bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Progression‐Free Survival, Objective Response Rate, and Overall Survival in Clinical Trials of PD‐1/PD‐L1 Immune Checkpoint Blockade: A Meta‐Analysis
Authors: Ye Jiabu , Ji Xiang , Dennis Phillip A. , Abdullah Hesham , Mukhopadhyay Pralay
Published: June 2020

PD‐1/PD‐L1 immune checkpoint blockade (ICB) has improved overall survival (OS) in solid tumor trials; however, parallel improvements in Response Evaluation Criteria in Solid Tumors (RECIST)‐based surrogate end points, progression‐free survival (PFS), and objective response rate (ORR), are not always observed. Here, we assess the surrogacy of PFS/ORR for OS with ICB therapy across advanced/metastatic tumors. In a trial‐level analysis (N = 40 randomized trials), PFS, ORR, and OS treatment effects were correlated (Spearman's rho). In a patient‐level analysis, data were extracted from available trials of durvalumab; the correlation of PFS and OS was evaluated (Bayesian normal‐induced‐copula‐estimation model) and the ordinal association between objective response and OS hazard ratio (HR) were assessed with concordance index measures. High correlation was observed between PFS HR and OS HR in intention‐to‐treat (ITT; rho = 0.76) and PD‐L1‐enriched populations (0.74); modest (or limited) benefit in PFS was associated with meaningful improvement in OS. Moderate correlations were observed between ΔORR and OS HR: ITT, −0.63; PD‐L1‐enriched, −0.53. At the patient level, a positive association was observed between PFS and OS in non‐small cell lung cancer (Kendall’s Tau = 0.793; 95% confidence interval, 0.789–0.797), head and neck squamous cell carcinoma (0.794; 0.789–0.798), and bladder cancer (0.872; 0.869–0.875). Objective responders had significantly better OS (concordance index > 0.9) than nonresponders across these tumor types. Modest (or limited) improvement in RECIST‐based end points did not rule out meaningful OS benefit, indicating they are imperfect surrogates and do not fully capture ICB clinical benefit. Therefore, caution is advised when basing early discontinuation of novel ICB agents on these end points.
Single‐Arm Clinical Trials as Pivotal Evidence for Cancer Drug Approval: A Retrospective Cohort Study of Centralized European Marketing Authorizations Between 2010 and 2019
Authors: Tenhunen Olli , Lasch Florian , Schiel Anja , Turpeinen Miia
Published: June 2020

The traditional drug development paradigm, consisting of sequential phases and randomized studies, has been challenged in oncology and hemato‐oncology. In the regulatory context, a number of new products have been authorized based on nonrandomized efficacy and safety data. We retrospectively analyzed the European public assessment reports for anticancer treatments authorized between 2010 and 2019 to describe the data behind such approvals. Twenty‐two initial marketing authorizations, mainly conditional, were identified. Fifty percent of the products had an orphan indication, and 77% had received previous scientific advice. Conclusions of clinical benefit were based on tumor responses, ranging between 15.8 and 88%. Our data shows that single‐arm clinical studies leading to positive regulatory outcomes share common methodological approaches and end points, mostly comparing the overall response rate with a fixed success threshold as the primary analysis. The clinical indications in these approvals are clustered in late‐line settings, hematological malignancies, and lung cancer. Our findings underline the need to reflect on the current practice, the methodological aspects, and end points in single‐arm studies, and develop specific regulatory guidance on nonrandomized and novel study designs.
HucMSC‐exosomes carrying miR‐326 inhibit neddylation to relieve inflammatory bowel disease in mice
Authors: Wang Gaoying , Yuan Jintao , Cai Xiu , Xu Zhiwei , Wang Jingyan , Ocansey Dickson K.W. , Yan Yongmin , Qian Hui , Zhang Xu , Xu Wenrong , Mao Fei
Published: June 2020

Background

Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammation that is a risk factor for many gastrointestinal cancers. Exosomes are gradually gaining attention as an emerging treatment method for IBD due to their important biological characteristics. NF‐κB is an important pro‐inflammatory transcription factor kept inactive by IκB protein in the cytoplasm by masking the nuclear localization signal of NF‐κB. The deterioration of IκB is mainly ubiquitination, and this depends on neddylation.

Methods

In this study, we established a dextran sulfate sodium (DSS)‐induced IBD model in BABL/C mice to evaluate the effect of human umbilical cord mesenchymal stem cell‐derived exosomes (hucMSC‐exosomes, hucMSC‐Ex) on the repair of IBD. At the same time, human colorectal mucosa cells (FHC) were stimulated by LPS (lipopolysaccharide) in vitro to activate the inflammatory environment to study the mechanism of hucMSC‐Ex regulating neddylation. The microRNA (miRNA) obtained by sequencing and transfection with hucMSC‐Ex was used to verify the role of miR‐326/neddylation/IκB/NF‐κB signaling pathway in IBD repair.

Results

HucMSC‐Ex inhibited the process of neddylation in relieving DSS‐induced IBD in mice. The binding of NEDD8 (neural precursor cell‐expressed, developmentally downregulated gene 8) to cullin 1 and the activation of NF‐κB signaling pathway were suppressed along with reduced expression levels of neddylation‐related enzyme molecules. The same phenomenon was observed in FHC cells. The miRNA comparison results showed that miR‐326 was highly expressed in hucMSC‐Ex and played an important role in inhibiting the neddylation process. The therapeutic effect of hucMSC‐Ex with high expression of miR‐326 on IBD mice was significantly stronger than that of ordinary hucMSC‐Ex.

