Signatures of a surface spin-orbital chiral metal.

The relation between crystal symmetries, electron correlations and electronic structure steers the formation of a large array of unconventional phases of matter, including magneto-electric loop currents and chiral magnetism1-6. The detection of such hidden orders is an important goal in condensed-matter physics. However, until now, non-standard forms of magnetism with chiral electronic ordering have been difficult to detect experimentally7. Here we develop a theory for symmetry-broken chiral ground states and propose a methodology based on circularly polarized, spin-selective, angular-resolved photoelectron spectroscopy to study them. We use the archetypal quantum material Sr2RuO4 and reveal spectroscopic signatures that, despite being subtle, can be reconciled with the formation of spin-orbital chiral currents at the surface of the material8-10. As we shed light on these chiral regimes, our findings pave the way for a deeper understanding of ordering phenomena and unconventional magnetism.

Evidence of magnetism-induced topological protection in the axion insulator candidate EuSn2P2.

We unravel the interplay of topological properties and the layered (anti)ferromagnetic ordering in EuSn2P2, using spin and chemical selective electron and X-ray spectroscopies supported by first-principle calculations. We reveal the presence of in-plane long-range ferromagnetic order triggering topological invariants and resulting in the multiple protection of topological Dirac states. We provide clear evidence that layer-dependent spin-momentum locking coexists with ferromagnetism in this material, a cohabitation that promotes EuSn2P2 as a prime candidate axion insulator for topological antiferromagnetic spintronics applications.

Evidence of Temperature-Dependent Interplay between Spin and Orbital Moment in van der Waals Ferromagnet VI3.

van der Waals materials provide a versatile toolbox for the emergence of new quantum phenomena and fabrication of functional heterostructures. Among them, the trihalide VI3 stands out for its unique magnetic and structural landscape. Here we investigate the spin and orbital magnetic degrees of freedom in the layered ferromagnet VI3 by means of temperature-dependent X-ray absorption spectroscopy and X-ray magnetic circular and linear dichroism. We detect localized electronic states and reduced magnetic dimensionality, due to electronic correlations. We furthermore provide experimental evidence of (a) an unquenched orbital magnetic moment (up to 0.66(7) µB/V atom) in the ferromagnetic state and (b) an instability of the orbital moment in the proximity of the spin reorientation transition. Our results support a coherent picture where electronic correlations give rise to a strong magnetic anisotropy and a large orbital moment and establish VI3 as a prime candidate for the study of orbital quantum effects.

Uncovering the Lowest Thickness Limit for Room-Temperature Ferromagnetism of Cr1.6Te2.

Metallic ferromagnetic transition metal dichalcogenides have emerged as important building blocks for scalable magnetic and memory applications. Downscaling such systems to the ultrathin limit is critical to integrate them into technology. Here, we achieved layer-by-layer control over the transition metal dichalcogenide Cr1.6Te2 by using pulsed laser deposition, and we uncovered the minimum critical thickness above which room-temperature magnetic order is maintained. The electronic and magnetic structures are explored experimentally and theoretically, and it is shown that the films exhibit strong in-plane magnetic anisotropy as a consequence of large spin-orbit effects. Our study elucidates both magnetic and electronic properties of Cr1.6Te2 and corroborates the importance of intercalation to tune the magnetic properties of nanoscale materials' architectures.

Crystallization kinetics of atomic crystals revealed by a single-shot and single-particle X-ray diffraction experiment.

Crystallization is a fundamental natural phenomenon and the ubiquitous physical process in materials science for the design of new materials. So far, experimental observations of the structural dynamics in crystallization have been mostly restricted to slow dynamics. We present here an exclusive way to explore the dynamics of crystallization in highly controlled conditions (i.e., in the absence of impurities acting as seeds of the crystallites) as it occurs in vacuum. We have measured the early formation stage of solid Xe nanoparticles nucleated in an expanding supercooled Xe jet by means of an X-ray diffraction experiment with 10-fs X-ray free-electron laser (XFEL) pulses. We found that the structure of Xe nanoparticles is not pure face-centered cubic (fcc), the expected stable phase, but a mixture of fcc and randomly stacked hexagonal close-packed (rhcp) structures. Furthermore, we identified the instantaneous coexistence of the comparably sized fcc and rhcp domains in single Xe nanoparticles. The observations are explained by the scenario of structural aging, in which the nanoparticles initially crystallize in the highly stacking-disordered rhcp phase and the structure later forms the stable fcc phase. The results are reminiscent of analogous observations in hard-sphere systems, indicating the universal role of the stacking-disordered phase in nucleation.

