The growing disparity between the number of liver transplant candidates and the supply of deceased donor organs has motivated the development of living donor liver transplantation (LDLT). Over the ...last two decades, the operation has been markedly improved by innovations rendering modern results comparable with those of deceased donor liver transplantation (DDLT). However, there remains room for further innovation, particularly in adult living donor liver transplantation (ALDLT). Unlike whole‐size DDLT and pediatric LDLT, size‐mismatching between ALDLT graft and recipient body weight and changing dynamics of posttransplant allograft regeneration have remained major challenges. A better understanding of the complex surgical anatomy and physiologic differences of ALDLT helps avoid small‐for‐size graft syndrome, graft congestion from outflow obstruction and graft hypoperfusion from portal flow steal. ALDLT for high‐urgency patients (Model for End‐Stage Liver Disease score >30) can achieve results comparable to DDLT in high volume centers. Size limitations of partial grafts and donor safety issues can be overcome with dual grafts and modified right‐lobe grafts that preserve the donor's middle hepatic vein trunk. Extended application of LDLT for unresectable hepatocellular carcinoma above Milan criteria is an optional strategy at the cost of slightly compromised survival. ABO‐blood group incompatibility obstacles have been broken down by introducing a paired donor exchange program and refined peri‐operative management of ABO‐incompatible ALDLT. This review focuses on recent innovations of surgical techniques, safe donor selection, current strategies to expand ALDLT with broadened patient selection criteria and important aspects of teamwork required for success.
Expanding a successful adult living donor liver transplantation program requires a better understanding of the physiologic differences between living donor and deceased donor liver transplantation, technical innovation, broadened recipient acceptance criteria, and consistently safe donor selection criteria. Companion videos demonstrating the techniques described in this comprehensive review can be found in the AJT Video Library at amjtransplant.com.
In patients with a recent transient ischemic attack or stroke attributed to 70 to 99% stenosis of a major intracranial artery, aggressive medical management was superior to aggressive medical ...management plus percutaneous transluminal angioplasty and stenting.
Atherosclerotic intracranial arterial stenosis is one of the most common causes of stroke worldwide
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and is associated with a high risk of recurrent stroke.
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Patients with a recent transient ischemic attack (TIA) or stroke and severe stenosis (70 to 99% of the diameter of a major intracranial artery) are at particularly high risk for recurrent stroke in the territory of the stenotic artery (approximately 23% at 1 year) despite treatment with aspirin and standard management of vascular risk factors.
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Therefore, alternative therapies are urgently needed for these patients.
Two strategies have emerged for the treatment of high-risk . . .
The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (νover ¯_{e}) ...oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) νover ¯_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor νover ¯_{e} is observed in the deficit of the measured number of νover ¯_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=2.68±0.12(stat)±0.07(syst)×10^{-3} eV^{2}.
Abstract
Understanding the interplay between the inherent disorder and the correlated fluctuating-spin ground state is a key element in the search for quantum spin liquids. H
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LiIr
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O
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is ...considered to be a spin liquid that is proximate to the Kitaev-limit quantum spin liquid. Its ground state shows no magnetic order or spin freezing as expected for the spin liquid state. However, hydrogen zero-point motion and stacking faults are known to be present. The resulting bond disorder has been invoked to explain the existence of unexpected low-energy spin excitations, although data interpretation remains challenging. Here, we use resonant X-ray spectroscopies to map the collective excitations in H
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LiIr
2
O
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and characterize its magnetic state. In the low-temperature correlated state, we reveal a broad bandwidth of magnetic excitations. The central energy and the high-energy tail of the continuum are consistent with expectations for dominant ferromagnetic Kitaev interactions between dynamically fluctuating spins. Furthermore, the absence of a momentum dependence to these excitations are consistent with disorder-induced broken translational invariance. Our low-energy data and the energy and width of the crystal field excitations support an interpretation of H
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LiIr
2
O
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as a disordered topological spin liquid in close proximity to bond-disordered versions of the Kitaev quantum spin liquid.