Conclusions

HucMSC‐Ex relieves DSS‐induced IBD in a mouse model by inhibiting neddylation through miR‐326.
Evidence for endothelial‐to‐mesenchymal transition in human brain arteriovenous malformations
Authors: Shoemaker Lorelei D. , McCormick Aaron K. , Allen Breanna M. , Chang Steven D.
Published: June 2020

Background

Brain arteriovenous malformations (AVMs) are rare, potentially devastating cerebrovascular lesions that can occur in both children and adults. AVMs are largely sporadic and the basic disease biology remains unclear, limiting advances in both detection and treatment. This study aimed to investigate human brain AVMs for endothelial‐to‐mesenchymal transition (EndMT), a process recently implicated in cerebral cavernous malformations (CCMs).

Methods

We used 29 paraffin‐embedded and 13 fresh/frozen human brain AVM samples to profile expression of panels of EndMT‐associated proteins and RNAs. CCMs, a cerebrovascular disease also characterized by abnormal vasculature, were used as a primary comparison, given that EndMT specifically contributes to CCM disease biology. AVM‐derived cell lines were isolated from three fresh, surgical AVM samples and characterized by protein expression.

Results

We observed high collagen deposition, high PAI‐1 expression, and expression of EndMT‐associated transcription factors such as KLF4, SNAI1, and SNAI2 and mesenchymal‐associated markers such as VIM, ACTA2, and S100A4. SMAD‐dependent TGF‐β signaling was not strongly activated in AVMs and this pathway may be only partially involved in mediating EndMT. Using serum‐free culture conditions, we isolated myofibroblast‐like cell populations from AVMs that expressed a unique range of proteins associated with mature cell types and with EndMT. Conditioned medium from these cells led to increased proliferation of HUVECs and SMCs.

Conclusions

Collectively, our results suggest a role for EndMT in AVM disease. This may lead to new avenues for disease models to further our understanding of disease mechanisms, and to the development of improved diagnostics and therapeutics.
Curriculum as place: The social relevance of the secondary school curriculum in Jamaica
Authors: Roofe Carmel
Published: June 2020

A socially relevant curriculum connects learning to the needs of students as members of families, communities and society. Curriculum as place is concerned with experience; how the curriculum nurtures students' learning, growth and development and how they in turn make meaning of what they are learning given their situatedness. This study, therefore, sought to explore students' views on how their school curriculum influenced their engagement at the personal, family and community levels thereby making it socially relevant. Data from interviews of 27 high school students provide thick descriptions of participants shared views and are used to theorise about how the curriculum influenced students' engagement. The main findings indicated that students' perception of what curriculum is, influenced their interpretation of how their curriculum experiences facilitated their engagement and this interpretation was linked to their situated agency. The findings also underscored the role of the curriculum as a critical tool for creating social consciousness and destroying coloniality of knowledge. Using the findings of the study, the author argues that for society to change and for curriculum to be socially relevant the purposes of the curriculum must facilitate agency and social consciousness at three levels; personal; family and community.
Understanding embryonic development for cell‐based therapies of intervertebral disc degeneration: Toward an effort to treat disc degeneration subphenotypes
Authors: Tessier Steven , Risbud Makarand V.
Published: June 2020

Chronic low back and neck pain are associated with intervertebral disc degeneration and are major contributors to the global burden of disability. New evidence now suggests that disc degeneration comprises a spectrum of subphenotypes influenced by genetic background, age, and environmental factors, which may be contributing to the mixed outcomes seen in clinical trials of cell‐based therapies that aim to treat disc degeneration. This problem is further compounded by the fact that disc degeneration and aging coincide with an exhaustion of endogenous progenitor cells, imposing limitations on the regenerative capacity of the disc. At the bench‐side, current work is focused on applying our knowledge of embryonic disc development to direct and refine differentiation of adult and human‐induced pluripotent stem cells into notochord‐like and nucleus pulposus‐like cells for use in novel cell‐based therapies. Accordingly, this review presents the salient features of intervertebral disc development, post‐natal maintenance, and regeneration, with emphasis on recent advancements. We also discuss how a stratified approach can be undertaken for the development of future cell‐based therapies to bring emerging subphenotypes into consideration.
Marine water environmental DNA metabarcoding provides a comprehensive fish diversity assessment and reveals spatial patterns in a large oceanic area
Authors: Fraija‐Fernández Natalia , Bouquieaux Marie‐Catherine , Rey Anaïs , Mendibil Iñaki , Cotano Unai , Irigoien Xabier , Santos María , Rodríguez‐Ezpeleta Naiara
Published: June 2020

