Search

Background: Pediatric-onset multiple sclerosis (POMS) represents the earliest stage of disease pathogenesis. Investigating the cerebrospinal fluid (CSF) proteome in POMS may provide novel insights into early MS processes. Objective: To analyze CSF obtained from children at time of initial central nervous system (CNS) acquired demyelinating syndrome (ADS), to compare CSF proteome of those subsequently ascertained as having POMS versus monophasic acquired demyelinating syndrome (mADS). Methods: Patients were selected from two prospective pediatric ADS studies. Liquid chromatography–mass spectrometry (LC-MS) was performed in a Dutch discovery cohort (POMS n = 28; mADS n = 39). Parallel reaction monitoring–mass spectrometry (PRM-MS) was performed on selected proteins more abundant in POMS in a combined Dutch and Canadian validation cohort (POMS n = 48; mADS n = 106). Results: Discovery identified 5580 peptides belonging to 576 proteins; 58 proteins were differentially abundant with ⩾2 peptides between POMS and mADS, of which 28 more abundant in POMS. Fourteen had increased abundance in POMS with ⩾8 unique peptides. Five selected proteins were all confirmed within validation. Adjusted for age, 2 out of 5 proteins remained more abundant in POMS, that is, Carboxypeptidase E (CPE) and Semaphorin-7A (SEMA7A). Conclusion: This exploratory study identified several CSF proteins associated with POMS and not mADS, potentially reflecting neurodegeneration, compensatory neuroprotection, and humoral response in POMS. The proteins associated with POMS highly correlated with age at CSF sampling.

To assess the feasibility of fetoscopy-guided bipolar umbilical cord coagulation for selective fetal reduction in complicated monochorionic diamniotic (MCDA) twin pregnancies.MCDA twins undergoing fetoscopy-guided bipolar cord coagulation (BCC) were enrolled prospectively between December 2015 to March 2020 in a fetal medicine center.Twenty-three cases undergoing fetoscopy-guided BCC were finally analyzed, including 11 cases for type 2 selective intrauterine growth restriction, 4 cases for twin-twin transfusion syndrome, and 8 cases for a severe discordant anomaly. The overall survival rate was 78.3% (18/23).Fetoscopy-guided BCC is effective for selective fetal reduction in complicated monochorionic twin pregnancies.

Background and purpose: Gut microbiota dysbiosis may lead to proinflammatory conditions contributing to multiple sclerosis (MS) etiology. Pediatric-onset MS patients are close to biological disease onset and less exposed to confounders. Therefore, this study investigated gut microbiota composition and functional pathways in pediatric-onset MS, compared to monophasic acquired demyelinating syndromes (mADS) and healthy controls (HCs). Methods: Pediatric participants were selected from the Dutch national prospective cohort study including ADS patients and HCs 2 = 3.7%, p = 0.013), and higher abundance of numerous individual resident microbes and functional microbial pathways. Conclusions: Previous results of gut microbiota composition and predicted functional features could not be validated in this Dutch pediatric-onset MS cohort using a more sensitive 16S pipeline, although it was limited by sample size and DMT use. Notably, several other host-related factors were found to associate with gut microbiota variation, especially BMI.

BackgroundCOVID-19 vaccination significantly reduces the risk of infection and its associated morbidity and mortality. However, poor uptake of the COVID-19 vaccination was reported among the high-risk group of older people amidst emerging variants of concern. This community case study reports an outreach program in Singapore, COVE (COVID-19 Vaccination for the Elderly) initiated by healthcare workers in a cluster of primary care clinics. They assessed the vaccine hesitancy among these older persons, addressed their concerns and facilitated their vaccination appointment during a brief phone conversation.MethodTwenty one thousand six hundred and sixty three unvaccinated adults aged ≥60 years were contacted by healthcare worker volunteers over two phases from June to October 2021. In phase I, they contacted adults aged above 70 years over 2 weeks. Adults who were uncontactable in phase I and those aged 60–69 years were sent SMS in phase II. Data were analyzed via descriptive data analysis.ResultsAfter phase 1, 65.5% (n = 5,646/8,617) of older adults had received at least one dose of the COVID-19 vaccine. The respondents expressed intention to vaccinate (39%, n = 3,390), requested to seek further information (25%, n = 2,138), reported access barrier (8%, n = 715), or were concerned of the vaccine adverse effects (3%, n = 288). Vaccination was refused by 24% (n = 2,086) of the respondents. Eventually 60.4% (n = 13,082/21,663) of them were vaccinated 3 months after COVE implementation.ConclusionThe COVE program increased the COVID-19 vaccination uptake of older adults from 84.6 to 96.3%. A person-centric proactive approach by healthcare workers addressed vaccine hesitancy and optimized vaccination. The outreach scheduling of vaccination appointments is key in promoting vaccination uptake among older adults.

Like other p38 MAPKs, C. elegans PMK-1 is activated by phosphorylation during stress responses and inactivated by phosphatases. PMK-1 initiates immune response and blocks development when hyperactivated. Here we show that PMK-1 signaling is essential for tissue homeostasis during aging. Loss of PMK-1 accelerates progressive declines in neuronal integrity and lysosome function compromising longevity. Enhancing p38 signaling with caspase cleavage-resistant PMK-1 protects lysosomal and neuronal integrity extending a youthful phase. The cleavage-resistant PMK-1 mutant behaves oppositely to the pmk-1 null in regulating both transcriptional and protein degradation programs supporting tissue homeostasis. PMK-1 activates a complex transcriptional program and requires UNC-62 (MEIS), FOS/JUN, and DAF-16 (FOXO) transcription factors to regulate lysosome formation which is both cell autonomous and non-cell autonomous. We show that during early aging the absolute phospho-p38 amount is nearly constant but maintained at a small percentage of total p38. The reservoir of non-phospho-p38 diminishes during early aging to enhance signaling without hyperactivation. CED-3 caspase cleavage limits phosphorylated PMK-1 and truncated PMK-1 is rapidly degraded by the proteasome. Modulating phospho-p38 ratio confers dynamic control for tissue-homeostasis without activating stress response to support longevity.

