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Background: The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB) ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort. Methods: A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide). In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months). Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69) served as controls. Results: The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098). In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038). The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4%) compared to NB90 MT (34 ± 5%, p = 0.026) and to no consolidation (35 ± 6%, p = 0.019). Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found. Conclusions: Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective.
Qualitätsstandards (QS) sind messbare Konstrukte, die helfen sollen, Versorgungslücken quantitativ zu erfassen, um langfristig die Versorgungsqualität zu verbessern. Die Assessment of SpondyloArthritis International Society (ASAS) hat kürzlich erstmals internationale QS für das Management von Patient*innen mit axialer Spondyloarthritis (axSpA) konsentiert und veröffentlicht. Die Deutsche Gesellschaft für Rheumatologie (DGRh) hat daraufhin beschlossen, diese Standards durch eine Gruppe von Expert*innen aus unterschiedlichen Versorgungsbereichen zu übersetzen, zu prüfen und ggf. zu übernehmen. Vor diesem Hintergrund wurden erstmals nationale QS für das Management von Patient*innen mit axSpA für Deutschland entwickelt. Hierbei wurde v. a. auf Machbarkeit und Praxisrelevanz geachtet. Letztlich wurden 9 QS definiert, mit denen die Qualität der Versorgung in Deutschland gemessen und verbessert werden kann bzw. soll.
Tyrosine kinase inhibitors (TKIs) are currently the standard chemotherapeutic agents for the treatment of chronic myeloid leukemia (CML). However, due to TKI resistance acquisition in CML patients, identification of new vulnerabilities is urgently required for a sustained response to therapy. In this study, we have investigated metabolic reprogramming induced by TKIs independent of BCR-ABL1 alterations. Proteomics and metabolomics profiling of imatinib-resistant CML cells (ImaR) was performed. KU812 ImaR cells enhanced pentose phosphate pathway, glycogen synthesis, serine-glycine-one-carbon metabolism, proline synthesis and mitochondrial respiration compared with their respective syngeneic parental counterparts. Moreover, the fact that only 36% of the main carbon sources were utilized for mitochondrial respiration pointed to glycerol-phosphate shuttle as mainly contributors to mitochondrial respiration. In conclusion, CML cells that acquire TKIs resistance present a severe metabolic reprogramming associated with an increase in metabolic plasticity needed to overcome TKI-induced cell death. Moreover, this study unveils that KU812 Parental and ImaR cells viability can be targeted with metabolic inhibitors paving the way to propose novel and promising therapeutic opportunities to overcome TKI resistance in CML.
TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly isolate human monoclonal antibodies. After immunizing these mice with DNA encoding the spike protein of SARS-CoV-2 and boosting with spike protein, we identified 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein. Nine antibodies neutralize SARS-CoV-2 infection at IC50 values in the subnanomolar range. ELISA-binding studies and DNA sequence analyses revealed one cluster of three clonally related neutralizing antibodies that target the receptor-binding domain and compete with the cellular receptor hACE2. A second cluster of six clonally related neutralizing antibodies bind to the N-terminal domain of the spike protein without competing with the binding of hACE2 or cluster 1 antibodies. SARS-CoV-2 mutants selected for resistance to an antibody from one cluster are still neutralized by an antibody from the other cluster. Antibodies from both clusters markedly reduced viral spread in mice transgenic for human ACE2 and protected the animals from SARS-CoV-2-induced weight loss. The two clusters of potent noncompeting SARS-CoV-2 neutralizing antibodies provide potential candidates for therapy and prophylaxis of COVID-19. The study further supports transgenic animals with a human immunoglobulin gene repertoire as a powerful platform in pandemic preparedness initiatives.
Background: Rare diseases are, by definition, very serious and chronic diseases with a high negative impact on quality of life. Approximately 350 million people worldwide live with rare diseases. The resulting high disease burden triggers health information search, but helpful, high-quality, and up-to-date information is often hard to find. Therefore, the improvement of health information provision has been integrated in many national plans for rare diseases, discussing the telephone as one access option. In this context, this study examines the need for a telephone service offering information for people affected by rare diseases, their relatives, and physicians.
Methods: In total, 107 individuals participated in a qualitative interview study conducted in Germany. Sixty-eight individuals suffering from a rare disease or related to somebody with rare diseases and 39 health care professionals took part. Individual interviews were conducted using a standardized semi-structured questionnaire. Interviews were analysed using the qualitative content analysis, triangulating patients, relatives, and health care professionals. The fulfilment of qualitative data processing standards has been controlled for.
Results: Out of 68 patients and relatives and 39 physicians, 52 and 18, respectively, advocated for the establishment of a rare diseases telephone service. Interviewees expected a helpline to include expert staffing, personal contact, good availability, low technical barriers, medical and psychosocial topics of counselling, guidance in reducing information chaos, and referrals. Health care professionals highlighted the importance of medical topics of counselling—in particular, differential diagnostics—and referrals.
Conclusions: Therefore, the need for a national rare diseases helpline was confirmed in this study. Due to limited financial resources, existing offers should be adapted in a stepwise procedure in accordance with the identified attributes.
Background: Recently, public and political interest has focused on people living with rare diseases and their health concerns. Due to the large number of different types of rare diseases and the sizable number of patients, taking action to improve the life of those affected is gaining importance. In 2013, the federal government of Germany adopted a national action plan for rare diseases, including the call to establish a central information portal on rare diseases (Zentrales Informationsportal über seltene Erkrankungen, ZIPSE).
Objective: The objective of this study, therefore, was to conduct scientific research on how such a portal must be designed to meet the needs of patients, their families, and medical professionals, and to provide high-quality information for information seekers.
Methods: We chose a 3-step procedure to develop a needs-based prototype of a central information portal. In the first step, we determined the information needs of patients with rare diseases, their relatives, and health care professionals by means of qualitative interviews and their content-analytical evaluation. On the basis of this, we developed the basic structure of the portal. In the second step, we identified quality criteria for websites on rare diseases to ensure that the information linked with ZIPSE meets the quality demands. Therefore, we gathered existing criteria catalogs and discussed them in an expert workshop. In the third step, we implemented and tested the developed prototypical information portal.
Results: A portal page was configured and made accessible on the Web. The structure of ZIPSE was based on the findings from 108 qualitative interviews with patients, their relatives, and health care professionals, through which numerous information needs were identified. We placed particularly important areas of information, such as symptoms, therapy, research, and advisory services, on the start page. Moreover, we defined 13 quality criteria, referring to factors such as author information, creation date, and privacy, enabling links with high-quality information. Moreover, 19 users tested all the developed routines based on usability and comprehensibility. Subsequently, we improved the visual presentation of search results and other important search functions.
Conclusions: The implemented information portal, ZIPSE, provides high-quality information on rare diseases from a central point of access. By integrating the targeted groups as well as different experts on medical information during the construction, the website can assure an improved search for information for users. ZIPSE can also serve as a model for other Web-based information systems in the field of rare diseases.
Registered Report Identifier: RR1-10.2196/7425.
