bluuebunny/crossref_metadata_2025 huggingface dataset:
Species Distribution, Antimicrobial Resistance, and Enterotoxigenicity of Non-aureus Staphylococci in Retail Chicken Meat
Authors: Lee Soo In , Kim Sun Do , Park Ji Heon , Yang Soo-Jin
Published: November 2020

Non-aureus staphylococci (NAS), including coagulase-negative staphylococci, have emerged as important causes of opportunistic infections in humans and animals and a potential cause of staphylococcal food poisoning. In this study, we investigated (i) the staphylococcal species profiles of NAS in in retail chicken meat, (ii) the phenotypic and genotypic factors associated with antimicrobial resistance in the NAS isolates, and (iii) the prevalence of classical and newer staphylococcal enterotoxin (SE) genes. A total of 58 NAS of nine different species were isolated from retail raw chicken meat samples. The occurrence of multidrug resistance in the NAS, particularly S. agnetis and S. chromogenes, with high resistance rates against tetracycline or fluoroquinolones were confirmed. The tetracycline resistance was associated with the presence of tet(L) in S. chromogenes and S. hyicus or tet(K) in S. saprophyticus. The occurrence of fluoroquinolone resistance in S. agnetis and S. chromogenes was usually associated with mutations in the quinolone resistance determining regions (QRDR) of gyrA and parC. In addition, the frequent presence of SE genes, especially seh, sej, and sep, was detected in S. agnetis and S. chromogenes. Our findings suggest that NAS in raw chicken meat can have potential roles as reservoirs for antimicrobial resistance and enterotoxin genes.
Low Dose Combined Treatment with Ultraviolet-C and Withaferin a Enhances Selective Killing of Oral Cancer Cells
Authors: Peng Sheng-Yao , Wang Yen-Yun , Lan Ting-Hsun , Lin Li-Ching , Yuan Shyng-Shiou F. , Tang Jen-Yang , Chang Hsueh-Wei
Published: November 2020

Withaferin A (WFA), a Withania somnifera-derived triterpenoid, is an anticancer natural product. The anticancer effect of nonionizing radiation such as ultraviolet-C (UVC) as well as the combined treatment of UVC and WFA is rarely investigated. Low dose UVC and/or WFA treatments (12 J/m2 and/or 1 μM) were chosen to evaluate antioral cancer cell line effects by examining cytotoxicity, cell cycle disruption, apoptosis induction, and DNA damage. For two cancer cell lines (Ca9-22 and HSC-3), single treatment (UVC or WFA) showed about 80% viability, while a combined treatment of UVC/WFA showed about 40% viability. In contrast, there was noncytotoxicity to normal oral cell lines (HGF-1). Compared to single treatment and control, low dose UVC/WFA shows high inductions of apoptosis in terms of flow cytometric detections for subG1, annexin V, pancaspase changes as well as Western blotting for detecting cleaved poly (ADP-ribose) polymerase (c-PARP) and caspase 3 (c-Cas 3) and luciferase assay for detecting Cas 3/7 activity. Low dose UVC/WFA also showed high inductions of oxidative stress and DNA damage in terms of flow cytometric detections of reactive oxygen species (ROS), mitochondrial superoxide (MitoSOX) generation, and membrane potential (MitoMP) destruction, γH2AX and 8-oxo-2’deoxyguanosine (8-oxodG) types of DNA damages. For comparison, low dose UVC/WFA show rare inductions of annexin V, Cas 3/7 activity, ROS, MitoSOX, and MitoMP changes to normal oral HGF-1 cells. Therefore, low dose UVC/WFA provides a novel selectively killing mechanism to oral cancer cells, suggesting that WFA is a UVC sensitizer to inhibit the proliferation of oral cancer cells.
Fermented Vinegars from Apple Peels, Raspberries, Rosehips, Lavender, Mint, and Rose Petals: The Composition, Antioxidant Power, and Genoprotective Abilities in Comparison to Acetic Macerates, Decoctions, and Tinctures
Authors: Kalemba-Drożdż Małgorzata , Kwiecień Inga , Szewczyk Agnieszka , Cierniak Agnieszka , Grzywacz-Kisielewska Agata
Published: November 2020

Acetic fermentation is a method for processing plant material which has been known since antiquity. Balsamic and apple cider vinegars are investigated as antibacterial, anti-obesity, and anti-diabetic remedies. However, there is little information about vinegars fermented from aromatic herbs and edible plants. The aim of this study was to compare extracts used for culinary and medicinal purposes according to their composition, antioxidant power, and genoprotective properties. Fermented vinegars, acetic macerates, decoctions, and tinctures in 70% ethanol from raspberries, apple peels, rosehips, lavender, mint, and rose petals were prepared. Polyphenols, ascorbate, carotenoid concentrations, and antioxidant power were analyzed. The polyphenols were identified using HPLC (high-performance liquid chromatography). The genoprotective properties were measured using a comet assay on lymphocytes. Fermented vinegars were poorest in phytochemicals in comparison to tinctures, decoctions, or acetic macerates, although they contained the highest concentration of metal ions. The antioxidant abilities were correlated to the phenolic content of extract. None of the extracts induced DNA damages into lymphocytes. The rosehip and rose petal extracts revealed the highest genoprotective abilities, while mint and apple fermented vinegars and decoctions had the lowest. Fermented vinegars are not a rich source of phytochemicals and they show weak genoprotective abilities, but, in increasing demand for antioxidants, any form of phytochemical sources is an added-value in diet.
Effects of Rutin on Wound Healing in Hyperglycemic Rats
Authors: Chen Li-You , Huang Chien-Ning , Liao Chih-Kai , Chang Hung-Ming , Kuan Yu-Hsiang , Tseng To-Jung , Yen Kai-Jung , Yang Kai-Lin , Lin Hsing-Chun
Published: November 2020