Discovery of a Magnetic Dirac System with a Large Intrinsic Nonlinear Hall Effect.

Magnetic materials exhibiting topological Dirac fermions are attracting significant attention for their promising technological potential in spintronics. In these systems, the combined effect of the spin-orbit coupling and magnetic order enables the realization of novel topological phases with exotic transport properties, including the anomalous Hall effect and magneto-chiral phenomena. Herein, we report experimental signature of topological Dirac antiferromagnetism in TaCoTe2 via angle-resolved photoelectron spectroscopy and first-principles density functional theory calculations. In particular, we find the existence of spin-orbit coupling-induced gaps at the Fermi level, consistent with the manifestation of a large intrinsic nonlinear Hall conductivity. Remarkably, we find that the latter is extremely sensitive to the orientation of the Néel vector, suggesting TaCoTe2 as a suitable candidate for the realization of non-volatile spintronic devices with an unprecedented level of intrinsic tunability.

Observation of Termination-Dependent Topological Connectivity in a Magnetic Weyl Kagome Lattice.

Engineering surfaces and interfaces of materials promises great potential in the field of heterostructures and quantum matter designers, with the opportunity to drive new many-body phases that are absent in the bulk compounds. Here, we focus on the magnetic Weyl kagome system Co3Sn2S2 and show how for the terminations of different samples the Weyl points connect differently, still preserving the bulk-boundary correspondence. Scanning tunneling microscopy has suggested such a scenario indirectly, and here, we probe the Fermiology of Co3Sn2S2 directly, by linking it to its real space surface distribution. By combining micro-ARPES and first-principles calculations, we measure the energy-momentum spectra and the Fermi surfaces of Co3Sn2S2 for different surface terminations and show the existence of topological features depending on the top-layer electronic environment. Our work helps to define a route for controlling bulk-derived topological properties by means of surface electrostatic potentials, offering a methodology for using Weyl kagome metals in responsive magnetic spintronics.

Anterior Cruciate Ligament Revision Plus Lateral Extra-Articular Procedure Results in Superior Stability and Lower Failure Rates Than Does Isolated Anterior Cruciate Ligament Revision but Shows No Difference in Patient-Reported Outcomes or Return to Sports.

PURPOSE: To determine whether comparative clinical studies demonstrate significant advantages of revision anterior cruciate ligament reconstruction (RACLR) combined with a lateral extra-articular procedure (LEAP), with respect to graft rupture rates, knee stability, return to sport rates, and patient-reported outcome measures, compared with isolated RACLR. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews & Meta-Analyses Guidelines. A PubMed search was conducted using the key words "revision anterior cruciate ligament reconstruction" combined with any of the following additional terms, "lateral extra-articular tenodesis" OR "anterolateral ligament reconstruction" OR "Lemaire." All relevant comparative clinical studies were included. Key clinical data were extracted and evaluated. RESULTS: Eight comparative studies (seven Level III studies and a one Level IV study) were identified and included. Most studies reported more favorable outcomes with combined procedures with respect to failure rates (0%-13% following RACLR+LEAP, and 4.4%-21.4% following isolated RACLR), postoperative side-to-side anteroposterior laxity difference (1.3-3.9 mm following RACLR+LEAP and 1.8-5.9 mm following isolated RACLR), and high-grade pivot shift (0%-11.1% following RACLR+LEAP and 10.2%-23.8% in patients following isolated RACLR). There were no consistent differences between isolated and combined procedures with respect to return to sport or patient-reported outcome measures. CONCLUSIONS: This systematic review demonstrates that the addition of a LEAP to RACLR was associated with an advantage with respect to ACL graft failure rates and avoidance of high-grade postoperative knee laxity across almost all included studies. LEVEL OF EVIDENCE: IV, Systematic review of level III to IV studies.

Disentangling Structural and Electronic Properties in V2O3 Thin Films: A Genuine Nonsymmetry Breaking Mott Transition.

