Robust Ru/Ce@Co Catalyst with an Optimized Support Structure for Propane Oxidation.

Short carbon chain alkanes, as typical volatile organic compounds (VOCs), have molecular structural stability and low molecular polarity, leading to an enormous challenge in the catalytic oxidation of propane. Although Ru-based catalysts exhibit a surprisingly high activity for the catalytic oxidation of propane to CO2 and H2O, active RuOx species are partially oxidized and sintered during the oxidation reaction, leading to a decrease in catalytic activity and significantly inhibiting their application in industrial processes. Herein, the Ru/Ce@Co catalyst is synthesized with a specific structure, in which cerium dioxide is dispersed in a thin layer on the surface of Co3O4, and Ru nanoparticles fall preferentially on cerium oxide with high dispersity. Compared with the Ru/CeO2 and Ru/Co3O4 catalysts, the Ru/Ce@Co catalyst demonstrates excellent catalytic activity and stability for the oxidation of propane, even under severe operating conditions, such as recycling reaction, high space velocity, a certain degree of moisture, and high temperature. Benefiting from this particular structure, the Ru/Ce@Co (5:95) catalyst with more Ce3+ species leads to the Ru species being anchored more firmly on the CeO2 surface with a low-valent state and has a strong potential for adsorption and activation of propane and oxygen, which is beneficial for RuOx species with high activity and stability. This work provides a novel strategy for designing high-efficiency Ru-based catalysts for the catalytic combustion of short carbon alkanes.

Title evaluation of FluSight influenza forecasting in the 2021-22 and 2022-23 seasons with a new target laboratory-confirmed influenza hospitalizations.

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble is the 2nd most accurate model measured by WIS in 2021-22 and the 5th most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change.

Optical Amplification at 1.5 µm in ErIII Coordination Polymer-Doped Waveguides Based on Intramolecular Energy Transfer.

9,9-bis (diphenylphosphorylphenyl) fluorene (FDPO) and dibenzotetrathienoacene (DBTTA), are synthesized as the neutral and anionic ligands, respectively, to prepare the ErIII coordination polymer [Er(DBTTA)3(FDPO)]n. Based on the intramolecular energy transfer, optical gains at 1.5 µm are demonstrated in [Er(DBTTA)3(FDPO)]n-doped polymer waveguides under excitations of low-power light-emitting diodes (LEDs) instead of laser pumping. A ligand-sensitization scheme between organic ligands and Er3+ ions under an excitation of an ultraviolet (UV) LED is established. Relative gains of 10.5 and 8.5 dB cm-1 are achieved at 1.53 and 1.55 µm, respectively, on a 1-cm-long SU-8 channel waveguide with a cross-section of 2 × 3 µm2 and a 1.5-µm-thick [Er(DBTTA)3(FDPO)]n-doped polymethylmethacrylate (PMMA) as upper cladding. The ErIII coordination polymer [Er(DBTTA)3(FDPO)]n can be conveniently integrated with various low-loss inorganic waveguides to compensate for optical losses in the C-band window. Moreover, by relying on the intramolecular energy transfer and UV LED top-pumping technology, it is easy to achieve coupling packaging of erbium-doped waveguide amplifiers (EDWAs) with pump sources in planar photonic integrated chips, effectively reducing the commercial costs.

CYP17A1 Pathogenic Variants in 26 Chinese Patients with 17α-Hydroxylase Deficiency by Targeted Long-read Sequencing.