Current methods for monitoring marine fish (including bony fishes and elasmobranchs) diversity mostly rely on trawling surveys, which are invasive, costly, and time‐consuming. Moreover, these methods are selective, targeting a subset of species at the time, and can be inaccessible to certain areas. Here, we used environmental DNA (eDNA), the DNA present in the water column as part of shed cells, tissues, or mucus, to provide comprehensive information about fish diversity in a large marine area. Further, eDNA results were compared to the fish diversity obtained in pelagic trawls. A total of 44 5 L‐water samples were collected onboard a wide‐scale oceanographic survey covering about 120,000 square kilometers in Northeast Atlantic Ocean. A short region of the 12S rRNA gene was amplified and sequenced through metabarcoding generating almost 3.5 million quality‐filtered reads. Trawl and eDNA samples resulted in the same most abundant species (European anchovy, European pilchard, Atlantic mackerel, and blue whiting), but eDNA metabarcoding resulted in more detected bony fish and elasmobranch species (116) than trawling (16). Although an overall correlation between fishes biomass and number of reads was observed, some species deviated from the common trend, which could be explained by inherent biases of each of the methods. Species distribution patterns inferred from eDNA metabarcoding data coincided with current ecological knowledge of the species, suggesting that eDNA has the potential to draw sound ecological conclusions that can contribute to fish surveillance programs. Our results support eDNA metabarcoding for broad‐scale marine fish diversity monitoring in the context of Directives such as the Common Fisheries Policy or the Marine Strategy Framework Directive.
Reduced pain and analgesic use after acoustic binaural beats therapy in chronic pain ‐ A double‐blind randomized control cross‐over trial
Authors: Gkolias Vasileios , Amaniti Aikaterini , Triantafyllou Areti , Papakonstantinou Panagiota , Kartsidis Panagiotis , Paraskevopoulos Evangelos , Bamidis Panagiotis D. , Hadjileontiadis Leontios , Kouvelas Dimitrios
Published: June 2020

Background

Binaural Beats (BB) consist of two artificial acoustic stimuli with different frequency, presented simultaneously but independently to each ear. The human brain perceives and synchronizes to this frequency difference (entrainment). Aim of this study was to test the hypothesis that brain entrainment to a lower function rhythm, with BB application, can decrease pain perception and analgesic medication use, in chronic pain patients.

Methods

In a double blind, randomized, cross‐over trial, BB at 5Hz (theta rhythm) were applied for 30 minutes, under simultaneous electroencephalogram recordings, followed by liberal, on demand use by chronic pain patients for a week, compared to sham stimulation (SS). Pain as the main outcome (numeric scale, NRS), stress (STAI) and medication usage (defined daily doses, DDD) were assessed at baseline, 30 minutes and week's end.

Results

Perceived pain (NRS) was significantly reduced in BB intervention (5.6±2.3 to 3.4±2.6, p<0.001), compared to SS (5.2±2.1 to 4.8±2.3, p=0.78), during the first 30‐minute phase, as well as at the week's end (to 3.9±2.5 compared to 5.5±2.6 respectively, p<0.001). The mean EEG theta power at 5Hz was significantly increased only during BB application. Stress was significantly reduced at 30 minutes in both interventions but remained reduced only in the BB group at the week's end. Analgesic medication consumption (DDD, g) during the week was significantly less in the BB intervention (3.9±3.7 vs. 4.6±4.1, p<0.05), while reporting equal to SS mean levels of pain.

Conclusions

Acoustic BB reduced pain intensity, stress and analgesic use, compared to SS, in chronic pain patients.

Significance

This study provides evidence that theta rhythm binaural beats can alleviate pain intensity, both after a brief 30 minute and a longer one week on‐demand intervention. The subsequent significant reduction in analgesic medication consumption in chronic pain patients' daily living could offer a valuable tool, augmenting the effect of existing pain therapies.
Standing up for whom? Targets’ different goals in the confrontation of discrimination
Authors: Munder Anja K. , Becker Julia C. , Christ Oliver
Published: June 2020

We challenge the common interpretation of targets’ immediate confrontation in reaction to discrimination as self‐serving behavior and propose different underlying motivations for this phenomenon. In five online scenario studies (Noverall = 1,447), we demonstrate across different samples and contexts that targets indicate a distinct pursuit of the following self‐reported confrontation goals: individual‐benefit (e.g., perpetrator apologizes); group‐benefit (e.g., prejudice reduction); and distancing (e.g., demonstrating that one is different from typical group members). Furthermore, meaningful associations of the pursuits of individual‐benefitting goals and group‐benefitting goals with group identification, disidentification, and further collective action intentions indicate that they represent different confrontation motivations: Individual‐benefitting confrontation serves to cope with the individual mistreatment of discrimination, whereas group‐benefitting confrontation represents a form of collective action. Distancing goals were associated with disidentification and—unexpectedly—group identification. Our results show that the phenomenon of confrontation in reaction to discrimination can be the result of different underlying psychological processes.
Ginsenoside Rg3 inhibits the biological activity of SGC‐7901
Authors: Yang Qing , Cai Ning , Che Daobiao , Chen Xing , Wang Dongliang
Published: June 2020

Aim

To explore the suppressive effects of ginsenoside Rg3 on the biological activities of gastric cancer and the mechanisms responsible therein, by conducting an in vitro study.

Materials and Methods

SGC‐7901 gastric cancer cells were divided into NC, DMSO, Gin‐Low (10 mg/L), Gin‐Middle (20 mg/L), and Gin‐High (40 mg/L) groups. Using MTT, flow cytometry, transwell, and wound‐healing assays, the cell biological activities in the different groups were evaluated; the protein expression levels of PTEN, p‐PI3K, AKT, and P53 were measured by Western blot assay, and p‐PI3K nuclear volume was evaluated by immunofluorescence.

Results

The SGC‐7901 cell proliferation rate was depressed significantly, and cell apoptosis increased significantly while cells were arrested in the G1 phase (p < .05) with ginsenoside Rg3 treatment in a dose‐dependent manner (p < .05). Meanwhile, the SGC‐7901 cell invasion number and wound‐healing rate of ginsenoside Rg3‐treated groups were significantly downregulated compared with those of the NC group, also in a dose‐dependent manner (p < .05). PTEN and P53 protein expression levels were significantly increased, and p‐PI3K and AKT protein expression levels were significantly depressed in ginsenoside Rg3‐treated groups in a dose‐dependent manner (p < .05).

