Systematic investigation of TetR-family transcriptional regulators and their roles on lignocellulosic inhibitor acetate tolerance in Zymomonas mobilis.

TetR-family transcriptional regulators are widely distributed among bacteria and involved in various cellular processes such as multidrug and inhibitor resistance. Zymomonas mobilis is a industrial bacterium for lignocellulosic ethanol production. Although TetR-family regulators and their associated RND-family efflux pumps in Z. mobilis have been identified to be differentially expressed under various inhibitors and stressful conditions, there are no systematic investigation yet. In this study, bioinformatic analyses indicated that there are three TetR-family transcriptional regulators (ZMO0281, ZMO0963, ZMO1547) and two RND-family efflux pumps (ZMO0282-0285, ZMO0964-0966) adjacent to corresponding TetR-family regulators of ZMO0281 and ZMO0963 in Z. mobilis. Genetics studies were then carried out with various mutants of TetR-family regulators constructed, and ZMO0281 was characterized to be related to acetate tolerance. Combining transcriptomics and dual-reporter gene system, this study demonstrated that three TetR-family regulators repressed their adjacent genes specifically. Moreover, TetR-family regulator ZMO0281 might also be involved in other cellular processes in the presence of acetate. In addition, the upregulation of RND-family efflux pumps due to ZMO0281 deletion might lead to an energy imbalance and decreased cell growth in Z. mobilis under acetate stress. The systematic investigation of all three TetR-family regulators and their roles on a major lignocellulosic inhibitor acetate tolerance in Z. mobilis thus not only unravels the molecular mechanisms of TetR-family regulators and their potential cross-talks on regulating RND-family efflux pumps and other genes in Z. mobilis, but also provides guidance on understanding the roles of multiple regulators of same family in Z. mobilis and other microorganisms for efficient lignocellulosic biochemical production.

Dynamic network biomarker C1QTNF1 regulates tumor formation at the tipping point of hepatocellular carcinoma.

Identifying the precise moment before the onset of hepatocellular carcinoma (HCC) remains a significant challenge in the medical field. The existing biomarkers fall short of pinpointing the critical point preceding HCC formation. This study aimed to determine the exact tipping point for the transition from cirrhosis to HCC, identify the core Dynamic Network Biomarker (DNB), and elucidate its regulatory effects on HCC. A spontaneous HCC mouse model was established to mimic HCC formation in patients with chronic hepatitis. Using the DNB method, C1q and tumor necrosis factor (TNF) related 1 (C1QTNF1) protein was identified as the key DNB at the crucial tipping time of spontaneous HCC development. Both in vitro and in vivo studies showed that C1QTNF1 could inhibit tumor growth. Overexpression of C1QTNF1 before the tipping point effectively prevented HCC occurrence. Patients with elevated C1QTNF1 expression demonstrated improved overall survival (OS) (P = 0.03) and disease-free survival (DFS) (P = 0.03). The diagnostic value of C1QTNF1 was comparable to that of alpha-fetoprotein (AFP) (area under the curve [AUC] = 0.84; sensitivity 85%; specificity 80%). Furthermore, our research indicated that platelet-expressed C1QTNF1 is involved in cancer-associated signaling pathways. Our findings introduce a novel perspective by highlighting C1QTNF1 as the pivotal biomarker at the tipping point of primary HCC formation using DNB. We propose C1QTNF1 as a prognostic biomarker for HCC, potentially influencing tumor development through a platelet-related cancer signaling pathway.

Cell-free DNA methylation profile potential in the diagnosis of lung squamous cell carcinoma.

