Barriers and challenges to global clinical cancer research.

BACKGROUND: There are concerns about growing barriers to cancer research. We explored the characteristics of and barriers to global clinical cancer research. METHODS: The American Society of Clinical Oncology International Affairs Committee invited 300 selected oncologists with research experience from 25 countries to complete a Web-based survey. Fisher's exact test was used to compare answers between participants from high-income countries (HICs) and low- and middle-income countries (LMICs). Barriers to clinical cancer research were ranked from 1 (most important) to 8 (least important). Mann-Whitney's nonparametric test was used to compare the ranks describing the importance of investigated obstacles. RESULTS: Eighty oncologists responded, 41 from HICs and 39 from LMICs. Most responders were medical oncologists (62%) at academic hospitals (90%). Researchers from HICs were more involved with academic and industry-driven research than were researchers from LMICs. Significantly higher proportions of those who considered their ability to conduct academic research and industry-driven research over the past 5 years more difficult were from HICs (73% vs. 27% and 70% vs. 30%, respectively). Concerning academic clinical cancer research, a lack of funding was ranked the most important (score: 3.16) barrier, without significant differences observed between HICs and LMICs. Lack of time or competing priorities and procedures from competent authorities were the second most important barriers to conducting academic clinical research in HICs and LMICs, respectively. CONCLUSION: Lack of funding, lack of time and competing priorities, and procedures from competent authorities might be the main global barriers to academic clinical cancer research.

Enhancing quorum sensing in biofilm anode to improve biosensing of naphthenic acids.

The feasibility of enhancing quorum sensing (QS) in anode biofilm to improve the quantifications of commercial naphthenic acid concentrations (9.4-94 mg/L) in a microbial electrochemical cell (MXC) based biosensor was demonstrated in this study. First, three calibration methods were systematically compared, and the charging-discharging operation was selected for further experiments due to its 71-227 folds higher electrical signal outputs than the continuous closed-circuit operation and cyclic voltammetry modes. Then, the addition of acylase (5 µg/L) as an exogenous QS autoinducer (acylase) was investigated, which further improved the biosensor's electrical signal output by ∼70%, as compared to the control (without acylase). The addition of acylase increased the relative expression of QS-associated genes (lasR, lasI, rhlR, rhlI, lasA, and luxR) by 7-100%, along with increased abundances of known electroactive bacterial genera, such as Geobacter (from 42% to 47%) and Desulfovibrio (from 6% to 11%). Furthermore, toxicities of different NAs concentrations measured with the Microtox bioassay test were correlated with corresponding electrical signals, indicating that MXC-biosensor can provide a dual platform for rapid assessment of both NA concentrations and NA-associated toxicity.

Optimization of thermal hydrolysis process for enhancing anaerobic digestion in a wastewater treatment plant with existing primary sludge fermentation.

Many wastewater treatment plants (WWTPs) adopted primary sludge fermentation to produce sludge liquor for the biological denitrification process. The fermented primary sludge (FPS) is usually co-digested with thickened waste activated sludge (TWAS) in the anaerobic digestion (AD) process. To date, there has been limited information on how the sludge thermal hydrolysis process (THP) could be retrofitted for enhancing AD in WWTPs with the existing primary sludge fermentation process. This study assessed two THP retrofitting schemes, (FPS + TWAS and TWAS alone) combining different exposure times (15, 30, and 60 min) and temperatures (140, 160, and 180 °C). The results suggested that temperature had more impact on sludge solubilization than exposure times. Notably, 180 °C was the most effective for sludge solubilization under both schemes. However, a higher degree of solubilization did not necessarily lead to higher methane yields. The THP of FPS + TWAS attained considerably higher methane yield than the pretreatment of TWAS alone.

Low-temperature thermal hydrolysis of sludge prior to anaerobic digestion: Principal component analysis (PCA) of experimental data.