Long-term poor glycemic control negatively affects macrovascular and microvascular diseases, as well as wound restoration. Buckwheat is a good source of rutin (quercetin-3-O-rutoside) and has benefits in regulating blood sugar. This study was to evaluate the antioxidant and anti-inflammatory effects of rutin on wound healing in streptozotocin-induced hyperglycemic rats. Eighteen male Wistar rats were randomly divided into three groups: normal (NDM), hyperglycemic (DM), and hyperglycemic with rutin (DMR). After induction of hyperglycemia for 2 days, a 15 × 15 mm wound was induced on the back of each rat. Intraperitoneal injection of rutin significantly ameliorated diabetes-induced body weight loss and improved metabolic dysfunctions of hyperglycemic rats. Based on appearance and histopathological staining, rutin promotes wound healing and inhibits production of inflammatory cells. The immunoblotting data indicated that rutin promotes production of antioxidant enzymes induced by nuclear factor erythroid 2-related factor 2 (NRF2), inhibits the expression of matrix metalloproteinases (MMPs) regulated by NF-κB, and decreases the expression of vascular endothelial growth factor (VEGF). It also promotes the expression of neurogenic-related protein (UCH-L1). The aforementioned results indicated that rutin reduces oxidative stress and inflammatory response in hyperglycemic rats, promoting wound healing and subsequently reducing the risk of wound ulcers.
Hydrogen Sulfide Relaxes Human Uterine Artery via Activating Smooth Muscle BKCa Channels
Authors: Li Yan , Bai Jin , Yang Yi-hua , Hoshi Naoto , Chen Dong-bao
Published: November 2020

Opening of large conductance calcium-activated and voltage-dependent potassium (BKCa) channels hyperpolarizes plasma membranes of smooth muscle (SM) to cause vasodilation, underling a key mechanism for mediating uterine artery (UA) dilation in pregnancy. Hydrogen sulfide (H2S) has been recently identified as a new UA vasodilator, yet the mechanism underlying H2S-induced UA dilation is unknown. Here, we tested whether H2S activated BKCa channels in human UA smooth muscle cells (hUASMC) to mediate UA relaxation. Multiple BKCa subunits were found in human UA in vitro and hUASMC in vitro, and high β1 and γ1 proteins were localized in SM cells in human UA. Baseline outward currents, recorded by whole-cell and single-channel patch clamps, were significantly inhibited by specific BKCa blockers iberiotoxin (IBTX) or tetraethylammonium, showing specific BKCa activity in hUASMC. H2S dose (NaHS, 1–1000 µM)-dependently potentiated BKCa currents and open probability. Co-incubation with a Ca2+ blocker nifedipine (5 µM) or a chelator (ethylene glycol-bis (β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), 5 mM) did not alter H2S-potentiated BKCa currents and open probability. NaHS also dose-dependently relaxed phenylephrine pre-constricted freshly prepared human UA rings, which was inhibited by IBTX. Thus, H2S stimulated human UA relaxation at least partially via activating SM BKCa channels independent of extracellular Ca2+.
A BIM Platform for the Manufacture of Prefabricated Steel Structure
Authors: Chen Shengxin , Wu Jie , Shi Jialin
Published: November 2020

In the design phase, building information modeling (BIM) software has been widely employed due to its high efficiency, precision, and synergy among different teams. However, the advantages of BIM have not been fully explored in the manufacturing stage where the progress is not so transparent, and information exchange is not so smooth. To deal with these problems, a BIM platform for the manufacture of steel structures is developed in this article, which aims for the management and visualization of manufacturing progress in a steel structure factory in China. The proposed platform was developed and tested by using practical projects. The requirement is analyzed with different users involved in the manufacturing progress. The platform is web-based, where Node.js is adopted for server-side scripting, Neo4j is used for data storage, hyper text markup language (HTML), cascading style sheets (CSS), and JavaScript are used to compile user interface. Besides, a quick response (QR) code is attached to components for traceability. By parsing the BIM model exported in the design phase, essential information of components is imported into the platform, which are the data that form the basis of the following operation. By introducing the platform as a collaborative tool, the traceability and visibility of real-time manufacturing progress of each steel component are significantly enhanced. As a result, this platform can help managers make decisions, workers check quality problems, and other stakeholders grasp the manufacturing progress.
A Novel Joint Localization Method for Acoustic Emission Source Based on Time Difference of Arrival and Beamforming
Authors: Wang Xiaoran , Liu Xiandong , He Tian , Tai Junfei , Shan Yingchun
Published: November 2020

Time difference of arrival (TDOA) method and beamforming method are often individually utilized in the localization of acoustic emission source of a plate. Based on the performances of the two methods, a novel joint localization method for acoustic emission source is proposed in this paper. Firstly, the performances of TDOA method and beamforming method are studied based on the simulation signals. Then, aiming at the advantages and disadvantages of these two methods, a joint localization method is proposed. Finally, the performances of joint localization method are verified by simulation and experiment. Both simulation and experimental results show that the accuracy of the joint localization method is improved, and the calculation amount is greatly reduced in comparison to the TDOA method and the beamforming method.
Effects of the Geometric Parameters of Mixer on the Mixing Process of Foam Concrete Mixture and Its Energy Efficiency
Authors: Stel’makh Sergey A. , Shcherban’ Evgenii M. , Shuiskii Anatolii I. , Prokopov Al’bert Yu. , Madatyan Sergey M. , Parinov Ivan A. , Cherpakov Alexander V.
Published: November 2020

