bluuebunny/crossref_metadata_2025 huggingface dataset:
Jahreszeitlicher Konzentrationsverlauf von Testosteron, Estron und Estronsulfat im peripheren Blut von Eselhengsten
Authors: Schuler Gerhard , Bernhardt-Welte Angelika W. , Failing Klaus , Hoffmann Bernd
Published: October 2019

Ziel Erfassung der endokrinen Hodenfunktion beim Esel (Equus asinus) im Jahresverlauf.

Material und Methodik Bei 5 Zwerg- und 4 Normaleselhengsten wurden die Konzentrationen von Testosteron (T), Estron (E1) und Estronsulfat (E1S) mittels radioimmunologischer Verfahren bestimmt.

Ergebnisse Für die Konzentrationen aller 3 Steroide ergab sich eine hochsignifikante (p < 0,0001) Abhängigkeit von der Jahreszeit. Niedrige Werte wurden in den Monaten November bis Januar, Höchstwerte in den Monaten April, Mai, Juni gemessen. Der Verlauf der E1-Konzentrationen wies die Rasse als zusätzlichen Einflussfaktor auf die Ausprägung der Saisonalität aus. Die mittlere T-Konzentration (X̅g × SF ± 1) lag bei 1,58 × 1,20 ± 1 ng/ml, die Werte schwankten zwischen 0,39 ng/ml und 5,95 ng/ml und waren damit ca. doppelt so hoch wie beim Pferdehengst. Die mit 0,10–0,17 ng/ml im unteren Messbereich liegenden E1-Konzentrationen entsprachen den beim Pferdehengst gemessenen. Die E1S-Konzentrationen lagen im Mittel bei 0,91 ± 0,23 ng/ml, sie schwankten zwischen 0,34 und 1,36 ng/ml und waren damit, orientiert an den Höchstwerten, ca. um den Faktor 300 niedriger als beim Pferdehengst.

Schlussfolgerung Die erhobenen Daten bestätigen den Esel als eine zur Gruppe der „Long Day Breeder“ gehörende Spezies. Unbeschadet der engen phylogenetischen Verwandtschaft ergeben sich hinsichtlich der Produktion von E1S erhebliche Unterschiede zwischen Pferd und Esel.

Klinische Relevanz Referenzwerte für Sexualsteroide können auch zwischen nahe verwandte Arten nicht ohne Weiteres übertragen werden.
Unilateral Adrenalectomy for Primary Bilateral Macronodular Adrenal Hyperplasia: Analysis of 71 Cases
Authors: Sheikh-Ahmad Mohammad , Dickstein Gabriel , Matter Ibrahim , Shechner Carmela , Bejar Jacob , Reut Maria , Sroka Gideon , Laniado Monica , Saiegh Leonard
Published: October 2019

Objective Primary bilateral macronodular adrenal hyperplasia (PBMAH) is characterized by benign bilateral enlarged adrenal masses, causing Cushing’s syndrome (CS). The aim of the current article is to define the role of unilateral adrenalectomy (UA) in treating patients with CS related to PBMAH.

Methods A PubMed database search was conducted to identify articles reporting UA to treat PBMAH. We also report cases of PBMAH from our medical center treated by UA.

Results A total number of 71 cases of PBMAH (62 cases reported in the literature and 9 cases from our center) are presented. Most patients were women (73.2%) and most UA involved the left side (64.3%). In most cases, the resected gland was the larger one. Following UA, 94.4% of cases had remission of hypercortisolism. Recurrence rate of CS was 19.4% and hypoadrenalism occurred in 29.6%. After UA, when the size of the remained adrenal gland was equal or greater than 3.5 cm, CS persisted in 21.4% of cases, and recurrence occurred in 27.3% of cases (after 20±9.2 months). However, when the size of the remained gland was less than 3.5 cm, CS resolved in all cases and recurrence occurred in 21.2% of cases after a long period (65.6±52.1 months). High levels of urinary free cortisol (UFC) were not correlated with post-surgical CS recurrence or persistence.

Conclusions UA leads to beneficial outcomes in patients with CS related to PBMAH, also in cases with pre-surgical elevated UFC or contralateral large gland.
Wie gefährlich ist die Kontrastmittelexposition für die Nieren? Strategien der Nephroprotektion
Authors: Erley Christiane , Siggemann Christian
Published: October 2019

Seit Einführung der kontrastmittelverstärkten Bildgebung vor mehr als 90 Jahren hat diese sowohl in diagnostischer als auch in therapeutisch-interventioneller Hinsicht einen beispiellosen Siegeszug hingelegt. Gleichzeitig wurde die Kontrastmittelexposition seit Ende der 1970er-Jahre zunehmend für akutes Nierenversagen – insbesondere von hospitalisierten Patienten – verantwortlich gemacht. In der Folge gab es eine Vielzahl von Untersuchungen zur Toxizität unterschiedlicher Kontrastmittel sowie zur Nephroprotektion mit verschiedenen Methoden und Substanzen. Neue Untersuchungen lassen sowohl die Toxizität für die Nieren als auch die bislang eingesetzten Methoden zur Nephroprotektion in einem anderen Licht erscheinen, sodass sich eine deutliche Trendwende in der Anwendung von Kontrastmitteln abzeichnet. Der folgende Artikel fasst prägnant die letzten Entwicklungen auf beiden Gebieten zusammen und gibt Empfehlungen für die Praxis im Umgang mit kontrastmittelverstärkter Bildgebung – insbesondere für nierenkranke Patienten mit bereits reduzierter glomerulärer Filtrationsrate.
Chronisch obstruktive Lungenerkrankung und koronare Herzkrankheit
Authors: Leschke Matthias
Published: October 2019