Supplemental material, sj-docx-3-msj-10.1177_13524585221125369 for Neurodegeneration and humoral response proteins in cerebrospinal fluid associate with pediatric-onset multiple sclerosis and not monophasic demyelinating syndromes in childhood by Arlette L Bruijstens, Christoph Stingl, Coşkun Güzel, Marcel P Stoop, Yu Yi M Wong, E Daniëlle van Pelt, Brenda L Banwell, Amit Bar-Or, Theo M Luider and Rinze F Neuteboom in Multiple Sclerosis Journal

Supplemental material, sj-docx-2-msj-10.1177_13524585221125369 for Neurodegeneration and humoral response proteins in cerebrospinal fluid associate with pediatric-onset multiple sclerosis and not monophasic demyelinating syndromes in childhood by Arlette L Bruijstens, Christoph Stingl, Coşkun Güzel, Marcel P Stoop, Yu Yi M Wong, E Daniëlle van Pelt, Brenda L Banwell, Amit Bar-Or, Theo M Luider and Rinze F Neuteboom in Multiple Sclerosis Journal

Supplemental material, sj-docx-4-msj-10.1177_13524585221125369 for Neurodegeneration and humoral response proteins in cerebrospinal fluid associate with pediatric-onset multiple sclerosis and not monophasic demyelinating syndromes in childhood by Arlette L Bruijstens, Christoph Stingl, Coşkun Güzel, Marcel P Stoop, Yu Yi M Wong, E Daniëlle van Pelt, Brenda L Banwell, Amit Bar-Or, Theo M Luider and Rinze F Neuteboom in Multiple Sclerosis Journal

Supplemental material, sj-docx-5-msj-10.1177_13524585221125369 for Neurodegeneration and humoral response proteins in cerebrospinal fluid associate with pediatric-onset multiple sclerosis and not monophasic demyelinating syndromes in childhood by Arlette L Bruijstens, Christoph Stingl, Coşkun Güzel, Marcel P Stoop, Yu Yi M Wong, E Daniëlle van Pelt, Brenda L Banwell, Amit Bar-Or, Theo M Luider and Rinze F Neuteboom in Multiple Sclerosis Journal

Supplemental material, sj-docx-1-msj-10.1177_13524585221125369 for Neurodegeneration and humoral response proteins in cerebrospinal fluid associate with pediatric-onset multiple sclerosis and not monophasic demyelinating syndromes in childhood by Arlette L Bruijstens, Christoph Stingl, Coşkun Güzel, Marcel P Stoop, Yu Yi M Wong, E Daniëlle van Pelt, Brenda L Banwell, Amit Bar-Or, Theo M Luider and Rinze F Neuteboom in Multiple Sclerosis Journal

Electronic nematicity is a ubiquitous phenomenon in iron-based superconductors but its origin is still debated. Most models consider either spin or orbital degrees of freedom as the driving force but typically do not take electronic correlations into account. However, mass enhancements, coherent-incoherent crossovers, and the strong orbital differentiation can only be understood using correlations in a Hund's metal framework. Here, we study the influence of nematicity on the quasiparticle coherence in detwinned FeSe using angle-resolved photoemission spectroscopy (ARPES). We compare photoemission spectral weight from dxz and dyz orbitals in the coherent quasiparticle peak and in the incoherent Hubbard band and find an anisotropy between the two orbitals. We interpret our observation in terms of a more coherent dxz orbital compared to the dyz orbital inside the nematic phase. This result is in contrast to earlier predictions of an incoherent dxz orbital and highlights the importance of electronic correlations in the description of nematicity.

Quasi-one-dimensional (1D) materials provide a superior platform for characterizing and tuning topological phases for two reasons: (i) existence for multiple cleavable surfaces that enables better experimental identification of topological classification and (ii) stronger response to perturbations such as strain for tuning topological phases compared to higher dimensional crystal structures. In this paper, we present experimental evidence for a room-temperature topological phase transition in the quasi-1D material Bi4I4, mediated via a first-order structural transition between two distinct stacking orders of the weakly coupled chains. Using high-resolution angle-resolved photoemission spectroscopy on the two natural cleavable surfaces, we identify the high-temperature β phase to be the first weak topological insulator with two gapless Dirac cones on the (100) surface and no Dirac crossing on the (001) surface, while in the low-temperature α phase, the topological surface state on the (100) surface opens a gap, consistent with a recent theoretical prediction of a higher-order topological insulator beyond the scope of the established topological materials databases that hosts gapless hinge states. Our results not only identify a rare topological phase transition between first-order and second-order topological insulators but also establish a novel quasi-1D material platform for exploring unprecedented physics.

Soil clay influences a range of processes, including vertical and lateral redistribution of water, runoff, and erosion. Knowledge of the spatial pattern of soil clay content (SCC) in cultivated soil region is important. The objective of this study was to determine the degree of spatial variability of SCC across depths in a cultivated black soil region in northeastern China. Data collected from each of 58 sites on a regular grid of 50 by 50 m were analyzed both statistically and geostatistically to describe the spatial distribution. The SCCs between different segments in soil profiles were significantly different. The 0- to 65-cm soil profile could be clustered into three segments: 0- to 30-cm, 30- to 35-cm, and 35- to 65-cm layers.The standard deviation (SD) and coefficients of variation (CV) for the SCC of the 30- to 35-cm segment were the largest. Experimental semivariograms of SCC were best fitted by spherical models. Nugget-to-sill ratios indicated a strong spatial dependence for SCC at other depths, except the 40- to 45-cm and 60- to 65-cm segments. The 35- to 40-cm layer had the largest spatial dependency compared with the other layers. Cross-validation of the kriging map indicated that prediction of SCC using semivariogram parameters was better than assuming the mean of the observed value for any unsampled location. The mapping displayed heterogeneity of SCC across the experimental site and revealed higher SCC close to the tail of an eroded gully and lower SCC neighbouring eroded gully margins. The fragmentation degree and clay-enriched patch amount increased from the near-surface down to 65-cm of depth, suggesting the higher evenness of SCC in the cultivated layer than that in the tillage pan.

Background Diabetes mellitus (DM) and thyroid dysfunction (TD) are two closely associated disorders. The coexistence of TD could adversely influence metabolic control and even increase the long-term mortality in patients with DM. The objective of the present study was to investigate the thyroid status and the relationship between thyroid hormones, diabetic complications and metabolic parameters in patients with newly diagnosed type 2 DM (T2DM). Methods This is an observational cross-sectional study, conducting on 340 patients with newly diagnosed T2DM who were admitted to ward of endocrinology department and 120 matched nondiabetic subjects. Clinical characteristics were collected and laboratory measurements were conducted. Results Levels of free T3 (FT3), free T4 (FT4) and TSH were significantly lower in patients with T2DM as compared to nondiabetic subjects. The prevalence of TD was 21.2% in patients with diabetes, higher than that of controls (4.2%). The low T3 syndrome was the most frequent TD, shown in 14.7% of patients. The presence of diabetic complications (diabetic nephropathy (DN), diabetic ketosis), metabolic and demographic factors, including age, glycemic control and insulin resistance were factors associated with levels of thyroid hormones. FT3 level was inversely correlated with the level of urinary total protein (mg/24h) and the presence of DN. Multivariate analysis indicated low FT3 level as a strong independent risk factor (OR = 0.364, P

