bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced renoprotective effect of GDNF-modified adipose-derived mesenchymal stem cells on renal interstitial fibrosis
Authors: Li Shulin , Wang Yanping , Wang Zhuojun , Chen Lu , Zuo Bangjie , Liu Caixia , Sun Dong
Published: January 2021

Background

The therapeutic effect of mesenchymal stem cells (MSCs) from human adipose tissue on renal interstitial fibrosis has been demonstrated by several groups. However, the way to enhance the renoprotective effect of adipose-derived mesenchymal stem cells (AMSCs) and the possible mechanisms are still unclear. The present study aimed to determine whether glial cell line-derived neurotrophic factor (GDNF)-modified AMSCs hold an enhanced protective effect on renal fibrosis.

Methods

AMSCs were isolated and purified for culture. The gene GDNF has been constructed to transfect into AMSCs. The ability of GFP-AMSCs and GDNF-AMSCs supernatants to promote tube formation of endothelial cells, repair damaged endothelial cell junctions, and improve endothelial cell function was compared by using tube formation assay, immunofluorescence techniques, and vascular ring assay, respectively. Furthermore, HE and Masson staining were used to observe the histological morphology of the kidney in vivo. Peritubular capillary changes were detected and analyzed by fluorescence microangiography (FMA). Meanwhile, the hypoxia, oxidative stress, fibrotic markers, and PI3K/Akt pathway proteins were measured by western blot or qRT-PCR technics.

Results

Compared with GFP-AMSCs only, GDNF-AMSCs could enhance the repair of injured endothelial cells and promote angiogenesis through secreting more growth factors in the supernatant of GDNF-AMSC culture media demonstrated in vitro studies. Studies in vivo, unilateral ureteral obstruction (UUO)-induced mice were injected with transfected AMSCs through their tail veins. We showed that enhanced homing of AMSCs was observed in the GDNF-AMSC group compared with the GFP-AMSC group. The animals treated with GDNF-AMSCs exhibited an improvement of capillary rarefaction and fibrosis induced by obstructed kidney compared with the GFP-AMSC group. Furthermore, we reported that GDNF-AMSCs protect renal tissues against microvascular injuries via activation of the PI3K/Akt signaling pathway. Therefore, GDNF-AMSCs further ameliorated the tissue hypoxia, suppressed oxidative stress, and finally inhibited endothelial to mesenchymal transition noting by decreased coexpression of endothelial cell (CD31) and myofibroblast (a-SMA) markers.

Conclusion

Collectively, our data indicated that the GDNF gene enhances the ability of AMSCs in improving renal microcirculation through PI3K/Akt/eNOS signaling pathway and afterward inhibit the EndMT process and kidney fibrogenesis, which should have a vast of implications in designing future remedies for chronic kidney disease (CKD) treatment.
PDGF-BB and IL-4 co-overexpression is a potential strategy to enhance mesenchymal stem cell-based bone regeneration
Authors: Zhang Ning , Lo Chi-Wen , Utsunomiya Takeshi , Maruyama Masahiro , Huang Ejun , Rhee Claire , Gao Qi , Yao Zhenyu , Goodman Stuart B.
Published: January 2021

Background

Mesenchymal stem cell (MSC)-based therapy has the potential for immunomodulation and enhancement of tissue regeneration. Genetically modified MSCs that over-express specific cytokines, growth factors, or chemokines have shown great promise in pre-clinical studies. In this regard, the anti-inflammatory cytokine interleukin (IL)-4 converts pro-inflammatory M1 macrophages into an anti-inflammatory M2 phenotype; M2 macrophages mitigate chronic inflammation and enhance osteogenesis by MSC lineage cells. However, exposure to IL-4 prematurely inhibits osteogenesis of MSCs in vitro; furthermore, IL-4 overexpressing MSCs inhibit osteogenesis in vivo during the acute inflammatory period. Platelet-derived growth factor (PDGF)-BB has been shown to enhance osteogenesis of MSCs with a dose-dependent effect.

Methods

In this study, we generated a lentiviral vector that produces PDGF-BB under a weak promoter (phosphoglycerate kinase, PGK) and lentiviral vector producing IL-4 under a strong promoter (cytomegalovirus, CMV). We infected MSCs with PDGF-BB and IL-4-producing lentiviral vectors separately or in combination to investigate cell proliferation and viability, protein expression, and the capability for osteogenesis.

Results

PDGF-BB and IL-4 co-overexpression was observed in the co-infected MSCs and shown to enhance cell proliferation and viability, and osteogenesis compared to IL-4 overexpressing MSCs alone.

Conclusions

Overexpression of PDGF-BB together with IL-4 mitigates the inhibitory effect of IL-4 on osteogenesis by IL-4 overexpressing MSCS. PDGF-BB and IL-4 overexpressing MSCs may be a potential strategy to facilitate osteogenesis in scenarios of both acute and chronic inflammation.
Precision regenerative medicine
Authors: Lightner Amy L. , Chan Timothy
Published: January 2021

Background

Precision or individualized medicine is increasingly pervasive across medical and surgical disciplines. However, the concept has not been introduced in regenerative medicine.

Main body

Targeted and engineered cellular and acellular therapy, specific to individuals or disease states, could significantly improve the efficacy of these autologous therapies. Currently, generic mesenchymal stem cell therapy is being widely used across multiple pathologies, some of which may not respond well to mesenchymal stem cell therapy. Engineered cell therapy may be a way to address this generic one-size-fits-all approach.