Die Diagnose einer koronaren Herzkrankheit (KHK) bei Patienten mit COPD (chronisch obstruktive Lungenerkrankung) wird häufig verspätet gestellt, da Symptome wie Dyspnoe, thorakale Schmerzen und Palpitationen sowie Herzrhythmusstörungen auf die zugrunde liegende COPD bezogen werden. Nach verschiedenen Studien ist die COPD durch ein bis zu 3-fach erhöhtes Mortalitätsrisiko gegenüber Nicht-COPD-Patienten belastet. Nach einer aktuellen Studie sind 69 % der COPD-Patienten kardiovaskulär erkrankt. So fand sich eine um 2,33 höhere Wahrscheinlichkeit einer stationären Aufnahme wegen einer kardiovaskulären Genese gegenüber Nicht-COPD-Patienten. Wesentlich dürfte dafür eine systemische Inflammation sein, die in Beziehung mit dem Ausmaß der bronchialen Obstruktion und der Air-Flow-Limitation steht und sich laborchemisch durch einen Anstieg des hochsensitiven CRP (C-reaktives Protein), aber auch der Fibrinogenkonzentration insbesondere bei akuten Exazerbationen zeigt. COPD-Patienten haben signifikant erhöhte Troponinkonzentrationen infolge eines Typ-2-Myokardinfarktes aufgrund von Hypoxie und Tachykardie, einer damit sekundären stressbedingten Myokardischämie. Demnach müssen COPD-Patienten sorgfältig bezüglich kardiovaskulärer Risikofaktoren untersucht und kardiale Komorbiditäten diagnostiziert werden.
Herzinsuffizienz, COPD und Betablocker-Therapie
Authors: Borst Mathias M.
Published: October 2019

Herzinsuffizienz und COPD sind häufig und begegnen uns vielfach gemeinsam. Jede der beiden Erkrankungen führt als Komorbidität der anderen zu einer erhöhten Morbidität und Mortalität, was eine erhöhte Aufmerksamkeit erfordert. Dies gilt in der stabilen Phase und besonders während akuter Dekompensation bzw. Exazerbation. Eine exakte Diagnostik ist notwendig. Sie sollte bei Patienten mit COPD neben klinischen Parametern EKG, Echokardiografie und die Bestimmung eines natriuretischen Peptids umfassen, bei solchen mit Herzinsuffizienz zumindest eine Spirometrie. COPD und Herzinsuffizienz werden jeweils ohne Abstriche leitliniengerecht behandelt. Eine Therapie mit kardioselektiven Betablockern aus kardiologischer Indikation darf COPD-Patienten nicht verweigert werden, wie es vielfach der Fall ist. Vielmehr verbessert sie deren Prognose signifikant.
Hämatologische Erkrankungen
Authors: Haas Rainer , Jäger Paul
Published: October 2019

Ein Umdenken bei der Diagnostik oder die Änderung bisheriger Therapiestandards – ganz gleich um welche Erkrankungen es sich handelt – erfolgt in der Regel aufgrund neuer Erkenntnisse, die auf den Ergebnissen grundlagenwissenschaftlicher Arbeiten oder klinischer Studien fußen. Um eine bisherige Standardtherapie abzulösen, müssen die Ergebnisse solcher Studien auf einer ausreichend großen Zahl von Patienten beruhen, die unter Einhaltung stringenter Einschlusskriterien in randomisierten Studien behandelt wurden. Für einen solchen Paradigmenwechsel bedarf es klarer „Evidence“, damit das Gros der Wissenschaftsgemeinde einem solchen Richtungswechsel folgt. Für das Gebiet der Hämatologie möchten wir Ihnen eine Auswahl von Publikationen für einige der häufigen hämatologischen Erkrankungen vorstellen. Dabei werden wir auf neue Diagnoseverfahren wie die „Liquid Biopsy“ eingehen, die am Beispiel eines Verlaufsmonitorings von Patienten mit myelodysplastischem Syndrom (MDS) einen großen Nutzen zeigt und damit in Zukunft eine mehr oder weniger belastende Knochenmarkspunktionen überflüssig macht. Daneben entwickeln sich auf der Grundlage von Sequenzierungsmethoden des „Next Generation Sequencings“ (NGS) Möglichkeiten, neue „molekulare Marker“ zu definieren, die zu einer Verbesserung der bisherigen Prognosescores führen. Dabei kommen auch in zunehmendem Maß Algorithmen zur Anwendung, die bioinformatisch Methoden nutzen, wie sie den „Learning machines“ der künstlichen Intelligenz entsprechen.
Early Inhibition of P-Selectin/P-Selectin Glycoprotein Ligand-1 Reduces Intimal Hyperplasia in Murine Vein Grafts through Platelet Adhesion
Authors: Tseng Chi-Nan , Chang Ya-Ting , Yen Cih-Yi , Lengquist Mariette , Kronqvist Malin , Eriksson Einar E. , Hedin Ulf
Published: October 2019

