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Abstract Non-trivial band topology along with magnetism leads to different novel quantum phases. When time-reversal symmetry is broken in three-dimensional topological insulators (TIs) through, e.g., the proximity effect, different phases such as the quantum Hall phase or the quantum anomalous Hall(QAH) phase emerge, displaying interesting transport properties for spintronic applications. The QAH phase displays sidewall chiral edge states, which leads to the QAH effect. We have considered a heterostructure consisting of a TI, namely Bi $$_2$$ Se $$_3$$ , sandwiched between two two-dimensional ferromagnetic monolayers of CrI $$_3$$ , to study how its topological and transport properties change due to the proximity effect. Combining DFT and tight-binding calculations, along with non-equilibrium Green’s function formalism, we show that a well-defined exchange gap appears in the band structure in which spin-polarised edge states flow. In a finite slab, the nature of the surface states depends on both the cross-section and thickness of the system. Therefore, we also study the width and finite-size effects on the transmission and topological properties of this magnetised TI nanoribbon.

Abstract Background Accurately distinguishing lymph node metastases (LNM) from papillary thyroid carcinomas (PTC) is crucial in clinical practice. The role of the immune system in PTC-LNM has attracted increasing attention. The aim of the present study was to evaluate the differential expression of 92 immune-related proteins in the serum and identify their potential diagnostic effects in patients with PTC-LNM. Methods The 92 immune-related proteins were analyzed using a proximity extension assay. In addition, logistic regression and least absolute shrinkage and selection operator regression methods were used to develop combined diagnostic markers for thyroid cancer. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic validity. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to analyze the potential regulatory pathways. Results Five proteins, including IL-22RA1, IL-12B, CCL4, CCL3, and IL-1α, were significantly elevated in the serum of patients with LNM. The combined diagnosis of these five proteins demonstrated excellent diagnostic performance in distinguishing patients with PTC-LNM (area under the curve = 0.967, sensitivity = 0.941, and specificity = 0.889). Further analysis revealed that IL12B and IL1A mRNAs were significantly overexpressed in patients with PTC-LNM. This study also showed that the IL12B and IL1A was closely related to the PI3K-AKT, NF-κB, and MAPK signaling pathways. Conclusion The combination of IL-22RA1, IL-12B, CCL4, CCL3, and IL-1α represents a promising diagnostic panel for PTC-LNM. These findings provide a novel set of diagnostic markers for PTC-LNM based on serum inflammatory protein levels.

Aims: To evaluate the efficacy of re-resection in recurrent hepatocellular carcinoma (rHCC), identify prognostic factors, and provide clinical guidance. Methods: A retrospective analysis was conducted on 130 rHCC patients undergoing re-resection and 60 primary HCC patients undergoing initial hepatectomy at Peking University People's Hospital (2014–2022). Disease-free survival (DFS) and overall survival (OS) were compared. Prognostic factors were identified using univariate and multivariate COX regression analyses. Results: Baseline characteristics were comparable between groups (P > 0.05). DFS was similar between groups (30.8 vs. 32.2 months, P = 0.612). The 1-year, 2-year, and 3-year DFS rates for the re-resection group were 88.5 %, 64.9 %, and 56.7 %, respectively, versus 88.3 %, 65.0 %, and 53.3 % for the primary resection group. OS was lower in the re-resection group (36.1 vs. 47.2 months, P = 0.041) with 1-year, 2-year, and 3-year OS rates of 90.8 %, 73.1 %, and 60.0 %, compared to 95.0 %, 80.0 %, and 68.3 % for the primary resection group. Significant factors affecting DFS were Child-Pugh classification (P = 0.044), time to recurrence (P = 0.002), tumor differentiation (P = 0.044), and satellite nodules (P = 0.019). Factors influencing OS included Child-Pugh classification (P = 0.040), time to recurrence (P = 0.002), and tumor differentiation (P = 0.032). Conclusions: Re-resection is an effective treatment option for rHCC, with favorable outcomes as measured by DFS and OS, though OS is lower compared to initial hepatectomy. Key prognostic factors include Child-Pugh classification, time to recurrence, tumor differentiation, and satellite nodules.

