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Abstract The analysis of magnetic near‐field radiation emissions (MNRE) has recently raised more attention in device‐level electromagnetic compatibility testing. Pattern clustering of MNRE for integrated circuits manually is very time‐consuming because of the multi‐dimensional characteristics of MNRE, such as frequency, spatial position, emission intensity, etc. This paper proposes a novel pattern clustering method of MNRE, including strong emission frequency extraction, feature extraction, and density‐based clustering. Ring oscillator and five working states are designed on a Field Programmable Gate Array with 256 Ball Grid Array package, which are used to create a complex multi‐source emission case for verifying the effectiveness of the clustering method. The verification results show that the proposed method can correctly cluster the multi‐source emission patterns. Further, the method is also applied to a Microcontroller Unit with unknown operating states; the results show that the proposed method also can effectively distinguish the unknown emission patterns and locate the unknown interference source. The accuracy of the interference source location is proven by 3D X‐ray microscope inspection.

Abstract Shared‐energy storage (SES) can break the energy interaction barrier between the demand side and the supply side, which is becoming an option for improving the flexibility of energy systems. This study designed a novel structure for the shared‐energy aggregator (SEA), incorporating a microgrid (MG), prosumer and SES. Then, a two‐level market transaction optimization model for SEA, considering the robust stochastic optimization method, is proposed; namely, at the day‐ahead stage, a robust stochastic operation optimization model is constructed to achieve the dispatching plan from the demand side under the objective of achieving the minimum energy consumption cost for the prosumer, and at the real‐time market stage, a robust stochastic operation optimization model from the supply side is constructed to arrange the optimal dispatching strategy under the objective of the maximum aggregator benefits of MG and SES. Finally, an industrial park micro‐grid in Qinghai Province, China, is selected as an example for analysis.

ABSTRACT Aims To develop multiple machine learning (ML) models based on the prognostic nutritional index (PNI) and determine the optimal model for predicting long‐term survival outcomes in hepatocellular carcinoma (HCC) patients after local ablation. Methods From January 2009 to December 2019, we analyzed data from 848 primary HCC patients who underwent local ablation. ML models were constructed and evaluated using the concordance index (C‐index), concordance‐discordance area under curve (C/D AUC), and Brier scores. The optimal ML model was interpreted using the partial dependence plot (PDP) and SHapley Additive exPlanations (SHAP) framework. Additionally, the prognostic performance of our model was compared with other models. Results Alkaline phosphatase, preoperation alpha‐fetoprotein level, PNI, tumor number, and tumor size were identified as independent prognostic factors for ML model construction. Among the 19 ML algorithms tested, the Aorsf model showed superior performance in both the training cohort (C/D AUC: 0.733; C‐index: 0.736; Brier score: 0.133) and validation cohort (C/D AUC: 0.713; C‐index: 0.793; Brier score: 0.117). The time‐dependent AUC of the Aorsf model for predicting overall survival was as follows: 1‐, 3‐, 5‐, 7‐, and 9‐year were 0.828, 0.765, 0.781, 0.817, and 0.812 in the training cohort, 0.846, 0.859, 0.824, 0.845, and 0.874 in the validation cohort, respectively. The PDP and SHAP algorithms were employed for visual interpretation. Furthermore, time‐AUC and decision curve analysis demonstrated that the Aorsf model provided superior clinical benefits compared to other models. Conclusion The PNI‐based Aorsf model effectively predicts long‐term survival outcomes after ablation therapy, making a significant contribution to HCC research by improving surveillance, prevention, and treatment strategies.

Abstract Soft molecule‐based ferroelectrics with unique structural flexibility hold a promise for versatile applications of non‐volatile memory, imaging and photovoltaic devices. Except for few polymers (e.g., polyvinylidene fluoride, PVDF), it is challenging to exploit soft ferroelectric crystals toward free‐standing flexible photoactive devices. We here report a multiaxial soft molecule‐based ferroelectric, (n‐PA)2PbCl4 (1, where n‐PA+ is n‐pentylammonium), of which spontaneous polarization can be reversibly switched in both crystal and powder forms. Strikingly, single crystals of 1 have unusual structural flexibility and bendability, achieving the self‐standing bending with a bending radius of ~0.22 mm. Besides, the pyroelectric activities are also preserved for these single crystals after several bending cycles. Further, the bendable crystal‐based photodetector of 1 allows broadband photoactivities via the photo‐pyroelectric effect, covering a wide range from 405 to 940 nm spectral region, breaking through the limit of optical absorption bandgap. As the first study of bendable free‐standing photo‐pyroelectric detectors in ferroelectric crystals, our work sheds light on the assembly of flexible smart photoelectric devices.

Abstract Graphene field‐effect transistors (GFETs) are widely used in biosensing due to their excellent properties in biomolecular signal amplification, exhibiting great potential for high‐sensitivity and point‐of‐care testing in clinical diagnosis. However, difficulties in complicated fabrication steps are the main limitations for the further studies and applications of GFETs. In this study, a modular fabrication technique is introduced to construct microfluidic GFET biosensors within 3 independent steps. The low‐melting metal electrodes and intricate flow channels are incorporated to maintain the structural integrity of graphene and facilitate subsequent sensing operations. The as‐fabricated GFET biosensor demonstrates excellent long‐term stability, and performs effectively in various ion environments. It also exhibits high sensitivity and selectivity for detecting single‐stranded nucleic acids at a 10 fm concentration. Furthermore, when combined with the CRISPR/Cas12a system, it facilitates amplification‐free and rapid detection of nucleic acids at a concentration of 1 fm. Thus, it is believed that this modular‐fabricated microfluidic GFET may shed light on further development of FET‐based biosensors in various applications.

