Search

Summary Background Pembrolizumab (PD-1 inhibitor) and cetuximab (EGFR inhibitor) are active as single agents and in combination with cytotoxic chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Given each drug's single agent activity and unique mechanism of action, we aimed to evaluate the anti-tumour activity of PD-1 blockade with EGFR inhibition in recurrent or metastatic HNSCC. Methods This study is an open-label, non-randomised, multi-arm, phase 2 trial done at four academic centres in the USA. Participants were required to have platinum-resistant or platinum-ineligible, recurrent or metastatic HNSCC, be at least 18 years old, have an Eastern Cooperative Oncology Group performance status 0–1, have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and to have received no previous immunotherapy or EGFR inhibition. All participants received pembrolizumab 200 mg intravenously every 3 weeks, combined with an initial loading dose of cetuximab 400 mg/m2 intravenously followed by 250 mg/m2 intravenously weekly (21 day cycle). The primary endpoint was overall response rate defined as the proportion of participants with a partial or complete responses (per RECIST version 1.1) by 6 months in the intention-to-treat population. The safety population included all participants who received at least one dose of pembrolizumab. Herein, the final analysis of cohort 1 (no previous PD-1, PD-L1, or EGFR inhibition for recurrent or metastatic HNSCC) is reported. Three additional cohorts (two for participants with a previous response to immunotherapy followed by relapse or progression, with or without previous cetuximab exposure, and one for cutaneous HNSCC) will be reported separately once fully accrued. This study is registered with ClinicalTrials.gov , NCT03082534 , and remains open as the three additional cohorts are actively accruing participants. Findings Between March 22, 2017, and July 16, 2019, 33 participants were enrolled to cohort 1. All 33 participants received at least one dose of pembrolizumab. Median follow-up duration was 7·3 months (IQR 3·9–10·9). By 6 months, the overall response rate was 45% (95% CI 28–62), with 15 of 33 participants achieving a partial response. The most common grade 3–4 treatment-related adverse event was oral mucositis (three [9%] of 33 participants), and serious treatment-related adverse events occurred in five (15%) participants. No treatment-related deaths occurred. Interpretation Pembrolizumab combined with cetuximab shows promising clinical activity for recurrent or metastatic HNSCC, and merits further investigation. Funding Merck Sharp & Dohme.

Electronic cigarettes (e-cigarettes) are the preferred smoking-cessation aid in the United States; however, there is little evidence regarding long-term effectiveness among those who use them. We used the Population Assessment of Tobacco and Health Study to compare long-term abstinence between matched US smokers who tried to quit with and without use of e-cigarettes as a cessation aid. We identified a nationally representative cohort of 2,535 adult US smokers in 2014–2015 (baseline assessment), who, in 2015–2016 (exposure assessment), reported a past-year attempt to quit and the cessation aids used, and reported smoking status in 2016–2017 (outcome assessment; self-reported ≥12 months continuous abstinence). We used propensity-score methods to match each e-cigarette user with similar nonusers. Among US smokers who used e-cigarettes to help quit, 12.9% (95% confidence interval (CI): 9.1%, 16.7%) successfully attained long-term abstinence. However, there was no difference compared with matched non–e-cigarette users (cigarette abstinence difference: 2%; 95% CI: −3%, 7%). Furthermore, fewer e-cigarette users were abstinent from nicotine products in the long term (nicotine abstinence difference: −4%; 95% CI: −7%, −1%); approximately two-thirds of e-cigarette users who successfully quit smoking continued to use e-cigarettes. These results suggest e-cigarettes may not be an effective cessation aid for adult smokers and, instead, may contribute to continuing nicotine dependence.

