Management and outcomes of aortic dissection type B in late pregnancy: A retrospective case series.

OBJECTIVE: Pregnancy complicated with type B aortic dissection is a rare but devastating condition. Guidelines for managing this condition are lacking. We present our observation and experiences in managing five pregnant women with complicated type B aortic dissection in the second or third trimesters, aiming to gain insights that can aid in proposing an appropriate management strategy. DESIGN: A retrospective study. SETTING: Zhongnan Hospital of Wuhan University. POPULATION: Pregnant women with complicated type B aortic dissection. METHODS: Clinical data of five pregnant women with complicated type B aortic dissection admitted to Zhongnan Hospital of Wuhan University from January 2022 to June 2023 were collected. The clinical characteristics, treatment strategies, and corresponding maternal and infant outcomes were retrospectively analysed. MAIN OUTCOME MEASURES: Survival of mothers and foetuses. RESULTS: All five study participants were diagnosed with complicated type B aortic dissection by computed tomography angiography (CTA). The range of gestational weeks at admission was 27 weeks + 3 days to 36 weeks + 6 days. The first patient, planning a caesarean section (C-section) followed by thoracic endovascular aortic repair (TEVAR), died of aortic dissection rupture during C-section. Her neonate was successfully rescued. In contrast, the remaining four patients who underwent TEVAR first survived. Among them, three patients underwent single-stage aortic repair and delivery, while one patient received C-section 31 days after TEVAR. Three preterm live births were recorded among these surviving mothers. Neonatal death occurred in one case with a gestational age of 29 weeks + 5 days, who had foetal distress before surgery. During the follow-up period of up to 3 months, no maternal or infant death occurred. No device-related or systemic complications were observed in the surviving mothers after discharge. Routine physical examinations of the four live births showed no abnormalities. CONCLUSIONS: For pregnant women with thoracic back pain and high suspicion of aortic dissection, CTA should be conducted promptly to prevent missed or delayed diagnosis. Maternal survival should be prioritised over foetal outcome once diagnosed. TEVAR was demonstrated to be safe and feasible for such patients. For women with complicated type B aortic dissection in late pregnancy, TEVAR followed by C-section may be a promising treatment strategy.

Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records.

BACKGROUND: Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. METHODS: Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. FINDINGS: All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 109 cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8-9 and a 5-min Apgar score of 9-10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. INTERPRETATION: The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy. FUNDING: Hubei Science and Technology Plan, Wuhan University Medical Development Plan.

Lactobacilli Degrade Wheat Amylase Trypsin Inhibitors to Reduce Intestinal Dysfunction Induced by Immunogenic Wheat Proteins.

BACKGROUND & AIMS: Wheat-related disorders, a spectrum of conditions induced by the ingestion of gluten-containing cereals, have been increasing in prevalence. Patients with celiac disease have gluten-specific immune responses, but the contribution of non-gluten proteins to symptoms in patients with celiac disease or other wheat-related disorders is controversial. METHODS: C57BL/6 (control), Myd88-/-, Ticam1-/-, and Il15-/- mice were placed on diets that lacked wheat or gluten, with or without wheat amylase trypsin inhibitors (ATIs), for 1 week. Small intestine tissues were collected and intestinal intraepithelial lymphocytes (IELs) were measured; we also investigated gut permeability and intestinal transit. Control mice fed ATIs for 1 week were gavaged daily with Lactobacillus strains that had high or low ATI-degrading capacity. Nonobese diabetic/DQ8 mice were sensitized to gluten and fed an ATI diet, a gluten-containing diet or a diet with ATIs and gluten for 2 weeks. Mice were also treated with Lactobacillus strains that had high or low ATI-degrading capacity. Intestinal tissues were collected and IELs, gene expression, gut permeability and intestinal microbiota profiles were measured. RESULTS: In intestinal tissues from control mice, ATIs induced an innate immune response by activation of Toll-like receptor 4 signaling to MD2 and CD14, and caused barrier dysfunction in the absence of mucosal damage. Administration of ATIs to gluten-sensitized mice expressing HLA-DQ8 increased intestinal inflammation in response to gluten in the diet. We found ATIs to be degraded by Lactobacillus, which reduced the inflammatory effects of ATIs. CONCLUSIONS: ATIs mediate wheat-induced intestinal dysfunction in wild-type mice and exacerbate inflammation to gluten in susceptible mice. Microbiome-modulating strategies, such as administration of bacteria with ATI-degrading capacity, may be effective in patients with wheat-sensitive disorders.