ObjectiveTo explore the correlation between serum and CSF neurofilament light chain (NfL) and the association of NfL levels and future disease activity in pediatric patients with a first attack of acquired demyelinating syndromes (ADS).MethodsIn total, 102 children ResultsOf the 102 patients, 47 (46%) were tested for CSF NfL. CSF and serum NfL correlated significantly in the total group (ρ 0.532, p < 0.001) and even more significantly in the subgroup of patients with future CDMS diagnosis (ρ 0.773, p < 0.001). sNfL was higher in patients than in controls (geometric mean 6.1 pg/mL, p < 0.001), and was highest in ADS presenting with encephalopathy (acute disseminated encephalomyelitis, n = 28, 100.4 pg/mL), followed by patients without encephalopathy (ADS−) with future CDMS diagnosis (n = 40, 32.5 pg/mL), and ADS− who remained monophasic (n = 34, 17.6 pg/mL). sNfL levels higher than a median of 26.7 pg/mL at baseline are associated with a shorter time to CDMS diagnosis in ADS− (p = 0.045). HR for CDMS diagnosis was 1.09 for each 10 pg/mL increase of sNfL, after correction for age, oligoclonal bands, and MRI measures (p = 0.012).ConclusionThe significant correlation between CSF and serum NfL strengthens its reliability as a peripheral marker of neuroaxonal damage. Higher sNfL levels at baseline were associated with higher probability of future CDMS diagnosis in ADS−.

ACo2Se2 (A=K, Rb, Cs) is a homologue of the iron-based superconductor AFe2Se2. From a comprehensive study of RbCo2Se2 via measurements of magnetization, transport, neutron diffraction, angle-resolved photoemission spectroscopy, and first-principles calculations, we identify a ferromagnetic order accompanied by an orbital-dependent spin splitting of the electronic dispersions. Furthermore, we identify the ordered moment to be dominated by a dx2-y2 flat band near the Fermi level, which exhibits the largest spin splitting across the ferromagnetic transition, suggesting an itinerant origin of the ferromagnetism. In the broader context of the iron-based superconductors, we find this dx2-y2 flat band to be a common feature in the band structures of both iron chalcogenides and iron pnictides, accessible via heavy electron doping.

The lamellar cuprate superconductors exhibit the highest ambient-pressure superconducting transition temperatures (Tc), and after more than three decades of extraordinary research activity, continue to pose formidable scientific challenges. A major experimental obstacle has been to distinguish universal phenomena from materials- or technique-dependent ones. Angle-resolved photoemission spectroscopy (ARPES) measures momentum-dependent single-particle electronic excitations and has been invaluable in the endeavor to determine the anisotropic momentum-space properties of the cuprates. HgBa2CuO4+δ (Hg1201) is a single-CuO2-layer cuprate with a particularly high optimal Tc and a simple crystal structure, yet there exists little information from ARPES about the electronic properties of this model system. Here we present an ARPES study of doping-, temperature-, and momentum-dependent systematics of near-nodal dispersion anomalies in Hg1201. The data reveal a hierarchy of three distinct energy scales: a subgap low-energy kink, an intermediate-energy kink near 55 meV, and a peak-dip-hump structure. The first two features are attributed to the coupling of electrons to Ba-derived optical phonons and in-plane bond-stretching phonons, respectively. The nodal peak-dip-hump structure appears to have a common doping dependence in several single-layer cuprates and is interpreted as a manifestation of pseudogap physics at the node. These results establish several universal phenomena, both in terms of connecting multiple experimental techniques for a single material and in terms of connecting comparable spectral features in multiple structurally similar cuprates.

Nematicity, where rotational symmetry is broken while translational symmetry is conserved, is prevalent in higherature superconductors. In particular, nematic quantum critical point has been universally found near the optimum doping of the superconducting dome of several iron-based superconductor families. In such a regime, evidence for strong nematic fluctuations have been observed. As the precursor to this order, nematic fluctuations emerge before nematicity, providing favorable ground to study how nematic order modifies the electronic structure in the absence of structural distortion. Here we use spatially resolved angle-resolved photoemission spectroscopy to investigate the correlation between the onset of nematic fluctuations and electronic structure in an optimally doped BaFe2(As1-xPx)2 (x∼0.3) superconductor. We reveal a strong spatially varying anisotropy of the Fermi surface on a length scale of tens of microns with strong correlation between the changes in the hole and electron Fermi pockets, consistent with the variations expected in the presence of fluctuating nematic order. These results provide direct evidence for spatial nematic fluctuations in the optimal doping regime of iron-based superconductors.

The lamellar cuprate superconductors exhibit the highest ambient-pressure superconducting transition temperatures (T$_C$) and, after more than three decades of extraordinary research activity, continue to pose formidable scientific challenges. A major experimental obstacle has been to distinguish universal phenomena from materials- or technique-dependent ones. Angle-resolved photoemission spectroscopy (ARPES) measures momentum-dependent single-particle electronic excitations and has been invaluable in the endeavor to determine the anisotropic momentum-space properties of the cuprates. HgBa$_2$CuO$_{4+��}$ (Hg1201) is a single-CuO$_2$-layer cuprate with a particularly high optimal T$_C$ and a simple crystal structure; yet there exists little information from ARPES about the electronic properties of this model system. Here we present an ARPES study of doping-, temperature-, and momentum-dependent systematics of near-nodal dispersion anomalies in Hg1201. The data reveal a hierarchy of three distinct energy scales -a sub-gap low-energy kink, an intermediate-energy kink near 55 meV, and a peak-dip-hump structure. The first two features are attributed to the coupling of electrons to Ba-derived optical phonons and in-plane bond-stretching phonons, respectively. The nodal peak-dip-hump structure appears to have a common doping-dependence in several single-layer cuprates, and is interpreted as a manifestation of pseudogap physics at the node. These results establish several universal phenomena, both in terms of connecting multiple experimental techniques for a single material, and in terms of connecting comparable spectral features in multiple structurally similar cuprates.

The relevance of magnetic, structural, orbital, and charge degrees of freedom in the iron-based superconductors (FeSCs) and related materials occupies a central focus in condensed matter physics. While the majority of iron-based materials exhibit the same two-dimensional iron square lattice structural motif, a family of AFe2X3 (X = Se,S) compounds introduces a quasi-one-dimensional (1D) ladder motif, which resembles the two-legged spin ladder copper oxide materials. Furthermore, unlike most parent compounds of FeSCs, the members of this spin ladder family are insulators. Recently, a superconducting transition has been observed under pressure with Tc up to 24 K, similar to the pressure-induced superconductivity in the copper oxide ladder Sr14−xCaxCu24O41 material, stimulating much interest. Here, we review the magnetic, structural, and electronic properties in this family, particularly in the BaFe2X3 series tuned by pressure and by chemical substitution. The established pressure-temperature (P-T) and carrier concentration-temperature (x-T) phase diagrams in related materials provide useful information to extend the variety of high-temperature superconductors and compare with other FeSCs. We also review some essential information about analogous square lattice FeSCs.

