Early determination of potential critical quality attributes of therapeutic antibodies in developability studies through surface plasmon resonance-based relative binding activity assessment.

Precise measurement of the binding activity changes of therapeutic antibodies is important to determine the potential critical quality attributes (CQAs) in developability assessment at the early stage of antibody development. Here, we report a surface plasmon resonance (SPR)-based relative binding activity method, which incorporates both binding affinity and binding response and allows us to determine relative binding activity of antibodies with high accuracy and precision. We applied the SPR-based relative binding activity method in multiple forced degradation studies of antibody developability assessment. The current developability assessment strategy provided comprehensive, precise characterization of antibody binding activity in the stability studies, enabling us to perform correlation analysis and establish the structure-function relationship between relative binding activity and quality attributes. The impact of a given quality attribute on binding activity could be confidently determined without isolating antibody variants. We identified several potential CQAs, including Asp isomerization, Asn deamidation, and fragmentation. Some potential CQAs affected binding affinity of antibody and resulted in a reduction of binding activity. Certain potential CQAs impaired antibody binding to antigen and led to a loss of binding activity. A few potential CQAs could influence both binding affinity and binding response and cause a substantial decrease in antibody binding activity. Specifically, we identified low abundance Asn33 deamidation in the light chain complementarity-determining region as a potential CQA, in which all the stressed antibody samples showed Asn33 deamidation abundances ranging from 4.2% to 27.5% and a mild binding affinity change from 1.76 nM to 2.16 nM.

Case Report: Assessment of primary myxofibrosarcoma in the left atrium using multimodal ultrasonography.

Primary myxofibrosarcoma of the heart, a rare cardiac malignancy, was diagnosed in a middle-aged female patient exhibiting progressive dyspnea following transthoracic echocardiography and pathological analysis. Postoperatively, the patient underwent chemotherapy and Lenvatinib mesylate therapy, with regular check-ups confirming her survival. After 10 months the patient is still alive and well.

Comparison of nutrients status in Liaodong Bay and Northern Yellow Sea, China: Controlling factors and nutrient budgets.

Under the dual stress of global warming and human interaction, Liaodong Bay (LDB) and northern Yellow Sea (NYS) are undergoing significant ecological changes. Little is known about the driving nutrients characteristics supporting fishery resource output in these areas. We carried out three field observations in 2019 to investigate nutrient status. Results showed that dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP), and dissolved silica (DSi) concentrations changed seasonally, with lowest values in spring, and highest values in autumn. High DIN, DIP, and DSi concentrations were detected in LDB and NYS's estuary areas. The Yellow Sea Cold Water Mass plays a role in the distribution and seasonal variation of nutrients. Exchanges across the sediment-water interface, SFGD, atmospheric deposition, and the adjacent sea input dominated DIN dynamics of these areas. DIP primarily came from the adjacent sea input and DSi mainly originated from sediment release and the adjacent sea input. NYS seawater invasion accounted for 13.8% of DIN, 63.4% of DIP, and 35.1% of DSi in LDB. These results provide new insights to better facilitate the formulation of nitrogen and phosphorus reduction and control policies in these marginal seas.

Risk assessment of eighteen elements leaching from ceramic tableware in China.

Ceramic products are among the most frequently used food contact materials. Health risks associated with ceramic tableware usually arise from the migration of heavy metals. In this study, 767 pieces of ceramic tableware of different shapes and types were collected across China, and the migration levels of 18 elements were determined using inductively coupled plasma mass spectrometry. Migration tests were conducted according to the Chinese National Food Safety Standard - Ceramic Ware (GB 4806.4) with microwaveable and non-microwavable samples under different conditions. The food consumption of consumers via different shapes of ceramic tableware was obtained through a self-reported web-based survey, and the estimated dietary intakes of the studied elements were calculated accordingly. The exposure assessment showed that certain metals leached from the ceramic tableware at levels of concern. In addition, the applicability of the migration experiment conditions for microwaveable ceramic ware in GB 4806.4 needs to be further investigated.