Phase transitions are key in determining and controlling the quantum properties of correlated materials. Here, by using the combination of material synthesis and photoelectron spectroscopy, we demonstrate a genuine Mott transition undressed of any symmetry breaking side effects in the thin films of V2O3. In particular and in contrast with the bulk V2O3, we unveil the purely electronic dynamics approaching the metal-insulator transition, disentangled from the structural transformation that is prevented by the residual substrate-induced strain. On approaching the transition, the spectral signal evolves slowly over a wide temperature range, the Fermi wave-vector does not change, and the critical temperature is lower than the one reported for the bulk. Our findings are fundamental in demonstrating the universal benchmarks of a genuine nonsymmetry breaking Mott transition, extendable to a large array of correlated quantum systems, and hold promise of exploiting the metal-insulator transition by implementing V2O3 thin films in devices.

Influence of Orbital Character on the Ground State Electronic Properties in the van Der Waals Transition Metal Iodides VI3 and CrI3.

Two-dimensional van der Waals magnetic semiconductors display emergent chemical and physical properties and hold promise for novel optical, electronic and magnetic "few-layers" functionalities. Transition-metal iodides such as CrI3 and VI3 are relevant for future electronic and spintronic applications; however, detailed experimental information on their ground state electronic properties is lacking often due to their challenging chemical environment. By combining X-ray electron spectroscopies and first-principles calculations, we report a complete determination of CrI3 and VI3 electronic ground states. We show that the transition metal-induced orbital filling drives the stabilization of distinct electronic phases: a wide bandgap in CrI3 and a Mott insulating state in VI3. Comparison of surface-sensitive (angular-resolved photoemission spectroscopy) and bulk-sensitive (X-ray absorption spectroscopy) measurements in VI3 reveals a surface-only V2+ oxidation state, suggesting that ground state electronic properties are strongly influenced by dimensionality effects. Our results have direct implications in band engineering and layer-dependent properties of two-dimensional systems.

A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation.

BACKGROUND & AIMS: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values. METHODS: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. RESULTS: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups and to provide a valid comparator cohort for future clinical trials. LAY SUMMARY: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2,219 liver transplantations following controlled DCD donation in 17 centres worldwide. Donor and recipient combinations with higher risk had significantly worse outcomes. However, the use of novel organ perfusion technology helped high-risk patients achieve similar outcomes as the benchmark cohort.

Migration rate using fully covered metal stent in anastomotic strictures after liver transplantation: Results from the BASALT study group.

BACKGROUND AND STUDY AIM: The traditional endoscopic therapy of anastomotic strictures (AS) after orthotopic liver transplantation (OLT) is multiple ERCPs with the insertion of an increasing number of plastic stents side-by-side. Fully covered self-expanding metal stents (cSEMS) could be a valuable option to decrease the number of procedures needed or non-responders to plastic stents. This study aims to retrospectively analyse the results of AS endoscopic treatment by cSEMS and to identify any factors associated with its success. PATIENTS AND METHODS: Ninety-one patients (mean age 55.9 ± 7.6 SD; 73 males) from nine Italian transplantation centres, had a cSEMS positioned for post-OLT-AS between 2007 and 2017. Forty-nine (54%) patients were treated with cSEMS as a second-line treatment. RESULTS: All the procedures were successfully performed without immediate complications. After ERCP, adverse events occurred in 11% of cases (2 moderate pancreatitis and 8 cholangitis). In 49 patients (54%), cSEMSs migrated. After cSEMS removal, 46 patients (51%) needed further endoscopic (45 patients) or radiological (1 patient) treatments to solve the AS. Lastly, seven patients underwent surgery. Multivariable stepwise logistic regression showed that cSEMS migration was the only factor associated with further treatments (OR 2.6, 95% CI 1.0-6.6; p value 0.03); cSEMS implantation before 12 months from OLT was associated with stent migration (OR 5.2, 95% CI 1.7-16.0; p value 0.004). CONCLUSIONS: cSEMS appears to be a safe tool to treat AS. cSEMS migration is the main limitation to its routinary implantation and needs to be prevented, probably with the use of new generation anti-migration stents.

Sequential Use of Normothermic Regional and Ex Situ Machine Perfusion in Donation After Circulatory Death Liver Transplant.