Background: Aberrant methylation plays an essential role in early cancer development. In this study, we investigated methylation patterns in lung squamous cell carcinoma (LUSC) and matched non-tumor tissue and plasma samples to evaluate the potential of these patterns in the diagnosis of LUSC. Methods: The study group included 49 patients with stage I-III LUSC. We collected resected tumor tissue, paired peritumoral tissue, distant normal tissue, and corresponding plasma samples. A bespoke lung cancer bisulfite sequencing panel was used to profile the methylation level. Another 48 healthy volunteers provided control plasma samples. Results: Peritumoral and distant normal tissues presented similar methylation signatures, distinct from those in tumor tissue samples. A comparison of methylation profiles led to the identification of 871 tumor-specific differentially methylated blocks, including 847 hypermethylated and 24 hypomethylated blocks (adjusted P value <0.05). All top-ranked blocks were tumor-related. Tissue samples were analyzed for field cancerization to identify progressively aggravating aberrant methylations during tumor initiation and development. The analysis revealed that 221 blocks presented a stepwise increase in methylation levels, while seven blocks presented a stepwise decrease in methylation pattern as the sampling drew nearer to the tumor. The malignant contaminated ratio (MCR) confirmed the presence of distinct methylation patterns between tumor and peritumoral tissue samples. We then constructed a diagnostic panel using a combined diagnostic score of cell-free DNA (cfDNA) that showed high sensitivity and specificity. The healthy controls had a significantly lower combined diagnostic score (cd-score) than LUSC patients. Additionally, based on the methylation profiles, LUSC could be classified into two subgroups, C1 and C2. The methylation profile of the C2 group was not distinct from the healthy controls, which had a significantly lower cd-score than did the C1 group. Conclusions: LUSC-specific methylation patterns could potentially discriminate between peritumoral tissue, distant normal tumor tissue, and tumor tissues. This preliminary study also supported the potential utility of cfDNA methylation analysis in diagnosing LUSC.

PET Imaging of Peptide Probe Al[18F]F-NOTA-PCP1 for Monitoring the Engagement of PD-L1 Antibodies in Tumors.

Immune checkpoint inhibitors (ICIs) are a powerful treatment modality for various types of cancer. The effectiveness of ICIs is intimately connected to the binding status of antibodies to receptors. However, validated means to accurately evaluate target specificity and predict antibody efficacy in vivo are lacking. A novel peptide-based probe called Al[18F]F-NOTA-PCP1 was developed and validated for its specificity to PD-L1 in A549, U87MG, GL261, and GL261-iPDL1 cell lines, as well as in xenograft models. Then the probe was used in PET/CT scans to determine the binding status of PD-L1 antibodies (atezolizumab, avelumab, and durvalumab) in U87MG xenograft model mice. Moreover, Al[18F]F-NOTA-PCP1 was used to evaluate the impact of different treatment times and doses. Al[18F]F-NOTA-PCP1 PET/CT can be used to evaluate the interaction between PD-L1 and antibodies to determine the effectiveness of immunotherapy. By quantifying target engagement, the probe has the potential to predict the efficacy of immunotherapy and optimize the dose and treatment schedules for PD-L1 immunotherapy. This imaging agent could be a valuable tool in guiding personalized treatment strategies and improving cancer patient outcomes.

Neo-adjuvant chemotherapy plus immunotherapy in resectable N1/N2 NSCLC.

BACKGROUND: Locally advanced non-small cell lung cancer (NSCLC) with N1/N2 lymph node metastasis is challenging with poor survival. Neo-adjuvant chemo-immunotherapy has gained benefits in a proportion of these patients. However no specific biomarker has been proved to predict the effect before therapy. In addition, the relationship of nodal status and survival after neo-adjuvant chemo-immunotherapy is still not well stated. METHODS: A total of 75 resectable NSCLC patients with N1/N2 stage who received neo-adjuvant chemo-immunotherapy plus surgery were retrospectively studied. The clinical characteristics, surgical information and safety parameters were collected. The correlations of major pathological response (MPR) and pathological complete response (pCR) with clinical data were analyzed. The progression free disease(PFS) and overall survival(OS) were evaluated with pathological response and nodal status. RESULTS: Of the 75 patients, 69 (92%) patients experienced treatment related adverse effects, while grade 3-4 adverse effects occurred in 8 (10%) patients. All the patients received surgical R0 resection with a MPR rate of 60% and a pCR rate of 36%. 67% of N1 patients and 77% of N2 patients had nodal clearance after neo-adjuvant treatment. A significant difference was observed between pathological response with age, histology and multiple lymph node metastasis. The PFS was better in the MPR cohort. The PFS was 90.1% and 83.6% at the nodal clearance group at the time of 12 and 18 months, compared with 70.1% and 63.7% at the nodal residual group. CONCLUSIONS: The neo-adjuvant chemo-immunotherapy for locally advanced NSCLC with nodal positive was safe and feasible. The patients with elder age and squamous-cell carcinoma (SCC) were more likely to have better pathological response, while multiple nodal metastasis was a negative predictor. The clearance of lymph node resulted in significantly longer PFS and OS.