ABSTRACT Background Exosomes have been established to be enriched with various long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) that exert various biological effects. However, the lncRNA‐ and circRNA‐mediated coexpression competing endogenous RNA (ceRNA) regulatory network in exosomes derived from the plasma of patients with lung adenocarcinoma (LUAD) remains elusive. Methods and Results This study enrolled nine patients with lung adenocarcinoma and three healthy individuals, and the differential expression of messenger RNAs (mRNAs), lncRNAs, and circRNAs was detected using microarray analysis, while microRNAs (miRNAs) were detected through RNA sequencing. Additionally, bioinformatics algorithms were applied to evaluate the lncRNA–miRNA–mRNAs/circRNA–miRNA–mRNA network. Differentially expressed cicRNAs were identified via quantitative reverse transcription polymerase chain reaction (RT‐qPCR). A total of 1016 lncRNAs, 1396 circRNAs, 45 miRNAs, and 699 mRNAs were differentially expressed in the plasma exosomes of patients with LUAD compared with healthy controls. Among them, 881 lncRNAs were upregulated and 135 were downregulated, 916 circRNAs were upregulated while 480 were downregulated, 45 miRNAs were upregulated while none were downregulated, and 591 mRNAs were upregulated while 108 were downregulated (p ≤ 0.05, and fold change ≥ 2). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the biological functions of differentially expressed RNAs. Meanwhile, the RNA networks displayed the regulatory relationship between dysregulated RNAs. Finally, RT‐qPCR validated that the expression of circ‐0033861, circ‐0043273, and circ‐0011959 was upregulated in the plasma exosome of patients with LUAD compared to healthy controls (p = 0.0327, p = 0.0002, p = 0.0437, respectively). Conclusion This study proposed a newly discovered ncRNA–miRNA–mRNA/circRNA–miRNA–mRNA ceRNA network and identified that the expression of circulating circ‐0033861, circ‐0043273, and circ‐0011959 was up‐regulated in the plasma exosomes of patients with LUAD, offering valuable insights for exploring the potential function of exosomal noncoding RNA and identifying potential biomarkers for LUAD.

ABSTRACT Introduction Staged bilateral surgery is widely used to treat synchronous multiple primary lung cancer (SMPLC); however, the prognostic factors for survival outcomes remain unclear. This study aimed to identify prognostic factors and construct a predictive model for overall survival (OS) and recurrence‐free survival (RFS) in patients with SMPLC who underwent staged bilateral surgery. Methods The study included 256 patients diagnosed with SMPLC and treated with staged bilateral surgery at our hospital between January 2010 and July 2017. Multivariate Cox proportional‐hazard regression was used to identify prognostic factors for OS and RFS. Additionally, a predictive model was constructed using time‐dependent receiver operating characteristic curves. Results Among the 256 patients, 10 (3.95%) succumbed to the disease and 24 (9.41%) experienced recurrence. Smoking (hazard ratio [HR]: 5.128; 95% confidence interval [CI]: 1.442–18.233; p = 0.012) and most advanced pathological TNM (pTNM) stage (II + III) (HR: 12.938; 95% CI: 2.650–63.176; p = 0.002) were identified as significant predictors of poor OS. A prognostic model was developed for predicting OS, with a 5‐year area under the curve (AUC) of 0.854. Furthermore, most advanced pTNM stage (II + III) was associated with poor RFS (HR: 5.964; 95% CI: 2.669–13.327; p

Abstract Background The tumor microenvironment (TME) plays a critical role in cancer progression and response to immunotherapy. Immunotherapy targeting the immune system has emerged as a promising treatment modality, but challenges in understanding the TME limit its efficacy. Optical imaging strategies offer noninvasive, real‐time insights into the interactions between immune cells and the TME. Objective This review assesses the progress of optical imaging technologies in monitoring immunotherapy within the TME and explores their potential applications in clinical trials and personalized cancer treatment. Methods This is a comprehensive literature review based on the advances in optical imaging modalities including fluorescence imaging (FLI), bioluminescence imaging (BLI), and photoacoustic imaging (PAI). These modalities were analyzed for their capacity to provide high‐resolution, real‐time imaging of immune cell dynamics, tumor vasculature, and other critical components of the TME. Results Optical imaging techniques have shown significant potential in tracking immune cell infiltration, assessing immune checkpoint inhibitors, and visualizing drug delivery within the TME. Technologies like FLI and BLI are pivotal in tracking immune responses in preclinical models, while PAI provides functional imaging with deeper tissue penetration. The integration of these modalities with immunotherapy holds promise for improving treatment monitoring and outcomes. Conclusion Optical imaging is a powerful tool for understanding the complexities of the TME and optimizing immunotherapy. Further advancements in imaging technologies, combined with nanomaterial‐based approaches, could pave the way for enhanced diagnostic accuracy and therapeutic efficacy in cancer treatment.

Abstract Carbon dots (CDs)‐based zero‐dimensional nanomaterials with dimensions ranging from 1 to 10 nm have shown tremendous potential in the application of regenerative medicine, because of their unique physicochemical properties and favorable attributes like good biocompatibility, unique biological functions, low cost and high stability. These newly synthesized CDs‐based nanomaterials could replace traditional semiconductor quantum dots, which have obvious toxicity drawbacks and higher costs. CDs not only show sustained fluorescent quality and biocompatibility, but also serve as superior carriers for drug delivery, as well as for bioimaging‐guided detection of cells, drugs, and growth factors. So, they have been shown to play a role in various fields such as chemical and biological sensing, bioimaging, drug delivery, and photocatalysis. Thus, they are considered potential candidates for regenerative medicine applications. In this review, we provide a comprehensive summary of the classification of CDs, focusing on their formation mechanisms, micro‐/nanostructures, and distinctive properties. We describe their properties and synthesis methods in detail. Furthermore, we systematically highlight recent remarkable advances in the applications of CDs in regenerative medicine, such as bone and cartilage repair, wound healing, nerve regeneration, and myocardial regeneration, are systematically highlighted. Finally, we discuss the key challenges that lie ahead, outline future research directions, and explore the prospects of CDs‐based materials in regenerative medicine.

Abstract Mechanical antennas have garnered considerable attention due to their ability to address the challenges posed by the significant size and high energy consumption associated with traditional electric antennas when operating at low frequencies. Here, a compact and structurally stable mechanical antenna design is presented. The proposed antenna is constructed using cylindrical piezoelectric ceramics, which have dimensions smaller than 1/1000 of the wavelength. The scrutiny of the influence exerted by the antenna feed area and material thickness on the radiation performance was undertaken, followed by an exhaustive discourse on these effects. Experimental measurements demonstrate the practical functionalities of signal coding, transmission, and reception in the low‐frequency communication system. Notably, at a frequency of 288 kHz, a single proposed antenna achieves an effective information transmission distance of 60 m using binary information coding. This remarkable outcome underscores the potential of this design in facilitating the development of portable and cost‐effective wireless communication equipment for low‐frequency applications.

Abstract The DNA‐dependent protein kinase (DNA‐PK), catalytic subunit, also known as DNA‐PKcs, is complexed with the heterodimer Ku70/Ku80 to form DNA‐PK holoenzyme, which is well recognized as initiator in the nonhomologous end joining (NHEJ) repair after double strand break (DSB). During NHEJ, DNA‐PKcs is essential for both DNA end processing and end joining. Besides its classical function in DSB repair, DNA‐PKcs also shows multifaceted functions in various biological activities such as class switch recombination (CSR) and variable (V) diversity (D) joining (J) recombination in B/T lymphocytes development, innate immunity through cGAS–STING pathway, transcription, alternative splicing, and so on, which are dependent on its function in NHEJ or not. Moreover, DNA‐PKcs deficiency has been proven to be related with human diseases such as neurological pathogenesis, cancer, immunological disorder, and so on through different mechanisms. Therefore, it is imperative to summarize the latest findings about DNA‐PKcs and diseases for better targeting DNA‐PKcs, which have shown efficacy in cancer treatment in preclinical models. Here, we discuss the multifaceted roles of DNA‐PKcs in human diseases, meanwhile, we discuss the progresses of DNA‐PKcs inhibitors and their potential in clinical trials. The most updated review about DNA‐PKcs will hopefully provide insights and ideas to understand DNA‐PKcs associated diseases.

