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Phenotyping robots have the potential to obtain crop phenotypic traits on a large scale with high throughput. Autonomous navigation technology for phenotyping robots can significantly improve the efficiency of phenotypic traits collection. This study developed an autonomous navigation method utilizing an RGB‐D camera, specifically designed for phenotyping robots in field environments. The PP‐LiteSeg semantic segmentation model was employed due to its real‐time and accurate segmentation capabilities, enabling the distinction of crop areas in images captured by the RGB‐D camera. Navigation feature points were extracted from these segmented areas, with their three‐dimensional coordinates determined from pixel and depth information, facilitating the computation of angle deviation (α) and lateral deviation (d). Fuzzy controllers were designed with α and d as inputs for real‐time deviation correction during the walking of phenotyping robot. Additionally, the method includes end‐of‐row recognition and row spacing calculation, based on both visible and depth data, enabling automatic turning and row transition. The experimental results showed that the adopted PP‐LiteSeg semantic segmentation model had a testing accuracy of 95.379% and a mean intersection over union of 90.615%. The robot's navigation demonstrated an average walking deviation of 1.33 cm, with a maximum of 3.82 cm. Additionally, the average error in row spacing measurement was 2.71 cm, while the success rate of row transition at the end of the row was 100%. These findings indicate that the proposed method provides effective support for the autonomous operation of phenotyping robots. [ABSTRACT FROM AUTHOR]

This study examined how the nutrient flow environment affects lettuce root morphology in hydroponics using multi‐omics analysis. The results indicate that increasing the nutrient flow rate initially increased indicators such as fresh root weight, root length, surface area, volume, and average diameter before declining, which mirrors the trend observed for shoot fresh weight. Furthermore, a high‐flow environment significantly increased root tissue density. Further analysis using Weighted Gene Co‐expression Network Analysis (WGCNA) and Weighted Protein Co‐expression Network Analysis (WPCNA) identified modules that were highly correlated with phenotypes and hormones. The analysis revealed a significant enrichment of hormone signal transduction pathways. Differences in the expression of genes and proteins related to hormone synthesis and transduction pathways were observed among the different flow conditions. These findings suggest that nutrient flow may regulate hormone levels and signal transmission by modulating the genes and proteins associated with hormone biosynthesis and signaling pathways, thereby influencing root morphology. These findings should support the development of effective methods for regulating the flow of nutrients in hydroponic contexts. [ABSTRACT FROM AUTHOR]

Intraperitoneal dissemination is the main method of epithelial ovarian cancer (EOC) metastasis, which is related to poor prognosis and a high recurrence rate. Circular RNAs (circRNAs) are a novel class of endogenous RNAs with covalently closed loop structures that are implicated in the regulation of tumor development. In this study, hsa_circ_0001546 is downregulated in EOC primary and metastatic tissues vs. control tissues and this phenotype has a favorable effect on EOC OS and DFS. hsa_circ_0001546 can directly bind with 14‐3‐3 proteins to act as a chaperone molecule and has a limited positive effect on 14‐3‐3 protein stability. This complex recruits CAMK2D to induce the Ser324 phosphorylation of Tau proteins, changing the phosphorylation status of Tau bound to 14‐3‐3 and ultimately forming the hsa_circ_0001546/14‐3‐3/CAMK2D/Tau complex. The existence of this complex stimulates the production of Tau aggregation, which then induces the accumulation of lipid peroxides (LPOs) and causes LPO‐dependent ferroptosis. In vivo, treatment with ferrostatin‐1 and TRx0237 rescued the inhibitory effect of hsa_circ_0001546 on EOC cell spreading. Therefore, based on this results, ferroptosis caused by Tau aggregation occurs in EOC cells, which is not only in Alzheimer's disease‐ or Parkinson's disease‐related cells and this kind of ferroptosis driven by the hsa_circ_0001546/14‐3‐3/CAMK2D/Tau complex is LPO‐dependent rather than GPX4‐dependent is hypothesized. [ABSTRACT FROM AUTHOR]

Nature‐inspired supramolecular self‐assemblies are attractive photocatalysts, but their quantum yields are limited by poor charge separation and transportation. A promising strategy for efficient charge transfer is to enhance the built‐in electric field by symmetry breaking. Herein, an unsymmetric protonation, N‐heterocyclic π‐conjugated anthrazoline‐based supramolecular photocatalyst SA‐DADK‐H+ was developed. The unsymmetric protonation breaks the initial structural symmetry of DADK, resulting in ca. 50‐fold increase in the molecular dipole, and facilitates efficient charge separation and transfer within SA‐DADK‐H+. The protonation process also creates numerous active sites for H2O adsorption, and serves as crucial proton relays, significantly improving the photocatalytic efficiency. Remarkably, SA‐DADK‐H+ exhibits an outstanding hydrogen evolution rate of 278.2 mmol g−1 h−1 and a remarkable apparent quantum efficiency of 25.1 % at 450 nm, placing it among the state‐of‐the‐art performances in organic semiconductor photocatalysts. Furthermore, the versatility of the unsymmetric protonation approach has been successfully applied to four other photocatalysts, enhancing their photocatalytic performance by 39 to 533 times. These findings highlight the considerable potential of unsymmetric protonation induced symmetry breaking strategy in tailoring supramolecular photocatalysts for efficient solar‐to‐fuel production. [ABSTRACT FROM AUTHOR]

Internet‐of‐Things and Cyber‐Physical‐System applications demand compact power converters, which require inductors to have small footprints but considerable power handling abilities. 3D air‐core tubular inductors fabricated using the self‐rolled‐up membrane (S‐RuM) technology have demonstrated significantly higher inductance density compared to conventional planar structures. However, previous design options and associated performance are constrained by the resistive loss due to the thickness of the metal and magnetic coupling limited by the air core. Here, the study reports a post‐rolling electroplating scheme aimed at enhancing the metal conductivity and core magnetic permeability in S‐RuM inductors, all while maintaining their compact footprint. A DC resistance improvement of over 10X and an inductance enhancement of over 30X are achieved by the 3D S‐RuM inductors, via parallel‐processed Cu‐electroplated strips on the cylindrical shells and partially permalloy‐electroplated core. The improvement is projected to continue to improve as the entire core is filled. This advancement paves the way for scalable applications of this technology in ultra‐compact, low‐loss passive power electronics, such as converters and filters. [ABSTRACT FROM AUTHOR]

Genetic factors play significant roles in the tumorigenicity of lung cancer; however, there is lack of systematic and large‐scale characterization of pathogenic germline variants for lung cancer. In this study, germline variants in 146 preselected cancer‐susceptibility genes were detected in 17 904 Chinese lung cancer patients by clinical next‐generation sequencing. Among 17 904 patients, 1738 patients (9.7%) carried 1840 pathogenic/likely pathogenic (P/LP) variants from 87 cancer‐susceptibility genes. SBDS (SBDS ribosome maturation factor) (1.37%), TSHR (thyroid stimulating hormone receptor) (1.20%), BLM (BLM RecQ like helicase) (0.62%), BRCA2 (BRCA2 DNA repair associated) (0.62%), and ATM (ATM serine/threonine kinase) (0.45%) were the top five genes with the highest overall prevalence. The top mutated pathways were all involved in DNA damage repair (DDR). Case–control analysis showed SBDS c.184A>T(p.K62*), TSHR c.1574T>C(p.F525S), BRIP1 (BRCA1 interacting helicase 1) c.1018C>T(p.L340F), and MUTYH (mutY DNA glycosylase) c.55C>T(p.R19*) were significantly associated with increased lung cancer risk (q value < 0.05). P/LP variants in certain genes were associated with early onset of lung cancer. Our study indicates that Chinese lung cancer patients have a higher prevalence of P/LP variants than previously reported. P/LP variants are distributed in multiple pathways and dominated by DNA damage repair‐associated pathways. The association between identified P/LP variants and lung cancer risk requires further studies for verification. [ABSTRACT FROM AUTHOR]