Risk factor analysis and prediction model for papillary thyroid carcinoma with lymph node metastasis.

Objective: We aimed to identify the clinical factors associated with lymph node metastasis (LNM) based on ultrasound characteristics and clinical data, and develop a nomogram for personalized clinical decision-making. Methods: A retrospective analysis was performed on 252 patients with papillary thyroid carcinoma (PTC). The patient's information was subjected to univariate and multivariate logistic regression analyses to identify risk factors. A nomogram to predict LNM was established combining the risk factors. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curve, calibration curve, cross-validation, decision curve analysis (DCA), and clinical impact curve. Results: There are significant differences between LNM and non-LNM groups in terms of age, sex, tumor size, hypoechoic halo around the nodule, thyroid capsule invasion, lymph node microcalcification, lymph node hyperechoic area, peak intensity of contrast (PI), and area under the curve (AUC) of the time intensity curve of contrast (P<0.05). Age, sex, thyroid capsule invasion, lymph node microcalcification were independent predictors of LNM and were used to establish the predictive nomogram. The ROC was 0.800, with excellent discrimination and calibration. The predictive accuracy of 0.757 and the Kappa value was 0.508. The calibration curve, DCA and calibration curve demonstrated that the prediction model had excellent net benefits and clinical practicability. Conclusion: Age, sex, thyroid capsule invasion, and lymph node microcalcification were identified as significant risk factors for predicting LNM in patients with PTC. The visualized nomogram model may assist clinicians in predicting the likelihood of LNM in patients with PTC prior to surgery.

N6 -methyladenosine-modified circSTX6 promotes hepatocellular carcinoma progression by regulating the HNRNPD/ATF3 axis and encoding a 144 amino acid polypeptide.

BACKGROUND: Circular RNAs (circRNAs) play a significant role in the initiation and progression of various cancers, including hepatocellular carcinoma (HCC). Circular syntaxin 6 (circSTX6, also known as hsa_circ_0007905) has been identified as a microRNA (miRNA) sponge in pancreatic adenocarcinoma. However, its full range of functions in terms of protein scaffold and translation remain largely unexplored in the context of HCC. METHODS: The expression of circSTX6 and its encoded protein was examined in HCC tumour tissues. N6 -methyladenosine (m6 A) on circSTX6 was verified and quantified by methylated RNA immunoprecipitation (Me-RIP), RIP and dual luciferase reporter assays. The biological functions of circSTX6 and its encoded protein in HCC were clarified by in vitro and in vivo experiments. Mechanistically, the interaction between circSTX6 and heterogeneous nuclear ribonucleoprotein D (HNRNPD) was investigated by RNA pull-down, RIP and fluorescence in situ hybridization (FISH)/IF. The regulatory effects of circSTX6 and HNRNPD on activating transcription factor 3 (ATF3) mRNA were determined by mRNA stability and RIP assays. Furthermore, the presence of circSTX6-encoded protein was verified by mass spectrometry. RESULTS: CircSTX6 and its encoded 144 amino acid polypeptide, circSTX6-144aa, were highly expressed in HCC tumour tissues and served as independent risk factors for overall survival in HCC patients. The expression of circSTX6 was regulated by METTL14 in an m6 A-dependent manner. Functionally, circSTX6 accelerated HCC proliferation and tumourigenicity and reinforced tumour metastasis in vitro and in vivo. Mechanistically, circSTX6 acted as a sponge for HNRNPD protein, facilitating its binding to ATF3 mRNA, consequently promoting ATF3 mRNA decay. Meanwhile, circSTX6-144aa promoted HCC proliferation, migration and invasion independent of circSTX6 itself. CONCLUSION: Collectively, our study reveals that m6 A-modified circSTX6 drives malignancy in HCC through the HNRNPD/ATF3 axis, while its encoded circSTX6-144aa contributes to HCC progression independent of circSTX6. CirSTX6 and its encoded protein hold promise as potential biomarkers and therapeutic targets in HCC.

An overview of current advances of PD-L1 targeting immuno-imaging in cancers.