Conclusion

Ginsenoside Rg3 suppresses gastric cancer via regulation of the PTEN/p‐PI3K/AKT pathway.
Comparison of reactions with different calcium sources for CaCO3 production using carbonic anhydrase
Authors: Moon Dea Hyun , Eu Jun , Lee Wonhee , Kim Young Eun , Park Ki Tae , Ko You Na , Jeong Soon Kwan , Youn Min Hye
Published: June 2020

In this study, we investigated the effect of calcium sources with different solubilities and the carbonic anhydrase (CA) enzyme on carbonate mineralization reaction, and analyzed the reaction rate, the morphology of the formed precipitate, and the surface. The CO2 mineralization rate was affected by the rate of CO2 hydration and the rate of Ca ionization. For all of the calcium sources tested, CA improved the overall carbonate mineralization rate, but depending on the solubility of each calcium source, the reaction rates were in the order of CaCl2 > Ca(OH)2 > CaO. From CaCl2, calcium carbonate was generated rapidly. This was due to the high concentration of calcium ions in the solution because it was easily dissolved. But because of its high surface energy, calcite and vaterite coexisted. On the other hand, Ca(OH)2 and CaO had relatively low solubility and the rate of calcium carbonate production was slow, but after the reaction, CaCO3 with a calcite structure was formed. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd.
Greenhouse gas emissions, grain yield and water productivity: a paddy rice field case study based in Myanmar
Authors: Win Ei Phyu , Win Kyaw Kyaw , Bellingrath‐Kimura Sonoko D. , Oo Aung Zaw
Published: June 2020

Climate change is a vital environmental issue that significantly affects rice productivity. Rice paddy fields are one of the greatest anthropogenic sources of methane (CH4) and nitrous oxide (N2O) emissions. To evaluate the combined effects of manure amendment and water management on GHG emissions, grain yield and water productivity per rice yield in a lowland rice field with a sandy clay loam soil in Myanmar, this study was conducted with a split‐plot design. Two water management practices (continuous flooding [CF] and alternate wetting and drying [AWD]) and four levels of cow dung manure (0, 2.5, 5.0 and 7.5 t ha−1) were applied with three replications in the dry (February–May) and wet (July–October) seasons in 2017. In the dry season, significantly higher cumulative methane (CH4) emissions (50.5%) were recorded in CF than in AWD, while cumulative nitrous oxide (N2O) emissions were 70% higher in AWD than in CF, although the difference was not significant. Manure application showed no effect on CH4 and N2O emissions compared with the no‐manure control, irrespective of application level. In the wet season, significantly higher cumulative CH4 emissions (65.2%) were again recorded in CF than in AWD; however, the cumulative N2O emissions were similar between CF and AWD. Methane and N2O emissions in the wet season were 65.8 and 35.8% higher, respectively, than those in the dry season. In both seasons, higher grain yields (1.8% in dry and 7.6% in wet) and higher water productivity (130% in dry and 31% in wet) were recorded in AWD than in CF. Increased grain yields (18.9% in dry and 7.7% in wet) and water productivity (25.5% in dry and 15.8% in wet) were recorded in the manure treatments compared to those in the no‐manure treatment. This study presents quantitative data on how manure amendment and water management affected GHG emissions in a paddy field in Myanmar. © 2020 The Authors. Greenhouse Gases: Science and Technology published by Society of Chemical Industry and John Wiley & Sons, Ltd.
Primary Treatment with Molecular‐Targeted Agents for Hepatocellular Carcinoma: A Propensity Score‐matching Analysis
Authors: Nakano Masahito , Kuromatsu Ryoko , Niizeki Takashi , Okamura Shusuke , Iwamoto Hideki , Shimose Shigeo , Shirono Tomotake , Noda Yu , Kamachi Naoki , Koga Hironori , Torimura Takuji ,   The Kurume Liver Cancer Study Group of Japan
Published: June 2020