Inflammatory processes contribute to intimal hyperplasia (IH) and long-term failure of vein grafts used in bypass surgery. Leukocyte recruitment on endothelial cells of vessels during inflammation is regulated by P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1), which also mediates the interaction between platelets and endothelial cells in vein grafts transferred to arteries. However, how this pathway causes IH in vein grafts is unclear. In this study, we used a murine model of vein grafting to investigate P-selectin-mediated platelet adhesion, followed by IH. On the luminal surface of the vein graft, leukocyte recruitment occurred mainly in areas with adhered platelets rather than on endothelial cells without adherent platelets 1 hour after vein grafting. Blockage of either P-selectin or PSGL-1 reduced platelet adhesion and leukocyte recruitment on the luminal surface of vein grafts. Inhibition of the P-selectin pathway in vein grafts significantly reduced platelet-mediated leukocyte recruitment and IH of vein grafts 28 days after surgery. The study demonstrates that functional blockage of the P-selectin/PSGL-1 pathway in the early inflammatory phase after vein grafting reduced leukocyte invasion in the vein graft wall and later IH development. The findings imply an attractive early time window for prevention of vein graft failure by manipulating platelet adhesion.
Prophylaxis of Venous Thromboembolism after Hospital Discharge in Internal Medicine: Findings from the Observational FADOI-NoTEVole Study
Authors: Squizzato Alessandro , Agnelli Giancarlo , Campanini Mauro , Dentali Francesco , Agnelli Francesca , Bonizzoni Erminio , Franco Alessandro , Gallo Andrea , Gussoni Gualberto , Nitti Cinzia , Triolo Giuseppa , Valerio Antonella , Ventrella Francesco , Fontanella Andrea ,   for the FADOI-NoTEVole Study Group
Published: October 2019

Background and Aim Post-discharge prophylaxis for venous thromboembolism (VTE) is a challenging issue in patients hospitalised in Internal Medicine Units (IMUs). The aim of this study was to evaluate the frequency and the factors associated with post-discharge prophylaxis for VTE in IMUs.

Methods Multi-centre, retrospective study including consecutive patients who were admitted for any cause and discharged from an IMU.

Results Overall, 3,740 patients (mean age 74.1 ± 15.7 years) were included in the study at 38 IMUs in Italy. At discharge, the percentage of patients receiving pharmacological thromboprophylaxis was 16.0% (20.1% after excluding patients treated with anticoagulants for indications other than VTE prophylaxis). At multivariable analysis, history of ischaemic stroke, hypomobility ≥ 7 days, central venous catheter, ≥ 10 versus ≤ 5 days of hospital stay, use of corticosteroids, cancer, history of falls, availability of a caregiver, infections and age were significantly associated with thromboprophylaxis, while an inverse correlation was observed with concomitant anti-platelet drugs and platelet count < 70,000/mm3. Patients with a Padua Prediction Score ≥ 4 versus < 4 and with an IMPROVE bleeding score ≥ 7 versus < 7 more frequently received prophylaxis at discharge (31.2% vs. 10.6%, p < 0.0001, and 25.7% vs. 19.6%, p = 0.028, respectively).

Conclusion In this study, one in five patients discharged from an Italian IMU received prophylaxis for VTE. The perceived thrombotic risk is significantly related to the use of prophylaxis.
Further Insights into Developmental Brain Malformations and Leukoencephalopathy Associated with 6p25.3 Deletion
Authors: Eid Maha , Eid Ola , Hegazy Ibrahim , Girgis Marian , Mohamed Amal , Abdel-Salam Ghada M.H.
Published: October 2019

We report a new patient who presented with dysmorphic features and congenital heart disease. In addition, her brain magnetic resonance imaging revealed leukoencephalopathy, cavum septum pellucidum, perisylvian polymicrogyria, and focal occipital pachygyria. Her regular karyotype showed 46,XX add 6 (p25) due to malsegregation of a maternal balanced translocation 46,XX,t(6;7)(p25;q33) while the array-comparative genomic hybridization identified a 3.307 Mb heterozygous deletion at 6p25.3-p25.2 and 23.95 Mb duplication at 7q33-q36.3. A previous patient with the same developmental brain malformations and leukoencephalopathy with 6p25 deletion including TUBB2A and TUBB2B genes had been reported. Thus, confirming that these specific developmental brain malformations are due to TUBB2A and TUBB2B haploinsufficiency. Our report is the first to present the developmental brain malformations associated with whole gene deletions of the two tubulin genes and provide further insights into the etiology of developmental brain malformations and white matter abnormalities associated with 6p25 deletions.
Neuroimaging Spectrum of Inherited Neurotransmitter Disorders
Authors: Lim Yi Ting , Mankad Kshitij , Kinali Maria , Tan Ai Peng
Published: October 2019

Inherited neurotransmitter disorders are rare neurometabolic conditions which encompass genetic disorders of neurotransmitter metabolism or transport. The clinical manifestations of these rare disorders are often nonspecific, ranging from encephalopathies and seizures to movement disorders. As a consequence, neurotransmitter disorders are underrecognized and often misdiagnosed. Accurate and timely diagnosis is, however, of utmost importance, given the availability of therapeutic strategies. A high index of clinical suspicion and familiarity with the neuroimaging phenotypes is therefore crucial. While the imaging features of various neurotransmitter disorders often overlap and are nonspecific, imaging can be helpful in providing useful clues to guide the diagnostic algorithm for uncommon conditions in a neonate presenting with nonspecific neurological symptoms. In this review paper, we aim to bring together current knowledge of neuroimaging phenotypes associated with inherited (primary) disorders of neurotransmitter biosynthesis. Magnetic resonance imaging phenotypes of disorders of monoamine biosynthesis, primary cerebral folate deficiency, disorders of pyridoxine metabolism, disorders of gamma-aminobutyric acid metabolism, nonketotic hyperglycinemia (glycine encephalopathy), disorders of serine biosynthesis, and cerebral creatine deficiency syndrome will be discussed and illustrated with case examples.
Novel Pathogenic Variant in the Cys110 Residue: A Genotype–Phenotype Report of a Patient with Norrie Disease
Authors: Garcha Jaspreet , Jain Angita , Atwal Herjot , Sevlam Pavalan , Atwal Paldeep S.
Published: October 2019