The programmed death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway plays a significant role in immune evasion. PD-1 or PD-L1 immune checkpoint inhibitors (ICIs) have become a standard treatment for multiple types of cancer. To date, PD-L1 has served as a biomarker for predicting the efficacy of ICIs in several cancers. The need to establish an effective detection method that could visualize PD-L1 expression and predict the efficacy of PD-1/PD-L1 ICIs has promoted a search for new imaging strategies. PD-L1-targeting immuno-imaging could provide a noninvasive, real-time, repeatable, dynamic, and quantitative assessment of the characteristics of all tumor lesions in individual patients. This study analyzed the existing evidence in the literature on PD-L1-based immuno-imaging (2015-2022). Original English-language articles were searched using PubMed and Google Scholar. Keywords, such as "PD-L1," "PET," "SPECT," "PET/CT," and "SPECT/CT," were used in various combinations. A total of nearly 50 preclinical and clinical studies of PD-L1-targeting immuno-imaging were selected, reviewed, and included in this study. Therefore, in this review, we conducted a study of the advances in PD-L1-targeting immuno-imaging for detecting the expression of PD-L1 and the efficacy of ICIs. We focused on the different types of PD-L1-targeting agents, including antibodies and small PD-L1-binding agents, and illustrated the strength and weakness of these probes. Furthermore, we summarized the trends in the development of PD-L1-targeting immuno-imaging, as well as the current challenges and future directions for clinical workflow.

Grading surface urban heat island and investigating factor weight based on interpretable deep learning model across global cities.

Significant urbanization resulted in increasing surface urban heat island (SUHI) that caused negative impacts on urban ecological environment, and residential comfort. Accurately monitoring the spatiotemporal variations and understanding controls of SUHI were essential to propose effective mitigation measurements. However, SUHI grades across global cities remained unknown, which cloud greatly support for global mitigations. Additionally, quantitative evaluating factor weights for different SUHI indicators and grades worldwide remained further investigations. Therefore, this paper proposed SUHI grading based on agglomerative hierarchical clustering, and further quantified factor weights for different indicators and grades based on an interoperable machine learning named TabNet. There were three major findings. (1) Global cities were grouped into five grades, including SUCI (surface urban cool island), insignificant, low-value, medium-value, and high-value SUHI grades, indicating significant differences among different grades. SUHI grades showed significant climate-based variations, wherein the arid climate was dominated by the SUCI grade at daytime but the high-value grade at nighttime. (2) Vegetation difference was an important factor for daytime SUHII accounting for 27%. Daytime frequency of SUHI was controlled by vegetation difference, temperature, evaporation and nighttime light, accounting for 78%. The major factors for nighttime frequency were albedo differences and nighttime light, accounting for 45%. (3) Related factors contributed differently to various SUHI grades. The weight of △EVI for daytime SUHII gradually increased with grades, while it for daytime frequency and maximum duration of SUHI decreased with grades. The nighttime SUHII of the low-value grade was greatly affected by the background climate, while that of the medium-value and high-value grades were strongly impacted by anthropogenic heat flux. The diurnal contrast of grades and coupling effects with heat wave were further discussed. This paper aimed to provide information on grades and controls of SUHI for further mitigation proposal.

Time course of changes in the transcriptome during russet induction in apple fruit.

BACKGROUND: Russeting is a major problem in many fruit crops. Russeting is caused by environmental factors such as wounding or moisture exposure of the fruit surface. Despite extensive research, the molecular sequence that triggers russet initiation remains unclear. Here, we present high-resolution transcriptomic data by controlled russet induction at very early stages of fruit development. During Phase I, a patch of the fruit surface is exposed to surface moisture. For Phase II, moisture exposure is terminated, and the formerly exposed surface remains dry. We targeted differentially expressed transcripts as soon as 24 h after russet induction. RESULTS: During moisture exposure (Phase I) of 'Pinova' apple, transcripts associated with the cell cycle, cell wall, and cuticle synthesis (SHN3) decrease, while those related to abiotic stress increase. NAC35 and MYB17 were the earliest induced genes during Phase I. They are therefore linked to the initial processes of cuticle microcracking. After moisture removal (Phase II), the expression of genes related to meristematic activity increased (WOX4 within 24 h, MYB84 within 48 h). Genes related to lignin synthesis (MYB52) and suberin synthesis (MYB93, WRKY56) were upregulated within 3 d after moisture removal. WOX4 and AP2B3 are the earliest differentially expressed genes induced in Phase II. They are therefore linked to early events in periderm formation. The expression profiles were consistent between two different seasons and mirrored differences in russet susceptibility in a comparison of cultivars. Furthermore, expression profiles during Phase II of moisture induction were largely identical to those following wounding. CONCLUSIONS: The combination of a unique controlled russet induction technique with high-resolution transcriptomic data allowed for the very first time to analyse the formation of cuticular microcracks and periderm in apple fruit immediately after the onset of triggering factors. This data provides valuable insights into the spatial-temporal dynamics of russeting, including the synthesis of cuticles, dedifferentiation of cells, and impregnation of cell walls with suberin and lignin.