Here, we report data of the principal component analysis (PCA) assessment and clustering analysis related to low-temperature thermal hydrolysis process (THP) for enhancing the anaerobic digestion (AD) of sludge in wastewater treatment plants (WWTPs) with primary sludge fermentation (Azizi et al., 2021). The PCA was examined to pinpoint the influence of different THP schemes on the variations of macromolecular compounds solubilization after low-temperature THP and the relative performances in enhancing methane potential in AD. We established 2 experimental setups with a total of 18 treatment conditions (3 exposure times, 30, 60, and 90 min at three temperature levels 50, 70 and 90 °C) in comparison to the untreated control samples. Scheme-1 comprises the THP of a mixture of (1:1 vol ratio) fermented primary sludge (FPS) and thickened waste activated sludge (TWAS); while scheme-2 comprised the THP of TWAS only. The factors employed in the assessment of the PCA encompassed the variations in the macromolecular compounds and other solubilization metrics. This included the variations in the levels of carbohydrates, lipids, proteins, and solubilization of chemical oxygen demand (COD) and volatile suspended solids (VSS). Furthermore, the evaluation considered the changes of volatile fatty acids (VFAs) and total ammonia nitrogen (TAN) with respect to time and temperature. The assessment of PCA classified the THP based on their differences and alterations that occurred after the treatment. The indices of the PCA assessments differed based on the factors of concern and the focus of each individual PCA assessment. In every individual PCA assessment, the respective contribution to the total variance in PCA analysis was calculated and manifested by the highest distribution of the principal components (PCs) axis PC1 and PC2. The differences in distributions of PCs after various PCA examinations can describe the relative influence of THP schemes and the most significant variables that can trigger major differences among THP conditions. The comparative differences demonstrated by PCA support the potential investigations of the efficiency of THPs conditions and their performance categories.

Microbial electrochemical systems for hydrogen peroxide synthesis: Critical review of process optimization, prospective environmental applications, and challenges.

Hydrogen peroxide (H2O2) is an industrial chemical that has been widely adopted for various industrial applications, including water and wastewater treatment. Currently, the majority of H2O2 is being produced through the anthraquinone oxidation process, which is disadvantageous due to the requirement of toxic raw materials and high energy input. Recently, microbial electrochemical cells (MXCs), such as microbial fuel cells and microbial electrolysis cells, have demonstrated great potential for effective H2O2 production via cathodic oxygen-reduction reaction (ORR). Previous studies have specified key operational parameters for scaling-up of H2O2-producing MXCs, where improvements in production rate, conversion efficiency, product concentration and stability are attainable. Moreover, various systems have demonstrated their value proposition in the contaminant removal aspects through direct removal of various environmental pollutants, water disinfection, and many more. This review is intended to highlight promising ways of H2O2 production with MXCs and on-site environmental applications of bioelectrochemically-produced H2O2.

Fourier transform infrared spectroscopy as a surrogate tool for the quantification of naphthenic acids in oil sands process water and groundwater.

Naphthenic acid fraction compounds (NAFCs), defined herein as the polar organic compounds extracted from the acidified oil sands process water (OSPW) samples using dichloromethane, are becoming the research hotspot due to their presence in large amount in OSPW and along with other potentially NA-contaminated water streams from the mining site. Fourier transform infrared spectroscopy (FTIR) method is commonly used to quantify NAFCs and assumes that the total NA concentration is measured as the sum of the responses for all carboxylic acid functional groups. In this study, the NAFCs in various OSPW and groundwater (GW) samples from an active oil sands mining site were analyzed using FTIR. All water samples were pretreated using either solid-phase extraction (SPE) or liquid-liquid extraction (LLE) methods before analysis. The results showed that SPE produced higher recoveries of NAFCs than LLE for most water samples under current experimental conditions. For the quantification of NAFCs, commercial Fluka NA mixture and a pre-calibrated OSPW extract were employed as the calibration standards. The NAFCs calibrated with Fluka NA mixture and OSPW extract had clear linear relationships. The concentrations of NAFCs obtained using OSPW extract standard curve were 2.5 times the NAFC concentrations obtained using the Fluka NA mixture standard curve. Additionally, good linear correlations were observed between the total NAs and O2-O6 NA species determined by ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-TOFMS) and the NAFCs measured by FTIR. According to these correlations, the NA compositions in NAFCs were developed, and the relative abundances of O2-O6 NA species in NAFCs were similar for SPE and LLE pretreated samples. The findings of this study demonstrated that FTIR could be used as a promising tool to monitor total NA species and to estimate the NA profile in different environmental water samples.