Edge localized modes (ELMs) in high-confinement mode plasmas were completely suppressed in KSTAR by applying n=1 nonaxisymmetric magnetic perturbations. Initially, the ELMs were intensified with a ...reduction of frequency, but completely suppressed later. The electron density had an initial 10% decrease followed by a gradual increase as ELMs were suppressed. Interesting phenomena such as a saturated evolution of edge T(e) and broadband changes of magnetic fluctuations were observed, suggesting the change of edge transport by the applied magnetic perturbations.
Hierarchical hollow spheres of Fe2O3@polyaniline are fabricated by template‐free synthesis of iron oxides followed by a post in‐ and exterior construction. A combination of large surface area with ...porous structure, fast ion/electron transport, and mechanical integrity renders this material attractive as a lithium‐ion anode, showing superior rate capability and cycling performance.
Arc/Arg3.1 is required for synaptic plasticity and cognition, and mutations in this gene are linked to autism and schizophrenia. Arc bears a domain resembling retroviral/retrotransposon Gag-like ...proteins, which multimerize into a capsid that packages viral RNA. The significance of such a domain in a plasticity molecule is uncertain. Here, we report that the Drosophila Arc1 protein forms capsid-like structures that bind darc1 mRNA in neurons and is loaded into extracellular vesicles that are transferred from motorneurons to muscles. This loading and transfer depends on the darc1-mRNA 3′ untranslated region, which contains retrotransposon-like sequences. Disrupting transfer blocks synaptic plasticity, suggesting that transfer of dArc1 complexed with its mRNA is required for this function. Notably, cultured cells also release extracellular vesicles containing the Gag region of the Copia retrotransposon complexed with its own mRNA. Taken together, our results point to a trans-synaptic mRNA transport mechanism involving retrovirus-like capsids and extracellular vesicles.
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•arc1 mRNA/protein traffic across synapses via exovesicles, requiring its 3′ UTR•dArc-protein Gag binds darc1 mRNA, and the protein forms capsid-like structures•Exovesicles contain GAG-protein and Gag-encoding-mRNA of the retrotransposon Copia•Transfer of darc1 protein and/or mRNA is required for synaptic plasticity
The neuronal protein Arc is evolutionarily related to retrotransposon Gag proteins and forms virus-like capsid structures to transmit mRNA between cells in the nervous system.
Transposable elements (TEs) are genomic parasites that selfishly replicate at the expense of host fitness. Fifty years of evolutionary studies of TEs have concentrated on the deleterious genetic ...effects of TEs, such as their effects on disrupting genes and regulatory sequences. However, a flurry of recent work suggests that there is another important source of TEs' harmful effects-epigenetic silencing. Host genomes typically silence TEs by the deposition of repressive epigenetic marks. While this silencing reduces the selfish replication of TEs and should benefit hosts, a picture is emerging that the epigenetic silencing of TEs triggers inadvertent spreading of repressive marks to otherwise expressed neighboring genes, ultimately jeopardizing host fitness. In this Review, we provide a long-overdue overview of the recent genome-wide evidence for the presence and prevalence of TEs' epigenetic effects, highlighting both the similarities and differences across mammals, insects, and plants. We lay out the current understanding of the functional and fitness consequences of TEs' epigenetic effects, and propose possible influences of such effects on the evolution of both hosts and TEs themselves. These unique evolutionary consequences indicate that TEs' epigenetic effect is not only a crucial component of TE biology but could also be a significant contributor to genome function and evolution.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
This study aimed to investigate whether radiofrequency ablation (RFA) is an alternative to surgical resection for hepatocellular carcinoma (HCC) within the context of current guidelines.
...Methods
This retrospective study included patients with normal portal pressure and serum bilirubin level who initially underwent liver resection or RFA for a single HCC of maximum size 3 cm. Between‐group differences in cumulative rates of survival and recurrence specific for HCC were analysed in the entire cohort and in a propensity score‐matched cohort.
