bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat attenuates sensitivity of mammalian cells to capsaicin
Authors: Sugimoto Naotoshi , Matsuzaki Kentaro , Katakura Masanori , Nakamura Hiroyuki , Ueda Yoshibumi , Yachie Akihiro , Shido Osamu
Published: January 2019

The transient receptor potential (TRP) channels are thermo‐sensors, and transient receptor potential vanilloid (TRPV)1 and V4 are widely expressed in primary afferent neurons and nonneuronal cells. Although heat acclimation is considered as changes of thermoregulatory responses by thermo‐effectors to heat, functional changes of TRP channels in heat acclimation has not been fully elucidated. Here, we investigated whether heat acclimation induces capsaicin tolerance. NIH3T3 cells were incubated at 39.5°C. We determined the expression level of TRPV1 and TRPV4 messenger RNA (mRNA), performed cellular staining of TRPV1 and TRPV4, and investigated actin assembly and activation of the extracellular signal‐regulated kinase (ERK). Exposure to moderate heat decreased the levels of TRPV1 but not TRPV4 mRNA. It also induced stress fiber formation and the intensity of TRPV1 seemed to be decreased by chronic heat stimuli. In addition, heat acclimation attenuated the capsaicin‐induced activation of ERK. Heat acclimation may induce capsaicin tolerance via the downregulation of TRPV1.
Crocin inhibits proliferation and induces apoptosis through suppressing MYCN expression in retinoblastoma
Authors: Deng Liya , Li Jincun , Lu Shiyou , Su Yan
Published: January 2019

The pathogenetic mechanisms of retinoblastoma are still not yet fully elucidated, putting limits to efficacious treatment. Crocin is the main component of saffron, which exhibits significant antitumorigenic properties. The aim of this paper is to investigate the effect of crocin on retinoblastoma. The effects of crocin on the proliferation of human retinoblastoma cells were determined by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, cell number assay, and colony formation assay. Cell apoptosis induced by crocin was measured by flow cytometry analysis. Cleaved poly(ADP‐ribose) polymerase and cleaved caspase‐3 were tested by western blot analysis. The expression levels of MYCN were assessed by western blot and quantitative polymerase chain reaction and the stability of MYCN messenger RNA was determined by in vitro RNA degradation assays. We found that crocin significantly inhibited the cell proliferation and clonogenicity and induced cell apoptosis in Y79 and WERI‐RB‐1 cells. In addition, crocin treatment significantly reduced the expression and the stability of MYCN. Besides, overexpression of MYCN rescued the inhibitory effect of crocin in Y79 cells. Our findings suggest that crocin exhibits antitumorigenic effects in human retinoblastoma cell lines through a MYCN‐dependent manner, which may provide guidance to logical therapeutic designs in prevention and treatment of retinoblastoma.
Long noncoding RNA GAS5 inhibits angiogenesis and metastasis of colorectal cancer through the Wnt/β‐catenin signaling pathway
Authors: Song Jianping , Shu Hongchun , Zhang Ling , Xiong Jianping
Published: January 2019

Objective

Angiogenesis plays a key role in the tumorigenesis and progression of colorectal cancer (CRC). In this study, we investigated the effect of long noncoding RNA (lncRNA) GAS5 on the angiogenesis, invasion, and metastasis of CRC, and the involvement of the Wnt/β‐catenin signaling pathway.

Methods

CRC tissues and adjacent normal tissues were collected from 52 patients with CRC. GAS5 expression was determined in vivo and in vitro by real‐time quantitative polymerase chain reaction (RT‐qPCR). Then RT‐qPCR and Western blot were used to identify expression of key genes of Wnt/β‐catenin signaling pathway. CRC cells with lowest GAS5 expression were selected and subjected to si‐GAS5, oe‐GAS5, or XAV939 to validate the effect of GAS5 and Wnt/β‐catenin signaling pathway on CRC cell activities. The activation of Wnt/β‐catenin signaling pathway was determined in response to GAS5. Subcutaneous tumor growth and microvascular density were observed in nude mice, in which in vivo metastasis was observed following tail vein injection of CRC cells.