Fast Detection of Cadmium in Chocolate by Solid Sampling Electrothermal Vaporization Atomic Absorption Spectrometry and Its Application on Dietary Exposure Risk Assessment.

In this work, a rapid detection method using solid sampling electrothermal vaporization atomic absorption spectrometry (SS-ETV-AAS) was established for cadmium in chocolate. The instrumental system includes a solid sampling ETV unit, a catalytic pyrolysis furnace, an AAS detector, and a gas supply system with only an air pump and a hydrogen generator. Herein, MgO material with 1.0−1.5 mm particle size was first employed to replace the kaolin filler previously used to further shorten the peak width and to thereby improve the sensitivity. With 350 mL/min of air, a chocolate sample was heated for 25 s from 435 to 464 °C to remove water and organic matrices; then, after supplying 240 mL/min hydrogen and turning down air to 120 mL/min, a N2/H2 mixture gas was formed to accelerate Cd vaporization from chocolate residue under 465 to 765 °C. Under the optimized conditions, the detection limit (LOD) was obviously lowered to 70 pg/g (vs. previous 150 pg/g) with R2 > 0.999; the relative standard deviations (RSD) of repeated measurements for real chocolate samples ranged from 1.5% to 6.4%, indicating a favorable precision; and the Cd recoveries were in the range of 93−107%, proving a satisfied accuracy. Thus, the total analysis time is less than 3 min without the sample digestion process. Thereafter, 78 chocolate samples with different brands from 9 producing countries in China market were collected and measured by this proposed method. Based on the measured Cd concentrations, a dietary exposure assessment was performed for Chinese residents, and the target hazard quotient (THQ) values are all less than 1, proving no significant health risk from intaking chocolate cadmium for Chinese residents.

Cavitation based cleaner technologies for biodiesel production and processing of hydrocarbon streams: A perspective on key fundamentals, missing process data and economic feasibility - A review.

The present review emphasizes the role of hydrodynamic cavitation (HC) and acoustic cavitation in clean and green technologies for selected fuels (of hydrocarbon origins such as gasoline, naphtha, diesel, heavy oil, and crude oil) processing applications including biodiesel production. Herein, the role of cavitation reactors, their geometrical parameters, physicochemical properties of liquid media, liquid oxidants, catalyst loading, reactive oxygen species, and different types of emulsification and formation of radicals, formation as well as extraction of formed by-products are systematically reviewed. Among all types of HC reactors, vortex diode and single hole orifices revealed more than 95 % desulfurization yield and a 20 % viscosity reduction in heavy oil upgrading, while multi-hole orifice (100 holes) and slit Venturi allowed obtaining the best biodiesel production processes in terms of high (%) yield, low cost of treatment, and short processing time (5 min; 99 % biodiesel; 4.80 USD/m3). On the other hand, the acoustic cavitation devices are likely to be the most effective in biodiesel production based on ultrasonic bath (90 min; 95 %; 6.7 $/m3) and desulfurization treatment based on ultrasonic transducers (15 min; 98.3 % desulfurization; 10.8 $/m3). The implementation of HC-based processes reveals to be the most cost-effective method over acoustic cavitation-based devices. Finally, by reviewing the ongoing applications and development works, the limitations and challenges for further research are addressed emphasizing the cleaner production and guidelines for future scientists to assure obtaining comprehensive data useful for the research community.

Risk on assessment of 15 REEs and mixtures by DGT in Songhua River system sediments of China's largest old industrial base.

Rare earth elements (REEs) are increasingly used in the high-tech sectors in the world and are therefore called burgeoning contaminants. As diffusive gradients in thin films (DGT) can be used to assess the bioavailability of inorganic matters, in this paper, we evaluated, for the first time, the ecotoxicology risks of REEs and their mixtures in river sediments of China's old industrial base by DGT. During our research, taking the Songhua River system (SRS) as an example, we detected its surficial sediments, of which the DGT-labile concentration of REEs (∑REEs) was 2.07-8.76 µg/L. As for the single toxicity, the risk quotient (RQ) values of Y at all sites were significantly greater than 1; while the values of Nd and Pr in some upstream reaches were all significantly greater than the threshold (1), indicating that these adverse effects of single REEs were not neglected. In terms of the combined toxicity of REEs mixtures, we carried out an assessment of the risks of probabilistic ecotoxicology, which showed that the SRS superficial sediments had a low probability of toxicity to aquatic organisms (0.54%).

