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nce/prevalence of narcolepsy could not be pooled reliably with substantial heterogeneity. Incidence/prevalence studies using ICSD and Brighton provided lower estimates than studies using ICD and other criteria. Diagnostic criteria should be standardized when comparing or pooling the incidence/prevalence to understand the epidemiology of narcolepsy. Future studies are needed to focus on the at-risk population for the etiology investigation of narcolepsy.

Estimates of incidence/prevalence of narcolepsy could not be pooled reliably with substantial heterogeneity. Incidence/prevalence studies using ICSD and Brighton provided lower estimates than studies using ICD and other criteria. Diagnostic criteria should be standardized when comparing or pooling the incidence/prevalence to understand the epidemiology of narcolepsy. Future studies are needed to focus on the at-risk population for the etiology investigation of narcolepsy.Resistive random-access memories (RRAMs) based on metal-oxide thin films have been studied extensively for application as synaptic devices in neuromorphic systems. The use of graphene oxide (GO) as a switching layer offers an exciting alternative to other materials such as metal-oxides. We present a newly developed RRAM device fabricated by implementing highly-packed GO layers on a highly doped Si wafer to yield a gradual modulation of the memory as a function of the number of input pulses. By using flow-enabled self-assembly, highly uniform GO thin films can be formed on flat Si wafers in a rapid and simple process. The switching mechanism was explored through proposed scenarios reconstructing the density change of the sp2cluster in the GO layer, resulting in a gradual conductance modulation. We analyzed that the current in a low resistance state could flow by tunneling or hopping via clusters because the distance between the sp2clusters in closely-packed GO layers is short. Finally, through a pattern-recognition simulation with a Modified National Institute of Standards and Technology database, the feasibility of using close-packed GO layers as synapse devices was successfully demonstrated.We report a phase II study of 50 advanced non-small cell lung cancer (NSCLC) patients with point mutations or insertions in EGFR exon 20 treated with poziotinib (NCT03066206). The study achieved its primary endpoint, with confirmed objective response rates (ORRs) of 32% and 31% by investigator and blinded independent review, respectively, with a median progression-free survival of 5.5 months. Using preclinical studies, in silico modeling, and molecular dynamics simulations, we found that poziotinib sensitivity was highly dependent on the insertion location, with near-loop insertions (amino acids A767 to P772) being more sensitive than far-loop insertions, an observation confirmed clinically with ORRs of 46% and 0% observed in near versus far-loop, respectively (p = 0.0015). Putative mechanisms of acquired resistance included EGFR T790M, MET amplifications, and epithelial-to-mesenchymal transition (EMT). Our data demonstrate that poziotinib is active in EGFR exon 20-mutant NSCLC, although this activity is influenced by insertion location.Immunoediting, the loss of tumor (neo)antigens due to T cell-dependent selection, sculpts tumor immunogenicity. In Nature, Łuksza et al. conceive a model to score neoantigens' immunogenicity and predict tumor clonal evolution. With this model, they demonstrate that durable tumor control associates with selective limited acquisition of high-quality mutations.In this issue of Cancer Cell, Belk et al. perform an in vitro CRISPR screen to identify genes that regulate CD8+ T cell exhaustion. They find several genes related to epigenetic modification and show that by eliminating Arid1a, CD8+ T cells retain proliferative and cytotoxic function in vivo, leading to better anti-tumor activity.EGFR exon 20 insertions represent a subgroup of NSCLC patients posed with a therapy dilemma. In this issue of Cancer Cell, Elamin and colleagues demonstrate that only insertions localized in the near loop respond to poziotinib. Pharmacological inhibition of spindle assembly checkpoint components inhibits tumor growth in poziotinib-resistant exon 20 insertions.

Atrial fibrillation (AF) is common in chronic kidney disease (CKD) patients and is difficult to treat with anti-arrhythmics and anticoagulants due to abnormal metabolism and increased side effects. Catheter ablation, if successful, may be a safer alternative. This review aimed to analyse the effect of CKD or haemodialysis (HD) on recurrence of AF after catheter ablation.

MEDLINE, Embase, and PubMed databases were searched until December 2020. Two authors abstracted the data independently. Relative risks were derived using random-effects meta-analysis.

Of the initially identified 782 studies, 6 and 4 observational studies investigating CKD and HD patients, respectively reported AF recurrence rates. During a mean (SD) follow-up of 25.5 (9.8) months, CKD patients demonstrated a higher risk of AF recurrence compared to patients without CKD (RR 2.34, 95% CI 1.36-4.02, p < 0.01). The heterogenicity test highlighted significant differences between individual studies (I2 = 91.0%, 95% CI 82.2-95.6%). In a mean (SD) follow-up of 32.6 (26.8) months, HD patients may be at a higher risk of AF recurrence compared to healthy non-dialysis AF patients (RR 1.50, 95% CI 0.84-2.67, p = 0.17). Heterogeneity analysis showed the studies were heterogeneous (I2 = 90.1%, 95% CI 77.5-95.6%, p < 0.01).