Coronavirus disease 2019 in pregnant women: a report based on 116 cases.

BACKGROUND: The coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, is a global public health emergency. Data on the effect of coronavirus disease 2019 in pregnancy are limited to small case series. OBJECTIVE: To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: Clinical records were retrospectively reviewed for 116 pregnant women with coronavirus disease 2019 pneumonia from 25 hospitals in China between January 20, 2020, and March 24, 2020. Evidence of vertical transmission was assessed by testing for severe acute respiratory syndrome coronavirus 2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. RESULTS: The median gestational age on admission was 38+0 (interquartile range, 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. Of the 116 cases, there were 8 cases (6.9%) of severe pneumonia but no maternal deaths. One of 8 patients who presented in the first trimester and early second trimester had a missed spontaneous abortion. Of 99 patients, 21 (21.2%) who delivered had preterm birth, including 6 with preterm premature rupture of membranes. The rate of spontaneous preterm birth before 37 weeks' gestation was 6.1% (6/99). One case of severe neonatal asphyxia resulted in neonatal death. Furthermore, 86 of the 100 neonates tested for severe acute respiratory syndrome coronavirus 2 had negative results; of these, paired amniotic fluid and cord blood samples from 10 neonates used to test for severe acute respiratory syndrome coronavirus 2 had negative results. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of severe acute respiratory syndrome coronavirus 2 infection when the infection manifests during the third trimester of pregnancy.

Inhibitory short peptides targeting EPS8/ABI1/SOS1 tri-complex suppress invasion and metastasis of ovarian cancer cells.

BACKGROUND: We aimed to develop inhibitory short peptides that can prevent protein interactions of SOS1/EPS8/ABI1 tri-complex, a key component essential for ovarian cancer metastasis. METHODS: Plasmids containing various regions of HA-tagged ABI1 were co-transfected into ovarian cancer cells with Flag-tagged SOS1 or Myc-tagged EPS8. Co-immunoprecipitation and GST-pulldown assay were used to identify the regions of ABI1 responsible for SOS1 and EPS8 binding. Inhibitory short peptides of these binding regions were synthesized and modified with HIV-TAT sequence. The blocking effects of the peptides on ABI1-SOS1 or ABI1-EPS8 interactions in vitro and in vivo were determined by GST-pulldown assay. The capability of these short peptides in inhibiting invasion and metastasis of ovarian cancer cell was tested by Matrigel invasion assay and peritoneal metastatic colonization assay. RESULTS: The formation of endogenous SOS1/EPS8/ABI1 tri-complex was detected in the event of LPA-induced ovarian cancer cell invasion. In the tri-complex, ABI1 acted as a scaffold protein holding together SOS1 and EPS8. The SH3 and poly-proline+PxxDY regions of ABI1 were responsible for SOS1 and EPS8 binding, respectively. Inhibitory short peptides p + p-8 (ppppppppvdyedee) and SH3-3 (ekvvaiydytkdkddelsfmegaii) could block ABI1-SOS1 and ABI1-EPS8 interaction in vitro. TAT-p + p-8 peptide could disrupt ABI1-EPS8 interaction and suppress the invasion and metastasis of ovarian cancer cells in vivo. CONCLUSIONS: TAT-p + p-8 peptide could efficiently disrupt the ABI1-EPS8 interaction, tri-complex formation, and block the invasion and metastasis of ovarian cancer cells.

LPA receptor 1 mediates LPA-induced ovarian cancer metastasis: an in vitro and in vivo study.