Abstract Background Sequential CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy offers a promising approach to antigen-loss relapse in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL); however, research in adults remains limited. Methods This study aimed to evaluate the efficacy and safety of sequential CD19 and CD22 CAR-T cell therapy in adult patients with R/R B-ALL between November 2020 and November 2023 (ChiCTR2100053871). Key endpoints included the adverse event incidence, overall survival (OS), and leukemia-free survival (LFS). Results Twenty-three patients with a median age of 58.1 years (range 25.9–75.0) were enrolled. High-risk cytogenetic and genomic aberrations were identified in 43.5% of patients, and five patients had baseline extramedullary disease (EMD). The median interval between the two infusions was 3.8 months. Grade ≥ 3 hematological adverse events occurred at comparable rates after both infusions. Cytokine release syndrome was observed in 78.3% and 39.1% of patients after CD19 and CD22 CAR-T therapy, respectively. Two patients experienced grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) during CD19 CAR-T, and no ICANS was reported during CD22 CAR-T. The median OS was not reached with a median follow-up of 19.4 months (range 8.7–45.6), while the median LFS was 20.8 months. OS and LFS rates were 91.3% and 67.1% at 1 year and 58.6% and 47.0% at 2 years, respectively. Eight patients experienced relapse, with the cumulative incidence of relapse being 28.6% at 1 year and 42.5% at 2 years. Higher baseline leukemia burden (≥ 64% bone marrow blasts) and the presence of EMD were significant risk factors for inferior OS and LFS, respectively. Conclusions Sequential CAR-T cell therapy demonstrated durable efficacy and a manageable safety profile in R/R B-ALL, providing a viable option to address antigen-loss relapse and improve long-term outcomes in high-risk adult patients.

Abstract XPR1 is the sole protein known to transport inorganic phosphate (Pi) out of cells, a function conserved across species from yeast to mammals. Human XPR1 variants lead to cerebral calcium-phosphate deposition and primary familial brain calcification (PFBC), a hereditary neurodegenerative disorder. Here, we present the cryo-EM structure of human XPR1 in both its Pi-unbound and various Pi-bound states. XPR1 features 10 transmembrane α-helices forming an ion channel-like structure, with multiple Pi recognition sites along the channel. Pathogenic mutations in two arginine residues, which line the translocation channel, disrupt Pi transport. Molecular dynamics simulations reveal that Pi ion undergoes a stepwise transition through the sequential recognition sites during the transport process. Together with functional analyses, our results suggest that this sequential arrangement allows XPR1 to facilitate Pi ion passage via a “relay” process, and they establish a framework for the interpretation of disease-related mutations and for the development of future therapeutics.

Background: Bone marrow inflammaging is a low-grade chronic inflammation that induces bone marrow aging. Multiple age-related and inflammatory diseases involve bone marrow inflammaging. Whether common pathological pathways exist in bone marrow inflammaging remains unclear. Methods: We collected bone marrow from telomerase-deficient mice (telomerase RNA component, TERCko/ko), 5 × FAD mice and Dmp1Cre-DTAki/wt mice and High-fat diet-fed mice (HFD), and lumbar 5 nerve compression mice. We performed scRNA-Seq analysis on bone marrow obtained from these mouse models to investigate the potential shared pathway of bone marrow inflammation. Results: We identified the monocyte/macrophage lineage was activated via the App-Cd74 axis in multiple aging and inflammatory mouse models. Increased expression of CD38 and Ly6a, and decreased expression of Col1a and Lif in macrophages serve as shared changes in different mouse models. The activated macrophages, interacting with other cells, control the expansion of B cells via the CD52-Siglec-G axis. The Ccl6-Ccr2 and Ccl9-Ccr1 ligand-receptor pairs, along with Fn1 and C3-related pathways in macrophages, were associated with immune cell activation and the recruitment of lymphocytes. Interactions with mesenchymal cells were enriched for integrins (Itga4), Fn1, and adhesion molecules (Vcam1). Conclusion: Our study demonstrates that monocyte/macrophage lineage stimulation is a key event in bone marrow inflammaging. We identified common differentially expressed genes and activated pathways in this lineage, suggesting potential targets for future interventions. The translational potential of this article: Our study revealed shared genes and ligand-receptor pairs in the activated monocyte/macrophage lineage within inflammaging bone marrow. These findings offer potential therapeutic targets for cell-specific anti-inflammatory treatments.

