Efficacy of combining a medial superior malleolar perforator flap from the posterior tibial artery with a vacuum-assisted closure dressing for skin and soft tissue defects of the Achilles tendon area.

OBJECTIVE: This randomized clinical trial aimed to investigate the clinical efficacy of combining a medial superior malleolar perforator flap from the posterior tibial artery (PTAPF) with a vacuum-assisted closure (VAC) dressing for skin and soft tissue defects in the Achilles tendon area. METHODS: Twenty-eight patients were randomly divided into two equally sized groups: the control group received treatment with a medial superior malleolar perforator flap, while the experimental group was treated with a perforator flap from the posterior tibial artery in combination with a VAC dressing. Perioperative data, including average operative time, intraoperative blood loss, intraoperative complications, time to ambulation, and hospital stay after surgery, were recorded. Clinical outcomes were assessed based on the time to first weight-bearing walking, time to full weight-bearing activity, Visual Analog Scale (VAS) score, American Orthopaedic Foot and Ankle Society hindfoot and ankle score, and the range of motion for ankle plantar flexion. RESULTS: The patients were monitored for 3-12 months (average, 8.5), and it was observed that the flaps remained stable without enlargement, and their texture and color were similar to the surrounding tissue. Significantly enhanced postoperative indices were noted in the experimental group compared to the control group (P<0.05). CONCLUSION: The medial superior malleolar perforator flap from the posterior tibial artery, especially when combined with a VAC dressing, proves to be an effective method for repairing medium-sized skin defects in the Achilles tendon area. This approach offers several benefits, including a reliable blood supply, simplicity of the procedure, decreased damage to the donor site, improved aesthetic outcomes, and fewer postoperative complications.

Bias of AI-generated content: an examination of news produced by large language models.

Large language models (LLMs) have the potential to transform our lives and work through the content they generate, known as AI-Generated Content (AIGC). To harness this transformation, we need to understand the limitations of LLMs. Here, we investigate the bias of AIGC produced by seven representative LLMs, including ChatGPT and LLaMA. We collect news articles from The New York Times and Reuters, both known for their dedication to provide unbiased news. We then apply each examined LLM to generate news content with headlines of these news articles as prompts, and evaluate the gender and racial biases of the AIGC produced by the LLM by comparing the AIGC and the original news articles. We further analyze the gender bias of each LLM under biased prompts by adding gender-biased messages to prompts constructed from these news headlines. Our study reveals that the AIGC produced by each examined LLM demonstrates substantial gender and racial biases. Moreover, the AIGC generated by each LLM exhibits notable discrimination against females and individuals of the Black race. Among the LLMs, the AIGC generated by ChatGPT demonstrates the lowest level of bias, and ChatGPT is the sole model capable of declining content generation when provided with biased prompts.

Bidirectional Association Between Internet Use and Episodic Memory Among Older Adults: A Longitudinal Mediation Study.

Using nationally representative longitudinal data from three waves of the China Health and Retirement Longitudinal Study (CHARLS), we assessed whether social participation and mental health were channels through which internet use and episodic memory mutually influenced each other. Cross-lagged panel models with multiple mediators were employed for the mediation analysis. The results reveal that social participation and depressive symptoms were mechanisms underlying the internet-cognition interplay. Among men, an increased chance of contacting friends served as a pathway connecting internet use with better episodic memory. Conversely, men with better episodic memory were more likely to use the internet partially due to their higher chances of having contact with friends and engaging in group activities. Among women, engagement in group activities and depressive symptoms were two channels through which internet use and episodic memory positively influenced each other. Our findings provide practical implications for slowing cognitive aging and narrowing the digital divide.

An Innovative Approach for Removing Stripe Noise in Infrared Images.