BACKGROUND: The facts that LPA is present at high concentration in ovarian cancer patients' ascites and it may serve as a stimulator to cell migration, implicate the role of LPA in the ovarian cancer metastasis. Since LPA mediates various biological functions through its interaction with LPA receptors, we aim to investigate the correlation between the expression of LPA receptors and the metastasis of ovarian cancer. METHODS: To test whether the LPA responsiveness correlated with the metastatic capability of ovarian cancer cells, we performed LPA induced invasion assay and peritoneal metastatic colonization assay with a panel of established human ovarian cancer cell lines. The expression of LPAR1-3 in different ovarian cancer lines was examined by qRT-PCR. We also tested the effects of LPAR1 inhibition or overexpression on ovarian cancer cell's invasiveness. To confirm our laboratory results, we detected LPARs expression in specimens from 52 ovarian cancer patients by qRT-PCR and immunohistochemistry. RESULTS: Thirteen ovarian cancer cells were enrolled in the invasion assay. Ovarian cancer cell lines which responded well to LPA-induced invasion, also displayed good capability for metastatic colonization. On the contrary, cell lines with poor LPA responsiveness showed inferior metastatic potential in peritoneal colonization assay. High expression level of LPAR1 was detected in all of the metastatic ovarian cancer cell lines. T-test showed that LPAR1, not LPAR2 or LPAR3, expression was significantly higher in the metastatic cell lines than in the non-metastatic cell lines (P = 0.003). Furthermore, silencing LPAR1 alone could significantly reduce LPA-induced invasion (P < 0.001). Finally, we analyzed the correlation between the LPARs expression and clinicopathological features of the clinical cases. It indicated that LPAR1 expression rate increased significantly along with the more advanced stages (stage I: 16.67 %; II 50.00 %; III: 75.00 %; and IV: 100.00 %; P = 0.003). Besides that, LPAR1 expression was detected in all the 13 cases with abdominal metastasis more than 2 cm, 10 cases with retroperitoneal lymph node metastasis and 6 cases with hepatic metastasis. Moreover, the expression rate of LPAR2 significantly increased in ovarian cancer than in normal specimens (P = 0.039). LPAR3 expression showed the same trend as LPAR2, though the difference is not statistically significant (P = 0.275). Besides that LPAR2 and LPAR3 expression increased along with poorer differentiation (P = 0.002, P = 0.034, respectively). CONCLUSIONS: Metastatic capability of ovarian cancer cells correlated well with their responsiveness to LPA for cell invasion. LPAR1 acts as the main mediator responsible for LPA-stimulated ovarian cancer cell invasion. LPAR2 and LPAR3 might play an role in carcinogenesis of ovarian cancer.

[Lysophosphatidic acid (LPA) stimulates invasion and metastatic colonization of ovarian cancer cells through Rac activation].