Abstract The quantitative relationship between Mesoscale Convective Systems (MCSs) and floods over East Asia has not been established. In this study, MCSs are clustered into four types with Self‐Organizing Map approach. Floods in June‐August of 2000–2021 are linked with different types of MCS by automated algorithms we constructed. We find that among the major floods (potential flood peak periods), 91% (87%) are related to MCS, 65% (78%) are dominated by MCS, and 38% (20%) are dominated by multi‐types of MCS. Types 1 and 2 MCS have higher flood‐inducing efficiencies than common MCS (Type‐4). Type‐1 MCS, characterized by the least number (2% of the total number), the largest precipitation volume, longest lifetime, slowest moving, strongest precipitation, can most efficiently produce floods. Type‐2 MCS, characterized by the second largest precipitation volume, more numerous than Type‐1 particularly over land, can induce floods not only relatively efficiently but also more frequently than Type‐1.

Abstract Solar panels often suffer from dust accumulation, significantly reducing their output, especially in desert regions where many of the world's largest solar plants are located. Here, an autonomous dust removal system for solar panels, powered by a wind‐driven rotary electret generator is proposed. The generator applies a high voltage between one solar panel's output electrode and an upper mesh electrode to generate a strong electrostatic field. It is discovered that dust particles on the insulative glass cover of the panel can be charged under the high electrical field, assisted by adsorbed water, even in low‐humidity environments. The charged particles are subsequently repelled from the solar panel with the significant Coulomb force. Two panels covered with sand dust are cleaned in only 6.6 min by a 15 cm diameter rotary electret generator at 1.6 m s−1 wind speed. Experimental results manifest that the system can work effectively in a wide range of environmental conditions, and doesn't impact the panel performance for long‐term operation. This autonomous system, with its high dust removal efficiency, simplicity, and low cost, holds great potential in practical applications.

Abstract Patients with brain cancers including medulloblastoma lack treatments that are effective long‐term and without side effects. In this study, a multifunctional fluoropolymer‐engineered iron oxide nanoparticle gene‐therapeutic platform is presented to overcome these challenges. The fluoropolymers are designed and synthesized to incorporate various properties including robust anchoring moieties for efficient surface coating, cationic components to facilitate short interference RNA (siRNA) binding, and a fluorinated tail to ensure stability in serum. The blood‐brain barrier (BBB) tailored system demonstrates enhanced BBB penetration, facilitates delivery of functionally active siRNA to medulloblastoma cells, and delivers a significant, almost complete block in protein expression within an in vitro extracellular acidic environment (pH 6.7) – as favored by most cancer cells. In vivo, it effectively crosses an intact BBB, provides contrast for magnetic resonance imaging (MRI), and delivers siRNA capable of slowing tumor growth without causing signs of toxicity – meaning it possesses a safe theranostic function. The pioneering methodology applied shows significant promise in the advancement of brain and tumor microenvironment‐focused MRI‐siRNA theranostics for the better treatment and diagnosis of medulloblastoma.

Abstract Microbial factories lacking the ability of dynamically regulating the pathway enzymes overexpression, according to in situ metabolite concentrations, are suboptimal, especially when the metabolic intermediates are competed by growth and chemical production. The production of higher alcohols (HAs), which hijacks the amino acids (AAs) from protein biosynthesis, minimizes the intracellular concentration of AAs and thus inhibits the host growth. To balance the resource allocation and maintain stable AA flux, this work utilizes AA‐responsive transcriptional attenuator ivbL and HA‐responsive transcriptional activator BmoR to establish a concentration recognition‐based auto‐dynamic regulation system (CRUISE). This system ultimately maintains the intracellular homeostasis of AA and maximizes the production of HA. It is demonstrated that ivbL‐driven enzymes overexpression can dynamically regulate the AA‐to‐HA conversion while BmoR‐driven enzymes overexpression can accelerate the AA biosynthesis during the HA production in a feedback activation mode. The AA flux in biosynthesis and conversion pathways is balanced via the intracellular AA concentration, which is vice versa stabilized by the competition between AA biosynthesis and conversion. The CRUISE, further aided by scaffold‐based self‐assembly, enables 40.4 g L−1 of isobutanol production in a bioreactor. Taken together, CRUISE realizes robust HA production and sheds new light on the dynamic flux control during the process of chemical production.

E3 SUMO‐protein ligase CBX4 (CBX4), a key component of polycomb‐repressive complexes 1 (PRC1), has been reported to regulate a variety of genes implicated in tumor growth, metastasis, and angiogenesis. However, its role in T‐cell‐mediated antitumor immunity remains elusive. To shed light on this issue, we generated mice with T‐cell‐specific deletion of Cbx4. Tumor growth was increased in the knockout mice. Additionally, their tumor‐infiltrating lymphocytes exhibited impaired tumor necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ) production, with an elevated programmed cell death protein 1 (PD‐1) level. In fact, dysregulated Pdcd1 expression was observed in all major subsets of peripheral T cells from the knockout mice, which was accompanied by a functional defect in response to T‐cell receptor (TCR) stimulation. In support of a direct link between CBX4 and PD‐1, Cbx4 overexpression resulted in the downregulation of Pdcd1 expression. Epigenetic analyses indicated that Cbx4 deficiency leads to diminished accumulation of inhibitory histone modifications at conserved region (CR)‐C and CR‐B sites of the Pdcd1 promoter, namely mono‐ubiquitinated histone H2A at lysine 119 (H2AK119ub1) and trimethylated histone H3 at lysine 27 (H3K27me3). Moreover, inhibition of either the E3 ligase activity of polycomb‐repressive complexes 1 (PRC1) or the methyltransferase activity of polycomb‐repressive complexes 2 (PRC2) restores Pdcd1 expression in Cbx4‐transfected cells. Cumulatively, this study reveals a novel function of CBX4 in the regulation of T‐cell function and expands our understanding of the epigenetic control of Pdcd1 expression.