The non-uniformity of infrared detectors' readout circuits can lead to stripe noise in infrared images, which affects their effective information and poses challenges for subsequent applications. Traditional denoising algorithms have limited effectiveness in maintaining effective information. This paper proposes a multi-level image decomposition method based on an improved LatLRR (MIDILatLRR). By utilizing the global low-rank structural characteristics of stripe noise, the noise and smooth information are decomposed into low-rank part images, and texture information is adaptively decomposed into several salient part images, thereby better preserving texture edge information in the image. Sparse terms are constructed according to the smoothness of the effective information in the final low-rank part of the image and the sparsity of the stripe noise direction. The modeling of stripe noise is achieved using multi-sparse constraint representation (MSCR), and the Alternating Direction Method of Multipliers (ADMM) is used for calculation. Extensive experiments demonstrated the proposed algorithm's effectiveness and compared it with state-of-the-art algorithms in subjective judgments and objective indicators. The experimental results fully demonstrate the proposed algorithm's superiority and efficacy.

Tumor-derived proliferative CTCs and CTC clusters predict aggressiveness and early recurrence in hepatocellular carcinoma patients.

BACKGROUND: Circulating tumor cells (CTCs), an indispensable liquid biopsy classifier, can provide extra information for the diagnosis and prognosis of hepatocellular carcinoma (HCC). METHODS: We systematically analyzed the peripheral blood of preoperative HCC patients (n = 270) for CTC number, Ki67 index reflecting the proliferative CTC percentage (PCP), and CTC clusters correlated with the characteristics of malignant HCC tumors. RESULTS: Driver gene mutations were found with high levels of consistency between CTCs and primary tumors (n = 73). CTC number and PCP were associated with tumor size, microvascular invasion (MVI), presence or absence of multiple tumors, and thrombosis significantly. CTC number and PCP robustly separated patients with and without relapse, with a sensitivity of 88.89%/81.48% and a specificity of 72.73%/94.81% in the training set (n = 104) and corresponding values of 80.00%/86.67% and 78.38%/89.19% in the validation set (n = 52), showing a better performance than that associated with the alpha-fetoprotein (AFP) level. CTC number, PCP, CTC clusters, and MVI were independent significant risk factors for HCC recurrence (P = 0.0375, P < 0.0001, P = 0.0017, and P = 0.0157). A nomogram model based on these risk factors showed a considerable prediction ability for HCC recurrence (area under the curve = 0.947). PCP (training: log-rank P < 0.0001; hazard ratio [HR] 30.13, 95% confidence interval [CI] = 11.12-81.62; validation: log-rank P < 0.0001; HR 25.73, 95% CI = 5.28-106.60) and CTC clusters (training: log-rank P < 0.0001; HR 17.34, 95% CI = 7.46-40.30; validation: log-rank P < 0.0001; HR 9.92, 95% CI = 2.55-38.58) were more significantly correlated with worse recurrence-free survival than CTC number (training: log-rank P < 0.0001; HR 14.93, 95% CI = 4.48-49.78; validation: log-rank P = 0.0007; HR 9.03, 95% CI = 2.53-32.24). CONCLUSION: PCP and CTC clusters may predict HCC recurrence and improve the performance of the serum biomarker AFP.

In-Depth Serum Proteomics Reveals the Trajectory of Hallmarks of Cancer in Hepatitis B Virus-Related Liver Diseases.

Hepatocellular carcinoma (HCC) is a prevalent cancer in China, with chronic hepatitis B (CHB) and liver cirrhosis (LC) being high-risk factors for developing HCC. Here, we determined the serum proteomes (762 proteins) of 125 healthy controls and Hepatitis B virus-infected CHB, LC, and HCC patients and constructed the first cancerous trajectory of liver diseases. The results not only reveal that the majority of altered biological processes were involved in the hallmarks of cancer (inflammation, metastasis, metabolism, vasculature, and coagulation) but also identify potential therapeutic targets in cancerous pathways (i.e., IL17 signaling pathway). Notably, the biomarker panels for detecting HCC in CHB and LC high-risk populations were further developed using machine learning in two cohorts comprised of 200 samples (discovery cohort = 125 and validation cohort = 75). The protein signatures significantly improved the area under the receiver operating characteristic curve of HCC (CHB discovery and validation cohort = 0.953 and 0.891, respectively; LC discovery and validation cohort = 0.966 and 0.818, respectively) compared to using the traditional biomarker, alpha-fetoprotein, alone. Finally, selected biomarkers were validated with parallel reaction monitoring mass spectrometry in an additional cohort (n = 120). Altogether, our results provide fundamental insights into the continuous changes of cancer biology processes in liver diseases and identify candidate protein targets for early detection and intervention.

