Search

Abstract The third most prevalent type of epidermal growth factor receptor (EGFR) mutation, EGFR exon 20 insertions (EGFRex20ins), involves 2%–12% of all cases of EGFR‐positive non‐small cell lung cancer (NSCLC). Approximately 90% of the mutations occur within the loop structure region, and the most frequently reported subtypes are A767_V769dup and S768_D770dup, which together account for almost 50% of instances. Apart from the unique subtype of A763_Y764insFQEA, NSCLCs with EGFRex20ins are resistant to approved EGFR tyrosine kinase inhibitors (TKIs) and are also insensitive to chemotherapy or immunotherapy. A new modality of treatment for NSCLC patients with EGFRx20ins has been established with the approval of mobocertinib and amivantamab. There are also numerous novel targeted treatments for NSCLC with EGFRex20ins in development, which are anticipated to improve this patient population's survival even further. This review provides a reference for the clinical management of these patients by summarizing the most recent epidemiological, and clinicopathological characteristics, diagnostic techniques, and therapeutic advances of EGFRex20ins in NSCLC.

Abstract Background Approximately 30% of dogs with idiopathic epilepsy (IE) are drug‐resistant. Recent studies have suggested cannabidiol (CBD) may be an effective anticonvulsant in dogs with IE. Objective To evaluate the addition of CBD to antiseizure drugs (ASDs) on seizure frequency and to report adverse events in dogs with drug‐resistant IE. Animals Fifty‐one dogs. Dogs having at least 2 seizures per month while receiving at least 1 ASD were included in the trial. Methods Double‐blinded placebo‐controlled crossover study. The 5 mg/kg/day dosage met futility requirements after 12 dogs, and a dosage of 9 mg/kg/day was used in the next 39 dogs. Dogs were randomly assigned to receive CBD or placebo for 3 months, with a 1‐month washout period between oils. Total numbers of seizures and seizure days were recorded. Diagnostic testing was performed periodically throughout the trial. Results At the 9 mg/kg/day dose, the decrease in total seizure frequency was significant compared with placebo. A 24.1% decrease in seizure days occurred in dogs receiving CBD and a 5.8% increase occurred in dogs receiving placebo (P ≤ .05). No significant difference was found in the number of responders (≥50% decrease in total seizures or seizure days). Liver enzyme activities increased at both dosages. Decreased appetite and vomiting were more common in the CBD phase (P ≤ .05). Conclusions and Clinical Importance Cannabidiol decreased total seizures and seizure days compared to placebo when administered to dogs PO at 9 mg/kg/day. Liver enzymes should be monitored with administration of CBD in dogs.

Abstract The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

Abstract Most reactors for non‐thermal plasma excitation are capacitive to pulse generators. The density and temperature of electrons in plasma are dominated by the discharging currents which are proportional to the pulse edges. However, adjusting the pulse edges is quite challenging since the switching speed and the inductance and capacitance in the discharging loops dominate them. This study proposes a drive circuit for solid‐state Marx generators with adjustable edges. The drive circuit controls the Miller plateau by adjusting the gate voltage amplitude to adjust both the rise time and fall time of pulses continuously and independently. The influence of the gate voltage on the Miller plateau and the rise time is studied. The feasibility is verified by both simulating and experimental results. An 8‐stage solid‐state Marx generator prototype was built, and 4.8‐kV pulses with a rise time in the range of 79 ns‐22.21 μs were obtained over capacitive loads. Adjusting pulse edges can control the current amplitudes in dielectric barrier discharge loads.

Abstract This letter proposes a class of sine corrugated cavity resonators (SCCR). The SCCR can present slow‐wave features and provide dual‐mode (TE104 and TE105) wideband responses with reasonable sine period and depth. Based on it, a compact high‐gain bandwidth‐enhanced SCCR slot antenna array is designed. The high gain is obtained with seven radiation slots and the wideband is achieved due to three modes being utilised. The three modes include the modes of TE104 and TE105 of the SCCR and one feed slot mode. Compared with published works, the desired TE104 and TE105 can be obtained straightforwardly based on SCCR. The standard WR62 waveguide is utilised to feed the antenna. For validation, direct metal 3D printing technology is used to fabricate it with aluminium and copper powders as a comparison. Both measured results were discussed and showed a good agreement with the simulated ones.

Abstract Aim Patients with chronic liver disease (CLD), especially cirrhosis, are at a high risk of severe illness or death from coronavirus disease‐2019 (COVID‐19) and may have a suboptimal immune response to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine. This study aimed to evaluate the safety and immunogenicity of the COVID‐19 booster vaccination in patients with CLD. Methods The study protocol was prospectively registered at ClinicalTrials.gov (No. NCT05204602) after approval by the Ethics Committee. Adult participants with CLD were enrolled in this multicenter prospective study. They completed two doses of the inactivated COVID‐19 vaccine and received booster doses at least 6 months later. Adverse reactions were recorded within 14 days after the booster dose. Serum samples of the enrolled patients were collected before and after booster vaccination and tested for SARS‐CoV‐2 receptor‐binding domain (RBD) immunoglobulin G and neutralizing antibodies. The chi‐squared or Fisher's exact test was used to compare categorical data, and the Mann–Whitney U test was used to compare continuous variables. Two‐sided p

Abstract Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high‐risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow‐up.

Abstract Point cloud completion is prevalent due to the insufficient results from current point cloud acquisition equipments, where a large number of point data failed to represent a relatively complete shape. Existing point cloud completion algorithms, mostly encoder‐decoder structures with grids transform (also presented as folding operation), can hardly obtain a persuasive representation of input clouds due to the issue that their bottleneck‐shape result cannot tell a precise relationship between the global and local structures. For this reason, this article proposes a novel point cloud completion model based on a Stack‐Style Folding Network (SSFN). Firstly, to enhance the deep latent feature extraction, SSFN enhances the exploitation of shape feature extractor by integrating both low‐level point feature and high‐level graphical feature. Next, a precise presentation is obtained from a high dimensional semantic space to improve the reconstruction ability. Finally, a refining module is designed to make a more evenly distributed result. Experimental results shows that our SSFN produces the most promising results of multiple representative metrics with a smaller scale parameters than current models.

Abstract Objective HIV disease is evolving with more HIV+ persons experiencing a high quality of life with well‐controlled viremia. We recently enrolled a large cohort of HIV+ and clinically relevant HIV− persons for oral microbiome analyses that included a questionnaire related to oral hygiene and recreational behaviors. Here, the questionnaire responses were analyzed for behavioral trends within the cohort, together with trends over time by comparison to a previous geographically centered HIV+ cohort. Methods Data were collected by questionnaire at baseline visits as cross‐sectional assessments. Multivariable analyses were conducted for associations of HIV status as well as age, race, and sex, on oral hygiene/recreational behaviors. Results HIV+ subjects had reduced brushing frequency, but increased incidence of past cleanings and frequency of dry mouth, compared to the HIV− subjects. Within the entire cohort, positive associations were identified between age and several oral hygiene practices, and between age, race, and sex for several recreational behaviors. In comparison to the historical cohort, the contemporary HIV+ cohort participated in fewer high‐risk behaviors, but with similar trends for smoking and oral hygiene practices. Conclusion HIV status had little association with oral hygiene and recreational behaviors despite several differences in age, race, and sex. Behavioral trends over time support a higher quality of life in people currently living with HIV.