Conclusions

The future of regenerative medicine lies in the concept of precision cell-based therapy.
Bleomycin induces fibrotic transformation of bone marrow stromal cells to treat height loss of intervertebral disc through the TGFβR1/Smad2/3 pathway
Authors: Yang Xiao , Chen Zhiqian , Chen Chen , Han Chen , Zhou Yifan , Li Xunlin , Tian Haijun , Cheng Xiaofei , Zhang Kai , Qin An , Zhou Tangjun , Zhao Jie
Published: January 2021

Background

Lower back pain is often accredited to loss of intervertebral disc (IVD) height and compromised spine stability as a result of intervertebral disc degeneration (IVDD). We aim to locally use bleomycin to induce the fibrotic transformation of bone marrow stromal cells (BMSCs) as a means to induce reparative fibrosis to slow down the height loss.

Methods

IVDs from patients were gathered for histological examination. The expression of the transforming growth factor beta 1 (TGF-β) signaling pathway was determined by qPCR and western blotting. Nucleus pulposus (NP) cells, annulus fibrosus (AF) cells, and the rats’ bone marrow stromal cells (BMSC) were cultured and their responsiveness to bleomycin was evaluated by Cell Counting Kit-8, comet assay, transwell migration, and wound healing assays. Rat IVDD models were created by puncture and rescued by bleomycin injection, and the effectiveness was evaluated by images (X-ray and MRI) and atomic force microscope.

Results

Histological examination showed increased levels of pro-fibrotic markers in IVDD tissues from patients. AF cells and BMSC cells were induced to adopt a pro-fibrotic phenotype with increased expression fibrotic markers Col1a1, Col3a1, and FSP1. The pro-fibrotic effect of bleomycin on AF cells and BMSCs was in part due to the activation of the TGFβ-TGFβR1-SMAD2/3 signaling pathway. Pharmacological inhibition or gene knock-down of TGFβR1 could mitigate the pro-fibrotic effects.

Conclusion

Locally, injection of bleomycin in rats’ IVD induced rapid fibrosis and maintained its height through the TGFβ-TGFβR1-SMAD2/3 signaling pathway.
Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells
Authors: Bicer Mesude , Cottrell Graeme S. , Widera Darius
Published: January 2021

As populations age across the world, osteoporosis and osteoporosis-related fractures are becoming the most prevalent degenerative bone diseases. More than 75 million patients suffer from osteoporosis in the USA, the EU and Japan. Furthermore, it is anticipated that the number of patients affected by osteoporosis will increase by a third by 2050. Although conventional therapies including bisphosphonates, calcitonin and oestrogen-like drugs can be used to treat degenerative diseases of the bone, they are often associated with serious side effects including the development of oesophageal cancer, ocular inflammation, severe musculoskeletal pain and osteonecrosis of the jaw.

The use of autologous mesenchymal stromal cells/mesenchymal stem cells (MSCs) is a possible alternative therapeutic approach to tackle osteoporosis while overcoming the limitations of traditional treatment options. However, osteoporosis can cause a decrease in the numbers of MSCs, induce their senescence and lower their osteogenic differentiation potential.

Three-dimensional (3D) cell culture is an emerging technology that allows a more physiological expansion and differentiation of stem cells compared to cultivation on conventional flat systems.

This review will discuss current understanding of the effects of different 3D cell culture systems on proliferation, viability and osteogenic differentiation, as well as on the immunomodulatory and anti-inflammatory potential of MSCs.
Extracellular vesicle mimics made from iPS cell-derived mesenchymal stem cells improve the treatment of metastatic prostate cancer
Authors: Zhao Qingguo , Hai Bo , Kelly Jack , Wu Samuel , Liu Fei
Published: January 2021

Background

Extracellular vesicles (EVs) and their mimics from mesenchymal stem cells (MSCs) are promising drug carriers to improve cancer treatment, but their application is hindered by donor variations and expansion limitations of conventional tissue-derived MSCs. To circumvent these issues, we made EV-mimicking nanovesicles from standardized MSCs derived from human induced pluripotent stem cells (iPSCs) with a theoretically limitless expandability, and examined the targeting capacity of these nanovesicles to prostate cancer.

Methods

Nanovesicles are made from intact iPSC-MSCs through serial extrusion. The selective uptake of fluorescently labeled nanovesicles by prostate cancer cells vs. non-tumor cells was examined with flow cytometry. For in vivo tracing, nanovesicles were labeled with fluorescent dye DiR or renilla luciferase. In mice carrying subcutaneous or bone metastatic PC3 prostate cancer, the biodistribution of systemically infused nanovesicles was examined with in vivo and ex vivo imaging of DiR and luminescent signals. A chemotherapeutic drug, docetaxel, was loaded into nanovesicles during extrusion. The cytotoxicities of nanovesicle-encapsulated docetaxel on docetaxel-sensitive and -resistant prostate cancer cells and non-tumor cells were examined in comparison with free docetaxel. Therapeutic effects of nanovesicle-encapsulated docetaxel were examined in mice carrying subcutaneous or bone metastatic prostate cancer by monitoring tumor growth in comparison with free docetaxel.