The pursuit of device miniaturization and the generation of complex output responses has driven the development of optically tunable metasurfaces. Among these advancements, metasurface‐based vortex beams (VBs) have emerged as promising optically tunable knob technology due to their infinite output states through various orbital angular momentum (OAM) modes. In this study, the metasurface‐based VBs are successfully fabricated with exceptionally high OAM modes of 32 and 16, carefully examined using the Mach‐Zehnder interferometer. Throughout this study, these devices are referred to as infinite‐OAM meta‐knobs (IOMKs). The optical tunability of IOMKs is demonstrated by illuminating them with incident light possessing diverse degrees of freedom, including different polarizations and wavelengths. Furthermore, the interference nature of the IOMKs is experimentally explored by incorporating them into interference eraser measurements, providing an additional degree of freedom to the optical knob. In the interference eraser experiment, the broadband capability and the high reproducibility of the IOMKs with the OAM modes of 32 and 16 at three distinct wavelengths of 450, 530, and 610 nm is demonstrated. These findings represent a significant step toward understanding the potential applications of IOMKs in quantum optics and their promising role in the generation of complex output states. [ABSTRACT FROM AUTHOR]

Singleton distractors may inadvertently capture attention, interfering with the task at hand. The underlying neural mechanisms of how we prevent or handle distractor interference remain elusive. Here, we varied the type of salient distractor introduced in a visual search task: the distractor could be defined in the same (shape) dimension as the target, a different (color) dimension, or a different (tactile) modality (intra‐dimensional, cross‐dimensional, and, respectively, cross‐modal distractor, all matched for physical salience); and besides behavioral interference, we measured lateralized electrophysiological indicators of attentional selectivity (the N2pc, Ppc, PD, CCN/CCP, CDA, and cCDA). The results revealed the intra‐dimensional distractor to produce the strongest reaction‐time interference, associated with the smallest target‐elicited N2pc. In contrast, the cross‐dimensional and cross‐modal distractors did not engender any significant interference, and the target‐elicited N2pc was comparable to the condition in which the search display contained only the target singleton, thus ruling out early attentional capture. Moreover, the cross‐modal distractor elicited a significant early CCN/CCP, but did not influence the target‐elicited N2pc, suggesting that the tactile distractor is registered by the somatosensory system (rather than being proactively suppressed), without, however, engaging attention. Together, our findings indicate that, in contrast to distractors defined in the same dimension as the target, distractors singled out in a different dimension or modality can be effectively prevented to engage attention, consistent with dimension‐ or modality‐weighting accounts of attentional priority computation. This study contributes to resolving hot debates of attentional capture. Participants ignored task‐irrelevant distractors without attentional engagement rather than actively suppressing them. Especially, the cross‐modal distractor elicited sensorimotor ERPs, but participants did not deploy attentional resources to it. The results supported distractor handling via down‐weighted or no‐engagement to task‐irrelevant features. [ABSTRACT FROM AUTHOR]

Exome sequencing of in situ tumor samples reveals that mutated genes can predict the prognosis of patients with T‐cell lymphoma (TCL). However, how tumor mutation burden (TMB) derived from circulating tumor DNA (ctDNA) may stratify TCL patients remains unclear.The plasma ctDNA of 79 newly diagnosed TCL patients from the clinical center is used for targeted exome sequencing, and the exome data of 4035 TCL patients from the Catalogue of Somatic Mutations in Cancer (COSMIC) database is obtained for comparison analysis.TCL patients with higher TMB, as evaluated with a panel of 120 genes (panel‐TMB120), are associated with poor prognosis. More importantly, COX regression analysis identifies a subset of 13 genes in panel‐TMB120, including AP3B1 (Adaptor related protein complex 3 subunit beta 1), ATM (Ataxia‐telangiectasia mutated), BCL6 (B cell lymphoma 6), BRAF (B‐Raf proto‐oncogene, serine/threonine kinase), CDKN2B (Cyclin dependent kinase inhibitor 2B), EPCAM (Epithelial cell adhesion molecule), FBXO11 (F‐box protein 11), JAK1 (Janus kinase 1), MDM2 (Murine double minute 2), NF1 (Neurofibromin 1), STAT5B (Signal transducer and activator of transcription 5B), STAT6 (Signal transducer and activator of transcription 6), and TET2 (Tet methylcytosine dioxygenase 2), which are significantly associated with prognosis. Specifically, higher TMB values calculated with these 13 genes (panel‐TMB13) are able to significantly predict unfavorable prognosis for these patients. Together, panel‐TMB13 and the International Prognostic Index (IPI) are used for risk stratification.Panel‐TMB13 is identified, which can predict poor prognosis for TCL patients carrying higher panel‐TMB13 scores and suggest that panel‐TMB13 may be a potential biomarker for supplement risk stratification of TCL patients. [ABSTRACT FROM AUTHOR]

One major characteristic of tumor cells is the aberrant activation of epigenetic regulatory elements, which remodel the tumor transcriptome and ultimately promote cancer progression and drug resistance. However, the oncogenic functions and mechanisms of ovarian cancer (OC) remain elusive. Here, super‐enhancer (SE) regulatory elements that are aberrantly activated in OC are identified and it is found that SEs drive the relative specific expression of the transcription factor KLF5 in OC patients and poly(ADP‐ribose) polymerase inhibitor (PARPi)‐resistant patients. KLF5 expression is associated with poor outcomes in OC patients and can drive tumor progression in vitro and in vivo. Mechanistically, KLF5 forms a transcriptional complex with EHF and ELF3 and binds to the promoter region of RAD51 to enhance its transcription, strengthening the homologous recombination repair (HRR) pathway. Notably, the combination of suberoylanilide hydroxamic acid (SAHA) and olaparib significantly inhibits tumor growth and metastasis of PARPi‐resistant OC cells with high KLF5. In conclusion, it is discovered that SEs‐driven KLF5 is a key regulatory factor in OC progression and PARPi resistance; and potential therapeutic strategies for OC patients with PARPi resistance and high KLF5 are identified. [ABSTRACT FROM AUTHOR]

A salient distractor interferes less with visual search if it appears at a location where it is likely to occur, referred to as distractor‐location probability cueing. Conversely, if the current target appears at the same location as a distractor on the preceding trial, search is impeded. While these two location‐specific "suppression" effects reflect long‐term, statistically learnt and short‐term, inter‐trial adaptations of the system to distractors, it is unclear at what stage(s) of processing they arise. Here, we adopted the additional‐singleton paradigm and examined lateralized event‐related potentials (L‐ERPs) and lateralized alpha (8–12 Hz) power to track the temporal dynamics of these effects. Behaviorally, we confirmed both effects: reaction times (RTs) interference was reduced for distractors at frequent versus rare (distractor) locations, and RTs were delayed for targets that appeared at previous distractor versus non‐distractor locations. Electrophysiologically, the statistical‐learning effect was not associated with lateralized alpha power during the pre‐stimulus period. Rather, it was seen in an early N1pc referenced to the frequent distractor location (whether or not a distractor or a target occurred there), indicative of a learnt top‐down prioritization of this location. This early top‐down influence was systematically modulated by (competing) target‐ and distractor‐generated bottom‐up saliency signals in the display. In contrast, the inter‐trial effect was reflected in an enhanced SPCN when the target was preceded by a distractor at its location. This suggests that establishing that an attentionally selected item is a task‐relevant target, rather than an irrelevant distractor, is more demanding at a previously "rejected" distractor location. Our study investigated how spatial statistical learning of a salient distractor affects visual search performance and related electrophysiological mechanisms. We found that statistical learning of spatial information of distractors could facilitate visual search by proactive suppression, but when a target appeared at the previous distractor location, it caused a cost. The statistical learning effect was reflected in the early N1pc/Ppc components, while the short‐term inter‐trial effect was shown in the late SPCN component. [ABSTRACT FROM AUTHOR]