Abstract We conducted a mesocosm experiment to examine how ocean acidification (OA) affects communities of prokaryotes and eukaryotes growing on single‐use drinking bottles in subtropical eutrophic waters of the East China Sea. Based on 16S rDNA gene sequencing, simulated high CO2 significantly altered the prokaryotic community, with the relative abundance of the phylum Planctomycetota increasing by 49%. Under high CO2, prokaryotes in the plastisphere had enhanced nitrogen dissimilation and ureolysis, raising the possibility that OA may modify nutrient cycling in subtropical eutrophic waters. The relative abundance of pathogenic and animal parasite bacteria also increased under simulated high CO2. Our results show that elevated CO2 levels significantly affected several animal taxa based on 18S rDNA gene sequencing. For example, Mayorella amoebae were highly resistant, whereas Labyrinthula were sensitive to OA. Thus, OA may alter plastisphere food chains in subtropical eutrophic waters.

Abstract A transmitarray adopting dual‐layer polarisation rotating (PR) elements is proposed. The element comprises a pair of perpendicularly placed C‐shaped slots etched on the two sides of a single‐layer substrate and orthogonally rotates transmission wave polarisation with regard to the incidence. By adjusting C‐shaped slot's dimension as well as mirroring the bottom layer of the element, a 360° phase shift with a high transmission magnitude is achieved. Based on the proposed unit‐cell, a dual‐layer transmitarray composed of 529 elements is designed and developed. The experimental 1‐dB gain bandwidth and peak aperture efficiency are 13% and 44% respectively. Furthermore, sidelobe level of 20 dB and cross polarisation level of 26 dB are obtained at 10 GHz. These promising properties demonstrate the superiority of the element for transmitarray designs. In addition, this element can be also a good candidate for folded transmitarray designs.

Abstract Old age is the leading cause of impaired bodily function, which gradually increases healthcare service needs. To offer the best possible care in the home and to be able to detect health‐related functional impairment at an early stage, it is necessary to carry out systematic and structured observations. The assessment tool Subacute and Acute Dysfunction in the Elderly (SAFE) has been developed explicitly for these structured observations. This study aims to explore the experiences and challenges of home‐based care work team coordinators (WTCs) regarding the introduction and use of SAFE. Method The present qualitative study was performed following Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. The data were collected through individual interviews (n = 3) and focus group (FG) interviews (n = 7). The interview transcripts were analysed using the Gioia method. Results Five aggregated dimensions were identified: Varying acceptance of SAFE, Structuring and quality‐assurance of home‐based nursing practice, Obstacles for the integration of SAFE in daily practice, Acceptance and use of SAFE require continuous supervision and SAFE contributes to increased quality of nursing care. Conclusion The introduction of SAFE contributes to a structured follow‐up of functional status in patients receiving home care. In order to incorporate the tool into home care practice, it is essential to set aside time to introduce the tool and to support nurses' use of it by offering continuous supervision.

Abstract Background Refractory and relapsed acute myeloid leukemia (r/rAML) is associated with a difficult prognosis; clinical trials are typically suggested despite lack of a recognized standard of care. Combinatorial chemotherapy regimens utilized for r/rAML salvage play a crucial role in battling this invasive phase. Although it is characterized by a low response rate, CLAG is a traditional regimen used in r/rAML. We aimed to compare the efficacy and toxicity of CLAG+PLD to explore whether there was any improvement with the addition of pegylated liposomal doxorubicin (PLD) to CLAG Methods A total of 110 r/rAML patients were retrospectively analyzed from February 2017 to June 2020 at the Medical Center of Hematology, XinQiao Hospital, the 303rd Hospital of the Chinese People's Liberation Army, and Central Hospital of Chang Sha, Hunan Province. The response, overall survival (OS), disease‐free survival (DFS), and side effects in 110 r/rAML patients were evaluated retrospectively. Of these, 55 patients were administered CLAG+PLD, while 55 patients received CLAG alone as salvage therapy. Results In the CLAG+PLD group, there were 27 (49.1%) cases of complete response (CR) with no measurable residual disease (MRD−), 12 (21.8%) cases of CR with positive MRD (MRD+), 5 (9.1%) cases of partial response (PR), 11 (20%) cases of no response (NR), and no cases of death during the cycles. The response rates in the CLAG group were lower: CR was reached in 24 (46.6%) patients with MRD−, 6 (10.9%) patients with MRD+, 10 (18.2%) patients with PR, 13 (23.6%) patients with NR, and 2 (3.6%) patients who passed away, one from infection and the other from cerebral hemorrhage. The median OS and DFS were not attained in the CLAG+PLD group during the 2‐year OS and DFS follow‐up, while both values were 10 months in the CLAG group (p = 0.023 and p = 0.045, respectively). The results of the Cox regression analysis for the CLAG+PLD group were strongly illustrative of the importance of hematopoietic stem cell transplantation (HSCT) following salvage therapy. No increased toxicity was observed in the CLAG+PLD group. Conclusion CLAG+PLD is a potential salvage regimen for r/r AML that has a similar toxicity profile to CLAG and that improves response rates, 2‐year OS, and DFS relative to CLAG.

Abstract Objective Exposure to the nerve agent, soman (GD), induces status epilepticus (SE), epileptogenesis, and even death. Although rodent models studying the pathophysiological mechanisms show females to be more reactive to soman, no tangible sex differences in brains postexposure have been reported. In this study, we used multimodal imaging using MRI in adult rats to determine potential sex‐based biomarkers of soman effects. Methods Male and female Sprague Dawley rats were challenged with 1.2 × LD50 soman followed by medical countermeasures. Ten weeks later, the brains were analyzed via structural and functional MRI. Results Despite no significant sex differences in the initial SE severity after soman exposure, long‐term MRI‐based structural and functional differences were evident in the brains of both sexes. While T2 MRI showed lesser soman‐induced neurodegeneration, large areas of T1 enhancements occurred in females than in males, indicating a distinct pathophysiology unrelated to neurodegeneration. fMRI‐based resting‐state functional connectivity (RSFC), indicated greater reductions in soman‐exposed females than in males, associating with the T1 enhancements (unrelated to neurodegeneration) rather than T2‐hyperintensity or T1‐hypointensity (representing neurodegeneration). The wider T1 enhancements associating with the decreased spontaneous neuronal activity in multiple resting‐state networks in soman‐exposed females than males suggest that neural changes unrelated to cellular atrophy impinge on brain function postexposure. Taken together with lower spontaneous neural activity in soman‐exposed females, the results indicate some form of neuroprotective state that was not present in males. Significance The results indicate that endpoints other than neurodegeneration may need to be considered to translate sex‐based nerve agent effects in humans.