The paper studies the influence of the geometric parameters of the mixer on the mixing process, the construction of the mixing body, its location in the mixer bulk, and the mixer shape and geometry. The technique of calculating the power spent on mixing the foam concrete mixture is described. The effects of the ratio of the mixture height to the mixer diameter, the number and width of reflective partitions, and the shape of the conical part of the mixer on the homogeneity of the foam concrete mixture and the power consumption are considered. The optimal ratios of the foam concrete mixture height to the mixer diameter have been determined. Moreover, the optimal range of the ratios of the partition width to the mixer diameter has been established, in order to obtain a homogeneous foam concrete mixture throughout the volume with lower energy consumption. The optimal values of the angle of the mixer conical part for the preparation of a foam concrete mixture have been determined.
Seismic Reliability Assessment of Water Supply Systems Considering Critical Paths
Authors: Lee Chan Wook , Kwon Hyuk Jae , Yoo Do Guen
Published: November 2020

In general, studies of the seismic reliability of water supply systems through hydraulic analysis models fall into three categories: (1) model development through hydraulic analysis, (2) establishment of post-earthquake recovery strategies, and (3) robust design in preparation for earthquakes and the development of improvement techniques. In this study, with regard to the design of earthquake resistance techniques, which is the third category, a seismic reliability assessment was conducted that considers the water supply system, and a plan to maximize the seismic reliability was determined as a result of the analysis. The degree of improvement in seismic reliability was quantified for water supply systems with various sources and water supply routes via modeling of seismic protection for each water supply route. Korea’s A industrial water system, which has a history of large-scale earthquakes, was divided into nine paths, and the reliability of the water supply system and the cost of earthquake resistance were calculated and compared between the different paths. A water supply path consists of a combination of pipes of various sizes and lengths, and the amount of water to be supplied differs between paths. Quantifying the effect of the water supply system and the seismic reliability of a route is intended to provide a basic methodology for identifying the critical path that should be the target of seismic protection when money and resources available for construction are limited. This methodology was used to confirm that the reliability of the water supply, the demand for water, and the cost of earthquake resistance should be considered together to establish an earthquake resistance strategy for the critical path in a water supply system. We expect that the results of this study will be used to establish detailed strategies for preliminary reinforcement against earthquake damage based on critical paths rather than all or individual pipelines in a water supply network.
The Significance of Sky Temperature in the Assessment of the Thermal Performance of Buildings
Authors: Albatayneh Aiman , Alterman Dariusz , Page Adrian , Moghtaderi Behdad
Published: November 2020

Energy-efficient building design needs an accurate way to estimate temperature inside the building which facilitates the calculation of heating and cooling energy requirements in order to achieve appropriate thermal comfort for occupants. Sky temperature is an important factor for any building assessment tool which needs to be precisely determined for accurate estimation of the energy requirement. Many building simulation tools have been used to calculate building thermal performance such as Autodesk Computational Fluid Dynamics (CFD) software, which can be used to calculate building internal air temperature but requires sky temperature as a key input factor for the simulation. Real data obtained from real-sized house modules located at University of Newcastle, Australia (southern hemisphere), were used to find the impact of different sky temperatures on the building’s thermal performance using CFD simulation. Various sky temperatures were considered to determine the accurate response which aligns with a real trend of buildings’ internal air temperature. It was found that the internal air temperature in a building keeps either rising or decreasing if higher or lower sky temperature is chosen. This significantly decreases the accuracy of the simulation. It was found that using the right sky temperature values for each module, Cavity Brick Module (CB) Insulated Cavity Brick Module (InsCB), Insulated Brick Veneer Module (InsBV) and Insulated Reverse Brick Veneer Module (InsRBV), will result in 6.5%, 7.1%, 6.2% and 6.4% error correspondingly compared with the real data. These errors mainly refer to the simulation error. On the other hand using higher sky temperatures by +10 °C will significantly increase the simulation error to 16.5%, 17.5%, 17.1% and 16.8% and lower sky temperature by +10 °C will also increase the error to 19.3%, 22.6%, 21.9% and 19.1% for CB, InsCB, InsBV and InsRBV modules, respectively.
Personal Atmosphere: Estimation of Air Conditioner Parameters for Personalizing Thermal Comfort
Authors: Mashita Tomohiro , Kanayama Tetsuya , Ratsamee Photchara
Published: November 2020

