bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of lncRNA MALAT1 by betulinic acid inhibits hepatocellular carcinoma progression by targeting IAPs via miR‐22‐3p
Authors: Chen Feiyu , Zhong Zhangfeng , Tan Hor Yue , Guo Wei , Zhang Cheng , Cheng Chien‐Shan , Wang Ning , Ren Junguo , Feng Yibin
Published: October 2020

Betulinic acid (BA) is a natural product extracted from a broad range of medicinal and edible herbal plants. Previous studies showed that BA induces cell death in tumors derived from multiple tissues; however, the underlying mechanism remains obscure. The present study aimed to study the effects of BA on autophagy and apoptosis of hepatocellular carcinoma (HCC). Human HCC cell lines and orthotopic HCC implanted mice were employed to examine the BA‐induced tumor suppression; RT2 long noncoding RNA (lncRNA) PCR array and database analysis were used to explore the possible mechanisms; validation of pathways was performed using siRNA and miRNA inhibitors. The results indicated that BA regulated autophagy and induced apoptosis in HCC. The degradation of inhibitor of apoptosis proteins (IAPs), the conversion of LC3‐I to LC3‐II, and p62 accumulation were enhanced by BA, thereby suggesting that the downregulation of IAPs and autophagic cell death are induced by BA. The addition of autophagy and lysosomal inhibitors indicated that BA induced autophagy‐independent apoptosis via degradation of IAPs. Moreover, RT2 lncRNA PCR array and database analysis suggested that BA downregulated the levels of lncRNA MALAT1, which is considered to be an oncogene. Further investigations demonstrated that lncRNA MALAT1 functioned as a ceRNA (competing endogenous RNA) to contribute to BA‐mediated degradation of IAPs by sponging miR‐22‐3p. Therefore, BA could be developed as a potential anticancer agent for HCC.
Progress and applications of mass cytometry in sketching immune landscapes
Authors: Zhang Ting , Warden Antony R. , Li Yiyang , Ding Xianting
Published: October 2020

Recently emerged mass cytometry (cytometry by time‐of‐flight [CyTOF]) technology permits the identification and quantification of inherently diverse cellular systems, and the simultaneous measurement of functional attributes at the single‐cell resolution. By virtue of its multiplex ability with limited need for compensation, CyTOF has led a critical role in immunological research fields. Here, we present an overview of CyTOF, including the introduction of CyTOF principle and advantages that make it a standalone tool in deciphering immune mysteries. We then discuss the functional assays, introduce the bioinformatics to interpret the data yield via CyTOF, and depict the emerging clinical and research applications of CyTOF technology in sketching immune landscape in a wide variety of diseases.
Drivers of distributions and niches of North American cold‐adapted amphibians: evaluating both climate and land use
Authors: Seaborn Travis , Goldberg Caren S. , Crespi Erica J.
Published: October 2020

Species distribution estimates are often used to understand the niche of a species; however, these are often based solely on climatic predictors. When the influences of biotic factors are ignored, erroneous inferences about range and niche may be made. We aimed to integrate climate data with a unique set of available land cover and land use data for the six cold‐adapted amphibians of North America (Ambystoma macrodactylum,Anaxyrus hemiophrys,Anaxyrus boreas,Pseudacris maculata,Rana sylvatica,Rana luteiventris) to determine the relative importance of climate and non‐climate drivers through the use of ecological niche models for present‐day range estimates. We compared climate‐only, land use‐only, and combination models of climate and land use, derived from two different model selection techniques, to determine which was most likely to drive current distributions of cold‐adapted amphibian species. Land use layers included land cover type, human population, vegetation type, ecoregion, and the overall human footprint. The most supported models included both climate and land use, with climate and human footprint variables having the highest permutation importance and percent contribution. Models that incorporated climate and land use data performed best as measured with AIC and AUC, although qualitatively most underestimated the northern range edge, implying potential sampling bias or locations of reduced habitat quality for these species in the northern area of the ranges. There were small differences in overall combination models dependent on the method of model selection. The overall effect sizes of landscape factors within the combination models were small except for one landscape feature: human footprint, which incorporated multiple aspects of anthropogenic change on the landscape, including human population density, travel access, and agricultural impact. This aspect of the landscape was just as important as climate, and counter to what we expected, the association was mostly positive, with a negative response only occurring at very high levels. This highlights the importance of moving beyond climate only species range estimates as land cover, specifically human impact, may be driving the patterns of species' ranges.
Seed quality and seed quantity in red maple depends on weather and individual tree characteristics
Authors: Goszka Abigail R. , Snell Rebecca S.
Published: October 2020

Under future climate change, plant species are expected to shift their ranges in response to increasing temperatures and altered precipitation patterns. As seeds represent the single opportunity for plants to move, it is critical to quantify the factors that influence reproduction. While total seed production is clearly important, seed quality is equally as critical and often overlooked. Thus, to quantify how environmental and tree‐level characteristics affect seed quality and quantity, the reproductive output of red maple (Acer rubrum) was measured along an elevation gradient in the Monongahela National Forest, WV. A variety of individual‐level characteristics were measured (e.g., DBH, canopy area, height, and tree cores were taken to quantify growth), and seed traps were placed under seed‐bearing trees to collect samaras and quantify total seed production. A random subsample of collected seeds from each tree was micro‐CT scanned to determine embryo volume, photographed for morphology measurements, and used for germination trials. The number of seeds produced was negatively affected by frost events during flowering, and stand density. The trees with the most seeds also showed reduced growth in recent years. Only 63% of scanned seeds showed embryo development, and of those seeds—only 23% germinated. The likelihood of embryo presence increased as growth rate decreased, while embryo size increased with tree height, smaller DBH, and in areas dominated by hemlock. Both larger embryo volume and larger overall seed size increased the likelihood of germination. The results highlight the importance of including seed quality in addition to seed quantity for a more complete representation of reproductive output.
Bcl‐xL expression following articular cartilage injury and its effects on the biological function of chondrocytes
Authors: Pan Zhengjun , Yin Hao , Wang Shuangli , Xiong Gaoxin , Yin Zongsheng
Published: October 2020