Sorafenib and lenvatinib, as molecular‐targeted agents, constitute effective primary treatment options for advanced hepatocellular carcinoma (HCC). However, the choice of optimal primary treatment agent remains controversial. Here, we aimed to assess the respective outcomes between these agents as primary treatment in patients with advanced HCC through use of propensity score–matching analysis (PSMA). We enrolled 670 consecutive patients who were diagnosed with advanced HCC and received sorafenib (n = 524) or lenvatinib (n = 146) as the primary treatment among 18 participating institutions between May 2009 and October 2019. To reduce confounding, we used PSMA regarding seven variables related to advanced HCC prognosis, resulting in the selection of 292 patients (n = 146 for each agent). Following PSMA, no significant difference was observed in the outcome of overall survival time between patients treated with sorafenib or lenvatinib (median survival time 15.3 or 14.9 months, respectively; P = 0.2358). Patients treated with lenvatinib exhibited significantly greater therapeutic effects (response rate: 5% and 31%; disease control rate: 46% and 69% for sorafenib and lenvatinib, respectively; P < 0.0001), but showed significantly lower probability of transition to secondary treatment (sorafenib, 60%; lenvatinib, 45%; P < 0.0269) and higher any adverse events rate (sorafenib, 86%; lenvatinib, 95%; P = 0.0207). Conclusion: As a primary molecular‐targeted agent–based treatment for advanced HCC, our findings suggested that sorafenib is generally appropriate as it offers significantly lower frequency of adverse events and higher probability of transition to secondary treatment, in consideration of the enhanced postprogression survival mediated by sequential treatment. Alternatively, lenvatinib affords a significantly higher therapeutic effect and should be used when immediate tumor reduction is required.
Association of genomic variants at the human leukocyte antigen locus with cervical cancer risk, HPV status and gene expression levels
Authors: Ramachandran Dhanya , Schürmann Peter , Mao Qianqian , Wang Yingying , Bretschneider Lisa‐Marie , Speith Lisa‐Marie , Hülse Fabienne , Enßen Julia , Bousset Kristine , Jentschke Matthias , Böhmer Gerd , Strauß Hans‐Georg , Hirchenhain Christine , Schmidmayr Monika , Tarbiat Johanna , Runnebaum Ingo , Dürst Matthias , Hein Alexander , Koch Martin , Ruebner Matthias , Ekici Arif , Beckmann Matthias W. , Fasching Peter A. , Luyten Alexander , Petry Karl‐Ulrich , Hillemanns Peter , Dörk Thilo
Published: June 2020

The human leukocyte antigen (HLA) locus on chromosome 6 has been reported to be associated with cervical cancer. We investigated two independent single‐nucleotide polymorphisms in a large case‐control series of cervical dysplasia and carcinoma that has been newly established by the German Cervigen Consortium, comprising a total of 2481 cases and 1556 healthy females. We find significant associations for both variants, rs9272117 at HLA‐DQA1 and rs2844511 at MICA and HCP5, with cervical disease. Both variants showed evidence of association with invasive cervical cancer (rs9272117: OR 0.89, 95% CI 0.79‐0.99, P = .036; rs2844511: OR 1.17, 95% CI 1.04‐1.31, P = .008) and with high‐grade dysplasia (rs9272117: OR 0.78, 95% CI 0.70‐0.87, P = 7.1 × 10−6; rs2844511: OR 1.13, 95% CI 1.01‐1.26, P = .035), as well as in a combined analysis of both groups (rs9272117: OR 0.83, 95% CI 0.75‐0.91, P = 6.9 × 10−5; rs2844511: OR 1.14, 95% CI 1.04‐1.26, P = .005). Variant rs2844511, but not rs9272117, also showed modest evidence of association with low‐grade dysplasia (OR 1.26, 95% CI 1.04‐1.54, P = .019). In case‐only analyses, rs2844511 tended to predict HPV status (P = .044) and rs9272117 tended to associate with HPV16 (P = .022). RNA studies in cervical samples showed a significant correlation in the transcript levels of MICA, HCP5 and HLA‐DQA1, suggesting extensive co‐regulation. All three genes were upregulated in HPV16‐positive samples. In stratified analyses, rs9272117 was associated with HLA‐DQA1 levels, specifically in HPV‐positive samples, while rs2844511 was associated with MICA and HCP5 levels. The risk allele of rs2844511 was required for correlations between MICA or HCP5 with HLA‐DQA1. Altogether, our results support 6p21.32‐33 as the first consistent cervical cancer susceptibility locus and provide evidence for a link between genetic risk variants, HPV16 status and transcript levels of HLA‐DQA1, HCP5 and MICA, which may contribute to tumor immune evasion.
Tick size and market quality: Simulations based on agent‐based artificial stock markets
Authors: Yang Xinhui , Zhang Jie , Ye Qing
Published: June 2020

This paper investigates the way that minimum tick size affects market quality based on an agent‐based artificial stock market. Our results indicate that stepwise and combination systems can promote market quality in certain aspects, compared with a uniform system. A minimal combination system performed the best to improve market quality. This is the first study to analyse tick size systems that remain at the theory stage and compare four types of system under the same experimental environment. The results suggests that a minimal combination system could be considered a new direction for market policy reform to improve market quality.
Regular Supplementation With Resveratrol Improves Bone Mineral Density in Postmenopausal Women: A Randomized, Placebo-Controlled Trial
Authors: Wong Rachel HX , Thaung Zaw Jay Jay , Xian Cory J , Howe Peter RC
Published: June 2020