The current advances and future directions of PD-1/PD-L1 blockade in head and neck squamous cell carcinoma (HNSCC) in the era of immunotherapy.

Immune checkpoint inhibitors (ICIs) have previously demonstrated their efficacy and safety in various solid tumors, and with the growing interest in the application of ICIs in head and neck squamous cell carcinoma (HNSCC), various data have been reported. Mechanistically, HNSCC cells express programmed death ligand 1 (PD-L1), which binds to its receptor programmed death 1 (PD-1). Immune escape plays a key role in disease initiation and progression. Studying the abnormal activation of related pathways of PD-1/PD-L1 will help to understand the way of immunotherapy and find the advantageous population of immunotherapy. How to reduce HNSCC-related mortality and morbidity in this process has promoted the search for new therapeutic strategies, especially in the era of immunotherapy. PD-1 inhibitors have demonstrated significant prolongation of survival in recurrent/metastatic (R/M) HNSCC with a favorable safety profile. It also holds great promise in locally advanced (LA) HNSCC, where numerous studies are underway. Although immunotherapy has made great progress in HNSCC research, there are still many challenges. Therefore, in the review, we conducted an in-depth study on the expression of PD-L1 and the regulatory, immunosuppressive mechanisms caused by PD-L1, especially in head and neck squamous cell carcinoma, which is different from other tumors. And further summarize the situation, challenges and development trends of PD-1 and PD-L1 blockade in clinical practice.

Adaptive Laboratory Evolution and Metabolic Engineering of Zymomonas mobilis for Bioethanol Production Using Molasses.

Molasses with abundant sugars is widely used for bioethanol production. Although the ethanologenic bacterium Zymomonas mobilis can use glucose, fructose, and sucrose for ethanol production, levan production from sucrose reduces the ethanol yield of molasses fermentation. To increase ethanol production from sucrose-rich molasses, Z. mobilis was adapted in molasses, sucrose, and fructose in parallel. Adaptation in fructose is the most effective route to generate an evolved strain F74 with improved molasses utilization, which is majorly due to a G99S mutation in Glf for enhanced fructose import. Subsequent sacB deletion and sacC overexpression in F74 to divert sucrose metabolism from levan production to ethanol production further enhanced ethanol productivity 28.6% to 1.35 g/L/h. The efficient utilization of molasses by diverting sucrose metabolic flux through adaptation and genome engineering not only generated an excellent ethanol producer using molasses but also provided the strategy for developing microbial cell factories.

m6A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression.

Background: Circular RNA (circRNA) plays a critical role in tumour progression. Circ-CCT3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, the role of circ-CCT3 in hepatocellular carcinoma remains elusive.Methods: Here, circ-CCT3 (a circRNA derived from exons 3, 4 and 5 of the CCT3 gene, hsa_circ_0004680) was identified by circRNA microarray and validated by qRT-PCR. RNA immunoprecipitation (RIP) was performed to confirm the binding between ALKBH5 along with METTL3 and circ-CCT3. Methylated RNA Immunoprecipitation (MeRIP) was used to detect the N6-methyladenosine (m 2A) levels of circ-CCT3. CircRNAs in vivo precipitation, luciferase reporter assay, biotin-coupled microRNA capture, and fluorescence in situ hybridization were conducted to assess the interaction between circ-CCT3 and miR-378a-3p. The functions of circ-CCT3 in HCC were evaluated both in vitro and in vivo.Results: We demonstrated that circ-CCT3 was highly expressed in HCC which indicated the poor prognosis. Circ-CCT3 expression served as an independent risk factor for overall survival in patients with HCC. Knocking-down of circ-CCT3 inhibited the proliferation, invasion and migration of HCC cells, and angiogenesis of HUVEC. Mechanistically, ALKBH5 and METTL3 could bind and regulate m A-modification of circ-CCT3. Further, circ-CCT3 upregulated the expression of FLT-1 by sponging miR-378a-3p.Conclusions: Circ-CCT3 was significantly up-regulated in HCC and promoted liver cancer development via miR-378a-3p-FLT1 axis. It was also found that circ-CCT3 was under m A-modification mediated by ALKBH5 and METTL3. Our study highlights circ-CCT3 as a potential therapeutic target of HCC treatment, which provides a novel understanding on mechanisms of circRNAs in HCC progression.