Norrie disease is an X-linked genetic disorder caused by pathogenic mutations in the NDP. Here, we describe the clinical phenotype and genotype in a 19-week-old male infant with bilateral retinal detachment. Whole exome sequencing using available commercial methods on the proband revealed a hemizygous substitution in exon 3 of NDP, which suggests the etiology behind retinal detachment. This report not only adds to the expanding mutational spectrum of NDP-related retinopathies but also highlights the recurrence of pathogenic variants in the Cys110 residue, adding additional evidence to this residue as a potential mutational hot spot.
Time-dependent vibrational coupled cluster theory: Theory and implementation at the two-mode coupling level
Authors: Hansen Mads Bøttger , Madsen Niels Kristian , Zoccante Alberto , Christiansen Ove
Published: October 2019

Equations are derived for the time evolution of time-dependent vibrational coupled cluster (TDVCC) wave functions covering both the TDVCC ket state and the associated so-called Λ bra state. The equations are implemented in the special case of both the Hamiltonian and the cluster operator containing at most two-mode coupling terms. The nontrivial behavior of the evolution of norm, energy, and expectation values due to the nonunitary time-evolution of the nonvariational TDVCC theory is analyzed theoretically and confirmed in numerical experiments that also include time-dependent Hamiltonians. In the spirit of time-independent size-consistency analysis, the separability of both the coupled cluster and Λ states for noninteracting systems is studied. While the coupled cluster state clearly has the correct behavior, the behavior of the Λ state is more intricate, and the consequence for different properties is shown theoretically and numerically. Overall, the numerical experiments show that TDVCC in incomplete expansions gives higher accuracy than a standard linear variational wave function parameterization with the same number of independent parameters, while equivalent results are obtained for complete expansions. The efficiency of the methodology is illustrated in computations on polycyclic aromatic hydrocarbons with up to 156 modes.
Line-defect photonic crystal terahertz quantum cascade laser
Authors: Klimont A. , Ottomaniello A. , Degl’Innocenti R. , Masini L. , Bianco F. , Wu Y. , Shah Y. D. , Ren Y. , Jessop D. S. , Tredicucci A. , Beere H. E. , Ritchie D. A.
Published: October 2019

The terahertz (THz) quantum cascade laser (QCL) provides a versatile tool in a plethora of applications ranging from spectroscopy to astronomy and communications. In many of these fields, compactness, single mode frequency emission, and low threshold are highly desirable. The proposed approach, based on line defects in a photonic crystal (PhC) matrix, addresses all these features while offering unprecedented capabilities in terms of flexibility, light waveguiding, and emission directionality. Nine line-defect QCLs were realized in a triangular lattice of pillars fabricated in the laser active region (AR), centered around ∼2 THz by tuning the photonic design. A maximal 36% threshold reduction was recorded for these ultraflat dispersion line-defect QCLs in comparison to standard metal-metal QCL. The mode selectivity is an intrinsic property of the chosen fabrication design and has been achieved by lithographically scaling the dimension of the defect pillars and by acting on the PhC parameters in order to match the AR emission bandwidth. The measured line-defect QCLs emitted preferentially in the single frequency mode in the propagation direction throughout the entire dynamic range. An integrated active platform with multiple directional outputs was also fabricated as proof-of-principle to demonstrate the potential of this approach. The presented results pave the way for integrated circuitry operating in the THz regime and for fundamental studies on microcavity lasers.
Efficient and sideband-free 1H-detected 14N magic-angle spinning NMR
Authors: Hung Ivan , Gor’kov Peter , Gan Zhehong
Published: October 2019

Indirect detection via sensitive spin-1/2 nuclei like protons under magic-angle spinning (MAS) has been developed to overcome the low spectral sensitivity and resolution of 14N NMR. The 14N quadrupolar couplings cause inefficient encoding of the 14N frequency due to large frequency offsets and make the rotor-synchronization of the evolution time necessary. It is shown that 14N rf pulses longer than the rotor period can efficiently encode 14N frequencies and generate spinning sideband free spectra along the indirect dimension. Average Hamiltonian and Floquet theories in the quadrupolar jolting frame (QJF) are used to treat the spin dynamics of the spin-1 quadrupolar nucleus under long 14N rf pulses and MAS. The results show that the rf action can be described by a scaled and phase-shifted effective rf field. The large quadrupolar frequency offset becomes absent in the QJF and therefore leads to sideband-free spectra along the indirect dimension. More importantly, when a pair of long 14N rf pulses are used, the distribution of the phase shift of the effective rf field does not affect the 14N encoding for powder samples; thus, high efficiencies can be obtained. The efficient and sideband-free features are demonstrated for three 1H/14N indirectly detected experiments using long 14N pulses under fast MAS.
MicroRNA-4461 derived from bone marrow mesenchymal stem cell exosomes inhibits tumorigenesis by downregulating COPB2 expression in colorectal cancer
Authors: Chen Hui-Li , Li Jiu-Jiang , Jiang Fei , Shi Wen-Jing , Chang Ge-Yun
Published: October 2019