Abstract Background This study aimed to examine the treatment and prognosis of patients with type B2 + B3 thymoma and compare it with those patients with type B2 and B3 thymoma. Methods We conducted a retrospective analysis of the results of 39 patients with type B2 + B3 thymoma, 133 patients with type B2 thymoma, and 64 patients with type B3 thymoma. The Kaplan–Meier technique was used to generate survival curves. For multivariate analysis, the Cox proportional hazard model was applied. Results With a median follow‐up of 60 months (range: 1–128 months), the percentage of patients with tumor, node, metastasis (TNM) stage III and IV disease gradually increased from 19.5% to 25.6% to 35.9% among those with histological subtypes B2, B2 + B3, and B3, respectively, p = 0.045. Twenty‐three patients experienced recurrence or metastasis. The total 10‐year progression‐free survival (PFS) rates were 86.0% overall (85.0% in type B2, 87.2% in type B2 + B3, and 87.5% in type B3). Age, R0 resection, and Masaoka–Koga stage were found to have a significant on PFS in all patients. There was no statistically significant difference in PFS between different histotypes of thymoma, p = 0.650. PFS was predicted by R0 resection in all histotypes and by the Masaoka–Koga stage in the type B2 subgroup. Conclusion Combining the two staging methods to guide the diagnosis and treatment of patients with B2 + B3 thymoma is recommended. R0 resection is recommended to reduce recurrence. Patients with B2 + B3 thymoma have a prognosis similar to those with a B2 thymoma or a B3 thymoma alone.

Abstract Background Diacylglycerol kinase α (DGKA) is the first member discovered from the diacylglycerol kinase family, and it has been linked to the progression of various types of tumors. However, it is unclear whether DGKA is linked to the development of lung cancer. Methods We investigated the levels of DGKA in the lung cancer tissues. Cell growth assay, colony formation assay and EdU assay were used to examine the effects of DGKA‐targeted siRNAs/shRNAs/drugs on the proliferation of lung cancer cells in vitro. Xenograft mouse model was used to investigate the role of DGKA inhibitor ritanserin on the proliferation of lung cancer cells in vivo. The downstream target of DGKA in lung tumorigenesis was identified by RNA sequencing. Results DGKA is upregulated in the lung cancer cells. Functional assays and xenograft mouse model indicated that the proliferation ability of lung cancer cells was impaired after inhibiting DGKA. And cyclin D3(CCND3) is the downstream target of DGKA promoting lung cancer. Conclusions Our study demonstrated that DGKA promotes lung tumorigenesis by regulating the CCND3 expression and hence it can be considered as a potential molecular biomarker to evaluate the prognosis of lung cancer patients. What's more, we also demonstrated the efficacy of ritanserin as a promising new medication for treating lung cancer.

Abstract Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first‐ and second‐line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow‐up of TETs.

Abstract Objective Uniquely, state legislators may enact obesity prevention policies tailored to each state's needs and take diverse policy approaches to address obesity prevalence. The objective of this study was to identify and describe state‐level obesity‐related policies between 2009 and 2019. Methods Using a database of legislation covering 2009–2019, researchers categorized obesity‐related legislation by status (proposed/enacted), topic, and environment impacted. Researchers determined the number of policies proposed; enacted, by political party control; obesity prevalence, by states over time. Results 3256 obesity‐related policies were proposed among 50 states and Washington DC between 2009 and 2019. Collectively, 18% (593) of policies were enacted; California (96), New and Jersey (57) enacted the most. Across environment and topics, the most enacted policies categorized in school environment (226) and school nutrition (150) topic area. Most policies were proposed (496) and enacted (77) in 2011. On average, Democrat‐controlled states had higher enactment rates than Republican‐controlled states, as did states with lower (vs. higher) obesity prevalence. Conclusions States have actively pursued obesity‐related legislation across multiple topics and environments from 2009 to 2019, with mixed enactment rates. Evaluating the impact of these policies, alone and in combination, will be important to determine whether these state‐level efforts reduce obesity.

Abstract Objective Syncope is a common clinical condition in the elderly, associated with significant morbidity and risk of recurrence. Recurrent syncope causing a repeated reduction in the cerebral blood flow can predispose to progressive neurodegeneration, a decline in overall health and functionality. Hence, this study was conducted to study the common causes of recurrent syncope and its association with various geriatric syndromes. Methodology This case–control study recruited 50 cases of recurrent syncope and 50 controls, aged 75 years and older. A detailed history and sequential evaluation for aetiologies of recurrent syncope were done. Cognition, frailty, activities of daily living, depression, and nutrition were assessed using various scales. Results Most (80%, 80/100) of the participants were males and the mean age was 80.04 ± 4.3 years. In the syncope group, 42% (21/50) of patients had arrhythmia, and 30% (15/30) had valvular heart disease. Recurrent syncope was significantly associated with lower scores on Montreal cognitive assessment scale (OR: 6.47 P

Abstract Objective This study aims to demonstrate the advantages of NGS molecular classification in EC diagnosis and to assess whether molecular classification could be performed on curettage specimens and its concordance with subsequent hysterectomy specimens. Methods 80 patients with hysterectomy specimens and 35/80 patients with paired curettage specimens were stratified as POLE mut, MSI‐H, TP53 wt, or TP53 abn group by NGS panel. Histotype, tumor grade, IHC results, and other pathological details were taken from original pathological reports. Results The correlation analysis of 80 patients with hysterectomy specimens between NGS molecular classification and clinicopathological characters displayed that the POLE mut group was associated with EEC (87.5%) and TP53 abn subtype was correlated to a later stage (Stage II–IV, 47.6%), G3 (76.2%), serous histology (61.9%) and myometrial invasion ≥50% (47.6%). A favorable concordance (31/32, 96.9%) was shown in MSI analysis and MMR IHC results, and the agreement rate of p53 IHC and TP53 mutation was 81.5% (53/65). Compared with the p53 IHC abnormal group, the TP53 mutation group had a higher correlation with high‐risk factors. A high level of concordance (31/35, 88.0%) of NGS molecular classification was achieved between curettage specimens and hysterectomy specimens while grade and histotype (including unclassified group) from curettage specimens and hysterectomy specimens showed only moderate levels of agreement, 54.3% (19/35) and 68.6% (24/35), respectively. Conclusion NGS molecular classification achieved on curettage samples showed high concordance with the final hysterectomy specimens, demonstrating superior to the conventional pathological assessment of grade and histotype and potential utilization in clinical practice.