Monitoring of classical, oxidized, and heteroatomic naphthenic acids species in oil sands process water and groundwater from the active oil sands operation area.

The classical, oxidized, and heteroatomic naphthenic acids (NAs) species were monitored in the oil sands process water (OSPW) and groundwater from the active oil sands operation area, using solid phase extraction sample preparation and high resolution mass spectrometry analysis. Groundwater samples include Pleistocene channel aquifer groundwater (PLCA) and oil sands basal aquifer groundwater (OSBA) from different depth of underground. The concentrations of Ox-NAs decreased from OSPW to PLCA, and then increased from PLCA to OSBA, which is deeper than PLCA. The NAs in PLCA mainly comprised of Ox-NAs and N-NAs and the percentage of S-NAs was negligible. Results revealed relative abundances of individual NA species in total NAs varies among different water layers and the potential environmental impacts are expected to be variable. Principal component analysis results of O2-NAs or O4-NAs could be used for differentiation of water types. O2-NAs with n = 12-16 and |Z| = 4-6, and O4-NAs with n = 14-20 and |Z| = 6-8, were identified as marker compounds that could serve as surrogates of the larger complex NA mixture for source differentiation. This work utilized a combination of sample preparation, instrumental analysis, and statistical analysis methods to obtain knowledge of the occurrence, composition, and transfer of NAs in the groundwater of the Alberta oil sands operation area.

Characterization and determination of naphthenic acids species in oil sands process-affected water and groundwater from oil sands development area of Alberta, Canada.

This work reports the monitoring and assessment of naphthenic acids (NAs) in oil sands process-affected water (OSPW), Pleistocene channel aquifer groundwater (PLCA), and oil sands basal aquifer groundwater (OSBA) from an active oil sands development in Alberta, Canada, using ultra performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) analysis with internal standard (ISTD) and external standard (ESTD) calibration methods and Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) for compositional analysis. PLCA was collected at 45-51 m depth and OSBA was collected at 67-144 m depth. Results of Ox-NA concentrations follow an order as OSPW > OSBA > PLCA, indicating that occurrences of NAs in OSBA were likely related to natural bitumen deposits instead of OSPW. Liquid-liquid extraction (LLE) was applied to avoid the matrix effect for the ESTD method. Reduced LLE efficiency accounted for the divergence of the ISTD and ESTD calibrated results for oxidized NAs. Principle component analysis results of O2 and O4 species could be employed for differentiation of water types, while classical NAs with C13-15 and Z (-4)-(-6) and aromatic O2-NAs with C16-18 and Z (-14)-(-16) could be measured as marker compounds to characterize water sources and potential temporal variations of samples, respectively. FTICR-MS results revealed that compositions of NA species varied greatly among OSPW, PLCA, and OSBA, because of NA transfer and transformation processes. This work contributed to the understanding of the concentration and composition of NAs in various types of water, and provided a useful combination of analytical and statistical tools for monitoring studies, in support of future safe discharge of treated OSPW.

Fate and abundance of classical and heteroatomic naphthenic acid species after advanced oxidation processes: Insights and indicators of transformation and degradation.

The toxicological effects from all components in oil sands process-affected water (OSPW) are not known. Alternatively, monitoring the variations and abundance of different classes and compounds after treatments might be a useful approach in OSPW remediation. In this study, the variations in the compositions of classical and heteroatomic naphthenic acids (NAs) after treatment using advanced oxidation processes (AOPs), mainly ozone and peroxone, and two different mass spectrometry methods; ultra-performance liquid chromatography time-of-flight (UPLC-TOFMS) and Fourier transform ion cyclotron resonance (FTICR-MS), were examined. Two markers (O2S:O3S:O4S and O2:O4 ratios) were used to reveal changes and similarities of the treated water characteristics with those in natural waters. Both ratios decreased after all treatments, from 2.7:4.8:2.1 and 3.59 in raw OSPW to 0:1.4:0.5 and 0.7, respectively, in peroxone (1:2), becoming close to the reported ratios in natural waters. Toxicity toward Vibrio fischeri showed residual toxic effects after AOPs, suggesting that part of OSPW toxicity may be caused by specific compounds of NAs (i.e., similar reduction (50%) was achieved in both toxicity and abundance in O2 species with carbon 15-26) and/or generated by-products (e.g., O3S classes at double bond equivalent (DBE) = 4 and C9H12O2 at DBE = 4). Although by-products were generated, the best biodegradability enhancement and chemical oxygen demand reduction were achieved in peroxone (1:2) compared to ozone, suggesting the possibility of using combined OSPW remediation approaches (i.e., peroxone coupled with biological process). The recommended indicators can assist in evaluating the treatments' performance and in examining the best removal levels to accomplish significant toxicity reduction.

