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The relationship between metabolism and immune microenvironment remains to be studied in bladder cancer (BCa). We aimed to construct a metabolic-associated signature for prognostic prediction and investigate its relationship with the immune microenvironment in BCa. The RNA expression of metabolism associated genes was obtained from a combined data set including The Cancer Genome Atlas, GSE48075, and GSE13507 to divide BCa patients into different clusters. A metabolic-associated signature was constructed using the differentially expressed genes between clusters in the combined data set and validated in the IMvigor210 trial and our center. The composition of tumor-infiltrating immune cells (TIICs) was evaluated using the single-sample Gene Set Variation Analysis. BCa patients in Cluster A or high-risk level were associated with advanced clinicopathological features and poor survival outcomes. The percentage of high-risk patients was significantly lower in patients responding to anti-PD-L1 treatment. Compared with low-risk patients, the IC50 values of cisplatin and gemcitabine were significantly lower in high-risk patients. Thiosulfate transferase (TST) and S100A16 were significantly associated with clinicopathological features and prognosis. Downregulation of TST promoted BCa cell invasion, migration, and epithelial-to-mesenchymal transition, which are inhibited by downregulation of S100A16. CD8 + T cells, neutrophils, and dendritic cells had higher infiltration in the TST low-level and the S100A16 high-level. Furthermore, loss of function TST and S100A16 significantly affected the expression of PD-L1 and CD47. The metabolic-associated signature can stratify BCa patients into distinct risk levels with different immunotherapeutic susceptibility and survival outcomes. Metabolism disorder promoted the dysregulation of immune microenvironment, thus contributing to immunosuppression.

BackgroundIt is well known that influenza and other respiratory viruses are wintertime-seasonal in temperate regions. However, respiratory disease seasonality in the tropics remains elusive. In this study, we aimed to characterize the seasonality of influenza-like illness (ILI) and influenza virus in Ho Chi Minh City (HCMC), Vietnam.MethodsWe monitored the daily number of ILI patients in 89 outpatient clinics from January 2010 to December 2019. We collected nasal swabs and tested for influenza from a subset of clinics from May 2012 to December 2019. We used spectral analysis to describe the periodicities in the system. We evaluated the contribution of these periodicities to predicting ILI and influenza patterns through lognormal and gamma hurdle models.FindingsDuring ten years of community surveillance, 66,799 ILI reports were collected covering 2.9 million patient visits; 2604 nasal swabs were collected 559 of which were PCR-positive for influenza virus. Both annual and nonannual cycles were detected in the ILI time series, with the annual cycle showing 8.9% lower ILI activity (95% CI: 8.8%-9.0%) from February 24 to May 15. Nonannual cycles had substantial explanatory power for ILI trends (ΔAIC = 183) compared to all annual covariates (ΔAIC = 263). Near-annual signals were observed for PCR-confirmed influenza but were not consistent along in time or across influenza (sub)types.InterpretationOur study reveals a unique pattern of respiratory disease dynamics in a tropical setting influenced by both annual and nonannual drivers. Timing of vaccination campaigns and hospital capacity planning may require a complex forecasting approach.FundingNational Institutes of Health, Wellcome Trust.

Polyphenols display potential functional activities especially for rosmarinic acid (RosA) and caffeic acid (CafA). In this study, two different methods including ultrasonic-assisted ethanol extraction (60%) and ultrasound-assisted cellulase (≥ 15000 U/g, 2%) hydrolysis were applied for the extraction of total phenolics from 44 species of Perilla frutescens. Folin-Ciocalteu method detection showed that the content of total phenolics extracted by cellulase hydrolysis was the highest and attained to 28.00 mgGAE/gextracts for ZB1. Continuously, the extracts were purified by XDA-8 macroporous resin and medium-pressure liquid chromatography (MPLC), and the content of total phenolics improved to 66.62 mgGAE/gextract. High-performance liquid chromatography (HPLC) assay showed that the total polyphenols were mainly composed of gallic acid, caffeic acid, rosmarinic acid, luteolin and apigenin. Besides, a sequential XDA-8 macroporous resin combined with high-speed counter-current chromatography (HSCCC)/MPLC system was established for simultaneously isolation and preparation of RosA (purity 98.29%) and CafA (purity 97.01%) from the extracts. Further, antibacterial activities of the total polyphenols were evaluated by disc diffusion method and scanning electron microscope (SEM) observation. The results verified that the total polyphenols had effective antibacterial capacity on three kinds of bacteria including E. coli, S. aureus, and B. subtilis in a concentration-dependent manner. All these results demonstrated that the ultrasound-assisted cellulase hydrolysis extraction of total polyphenols and proposed three-step separation of RosA and CafA had a high yield and good purity, and they exhibited an effective antibacterial ability.