Background: Cirmtuzumab is a humanized monoclonal antibody that targets the receptor tyrosine kinase like orphan receptor 1 (ROR1), which is expressed on poor prognosis breast cancer, ovarian cancer, other solid tumors, CLL and mantle cell lymphoma. One clinical study showed increased expression of ROR1 in breast cancers after neoadjuvant chemotherapy and a preclinical PDX breast cancer model showed cirmtuzumab and paclitaxel to have at least additive efficacy1. A recently completed Phase 1 trial of cirmtuzumab in CLL showed the antibody to be both safe and effective in inhibiting tumor cell ROR1 signaling in patients with CLL2. Methods: The primary aim of this trial was to determine the safety of cirmtuzumab and weekly paclitaxel in patients with advanced Her2 negative breast cancer based upon dose limiting toxicities (DLTs) in the first cycle of treatment. Secondary endpoints were clinical activity, pharmacokinetics and correlative biomarkers on tumor specimens. Eligible patients were those with locally advanced, unresectable or metastatic Her2 negative breast cancer who had not received paclitaxel in the metastatic setting, had not developed metastatic disease within 6 months of (neo)adjuvant paclitaxel, had ECOG performance status of 0-2, and had adequate laboratory parameters. Any number of prior lines of therapy were allowed. Study treatment included fixed dose 600 mg cirmtuzumab given days 1 and 15 of cycle 1 and then day 1 of each subsequent 28-day cycle. Paclitaxel was given weekly at a dose of 80mg/m2. Patients were evaluated in dose cohorts of 5 for DLTs with a target of 15 evaluable patients. Results: To date, 6 patients evaluable for safety and 5 patients evaluable for DLTs were treated. Age range was 30 to 59 years. Three of 6 safety-evaluable patients had triple negative breast cancer at study enrollment. Prior lines of chemotherapy in the metastatic setting ranged from 0-3. No discontinuations for toxicity and no DLTs have been observed to date. Adverse events (AEs) have been consistent with the known safety profile of paclitaxel, with 3 episodes of grade 3 neutropenia in 2 patients and 1 episode of grade 3 hyperglycemia. All other AEs were grade 1 or 2. Partial responses have been observed in 2/5 patients with one patient response ongoing with cirmtuzumab alone for at least 17 weeks after stopping paclitaxel. Pharmacokinetic analysis of serial plasma samples for free unbound antibody from two patients provided results similar to those observed in CLL patients treated with cirmtuzumabwith a projected half-life of 30 days2. No decline in antibody concentration over time was observed consistent with the absence of neutralizing antibodies. Conclusions: Preliminary information indicates that the combination of fixed dose cirmtuzumab plus paclitaxel is well-tolerated and safe. Responses to therapy have been observed and preliminary pharmacokinetic results are consistent with sustained potentially therapeutic levels. Updated safety, clinical activity, pharmacokinetics and biomarker analyses will be presented. 1Zhang S et al. Proc Natl Acad Sci USA. 116(4): 1370-1377. PMID 30622177. 2Choi MY et al. Cell Stem Cell 22(6): 951-959. PMID 29859176. Funding sources: CIRM UC San Diego Alpha Stem Cell Clinic and Sanford Stem Cell Clinical Center; Oncternal Therapeutics, Inc.; UC San Diego Moores Cancer Center Padres Pedal the Cause Grant; Gonick Breast Cancer Research Fund Citation Format: Rebecca A Shatsky, Richard B Schwab, Teresa L Helsten, Emily I Pittman, Ruifeng Chen, James B Breitmeyer, Catriona HM Jamieson, Thomas J Kipps, Barbara A Parker. Phase 1b trial of cirmtuzumab and paclitaxel for locally advanced, unresectable and metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-10-18.