BACKGROUND: 17α-hydroxylase/17,20-lyase deficiency (17-OHD) is a rare subtype of congenital adrenal hyperplasia (CAH) caused by homozygous or compound heterozygous pathogenic variants in the CYP17A1 gene. PURPOSE: This study aimed to identify and characterize pathogenic variants in individuals with 17-OHD, and to classify and validate the pathogenicity of novel variants. METHODS: Variants were identified via targeted long-read sequencing (TLRS) of the entire CYP17A1 gene in enrolled 17-OHD patients. The American College of Medical Genetics and Genomics guidelines were employed to assess the pathogenicity of novel variants. A minigene splicing assay was utilized to determine the impact of variants on RNA splicing. RESULTS: This study encompassed 26 patients with 17-OHD, detecting two trans pathogenic variants per patient using the TLRS method. A total of 20 pathogenic variants in the CYP17A1 were identified, with variant c.985_987delinsAA being the most frequent (28/52 alleles), followed by variant c.1459_1467del (4/52 alleles). Five novel variants including c.280T>C, c.470T>A, c.636_637del, c.866A>G, and c.1095del, were classified as pathogenic/likely pathogenic ones according to ACMG criteria. The minigene assay revealed c.866A>G in exon 5 causes a frameshift due to a 104 base pair deletion, while c.470T>A generates two transcripts, with vast majority spliced like the wild-type, and a small fraction lack 35 base pairs in the 5' flank of exon 3. CONCLUSION: The TLRS can determine the cis/trans orientation of two distant variants. Five novel pathogenic variants were reported, broadening the spectrum of CYP17A1 pathogenic variant. The variant c.866A>G, located deep in exon, affects gene function through mechanisms of aberrant splicing.

A Recursive Prediction-Based Feature Enhancement for Small Object Detection.

Transformer-based methodologies in object detection have recently piqued considerable interest and have produced impressive results. DETR, an end-to-end object detection framework, ingeniously integrates the Transformer architecture, traditionally used in NLP, into computer vision for sequence-to-sequence prediction. Its enhanced variant, DINO, featuring improved denoising anchor boxes, has showcased remarkable performance on the COCO val2017 dataset. However, it often encounters challenges when applied to scenarios involving small object detection. Thus, we propose an innovative method for feature enhancement tailored to recursive prediction tasks, with a particular emphasis on augmenting small object detection performance. It primarily involves three enhancements: refining the backbone to favor feature maps that are more sensitive to small targets, incrementally augmenting the number of queries for small objects, and advancing the loss function for better performance. Specifically, The study incorporated the Switchable Atrous Convolution (SAC) mechanism, which features adaptable dilated convolutions, to increment the receptive field and thus elevate the innate feature extraction capabilities of the primary network concerning diminutive objects. Subsequently, a Recursive Small Object Prediction (RSP) module was designed to enhance the feature extraction of the prediction head for more precise network operations. Finally, the loss function was augmented with the Normalized Wasserstein Distance (NWD) metric, tailoring the loss function to suit small object detection better. The efficacy of the proposed model is empirically confirmed via testing on the VISDRONE2019 dataset. The comprehensive array of experiments indicates that our proposed model outperforms the extant DINO model in terms of average precision (AP) small object detection.

Tracing the contribution and fate of synthetic nitrogen fertilizer in young apple orchard agrosystems.

Excessive synthetic nitrogen (N) inputs in intensive orchard agrosystems of developing countries are a growing concern regarding their adverse impacts on fruit production and the environment. Quantifying the distribution and contribution of fertilizer N is essential for increasing N use efficiency and minimizing N loss in orchards. A 15N tracer experiment was performed in a young dwarf apple orchard over two growing seasons to determine the fertilizer N transformation and fate. Fertilizer N primarily contributed to 25 % to 75 % of soil nitrate in the top 60 cm, but the contribution to soil microbial biomass N and fixed ammonium was <8 %, with the contribution to plant N ranging from 9 % to 19 %. In most growth periods, soil nitrate and fixed ammonium contents derived from native soil with N fertilization were higher than those not receiving N fertilizer. The N use efficiency of plants was only 2.6 % and 4.9 % in the first and second seasons, respectively, in contrast to 56.6 % and 54.0 % of N recovered in soil. Meanwhile, N assimilated into microbial biomass accounted for 0.8 %, and the proportion fixed by clay minerals was 3.5 %-5.2 %. One season after N fertilization, the nitrate below the 1 m soil layers accounted for 4.6 % of the applied N fertilizer, and the proportion increased to 22.5 % after two seasons. The N loss rate via N2O emission was 0.4 % over two years. The application of N fertilizer facilitated indigenous soil N mineralization, and abiotic ammonium fixation more efficiently retained synthetic N than microbial immobilization. These findings provide new insight into orchard N cycling, and attention should be given to the improvement of soil N retention and turnover capacity regulated by soil microbial and abiotic processes, as well as the potential environmental impacts of additional soil N mineralization resulting from prolonged chemical N fertilization.

Odd Response-Induced Phase Separation of Active Spinners.