Results
A total of 604 patients were enrolled, 273 in the liver resection group and 331 in the RFA group. The 5‐ and 10‐year HCC‐specific survival rates for the resection and RFA groups were 87·6 versus 82·1 per cent and 59·0 versus 61·2 per cent respectively (P = 0·214), whereas overall 5‐ and 10‐year recurrence‐free survival rates for the corresponding groups were 60·6 versus 39·4 per cent and 37·5 versus 25·1 per cent respectively (P < 0·001). In the propensity score‐matched cohort (152 pairs), there were no differences in HCC‐specific survival (hazard ratio (HR) 1·03 for RFA versus resection; P = 0·899), whereas recurrence‐free survival again differed between the treatment groups (HR 1·75; P < 0·001). RFA was independently associated with poorer outcomes in terms of treatment‐site recurrence‐free survival (adjusted HR 1·66; P = 0·026), but not non‐treatment‐site recurrence‐free survival (adjusted HR 1·15; P = 0·354).
Conclusion
Although RFA carries a higher risk of treatment‐site recurrence than hepatic resection, it provides comparable overall survival in patients with a single small HCC without portal hypertension or a raised bilirubin level.
Good alternative in small hepatocellular carcinoma
We unveil the complex shape of a proto-supercluster at z ∼ 2.45 in the COSMOS field exploiting the synergy of both spectroscopic and photometric redshifts. Thanks to the spectroscopic redshifts of ...the VIMOS Ultra-Deep Survey (VUDS), complemented by the zCOSMOS-Deep spectroscopic sample and high-quality photometric redshifts, we compute the three-dimensional (3D) overdensity field in a volume of ∼100 × 100 × 250 comoving Mpc3 in the central region of the COSMOS field, centred at z ∼ 2.45 along the line of sight. The method relies on a two-dimensional (2D) Voronoi tessellation in overlapping redshift slices that is converted into a 3D density field, where the galaxy distribution in each slice is constructed using a statistical treatment of both spectroscopic and photometric redshifts. In this volume, we identify a proto-supercluster, dubbed “Hyperion” for its immense size and mass, which extends over a volume of ∼60 × 60 × 150 comoving Mpc3 and has an estimated total mass of ∼4.8 × 1015 M⊙. This immensely complex structure contains at least seven density peaks within 2.4 ≲ z ≲ 2.5 connected by filaments that exceed the average density of the volume. We estimate the total mass of the individual peaks, Mtot, based on their inferred average matter density, and find a range of masses from ∼0.1 × 1014 M⊙ to ∼2.7 × 1014 M⊙. By using spectroscopic members of each peak, we obtain the velocity dispersion of the galaxies in the peaks, and then their virial mass Mvir (under the strong assumption that they are virialised). The agreement between Mvir and Mtot is surprisingly good, at less than 1−2σ, considering that (almost all) the peaks are probably not yet virialised. According to the spherical collapse model, these peaks have already started or are about to start collapsing, and they are all predicted to be virialised by redshift z ∼ 0.8−1.6. We finally perform a careful comparison with the literature, given that smaller components of this proto-supercluster had previously been identified using either heterogeneous galaxy samples (Lyα emitters, sub-mm starbursting galaxies, CO emitting galaxies) or 3D Lyα forest tomography on a smaller area. With VUDS, we obtain, for the first time across the central ∼1 deg2 of the COSMOS field, a panoramic view of this large structure, that encompasses, connects, and considerably expands in a homogeneous way on all previous detections of the various sub-components. The characteristics of this exceptional proto-supercluster, its redshift, its richness over a large volume, the clear detection of its sub-components, together with the extensive multi-wavelength imaging and spectroscopy granted by the COSMOS field, provide us the unique possibility to study a rich supercluster in formation.
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