BACH1-induced ferroptosis drives lymphatic metastasis by repressing the biosynthesis of monounsaturated fatty acids.

Esophageal squamous cell carcinoma (ESCC) is one of the fatal malignancies worldwide. It has an increased propensity to metastasize via lymphogenous routes in an early stage. The prognosis of patients with lymph node metastases (LNM) is often worse than that of patients without metastases. Although several factors have been found to influence metastasis, the mechanisms of preference for specific metastatic routes remain poorly understood. Herein, we provide evidence that the intrinsic hypersensitivity of tumor cells to ferroptosis may proactively drive lymphatic metastasis. Serum autoantibodies associated with LNM of early ESCC were screened using a whole-proteome protein array containing 19 394 human recombinant proteins, and an anti-BACH1 autoantibody was first identified. Pan-cancer analysis of ferroptosis-related genes with preferential lymphatic metastasis and preferential hematogenous metastasis based on The Cancer Genome Atlas data was performed. Only BACH1 showed significant overexpression in tumors with preferential lymphatic metastasis, whereas it was downregulated in most tumors with preferential nonlymphatic metastasis. In addition, it was found that the serum levels of autoantibodies against BACH1 were elevated in early-stage patients with LNM. Interestingly, BACH1 overexpression and ferroptosis induction promoted LNM but inhibited hematogenous metastasis in mouse models. Transcriptomic and lipidomic analyses found that BACH1 repressed SCD1-mediated biosynthesis of monounsaturated fatty acids, especially oleic acid (OA). OA significantly attenuated the ferroptotic phenotypes and reversed the metastatic properties of BACH1-overexpressing cells. OA addition significantly rescued the ferroptotic phenotypes and reversed the metastatic properties of BACH1-overexpressing cells. Importantly, the concentration gradient of OA between primary lesions and the lymph resulted in the chemoattraction of tumor cells to promote invasion, thus facilitating lymphatic metastasis. BACH1-induced ferroptosis drives lymphatic metastasis via the BACH1-SCD1-OA axis. More importantly, this study confirms that ferroptosis is a double-edged sword in tumorigenesis and tumor progression. The clinical application of ferroptosis-associated agents requires a great caution.

MARCKSL1 interacted with F-actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia.

BACKGROUND: Emerging evidence indicates that myristoylated alanine-rich C kinase substrate like 1 (MARCKSL1) is involved in the progression of esophageal squamous cell carcinoma (ESCC). However, the underpinning mechanism is unclear. Here, we investigated the mechanisms involving MARCKSL1 in ESCC progression. METHODS: CCK8, Transwell and wound-healing assays were employed to test the effect of MARCKSL1 on proliferation, invasion and migration in vitro. Next, transcriptome profiling was conducted through RNA sequencing to reveal the underlying mechanism of MARCKSL1 in ESCC progression, which was subsequently verified by western blot and qPCR analysis. Moreover, immunofluorescence and gelatin degradation assays were performed to reveal the ability of MARCKSL1 to mediate invadopodia formation and extracellular matrix (ECM) degradation. Finally, the correlation between MARCKSL1 and the clinicopathological features of ESCC patients was assessed based on TCGA database analysis and immunohistochemistry staining of tissue microarrays. RESULTS: Knockdown of MARCKSL1 markedly attenuated the cell motility capacity of ESCC cells in vitro, while MARCKSL1 overexpression had the opposite effect. Transcriptomic analysis showed that MARCKSL1 mediated the mobility and migration of ESCC cells. In addition, overexpression of MARCKSL1 increased the colocalization of F-actin and cortactin at the frontier edge of migrating cells and ECM degradation. Furthermore, in ESCC patients, the mRNA level of MARCKSL1 in esophageal carcinomas (n = 182) was found to be notably higher than that in adjacent esophageal epithelia (n = 286) and the expression levels of MARCKSL1 in the tumor tissues (n = 811) were significantly increased compared to those in noncancerous esophageal tissues (n = 442) with a large sample size. Higher expression of MARCKSL1 was positively correlated with lymph node metastasis and associated with worse survival rates of patients with ESCC. CONCLUSION: MARCKSL1 promotes cell migration and invasion by interacting with F-actin and cortactin to regulate invadopodia formation and ECM degeneration. High MARCKSL1 expression is positively correlated with poor prognosis in ESCC patients with lymph node metastasis.