Air conditioners enable a comfortable environment for people in a variety of scenarios. However, in the case of a room with multiple people, the specific comfort for a particular person is highly dependent on their clothes, metabolism, preference, and so on, and the ideal conditions for each person in a room can conflict with each other. An ideal way to resolve these kinds of conflicts is an intelligent air conditioning system that can independently control air temperature and flow at different areas in a room and then produce thermal comfort for multiple users, which we define as the personal preference of air flow and temperature. In this paper, we propose Personal Atmosphere, a machine learning based method to obtain parameters of air conditioners which generate non-uniform distributions of air temperature and flow in a room. In this method, two dimensional air-temperature and -flow distributions in a room are used as input to a machine learning model. These inputs can be considered a summary of each user’s preference. Then the model outputs a parameter set for air conditioners in a given room. We utilized ResNet-50 as the model and generated a data set of air temperature and flow distributions using computational fluid dynamics (CFD) software. We then conducted evaluations with two rooms that have two and four air conditioners under the ceiling. We then confirmed that the estimated parameters of the air conditioners can generate air temperature and flow distributions close to those required in simulation. We also evaluated the performance of a ResNet-50 with fine tuning. This result shows that its learning time is significantly decreased, but performance is also decreased.
Advanced Rainfall Trend Analysis of 117 Years over West Coast Plain and Hill Agro-Climatic Region of India
Authors: Saini Atul , Sahu Netrananda , Kumar Pankaj , Nayak Sridhara , Duan Weili , Avtar Ram , Behera Swadhin
Published: November 2020

In this paper, the rainfall trend of the West Coast Plain and Hill Agro-Climatic Region is analyzed for 117 years (1901–2017). This region is a globally recognized biodiversity hotspot and known for one of the highest rainfall receiving regions in India. Rainfall grid dataset is used for the analysis of rainfall trends on monthly, seasonal, and decadal time scales. Modified Mann–Kendall’s test, Linear Regression, Innovative Trend Analysis, Sen’s Slope test, Weibull’s Recurrence Interval, Pearson’s Coefficient of Skewness, Consecutive Disparity Index, Kurtosis, and some other important statistical techniques are employed for trend analysis. Results indicate that the rainfall trend is significant in January, July, August, September as well as the Winter season. Among all the significant trends, January and July showed a decreasing rainfall trend. July has the highest contribution (30%) among all the obtained monotonic trend to annual rainfall and coincidentally has the highest trend magnitude. August and September months with a combined contribution of 30% to annual rainfall, show an increasing monotonic trend with high magnitude whereas Winter season shows a monotonic decreasing rainfall trend with comparatively low magnitudes. Decadal analysis along with the study of recurrence interval of excess and deficit years helps to understand the decadal rhythm of trend and the magnitude of extreme monthly and seasonal events. Skewness reveals that rainfall dataset of all the periodic results is right-skewed and the recurrence interval also supports the skewness results. Sharply decreasing rainfall in July and rising rainfall in August and September is predictive of the impact on agriculture, biodiversity and indicates the rainfall regime shift in the region.
USP25 Regulates EGFR Fate by Modulating EGF-Induced Ubiquitylation Dynamics
Authors: Niño Carlos A. , Wollscheid Nadine , Giangreco Giovanni , Maspero Elena , Polo Simona
Published: November 2020

Deregulated epidermal growth factor receptor (EGFR) signaling is a key feature in different stages of oncogenesis. One important mechanism whereby cancer cells achieve increased and uncontrolled EGFR signaling is escaping down-modulation of the receptor. Ubiquitylation of the EGFR plays a decisive role in this process, as it regulates receptor internalization, trafficking and degradation. Deubiquitinating enzymes (DUBs) may oppose the ubiquitylation process, antagonizing or even promoting receptor degradation. Here, we use qualitative and quantitative assays to measure EGFR internalization and degradation after Ubiquitin Specific Peptidase 25 (USP25) depletion. We show that, by acting at the early steps of EGFR internalization, USP25 restrains the degradation of the EGFR by assisting in the association of the E3 ubiquitin ligase c-Cbl with EGFR, thereby modulating the amplitude of ubiquitylation on the receptor. This study establishes USP25 as a negative regulator of the EGFR down-modulation process and suggests that it is a promising target for pharmacological intervention to hamper oncogenic growth signals in tumors that depend on the EGFR.
Glutathione Enhances Auxin Sensitivity in Arabidopsis Roots
Authors: Pasternak Taras , Palme Klaus , Paponov Ivan A.
Published: November 2020

Root development is regulated by the tripeptide glutathione (GSH), a strong non-enzymatic antioxidant found in plants but with a poorly understood function in roots. Here, Arabidopsis mutants deficient in GSH biosynthesis (cad2, rax1, and rml1) and plants treated with the GSH biosynthesis inhibitor buthionine sulfoximine (BSO) showed root growth inhibition, significant alterations in the root apical meristem (RAM) structure (length and cell division), and defects in lateral root formation. Investigation of the molecular mechanisms of GSH action showed that GSH deficiency modulated total ubiquitination of proteins and inhibited the auxin-related, ubiquitination-dependent degradation of Aux/IAA proteins and the transcriptional activation of early auxin-responsive genes. However, the DR5 auxin transcriptional response differed in root apical meristem (RAM) and pericycle cells. The RAM DR5 signal was increased due to the up-regulation of the auxin biosynthesis TAA1 protein and down-regulation of PIN4 and PIN2, which can act as auxin sinks in the root tip. The transcription auxin response (the DR5 signal and expression of auxin responsive genes) in isolated roots, induced by a low (0.1 µM) auxin concentration, was blocked following GSH depletion of the roots by BSO treatment. A higher auxin concentration (0.5 µM) offset this GSH deficiency effect on DR5 expression, indicating that GSH deficiency does not completely block the transcriptional auxin response, but decreases its sensitivity. The ROS regulation of GSH, the active GSH role in cell proliferation, and GSH cross-talk with auxin assume a potential role for GSH in the modulation of root architecture under stress conditions.
Plasmacytoid Dendritic Cell (pDC) Infiltration Correlate with Tumor Infiltrating Lymphocytes, Cancer Immunity, and Better Survival in Triple Negative Breast Cancer (TNBC) More Strongly than Conventional Dendritic Cell (cDC)
Authors: Oshi Masanori , Newman Stephanie , Tokumaru Yoshihisa , Yan Li , Matsuyama Ryusei , Kalinski Pawel , Endo Itaru , Takabe Kazuaki
Published: November 2020