Resveratrol, a naturally occurring polyphenol in red grapes and berries, can act as a phytoestrogen. It has been shown to improve both systemic and cerebral circulatory functions, possibly through activation of endothelial estrogen receptors. in vitro and in vivo studies in rodent models also indicate a bone-protective role for resveratrol, particularly in ovariectomized rat models that mimic postmenopausal osteoporosis caused by estrogen deficiency. Hypothesizing a circulatory benefit of resveratrol in bone tissue, we investigated whether resveratrol supplementation could improve bone health in postmenopausal women. The Resveratrol for Healthy Aging in Women (RESHAW) trial was a 24-month randomized, double-blind, placebo-controlled, two-period crossover intervention conducted to evaluate the effects of resveratrol (75 mg twice daily) on cognition, cerebrovascular function, bone health, cardiometabolic markers, and well-being in postmenopausal women. After 12 months of supplementation with resveratrol versus placebo, there were positive effects on bone density in the lumbar spine (+0.016 ± 0.003 g/cm2) and neck of femur (+0.005 ± 0.002 g/cm2), which were accompanied by a 7.24% reduction in C-terminal telopeptide type-1 collagen levels, a bone resorption marker, compared with placebo. The increase in bone mineral density in the femoral neck resulted in an improvement in T-score (+0.070 ± 0.018) and a reduction in the 10-year probability of major and hip fracture risk. The magnitude of improvement was higher in women with poor bone health biomarker status. Importantly, the improvement in femoral neck T-score with resveratrol correlated with improvement in perfusion. Our subanalysis also revealed that the bone-protective benefit of resveratrol was greater in participants who supplemented with vitamin D plus calcium. Regular supplementation with 75 mg of resveratrol twice daily has the potential to slow bone loss in the lumbar spine and femoral neck, common fracture sites in postmenopausal women without overt osteoporosis. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
Age-, Site-, and Sex-Specific Normative Centile Curves for HR-pQCT-Derived Microarchitectural and Bone Strength Parameters in a Chinese Mainland Population
Authors: Yu Fan , Xu Yuping , Hou Yanfang , Lin Yuanyuan , Jiajue Ruizhi , Jiang Yan , Wang Ou , Li Mei , Xing Xiaoping , Zhang Li , Qin Ling , Hsieh Evelyn , Xia Weibo
Published: June 2020

High-resolution peripheral quantitative computed tomography (HR-pQCT) is an advanced 3D imaging technology that has the potential to contribute to fracture risk assessment and early diagnosis of osteoporosis. However, to date no studies have sought to establish normative reference ranges for HR-pQCT measures among individuals from the Chinese mainland, significantly restricting its use. In this study, we collected HR-pQCT scans from 863 healthy Chinese men and women aged 20 to 80 years using the latest-generation scanner (Scanco XtremeCT II, Scanco Medical AG, Brüttisellen, Switzerland). Parameters including volumetric bone mineral density, bone geometry, bone microarchitecture, and bone strength were evaluated. Age-, site-, and sex-specific centile curves were established using generalized additive models for location, scale, and shape with age as the only explanatory variable. Based on established models, age-related variations for different parameters were also quantified. For clinical purposes, the expected values of HR-pQCT parameters for a defined age and a defined percentile or Z-score were provided. We found that the majority of trabecular and bone strength parameters reached their peak at 20 years of age, regardless of sex and site, then declined steadily thereafter. However, most of the cortical bone loss was observed after the age of 50 years. Among the measures, cortical porosity changed most dramatically, and overall, changes were more notable at the radius than the tibia and among women compared with men. Establishing such normative HR-pQCT reference data will provide an important basis for clinical and research applications in mainland China aimed at elucidating microstructural bone damage driven by different disease states or nutritional status. © 2020 American Society for Bone and Mineral Research.
Comparative removal of imidacloprid, bisphenol‐S, and azithromycin with ferrate and FeCl3 and assessment of the resulting toxicity
Authors: Zhang Shaoqing , Jiang Jia‐Qian
Published: June 2020

BACKGROUND

Emerging micro‐pollutants (EMPs) in water have received much attention due to their potential hazards to human health and ecological security. Ferrate has been researched in recent years to remove both particulate and dissolved impurities (including EMPs) from water, and its promising performance has been attributed to the high oxidation capacity and coagulation functions. However, limited research has compared ferrate with coagulation alone in the treatment of EMPs, which is one of the major objectives of this study.

RESULTS

Three emerging micro‐pollutants (EMPs), imidacloprid (IMP), bisphenol‐S (BS), and azithromycin (AZM) were chosen for this study. In all cases, ferrate outperformed to ferric chloride in the removal of the EMPs. For a given ferrate dose of 0.05 mM, 99% of BS, 85% of AZM, and 78% of IMP were removed for a start concentration of 10 μg L−1. However, if the start concentration was 1000 μg L−1, removal efficiency was decreased to 82% for BS, 62% for AZM, and 22% for IMP. pH 5 was favorable to the EMP removal by ferrate for the study conditions. Although higher removals of IMP, BS, and AZM were achieved by ferrate in comparison to those by ferric chloride, only 20% DOC removal was achieved by the ferrate. The formation of various oxidation products in the degradation process resulted in the disparity of the solution toxicity; that of BS was reduced but those of IMP and AZM increased after ferrate treatment. Nevertheless, the toxicity of ferric chloride treated samples was all increased.

CONCLUSION

Ferrate has higher efficiency comparing with FeCl3 to remove IMP, BS, and AZM. Degradation of the EMPs by ferrate was more efficient in acidic conditions (pH 5) and at the EMPs' lower initial concentrations for the given conditions. IMP was more resistant to the ferrate treatment compared to BS and AZM under the same conditions. Overall, 20% DOC reduction was achieved by ferrate for pH 5. Finally, the toxicity of BS can be reduced but those of IMP and AZM were increased after ferrate treatment, whilst the toxicity of ferric chloride treated samples was all increased. © 2020 Society of Chemical Industry
Application of mechanistic modelling and machine learning for cream cheese fermentation pH prediction
Authors: Li Bing , Lin Yinzi , Yu Wei , Wilson David I , Young Brent R
Published: June 2020

BACKGROUND

Cheese production occupies a small but growing share of the current dairy industry. Industrial cream cheese production involves the complex scheduling of multiple batch fermenters and various downstream units. However, significant end‐time variation from different fermentation batches makes downstream scheduling challenging and thus decreases the process throughput.