Due to the breaking of time-reversal and parity symmetries and the presence of non-conservative microscopic interactions, active spinner fluids and solids respectively exhibit nondissipative odd viscosity and nonstorage odd elasticity, engendering phenomena unattainable in traditional passive or active systems. Here, we study the effects of odd viscosity and elasticity on phase behaviors of active spinner systems. We find the spinner fluid under a simple shear experiences an anisotropic gas-liquid phase separation driven by the odd-viscosity stress. This phase separation exhibits equilibrium-like behavior, with both binodal-like and spinodal curves and critical point. However, the formed dense liquid phase is unstable, since the odd elasticity instantly takes over the odd viscosity to condense the liquid into a solid-like phase. The unusual phase behavior essentially arises from the competition between thermal fluctuations and the odd response-induced effective attraction. Our results demonstrate that the cooperation of odd viscosity and elasticity can lead to exotic phase behavior, revealing their fundamental roles in phase transition.

Giant Spin-Orbit Torque in Antiferromagnetic-Coupled Pt/[Co/Gd]N Multilayers with Suppressed Spin Dephasing and Robust Thermal Stability.

Manipulating magnetization via power-efficient spin-orbit torque (SOT) has garnered significant attention in the field of spin-based memory and logic devices. However, the damping-like SOT efficiency (ξDL) in heavy metal (HM)/ferromagnetic metal (FM) bilayers is relatively small due to the strong spin dephasing accompanied by additional spin polarization decay. Furthermore, the perpendicular magnetic anisotropy (PMA) originating from the HM/FM interface is constrained by the thickness of FM, which is unfavorable for thermal stability in practical applications. Consequently, it is valuable to develop systems that not only exhibit large ξDL but also balance thermal stability. In this work, we designed antiferromagnetic-coupled [Co/Gd]N multilayers, where staggered Co and Gd magnetic moments effectively suppress the spin dephasing and additional spin polarization decay. The ordered Co-Gd arrangements along the out-of-plane direction provide bulk PMA, endowing Pt/[Co/Gd]N high thermal stability. The SOT of Pt/[Co/Gd]N was systematically studied with N, demonstrating a significantly large ξDL of up to 0.66. The ξDL of Pt/[Co/Gd]N is greater than those of Pt/Co and Pt/ferrimagnetic alloys. This significant enhancement relies on the effective suppression of spin dephasing in [Co/Gd]N. Our work highlights that the antiferromagnetic-coupled [Co/Gd]N multilayer is a promising candidate for low-consumption and high-density spintronic devices.

Enantioselective Dearomatization of Pyridinium Salts by Copper-Catalyzed C4-Selective Addition of Silicon Nucleophiles.

A copper-catalyzed C4-selective addition of silicon nucleophiles released from an Si-B reagent to prochiral pyridinium triflates is reported. The dearomatization proceeds with excellent enantioselectivity using Cu(CH3CN)4PF6 as the precatalyst and (R,R)-Ph-BPE (1,2-bis[(2R,5R)-2,5-diphenylphospholan-1-yl]ethane) as the chiral ligand. A carbonyl group at C3 is required for this, likely acting a weak donor group to preorganize and direct the nucleophilic attack towards C4. The resulting 4-silylated 1,4-dihydropyridines can be further converted into functionalized piperidine derivatives.

Real-time soft body dissection simulation with parallelized graph-based shape matching on GPU.

BACKGROUND AND OBJECTIVE: Interactive soft tissue dissection has been a fundamental procedure in virtual surgery systems. Existing cutting algorithms involve complex topology changes of simulation meshes, which can increase simulation overhead and produce visual artifacts. In this paper, we proposed a novel graph-based shape-matching method that allows for real-time, flexible, progressive, and discontinuous cuts on soft tissue. METHODS: We employed shape-matching constraints within the position-based dynamics (PBD) framework, a widely adopted approach for real-time simulation applications. The soft tissue was effectively modeled using overlapping clusters, each governed by shape-matching constraints. The dissection process was bifurcated into two distinct stages. In the first stage, the surgical scalpel presses the surface of the soft tissue. The soft tissue is cut apart when the surface pressure exceeds a threshold, entering the second stage. To address the discrepancy between the visual mesh and the simulation model during cluster separation, we developed an Aggregate Finding Connected Components (AFCC) algorithm, optimized for GPU computation and integrated with a background grid. This approach also avoids ghost forces and fragmentation artifacts. To control the increase in the number of clusters, we also propose a merging strategy that can run in parallel. RESULTS: Our simulation outcomes demonstrated that the AFCC dissection algorithm effectively manages cluster separation and expansion with robustness. There were no ghost forces between the cutting surface and unrealistic fragments. Our simulation capability extended to supporting intricate and discontinuous cutting routes. Our dissection simulation maintained real-time performance even with over 100,000 particles constituting the soft tissue. CONCLUSIONS: Our real-time and robust surgical dissection simulation technique enables the performance of complex cuts in various surgical scenarios, demonstrating its potential in virtual surgery applications.