Forming cytoplasmic stress granules PURα suppresses mRNA translation initiation of IGFBP3 to promote esophageal squamous cell carcinoma progression.

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies worldwide. Recently, our group identified purine-rich element binding protein alpha (PURα), a single-stranded DNA/RNA-binding protein, to be significantly associated with the progression of ESCC. Additional immunofluorescence staining demonstrated that PURα forms cytoplasmic stress granules to suppress mRNA translation initiation. The expression level of cytoplasmic PURα in ESCC tumor tissues was significantly higher than that in adjacent epithelia and correlated with a worse patient survival rate by immunohistochemistry. Functionally, PURα strongly preferred to bind to UG-/U-rich motifs and mRNA 3´UTR by CLIP-seq analysis. Moreover, PURα knockout significantly increased the protein level of insulin-like growth factor binding protein 3 (IGFBP3). In addition, it was further demonstrated that PURα-interacting proteins are remarkably associated with translation initiation factors and ribosome-related proteins and that PURα regulates protein expression by interacting with translation initiation factors, such as PABPC1, eIF3B and eIF3F, in an RNA-independent manner, while the interaction with ribosome-related proteins is significantly dependent on RNA. Specifically, PURα was shown to interact with the mRNA 3´UTR of IGFBP3 and inhibit its expression by suppressing mRNA translation initiation. Together, this study identifies cytoplasmic PURα as a modulator of IGFBP3, which could be a promising therapeutic target for ESCC treatment.

Early-life interparental relationship quality and late-life depressive symptoms: A mediation analysis.

BACKGROUND: A growing body of literature has demonstrated that poor relationships between parents are associated with offspring's elevated depressive symptoms among children and adolescents. However, researchers have paid scant attention to whether marital discord during offspring's childhood casts a long shadow on their late-life depressive symptoms. This study examines the association between early exposure to a poor interparental relationship and offspring's late-life depressive symptoms among Chinese and identifies underlying mechanisms. METHODS: We employed path models to analyze data from the China Health and Retirement Longitudinal Study (CHARLS). The analytic sample consisted of 4107 respondents aged 60 and older in 2015. Depressive symptoms were assessed with a 10-item Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: Individuals who had experienced poor interparental relationships in childhood showed higher levels of and faster increases in depressive symptoms in late adulthood. The mediators were offspring's experiences of physical abuse by their parents in childhood and their poor relationships with spouses and children in adulthood. LIMITATIONS: Limitations include recall bias on childhood conditions, absence of personality traits, and limited measures of parenting practices. CONCLUSIONS: Early-life interparental relationships exert a long-term effect on offspring's mental health. Individuals who suffered from poor interparental relationships during childhood might be at relatively high risk of developing depressive symptoms in late adulthood. Possible measures to relieve these depressive symptoms include protecting offspring from physical abuse in childhood and improving their relationships with their spouses and children later in life.

Noninvasive urinary protein signatures associated with colorectal cancer diagnosis and metastasis.

Currently, imaging, fecal immunochemical tests (FITs) and serum carcinoembryonic antigen (CEA) tests are not adequate for the early detection and evaluation of metastasis and recurrence in colorectal cancer (CRC). To comprehensively identify and validate more accurate noninvasive biomarkers in urine, we implement a staged discovery-verification-validation pipeline in 657 urine and 993 tissue samples from healthy controls and CRC patients with a distinct metastatic risk. The generated diagnostic signature combined with the FIT test reveals a significantly increased sensitivity (+21.2% in the training set, +43.7% in the validation set) compared to FIT alone. Moreover, the generated metastatic signature for risk stratification correctly predicts over 50% of CEA-negative metastatic patients. The tissue validation shows that elevated urinary protein biomarkers reflect their alterations in tissue. Here, we show promising urinary protein signatures and provide potential interventional targets to reliably detect CRC, although further multi-center external validation is needed to generalize the findings.