Colorectal cancer (CRC) is one of the main cause of cancer-related deaths. It’s reported that bone marrow mesenchymal stem cells (BMSCs) affects tumor development through secreting exosomes. This study aims to investigate the function of BMSCs-derived exosome miR-4461 in CRC. The results of qRT-PCR showed that miR-4461 expression in DLD1, HCT116 and SW480 CRC cells and CRC tissues was lower than that in FHC cells and normal tissues, respectively. And COPB2 mRNA expression was negatively correlated with miR-4461. Western blot was used to detect COPB2 protein expression. Dual-luciferase reporter assay results revealed that miR-4461 targeted COPB2. Transwell assay and CCK-8 assay demonstrated that COPB2 knockdown inhibited HCT116 and SW480 cells proliferation, migration and invasion abilities. Furthermore, BMSCs-derived exosome miR-4461 downregulated COPB2 expression and inhibited HCT116 and SW480 cells migration and invasion. The findings demonstrated that miR-4461 could be a potential target for the diagnosis and treatment of colorectal cancer.
Nucleoplasmin is a limiting component in the scaling of nuclear size with cytoplasmic volume
Authors: Chen Pan , Tomschik Miroslav , Nelson Katherine M. , Oakey John , Gatlin Jesse C. , Levy Daniel L.
Published: October 2019

How nuclear size is regulated relative to cell size is a fundamental cell biological question. Reductions in both cell and nuclear sizes during Xenopus laevis embryogenesis provide a robust scaling system to study mechanisms of nuclear size regulation. To test if the volume of embryonic cytoplasm is limiting for nuclear growth, we encapsulated gastrula-stage embryonic cytoplasm and nuclei in droplets of defined volume using microfluidics. Nuclei grew and reached new steady-state sizes as a function of cytoplasmic volume, supporting a limiting component mechanism of nuclear size control. Through biochemical fractionation, we identified the histone chaperone nucleoplasmin (Npm2) as a putative nuclear size effector. Cellular amounts of Npm2 decrease over development, and nuclear size was sensitive to Npm2 levels both in vitro and in vivo, affecting nuclear histone levels and chromatin organization. We propose that reductions in cell volume and the amounts of limiting components, such as Npm2, contribute to developmental nuclear size scaling.
Charmonium production in pp, p+Pb and Pb+Pb collisions with CMS experiment
Authors: Abdulsalam Abdulla
Published: October 2019

We report the measurements of the prompt and non-prompt J/ψ and ψ(2S) nuclear modification factors (R
AA) using pp and PbPb data and the RpPb using pPb data collected by CMS at the LHC. All measurements were performed via the dimuon decay channel. The R
AA analysis is based on PbPb and pp data samples collected at √s
NN = 5.02 TeV in 2015, corresponding to integrated luminosities of 464 μb−1 and 28 pb−1. These measurements are performed in the dimuon rapidity range of |y| < 2.4 as a function of centrality, rapidity, and transverse momentum (p
T) from p
T = 3GeV/c in the most forward region and up to 50 GeV/c. The R
pPb analysis based on pPb data, is performed for prompt J/ψ and ψ(2S) in different kinematic bins of p
T and rapidity.
Dark Matter and Neutrino Mass Models: Phenomenology of the Scalar Sector
Authors: Ahriche Amine , Nasri Salah
Published: October 2019

Many standard model (SM) extensions that are motivated by the problems of dark matter (DM) and neutrino mass and oscillations, include extra scalars. The existence of extra singlets may modify the strength of the Higgs decay (h → γγ), the Hoggs triple coupling and the electroweak phase transition (EWPT). During the EWPT dynamics gravitational waves (GWs) could be generated, and could be detected by future experiments such as DECIGO and LISA. In this work, we investigate these aspects.
Quark polarimetry with a recursive fragmentation model including the spin degree of freedom
Authors: Artru X , Belghobsi Z
Published: October 2019

Several estimators of the initial transverse polarization of a quark fragmenting into a jet are proposed and compared using Monte Carlo simulations. These are based on the simplified version of a recursive model [A. Kerbizi et al, Phys. Rev. D97, 074010 (2018)] which includes the quark spin degree of freedom.
Exotic searches with the ATLAS detector
Authors: Bawa Harinder Singh
Published: October 2019

The summary is given for the exotic, non-SUSY searches for new physics with the ATLAS detector at Large Hadron Collider(LHC). The results presented use data collected at center-of-mass energies of

s

=
13
T
e
V

, for data sets corresponding to a variety of integrated luminosities. Searches using leptons, photons, missing transverse energy, and jets are performed, as well as searches requiring custom jet and track reconstruction, and searches for so-called lepton jets. No deviations from Standard Model expectations are observed, hence constraints are placed on the phase space of available theoretical models.
Improved extraction of the up- and down-quark contributions to the nucleon electromagnetic form factors
Authors: Qattan I A , Arrington J
Published: October 2019

The nucleon (proton and neutron) electromagnetic form factors (FFs) are fundamental quantities in nuclear and elementary particle physics as they are essential ingredients needed to parametrize the internal structure of composite particles. The spatial distribution of charge and magnetization within the nucleon is encoded in the electric

G
E

(

p
,
n

)

and magnetic

G
M

(

p
,
n

)

FFs. These FFs have been extensively and precisely measured using elastic electron scattering. In addition, the combination of the proton and neutron FFs allows for the separation of the up- and down-quark contributions to the nucleon FFs. In this work, we improve on and extend to low- and high-Q
2 values our original analysis and extract the up- and down-quark contributions to the nucleon electromagnetic FFs using worldwide data. In particular, we emphasize new precise data which cover the low-Q
2 region which is sensitive to the large-scale structure of the nucleon. We compare our results to previous extractions and several recent theoretical calculations and models.
Dark Matter Searches as New Physics at the Future Circular Collider (FCC)
Authors: Naseem Safa , Nasri Salah , Soualah Rachik
Published: October 2019