In Italy, 20 minutes of a continuous flat line on an electrocardiogram are required for declaration of death. In the setting of donation after circulatory death (DCD), prolonged warm ischemia time prompted the introduction of abdominal normothermic regional perfusion (NRP) followed by postprocurement ex situ machine perfusion (MP). This is a retrospective review of DCD liver transplantations (LTs) performed at 2 centers using sequential NRP and ex situ MP. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, and 11 (32.4%) were discarded based on NRP parameters (n = 1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n = 9, 26.5%), or severe macroangiopathy at back-table evaluation (n = 1, 3.0%). A total of 20 grafts (58.8%; 11 uncontrolled DCDs, 9 controlled DCDs) were considered eligible for LT, procured and perfused ex situ (9 normothermic and 11 dual hypothermic MPs). In total, 18 (52.9%; 11 uncontrolled) livers were eventually transplanted. Median (interquartile range) no-flow time was 32.5 (30-39) minutes, whereas median functional warm ischemia time was 52.5 (47-74) minutes (controlled DCD), and median low-flow time was 112 minutes (105-129 minutes; uncontrolled DCD). There was no primary nonfunction, while postreperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury occurred in 5 (28%). After a median follow-up of 15.1 (9.5-22.3) months, 1 case of ischemic-type biliary lesions and 1 patient death were reported. DCD LT is feasible even with the 20-minute no-touch rule. Strict NRP and ex situ MP selection criteria are needed to optimize postoperative results.

The Role of Ex Situ Hypothermic Oxygenated Machine Perfusion and Cold Preservation Time in Extended Criteria Donation After Circulatory Death and Donation After Brain Death.

Hypothermic oxygenated machine perfusion (HOPE) has the potential to counterbalance the detrimental consequences of cold and warm ischemia time (WIT) in both donation after brain death (DBD) and donation after circulatory death (DCD). Herein we investigated the protective effects of HOPE in extended criteria donor (ECD) DBD and overextended WIT DCD grafts. The present retrospective case series included 50 livers subjected to end-ischemic HOPE or dual DHOPE in 2 liver transplantation (LT) centers from January 2018 to December 2019. All DCD donors were subjected to normothermic regional perfusion before organ procurement. Results are expressed as median (interquartile range [IQR]). In the study period, 21 grafts were derived from overextended WIT DCD donors (total WIT 54 [IQR, 40-60] minutes and 75% classified as futile), whereas 29 were from ECD DBD. A total of 3 biliary complications and 1 case of ischemia-type biliary lesion were diagnosed. The rate of early allograft dysfunction (EAD) was 20%, and those patients had higher Comprehensive Complication Index scores. Through a changing point analysis, cold preservation time >9 hours was associated with prolonged hospital stays (P = 0.02), higher rates of EAD (P = 0.009), and worst post-LT complications (P = 0.02). Logistic regression analyses indicated a significant relationship between cold preservation time and EAD. No differences were shown in terms of the early post-LT results between LTs performed with DCD and DBD. Overall, our data are fully comparable with benchmark criteria in LT. In conclusion, the application of DHOPE obtained satisfactory and promising results using ECD-DBD and overextended DCD grafts. Our findings indicate the need to reduce cold preservation time also in the setting of DHOPE, particularly for grafts showing poor quality.

Normothermic with or without hypothermic oxygenated perfusion for DCD before liver transplantation: European multicentric experience.

Grafts from donors with cardiac death (DCD) are subject to warm ischemia time (WIT) due to the no-touch-period (20 min in Italy and 5 min in France). These livers (LT) have higher rates of early allograft dysfunction (EAD), primary non-function (PNF), and ischemic cholangiopathy (IC) compared to LT from brain dead donors (DBD). Normothermic regional perfusion (NRP) is a beneficial strategy to mitigate organ damage; a further approach is the application of ex vivo hypothermic oxygenated perfusion (HOPE) after cold storage (CS). We retrospectively analyzed LTs performed from 2016 to 2019 at three transplant centers using NRP-DCD grafts: Bologna and Milan treated with HOPE (group A), Rennes preserved using CS (group B). No-flow period, total and functional WIT were significantly higher in group A than in group B (30.5±7.7 vs. 20.5±4.1; 56.5±20.4 vs. 39.1±21.6; 41.9±12.5 vs. 25.5±3.7; respectively, P < .05), without differences in the postoperative course. In particular, the two groups had similar rates of EAD (21.1% vs. 25.0%), PNF (5.3% vs. 6.3%), IC (0% vs. 12.5%, P = .112), and non-IC biliary complications (0% vs. 6.3%, P = .457), re-LT (10.5% vs.12.5%). This occurred despite a high rate of UK DCD risk score > 10 (63.2% A vs. 17.6% B, P = .000), which theoretically would make a large number of these transplants "futile." In conclusion, Italian and French groups had similar post-LT outcomes, probably related to the use of HOPE after CS in the case of long WIT.