Abstract High‐valent iron‐oxo species are one of the common intermediates in both biological and biomimetic catalytic oxidation reactions. Recently, hydrogen‐bonding (H‐bonding) has been proved to be critical in determining the selectivity and reactivity. However, few examples have been established for mechanistic insights into the H‐bonding effect. Moreover, intramolecular H‐bonding effect on both C‐H activation and oxygen atom transfer (OAT) reactions in synthetic porphyrin model system has not been investigated yet. In this study, a series of heme‐containing iron(IV)‐oxo porphyrin species with or without intramolecular H‐bonding are synthesized and characterized. Kinetic studies revealed that intramolecular H‐bonding can significantly enhance the reactivity of iron(IV)‐oxo species in OAT, C‐H activation, and electron‐transfer reactions. This unprecedented unified H‐bonding effect is elucidated by theoretical calculations, which showed that intramolecular H‐bonding interactions lower the energy of the anti‐bonding orbital of iron(IV)‐oxo porphyrin species, resulting in the enhanced reactivities in oxidation reactions irrespective of the reaction type. To the best of the knowledge, this is the first extensive investigation on the intramolecular H‐bonding effect in heme system. The results show that H‐bonding interactions have a unified effect with iron(IV)‐oxo porphyrin species in all three investigated reactions.

Abstract INTRODUCTION Mounting evidence suggests that certain comorbidities may influence the clinical evolution of Alzheimer's dementia (AD). METHODS We conducted logistic regression analyses on the medical history and cognitive health diagnoses of participants in the Australian Imaging, Biomarker & Lifestyle study (n = 2443) to investigate cross‐sectional associations between various comorbidities and mild cognitive impairment (MCI)/AD. RESULTS A mixture of associations were observed. Higher comorbidity of anxiety and other neurological disorders was associated with higher odds of AD, while arthritis, cancer, gastric complaints, high cholesterol, joint replacement, visual defect, kidney and liver disease were associated with lower odds of AD. DISCUSSION This study underscores the links between specific comorbidities and MCI/AD. Further research is needed to elucidate the longitudinal comorbidity‐MCI/AD associations and underlying mechanisms of these associations. Highlights Comorbidities that significantly increased AD odds included anxiety and other neurological disorders. Arthritis, cancer, gastric complaints, high cholesterol, joint replacement, visual defect, kidney and liver disease were associated with lower odds of AD. Alcohol consumption had the most significant confounding effect in the study. Visual‐AD association was modified by age, sex, and APOE ε4 allele status. Anxiety‐AD and depression‐AD associations were modified by sex.

Abstract The modern East Asian summer monsoon (EASM) features an extension from tropical to subtropical areas. However, the fundamental process that determines the northward extension of EASM in the geological history remains unclear. Here, we showed evidence from proxy data, climate modeling, and theoretical solutions that the northward extension of EASM to today's boundary emerged no later than the Miocene. The extension was driven by the monsoon seasonal march which features stepwise northward rainfall stages. The seasonal progression of monsoon was determined by Rossby wave responses from early summer to late summer and caused by the weakening of westerly jet colliding with the Tibetan Plateau (TP). The Rossby wave responses further led to a northward migration of the western Pacific subtropical high and thereby monsoon precipitation. Our findings propose a novel physical linkage between the geological evolution of EASM and the TP uplift in the context of monsoon seasonal march.

Abstract Cancer remains a global health challenge, demanding early detection and accurate diagnosis for improved patient outcomes. An intelligent paradigm is introduced that elevates label‐free nonlinear optical imaging with contrastive patch‐wise learning, yielding stain‐free nonlinear optical computational histology (NOCH). NOCH enables swift, precise diagnostic analysis of fresh tissues, reducing patient anxiety and healthcare costs. Nonlinear modalities are evaluated, including stimulated Raman scattering and multiphoton imaging, for their ability to enhance tumor microenvironment sensitivity, pathological analysis, and cancer examination. Quantitative analysis confirmed that NOCH images accurately reproduce nuclear morphometric features across different cancer stages. Key diagnostic features, such as nuclear morphology, size, and nuclear‐cytoplasmic contrast, are well preserved. NOCH models also demonstrate promising generalization when applied to other pathological tissues. The study unites label‐free nonlinear optical imaging with histopathology using contrastive learning to establish stain‐free computational histology. NOCH provides a rapid, non‐invasive, and precise approach to surgical pathology, holding immense potential for revolutionizing cancer diagnosis and surgical interventions.

Abstract The clinical requirements for wound care are increasing daily, and the global wound dressing market is expanding; however, the research and development of new wound dressings are imminent. Natural biomolecules such as polyphenols, have been widely used in this field of vision. Owing to their unique anti‐oxidative, adhesive, antibacterial and other bioactive functions, researchers have developed a series of wound dressings with excellent performance and applied them to a variety of biomaterials, such as hydrogels, nanofibers, films and scaffolds. They can effectively promote angiogenesis and fibroblast migration and proliferation, scavenge active oxygen free radicals, inhibit excessive inflammatory reactions at wound sites and ultimately accelerate wound healing. The authors summarise the latest progress in polyphenol‐derived biomaterials in skin wound repair to provide inspiration for future wound dressing research.

Abstract Background Patient survival in advanced/metastatic melanoma, non‐small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) has improved with immune checkpoint inhibitors (ICI). Biomarkers' role in prognosis and treatment has been limited by conflicting trial results. Methods This retrospective, observational study analyzed baseline demographic, clinical, laboratory, and treatment data versus outcomes of The US Oncology Network adult outpatients. Patients with advanced/metastatic melanoma, NSCLC, or RCC treated between January 1, 2015 and November 30, 2020 were given ICI monotherapy or combination therapy with ipilimumab, pembrolizumab, nivolumab, or atezolizumab. Treatment outcomes (overall survival [OS], time to treatment discontinuation, time to next treatment) were followed longitudinally until May 31, 2021, last patient record, or date of death. Baseline blood cell counts, including absolute monocyte count (AMC), absolute lymphocyte count (ALC), monocyte‐to‐lymphocyte ratio (MLR), absolute neutrophil count (ANC), and eosinophil count, were subdivided into quintiles for univariate and multivariable Cox regression analyses. Results Data from 18,186 patients with advanced/metastatic melanoma (n = 3314), NSCLC (n = 12,416), and RCC (n = 2456) were analyzed. Better OS correlated with increased baseline serum albumin concentration, increased eosinophil and lymphocyte counts, and Western United States physician practice location. Decreased OS correlated with increased AMC, MLR, ANC, age, and worse Eastern Cooperative Oncology Group performance status. Conclusions To our knowledge, this study is the largest to date to associate baseline survival indicators and outcomes in outpatients with advanced/metastatic melanoma, NSCLC, or RCC and receiving ICIs. Results may inform disease‐specific prognostic models and help providers identify patients most likely to benefit from ICI therapy.