We highlight the importance of the Future Circular Collider (FCC) in the search for possible Dark Matter (DM) signatures. The focus will be on well motivated Beyond the Standard Model (BSM) extensions. We consider a class of radiative neutrino mass models which extend the SM by adding heavy right handed neutrinos (RHNs), where the neutrino masses are generated at loop level. Within this class of models, the lightest RHN is considered to be stable and serves as DM candidate. We perform preliminary studies of final states which involve missing energy contributions from DM candidates to learn about the feasibility of observing these final states at the expected FCC-hh, FCC-eh and FCC-ee beam colliders. Some of our results are discussed where the topology of the the final states are analysed depending on the obtained sensitivity of the signal. The study also yields the most common promising discovery channels in exploring potential indirect DM signatures at future lepton and hadron colliders.
Quantifying inhomogeneities in the HI distributions of simulated galaxies
Authors: Al Noori Hind , Macciò Andrea V. , Dutton Aaron A. , Dixon Keri L.
Published: October 2019

The NIHAO cosmological simulations form a collection of a hundred high-resolution galaxies. We used these simulations to test the impact of stellar feedback on the morphology of the HI distribution in galaxies. We ran a subsample of twenty of the galaxies with different parameterizations of stellar feedback, looking for differences in the HI spatial distribution and morphology. We found that different feedback models do leave a signature in HI, and can potentially be compared with current and future observations. These findings can help inform future modeling efforts in the parameterization of stellar feedback in cosmological simulations of galaxy formation and evolution.
Phylogenomic insights into the Fascicularia-Ochagavia group (Bromelioideae, Bromeliaceae)
Authors: Paule Juraj , Schmickl Roswitha , Fér Tomáš , Matuszak-Renger Sabine , Halbritter Heidemarie , Zizka Georg
Published: October 2019

Ochagavia (four species) and Fascicularia (one species) form a well-supported clade of the early-diverging Bromelioideae. The two genera are morphologically similar, but they can be easily discerned on the basis of generative characters. Besides the species distributed on the Chilean mainland, the group includes O. elegans, endemic to the Robinson Crusoe Island of the Juan Fernández Islands. In previous molecular phylogenetic studies, O. elegans formed a sister clade to the remainder of Fascicularia and Ochagavia. A phylogenomic approach, including nearly complete and, in five cases, full plastomes (c. 160 kbp) and the nuclear rDNA cistron (c. 6 kbp), and scanning electron microscope (SEM) images of pollen were used to analyse relationships in the Fascicularia-Ochagavia group. Plastome and nuclear trees were largely congruent and supported previous phylogenetic analyses of O. elegans being sister to the remainder of the group. A divergent phylogenetic position was suggested for O. carnea using different organellar trees. SEM analysis of pollen supported the division of Fascicularia and Ochagavia. Evolutionary and taxonomic implications of our results are discussed.
The influence of floral variation and geographic disjunction on the evolutionary dynamics of Ronnbergia and Wittmackia (Bromeliaceae: Bromelioideae)
Authors: Aguirre-Santoro Julián , Salinas Nelson R , Michelangeli Fabián A
Published: October 2019

The Ronnbergia alliance is a lineage of two genera, Ronnbergia and Wittmackia, which diversified in three centres of distribution; the Pacific Forest, the Atlantic Forest and the Caribbean. In this study, we reconstructed the most plausible biogeographic scenario that explain the disjunct evolution of the Ronnbergia alliance in these centres of diversity. We also compared the evolutionary rate dynamics of lineage diversification and floral evolution in each of these areas. Our results suggested that the Ronnbergia alliance originated in the Atlantic Forest c. 5.2 Mya. Ronnbergia originated c. 3.5 Mya after a long-distance dispersal event to the Pacific Forest. The diversification of Wittmackia started in the Atlantic Forest, c. 3.2 Mya, and experienced more heterogeneous evolutionary rate dynamics than Ronnbergia during its radiation. In Wittmackia a long-distance dispersal from the Atlantic Forest to Jamaica gave rise to the Caribbean clade, which diversified rapidly and experienced significantly higher rates of floral evolution. This study helped in understanding how bromeliad diversification occurs differently among major centres of biodiversity. In our case, we found how the Caribbean is a much more dynamic area of diversification than the Atlantic Forest or the Pacific Forest.
Activation of both transforming growth factor-β and bone morphogenetic protein signalling pathways upon traumatic brain injury restrains pro-inflammatory and boosts tissue reparatory responses of reactive astrocytes and microglia
Authors: Divolis Georgios , Stavropoulos Athanasios , Manioudaki Maria , Apostolidou Anastasia , Doulou Athanasia , Gavriil Ariana , Dafnis Ioannis , Chroni Angeliki , Mummery Christine , Xilouri Maria , Sideras Paschalis
Published: October 2019

Various ligands and receptors of the transforming growth factor-β superfamily have been found upregulated following traumatic brain injury; however, the role of this signalling system in brain injury pathophysiology is not fully characterized. To address this, we utilized an acute stab wound brain injury model to demonstrate that hallmarks of transforming growth factor-β superfamily system activation, such as levels of phosphorylated Smads, ligands and target genes for both transforming growth factor-β and bone morphogenetic protein pathways, were upregulated within injured tissues. Using a bone morphogenetic protein-responsive reporter mouse model, we showed that activation of the bone morphogenetic protein signalling pathway involves primarily astrocytes that demarcate the wound area. Insights regarding the potential role of transforming growth factor-β superfamily activation in glia cells within the injured tissues were obtained indirectly by treating purified reactive astrocytes and microglia with bone morphogenetic protein-4 or transforming growth factor-β1 and characterizing changes in their transcriptional profiles. Astrocytes responded to both ligands with considerably overlapping profiles, whereas, microglia responded selectively to transforming growth factor-β1. Novel pathways, crucial for repair of tissue-injury and blood–brain barrier, such as activation of cholesterol biosynthesis and transport, production of axonal guidance and extracellular matrix components were upregulated by transforming growth factor-β1 and/or bone morphogenetic protein-4 in astrocytes. Moreover, both ligands in astrocytes and transforming growth factor-β1 in microglia shifted the phenotype of reactive glia cells towards the anti-inflammatory and tissue reparatory ‘A2’-like and ‘M0/M2’-like phenotypes, respectively. Increased expression of selected key components of the in vitro modulated pathways and markers of ‘A2’-like astrocytes was confirmed within the wound area, suggesting that these processes could also be modulated in situ by the integrated action of transforming growth factor-β and/or bone morphogenetic protein-mediated signalling. Collectively, our study provides a comprehensive comparative analysis of transforming growth factor-β superfamily signalling in reactive astrocytes and microglia and points towards a crucial role of both transforming growth factor-β and bone morphogenetic protein pathways in modulating the inflammatory and brain injury reparatory functions of activated glia cells.
Arsenite and cadmium promote the development of mammary tumors
Authors: Divekar Shailaja D , Li Heng-Hong , Parodi Daniela A , Ghafouri Tiffany Bita , Chen Renxiang , Cyrus Kedra , Foxworth Aaron E , Fornace Albert J , Byrne Celia , Martin Mary Beth
Published: October 2019