Understanding the similarities and differences between ozone and peroxone in the degradation of naphthenic acids: Comparative performance for potential treatment.

Ozonation at high doses is a costly treatment for oil sands process-affected water (OSPW) naphthenic acids (NAs) degradation. To decrease costs and limit doses, different peroxone (hydrogen peroxide/ozone; H2O2:O3) processes using mild-ozone doses of 30 and 50 mg/L were investigated. The degradation efficiency of Ox-NAs (classical (O2-NAs) + oxidized NAs) improved from 58% at 30 mg/L ozone to 59%, 63% and 76% at peroxone (1:1), 50 mg/L ozone, and peroxone (1:2), respectively. Suppressing the hydroxyl radical (•OH) pathway by adding tert-butyl alcohol did significantly reduce the degradation in all treatments, while molecular ozone contribution was around 50% and 34% for O2-NAs and Ox-NAs, respectively. Structure reactivity toward degradation was observed with degradation increase for both O2-NAs and Ox-NAs with increase of both carbon (n) and hydrogen deficiency/or |-Z| numbers in all treatments. However, the combined effect of n and Z showed specific insights and differences between ozone and peroxone treatments. The degradation pathway for |-Z|≥10 isomers in ozone treatments through molecular ozone was significant compared to •OH. Though peroxone (1:2) highly reduced the fluorophore organics and toxicity to Vibrio fischeri, the best oxidant utilization in the degradation of O2-NAs (mg/L) per ozone dose (mg/L) was observed in the peroxone (1:1) (0.91) and 30 mg/L ozone treatments (0.92). At n = 9-11, peroxone (1:1) had similar or enhanced effect on the O2-NAs degradation compared to 50 mg/L ozone. Enhancing •OH pathway through peroxone versus ozone may be an effective OSPW treatment that will allow its safe release into receiving environments with marginal cost addition.

Comparison of methods for determination of total oil sands-derived naphthenic acids in water samples.

There are several established methods for the determination of naphthenic acids (NAs) in waters associated with oil sands mining operations. Due to their highly complex nature, measured concentration and composition of NAs vary depending on the method used. This study compared different common sample preparation techniques, analytical instrument methods, and analytical standards to measure NAs in groundwater and process water samples collected from an active oil sands operation. In general, the high- and ultrahigh-resolution methods, namely high performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) and Orbitrap mass spectrometry (Orbitrap-MS), were within an order of magnitude of the Fourier transform infrared spectroscopy (FTIR) methods. The gas chromatography mass spectrometry (GC-MS) methods consistently had the highest NA concentrations and greatest standard error. Total NAs concentration was not statistically different between sample preparation of solid phase extraction and liquid-liquid extraction. Calibration standards influenced quantitation results. This work provided a comprehensive understanding of the inherent differences in the various techniques available to measure NAs and hence the potential differences in measured amounts of NAs in samples. Results from this study will contribute to the analytical method standardization for NA analysis in oil sands related water samples.

Smoking and prognostic factors in an observational setting in patients with advanced non-small cell lung carcinoma.

BACKGROUND: This prospective observational study estimated the effect of prognostic factors, particularly continued smoking during therapy, on survival in advanced non-small cell lung cancer (NSCLC) patients receiving gemcitabine-platinum. Further, prognostic factors were used to build a survival model to improve prognosis prediction in naturalistic clinical settings. METHODS: Eligibility criteria included: Stage IIIB/IV NSCLC, no prior chemotherapy, and Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. A Cox regression model was constructed and validated by randomizing patients into two datasets (Construction [C]:Validation [V]; 3:1 ratio). Country, disease stage, hypercalcemia, "N" factor, weight reduction, performance status, and superior vena cava obstruction were pre-defined variables forced into the model. Continued smoking was tested with adjustment for these variables. RESULTS: One thousand two hundred and fourteen patients (C=891 and V=323) were enrolled. The final predictive model, established in the Construction dataset, identified four significant (p≤0.05) and independent predictors of survival, which were disease stage, performance status, gemcitabine-platinum regimen, and T-stage. Smoking during therapy was not significantly associated with survival (Hazard Ratio [95% CI]: 0.955 [0.572, 1.596], p=0.8618; versus never smokers). CONCLUSIONS: Although continued smoking during therapy was not significantly associated with shorter survival, the model developed in this study forms an evidence-based approach to assessing prognosis in advanced stage NSCLC.