This study aimed to investigate the expression of B‐cell lymphoma‐extra large (Bcl‐xL) in cartilage tissues following articular cartilage injury and to determine its effects on the biological function of chondrocytes. A total of 25 necrotic cartilage tissue samples and 25 normal tissue samples were collected from patients diagnosed with osteoarthritis at our hospital from December 2015 to December 2018. The mRNA expression levels of Bcl‐xL, caspase‐3, and matrix metalloproteinase‐3 (MMP‐3) in the normal and necrotic tissues were examined via quantitative polymerase chain reaction, and their protein expression levels were detected via western blotting. The expression levels of Bcl‐xL, insulin‐like growth factor‐1 (IGF‐1), and bone morphogenetic protein (BMP) were significantly lower but those of caspase‐3, MMP‐3, interleukin‐1β (IL‐1β), and chemokine‐like factor 1 (CKLF1) levels were markedly higher in necrotic cartilage tissues than in normal tissues. Following cell transfection, the expression levels of Bcl‐xL, IGF‐1, and BMP were remarkably higher but those of caspase‐3, MMP‐3, IL‐1β, and CKLF1 were notably lower in the Si‐Bcl‐xL group than in the NC group. The Si‐Bcl‐xL group showed significantly lower cell growth and noticeably higher apoptosis rate than the NC group (normal control group). The expression of Bcl‐xL is reduced following articular cartilage injury, and this reduction promotes the proliferation and inhibits the apoptosis of chondrocytes. Therefore, Bcl‐xL could serve as a relevant molecular target in the clinical practice of osteoarthritis and other diseases causing cartilage damage.
Experimental investigation of the use of waste engine oil improved with manganese additive as fuel in a diesel power generator
Authors: Arabacı Emre , Orman Recep Çağrı
Published: October 2020

Today, there is an effort to obtain energy from every possible source and waste to meet the oil demand. Waste engine oil is one of them. Although waste lubricating oils have an important economic potential, the environmental effect of these oils is much more important than their economic effect. In this study, various waste engine oil‐diesel mixture (0:100, 10:90, 20:80, and 30:70) and various fuel pressure conditions (195–255 bar) experiments were performed for various engine loads (3–12 Nm) in a DI diesel power generator. It was aimed to increase the potential of using waste engine oil as fuel by adding 16 μmol/L Mn additive to the waste engine oil. For the design of the experiment, 1/8 fractional factorial Taguchi method was applied and the relationship between engine load, waste engine oil, fuel injection pressure and Mn additive with experimental factors has been successfully determined with variance analysis. Using regression analysis, regression equations were obtained for exhaust temperature, specific fuel consumption, light absorption coefficient, and nitrogen oxides. Finally, although waste engine oil causes deterioration on engine performance and emissions, it has been determined that the use of waste engine oil as fuel can be improved thanks to the Mn additive.
Secure smart contracts for cloud‐based manufacturing using Ethereum blockchain
Authors: Kumar Ajay , Abhishek Kumar , Nerurkar Pranav , Ghalib Muhammad Rukunuddin , Shankar Achyut , Cheng Xiaochun
Published: October 2020

Past international trade practices have been associated with opaque information flows that have hindered traceability and created hurdles in hassle‐free trade. Blockchain and allied technologies have been investigated as a panacea for the problems faced by the Cloud‐Based Manufacturing industry. However, previous literature has focused on limited aspects of a typical Cloud‐Based Manufacturing chain, such as monitoring assets and securing traceability, which is widely neglecting data integrity and data access. To overcome such drawbacks, the current paper proposes secure smart contracts based on the ERC20 interface in a permissioned blockchain with relevant processes and functions to obtain a holistic framework for securing Cloud‐Based Manufacturing operations. The efficacy of the proposed framework was demonstrated on the case study. It was found that critical loopholes in a current supply chain can be overcome using the proposed framework. Additionally, several outlines for future research are outlined.
The determination of lycopene Z‐isomer absorption coefficient on C30‐HPLC
Authors: Huang Jin , Hui Bodi
Published: October 2020

