Activity

Potential usage of recently developed drugs that suppress the SASP (senomorphics) or selectively kill senescence cells (senolytics) in cancer therapy are also discussed.Current meta‐analysis suggests that outcomes with novel oral anticoagulants (NOACs) do not significantly differ compared to vitamin K antagonists (VKAs) after transcatheter aortic valve replacement (TAVR) in patients with atrial fibrillation (AF), in particular, NOACs failed to demonstrate a better safety profile than VKAs in this clinical setting. Accordingly, the choice between NOACs and VKAs in AF patients after TAVR is left to clinical judgment. Future large‐scale clinical trials are warranted to establish a clinically superior anticoagulant regime in this clinical setting, based on risk profile and need for concomitant antiplatelet therapy.

Despite a large descriptive literature linking creativity and risk for psychiatric illness, the magnitude and specificity of this relationship remain controversial.

We examined, in 1 137 354 native Swedes with one of 59 3-digit official and objective occupational codes in managerial and educated classes, their familial genetic risk score (FGRS) for ten major disorders, calculated from 1

through 5

degree relatives. Mean FGRS across disorders were calculated, in 3- and 4-digit occupational groups, and then controlled for those whose disorder onset preceded occupational choice. Using sequential analyses,

values were evaluated using Bonferroni correction.

3-digit professions considered to reflect creativity (e.g. ‘artists’ and ‘authors’) were among those with statistically significant elevations of FGRS. Among more specific 4-digit codes, visual artists, actors, and authors stood out with elevated genetic risks, highest for major depression (MD), anxiety disorders (AD) and OCD, more modest for bipolaic disorders.

CVCs are defined ‘complex’ when they are inserted through non-conventional accesses or positioned in non-usual sites or substituted by IR endovascular procedures. We report our experience in using diagnostic and interventional radiology techniques for complex CVC insertion and management; we recommend some precautions and techniques that could lead to long-term availability of central venous access and to avoid non-conventional sites CVC insertion.

We retrospectively evaluated 617 patients, between January 2010 and December 2019, (mean age 71 ± 13; male 448/617), treated in our department for insertion of tunnelled CVC for haemodialysis.

Among 617 patients, 241 cases (39%) are considered ‘complex’ because they required either a PTA with or without stenting to restore/maintain venous access or had an unusual positioning site or required unconventional access. A direct correlation between CT angiography and PTA (

= 0.95;

-value <0.001) and an inverse correlation between CT angiography and unconventional ‘rescue’ access (

= -0.92;

-value <0.001) were found.

Precise pre-operative planning of treatment in a multidisciplinary setting and diagnostic and interventional radiology procedures knowledge allows reducing complex catheterisms in haemodialysis patient.