An important question concerning inter-areal communication in the cortex, is whether these interactions are synergistic, i.e. convey information beyond what can be performed by isolated signals. Here, we dissociated cortical interactions sharing common information from those encoding complementary information during prediction error processing. To this end, we computed co-information, an information-theoretical measure that distinguishes redundant from synergistic information among brain signals. We analyzed auditory and frontal electrocorticography (ECoG) signals in three common awake marmosets and investigated to what extent event-related-potentials (ERP) and broadband (BB) dynamics exhibit redundancy and synergy in auditory prediction error signals. We observed multiple patterns of redundancy and synergy across the entire cortical hierarchy with distinct dynamics. The information conveyed by ERPs and BB signals was highly synergistic even at lower stages of the hierarchy in the auditory cortex, as well as between lower and higher areas in the frontal cortex. These results indicate that the distributed representations of prediction error signals across the cortical hierarchy can be highly synergistic.
The ability of hematopoietic stem cells (HSCs) to self-renew is a prerequisite for the establishment of definitive hematopoiesis and life-long blood regeneration. Here, we report the single-stranded DNA-binding transcriptional regulator far upstream element (FUSE)-binding protein 1 (FUBP1) as an essential factor of HSC self-renewal. Functional inactivation of FUBP1 in two different mouse models resulted in embryonic lethal anemia at around E15.5 caused by severely diminished HSCs. Fetal and adult HSCs lacking FUBP1 revealed an HSC-intrinsic defect in their maintenance, expansion, and long-term blood reconstitution, but could differentiate into all hematopoietic lineages. FUBP1-deficient adult HSCs exhibit significant transcriptional changes, including upregulation of the cell-cycle inhibitor p21 and the pro-apoptotic Noxa molecule. These changes caused an increase in generation time and death of HSCs as determined by video-microscopy-based tracking. Our data establish FUBP1 and its recognition of single-stranded genomic DNA as an important element in the transcriptional regulation of HSC self-renewal.
Novel treatment options are needed for the successful therapy of patients with high-risk neuroblastoma. Here, we investigated the cyclin-dependent kinase (CDK) inhibitor SNS-032 in a panel of 109 neuroblastoma cell lines consisting of 19 parental cell lines and 90 sublines with acquired resistance to 14 different anticancer drugs. Seventy-three percent of the investigated neuroblastoma cell lines and all four investigated primary tumor samples displayed concentrations that reduce cell viability by 50% in the range of the therapeutic plasma levels reported for SNS-032 (<754 nM). Sixty-two percent of the cell lines and two of the primary samples displayed concentrations that reduce cell viability by 90% in this concentration range. SNS-032 also impaired the growth of the multidrug-resistant cisplatin-adapted UKF-NB-3 subline UKF-NB-3rCDDP1000 in mice. ABCB1 expression (but not ABCG2 expression) conferred resistance to SNS-032. The antineuroblastoma effects of SNS-032 did not depend on functional p53. The antineuroblastoma mechanism of SNS-032 included CDK7 and CDK9 inhibition-mediated suppression of RNA synthesis and subsequent depletion of antiapoptotic proteins with a fast turnover rate including X-linked inhibitor of apoptosis (XIAP), myeloid cell leukemia sequence 1 (Mcl-1), baculoviral IAP repeat containing 2 (BIRC2; cIAP-1), and survivin. In conclusion, CDK7 and CDK9 represent promising drug targets and SNS-032 represents a potential treatment option for neuroblastoma including therapy-refractory cases.
Species distributed across vast continental areas and across major biomes provide unique model systems for studies of biotic diversification, yet also constitute daunting financial, logistic and political challenges for data collection across such regions. The tree frog Dendropsophus minutus (Anura: Hylidae) is a nominal species, continentally distributed in South America, that may represent a complex of multiple species, each with a more limited distribution. To understand the spatial pattern of molecular diversity throughout the range of this species complex, we obtained DNA sequence data from two mitochondrial genes, cytochrome oxidase I (COI) and the 16S rhibosomal gene (16S) for 407 samples of D. minutus and closely related species distributed across eleven countries, effectively comprising the entire range of the group. We performed phylogenetic and spatially explicit phylogeographic analyses to assess the genetic structure of lineages and infer ancestral areas. We found 43 statistically supported, deep mitochondrial lineages, several of which may represent currently unrecognized distinct species. One major clade, containing 25 divergent lineages, includes samples from the type locality of D. minutus. We defined that clade as the D. minutus complex. The remaining lineages together with the D. minutus complex constitute the D. minutus species group. Historical analyses support an Amazonian origin for the D. minutus species group with a subsequent dispersal to eastern Brazil where the D. minutus complex originated. According to our dataset, a total of eight mtDNA lineages have ranges >100,000 km2. One of them occupies an area of almost one million km2 encompassing multiple biomes. Our results, at a spatial scale and resolution unprecedented for a Neotropical vertebrate, confirm that widespread amphibian species occur in lowland South America, yet at the same time a large proportion of cryptic diversity still remains to be discovered.
Background The arterial in line application of the leukocyte inhibition module (LIM) in the cardiopulmonary bypass (CPB) limits overshooting leukocyte activity during cardiac surgery. We now studied in a porcine model whether LIM may have beneficial effects on cardiac function after CPB. Methods German landrace pigs underwent CPB (60 min myocardial ischemia; 30 min reperfusion)without (group I; n=6) or with LIM (group II; n=6). The cardiac indices (CI) and cardiac function were analyzed pre and post CPB with a Swan-Ganz catheter and the cardiac function analyzer. Neutrophil labeling with technetium, scintigraphy, and histological analyses were done to track activated neutrophils within the organs. Results LIM prevented CPB-associated increase of neutrophil counts in peripheral blood. In group I, the CI significantly declined post CPB (post: 3.26 +/- 0.31; pre: 4.05 +/- 0.45 l/min/m2; p<0.01). In group II, the CI was only slightly reduced (post: 3.86 +/- 0.49; pre 4.21 +/- 1.32 l/min/m2; p=0.23). Post CPB, the intergroup difference showed significantly higher CI values in the LIM group (p<0.05) which was in conjunction with higher pre-load independent endsystolic pressure volume relationship (ESPVR) values (group I: 1.57 +/- 0.18; group II: 1.93 +/- 0.16; p<0.001). Moreover, the systemic vascular resistance and pulmonary vascular resistance were lower in the LIM group. LIM appeared to accelerate the sequestration of hyperactivated neutrophils in the spleen and to reduce neutrophil infiltration of heart and lung. Conclusions Our data provide strong evidence that LIM improves perioperative hemodynamics and cardiac function after CPB by limiting neutrophil activity and inducing accelerated sequestration of neutrophils in the spleen.
We have isolated the human protein SNEV as downregulated in replicatively senescent cells. Sequence homology to the yeast splicing factor Prp19 suggested that SNEV might be the orthologue of Prp19 and therefore might also be involved in pre-mRNA splicing. We have used various approaches including gene complementation studies in yeast using a temperature sensitive mutant with a pleiotropic phenotype and SNEV immunodepletion from human HeLa nuclear extracts to determine its function. A human–yeast chimera was indeed capable of restoring the wild-type phenotype of the yeast mutant strain. In addition, immunodepletion of SNEV from human nuclear extracts resulted in a decrease of in vitro pre-mRNA splicing efficiency. Furthermore, as part of our analysis of protein–protein interactions within the CDC5L complex, we found that SNEV interacts with itself. The self-interaction domain was mapped to amino acids 56–74 in the protein's sequence and synthetic peptides derived from this region inhibit in vitro splicing by surprisingly interfering with spliceosome formation and stability. These results indicate that SNEV is the human orthologue of yeast PRP19, functions in splicing and that homo-oligomerization of SNEV in HeLa nuclear extract is essential for spliceosome assembly and that it might also be important for spliceosome stability.