Both E‐ and Z‐isomers of lycopene are encountered in nature. Although they were separated on C30‐HPLC by the mobile phase consisting of CH3CN‐MeOH (A) and MTBE (B), the quantification of Z‐isomers cannot be archived at present because either their commercially available reference samples are currently lacking, or they are unstable. In this study, both the specific and molar absorption coefficients of 5, 9, and 13 Z‐isomers in the mobile phase were determined on the analytical C30‐HPLC‐PDA‐ELSD, and further verified on the preparative C30‐HPLC‐PDA. The specific and molar absorption coefficients of 5, 9, and 13 Z‐isomers were finally verified to be  = 3,422 and εmol = 183,717,  = 2,183 and εmol = 117,199, and  = 1,119 and εmol = 60,076, respectively, in the mobile phase. With these determined coefficients, the quantifications of 5, 9, and 13 Z‐isomers were able to be archived on C30‐HPLC‐PDA with the mobile phase applied in this investigation.
The impact of Qodume Shirazi seed mucilage‐based edible coating containing lavender essential oil on the quality enhancement and shelf life improvement of fresh ostrich meat: An experimental and modeling study
Authors: Heydari Samaneh , Jooyandeh Hossein , Alizadeh Behbahani Behrooz , Noshad Mohammad
Published: October 2020

Today, food consumers prefer to use the foods that contain natural preservatives. The purpose of this study was to investigate the effect of Qodume Shirazi seed mucilage (QSSM) and lavender essential oil (LO) on the preservation of ostrich meat during cold storage. The chemical compounds of LO were identified through gas chromatography–mass spectrometry (GC/MS). The ostrich meat samples were coated with the mucilage containing the essential oil at concentrations of 0%, 0.5%, 1%, 1.5%, and 2%, v/v. The control and the coated ostrich meat samples were kept at 4°C and analyzed for microbiological (total viable count, psychrotrophic count,Escherichia coli,Staphylococcus aureus, coliforms, and fungi), physicochemical (moisture content, pH, texture, and color parameters), and sensorial (odor, color, and total acceptance) characteristics during 9 days of storage. GC/MS identified 12 compounds in the essential oil, among which linalool was the major one (43.3%). The lightness (L* value) and hardness of all the ostrich meat samples were reduced during the storage. From a microbiological point of view, the cold storage duration for the control and the coated sample without the essential oil was only 3 days, while for coated samples containing 0.5%, 1%, 1.5%, and 2% essential oil, it was 3, 3, 6, and 9 days, respectively. The coated ostrich meat containing 2% LO had an appropriate quality with an expanded shelf life. The results showed that neural network with 10 neurons in the hidden layer had the lowest mean squared error and mean absolute error and the highest correlation coefficient for predicting the quality and microbial properties of the coated meat samples during storage.
Glial restricted precursor cells in central nervous system disorders: Current applications and future perspectives
Authors: Martins‐Macedo Joana , Lepore Angelo C. , Domingues Helena S. , Salgado António J. , Gomes Eduardo D. , Pinto Luísa
Published: October 2020

The crosstalk between glial cells and neurons represents an exceptional feature for maintaining the normal function of the central nervous system (CNS). Increasing evidence has revealed the importance of glial progenitor cells in adult neurogenesis, reestablishment of cellular pools, neuroregeneration, and axonal (re)myelination. Several types of glial progenitors have been described, as well as their potentialities for recovering the CNS from certain traumas or pathologies. Among these precursors, glial‐restricted precursor cells (GRPs) are considered the earliest glial progenitors and exhibit tripotency for both Type I/II astrocytes and oligodendrocytes. GRPs have been derived from embryos and embryonic stem cells in animal models and have maintained their capacity for self‐renewal. Despite the relatively limited knowledge regarding the isolation, characterization, and function of these progenitors, GRPs are promising candidates for transplantation therapy and reestablishment/repair of CNS functions in neurodegenerative and neuropsychiatric disorders, as well as in traumatic injuries. Herein, we review the definition, isolation, characterization and potentialities of GRPs as cell‐based therapies in different neurological conditions. We briefly discuss the implications of using GRPs in CNS regenerative medicine and their possible application in a clinical setting.

Main Points

GRPs are progenitors present in the CNS with differentiation potential restricted to the glial lineage. These cells have been employed in the treatment of a myriad of neurodegenerative and traumatic pathologies, accompanied by promising results, herein reviewed.
Common and separable neural alterations in substance use disorders: A coordinate‐based meta‐analyses of functional neuroimaging studies in humans
Authors: Klugah‐Brown Benjamin , Di Xin , Zweerings Jana , Mathiak Klaus , Becker Benjamin , Biswal Bharat
Published: October 2020

Delineating common and separable neural alterations in substance use disorders (SUD) is imperative to understand the neurobiological basis of the addictive process and to inform substance‐specific treatment strategies. Given numerous functional MRI (fMRI) studies in different SUDs, a meta‐analysis could provide an opportunity to determine robust shared and substance‐specific alterations. The present study employed a coordinate‐based meta‐analysis covering fMRI studies in individuals with addictive cocaine, cannabis, alcohol, and nicotine use. The primary meta‐analysis demonstrated common alterations in primary dorsal striatal, and frontal circuits engaged in reward/salience processing, habit formation, and executive control across different substances and task‐paradigms. Subsequent sub‐analyses revealed substance‐specific alterations in frontal and limbic regions, with marked frontal and insula‐thalamic alterations in alcohol and nicotine use disorders respectively. Examining task‐specific alterations across substances revealed pronounced frontal alterations during cognitive processes yet stronger striatal alterations during reward‐related processes. Finally, an exploratory meta‐analysis revealed that neurofunctional alterations in striatal and frontal reward processing regions can already be determined with a high probability in studies with subjects with comparably short durations of use. Together the findings emphasize the role of dysregulations in frontostriatal circuits and dissociable contributions of these systems in the domains of reward‐related and cognitive processes which may contribute to substance‐specific behavioral alterations.
Reverse payments, patent strength, and asymmetric information
Authors: Manganelli Anton‐Giulio
Published: October 2020