OBJECTIVE: To investigate the mechanisms of lysophosphatidic acid (LPA) in stimulating invasion and metastatic colonization of ovarian cancer cells. METHODS: The metastatic ability in vivo of ovarian cancer SK-OV3, HEY, OVCAR3, and IGROV1 cells was determined in tumor-bearing nude mouse models. Matrigel assay was used to detect the changes of response in vitro of ovarian cancer cells to LPA after Rac(-) or Rac(+) adenovirus treatment. LPA-induced Rho GTPase activation was detected by GST-fusion protein binding assay. RESULTS: The peritoneal metastatic colonization assay showed overt metastatic colonization in mice receiving SK-OV3 and HEY cell inoculation, indicating that they are invasive cells. Metastatic colonization was not detected in animals receiving OVCAR3 and IGROV1 cells, indicating that these cells are non-invasive cells. In the matrigel invasion assay, exposure to LPA led to a notably greater migratory response in metastatic SK-OV3 and HEY cells (Optical density: SK-OV3 cells: 0.594±0.023 vs. 1.697±0.049, P<0.01; HEY cells: 0.804±0.070 vs. 1.851±0.095, P<0.01). But LPA did little in the non-metastatic OVCAR3 and IGROV1 cells (Optical density A: OVCAR3 cells: 0.336±0.017 vs. 0.374±0.007, P>0.05; IGROV1 cells: 0.491±0.036 vs. 0.479±0.061, P>0.05). LPA migratory responses of ovarian cancer cells were closely related to their metastatic colonization capabilities (r = 0.983, P<0.05). Rac(-) blocked the LPA response of invasive SK-OV3 and HEY cells (LPA-induced fold increase of cell migration: SK-OV3 cells: 2.988±0.095 vs. 0.997±0.100,P=0.01; HEY cells: 2.404±0.059 vs. 0.901±0.072, P=0.01). But Rac(+) confered the non-invasive cells with LPA response and invasion capability (LPA-induced fold increase of cell migration: OVCAR3 cells: 1.072±0.080 vs. 1.898±0.078, P<0.01; IGROV1 cells: 1.002±0.044 vs. 2.141±0.057, P<0.05). Among Rho GTPases, only Rac activation was different between ovarian cancer cell lines with different metastatic capability after LPA stimulation: Cdc42 could not be activated in both the invasive and non-invasive cell lines. RhoA could be activated in both the invasive and non-invasive cell lines. Rac could be activated by LPA in the invasive ovarian cancer cell lines. However, Rac could not be activated in the non-invasive cell lines. CONCLUSION: Lysophosphatidic acid stimulates invasion and metastasis of ovarian cancer cells through Rac activation.

Integrated epigenomic exposure signature discovery.

Aim: The epigenome influences gene regulation and phenotypes in response to exposures. Epigenome assessment can determine exposure history aiding in diagnosis.Materials & methods: Here we developed and implemented a machine learning algorithm, the exposure signature discovery algorithm (ESDA), to identify the most important features present in multiple epigenomic and transcriptomic datasets to produce an integrated exposure signature (ES).Results: Signatures were developed for seven exposures including Staphylococcus aureus, human immunodeficiency virus, SARS-CoV-2, influenza A (H3N2) virus and Bacillus anthracis vaccinations. ESs differed in the assays and features selected and predictive value.Conclusion: Integrated ESs can potentially be utilized for diagnosis or forensic attribution. The ESDA identifies the most distinguishing features enabling diagnostic panel development for future precision health deployment.

This article introduces ESDA, a new analytic tool for integrating multiple data types to identify the most distinguishing features following an exposure. Using the ESDA, we were able to identify signatures of infectious diseases. The results of the study indicate that integration of multiple types of large datasets can be used to identify distinguishing features for infectious diseases. Understanding the changes from different exposures will enable development of diagnostic tests for infectious diseases that target responses from the patient. Using the ESDA, we will be able to build a database of human response signatures to different infections and simplify diagnostic testing in the future.

Prediction of OCT images of short-term response to anti-VEGF treatment for diabetic macular edema using different generative adversarial networks.

PURPOSE: This study sought to assess the predictive performance of optical coherence tomography (OCT) images for the response of diabetic macular edema (DME) patients to anti-vascular endothelial growth factor (VEGF) therapy generated from baseline images using generative adversarial networks (GANs). METHODS: Patient information, including clinical and imaging data, was obtained from inpatients at the Ophthalmology Department of Qilu Hospital. 715 and 103 pairs of pre-and post-treatment OCT images of DME patients were included in the training and validation sets, respectively. The post-treatment OCT images were used to assess the validity of the generated images. Six different GAN models (CycleGAN, PairGAN, Pix2pixHD, RegGAN, SPADE, UNIT) were applied to predict the efficacy of anti-VEGF treatment by generating OCT images. Independent screening and evaluation experiments were conducted to validate the quality and comparability of images generated by different GAN models. RESULTS: OCT images generated f GAN models exhibited high comparability to the real images, especially for edema absorption. RegGAN exhibited the highest prediction accuracy over the CycleGAN, PairGAN, Pix2pixHD, SPADE, and UNIT models. Further analyses were conducted based on the RegGAN. Most post-therapeutic OCT images (95/103) were difficult to differentiate from the real OCT images by retinal specialists. A mean absolute error of 26.74 ± 21.28 µm was observed for central macular thickness (CMT) between the synthetic and real OCT images. CONCLUSION: Different generative adversarial networks have different prognostic efficacy for DME, and RegGAN yielded the best performance in our study. Different GAN models yielded good accuracy in predicting the OCT-based response to anti-VEGF treatment at one month. Overall, the application of GAN models can assist clinicians in prognosis prediction of patients with DME to design better treatment strategies and follow-up schedules.