Dendritic cells (DC) represent a major antigen-presenting cell type in the tumor immune microenvironment (TIME) and play an essential role in cancer immunity. Conventional DC (cDC) and plasmacytoid DC (pDC) were defined by the xCell algorithm and a total of 2968 breast cancer patients (TCGA and METABRIC) were analyzed. We found that triple-negative breast cancer (TNBC) had a high fraction of cDC and pDC compared to the other subtypes. In contrast to cDC, high pDC in TNBC was significantly associated with better disease-specific and disease-free survival consistently in both cohorts. High cDC TNBC tumors enriched not only inflammation and immune-related, but also metastasis-related gene sets in Gene Set Enrichment Analysis, whereas high pDC TNBC enriched inflammation and immune -related gene sets including IFN-γ signaling more strongly than cDC. pDC TNBC correlated with CD8+, CD4+ memory, IFN-γ score, and cytolytic activity stronger than cDC TNBC. High pDC TNBC were associated with a high fraction of anti-cancer immune cells and high expression of all the immune check point molecules examined. In conclusion, pDC levels correlated with the infiltration of immune cells and patient survival in TNBC more strongly than cDC; this is the first study suggesting the clinical relevance of pDC infiltration in TNBC.
Serum Myostatin Predicts the Risk of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Multicenter Study
Authors: Kim Ji Hyun , Kang Seong Hee , Lee Minjong , Youn Gi Soo , Kim Tae Suk , Jun Baek Gyu , Kim Moon Young , Kim Young Don , Cheon Gab Jin , Kim Dong Joon , Baik Soon Koo , Choi Dae Hee , Suk Ki Tae
Published: November 2020

Background and Aim: Previous studies reported that serum myostatin is associated with sarcopenia. We aimed to elucidate the association between serum myostatin levels and hepatocellular carcinoma (HCC) development in patients with alcoholic liver cirrhosis (ALC). Methods: This retrospective, multicenter study assessed 1077 Asian ALC patients enrolled from 2007 to 2017. The primary endpoint was the development of HCC within 5 years. Cox proportional hazards model analyses were used to assess the association of serum myostatin levels and HCC development. The time-dependent areas under the receiver operating characteristic curve (AUROC) of serum myostatin for 5-year HCC development were calculated. Serum myostatin levels were measured using an enzyme-linked immunosorbent assay with samples collected on the index date. Results: During a median follow-up of 2.5 years, 5-year cumulative HCC incidence rates were 6.7% in the total population. The median level of serum myostatin was 3.3 ng/mL (interquartile, 2.1–5.2 ng/mL). The AUROC of serum myostatin for 5-year HCC development was 0.78 (95% confidence interval [CI], 0.76–0.81). In Cox proportional hazards model analyses, age, gender, platelet counts, and serum myostatin levels were independent risk factors for HCC development (adjusted hazard ratios [HRs] of age, male gender, platelet counts, and serum myostatin: 1.03, 2.79, 0.996, 1.18, respectively; all p < 0.05). Patients with high myostatin levels had a significantly higher risk of 5-year HCC development than those with low myostatin levels (HR 7.53, p < 0.001). Conclusion: Higher serum myostatin levels were significantly associated with a higher risk of developing HCC in ALC patients, which could identify high-risk patients who need stringent surveillance.
Severe Salmonella spp. or Campylobacter spp. Infection and the Risk of Biliary Tract Cancer: A Population-Based Study
Authors: de Savornin Lohman Elise , Duijster Janneke , Groot Koerkamp Bas , van der Post Rachel , Franz Eelco , Mughini Gras Lapo , de Reuver Philip
Published: November 2020

Salmonella spp. infection has shown to have oncogenic transformative effects and thereby increases the risk of certain cancers. For Campylobacter spp., similar effects have been demonstrated. Risk factor identification may allow for timely diagnosis and preventive treatment. To substantiate the oncogenic potential of Salmonella and Campylobacter spp., this study compared the incidence of extrahepatic biliary tract cancer (BTC) in patients with diagnosed Salmonella or Campylobacter spp. infection with BTC incidence in the Netherlands. National infectious diseases surveillance records of patients diagnosed with a laboratory-confirmed Salmonella or Campylobacter spp. infection during 1999–2016 were linked to the Netherlands Cancer Registry. Incidence of BTC in Salmonella and Campylobacter spp. patients was compared to the incidence of BTC in the general population using Standardized Incidence Ratios (SIRs). In total, 16,252 patients were diagnosed with Salmonella spp. and 27,668 with Campylobacter spp. infection. Nine patients developed BTC at a median of 46 months (13–67) after Salmonella spp. infection and seven at a median of 60 months (18–138) after Campylobacter spp. infection. SIR of BTC in salmonellosis patients was 1.53 (95% CI 0.70–2.91). In patients aged <60 years, the SIR was 1.74 (95% CI 0.36–5.04). For campylobacteriosis patients, the SIR was 0.97 (95% CI 0.39–2.00). Even though Salmonella or Campylobacter spp. infection was not significantly associated with increased BTC risk in this cohort, it remains extremely important to study potential risk factors for cancer to facilitate screening and ultimately improve prognosis of cancer patients.
Colon Capsule Endoscopy vs. CT Colonography Following Incomplete Colonoscopy: A Systematic Review with Meta-Analysis
Authors: Deding Ulrik , Kaalby Lasse , Bøggild Henrik , Plantener Eva , Wollesen Mie Kruse , Kobaek-Larsen Morten , Hansen Siri Juul , Baatrup Gunnar
Published: November 2020