Reverse payments (pay‐for‐delay) are payments from an originator to a generic pharmaceutical producer to settle a potential litigation. In many jurisdictions, these payments are banned. This study shows that when the parties' investments are considered and the information about the patent strength is asymmetric, reverse payments increase both the possibility of generic entry and the litigation rate—both of which increase consumer surplus and do not necessarily delay generic entry. Reverse payments typically increase consumer surplus when the asymmetry between the parties is low, the competitiveness in the market is soft, and their size is small. Results suggest that a ban per se may be suboptimal.
Patient–public engagement interventions for health system improvement in Sub‐Saharan Africa: A systematic scoping review protocol
Authors: Ankomah Samuel Egyakwa , Fusheini Adam , Ballard Christy , Kumah Emmanuel , Gurung Gagan , Derrett Sarah
Published: October 2020

Background

Research has found health system improvement cannot be achieved without continuously engaging patients, their families and all stakeholders in the design, management and delivery of health care services. Following the Alma Ata declaration on Primary Health Care in 1978, the focus of health system improvement has tended to shift from physician or hospital‐centric approaches to a more democratic vision of engaging the public and/or patients in the commissioning, planning, organisation, operation and control of the health care system. Thus, patient–public engagement (PPE) has become an important tool in health system improvement particularly for countries with poor health outcomes including countries in sub‐Saharan Africa which carries an estimated 24% of the global burden of diseases in both human and financial costs. The aim of this scoping review is to describe and systematically map PPE research in sub‐Saharan Africa, and then to synthesise this research in relation to key theories of PPE, identify the key drivers and barriers of PPE and to identify the knowledge gaps that may usefully be addressed by future research.

Methods

This scoping review will follow Arksey and O'Malley's best guidelines for conducting scoping reviews and also follow the standard guidelines for reporting using the Reporting Items for Systematic Reviews and Meta‐Analysis extension for scoping reviews checklist. A systematic search of peer‐reviewed English language literature published between January 1999 and December 2019 will be conducted on four databases: Scopus, CINAHL, Medline (Ovid) and Embase. The initial screening of titles and abstracts will be undertaken independently by two reviewers, followed by full text screening involving three independent reviewers. A thematic framework synthesis will be employed in the analysis of data to identify the various PPE interventions, and outcomes mapped to a framework of engagement continuum to understand its overall effect on health system improvement in sub‐Saharan Africa.

Discussion

To our knowledge, this scoping review will be the first to systematically investigate PPE interventions implemented across sub‐Saharan Africa, map the outcomes of identified interventions to a framework of engagement continuum and to understand its overall effect on health system improvement. Findings of this review will be published in an open‐access peer review journal and disseminated at scientific conferences.
The experience of commitment in the contemporary workplace: An exploratory reexamination of commitment model antecedents
Authors: Klein Howard J. , Brinsfield Chad T. , Cooper Joseph T.
Published: October 2020

To reassess and enhance our understanding of employee commitments in contemporary organizations, we conducted a mixed‐method study. In open‐ended surveys, we asked employees (N = 712) to explain why they are committed to various work‐related targets (organization, coworker, organizational goal, and occupation). We content analyzed the responses and derived 15 distinct explanations for those commitments. We then compared these explanations to extant commitment models and examined how explanations varied across commitment targets. Finally, we examined the relationship between these explanations and commitment strength. Our findings indicate that many factors in extant commitment models are still relevant (e.g., Social Exchange), but other aspects of those models were not mentioned by participants (e.g., competition) or mentioned very infrequently (e.g., No Choice). Perhaps most importantly, some current explanations (e.g., Altruism) are not represented in extant models. In addition, some explanations were provided more or less often for different commitment targets. For example, Social Exchange was provided more frequently for coworker commitment but less frequently than expected by chance for organizational goal commitment. Finally, explanations differentially related to commitment strength, with stronger commitment associated with Social Exchange than with Financial Exchange. The implications of these findings for theory and human resource management practice are discussed.
Letrozole versus clomiphene citrate for ovulation induction in anovulatory women with polycystic ovarian syndrome: A randomized controlled trial
Authors: Bansal Shavina , Goyal Manu , Sharma Charu , Shekhar Shashank
Published: October 2020

Objective

To compare the efficacy of letrozole and clomiphene citrate (CC) for ovulation induction in infertile women with polycystic ovarian syndrome (PCOS).

Methods

In this assessor blind, randomized controlled trial, 90 infertile women with PCOS were randomized to receive either letrozole or CC for ovulation induction in incremental doses for a maximum of three cycles. Main outcome measures studied were endometrial thickness, ovulation rate, pregnancy rate, rate of monofollicular development, and time to conception.

Results

Mean endometrial thicknesses were 9.86 ± 2.32 mm and 9.39 ± 2.06 mm with letrozole and CC, respectively (P=0.751). Cumulative ovulation rates were 86.7% and 85.2% with letrozole and CC, respectively (P=0.751). Pregnancy was achieved in 42.2% of women in the letrozole group and 20.0% of women in the CC group (P=0.04). Monofollicular development was seen in 68.4% of ovulatory cycles in the letrozole group compared with 44.8% in the CC group (P=0.000). Mean time to achieve pregnancy was significantly shorter (log rank P=0.042) with letrozole (9.65 weeks) than with CC (11.07 weeks).