Gluten induces rapid reprogramming of natural memory αß and γδ intraepithelial T cells to induce cytotoxicity in celiac disease.

Celiac disease (CD) is an autoimmune disease in which intestinal inflammation is induced by dietary gluten. The means through which gluten-specific CD4+ T cell activation culminates in intraepithelial T cell (T-IEL)-mediated intestinal damage remain unclear. Here, we performed multiplexed single-cell analysis of intestinal and gluten-induced peripheral blood T cells from patients in different CD states and healthy controls. Untreated, active, and potential CD were associated with an enrichment of activated intestinal T cell populations, including CD4+ follicular T helper (TFH) cells, regulatory T cells (Tregs), and natural CD8+ αß and γδ T-IELs. Natural CD8+ αß and γδ T-IELs expressing activating natural killer cell receptors (NKRs) exhibited a distinct TCR repertoire in CD and persisted in patients on a gluten-free diet without intestinal inflammation. Our data further show that NKR-expressing cytotoxic cells, which appear to mediate intestinal damage in CD, arise from a distinct NKR-expressing memory population of T-IELs. After gluten ingestion, both αß and γδ T cell clones from this memory population of T-IELs circulated systemically along with gluten-specific CD4+ T cells and assumed a cytotoxic and activating NKR-expressing phenotype. Collectively, these findings suggest that cytotoxic T cells in CD are rapidly mobilized in parallel with gluten-specific CD4+ T cells after gluten ingestion.

KIAA1529 regulates RAD51 expression to confer PARP inhibitors resistance in ovarian cancer.

PARP inhibitors (PARPi) are currently used as first-line therapy for advanced and recurrent ovarian cancer, but the clinical efficacy is limited by drug resistance. We aimed to investigate the role of KIAA1529 in PARPi resistance in ovarian cancer. The expression of KIAA1529 was determined in ovarian cancer cells using qRT‒PCR and western blotting. Immunohistochemistry was used to examine the expression of KIAA1529 in primary ovarian cancer and recurrent ovarian cancer tissues. The effects of KIAA1529 on PARPi resistance were evaluated by knocking down KIAA1529 expression in ovarian cancer cells and assessing cell viability by CCK8 assays, apoptosis by flow cytometry, and homologous recombination (HR) repair by immunofluorescence analysis. The interaction between KIAA1529 and RAD51 was examined by western blotting. KIAA1529 was confirmed to be expressed in all ovarian cancer cell lines, and high expression of KIAA1529 was observed in recurrent ovarian cancer tissues. Inhibiting KIAA1529 expression increased the sensitivity of ovarian cancer cells to PARPi treatment. Furthermore, KIAA1529 increased the expression of the downstream effector RAD51 via Aurora-A, and HR was restored in ovarian cancer cells. This study demonstrates that KIAA1529 regulates RAD51 expression through Aurora-A to restore HR, which confers resistance to PARPi in ovarian cancer cells. These findings could provide a novel therapeutic target to overcome PARPi resistance in ovarian cancer.

Predicting OCT images of short-term response to anti-VEGF treatment for retinal vein occlusion using generative adversarial network.