Because of its high infectivity in humans and the lack of effective vaccines, Nipah virus is classified as a category C agent and handling has to be performed under biosafety level 4 conditions in non-endemic countries, which has hindered the development of vaccines. Based on a highly efficient pseudovirus production system using a modified HIV backbone vector, a pseudovirus-based mouse model has been developed for evaluating the efficacy of Nipah vaccines in biosafety level 2 facilities. For the first time, the correlates of protection have been identified in a mouse model. The limited levels of neutralizing antibodies against immunogens fusion protein (F), glycoprotein (G), and combination of F and G (FG) were found to be 148, 275, and 115, respectively, in passive immunization. Relatively lower limited levels of protection of 52, and 170 were observed for immunogens F, and G, respectively, in an active immunization model. Although the minimal levels for protection of neutralizing antibody in passive immunization were slightly higher than those in active immunization, neutralizing antibody played a key role in protection against Nipah virus infection. The immunogens F and G provided similar protection, and the combination of these immunogens did not provide better outcomes. Either immunogen F or G would provide sufficient protection for Nipah vaccine. The Nipah pseudovirus mouse model, which does not involve highly pathogenic virus, has the potential to greatly facilitate the standardization and implementation of an assay to propel the development of NiV vaccines.

With an almost 100% mortality rate, rabies virus (RABV) infection is a global concern. Limited post-exposure prophylaxis and lack of an effective treatment necessitate novel antiviral therapies against RABV. Here, using a high-throughput screening (HTS) method developed in our lab, 11 candidates with anti-RABV activity were identified from a library of 767 clinical drugs. Clofazimine (CFZ), an anti-leprosy drug, displayed an EC50 of 2.28 μM, and SI over 967 against RABV. Investigations into the underlying mechanisms revealed that CFZ targeted viral membrane fusion at the early stages of virus replication. Moreover, CFZ and Clofazimine salicylates (CFZS) exhibited elevated survival rates in vivo, compared with the positive control T-705. Thus, this study revealed CFZ as a promising drug against RABV infection.

Primary influenza virus (IV) infection can predispose hosts to secondary infection with Haemophilus influenzae (H. influenzae), which further increases the severity and mortality of the disease. While adhesion molecules play a key role in the host inflammatory response and H. influenzae colonization, it remains to be clarified which types of adhesion molecules are associated with H. influenzae colonization and invasion following IV infection. In this study, we established a mouse model of co-infection with influenza A virus (A/Puerto Rico/8/34, H1N1) (PR8) and non-typeable H. influenzae (NTHi) and found that sequential infection with PR8 and NTHi induced a lethal synergy in mice. This outcome may be possibly due to increased NTHi loads, greater lung damage and higher levels of cytokines. Furthermore, the protein levels of intracellular adhesion molecules-1 (ICAM-1) and Fibronectin (Fn) were significantly increased in the lungs of coinfected mice, but the levels of carcinoembryonic adhesion molecule (CEACAM)-1, CEACAM-5 and platelet-activating factor receptor (PAFr) were unaffected. Both the protein levels of ICAM-1 and Fn were positively correlated with NTHi growth. These results indicat e the correlation between adhesion molecules, including ICAM-1 and Fn, and NTHi growth in secondary NTHi pneumonia following primary IV infection.