Conclusion

Letrozole is a better alternative for ovulation induction in anovulatory women with PCOS as pregnancy rates are higher, time to pregnancy is shorter, and chances of multiple pregnancy are less because of high monofollicular growth.
Flexible 3D memristor array for binary storage and multi‐states neuromorphic computing applications
Authors: Wang Tian‐Yu , Meng Jia‐Lin , Chen Lin , Zhu Hao , Sun Qing‐Qing , Ding Shi‐Jin , Bao Wen‐Zhong , Zhang David Wei
Published: October 2020

The demand of flexible neuromorphic computing electronics is increasing with the rapid development of wearable artificial intelligent devices. The flexible resistive random‐access memory (RRAM) is one excellent candidate of high‐density storage devices. However, due to the limitations of fabrication process, materials system and device structure, it is difficult to prepare flexible 3D high‐density network for neuromorphic computing. In this paper, a 3D flexible memristors network is developed via low‐temperature atomic layer deposition (ALD) at 130°C, with potential of extending to various flexible electronics. The typical bipolar switching characteristics are verified in RRAM units of 3D network, including first, second and third layers. Besides binary storage, the multibit storage in single unit is demonstrated and the storage density is further increased. As a connection link between binary storage and brain‐inspired neuromorphic computing, the multibit storage capability paves the way for the tunable synaptic plasticity, for example, long‐term potentiation/depression (LTP/LTD). The 3D memristors network successfully mimicked the typical neuromorphic functionality and realized ultra‐multi conductance states modulation under 600 spikes. The robust mechanical flexibility is further demonstrated via LTP/LTD emulation under bending states (radius = 10 mm). The 3D flexible memristors network shows significant potential of applications in high‐performance, high‐density and reliable wearable neuromorphic computing system.

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Anti-Interleukin-6 Therapy Decreases Hip Synovitis and Bone Resorption and Increases Bone Formation Following Ischemic Osteonecrosis of the Femoral Head
Authors: Ren Yinshi , Deng Zhuo , Gokani Vishal , Kutschke Michael , Mitchell Thomas Wesley , Aruwajoye Olumide , Adapala Naga Suresh , Kamiya Nobuhiro , Abu-Amer Yousef , Kim Harry KW
Published: October 2020

Legg-Calvé-Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis, which produces chronic hip synovitis, permanent femoral head deformity, and premature osteoarthritis. Currently, there is no medical therapy for LCPD. Interleukin-6 (IL-6) is significantly elevated in the synovial fluid of patients with LCPD. We hypothesize that IL-6 elevation promotes chronic hip synovitis and impairs bone healing after ischemic osteonecrosis. We set out to test if anti-IL-6 therapy using tocilizumab can decrease hip synovitis and improve bone healing in the piglet model of LCPD. Fourteen piglets were surgically induced with ischemic osteonecrosis and assigned to two groups: the no treatment group (n = 7) and the tocilizumab group (15 to 20 mg/kg, biweekly intravenous injection, n = 7). All animals were euthanized 8 weeks after the induction of osteonecrosis. Hip synovium and femoral heads were assessed for hip synovitis and bone healing using histology, micro-CT, and histomorphometry. The mean hip synovitis score and the number of synovial macrophages and vessels were significantly lower in the tocilizumab group compared with the no treatment group (p < .0001, p = .01, and p < .01, respectively). Micro-CT analysis of the femoral heads showed a significantly higher bone volume in the tocilizumab group compared with the no treatment group (p = .02). The histologic assessment revealed a significantly lower number of osteoclasts per bone surface (p < .001) in the tocilizumab group compared with the no treatment group. Moreover, fluorochrome labeling showed a significantly higher percent of mineralizing bone surface (p < .01), bone formation rate per bone surface (p < .01), and mineral apposition rate (p = .04) in the tocilizumab group. Taken together, tocilizumab therapy decreased hip synovitis and osteoclastic bone resorption and increased new bone formation after ischemic osteonecrosis. This study provides preclinical evidence that tocilizumab decreases synovitis and improves bone healing in a large animal model of LCPD. © 2020 American Society for Bone and Mineral Research (ASBMR).
Marine bioactive compound dieckol induces apoptosis and inhibits the growth of human pancreatic cancer cells PANC‐1
Authors: Xu Jian Wei , Yan Ye , Wang Lei , Wu Dong , Ye Nai Kuan , Chen Shi Hong , Li Feng
Published: October 2020