Anisomycin (compound 1), a multifunctional pyrrolidine antibiotic, primarily inhibits protein biosynthesis by binding to the ribosome. Upon binding to the ribosome, the para-phenol moiety of anisomycin inserts completely into the hydrophobic crevice of the A-site and blocks the access of the incoming aminoacyl-tRNAs, disrupting peptide bond formation. Hence, the para-methoxyphenyl group serves as a starting point for developing novel anisomycin analogs with potent antifungal and insecticidal properties. However, the activation and condensation mechanism of phenylpyruvic acid has not yet been elucidated. In this study, genetic manipulations of aniP and its homologue siAniP confirmed their indispensable role in 1 biosynthesis. Bioinformatics analysis suggested that AniP and siAniP function as transketolase. siAniP was found to catalyzed condensation between 4-hydroxyphenylpyruvic acid (3) and glyceraldehyde (GA), initiating pyrrolidine synthesis. siAniP was specific for aromatic keto acids and tolerant of aliphatic and aromatic aldehydes, and was able to catalyze the asymmetric intermolecular condensation of two keto acids, leading to the formation of 24 α-hydroxy ketone. To the best of our knowledge, siAniP is the first TK that catalyzes the transfer of a C2 ketol and symmetrical intermolecular coupling using aromatic keto acids as donor substrates. Structural analysis, docking model construction, and site-directed mutagenesis identified that I220, H275, R322 and W391 were crucial for substrate binding. Moreover, sequence similarity network (SSN)-based genome neighborhood network (GNN) analyses of AniP suggested the widespread occurrence of the AniP-like-mediated reaction in the biosynthesis of 1 and its analogs, particularly in the assembly of benzylpyrrolidine. These findings not only expand the repertoire of TKs but also provide a potent biocatalyst that could be used for the structural innovation of 1 and its derivatives.

ABSTRACT Background The 2021 WHO Classification of Central Nervous System Tumors introduces more molecular markers for glioma reclassification, including TERT promoter (TERTp) mutation as a key feature in glioblastoma diagnosis. Aims Given the changes in the entities included in each subtype under the new classification, this research investigated the distribution, prognostic value, and correlations with other molecular alterations of TERTp mutation in different subgroups under this latest classification. Methods All glioma patients admitted to Peking Union Medical College Hospital for surgical resection or biopsy from 2011 to 2022 were included. Samples were analyzed for TERTp mutation and 59 other gene alterations and chromosome copy number variations. Results A total of 207 patients were included. The occurrence of TERTp mutations varied with percentages of 4.55%, 100%, and 77.92% in astrocytoma, oligodendroglioma, and glioblastoma, respectively. 65% of all adult‐type glioma patients and 42.6% of IDH‐wildtype histology grade 2 or 3 patients were TERTp‐mutant. Survival analysis showed that TERTp mutation was a predictor of better prognosis in IDH‐mutant grade 2 gliomas (median OS (mOS): not reached (NA) (95% CI: NA–NA) vs. 75.9 (95% CI: 55.4–NA) months, HR = 0.077 (95% CI: 0.01–0.64), p = 0.003), while poor OS was associated with all Grade 4 gliomas (mOS: 17.5 (95% CI: 12.6–24.2) vs. 40.5 (95% CI: 24.4–83.8) months, HR = 2.014 (95% CI: 1.17–3.47), p = 0.01) and all IDH‐wildtype histology grade 2 or 3 gliomas (median OS: 12.6 (95% CI: 11–24.2) vs. 83.8 (95% CI: 35.2–NA) months, HR = 3.768 (95% CI: 1.83–7.78), p

