The three major axes of terrestrial ecosystem function.

The leaf economics spectrum1,2 and the global spectrum of plant forms and functions3 revealed fundamental axes of variation in plant traits, which represent different ecological strategies that are shaped by the evolutionary development of plant species2. Ecosystem functions depend on environmental conditions and the traits of species that comprise the ecological communities4. However, the axes of variation of ecosystem functions are largely unknown, which limits our understanding of how ecosystems respond as a whole to anthropogenic drivers, climate and environmental variability4,5. Here we derive a set of ecosystem functions6 from a dataset of surface gas exchange measurements across major terrestrial biomes. We find that most of the variability within ecosystem functions (71.8%) is captured by three key axes. The first axis reflects maximum ecosystem productivity and is mostly explained by vegetation structure. The second axis reflects ecosystem water-use strategies and is jointly explained by variation in vegetation height and climate. The third axis, which represents ecosystem carbon-use efficiency, features a gradient related to aridity, and is explained primarily by variation in vegetation structure. We show that two state-of-the-art land surface models reproduce the first and most important axis of ecosystem functions. However, the models tend to simulate more strongly correlated functions than those observed, which limits their ability to accurately predict the full range of responses to environmental changes in carbon, water and energy cycling in terrestrial ecosystems7,8.

2D Co-Directed Metal-Organic Networks Featuring Strong Antiferromagnetism and Perpendicular Anisotropy.

Antiferromagnetic spintronics is a rapidly emerging field with the potential to revolutionize the way information is stored and processed. One of the key challenges in this field is the development of novel 2D antiferromagnetic materials. In this paper, the first on-surface synthesis of a Co-directed metal-organic network is reported in which the Co atoms are strongly antiferromagnetically coupled, while featuring a perpendicular magnetic anisotropy. This material is a promising candidate for future antiferromagnetic spintronic devices, as it combines the advantages of 2D and metal-organic chemistry with strong antiferromagnetic order and perpendicular magnetic anisotropy.

Somatic mutational profiling and clinical impact of driver genes in Latin-Iberian medulloblastomas: Towards precision medicine.

Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity. Among the patients, 66.7% were MBSHH, 13.0% MBWNT, 7.3% MBGrp3, and 13.0% MBGrp4. Among the 63 variants found, 54% were classified as Tier I/II and 31.7% as oncogenic/likely oncogenic. We observed 33.3% of cases harboring at least one mutation. TP53 (23.2%, 16/69) was the most mutated gene, followed by PIK3CA (5.8%, 4/69), KIT (4.3%, 3/69), PDGFRA (2.9%, 2/69), EGFR (1.4%, 1/69), ERBB2 (1.4%, 1/69), and NRAS (1.4%, 1/69). Approximately 41% of MBSHH tumors exhibited mutations, TP53 (32.6%) being the most frequently mutated gene. Tier I/II and oncogenic/likely oncogenic TP53 variants were associated with relapse, progression, and lower survival rates. Potentially actionable variants in the PIK3CA and KIT genes were identified. Latin-Iberian medulloblastomas, particularly the MBSHH, exhibit higher mutation frequencies than other populations. We corroborate the TP53 mutation status as an important prognostic factor, while PIK3CA and KIT are potential therapeutic targets.

Stoichiometry-Directed Two-Level Hierarchical Growth of Lanthanide-Based Supramolecular Nanoarchitectures.

The design of a well-ordered arrangement of atoms on a solid surface has long been sought due to the envisioned applications in many different fields. On-surface synthesis of metal-organic networks is one of the most promising fabrication techniques. Hierarchical growth, which involves coordinative schemes with weaker interactions, favours the formation of extended areas with the desired complex structure. However, the control of such hierarchical growth is in its infancy, particularly for lanthanide-based architectures. Here the hierarchical growth of a Dy-based supramolecular nanoarchitecture on Au(111) is described. Such an assembly is based on a first hierarchical level of metallo-supramolecular motifs, which in a second level of hierarchy self-assemble through directional hydrogen bonds, giving rise to a periodic two-dimensional supramolecular porous network. Notably, the size of the metal-organic based tecton of the first level of hierarchy can be tailored by modifying the metal-ligand stoichiometric ratio.

Comparison of the Antibacterial Effect of Silver Nanoparticles and a Multifunctional Antimicrobial Peptide on Titanium Surface.