Abstract Objectives This study aimed to investigate the survival outcomes and potential prognostic factors of patients with temporal bone squamous cell carcinoma (TBSCC) treated at our institution. Methods We retrospectively included patients who were diagnosed with TBSCC between 2008 and 2019. The Kaplan–Meier (KM) method was used to describe overall survival (OS), and the association between baseline characteristics and prognoses was examined using Cox proportional hazards models. Results Fifty consecutive patients with TBSCC were included in this study. The results showed that patients with advanced modified Pittsburgh (MPB)‐ T classifications had a poorer prognosis (T3 vs. T1‐2: HR: 2.81, 95% CI: 0.34–23.43; T4 vs. T1‐2: HR: 7.25, 95% CI: 0.95–55.41; p = 0.041). Meanwhile, middle ear squamous cell carcinoma (MESCC) showed a significantly worse prognosis than external auditory canal squamous cell carcinoma (EACSCC, HR: 2.65, 95% CI: 1.04–6.76, p = 0.04). Conclusions MESCC and advanced MPB‐T classifications might be considered predictors of unfavorable outcomes in patients with TBSCC, indicating that special attention should be paid to the original tumor subsite and tumor extension in the management of patients with TBSCC.

Abstract Objective To explore the factors affecting the prognosis of cervical cancer (CC), and to construct and evaluate predictive nomograms to guide individualized clinical treatment. Methods The clinicopathological and follow‐up data of CC patients from June 2013 to December 2019 in Sun Yat‐sen Memorial Hospital of Sun Yat‐sen University were retrospectively analyzed. Log‐rank test was used for univariate survival analysis, and Cox multivariate regression was used to identify independent prognostic factors, based on which nomogram models were established and evaluated in multiple aspects. Results Patients were randomly assigned into the training (n = 746) and validation sets (n = 329). Survival analysis of the training set identified cervical myometrial invasion, parametrial involvement, and malignant tumor history as prognosticators of postoperative DFS and pathological type, cervical myometrial invasion, and history of STD for OS. C‐index was 0.799 and 0.839 for the nomograms for DFS and OS, respectively. Calibration curves and Brier scores also indicated high performance. Importantly, decision curve analysis suggested great clinical applicability of these nomograms. Conclusions In this study, we analyzed a cohort of 1075 CC patients and identified DFS‐ or OS‐associated clinicohistologic characteristics. Two nomograms were subsequently constructed for DFS and OS prognostication, respectively, and showed high performance in terms of discrimination, calibration, and clinical applicability. These models may facilitate individualized treatment and patient selection for clinical trials. Future investigations with larger cohorts and prospective designs are warranted for validating these prognostic models.

Abstract Carbapenemase‐resistant Klebsiella pneumoniae (KP) resistant to multiple antibiotic classes necessitates optimized combination therapy. Our objective is to build a workflow leveraging omics and bacterial count data to identify antibiotic mechanisms that can be used to design and optimize combination regimens. For pharmacodynamic (PD) analysis, previously published static time‐kill studies (J Antimicrob Chemother 70, 2015, 2589) were used with polymyxin B (PMB) and chloramphenicol (CHL) mono and combination therapy against three KP clinical isolates over 24 h. A mechanism‐based model (MBM) was developed using time‐kill data in S‐ADAPT describing PMB‐CHL PD activity against each isolate. Previously published results of PMB (1 mg/L continuous infusion) and CHL (Cmax: 8 mg/L; bolus q6h) mono and combination regimens were evaluated using an in vitro one‐compartment dynamic infection model against a KP clinical isolate (108 CFU/ml inoculum) over 24 h to obtain bacterial samples for multi‐omics analyses. The differentially expressed genes and metabolites in these bacterial samples served as input to develop a partial least squares regression (PLSR) in R that links PD responses with the multi‐omics responses via a multi‐omics pathway analysis. PMB efficacy was increased when combined with CHL, and the MBM described the observed PD well for all strains. The PLSR consisted of 29 omics inputs and predicted MBM PD response (R2 = 0.946). Our analysis found that CHL downregulated metabolites and genes pertinent to lipid A, hence limiting the emergence of PMB resistance. Our workflow linked insights from analysis of multi‐omics data with MBM to identify biological mechanisms explaining observed PD activity in combination therapy.

Abstract Objectives To develop a novel laryngoscope device capable of dynamically measuring force and torque measurements in real‐time during intubation and to explore the efficacy of such a device through a face validation simulation. Methods The torque sensor laryngoscope is designed for use during intubation and is modeled after a standard, single‐use plastic laryngoscope. After device calibration, a face validation study was performed with intubation experts in the field. Quantitative data (intubation force metrics) and qualitative data (expert feedback on the device) were collected from three intubations using a Mac blade and three intubations with the Miller blade. Results Three experts (two anesthesiologists and one otolaryngologist) participated in the study. The mean maximum force exerted with the Mac blade was 24.5 N (95% confidence interval [CI], 22.3–26.8). The average force exerted was 13.6 N (95% CI, 11.7–15.5). The average total suspension time was 13.1 s (95% CI, 10.4–15.8). The average total impulse was 164.6 N·s (95% CI, 147.9–181.4). The mean maximum force exerted with the Miller blade was 31.6 N (95% CI, 26.4–36.8). The average force exerted was 15.8 N (95% CI, 13.8–17.9). The average total suspension time was 11.3 s (95% CI, 9.9–12.6). The average total impulse was 216.2 N·s (95% CI, 186.5–245.9). The mean maximum force (p = .0265) and total impulse (p = .009) were significantly higher in the Miller blade trials than in the Mac blade trials. Survey results found that this device, while bulky, intubated similarly to standard‐use models and has potential as an intubation teaching tool. Conclusion The torque sensor laryngoscope can measure and display real‐time intubation force metrics for multiple laryngoscope blades. Initial validation studies showed a significantly lower maximum force and total impulse when intubating with the Mac blade than with the Miller blade. Face validation survey results were positive and suggested the potential for this device as a teaching tool. Level of Evidence Level 5.

Abstract Background Renal fibrosis is the final development pathway and the most common pathological manifestation of chronic kidney disease. Epigenetic alteration is a significant intrinsic factor contributing to the development of renal fibrosis. SET domain‐containing 2 (SETD2) is the sole histone H3K36 trimethyltransferase, catalysing H3K36 trimethylation. There is evidence that SETD2‐mediated epigenetic alterations are implicated in many diseases. However, it is unclear what role SETD2 plays in the development of renal fibrosis. Methods Kidney tissues from mice as well as HK2 cells were used as research subjects. Clinical databases of patients with renal fibrosis were analysed to investigate whether SETD2 expression is reduced in the occurrence of renal fibrosis. SETD2 and Von Hippel–Lindau (VHL) double‐knockout mice were used to further investigate the role of SETD2 in renal fibrosis. Renal tubular epithelial cells isolated from mice were used for RNA sequencing and chromatin immunoprecipitation sequencing to search for molecular signalling pathways and key molecules leading to renal fibrosis in mice. Molecular and cell biology experiments were conducted to analyse and validate the role of SETD2 in the development of renal fibrosis. Finally, rescue experiments were performed to determine the molecular mechanism of SETD2 deficiency in the development of renal fibrosis. Results SETD2 deficiency leads to severe renal fibrosis in VHL‐deficient mice. Mechanically, SETD2 maintains the transcriptional level of Smad7, a negative feedback factor of the transforming growth factor‐β (TGF‐β)/Smad signalling pathway, thereby preventing the activation of the TGF‐β/Smad signalling pathway. Deletion of SETD2 leads to reduced Smad7 expression, which results in activation of the TGF‐β/Smad signalling pathway and ultimately renal fibrosis in the absence of VHL. Conclusions Our findings reveal the role of SETD2‐mediated H3K36me3 of Smad7 in regulating the TGF‐β/Smad signalling pathway in renal fibrogenesis and provide an innovative insight into SETD2 as a potential therapeutic target for the treatment of renal fibrosis.