Following incomplete colonoscopy (IC) patients often undergo computed tomography colonography (CTC), but colon capsule endoscopy (CCE) may be an alternative. We compared the completion rate, sensitivity and diagnostic yield for polyp detection from CCE and CTC following IC. A systematic literature search resulted in twenty-six studies. Extracted data included inter alia, complete/incomplete investigations and polyp findings. Pooled estimates of completion rates of CCE and CTC and complete colonic view rates (CCE reaching the most proximal point of IC) of CCE were calculated. Per patient diagnostic yields of CCE and CTC were calculated stratified by polyp sizes. CCE completion rate and complete colonic view rate were 76% (CI 95% 68–84%) and 90% (CI 95% 83–95%). CTC completion rate was 98% (CI 95% 96–100%). Diagnostic yields of CTC and CCE were 10% (CI 95% 7–15%) and 37% (CI 95% 30–43%) for any size, 13% (CI 95% 9–18%) and 21% (CI 95% 12–32%) for >5-mm and 4% (CI 95% 2–7%) and 9% (CI 95% 3–17%) for >9-mm polyps. No study performed a reference standard follow-up after CCE/CTC in individuals without findings, rendering sensitivity calculations unfeasible. The increased diagnostic yield of CCE could outweigh its slightly lower complete colonic view rate compared to the superior CTC completion rate. Hence, CCE following IC appears feasible for an introduction to clinical practice. Therefore, randomized studies investigating CCE and/or CTC following incomplete colonoscopy with a golden standard reference for the entire population enabling estimates for sensitivity and specificity are needed.
Biotechnological Approach for the Production of Enantiomeric Hydroxylactones Derived from Benzaldehyde and Evaluation of Their Cytotoxic Activity
Authors: Mazur Marcelina , Kudrynska Anna , Pawlak Aleksandra , Hernandez-Suarez Beatriz , Obmińska-Mrukowicz Bożena , Gładkowski Witold
Published: November 2020

The β-aryl-δ-halo-γ-lactones are known for their antiproliferative activity towards numerous cancer cell lines. The aim of this study was to obtain in the biotransformation process new β-aryl-δ-hydroxy-γ-lactones and compare their activity with the antiproliferative activity of parent compounds. The racemic cis-5-(1-iodoethyl)-4-phenyldihydrofuran-2-one as well as separate enantiomers were transformed in fungal cultures. Among ten tested biocatalysts, three (Absidia cylindrospora AM336, Absidia glauca AM254, and Fusarium culmorum AM10) were able to catalyze the hydrolytic dehalogenation process. The biotransformations processes were highly stereoselective and enantiomerically pure hydroxylactones were obtained (ee ≥ 99%). The iodo- and hydroxylactone enantiomers were subjected to cytotoxic activity evaluation on canine leukemia and lymphoma cell lines. The iodolactones exhibited higher biological potential towards tested cell lines than hydroxylactones. Higher cytotoxic potential was also characteristic for (+)-(4S,5S,6R)-enantiomer of iodolactone compared to its antipode.
Construction of Synthetic Models for Nitrogenase-Relevant NifB Biogenesis Intermediates and Iron-Carbide-Sulfide Clusters
Authors: Joseph Chris , Shupp John Patrick , Cobb Caitlyn R. , Rose Michael J.
Published: November 2020

The family of nitrogenase enzymes catalyzes the reduction of atmospheric dinitrogen (N2) to ammonia under remarkably benign conditions of temperature, pressure, and pH. Therefore, the development of synthetic complexes or materials that can similarly perform this reaction is of critical interest. The primary obstacle for obtaining realistic synthetic models of the active site iron-sulfur-carbide cluster (e.g., FeMoco) is the incorporation of a truly inorganic carbide. This review summarizes the present state of knowledge regarding biological and chemical (synthetic) incorporation of carbide into iron-sulfur clusters. This includes the Nif cluster of proteins and associated biochemistry involved in the endogenous biogenesis of FeMoco. We focus on the chemical (synthetic) incorporation portion of our own efforts to incorporate and modify C1 units in iron/sulfur clusters. We also highlight recent contributions from other research groups in the area toward C1 and/or inorganic carbide insertion.
Recent Advances in Continuous-Flow Reactions Using Metal-Free Homogeneous Catalysts
Authors: Sugisawa Naoto , Nakamura Hiroyuki , Fuse Shinichiro
Published: November 2020

