The ETS factor ESE3/EHF represses IL-6 preventing STAT3 activation and expansion of the prostate cancer stem-like compartment.

Metastatic prostate cancer represents a yet unsolved clinical problem due to the high frequency of relapse and treatment resistance. Understanding the pathways that lead to prostate cancer progression is an important task to prevent this deadly disease. The ETS transcription factor ESE3/EHF has an important role in differentiation of human prostate epithelial cells. Loss of ESE3/EHF in prostate epithelial cells determines transformation, epithelial-to-mesenchymal transition (EMT) and acquisition of stem-like properties. In this study we identify IL-6 as a direct target of ESE3/EHF that is activated in prostate epithelial cells upon loss of ESE3/EHF. ESE3/EHF and IL-6 were significantly inversely correlated in prostate tumors. Chromatin immunoprecipitation confirmed binding of ESE3/EHF to a novel ETS binding site in the IL-6 gene promoter. Inhibition of IL-6 reverted transformation and stem-like phenotype in tumorigenic ESE3/EHF knockdown prostate epithelial cell models. Conversely, IL-6 stimulation induced malignant phenotypes, stem-like behavior and STAT3 activation. Increased level of IL-6 was observed in prostatospheres compared with adherent bulk cancer cells and this was associated with stronger activation of STAT3. Human prostate tumors with IL-6 elevation and loss of ESE3/EHF were associated with STAT3 activation and displayed upregulation of genes related to cell adhesion, cancer stem-like and metastatic spread. Pharmacological inhibition of IL-6/STAT3 activation by a JAK inhibitor restrained cancer stem cell growth in vitro and inhibited self-renewal in vivo. This study identifies a novel connection between the transcription factor ESE3/EHF and the IL-6/JAK/STAT3 pathway and suggests that targeting this axis might be preferentially beneficial in tumors with loss of ESE3/EHF

An integrated approach in a case of facioscapulohumeral dystrophy

BACKGROUND: Muscle fatigue, weakness and atrophy are basilar clinical features that accompany facioscapulohumeral dystrophy (FSHD) the third most common muscular dystrophy.No therapy is available for FSHD. CASE PRESENTATION: We describe the effects of 6mo exercise therapy and nutritional supplementation in a 43-year-old woman severely affected by FSHD. CONCLUSION: A mixed exercise program combined with nutritional supplementation can be safely used with beneficial effects in selected patients with FSHD

Strong Coupling Constant from the Photon Structure Function

We extract the value of the strong coupling constant alpha_s from a single-parameter pointlike fit to the photon structure function F_2^gamma at large x and Q^2 and from a first five-parameter full (pointlike and hadronic) fit to the complete F_2^gamma data set taken at PETRA, TRISTAN, and LEP. In next-to-leading order and the MSbar renormalization and factorization schemes, we obtain alpha_s(m_Z)=0.1183 +/- 0.0050(exp.)^+0.0029_-0.0028(theor.) [pointlike] and alpha_s(m_Z)=0.1198 +/- 0.0028(exp.)^+0.0034_-0.0046(theor.) [pointlike and hadronic]. We demonstrate that the data taken at LEP have reduced the experimental error by about a factor of two, so that a competitive determination of alpha_s from F_2^gamma is now possible.Comment: 11 pages, 2 tables, 2 figures. Version accepted for publication by Phys. Rev. Let

Jet color chemistry and anomalous baryon production in AAAA-collisions

We study anomalous high-$p_T$ baryon production in $AA$-collisions due to formation of the two parton collinear $gq$ system in the anti-sextet color state for quark jets and $gg$ system in the decuplet/anti-decuplet color states for gluon jets. Fragmentation of these states, which are absent for $NN$-collisions, after escaping from the quark-gluon plasma leads to baryon production. Our qualitative estimates show that this mechanism can be potentially important at RHIC and LHC energies.Comment: 20 pages, 4 figures, Eur.Phys.J. versio

Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at sNN\sqrt{s_{NN}} = 5.02 TeV

Two-particle angular correlations between unidentified charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum range 0.7 $< p_{\rm{T}, assoc} < p_{\rm{T}, trig} <$ 5.0 GeV/$c$ is examined, to include correlations induced by jets originating from low momen\-tum-transfer scatterings (minijets). The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range $|\eta|<0.9$. The near-side long-range pseudorapidity correlations observed in high-multiplicity p-Pb collisions are subtracted from both near-side short-range and away-side correlations in order to remove the non-jet-like components. The yields in the jet-like peaks are found to be invariant with event multiplicity with the exception of events with low multiplicity. This invariance is consistent with the particles being produced via the incoherent fragmentation of multiple parton--parton scatterings, while the yield related to the previously observed ridge structures is not jet-related. The number of uncorrelated sources of particle production is found to increase linearly with multiplicity, suggesting no saturation of the number of multi-parton interactions even in the highest multiplicity p-Pb collisions. Further, the number scales in the intermediate multiplicity region with the number of binary nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/161

Multi-particle azimuthal correlations in p-Pb and Pb-Pb collisions at the CERN Large Hadron Collider