Previous studies demonstrate that the heavy metal cadmium and the metalloid arsenite activate estrogen receptor-alpha in breast cancer cells by forming a high-affinity complex with the ligand-binding domain of the receptor and that environmentally relevant doses of cadmium have estrogen-like activity in vivo. The present study showed that in estrogen-receptor positive cells, arsenite and cadmium increased the global expression of estrogen-responsive genes and that an environmentally relevant dose of arsenite also had estrogen-like activity in vivo. Similar to estrogens, exposure of ovariectomized animals to arsenite induced the expression of the progesterone receptor, GREB1, and c-fos in the mammary gland and the expression of complement C3, c-fos, and cyclin D1 in the uterus and the increase was blocked by the antiestrogen ICI-182,780. When virgin female animals were fed a diet, that mimics exposure to either arsenite or cadmium, and challenged with the chemical carcinogen dimethylbenzanthracene, there was an increase in the incidence of mammary tumors and a decrease in the time to tumor onset, but no difference in the total number of tumors, tumor multiplicity, or total tumor volume. Together with published results, these data showed that environmentally relevant amounts of arsenite and cadmium had estrogen-like activity in vivo and promoted mammary tumorigenesis.
Ending the Human Immunodeficiency Virus Pandemic: Optimizing the Prevention and Treatment Toolkits
Authors: Eisinger Robert W , Folkers Gregory K , Fauci Anthony S
Published: October 2019

Unprecedented basic and clinical biomedical research advances over the past 4 decades have led to the development of “toolkits” of highly effective interventions for preventing and treating human immunodeficiency virus (HIV). Despite many successes in decreasing the incidence and mortality of HIV, major challenges remain in the goal of ending the HIV pandemic in the United States and globally. Overcoming these challenges will require optimization of the implementation of existing interventions for HIV prevention and treatment together with the continued development of new and innovative approaches that can be readily utilized by individuals with HIV and those at risk of infection.
Treatment of chronic left ventricular assist device infection with local application of bacteriophages
Authors: Mulzer Johanna , Trampuz Andrej , Potapov Evgenij V
Published: October 2019

Left ventricular assist device-associated infections represent a major complication during long-term support. Driveline exit site infections harbour the risk of ascending into the pump, causing deep-seated infections. We report on the successful treatment of a chronic recurrent left ventricular assist device pump-associated infection by the local application of bacteriophages as adjunct to standard surgical and antimicrobial treatment.
3046High levels of MMP-cleaved mimecan is associated to carotid plaque stability and less future cardiovascular events
Authors: Goncalves I , Tengryd C , Nielsen S H , Genovese F , Bengtsson E , Karsdal M , Leeming D J , Nilsson J , Edsfeldt A
Published: October 2019

Introduction

The clinical consequences of atherosclerosis, myocardial infarction and stroke are the most common causes of death globally. Mimecan, a small leucine rich-repeat proteoglycan (SLRP), is cleaved by matrix metalloproteinases (MMPs) and known to be involved in collagen fibrillogenesis and angiogenesis. Circulating levels of MMP-cleaved mimecan (cMIM) has previously been identified as a marker of extracellular matrix remodelling in ApoE−/− knockout mice. The role of mimecan and its degradation in human atherosclerotic plaques has not been explored.

Purpose

We explored whether full-length mimecan and cleaved mimecan (cMIM) are associated to plaque composition and evaluated if they can predict future cardiovascular events.

Methods

Two hundred and eighteen human atherosclerotic plaques were stained for mimecan using immunohistochemistry. cMIM was measured in 202 plaque tissue homogenates using a competitive ELISA assay. Histological components (α-actin, CD68 and glycophorin A) were assessed using immunohistochemistry, neutral lipids were measured using Oil Red O and visible areas of calcium deposits were quantified. Matrix metalloproteinases (MMP-1, -2, -3, -9, -10 and -12), tissue inhibitors of matrix metalloproteinases (TIMP-1 and -2) were analysed in plaque tissue homogenates using ELISA assays and a proximity extension assay. ECM components (glycosaminoglycans, collagen and elastin) were detected with colorimetric assays and the TGF-β1, β2 and β3 were measured by a multiplex assay. Cardiovascular events were registered using national registers, patient records and telephone calls during a follow-up period of 59 months IQR (34–73).