The presence of large genomic rearrangements (LGRs) has been heavily investigated in breast and ovarian cancer. However, correlations between LGRs and cancer types beyond these two have not been extensively profiled, likely due to the highly inefficient methods of detecting these types of alterations. This study utilized next‐generation sequencing (NGS) to analyze and classify the germline LGR profile in 17 025 cancer patients across 22 cancer types. We characterized newly identified LGRs based on predicted pathogenicity and took a closer look at genes that acquire both germline and somatic mutations within our samples. The detection method for LGRs was validated using droplet digital polymerase chain reaction (ddPCR) assay of commonly investigated LGR genes. In total, 15 659 samples from across 22 cancer types were retained for analysis after filtering. We observed that, in our cohort, the cancer types with the highest proportion of germline LGRs were ovarian cancer (4.7%), renal cell carcinoma (2.5%), breast cancer (2%), glioma (1.8%) and thyroid carcinoma (1.8%). Annotation of detected germline variants revealed several genes—MSH2, FANCA and PMS2—that contain novel LGRs. We observed co‐occurrences between germline LGRs in MSH2 and somatic single nucleotide variants/insertion and deletions (SNVs/InDels) in BRCA2, KTM2B, KDM5A, CHD8, and HNF1A. Furthermore, our analysis showed that samples with pathogenic and likely pathogenic germline LGRs tended to also have higher mutational burden, chromosomal instability, and microsatellite instability ratio compared to samples with pathogenic germline SNVs/InDels. In this study, we demonstrated the prevalence of pathogenic germline LGRs beyond breast and ovarian cancer. The profiles of these pathogenic or likely pathogenic alterations will fuel further investigations and highlight new understanding of LGRs across multiple cancer types. [ABSTRACT FROM AUTHOR]

Background: Locoregional recurrence is of high risk and is associated with a poor prognosis in terms of OS for non‐small cell lung cancer (NSCLC). Local control is essential for radical cure of NSCLC. Previous studies have investigated the clinicopathological risk factors for locoregional recurrence, but the genomic biomarkers associated with locoregional recurrence have been inadequately studied. Methods: A total of 118 patients who underwent tumor resection with mutation‐detected tumor specimens were included. Tumor samples at surgery and pretreatment/postoperative blood samples were collected for mutational profiling. Results: Among 48 patients with disease recurrence, 46% developed locoregional recurrence (LR) and 75% developed distant metastasis (DM). The 3‐year actuarial risk of LR and DM was 25% and 43%, respectively. The first sites of failure were locoregional only (29%), locoregional and distant (10%), and distant only (61%). Patients with LR showed significantly higher ctDNA level than those with only DM at the time of initial recurrence. On multivariate analysis of baseline risk factors, the presence of allele frequency heterogeneity and baseline ctDNA shedding were found to be independently associated with a higher risk of LR. Patients with disruptive TP53 mutations had significantly lower LR‐free survival as compared to patients with wild‐type TP53 or nondisruptive mutations. EGFR mutations showed a favorable prognostic value for LR and is not induced by EGFR tyrosine kinase inhibitor therapy. Both disruptive TP53 mutation and EGFR mutation remained the significant prognostic factor after adjustment for histological type, pathologic nodal stage and adjuvant therapy. Conclusions: Nearly half of disease recurrences after surgery for NSCC involved locoregional sites. We identified genomic biomarkers from baseline tumor and ctDNA samples which showed promising prognostic value for LR only. This can help identify patients who had a higher risk of locoregional recurrence regardless of the risk of distant metastasis. [ABSTRACT FROM AUTHOR]

Problem: Immunomodulation profoundly affects the process of human implantation. Trophoblast cell‐derived microparticles (Tr‐MPs) may activate specific T cells to attack trophoblast cells, thus potentially acting as an immunocontraceptive vaccine. The safety and persistence of Tr‐MP vaccine are needed to address. Method of study: Flow cytometry and confocal fluorescent microscopy were conducted to detect cellular absorptivity and localization of Tr‐MPs in bone marrow‐derived dendritic cells (BMDCs). The phenotype and cytokine secretion of BMDC and T cells were performed by flow cytometry and enzyme‐linked immuno sorbent assay (ELISA). The constructed vaccine female moused model were used to observe the infertile effect and safety of Tr‐MPs. Results: As compared with non‐irradiation exposure groups, the number of MPs released by trophoblast cells in ultraviolet immunized groups significantly increased. The phagocytosis of Tr‐MPs led to the maturation of dendritic cells (DCs), which, in turn, activate T cells. Then cytotoxic T cells attacking trophoblast cells. In mouse model, female mice were infertile after receiving Tr‐MPs, and the effect of contraception is transient and safety. Conclusion: Using Tr‐MPs to initiate an adaptive immune response against alloantigens in trophoblast cells. Tr‐MPs may be a new candidate for the development of contraceptive vaccines due to its effectiveness, safety, and reversibility. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis (SAP) represents a common and serious disease that can cause intestinal barrier dysfunction. However, the pathogenesis of this barrier dysfunction remains unclear. Exosomes are a new intercellular communication method involved in multiple diseases. Consequently, the present study sought to determine the function of circulating exosomes in barrier dysfunction associated with SAP. A rat model of SAP was established by injecting biliopancreatic duct with 5% sodium taurocholate. Circulating exosomes were purified from SAP (SAP‐Exo) and sham operation rats (SO‐Exo) using a commercial kit. In vitro, SO‐Exo and SAP‐Exo were cocultured with rat intestinal epithelial (IEC‐6) cells. In vivo, naive rats were treated with SO‐Exo and SAP‐Exo. We found SAP‐Exo‐induced pyroptotic cell death and barrier dysfunction in vitro. In addition, miR‐155‐5p exhibited a remarkable increase in SAP‐Exo than SO‐Exo, and miR‐155‐5p inhibitor partially abolished the negative effect of SAP‐Exo on IEC‐6 cells. Furthermore, miRNA functional experiments revealed that miR‐155‐5p could induce pyroptosis and barrier loss in IEC‐6 cells. Overexpression of suppressor of cytokine signaling 1 (SOCS1), a miR‐155‐5p target, could partially reverse IEC‐6 cells from the harmful impact of miR‐155‐5p. In vivo, SAP‐Exo significantly triggered pyroptosis in intestinal epithelial cells and caused intestinal injury. In addition, blocking exosome release with GW4869 attenuated intestinal injury in SAP rats. In summary, our study demonstrated that miR‐155‐5p is highly enriched in circulating exosomes from SAP rat plasma and can be transported to intestinal epithelial cells, where it targets SOCS1 to activate NOD‐like receptor protein 3 (NLRP3) inflammasome‐mediated pyroptosis leading to intestinal barrier damage. [ABSTRACT FROM AUTHOR]

Objectives: Aberrantly expressed circular RNAs (circRNAs) have been detected in many types of tumors. Hence, they are currently investigated as candidate biomarkers for diagnostic and potential targets for therapy in cancers. The objective of this study was to assess the expression profile of circRNA in lung adenocarcinoma (LUAD). Methods: This study included 14 pairs of postoperative lung adenocarcinoma specimens, including cancer tissues and matched adjacent tissues. Second‐generation sequencing was applied to the specimens to determine the circRNA expression in them among the 5242 distinct circRNAs detected. Results: We identified a total of 18 significantly dysregulated circRNAs in the LUAD tissues: upregulation in four and downregulation in 14. ROC (The receiver operating characteristic curve) further suggested that hsa_circ_0120106, has_circ_0007342, has_circ_0005937, and circRNA_0000826 could potentially be used as biomarkers in the diagnosis of LUAD. Furthermore, study of the circRNA–microRNA (miRNA)–messenger RNA (mRNA) revealed interactions between the 18 dysregulated circRNA and several cancer‐related miRNAs. Finally, a further Kyoto Encyclopedia of Genes and Genomes analysis showed that the cell cycle phase transition, p53 signaling pathway, AMP‐activated protein kinase (AMPK) relative signaling pathway, and so on were key putative pathways in the process of LUAD. Conclusions: These findings demonstrated the correlation between abnormality in circRNA expression and LUAD, which lays the foundation of making CircRNAs candidate biomarkers in the diagnosis of LUAD. [ABSTRACT FROM AUTHOR]