Siglec-1 (sialoadhesin, CD169) is a surface receptor on human cells that mediates trans-enhancement of HIV-1 infection through recognition of sialic acid moieties in virus membrane gangliosides. Here, we demonstrate that mouse Siglec-1, expressed on the surface of primary macrophages in an interferon-α-responsive manner, captures murine leukemia virus (MLV) particles and mediates their transfer to proliferating lymphocytes. The MLV infection of primary B-cells was markedly more efficient than that of primary T-cells. The major structural protein of MLV particles, Gag, frequently co-localized with Siglec-1, and trans-infection, primarily of surface-bound MLV particles, efficiently occurred. To explore the role of sialic acid for MLV trans-infection at a submolecular level, we analyzed the potential of six sialic acid precursor analogs to modulate the sialylated ganglioside-dependent interaction of MLV particles with Siglec-1. Biosynthetically engineered sialic acids were detected in both the glycolipid and glycoprotein fractions of MLV producer cells. MLV released from cells carrying N-acyl-modified sialic acids displayed strikingly different capacities for Siglec-1-mediated capture and trans-infection; N-butanoyl, N-isobutanoyl, N-glycolyl, or N-pentanoyl side chain modifications resulted in up to 92 and 80% reduction of virus particle capture and trans-infection, respectively, whereas N-propanoyl or N-cyclopropylcarbamyl side chains had no effect. In agreement with these functional analyses, molecular modeling indicated reduced binding affinities for non-functional N-acyl modifications. Thus, Siglec-1 is a key receptor for macrophage/lymphocyte trans-infection of surface-bound virions, and the N-acyl side chain of sialic acid is a critical determinant for the Siglec-1/MLV interaction.
Starting from (MeO)3SiCH2Cl (10) and Ph2(H)SiCH2OH (16), respectively, the (hydroxymethyl)diphenyl(piperidinoalkyl)silanes (HOCH2)Ph2Si(CH2)2NC5H10 (6) and (HOCH2)Ph2Si(CH2)3NC5H10 (8) have been synthesized [10→Ph2(MeO)SiCH2Cl (11)→Ph2(CH2=CH)SiCH2Cl (12)→Ph2(CH2=CH)SiCH2OAc (13)→Ph2(CH2=CH)SiCH2OH (14)→Ph2(CH2=CH)SiCH2OSiMe3 (15)→6; 16→Ph2(H)SiCH2OSiMe3 (17)→8; NC5H10 = piperidino]. N-Quaternization of 6 and 8 with MeI gave the corresponding methiodides 7 and 9, respectively. As shown by IR-spectroscopic studies, compounds 6 and 8 form intramolecular O-H···N hydrogen bonds in solution (CCl4). In the crystal, 6 (space group Pna21; two crystallographically independent molecules) also forms intramolecular O-H···N hydrogen bonds whereas 8 (space group P1̅) forms intermolecular O-H···N hydrogen bonds leading to the formation of centrosymmetric dimers (single-crystal X-ray diffraction studies). The (hydroxymethyl) silanes 6-9 and the related silanols (HO)Ph2Si(CH2)2NC5H 10 (sila-pridinol; 1), sila-pridinol methiodide (2), (HO)Ph2Si(CH2)3NC5H10 (sila-difenidol; 3) and sila-difenidol methiodide (4) were investigated for their antimuscarinic properties. In functional pharmacological experiments as well as in radioligand competition studies, all compounds behaved as simple competitive antagonists at muscarinic M1-, M2-, M3- and M4-receptors. In general, the silanols 1-4 displayed higher receptor affinities (up to 100-fold) than the corresponding (hydroxymethyl) silanes 6-9 . In the (hydroxymethyl)silane series, compound 7 was found to be the most potent muscarinic antagonist [pA2/pKi= 8,71/8,6 (M1), 8,23/7,8 (M2), 8,19/7,8 (M3); pKi = 8,2 (M4)]. In the silanol series, the related compound 2 showed the most interesting antimuscarinic properties [pA2/pKi = 10,37/9,6 (M1), 8,97/8,8 (M2), 9,08/8,8 (M3); pKi = 9,4 (M4)].
The development of resistance to chemotherapeutic agents, such as Doxorubicin (DOX) and cytarabine (AraC), is one of the greatest challenges to the successful treatment of Acute Myeloid Leukemia (AML). Such acquisition is often underlined by a metabolic reprogramming that can provide a therapeutic opportunity, as it can lead to the emergence of vulnerabilities and dependencies to be exploited as targets against the resistant cells. In this regard, genome-scale metabolic models (GSMMs) have emerged as powerful tools to integrate multiple layers of data to build cancer-specific models and identify putative metabolic vulnerabilities. Here, we use genome-scale metabolic modelling to reconstruct a GSMM of the THP1 AML cell line and two derivative cell lines, one with acquired resistance to AraC and the second with acquired resistance to DOX. We also explore how, adding to the transcriptomic layer, the metabolomic layer enhances the selectivity of the resulting condition specific reconstructions. The resulting models enabled us to identify and experimentally validate that drug-resistant THP1 cells are sensitive to the FDA-approved antifolate methotrexate. Moreover, we discovered and validated that the resistant cell lines could be selectively targeted by inhibiting squalene synthase, providing a new and promising strategy to directly inhibit cholesterol synthesis in AML drug resistant cells.
Measurement of groomed jet substructure observables in p+p collisions at √s = 200 GeV with STAR
(2020)
In this letter, measurements of the shared momentum fraction (zg) and the groomed jet radius (Rg), as defined in the SoftDrop algorithm, are reported in p+p collisions at √s = 200 GeV collected by the STAR experiment. These substructure observables are differentially measured for jets of varying resolution parameters from R = 0.2 − 0.6 in the transverse momentum range 15 < pT,jet < 60 GeV/c. These studies show that, in the pT,jet range accessible at √s = 200 GeV and with increasing jet resolution parameter and jet transverse momentum, the zg distribution asymptotically converges to the DGLAP splitting kernel for a quark radiating a gluon. The groomed jet radius measurements reflect a momentum-dependent narrowing of the jet structure for jets of a given resolution parameter, i.e., the larger the pT,jet, the narrower the first splitting. For the first time, these fully corrected measurements are compared to Monte Carlo generators with leading order QCD matrix elements and leading log in the parton shower, and to state-of-the-art theoretical calculations at next-to-leading-log accuracy. We observe that PYTHIA 6 with parameters tuned to reproduce RHIC measurements is able to quantitatively describe data, whereas PYTHIA 8 and HERWIG 7, tuned to reproduce LHC data, are unable to provide a simultaneous description of both zg and Rg, resulting in opportunities for fine parameter tuning of these models for p+p collisions at RHIC energies. We also find that the theoretical calculations without non-perturbative corrections are able to qualitatively describe the trend in data for jets of large resolution parameters at high pT,jet, but fail at small jet resolution parameters and low jet transverse momenta.