Results

iPSC-MSC nanovesicles are more selectively taken up by prostate cancer cells vs. non-tumor cells in vitro compared with EVs, membrane-only EV-mimetic nanoghosts and liposomes, which is not affected by storage for up to 6 weeks. In mouse models of subcutaneous and bone metastatic PC3 prostate cancer, systemically infused nanovesicles accumulate in tumor regions with significantly higher selectivity than liposomes. The loading of docetaxel into nanovesicles was efficient and did not affect the selective uptake of nanovesicles by prostate cancer cells. The cytotoxicities of nanovesicle-encapsulated docetaxel are significantly stronger on docetaxel-resistant prostate cancer cells and weaker on non-tumor cells than free docetaxel. In mouse models of subcutaneous and bone metastatic prostate cancer, nanovesicle-encapsulated docetaxel significantly decreased the tumor growth and toxicity to white blood cells compared with free docetaxel.

Conclusions

Our data indicate that EV-mimicking iPSC-MSC nanovesicles are promising to improve the treatment of metastatic prostate cancer.
Intraperitoneal injection of Desferal® alleviated the age-related bone loss and senescence of bone marrow stromal cells in rats
Authors: Yi Lingxian , Ju Yue , He Ying , Yin Xiushan , Xu Ye , Weng Tujun
Published: January 2021

Background

Age-related bone loss plays a vital role in the development of osteoporosis and osteoporotic fracture. Bone marrow stromal cell (BMSC) senescence is highly associated with osteoporosis and limits the application of BMSCs in regenerative medicine. Hypoxia is an essential component for maintaining the normal physiology of BMSCs. We have reported that activation of hypoxia-induced factor by deletion of von Hippel-Lindau gene in osteochondral progenitor cells protected mice from aging-induced bone loss. However, whether pharmacologically manipulation of hypoxic niche would attenuate age-related bone loss and dysfunction of BMSCs is not well understood.

Methods

Twelve-month-old Sprague-Dawley rats were used as an aged model and were intraperitoneally injected with Desferal® (20, 60 mg/kg weight or vehicle), three times a week for a continuous 8-week period. Two-month-old young rats were set as a reference. After 8 weeks, micro-CT and HE staining were performed to determine the effect of Desferal® on bone loss. In order to investigate the effects of Desferal® on BMSC senescence, 12-month-old rats were treated with high-dose Desferal® (60 mg/kg weight) daily for 10 days. BMSCs were isolated and evaluated using CCK-8 assay, colony-forming cell assay, cell differentiation assay, laser confocal for reactive oxygen species (ROS) level, senescence-associated β-galactosidase (SA-β-gal) staining, and molecular expression test for stemness/senescence-associated genes.

Results

Micro-CT and HE staining showed that high-dose Desferal® significantly prevented bone loss in aged rats. Compared with vehicle group, the ex vivo experiments showed that short-term Desferal® administration could promote the potential of BMSC growth (proliferation and colony formation ability) and improve the rebalance of osteogenic and adipogenic differentiation, as well as rejuvenate senescent BMSCs (ROS level and SA-β-gal staining) and revise the expression of stemness/senescence-associated genes. The potential of BMSCs from 12M-H-Desferal® group at least partly revised to the level close to 2-month-old group.

Conclusions

The current study suggested that Desferal®, an iron-chelating agent, could alleviate age-related bone loss in middle-aged rats. Meanwhile, we found that short-term intraperitoneal injection of Desferal® partly rejuvenate BMSCs from aged rats. Overall, we demonstrated a novel role of Desferal® in rejuvenating aged BMSCs and preventing age-related bone loss.
Minimizing the number of origins in batches of weaned calves to reduce their risks of developing bovine respiratory diseases
Authors: Morel-Journel Thibaut , Assié Sébastien , Vergu Elisabeta , Mercier Jean-Baptiste , Bonnet-Beaugrand Florence , Ezanno Pauline
Published: January 2021

Bovine respiratory diseases (BRD) are a major concern for the beef cattle industry, as beef calves overwhelmingly develop BRD symptoms during the first weeks after their arrival at fattening units. These cases occur after weaned calves from various cow-calf producers are grouped into batches to be sold to fatteners. Cross-contaminations between calves from different origins (potentially carrying different pathogens), together with increased stress because of the process of batch creation, can increase their risks of developing BRD symptoms. This study investigated whether reducing the number of different origins per batch is a strategy to reduce the risk of BRD cases. We developed an algorithm aimed at creating batches with as few origins as possible, while respecting constraints on the number and breed of the calves. We tested this algorithm on a dataset of 137,726 weaned calves grouped into 9701 batches by a French organization. We also computed an index assessing the risks of developing BRD because of the batch composition by considering four pathogens involved in the BRD system. While increasing the heterogeneity of batches in calf bodyweight, which is not expected to strongly impact the performance, our algorithm successfully decreased the average number of origins in the same batch and their risk index. Both this algorithm and the risk index can be used as part of decision tool to assess and possibly minimize BRD risk at batch creation, but they are generic enough to assess health risk for other production animals, and optimize the homogeneity of selected characteristics.
Robust stability analysis of impulsive quaternion-valued neural networks with distributed delays and parameter uncertainties
Authors: Zhou Jielin , Tan Yuanshun , Chen Xiaofeng , Liu Zijian
Published: January 2021