Abstract Backgound Colorectal cancer (CRC) is a complex, multistep disease that arises from the interplay genetic mutations and epigenetic alterations. The histone H3K36 trimethyltransferase SET domain‐containing 2 (SETD2), as an epigenetic signalling molecule, has a 5% mutation rate in CRC. SETD2 expression is decreased in the development of human CRC and mice treated with Azoxymethane /Dextran sodium sulfate (AOM/DSS). Loss of SETD2 promoted CRC development. SMAD Family member 4 (SMAD4) has a 14% mutation rate in CRC, and SMAD4 ablation leads to CRC. The co‐mutation of SETD2 and SMAD4 predicted advanced CRC. However, little is known on the potential synergistic effect of SETD2 and SMAD4. Methods CRC tissues from mice and SW620 cells were used as research subjects. Clinical databases of CRC patients were analyzed to investigate the association between SETD2 and SMAD4. SETD2 and SMAD4 double‐knockout mice were established to further investigate the role of SETD2 in SMAD4‐deficient CRC. The intestinal epithelial cells (IECs) were isolated for RNA sequencing and chromatin immunoprecipitation sequencing (ChIP‐seq) to explore the mechanism and the key molecules resulting in CRC. Molecular and cellular experiments were conducted to analyze the role of SETD2 in SMAD4‐deficient CRC. Finally, rescue experiments were performed to confirm the molecular mechanism of SETD2 in the development of SMAD4‐dificient CRC. Results The deletion of SETD2 promotes the malignant progression of SMAD4‐deficient CRC. Smad4Vil‐KO; Setd2Vil‐KO mice developed a more severe CRC phenotype after AOM/DSS induction, with a larger tumour size and a more vigorous epithelial proliferation rate. Further mechanistic findings revealed that the loss of SETD2 resulted in the down‐regulation of DUSP7, which is involved in the inhibition of the RAS/ERK signalling pathway. Finally, the ERK1/2 inhibitor SCH772984 significantly attenuated the progression of CRC in Smad4Vil‐KO;Setd2Vil‐KO mice, and overexpression of DUSP7 significantly inhibited the proliferation rates of SETD2KO; SMAD4KO SW620 cells. Conclusions Our results demonstrated that SETD2 inhibits the RAS/ERK signaling pathway by facilitating the transcription of DUSP7 in SMAD4‐deficient CRC, which could provide a potential therapeutic target for the treatment of advanced CRC.

Key Clinical Message This case report highlights the importance of recognizing and accurately diagnosing ganglioneuroblastoma, an uncommon variant of neuroblastic tumors in children. Ganglioneuroblastomas have diverse clinical and morphological presentations, and histopathological examination is paramount in guiding treatment decisions, especially in cases with ambiguous symptoms. Early detection is crucial, as the prognosis varies significantly based on the subtype and the presence of metastatic disease. Clinicians should maintain a high index of suspicion and utilize radiological examinations to promptly identify and treat these tumors. Abstract Children are frequently affected by neuroblastic tumors, which grow from the sympathoadrenal lineage of the neural crest during its development. However, intermixed ganglioneuroblastomas are far less common within the same tumor spectrum, the diagnosis of which could become challenging amidst an unusual presentation. In our case report, we present a 4‐year‐old boy who had complaints of fever and difficulty in walking, with a supra‐renal mass on ultrasound, which was diagnosed as ganglioneuroblastoma‐intermixed type on histopathological examination. This report aims to contribute to the understanding of the diverse clinical and morphological spectrum of ganglioneuroblastomas and the importance of multidisciplinary collaboration and histopathological examination to enhance decision‐making in such ambiguous scenarios.

Abstract Aim Rheumatoid arthritis (RA) is a chronic inflammation mediated by an autoimmune response. Baculoviral IAP repeat‐containing 2 (BIRC2) and tumor necrosis factor receptor 1‐associated death domain protein (TRADD) have been reported to be highly expressed in RA, while their specific roles during RA progression remain unclear. This study aims to explore the specific regulation of BIRC2/TRADD during the progression of RA. Methods C28/I2 cells were stimulated by lipopolysaccharide (LPS) to establish an in vitro RA cellular model. The expression level of BIRC2 and TRADD was examined by quantitative real‐time polymerase chain reaction and western blot. Cell Counting Kit‐8 and flow cytometry assays were performed to examine cell viability and necroptosis, respectively. The oxidative stress markers were detected using commercial kits, and the pro‐inflammatory cytokines were measured by ELISA assay. The interaction between BIRC2 and TRADD was verified by co‐immunoprecipitation assay. Results BIRC2 and TRADD were discovered to be highly expressed in LPS‐mediated C28/I2 cells. BIRC2 knockdown was demonstrated to inhibit LPS‐induced cell viability loss, necroptosis, oxidative stress, and inflammation in C28/I2 cells. BIRC2 could interact with TRADD and positively regulate TRADD expression. In addition, the protective role of BIRC2 knockdown against LPS‐mediated injuries in C28/I2 cells was partly weakened by TRADD overexpression. Conclusion In summary, BIRC2 knockdown alleviated necroptosis, oxidative stress, and inflammation in LPS‐mediated C28/I2 cells, which might correlate to the regulatory role of TRADD, indicating a novel target for the treatment of RA.

Abstract L‐Sorbosone dehydrogenase (SNDH) is a key enzyme involved in the biosynthesis of 2‐keto‐L‐gulonic acid , which is a direct precursor for the industrial scale production of vitamin C. Elucidating the structure and the catalytic mechanism is essential for improving SNDH performance. By solving the crystal structures of SNDH from Gluconobacter oxydans WSH‐004, a reversible disulfide bond between Cys295 and the catalytic Cys296 residues is discovered. It allowed SNDH to switch between oxidation and reduction states, resulting in opening or closing the substrate pocket. Moreover, the Cys296 is found to affect the NADP+ binding pose with SNDH. Combining the in vitro biochemical and site‐directed mutagenesis studies, the redox‐based dynamic regulation and the catalytic mechanisms of SNDH are proposed. Moreover, the mutants with enhanced activity are obtained by extending substrate channels. This study not only elucidates the physiological control mechanism of the dehydrogenase, but also provides a theoretical basis for engineering similar enzymes.