Dynamic energy budget modeling of Atlantic surfclam, Spisula solidissima, under future ocean acidification and warming.

A dynamic energy budget (DEB) model integrating pCO2 was used to describe ocean acidification (OA) effects on Atlantic surfclam, Spisula solidissima, bioenergetics. Effects of elevated pCO2 on ingestion and somatic maintenance costs were simulated, validated, and adapted in the DEB model based upon growth and biological rates acquired during a 12-week laboratory experiment. Temperature and pCO2 were projected for the next 100 years following the intergovernmental panel on climate change representative concentration pathways scenarios (2.6, 6.0, and 8.5) and used as forcing variables to project surfclam growth and reproduction. End-of-century water warming and acidification conditions resulted in simulated faster growth for young surfclams and more energy allocated to reproduction until the beginning of the 22nd century when a reduction in maximum shell length and energy allocated to reproduction was observed for the RCP 8.5 scenario.

Assessment of the efficacy of tuina on treating cervicogenic headache: A protocol for systematic review and meta-analysis.

BACKGROUND: Cervicogenic headache is a secondary headache characterized by unilateral headache, symptoms, and signs of neck involvement. It is often worsened by neck movement, sustained awkward head position, or external pressure over the upper cervical or occipital region on the symptomatic side. In this systematic review, we aimed to evaluate the efficacy and safety of massage therapy for the treatment of cervicogenic headache. METHODS: We searched the China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, China Doctoral Dissertations Full-Text Database, China Master's Theses Full-Text Database, Cochrane Central Register of Controlled Trials, PubMed, and Embase. We will select all eligible studies published on or before April 1, 2021. We will use Review Manager 5.4, provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed the outcome measures. RESULTS: This meta-analysis further confirmed the benefits of tuina in the treatment of cervicogenic headache. CONCLUSION: The purpose of this meta-analysis was to explore the effect of tuina on patients with cervicogenic headache and to provide more options for clinicians and patients to treat cervicogenic headache. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of tuina in the treatment of cervicogenic headache. Since all the data included were published, the systematic review did not require ethical approval. REGISTRATION NUMBER: INPLASY202150053.

From Globalization to Regionalization: The United States, China, and the Post-Covid-19 World Economic Order.

The Covid-19 pandemic has intensified the debate among optimists, pessimists, and centrists about whether the world economic order is undergoing a fundamental change. While optimists foresee the continuation of economic globalization after the pandemic, pessimists expect localization instead of globalization, given the pandemic's structural negative consequence on the world economy. By contrast, the centrists anticipate a "U-shaped" recovery, where Covid-19 will not kill globalization but slow it down. The three existing perspectives on Covid-19's impact on the economic globalization are not without merit, but they do not take sufficient temporal distance from the ongoing issue. This article suggests employing the historical perspective to expand the time frame by examining the rise and fall of economic globalization before and after the 2008 global financial crisis. The authors argue that economic globalization has been in transition since the 2008 financial crisis, and one important but not exclusive factor to explain this change is the evolving US-China economic relationship, from symbiotic towards increasingly competitive. The economic restructuring in US and China has begun after both countries weathered the 2008 crisis and gained momentum since the outbreak of trade war and Covid-19. The article investigates this trend by distinguishing different types of production activities, and the empirical results confirm that localization and regionalization have been filling the vacuum of economic globalization in retreat in the last decade.

Increased Risk for New-Onset Psychiatric Adverse Events in Patients With Newly Diagnosed Primary Restless Legs Syndrome Who Initiate Treatment With Dopamine Agonists: A Large-Scale Retrospective Claims Matched-Cohort Analysis.