Pancreatic cancer, which threatens the global population, is a very aggressive disease with an increased mortality rate. Regarding the types of cancer, pancreatic cancer is prone to display significant resistance to conventional therapy, therefore there 5‐year survival rate is only 2% to 9%. Bioactive metabolites of marine algae such as polysaccharides, chitin, carternoids, and sterols possess immense pharmacological properties and tend to be promising alternatives for cancer treatment. Dieckol is one such polyphenolic bioactive compound extracted from brown algae Ecklonia cava, which is proven to possess antioxidant, anti‐inflammatory, antibacterial, antidiabetic properties. Therefore in the present study, we analyzed the anticancer property of dieckol on PANC‐1 pancreatic carcinoma cells. The cytotoxicity property of dieckol against PANC‐1 cells was assessed with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide assay, and cell morphological analysis. The generation of reactive oxygen species by dieckol on PANC‐1 was analyzed with DCFH‐DA staining and confirmed by quantifying antioxidants levels in untreated and dieckol‐treated PANC‐1 cells. The induction of apoptosis was further evaluated with different staining techniques such as Rhodamine 123 staining, acridine orange/ethidium bromide staining, DAPI staining, propidium iodide staining and was confirmed by estimating the protein expression of apoptotic genes, Bax and Bcl2. Cell adhesion assay and estimation of inflammatory cytokines were performed to detect the inhibitory effect of dieckol against cancer cell progression. It is further confirmed by analyzing cancer cell progression proteins, that is, proliferating cell nuclear antigen and cyclin D1 expressions in untreated and dieckol‐treated PANC‐1 cells. Our overall results authentically prove dieckol persuasively induces apoptosis and inhibits the progression of human pancreatic cancer cells in vitro, suggesting dieckol as a potent marine‐based phytochemical to treat pancreatic cancer.
The active E4 structure of nitrogenase studied with different DFT functionals
Authors: Wei Wen‐Jie , Siegbahn Per E. M.
Published: October 2020

The present study concerns the technical aspects of obtaining the energetics for the E4 state of nitrogenase, the enzyme that fixes N2 in nature. EPR experiments have shown that the critical E4 structure that activates N2 should contain two bridging hydrides in the FeMo‐cofactor. It is furthermore in equilibrium with a structure where the two hydrides have been released and N2 binds. These observations led to the suggestion that E4 should have two bridging hydrides and two protonated sulfides. It is important to note that the structure for E4 has not been determined, but only suggested. For a long time, no DFT study led to the suggested structure, independent of which functional was used. However, in two recent DFT studies a good agreement with the experimental suggestion was claimed to have been obtained. In one of them the TPSS functional was used. That was the first out of 11 functionals tried that led to the experimentally suggested structure. In the second of the recent DFT studies, a similar conclusion was reached using the TPSSh functional. The conclusions in the recent studies have here been studied in detail, by calculating a critical energetic value strongly implied by the same EPR experiments. Both the TPSS and TPSSh functionals have been used. The present calculations suggest that those DFT functionals would not lead to agreement with the experimental EPR results either.
Molecular cytogenetic studies of a male carrier with a unique (Y;14) translocation: Case report
Authors: Chen Shuang , Xi Qi , Zhang Xinyue , Jiang Yuting , Li Leilei , Liu Ruizhi , Zhang Hongguo
Published: October 2020

Background

Chromosome translocation is a genetic factor associated with male infertility. However, cases of Y chromosome/autosome translocation are rare. Individuals with translocation between the Y chromosome and an autosome have a variety of different clinical phenotypes. There is a need for further study of molecular cytogenetic feature of those with Y chromosome translocation.

Methods

We reported that an apparently healthy 31‐year‐old man, 168 cm tall and weighing 65 kg, had a 2‐year history of primary infertility after marriage. Clinical diagnostic techniques included semen analysis, hormone measurements, cytogenetic analysis, fluorescence in situ hybridization (FISH), and high‐throughput multiplex ligation‐dependent probe amplification semiconductor sequencing. Detailed genetic counseling was provided to the patient. Intracytoplasmic sperm injection treatment combined with preimplantation genetic diagnosis was chosen with the aim of achieving a successful pregnancy.

Results

Semen analysis revealed cryptozoospermia. Hormone levels were within the normal limits. Sequencing results indicated the presence of the sex‐determining region on Yp, and AZFa, AZFb, and AZFc regions on Yq. The patient's karyotype was 45,X,psu,dic(Y;14)(p11.3;q11.2), which was confirmed by cytogenetic analysis and FISH.

Conclusion

This study reports a case of cryptozoospermia in a male patient with a Y;14 chromosomal translocation. When clinical karyotyping has revealed potential Y chromosome abnormality, FISH or molecular detection should be further performed to facilitate identification of the chromosomal breakpoint.
Change in housing environment and residential satisfaction following exit from permanent supportive housing
Authors: Tiderington Emmy , Aykanian Amanda , Huang Billy , Tsai Jack
Published: October 2020

Moving On initiatives (MOIs) transition stable permanent supportive housing (PSH) residents into mainstream housing without embedded services. While this approach frees up PSH for homeless individuals in need, open questions remain regarding MOI recipients’ long‐term outcomes. This exploratory study examines how housing environment and residential satisfaction, potential predictors of housing retention, change from PSH to mainstream housing. Subjective assessments of housing and neighborhood quality and residential satisfaction, as well as objective neighborhood‐level data, are used to examine housing‐related change for New York City MOI recipients. Participants generally moved to less‐distressed neighborhoods with lower poverty and crime. Subjective perceptions of some aspects of neighborhood and housing quality also improved post‐move. Participants tended to move farther from public transportation but were on average located within one mile of the nearest subway station. Results can be taken as early indicators of the potential benefits of MOIs.
Worthy and able: How helping relationships alter the trajectories of young people who face severe and multiple disadvantages
Authors: Sandu Rebeca D.
Published: October 2020

Relationships with professional helpers, partly resembling family relationships, have the potential to help young people facing severe and multiple disadvantages. The aim of this study was to document how relationships alter the trajectories of young people in these circumstances. Young people (n = 30) and support workers (n = 35) were identified by the leaders of 11 UK and 5 US not‐for‐profit organisations providing support for this population. Thematic analysis of the semi‐structured interviews revealed that relationships helped young people feel positive about themselves, disrupted their maladaptive patterns of thinking, and fostered a sense of agency in themselves. The result was a self that was worthy and able. Findings provided an in‐depth exploration of the notion of support in the context of adversity.
Predictive value of carotid artery ultrasonography for the risk of coronary artery disease
Authors: Zhu Ye , You Jia , Xu Chao , Gu Xiang
Published: October 2020

Purpose

To assess carotid intima‐media thickness (IMT), carotid plaques, and cardiovascular risk factors in patients with suspected coronary artery disease (CHD) to determine their association and predictive value for CHD.