Spinal cord injury (SCI) is catastrophic to humans and society. However, there is currently no effective treatment for SCI. Autophagy is known to serve critical roles in both the physiological and pathological processes of the body, but its facilitatory and/or deleterious effects in SCI are yet to be completely elucidated. This study aimed to use primary Schwann cell-derived exosomes (SCDEs) to treat rats after SCI. In the present study, SCDEs were purified and their efficacy in ameliorating the components of SCI was examined. Using both in vivo and in vitro experiments, it was demonstrated that SCDEs increased autophagy and decreased apoptosis after SCI, which promoted axonal protection and the recovery of motor function. Furthermore, it was discovered that an increased number of SCDEs resulted in a decreased expression level of EGFR, which subsequently inhibited the Akt/mTOR signaling pathway, which upregulated the level of autophagy to ultimately induce microtubule acetylation and polymerization. Collectively, the present study identified that SCDEs could induce axonal protection after SCI by increasing autophagy and decreasing apoptosis, and it was suggested that this may involve the EGFR/Akt/mTOR signaling pathway.

Canna yellow streak virus (CaYSV) is a potyvirus that causes severe damage to the ornamental plant canna in the United Kingdom and Brazil. Here we identified CaYSV in China by isolating total RNA from infected plant, amplifying the virus genome segments, cloning and sequencing the amplicons. After assembly, the full-length genome of the virus was obtained and uploaded to the NCBI database. Phylogenetic analysis results showed that the Guizhou isolate (OL546222) was most closley related to the KS isolate (MG545919.1). Virus detection is essential for virus disease control, but the subclinical infection of CaYSV on canna in its early development increases the difficulty of CaYSV diagnosis. The goal of this study was to develop an efficient method for detection of CaYSV. We designed the primers, optimized the reaction conditions, and finally established a one-step reverse-transcription loop-mediated isothermal amplification (RT-LAMP) method. The product of RT-LAMP can be analyzed by both agarose gel electrophoresis and visible color change. The established one-step RT-LAMP assay showed high specificity and sensitivity in detecting CaYSV. This RT-LAMP method was also applied in analysis of 61 field samples collected from Guizhou and Jiangsu provinces. The results showed that the infection rates of CaYSV on canna samples from these two provinces were very high (63% and 96% respectively).

Background When three SARS-CoV-2 vaccines came to market in Europe and North America in the winter of 2020–2021, distribution networks were in a race against a major epidemiological wave of SARS-CoV-2 that began in autumn 2020. Rapid and optimized vaccine allocation was critical during this time. With 95% efficacy reported for two of the vaccines, near-term public health needs likely require that distribution is prioritized to the elderly, health care workers, teachers, essential workers, and individuals with comorbidities putting them at risk of severe clinical progression. Methods We evaluate various age-based vaccine distributions using a validated mathematical model based on current epidemic trends in Rhode Island and Massachusetts. We allow for varying waning efficacy of vaccine-induced immunity, as this has not yet been measured. We account for the fact that known COVID-positive cases may not have been included in the first round of vaccination. And, we account for age-specific immune patterns in both states at the time of the start of the vaccination program. Our analysis assumes that health systems during winter 2020–2021 had equal staffing and capacity to previous phases of the SARS-CoV-2 epidemic; we do not consider the effects of understaffed hospitals or unvaccinated medical staff. Results We find that allocating a substantial proportion (>75%) of vaccine supply to individuals over the age of 70 is optimal in terms of reducing total cumulative deaths through mid-2021. This result is robust to different profiles of waning vaccine efficacy and several different assumptions on age mixing during and after lockdown periods. As we do not explicitly model other high-mortality groups, our results on vaccine allocation apply to all groups at high risk of mortality if infected. A median of 327 to 340 deaths can be avoided in Rhode Island (3444 to 3647 in Massachusetts) by optimizing vaccine allocation and vaccinating the elderly first. The vaccination campaigns are expected to save a median of 639 to 664 lives in Rhode Island and 6278 to 6618 lives in Massachusetts in the first half of 2021 when compared to a scenario with no vaccine. A policy of vaccinating only seronegative individuals avoids redundancy in vaccine use on individuals that may already be immune, and would result in 0.5% to 1% reductions in cumulative hospitalizations and deaths by mid-2021. Conclusions Assuming high vaccination coverage (>28%) and no major changes in distancing, masking, gathering size, hygiene guidelines, and virus transmissibility between 1 January 2021 and 1 July 2021 a combination of vaccination and population immunity may lead to low or near-zero transmission levels by the second quarter of 2021.