Developments that result in high-yielding, low-cost, safe, scalable, and less-wasteful processes are the most important goals in synthetic organic chemistry. Continuous-flow reactions have garnered much attention due to many advantages over conventional batch reactions that include precise control of short reaction times and temperatures, low risk in handling dangerous compounds, and ease in scaling up synthesis. Combinations of continuous-flow reactions with homogeneous, metal-free catalysts further enhances advantages that include low-cost and ready availability, low toxicity, higher stability in air and water, and increased synthetic efficiency due to the avoidance of the time-consuming removal of toxic metal traces. This review summarizes recently reported continuous-flow reactions using metal-free homogeneous catalysts and classifies them either as acidic catalysts, basic catalysts, or miscellaneous catalysts. In addition, we compare the results between continuous-flow conditions and conventional batch conditions to reveal the advantages of using flow reactions with metal-free homogeneous catalysts.
Promotional Effect of Manganese on Selective Catalytic Reduction of NO by CO in the Presence of Excess O2 over M@La–Fe/AC (M = Mn, Ce) Catalyst
Authors: Gholami Fatemeh , Gholami Zahra , Tomas Martin , Vavrunkova Veronika , Mirzaei Somayeh , Vakili Mohammadtaghi
Published: November 2020

The catalytic performance of a series of La-Fe/AC catalysts was studied for the selective catalytic reduction (SCR) of NO by CO. With the increase in La content, the Fe2+/Fe3+ ratio and amount of surface oxygen vacancies (SOV) in the catalysts increased; thus the catalytic activity improved. Incorporating the promoters to La3-Fe1/active carbon (AC) catalyst could affect the catalyst activity by changing the electronic structure. The increase in Fe2+/Fe3+ ratio after the promoter addition is possibly due to the extra synergistic interaction of M (Mn and Ce) and Fe through the redox equilibrium of M3+ + Fe3+ ↔ M4+ + Fe2+. This phenomenon could have improved the redox cycle, enhanced the SOV formation, facilitated NO decomposition, and accelerated the CO-SCR process. The presence of O2 enhanced the formation of the C(O) complex and improved the activation of the metal site. Mn@La3-Fe1/AC catalyst revealed an excellent NO conversion of 93.8% at 400 °C in the presence of 10% oxygen. The high catalytic performance of MnOx and double exchange behavior of Mn3+ and Mn4+ can increase the number of SOV and improve the catalytic redox properties.
Pancreatic Fibroblast Heterogeneity: From Development to Cancer
Authors: Garcia Paloma E. , Scales Michael K. , Allen Benjamin L. , Pasca di Magliano Marina
Published: November 2020

Pancreatic ductal adenocarcinoma (PDA) is characterized by an extensive fibroinflammatory microenvironment that accumulates from the onset of disease progression. Cancer-associated fibroblasts (CAFs) are a prominent cellular component of the stroma, but their role during carcinogenesis remains controversial, with both tumor-supporting and tumor-restraining functions reported in different studies. One explanation for these contradictory findings is the heterogeneous nature of the fibroblast populations, and the different roles each subset might play in carcinogenesis. Here, we review the current literature on the origin and function of pancreatic fibroblasts, from the developing organ to the healthy adult pancreas, and throughout the initiation and progression of PDA. We also discuss clinical approaches to targeting fibroblasts in PDA.
Modification of a Constitutive to Glucose-Responsive Liver-Specific Promoter Resulted in Increased Efficacy of Adeno-Associated Virus Serotype 8-Insulin Gene Therapy of Diabetic Mice
Authors: Sia Kian Chuan , Fu Zhen Ying , Calne Roy Y. , Nathwani Amit C. , Lee Kok Onn , Gan Shu Uin
Published: November 2020

We have previously used a hepatotropic adeno-associated viral (AAV) vector with a modified human insulin gene to treat diabetic mice. The HLP (hybrid liver-specific promoter) used was constitutively active and non-responsive to glucose. In this study, we examined the effects of addition of glucose responsive elements (R3G) and incorporation of a 3′ albumin enhancer (3′iALB) on insulin expression. In comparison with the original promoter, glucose responsiveness was only observed in the modified promoters in vitro with a 36 h lag time before the peak expression. A 50% decrease in the number of viral particles at 5 × 109 vector genome (vg)/mouse was required by AAV8-R3GHLP-hINSco to reduce the blood sugar level to near normoglycemia when compared to the original AAV8-HLP-hINSco that needed 1 × 1010 vg/mouse. The further inclusion of an 860 base-pairs 3′iALB enhancer component in the 3′ untranslated region increased the in vitro gene expression significantly but this increase was not observed when the packaged virus was systemically injected in vivo. The addition of R3G to the HLP promoter in the AAV8-human insulin vector increased the insulin expression and secretion, thereby lowering the required dosage for basal insulin treatment. This in turn reduces the risk of liver toxicity and cost of vector production.
Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration
Authors: González-Sanmiguel Juliana , Schuh Christina M. A. P. , Muñoz-Montesino Carola , Contreras-Kallens Pamina , Aguayo Luis G. , Aguayo Sebastian
Published: November 2020

Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Creutzfeldt–Jakob disease (CJD) are brain conditions affecting millions of people worldwide. These diseases are associated with the presence of amyloid-β (Aβ), alpha synuclein (α-Syn) and prion protein (PrP) depositions in the brain, respectively, which lead to synaptic disconnection and subsequent progressive neuronal death. Although considerable progress has been made in elucidating the pathogenesis of these diseases, the specific mechanisms of their origins remain largely unknown. A body of research suggests a potential association between host microbiota, neuroinflammation and dementia, either directly due to bacterial brain invasion because of barrier leakage and production of toxins and inflammation, or indirectly by modulating the immune response. In the present review, we focus on the emerging topics of neuroinflammation and the association between components of the human microbiota and the deposition of Aβ, α-Syn and PrP in the brain. Special focus is given to gut and oral bacteria and biofilms and to the potential mechanisms associating microbiome dysbiosis and toxin production with neurodegeneration. The roles of neuroinflammation, protein misfolding and cellular mediators in membrane damage and increased permeability are also discussed.
Optimizing Piezoelectric Cantilever Design for Electronic Nose Applications
Authors: Korsa Matiyas Tsegay , Maria Carmona Domingo Josep , Nsubuga Lawrence , Hvam Jeanette , Niekiel Florian , Lofink Fabian , Rubahn Horst-Günter , Adam Jost , Hansen Roana de Oliveira
Published: November 2020