RESULTS

This research addressed this challenge by using an artificial neural network (a Long‐Short Term Memory Network, LSTM) in combination with a mechanistic model describing the changes in biomass, lactose, and lactic acid concentrations. The LSTM network/mechanistic modelling approach shows an end‐time difference of 3 min over batch times of 6 to 7 h compared to the laboratory experiment, with an overall accuracy (R2) of over 0.99.

CONCLUSION

The proposed hybrid fundamental/artificial neural network (ANN) model framework could reasonably predict the cheese fermentation pH with limited data. The outcome of this research enables fermentation end‐time prediction, makes the downstream scheduling possible, and thus, could help to improve the process throughput. The developed model could also be used for further cheese digital twin development, based on how better product quality control and higher process efficiency could be achieved. © 2020 Society of Chemical Industry
Sense of belonging predicts persistence intentions among diverse dental education students: A multi‐institutional investigation
Authors: Strayhorn Terrell L.
Published: June 2020

To succeed in dental school, students need both academic and social experiences that are correlated with perceived membership and persistence. In this study, survey data from 247 dental students were analyzed to test for racial differences in dental students' sense of belonging and to measure the extent to which sense of belonging predicted students' intent to persist in dental school, controlling for grade point average (GPA) and sex. Results indicate that sense of belonging varies by race with White dental students feeling stronger connections in school than underrepresented minority (URM) peers. Regression results reveal that sense of belonging is related to dental students' persistence intentions, all other things being equal. In fact, sense of belonging influenced students' intent to persist in dental school 3 times more than GPA alone. Findings have significant implications for future policy, practice, and research, but also raise important questions for dental educators in the U.S.
Development of a situational judgment test for global engineering competency
Authors: Jesiek Brent K. , Woo Sang Eun , Parrigon Scott , Porter Caitlin M.
Published: June 2020

Background

As globalization continues to impact the engineering profession, many programs aim to prepare current and future engineers to work across national and cultural boundaries. Yet there remains a lack of quality tools for assessing global competency among engineers and other technical professionals, including their behavioral tendencies in global work situations.

Purpose

We introduce development of a situational judgment test (SJT) covering three dimensions of global engineering competency (GEC) in Chinese national/cultural context. The main aim of this article is to describe how the SJT was developed through a systematic multistep process. Secondarily, we explore relationships between SJT performance and other theoretically relevant variables.

Methods

After generating a large initial pool of SJT scenarios and behavioral response items, we used ratings from subject matter experts (SMEs) to select six SJT scenarios and create scoring keys for 26 response items. To further explore the instrument's validity, we deployed the SJT items, other relevant measures, and a demographic survey to a sample of practicing engineers (n = 400).

Results

SME ratings provide strong evidence for the content relevance of the GEC–SJT tool. Survey results also suggest positive relationships between SJT performance and Chinese cultural knowledge, age, and years of work experience. However, more validity and reliability evidence is needed before recommending wider use of the instrument.

Conclusions

Our findings suggest the SJT format as a promising behavior‐based approach to measuring global competency and other professional attributes in engineering. We also discuss directions for future research and training efforts related to assessing and developing global competency.
Visible light promoted formation of N─S bond by photocatalyst Eosin Y
Authors: Verma Ankit , Srivastava Arjita , Tiwari Saurabh K , Yadav Neetu , Ansari Mohd Danish , Yadav Vijay B , Sagir Hozeyfa , Siddiqui Ibadur R
Published: June 2020

A novel efficient protocol for the synthesis of 5‐imino‐1,2,4‐thiadiazole motif in open air and visible light has been reported. The reaction involves Eosin Y as photocatalyst which is a cost‐effective organic dye. The designed protocol represents a novel, mild, metal free, green strategy for the construction of 1,2,4‐thiadiazole nucleus by intramolecular cyclization via N─S bond formation. The reaction has been carried out under visible light exposure in ethanol: water (4:1) mixture using 2‐aminopyridine and isocyanate as reactants.
Future of preventing and managing common chronic inflammatory diseases
Authors: Kornman Kenneth S.
Published: June 2020

Chronic inflammation has emerged as a key factor that contributes to some common chronic diseases and reduces lifespan. Studies have identified multiple types of chronic inflammation ranging from autoimmune disease, which attacks specific tissues, to autoinflammatory diseases, which cause low‐grade systemic inflammation and contribute to several common chronic diseases. This article highlights new perspectives on the role of chronic inflammation in cardiovascular disease (CVD). Such information is being leveraged to develop new treatment strategies for CVD and may inform how periodontal disease influences CVD.
Plant‐available N:P alters root litter N recycling in a Mediterranean tree–grass ecosystem
Authors: Nair Richard K. F. , Morris Kendalynn A. , Migliavacca Mirco , Moreno Gerado , Schrumpf Marion
Published: June 2020

Background: Nitrogen deposition can cause an ecosystem‐level shift in available N (nitrogen) to P (phosphorus) availability. However, most plant N nutrition is from edaphic sources rather than deposition and in seasonally dry grassland systems, root litter is the predominant nutrient source.

Aims: We were interested how litter turnover and altered nutrient recycling from dead biomass can compensate for these shifts in ecosystem stoichiometry.

Methods: We studied a Mediterranean savanna amended with N or NP treatments three years prior. We measured root and plant‐available soil N:P stoichiometry in two micro‐habitats: open pasture and beneath oak canopies. 15N‐labelled root litter incubated in topsoils without litterbags was used to trace uptake of litter N by herbaceous strata roots.