Ecosystems worldwide are facing significant challenges resulting from the dual pressures of global climate change and human activities, particularly in terms of significant biodiversity loss associated with land-use change. Focusing on the Yangtze River Economic Belt (YREB), this study uses the System Dynamics (SD) - Patch-generating Land Use Simulation (PLUS) model to simulate land-use development under different scenarios of shared socio-economic pathways (SSPs) and representative concentration pathways (RCPs) from 2030 to 2050. Furthermore, the InVEST model is applied to evaluate changes in habitat quality (HQ) over the period 2000 to 2050. A hotspot analysis further highlights the spatial heterogeneity of HQ within the YREB. The study showed that the land-use pattern in the YREB from 2020 to 2050 will be dominated by cropland in the eastern region, grassland in the north-west, and forest land in the central and southern regions, with a steady increase in built-up land in the east. The HQ index exhibits a gradual increase from east to west, ultimately declining to 0.726 under the SSP585 scenario for 2050. This trend reflects moderate habitat degradation (HD), with the degree of degradation shifting towards lower and higher proportions of HQ. Spatial analysis of HQ further reveals that the eastern region is identified as a cold spot, the central region is categorized as non-significant, while the western region emerges as a hot spot, where HQ exceeds 40%. These findings offer a scientific foundation for promoting high-quality development and enhancing biodiversity conservation in the YREB.

PurposeTo study the effects of breathing exercises on preventing pulmonary complications in patients undergoing coronary artery bypass graft surgery.MethodsObserving whether preoperative breathing exercises can reduce the incidence of postoperative pulmonary complications in patients undergoing coronary artery bypass graft surgery; observing whether these exercises can improve postoperative arterial oxygen pressure, oxygen saturation, and the distance walked in a six-minute walk test after surgery; as well as reduce hospital stay duration, lower treatment costs, and improve the quality of life as measured by the Short Form-36 Health Survey (SF-36).DesignThe study population includes patients undergoing coronary artery bypass graft surgery under general anesthesia; the research center is Capital Medical University Xuanwu Hospital; the sample size is 120. Preoperative standardized breathing exercises are utilized, and the incidence of postoperative pulmonary complications, postoperative arterial blood gases, oxygen saturation, six-minute walk test distances, and comparisons of hospital stay durations and costs will be observed.

Manufacturing and measurement sensors are an integral part of advanced manufacturing technology, which requires sensors that can precisely capture and analyze various physical parameters during the manufacturing process [...]

Ecosystems worldwide are facing significant challenges resulting from the dual pressures of global climate change and human activities, particularly in terms of significant biodiversity loss associated with land-use change. Focusing on the Yangtze River Economic Belt (YREB), this study uses the System Dynamics (SD) - Patch-generating Land Use Simulation (PLUS) model to simulate land-use development under different scenarios of shared socio-economic pathways (SSPs) and representative concentration pathways (RCPs) from 2030 to 2050. Furthermore, the InVEST model is applied to evaluate changes in habitat quality (HQ) over the period 2000 to 2050. A hotspot analysis further highlights the spatial heterogeneity of HQ within the YREB. The study showed that the land-use pattern in the YREB from 2020 to 2050 will be dominated by cropland in the eastern region, grassland in the north-west, and forest land in the central and southern regions, with a steady increase in built-up land in the east. The HQ index exhibits a gradual increase from east to west, ultimately declining to 0.726 under the SSP585 scenario for 2050. This trend reflects moderate habitat degradation (HD), with the degree of degradation shifting towards lower and higher proportions of HQ. Spatial analysis of HQ further reveals that the eastern region is identified as a cold spot, the central region is categorized as non-significant, while the western region emerges as a hot spot, where HQ exceeds 40%. These findings offer a scientific foundation for promoting high-quality development and enhancing biodiversity conservation in the YREB. [ABSTRACT FROM AUTHOR]