Methods

We performed duplex Doppler ultrasonography of the carotid arteries and coronary angiography or CT in 480 patients with suspected CHD, and investigated their personal and medical histories. Patients were then assigned to the CHD or the control group depending on the presence of coronary lesions. Ultrasonography was performed the morning after admission prior to any treatment, coronary angiography, or CT.

Results

Carotid plaques were mainly distributed in the common carotid artery bifurcation, with a significant difference between the CHD and control groups. Plaque incidence (80%) and IMT were significantly higher (P < .001 and P = .012, respectively) in the CHD (80% and 0.84 ± 0.21 mm) than in the control group (49% and 0.76 ± 0.18 mm). The factors significantly associated with CHD were introduced into a multivariate regression model. Male subject (OR = 1.569, 95%CI 1.004‐2.453; P = .048) and plaque burden (OR = 0.457, 95%CI 0.210‐0.993; P = .048) were significant predictors for CHD occurrence. The presence of carotid plaques performed significantly better than IMT and the Framingham risk score for predicting CHD lesions (P < .001 for both).

Conclusions

CHD patients showed higher percentage of clinical (plaques) or subclinical (IMT) carotid artery wall change, and the presence of carotid plaques showed better predictive value than IMT and Framingham risk score for the presence of coronary artery lesions.
Leaching losses from blueberries grown in sandy soils amended with pine bark
Authors: Bandaranayake Wije M. , Syvertsen James P. , Schumann Arnold , Kadyampakeni Davie M.
Published: October 2020

Leaching of irrigation water from blueberry (Vaccinium spp.) plants intensifies when sandy soils are amended with pine (Pinus spp.) bark. In a greenhouse study, leaching fractions of water (LFW) and nutrients (LFN) were determined from two blueberry (V. corymbosum L.) cultivars, ‘Emerald’ and ‘Jewel’, grown in biochar‐treated and nontreated sandy subsoil and irrigated with drip emitters using one of three pulse frequencies in a factorial design. The LFW was >50% under Emerald and <20% under Jewel, which has a more extensive root system. When the frequency of same volume of irrigation was increased from 2 (F2) to 10 (F10) pulses per day, the average LFW decreased from 46 to 30%. The LFN from a single fertigation was much lower than the total LFN after 6 d of irrigations applied between two fertigation events. The LFN increased linearly with LFW. Amending subsoil with 2% biochar increased soil pH, limited root growth, and did not reduce nutrient leaching. Eighteen months after plant establishment, 1.9% of applied NO3−‐N and 2.5% of applied PO43−‐P from Emerald and 0.8 and 1.0%, respectively, from Jewel leached below the root zone during a fertigation event. During irrigations following a fertigation event, 10.5% of both NO3−‐N and PO43−‐P from Emerald and 3.0 and 2.5% from Jewel leached below the root zone. All growth parameters including root/shoot ratio were higher in Jewel than Emerald. This study indicated that leaching rates could be reduced by selecting blueberry cultivars with a dense root system and using a drip irrigation system with >5 pulses d−1 to supply the daily water requirements in pine bark–amended sandy soil.
Perioperative assessment of indocyanine green elimination rate accurately predicts postoperative liver failure in patients undergoing hepatectomy
Authors: Sunagawa Yuki , Yamada Suguru , Kato Yoshiyasu , Sonohara Fuminori , Takami Hideki , Inokawa Yoshikuni , Hayashi Masamichi , Nakayama Goro , Koike Masahiko , Kodera Yasuhiro
Published: October 2020

Background

This study aimed to evaluate the usefulness of perioperative indocyanine green elimination rate (ICG‐K) as a predictive factor of posthepatectomy liver failure (PHLF).

Methods

This study enrolled 193 patients who underwent hepatectomy between 2013 and 2019. We analyzed the relationship between estimated ICG‐K (ICG‐Krem) calculated by the preoperative ICG‐K and the residual liver volume ratio, ICG‐K at days 1 and 7 after hepatectomy (ICG‐Kpod1, ICG‐Kpod7), and grade B or C PHLF.

Results

Grade B and C PHLF were observed in eight and two patients, respectively. ICG‐Krem and ICG‐Kpod1 were highly correlated (correlation coefficient [CC] 0.715), and ICG‐Krem and ICG‐Kpod7 were moderately correlated (CC 0.653). Receiver‐operating characteristic curve analyses indicated that ICG‐Krem and ICG‐Kpod1 had moderate diagnostic value, while ICG‐Kpod7 had high diagnostic value (area under the curve 0.703, 0.845 and 0.937, respectively). Multivariate analysis demonstrated that ICG‐Kpod7 (relative risk [RR] 26.04, P = .012) and postoperative bile leakage (PBL) (RR 226.0, P < .001) were independent predictive factors for PHLF. PBL induced PHLF in seven patients, respectively.