Investigation of the linear and mode-coupled flow harmonics in Au+Au collisions at √sNN = 200 GeV
(2020)
Flow harmonics (vn) of the Fourier expansion for the azimuthal distributions of hadrons are commonly employed to quantify the azimuthal anisotropy of particle production relative to the collision symmetry planes. While lower order Fourier coefficients (v2 and v3) are more directly related to the corresponding eccentricities of the initial state, the higher-order flow harmonics (vn>3) can be induced by a modecoupled response to the lower-order anisotropies, in addition to a linear response to the same-order anisotropies. These higher-order flow harmonics and their linear and mode-coupled contributions can be used to more precisely constrain the initial conditions and the transport properties of the medium in theoretical models. The multiparticle azimuthal cumulant method is used to measure the linear and mode-coupled contributions in the higher-order anisotropic flow, the mode-coupled response coefficients, and the correlations of the event plane angles for charged particles as functions of centrality and transverse momentum in Au+Au collisions at nucleon-nucleon center-of-mass energy √sN N= 200 GeV. The results are compared to similar LHC measurements as well as to several viscous hydrodynamic calculations with varying initial conditions.
We present a measurement of inclusive J /ψ production at mid-rapidity (|y| < 1) in p+p collisions at a center-of-mass energy of √s = 200 GeV with the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The differential production cross section for J /ψ as a function of transverse momentum (p T ) for 0 < p T < 14 GeV/c and the total cross section are reported and compared to calculations from the color evaporation model and the non-relativistic Quantum Chromodynamics model. The dependence of J /ψ relative yields in three p T intervals on charged-particle multiplicity at mid-rapidity is measured for the first time in p+p collisions at √s = 200 GeV and compared with that measured at √s = 7 TeV, PYTHIA8 and EPOS3 Monte Carlo generators, and the Percolation model prediction.
Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear.
Methods and results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events.
Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.
Background The differential diagnosis between follicular thyroid adenoma and minimal invasive follicular thyroid carcinoma is often difficult for several reasons. One major aspect is the lack of typical cytological criteria in well differentiated specimens. New marker molecules, shown by poly- or monoclonal antibodies proved helpful. Methods We performed global gene expression analysis of 12 follicular thyroid tumours (4 follicular adenomas, 4 minimal invasive follicular carcinomas and 4 widely invasive follicular carcinomas), followed by immunohistochemical staining of 149 cases. The specificity of the antibody was validated by western blot analysis Results In gene expression analysis QPRT was detected as differently expressed between follicular thyroid adenoma and follicular thyroid carcinoma. QPRT protein could be detected by immunohistochemistry in 65% of follicular thyroid carcinomas including minimal invasive variant and only 22% of follicular adenomas. Conclusion Consequently, QPRT is a potential new marker for the immunohistochemical screening of follicular thyroid nodules.
Background: Hypothermia has been discussed as playing a role in improving the early phase of systemic inflammation. However, information on the impact of hypothermia on the local inflammatory response is sparse. We therefore investigated the kinetics of local and systemic inflammation in the late posttraumatic phase after induction of hypothermia in an established porcine long-term model of combined trauma.
Materials & Methods: Male pigs (35 ± 5kg) were mechanically ventilated and monitored over the study period of 48 h. Combined trauma included tibia fracture, lung contusion, liver laceration and pressure-controlled hemorrhagic shock (MAP < 30 ± 5 mmHg for 90 min). After resuscitation, hypothermia (33°C) was induced for a period of 12 h (HT-T group) with subsequent re-warming over a period of 10 h. The NT-T group was kept normothermic. Systemic and local (fracture hematoma) cytokine levels (IL-6, -8, -10) and alarmins (HMGB1, HSP70) were measured via ELISA.
Results: Severe signs of shock as well as systemic and local increases of pro-inflammatory mediators were observed in both trauma groups. In general the local increase of pro- and anti-inflammatory mediator levels was significantly higher and prolonged compared to systemic concentrations. Induction of hypothermia resulted in a significantly prolonged elevation of both systemic and local HMGB1 levels at 48 h compared to the NT-T group. Correspondingly, local IL-6 levels demonstrated a significantly prolonged increase in the HT-T group at 48 h.
Conclusion: A prolonged inflammatory response might reduce the well-described protective effects on organ and immune function observed in the early phase after hypothermia induction. Furthermore, local immune response also seems to be affected. Future studies should aim to investigate the use of therapeutic hypothermia at different degrees and duration of application.
Background and Aim: Several studies observed alterations in the gut microbiota in patients with non‐alcoholic fatty liver disease (NAFLD). However, analyzed patient populations and methods strongly differ among these studies. The aim of this study was to prove the reproducibility of published results and to provide a detailed overview of all findings in our NAFLD cohort using next generation sequencing methods.
Methods: The individual taxonomic microbiota composition of fecal samples from 90 NAFLD patients and 21 healthy controls was analyzed using 16S rRNA gene sequencing. Study participants were grouped according to their disease stage and compared regarding their gut microbiota composition. Studies were identified from PubMed listed publications, and the results were compared with the findings in our cohort.
Results: Results from 13 identified studies were compared with our data. A decreased abundance of the Bacteroidetes and Ruminococcaceae as well as an increased abundance of Lactobacillaceae and Veillonellaceae and Dorea were the most frequently reported changes among NAFLD patients in 4/13, 5/13, 4/13, 2/13, and 3/13 studies, respectively. Even though these alterations in the gut microbiota composition were also observed in our patient cohort, the majority of published differences could not be reproduced, neither in our own nor in other NAFLD cohort studies.
Conclusion: Despite repeatedly reproduced abundance patterns of specific bacteria, the heterogeneous study results did not reveal a consistent disease specific gut microbiota signature. Further prospective studies with homogenous patient cohorts and standardized methods are necessary to phenotype NAFLD by the gut microbiota.
Objective: To evaluate the efficacy and tolerability of brivaracetam (BRV) in a severely drug refractory cohort of patients with epileptic encephalopathies (EE).
Method: A multicenter, retrospective cohort study recruiting all patients treated with EE who began treatment with BRV in an enrolling epilepsy center between 2016 and 2017.
Results: Forty-four patients (27 male [61%], mean age 29 years, range 6 to 62) were treated with BRV. The retention rate was 65% at 3 months, 52% at 6 months and 41% at 12 months. A mean retention time of 5 months resulted in a cumulative exposure to BRV of 310 months. Three patients were seizure free during the baseline. At 3 months, 20 (45%, 20/44 as per intention-to-treat analysis considering all patients that started BRV including three who were seizure free during baseline) were either seizure free (n = 4; 9%, three of them already seizure-free at baseline) or reported at least 25% (n = 4; 9%) or 50% (n = 12; 27%) reduction in seizures. An increase in seizure frequency was reported in two (5%) patients, while there was no change in the seizure frequency of the other patients. A 50% long-term responder rate was apparent in 19 patients (43%), with two (5%) free from seizures for more than six months and in nine patients (20%, with one [2 %] free from seizures) for more than 12 months. Treatment-emergent adverse events were predominantly of psychobehavioural nature and were observed in 16%.
