Urinary exosomal shuttle RNA: Promising cancer diagnosis biomarkers of lower urinary tract.

Background: Prostate and bladder cancers continue to be the first and fourth most common cancers in men worldwide; thus there is an urgent need for more accurate biomarkers that can detect these types of cancer in a non-invasive way. Liquid biopsy is a new non-invasive tool for diagnosis and with a virtually unlimited supply urine is even more attractive resource since urinary exosomes have been discovered to contain RNAs that are hallmarks of cancer. It is challenging to assay those secreting lower amounts of molecules. Methods: This review, based on articles identified through a PubMed/MEDLINE search, comprehensively summarizes state of the art approaches used in the discovery and validation of exosomal RNA biomarkers purified from the urine for lower urinary tract cancer. Results: The combination of PCA3 and ERG has shown a relatively good improvement in diagnostic performance; examples of other potential biomarkers and the methods utilized in their discovery are also discussed in this review. Conclusions: Of these last markers, to date there are still few data to implement these for routine diagnosis

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Search for Ultra-high-energy Photons from Gravitational Wave Sources with the Pierre Auger Observatory

A search for time-directional coincidences of ultra-high-energy (UHE) photons above 10 EeV with gravitational wave (GW) events from the LIGO/Virgo runs O1 to O3 is conducted with the Pierre Auger Observatory. Due to the distinctive properties of photon interactions and to the background expected from hadronic showers, a subset of the most interesting GW events is selected based on their localization quality and distance. Time periods of 1000 s around and 1 day after the GW events are analyzed. No coincidences are observed. Upper limits on the UHE photon fluence from a GW event are derived that are typically at & SIM;7 MeV cm(-2) (time period 1000 s) and & SIM;35 MeV cm(-2) (time period 1 day). Due to the proximity of the binary neutron star merger GW170817, the energy of the source transferred into UHE photons above 40 EeV is constrained to be less than 20% of its total GW energy. These are the first limits on UHE photons from GW sources

Arrival Directions of Cosmic Rays above 32 EeV from Phase One of the Pierre Auger Observatory

A promising energy range to look for angular correlations between cosmic rays of extragalactic origin and their sources is at the highest energies, above a few tens of EeV (1 EeV equivalent to 10^(18) eV). Despite the flux of these particles being extremely low, the area of similar to 3000 km^(2) covered at the Pierre Auger Observatory, and the 17 yr data-taking period of the Phase 1 of its operations, have enabled us to measure the arrival directions of more than 2600 ultra-high-energy cosmic rays above 32 EeV. We publish this data set, the largest available at such energies from an integrated exposure of 122,000 km^(2) sr yr, and search it for anisotropies over the 3.4 pi steradians covered with the Observatory. Evidence for a deviation in excess of isotropy at intermediate angular scales, with similar to 15 degrees Gaussian spread or similar to 25 degrees top-hat radius, is obtained at the 4 sigma significance level for cosmic-ray energies above similar to 40 EeV

The energy spectrum of cosmic rays beyond the turn-down around 10^17 eV as measured with the surface detector of the Pierre Auger Observatory

We present a measurement of the cosmic-ray spectrum above 100 PeV using the part of the surface detector of the Pierre Auger Observatory that has a spacing of 750 m. An inflection of the spectrum is observed, confirming the presence of the so-called second-knee feature. The spectrum is then combined with that of the 1500 m array to produce a single measurement of the flux, linking this spectral feature with the three additional breaks at the highest energies. The combined spectrum, with an energy scale set calorimetrically via fluorescence telescopes and using a single detector type, results in the most statistically and systematically precise measurement of spectral breaks yet obtained. These measurements are critical for furthering our understanding of the highest energy cosmic rays

Searches for Ultra-High-Energy Photons at the Pierre Auger Observatory

The Pierre Auger Observatory, being the largest air-shower experiment in the world, offers an unprecedented exposure to neutral particles at the highest energies. Since the start of data taking more than 18 years ago, various searches for ultra-high-energy (UHE, $E\gtrsim10^{17}\,\text{eV}$) photons have been performed: either for a diffuse flux of UHE photons, for point sources of UHE photons or for UHE photons associated with transient events like gravitational wave events. In the present paper, we summarize these searches and review the current results obtained using the wealth of data collected by the Pierre Auger Observatory.Comment: Review article accepted for publication in Universe (special issue on ultra-high energy photons

Status and performance of the underground muon detector of the Pierre Auger Observatory

The Auger Muons and Infill for the Ground Array (AMIGA) is an enhancement of the Pierre Auger Observatory, whose purpose is to lower the energy threshold of the observatory down to 1016.5 eV, and to measure the muonic content of air showers directly. These measurements will significantly contribute to the determination of primary particle masses in the range between the second knee and the ankle, to the study of hadronic interaction models with air showers, and, in turn, to the understanding of the muon puzzle. The underground muon detector of AMIGA is concomitant to two triangular grids of water-Cherenkov stations with spacings of 433 and 750 m; each grid position is equipped with a 30 m2 plastic scintillator buried at 2.3 m depth. After the engineering array completion in early 2018 and general improvements to the design, the production phase commenced. In this work, we report on the status of the underground muon detector, the progress of its deployment, and the performance achieved after two years of operation. The detector construction is foreseen to finish by mid-2022