ObjectiveTo investigate the possible human leukocyte antigen (HLA) association of both myelin oligodendrocyte glycoprotein (MOG-IgG)-associated diseases (MOGAD) and aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSDs) in the Dutch population with European ancestry to clarify similarities or differences in the immunogenetic background of both diseases.MethodsBlood samples from patients in the Dutch national MS/NMOSD expert clinic were tested for MOG-IgG and AQP4-IgG using a cell-based assay. HLA Class I and II genotyping was performed in 43 MOG-IgG–seropositive and 42 AQP4-IgG–seropositive Dutch patients with European ancestry and compared with those of 5,604 Dutch healthy blood donors.ResultsNo significant HLA association was found in MOG-IgG–seropositive patients. The AQP4-IgG–seropositive patients had a significant higher frequency of HLA-A*01 (61.9% vs 33.7%, OR 3.16, 95% CI, 1.707–5.863, p after correction [pc] = 0.0045), HLA-B*08 (61.9% vs 25.6%, OR 4.66, 95% CI, 2.513–8.643, pc < 0.0001), and HLA-DRB1*03 (51.2% vs 27.6%, OR 2.75, 95% CI, 1.495–5.042, pc = 0.0199) compared with controls.ConclusionsThe present study demonstrates differences in the immunogenetic background of MOGAD and AQP4-IgG–positive NMOSD. The strong positive association with HLA-A*01, -B*08, and -DRB1*03 is suggestive of a role of this haplotype in the etiology of AQP4-IgG–positive NMOSD in patients with European ancestry, whereas in MOGAD no evidence was found for any HLA association in these disorders.

Electronic correlation is of fundamental importance to high temperature superconductivity. Iron-based superconductors are believed to possess moderate correlation strength, which combined with their multi-orbital nature makes them a fascinating platform for the emergence of exotic phenomena. A particularly striking form is the emergence of an orbital selective Mott phase, where the localization of a subset of orbitals leads to a drastically reconstructed Fermi surface. Here, we report spectroscopic evidence of the reorganization of the Fermi surface from FeSe to FeTe as Se is substituted by Te. We uncover a particularly transparent way to visualize the localization of the $d_{xy}$ electron orbital through the suppression of its hybridization with the more coherent $d$ electron orbitals, which leads to a redistribution of the orbital-dependent spectral weight near the Fermi level. These noteworthy features of the Fermi surface are accompanied by a divergent behavior of a band renormalization in the $d_{xy}$ orbital. All of our observations are further supported by our theoretical calculations to be salient spectroscopic signatures of such a non-thermal evolution from a strongly correlated metallic phase towards an orbital-selective Mott phase in FeTe$_{1-x}$Se$_x$ as Se concentration is reduced., Comment: 11 pages, 5 figures

Importance: Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are consistently identified in a range of demyelinating disorders in adults and children. Current therapeutic strategies are largely center specific, and no treatments have been formally evaluated. Objective: To examine the clinical phenotypes, treatment responses, and outcomes of children with relapsing MOG-Ab-associated disease. Design, Setting, and Participants: This study prospectively collected demographic, clinical, and radiologic data from 102 patients from 8 countries of the EU Paediatric Demyelinating Disease Consortium from January 1, 2014, through December 31, 2016. Patients were treated according to local protocols. Main Outcomes and Measures: Annualized relapse rates (ARRs) and Expanded Disability Status Scale (EDSS) scores before and during treatment with disease-modifying drugs (DMDs). Results: A total of 102 children were identified (median [range] age, 7.0 [1.5-7.9] years; male to female ratio, 1.0:1.8; white to other race/ethnicity ratio, 3.6:1.0). Original diagnoses were neuromyelitis optica spectrum disorder (44 patients [43.1%]), acute disseminated encephalomyelitis followed by optic neuritis (20 [19.6%]), multiphasic disseminated encephalomyelitis (20 [19.6%]), and relapsing optic neuritis (18 [17.6%]). In all, 464 demyelinating events were reported. Treated patients had more relapses (median, 3.0; range, 1.0-17.0) than untreated patients (median, 1.0; range 1.0-7.0) (P = .009) and higher EDSS scores (median, 1.5; interquartile range, 0-2.5) than untreated patients (median, 1.0; interquartile range, 0-1.5) (P Conclusions and Relevance: Although commonly used to treat patients with multiple sclerosis, DMDs were not associated with clinical improvement in children with MOG-Ab-associated disease, whereas azathioprine, mycophenolate mofetil, rituximab, and particularly intravenous immunoglobulins were associated with a reduction in relapse frequency. A correct diagnosis of relapsing MOG-Ab-associated disorders is therefore important to optimize immune treatment.

Background This study aims to investigate the effect of diabetes on post-endovascular aneurysm repairs (EVARs) of abdominal aortic aneurysms (AAAs). Methods A total of 1,479 consecutive patients who underwent AAA EVAR were reviewed. The cohorts were divided based on their diabetes status and compared. Preoperative demographic and comorbidity data were analyzed using the t -test and chi-squared test, whereas post-EVAR outcomes were analyzed using Probit multivariate model, followed by Kaplan-Meier survival curve and Cox regression. Results Of our 1,479 patients, 993 met inclusion criteria. One hundred eighty-three were diabetics (18.4%) compared with 810 nondiabetics (81.6%). Coronary artery disease (CAD; diabetics: 70.49%, nondiabetics: 60.76%, P = 0.014) and hypertension (HTN; diabetics: 90.16%, nondiabetics: 79.46%, P = 0.0008) were the only comorbidities analyzed, including follow-up length, which had any significant differences between the diabetic and nondiabetic groups. Probit multivariate analysis using a combined cohort follow-up mean of 51 months showed a significant decrease in aneurysm sac enlargement in diabetic patients (diabetics: 13.11%, nondiabetics: 19.43%, model estimate: 0.3058; 95% confidence interval [CI]: 0.0486–0.5629, Pr > ChiSq = 0.0198) and trended toward significantly fewer reinterventions (diabetics: 23.50%, nondiabetics: 28.41%, model estimate: 0.1990; 95% CI: −0.0262 to 0.4243, Pr > ChiSq = 0.0833). In the Cox regressions, diabetes had a significant protective factor on reinterventions (hazard ratio [HR]: 0.697, Pr > ChiSq = 0.0151), and was trending toward significance for aneurysm sac enlargement (HR: 0.750, Pr > ChiSq = 0.1961). There was no significant difference across diabetic status in any other outcomes, including mortality and endoleak occurrence. Conclusions Although a higher proportion of diabetic patients present with HTN and CAD, they have decreased long-term rates of aneurysm sac enlargement after EVAR. As a result, this cohort trends toward a lower need for reintervention after EVAR.