Impact of energy saving on the financial performance of industrial enterprises in China: An empirical analysis based on propensity score matching.

Does energy-saving have a positive effect on the long-term development of enterprises? To answer this question, this study uses the propensity score matching (PSM) method to determine the impact of enterprises completing energy-saving objectives on their financial performance based on data from an industrial enterprise database in China. The results show that industrial enterprises that have completed the energy-saving target have advantages in profitability, operational and financial indicators but have deficiencies in debt indicators, and there is no significant difference in the ratio of profits to cost and expense. The research results of high energy-consuming industry are the same as the overall sample of industrial enterprises in terms of operational and financial indicators, and debt ratio indicators. Nevertheless, energy saving has no significant impact on profit and ratio of profits to cost of high energy-consuming industry.

"Gone with the land": Effects of land expropriation on health and subjective well-being in rural China.

OBJECTIVE: Few studies have investigated the relationship between land expropriation and health and subjective well-being (SWB) in China. This study examines the impacts of land expropriation on health and SWB among Chinese farmers aged 16-85 years and explores whether these impacts vary with socioeconomic conditions. METHODS: We utilized longitudinal data from the China Family Panel Studies, a nationally representative survey. The analytic samples included over 10,000 individuals and over 30,000 person-year observations. Individual fixed-effects models were employed to eliminate the omitted-variable bias derived from time-constant unobserved confounders. RESULTS: Land expropriation was harmful to health and SWB. First-time land expropriation increased the risks of physical discomfort, chronic diseases, hospitalization, and perceived health decline; raised the frequency of feeling depressed; and decreased self-rated health, life satisfaction, subjective social status, and confidence about the future. Repeated land expropriation and past land expropriation increased the risks of chronic diseases, raised depressive symptom severity, and lowered self-rated health and life satisfaction. Repeated land expropriation also elevated the risk of perceived health decline. In addition, preexisting household income per capita and baseline county-level GDP per capita buffered the adverse impacts of first-time land expropriation. CONCLUSION: This study reveals the adverse impacts of land expropriation on health and SWB and highlights the importance of providing support to land-taken farmers to alleviate such detrimental effects.

Tumor-stroma TGF-ß1-THBS2 feedback circuit drives pancreatic ductal adenocarcinoma progression via integrin αvß3/CD36-mediated activation of the MAPK pathway.

The pancreatic ductal adenocarcinoma (PDAC) microenvironment contains dense desmoplastic stroma dominated by cancer-associated fibroblasts (CAFs) and is crucial to cancer development and progression. Several studies have revealed that thrombospondin 2 (THBS2) is a valuable serological-marker in PDAC. However, the detailed mechanism of the cancer-stroma interactome remains unclear. Here we showed that elevated THBS2 expression in PDAC was predominantly restricted to stroma and correlated with tumor progression and poor prognosis by quantitative proteomics and immunohistochemistry analyses. RNA in situ hybridization confirmed that CAFs but not neoplastic cells expressed THBS2 in precancerous lesions and its levels gradually increased with disease progression in genetically engineered mouse models. Mechanistically, cancer cell-secreted TGF-ß1 activated CAFs to induce THBS2 expression via the p-Smad2/3 pathway. Consequently, CAF-derived THBS2 bound to the membrane receptors integrin αvß3/CD36 and activated the MAPK pathway in PDAC cells to promote tumor growth and adhesion in vitro and in vivo. Inhibition of integrin αvß3, CD36, MEK and JNK rescued THBS2-induced malignant phenotypes. In conclusion, the TGF-ß1-THBS2-integrin αvß3/CD36-MAPK cascade forms a complex feedback circuit to mediate reciprocal interactions of pancreatic cancer cells-CAFs. THBS2 may act as a novel therapeutic-target to block the cancer-stroma communication.

Cytoplasmic RAD23B interacts with CORO1C to synergistically promote colorectal cancer progression and metastasis.