Measurements of multi-particle azimuthal correlations (cumulants) for charged particles in p-Pb and Pb-Pb collisions are presented. They help address the question of whether there is evidence for global, flow-like, azimuthal correlations in the p-Pb system. Comparisons are made to measurements from the larger Pb-Pb system, where such evidence is established. In particular, the second harmonic two-particle cumulants are found to decrease with multiplicity, characteristic of a dominance of few-particle correlations in p-Pb collisions. However, when a $|\Delta \eta|$ gap is placed to suppress such correlations, the two-particle cumulants begin to rise at high-multiplicity, indicating the presence of global azimuthal correlations. The Pb-Pb values are higher than the p-Pb values at similar multiplicities. In both systems, the second harmonic four-particle cumulants exhibit a transition from positive to negative values when the multiplicity increases. The negative values allow for a measurement of $v_{2}\{4\}$ to be made, which is found to be higher in Pb-Pb collisions at similar multiplicities. The second harmonic six-particle cumulants are also found to be higher in Pb-Pb collisions. In Pb-Pb collisions, we generally find $v_{2}\{4\} \simeq v_{2}\{6\}\neq 0$ which is indicative of a Bessel-Gaussian function for the $v_{2}$ distribution. For very high-multiplicity Pb-Pb collisions, we observe that the four- and six-particle cumulants become consistent with 0. Finally, third harmonic two-particle cumulants in p-Pb and Pb-Pb are measured. These are found to be similar for overlapping multiplicities, when a $|\Delta\eta| > 1.4$ gap is placed.Comment: 25 pages, 11 captioned figures, 3 tables, authors from page 20, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/87

Unraveling the impact of upfront chemotherapy and proton beam therapy on treatment outcome and follow-up in central nervous system germ cell tumors: a single center experience

BackgroundGerm cell tumors (GCT) account for a minority of central nervous system (CNS) malignancies, highly prevalent in adolescents and young adults. Despite their aggressive biological behavior, prognosis is excellent in most cases with risk stratified treatment, consisting in a combination of chemotherapy and radiotherapy. Whole ventricular irradiation (WVI) and craniospinal irradiation, the treatment of choice for localized and metastatic disease, pose significant risk of collateral effects, therefore proton beam radiation (PBT) has been recently proposed for its steep dose fallout.Materials and methodsWe report our experience in a consecutive series of 17 patients treated for CNS GCT at our Institution from 2015 to 2021.ResultsMost frequent lesion location were sellar/suprasellar (35%) and bifocal germinoma (35%), followed by pineal (18%) and thalamic (12%). Two patients (12%), had evidence of disseminated disease at the time of diagnosis. At the latest follow-up all but one patient showed complete response to treatment. The only relapse was successfully rescued by additional chemotherapy and PBT. PBT was well tolerated in all cases. No visual, neurological or endocrinological worsening was documented during and after treatment. Neuropsychological evaluation demonstrated preservation of cognitive performance after PBT treatment.ConclusionsOur data, albeit preliminary, strongly support the favourable therapeutic profile of PBT for the treatment of CNS germ cell tumors

Documenting the Recovery of Vascular Services in European Centres Following the Initial COVID-19 Pandemic Peak: Results from a Multicentre Collaborative Study

Objective: To document the recovery of vascular services in Europe following the first COVID-19 pandemic peak. Methods: An online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March – May 2020, “period 1”), and then again between May and June (“period 2”) and June and July 2020 (“period 3”). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume. Results: The impact of the pandemic continued to be felt well after countries’ first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence. Conclusion: Centres reported a broad return of services approaching pre-pandemic “normal” by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries

Physical properties of the trans-Neptunian binary 2000 YW₁₃₄

The study of trans-Neptunian binaries (TNBs) remains one of the most active areas of progress in understanding the solar system beyond Neptune. TNBs have been found in every dynamical population of the trans-Neptunian region (Noll et al. 2020), with proportions ranging from 29 % in the cold classical population to 5.5 % for the remaining classes combined (Brunini 2020). The formation of the contact TNB Arrokoth is one of the challenges that formation models face nowadays. The current angular momentum of Arrokoth is too low and the current binary formation scenarios, by either rotational fission or streaming instability (Nesvorný et al. 2019), require also loss of angular momentum (McKinnon et al. 2020). Additionally, formation mechanisms of close binaries may be distinct from those for the wider pairs. As the angular momentum of a system approaches that of an object spinning near its critical rotation period, rotational fission is the most likely explanation for their formation (Descamps et al. 2008), which is thought to be the case for the proposed satellites of Varuna and 2002 TC302 systems (Fernández-Valenzuela et al. 2019; Ortiz et al. 2020). If close TNBs turn out to be common for objects rotating close to the breakup limit, that could reveal important clues about angular momentum evolution during accretion for TNOs (Petit et al. 2011). However, characterizing binary systems at such distances is challenging. From the ~120 known TNBs, only around 40 have their mutual orbit fully determined, let alone physical characterization. 2000 YW134 is a TNB in a 3:8 resonance with an orbital semi-major axis of 57.4 au (a rare occurrence). On February 23rd, 2022, it occulted the Gaia EDR3 star 627356458358636544 (V = 17.1 mag). The stellar occultation was initially predicted using the JPL orbit solution #24, and updated using data from the 1.5-m and 1.23-m telescopes at Sierra Nevada and Calar Alto Observatories, using the same methodology as explained in Ortiz et al (2020). From the 17 observatories involved, seven reported positive chords, with five of them corresponding to the main body and the other two chords corresponding to its satellite. We are currently working on the analysis of these data in order to obtain the physical properties that characterize the system. Preliminary results show that the lower limit for the equivalent projected diameter of the satellite is twice the previously estimated size from HST observations (Stephens et al. 2006). We will also compare our results with the area-equivalent diameter and albedo obtained using thermal data from Herschel and Spitzer observations (Farkas-Takács et al. 2020)