Titanium implantation success may be compromised by Staphylococcus aureus surface colonization and posterior infection. To avoid this issue, different strategies have been investigated to promote an antibacterial character to titanium. In this work, two antibacterial agents (silver nanoparticles and a multifunctional antimicrobial peptide) were used to coat titanium surfaces. The modulation of the nanoparticle (≈32.1 ± 9.4 nm) density on titanium could be optimized, and a sequential functionalization with both agents was achieved through a two-step functionalization method by means of surface silanization. The antibacterial character of the coating agents was assessed individually as well as combined. The results have shown that a reduction in bacteria after 4 h of incubation can be achieved on all the coated surfaces. After 24 h of incubation, however, the individual antimicrobial peptide coating was more effective than the silver nanoparticles or their combination against Staphylococcus aureus. All tested coatings were non-cytotoxic for eukaryotic cells.

USP15-USP7 Axis and UBE2T Differential Expression May Predict Pathogenesis and Poor Prognosis in De Novo Myelodysplastic Neoplasm.

The aim of this study was to evaluate the expression of USP7, USP15, UBE2O, and UBE2T genes in Myelodysplastic neoplasm (MDS) to identify possible targets of ubiquitination and deubiquitination in MDS pathobiology. To achieve this, eight datasets from the Gene Expression Omnibus (GEO) database were integrated, and the expression relationship of these genes was analyzed in 1092 MDS patients and healthy controls. Our results showed that UBE2O, UBE2T, and USP7 were upregulated in MDS patients compared with healthy individuals, but only in mononucleated cells collected from bone marrow samples (p < 0.001). In contrast, only the USP15 gene showed a downregulated expression compared with healthy individuals (p = 0.03). Additionally, the upregulation of UBE2T expression was identified in MDS patients with chromosomal abnormalities compared with patients with normal karyotypes (p = 0.0321), and the downregulation of UBE2T expression was associated with MDS hypoplastic patients (p = 0.033). Finally, the USP7 and USP15 genes were strongly correlated with MDS (r = 0.82; r2 = 0.67; p < 0.0001). These findings suggest that the differential expression of the USP15-USP7 axis and UBE2T may play an important role in controlling genomic instability and the chromosomal abnormalities that are a striking characteristic of MDS.

Upregulation in Inflammation and Collagen Expression in Perirenal but Not in Mesenteric Adipose Tissue from Diabetic Munich Wistar Frömter Rats.

Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.p.) at the start of dietary exposure (MWF-D). Phenotyping was performed at the end of treatment through determining water intake, urine excretion, and oral glucose tolerance; use of the homeostatic model assessment-insulin resistance index (HOMA-IR) evidenced the development of overt diabetes manifestation in MWF-D rats. The kidney damage markers Kim-1 and Ngal were significantly higher in MWF-D rats, as were the amounts of PRAT and MAT. A diabetes-induced upregulation in IL-1, IL-6, Tnf-α, and Tgf-ß was observed in both the PRAT and the MAT. Col1A1 was increased in the PRAT but not in the MAT of MWF-D, whereas IL-10 was lower and higher in the PRAT and the MAT, respectively. Urinary albumin excretion and blood pressure were not further increased by diabetes induction, while heart weight was higher in the MWF-D. In conclusion, our results show a proinflammatory and profibrotic in vivo environment in PRAT induced by diabetes which might be associated with kidney damage progression in the MWF strain.

Crop forcing technique and irrigation strategy modified the content and phenolic profile of cv. Tempranillo grape berries grown in a semi-arid climate.