Results

Mimecan was expressed in human atherosclerotic plaques. The expression correlated positively with neutral lipids and intraplaque hemorrhage and inversely with α-actin. In contrast cMIM correlated with α-actin and inversely with neutral lipids. cMIM correlated also with stabilizing extracellular matrix proteins elastin, collagen as well as TGF-β1, β2 and β3. Mimecan correlated to MMP-9 and cMIM correlated to MMP-2 and TIMP-2. Patient with high levels of cMIM had a lower risk of future cardiovascular events which remained significant after adjusting for risk factors (age, gender, diabetes and symptoms) in a multivariate Cox regression

Conclusion(s)

Mimecan was associated with vulnerable plaque features, whereas cMIM was related to stable plaque features. Low levels of cMIM predicted future cardiovascular events, independently of known risk factors. Taken together this suggests a possible role for mimecan and its cleavage in atherosclerosis that needs to be further explored.

Acknowledgement/Funding

Danish Research Foundation, Swedish Research Council, Swedish Heart and Lung Foundation, Skåne University Hospital and more.
3074Analyzing the regulation of a catecholamine-dependent altered cAMP signaling in a patient-specific induced pluripotent stem cell takotsubo-model
Authors: Huebscher D , Borchert T , Hasenfuss G , Nikolaev V , Streckfuss-Boemeke K
Published: October 2019

Background/Purpose

Takotsubo syndrome (TTS) is characterized by acute transient left ventricular dysfunction in the absence of obstructive coronary lesions. Although, we identified an enhanced β-adrenergic signaling and higher sensitivity to catecholamine-induced stress toxicity as mechanisms associated with the TTS phenotype in our former study, the pathogenesis of TTS is still not completely understood. Here, we aimed to prove the hypothesis of a phosphodiesterase (PDE)-dependent regulation of 3',5'-cyclic adenosine monophosphate (cAMP) signaling in TTS under catecholamine stress.

Methods and results

We generated functional TTS induced pluripotent stem cell-derived cardiomyocytes (TTS-iPSC-CMs) from 6 patients and treated the cells with catecholamines to mimic a TTS-phenotype. Using a cytosolic Förster resonance energy transfer (FRET) based cAMP sensor, we could observe that β-adrenergic receptor (β-AR) stimulations led to stronger FRET responses in the cytosol of TTS-CMs as compared to controls. Besides β-ARs, PDEs are main players involved in cAMP signaling in CMs. At basal level TTS-CM show a significantly higher PDE3A and a reduced PDE4D protein expression in the TTS-CMs compared to control. In addition, FRET experiments show that after β-AR stimulation, the strong effects of the PDE4 family in the cytosol of control cells were significantly decreased in TTS-CMs. This is in line with previously described reduced PDE4 activity in failing mouse hearts. By analyzing PDE-dependent cAMP downstream effects as PKA-dependent phosphorylation, we could show an additional increase of PLN phosphorylation (PLN-S16), especially in control, when treating iPSC-CMs with a combination of iso and PDE4 inhibitor. In contrast, in TTS-iPSC-CMs the contribution of the PDE-families PDE2, 3 or 4 to phosphorylation of PLN-S16 was increased over iso alone. This suggests that different PDEs in TTS and control are involved in functional segregation of the SERCA2a microdomain from the cytosol in terms of cAMP downstream effects. To directly address the hypothesis that local cAMP dynamics might be altered in TTS, we used a SERCA micro domain targeted FRET based cAMP sensor. In contrast to the cytosolic cAMP regulation, the PDE4 inhibitor effects in the SERCA2 micro domain were only slightly decreased in TTS. Instead, the contribution of PDE2 to local cAMP degradation was slightly increased.

Conclusion

Our data show for the first time alterations of local cAMP signaling in healthy and diseased TTS-iPSC-CMs. TTS leads to changes in PDE composition in the cytosol but not significantly in SERCA microdomain. Our results uncover a PDE-dependent altered β-adrenergic signaling as a potential disease cause. This data highlight that TTS-iPSC-CMs can be used to provide a versatile tool for evaluating new treatment options for TTS as therapeutic targets.
3076Individual patient meta-analysis of global longitudinal strain: is one normal range enough?
Authors: D'Elia N , Caselli S , Van Den Bosch A E , Kosmala W , Lancellotti P , Morris D , Muraru D , Takeuchi M , Van Grootel R W J , Villarraga H R , Marwick T H
Published: October 2019

Background

Despite over a decade of evidence, uptake of GLS into guidelines and practice has been slow. Age, BP, and software have been reported to influence GLS, and have led to uncertainty about defining the normal range (NR). As there have been software changes since the last meta-analysis, we sought to define NR in the current era.

Methods

Pubmed, Cochrane, and EMBASE were searched using the keywords “Left Ventricle”, “Normal global longitudinal strain”, and “Speckle tracking Echocardiography” and relevant synonyms from 2011. Studies were included if they reported GLS based on speckle tracking techniques, included at least 20 healthy individuals, and had up to date contact details available. Healthy was defined as lack of known disease. Platforms used included General Electric, Philips, Canon and Tomtec. The authors of 8 of the 12 studies (67% response) provided individual patient data. Linear regression was used to determine predictors of GLS.

Results

There were 2396 pts, mean age 42 years (range 18–92), weight 66±12kg, height 169±9cm, BSA 1.7±0.2m2, and SBP 120±13 mmHg. Normal range for GLS was 21.0±2.6%. In multivariable analysis age (β=-0.02, p<0.01), weight (β=-0.03, p<0.01), SBP (β=-0.01, p<0.01) and platform were associated with GLS. GLS tends to vary with extremes of age and BP (see Figure 1 and Figure 2).

GLS vs Age group

Conclusion

Extremes of age and BP may lead to low GLS, but generally, GLS is <16% is abnormal.

Acknowledgement/Funding

None