In this paper, an impulsive quaternion-valued neural networks (QVNNs) model with leakage, discrete, and distributed delays is considered. Based on the homeomorphic mapping method, Lyapunov stability theorem, and linear matrix inequality (LMI) approach, sufficient conditions for the existence, uniqueness, and global robust stability of the equilibrium point of the impulsive QVNNs are provided. A numerical example is provided to confirm the obtained results. A conclusion is presented in the end.
Dynamics analysis of an online gambling spreading model on scale-free networks
Authors: Kong Yu , Li Tao , Wang Yuanmei , Cheng Xinming , Wang He , Lei Yangmei
Published: January 2021

Nowadays, online gambling has a great negative impact on the society. In order to study the effect of people’s psychological factors, anti-gambling policy, and social network topology on online gambling dynamics, a newSHGD(susceptible–hesitator–gambler–disclaimer) online gambling spreading model is proposed on scale-free networks. The spreading dynamics of online gambling is studied. The basic reproductive number$R_{0}$R0is got and analyzed. The basic reproductive number$R_{0}$R0is related to anti-gambling policy and the network topology. Then, gambling-free equilibrium$E_{0}$E0and gambling-prevailing equilibrium$E_{ +} $E+are obtained. The global stability of$E_{0}$E0is analyzed. The global attractivity of$E_{ +} $E+and the persistence of online gambling phenomenon are studied. Finally, the theoretical results are verified by some simulations.
The influence of an infectious disease on a prey-predator model equipped with a fractional-order derivative
Authors: Djilali Salih , Ghanbari Behzad
Published: January 2021

In this research, we discuss the influence of an infectious disease in the evolution of ecological species. A computational predator-prey model of fractional order is considered. Also, we assume that there is a non-fatal infectious disease developed in the prey population. Indeed, it is considered that the predators have a cooperative hunting. This situation occurs when a pair or group of animals coordinate their activities as part of their hunting behavior in order to improve their chances of making a kill and feeding. In this model, we then shift the role of standard derivatives to fractional-order derivatives to take advantage of the valuable benefits of this class of derivatives. Moreover, the stability of equilibrium points is studied. The influence of this infection measured by the transmission rate on the evolution of predator-prey interaction is determined. Many scenarios are obtained, which implies the richness of the suggested model and the importance of this study. The graphical representation of the mathematical results is provided through a precise numerical scheme. This technique enables us to approximate other related models including fractional-derivative operators with high accuracy and efficiency.
On the characteristic polynomial of $(k,p)$-Fibonacci sequence
Authors: Trojovský Pavel
Published: January 2021

Recently, Bednarz introduced a new two-parameter generalization of the Fibonacci sequence, which is called the$(k,p)$(k,p)-Fibonacci sequence and denoted by$(F_{k,p}(n))_{n\geq0}$(Fk,p(n))n≥0. In this paper, we study the geometry of roots of the characteristic polynomial of this sequence.
Some k-fractional extension of Grüss-type inequalities via generalized Hilfer–Katugampola derivative
Authors: Naz Samaira , Naeem Muhammad Nawaz , Chu Yu-Ming
Published: January 2021

In this paper, we prove several inequalities of the Grüss type involving generalized k-fractional Hilfer–Katugampola derivative. In 1935, Grüss demonstrated a fascinating integral inequality, which gives approximation for the product of two functions. For these functions, we develop some new fractional integral inequalities. Our results with this new derivative operator are capable of evaluating several mathematical problems relevant to practical applications.
Reciprocity of poly-Dedekind-type DC sums involving poly-Euler functions
Authors: Ma Yuankui , Kim Dae San , Lee Hyunseok , Kim Hanyoung , Kim Taekyun
Published: January 2021

The classical Dedekind sums appear in the transformation behavior of the logarithm of the Dedekind eta-function under substitutions from the modular group. The Dedekind sums and their generalizations are defined in terms of Bernoulli functions and their generalizations, and are shown to satisfy some reciprocity relations. In contrast, Dedekind-type DC (Daehee and Changhee) sums and their generalizations are defined in terms of Euler functions and their generalizations. The purpose of this paper is to introduce the poly-Dedekind-type DC sums, which are obtained from the Dedekind-type DC sums by replacing the Euler function by poly-Euler functions of arbitrary indices, and to show that those sums satisfy, among other things, a reciprocity relation.
Approximation of function using generalized Zygmund class
Authors: Nigam H. K. , Mursaleen Mohammad , Rani Supriya
Published: January 2021

In this paper we review some of the previous work done by the earlier authors (Singh et al. in J. Inequal. Appl. 2017:101, 2017; Lal and Shireen in Bull. Math. Anal. Appl. 5(4):1–13, 2013), etc., on error approximation of a functiongin the generalized Zygmund space and resolve the issue of these works. We also determine the best error approximation of the functionsgand$g^{\prime }$g′, where$g^{\prime }$g′is a derived function of a 2π-periodic functiong, in the generalized Zygmund class$X_{z}^{(\eta )}$Xz(η),$z\geq 1$z≥1, using matrix-Cesàro$(TC^{\delta })$(TCδ)means of its Fourier series and its derived Fourier series, respectively. Theorem 2.1 of the present paper generalizes eight earlier results, which become its particular cases. Thus, the results of (Dhakal in Int. Math. Forum 5(35):1729–1735, 2010; Dhakal in Int. J. Eng. Technol. 2(3):1–15, 2013; Nigam in Surv. Math. Appl. 5:113–122, 2010; Nigam in Commun. Appl. Anal. 14(4):607–614, 2010; Nigam and Sharma in Kyungpook Math. J. 50:545–556, 2010; Nigam and Sharma in Int. J. Pure Appl. Math. 70(6):775–784, 2011; Kushwaha and Dhakal in Nepal J. Sci. Technol. 14(2):117–122, 2013; Shrivastava et al. in IOSR J. Math. 10(1 Ver. I):39–41, 2014) become particular cases of our Theorem 2.1. Several corollaries are also deduced from our Theorem 2.1.
Some fractional Hermite–Hadamard-type inequalities for interval-valued coordinated functions
Authors: Shi Fangfang , Ye Guoju , Zhao Dafang , Liu Wei
Published: January 2021