Influenza virus infection is widely believed to cause mild symptoms, but can lead to high mortality and severe disease complicated by secondary bacterial pneumonia. Traditional Chinese medicine (TCM) has been proposed as a promising agent to treat respiratory viral infections. A herbal formula Lianhuaqingwen capsule (LHQW) comprising two prescriptions: Maxing Shigan decoction and Yinqiao San, has been used clinically to treat respiratory infection with immune regulatory effects. However, little is known about the capacity of LHQW against influenza-induced secondary bacterial pneumonia.This study aimed to evaluate the efficacy and underlying mechanism of LHQW on influenza A virus A/PR/8/34 (PR8) secondary methicillin-resistant Staphy-lococcus aureus (MRSA) infection.The anti-adhesion activity of LHQW against PR8-induced MRSA infection was assessed in human lung epithelial (A549) cells and the effect of LHQW on the expression of intracellular adhesion molecule 1 (ICAM-1) was detected. Also, the mRNA expression levels of inflammatory cytokines upon lipopolysaccharide (LPS) stimulation in PR8-infected A549 cells were determined. The body weight change, survivals, viral titers, colonies and the pathological parameters after LHQW treatment in severe pneumonia model have all been systematically determined.LHQW significantly reduced the adhesion of MRSA to PR8-infected A549 cells in a dose-dependent manner by suppressing the up-regulation of bacterial receptors. LHQW also markedly declined the overexpression of IL-6, IL-8, and TNF-α induced by LPS stimulated-A549 cells following influenza virus infection. Furthermore, the abnormal changes of lung index in dual-infection mice were relieved after administered with LHQW in preventive and therapeutic mode, but with no significantly difference (P 0.05). LHQW could not effectively improve survival rate or prolong the survival time of mice (P 0.05). LHQW (1000 mg/kg/d) administered prophylactically significantly decreased the lung viral titers (P 0.05), slightly downregulated IL-6 but TNF-α, IL-1β levels and improved lung pathological inflammation including neutrophil infiltration, necrosis, which is consistent with the expression of inflammatory factors.LHQW inhibited influenza-induced bacterial adhesion by down-regulating the adhesion molecules with the improvement trend on severe pneumonia, indicating that it can be used as an adjuvant medication in severe viral-bacterial pneumonia therapy rather than as a single medication.

Background The US lags behind >120 countries in implementing graphic warning labels (GWLs) on cigarette packs. US courts prevented implementation of FDA's 2012 rule requiring GWLs citing the need for more evidence on effectiveness. After more research, in 2020, the FDA proposed a revised rule mandating GWLs. This trial will test how the introduction of GWLs influence cognitions and behavior in US smokers. Method To investigate the “real-world” impact of GWLs in US smokers, we are conducting a randomized trial involving a 3-month intervention and 8-month follow-up. The study recruited California smokers between September 2016 through December 2019 and randomly assigned them into 3 groups (1) Blank Pack devoid of any cigarette branding; (2) GWL Pack featuring 1 of 3 rotating images added to blank pack; or (3) their usual Standard US Pack. Throughout the 3-month intervention, participants purchased study-packaged cigarettes and reported daily cognitions and behavior through ecological momentary assessments. We will validate self-reported tobacco use with saliva cotinine concentrations following the 3-month intervention and 8-month follow-up. Results The trial enrolled 359 participants (average age 39 years; average cigarette consumption half a pack/day). The 3 study groups were balanced on age, gender, race-ethnicity, education and income (17% low income) as well as on smoking related variables. Conclusions This 3-month real-world randomized trial will test the effect of repackaging cigarettes from standard US packs to GWL plain packs on smokers' perceptions of the risks of smoking, their perception of the appeal of their cigarettes, and on their smoking behavior., Highlights • The efficacy of Graphic Warning Labels (GWLs) on Cigarette Packs has been disputed in US courts. • This trial randomly assigned US smokers to receive cigarettes in one of three study pack groups. • Study packs were:1-Blank Pack devoid of tobacco imagery; 2-GWL Pack; 3- Standard US pack. • We assessed smoking cognitions and behavior pre-randomization and during the intervention. • Smoking behavior is validated by saliva cotinine.