Abstract Aims Left ventricular (LV) remodelling after acute myocardial infarction (AMI) is associated with heart failure and increased mortality. There was no consensus on the definition of LV remodelling, and the prognostic value of LV remodelling with different definitions has not been compared. We aimed to find the optimal definition and develop a prediction nomogram as well as online calculator that can identify patients at risk of LV remodelling. Methods and results This prospective, observational study included 829 AMI patients undergoing percutaneous coronary intervention from January 2015 to January 2020. Echocardiography was performed within the 48 h of admission and at 6 months after infarction to evaluate LV remodelling, defined as a 20% increase in LV end‐diastolic volume (LVEDV), a 15% increase in LV end‐systolic volume (LVESV), or LV ejection fraction (LVEF)

Abstract Due to the increasing interdependencies of power networks (PNs) and communication networks (CNs) in cyber‐physical power systems (CPPSs), the interdependent networks tend to be more vulnerable since failures could propagate recursively between the two networks. However, there is little study on the vulnerability analysis of CPPSs considering unexpected disruptive events or adversarial attacks. Despite being a useful tool for evaluating cascading failures in interdependent networks, the topology‐based percolation theory does not apply to CPPSs as neglecting the propagation dynamics and power flow characteristics. To this end, this paper improves the percolation theory by modelling the failure propagation mechanism to assess the vulnerability of CPPSs. Firstly, a percolation‐based failure propagation simulator (PFPS) is developed, wherein the virus‐caused propagation dynamics of the cyber layer, flow‐based failure propagation mode of the physical layer, and multi‐state interdependences between the cyber layer and physical layer are incorporated. By considering the nodal states and flow‐related operating states, percolation equations and termination conditions of PFPS are formulated. Based on the calculation results of PFPS, metrics in terms of topological integrity, power supply reliability, and failure probability are constructed to quantify both system and component vulnerability. The effectiveness of the proposed method is validated by the test CPPSs.

Abstract Background Additional efficacious immunomodulatory treatment is needed for the management of immune‐mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses. Hypothesis/Objectives To evaluate the pharmacokinetics (PK) of multiple‐day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen. Animals Six healthy Standardbred mares. Methods Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough samples collected every 24 hours, immediately before morning drug administration. Noncompartmental PK analyses were performed to determine primary PK parameters, followed by calculation of geometric means and coefficients of variation. A CBC, serum biochemical profile, physical examination, and fecal scoring were used to assess dose tolerability. Results Seven days of treatment resulted in a mycophenolic acid (MPA) area under the curve (AUC0‐12) of 12 594 h × ng/mL (8567‐19 488 h × ng/mL) and terminal half‐life (T1/2) of 11.3 hours (7.5‐15.9 hours), yielding minor metabolite accumulation in all horses treated. Salmonellosis was detected in the feces of 2 horses by Day 7, and all horses developed myelosuppression, hyperbilirubinemia, hyporexia, decreased gastrointestinal motility, and decreased fecal output by the seventh day of treatment. Conclusion and Clinical Importance Administration of MMF at 10 mg/kg PO q12h resulted in hematologic and clinical toxicity within 1 week of treatment. A decreased MMF dose, frequency, or both is needed to avoid colic. Drug monitoring should include frequent hemograms, serum biochemical profiles, and strict biosecurity protocols.

Abstract Cuproptosis is a novel cell death pathway, and the regulatory mechanism in pancreatic cancer (PC) is unclear. The authors aimed to figure out whether cuproptosis‐related lncRNAs (CRLs) could predict prognosis in PC and the underlying mechanism. First, the prognostic model based on seven CRLs screened by the least absolute shrinkage and selection operator Cox analysis was constructed. Following this, the risk score was calculated for pancreatic cancer patients and divided patients into high and low‐risk groups. In our prognostic model, PC patients with higher risk scores had poorer outcomes. Based on several prognostic features, a predictive nomogram was established. Furthermore, the functional enrichment analysis of differentially expressed genes between risk groups was performed, indicating that endocrine and metabolic pathways were potential regulatory pathways between risk groups. TP53, KRAS, CDKN2A, and SMAD4 were dominant mutated genes in the high‐risk group and tumour mutational burden was positively correlated with the risk score. Finally, the tumour immune landscape indicated patients in the high‐risk group were more immunosuppressive than that in the low‐risk group, with lower infiltration of CD8+ T cells and higher M2 macrophages. Above all, CRLs can be applied to predict PC prognosis, which is closely correlated with the tumour metabolism and immune microenvironment.

Objective Studies on extremely severe elbow stiffness after chronic dislocation in children are scarce. This study aims to investigate the choice of surgical treatment modalities and to analyze their treatment efficacy in children with chronic elbow dislocation with extremely severe periarticular stiffness. Methods Data of 21 children with chronic elbow dislocation with extremely severe periarticular stiffness diagnosed and treated in our department between February 2015 and February 2021 were retrospectively analyzed. Twenty boys and one girl were included in the study, their mean age was 11 ± 2.5 years, and they had concomitant distal humerus fractures. For the treatment protocol, all children with extremely severe elbow stiffness were treated with open arthrolysis, and elbow joint stability was intraoperatively assessed. All children performed passive functional exercises the day after surgery. The elbow flexion and extension angles, range of motion (ROM), and Mayo score were evaluated preoperatively and at the final follow‐up. Results Of the 21 children, only one had recurrent severe stiffness of the elbow joint after surgery; nevertheless, the function was still improved compared with that before surgery. Preoperatively, the mean elbow extension and flexion angles were 72.2° ± 12.7° and 93.6° ± 11.1°, respectively, and the range of motion (ROM) of the elbow joint was 17.8° ± 8.3°. At the final follow‐up, the mean elbow extension and flexion angles were 22.7° ± 18.6° and 118.8° ± 15.4°, respectively, and the elbow joint ROM was 96.1° ± 17.4°. The differences in the preoperative and postoperative ROMs, flexion angles, and extension angles of the elbow joint were significant (p

Abstract Imaging biomolecules in real space is crucial for gaining a comprehensive understanding of the properties and functions of biological systems at the most fundamental level. Among the various imaging techniques available for biomolecules and their assembled nanostructures, scanning probe microscopy (SPM) provides a powerful and nondestructive imaging option. SPM is unique in visualizing intrinsically disordered biomolecules at the nanometer scale (e.g., glycans). This review highlights recent achievements in studying biomolecules using SPM technique, focusing on DNA bases, amino acids, proteins, and glycans. The atomic‐level analysis of biomolecules made possible by SPM allows for a more accurate definition of the local structure–property relationship. High‐resolution SPM imaging of single biomolecules offers a new way to study basic processes of life at the molecular level.