Colorectal cancers (CRCs) are characterized by diffuse infiltration of tumor cells into the regional lymph nodes and metastasis to distant organs, and its highly invasive nature contributes to disease recurrence and poor outcomes. The molecular mechanisms underlying CRC cell invasion remain incompletely understood. Here, we identified the upregulation of DNA damage repair-related protein RAD23B in CRC cells and tissues and showed that it associates with coronin 1C or coronin 3 (CORO1C) to facilitate invasion. We found that knockdown of RAD23B expression significantly inhibited the proliferation, invasion, and migration abilities of CRC cells both in vitro and in vivo, and suppressed the talin1/2/integrin/FAK/RhoA/Rac1/CORO1C signaling pathways. Interestingly, RAD23B interacted and co-localized with CORO1C, and CORO1C aggregated toward the margin of cancer cells in both CRC cells and tissues when RAD23B overexpressed. Mechanistically, overexpression of RAD23B and/or CORO1C further increased invadopodia formation and matrix degradation in SW480 and HCT8 CRC cells. Conversely, silencing of RAD23B expression suppressed tumorigenesis and liver metastasis in xenotransplant murine models. Furthermore, we found that RAD23B was significantly overexpressed in tumor tissues (n = 720) compared to adjacent non-tumor tissues (n = 694) of patients with CRC. Finally, we identified a strong correlation between higher levels of cytoplasmic expression of RAD23B, and poor prognosis and liver metastasis in CRC patients. Taken together, our data highlight a novel RAD23B-CORO1C signaling axis in CRC cell invasion and metastasis that may be of clinical significance.

Acetylation-induced PCK isoenzyme transition promotes metabolic adaption of liver cancer to systemic therapy.

Sorafenib and lenvatinib are approved first-line targeted therapies for advanced liver cancer, but most patients develop acquired resistance. Herein, we found that sorafenib induced extensive acetylation changes towards a more energetic metabolic phenotype. Metabolic adaptation was mediated via acetylation of the Lys-491 (K491) residue of phosphoenolpyruvate carboxykinase isoform 2 (PCK2) (PCK2-K491) and Lys-473 (K473) residue of PCK1 (PCK1-K473) by the lysine acetyltransferase 8 (KAT8), resulting in isoenzyme transition from cytoplasmic PCK1 to mitochondrial PCK2. KAT8-catalyzed PCK2 acetylation at K491 impeded lysosomal degradation to increase the level of PCK2 in resistant cells. PCK2 inhibition in sorafenib-resistant cells significantly reversed drug resistance in vitro and in vivo. High levels of PCK2 predicted a shorter progression-free survival time in patients who received sorafenib treatment. Therefore, acetylation-induced isoenzyme transition from PCK1 to PCK2 contributes to resistance to systemic therapeutic drugs in liver cancer. PCK2 may be an emerging target for delaying tumor recurrence.

BACH1 promotes the progression of esophageal squamous cell carcinoma by inducing the epithelial-mesenchymal transition and angiogenesis.

Metastasis to regional lymph nodes or distal organs predicts the progression of the disease and poor prognosis in esophageal squamous cell carcinoma (ESCC). Previous studies demonstrated that BTB and CNC homology 1 (BACH1) participates in various types of tumor metastasis. However, the function of BACH1 in ESCC was rarely reported. The present study demonstrated that BACH1 protein was overexpressed in ESCC tissues compared with paired esophageal epithelial tissues according to immunohistochemical staining (IHC). Higher levels of BACH1 mRNA were associated with decreased overall survival (OS) and shorter disease-free survival (DFS) of ESCC patients based on an analysis of The Cancer Genome Atlas (TCGA) datasets. BACH1 significantly enhanced the migration and invasion of ESCC in vitro. Mechanistically, BACH1 promoted the epithelial-mesenchymal transition (EMT) by directly activating the transcription of CDH2, SNAI2, and VIM, as determined by chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). BACH1 overexpression significantly enhanced CDH2 promoter activity according to the results of a luciferase assay. The results of subsequent experiments indicated that BACH1 enhanced the growth of tumor xenografts. The density of CD31+ blood vessels and the expression of vascular endothelial growth factor C (VEGFC) in tumor xenografts were significantly associated with BACH1 levels according to the results of IHC and immunofluorescence (IF) analyses performed in vivo. Moreover, ChIP-qPCR analysis demonstrated that the transcriptional activity of VEGFC was also upregulated by BACH1. Thus, BACH1 contributes to ESCC metastasis and tumorigenesis by partially facilitating the EMT and angiogenesis, and BACH1 may be a promising therapeutic target or molecular marker in ESCC.