In the United States, state-level re-openings in spring 2020 presented an opportunity for the resurgence of SARS-CoV-2 transmission. One important question during this time was whether human contact and mixing patterns could increase gradually without increasing viral transmission, the rationale being that new mixing patterns would likely be associated with improved distancing, masking, and hygiene practices. A second key question to follow during this time was whether clinical characteristics of the epidemic would improve after the initial surge of cases. Here, we analyze age-structured case, hospitalization, and death time series from three states – Rhode Island, Massachusetts, and Pennsylvania – that had successful reopenings in May 2020 without summer waves of infection. Using a Bayesian inference framework on eleven daily data streams and flexible daily population contact parameters, we show that population-average mixing rates dropped by >50% during the lockdown period in March/April, and that the correlation between overall population mobility and transmission-capable mixing was broken in May as these states partially re-opened. We estimate the reporting rates (fraction of symptomatic cases reporting to health system) at 96.3% (RI), 62.5% (MA), and 98.9% (PA). We show that elderly individuals were less able to reduce contacts during the lockdown period when compared to younger individuals, leading to the outbreak being concentrated in elderly congregate settings despite the lockdown. Attack rate estimates through August 31 2020 are 6.2% (95% CI: 5.7% – 6.8%) of the total population infected for Rhode Island, 6.7% (95% CI: 5.4% – 7.6%) in Massachusetts, and 2.7% (95% CI: 2.5% – 3.1%) in Pennsylvania, with some validation available through published seroprevalence studies. Infection fatality rates (IFR) estimates are higher in our analysis (>2%) than previously reported values, likely resulting from the epidemics in these three states affecting the most vulnerable sub-populations and the close matches between the states’ reported COVID-19 deaths and excess deaths. Data in Pennsylvania may have been underreported for both non-hospitalized and hospitalized patients, casting substantial uncertainty on estimates of attack rate and infection fatality rate.

Background. Mortality from noncancer causes in patients with prostate cancer (PCa) is unclear. This study assesses the causes and risks of noncancer death with each follow-up time period after PCa diagnosis. Methods. Data from the Surveillance, Epidemiology, and End Results (SEER) program were analyzed for noncancer causes of death in PCa patients from 2000 to 2016. The standard mortality ratio (SMR) was calculated for noncancer mortality. Results. Altogether, 752,352 patients with PCa were identified, and 180,862 (24.0%) died during follow-up. The largest proportion of deaths from noncancer causes (36%) occurred within 5 to 10 years after diagnosis. The most common causes of noncancer death are cardiovascular and cerebrovascular diseases and chronic obstructive pulmonary disease (COPD). Compared with the general age-matched male population, patients with PCa had a higher risk of death from any noncancer cause within 5 years, in particular other infectious diseases and suicide and self-inflicted injury. However, the risk of death from noncancer causes of PCa for more than 5 years is lower, except for Alzheimer’s disease and hypertension from 5 to 10 years after diagnosis. In addition, the risk of death from noncancer causes was influenced by treatment, ethnicity, and staging differences. In particular, compared with the general population, many noncancer causes of death have higher risk of death in patients with or without treatment within 1 to 5 years after diagnosis, whereas patients undergoing radical prostatectomy (RP) with or without radiotherapy (RT) or chemotherapy (CTx) are not at high risk of death from COPD, pneumonia and influenza, nephritis, nephrotic syndrome and nephrosis, septicemia, and atherosclerosis. Conclusion. The risk of death from noncancer causes gradually decreased in all patients with PCa during each follow-up period after diagnosis In addition, the risk of dying from noncancer causes are influenced by differences in stage, ethnicity, and treatment. In particular, patients undergoing RP±RT/CTx and RT/CTx have a lower risk of death compared to the general population. These findings provide important implications for the healthcare management of patients with PCa.