BACKGROUND: Climate change modifies the content and phenolic profiles of grapes and wines. It is known that high temperatures, related to climate change, reduce anthocyanins and procyanidin (catechin and tannin) compounds accumulated in the berries. In recent years, with the aim of improving the phenolic composition of the berries, the technique of crop forcing has been proposed to delay grape ripening to a more favourable period of temperatures. RESULTS: In this study, crop forcing was applied to cv. Tempranillo vines on two different dates, after flowering (F1) and after fruit set (F2), and compared to a treatment control (NF, without forcing). Additionally, as a secondary factor, two irrigation strategies were established in each treatment: irrigation with no water stress, and a pre-veraison deficit irrigation. The study was carried out in three consecutive years (2017-2019). For most of the parameters analysed, no interaction was found. Therefore, for these parameters, the effect of each of these techniques was investigated independently. Regardless of the irrigation strategy, F2 berries achieved higher contents of catechins and anthocyanins than NF berries. Each year, regardless of the irrigation strategy, crop forcing increased the content of monoglucoside forms, and had a positive effect on the total content of malvidin, petunidin, delphinidin, peonidin and malvidin derivatives, but only affected acetyl and coumaryl forms in 2017. However, the effect of irrigation strategy was less significant and consistent, being more dependent on the vintage. CONCLUSION: Regardless of vine water status, crop forcing technique applied after fruit set could be used by vine growers to delay ripening of the grapes and thus achieve an increase in the anthocyanin characteristics of the grapes. © 2023 Society of Chemical Industry.

On-Surface Design of a 2D Cobalt-Organic Network Preserving Large Orbital Magnetic Moment.

The design of antiferromagnetic nanomaterials preserving large orbital magnetic moments is important to protect their functionalities against magnetic perturbations. Here, we exploit an archetype H6HOTP species for conductive metal-organic frameworks to design a Co-HOTP one-atom-thick metal-organic architecture on a Au(111) surface. Our multidisciplinary scanning probe microscopy, X-ray absorption spectroscopy, X-ray linear dichroism, and X-ray magnetic circular dichroism study, combined with density functional theory simulations, reveals the formation of a unique network design based on threefold Co+2 coordination with deprotonated ligands, which displays a large orbital magnetic moment with an orbital to effective spin moment ratio of 0.8, an in-plane easy axis of magnetization, and large magnetic anisotropy. Our simulations suggest an antiferromagnetic ground state, which is compatible with the experimental findings. Such a Co-HOTP metal-organic network exemplifies how on-surface chemistry can enable the design of field-robust antiferromagnetic materials.

Engineering Periodic Dinuclear Lanthanide-Directed Networks Featuring Tunable Energy Level Alignment and Magnetic Anisotropy by Metal Exchange.

The design of lanthanide multinuclear networks is an emerging field of research due to the potential of such materials for nanomagnetism, spintronics, and quantum information. Therefore, controlling their electronic and magnetic properties is of paramount importance to tailor the envisioned functionalities. In this work, a multidisciplinary study is presented combining scanning tunneling microscopy, scanning tunneling spectroscopy, X-ray absorption spectroscopy, X-ray linear dichroism, X-ray magnetic circular dichroism, density functional theory, and multiplet calculations, about the supramolecular assembly, electronic and magnetic properties of periodic dinuclear 2D networks based on lanthanide-pyridyl interactions on Au(111). Er- and Dy-directed assemblies feature identical structural architectures stabilized by metal-organic coordination. Notably, despite exhibiting the same +3 oxidation state, there is a shift of the energy level alignment of the unoccupied molecular orbitals between Er- and Dy-directed networks. In addition, there is a reorientation of the easy axis of magnetization and an increment of the magnetic anisotropy when the metallic center is changed from Er to Dy. Thus, the results show that it is feasible to tune the energy level alignment and magnetic anisotropy of a lanthanide-based metal-organic architecture by metal exchange, while preserving the network design.

Xq27.1 palindrome mediated interchromosomal insertion likely causes familial congenital bilateral laryngeal abductor paralysis (Plott syndrome).

Bilateral laryngeal abductor paralysis is a rare entity and the second most common cause of stridor in newborns. So far, no conclusive genetic or chromosomal aberration has been reported for X-linked isolated bilateral vocal cord paralysis, also referred to as Plott syndrome. Via whole genome sequencing (WGS), we identified a complex interchromosomal insertion in a large family with seven affected males. The 404 kb inserted fragment originates from chromosome 10q21.3, contains no genes and is inserted inversionally into the intergenic chromosomal region Xq27.1, 82 kb centromeric to the nearest gene SOX3. The patterns found at the breakpoint junctions resemble typical characteristics that arise in replication-based mechanisms with long-distance template switching. Non protein-coding insertions into the same genomic region have been described to result in different phenotypes, indicating that the phenotypic outcome likely depends on the introduction of regulatory elements. In conclusion, our data adds Plott syndrome as another entity, likely caused by the insertion of non-coding DNA into the intergenic chromosomal region Xq27.1. In this regard, we demonstrate the importance of WGS as a powerful diagnostic test in unsolved genetic diseases, as this genomic rearrangement has not been detected by current first-line diagnostic tests, i.e., exome sequencing and chromosomal microarray analysis.