Local iodine pleurodesis versus thoracoscopic talc insufflation in recurrent malignant pleural effusion: a prospective randomized control trial.

OBJECTIVE: To compare the efficacy, safety, and outcome of thoracoscopic talc poudrage (TTP) versus povidone-iodine pleurodesis (PIP) through a thoracostomy tube as a palliative treatment of pleural effusion due to metastatic breast carcinoma (MBC). METHODS: A total of 42 MBC patients were prospectively enrolled in a randomized controlled trial. Twenty-two patients received TTP (group A), whereas 20 patients (group B) underwent pleurodesis by instilling povidone-iodine through a thoracostomy tube, as a bedside procedure. RESULTS: The mean age was 48.2 ± 9.9 (range: 29-64) years and 50.2 ± 7 (range: 32-62) years for groups A and B, respectively (p=ns). At presentation, all patients had moderate to severe dyspnea, New York Heart Association (NYHA)>II and Medical Research Council (MRC) dyspnea scale 3-5. Morbidity in both groups was low. Post-procedure analgesic requirements due to severe pleuritic chest pain were higher in group A (18% vs 0%, p=0.2). Four patients in group A (18%) and one in group B (5%) were febrile (>38°C) within 48 h of the procedure. Both groups achieved good symptom control, with improvement in MRC dyspnea scale (1-3). There were no in-hospital deaths. Post-procedure hospital stay was lower in group B (p=0.009). The mean progression-free interval was 6.6 (range 3-15) months. At follow-up (mean: 22.6 (range: 8-48) months), recurrence of significant pleural effusion requiring intervention was noted in two and three patients in group A and group B, respectively (p=ns). CONCLUSION: Povidone-iodine can be considered as a good alternative to TTP to ensure effective pleurodesis for patients with malignant pleural effusion due to MBC. The drug is available, cost effective and safe, can be given through a thoracostomy tube and can be repeated if necessary.

A phase II study of gemcitabine combined with vinorelbine as first-line chemotherapy for metastatic breast cancer.

BACKGROUND AND OBJECTIVES: There is an unmet need for new combination treatments, especially for aggressive, visceral, and high tumor burden metastatic breast cancer. Gemcitabine (GEM) has shown synergy with vinorelbine (VRL) in preclinical models, and has a toxicity profile that is different from VRL, another recently approved cytotoxic drug that seems to be effective in the treatment of breast cancer. METHODS: We studied the efficacy and side effects of the GEM-VRL combination as first-line chemotherapy in patients in an open-label, single arm, phase II study in patients with locally advanced or metastatic breast cancer who had been previously treated with an anthracycline-based regimen in the adjuvant/neoadjuvant setting. RESULTS: Of the 74 patients enrolled, 72 patients were evaluable for the primary treatment outcome (tumor response rates). Four patients (6%) had a complete response and 26 patients (36%) had a partial response. Nineteen patients (26%) had stable disease. The median time to disease progression was 37 weeks (range, 1-60 weeks). Median duration of response was 43 weeks (range, 8.6 to 55 weeks) and one-year survival was 77% (95% confidence interval, 64% to 86%). Grade 3-4 neutropenia without fever was reported in 10% of patients, thrombocytopenia in 1%, and febrile neutropenia in 11%. The most common clinical grade 3-4 toxicities were nausea (24%) and diarrhea and stomatitis (11% each). Hospitalizations for adverse events mainly due to anemia, febrile neutropenia, septic shock and hepatic failure occurred in 7%. CONCLUSION: With an overall response rate of 42%, the GEM-VRL combination had promising efficacy and good tolerability in metastatic breast cancer patients.