Background: Accurately distinguishing lymph node metastases (LNM) from papillary thyroid carcinomas (PTC) is crucial in clinical practice. The role of the immune system in PTC-LNM has attracted increasing attention. The aim of the present study was to evaluate the differential expression of 92 immune-related proteins in the serum and identify their potential diagnostic effects in patients with PTC-LNM. Methods: The 92 immune-related proteins were analyzed using a proximity extension assay. In addition, logistic regression and least absolute shrinkage and selection operator regression methods were used to develop combined diagnostic markers for thyroid cancer. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic validity. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to analyze the potential regulatory pathways. Results: Five proteins, including IL-22RA1, IL-12B, CCL4, CCL3, and IL-1α, were significantly elevated in the serum of patients with LNM. The combined diagnosis of these five proteins demonstrated excellent diagnostic performance in distinguishing patients with PTC-LNM (area under the curve = 0.967, sensitivity = 0.941, and specificity = 0.889). Further analysis revealed that IL12B and IL1A mRNAs were significantly overexpressed in patients with PTC-LNM. This study also showed that the IL12B and IL1A was closely related to the PI3K-AKT, NF-κB, and MAPK signaling pathways. Conclusion: The combination of IL-22RA1, IL-12B, CCL4, CCL3, and IL-1α represents a promising diagnostic panel for PTC-LNM. These findings provide a novel set of diagnostic markers for PTC-LNM based on serum inflammatory protein levels. [ABSTRACT FROM AUTHOR]

The electric arc furnace (EAF) is a promising approach to decarbonize the iron and steel industry. In EAF steelmaking, injecting carbon into the molten slag remains crucial for creating a foamy slag, which enhances the energy efficiency of the process and protects the furnace. Biochar (BC) has emerged as a potential alternative to traditional fossil carbon for slag foaming. However, fully replacing fossil carbon with BC poses technical challenges. In this study, the partial replacement of fossil carbon with BC is considered, in the form of a petroleum coke (petcoke) and BC blend. Interestingly, a blend of petcoke and BC matches or possibly outperforms either carbon type individually, due to a synergistic effect. Using an induction furnace to simulate EAF conditions, a synthetic slag is melted, and injection carbon is added into the slag layer. The slag foaming effectiveness of petcoke, BC, and three blend cases are studied. Thermogravimetric analysis reveals that the BC is more reactive with slag compared to petcoke, which leads to an initial high intensity of CO generation. However, the CO generation was not continuous or consistent. All experimental results are combined to propose a mechanistic description of the slag foaming behavior of BC blends. [ABSTRACT FROM AUTHOR]

Background: Sequential CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy offers a promising approach to antigen-loss relapse in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL); however, research in adults remains limited. Methods: This study aimed to evaluate the efficacy and safety of sequential CD19 and CD22 CAR-T cell therapy in adult patients with R/R B-ALL between November 2020 and November 2023 (ChiCTR2100053871). Key endpoints included the adverse event incidence, overall survival (OS), and leukemia-free survival (LFS). Results: Twenty-three patients with a median age of 58.1 years (range 25.9–75.0) were enrolled. High-risk cytogenetic and genomic aberrations were identified in 43.5% of patients, and five patients had baseline extramedullary disease (EMD). The median interval between the two infusions was 3.8 months. Grade ≥ 3 hematological adverse events occurred at comparable rates after both infusions. Cytokine release syndrome was observed in 78.3% and 39.1% of patients after CD19 and CD22 CAR-T therapy, respectively. Two patients experienced grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) during CD19 CAR-T, and no ICANS was reported during CD22 CAR-T. The median OS was not reached with a median follow-up of 19.4 months (range 8.7–45.6), while the median LFS was 20.8 months. OS and LFS rates were 91.3% and 67.1% at 1 year and 58.6% and 47.0% at 2 years, respectively. Eight patients experienced relapse, with the cumulative incidence of relapse being 28.6% at 1 year and 42.5% at 2 years. Higher baseline leukemia burden (≥ 64% bone marrow blasts) and the presence of EMD were significant risk factors for inferior OS and LFS, respectively. Conclusions: Sequential CAR-T cell therapy demonstrated durable efficacy and a manageable safety profile in R/R B-ALL, providing a viable option to address antigen-loss relapse and improve long-term outcomes in high-risk adult patients. [ABSTRACT FROM AUTHOR]