Clustering-based data detection for spectral signature multiplexing in multispectral camera communication.

Optical camera communication (OCC) is a promising technology to be used in future wireless communication systems. In this work, a cluster-based data detection procedure is applied to enhance the performance of an OCC system. A multispectral camera is employed to capture the spectral variations in light-emitting diodes (LEDs) caused by temperature. This strategy's system performance is compared with a system that uses traditional linear methods, such as zero-forcing (ZF) and minimum mean square error (MMSE) equalizers. The findings of this study indicate that an improvement in the bit error rate (BER) can be achieved by applying a clustering approach.

Single nCounter assay for prediction of MYCN amplification and molecular classification of medulloblastomas: a multicentric study.

PURPOSE: Medulloblastoma is the most frequent pediatric malignant brain tumor, and is divided into four main subgroups: WNT, SHH, group 3, and group 4. MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single assay. METHODS: It was included 209 medulloblastomas from 205 patients (Brazil, Argentina, and Portugal), divided into training (n = 50) and validation (n = 159) sets. A nCounter assay was carried out using a custom panel for molecular classification, with additional genes, including MYCN. nSolver 4.0 software and the R environment were used for profiling and MYCN mRNA analysis. MYCN amplification by FISH was performed in 64 cases. RESULTS: The 205 medulloblastomas were classified in SHH (44.9%), WNT (15.6%), group 3 (18.1%) and group 4 (21.4%). In the training set, MYCN amplification was detected in three SHH medulloblastomas by FISH, which showed significantly higher MYCN mRNA counts than non-FISH amplified cases, and a cutoff for MYCN amplification was established ([Formula: see text] + 4σ = 11,124.3). Applying this threshold value in the validation set, we identified MYCN mRNA counts above the cutoff in three cases, which were FISH validated. CONCLUSION: We successfully stratified medulloblastoma molecular subgroups and predicted MYCN amplification using a single nCounter assay without the requirement of additional biological tissue, costs, or bench time.

A Unique Case Report of Infant-Type Hemispheric Glioma (Gliosarcoma Subtype) with TPR-NTRK1 Fusion Treated with Larotrectinib.

Herein, we present a rare case of a nine-month-old boy diagnosed with infant-type hemispheric glioma (gliosarcoma subtype) at the left frontal lobe. Following subtotal resection, the patient started chemotherapy with the BABY POG protocol. We describe the clinical diagnosis, histological characteristics, radiological features, molecular aspects, and management of this tumor. A comprehensive molecular analysis on the tumor tissue showed a TPR-NTRK1 gene fusion. The patient was treated with a TRK inhibitor, larotrectinib, and exhibited a stable disease with residual lesion following 8 months of target therapy. The present study is the first report of an infantile gliosarcoma harboring NTRK1 rearrangement treated with larotrectinib.

NTRK2 gene fusions are uncommon in pilocytic astrocytoma.

BACKGROUND: Pilocytic astrocytoma is the most frequent pediatric glioma. Despite its overall good prognosis, complete surgical resection is sometimes unfeasible, especially for patients with deep-seated tumors. For these patients, the identification of targetable genetic alterations such as NTRK fusions, raised as a new hope for therapy. The presence of gene fusions involving NTRK2 has been rarely reported in pilocytic astrocytoma. The aim of the present study was to investigate the frequency of NTRK2 alterations in a series of Brazilian pilocytic astrocytomas. METHODS: Sixty-nine pilocytic astrocytomas, previously characterized for BRAF and FGFR1 alterations were evaluated. The analysis of NTRK2 alterations was performed using a dual color break apart fluorescence in situ hybridization (FISH) assay. RESULTS: NTRK2 fusions were successfully evaluated by FISH in 62 of the 69 cases. Neither evidence of NTRK2 gene rearrangements nor NTRK2 copy number alterations were found. CONCLUSIONS: NTRK2 alterations are uncommon genetic events in pilocytic astrocytomas, regardless of patients' clinicopathological and molecular features.