BackgroundMore smokers report using e-cigarettes to help them quit than FDA-approved pharmacotherapy.ObjectiveTo assess the association of e-cigarettes with future abstinence from cigarette and tobacco use.DesignCohort study of US sample, with annual follow-up.ParticipantsUS adult (ages 18+) daily cigarette smokers identified at Wave 1 (W1; 2013-14) of the PATH Study, who reported a quit attempt before W2 and completed W3 (n = 2443).ExposuresUse of e-cigarettes, pharmacotherapy (including nicotine replacement therapy), or no product for last quit attempt (LQA), and current daily e-cigarette use at W2.AnalysisPropensity score matching (PSM) of groups using different methods to quit.Outcome measures12+ months abstinence at W3 from cigarettes and from all tobacco (including e-cigarettes). 30+ days abstinence at W3 was a secondary outcome.ResultsAmong daily smokers with an LQA, 23.5% used e-cigarettes, 19.3% used pharmacotherapy only (including NRT) and 57.2% used no product. Cigarette abstinence for 12+ months at W3 was ~10% in each group. Half of the cigarette abstainers in the e-cigarette group were using e-cigarettes at W3. Different methods to help quitting had statistically comparable 12+ month cigarette abstinence at W3 (e-cigarettes vs no product: Risk Difference (RD) = 0.01, 95% CI: -0.04 to 0.06; e-cigarettes vs pharmacotherapy: RD = 0.02, 95% CI:-0.04 to 0.09). Likewise, daily e-cigarette users at W2 did not show a cessation benefit over comparable no-e-cigarette users and this finding was robust to sensitivity analyses. Abstinence for 30+ days at W3 was also similar across products.LimitationsThe frequency of e-cigarette use during the LQA was not assessed, nor was it possible to assess continuous abstinence from the LQA.ConclusionAmong US daily smokers who quit cigarettes in 2014-15, use of e-cigarettes in that attempt compared to approved cessation aids or no products showed similar abstinence rates 1-2 years later.

Jianpiyifei II granule (JPYF II) is an oriental herbal formula used clinically in China to treat chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the anti-inflammatory and antioxidative activities of JPYF II in a mouse model of COPD induced by lipopolysaccharide (LPS) and cigarette smoke (CS) and in RAW264.7 cells stimulated with cigarette smoke extract (CSE). Mice were given LPS via intratracheal instillation on days 1 and 15 and exposed to CS generated from 4 cigarettes/day for 28 days. The mice were treated with 0.75, 1.5, or 3 g/kg/d JPYF II by intragastric administration in low, middle, and high dose groups, respectively, for two weeks. RAW264.7 cells were stimulated by CSE and treated with JPYF II at doses of 12.5, 25, or 50 μg/mL. In the mouse model of LPS and CS-induced COPD, JPYF II decreased inflammatory cell counts in broncho alveolar lavage fluid (BALF), in addition to mRNA expression of proinflammatory cytokines and metalloproteinases (MMPs) in lung tissues. In addition, JPYF II elevated catalase (CAT) and glutathione peroxidase (GSH-Px) activities and reduced the levels of malondialdehyde (MDA) and IκBα and p65 phosphorylation and inflammatory cell infiltration in the lung tissues. In RAW264.7 cells stimulated with CSE, JPYF II inhibited the mRNA levels of inflammatory mediators and the phosphorylation of IκBα and p65. Our results suggest that JPYF II enhanced anti-inflammatory and antioxidative activities in a mouse model of COPD induced by LPS and CS and in RAW264.7 cells stimulated with CSE via inhibition of the NF-κB pathway.

Toll-like receptors (TLRs) are the primary sensors detecting conserved molecular patterns on microorganisms, thus acting as important components of innate immunity against invading pathogens. Many positive and negative regulators of TLR-triggered signaling have been identified. The Rho GTPase RhoB plays a key role in cell migration, division and polarity; however, the function and regulatory mechanisms of RhoB in TLR ligand-triggered innate immune responses remain to be investigated. Here, we report that the expression of RhoB is induced by TLR agonists (lipopolysaccharide (LPS), CpG, poly(I:C)) in macrophages. Knockdown of RhoB expression markedly decreased TLR ligand-induced activation of mitogen activated protein kinases and nuclear factor-κB (NF-κB), and the production of tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-1β in macrophages stimulated with TLR ligands. Furthermore, we demonstrated that RhoB interacts with major histocompatibility complex class II (MHCII) α chain, but not β chain, in endosomes of macrophages. Knockdown of MHCII expression greatly reduced the interaction of RhoB with Btk, and attenuated the induction of NF-κB and interferon β activity by RhoB upon LPS stimulation. These findings suggest that RhoB is a positive physiological regulator of TLRs signaling via binding to MHCII in macrophages, and therefore RhoB may be a potential therapeutic target in inflammatory diseases.