Significance: In this retrospective analysis the rate of patients with a 50% seizure reduction under BRV proofed to be similar to those seen in regulatory trials for focal epilepsies. BRV appears to be safe and relatively well tolerated in EE and might be considered in patients with psychobehavioral adverse events while on levetiracetam.
An important question concerning inter-areal communication in the cortex is whether these interactions are synergistic, i.e. brain signals can either share common information (redundancy) or they can encode complementary information that is only available when both signals are considered together (synergy). Here, we dissociated cortical interactions sharing common information from those encoding complementary information during prediction error processing. To this end, we computed co-information, an information-theoretical measure that distinguishes redundant from synergistic information among brain signals. We analyzed auditory and frontal electrocorticography (ECoG) signals in five common awake marmosets performing two distinct auditory oddball tasks and investigated to what extent event-related potentials (ERP) and broadband (BB) dynamics encoded redundant and synergistic information during auditory prediction error processing. In both tasks, we observed multiple patterns of synergy across the entire cortical hierarchy with distinct dynamics. The information conveyed by ERPs and BB signals was highly synergistic even at lower stages of the hierarchy in the auditory cortex, as well as between auditory and frontal regions. Using a brain-constrained neural network, we simulated the spatio-temporal patterns of synergy and redundancy observed in the experimental results and further demonstrated that the emergence of synergy between auditory and frontal regions requires the presence of strong, long-distance, feedback and feedforward connections. These results indicate that the distributed representations of prediction error signals across the cortical hierarchy can be highly synergistic.
This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, |GE | and |GM|, using the ¯pp → μ+μ− reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is ¯pp → π+π−,due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distribuations of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
Background and Objectives: Proteins of the coagulation system contribute to autoimmune inflammation in patients with multiple sclerosis (MS). On blood-brain barrier (BBB) disruption, fibrinogen enters the CNS and is rapidly converted to fibrin, unfolding pleiotropic autoimmune mechanisms. Fibrin accumulation leads to subsequent proteolytic degradation that results in D-dimer generation. The primary objective of this study was to determine intrathecal levels of D-dimer in CSF as a measure of intrathecal coagulation cascade activation and to evaluate its diagnostic utility in patients with MS in contrast to healthy subjects. Key secondary objectives included analysis of CSF D-dimer in differential diagnoses of MS and its relation to routine clinical markers of disease activity.
Methods: Patients admitted for the assessment of suspected MS were prospectively recruited from October 2017 to December 2020. Blood plasma and citrated CSF samples were analyzed using a highly sensitive luminescent oxygen channeling immunoassay. Intrathecal generation of D-dimer was analyzed by adjusting for CSF/serum albumin (Qalb) and CSF/plasma D-dimer quotients (QD-dimer), and corresponding CSF fibrinogen levels were determined. Final diagnoses after full evaluation and clinical data were recorded.
Results: Of 187 patients, 113 patients received a diagnosis of MS or clinically/radiologically isolated syndrome. We found increased intrathecal CSF D-dimer generation levels (QD-dimer/Qalb-index) for patients with relapsing-remitting MS (RRMS; n = 71, median 4.7, interquartile range [IQR] 2.5–8.0) when compared with those for disease controls (n = 22, median 2.6, IQR 2.1–4.8, p = 0.031). Absolute CSF D-dimer values correlated with CSF fibrinogen levels (r = 0.463; p < 0 .001) and CSF leukocytes (r = 0.273; p = 0.003) and were elevated in MS patients with contrast enhancement (CE) compared with MS patients without CE on MRI (n = 48, median 6 ng/mL, and IQR 3–15.25 vs n = 41, median 4 ng/mL, and IQR 2–7; p = 0.026). Exploratory subgroup analyses indicated a correlation of intrathecal inflammatory activity and CSF D-dimer levels.
Discussion: D-dimer in CSF can be reliably determined and correlates with markers of CNS inflammation and CSF fibrinogen levels. Adjusted for BBB dysfunction, CSF D-dimer may allow the identification of intrathecal coagulation cascade activation in patients with MS.
Classification of Evidence: This study provides Class I evidence that CSF D-dimer levels are elevated in patients with RRMS.
The polarization of Λ and Λ¯ hyperons along the beam direction has been measured relative to the second and third harmonic event planes in isobar Ru+Ru and Zr+Zr collisions at √sNN = 200 GeV. This is the first experimental evidence of the hyperon polarization by the triangular flow originating from the initial density fluctuations. The amplitudes of the sine modulation for the second and third harmonic results are comparable in magnitude, increase from central to peripheral collisions, and show a mild pT dependence. The azimuthal angle dependence of the polarization follows the vorticity pattern expected due to elliptic and triangular anisotropic flow, and qualitatively disagree with most hydrodynamic model calculations based on thermal vorticity and shear induced contributions. The model results based on one of existing implementations of the shear contribution lead to a correct azimuthal angle dependence, but predict centrality and pT dependence that still disagree with experimental measurements. Thus, our results provide stringent constraints on the thermal vorticity and shear-induced contributions to hyperon polarization. Comparison to previous measurements at RHIC and the LHC for the second-order harmonic results shows little dependence on the collision system size and collision energy.
Measurement of cold nuclear matter effects for inclusive J/ψ in p+Au collisions at √sNN = 200 GeV
(2022)
Measurement by the STAR experiment at RHIC of the cold nuclear matter (CNM) effects experienced by inclusive J/ψ at mid-rapidity in 0-100% p+Au collisions at √sNN = 200 GeV is presented. Such effects are quantified utilizing the nuclear modification factor, RpAu, obtained by taking a ratio of J/ψ yield in p+Au collisions to that in p+p collisions scaled by the number of binary nucleon-nucleon collisions. The differential J/ψ yield in both p+p and p+Au collisions is measured through the dimuon decay channel, taking advantage of the trigger capability provided by the Muon Telescope Detector in the RHIC 2015 run. Consequently, the J/ψ RpAu is derived within the transverse momentum (pT) range of 0 to 10 GeV/c. A suppression of approximately 30% is observed for pT < 2 GeV/c, while J/ψ RpAu becomes compatible with unity for pT greater than 3 GeV/c, indicating the J/ψ yield is minimally affected by the CNM effects at high pT. Comparison to a similar measurement from 0-20% central Au+Au collisions reveals that the observed strong J/ψ suppression above 3 GeV/c is mostly due to the hot medium effects, providing strong evidence for the formation of the quark-gluon plasma in these collisions. Several model calculations show qualitative agreement with the measured J/ψ RpAu, while their agreement with the J/ψ yields in p+p and p+Au collisions is worse.
We report the first multi-differential measurements of strange hadrons of K −, φ and − yields as well as the ratios of φ/K − and φ/− in Au+Au collisions at √sNN = 3 GeV with the STAR experiment fixed target configuration at RHIC. The φ mesons and − hyperons are measured through hadronic decay channels, φ → K + K − and Ξ− → Λπ−. Collision centrality and rapidity dependence of the transverse momentum spectra for these strange hadrons are presented. The 4π yields and ratios are compared to thermal model and hadronic transport model predictions. At this collision energy, thermal model with grand canonical ensemble (GCE) under-predicts the φ/K − and φ/− ratios while the result of canonical ensemble (CE) calculations reproduce φ/K −, with the correlation length rc ∼ 2.7 fm, and φ/−, rc ∼ 4.2 fm, for the 0-10% central collisions. Hadronic transport models including high mass resonance decays could also describe the ratios. While thermal calculations with GCE work well for strangeness production in high energy collisions, the change to CE at 3 GeV implies a rather different medium property at high baryon density.