Abbreviation: nCRT, neoadjuvant chemoradiotherapy. gl Next, we analysed nCRT-induced genomic changes ( I n i = 72 patients, Figure 2A), and 15 (20.8%) patients had no detectable mutations after nCRT. The efficacy of nCRT was assessed using tumour regression grade (TRG),[7] with TRG0 representing complete tumour regression and TRG3 representing little tumour regression. Dear Editor, Locally advanced rectal cancers (LARCs) are characterized by stage II/III diseases and account for about 15% of colorectal cancer cases.[1] Currently, a comprehensive trimodality approach of neoadjuvant chemoradiotherapy (nCRT), total mesorectal excision (TME) and adjuvant chemotherapy is the standard of care for LARC.[2] Previous studies have shown that nCRT could help control locoregional recurrence and improve pathologic complete response rate.[[3]] Nevertheless, up to 30% of patients showed poor response to nCRT, and as high as 35% of patients suffered from systemic recurrence.[[5]] This study aimed to use comprehensive genomic profiling to identify reliable molecular biomarkers to stratify LARC patients based on their treatment response, recurrence risk and prognosis. [Extracted from the article]

Background: Kinase domain duplications (KDDs) have recently been recognized as oncogenic mutations and possible association with drug resistance in cancers. Method: Here, targeted sequencing was performed with the tumor tissue and/or plasma from 65 cancer patients with KDDs. Result: Intact KDDs were identified in approximately 0.1% of the total population across multiple cancer types. EGFR KDD was first identified in colorectal cancer and breast cancer, whereas FGFR2 KDD was first identified in gastric cancer. Tumors with EGFR KDD displayed lower concurrent TP53 gene alterations (p = 0.03) and slightly higher chromosome instability (p = 0.27) compared to tumors with non‐EGFR‐KDDs. Immune pathway analysis further revealed the enrichment of the cytokine receptors pathway (93%) in the KDD carriers. Hyperprogression‐related gene mutations were identified in four cases. Conclusion: Collectively, our data revealed the genomic features of KDD alterations in a multi‐cancer cohort, providing more information for the potential treatment application in the KDD carriers. [ABSTRACT FROM AUTHOR]

Solar desalination is one of the most promising ways to produce freshwater. Interfacial solar steam generation system is especially studied for its high solar–thermal conversion efficiency. However, the phase transition process of water evaporation is energy intensive and a salt cluster is easily accumulated at the surface of the evaporator, which limits the water yield and stability of the distiller. Herein, a hybrid design involving tuning the water state, recycling latent heat, and spatial localizing low‐concentration zone to distill for stable and efficient solar‐water harvesting is demonstrated. In a two‐stage distiller, the water yield can reach 1.62 kg m−2 h−1 under one sun irradiation, corresponding to the solar‐to‐vapor conversion efficiency of 110%. The scale‐up device can also steadily operate for 1 week outdoors. This work provides an effective strategy for high‐efficiency solar distillation, holding the promise of application in seawater desalination and domestic water supply. [ABSTRACT FROM AUTHOR]

(A) ROC curves evaluating the performance of brain metastases (BM) predictive models (BPM and integrated) in distinguishing BM-positive patients from BM-negative patients in the training cohort (N = 70). Early diagnosis of brain metastases using cerebrospinal fluid cell-free DNA-based breakpoint motif and mutational features in lung cancer (A) Receiver operating characteristics (ROC) curves evaluating the performance of brain metastases (BM) predictive models in distinguishing BM-positive patients from BM-negative patients in the testing cohort (N = 11). In this study, we developed a sensitive machine learning model with a remarkable capacity to predict brain metastases (BM) in lung cancer patients using the breakpoint motif (BPM) features in cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA). [Extracted from the article]

Multifocal esophageal squamous cell carcinomas (ESCCs) can be diagnosed as of multicentric origin (MO) or intramural metastasis (IMM). We aimed here to accurately discriminate MO from IMM and explore the tumor immune microenvironment of multifocal ESCCs. Multifocal ESCCs were identified in 333 ESCC patients, and in 145 patients discrimination between MO and IMM was not possible by histopathological examination. Of the 145 patients, tissues of 14 were analyzed by whole‐exome sequencing (WES) of 71 different tumor regions, and MO, IMM, and MO/IMM mixed groups were identified in three, ten, and one cases, respectively, based on the similarity of genomic architecture between or among different tumors from one patient. Further phylogenetic analyses revealed complex clonal evolution patterns in IMM cases, and tumor cells disseminated from the primary tumors to IMM tumors were independent of lymph node metastasis. The NanoString‐based assay showed that immune cell infiltrates were significantly enriched, and that the immune and proliferation pathways were more activated, in large tumors than in small ones in MO but not IMM cases. Similarly, PD‐L1 expression and the density of paratumoral CD8+ T cells were higher in large tumors than in small tumors in MO. Taken together, through analysis of the genomic and immune landscapes, our study has comprehensively characterized the heterogeneity and clonal relationship of multifocal ESCCs, which may be helpful in distinguishing MO from IMM, and for interpreting the immunotherapy responses for multifocal ESCC patients. © 2022 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Background: Soft‐tissue sarcoma (STS) is a rare solid malignant tumor with numerous histologic subtypes. Current studies on targeted therapy for STS are in preclinical and early‐phase trials. Genomic differences largely influence the prognosis of patients even with the same subtype. To investigate the genomic alterations (GAs) and the potential of targeted therapy in STS, we analyzed the genomic landscape, the therapeutic GAs, and biomarkers of immunotherapy in Chinese STS patients. Methods: Targeted sequencing covering 425 genes was performed, from which we obtained the results of tissue samples from 351 Chinese STS patients of all ages covering different histologic subtypes. Bioinformatics analysis of altered genes with nonsynonymous mutations, copy‐number variations, and gene fusions were performed. OncoKB therapeutic GAs and relevant biomarkers including TMB, MSI, and HRD were further examined for potential targeted therapy. Results: In total, 2743 GAs were identified in 330 genes with a median of 6 (1–38) per case. The top 11 frequently altered genes were: TP53, MCL1, MDM2, CDK4, MYC, CDKN2A, GNAS, RB1, ATRX, CDKN2B, and FGFR1. OncoKB defined therapeutic GAs were found in 23 genes in 43% of the patients. In general, 9.4% of the patients had high‐TMB, 2.8% had MSI, and 13.7% had HRD. A significant difference in the percentage of patients with OncoKB therapeutic GAs were observed between the most frequent two subtypes, leiomyosarcoma and liposarcoma. Altogether, 54% of the patients had the potential to respond to a targeted therapy. Conclusion: This study indicated the potential efficacy of targeted therapy on many STS patients, and also provided insight for novel precision therapy. The clinical efficacy of combining targeted therapy and immunotherapy can be further investigated. [ABSTRACT FROM AUTHOR]

Tumor‐infiltrating lymphocytes (TILs) offer a key for morphological diagnosis of lymphoepithelioma‐like carcinoma (LELC) and are the foundation of oncoimmunology. To date, no reports have found a specific risk stratification value of TILs and related it to genomic variation in LELC. Based on the stromal TILs (str‐TILs) ratio, we classified 105 Epstein–Barr virus (EBV)‐associated LELC cases into two subtypes: patients with ≥60% str‐TILs area ratio in tumor were classified as subtype I, and otherwise as subtype II. Subtype I patients had significantly better progression‐free survival (PFS) and overall survival (OS). We also explored the genomic characteristics of EBV‐associated LELC within different involved organs. We performed whole‐exome sequencing for 51 patients with enough tissue and analyzed the genomic characteristics of EBV‐associated LELC. Overall, EBV‐associated LELCs were characterized by a low somatic mutation rate and copy number variations; the enriched genetic lesions affected RTK‐RAS, PI3K, and cell cycle pathways. Moreover, EBV‐associated LELCs from different organs were more similar to each other genetically as compared with other traditional carcinomas of the same sites―as evidenced by unsupervised clustering based on the quantitative data from both mutation signature and chromosomal aneuploidies. Notably, EBV‐associated LELC patients with oncogenic driver alterations showed a worse prognosis compared with patients without such alterations. © 2022 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