Cost analysis of a long-term randomized controlled study in biliary duct-to-duct anastomotic stricture after liver transplantation.

Multiple plastic stent (MPS) for biliary anastomotic stricture (AS) after liver transplantation requires multiple procedures with consequent costs. To compare the success, adverse events and treatment-related costs of fully covered self-expandable metal stents (FCSEMS) versus MPS. Thirty liver transplant (LT) patients with clinically relevant naïve AS were prospectively randomized to FCSEMS or MPS, with stent numbers increased at 3-month intervals. Treatment costs per patient were calculated for endoscopic retrograde cholangiopancreatography (including all devices and stents) and overall hospital stay. Radiological success was achieved in 73% of FCSEMS (median indwelling period of 6 mos) and 93% of MPS patients (P = NS) (median period of 11 mos). AS recurrence occurred in 36% of FCSEMS and 7% of MPS patients (P = NS), and AS re-treatment was needed in 53% and 13% (P < 0.01), respectively, during follow-up of 60 (34-80) months. Stents migrated after 29% and 2.6% of FCSEMS and MPS procedures, respectively (P < 0.01). Including re-treatments, long-term clinical success was achieved in 28/30 (93%) patients. Overall treatment-related costs were similar between groups. In the subgroup of LT patients in clinical remission after first-line treatment, treatment costs were 41% lower per FCSEMS patient compared with MPS patients. FCSEMS did not perform better than MPS. FCSEMS migration increased the rate of re-treatment and costs.

Preoperative predictors of liver decompensation after mini-invasive liver resection.

BACKGROUND: Post-hepatectomy liver failure (PHLF) represents the most frequent complication after liver surgery, and the most common cause of morbidity and mortality. Aim of the study is to identify the predictors of PHLF after mini-invasive liver surgery in cirrhosis and chronic liver disease, and to develop a model for risk prediction. METHODS: The present study is a multicentric prospective cohort study on 490 consecutive patients who underwent mini-invasive liver resection from the Italian Registry of Mini-invasive Liver Surgery (I go MILS). Retrospective additional biochemical and clinical data were collected. RESULTS: On 490 patients (26.5% females), PHLF occurred in 89 patients (18.2%). The only independent predictors of PHLF were Albumin-Bilirubin (ALBI) score (OR 3.213; 95% CI 1.661-6.215; p < .0.0001) and presence of ascites (OR 3.320; 95% CI 1.468-7.508; p = 0.004). Classification and regression tree (CART) modeling led to the identification of three risk groups: PHLF occurred in 23/217 patients with ALBI grade 1 (10.6%, low risk group), in 54/254 patients with ALBI score 2 or 3 and absence of ascites (21.3%, intermediate risk group) and in 12/19 patients with ALBI score 2 or 3 and evidence of ascites (63.2%, high risk group), p < 0.0001. The three groups showed a corresponding increase in postoperative complications (20.0%, 27.5% and 66.7%), Comprehensive Complication Index (5.1 ± 11.1, 6.0 ± 10.9 and 18.8 ± 18.9) and hospital stay (6.0 ± 4.0, 6.0 ± 6.0 and 8.0 ± 5.0 days). CONCLUSION: The risk of PHLF can be stratified by determining two easily available preoperative factors: ALBI and ascites. This model of risk prediction offers an objective instrument for a correct clinical decision-making.

Concurrent Thoracic Endovascular Aortic Repair and Liver Transplant: Multidisciplinary Management of Multiple Posttraumatic Lesions.