We report on the measurements of directed flow v1 and elliptic flow v2 for hadrons (π±, K ±, K0 S , p, φ, Λ and ) from Au+Au collisions at √sN N = 3 GeV and v2 for (π±, K ±, p and p) at 27 and 54.4 GeV with the STAR experiment. While at the two higher energy midcentral collisions the numberof-constituent-quark (NCQ) scaling holds, at 3 GeV the v2 at midrapidity is negative for all hadrons and the NCQ scaling is absent. In addition, the v1 slopes at midrapidity for almost all observed hadrons are found to be positive, implying dominant repulsive baryonic interactions. The features of negative v2 and positive v1 slope at 3 GeV can be reproduced with a baryonic mean-field in transport model calculations. These results imply that the medium in such collisions is likely characterized by baryonic interactions.
In high-energy heavy-ion collisions, partonic collectivity is evidenced by the constituent quark number scaling of elliptic flow anisotropy for identified hadrons. A breaking of this scaling and dominance of baryonic interactions is found for identified hadron collective flow measurements in √sNN = 3 GeV Au+Au collisions. In this paper, we report measurements of the first- and second-order azimuthal anisotropic parameters, v1 and v2, of light nuclei (d, t, 3He, 4He) produced in √sNN = 3 GeV Au+Au collisions at the STAR experiment. An atomic mass number scaling is found in the measured v1 slopes of light nuclei at mid-rapidity. For the measured v2 magnitude, a strong rapidity dependence is observed. Unlike v2 at higher collision energies, the v2 values at mid-rapidity for all light nuclei are negative and no scaling is observed with the atomic mass number. Calculations by the Jet AA Microscopic Transport Model (JAM), with baryonic mean-field plus nucleon coalescence, are in good agreement with our observations, implying baryonic interactions dominate the collective dynamics in 3 GeV Au+Au collisions at RHIC.
We report results on the total and elastic cross sections in proton-proton collisions at √s = 200 GeV obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section was measured in the squared four-momentum transfer range 0.045 ≤ −t ≤ 0.135 GeV2. The value of the exponential slope parameter B of the elastic differential cross section dσ/dt ∼ e−Bt in the measured −t range was found to be B = 14.32 ± 0.09(stat.)+0.13 −0.28(syst.) GeV−2. The total cross section σtot, obtained from extrapolation of the dσ/dt to the optical point at −t = 0, is σtot = 54.67 ± 0.21(stat.)+1.28 −1.38(syst.) mb. We also present the values of the elastic cross section σel = 10.85 ± 0.03(stat.)+0..49 −0.41(syst.) mb, the elastic cross section integrated within the STAR t-range σ det el = 4.05 ± 0.01(stat.)+0.18−0.17(syst.) mb, and the inelastic cross section σinel = 43.82 ± 0.21(stat.)+1.37−1.44(syst.) mb. The results are compared with the world data
J/ψ suppression has long been considered a sensitive signature of the formation of the Quark-Gluon Plasma (QGP) in relativistic heavy-ion collisions. In this letter, we present the first measurement of inclusive J/ψ production at mid-rapidity through the dimuon decay channel in Au+Au collisions at √sNN = 200 GeV with the STAR experiment. These measurements became possible after the installation of the Muon Telescope Detector was completed in 2014. The J/ψ yields are measured in a wide transverse momentum (pT) range of 0.15 GeV/c to 12 GeV/c from central to peripheral collisions. They extend the kinematic reach of previous measurements at RHIC with improved precision. In the 0-10% most central collisions, the J/ψ yield is suppressed by a factor of approximately 3 for pT > 5 GeV/c relative to that in p + p collisions scaled by the number of binary nucleon-nucleon collisions. The J/ψ nuclear modification factor displays little dependence on pT in all centrality bins. Model calculations can qualitatively describe the data, providing further evidence for the color-screening effect experienced by J/ψ mesons in the QGP.
Background: Protective effects of vitamin D have been reported in autoimmune and malignant thyroid diseases, though little is known about the underlying mechanism. Sirtuin 1 histon deacethylase (SIRT1) links the vitamin D pathway with regulation of transcription factor FOXO3a, a key player in cell cycle regulation and apoptosis. Aim of the present study was to investigate common single nucleotide polymorphisms (SNP's) in FOXO3a gene in respect to thyroid diseases, as well as to evaluate the hypothesis of Sirtuin1-FOXO3a interaction being a mediator of anti-proliferative vitamin D effects.
Methods: The SNP's FOXO3a rs4946936/rs4945816/rs9400239 were genotyped in 257 patients with differentiated thyroid carcinoma (DTC), 139 patients with Hashimoto thyroiditis (HT) and 463 healthy controls (HC). Moreover, T-helper cells of HC and papillary thyroid cancer cell line BCPAP were incubated with 1,25(OH)2D3 and/or SIRT1 inhibitor Ex-527 in order to elucidate SIRT1- dependent vitamin D effects on cell proliferation and FOXO3a gene expression in vitro.
Results: Patients with DTC tended to carry more often allele C in FOXO3a rs4946936 in comparison to HC (pcorrected = pc = 0.08). FOXO3a rs9400239T and rs4945816C was more frequent in HT in comparison to HC (pc = 0.02 and pc = 0.01, respectively). In both DTC and HT, we could not find a correlation of FOXO3a SNP's with vitamin D status. However, on in vitro level, 1,25(OH)2D3 showed an anti-proliferative effect in both T-helper cells and BCPAP, that was blocked by SIRT1 inhibition (T-helper cells: p = 0.0059, BCPAP: p = 0.04) and accompanied by elevated FOXO3a gene expression in T-helper cells (p = 0.05).
Conclusions: FOXO3a rs9400239T and rs4945816C may constitute risk factors for HT, independent of the vitamin D status.This indicates the implication of FOXO3a in pathogenesis of autoimmune thyroid diseases. The dependency of anti-proliferative vitamin D effects on SIRT1 activity further suggests a key role of vitamin D-SIRT1-FOXO3a axis for protective vitamin D effects.
Quark interactions with topological gluon configurations can induce chirality imbalance and local parity violation in quantum chromodynamics. This can lead to electric charge separation along the strong magnetic field in relativistic heavy-ion collisions – the chiral magnetic effect (CME). We report measurements by the STAR collaboration of a CME-sensitive observable in p + Au and d + Au collisions at 200 GeV, where the CME is not expected, using charge-dependent pair correlations relative to a third particle. We observe strong charge-dependent correlations similar to those measured in heavy-ion collisions. This bears important implications for the interpretation of the heavy-ion data.
Background and Aims: Monocyte chemotactic protein-1 (MCP-1) is a potent chemoattractant for monocytes. It is involved in pathogenesis of several inflammatory diseases. Hepatic MCP-1 is a readout of macrophage activation. While inflammation is a major driver of liver disease progression, the origin and role of circulating MCP-1 as a biomarker remains unclear.