Abstract To solve the insufficient energy for reverse circulation fishing tools in complex structure wells, it is necessary to further optimize the design of the tools to improve the impurity salvage efficiency. In this work, a three‐dimensional (3D) flow field simulation model of reverse circulation fishing tool with venturi negative pressure is employed to identify the vortex zone of circulation channel and to investigate the negative pressure and jet velocity distribution around the spray nozzle based on the ANSYS‐CFX. The effects of the spray angle, diameter of the suction nozzle, and the nonstructural parameters on negative pressure and jet velocity are investigated through sensitivity analysis. As revealed from the results, there may be an optimum value for the spray angle, and the nozzle jet direction can indeed affect the propagation and attenuation of the bottom hole flow field greatly. The combination of the inner diameter of the nozzle outlet and that of the nozzle inlet (Φ + Φ′ = 3 mm + 6 mm) is the best design solution when the negative pressure at the nozzle outlet can be the highest. The negative pressure and jet velocity increase with the increasement of the inlet flow rate. The comparative analysis of different bottom hole impurity mass in the cases of the borehole inner diameter 5′ and 8.5″ on the salvage efficiency are conducted numerically. It is observed that the impurity mass salvaged and salvage time are not directly related to its total amount, but only related to the flow rate of the sucked fluid flow. The impurity salvage efficiency can be as high as 95.4%, which meets the engineering requirements in the field. This work improves the working performance of the reverse circulation fishing tool and provides theoretical guidance for well washing.

Abstract Terrestrial ecosystems can exhibit various behaviors in response to climate change and human activities. Nonlinear and abrupt shifts in ecosystems are particularly important as they indicate substantial modifications in ecosystem structure and function, posing a threat to the provision of ecosystem services. Here we distinguish between linear, curvilinear, and abrupt shifts in ecosystem productivity from 2000 to 2020 in China's Loess Plateau. We utilize spatial Random Forest models to analyze the driving factors behind these change patterns. Our findings indicate that 84.1% of the ecosystems experienced a positive change in plant productivity, while a small proportion (2.5%) exhibited a negative change. Abrupt shifts are prevalent in both positive and negative changes in ecosystem productivity, with negative changes often manifesting as abrupt shifts (79.3%). Negative changes in plant productivity, particularly the negative abrupt shifts, are primarily associated with human activities characterized by increased nighttime light and urbanization. Land conversion to forest is linked to a curvilinear trajectory in plant productivity, characterized by nonlinear changes with acceleration. Higher water availability and a wetter environment are more likely to promote positive changes in plant productivity. Moderate warming trends contribute to abrupt positive changes in plant productivity, while high warming trends are associated with increased negative abrupt and curvilinear changes. We highlight the importance of accounting for diverse change behaviors in ecosystems for the development of targeted conservation and restoration measures.

Abstract Advanced atomic tracking techniques play a critical role in characterizing structural evolution, elucidating fundamental mechanisms of exotic phenomena and tailoring delicate properties. Thermally driven structural modulation in 2D crystals, such as the charge density wave (CDW), often leads to intriguing quantum properties, making them a valuable platform for exploring fundamental physics and potential device applications. However, despite their significance, experimental studies addressing atomic tracking of thermally‐driven structural evolution in 2D crystals have been limited. Herein, we utilize high‐accuracy variable‐temperature atomic tracking measurements with scanning tunneling microscopy (STM) to directly observe a series of structural transitions in a model 2D crystal, namely NbSe2. With the atomic tracking technique, we confirm the existence of the universal thermally‐driven CDW transition hysteresis between the heating and cooling cycles. This transition hysteresis, characterized by a constant temperature offset, represents a new phenomenon of structural evolution. Our findings provide a feasible method to track CDW transitions at the atomic scale in 2D crystals, significantly contributing to a better understanding and the potential modulation of these materials' functions in nanodevices.

Abstract Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single‐cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA‐seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high‐throughput and high‐sensitivity method called snHH‐seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full‐length RNA‐seq data is also established. snHH‐seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan‐cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full‐length RNA at the single‐nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology.

Abstract Objectives Seasonal influenza viruses cause roughly 650 000 deaths annually despite available vaccines. CD8+ T cells typically recognise influenza‐derived peptides from internal structural and non‐structural influenza proteins and are an attractive avenue for future vaccine design as they could reduce the severity of disease following infection with diverse influenza strains. CD8+ T cells recognise peptides presented by the highly polymorphic Human Leukocyte Antigens class I molecules (HLA‐I). Each HLA‐I variant has distinct peptide binding preferences, representing a significant obstacle for designing vaccines that elicit CD8+ T cell responses across broad populations. Consequently, the rational design of a CD8+ T cell‐mediated vaccine would require the identification of highly immunogenic peptides restricted to a range of different HLA molecules. Methods Here, we assessed the immunogenicity of six recently published novel influenza‐derived peptides identified by mass‐spectrometry and predicted to bind to the prevalent HLA‐B*18:01 molecule. Results Using CD8+ T cell activation assays and protein biochemistry, we showed that 3/6 of the novel peptides were immunogenic in several HLA‐B*18:01+ individuals and confirmed their HLA‐B*18:01 restriction. We subsequently compared CD8+ T cell responses towards the previously identified highly immunogenic HLA‐B*18:01‐restricted NP219 peptide. Using X‐ray crystallography, we solved the first crystal structures of HLA‐B*18:01 presenting immunogenic influenza‐derived peptides. Finally, we dissected the first TCR repertoires specific for HLA‐B*18:01 restricted pathogen‐derived peptides, identifying private and restricted repertoires against each of the four peptides. Conclusion Overall the characterisation of these novel immunogenic peptides provides additional HLA‐B*18:01‐restricted vaccine targets derived from the Matrix protein 1 and potentially the non‐structural protein and the RNA polymerase catalytic subunit of influenza viruses.

Abstract Seasonal influenza viruses continue to cause severe medical and financial complications annually. Although there are many licenced influenza vaccines, there are billions of cases of influenza infection every year, resulting in the death of over half a million individuals. Furthermore, these figures can rise in the event of a pandemic, as seen throughout history, like the 1918 Spanish influenza pandemic (50 million deaths) and the 1968 Hong Kong influenza pandemic (~4 million deaths). In this review, we have summarised many of the currently licenced influenza vaccines available across the world and current vaccines in clinical trials. We then briefly discuss the important role of CD8+ T cells during influenza infection and why future influenza vaccines should consider targeting CD8+ T cells. Finally, we assess the current landscape of known immunogenic CD8+ T‐cell epitopes and highlight the knowledge gaps required to be filled for the design of rational future influenza vaccines that incorporate CD8+ T cells.