Suppression of cracking in drying colloidal suspensions with chain-like particles.

The prevention of drying-induced cracking is crucial in maintaining the mechanical integrity and functionality of colloidal deposits and coatings. Despite exploring various approaches, controlling drying-induced cracking remains a subject of great scientific interest and practical importance. By introducing chain-like particles composed of the same material and with comparable size into commonly used colloidal suspensions of spherical silica nanoparticles, we can significantly reduce the cracks formed in dried particle deposits and achieve a fivefold increase in the critical cracking thickness of colloidal silica coatings. The mechanism underlying the crack suppression is attributed to the increased porosity and pore sizes in dried particle deposits containing chain-like particle, which essentially leads to reduction in internal stresses developed during the drying process. Meanwhile, the nanoindentation measurements reveal that colloidal deposits with chain-like particles exhibit a smaller reduction in hardness compared to those reported using other cracking suppression approaches. This work demonstrates a promising technique for preparing colloidal coatings with enhanced crack resistance while maintaining desirable mechanical properties.

Strain-insensitive viscoelastic perovskite film for intrinsically stretchable neuromorphic vision-adaptive transistors.

Stretchable neuromorphic optoelectronics present tantalizing opportunities for intelligent vision applications that necessitate high spatial resolution and multimodal interaction. Existing neuromorphic devices are either stretchable but not reconcilable with multifunctionality, or discrete but with low-end neurological function and limited flexibility. Herein, we propose a defect-tunable viscoelastic perovskite film that is assembled into strain-insensitive quasi-continuous microsphere morphologies for intrinsically stretchable neuromorphic vision-adaptive transistors. The resulting device achieves trichromatic photoadaptation and a rapid adaptive speed (<150 s) beyond human eyes (3 ~ 30 min) even under 100% mechanical strain. When acted as an artificial synapse, the device can operate at an ultra-low energy consumption (15 aJ) (far below the human brain of 1 ~ 10 fJ) with a high paired-pulse facilitation index of 270% (one of the best figures of merit in stretchable synaptic phototransistors). Furthermore, adaptive optical imaging is achieved by the strain-insensitive perovskite films, accelerating the implementation of next-generation neuromorphic vision systems.

A detachable interface for stable low-voltage stretchable transistor arrays and high-resolution X-ray imaging.

Challenges associated with stretchable optoelectronic devices, such as pixel size, power consumption and stability, severely brock their realization in high-resolution digital imaging. Herein, we develop a universal detachable interface technique that allows uniform, damage-free and reproducible integration of micropatterned stretchable electrodes for pixel-dense intrinsically stretchable organic transistor arrays. Benefiting from the ideal heterocontact and short channel length (2 µm) in our transistors, switching current ratio exceeding 106, device density of 41,000 transistors/cm2, operational voltage down to 5 V and excellent stability are simultaneously achieved. The resultant stretchable transistor-based image sensors exhibit ultrasensitive X-ray detection and high-resolution imaging capability. A megapixel image is demonstrated, which is unprecedented for stretchable direct-conversion X-ray detectors. These results forge a bright future for the stretchable photonic integration toward next-generation visualization equipment.

Sensitivity-enhanced strain sensor based on a shape-modulated multimode fiber.