The primary objective of this paper is establishing new Hermite–Hadamard-type inequalities for interval-valued coordinated functions via Riemann–Liouville-type fractional integrals. Moreover, we obtain some fractional Hermite–Hadamard-type inequalities for the product of two coordinatedh-convex interval-valued functions. Our results generalize several well-known inequalities.
Fundamental solutions for semidiscrete evolution equations via Banach algebras
Authors: González-Camus Jorge , Lizama Carlos , Miana Pedro J.
Published: January 2021

We give representations for solutions of time-fractional differential equations that involve operators on Lebesgue spaces of sequences defined by discrete convolutions involving kernels through the discrete Fourier transform. We consider finite difference operators of first and second orders, which are generators of uniformly continuous semigroups and cosine functions. We present the linear and algebraic structures (in particular, factorization properties) and their norms and spectra in the Lebesgue space of summable sequences. We identify fractional powers of these generators and apply to them the subordination principle. We also give some applications and consequences of our results.
The identification of wildlife-vehicle collision hotspots: Citizen science reveals spatial and temporal patterns
Authors: Valerio Francesco , Basile Marco , Balestrieri Rosario
Published: January 2021

Linear infrastructures (e.g., roads, railways, pipelines, and powerlines) pose a serious threat to wildlife, due to the risk of wildlife-vehicle collisions (roadkills). The placement of mitigation measures, such as crossing structures, should consider species’ life cycles and ecological requirements. Such an assessment would require data collection over large areas, which may be possible by employing citizen science. In this study, we aimed to identify spatio-temporal trends of roadkill occurrence using citizen science data from one of the most urbanized and biodiversity-rich regions of Italy. Temporal trends were analyzed using generalized additive models, while landscape patterns were assessed by identifying significant thresholds over land cover gradients, related to increases in relative roadkill abundance, by employing threshold indicator taxa analysis. Our approach recorded a total of 529 roadkills, including 33 different species, comprising 13 mammal, 10 bird, 6 reptile, and 2 amphibian species. Statistical analysis indicated significant temporal trends for the red fox, the European hedgehog, the stone marten and the European badger, with peaks in roadkill occurrence between the winter and spring months. Relative roadkill abundance increased mostly in landscapes with anthropogenic land cover classes, such as complex cultivations, orchards, or urban surfaces. Our results allowed us to develop a map of potential roadkill risk that could assist in planning the placement of mitigation measures. Citizen science contributions from highly populated areas allowed data collection over a large area and a dense road network, and also directly led to the evaluation of management decisional options.
Investigation on the Mechanical Properties and Microstructure of Eco-friendly Mortar Containing WGP at Elevated Temperature
Authors: Sedaghatdoost Arash , Behfarnia Kiachehr , Moosaei Hamidreza , Bayati Mohammad , Vaezi Mohammad Sadegh
Published: January 2021

The properties of mortars containing waste glass powder (WGP) as a cement substitute for sustainable construction at various high temperatures were investigated. For this purpose, specimens from four mixtures with WGP at various percentage levels of 0, 5, 10 and 15% were prepared and exposed to the specified temperatures. After that, the compressive and flexural strength were determined at high temperatures. The mass loss was also measured by weighing the samples before and after exposing to the high temperatures. The microstructure of mortars was analyzed by petrographic examination. Based on the obtained results, incorporation of WGP as partial replacement of cement could improve strength characteristics of the mortars at the elevated temperatures up to 17%. Also, the optimum ratio of cement replacement level was found to be 10%. In addition, the petrographic images of the mortars showed that at the same time with the strength loss of specimens, the red discoloration of WGP occurred that is attributed to the oxidation of iron compounds that starts at temperatures above 200 °C.
The diversity and breadth of cancer cell fatty acid metabolism
Authors: Nagarajan Shilpa R. , Butler Lisa M. , Hoy Andrew J.
Published: January 2021

Tumor cellular metabolism exhibits distinguishing features that collectively enhance biomass synthesis while maintaining redox balance and cellular homeostasis. These attributes reflect the complex interactions between cell-intrinsic factors such as genomic-transcriptomic regulation and cell-extrinsic influences, including growth factor and nutrient availability. Alongside glucose and amino acid metabolism, fatty acid metabolism supports tumorigenesis and disease progression through a range of processes including membrane biosynthesis, energy storage and production, and generation of signaling intermediates. Here, we highlight the complexity of cellular fatty acid metabolism in cancer, the various inputs and outputs of the intracellular free fatty acid pool, and the numerous ways that these pathways influence disease behavior.
Electrical conductive fluid-rich zones and their influence on the earthquake initiation, growth, and arrest processes: observations from the 2016 Kumamoto earthquake sequence, Kyushu Island, Japan
Authors: Aizawa Koki , Takakura Shinichi , Asaue Hisafumi , Koike Katsuaki , Yoshimura Ryokei , Yamazaki Ken’ichi , Komatsu Shintaro , Utsugi Mitsuru , Inoue Hiroyuki , Tsukamoto Kaori , Uyeshima Makoto , Koyama Takao , Kanda Wataru , Yoshinaga Tohru , Matsushima Nobuo , Uchida Kazunari , Tsukashima Yuko , Matsushima Takeshi , Ichihara Hiroshi , Muramatsu Dan , Teguri Yoshiko , Shito Azusa , Matsumoto Satoshi , Shimizu Hiroshi
Published: January 2021