TRK fusions are rare but targetable mutations which occur across a wide variety of cancer types. We report the prevalence of approximately 0.7% for NTRK‐positive colorectal cancer (CRC) by genetically profiling 2519 colonic and rectal tumors. The aberrations of APC and TP53 frequently co‐occurred with NTRK gene fusions, whereas RAS/BRAF oncogenic alterations and NTRK fusions were almost always mutually exclusive. NTRK‐driven colorectal cancer patients demonstrated increased TMB (median = 53 mut/MB, 95% CI: 36.8–68.0 mut/MB), high microsatellite instability, and an enrichment for POLE/POLD1 mutations when compared to molecularly unstratified colorectal cancer population. These data shed light on possible future approach of multimodality treatment regimen including TRK‐targeted therapy and immune checkpoint inhibitor therapy in NTRK‐positive CRCs. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to recapitulate the change trajectory of postoperative weight and investigate the association between postoperative hypothalamic damage and weight gain and hypothalamic obesity (HO) in patients with adult‐onset craniopharyngioma. Methods: The data of 96 patients with surgically treated primary adult‐onset craniopharyngioma were retrospectively analyzed. The association between postoperative hypothalamic damage based on magnetic resonance images or endoscopic observation and postoperative weight gain and HO was determined by multivariable logistic regression. Results: Forty‐seven (49.0%) patients and 18 (18.8%) patients experienced clinically meaningful weight gain (≥5%) and HO at last follow‐up, respectively. Postoperative weight significantly increased during the first 6 months following surgery, followed by stabilization. Both grade 2 postoperative hypothalamus damage, as evaluated by the magnetic resonance imaging classification system of Müller et al., and higher scores based on the Roth et al. hypothalamic lesion score were significantly associated with postoperative weight gain of ≥5% (p = 0.005 and p = 0.002) and with HO (p = 0.001 and p = 0.008). Additionally, bilateral hypothalamic injury as evaluated by the Hong et al. hypothalamic injury pattern based on endoscopic observation (p = 0.008) could predict postoperative weight gain ≥5%. Conclusions: Significant postoperative weight gain is common in patients with adult‐onset craniopharyngioma. Postoperative hypothalamic damage can predict clinically meaningful weight gain and HO. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence has underscored infiltrating immune cells in the tumor microenvironment (TME) of non‐small cell lung cancer (NSCLC). Owing to screening programs, the prevalence of early‐stage NSCLC is growing, but its high recurrence risk and poor survival impose an increasing demand for further understanding the TME. Methods: Tissue and plasma samples from 33 resectable stage IA NSCLC patients were collected from the surgery and subject to histological and genomic analyses. The distribution of CD8+ T cells, tumor‐associated macrophages (TAMs, M1 polarization and M2 polarization), and natural killer (NK) cells (CD56dim and CD56bright) was analyzed. The impact of clinical characteristics and immunotherapy‐related biomarkers on immune cell infiltration were also investigated. Results: Using multiplex immunohistochemistry (mIHC), we found a significantly higher M1 polarization proportion of total TAMs in tumor parenchyma than in other tissues, while other immune cells remained stable. Patients under 50 showed higher infiltrating CD8+ T cell density and M1 ratio in tumor tissues. Tumors carrying RAS‐MAPK mutations were associated with significantly increased infiltration of CD8+ T cells. We also identified significantly higher infiltration of CD8+ T cells and enrichment of CD56bright NK cells in high tumor mutation burden (TMB) and high programmed cell death ligand 1 (PD‐L1) samples, respectively. Conclusions: Our study highlighted the heterogeneity and dynamics of infiltrating immune cells in stage IA NSCLC TME, featured by M1 TAM enrichment in tumor parenchyma. Age, driver mutation type, TMB, and PD‐L1 level were found to associate with immune cell infiltration in the TME, shedding light on immunotherapy development. [ABSTRACT FROM AUTHOR]

(D) Association between V 6-6J 1-3 and V 6-6J 1-6 combination based risk score and OS or disease-free survival (DFS) in EGFR-mutant non-small-cell lung cancer (NSCLC) patients. When patients carried high frequency of V 6-6J 1-3 or V 6-6J 1-6, the application of V 6-6 antibody or other treatment options should be considered. Overall, the results indicated both V 6-6J 1-3 and V 6-6J 1-6 associated with poor OS of I EGFR i -mutant NSCLC patients. These results not only show that specific TCR rearrangements (V 6-6J 1-3 and V 6-6J 1-6) are prognostic on their own, but the optimal model with a combination of these TCRs have the greatest predictive potential for prognosis of I EGFR i -mutant NSCLC patients. [Extracted from the article]

Alpha‐fetoprotein–producing gastric cancer (AFPGC) is associated with high invasion and poor prognosis, but has not been well‐documented due to its rarity. To develop the understanding of AFPGC, and further facilitate its clinical decision‐making and treatment, we performed clinicopathological and molecular characterization of AFPGC and its two major subtypes, namely, gastric adenocarcinoma with enteroblastic differentiation (GAED) and hepatoid adenocarcinoma (HAC). The clinicopathological and molecular characteristics of AFPGC patients (n = 54) were mainly investigated by immunohistochemistry and next‐generation sequencing (NGS) approaches. AFPGC exhibited a higher incidence of lymphatic and vascular invasion than conventional gastric adenocarcinoma (CGA). Despite various morphological patterns, there was mostly no evident difference in clinicopathological characteristics between the GAED and HAC subtypes. Target‐enriched NGS profiling of disease mutation landscapes discovered 17 differentially mutated genes between AFPGC and CGA. The AFPGC patients carrying ZNF217 mutations had poorer overall survival than the ZNF217 wildtype. Furthermore, ATR showed a significantly higher mutation rate in GAED than in HAC. Overall, our study of clinicopathological characteristics shed light on the differences between CGA and AFPGC, as well as the relationships between the GAED and HAC subtypes of AFPGC. Furthermore, mutation landscape profiling revealed potential diagnostic and prognostic markers for AFPGC and its two subtypes. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor DNA (ctDNA) has emerged as a noninvasive biomarker for dynamically monitoring tumors. However, published data on perioperative ctDNA in patients with operable non-small cell lung cancer (NSCLC) are currently limited.Methods: This prospective study recruited 123 patients with resectable stage I to IIIA NSCLC. Preoperative and postoperative plasma samples and tumor tissue samples were subjected to next-generation sequencing with a panel of 425 cancer-related genes. Peripheral blood samples were collected before surgery, postoperatively within 1 month, and every 3 to 6 months for up to 3 years.Results: After 4 exclusions, 119 eligible patients were enrolled from June 2016 to February 2019. Presurgical ctDNA was detectable in 29 of 117 patients (24.8%) and was associated with inferior recurrence-free survival (RFS; hazard ratio [HR], 2.42; 95% CI, 1.11-5.27; P = .022) and inferior overall survival (OS; HR, 5.54; 95% CI, 1.01-30.35; P = .026). Similarly, ctDNA was detected in 12 of 116 first postsurgical samples (10.3%) and was associated with shorter RFS (HR, 3.04; 95% CI, 1.22-7.58; P = .012). During surveillance after surgery, longitudinal ctDNA-positive patients (37 of 119; 31.1%) had significantly shorter RFS (HR, 3.46; 95% CI, 1.59-7.55; P < .001) and significantly shorter OS (HR, 9.99; 95% CI, 1.17-85.78; P = .010) in comparison with longitudinal ctDNA-negative patients. Serial ctDNA detection preceded radiologic disease recurrence by a median lead time of 8.71 months.Conclusions: These results suggest that perioperative ctDNA analyses can predict recurrence and survival, and serial ctDNA analyses can identify disease recurrence/metastasis earlier than routine radiologic imaging in patients with resectable NSCLC.Lay Summary: The utility of serial circulating tumor DNA (ctDNA) monitoring for predicting disease recurrence and survival for early-stage non-small cell lung cancer (NSCLC) has not been well characterized. The detection of ctDNA before and after surgery is associated with the identification of a high risk of disease recurrence and long-term patient outcomes for resectable NSCLC. Perioperative ctDNA analyses identify disease recurrence earlier than routine radiologic imaging. ctDNA analyses can detect minimal residual disease for resectable NSCLC and thus can facilitate early intervention. [ABSTRACT FROM AUTHOR]