Objective Imaging examination, tumor marker detection, bladder biopsy, and other methods are the common methods for the diagnosis of bladder cancer (BC). This study was aimed to assess the value of contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) in the diagnosis of BC. Materials and Methods Fifty-nine patients with BC were recruited in our hospital from September 2012 to December 2015, who had CEUS and magnetic resonance diffusion-weighted imaging (MRI + DWI). All patients underwent surgical treatment and definite pathological stage. The series and parallel combined diagnosis methods were applied to calculate the diagnostic sensitivity, specificity, and accuracy through using quantitative apparent diffusion coefficient (ADC) and receiver operating characteristic curve. Results The accuracies of CEUS and MRI + DWI examination for T staging of BC were 74.6% and 76.3%, respectively. Compared with the single diagnostic methods, the two combined diagnosis accuracy was 91.5%, which was significantly improved in diagnosis accuracy (P < 0.05). The diagnostic accuracies of CEUS, MRI + DWI, and ADC for muscle invasion of BC were 81.4%, 83.1%, and 84.7%, respectively. The diagnostic accuracy of CEUS parallel combined with MRI + DWI (91.5%) was obviously enhanced, compared with that with the single diagnostic method. Conclusion The accuracy of CEUS and MRI + DWI combined diagnosis was higher than that with the single diagnostic method. CEUS and MRI + DWI combined diagnosis was a feasible and effective method for the clinical diagnosis of BC.

In emergency epidemic and pandemic settings, public health agencies need to be able to measure the population-level attack rate, defined as the total percentage of the population infected thus far. During vaccination campaigns in such settings, public health agencies need to be able to assess how much the vaccination campaign is contributing to population immunity; specifically, the proportion of vaccines being administered to individuals who are already seropositive must be estimated.To estimate population-level immunity to SARS-CoV-2 through May 31, 2021, in Rhode Island, Massachusetts, and Connecticut.This observational case series assessed cases, hospitalizations, intensive care unit occupancy, ventilator occupancy, and deaths from March 1, 2020, to May 31, 2021, in Rhode Island, Massachusetts, and Connecticut. Data were analyzed from July 2021 to November 2021.COVID-19-positive test result reported to state department of health.The main outcomes were statistical estimates, from a bayesian inference framework, of the percentage of individuals as of May 31, 2021, who were (1) previously infected and vaccinated, (2) previously uninfected and vaccinated, and (3) previously infected but not vaccinated.At the state level, there were a total of 1 160 435 confirmed COVID-19 cases in Rhode Island, Massachusetts, and Connecticut. The median age among individuals with confirmed COVID-19 was 38 years. In autumn 2020, SARS-CoV-2 population immunity (equal to the attack rate at that point) in these states was less than 15%, setting the stage for a large epidemic wave during winter 2020 to 2021. Population immunity estimates for May 31, 2021, were 73.4% (95% credible interval [CrI], 72.9%-74.1%) for Rhode Island, 64.1% (95% CrI, 64.0%-64.4%) for Connecticut, and 66.3% (95% CrI, 65.9%-66.9%) for Massachusetts, indicating that more than 33% of residents in these states were fully susceptible to infection when the Delta variant began spreading in July 2021. Despite high vaccine coverage in these states, population immunity in summer 2021 was lower than planned owing to an estimated 34.1% (95% CrI, 32.9%-35.2%) of vaccines in Rhode Island, 24.6% (95% CrI, 24.3%-25.1%) of vaccines in Connecticut, and 27.6% (95% CrI, 26.8%-28.6%) of vaccines in Massachusetts being distributed to individuals who were already seropositive.These findings suggest that future emergency-setting vaccination planning may have to prioritize high vaccine coverage over optimized vaccine distribution to ensure that sufficient levels of population immunity are reached during the course of an ongoing epidemic or pandemic.