Background and Objective: Fatigue and physical impairments are a major concern in children with multiple sclerosis (MS) and after acute disseminated encephalomyelitis (post-ADEM). We here aimed to evaluate the interaction between fatigue, exercise capacity, motor performance, neurological status, and quality of life (HRQoL). Methods: In this cross-sectional study, data of 38 children (MS n = 22, post-ADEM n = 16), aged 4–17 years attending our national pediatric MS center, were studied. Fatigue was measured with the Pediatric Quality of Life Multidimensional Fatigue Scale, exercise capacity with the Bruce Protocol, motor performance with the Movement Assessment Battery for Children second edition, HRQoL with the Pediatric Quality of Life Questionnaire, and extent of disability with the Expanded Disability Status Scale (EDSS). Results: Children with MS and post-ADEM experienced more fatigue ( p < 0.001), reduced exercise capacity ( p < 0.001), and impaired motor performance ( p < 0.001), despite low scores on the EDSS. Fatigue, but not the other parameters, was significantly correlated with HRQoL. Fatigue was not correlated with exercise capacity. Conclusion: We confirm the major impact of fatigue on quality of life in children with MS and post-ADEM. Fatigue was not explained by reduced exercise capacity or impaired motor performance. An important finding for clinical practice is that the low EDSS score did not reflect the poor physical functioning.

Objective Acute disseminating encephalomyelitis (ADEM) is an inflammatory demyelinating disease affecting the central nervous system and mainly occurs in young children. Children who initially presented with ADEM can be diagnosed with multiple sclerosis (MS) in case new non-encephalopathic clinical symptoms occur with new lesions on MRI at least three months after onset of ADEM. We aim to study the timing of MRI abnormalities related to the evolution of clinical symptoms in our Dutch paediatric ADEM cohort. Methods The Dutch database for acquired demyelinating syndromes (ADS) was screened for children under age eighteen fulfilling the international consensus diagnostic criteria for ADEM. Children were eligible when the first MRI was performed within the first three months after onset of clinical symptoms and at least one brain follow-up MRI was available for evaluation. Forty-two children with ADEM were included (median age four years two months). All available MRIs and medical records were assessed and categorised as ‘improved', ‘deteriorated' and ‘unchanged'. Results We found that during clinical recovery, new lesions and enlargement of existing MRI lesions occurred in the first three months in about 50% of the performed MRIs. In contrast, this was rarely seen more than three months after first onset of ADEM. Conclusion We recommend to perform a brain MRI as a reference scan three months after onset. Follow-up imaging should be compared with this scan in order to prevent an incorrect diagnosis of MS after ADEM.

We have shown that vascular surgeon- hospitalist co management resulted in improved in-hospital mortality rates. We now aim to assess the impact of the hospitalist co management service (HCS) on healthcare cost.A total of 1558 patients were divided into three cohorts and compared: 516 in 2012, 525 in 2013, and 517 in 2014. The HCS began in January 2013. Data were standardized for six vascular surgeons that were present 2012-2014. New attendings were excluded. Ten hospitalists participated. Case mix index (CMI), contribution margin, total hospital charges (THCs), length of stay (LOS), actual direct costs (ADCs), and actual variable indirect costs (AVICs) were compared. Analysis of variance with post-hoc tests, t-tests, and linear regressions were performed.THC rose by a mean difference of $14,578.31 between 2012 and 2014 (P .001) with a significant difference found between all groups during the study period (P = .0004). ADC increased more than AVIC; however, both significantly increased over time (P = .0002 and P = .014, respectively). A mean $3326.63 increase in ADC was observed from 2012 to 2014 (P .0001). AVIC only increased by an average $392.86 during the study period (P = .01). This increased cost was observed in the context of a higher CMI and longer LOS. CMI increased from 2.25 in 2012 to 2.53 in 2014 (P = .006). LOS increased by a mean 1.02 days between 2012 and 2014 (P = .016), and significantly during the study period overall (P = .018). After adjusting for CMI, LOS increases by only 0.61 days between 2012 and 2014 (P = .07). In a final regression model, THC is independently predicted by comanagement, CMI, and LOS. After adjusting for CMI and LOS, the increase in THC because of comanagement (2012 vs 2014) accounts for only $4073.08 of the total increase (P .001). During this time, 30-day readmission rates decreased by ∼7% (P = .005), while related 30-day readmission rates decreased by ∼2% (P = .32). Physician contribution margin remained unchanged over the 3-year period (P = .76). The most prevalent diagnosis-related group was consistent across all years. Variation in the principal diagnosis code was observed with the prevalence of circulatory disorders because of type II diabetes replacing atherosclerosis with gangrene as the most prevalent diagnosis in 2013 and 2014 compared with 2012.In-hospital cost is significantly higher since the start of the HCS. This surge may relate to increased CMI, LOS, and improved coding. This increase in cost may be justified as we have observed sustained reduction in in-hospital mortality and slightly improved readmission rates.

The Galinge skarn deposit, the largest iron polymetallic skarn deposit in the Qiman Tagh metallogenic belt (western China), was formed via multi-stage fluid-rock interactions. It is divided into six ore domains from east to the west. Skarn-related tourmaline is ubiquitous in the V ore domain of the Galinge deposit, occurring both in the altered basaltic andesite (Tour-I) and in the sandstone (Tour-II). The tourmaline composition in both rock types is within the dravite–uvite solid solution. Some Tour-I crystals show compositional growth zoning in which the early stage uvite cores (Gen-1) are overgrown by second-stage dravite rims (Gen-2). Some Tour-I crystals also show overgrowth rims and fracture-infilled textures (Gen-3). Some other Tour-1 tourmalines without clear growth zoning (Others) show an intermediate composition between Gen-2 and Gen-3. The varying composition of the zoned tourmalines records important information about the evolving hydrothermal fluids and host rocks. Gen-1 and Gen-2, displaying a narrow and high range of Fe 2+ /(Fe 2+ + Mg) ratios, are much more equilibrated with mafic host rocks. The alkaline (K + Na) content of tourmalines is associated with the salinities of the ore-forming fluids. The lowest Na + K content of Gen-3 indicates that it may have been equilibrated with a low-salinity fluid environment in which the concentration of metal-chlorite complexes decreased. The Gen-3 stage is considered to be the main ore-forming event. Tour-II have similar Ca/(K + Na + Ca) ratios with Gen-1 and Gen-2 ratios, which indicates that they are contemporarily formed by the same fluid as Tour-I. Through compositional comparison of the tourmalines with those from other hydrothermal deposit types, the Galinge skarn-related tourmalines are overwhelmingly controlled by the MgFe –1 substitution mechanism. This is different from the compositions of tourmalines in porphyry, VMS, and vein-greisen type deposits, which are, respectively, controlled by the Fe 3+ Al –1 , (CaMg)(NaAl) –1 and (NaMg)(□Al) –1 , and (Fe 2+ Fe 3+ )(MgAl) –1 substitution mechanisms. Different tourmaline compositions and substitution mechanisms could be used as guides for mineral exploration.