For sustainable hydrogen production, electrochemical water splitting is a promising method whose efficiency is limited by its anodic reaction, i.e., the oxygen evolution reaction (OER). One of the best electrocatalysts for the OER is the self‐supported nickel–iron layered double hydroxides on iron foam (NiFe‐LDH@IF) prepared by corrosion engineering. However, the further development of NiFe‐LDH@IF is hampered by a lack of understanding regarding the growth mechanism and the effects of corrosion conditions on the electrocatalytic activity. Herein, the growth mechanism is studied, revealing for the first time that NiFe‐LDH@IF is formed by the preferential precipitation of NiFe‐LDH on the NiFe‐alloy cathode around which the local pH is high due to the reduction of dissolved oxygen. Guided by this growth mechanism, it is found that corrosion conditions mainly affect the electrocatalytic activity of NiFe‐LDH@IF via changing the amount of α‐FeOOH and NiFe‐LDH along with the Fe2+‐doping level of NiFe‐LDH. With the aid of these findings, corrosion conditions are optimized and the prepared NiFe‐LDH@IF exhibits the best reported comprehensive electrocatalytic performance. More importantly, the growth mechanism of NiFe‐LDH@IF can be generalized to various self‐supported LDH on different substrates prepared by corrosion engineering. [ABSTRACT FROM AUTHOR]

Plant salt tolerance is associated with a high rate of root growth. Although root growth is governed by cell wall and apoplastic pH, the relationship between these factors in the root elongation zone under salinity stress remains unclear. Herein, we assess apoplastic pH, pH‐ and expansin‐dependent cell wall extensibility, and expansin expression in the root elongation zone of salt‐sensitive (Yongliang‐15) and ‐tolerant (JS‐7) cultivars under salinity stress. A six‐day 80 mM NaCl treatment significantly reduced apical root apoplastic pH in both cultivars. Using a pH‐dependent cell wall extensibility experiment, we found that, under 0 mM NaCl treatment, the optimal pH for cell wall loosening was 6.0 in the salinity‐tolerant cultivar and 4.6 in the salinity‐sensitive cultivar. Under 80 mM treatment, a pH of 5.0 mitigated the cell wall stiffness caused by salinity stress in the salinity‐tolerant cultivar but promoted cell wall stiffening in the salinity‐sensitive cultivar. Salinity stress altered expansin expression and differentially affecting cell wall extensibility under pH 5.0 and 6.0. TaEXPA8 might be relative to cell wall loosening at pH 5.0, whereas TaEXPA5 relative to cell wall loosening at pH 6.0. These results elucidate the relationship between expansins and cell wall extensibility in the root elongation zone, with important implications for enhancing plant growth under salinity stress. [ABSTRACT FROM AUTHOR]

BACKGROUND: Plant diseases have been gripping agricultural production, seriously affecting the growth and yields of crops. Marine natural products are an important source for novel drugs discovery. In this work, pityriacitrin marine alkaloids were selected as the parent structures. A series of pityriacitrin alkaloid analogues were rationally designed, synthesized and evaluated for their antiviral activities and fungicidal activities. RESULT: Most of these compounds were demonstrated to have higher antiviral activities than ribavirin. Particularly, compounds 3a, 3e, 8f, 8g, and 9g displayed higher anti‐TMV activities than ningnanmycin at 500 μg·mL−1. Mechanism research revealed that 3a could bind to TMV CP with an excellent affinity (Ka = 8.67 × 106 L·mol−1), thus interfere with the assembly of virus particles. These alkaloids also showed broad‐spectrum fungicidal activities against eight kinds of phytopathogenic fungi. Compound 5f with 1.43–3.84 μg·mL−1 EC50 value against three fungi emerged as a new fungicidal candidate. CONCLUSION: Pityriacitrin alkaloids and their derivatives were synthesized and evaluated for anti‐TMV and fungicidal activities for the first time. Compounds 3a and 5f with excellent activities emerged as new candidates for antiviral research and fungicidal research, respectively. Current work provided a new idea for the molecular design and development of novel plant virus and fungi inhibitors in the future. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate age‐dependent tendency of genomic alterations in lung cancer, and also to examine mutational profiles and its association with clinical treatment outcomes in young adenocarcinoma patients. By studying 7858 lung cancer samples using targeted‐gene sequencing, we investigated genomic differences and clinical on‐treatment time (OTT) to different therapies between young (≤ 45 years) and old (> 45 years) patients. The age‐dependent trend test for genomic alterations in all patients revealed steady increases in tumor mutation burden and alterations in a number of genes with age, including KRAS, MET, CDKN2A, PIK3CA and MDM2, while the frequencies of ALK, ROS1 and RET fusions and ERBB2 mutations were decreasing. The highest rate of EGFR alterations was observed in the 45 ~ 50 years age group. Comparisons of young and old adenocarcinoma patients found that young patients were characterized by a higher prevalence of ALK, ROS1 and RET fusions, and ERBB2 exon‐20 insertions and EGFR exon‐19 deletions. Actionable mutations were highly prevalent in young adenocarcinoma patients, with 88% of patients harboring at least one actionable genetic alteration. First‐line therapies in EGFR‐positive patients (n = 979) by EGFR tyrosine kinase inhibitors or chemotherapy resulted in similar OTT between young and old patients. Somatic interaction analyses implied that young EGFR‐positive patients were more likely to also have PIK3CA, MET, TP53 and RB1 mutations than old patients. Lung cancer in young patients, and especially those with adenocarcinoma, exhibited different clinical features and genomic attributes compared to old patients, which should be considered for therapeutic decision‐making purposes. What's new? Young patients with lung cancer represent a sub‐group with distinct clinical features compared to older patients. This large retrospective cohort study with a targeted sequencing panel covering over 400 cancer‐related genes suggests that young adenocarcinoma patients (≤45 years) have a different spectrum of driver mutations and a higher ratio of actionable genetic alterations compared to older patients. Over a third of young patients have multiple drivers, and the co‐mutation rate of EGFR with other oncogenes is high. These findings highlight genetic differences between young and older patients that possibly associate with different treatment outcomes. [ABSTRACT FROM AUTHOR]

To improve the performance of dye‐sensitized photoelectrochemical cell (DS‐PEC) devices for splitting water, the tailoring of the photocatalytic four‐photon water oxidation half‐reaction represents a principle challenge of fundamental significance. In this study, a Ru‐based water oxidation catalyst (WOC) covalently bound to two 2,6‐diethoxy‐1,4,5,8‐diimide‐naphthalene (NDI) dye functionalities provides comparable driving forces and channels for electron transfer. Constrained ab initio molecular dynamics simulations are performed to investigate the photocatalytic cycle of this two‐channel model for photocatalytic water splitting. The introduction of a second light‐harvesting dye in the Ru‐based dye‐WOC‐dye supramolecular complex enables two separate parallel electron‐transfer channels, leading to a five‐step catalytic cycle with three intermediates and two doubly oxidized states. The total spin S=1 is conserved during the catalytic process and the system with opposite spin on the oxidized NDI proceeds from the Ru=O intermediate to the final Ru‐O2 intermediate with a triplet molecular 3O2 ligand that is eventually released into the environment. The in‐depth insight into the proposed photocatalytic cycle of the two‐channel model provides a strategy for the development of novel high‐efficiency supramolecular complexes for DS‐PEC devices with buildup and conservation of spin multiplicity along the reaction coordinate as a design principle. [ABSTRACT FROM AUTHOR]