Key Clinical Message Peripheral eosinophilia is a rare but potential sign of TB infection. Physicians should assess patients for TB, especially if they display related symptoms or risk factors, and consider TB as a differential diagnosis, especially in idiopathic cases. Abstract Millions of new tuberculosis (TB) cases are reported annually. Peripheral eosinophilia is rare in tuberculosis. We describe a rare case of tuberculosis with a high peripheral eosinophil count. A 9‐year‐old male presented with fever, cough, and respiratory discomfort for a month. The patient's cough did not respond to treatment, along with weight loss and a loss of appetite. A physical examination revealed cervical lymphadenopathy and bilateral lung crepitations. A hematological investigation showed a high eosinophil count of 25,920 cells per cubic millimeter and medical imaging abnormalities consistent with TB. Some malignancies, allergies, and parasitic infections produce peripheral eosinophilia. However, medical literature rarely discusses TB‐induced eosinophilia. Several studies attribute it to mycobacterium antigen hyperreactivity. Eosinophilic release of cytotoxic chemicals may cause tissue damage, and TB patients' eosinophil levels may fluctuate. This case report emphasizes the need to investigate TB in peripheral eosinophilia patients after ruling out other explanations. Our patient benefited from early detection and anti‐TB medication. More studies are required to investigate the causes of TB eosinophilia and its consequences. A detailed medical history and physical examination are essential to diagnose and treat atypical presentations of TB.

Abstract Study hypothesis Our objective was to evaluate 30‐day major adverse cardiac events (MACE) in emergency department (ED) patients with normal high‐sensitivity troponins (hs‐trop). We hypothesized that MACE rates would be

Abstract MCT1 is a critical protein found in monocarboxylate transporters that plays a significant role in regulating the lactate shuttle. However, the post‐transcriptional modifications that regulate MCT1 are not clearly identified. In this study, it is reported that SETDB1 interacts with MCT1, leading to its stabilization. These findings reveal a novel post‐translational modification of MCT1, in which SETDB1 methylation occurs at K473 in vitro and in vivo. This methylation inhibits the interaction between MCT1 and Tollip, which blocks Tollip‐mediated autophagic degradation of MCT1. Furthermore, MCT1 K473 tri‐methylation promotes tumor glycolysis and M2‐like polarization of tumor‐associated macrophages in colorectal cancer (CRC), which enhances the lactate shuttle. In clinical studies, MCT1 K473 tri‐methylation is found to be upregulated and positively correlated with tumor progression and overall survival in CRC. This discovery suggests that SETDB1‐mediated tri‐methylation at K473 is a vital regulatory mechanism for lactate shuttle and tumor progression. Additionally, MCT1 K473 methylation may be a potential prognostic biomarker and promising therapeutic target for CRC.

Abstract Background Rabies expert on demand (REOD) telehealth service is provided by the U.S. Centers for Disease Control and Prevention (CDC) to assist public health practitioners, health providers, and the public to interpret national and international rabies prevention guidelines. REOD is staffed by subject matter experts of the CDC Poxvirus and Rabies Branch to assess each unique situation and provide evidence‐based guidance to stakeholders. This study aims to describe the utilization of a rabies telehealth system and provide insight into common consultations. Methods A cross‐sectional study of the nature of inquiries to REOD was done using the data collected from September 1, 2017 to September 30, 2021. An inquiry tracking form and Microsoft Access database were developed to document all inquiries received. Inquired ones were summarized to determine the frequency of inquiries by month, category, and location. Results Over a 49‐month period, REOD received 5228 inquiries. Peak inquiries (n = 108) occurred during August 2019. The most frequent inquiries received pertained to risk assessment and management of rabies exposures (n = 1109), requests for testing assistance (n = 912), consultation for suspected human rabies (n = 746), rabies exposures and post‐bite treatment occurring internationally (n = 310), and consultation for deviations in the recommended pre‐ and postexposure prophylaxis regimen (n = 300). Conclusion REOD is a global resource for consultation related to managing rabies exposures, diagnostic issues, and rabies control strategies. REOD is a regularly utilized CDC service, as the demand for up‐to‐date rabies guidance remains high. REOD fulfills a critical role for the interpretation and consultation on rabies prevention guidelines to stakeholder.

Abstract Background and Aims Interns must be proficient in obtaining informed consent (IC), which is the Association of American Medical College's 11th of 13 Entrustable Professional Activities (EPAs). Medical students have limited opportunity to practice IC during clerkships, resulting in inconsistent proficiency. We aimed to create a tool to assess whether our transition to residency (TTR) workshop enables fourth‐year medical students to meet a minimum standard of obtaining IC. Methods Sixty fourth‐year medical students were enrolled in the internal medicine virtual TTR course during AY2021. The curriculum prioritizes deliberate practice activities. Pre‐ and postworkshop assignments involved students typing verbatim what they would say during IC encounters. We modified an IC abstraction tool created by Spatz et al. to assess a minimum standard for students' IC assignments. Our final 7‐item tool consisted of the following domains: “What,” “Why,” “How,” “Benefits,” “Quantitative Risks,” “Qualitative Risks,” and “Alternatives,” weighing 1 point each. A minimum standard was obtained with a score of 6 or more points by appropriately discussing at least one domain involving risk and all other domains. Results Students scored highly on the prework domains pertaining to “What,” “Why,” and “How” of the procedure with no significant difference on postwork. Significant improvement was achieved on postwork domains covering “Benefits” (p = 0.039) and “Alternatives” (p = 0.031). For domains involving “Qualitative” and “Quantitative Risks,” there were no statistically significant improvements from pre‐ to postwork scores. Fifteen and 22 students met the minimum standard for IC on pre‐ and postwork, respectively. Conclusion Our students demonstrated a good a priori understanding of the “What,” “Why,” and “How” domains. After the workshop, they more reliably discussed “Benefits” and “Alternatives.” Our abstraction tool helped assess the strengths and weaknesses in our students' IC skillset and helped recognize areas of our curriculum that will benefit from improvements to bring students to meet the minimum standard.

Key Clinical Message For practitioners experiencing worsening psoriasis, subacute cutaneous lupus erythematosus (SCLE) with a psoriasiform presentation should be ruled out. Initial treatment for a presumptive diagnosis of psoriasis using hydroxychloroquine or ultraviolet phototherapy may cause SCLE to worsen. Abstract Psoriasiform subacute cutaneous lupus erythematosus is an unusual presentation scarcely reported in literature. We report a case of a 54‐year‐old man who presented with an itchy, papulosquamous rash of the upper extremities and face for 7 months. The initial physical examination revealed the classical morphology of psoriasis. One and a half years after the diagnosis of clinical worsening, the patient noticed a new papular eruption on the right posterior upper arm. A skin biopsy was performed, confirming a diagnosis of subacute cutaneous lupus erythematosus. This case report highlights the importance of considering rare presentations of cutaneous lupus erythematosus and therapeutic challenges in management.