STUDY OBJECTIVES: Published literature documents increased risk for psychiatric adverse events (P-AEs) following dopamine agonist (DA) initiation for treatment of primary restless legs syndrome (RLS). We examined the association between DA initiation and subsequent new-onset P-AEs among patients with a new diagnosis of RLS who had no history of psychiatric disorder or DA use. METHODS: Selected were adults (age 18 years or older) enrolled through United States employer-sponsored plans and Medicare Advantage from 7/1/2008-12/31/2014, with ≥ 2 years of claims data preceding their first RLS diagnosis ("preindex period"). Excluded were those with psychiatric diagnoses (International Classification of Diseases, Ninth Revision [ICD-9] 290-319) or DA use during the preindex period, and those with possible secondary RLS. Patients who initiated (DA+) versus did not initiate (DA-) DAs were matched 1:1 on age at index RLS diagnosis, sex, geographic region, and employment status, and preindex period comorbid illness burden and number of non-DA drug fills. Using a validated ICD-9-based severity-of-illness psychiatric disorder classification system, we compared likelihoods of new-onset P-AEs between matched pairs during parallel follow-up periods. RESULTS: Identified were 889 matched pairs. Compared with their DA- counterparts, DA+ patients were nearly two times more likely to experience development of any P-AE (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.31-2.24, P < .0001); and similarly more likely to experience the development of a severe (OR 1.68, 95% CI 1.03-2.86, P = .04), moderately severe (OR 1.63, 95% CI 1.17-2.29, P = .004), or mild (OR 1.72, 95% CI 1.12-2.65, P = .01) P-AE. CONCLUSIONS: Compared to DA- matched control patients, patients in whom RLS was newly diagnosed and who initiated de novo DAs demonstrated significantly increased risk for subsequent development of P-AEs of any severity. CITATION: Hankin C, Lee D, Garcia-Borreguero D, Wang Z. Increased risk for new-onset psychiatric adverse events in patients with newly diagnosed primary restless legs syndrome who initiate treatment with dopamine agonists: a large-scale retrospective claims matched-cohort analysis. J Clin Sleep Med. 2019;15(9): 1225-1232.

Clinical Assessment of Histidine-Tryptophan-Ketoglutarate Solution and Modified St. Thomas' Solution in Pediatric Cardiac Surgery of Tetralogy of Fallot.

The objective of this study is to compare the myocardium protective effect of Bretschneider's histidine-tryptophan-ketoglutarate (HTK) solution versus Modified St. Thomas' (STH) solution in pediatric cardiac surgery of Tetralogy of Fallot (TOF). Seventy-seven pediatric patients of TOF who received the total surgical repair were reviewed, from January 2014 to October 2015. A horizontal comparison between HTK solution and modified STH solution has been made since the HTK solutions were started to be used in our hospital. The patients were divided into the HTK group (n = 35) and the STH group (n = 33). The perioperative values of the groups were assessed in this study. The primary endpoints including spontaneous cardiac re-beating time, intensive care unit (ICU) stay, overall stay, mechanical ventilation postoperation, postoperation stay, overall stay, and perioperative echocardiographic results were analyzed in this study. We found that spontaneous cardiac re-beating time of the HTK group was significantly shorter than that of the STH group (0.26 min ± 0.56 vs. 1.33 ± 1.02, P < 0.001). There were no significant differences between the two groups in ICU stay (P = 0.29), postoperative mechanical ventilation time (P = 0.84), overall stay (0.73); and the mortalities of the two groups were similar (2.9 vs. 3.0%). Aimed at pediatric cardiac surgery of TOF, this study suggests that with similar aorta cross-clamping time, modified STH solution is as safe as HTK solution.

Toxic assessment of the leachates of paddy soils and river sediments from e-waste dismantling sites to microalga, Pseudokirchneriella subcapitata.