Precise pre-operative planning of treatment in a multidisciplinary setting and diagnostic and interventional radiology procedures knowledge allows reducing complex catheterisms in haemodialysis patient.In China, as elsewhere, amphibians are highly endangered. Anthropogenic environmental change has affected the distribution and population dynamics of species, and species distributions at a broad scale are strongly driven by climate and species’ ability to disperse. Yet, current knowledge remains limited on how widespread human activity affects the distribution patterns of amphibians in China and whether this effect extends beyond climate. We compiled a relatively comprehensive database on the distribution of 196 amphibian species in China from the literature, public databases, and field data. We obtained 25,826 records on almost 50% of known species in China. To test how environmental factors and human activities influence the current distribution of amphibians (1960-1990), we used range filling, which is species realized ranges relative to their potential climate distribution. We used all species occurrence records to represent realized range and niche models to predict potential distribution range. To reduce uncertainty, we used 3 regression methods (beta regression, generalized boosted regression models, and random forest) to test the associations of species range filling with human activity, climate, topography, and range size. The results of the 3 approaches were consistent. At the species level, mean annual precipitation (climate) had the most effect on spatial distribution pattern of amphibians in China, followed by range size. Human activity ranked last. At the spatial level, mean annual precipitation remained the most important factor. Regions in southeastern of China that are currently moist supported the highest amphibian diversity, but were predicted to experience a decline in precipitation under climate change scenarios. Consequently, the distributions of amphibians will likely shift to the northwest in the future, which could affect future conservation efforts.Stage II-IIIA nonsmall cell lung cancer (NSCLC) patients receive adjuvant chemotherapy after surgery as standard-of-care treatment, even though only approximately 5.8% of patients will benefit. Identifying patients with minimal residual disease (MRD) after surgery using tissue-informed testing of postoperative plasma circulating cell-free tumour DNA (ctDNA) may allow adjuvant therapy to be withheld from patients without MRD. However, the detection of MRD in the postoperative setting is challenging, and more sensitive methods are urgently needed. We developed a method that combines variant calling and a novel ctDNA fragment length analysis using hybrid capture sequencing data. Among 36 stage II-IIIA NSCLC patients, this method distinguished patients with and without recurrence of disease in a 20 times repeated 10-fold cross validation with 75% accuracy (P = 0.0029). In contrast, using only variant calling or only fragment length analysis, no signification distinction between patients was shown (P = 0.24 and P = 0.074 respectively). In addition, a variant-level fragmentation score was developed that was able to classify variants detected in plasma cfDNA into tumour-derived or white-blood-cell-derived variants with 84% accuracy. The findings in this study may help drive the integration of various types of information from the same data, eventually leading to cheaper and more sensitive techniques to be used in this challenging clinical setting.Leukemogenesis is proposed to result from the continuous interplay between inducive bone marrow (BM) microenvironments and malignant precursor cells. Recent findings point toward an abnormal production of proinflammatory mediators within the BM from acute lymphoblastic leukemia (ALL) patients, although the mechanism underlying this phenomenon is uncertain. Here, we have identified 3 miRNAs, miR-146a-5p, miR-181b-5p, and miR-199b-3p, as potential candidates for TLR8 ligation, which are overexpressed in ALL and show agonist functional binding. When purified from ALL exosomes, they demonstrated their capacity of inducing cytokine production by both, hematopoietic and stromal BM cells. Of note, the exposure of BM cells from ALL patients to the proinflammatory milieu resulting from these miRNAs agonist activity revealed the proliferation of normal progenitors, while poor effects were recorded in the leukemic counterpart. The unconventional roles of the tumor-secreted miRNAs as TLR8 agonist ligands may provide a novel mechanism contributing a tumor-microenvironment feedback loop by switching on proinflammatory pathways that further activate normal hematopoietic precursors and support ALL progression. Secreted B-ALL TLR8-agonist miRNAs are involved in the promotion of proinflammatory microenvironments that target normal hematopoietic cells. Bozitinib in vitro B-lineage ALL cells secrete exosomes containing miRNAs endowed with the ability of functionally binding TLR8 in hematopoietic and BM mesenchymal stromal cells. Upon TLR8 signaling, the activation of the NF-kB pathway induces secretion of proinflammatory cytokines that, in turn, promotes cell proliferation in early hematopoietic cell populations, driving a tumor-microenvironment-hematopoietic activation feedback loop that may reduce the normal hematopoietic stem and progenitor cell compartment and facilitate cancer progression.Neutrophil (PMN) infiltration during active inflammation imprints changes in the local tissue environment. Such responses are often accompanied by significant extracellular acidosis that result in predictable transcriptional responses. In this study, we explore the mechanisms involved in inflammatory acidification as a result of PMN-intestinal epithelial cell (IEC) interactions. Using recently developed tools, we revealed that PMN transepithelial migration (TEM)-associated inflammatory acidosis is dependent on the total number of PMNs present during TEM and is polarized toward the apical surface. Extending these studies, we demonstrate that physical separation of the PMNs and IECs prevented acidification, whereas inhibition of PMN TEM using neutralizing antibodies enhanced extracellular acidification. Utilizing pharmaceutical inhibitors, we demonstrate that the acidification response is independent of myeloperoxidase and dependent on reactive oxygen species generated during PMN TEM. In conclusion, inflammatory acidosis represents a polarized PMN-IEC-dependent response by an as yet to be fully determined mechanism.Precise control of the structures and magnetic properties of a molecular material constitutes an important challenge to realize tailor-made magnetic function. Herein, we report that the ligand-directed coordination self-assembly of a dianionic cobalt(II) mononuclear complex and selective organic linkers has led to two distinct dicobalt(II) complexes, [Co2(pdms)2(bpym)3]·2MeCN (1) and [Co(pdms)(bipm)]2·3DMF (2) (H2pdms = 1,2-bis(methanesulfonamide)benzene; bpym = 2,2′-bipyrimidine; bimp = 1,4-bis[(1H-imidazol-1-yl)methyl]benzene). Structural analyses revealed that complexes 1 and 2 are discrete binuclear molecules containing two neutral Co(pdms) species bridged by bpym and bimp ligands, respectively, forming an exchange-coupled CoII2 dimer and a rare CoII2 metallocycle. Magnetic studies found that 1 exhibits considerable antiferromagnetic interactions transferred by the bpym bridge while negligible magnetic interactions in 2 due to the long bimp ligands. Interestingly, both the complexes show significant magnetic anisotropy and thus exhibit slow magnetic relaxation under an external dc field originating from spin-lattice relaxation. Detailed theoretical calculations were further applied to understand the magnetic interactions and magnetic anisotropy in 1 and 2. The foregoing results highlight that coordination solids with programmed structures and magnetic properties can be designed and prepared through a judicious selection of molecular complex building blocks and organic linkers.