Abstract Cystoscopy is the current gold standard for diagnosing bladder cancer (Bca), but its invasive nature often results in patient discomfort. This study aims to debise a new strategy to enhance BCa detection. We collected data from 30 BCa patients between January and June 2022. We obtained spontaneously voided urine specimens from these patients before and after administering extracorporeal bladder vibration. These specimens underwent routine cytologic examination and fluorescence in situ hybridization (FISH). Furthermore, we conducted a follow‐up 3 months postoperation. We recollected urine specimens before and after extracorporeal bladder vibration, repeating the cytologic examination and FISH. Our findings indicated an increase in the number of exfoliated cells in patients' urine postvibration compared to previbration. The liquid‐based cell staining results showed an increased detection rate of abnormal cells in the urinary sediment of patients with both low and high‐grade urothelial carcinoma postvibration. Similarly, the FISH results revealed an increased detection rate of CEP3 and CEP7 positive cells postvibration. Additionally, 3 months postoperation, we found abnormal cells in the urine of one patient previbration and in three patients postvibration. Further cystoscopic biopsy confirmed that these three patients had developed tumor recurrence. Our study substantiates that the extracorporeal bladder vibration assay significantly enhances BCa detection and the prediction of tumor recurrence. This method is simple, quick, and cost‐effective, making it a promising approach worthy of widespread clinical application.

Acute myocardial infarction is an important cause of death worldwide. While it often affects patients of older age, acute myocardial infarction is garnering more attention as a significant cause of morbidity and mortality among young patients (

Abstract Phase‐change random‐access memory (PCRAM) devices suffer from pronounced resistance drift originating from considerable structural relaxation of phase‐change materials (PCMs), which hinders current developments of high‐capacity memory and high‐parallelism computing that both need reliable multibit programming. This work realizes that compositional simplification and geometrical miniaturization of traditional GeSbTe‐like PCMs are feasible routes to suppress relaxation. While to date, the aging mechanisms of the simplest PCM, Sb, at nanoscale, have not yet been unveiled. Here, this work demonstrates that in an optimal thickness of only 4 nm, the thin Sb film can enable a precise multilevel programming with ultralow resistance drift coefficients, in a regime of ≈10−4–10−3. This advancement is mainly owed to the slightly changed Peierls distortion in Sb and the less‐distorted octahedral‐like atomic configurations across the Sb/SiO2 interfaces. This work highlights a new indispensable approach, interfacial regulation of nanoscale PCMs, for pursuing ultimately reliable resistance control in aggressively‐miniaturized PCRAM devices, to boost the storage and computing efficiencies substantially.

Summary Pseudomonas aeruginosa is an important opportunistic human pathogen, which raises a worldwide concern for its increasing resistance. Nonthermal plasma, which is also called cold atmospheric plasma (CAP), is an alternative therapeutic approach for clinical infectious diseases. However, the bacterial factors that affect CAP treatment remain unclear. The sterilization effect of a portable CAP device on different P. aeruginosa strains was investigated in this study. Results revealed that CAP can directly or indirectly kill P. aeruginosa in a time‐dependent manner. Scanning electron microscopy and transmission electron microscope showed negligible surface changes between CAP‐treated and untreated P. aeruginosa cells. However, cell leakage occurred during the CAP process with increased bacterial lactate dehydrogenase release. More importantly, pigmentation of the P. aeruginosa culture was remarkably reduced after CAP treatment. Further mechanical exploration was performed by utilizing mutants with loss of functional genes involved in pyocyanin biosynthesis, including P. aeruginosa PAO1 strain‐derived phzA1::Tn, phzA2::Tn, ΔphzA1/ΔphzA2, phzM::Tn and phzS::Tn, as well as corresponding gene deletion mutants based on clinical PA1 isolate. The results indicated that pyocyanin and its intermediate 5‐methyl phenazine‐1‐carboxylic acid (5‐Me‐PCA) play important roles in P. aeruginosa resistance to CAP treatment. The unique enzymes, such as PhzM in the pyocyanin biosynthetic pathway, could be novel targets for the therapeutic strategy design to control the growing P. aeruginosa infections.

Abstract Background Intraductal papillary mucinous neoplasms (IPMNs) are the precursor lesions of pancreatic cancers, requiring active surgical intervention during cancer development. However, the current criteria for predicting malignant IPMNs remain challenging and limited. Hence, this study aimed to assess the discriminatory performance of circulating cytokines, including TNF‐α, IL‐2R, IL‐6, and IL‐8, then build a novel predictive model to improve the diagnostic accuracy. Method A total of 131 retrospective (from March 2016 to December 2019) and 53 prospective (from March 2020 to January 2021) patients who were histologically confirmed as IPMNs were consecutively collected and analyzed. Result The circulating levels of TNF‐α, IL‐2R, IL‐6, and IL‐8 were significantly elevated in malignant IPMNs, and were verified as independent factors for malignant IPMNs (p

Abstract Background Inflammation is known to have an intricate relationship with tumorigenesis and tumor progression while it is also closely related to tumor immune microenvironment. Whereas the role of inflammation‐related genes (IRGs) in lung squamous carcinoma (LUSC) is barely understood. Herein, we recognized IRGs associated with overall survival (OS), built an IRGs signature for risk stratification and explored the impact of IRGs on immune infiltration landscape of LUSC patients. Methods The RNA‐sequencing and clinicopathological data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, which were defined as training and validation cohorts. Cox regression and least absolute shrinkage and selection operator analyses were performed to build an IRG signature. CIBERSORT, microenvironment cell populations‐counter and tumor immune dysfunction and rejection (TIDE) algorithm were used to perform immune infiltration analysis. Results A two‐IRG signature consisting of KLF6 and SGMS2 was identified according to the training set, which could categorize patients into two different risk groups with distinct OS. Patients in the low‐risk group had more anti‐tumor immune cells infiltrated while patient with high‐risk had lower TIDE score and higher levels of immune checkpoint molecules expressed. The IRG signature was further identified as an independent prognostic factor of OS. Subsequently, a prognostic nomogram including IRG signature, age, and cancer stage was constructed for predicting individualized OS, whose concordance index values were 0.610 (95% CI: 0.568–0.651) in the training set and 0.652 (95% CI: 0.580–0.724) in validation set. Time‐dependent receiver operator characteristic curves revealed that the nomogram had higher prediction accuracy compared with the traditional tumor stage alone. Conclusion The IRG signature was a predictor for patients with LUSC and might serve as a potential indicator of the efficacy of immunotherapy. The nomogram based on the IRG signature showed a relatively good predictive performance in survival.

Abstract The present study investigated ice accretion thickness under non‐incoming flow icing conditions on the ground using an infrared thermography system that converts infrared radiation temperature. Two back propagation (BP) neural network models were developed to measure ice thickness. Both theoretical model and polynomials were employed to fit the icing surface temperature elevation sequence to extract the pixel‐level temperature attenuation characteristics, which were served as the input to the BP neural networks. The prediction method of ice thickness by the BP neural network was analysed from three perspectives of sensitivity, dimension, and precision. In addition, K‐nearest neighbour (KNN) and support vector regression (SVR) algorithms were compared with BP neural network. In terms of prediction effect, the BP neural network performed the best. The verification of the BP neural network based on the characteristics of the theoretical model proved that the method can effectively predict the thickness of ice accretion, and its prediction error does not exceed 10%.