Background: A promising biomarker for axonal damage early in the disease course of multiple sclerosis (MS) is neurofilament light chain (NfL). It is unknown whether NfL has the same predictive value for MS diagnosis in children as in adults. Objective: To explore the predictive value of NfL levels in cerebrospinal fluid (CSF) for MS diagnosis in paediatric and adult clinically isolated syndrome (CIS) patients. Methods: A total of 88 adult and 65 paediatric patients with a first attack of demyelination were included and followed (mean follow up-time in adults: 62.8 months (standard deviation (SD) ±38.7 months) and 43.8 months (SD ±27.1 months) in children). Thirty control patients were also included. Lumbar puncture was done within 6 months after onset of symptoms. NfL was determined in CSF using enzyme-linked immunosorbent assay (ELISA). COX regression analyses were used to calculate hazard ratios (HR) for clinically definite multiple sclerosis (CDMS) diagnosis. Results: After adjustments for age, oligoclonal bands (OCB), and asymptomatic T2 lesions on baseline magnetic resonance imaging (MRI), increased NfL levels in both paediatric and adult CIS patients were associated with a shorter time to CDMS diagnosis (children HR = 3.7; p = 0.007, adults HR = 2.1; p = 0.032). For CIS patients with a future CDMS diagnosis, children showed higher NfL levels than adults (geometric mean 4888 vs 2156 pg/mL; p = 0.007). Conclusion: CSF NfL levels are associated with CDMS diagnosis in children and adults with CIS. This makes NfL a promising predictive marker for disease course with potential value in clinical practice.

Although tight junctions between human brain microvascular endothelial cells in the blood–brain barrier prevent molecules or cells in the bloodstream from entering the brain, in Alzheimer’s disease, peripheral blood monocytes can “open” these tight junctions and trigger subsequent transendothelial migration. However, the mechanism underlying this migration is unclear. Here, we found that the CSF2RB, but not CSF2RA, subunit of the granulocyte-macrophage colony-stimulating factor receptor was overexpressed on monocytes from Alzheimer’s disease patients. CSF2RB contributes to granulocyte-macrophage colony-stimulating factor-induced transendothelial monocyte migration. Granulocyte-macrophage colony-stimulating factor triggers human brain microvascular endothelial cells monolayer tight junction disassembly by downregulating ZO-1 expression via transcription modulation and claudin-5 expression via the ubiquitination pathway. Interestingly, intracerebral granulocyte-macrophage colony-stimulating factor blockade abolished the increased monocyte infiltration in the brains of APP/PS1 Alzheimer’s disease model mice. Our results suggest that in Alzheimer’s disease patients, high granulocyte-macrophage colony-stimulating factor levels in the brain parenchyma and cerebrospinal fluid induced blood–brain barrier opening, facilitating the infiltration of CSF2RB-expressing peripheral monocytes across blood–brain barrier and into the brain. CSF2RB might be useful as an Alzheimer’s disease biomarker. Thus, our findings will help to understand the mechanism of monocyte infiltration in Alzheimer’s disease pathogenesis.

Type V collagen (COLV) is a regulatory fibril-forming collagen. It has at least three different molecular isoforms-α1(V)2 α2(V), α1(V)3, and α1(V)α2(V)α3(V)-formed by combinations of three different polypeptide α chains-α1(V), α2(V), and α3(V). COL V is a relatively minor collagen of the extracellular matrix (ECM). Morphologically, COLV occurs as heterotypic fibrils with type I collagen (COLI), microfilaments, or 12-nm-thick fibrils. COLV is synthesized in various mesenchymal cells and its gene expression is modulated by TGF-β and growth factors. While resistant to digestion by interstitial collagenases, native and denatured COLV are degraded by metalloproteinases and gelatinases, thereby promoting ECM remodeling. COLV interacts with matrix collagens and structural proteins, conferring structural integrity to tissue scaffolds. It binds matrix macromolecules, modulating cellular behavior, and functions. COLV co-assembles with COLI into heterotypic fibrils in the cornea and skin dermis, acting as a dominant regulator of collagen fibrillogenesis. COLV deficiency is associated with loss of corneal transparency and classic Ehlers-Danlos syndrome, while COLV overexpression is found in cancer, granulation tissue, inflammation, atherosclerosis, and fibrosis of lungs, skin, kidneys, adipose tissue, and liver. COLV isoform containing the α3(V) chain is involved in mediating pancreatic islet cell functions. In the liver, COLV is a minor but regular component of the ECM. Increases in COLV are associated with both early and advanced hepatic fibrosis. The neoepitopes of COLV have been shown to be a useful noninvasive serum biomarker for assessing fibrotic progression and resolution in experimental hepatic fibrosis. COLV is multifunctional in health, disease, and fibrosis.

Neurogenic lower urinary tract dysfunction (LUTD) in multiple sclerosis (MS) is highly prevalent in adults, but has not previously been described in paediatric MS. A total of 24 consecutive children with newly diagnosed MS were prospectively assessed for bladder and bowel problems early after diagnosis. Five of 24 children (21%) showed LUTD during assessment. One of these patients did not report voiding complaints. This high prevalence of LUTD indicates that all recently diagnosed patients with paediatric MS should be evaluated early in their disease and treated for urinary problems in order to prevent potential damage to the upper urinary tract.

The photosynthetic performance of variegated leaves can be very important in the cultivation and management of variegated plants. Actinidia kolomikta (Rupr. & Maxim.) Maxim. leaves have striking color variation. To clarify the variegated leaf type and photosynthetic cost, we measured leaf structure and ultrastructure, spectral properties, chlorophyll fluorescence and net photosynthetic rate (Pn). The study was conducted in Jilin during spring, summer, and fall in 2013. Leaf anatomy and ultrastructure were observed with light and electron microscopy. Leaf reflectance and pigment content were measured with a Unispec spectrometer and high performance liquid chromatography. Photosynthetic characterization was performed with a photosynthesis system and plant efficiency analyzer. In the palisade tissue of variegated areas, intercellular spaces were found, and cells contained fewer and abnormally developed chloroplasts. Normal chloroplasts were distributed mostly in spongy tissue. The reflectance of the adaxial surface was higher in variegated leaves than in green leaves. The Pn of variegated leaves was 80 to 94% of green leaves, the maximum photosystem II efficiency of the adaxial and abaxial surfaces in variegated leaves was similar to green leaves, and the quantum use efficiency of the abaxial surface was higher than the adaxial surface in variegated leaves. These results show that the photosynthetic performance of variegated leaves was retained well. Thus, variegated leaves are not a limiting factor for cultivation and application in A. kolomikta, and do not need to be removed as parasitic leaves during cultivation and management.