Percutaneous thrombectomy or ultrasound-accelerated thrombolysis for initial management of acute limb ischaemia.

BACKGROUND: Acute limb ischaemia (ALI), the sudden and significant reduction of blood flow to the limb, is considered a vascular emergency. In the general population, the incidence is estimated as 14 per 100,000. Prognosis depends on the time it takes to diagnose the condition and begin appropriate treatment. Standard initial interventional treatments include conventional open surgery and endovascular interventions such as catheter-directed thrombolysis (CDT). Percutaneous interventions, such as percutaneous thrombectomy (PT, including mechanical thrombectomy or pharmomechanical thrombectomy) and ultrasound-accelerated thrombolysis (USAT), are also performed as alternative endovascular techniques. The proposed advantages of PT and USAT include reduced time to revascularisation and when combined with catheter-directed thrombolysis, a reduction in dose of thrombolytic agents and infusion time. The benefits of PT or USAT versus open surgery or thrombolysis alone are still uncertain. In this review, we compared PT or USAT against standard treatment for ALI, in an attempt to determine if any technique is comparatively safer and more effective. OBJECTIVES: To assess the safety and effectiveness of percutaneous thrombectomy or ultrasound-accelerated thrombolysis for the initial management of acute limb ischaemia in adults. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, the World Health Organization (WHO) International Clinical Trials Registry Platform, and ClinicalTrials.gov to 3 March 2021. We searched reference lists of relevant studies and papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared PT (any modality, including mechanical thrombectomy (aspiration, rheolysis, rotation) or pharmomechanical thrombectomy) or USAT with open surgery, thrombolysis alone, no treatment, or another PT modality for the treatment of ALI. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, assessed risk of bias, extracted data, performed data analysis, and assessed the certainty of evidence according to GRADE. Outcomes of interest were primary patency, amputation rate, major bleeding, clinical success, secondary patency, and adverse effects. MAIN RESULTS: We included one RCT in this review. This study had a total of 60 participants and compared USAT with standard treatment (CDT). The study included 32 participants in the CDT group and 28 participants in the USAT group. We found no evidence of a difference between USAT and CDT alone for the following evaluated outcomes: amputation rate (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.17 to 7.59); major bleeding (RR 1.71, 95% CI 0.31 to 9.53); clinical success (RR 1.00, 95% CI 0.94 to 1.07); and adverse effects (RR 5.69, 95% CI 0.28 to 113.72). We rated the certainty of the evidence as very low for these outcomes. We downgraded the certainty of the evidence for amputation rate, major bleeding, clinical success, and adverse effects by two levels due to serious limitations in the design (there was a high risk of bias in critical domains) and by two further levels due to imprecision (a small number of participants and only one study included). The study authors reported 30-day patency, but did not report primary and secondary patency separately. The patency rate in the successfully lysed participants was 71% (15/21) in the USAT group and 82% (22/27) in the CDT group. The study authors did not directly report secondary patency, which is patency after secondary procedures, but they did report on secondary procedures. Secondary procedures were subdivided into embolectomy and bypass grafting. Embolectomy was performed on 14% (4/28) of participants in the USAT group versus 3% (1/32) of participants in the CDT group. Bypass grafting was performed on 4% (1/28) of participants in the USAT group versus 0% in the CDT group. As we did not have access to the specific participant data, it was not possible to assess these outcomes further. We did not identify studies comparing the other planned interventions. AUTHORS' CONCLUSIONS: There is insufficient evidence to assess the safety and effectiveness of USAT versus CDT alone for ALI for our evaluated outcomes: amputation rate, major bleeding, clinical success, and adverse effects. Primary and secondary patency were not reported separately. There was no RCT evidence for PT. Limitations of this systematic review derive from the single included study, small sample size, short clinical follow-up period, and high risk of bias in critical domains. For this reason, the applicability of the results is limited. There is a need for high-quality studies to compare PT or USAT against open surgery, thrombolysis alone, no treatment, or other PT modalities for ALI. Future trials should assess outcomes, such as primary patency, amputation rate, major bleeding, clinical success, secondary patency, and adverse effects.

Interventions for treating catheter-related bloodstream infections in people receiving maintenance haemodialysis.