Conclusions

ICG‐Krem correlated well with postoperative ICG‐K, having moderate accuracy as a predictor of PHLF. However, the clinical relevance of postoperatively measuring ICG‐K is limited because PHLF is greatly affected by surgical and postoperative factors.
Conservative drain management increases the incidence of grade B postoperative pancreatic fistula without increasing serious complications: Does persistent drainage reflect the quality of pancreatic surgery or institutional policy?
Authors: Takeda Yoshinori , Saiura Akio , Takahashi Yu , Inoue Yosuke , Mise Yoshihiro , Ito Hiromichi
Published: October 2020

Background

Among grade B/C postoperative pancreatic fistula (POPF), the clinical burden of patients treated with persistent drainage alone was reported to be less. As the clinical difference might depend on drain management, we evaluated their clinical burden under conservative drain management.

Methods

We included 292 patients who underwent pancreaticoduodenectomy or distal pancreatectomy between 2013 and 2015. Patients with grade B POPF were categorized into those receiving persistent drainage alone (B‐drain) and those receiving other treatments (B‐other). The clinical burden of these groups and patients with biochemical leakage (BL) was compared.

Results

BL, grade B POPF, and grade C POPF occurred in 42 (14%), 93 (32%), and 4 (1.4%) patients, respectively. The B‐drain group comprised 61% of grade B POPF. The overall major morbidity (Clavien–Dindo grade ≥ 3) in the B‐drain group was significantly lower than in the B‐other group (18% vs 50%, P = .001) but was comparable to that of the BL group (19%, P = .848). The POPF‐related major morbidity in the B‐drain and B‐other group were 0% and 25%, respectively (P < .001).

Conclusions

Under conservative drain management, patients with grade B POPF frequently experienced persistent drainage alone and the clinical burden of B‐drain group and BL group was comparable.
Syntheses of novel 1,5‐benzodiazepinederivatives: Crystal structures, spectroscopic characterizations, Hirshfeld surface analyses, molecular docking studies,DFTcalculations, corrosion inhibition anticipation, and antibacterial activities
Authors: El Ghayati Lhoussaine , Sert Yusuf , Sebbar Nada Kheira , Ramli Youssef , Ahabchane Noureddine Hamou , Talbaoui Ahmed , Mague Joel T. , El Ibrahimi Brahim , Taha Mohamed Labd , Essassi El Mokhtar , Al‐Zaqri Nabil , Alsalme Ali
Published: October 2020

A series of newly pyrazolo‐1,5‐benzodiazepine derivatives (5‐7) was performed and characterized by using1H,13C‐NMR spectroscopic measurements. The molecular and crystal structures of two compounds2and7have also been further examined by single‐crystal X‐ray crystallography showing that the alkyl groups are beard by sulfur atom and to pyrazolic nitrogen atom in position 2 and not in position 1 of the tricyclic compounds as described in the literature. In addition, through Hirshfeld surface analysis, molecular docking studies, and DFT calculations, the closest contact between the active atoms of the compound can be determined. Also, the Monte Carlo simulations outcomes show that compounds2and7can be considered as a good acidic corrosion inhibitor for the aluminum metal, while emphasizing that the compound7provides enhanced prevention. Finally, compounds1to7were evaluated for their antibacterial activity against Gram‐positive and Gram‐negative microbial strains such asEscherichia coli,Pseudomonas aeruginosa,Staphylococcus aureus, andStreptococcus. The results obtained demonstrated the antibacterial activity of compounds 1 to 7 tested using the minimal inhibitory concentration.
Vaccine design based on 16 epitopes of SARS‐CoV‐2 spike protein
Authors: He Jinlei , Huang Fan , Zhang Jianhui , Chen Qiwei , Zheng Zhiwan , Zhou Qi , Chen Dali , Li Jiao , Chen Jianping
Published: October 2020

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) urgently requires an effective vaccine for prevention. In this study, 66 epitopes containing pentapeptides of SARS‐CoV‐2 spike protein in the IEDB database were compared with the amino acid sequence of SARS‐CoV‐2 spike protein, and 66 potentially immune‐related peptides of SARS‐CoV‐2 spike protein were obtained. Based on the single‐nucleotide polymorphisms analysis of spike protein of 1218 SARS‐CoV‐2 isolates, 52 easily mutated sites were identified and used for vaccine epitope screening. The best vaccine candidate epitopes in the 66 peptides of SARS‐CoV‐2 spike protein were screened out through mutation and immunoinformatics analysis. The best candidate epitopes were connected by different linkers in silico to obtain vaccine candidate sequences. The results showed that 16 epitopes were relatively conservative, immunological, nontoxic, and nonallergenic, could induce the secretion of cytokines, and were more likely to be exposed on the surface of the spike protein. They were both B‐ and T‐cell epitopes, and could recognize a certain number of HLA molecules and had high coverage rates in different populations. Moreover, epitopes 897‐913 were predicted to have possible cross‐immunoprotection for SARS‐CoV and SARS‐CoV‐2. The results of vaccine candidate sequences screening suggested that sequences (without linker, with linker GGGSGGG, EAAAK, GPGPG, and KK, respectively) were the best. The proteins translated by these sequences were relatively stable, with a high antigenic index and good biological activity. Our study provided vaccine candidate epitopes and sequences for the research of the SARS‐CoV‐2 vaccine.