Background and purpose Neuromyelitis optica spectrum disorders (NMOSDs) are a group of rare inflammatory demyelinating disorders of the central nervous system. The identification of specific antibodies directed to aquaporin 4 (AQP4-IgG) led to the distinction from multiple sclerosis. However, up to 25% of the clinically diagnosed NMO patients are seronegative for AQP4-IgG. A subgroup of these patients might be identified by antibodies directed to myelin oligodendrocyte glycoprotein (MOG-IgG). Our objective was to investigate whether the clinical characteristics of these patients differ. Methods Using a cell-based assay, samples of 61 AQP4-IgG seronegative patients and 41 AQP4-IgG seropositive patients with clinically NMOSD were analysed for the presence of MOG-IgG. Clinical characteristics of the AQP4-IgG, MOG-IgG seropositive and double seronegative NMOSD patients were compared. Results Twenty of the 61 AQP4-IgG seronegative patients tested MOG-IgG seropositive (33%). MOG-IgG seropositive patients were more frequently males in contrast to AQP4-IgG seropositive patients (55% vs. 15%, P < 0.01) and Caucasians (90% vs. 63%, P = 0.03). They more frequently presented with coincident optic neuritis and transverse myelitis (40% vs. 12%, P = 0.02) and had a monophasic disease course (70% vs. 29%, P < 0.01). AQP4-IgG seropositive patients were 2.4 times more likely to suffer from relapses compared with MOG-IgG seropositive patients (relative risk 2.4, 95% confidence interval 1.2–4.7). AQP4-IgG seropositive patients had higher Expanded Disability Status Scale levels at last follow-up (P < 0.01). Conclusion Antibodies directed to MOG identify a subgroup of AQP4-IgG seronegative NMO patients with generally a favourable monophasic disease course.

Purpose: To report an investigation of a purely endovascular procedure to address access-induced hand ischemia in dialysis patients. Case Report: Two dialysis patients presented with stage III steal syndrome consisting of severe pain and numbness in their fingers. Preoperative fistulograms distal to the anastomosis showed alternating antegrade and retrograde flow. Under ultrasound guidance, the fistula was accessed and a 4-F micropuncture sheath placed. An angled guidewire was then advanced proximally into the brachial artery. A 6-F short sheath with marker was placed followed by a 4-F straight guide catheter inserted into the proximal brachial artery. A 9-F Flair endovascular stent-graft was advanced over a 0.035-inch stiff angled Glidewire into the fistula just distal to the arterial anastomosis and deployed. Postoperatively, pain and numbness resolved in both patients immediately. Postoperative fistulograms documented antegrade flow. Access flow velocity readings decreased significantly and pulse oximetry readings increased significantly in both patients, who were followed for >6 months with no reported complications. Conclusion: These 2 cases suggest that this endovascular approach to access-induced hand ischemia may be a viable alternative to open/hybrid surgery.

Recent studies have revealed non-canonical activities of apoptotic caspases involving specific modulation of gene expression, such as limiting asymmetric divisions of stem-like cell types. Here we report that CED-3 caspase negatively regulates an epidermal p38 stress-responsive MAPK pathway to promote larval development in C. elegans. We show that PMK-1 (p38 MAPK) primes animals for encounters with hostile environments at the expense of retarding post-embryonic development. CED-3 counters this function by directly cleaving PMK-1 to promote development. Moreover, we found that CED-3 and PMK-1 oppose each other to balance developmental and stress-responsive gene expression programs. Specifically, expression of more than 300 genes is inversely regulated by CED-3 and PMK-1. Analyses of these genes showed enrichment for epidermal stress-responsive factors, including the fatty acid synthase FASN-1, anti-microbial peptides, and genes involved in lethargus states. Our findings demonstrate a non-canonical role for a caspase in promoting development by limiting epidermal stress response programs.

We report an angle-resolved photoemission spectroscopy study of the iron-based superconductor family, Ba$_{1-x}$Na$_x$Fe$_2$As$_2$. This system harbors the recently discovered double-Q magnetic order appearing in a reentrant C$_4$ phase deep within the underdoped regime of the phase diagram that is otherwise dominated by the coupled nematic phase and collinear antiferromagnetic order. From a detailed temperature-dependence study, we identify the electronic response to the nematic phase in an orbital-dependent band shift that strictly follows the rotational symmetry of the lattice and disappears when the system restores C$_4$ symmetry in the low temperature phase. In addition, we report the observation of a distinct electronic reconstruction that cannot be explained by the known electronic orders in the system.

ObjectiveTo compare the diagnostic accuracy of the McDonald 2017 vs the McDonald 2010 criteria to predict a second attack of MS (clinically definite MS [CDMS]) at the first attack of acquired demyelinating syndromes (ADS).MethodsOne hundred sixty-four children (aged ResultsAmong the 164 patients, 110 patients (67%) presented without encephalopathy (ADS–, female 63%; median age 14.8 years, IQR 11.3–16.1years) and 54 (33%) with encephalopathy (acute disseminated encephalomyelitis [ADEM], female 52%; median age 4.0 years, IQR 2.6–6.1 years). Of the 110 ADS– patients, 52 (47%) were diagnosed with CDMS within a median follow-up of 4.5 years (IQR 2.6–6.7 years). The sensitivity was higher for the 2017 criteria than for the 2010 criteria (83%; 95% CI 67–92, vs 49%; 95% CI 33–65; p < 0.001), but the specificity was lower (73%; 95% CI 59–84 vs 87%; 95% CI 74–94, p = 0.02). At baseline, 48 patients fulfilled the 2017 criteria compared with 27 patients when using the 2010 criteria. The results for children aged ConclusionsThe McDonald 2017 criteria are more sensitive than the McDonald 2010 criteria for predicting CDMS at baseline. These criteria can also be applied in children aged Classification of evidenceThis study provides Class II evidence that in children with ADS, the 2017 McDonald criteria are more sensitive but less specific than the 2010 McDonald criteria for predicting CDMS.

We focus on another kind of square-type unit nanogrids with starlike divergent extensibility. As a result, square windmill-like nanogrid WG4 have been successfully synthesized by two different kinds of fluorene-based nanosynthons, namely I-shape nanosynthon and L-shape nanosynthon synthesis method. Besides WG4, triangle and hexagon windmill-like nanogrids (WG3 and WG5) are also obtained via one-pot nanosynthesis of I-shape nanosynthon with WG3 as the main product. For the L-shape nanosynthon synthetic method, the cyclization process possesses higher selectivity, resulting to an excellent yield for WG4. In addition, two stereoisomers of the triangle nanogrids, cis-trans-WG3 and cis-cis-WG3, were separated and characterized from the single-crystal X-ray diffraction and 1H NMR analyses for getting insight into the configuration of the triangle nanogrids with the skeleton planarization for the trans-configuration and deplanarization for the cis-configuration.

© 2018 American Physical Society. We report a persistent low-energy phonon broadening around qB∼0.28 reciprocal lattice unit (r.l.u.) along the Cu-O bond direction in the high-Tc cuprate Bi2Sr2CaCu2O8+δ (Bi-2212). We show that such broadening exists both inside and outside the conventional charge-density wave (CDW) phase, via temperature-dependent measurements in both underdoped and heavily overdoped samples. Combining inelastic hard x-ray scattering, diffuse scattering, angle-resolved photoemission spectroscopy, and resonant soft x-ray scattering at the Cu L3-edge, we exclude the presence of a CDW in the heavily overdoped Bi-2212 similar to that observed in the underdoped systems. Finally, we discuss the origin of such anisotropic low-energy phonon broadening and its potential precursory role to the CDW phase in the underdoped region.