Author(s): Pierce, John P; Leas, Eric C; Benmarhnia, Tarik; McMenamin, Sara B; Strong, David R; Chen, Ruifeng; Messer, Karen

Treatment with chimeric antigen receptor (CAR)-modified T cells targeting CD19 has proved successful in patients with relapsed/refractory B cell malignancies. However, long-term follow-up indicates that remission in a substantial proportion of patients is not sustainable. Most patients that experience recurrence have tumors and lost the CAR-T cells. To maintain the activity of CAR-T cells, Raji-B-NDG mice were treated sequentially with CAR-T-19 cells and homologous cells expressing human CD19 to promote expansion of CAR-T cells. Sequential treatment of mice with CAR-T-19 cells followed by Raji tumor cells led to marked prolongation of survival. The best case scenario after sequential treatment was a survival time of more than 200 days; the average survival time of mice in the non-sequential treatment group was 80 days. We treated mice with autologous CD19-modified T cells after initial treatment with CAR-T-19 cells. The overall survival and recurrence-free survival times of mice receiving sequential treatment were significantly longer. The percentages of CAR+ T cells in peripheral blood increased. Sequential therapy with autologous CAR-T-19 and aT19 cells provides a new strategy for generating memory CAR-T cells, which may lead ultimately to increased clinical efficacy.

Rift Valley fever virus (RVFV), a recognized category A priority pathogen, causes large outbreaks of Rift Valley fever with some fatalities in humans in humans and huge economic losses in livestock. As wild-type RVFV must be handled in BSL-3 or BSL-4 laboratories, we constructed a high-titer vesicular stomatitis virus (VSV) pseudotype bearing RVFV envelope glycoproteins to detect neutralizing antibodies in vitro under BSL-2 conditions. The neutralizing properties of 39 amino acid mutant sites that have occurred naturally over time in the RVFV envelope glycoproteins were analyzed with their corresponding pseudoviral mutants separately. Compared with the results in the primary strain, the variants showed no statistically significant differences. We next established a Balb/c mouse pseudovirus infection model for detecting neutralizing antibodies against pseudovirus. Five immunizations with pseudoviral DNA protected the mice from infection with the pseudovirus. Bioluminescence imaging, which we used to evaluate viral dissemination and distribution in the mice, showed a good relationship between the neutralizing antibodies titers in vitro. These pseudovirus methods will allow for the safe determination of neutralizing antibodies in vivo and in vitro, and will assist with studies on vaccines and drugs against RVFV with the long term objective of Rift Valley fever prevention.

Background Alstonia scholaris is a folk medicine used to treat cough, asthma and chronic obstructive pulmonary disease in China. Total alkaloids (TA) from A. scholaris exhibit anti-inflammatory properties in acute respiratory disease, which suggests their possible anti-inflammatory effect on influenza virus infection. Purpose To assess the clinical use of TA by demonstrating their anti-influenza and anti-inflammatory effects and the possible mechanism underlying the effect of TA on influenza A virus (IAV) infection in vitro and to reveal the inhibitory effect of TA on lung immunopathology caused by IAV infection. Methods Antiviral and anti-inflammatory activities were assessed in Madin-Darby canine kidney (MDCK) and A549 cells and U937-derived macrophages infected with influenza A/PR/8/34 (H1N1) virus. Proinflammatory cytokine levels were measured by real-time quantitative PCR and Bio-Plex assays. The activation of innate immune signaling induced by H1N1 virus in the absence or presence of TA was detected in A549 cells by Western blot. Furthermore, mice were infected intranasally with H1N1 virus and treated with TA (50, 25 and 12.5 mg/kg/d) or oseltamivir (60 mg/kg/d) for 5 days in vivo. The survival rates and body weight were recorded, and the viral titer, proinflammatory cytokine levels, innate immune cell populations and histopathological changes in the lungs were analyzed. Results TA significantly inhibited viral replication in A549 cells and U937-derived macrophages and markedly reduced cytokine and chemokine production at the mRNA and protein levels. Furthermore, TA blocked the activation of pattern recognition receptor (PRR)- and IFN-activated signal transduction in A549 cells. Critically, TA also increased the survival rate, reduced the viral titer, suppressed proinflammatory cytokine production and innate immune cell infiltration and improved lung histopathology in a lethal PR8 mouse model. Conclusion TA exhibits anti-viral and anti-inflammatory effects against IAV infection by interfering with PRR- and IFN-activated signal transduction.