Background: The relationship between metabolism and immune microenvironment remains to be studied in bladder cancer (BCa). We aimed to construct a metabolic-associated signature for prognostic prediction and investigate its relationship with the immune microenvironment in BCa. Methods: The RNA expression of metabolism associated genes was obtained from a combined data set including The Cancer Genome Atlas, GSE48075, and GSE13507 to divide BCa patients into different clusters. A metabolic-associated signature was constructed using the differentially expressed genes between clusters in the combined TCGA and validated in the IMvigor210 trial and our center. The sensitivity of metabolic-associated signature to chemotherapy and immunotherapy for predicting BCa was assessed. The proportion of 28 subtypes of tumor-infiltrating immune cells (TIICs) in each BCa sample was assessed using a single sample gene set enrichment analysis (ssGSEA). TST and S100A16 were identified by hub genes screening. Survival analysis and nomograms were used to evaluate the prognosis and predictive value in BCa based on TST and S100A16. The loss of function study further investigated the effects of TST and S100A16 on the biological function and immune microenvironment of BCa cells. Results: BCa patients in high-risk group were associated with advanced clinicopathological features and poor survival outcomes. The percentage of high-risk patients was significantly lower in patients responding to anti-PD-L1 treatment (complete response/partial response). Compared with low-risk patients, the IC50 values of cisplatin and gemcitabine were significantly lower in high-risk patients. ssGSEA revealed that the composition of TIICs including macrophages and regulatory T cells between risk groups. TST and S100A16 were significantly associated with clinicopathological features and prognosis. Down-regulation of TST promoted BCa cell invasion, migration, and EMT, which are inhibited by down-regulation of S100A16. CD8+T cells, neutrophils, and dendritic cells had higher infiltration in the TST low-group and the S100A16 high-group. Furthermore, loss of function TST and S100A16 significantly affected the expression of PD-L1 and CD47. Conclusion: The metabolic-associated signature can stratify BCa patients into distinct risk groups with different immunotherapeutic susceptibility and survival outcomes, may contribute to effective individualized treatment. Dysexpression of TST or S100A16 contributes to the tumor progression and dysregulation of immune microenvironment in BCa.

Sulfatase 2 (SULF2) affects the occurrence and development of cancer by regulating HSPG-binding factors. However, the mechanism of SULF2 in bladder cancer (BCa) is unknown. To determine this, we analyzed the RNA sequencing of 90 patients with BCa. The results showed that the expression of SULF2 was closely related to the prognosis of BCa. Moreover, in vivo and in vitro experiments revealed that SULF2 promotes tumor proliferation and invasion. Furthermore, using a mouse orthotopic BCa model and flow cytometric analysis, we identified that SULF2 affects the polarization of macrophages. Mechanism studies clarified that SULF2 promoted the release of HSPG-binding factors, such as IL-8, in the microenvironment through β-catenin. Meanwhile, IL-8 activated the JAK2/STAT3 pathway of macrophages to promote the expression of CD163 and CD206, thereby regulating the polarization of macrophages to the M2-type. Conclusively, these results indicate that SULF2 plays an important role in regulating the microenvironment of BCa and promotes the polarization of macrophages to the M2-type by secreting IL-8, which further deepens the malignant progression of BCa.

BACKGROUND: At present, the low risk of bladder cancer (BCa)-specific death has allowed for investigation into treatment-related cardiotoxicity. To aid clinicians in selecting appropriate cardiovascular disease screening strategies and interventions, this study explored the heart-specific mortality and prognostic factors of patients with BCa after radical cystectomy (RC), radiotherapy (RT), or chemotherapy (CT), and compared their long-term heart-specific mortality with that of the general male population. METHODS: We identified three different treatments for BCa patients from the Surveillance, Epidemiology, and End Results (SEER) database: RC, RT, and CT. Patients were included from 2000 to 2012 and followed through 2015. A cumulative mortality curve and competitive risk regression model were applied to evaluate the prognostic factors of heart-specific mortality, and standardized mortality ratios (SMRs) were calculated. RESULTS: Of 39,500 men, 30.3%, 18.8%, and 50.9% received RC, RT, and CT, respectively. For patients with a survival period of less than 50 months, tumor-specific death exhibited a rapidly increasing trend, which subsequently flatlined. However, the rates heart-specific mortality and other causes exhibited a tendency to increase stably. The heart-specific and all-cause mortality rates of patients in any age group treated with the three abovementioned strategies were higher than those of the general population. The heart-specific mortality of patients with carcinoma in situ treated with RC and CT exceeded their all-cause mortality, while that of other tumor stages did not. The risks of heart-specific [sub-distribution hazard ratio (SHR) =1.38; 95% confidence interval (CI): 1.22–1.57] and tumor-specific (SHR =1.68; 95% CI: 1.60–1.77) deaths in patients who received RT were higher than those of patients who underwent CT. CONCLUSIONS: The risks of heart-specific and tumor-specific deaths in patients who received RT were higher than those of the RC and CT groups, especially in patients over 65 years of age who received RT.