Abstract Because of a spring predictability barrier, the seasonal forecast skill of Arctic summer sea ice is limited by the availability of melt‐season sea ice thickness (SIT) observations. The first year‐round SIT observations, retrieved from CryoSat‐2 from 2011 to 2020, are assimilated into the GFDL ocean–sea ice model. The model's SIT anomaly field is brought into significantly better agreement with the observations, particularly in the Central Arctic. Although the short observational period makes forecast assessment challenging, we find that the addition of May–August SIT assimilation improves September local sea ice concentration (SIC) and extent forecasts similarly to SIC‐only assimilation. Although most regional forecasts are improved by SIT assimilation, the Chukchi Sea forecasts are degraded. This degradation is likely due to the introduction of negative correlations between September SIC and earlier SIT introduced by SIT assimilation, contrary to the increased correlations found in other regions.

Abstract The frequency and intensity of heat extremes over the United States have increased since the mid‐20th century and are projected to increase with additional anthropogenic greenhouse gas forcing. We define heat extremes as summertime (June–August) daily maximum 2m temperatures that exceed historical records. We examine characteristics of historical and near‐future heat extremes using observations and past and future projections using 100 ensemble members from three coupled global climate models large ensemble simulations. We find that the large ensembles capture the trend and variability of heat extremes over the period 2006–2020 relative to the 1991–2005 climatology but overestimate the frequency at which the heat extremes occur. In future warming scenarios, heat extremes continue to increase over the next 30 years, with high amplitude records in the Northwest and Central US. After 2050, we find there is a spread in the frequency of heat extremes that is dependent on the emissions scenario, with a high emissions until mid‐century followed by a high mitigation scenario showing a decrease in heat extremes by the end of the century. Although the frequency of future heat extremes is likely overestimated in the large ensembles, they are still a powerful tool for researching extreme temperatures in the climate system.

Abstract Aim To develop a competency framework applicable to Chinese extracorporeal membrane oxygenation (ECMO) nurses. Design A qualitative study was performed following the consolidated criteria for reporting qualitative research. Methods Semi‐structured interviews based on the critical incident technique were conducted among 21 ECMO care providers recruited from five well‐known ECMO centres in Guangzhou, China. Interview transcripts were coded and analysed using the constant comparative method. The data collection period lasted from November 2021 to April 2022. Results A competency framework for ECMO nurses was identified. It included four domains: knowledge, skills, behaviours and attitudes, containing 33 subcompetencies and 66 items. Relevance to clinical practice This framework can be a reference for the assessment and training of ECMO nurses.

Abstract Objective To evaluate the ability of 68Ga‐PSMA PET/CT maximum standard uptake value (SUVmax) to distinguish prostate cancer (PCa) International Society of Urological Pathology ISUP grade group (GG) 2 and GG3. Methods The PET/CT images and data of 147 patients were analyzed retrospectively, and the SUVmax of the index lesions were measured. The receiver operating characteristic curve was used to analyze the diagnostic value of PET/CT for PCa. The correlation between SUVmax and ISUP GG was analyzed. A logistic regression model was established with SUVmax and was validated to predict its value of diagnosing intermediate‐ and high‐risk PCa (ihPCa). Results Of the 147 patients, 112 cases were PCa (76.2%), and 35 cases were benign lesions (23.8%). There was a significant difference between the benign and the malignant groups (p 0.05). The specificity and the positive predictive value of 68Ga‐PSMA PET/CT in the diagnosis of PCa were 97% and 99% with cut‐off SUVmax of 6.94, while the specificity and the positive predictive value of ihPCa were 95% and 96% with cut‐off SUVmax of 10.12. Conclusion 68Ga‐PSMA PET/CT can reliably distinguish GG2 from GG3 PCa.

Abstract An increasing number of studies have reported using natural language processing (NLP) to assist observational research by extracting clinical information from electronic health records (EHRs). Currently, no standardized reporting guidelines for NLP‐assisted observational studies exist. The absence of detailed reporting guidelines may create ambiguity in the use of NLP‐derived content, knowledge gaps in the current research reporting practices, and reproducibility challenges. To address these issues, we conducted a scoping review of NLP‐assisted observational clinical studies and examined their reporting practices, focusing on NLP methodology and evaluation. Through our investigation, we discovered a high variation regarding the reporting practices, such as inconsistent use of references for measurement studies, variation in the reporting location (reference, appendix, and manuscript), and different granularity of NLP methodology and evaluation details. To promote the wide adoption and utilization of NLP solutions in clinical research, we outline several perspectives that align with the six principles released by the World Health Organization (WHO) that guide the ethical use of artificial intelligence for health.

Abstract Limited by preparation time and ligand solubility, synthetic protocols for cyclodextrin‐based metal‐organic framework (CD‐MOF), as well as subsequent derived materials with improved stability and properties, still remains a challenge. Herein, an ultrafast, environmentally friendly, and cost‐effective microwave method is proposed, which is induced by graphene oxide (GO) to design CD‐MOF/GOs. This applicable technique can control the crystal size of CD‐MOFs from macro‐ to nanocrystals. CD‐MOF/GOs are investigated as a new type of supramolecular adsorbent. It can selectively adsorb the dye molecule methylene green (MG) owing to the synergistic effect between the hydrophobic nanocavity of CDs, and the abundant O‐containing functional groups of GO in the composites. Following high temperature calcination, the resulting N, S co‐doped porous carbons derived from CD‐MOF/GOs exhibit a high capacitance of 501 F g−1 at 0.5 A g−1, as well as stable cycling stability with 90.1% capacity retention after 5000 cycles. The porous carbon exhibits good electrochemical performance due to its porous surface containing numerous electrochemically active sites after dye adsorption and carbonization. The design strategy by supramolecular incorporating a variety of active molecules into CD‐MOFs optimizes the properties of their derived materials, furthering development toward the fabrication of zeitgeisty and high‐performance energy storage devices.

Abstract Methane seepage, generated from natural processes or gas hydrate dissociation, drives the development of cold seep ecosystems and leads to atmosphere methane emission, thereby influencing climate change. Uncovering the intrinsic interactions among methane seepage intensities, biogeochemical processes in the sediment, and benthic community characteristics at the seafloor is essential to clarify and predict the ultimate fate of methane leakage from the deep sea. Here, we conducted a systematic investigation of methane intensity, pore fluid migration characteristics, sediment mineral fraction features, and the evolution of biological communities in areas with different methane intensities. Furthermore, analyses of high‐resolution images, pore fluid geochemical feature, and lithologic characteristics of the sediment in the Haima cold seep were also carried out in this study. The results showed that, in areas with different methane intensities, organic matter sulfate reduction and anaerobic oxidation of methane were heterogeneous. The heterogeneity led to the methane transformation zones at different depths, which changed the mineral composition of the sediment and biological communities in the seabed. In addition, a hypothesis of successional sequence of biomes in cold seep was established. This study revealed that the methane seepage intensity was a key factor in determining the biogeochemical process in the sediment of cold seep. The coupling effects of biogeochemical processes and methane seepage intensities dominated the community succession of cold seep. These findings could provide important implications for understanding the dynamic deep marine methane cycle mechanism and the contribution of deep‐sea methane released to climate change.