Rabies is a fatal zoonosis which could affect all mammals. Glycoprotein (G protein) from the rabies virus plays an important role in the binding of virus to target cells. However, expression of the G protein with native conformation has been a great challenge for many years. In this study, we solved this problem by replacing the original signal peptide of rabies virus G protein with the one from the heavy chain of human IgG. The expression levels of recombinant G protein dramatically increased from a few μg/L to 50 mg/L in the culture supernatants. The identity of the recombinant G protein was confirmed by western blotting using both 6XHis mAb 6E2 and rabies G protein mAb 7G3. The correct conformation of the recombinant G protein was shown by using rabies virus neutralizing antibodies. In addition, the recombinant G protein had immune-reactivities with mice sera raised against rabies vaccines and vice versa. Taken together, our data suggested that by replacing the signal peptide, the expression level of the G protein with native conformation could be significantly improved. This would help the development of a rabies subunit vaccine, structural studies of rabies G protein, elucidation of the signal pathway of RABV infection.

Background and objective Automatic cardiac left ventricle (LV) quantification plays an important role in assessing cardiac function. Although many advanced methods have been put forward to quantify related LV parameters, automatic cardiac LV quantification is still a challenge task due to the anatomy construction complexity of heart. Methods In this work, we propose a novel deep multi-task conditional quantification learning model (DeepCQ) which contains Segmentation module, Quantification encoder, and Dynamic analysis module. Besides, we also use task uncertainty loss function to update the parameters of the network in training. Results The proposed framework is validated on the dataset from Left Ventricle Full Quantification Challenge MICCAI 2018 ( https://lvquan18.github.io/ ). The experimental results show that DeepCQ outperforms the other advanced methods. Conclusions It illustrates that our method has a great potential in comprehensive cardiac function assessment and could play an auxiliary role in clinicians’ diagnosis.

Optimization of compatible solutes (ectoine) extraction and purification from Halomonas elongata cell fermentation had been investigated in the laboratory tests of a large scale commercial production project. After culturing H. elongata cells in developed medium at 28 °C for 23–30 h, we obtained an average yield and biomass of ectoine for 15.9 g/L and 92.9 (OD600), respectively. Cell lysis was performed with acid treatment at moderate high temperature (60–70 °C). The downstream processing operations were designed to be as follows: filtration, desalination, cation exchange, extraction of crude product and three times of refining. Among which the cation exchange and extraction of crude product acquired a high average recovery rate of 95 and 96%; whereas a great loss rate of 19 and 15% was observed during the filtration and desalination, respectively. Combined with the recovering of ectoine from the mother liquor of the three times refining, the average of overall yield (referring to the amount of ectoine synthesized in cells) and purity of final product obtained were 43% and over 98%, respectively. However, key factors that affected the production efficiency were not yields but the time used in the extraction of crude product, involving the crystallization step from water, which spended 24–72 h according to the production scale. Although regarding to the productivity and simplicity on laboratory scale, the method described here can not compete with other investigations, in this study we acquired higher purity of ectoine and provided downstream processes that are capable of operating on industrial scale.

6033Background: Pembrolizumab (a humanized monoclonal antibody blocking programmed death receptor-1[PD-1]), and cetuximab (a chimeric monoclonal antibody inhibiting epidermal growth factor receptor...