Background Circular RNAs (circRNAs) have been shown to play vital biological functions in various tumors, including prostate cancer (PCa). However, the roles of circRNAs in the metastasis of PCa remain unclear. In the present study, differentially expressed circRNAs associated with PCa metastasis were screened using high-throughput RNA sequencing, from which hsa_circ_0004296 was identified. Methods Quantitative real-time PCR (qRT-PCR) was used to detect the expression of circ_0004296 in PCa tissues and adjacent normal tissues as well as in blood and urine. Gain and loss of function experiments were performed to investigate the function of circ_0004296 in PCa. Bioinformatics analyses, RNA pull-down assay, and mass spectrometry were conducted to identify RNA-binding proteins. RNA immunoprecipitation and RNA and protein nuclear-cytoplasmic fractionation were performed to investigate the underlying mechanism. A xenograft mouse model was used to analyze the effect of circ_0004296 on PCa growth and metastasis in vivo. Results The expression of circ_0004296 was decreased in PCa tissues, blood, and urine, which was negatively associated with metastasis. Furthermore, gain and loss of function experiments in vitro and in vivo showed that circ_0004296 inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of PCa cells. Mechanistically, circ_0004296 regulated host gene ETS1 expression at the post-transcriptional level. EIF4A3 was identified and confirmed as the downstream binding protein of circ_0004296. EIF4A3 expression was significantly upregulated in PCa tissues and associated with PCa metastasis. Silencing EIF4A3 suppressed PCa cell proliferation, migration, invasion, and EMT. Conclusions Circ_0004296 overexpression efficiently inhibited ETS1 mRNA nuclear export by promoting EIF4A3 retention in the nucleus, leading to the downregulation of ETS1 expression and suppression of PCa metastasis; thus, circ_0004296 might be a potential biomarker and therapeutic target for patients with PCa.

Background Bladder cancer (BC) is a common malignant neoplasm with a high rate of recurrence and progression, despite optimal treatment. There is a pressing need to identify new effective biomarkers for the targeted treatment of BC. Methods The key gene CALD1 was screened via weighed gene co-expression network analysis (WGCNA) from encoding protein genes of BC. Clinical and prognostic significance was explored in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Cell Counting Kit-8 (CCK-8), flow cytometry, transwell chamber experiment and nude mouse xenograft assay were performed to test cell growth, apoptosis, migration, invasion and tumorigenesis capacities. Immune correlation was analyzed in The Tumor Immune Estimation Resource (TIMER) database. Relevant signaling pathways were explored using gene set enrichment analysis (GSEA). Results Increased expression of CALD1 was significantly correlated with histological grade, clinical stage, T stage, and lymphatic metastasis. Kaplan-Meier survival curves showed that high CALD1 expression was associated with poor overall survival (OS) and disease-free survival (DFS) in TCGA database, and with poor OS in the four GEO databases. CALD1 promotes growth, migration, invasion, and cell cycle of tumor cell, and inhibits tumor cell apoptosis in vitro and in vivo. CADL1 expression was positively correlated with increased CD274 levels (r=0.357, P=9.71e-14). JAK/STAT signaling pathway was significantly enriched in the high CALD1 expression group. CALD1-mediated PD-L1 overexpression (OE) was via the activation of the JAK/STAT signaling pathway; this effect was blocked by the specific JAK inhibitor Ruxolitinib. Conclusions CALD1 is a potential molecular marker associated with prognosis. It promotes the malignant progression of BC and upregulates the PD-L1 expression via the JAK/STAT signaling pathway.