We collected 26 cases of bronchiolar adenoma (BA) and its variants, and performed a comprehensive characterization using a combination of morphological, immunohistochemical, and genetic assessments. Of these 26, 13 were classic bilayered cases, including 10 proximal and 3 distal‐type BAs. Of note, we also identified 13 cases that lacked a continuous basal cell layer. In five cases, the adenomas were partially classic bilayered, leaving a single layer of columnar or cuboidal epithelial cells in some areas of the lesion (BA with monolayered cell lesions). In the other eight cases, the glandular or papillary structures were entirely composed of monolayered columnar or cuboidal epithelial cells, which were morphologically identical to the luminal epithelial cells of classic BA (monolayered BA‐like lesions). Immunohistochemical analysis revealed thyroid transcription factor 1 expression by ciliated columnar epithelial cells, basal cells, and nonciliated columnar and cuboidal epithelial cells. Basal cells also expressed p40 and p63. Twenty‐five cases underwent next‐generation sequencing using a 422‐cancer‐gene panel (GeneseeqPrime). Oncogenic driver mutations were detected in 23 cases, including 13 (52%) with EGFR mutations, 4 (16%) with KRAS G12D/V mutations, 3 (12%) with BRAF V600E mutations, 2 (8%) with ERBB2 exon 20 insertions, and 1 (4%) with a RET fusion. EGFR exon 20 insertions were present in 100% of BAs with monolayered cell lesions, 37.5% of monolayered BA‐like lesions, and 8% of classic BA (Fisher's exact test, p = 0.002, false discovery rate = 0.014). Collectively, our study revealed a gradual morphological transition between BA and its variants. The genetic composition of BAs with monolayered structures differed significantly from those of classic BAs or lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Guidelines for laboratory assessment of fetomaternal haemorrhage (FMH) was published by the Australian and New Zealand Society of Blood Transfusion (ANZSBT) in 2002. However, data on adherence by practitioners and clinical outcomes are lacking. Aims: The primary objective is to examine the follow‐up testing and dosing of additional RhD immunoglobulin in RhD negative women who experienced large‐volume FMH for whom additional intravenous RhD immunoglobulin was requested in Queensland, Australia. The secondary objectives are to examine the rate and risk factors of RhD alloimmunisation in these women. Materials and Methods: RhD negative women with FMH >6 mL for whom additional dose(s) of intravenous RhD immunoglobulin was requested through Australian Red Cross Lifeblood from February 2007 to February 2018 were identified. For each patient, the volume of FMH, methods and timing of FMH quantitation, dose of RhD immunoglobulin, maternal and cord blood groups were analysed against the corresponding antibody screen and identification. Results: Following FMH >6 mL, only 15% and 11.5% of cases adhered to current ANZSBT guideline on follow‐up testing and supplemental RhD immunoglobulin dosing respectively. Despite the provision of single supplemental RhD immunoglobulin at a ratio of 100 IU to 1 mL fetal red cells, the rate of RhD alloimmunisation in RhD negative women with RhD positive fetus or fetus of unknown RhD status following FMH >6 mL is at least 4%. Conclusions: Poor compliance with guidelines for follow‐up and management of large‐volume FMH may contribute to increased risk of RhD alloimmunisation. Further analysis of data is warranted. [ABSTRACT FROM AUTHOR]

Objectives: Pancreatic cancer (PC) is one of the most lethal malignancies with an increasing death rate over the years. We performed targeted sequencing and survival analyses on 90 Chinese pancreatic cancer patients, hoping to identify genomic biomarkers associated with clinical outcomes and therapeutic options. Method: Genomic DNA was extracted from formalin‐fixed paraffin‐embedded (FFPE) tissue specimens of 90 pancreatic cancer patients and sequenced. The associations with clinicopathological factors were analyzed. Result: High prevalence of driver mutations in KRAS, TP53, CDKN2A, SMAD4, and ARID1A genes were found. Most mutated genes in PC belonged to cell cycle and DNA damage repair pathways. Tumors that arise from the pancreas' body and tail (BT tumors) displayed a higher ratio of mutated KRAS and TP53 than those that arise from the pancreas' head and neck (HN tumors), who showed less diverse KRAS subtypes. Patients with a KRAS p.G12R mutated tumor tended to have a prolonged disease‐free survival (DFS) and overall survival (OS) than other KRAS subtypes. Those with an altered ARID1A gene and more than two mutated driver genes tended to have a shorter DFS and OS. Conclusion: HN and BT tumors of the pancreas displayed different mutational profiles, which had prognostic significances and indicated different potential therapeutic options. [ABSTRACT FROM AUTHOR]

Association of circulating tumor DNA from the cerebrospinal fluid with high-risk CNS involvement in patients with diffuse large B-cell lymphoma Dear Editor, Central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) patients correlates with dismal outcomes, and the detection sensitivity of conventional diagnosis of lymphoma is restricted.1-4 Circulating tumor DNA from cerebrospinal fluid (CSF-ctDNA) has played an important part in the application of liquid biopsy for patients with CNS cancers.5 In this study, we provided new insights into feasibility of CSF-derived biomarkers for CNS relapse diagnosis in DLBCL patients. Moreover, we compared alterations in five CSF-CNS genes from systemic tumor tissue of DLBCL patients in high-risk (HR) group with an additional dataset of 40 patients clinically diagnosed as low risk (LR) for CNS relapse. Five CSF-CNS genes in CSF was found to be associated with CNS risk in DLBCL patients, which deserve further investigation to determine their relevance among the diagnosis, treatment, and outcome. [Extracted from the article]

Comprehensive next-generation profiling of clonal hematopoiesis in cancer patients using paired tumor-blood sequencing for guiding personalized therapies Dear Editor: In this study, we report for the first time the landscape and clinical relevance of clonal hematopoiesis (CH) in Chinese cancer patients using next-generation sequencing (NGS) and emphasize the need for paired tumor-blood sequencing to better inform clinical actions given the high prevalence and largely nonrecurrent nature of CH mutations. CH was defined as nonsynonymous mutations in which the blood variant allele fraction (VAF) is >=2× that in the respective tumor.5 GLO:F2H7/01nov20:ctm2222-fig-0001.jpg PHOTO (COLOR): 1 Distribution of CH variants across patients with diverse solid tumor types. A, Age distributions of the entire cohort (N = 4544) with CH (CH+), with CH detected in solid tumor (CH-ST), and without CH-associated mutations in the blood (CH-). [Extracted from the article]

This work reports a three‐dimensional (3D) radio frequency L−C filter network enabled by a CMOS‐compatible two‐dimensional (2D) fabrication approach, which combines inductive (L) and capacitive (C) self‐rolled‐up membrane (S‐RuM) components monolithically into a single L−C network structure, thereby greatly reducing the on‐chip area footprint. The individual L−C elements are fabricated in‐plane using standard semiconductor processing techniques, and subsequently triggered by the built‐in stress to self‐assemble and roll into cylindrical air‐core architectures. By designing the planar structure geometry and constituent layer properties to achieve a specific number of turns with a desired inner diameter when the device is rolled up, the electrical characteristics can be engineered. The network layouts of the L and C components are also reconfigurable by selecting appropriate input, output, and ground contact routing topographies. The devices demonstrated here operate over the range of ≈1−10 GHz. Their area and volume footprints are ≈0.09 mm2 and ≈0.01 mm3, respectively, which are ≈10× smaller than most of the comparable conventional filter designs. These S‐RuM‐enabled 3D microtubular L−C filter networks represent significant advancement for miniaturization and integration of passive electronic components for applications in mobile connectivity and other frequency range. [ABSTRACT FROM AUTHOR]