Association of thoracic and abdominal injuries in patients with major trauma is common. Under emergency conditions, it is often difficult to promptly perform a certain diagnosis and identify treatment priorities of life-threatening lesions. We present the case of a young man with combined thoracic and abdominal injuries after a motorcycle accident. Primary evaluation through echography and X-ray showed fluid within the hepatorenal recess and an enlarged mediastinum. Volume load, blood transfusions, and vasoactive agents were initiated to sustain circulation. Despite hemodynamic instability, we decided to perform computed tomographic angiography (CTA) scan that revealed a high-grade traumatic aortic pseudoaneurysm, multiple and severe areas of liver contusion, and a small amount of hemoperitoneum, without active bleeding spots. The patient was successfully submitted to thoracic endovascular aortic repair (TEVAR). Immediately after the end of the successful TEVAR, signs of massive abdominal bleeding revealed. Immediate explorative laparotomy was performed showing massive hepatic hemorrhage. After liver packing and Pringle's maneuver, control of bleeding was lastly obtained with hemostatic devices and selective cross-clamping of the right hepatic artery. The patient was then transferred to intensive care unit where, despite absence of further hemorrhage, hemodynamic instability, anuria, severe lactic acidosis together with liver necrosis indices appeared. A new CTA demonstrated massive parenchymal disruption within the right lobe of the liver and multiple hematomas in the left lobe. Considering the high-grade lesions of the hepatic vascular tree and liver failure, patient was listed for emergency liver transplantation (LT). LT occurred few hours later, and patient's clinical conditions rapidly improved even if the subsequent clinical course was characterized by a severe fungal infection because of immunosuppression. Evaluation of life-threatening lesions and treatment priorities, availability of different excellence skills, and multidisciplinary collaboration have a key role to achieve clinical success in such severe cases.

Unveiling Oxygen Vacancy Superstructures in Reduced Anatase Thin Films.

Oxygen vacancies are known to play a crucial role in tuning the physical properties and technological applications of titanium dioxide TiO2. Over the last decades, defects in substoichiometric TiO2 have been commonly associated with the formation of TinO2n-x Magnéli phases, which are extended planar defects originating from crystallographic shear planes. By combining advanced transmission electron microscopy techniques, electron energy-loss spectroscopy and atomistic simulations, we reach new understanding of the oxygen vacancy induced structural modulations in anatase, ruling out the earlier shear-plane model. Structural modulations are instead shown to be due to the formation of oxygen vacancy superstructures that extend periodically inside the films, preserving the crystalline order of anatase. Elucidating the structure of oxygen defects in anatase is a crucial step for improving the functionalities of such material system and to engineer devices with targeted properties.

Liver transcriptomics highlights interleukin-32 as novel NAFLD-related cytokine and candidate biomarker.

OBJECTIVE: Efforts to manage non-alcoholic fatty liver disease (NAFLD) are limited by the incomplete understanding of the pathogenic mechanisms and the absence of accurate non-invasive biomarkers. The aim of this study was to identify novel NAFLD therapeutic targets andbiomarkers by conducting liver transcriptomic analysis in patients stratified by the presence of the PNPLA3 I148M genetic risk variant. DESIGN: We sequenced the hepatic transcriptome of 125 obese individuals. 'Severe NAFLD' was defined as the presence of steatohepatitis, NAFLD activity score ≥4 or fibrosis stage ≥2. The circulating levels of the most upregulated transcript, interleukin-32 (IL32), were measured by ELISA. RESULTS: Carriage of the PNPLA3 I148M variant correlated with the two major components of hepatic transcriptome variability and broadly influenced gene expression. In patients with severe NAFLD, there was an upregulation of inflammatory and lipid metabolism pathways. IL32 was the most robustly upregulated gene in the severe NAFLD group (adjusted p=1×10-6), and its expression correlated with steatosis severity, both in I148M variant carriers and non-carriers. In 77 severely obese, and in a replication cohort of 160 individuals evaluated at the hepatology service, circulating IL32 levels were associated with both NAFLD and severe NAFLD independently of aminotransferases (p<0.01 for both). A linear combination of IL32-ALT-AST showed a better performance than ALT-AST alone in NAFLD diagnosis (area under the curve=0.92 vs 0.81, p=5×10-5). CONCLUSION: Hepatic IL32 is overexpressed in NAFLD, correlates with hepatic fat and liver damage, and is detectable in the circulation, where it is independently associated with the presence and severity of NAFLD.