The potential adverse effects of e-waste recycling activity on environment are getting increasing concern. In this work, a model alga, Pseudokirchneriella subcapitata, was employed to assess the toxic effects of the leachates of paddy soils and river sediments collected from e-waste dismantling sites. Chemical analysis of the paddy soils and river sediments and their leachates were carried out and the growth rate, chlorophyll a fluorescence and anti-oxidative systems of the alga were measured. Results showed that two leachates decreased the amount of PSII active reaction centers and affected photosynthesis performance, interfered with chlorophyll synthesis and inhibited algal growth. Some chemical pollutants in the sediments and soils such as polybrominated diphenyl ethers (PBDEs) and metals derived from e-waste recycling activity may impose oxidative stress on algae and affect the activity of anti-oxidative enzymes such as GST, SOD, CAT and APX. The leachates of both river sediments and paddy soils are potentially toxic to the primary producers, P. subcapitata and the leachate from sediments was more deleterious than that from soils.

Producing more grain with lower environmental costs.

Agriculture faces great challenges to ensure global food security by increasing yields while reducing environmental costs. Here we address this challenge by conducting a total of 153 site-year field experiments covering the main agro-ecological areas for rice, wheat and maize production in China. A set of integrated soil-crop system management practices based on a modern understanding of crop ecophysiology and soil biogeochemistry increases average yields for rice, wheat and maize from 7.2 million grams per hectare (Mg ha(-1)), 7.2 Mg ha(-1) and 10.5 Mg ha(-1) to 8.5 Mg ha(-1), 8.9 Mg ha(-1) and 14.2 Mg ha(-1), respectively, without any increase in nitrogen fertilizer. Model simulation and life-cycle assessment show that reactive nitrogen losses and greenhouse gas emissions are reduced substantially by integrated soil-crop system management. If farmers in China could achieve average grain yields equivalent to 80% of this treatment by 2030, over the same planting area as in 2012, total production of rice, wheat and maize in China would be more than enough to meet the demand for direct human consumption and a substantially increased demand for animal feed, while decreasing the environmental costs of intensive agriculture.

Assessment of metal contamination in surface sediments from Zhelin Bay, the South China Sea.

Metals and biogenic elements were analyzed from surface sediments collected from Zhelin Bay in the South China Sea in December 2008. The high concentrations of TOC, TN and BSi indicate the high nutrient level and diatom productivity in Zhelin Bay. The concentrations of metals were generally far lower than the effects-range-low (ERL) values that define pollutant levels. Enrichment factors (EF) and geoaccumulation indices (Igeo) suggest there are pollution levels of Cd, Cu and Zn at some stations. As, Cu, and Pb are potentially biotoxic in some stations. Correlation and principal component analyses indicate that most of the metals primarily originate from natural sources, and from maricultural activities as well. Mariculture contributes considerable Cd and Cu contamination. As and Pb comes primarily from combustion of gasoline and diesel fuel by ships.

Rates of guideline adherence among US community oncologists treating NSCLC.

OBJECTIVES: To evaluate chemotherapy regimen utilization in patients with non-small cell lung cancer (NSCLC) treated in US community oncology practices, to examine the relationship between evidence-based guideline adherence and the follow-up monitoring period (FUMP) over 1.5 years, and to understand the relative costs of commonly administered chemotherapy regimens. STUDY DESIGN: Retrospective data analysis. METHODS: Using a large US medical oncology clinical database derived from a proprietary web-based drug dispensing technology, we identified adult patients with NSCLC who started adjuvant therapy for early-stage disease or first-line therapy for advanced and metastatic disease from July 1, 2009, through June 30, 2010. Adjuvant or first-line regimen utilization and the FUMP within 1.5 years were analyzed with respect to national evidence-based guideline adherence. Costs for commonly administered regimens based on 2010 Medicare reimbursement were compared. RESULTS: A total of 3505 patient treatment regimens were included in this study. Rates of guideline adherence were 75.0% and 61.3% for the first-line and the adjuvant treatment groups, respectively (P < .0001). Treatment with guidelinebased regimens correlated with a significantly longer FUMP in the first-line treatment groupcompared with non-guideline-based regimens (P = .005). Regimen costs for the top 11 regimens in the adjuvant and first-line treatment settings varied greatly. Low-cost regimens were prescribed more commonly. CONCLUSIONS: Rates of guideline adherence were significantly higher in the first-line than in the adjuvant NSCLC treatment group. First-line treatment with guideline-based regimens correlated with an extended FUMP for advanced NSCLC patients.