Methods: Hepatic CC-chemokine ligand 2 (CCL2) expression and F4/80 staining for Kupffer cells were measured and correlated in a mouse model of chronic liver disease (inhalative CCl4 for 7 weeks). Next, hepatic RNA levels of CCL2 were measured in explanted livers of 39 patients after transplantation and correlated with severity of disease. Changes in MCP-1 were further evaluated in a rat model of experimental cirrhosis and acute-on-chronic liver failure (ACLF). Finally, we analyzed portal and hepatic vein levels of MCP-1 in patients receiving transjugular intrahepatic portosystemic shunt insertion for complications of portal hypertension.
Results: In this mouse model of fibrotic hepatitis, hepatic expression of CCL2 (P = 0.009) and the amount of F4/80 positive cells in the liver (P < 0.001) significantly increased after induction of hepatitis by CCl4 compared to control animals. Moreover, strong correlation of hepatic CCL2 expression and F4/80 positive cells were seen (P = 0.023). Furthermore, in human liver explants, hepatic transcription levels of CCL2 correlated with the MELD score of the patients, and thus disease severity (P = 0.007). The experimental model of ACLF in rats revealed significantly higher levels of MCP-1 plasma (P = 0.028) and correlation of hepatic CCL2 expression (R = 0.69, P = 0.003). Particularly, plasma MCP-1 levels did not correlate with peripheral blood monocyte CCL2 expression. Finally, higher levels of MCP-1 were observed in the hepatic compared to the portal vein (P = 0.01) in patients receiving TIPS. Similarly, a positive correlation of MCP-1 with Child-Pugh score was observed (P = 0.018). Further, in the presence of ACLF, portal and hepatic vein levels of MCP-1 were significantly higher compared to patients without ACLF (both P = 0.039).
Conclusion: Circulating levels of MCP-1 mainly derive from the injured liver and are associated with severity of liver disease. Therefore, liver macrophages contribute significantly to disease progression. Circulating MCP-1 may reflect the extent of hepatic macrophage activation.
In relativistic heavy-ion collisions, a global spin polarization, PH, of Λ and Λ¯ hyperons along the direction of the system angular momentum was discovered and measured across a broad range of collision energies and demonstrated a trend of increasing PH with decreasing sNN−−−√. A splitting between Λ and Λ¯ polarization may be possible due to their different magnetic moments in a late-stage magnetic field sustained by the quark-gluon plasma which is formed in the collision. The results presented in this study find no significant splitting at the collision energies of sNN−−−√=19.6 and 27 GeV in the RHIC Beam Energy Scan Phase II using the STAR detector, with an upper limit of PΛ¯−PΛ<0.24% and PΛ¯−PΛ<0.35%, respectively, at a 95% confidence level. We derive an upper limit on the naïve extraction of the late-stage magnetic field of B<9.4⋅1012 T and B<1.4⋅1013 T at sNN−−−√=19.6 and 27 GeV, respectively, although more thorough derivations are needed. Differential measurements of PH were performed with respect to collision centrality, transverse momentum, and rapidity. With our current acceptance of |y|<1 and uncertainties, we observe no dependence on transverse momentum and rapidity in this analysis. These results challenge multiple existing model calculations following a variety of different assumptions which have each predicted a strong dependence on rapidity in this collision-energy range.
In relativistic heavy-ion collisions, a global spin polarization, PH, of Λ and Λ¯ hyperons along the direction of the system angular momentum was discovered and measured across a broad range of collision energies and demonstrated a trend of increasing PH with decreasing sNN−−−√. A splitting between Λ and Λ¯ polarization may be possible due to their different magnetic moments in a late-stage magnetic field sustained by the quark-gluon plasma which is formed in the collision. The results presented in this study find no significant splitting at the collision energies of sNN−−−√=19.6 and 27 GeV in the RHIC Beam Energy Scan Phase II using the STAR detector, with an upper limit of PΛ¯−PΛ<0.24% and PΛ¯−PΛ<0.35%, respectively, at a 95% confidence level. We derive an upper limit on the naïve extraction of the late-stage magnetic field of B<9.4⋅1012 T and B<1.4⋅1013 T at sNN−−−√=19.6 and 27 GeV, respectively, although more thorough derivations are needed. Differential measurements of PH were performed with respect to collision centrality, transverse momentum, and rapidity. With our current acceptance of |y|<1 and uncertainties, we observe no dependence on transverse momentum and rapidity in this analysis. These results challenge multiple existing model calculations following a variety of different assumptions which have each predicted a strong dependence on rapidity in this collision-energy range.
In relativistic heavy-ion collisions, a global spin polarization, PH, of Λ and Λ¯ hyperons along the direction of the system angular momentum was discovered and measured across a broad range of collision energies and demonstrated a trend of increasing PH with decreasing sNN−−−√. A splitting between Λ and Λ¯ polarization may be possible due to their different magnetic moments in a late-stage magnetic field sustained by the quark-gluon plasma which is formed in the collision. The results presented in this study find no significant splitting at the collision energies of sNN−−−√=19.6 and 27 GeV in the RHIC Beam Energy Scan Phase II using the STAR detector, with an upper limit of PΛ¯−PΛ<0.24% and PΛ¯−PΛ<0.35%, respectively, at a 95% confidence level. We derive an upper limit on the naïve extraction of the late-stage magnetic field of B<9.4⋅1012 T and B<1.4⋅1013 T at sNN−−−√=19.6 and 27 GeV, respectively, although more thorough derivations are needed. Differential measurements of PH were performed with respect to collision centrality, transverse momentum, and rapidity. With our current acceptance of |y|<1 and uncertainties, we observe no dependence on transverse momentum and rapidity in this analysis. These results challenge multiple existing model calculations following a variety of different assumptions which have each predicted a strong dependence on rapidity in this collision-energy range.
The transversity distribution, which describes transversely polarized quarks in transversely polarized nucleons, is a fundamental component of the spin structure of the nucleon, and is only loosely constrained by global fits to existing semi-inclusive deep inelastic scattering (SIDIS) data. In transversely polarized p↑+p collisions it can be accessed using transverse polarization dependent fragmentation functions which give rise to azimuthal correlations between the polarization of the struck parton and the final state scalar mesons.This letter reports on spin dependent di-hadron correlations measured by the STAR experiment. The new dataset corresponds to 25 pb−1 integrated luminosity of p↑+p collisions at s=500 GeV, an increase of more than a factor of ten compared to our previous measurement at s=200 GeV. Non-zero asymmetries sensitive to transversity are observed at a Q2 of several hundred GeV and are found to be consistent with the former measurement and a model calculation. We expect that these data will enable an extraction of transversity with comparable precision to current SIDIS datasets but at much higher momentum transfers where subleading effects are suppressed.
New measurements of directed flow for charged hadrons, characterized by the Fourier coefficient v1, are presented for transverse momenta pT, and centrality intervals in Au+Au collisions recorded by the STAR experiment for the center-of-mass energy range √sN N = 7.7–200 GeV. The measurements underscore the importance of momentum conservation, and the characteristic dependencies on √sN N , centrality and pT are consistent with the expectations of geometric fluctuations generated in the initial stages of the collision, acting in concert with a hydrodynamic-like expansion. The centrality and pT dependencies of veven 1 , as well as an observed similarity between its excitation function and that for v3, could serve as constraints for initial-state models. The veven 1 excitation function could also provide an important supplement to the flow measurements employed for precision extraction of the temperature dependence of the specific shear viscosity.