To generate and evaluate post-therapeutic optical coherence tomography (OCT) images based on pre-therapeutic images with generative adversarial network (GAN) to predict the short-term response of patients with retinal vein occlusion (RVO) to anti-vascular endothelial growth factor (anti-VEGF) therapy. Real-world imaging data were retrospectively collected from 1 May 2017, to 1 June 2021. A total of 515 pairs of pre-and post-therapeutic OCT images of patients with RVO were included in the training set, while 68 pre-and post-therapeutic OCT images were included in the validation set. A pix2pixHD method was adopted to predict post-therapeutic OCT images in RVO patients after anti-VEGF therapy. The quality and similarity of synthetic OCT images were evaluated by screening and evaluation experiments. We quantitatively and qualitatively assessed the prognostic accuracy of the synthetic post-therapeutic OCT images. The post-therapeutic OCT images generated by the pix2pixHD algorithm were comparable to the actual images in edema resorption response. Retinal specialists found most synthetic images (62/68) difficult to differentiate from the real ones. The mean absolute error (MAE) of the central macular thickness (CMT) between the synthetic and real OCT images was 26.33 ± 15.81 µm. There was no statistical difference in CMT between the synthetic and the real images. In this retrospective study, the application of the pix2pixHD algorithm objectively predicted the short-term response of each patient to anti-VEGF therapy based on OCT images with high accuracy, suggestive of its clinical value, especially for screening patients with relatively poor prognosis and potentially guiding clinical treatment. Importantly, our artificial intelligence-based prediction approach's non-invasiveness, repeatability, and cost-effectiveness can improve compliance and follow-up management of this patient population.

Prediction of the Short-Term Therapeutic Effect of Anti-VEGF Therapy for Diabetic Macular Edema Using a Generative Adversarial Network with OCT Images.

PURPOSE: To generate and evaluate individualized post-therapeutic optical coherence tomography (OCT) images that could predict the short-term response of anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) based on pre-therapeutic images using generative adversarial network (GAN). METHODS: Real-world imaging data were collected at the Department of Ophthalmology, Qilu Hospital. A total of 561 pairs of pre-therapeutic and post-therapeutic OCT images of patients with DME were retrospectively included in the training set, 71 pre-therapeutic OCT images were included in the validation set, and their corresponding post-therapeutic OCT images were used to evaluate the synthetic images. A pix2pixHD method was adopted to predict post-therapeutic OCT images in DME patients that received anti-VEGF therapy. The quality and similarity of synthetic OCT images were evaluated independently by a screening experiment and an evaluation experiment. RESULTS: The post-therapeutic OCT images generated by the GAN model based on big data were comparable to the actual images, and the response of edema resorption was also close to the ground truth. Most synthetic images (65/71) were difficult to differentiate from the actual OCT images by retinal specialists. The mean absolute error (MAE) of the central macular thickness (CMT) between the synthetic OCT images and the actual images was 24.51 ± 18.56 µm. CONCLUSIONS: The application of GAN can objectively demonstrate the individual short-term response of anti-VEGF therapy one month in advance based on OCT images with high accuracy, which could potentially help to improve treatment compliance of DME patients, identify patients who are not responding well to treatment and optimize the treatment program.

Recent trends in the incidence and survival of stage I liver cancer: a surveillance, epidemiology, and end results analysis.

BACKGROUND: Improvements in screening and imaging technologies and treatment of liver disease have influenced the trend in diagnosis for stage I liver cancer. In this article, recent trends in age, incidence, tumour size, and survival of different stages of liver cancer are analysed. METHODS: Surveillance, Epidemiology, and end results data from the National Cancer Institute were used to analyse trends in age-adjusted incidence rate, mean tumour size at diagnosis, age at diagnosis, and 5-year survival probability for stage I liver cancer. RESULTS: Stage I cases of liver cancer increased most tremendously over the study period, with a greater increase from 2004 to 2012 following a smaller increase from 2012 to 2015. Moreover, the mean age of stage I liver cancer increased by 1.72 years from 2004 to 2015. The 5-year-overall survival for stage I liver cases worsened from 97.9% to 83.7% from 2004 to 2011, whereas the 10-year survival probability for stage I cases worsened from 97.3% in 2004 to 79.6% in 2006. Comparing with higher stage cases, stage I liver cancer were more likely to be females, be married, live in metro areas, receive chemotherapy, and carry medical insurance. CONCLUSIONS: The incidence of stage I liver cancer has increased over the study period, with an increase in age of diagnosis, decrease in tumour size, and generally stable overall survival rate with slight decrease. These trends emphasized the importance of early detection of liver cancer and regular screening and better treatment for high-risk populations.RESEARCH HIGHLIGHTSImprovements in screening and imaging technologies and treatment of liver disease have influenced the trend in diagnosis for liver cancer.Stage I cases of liver cancer increased most tremendously over the study period, with a greater increase from 2004 to 2012 following a smaller increase from 2012 to 2015.These trends emphasized the importance of early detection of liver cancer and regular screening and better treatment for high-risk populations.