This work demonstrates a method to optimize materials and dimensions of piezoelectric cantilevers for electronic nose applications via finite element analysis simulations. Here we studied the optimum piezoelectric cantilever configuration for detection of cadaverine, a biomarker for meat ageing, to develop a potential electronic nose for the meat industry. The optimized cantilevers were fabricated, characterized, interfaced using custom-made electronics, and tested by approaching meat pieces. The results show successful measurements of cadaverine levels for meat pieces with different ages, hence, have a great potential for applications within the meat industry shelf-life prediction.
The Surface Characterisation of Polyetheretherketone (PEEK) Modified via the Direct Sputter Deposition of Calcium Phosphate Thin Films
Authors: Hussain Shahzad , Rutledge Leanne , Acheson Jonathan G. , Meenan Brian J. , Boyd Adrian R.
Published: November 2020

Polyetheretherketone (PEEK) has emerged as the material of choice for spinal fusion devices, replacing conventional materials such as titanium and its alloys due to its ability to easily overcome a lot of the limitations of traditional metallic biomaterials. However, one of the major drawbacks of this material is that it is not osteoinductive, nor osteoconductive, preventing direct bone apposition. One way to overcome this is through the modification of the PEEK with bioactive calcium phosphate (CaP) materials, such as hydroxyapatite (HA–Ca10(PO4)6(OH)2). RF magnetron sputtering has been shown to be a particularly useful technique for the deposition of CaP coatings due to the ability of the technique to provide greater control of the coating’s properties. The work undertaken here involved the deposition of HA directly onto PEEK via RF magnetron at a range of deposition times between 10–600 min to provide more bioactive surfaces. The surfaces produced have been extensively characterised using X-Ray Photoelectron Spectroscopy (XPS), Scanning Electron Microscopy (SEM), stylus profilometry, and Time of Flight Secondary Ion Mass Spectrometry (ToFSIMS). XPS results indicated that both Ca and P had successfully deposited onto the surface, albeit with low Ca/P ratios of around 0.85. ToFSIMS analysis indicated that Ca and P had been homogeneously deposited across all the surfaces. The SEM results showed that the CaP surfaces produced were a porous micro-/nano-structured lattice network and that the deposition rate influenced the pore area, pore diameter and number of pores. Depth profiling, using ToFSIMS, highlighted that Ca and P were embedded into the PEEK matrix up to a depth of around 1.21 µm and that the interface between the CaP surface and PEEK substrate was an intermixed layer. In summary, the results highlighted that RF magnetron sputtering can deliver homogenous CaP lattice-like surfaces onto PEEK in a direct, one-step process, without the need for any interlayers, and provides a basis for enhancing the potential bioactivity of PEEK.
Effect of Computational Schemes on Coupled Flow and Geo-Mechanical Modeling of CO2 Leakage through a Compromised Well
Authors: Islam Mohammad , Huerta Nicolas , Dilmore Robert
Published: November 2020

Carbon capture, utilization, and storage (CCUS) describes a set of technically viable processes to separate carbon dioxide (CO2) from industrial byproduct streams and inject it into deep geologic formations for long-term storage. Legacy wells located within the spatial domain of new injection and production activities represent potential pathways for fluids (i.e., CO2 and aqueous phase) to leak through compromised components (e.g., through fractures or micro-annulus pathways). The finite element (FE) method is a well-established numerical approach to simulate the coupling between multi-phase fluid flow and solid phase deformation interactions that occur in a compromised well system. We assumed the spatial domain consists of a three-phases system: a solid, liquid, and gas phase. For flow in the two fluids phases, we considered two sets of primary variables: the first considering capillary pressure and gas pressure (PP) scheme, and the second considering liquid pressure and gas saturation (PS) scheme. Fluid phases were coupled with the solid phase using the full coupling (i.e., monolithic coupling) and iterative coupling (i.e., sequential coupling) approaches. The challenge of achieving numerical stability in the coupled formulation in heterogeneous media was addressed using the mass lumping and the upwinding techniques. Numerical results were compared with three benchmark problems to assess the performance of coupled FE solutions: 1D Terzaghi’s consolidation, Liakopoulos experiments, and the Kueper and Frind experiments. We found good agreement between our results and the three benchmark problems. For the Kueper and Frind test, the PP scheme successfully captured the observed experimental response of the non-aqueous phase infiltration, in contrast to the PS scheme. These exercises demonstrate the importance of fluid phase primary variable selection for heterogeneous porous media. We then applied the developed model to the hypothetical case of leakage along a compromised well representing a heterogeneous media. Considering the mass lumping and the upwinding techniques, both the monotonic and the sequential coupling provided identical results, but mass lumping was needed to avoid numerical instabilities in the sequential coupling. Additionally, in the monolithic coupling, the magnitude of primary variables in the coupled solution without mass lumping and the upwinding is higher, which is essential for the risk-based analyses.