Elliptic flow of heavy-flavor decay electrons in Au+Au collisions at √sNN = 27 and 54.4 GeV at RHIC
(2023)
We report on new measurements of elliptic flow (v2) of electrons from heavy-flavor hadron decays at mid-rapidity (|y|<0.8) in Au+Au collisions at sNN−−−√ = 27 and 54.4 GeV from the STAR experiment. Heavy-flavor decay electrons (eHF) in Au+Au collisions at sNN−−−√ = 54.4 GeV exhibit a non-zero v2 in the transverse momentum (pT) region of pT< 2 GeV/c with the magnitude comparable to that at sNN−−−√=200 GeV. The measured eHF v2 at 54.4 GeV is also consistent with the expectation of their parent charm hadron v2 following number-of-constituent-quark scaling as other light and strange flavor hadrons at this energy. These suggest that charm quarks gain significant collectivity through the evolution of the QCD medium and may reach local thermal equilibrium in Au+Au collisions at sNN−−−√=54.4 GeV. The measured eHF v2 in Au+Au collisions at sNN−−−√= 27 GeV is consistent with zero within large uncertainties. The energy dependence of v2 for different flavor particles (π,ϕ,D0/eHF) shows an indication of quark mass hierarchy in reaching thermalization in high-energy nuclear collisions.
Elliptic flow of heavy-flavor decay electrons in Au+Au collisions at √sNN = 27 and 54.4 GeV at RHIC
(2023)
We report on new measurements of elliptic flow (v2) of electrons from heavy-flavor hadron decays at mid-rapidity (|y|<0.8) in Au+Au collisions at sNN−−−√ = 27 and 54.4 GeV from the STAR experiment. Heavy-flavor decay electrons (eHF) in Au+Au collisions at sNN−−−√ = 54.4 GeV exhibit a non-zero v2 in the transverse momentum (pT) region of pT< 2 GeV/c with the magnitude comparable to that at sNN−−−√=200 GeV. The measured eHF v2 at 54.4 GeV is also consistent with the expectation of their parent charm hadron v2 following number-of-constituent-quark scaling as other light and strange flavor hadrons at this energy. These suggest that charm quarks gain significant collectivity through the evolution of the QCD medium and may reach local thermal equilibrium in Au+Au collisions at sNN−−−√=54.4 GeV. The measured eHF v2 in Au+Au collisions at sNN−−−√= 27 GeV is consistent with zero within large uncertainties. The energy dependence of v2 for different flavor particles (π,ϕ,D0/eHF) shows an indication of quark mass hierarchy in reaching thermalization in high-energy nuclear collisions.
Density fluctuations near the QCD critical point can be probed via an intermittency analysis in relativistic heavy-ion collisions. We report the first measurement of intermittency in Au+Au collisions at sNN−−−√ = 7.7-200 GeV measured by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The scaled factorial moments of identified charged hadrons are analyzed at mid-rapidity and within the transverse momentum phase space. We observe a power-law behavior of scaled factorial moments in Au+Au collisions and a decrease in the extracted scaling exponent (ν) from peripheral to central collisions. The ν is consistent with a constant for different collisions energies in the mid-central (10-40\%) collisions. Moreover, the ν in the 0-5\% most central Au+Au collisions exhibits a non-monotonic energy dependence that reaches a possible minimum around sNN−−−√ = 27 GeV. The physics implications on the QCD phase structure are discussed.
Density fluctuations near the QCD critical point can be probed via an intermittency analysis in relativistic heavy-ion collisions. We report the first measurement of intermittency in Au+Au collisions at √sNN = 7.7-200 GeV measured by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The scaled factorial moments of identified charged hadrons are analyzed at mid-rapidity and within the transverse momentum phase space. We observe a power-law behavior of scaled factorial moments in Au+Au collisions and a decrease in the extracted scaling exponent (ν) from peripheral to central collisions. The ν is consistent with a constant for different collisions energies in the mid-central (10-40%) collisions. Moreover, the ν in the 0-5% most central Au+Au collisions exhibits a non-monotonic energy dependence that reaches a minimum around √sNN = 27 GeV. The physics implications on the QCD phase structure are discussed.
Observation of directed flow of hypernuclei Λ³H and Λ⁴H in √sNN = 3 GeV Au+Au collisions at RHIC
(2023)
We report here the first observation of directed flow (v1) of the hypernuclei 3ΛH and 4ΛH in mid-central Au+Au collisions at sNN−−−√ = 3 GeV at RHIC. These data are taken as part of the beam energy scan program carried out by the STAR experiment. From 165 × 106 events in 5%-40% centrality, about 8400 3ΛH and 5200 4ΛH candidates are reconstructed through two- and three-body decay channels. We observe that these hypernuclei exhibit significant directed flow. Comparing to that of light nuclei, it is found that the midrapidity v1 slopes of 3ΛH and 4ΛH follow baryon number scaling, implying that the coalescence is the dominant mechanism for these hypernuclei production in such collisions.
The linear and mode-coupled contributions to higher-order anisotropic flow are presented for Au+Au collisions at √sN N = 27, 39, 54.4, and 200 GeV and compared to similar measurements for Pb+Pb collisions at the Large Hadron Collider (LHC). The coefficients and the flow harmonics’ correlations, which characterize the linear and mode-coupled response to the lower-order anisotropies, indicate a beam energy dependence consistent with an influence from the specific shear viscosity (η/s). In contrast, the dimensionless coefficients, mode-coupled response coefficients, and normalized symmetric cumulants are approximately beam-energy independent, consistent with a significant role from initialstate effects. These measurements could provide unique supplemental constraints to (i) distinguish between different initial-state models and (ii) delineate the temperature (T ) and baryon chemical potential (μB ) dependence of the specific shear viscosity η s (T ,μB ).
The linear and mode-coupled contributions to higher-order anisotropic flow are presented for Au+Au collisions at sNN−−−√ = 27, 39, 54.4, and 200 GeV and compared to similar measurements for Pb+Pb collisions at the Large Hadron Collider (LHC). The coefficients and the flow harmonics' correlations, which characterize the linear and mode-coupled response to the lower-order anisotropies, indicate a beam energy dependence consistent with an influence from the specific shear viscosity (η/s). In contrast, the dimensionless coefficients, mode-coupled response coefficients, and normalized symmetric cumulants are approximately beam-energy independent, consistent with a significant role from initial-state effects. These measurements could provide unique supplemental constraints to (i) distinguish between different initial-state models and (ii) delineate the temperature (T) and baryon chemical potential (μB) dependence of the specific shear viscosity ηs(T,μB).
We measure triangular flow relative to the reaction plane at 3 GeV center-of-mass energy in Au+Au collisions at the BNL Relativistic Heavy Ion Collider. A significant v3 signal for protons is observed, which increases for higher rapidity, higher transverse momentum, and more peripheral collisions. The triangular flow is essentially rapidity-odd with a slope at mid-rapidity, dv3/dy|(y=0), opposite in sign compared to the slope for directed flow. No significant v3 signal is observed for charged pions and kaons. Comparisons with models suggest that a mean field potential is required to describe these results, and that the triangular shape of the participant nucleons is the result of stopping and nuclear geometry.