BACKGROUND: Patients with kidney failure require vascular access to receive maintenance haemodialysis (HD), which can be achieved by an arteriovenous fistula or a central venous catheter (CVC). CVC use is related to frequent complications such as venous stenosis and infection. Venous stenosis occurs mainly due to trauma caused by the entrance of the catheter into the venous lumen and repeated contact with the vein wall.  A biofilm, a colony of irreversible adherent and self-sufficient micro-organisms embedded in a self-produced matrix of exopolysaccharides, is associated with the development of infections in patients with indwelling catheters. Despite its clinical relevance, the treatment of catheter-related bloodstream infections (CRBSIs) in patients receiving maintenance HD remains controversial, especially regarding catheter management. Antibiotic lock solutions may sterilise the catheter, treat the infection and prevent unnecessary catheter procedures. However, such treatment may also lead to antibiotic resistance or even clinical worsening in certain more virulent pathogens. Catheter removal and delayed replacement may remove the source of infection, improving infectious outcomes, but this approach may also increase vascular access stenosis, thrombosis or both, or even central vein access failure. Catheter guidewire exchange attempts to remove the source of infection while maintaining access to the same vein and, therefore, may improve clinical outcomes and preserve central veins for future access. OBJECTIVES: To assess the benefits and harms of different interventions for CRBSI treatment in patients receiving maintenance HD through a permanent CVC, such as systemic antibiotics alone or systemic antibiotics combined with either lock solutions or catheter guidewire exchange or catheter replacement. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 21 December 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs evaluating the management of CRBSI in permanent CVCs in people receiving maintenance HD. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, assessed their risk of bias, and performed data extraction. Results were expressed as risk ratios (RR) or hazard ratios (HR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with their 95% confidence intervals (CI). The certainty of the evidence was assessed using GRADE. MAIN RESULTS: We identified two RCTs and one quasi-RCT that enrolled 760 participants addressing the treatment of CRBSIs in people (children and adults) receiving maintenance HD through CVC. No two studies compared the same interventions. The quasi-RCT compared two different lock solutions (tissue plasminogen activator (TPA) and heparin) with concurrent systemic antibiotics. One RCT compared systemic antibiotics alone and in association with an ethanol lock solution, and the other compared systemic antibiotics with different catheter management strategies (guidewire exchange versus removal and replacement). The overall certainty of the evidence was downgraded due to the small number of participants, high risk of bias in many domains, especially randomisation, allocation, and other sources of bias, and missing outcome data. It is uncertain whether an ethanol lock solution used with concurrent systemic antibiotics improved CRBSI eradication compared to systemic antibiotics alone (RR 1.61, 95% CI 1.16 to 2.23) because the certainty of this evidence is very low. There were no reported differences between the effects of TPA and heparin lock solutions on cure rates (RR 0.92, 95% CI 0.74 to 1.15) or between catheter guidewire exchange versus catheter removal with delayed replacement, expressed as catheter infection-free survival (HR 0.88, 95% CI 0.43 to 1.79). To date, no results are available comparing other interventions. Outcomes such as venous stenosis and/or thrombosis, antibiotic resistance, death, and adverse events were not reported. AUTHORS' CONCLUSIONS: Currently, there is no available high certainty evidence to support one treatment over another for CRBSIs. The benefit of using ethanol lock treatment in combination with systemic antibiotics compared to systemic antibiotics alone for CRBSIs in patients receiving maintenance HD remains uncertain due to the very low certainty of the evidence. Hence, further RCTs to identify the benefits and harms of CRBSI treatment options are needed. Future studies should unify CRBSI and cure definitions and improve methodological design.

Imbalance in Bone Morphogenic Proteins 2 and 7 Is Associated with Renal and Cardiovascular Damage in Chronic Kidney Disease.