Background: Cerebrospinal fluid (CSF) levels of T-cell activation marker soluble CD27 (sCD27) are associated with subsequent disease activity after a first attack of suspected MS in adults. The predictive value for disease course in children with acquired demyelinating syndromes (ADS) is unknown. Objectives: To assess the predictive value of sCD27 levels for clinically definite multiple sclerosis (CDMS) diagnosis in childhood ADS. Methods: Children Results: A total of 94 ADS children were included (ADS with encephalopathy (ADS+) n = 33 and ADS without encephalopathy (ADS–) n = 61). Of the 61 ADS– children, 21 (48%) were diagnosed with CDMS during follow-up. At baseline, sCD27 levels were higher in patients with a future CDMS diagnosis ( n = 29) than in monophasic ADS+ ( n = 30), monophasic ADS– ( n = 28) and relapsing non-MS patients ( n = 7; p Conclusion: CSF sCD27 levels at first attack of demyelination were associated with CDMS diagnosis in children. This makes sCD27 a potential clinically relevant quantitative marker when performing routine CSF diagnostics.

We report a persistent low energy phonon broadening around qB amp; 8764;0.28 reciprocal lattice unit r.l.u. along the Cu O bond direction in the high Tc cuprate Bi2Sr2CaCu2O8 amp; 948; Bi 2212 . We show that such broadening exists both inside and outside the conventional charge density wave CDW phase, via temperature dependent measurements in both underdoped and heavily overdoped samples. Combining inelastic hard x ray scattering, diffuse scattering, angle resolved photoemission spectroscopy, and resonant soft x ray scattering at the Cu L3 edge, we exclude the presence of a CDW in the heavily overdoped Bi 2212 similar to that observed in the underdoped systems. Finally, we discuss the origin of such anisotropic low energy phonon broadening and its potential precursory role to the CDW phase in the underdoped region

BACKGROUND AND PURPOSE: Acute disseminated encephalomyelitis followed by optic neuritis (ADEM-ON) is a rare demyelinating syndrome that is different from multiple sclerosis and neuromyelitis optica spectrum disorder. The aim of this study was to describe the disease course, treatment response and outcome of children with ADEM-ON. METHODS: Children of 10 mg/day. Visual and cognitive residual deficits were common in this group. CONCLUSIONS: Acute disseminated encephalomyelitis followed by optic neuritis is an anti-MOG antibody-associated relapsing disorder that can have a heterogeneous disease course. Patients were refractory for maintenance immunosuppression and appeared to be corticosteroid-dependent. Further international collaborations are now required to unify guidelines in this difficult-to-manage group of patients.

Autotaxin is a secreted enzyme that converts extracellular lysophosphatidylcholine to lysophosphatidate (LPA). In cancers, LPA increases tumour growth, metastasis and chemoresistance by activating six G-protein coupled receptors. We examined >200 human thyroid biopsies. Autotaxin expression in metastatic deposits and primary carcinomas was four- to tenfold higher than in benign neoplasms or normal thyroid tissue. Autotaxin immunohistochemical staining was also increased in benign neoplasms with leukocytic infiltrations. Malignant tumours were distinguished from benign tumours by high tumour autotaxin, LPA levels and inflammatory mediators including IL1β, IL6, IL8, GMCSF, TNFα, CCL2, CXCL10 and platelet-derived growth factor (PDGF)-AA. We determined the mechanistic explanation for these results and revealed a vicious regulatory cycle in which LPA increased the secretion of 16 inflammatory modulators in papillary thyroid cancer cultures. Conversely, treating cancer cells with ten inflammatory cytokines and chemokines or PDGF-AA and PDGF-BB increased autotaxin secretion. We confirmed that this autotaxin/inflammatory cycle occurs in two SCID mouse models of papillary thyroid cancer by blocking LPA signalling using the autotaxin inhibitor ONO-8430506. This decreased the levels of 16 inflammatory mediators in the tumours and was accompanied by a 50–60% decrease in tumour volume. This resulted from a decreased mitotic index for the cancer cells and decreased levels of vascular endothelial growth factor and angiogenesis in the tumours. Our results demonstrate that the autotaxin/inflammatory cycle is a focal point for driving malignant thyroid tumour progression and possibly treatment resistance. Inhibiting autotaxin activity provides an effective and novel strategy for decreasing the inflammatory phenotype in thyroid carcinomas, which should complement other treatment modalities.

© 2017 American Physical Society. Inelastic neutron scattering measurements have been performed to investigate the spin waves of the quasi-one-dimensional antiferromagnetic ladder compound BaFe2S3, where a superconducting transition was observed under pressure [H. Takahashi, Nat. Mater. 14, 1008 (2015)1476-112210.1038/nmat4351; T. Yamauchi, Phys. Rev. Lett. 115, 246402 (2015)PRLTAO0031-900710.1103/PhysRevLett.115.246402]. By fitting the spherically averaged experimental data collected on a powder sample to a Heisenberg Hamiltonian, we find that the one-dimensional antiferromagnetic ladder exhibits a strong nearest-neighbor ferromagnetic exchange interaction (SJR=-71±4 meV) along the rung direction, an antiferromagnetic SJL=49±3 meV along the leg direction, and a ferromagnetic SJ2=-15±2 meV along the diagonal direction. Our data demonstrate that the antiferromagnetic spin excitations are a common characteristic for the iron-based superconductors, while specific relative values for the exchange interactions do not appear to be unique for the parent states of the superconducting materials.

The insulin hexamer is resistant to degradation and fibrillation, which makes it an important quaternary structure for its in vivo storage in Zn(2+)- and Ca(2+)-rich vesicles in the pancreas and for pharmaceutical formulations. In addition to the two Zn(2+) ions that are required for its formation, three other species, Zn-coordinating anions (e.g., Cl(-)), Ca(2+), and phenols (e.g., resorcinol), bind to the hexamer and affect the subunit conformation and stability. The contributions of these four species to the thermodynamics of insulin unfolding have been quantified by differential scanning calorimetry and thermal unfolding measurements to determine the extent and nature of their stabilization of the insulin hexamer. Both Zn(2+) and resorcinol make a significant enthalpic contribution, while Ca(2+) primarily affects the protein heat capacity (solvation) by its interactions in the central cation-binding cavity, which is modulated by the surrounding subunit conformations. Coordinating anions have a negligible effect on the stability of the hexamer, even though subunits shift to an alternate conformation when these anions bind to the Zn(2+) ions. Finally, Zn(2+) in excess of the two that are required to form the hexamer further stabilizes the protein by additional enthalpic contributions.