Allergy immunotherapy: reduced health care costs in adults and children with allergic rhinitis.

BACKGROUND: Research demonstrates significant health care cost savings conferred by allergen-specific immunotherapy (AIT) to US children with allergic rhinitis (AR). OBJECTIVE: We sought to examine whether AIT-related cost benefits conferred to US children with AR similarly extend to adults. METHODS: A retrospective (1997-2009) Florida Medicaid claims analysis compared mean 18-month health care costs of patients with newly diagnosed AR who received de novo AIT and were continuously enrolled for 18 months or more versus matched control subjects not receiving AIT. Analyses were conducted for the total sample and separately for adults (age≥18 years) and children (age<18 years). RESULTS: Matched were 4,967 patients receiving AIT (1,319 adults and 3,648 children) and 19,278 control subjects (4,815 adults and 14,463 children). AIT-treated enrollees incurred 38% ($6,637 vs $10,644, P<.0001) lower mean 18-month total health care costs than matched control subjects, with significant savings observed within 3 months of AIT initiation. Compared with control subjects, significantly lower 18-month mean health care costs were demonstrated overall (38%; $6,637 for patients receiving AIT vs $10,644 for control subjects, P<.0001), and for both AIT-treated adults (30%; $10,457 AIT vs $14,854 controls, P<.0001) and children (42%; $5,253 AIT vs $9,118 controls, P<.0001). The magnitude of 18-month health care cost savings realized by AIT-treated adults and children did not significantly differ ($4,397 vs $3,965, P=.435). CONCLUSIONS: Patients with newly diagnosed AR initiating AIT incurred significantly lower health care costs than matched control subjects beginning 3 months after AIT initiation and continuing throughout the 18-month follow-up period. The significant cost benefits achieved by children with AR diagnoses who initiated AIT were also observed for adults with AR diagnoses who initiated AIT.

Medical costs and adherence in patients receiving aqueous versus pressurized aerosol formulations of intranasal corticosteroids.

Intranasal corticosteroid (INS) formulations have different sensory attributes that influence patient preferences, and thereby possibly adherence and health outcomes. This study compares health care use and costs and medication adherence in matched cohorts of patients with allergic rhinitis (AR) using a chlorofluorocarbon-propelled pressurized metered-dose inhaler (pMDI) or aqueous intranasal corticosteroid (A-INS). Florida Medicaid retrospective claims analysis was performed of enrollees aged ≥12 years with at least 1 year of continuous enrollment before their initial AR diagnosis, 1 year for continuous enrollment before their index INS claim, and 18 months of continuous enrollment after their index INS claim during which they received either pMDI or A-INS. pMDI and A-INS patients were matched 1:2 using propensity scores. Nonparametric analyses compared outcomes between matched cohorts at 6, 12, and 18 months of follow-up. A total of 585 patients were matched (pMDI = 195, A-INS = 390). pMDI patients were more adherent to INS, as reflected in their higher median medication possession ratio (53.2% versus 32.7%; p < 0.0001) and fewer median days between fills (73 days versus 111 days; p = 0.0003). Significantly lower median per patient pharmacy fills (34.0 versus 50.5; p < 0.05) and costs ($1282 versus $2178; p < 0.01) were observed among pMDI patients versus A-INS patients 18 months after INS initiation and were maintained when analyses excluded INS fills. Adherence to INS and health care utilization and costs following INS initiation for AR differed by type of formulation received. Our findings suggest patient preferences for INS sensory attributes can drive adherence and affect disease control, and ultimately impact health care costs.

Molecular crystal lithography: a facile and low-cost approach to fabricate nanogap electrodes.

A novel cost-efficient and facile technique, molecular crystal lithography, to fabricate nanogap electrodes efficiently is reported. The gap width of the electrodes can be tuned from ∼9 nm to several micrometers. Organic field-effect transistors based on the nanogap electrodes all exhibit a high performance, indicating the effectiveness and practicability of molecular crystal lithography for mass production of nanogap electrodes.