Messenger RNA electroporated hepatitis B virus (HBV) antigen-specific T cell receptor (TCR) redirected T cell therapy is well-tolerated in patients with recurrent HBV-related hepatocellular carcinoma post-liver transplantation: results from a phase I trial.

BACKGROUND AND AIMS: Liver transplantation (LT) is the primary curative option for cirrhotic patients with early-stage hepatocellular carcinoma (HCC). However, tumor recurrence occurs in 15-20% of cases with unfavorable prognosis. We have developed a library of T cell receptors (TCRs) specific for different hepatitis B virus (HBV) antigens, restricted by different molecules of human leucocyte antigen (HLA)-class I, to redirect T cells against HBV antigens (Banu in Sci Rep 4:4166, 2014). We further demonstrated that these transiently functional T cells specific for HBV obtained through messenger RNA (mRNA) electroporation can eliminate HCC cells expressing HBV antigens in vitro and in vivo (Kah in J Clin Invest 127:3177-3188, 2017). A phase I clinical trial for patients with HCC recurrence post-liver transplant was conducted to assess the safety, tolerability, and anti-tumor efficacy of transiently functional HBV-TCR T cells. Here, we report the clinical findings with regard to the safety and anti-tumor efficacy of mRNA electroporated HBV-specific TCR-T cells. (ClinicalTrials.gov identifier: NCT02719782). PATIENTS AND METHODS: A total of six patients with HBV-positive recurrent HCC post-liver transplant and HLA-matched to TCR targeting hepatitis B surface antigen (HBsAg) or hepatitis B core antigen (HBcAg) (HLA-A*02:01/HBsAg, HLA-A*11:01/HBcAg, HLA-B*58:01/HBsAg or HLA-C*08:01/HBsAg) were enrolled in this study. The primary objective was to assess the safety of short-lived mRNA electroporated HBV-TCR T cells based on the incidence and severity of the adverse event (AE) graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0. The secondary objective was to determine the effectiveness of HBV-TCR T cells as per RECIST 1.1 criteria. Patients were followed up for survival for 2 years post-end of treatment. RESULTS: The median age of the six patients was 35.5 years (range: 28-47). The median number of HBV-TCR T cell infusions administered was 6.5 (range: 4-12). The treatment-related AE included grade 1 pyrexia. This study reported no cytokine release syndrome nor neurotoxicity. One patient remained alive and five were deceased at the time of the data cutoff (30 April 2020). CONCLUSION: This study has demonstrated that multiple infusions of mRNA electroporated HBV-specific TCR T cells were well-tolerated in patients with HBV-positive recurrent HCC post-liver transplant.

Point-of-Care Ultrasonography Helped to Rapidly Detect Pneumomediastinum in a Vomiting Female.

Vomiting-induced pneumomediastinum is a rare presentation and can be a result of alveolar rupture (Mackler effect) or Boerhaave syndrome. Patients diagnosed with Boerhaave syndrome may present with the classic Mackler triad of vomiting, chest pain, and subcutaneous emphysema. However, there exists a large overlap of symptoms accompanying Boerhaave syndrome and the Macklin effect, including retrosternal chest pain, neck discomfort, cough, sore throat, dysphagia, dysphonia, and dyspnea. Boerhaave syndrome is a dangerous condition. Delayed diagnosis of Boerhaave syndrome may worsen sepsis and cause mortality. Therefore, early diagnosis and timely management are important to prevent further complications. Here, we present a case of vomiting-induced pneumomediastinum, which supports the use of bedside ultrasonography to aid in the diagnosis and rapid differentiation of etiology of pneumomediastinum.