Asymptomatic SARS-CoV-2 Infection Is Associated With Higher Levels of Serum IL-17C, Matrix Metalloproteinase 10 and Fibroblast Growth Factors Than Mild Symptomatic COVID-19.

Young adults infected with SARS-CoV-2 are frequently asymptomatic or develop only mild disease. Because capturing representative mild and asymptomatic cases require active surveillance, they are less characterized than moderate or severe cases of COVID-19. However, a better understanding of SARS-CoV-2 asymptomatic infections might shed light into the immune mechanisms associated with the control of symptoms and protection. To this aim, we have determined the temporal dynamics of the humoral immune response, as well as the serum inflammatory profile, of mild and asymptomatic SARS-CoV-2 infections in a cohort of 172 initially seronegative prospectively studied United States Marine recruits, 149 of whom were subsequently found to be SARS-CoV-2 infected. The participants had blood samples taken, symptoms surveyed and PCR tests for SARS-CoV-2 performed periodically for up to 105 days. We found similar dynamics in the profiles of viral load and in the generation of specific antibody responses in asymptomatic and mild symptomatic participants. A proteomic analysis using an inflammatory panel including 92 analytes revealed a pattern of three temporal waves of inflammatory and immunoregulatory mediators, and a return to baseline for most of the inflammatory markers by 35 days post-infection. We found that 23 analytes were significantly higher in those participants that reported symptoms at the time of the first positive SARS-CoV-2 PCR compared with asymptomatic participants, including mostly chemokines and cytokines associated with inflammatory response or immune activation (i.e., TNF-α, TNF-ß, CXCL10, IL-8). Notably, we detected 7 analytes (IL-17C, MMP-10, FGF-19, FGF-21, FGF-23, CXCL5 and CCL23) that were higher in asymptomatic participants than in participants with symptoms; these are known to be involved in tissue repair and may be related to the control of symptoms. Overall, we found a serum proteomic signature that differentiates asymptomatic and mild symptomatic infections in young adults, including potential targets for developing new therapies and prognostic tests.

Serum Fc-Mediated Monocyte Phagocytosis Activity Is Stable for Several Months after SARS-CoV-2 Asymptomatic and Mildly Symptomatic Infection.