Crustal earthquake ruptures tend to initiate near fluid-rich zones. However, it is relatively unknown whether fluid-rich zones can further promote or arrest these ruptures. We image the electrical resistivity structure around the focal area of the 2016 Kumamoto earthquake sequence by using 200 sites broadband magnetotelluric data, and discuss its quantitative relationship to earthquake initiation, growth, and arrest processes. The ruptures that initiated along the outer edge of the low-resistivity fluid-rich zones (< 30 Ωm) tended to become large earthquakes, whereas those that initiated either distal to or within the fluid-rich zones did not. The ruptures were arrested by high-temperature (> 400 °C) fluid-rich zones, whereas shallower low-temperature (200–400 °C) fluid-rich zones either promoted or arrested the ruptures. These results suggest that the distribution of mid-crustal fluids contributes to the initiation, growth, and arrest of crustal earthquakes. The pre-failure pressure/temperature gradient (spatial difference) of the pore fluids may contribute to the rupture initiation, propagation, and arrest.
Dual-energy CT quantitative parameters for evaluating Immunohistochemical biomarkers of invasive breast cancer
Authors: Wang Xiaoxia , Liu Daihong , Zeng Xiangfei , Jiang Shixi , Li Lan , Yu Tao , Zhang Jiuquan
Published: January 2021

Background

Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67 are the most useful immunohistochemical biomarkers of invasive breast cancer. The purpose of this study is to investigate the possibility of quantitative parameters derived from dual-energy CT (DECT) to discriminate immunohistochemical biomarkers of invasive breast cancer.

Methods

This prospective study enrolled 120 patients with invasive breast cancer who underwent preoperative contrast-enhanced DECT for staging purposes from June 2019 to January 2020. DECT quantitative parameters, including normalized iodine concentration (NIC), the slope of the spectral Hounsfield unit curve (λHu), and the normalized effective atomic number (nZeff), were obtained from reconstructed images. DECT quantitative parameters were compared with the expression status, and the correlations with the value of immunohistochemical biomarkers were evaluated. Inter-observer reproducibility analysis was performed to assess the measurement reproducibility of quantitative parameters. The diagnostic performance of the quantitative parameters was analyzed by receiver operating characteristic curve.

Results

The ER-negative group tended to display higher venous phase NIC and nZeff compared with the ER-positive group (individually, p = 0.003, 0.011; area under the curve [AUC] of 0.65, 0.60). The PR-negative group demonstrated higher arterial and venous phase NIC compared with the PR-positive group (individually, p = 0.022, 0.005; AUC of 0.63, 0.65). NIC was correlated negatively with the value of ER and PR expression (r = − 0.175 ~ − 0.265, p = 0.002 ~ 0.042). The HER2-positive group tended to display higher venous phase nZeff than the HER2-negative group (p = 0.022; AUC of 0.59). The Ki67 high-proliferation group demonstrated higher arterial phase, venous phase NIC and nZeff than the Ki67 low-proliferation group (p < 0.001 ~ 0.005; AUC of 0.67 ~ 0.75). Both the NIC and nZeff were correlated positively with the value of Ki67 (r = 0.240 ~ 0.490, p < 0.001 ~ 0.014).

Conclusions

NIC and nZeff derived from DECT could be used to discriminate expression status and may associate with the value of immunohistochemical biomarkers of invasive breast cancer.
Relationship between clinicopathologic factors and FDG avidity in radioiodine-negative recurrent or metastatic differentiated thyroid carcinoma
Authors: Ha Le Ngoc , Iravani Amir , Nhung Nguyen Thi , Hanh Ngo Thi Minh , Hutomo Febby , Son Mai Hong
Published: January 2021

Background

In this study, we investigated the relationship between clinicopathologic factors, BRAFV600E mutation status and [18F] F-fluoro-2-deoxyglucose (FDG) avidity in patients with radioiodine (RAI)-negative recurrent or metastatic differentiated thyroid cancer (DTC).

Methods

From 2015 to 2018 all patients with suspected recurrent or metastatic radioiodine-negative DTC patients who underwent FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. Suspected lesions on FDG PET/CT were biopsied and underwent BRAFV600E mutation testing by immunohistochemistry and real-time PCR. Tumor size, recurrent versus metastatic disease, histopathologic features including classical type versus aggressive subtypes (poorly differentiated, tall cell, columnar cell, hobnail variants) and BRAFV600E mutation status were correlated with the SUVmax of highest hypermetabolic lesions on FDG PET/CT by the univariate analysis using logistic regression.