Retraction Notice to: LINC01234/MicroRNA-31-5p/MAGEA3 Axis Mediates the Proliferation and Chemoresistance of Hepatocellular Carcinoma Cells.

[This retracts the article DOI: 10.1016/j.omtn.2019.10.035.].

Identifying and characterizing frequency and maximum durations of surface urban heat and cool island across global cities.

Surface urban heat island (SUHI) has been widely reported from a local to global scale. However, variations and controls of temporal indicators for SUHI and SUCI (surface urban cool island) remain unclear. This paper firstly reconstructed the seamless daily LST (land surface temperature) based on ATC-SKT (annual temperature cycle-skin temperature) and comprehensively validated for SUHI applications across 1112 global cities. Based on the seamless daily LST, this paper further characterized the spatiotemporal variations of the frequency (SUHIF and SUCIF) and maximum duration (SUHID and SUCID) and investigated the impacts from related factors, inconsideration of the different characteristics of SUHI and SUCI. There are five major findings. (1) The seamless daily LST reconstructed based on ATC-SKT is validated through pixel-based temperature and city-based SUHII accuracy assessments. (2) The selection of the frequency threshold is based on robustness for LST accuracy, approximation to SUHII global average, and mitigation of frequency saturation. (3) The average daytime SUHIF is 214 days/year, with 44 % of cities exhibiting SUHI occurrences for almost every day in summer. The nighttime SUHIF is 175 days/year, with increasing latitudinal variations from equatorial to polar regions. The daytime SUCIF is 41 days/year, with the greatest average frequency of 172 days/year exhibited in arid regions. (4) The average SUHID is 147 days at daytime and 58 days at nighttime, with relatively opposite geographical distributions between day and night. (5) Greater vegetation difference at daytime and greater albedo difference at nighttime result in more occurrences and longer consecutive durations of SUHI, with opposite effects on the temporal indicators of SUCI. Furthermore, the improvements in daily SUHII and impacts from the maximum duration were discussed. This paper aims to identify and highlight the period with significant SUHI and SUCI effects across global cities for further mitigation.

Evaluation of diagnostic efficacy of multimode ultrasound in BI-RADS 4 breast neoplasms and establishment of a predictive model.

Objectives: To explore the diagnostic efficacy of ultrasound (US), two-dimensional and three-dimensional shear-wave elastography (2D-SWE and 3D-SWE), and contrast-enhanced ultrasound (CEUS) in breast neoplasms in category 4 based on the Breast Imaging Reporting and Data System (BI-RADS) from the American College of Radiology (ACR) and to develop a risk-prediction nomogram based on the optimal combination to provide a reference for the clinical management of BI-RADS 4 breast neoplasms. Methods: From September 2021 to April 2022, a total of 104 breast neoplasms categorized as BI-RADS 4 by US were included in this prospective study. There were 78 breast neoplasms randomly assigned to the training cohort; the area under the receiver-operating characteristic curve (AUC), 95% confidence interval (95% CI), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 2D-SWE, 3D-SWE, CEUS, and their combination were analyzed and compared. The optimal combination was selected to develop a risk-prediction nomogram. The performance of the nomogram was assessed by a validation cohort of 26 neoplasms. Results: Of the 78 neoplasms in the training cohort, 16 were malignant and 62 were benign. Among the 26 neoplasms in the validation cohort, 6 were malignant and 20 were benign. The AUC values of 2D-SWE, 3D-SWE, and CEUS were not significantly different. After a comparison of the different combinations, 2D-SWE+CEUS showed the optimal performance. Least absolute shrinkage and selection operator (LASSO) regression was used to filter the variables in this combination, and the variables included Emax, Eratio, enhancement mode, perfusion defect, and area ratio. Then, a risk-prediction nomogram with BI-RADS was built. The performance of the nomogram was better than that of the radiologists in the training cohort (AUC: 0.974 vs. 0.863). In the validation cohort, there was no significant difference in diagnostic accuracy between the nomogram and the experienced radiologists (AUC: 0.946 vs. 0.842). Conclusions: US, 2D-SWE, 3D-SWE, CEUS, and their combination could improve the diagnostic efficiency of BI-RADS 4 breast neoplasms. The diagnostic efficacy of US+3D-SWE was not better than US+2D-SWE. US+2D-SWE+CEUS showed the optimal diagnostic performance. The nomogram based on US+2D-SWE+CEUS performs well.