Our meta-analysis suggests patients with CKD and on HD are more likely to have AF recurrences compared to AF patients who do not have CKD. However, more robust evidence from randomized controlled trials comparing catheter ablation to pharmaceutical rhythm therapy is urgently needed to guide therapy in this difficult to treat population.

Our meta-analysis suggests patients with CKD and on HD are more likely to have AF recurrences compared to AF patients who do not have CKD. However, more robust evidence from randomized controlled trials comparing catheter ablation to pharmaceutical rhythm therapy is urgently needed to guide therapy in this difficult to treat population.During meiosis, microtubules emanate from the centrosome to cluster telomeres in the bouquet configuration and facilitate chromosome pairing. In a recent issue of Science, Mytlis et al. establish that a cilium in zebrafish anchors the centrosome and is important for telomere clustering and germ cell development.Mechanical stimuli have profound effects on the structure and function of various cells and tissues. In this issue of Developmental Cell, Tao et al. report that mechanosensory ion channels mediate the effects of cell membrane guidance cues on the morphogenesis of neuronal dendrites.Autonomic nerves innervate the lungs, but how these nerves guide lung development remains unclear. In this issue of Developmental Cell, Zhang et al. reveal that myofibroblasts and developing nerves cross-communicate through neurotrophins and neurotransmitters to drive alveologenesi-and that planar cell polarity signaling is critical to this process.A new study finds an inverse correlation between lifespan and somatic mutation rate in mammals. This suggests an evolutionary relationship between aging and somatic mutation rates, perhaps mediated by selection against noncancerous selfish lineages.When confronted with illness, humans and animals undergo critical changes in their behavior and physiology. New research shows how neuronal circuits detect sickness and coordinate illness-specific responses.A new study uses reconstituted, functional octameric exocyst complex to provide new insights into the assembly of this tethering complex and reveal how the activity of the lipid kinase PIP5K1C stimulated by Arf6 on exocytic vesicles allows for exocyst-mediated tethering at the plasma membrane.A new study shows that bumblebees can display path integration while walking in a small laboratory arena. This opens a new avenue for studying how insects' brains can encode direction and distance.During mitosis, chromosomes must bind spindle microtubules via kinetochores in a stable yet dynamic manner to ensure rapid frictionless movements. A recent study identifies the first complex that specifically reduces friction in the kinetochore-microtubule interface to ensure efficient chromosome segregation.Mice detect decreases in illumination in dim light near the visual threshold with OFF retinal ganglion cells.Many migrations during human history have made the Carpathian Basin the melting pot of Europe. New ancient genomes confirm the Asian origin of European Huns, Avars and Magyars and huge within-group variability that is linked with social structure.Satellite DNA sequences can rapidly expand, and pressure to preserve genome integrity is thought to trigger the adaptive evolution of satellite-associated proteins. The authors of a new study manipulate both sides of this co-evolution in Drosophila to reveal how DNA entanglements can trigger the rapid adaptive evolution of chromatin proteins.Pocket gophers (Geomys spp.) are solitary, root-eating fossorial rodents native to North and Central American grasslands and are presumed to acquire most of their food through excavation of tunnels maintained as part of tunnel systems up to 160 m long1,2. Given that burrowing is 360-3,400 times more energetically costly than surface walking, pocket gophers have high energy requirements3. Roots are scarce at the depths of their tunnels in the sandy soil of our study site (20-64 cm), but here we describe a novel food source for southeastern pocket gophers (Geomys pinetis, hereafter gophers) roots that grow into their tunnels. These roots could supply an average of 21% but up to 62% of their daily basal energetic needs.Cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING, also known as TMEM173) constitute the major signaling pathway in vertebrates that senses non-self DNA and elicits potent immune responses. At the core of this pathway, cGAS senses double-stranded DNA (dsDNA) and synthesizes cyclic GMP-AMP (cGAMP). cGAMP serves as a second messenger that relays its signal to downstream innate immune responses through STING. selleck One of the major consequences triggered by the cGAS-STING pathway is the production of antiviral cytokines of the type I interferon family, which in turn induce expression of hundreds of interferon-stimulated genes (ISGs) with diverse antiviral functions. Recent studies have also revealed functional homologs across phylogenetic kingdoms with innate defense functions, suggesting an ancient evolutionary origin of cGAS-STING signaling. Aberrant activation of the cGAS-STING pathway by host DNA can lead to sterile inflammation associated with tissue damage, degeneration as well as premature aging. In this primer, we will introduce the basic principles of cGAS-STING signaling in the vertebrate system and highlight recent discoveries regarding its connection to other fundamental cellular processes in the context of human diseases.In this Quick guide, Bertram et al. discuss the environmental sources of endocrine-disrupting chemicals and their effects on biological systems.