Arterial stiffness is a major vascular complication of chronic kidney disease (CKD). The development of renal damage, hypertension, and increased pulse wave velocity (PWV) in CKD might be associated with an imbalance in bone morphogenetic proteins (BMP)-2 and BMP-7. Plasma BMP-2 and BMP-7 were determined by ELISA in CKD patients (stages I-III; n = 95) and Munich Wistar Frömter (MWF) rats. Age-matched Wistar rats were used as a control. The expression of BMP-2, BMP-7, and profibrotic and calcification factors was determined in kidney and perivascular adipose tissues (PVAT). BMP-2 was higher in stage III CKD patients compared to control subjects. BMP-7 was lower at any CKD stage compared to controls, with a significant further reduction in stage III patients. A similar imbalance was observed in MWF rats together with the increase in systolic (SBP) and diastolic blood pressure (DBP), or pulse wave velocity (PWV). MWF exhibited elevated urinary albumin excretion (UAE) and renal expression of BMP-2 or kidney damage markers, Kim-1 and Ngal, whereas renal BMP-7 was significantly lower than in Wistar rats. SBP, DBP, PWV, UAE, and plasma creatinine positively correlated with the plasma BMP-2/BMP-7 ratio. Periaortic and mesenteric PVAT from MWF rats showed an increased expression of BMP-2 and profibrotic and calcification markers compared to Wistar rats, together with a reduced BMP-7 expression. BMP-2 and BMP-7 imbalance in plasma, kidney, and PVATs is associated with vascular damage, suggesting a profibrotic/pro-calcifying propensity associated with progressive CKD. Thus, their combined analysis stratified by CKD stages might be of clinical interest to provide information about the degree of renal and vascular damage in CKD.

Tuning the Magnetic Anisotropy of Lanthanides on a Metal Substrate by Metal-Organic Coordination.

Taming the magnetic anisotropy of lanthanides through coordination environments is crucial to take advantage of the lanthanides properties in thermally robust nanomaterials. In this work, the electronic and magnetic properties of Dy-carboxylate metal-organic networks on Cu(111) based on an eightfold coordination between Dy and ditopic linkers are inspected. This surface science study based on scanning probe microscopy and X-ray magnetic circular dichroism, complemented with density functional theory and multiplet calculations, reveals that the magnetic anisotropy landscape of the system is complex. Surface-supported metal-organic coordination is able to induce a change in the orientation of the easy magnetization axis of the Dy coordinative centers as compared to isolated Dy atoms and Dy clusters, and significantly increases the magnetic anisotropy. Surprisingly, Dy atoms coordinated in the metallosupramolecular networks display a nearly in-plane easy magnetization axis despite the out-of-plane symmetry axis of the coordinative molecular lattice. Multiplet calculations highlight the decisive role of the metal-organic coordination, revealing that the tilted orientation is the result of a very delicate balance between the interaction of Dy with O atoms and the precise geometry of the crystal field. This study opens new avenues to tailor the magnetic anisotropy and magnetic moments of lanthanide elements on surfaces.

Low MGMT digital expression is associated with a better outcome of IDH1 wildtype glioblastomas treated with temozolomide.

INTRODUCTION: Glioblastoma (GBM) is the deadliest primary brain tumor. The standard treatment consists of surgery, radiotherapy, and temozolomide (TMZ). TMZ response is heterogeneous, and MGMT promoter (MGMTp) methylation has been the major predictive biomarker. We aimed to describe the clinical and molecular data of GBMs treated with TMZ, compare MGMT methylation with MGMT expression, and further associate with patient's outcome. METHODS: We evaluate 112 FFPE adult GBM cases. IDH1 and ATRX expression was analyzed by immunohistochemistry, hotspot TERT promoter (TERTp) mutations were evaluated by Sanger or pyrosequencing, and MGMTp methylation was assessed by pyrosequencing and MGMT mRNA expression using the nCounter® Vantage 3D™ DNA damage and repair panel. RESULTS: Of the 112 GBMs, 96 were IDH1WT, and 16 were IDH1MUT. Positive ATRX expression was found in 91.6% (88/96) of IDHWT and 43.7% (7/16) of IDHMUT. TERTp mutations were detected in 70.4% (50/71) of IDHWT. MGMTp methylation was found in 55.5% (35/63) of IDHWT and 84.6% (11/13) of IDHMUT, and as expected, MGMTp methylation was significantly associated with a better response to TMZ. MGMT expression was inversely correlated with MGMTp methylation levels (- 0.506, p < 0.0001), and MGMT low expression were significantly associated with better patient survival. It was also observed that integrating MGMTp methylation and expression, significantly improved the prognostication value. CONCLUSIONS: MGMT mRNA levels evaluated by digital expression were associated with the outcome of TMZ-treated GBM patients. The combination of MGMT methylation and mRNA expression may provide a more accurate prediction of TMZ response in GBM patients.