Transmembrane domain (TMD) mutations of ERBB2 have previously been reported in lung cancer patients in addition to well‐studied kinase domain (KD) mutations, which may stabilize ERBB2 heterodimerization with other EGFR family members and favor a kinase active conformation. However, the frequency and clinical significance of ERBB2 TMD mutations in Chinese population is unknown. We prospectively analyzed the next‐generation sequencing data of 34 368 Chinese lung cancer patients with different sample types, including tumor tissue, plasma, cerebrospinal fluid, and pleural effusion. Patients' clinical characteristics and treatment history were retrieved from the database for further evaluation. Our findings show that ERBB2 V659/G660 mutations were detected at a frequency of 0.13% (45/34 368), of which the most frequent was V659D/E (88.9%), with a trend in nonsmokers and male. Moreover, 18% of patients (8/45) showed EGFR and/or ERBB2 amplification, whereas nine patients presented EGFR L858R or exon19 deletion. Interestingly, novel ERBB3 TMD mutation I646R was found coexisting in three patients with ERBB2 V659D and one patient with ERBB2 G660D, which might influence its heterodimerization with ERBB2 and further activate ERBB2. Four ERBB2 TMD mutation‐positive patients received afatinib monotherapy or combination therapy, but showed variable responses. One patient with V659E responded well to ERBB2 inhibitor lapatinib plus capecitabine as well as subsequent afatinib treatment upon progression. Our study provides valuable insights into the distribution of ERBB2 TMD mutations by employing the largest Asian lung cancer cohort thus far. Patients with ERBB2 TMD mutations who received afatinib, a pan‐ERBB inhibitor, demonstrated mixed responses, posing the urgent need to develop more effective therapeutic strategy for patients who carry ERBB2 TMD mutations. [ABSTRACT FROM AUTHOR]

EGFR exon 20 insertions (EGFR e20ins) account for up to 10% of EGFR mutations in lung cancer; however, tumors with EGFR e20ins had poor response rates to EGFR tyrosine kinase inhibitors (TKIs) including gefitinib, erlotinib, afatinib, and osimertinib, and the heterogeneity of EGFR e20ins further complicates the clinical studies. Here, we retrospectively screened next‐generation sequencing (NGS) data from 24 468 lung cancer patients, and a total of 85 unique EGFR e20ins variants were identified in 547 cases (2.24%), with p.A767_V769dup (25.1%) and p.S768_D770dup (17.6%) being the most prevalent ones. Comprehensive genomic profiling revealed that TP53 mutations frequently coexisted with p.H773dup (77.8%, P = 0.0558) and p.A767_V769dup (62.8%, P = 0.0325), while RB1 mutations usually co‐occurred with p.H773_V774insAH (33.3%, P = 0.0551), implying that different EGFR e20ins variants might require distinct genomic context for tumorigenesis and/or maintenance. Despite that treatment regimens were highly diverse for EGFR e20ins‐positive patients, we observed an overall response rate of 14% and a disease control rate (DCR) of 38.4% in 65 patients who received at least one EGFR TKI. The progression‐free survival (PFS) differs significantly in six representative EGFR e20ins variants (P = 0.017), and EGFR p.A763_Y764insFQEA was associated with better PFS than other EGFR e20ins when treating with various EGFR TKIs. Some EGFR e20ins variants showed at least partial response to first‐generation EGFR TKIs, including p.A767_V769dup, p.S768_D770dup, p.N771_H773dup, p.A763_Y764insFQEA, and p.D770_N771insG. Poziotinib achieved higher DCR for p.S768_D770dup than for p.A767_V769dup, whereas osimertinib showed limited effects for these two insertions when used as the first‐line treatment. Overall, our results demonstrated that EGFR e20ins were highly diversified in terms of insertion patterns and co‐occurring mutations and these EGFR e20ins variants showed different clinical responses to various EGFR TKIs, suggesting the clinical importance of selecting proper EGFR TKI treatment based on the specific EGFR e20ins type. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the usefulness of the contrast‐enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI‐RADS) in diagnosing focal liver lesions (FLLs) by inexperienced radiologists. Methods: Images and clinical data from 258 patients at risk for hepatocellular carcinoma who underwent CEUS were collected retrospectively. Two trained inexperienced radiologists and 2 experienced radiologists reviewed all CEUS clips. Each inexperienced radiologist assigned a CEUS LI‐RADS category for each observation and labeled it benign or malignant independently. Each experienced radiologist labeled each lesion malignant or benign independently using a conventional diagnostic method. Interobserver agreement of CEUS LI‐RADS was analyzed by the κ test. The overall diagnostic accuracy of the LI‐RADS category and conventional diagnosis was described by the sensitivity, specificity, positive predictive value, and negative predictive value. All test results were considered significant at P <.05. Results: A κ value of 0.774 indicated that the CEUS LI‐RADS algorithm resulted in substantial consistency between the inexperienced radiologists. For the diagnosis of hepatocellular carcinoma, the sensitivity, specificity, positive predictive value, and negative predictive value were improved significantly in inexperienced radiologists using the CEUS LI‐RADS compared to conventional methods. The overall diagnostic accuracy of the experienced radiologists was almost equal to that of CEUS LI‐RADS categories assigned by the inexperienced radiologists. Conclusions: The CEUS LI‐RADS algorithm can not only obtain substantial consistency among inexperienced radiologists but also have excellent diagnostic efficacy in the differentiation of benign from malignant FLLs compared to conventional methods. As a comprehensive algorithm, the CEUS LI‐RADS can act as a guide for trainees in learning how to diagnose FLLs. [ABSTRACT FROM AUTHOR]

Background: While there have been encouraging preliminary clinical results for immune checkpoint inhibitors (ICIs) in BTCs, it remains a challenge to identify the subset of patients who may benefit. In this study, we evaluated the efficacy of ICI treatment in patients with advanced BTCs, and explored potential biomarkers that are predictive of response. Methods: The study enrolled 26 patients with advanced microsatellite stable BTCs (15 with gallbladder cancers [GCs] and 11 with intrahepatic cholangiocarcinoma [ICCs]) who received ICI treatment. Targeted next‐generation sequencing (NGS) was performed on tumor tissue samples collected from 17 patients. Clinical and genomic characteristics were assessed for the correlation with clinical outcome. Results: Analysis of the baseline clinical characteristics showed that performance score (PS) of 0 was associated with a better prognosis than PS of 1 (HR = 1.08 × 109; 95% CI, 0∼Inf; P =.002). No significant correlations were found between clinical outcome and inflammation‐related indicators. NGS profiling of the available tumor tissues, revealed largely non‐overlapping somatic alterations between GCs and ICCs. Mutations in LRP1B (HR = 0.26; 95% CI, 0.06‐1.21; P =.067), ERBB2 (HR = 0.15; 95% CI, 0.02‐1.19; P =.04), or PKHD1 (HR < 0.01; 95% CI, 0‐Inf; P =.04) showed strong association with increased progression‐free survival (PFS) benefit. Subsequent analysis showed that alterations in the RTK‐RAS pathway were associated with improved outcomes (HR = 0.12; 95% CI, 0.02‐0.63; P =.003). Tumor mutation burden (TMB) was higher in patients with GC than those with ICC, and was associated with LRP1B mutations (P =.032). We found that patients with 19q amplification (19q Amp) and 9p deletion (9p Del) had poor PFS outcome (19q Amp, HR = 15.4; 95% CI, 2.7‐88.5; P <.001; 9p Del; HR = 4.88 × 109; 95% CI, 0‐Inf; P <.001), while those with chromosomal instability derived PFS benefit (HR = 0.24; 95% CI, 0.05‐1.17; P =.057). Conclusion: Our study identified several potential clinical and genomic features that may serve as biomarkers of clinical response to ICIs in advanced BTCs patients. A larger sample size is required for further verification. [ABSTRACT FROM AUTHOR]