In this Letter, we demonstrate a sensitivity-enhanced strain sensor based on a shape-modulated multimode fiber (MMF). In contrast to conventional single-mode-multimode-single-mode (SMS) fiber structures, which typically contain a single cylindrical homogeneous MMF section, the shape of the MMF section in this investigation is modulated by lateral offset splicing of multiple MMF segments. Simulation results show that the designed shape-modulated MMF has a higher peak mechanical strain than that of a cylindrical MMF. Experimental results demonstrate that the strain sensitivity achieved by the shaped-modulated MMF-formed SMS fiber structure is as high as -55.63 pm/µÎµ, which is 33 times higher than that for a cylindrical MMF-formed conventional SMS fiber structure at -1.65 pm/µÎµ. This high sensitivity and low-fabrication cost SMS fiber sensor has the potential to be a promising candidate in precise strain measurement applications.

Point convolutional neural network algorithm for Ising model ground state research based on spring vibration.

The ground state search of the Ising model can be used to solve many combinatorial optimization problems. Under the current computer architecture, an Ising ground state search algorithm suitable for hardware computing is necessary for solving practical problems. Inspired by the potential energy conversion of the springs, we propose the Spring-Ising Algorithm, a point convolutional neural network algorithm for ground state search based on the spring vibration model. Spring-Ising Algorithm regards the spin as a moving mass point connected to a spring and establishes the equation of motion for all spins. Spring-Ising Algorithm can be mapped on AI chips through the basic structure of the neural network for fast and efficient parallel computing. The algorithm has shown promising results in solving the Ising model and has been tested in the recognized test benchmark K2000. The optimal results of this algorithm after 10,000 steps of iteration are 2.9% of all results. The algorithm introduces the concept of dynamic equilibrium to achieve a more detailed local search by dynamically adjusting the weight of the Ising model in the spring oscillation model. Spring-Ising Algorithm offers the possibility to calculate the Ising model on a chip which focuses on accelerating neural network calculations.

Pan-transcriptomic analysis reveals alternative splicing control of cold tolerance in rice.

Plants have evolved complex mechanisms to adapt to harsh environmental conditions. Rice (Oryza sativa) is a staple food crop that is sensitive to low temperatures. However, its cold stress responses remain poorly understood, thus limiting possibilities for crop engineering to achieve greater cold tolerance. In this study, we constructed a rice pan-transcriptome and characterized its transcriptional regulatory landscape in response to cold stress. We performed Iso-Seq and RNA-Seq of 11 rice cultivars subjected to a time-course cold treatment. Our analyses revealed that alternative splicing-regulated gene expression plays a significant role in the cold stress response. Moreover, we identified CATALASE C (OsCATC) and Os03g0701200 as candidate genes for engineering enhanced cold tolerance. Importantly, we uncovered central roles for the 2 serine-arginine-rich proteins OsRS33 and OsRS2Z38 in cold tolerance. Our analysis of cold tolerance and resequencing data from a diverse collection of 165 rice cultivars suggested that OsRS2Z38 may be a key selection gene in japonica domestication for cold adaptation, associated with the adaptive evolution of rice. This study systematically investigated the distribution, dynamic changes, and regulatory mechanisms of alternative splicing in rice under cold stress. Overall, our work generates a rich resource with broad implications for understanding the genetic basis of cold response mechanisms in plants.

Chemical Constituents of a Marine-derived Fungus Fusarium oxysporum F0888 and their Antibacterial Activity.

Five new compounds, including four hydroxyphenylacetic acid derivatives, stachylines H-K (1-4), a derivative of hydroxyphenylethanol (5), as well as seven known compounds were obtained from a marine-derived fungus Fusarium oxysporum F0888 isolated from sediments in the South China Sea. The structures and absolute configurations of new compounds were determined by spectroscopic (IR, NMR, and HR-ESI-MS) analyses, comparison of optical rotations, and the modified Mosher's MTPA ester method. Antimicrobial and anti-inflammatory activities of compounds 1-12 were tested. Unfortunately, all of isolated compounds were inactivity.

Farrerol Alleviates Cerebral Ischemia-Reperfusion Injury by Promoting Neuronal Survival and Reducing Neuroinflammation.