Background When three SARS-CoV-2 vaccines came to market in Europe and North America in the winter of 2020–2021, distribution networks were in a race against a major epidemiological wave of SARS-CoV-2 that began in autumn 2020. Rapid and optimized vaccine allocation was critical during this time. With 95% efficacy reported for two of the vaccines, near-term public health needs likely require that distribution is prioritized to the elderly, health care workers, teachers, essential workers, and individuals with comorbidities putting them at risk of severe clinical progression. Methods We evaluate various age-based vaccine distributions using a validated mathematical model based on current epidemic trends in Rhode Island and Massachusetts. We allow for varying waning efficacy of vaccine-induced immunity, as this has not yet been measured. We account for the fact that known COVID-positive cases may not have been included in the first round of vaccination. And, we account for age-specific immune patterns in both states at the time of the start of the vaccination program. Our analysis assumes that health systems during winter 2020–2021 had equal staffing and capacity to previous phases of the SARS-CoV-2 epidemic; we do not consider the effects of understaffed hospitals or unvaccinated medical staff. Results We find that allocating a substantial proportion (>75%) of vaccine supply to individuals over the age of 70 is optimal in terms of reducing total cumulative deaths through mid-2021. This result is robust to different profiles of waning vaccine efficacy and several different assumptions on age mixing during and after lockdown periods. As we do not explicitly model other high-mortality groups, our results on vaccine allocation apply to all groups at high risk of mortality if infected. A median of 327 to 340 deaths can be avoided in Rhode Island (3444 to 3647 in Massachusetts) by optimizing vaccine allocation and vaccinating the elderly first. The vaccination campaigns are expected to save a median of 639 to 664 lives in Rhode Island and 6278 to 6618 lives in Massachusetts in the first half of 2021 when compared to a scenario with no vaccine. A policy of vaccinating only seronegative individuals avoids redundancy in vaccine use on individuals that may already be immune, and would result in 0.5% to 1% reductions in cumulative hospitalizations and deaths by mid-2021. Conclusions Assuming high vaccination coverage (>28%) and no major changes in distancing, masking, gathering size, hygiene guidelines, and virus transmissibility between 1 January 2021 and 1 July 2021 a combination of vaccination and population immunity may lead to low or near-zero transmission levels by the second quarter of 2021. Supplementary Information The online version contains supplementary material available at (10.1186/s12916-021-02038-w).

Background Mesenchymal stem cells (MSCs) have been proved to drive castration resistant prostate cancer (CRPC). In this study, we aim to investigate the contribution of MSCs to the development of docetaxel resistance in CRPC cells and its potential mechanisms. Methods The effect of MSCs on CRPC cells resistance to docetaxel was determined using in vivo and in vitro approaches. CCK8 and PI/Annexin V-FITC assay were used to examined the cell viability and apoptosis. The concentration of transforming growth factor-β1 was measured by enzyme-linked immunosorbent assay and small interfering RNA was used for functional analyses. Results MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion in vivo and in vitro. CRPC cells cocultured with MSCs under docetaxel administration have an increased autophagy activation, while autophagy inhibitor could effectively reversed MSCs-induced resistance to docetaxel. Additionally, MSCs-induced CRPC cell autophagy increase under docetaxel administration depends on MSCs secreting TGF-β1 and inhibition of TGF-β1 secretion in MSCs could consequently increase the sensitivity of CRPC cells to docetaxel. Conclusions These results suggest that docetaxel administrated CRPC cells may elicit MSCs secreting TGF-β1 increase, which desensitizes CRPC to docetaxel chemotherapy accelerating chemoresistance occurrence via inducing cell autophagy.

Objective. To investigate recent trends in the epidemiological and prognostic factors of clear cell adenocarcinoma (CCA) which is considered a relatively rare tumor with a glycogen-rich phenotype. Methods. Patients with CCA from years 2000 to 2016 were identified from the Surveillance, Epidemiological, and End Results (SEER) database. Relevant population data were used to analyze the rates age-adjusted incidence, age-standardized 3-year and 5-year relative survivals, and overall survival (OS). Results. Of the 104,206 CCA patients identified. The age-adjusted incidence of CCA increased 2.7-fold from the year 2000 (3.3/100,000) to 2016 (8.8/100,000). This increase occurred across all ages, races, stages, and grades. Of all these subgroups, the increase was largest in the grade IV group. The age-standardized 3-year and 5-year relative survivals increased during this study period, rising by 9.1% and 9.5% from 2000 to 2011, respectively. Among all the stages and grades, the relative survival increase was greatest in the grade IV group. According to multivariate analysis of all CCA patients, predictors of OS were: age, gender, year of diagnosis, marital status, race, grade, stage, and primary tumor site (P < 0.001). The OS of all CCA patients during the period 2008 to 2016 was significantly higher than that from 2000 to 2007 (hazard ratio [HR], 0.87; 95% CI: 0.85–0.89; P < 0.001). Conclusions. The incidence of CCA and survival of these patients improved over time. In particular, the highest increases were reported for grade IV CCA, which may be due to an earlier diagnosis and improved treatment.