Abstract Real‐time monitoring of vital sounds from cardiovascular and respiratory systems via wearable devices together with modern data analysis schemes have the potential to reveal a variety of health conditions. Here, a flexible piezoelectret sensing system is developed to examine audio physiological signals in an unobtrusive manner, including heart, Korotkoff, and breath sounds. A customized electromagnetic shielding structure is designed for precision and high‐fidelity measurements and several unique physiological sound patterns related to clinical applications are collected and analyzed. At the left chest location for the heart sounds, the S1 and S2 segments related to cardiac systole and diastole conditions, respectively, are successfully extracted and analyzed with good consistency from those of a commercial medical device. At the upper arm location, recorded Korotkoff sounds are used to characterize the systolic and diastolic blood pressure without a doctor or prior calibration. An Omron blood pressure monitor is used to validate these results. The breath sound detections from the lung/ trachea region are achieved a signal‐to‐noise ration comparable to those of a medical recorder, BIOPAC, with pattern classification capabilities for the diagnosis of viable respiratory diseases. Finally, a 6×6 sensor array is used to record heart sounds at different locations of the chest area simultaneously, including the Aortic, Pulmonic, Erb's point, Tricuspid, and Mitral regions in the form of mixed data resulting from the physiological activities of four heart valves. These signals are then separated by the independent component analysis algorithm and individual heart sound components from specific heart valves can reveal their instantaneous behaviors for the accurate diagnosis of heart diseases. The combination of these demonstrations illustrate a new class of wearable healthcare detection system for potentially advanced diagnostic schemes.

Abstract Background Nivolumab at a dose of 480 mg every 4 weeks (Q4W) is approved for the adjuvant treatment of melanoma. However, real‐world data on this regimen are limited in this setting. Methods This retrospective observational study utilized data from the US Oncology Network iKnowMed electronic health record database and patient medical charts. Eligible patients were diagnosed with melanoma and received adjuvant nivolumab monotherapy from March to August 2018. Patients were grouped by dosing regimen: cohort 1 (C1), de novo nivolumab 480 mg Q4W; cohort 2 (C2), switched to nivolumab 480 mg Q4W after nivolumab 240 mg or 3 mg/kg every 2 weeks (Q2W); cohort 3 (C3), de novo nivolumab 3 mg/kg Q2W; or cohort 4 (C4), de novo nivolumab 240 mg Q2W. Patients were followed for up to 12 months. Duration of therapy and safety/tolerability were assessed. Results One hundred ninety‐one patients were included (C1, n = 40; C2, n = 74; C3, n = 22; C4, n = 55). Duration of therapy was relatively consistent across cohorts (median, 10.3 months; range, 8.3–10.7). Likewise, proportions of patients experiencing treatment‐related adverse events (TRAEs) were similar (range, 54.5%–60.1%), as were the most common events (fatigue, rash, diarrhea, hypothyroidism, nausea, and pruritus). However, proportions experiencing ‘significant’ TRAEs varied between cohorts. Proportions discontinuing treatment were relatively consistent across cohorts. Propensity score matching and sensitivity analyses generally supported the unadjusted findings. Conclusions Real‐world safety profiles of nivolumab 240 mg Q2W and 480 mg Q4W were similar, and both were comparable to the well‐documented safety of weight‐based dosing (3 mg/kg Q2W), further supporting their approval and use in the adjuvant setting for melanoma.

Abstract With the widespread use of highly active antiretroviral therapy (HARRT), the survival time of AIDS patients has been greatly extended. However, the incidence of lung cancer in HIV‐infected patients is increasing and has become a major problem threatening the survival of AIDS patients. The aim of this study is to use Weighted Gene Co‐expression Network Analysis (WGCNA) and differential gene analysis to find possible key genes involved in HIV‐infected lung cancer. In this study, using lung tissue samples from five pairs of HIV‐infected lung cancer patients, second‐generation sequencing was performed and transcriptomic data were obtained. A total of 132 HIV‐infected lung cancer‐related genes were screened out by WGCNA and differential gene expression analysis methods. Based on gene annotation analysis, these genes were mainly enriched in mitosis‐related functions and pathways. In addition, in protein–protein interaction (PPI) analysis, a total of 39 hub genes were identified. Among them, five genes (ASPM, CDCA8, CENPF, CEP55, and PLK1) were present in both three hub gene lists (intersection gene, DEGs, and WCGNA module) suggesting that these five genes may become key genes involved in HIV‐infected lung cancer.

Abstract Aims/Introduction To explore the differences of serum fibroblast growth factor‐21 (FGF‐21) levels in pregnant women with normal glucose tolerance and gestational diabetes mellitus (GDM), and to analyze the relationship between FGF‐21 and glucose and lipid metabolic indicators, leptin, retinol binding protein 4 (RBP‐4) and adiponectin in GDM, in order to provide basis for the prevention and treatment of GDM. Materials and Methods Total of 120 women were included, and divided into normal glucose tolerance group (58 cases) and GDM group (62 cases) according to the 75 g oral glucose tolerance test results. General information were recorded; height, weight and blood pressure, blood glucose, lipids, insulin, FGF‐21, leptin, RMP‐4, and adiponectin were measured, and body mass index (BMI), homeostasis model assessment‐IR, homeostasis model assessment‐β and area under glucose curve were calculated. The t‐test, Pearson analysis and multiple linear regression analysis were used to evaluate the differences and related factors of FGF‐21 in GDM. Results The pre‐pregnancy BMI, pregnancy BMI, weight gain during pregnancy and FGF‐21 levels were higher in GDM group, whereas there were no statistically significant differences in leptin, RBP‐4 and adiponectin. Correlation analysis suggested that FGF‐21 level was correlated with age, pre‐pregnancy BMI, weight gain during pregnancy, high‐density lipoprotein cholesterol, leptin, RBP‐4 and adiponectin, and the results of multiple linear regression showed that serum FGF‐21 was related to pre‐pregnancy BMI, weight gain during pregnancy, leptin, RBP‐4 and adiponectin in GDM. Conclusions There were higher serum FGF‐21 levels in GDM, which might be related to pre‐pregnancy BMI, weight gain during pregnancy, leptin, RBP‐4 and adiponectin.