Abstract Aim The aim of this meta‐synthesis was to identify and synthesize qualitative research evaluating the real feelings, inner needs and emotional experience of women undergoing hysterectomy. Design Meta‐synthesis. Methods The PubMed, Web of Science, Cochrane Library, CINAHL, Embase, Ovid Medline and Sino Med were systematically searched until November 2021 and updated until June 2022. Two reviewers independently extracted data into a Microsoft Excel sheet. Qualitative meta‐synthesis was performed by coding relevant citations, organizing codes into descriptive themes and developing analytical themes. Results Qualitative meta‐synthesis yielded three themes and nine sub‐themes: comprehensive consideration before hysterectomy (a. disease factors; b. fertility factors; c. opinions of others); emotions and experience after hysterectomy (a. postoperative physical condition; b. psychological resilience to the loss of the uterus; c. changes in the couple's relationship); coping strategies (a. self‐denial and avoidance; b. change of perception and self‐adjustment; c. seek help from others).

Abstract Background Cutaneous metastases in pancreatic cancer (PC) are rare. Herein, we evaluate the clinical, genomic, and other descriptors of patients with PC and cutaneous metastases. Methods Institutional databases were queried, and clinical history, demographics, PC cutaneous metastasis details, and overall survival (OS) from cutaneous metastasis diagnosis were abstracted. OS was estimated using Kaplan–Meier methods. Results Forty patients were identified, and median age (Q1–Q3, IQR) of PC diagnosis was 66.0 (59.3–72.3, 12.9) years. Most patients had Stage IV disease at diagnosis (n = 26, 65%). The most common location of the primary tumor was the tail of the pancreas (n = 17, 43%). The most common cutaneous metastasis site was the abdomen (n = 31, 78%), with umbilical lesions occurring in 74% (n = 23) of abdominal lesions. The median OS (95% CI) was 11.4 months (7.0, 20.4). Twenty‐three patients had umbilical metastases (58%), and 17 patients had non‐umbilical metastases (43%). The median OS (95% CI) was 13.7 (7.0, 28.7) months in patients with umbilical metastases and 8.9 (4.1, Not reached) months in patients with non‐umbilical metastases (p = 0.1). Sixteen of 40 (40%) patients underwent somatic testing, and findings were consistent with known profiles. Germline testing in 12 (30%) patients identified pathogenic variants in patients: CHEK2, BRCA1, and ATM. Conclusion Cutaneous metastases from PC most frequently arise from a pancreas tail primary site and most frequently occur in the umbilicus. Cutaneous metastases may generally be categorized as umbilical or non‐umbilical metastases.

Abstract Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non–small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2‐altered NSCLC, including conventional chemotherapy, programmed death 1 (PD‐1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody‐drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T‐DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2‐mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2‐targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next‐generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a consensus on the clinical management of HER2‐altered NSCLC, focusing on the diagnosis and treatment strategies.

Abstract Precise localisation and navigation are the two most important tasks for mobile robots. Visual simultaneous localisation and mapping (VSLAM) is useful in localisation systems of mobile robots. The wide‐angle camera has a broad field of vision and more abundant information on images, so it is widely used in mobile robots, including legged robots. However, wide‐angle cameras are more complicated than ordinary cameras in the design of visual localisation systems, and higher requirements and challenges are put forward for VSLAM technologies based on wide‐angle cameras. In order to resolve the problem of distortion in wide‐angle images and improve the accuracy of localisation, a sampling VSLAM based on a wide‐angle camera model for legged mobile robots is proposed. For the predictability of the periodic motion of a legged robot, in the method, the images are sampled periodically, image blocks with clear texture are selected and the image details are enhanced to extract the feature points on the image. Then, the feature points of the blocks are extracted and by using the feature points of the blocks in the images, the feature points on the images are extracted. Finally, the points on the incident light through the normalised plane are selected as the template points; the relationship between the template points and the images is established through the wide‐angle camera model, and the pixel coordinates of the template points in the images and the descriptors are calculated. Moreover, many experiments are conducted on the TUM datasets with a quadruped robot . The experimental results show that the trajectory error and translation error measured by the proposed method are reduced compared with the VINS‐MONO, ORB‐SLAM3 and Periodic SLAM systems.

Abstract Background Accurate diagnostic biomarker testing is crucial to treatment decisions in breast cancer. Biomarker testing is performed on core needle biopsies (CNB) and is often repeated in the surgical specimen (SS) after resection. As differences between CNB and SS testing may alter treatment decisions, we evaluated concordance between CNB and SS as well as associated changes in treatment and clinical outcomes. Methods We performed a retrospective analysis of breast cancer patients at our institution between January 2010 and May 2020. Concordance between CNB and SS was assessed for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Survival in patients, including recurrence, metastatic recurrence, and death, were assessed using chi‐squared likelihood ratio. Results In total, 961 patients met eligibility criteria. Concordance, minor discordance, total concordance (concordance plus minor discordance), and major discordance between CNB and SS were reported for ER (87.7%, 9.2%, 90.8%, and 2.9%), PR (58.1%, 29.1%, 87.2%, and 12.8%), and HER2 IHC (52.5%, 20.9%, 73.4%, 26.6%), respectively. HER2 FISH concordance and major discordance were 58.5% and 1.2%, respectively. Of major discordance, ER (48.2%, p

Abstract Due to the cell size decrements and limited sojourn time on a high speed train mobility, unnecessary handovers (HOs) occur, which can lead to higher network communication costs, and affect passengers quality of service (QoS). This paper proposes a novel blockchain‐enabled privacy preserving HO skipping framework by using train mobility dataset from the city of London. Using a complex dataset parameters, passenger traffic flows are modelled by averaging various train lines and station's footfall numbers utilising blockchain to maintain privacy. The framework stores pseudonym addresses in order to track the path of users. The proposed framework allows for a better trade‐off in terms of 2% (approx.) gain in average throughput, over 100% gain in the last‐hop signal quality, and a 50% reduction in HO costs, while also addressing the needs for resources to operate the blockchain.

Abstract Solid‐state electrolytes (SSEs) are recognized as attractive candidates to realize safe and high‐energy‐density lithium metal batteries (LMBs). However, the practical application of SSEs still faces challenges such as insufficient room‐temperature ionic conductivity, unsatisfactory mechanical properties, and large internal resistance. Extensive research efforts have been made to explore new electrochemistry and technologies to address those challenges. Among them, the construction of order‐structured SSEs has emerged as a promising strategy. The anisotropic behavior induced by the orientation offers SSEs with desired properties targeting specific functions, and therefore the rational design of the order‐structured SSE provides an alternative solution to achieve an ideal SSE. This review discusses the structure‐property correlation of SSEs, and then summarizes the design strategies to construct order‐structured SSEs. Finally, the current challenges and possible future research directions for order‐structured SSEs for scalable high‐energy‐density LMBs are presented.