The flexible bearing is usually connected to the cam with an interference fit in harmonic reducers. Studies show that interference fit can cause changes in the structural parameters of the bearing and lead to changes in the service performance of the bearing and its supporting system. This paper proposes a general simulation method to investigate the influence of interference fit in harmonic reducers with the concept of the equivalent interference for non-circular fit between the flexible bearing and cam. Then, the four steps based on the sequential assembling and loading process are designed to ensure assembly concentricity and simulation convergence. The analysis results indicate that appropriately increasing the equivalent interference can improve the service life of the flexspline without degrading the meshing performance and, at the same time, increase the number of loaded balls to make the operation of the harmonic reducer more stable. Moreover, an optimal equivalent interference can be designed to ensure the harmonic reducer operates at its best, where the number of loaded balls and the maximum Mises stress of the inner ring appear inflection point, and the number of meshing tooth pairs reaches the maximum. [ABSTRACT FROM AUTHOR]

Details on anisotropic magnon dispersion in van der Waals (vdW) ferromagnetic insulators CrPS4 and CrSBr are reported, driven by anisotropic Heisenberg exchange couplings arising from in‐plane broken crystal symmetry. The anisotropic magnon dispersion contributes to longitudinal and transverse magnon currents generating the anisotropic spin Seebeck effect (ASSE) and the thermal Hall effect (THE) accompanied with spin Nernst effect (SNE), requiring neither external magnetic field nor Berry curvature. In CrPS4, the ASSE exhibits a very large anisotropy ratio of over 100% as the thermal gradient along different main axes, and this ratio can be further tuned by temperature or a gate current. The THE and SNE unconstrained by spin‐orbit coupling (SOC) emerge when the thermal gradient is not parallel to the main axis, characterized by a large Hall angle ≈ 0.4. Compared to CrPS4, CrSBr exhibits a more limited anisotropic magnon transport owing to the less variation in magnon group velocities along different main axes. Moreover, the reversed magnitude relationship of magnon group velocities leads to the transverse magnon current being oriented in the opposite direction. These findings identify low‐symmetry vdW magnetic materials as a promising framework for generation and manipulation of anisotropic magnon transport, relevant for spincaloritronic devices in the ultrathin regime. [ABSTRACT FROM AUTHOR]

A method is presented to characterise a crack in a thin plate with unknown acoustic properties when the position of the acoustic source is approximately known. Due to the unknown source generation waveform, a method based on the phase difference of Lamb wave propagation is proposed to determine the propagation distance difference between two different direct Lamb waves and extract the propagation distances of crack-scattered Lamb waves. The acoustic properties are inverted by establishing their relationship with the dispersion degree of intersections between any two hyperbolas formed by direct Lamb waves, and these intersections determine the source position. The difference in amplitude of crack-scattered Lamb waves is used to distinguish reflections from diffractions, and both edge points and endpoints of the crack are identified using the ellipse method to estimate the crack location, size, and shape. Linear, arc-shaped, and kinked cracks in aluminium plates are experimentally verified using a line-scanning laser vibrometer to collect Lamb wave signals from an acoustic source that is generated by a PZT transducer installed on the plate. The results show that the obtained cracks agree well with the actual cracks in terms of location, size, and shape, with mean relative errors of less than 1.59%. [ABSTRACT FROM AUTHOR]

Compared with green plants, brown algae are characterized by their ability to accumulate iodine, contributing to their ecological adaptability in high-iodide coastal environments. Vanadium-dependent haloperoxidase (V-HPO) is the key enzyme for iodine synthesis. Despite its significance, the evolutionary origin of V-HPO genes remains underexplored. This study investigates the genomic and evolutionary dynamics of V-HPOs in brown algae, focusing on Laminariales species, particularly Saccharina japonica. Genomic analyses revealed the extensive expansion of the V-HPO gene family in brown algae, with 88 V-HPOs identified in S. japonica, surpassing the number in red algae. Phylogenetic analysis demonstrated distinct evolutionary divergence between brown and red algal V-HPOs, with the brown algal clade closely related to bacterial V-HPOs. These findings suggest horizontal gene transfer (HGT) played a key role in acquiring V-HPO genes, particularly from Acidobacteriota, a bacterial phylum known for genomic plasticity. Additionally, enriched active transposable elements were identified around V-HPO genomic clusters, highlighting their role in tandem gene duplications and rapid HGT processes. Expression profiling further revealed dynamic regulation of V-HPOs in response to environmental conditions. This study provides new insights into how HGT has driven kelp genomic adaptations and enhances understanding of marine ecological success and evolutionary processes. [ABSTRACT FROM AUTHOR]