Results: Since fertilization, NP added sites have become relatively P enriched, resulting in lower N:P ratios in living roots than either when N was added alone or control sites. Total litter‐derived 15N uptake by roots was proportional to root ingrowth response but higher in the NP than N treatment, indicating a higher N demand when N and P were added together. We observed more 15N uptake by plants under tree canopies, indicating a tighter nutrient recycling loop in these micro‐habitats in contrast to treatment level ‘fertility' trends.

Conclusions: Root stoichiometry responded to manipulated soil nutrient availability and N uptake was altered as plants attempted to compensate for nutrient availability imbalances, indicating that these ecosystem perturbations have long term effects on nutrient cycling which can propagate to whole system function. This was also related to functional community‐level adaptions between micro‐habitats with under canopy communities more able to take advantage of the litter nutrient source.
Modified Two‐Phase Titration Methods to Quantify Surfactant Concentrations in Chemical‐Enhanced Oil Recovery Applications
Authors: Miller Chammi , Bageri Badr S. , Zeng Tongzhou , Patil Shirish , Mohanty Kishore K.
Published: June 2020

In enhanced oil recovery applications, surfactants are injected into reservoirs along with polymers and salts. The effluents eluted from lab experiments and field tests are analyzed by HPLC methods using an evaporative light scattering detector (ELSD) detector. When the surfactant concentrations are less than 100 ppm, HPLC methods are inaccurate. A novel two‐phase titration method is developed where surfactant concentrations can be quantified using a calibration curve constructed with UV/vis absorption. This method can analyze surfactant concentrations 5–80 ppm where dilution eliminates any high‐salinity interferences with the absorption measurements. The method is based on formation of a dye‐surfactant complex and the light absorption of the complex has a linear correlation with the surfactant concentration. Anionic surfactant concentrations lower than 100 ppm can be accurately quantified using this method with methylene blue. The method was also developed for low concentrations (<50 ppm) of cationic surfactants using methyl orange and indigo carmine. The indigo carmine method can be used without the use of an organic phase. All methods are applicable at salinities up to 3 wt%. Both the methylene blue method and the methyl orange method can be used to detect zwitterionic surfactants. These methods can be used in the presence of polymers without any prior treatments.
Black tea benefits short‐chain fatty acid producers but inhibits genus Lactobacillus in the gut of healthy Sprague–Dawley rats
Authors: Gao Ying , Xu Yongquan , Yin Junfeng
Published: June 2020

BACKGROUND

The gut microbiota plays important roles in physiological and pathological processes of the host. The effect of black tea on the gut microbiota of healthy individuals remains unclear.

RESULTS

Healthy Sprague–Dawley (SD) rats were given black tea for 4 weeks, and cecum content, serum, intestinal, and hepatic samples were collected. The results showed that black tea increased α‐diversity and modulated β‐diversity of the gut microbiota. Additionally, black tea enriched several short‐chain fatty acid (SCFA) producers but suppressed genus Lactobacillus. Further tests revealed that the enrichment of SCFA producers was associated with a decrease in the oxidative stress of cecum content caused by black tea, and related to increased luminal butyric acid levels and enhanced intestinal barrier function. The suppression of genus Lactobacillus was related to the increase in luminal total bile acids caused by black tea. In vitro tests showed that bile acids rather than black tea directly inhibited Lactobacillus strains. The reduction in genus Lactobacillus did not affect the effects of black tea on intestinal barrier function and lipid levels.

CONCLUSION

Our results imply that the effects of black tea on gut microbiota in healthy individuals are complex and provide a new perspective on the associations among black tea, gut microbiota, and health. © 2020 Society of Chemical Industry
Uncovering the biofumigant capacity of allyl isothiocyanate from several Brassicaceae crops against Fusarium pathogens in maize
Authors: Vandicke Jonas , De Visschere Katrien , Deconinck Sofie , Leenknecht Diederik , Vermeir Pieter , Audenaert Kris , Haesaert Geert
Published: June 2020

BACKGROUND

Driven by environmental concerns, chemical fumigants are no longer allowed in many countries. Therefore, other strategies for reducing fungal inoculum in soils and on crop debris are being explored. In the present study, several Brassicaceae crops were screened for their potential to control Fusarium gramineaum and Fusarium poae mycelial growth in an in vitro inverted Petri dish experiment. Volatile production was measured using gas chromatography‐mass spectrometry headspace analysis. A selection of cultivars from each crop species was further investigated using a pot experiment with maize.

RESULTS

Ethiopian mustard (Brassica carinata) and brown mustard (Brassica juncea) released volatile allyl isothiocyanate (AITC) and a higher concentration of AITC was correlated with a better fungal growth reduction in the in vitro screening. Brown mustard cultivar Etamine completely inhibited growth of both Fusarium spp. Pure AITC in a solution with methanol resulted in a sigmoid dose–response curve for both Fusarium spp. tested. Fusarium poae appeared to be more tolerant to AITC than F. graminearum. A pot experiment revealed that the incorporation of brown mustard plant material could alleviate the clear negative effect of F. graminearum infection on maize growth.

CONCLUSION

The present study demonstrated the correlation between the fungistatic effect of biofumigation crops on Fusarium spp. and their production of volatile AITC in vitro, without the addition of exogenous enzymes, and confirmed the biofumigation potential of brown mustard in a pot experiment with maize. These results may help farmers when selecting a green manure crop suitable for biofumigation. © 2020 Society of Chemical Industry