BACKGROUND: Sulfatase 2 (SULF2) is a member of the sulfatase family, and its expression and clinical significance in bladder cancer (BCa) are not currently known. In this study, we attempted to evaluate SULF2 expression in BCa patients who underwent radical cystectomy (RC) and the relationship between SULF2 expression and clinical-pathological characteristics. METHODS: Data on SULF2 expression in BCa tissues was obtained from the Oncomine database and the Gene Expression Omnibus (GEO). The expression of SULF2 and vascular endothelial growth factor-D (VEGF-D) in BCa was evaluated by immunohistochemistry (IHC) in tissues from 203 patients who had undergone RC. We also explored the value of the measurement of SULF2 and VEGF-D expression for diagnosis and prognosis in BCa patients with lymphatic metastasis. RESULTS: We found an increase in SULF2 messenger RNA (mRNA) levels and gene amplification in BCa tissues from the Oncomine database. High expression of SULF2 was detected in 91/203 (44.8%) of BCa patients. Among these patients, 27 of 42 (64.3%) with lymphatic metastasis showed high SULF2 expression. Univariate analysis showed that tumor size, pathological stage, lymphatic metastasis, vascular infiltration, perineural infiltration, hydronephrosis, and VEGF-D and SULF2 expression were related to prognosis in BCa patients, and multivariable Cox regression analysis showed that SULF2 expression was an independent prognostic indicator. Receiver operating characteristic (ROC) analysis revealed that SULF2 expression resulted in an increased area under the curve (AUC) of 0.707, with a sensitivity of 71.4% and a specificity of 61.5%. CONCLUSIONS: The upregulation of SULF2 is associated with poor prognosis in high-grade BCa patients. It might be a novel diagnostic marker for BCa patients with lymphatic metastasis.

BACKGROUND: Bladder cancer is one of the most common carcinomas and it brings about huge social economic burden. There is not a reliable way to predict the prognosis of bladder patients. We develop the nomogram to predict the prognosis of bladder cancer patients. METHODS: A total of 127 bladder cancer patients after radical cystectomy were studied retrospectively. Their clinicopathological data were collected for statistical analysis. RESULTS: The level of albumin/globulin ratio (AGR), C-reactive protein/albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) associated with pathological and hematological parameters like T stage and hemoglobin. Furthermore, the AGR was associated with overall survival (OS) and CAR, NLR, and PLR were associated with both OS and progression-free survival (PFS) (P

Background: Melanoma, an extremely malignant form of cancer, poses a significant health risk. Vasculogenic mimicry (VM), blood vessels formed by tumor cells instead of endothelial cells, is an important factor for the rapid progression of melanoma. Interleukin (IL)-33 is an inflammatory factor commonly found in the tumor microenvironment and plays an important role in the progression of many tumors. IL-33 acts on immune cells and tumor cells through its receptor ST2. This study hypothesized that IL-33 directly affects the progression of melanoma. Objectives: This study was designed to investigate the effect of IL-33 on VM of melanoma and its potential mechanism of action. Methods: The expression of ST2 was evaluated in 66 cases of melanoma collected from human patients, and the differences were analyzed. In vitro experiments were conducted to study the effects of the IL-33/ST2 axis on cell migration and invasion and to elucidate possible mechanisms. Results: ST2 expression is associated with that of matrix metalloproteinase (MMP)-2 and VM in melanoma of patients. IL-33 increases the abilities of proliferation, migration and invasion of melanoma cells and VM tube formation through ST2. IL-33 induces the production of MMP-2/9 via ERK1/2 phosphorylation. Conclusion: IL-33 can directly act on melanoma cells and promote its development.