Results

Sixty-three consecutive patients, 55 (87.3%) female, with median age of 48 (range 17–81) were included. The majority of patients had BRAFV600E mutation and classical subtype, 55/63 (87.3%) and 45/63(71.4%), respectively. Thyroglobulin at the time of suspected recurrence was 262.7 ng/ml (range 16.3–1000) and patients received a median 3 prior RAI treatments. Fifty-four patients (85.7%) had local recurrence. The majority of patients 58/63 (92.1%) had FDG-avid disease on PET/CT. On univariate analysis, tumor size aggressive histopathologic types and distant metastasis are the significant factors for predicting FDG uptake, p = 0.04, p = 0.001 and p = 0.004 respectively. Although FDG uptake of BRAFV600E bearing recurrent/metastatic RAIR DTC lesions was higher than those without the mutation, the difference did not reach statistical significance, SUVmax of 7.11 versus 4.91, respectively, p = 0.2.

Conclusion

The majority of recurrent or metastatic RAI-negative DTC have BRAFV600E mutation and detectable disease on FDG PET/CT. FDG avidity of the recurrent or metastatic RAI-negative DTC is independently associated with the aggressive histopathologic features.
Promoting traditional foods for human and environmental health: lessons from agroecology and Indigenous communities in Ecuador
Authors:   Ekomer, Deaconu Ana , Mercille Geneviève , Batal Malek
Published: January 2021

Background

The displacement of traditional dietary practices is associated with negative nutritional consequences for rural Indigenous people, who already face the brunt of both nutritional inadequacies and excesses. Traditional food (TF) consumption and production practices can improve nutritional security by mitigating disruptive dietary transitions, providing nutrients and improving agricultural resilience. Meanwhile, traditional agricultural practices regenerate biodiversity to support healthy ecosystems. In Ecuador, Indigenous people have inserted TF agricultural and dietary practices as central elements of the country’s agroecological farming movement. This study assesses factors that may promote TF practices in rural populations and explores the role of agroecology in strengthening such factors.

Methods

Mixed methods include a cross-sectional comparative survey of dietary, food acquisition, production and socioeconomic characteristics of agroecological farmers (n = 61) and neighboring reference farmers (n = 30) in Ecuador’s Imbabura province. Instruments include 24-h dietary recall and a food frequency questionnaire of indicator traditional foods. We triangulate results using eight focus group discussions with farmers’ associations.

Results

Compared to their neighbors, agroecological farmers produce and consume more TFs, and particularly underutilized TFs. Farm production diversity, reliance on non-market foods and agroecology participation act on a pathway in which TF production diversity predicts higher TF consumption diversity and ultimately TF consumption frequency. Age, income, market distance and education are not consistently associated with TF practices. Focus group discussions corroborate survey results and also identify affective (e.g. emotional) and commercial relationships in agroecological spaces as likely drivers of stronger TF practices.

Conclusions

Traditional food practices in the Ecuadorian highlands are not relics of old, poor and isolated populations but rather an established part of life for diverse rural people. However, many TFs are underutilized. Sustainable agriculture initiatives may improve TF practices by integrating TFs into production diversity increases and into consumption of own production. Agroecology may be particularly effective because it is a self-expanding global movement that not only promotes the agricultural practices that are associated with TF production, but also appears to intensify affective sentiments toward TFs and inserts TFs in commercial spaces. Understanding how to promote TFs is necessary in order to scale up their potential to strengthen nutritional health.
CardiO Cycle: a pilot feasibility study of in-bed cycling in critically ill patients post cardiac surgery
Authors:   for the Canadian Critical Care Trials Group, Newman Anastasia N. L. , Kho Michelle E. , Harris Jocelyn E. , Zamir Nasim , McDonald Ellen , Fox-Robichaud Alison , Solomon Patricia
Published: January 2021

Background

In-bed cycling is a novel modality for the initiation of early mobilization in the intensive care unit. No study has investigated its use in the critically ill, off-track post cardiac surgery population. Before conducting an effectiveness trial, feasibility data are needed. The aim of this study was to determine the feasibility of in-bed cycling in a population of off-track cardiac surgery patients.

Methods

We conducted a prospective feasibility study in a 16-bed adult cardiac surgery intensive care unit in Ontario, Canada. Previously ambulatory adults (≥ 18 years) who were mechanically ventilated for ≥ 72 h were enrolled within 3 to 7 days post cardiac surgery. Twenty minutes of in-bed cycling was delivered by ICU physiotherapists 5 days/week. The primary outcome, feasibility, was the percent of patient-cycling sessions that occurred when cycling was appropriate. The secondary outcome was cycling safety, measured as cycling discontinuation due to predetermined adverse events.

Results

We screened 2074 patients, 29 met eligibility criteria, and 23 (92%) consented. Patients were male (78.26%) with a median [IQR] age of 76 [11] years, underwent isolated coronary bypass (39.1%), and had a median EuroScore II of 5.4 [7.8]. The mean (SD) time post-surgery to start of cycling was 5.9 (1.4) days. Patients were cycled on 80.5% (136/169) of eligible days, with limited physiotherapy staffing accounting for 48.5% of the missed patient-cycling sessions. During 136 sessions of cycling, 3 adverse events occurred in 3 individual patients. The incidence of an adverse event was 2.2 per 100 patient-cycling sessions (95% CI 0.50, 6.4).

Conclusions

In-bed cycling with critically ill cardiac surgery patients is feasible with adequate physiotherapy staffing and appears to be safe. Future studies are needed to determine the effectiveness of this intervention in a larger sample.