Ischemia-reperfusion (I/R) injury is a key influencing factor in the outcome of stroke. Inflammatory response, oxidative stress, and neuronal apoptosis are among the main factors that affect the progression of I/R injury. Farrerol (FAR) is a natural compound that can effectively inhibit the inflammatory response and oxidative stress. However, the role of FAR in cerebral I/R injury remains unknown. In this study, we found that FAR reduced brain injury and neuronal viability after cerebral I/R injury. Meanwhile, administration of FAR also reduced the inflammatory response of microglia after brain injury. Mechanistically, FAR treatment directly reduced neuronal death after oxygen glucose deprivation/re-oxygenation (OGD/R) through enhancing cAMP-response element binding protein (CREB) activation to increase the expression of downstream neurotrophic factors and anti-apoptotic genes. Moreover, FAR decreased the activation of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, inhibited microglia activation, and reduced the production of inflammatory cytokines in microglia after OGD/R treatment or LPS stimulation. The compromised inflammatory response by FAR directly promoted the survival of neurons after OGD/R. In conclusion, FAR exerted a protective effect on cerebral I/R injury by directly decreasing neuronal death through upregulating CREB expression and attenuating neuroinflammation. Therefore, FAR could be a potentially effective drug for the treatment of cerebral I/R injury.

The greenhouse gas emissions from meat sheep production contribute double of household consumption in a Eurasian meadow steppe.

With the rapid development of the economy, household activities have emerged as an important source of greenhouse gas (GHG) emissions, making them a crucial focal point for research in the pursuit of sustainable development and carbon emission reduction. Hulunber, as a typical steppe region in eastern Eurasia, is representative of studying the GHG emissions from household ranches, which are the basic production units in this region. In this paper, based on survey data of 2018 and 2019, we quantified and assessed GHG emissions from household ranches by combining life cycle assessment (LCA) and structural equation modeling (SEM) approaches, with LCA to define household ranches system boundary and SEM to determine the key driving factors of emissions. The results showed that GHG emissions of meat sheep live weight was 23.54 kg CO2-eq/kg. The major contributor to household GHG emissions was enteric methane (55.23 %), followed by coal use (20.80 %) and manure management systems (9.16 %), and other contributing factors (14.81 %). The SEM results indicated that the GHG emissions from household ranches were derived primarily by economic level, while the economic level was significantly affected by income. This study also found a significant positive and linear correlation between household GHG emissions and the number of meat sheep (R2 = 0.89, P < 0.001). The GHG emissions from meat sheep production (67.52 %) were double times greater than household livelihood consumption (32.48 %). These findings emphasized the importance of reducing emissions from meat sheep production and adjusting the energy mix of household livelihood, contributing to the establishment of a low-carbon household livelihood operation.

Concentrations of S100B and neurofilament light chain in blood as biomarkers for checkpoint inhibitor-induced CNS inflammation.

BACKGROUND: Cancer treatment with immune checkpoint inhibition (ICI) can cause immune-related adverse events in the central nervous system (CNS irAE). There are no blood biomarkers to detect CNS irAE. We investigated if concentrations of S100-calcium-binding protein B (S100B) and neurofilament light chain (NfL) in blood can be used as biomarkers for CNS irAE and assessed the incidence of CNS irAE in a cohort of ICI-treated patients. METHODS: In this single-centre, retrospective cohort study, we examined medical records and laboratory data of 197 consecutive patients treated with combined CTLA-4 and PD-1 inhibition (ipilimumab; ipi + nivolumab; nivo) for metastatic melanoma or renal cell carcinoma. CNS irAE was diagnosed using established criteria. Concentrations of S100B and NfL in blood were measured in patients with CNS irAE and in 84 patients without CNS irAE. FINDINGS: Nine of 197 patients (4.6%) fulfilled criteria for CNS irAE. S100B and NfL in blood increased during CNS inflammation and normalized during immunosuppression. CNS irAE was detected with a sensitivity of 100% (S100B) and 79% (NfL) and a specificity of 89% (S100B) and 74% (NfL). Patients with CNS irAE had simultaneous increased concentration of C-reactive protein (CRP) (9/9) and alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) in blood (8/9). INTERPRETATION: Analysis of S100B, NfL and CRP in blood facilitates the diagnosis of CNS irAE. CNS irAE may be more common than previously reported. There may be shared immune mechanisms between CNS and hepatitis irAE. FUNDING: Supported by funding from the Swedish Cancer Foundation, the ALF-agreement, and Jubileumsklinikens Cancerfond.