alerts

Beginning in 2016, the IceCube Neutrino Observatory has sent out alerts in real time containing the information of high-energy (E ≳ 100 TeV) neutrino candidate events with moderate to high (≳30%) probability of astrophysical origin. In this work, we use a recent catalog of such alert events, which, in addition to events announced in real time, includes events that were identified retroactively and covers the time period of 2011-2020. We also search for additional, lower-energy neutrinos from the arrival directions of these IceCube alerts. We show how performing such an analysis can constrain the contribution of rare populations of cosmic neutrino sources to the diffuse astrophysical neutrino flux. After searching for neutrino emission coincident with these alert events on various timescales, we find no significant evidence of either minute-scale or day-scale transient neutrino emission or of steady neutrino emission in the direction of these alert events. This study also shows how numerous a population of neutrino sources has to be to account for the complete astrophysical neutrino flux. Assuming that sources have the same luminosity, an E −2.5 neutrino spectrum, and number densities that follow star formation rates, the population of sources has to be more numerous than 7 × 10−9 Mpc−3. This number changes to 3 × 10−7 Mpc−3 if number densities instead have no cosmic evolution