Dynamic estimation of epidemiological parameters of COVID-19 outbreak and effects of interventions on its spread.

BACKGROUND: A key challenge in estimating epidemiological parameters for a pandemic such as the initial COVID-19 outbreak in Wuhan is the discrepancy between the officially reported number of infections and the true number of infections. A common approach to tackling the challenge is to use the number of infections exported from the originating city to infer the true number. This approach can only provide a static estimate of the epidemiological parameters before city lockdown because there are almost no exported cases thereafter. METHODS: We propose a Bayesian estimation method that dynamically estimates the epidemiological parameters by recovering true numbers of infections from day-to-day official numbers. To illustrate the use of this method, we provide a comprehensive retrospection on how the COVID-19 had progressed in Wuhan from January 19 to March 5, 2020. Particularly, we estimate that the outbreak sizes by January 23 and March 5 were 11,239 [95% CI 4,794-22,372] and 124,506 [95% CI 69,526-265,113], respectively. RESULTS: The effective reproduction number attained its maximum on January 24 (3.42 [95% CI 3.34-3.50]) and became less than 1 from February 7 (0.76 [95% CI 0.65-0.92]). We also estimate the effects of two major government interventions on the spread of COVID-19 in Wuhan. CONCLUSIONS: This case study by our proposed method affirms the believed importance and effectiveness of imposing tight non-essential travel restrictions and affirm the importance and effectiveness of government interventions (e.g., transportation suspension and large scale hospitalization) for effective mitigation of COVID-19 community spread.

Molecular characterization of circulating tumor cells in pancreatic ductal adenocarcinoma: potential diagnostic and prognostic significance in clinical practice.

BACKGROUND: The clinical value of heterogeneous sub-populations of circulating tumor cells (CTCs) in pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: Peripheral blood samples were obtained from 67 PDAC patients. CTCs were isolated by employing CD45 negative enrichment technique and further characterized for epithelial to mesenchymal transition (EMT) or human equilibrative nucleoside transporter-1 (hENT-1). The relationships between CTCs sub-phenotypes with clinicopathological factors or post-operative recurrence in PDAC patients were analyzed. RESULTS: EMT related CTCs could be isolated and identified from the 81% of patients (54/67), and both the total count (median: 5 vs. 17/mL, P<0.0001) and M-CTC percentage (median: 0.2 vs. 0.345, P=0.0244) of CTCs could differentiate local/regional with metastatic disease. Multivariate analysis showed that both AJCC stage (P=0.025) and M-CTC percentage (P=0.001) were independent prognostic indicators of recurrence free survival (RFS) in resected patients. Moreover, Kaplan-Meier survival analysis showed that M-CTC after 2 courses of chemotherapy was significantly associated with inferior RFS (49.5 weeks vs. undefined, P=0.0288). No significant correlation in hENT-1 expression was found between CTCs and matched tumor tissues, and further multivariate analysis suggested hENT-1 expression in CTCs as independent prognostic factor for RFS (P=0.016). Patients with low hENT-1 expression in CTCs had decreased RFS (32 weeks vs. undefined, P=0.0337). CONCLUSIONS: CTCs could be the promising diagnostic biomarkers in PDAC patients, and phenotypic profiling of CTCs based on EMT or hENT-1 could help establish novel prognostic biomarkers in resected patients undergoing adjuvant gemcitabine-based chemotherapy. KEYWORDS: Circulating tumor cells (CTCs); Pancreatic ductal adenocarcinoma (PDAC); Epithelial to mesenchymal transition (EMT); human equilibrative nucleoside transporter-1 (hENT-1).