Trial registration

This trial was registered with Clinicaltrials.gov (NCT02976415). Registered November 29, 2016.
Choriocapillaris Island: an optical coherence tomography angiography finding observed in central serous chorioretinopathy
Authors: Estawro Rania G. , Fayed Alaa E. , Gerges Teresa K. , Baddar Dina N.
Published: January 2021

Purpose

To report the observation of the choriocapillaris island (CCI) on optical coherence tomography angiography (OCTA) in eyes with active central serous chorioretinopathy (CSCR), and to investigate its associated clinical features.

Design

Retrospective observational study.

Methods

Patients diagnosed with active CSCR underwent OCTA imaging (Optovue Inc, Fremont, California, USA), and the software built-in en face choriocapillaris slab was examined to demonstrate CCI, defined as an area of detectable choriocapillaris flow surrounded by an area of undetectable or diminished flow. Electronic medical records (EMR) were reviewed for demographics, clinical data, other imaging modalities and any intervention, and these parameters were correlated with CCI findings.

Results

25 eyes of 25 patients were recruited. CCI was detected in all examined eyes and was best elucidated on the en face choriocapillaris density maps. 24 eyes had focal retinal pigment epithelium (RPE) alterations overlying CCI. All 14 eyes with simultaneous fundus fluorescein angiography (FA) showed actively leaking point(s) well corresponding to the CCI location. Resolution of sub-retinal fluid in 4 eyes was associated with disappearance of CCI on follow-up OCTA scans. 1 eye showed complicating neovascularization 5 months after the initial presentation at the same location of the CCI.

Conclusion

We demonstrate the observation of the “choriocapillaris island” an OCTA finding in eyes with active CSCR underneath the area of neurosensory detachment. CCI may constitute an angiographic representation of the focal area of choriocapillaris structural and functional affection, with secondary RPE alteration jeopardizing its barrier function. Larger longitudinal studies are needed to further elucidate this finding.
First records of Cuvier’s beaked whale (Ziphius cavirostris, G. Cuvier 1823) strandings along the Tunisian coast
Authors: Karaa Sami , Jerbi Hassen , Marouani Sondes , Bradai Mohamed Nejmeddine , Rosso Massimiliano
Published: January 2021

The Cuvier’s beaked whale (Ziphius cavirostris) is the only member of the Ziphiidae family with a regular occurrence in the Mediterranean Sea. Much of the knowledge of this species in the Mediterranean has come from stranding data. This note reports the first records of strandings of Cuvier’s beaked whales along the Tunisian coast. The two strandings described are about two specimens, likely adult animals. The first specimens was 530 cm long and beached at El Hicha (Gulf of Gabès, south Tunisia) on March 5th, 2019. The second specimens was 630 cm long and it was reported in Ras Angla (Bizerte, north Tunisia) on June 6th, 2019. Since this species faces multiple threats in the Mediterranean basin, this contribution is intended to extend previous knowledge of this species in the region and to push towards major efforts to be undertaken to fill the knowledge gaps regarding occurrence of Cuvier’s beaked whale along northern Tunisia.
Short-term outcome in ischemic stroke patients after thrombolytic therapy
Authors: Mohamed Wafaa S. , Abdel Ghaffar Adel S. , Abdel Gawad Ahmed E. , Agban Emad L.
Published: January 2021

Background

Stroke represents the second leading cause of death in the world after myocardial infarction. Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (alteplase, rt-PA) is the only pharmacological therapy that was approved for treatment within 4.5 h of acute ischemic stroke (AIS) onset. We aimed to predict the 3-month outcome of AIS patients who received alteplase regarding mortality, spontaneous intra-cerebral hemorrhage (sICH), and functional outcome in comparison with non-thrombolyzed patients and to evaluate the predictors of the outcome after 3 months.

Methods

All the clinical, National Institute of Health Stroke Scale (NIHSS) scores, radiological, and laboratory data of 40 AIS patients and received rt-PA during the period from 2016 to 2018 were collected and analyzed retrospectively. For comparison, 40 patients, as a control group, were selected to match the alteplase group as regards the baseline data and received regular treatment, rather than rt-PA within the first 24 h, that were obtained. The outcome of the thrombolyzed patients after 3 months was evaluated in comparison with controls by using a modified ranking scale.

Results

After a 90-day follow-up period, the death rate was slightly higher among the rt-PA group (7.5%) in comparison with the control group (5%). sICH occurred in 7.5% of the patients in the alteplase group and in 5% of the non-thrombolyzed patients; however, this difference was not significant. More patients had a favorable outcome (mRS = 0–2) in the rt-PA group than in the control group (65% vs 60%, OR 1.38, 95% CI 0.50–3.6, P = 0.51). NIHSS score on admission, body mass index (BMI) (≥ 30), and previous transient ischemic attacks (TIA)/previous ischemic stroke were significant predictors of outcome after IV thrombolysis. Age, sex, hypertension (HTN), diabetes mellitus (DM), dyslipidemia, smoking, atrial fibrillation (AF), stroke subtype, size of infarction, and hyperdense middle cerebral artery had a non-significant effect.

Conclusion

After 3 months of follow-up, rt-PA had a non-significant more increase of favorable outcome with increased risk of sICH and death than controls. Baseline NIHSS, BMI, and history of TIA or previous ischemic stroke were significant predictors of outcome after thrombolysis.