We investigated the temporal profile of multiple components of the serological response after asymptomatic or mildly symptomatic SARS-CoV-2 infection, in a cohort of 67 previously SARS-CoV-2 naive young adults, up to 8.5 months after infection. We found a significant decrease of spike IgG and neutralization antibody titers from early (11 to 56 days) to late (4 to 8.5 months) time points postinfection. Over the study period, S1-specific IgG levels declined significantly faster than that of the S2-specific IgG. Further, serum antibodies from PCR-confirmed participants cross-recognized S2, but not S1, of the betacoronaviruses HKU1 and OC43, suggesting a greater degree of cross-reactivity of S2 among betacoronaviruses. Antibody-Dependent Natural Killer cell Activation (ADNKA) was detected at the early time point but significantly decreased at the late time point. Induction of serum Antibody-Dependent Monocyte Phagocytosis (ADMP) was detected in all the infected participants, and its levels remained stable over time. Additionally, a reduced percentage of participants had detectable neutralizing activity against the Beta (50%), Gamma (61 to 67%), and Delta (90 to 94%) variants, both early and late postinfection, compared to the ancestral strain (100%). Antibody binding to S1 and RBD of Beta, Gamma, Delta (1.7 to 2.3-fold decrease), and Omicron (10 to 16-fold decrease) variants was also significantly reduced compared to the ancestral SARS-CoV-2 strain. Overall, we found variable temporal profiles of specific components and functionality of the serological response to SARS-CoV-2 in young adults, which is characterized by lasting, but decreased, neutralizing activity and antibody binding to S1, stable ADMP activity, and relatively stable S2-specific IgG levels. IMPORTANCE Adaptive immunity mediated by antibodies is important for controlling SARS-CoV-2 infection. While vaccines against COVID-19 are currently widely distributed, a high proportion of the global population is still unvaccinated. Therefore, understanding the dynamics and maintenance of the naive humoral immune response to SARS-CoV-2 is of great importance. In addition, long-term responses after asymptomatic infection are not well-characterized, given the challenges in identifying such cases. Here, we investigated the longitudinal humoral profile in a well-characterized cohort of young adults with documented asymptomatic or mildly symptomatic SARS-CoV-2 infection. By analyzing samples collected preinfection, early after infection and during late convalescence, we found that, while neutralizing activity decreased over time, high levels of serum S2 IgG and Antibody-Dependent Monocyte Phagocytosis (ADMP) activity were maintained up to 8.5 months after infection. This suggests that a subset of antibodies with specific functions could contribute to long-term protection against SARS-CoV-2 in convalescent unvaccinated individuals.

Corrigendum: Identification of a Two-Gene (PML-EPB41) Signature With Independent Prognostic Value in Osteosarcoma.

[This corrects the article DOI: 10.3389/fonc.2019.01578.].

Innate Lymphoid Cells and Celiac Disease: Current Perspective.

Celiac disease (CD) is a common autoimmune disorder triggered by the ingestion of gluten in genetically susceptible individuals. Although the mechanisms underlying gliadin-mediated activation of adaptive immunity in CD have been well-characterized, regulation of innate immune responses and the functions of certain immune cell populations within the epithelium and lamina propria are not well-understood at present. Innate lymphoid cells (ILCs) are types of innate immune cells that have lymphoid morphology, lack antigen-specific receptors, and play important roles in tissue homeostasis, inflammation, and protective immune responses against pathogens. Information regarding the diversity and functions of ILCs in lymphoid organs and at mucosal sites has grown over the past decade, and roles of different ILC subsets in the pathogenesis of some inflammatory intestinal diseases have been proposed. However, our understanding of the contribution of ILCs toward the initiation and progression of CD is still limited. In this review, we discuss current pathophysiological aspects of ILCs within the gastrointestinal tract, findings of recent investigations characterizing ILC alterations in CD and refractory CD, and suggest avenues for future research.

Intravitreal Conbercept for Idiopathic Choroidal Neovascularization in Nursing Women.

Purpose: To report the clinical course and vascular endothelial growth factor (VEGF) levels in breast milk among three nursing women diagnosed with idiopathic choroidal neovascularization (CNV) before and after intravitreal injection of conbercept. Methods: This was an observational case series. The main outcomes and measures included best-corrected visual acuity (BCVA), anatomical features using optical coherence tomography, and breast milk concentrations of VEGF before and after the intravitreal injection of conbercept. Results: BCVA was increased, and no ocular or systemic safety problems were observed in any of the three patients during the follow-up period. An enzyme-linked immunosorbent assay was used to measure VEGF concentrations in the breast milk samples. Samples were collected 1 day before and 1, 7, and 30 days after the first intravitreal injection of conbercept. After conbercept injection, VEGF levels in breast milk were slightly decreased and did not change significantly in the following week; levels recovered fully by 30 days post-treatment. Conclusions: Intravitreal injection of conbercept shows favorable effectiveness and safety in the treatment of idiopathic CNV in nursing women and does not result in a significant reduction in VEGF in human breast milk.