Results

Initially, poor expression of GAS5 was observed in CRC tissues and cells. Upregulated GAS5 repressed CRC cell invasion and migration in vitro, as well as subcutaneous tumor growth, angiogenesis, and liver metastases in vivo. Furthermore, the Wnt/β‐catenin signaling pathway was determined to be activated in CRC tissues and cells, while its activation was inhibited by GAS5. The Wnt/β‐catenin signaling pathway promoted the CRC cell invasion and migration in vitro, subcutaneous tumor growth, angiogenesis and, liver metastases in vivo.

Conclusion

Taken together, the results of the study conclude that lncRNA GAS5 inhibited the activation of the Wnt/β‐catenin signaling pathway, thereby suppressing the angiogenesis, invasion, and metastasis of CRC.
Construction of a chimeric antigen receptor bearing a nanobody against prostate a specific membrane antigen in prostate cancer
Authors: Hassani Mahmoud , Hajari Taheri Fatemeh , Sharifzadeh Zahra , Arashkia Arash , Hadjati Jamshid , van Weerden Wytske M. , Modarressi Mohammad Hossein , Abolhassani Mohsen
Published: January 2019

Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is considered to be a novel anticancer therapy. To date, in most cases, single‐chain variable fragments (scFvs) of murine origin have been used in CARs. However, this structure has limitations relating to the potential immunogenicity of mouse antigens in humans and the relatively large size of scFvs. For the first time, we used camelid nanobody (VHH) to construct CAR T cells against prostate specific membrane antigen (PSMA). The nanobody against PSMA (NBP) was used to show the feasibility of CAR T cells against prostate cancer cells. T cells were transfected, and then the surface expression of the CAR T cells was confirmed. Then, the functions of VHH‐CAR T cell were evaluated upon coculture with prostate cancer cells. At the end, the cytotoxicity potential of NBPII‐CAR in T cells was approximated by determining the cell surface expression of CD107a after encountering PSMA.

Our data show the specificity of VHH‐CAR T cells against PSMA+ cells (LNCaP), not only by increasing the interleukin 2 (IL‐2) cytokine (about 400 pg/mL), but also the expression of CD69 by almost 38%. In addition, VHH‐CAR T cells were proliferated by nearly 60% when cocultured with LNCaP, as compared with PSMA negative prostate cancer cell (DU‐145), which led to the upregulation of CD107a in T cells upto 31%.

These results clearly show the possibility of using VHH‐based CAR T cells for targeted immunotherapy, which may be developed to target virtually any tumor‐associated antigen for adoptive T‐cell immunotherapy of solid tumors.
lncRNA MIR503HG functioned as a tumor suppressor and inhibited cell proliferation, metastasis and epithelial‐mesenchymal transition in bladder cancer
Authors: Qiu Feng , Zhang Ming‐ran , Zhou Zhen , Pu Jin‐xian , Zhao Xiao‐jun
Published: January 2019

Bladder cancer is the most common malignancy with high recurrence. Currently, the long noncoding RNAs (lncRNAs) have been suggested to play vital roles in the pathogenesis of bladder cancer. The present study investigated the role of lncRNA MIR503 host gene (MIR503HG) in the pathogenesis of bladder cancer by using both in vitro and in vivo functional assays. The expression of MIR503HG was downregulated in bladder cancer tissues and cell lines. Low expression of MIR503HG was associated with advanced tumor stage, advanced histological grade, and lymph node metastasis. Ectopic expression of MIR503HG inhibited cell proliferation, cell growth, cell invasion, and migration, and also promoted cell apoptosis and inhibited cell cycle progression in SW780 cells. In parallel, T24 cells were used for loss‐of‐function studies. Knockdown of MIR503HG promoted the cancer cell proliferation and increased the migration and invasion abilities of T24 cells. In addition, knockdown of MIR503HG reduced the cell apoptotic rate in cancer cells and promoted cell cycle progression. Furthermore, MIR503HG overexpression decreased the epithelial‐mesenchymal transition‐related mRNA and protein levels of ZEB1, Snail, N‐cadherin, and vimentin, with an increase in E‐cadherin level. Consistently, knockdown of MIR503HG showed the opposite effects. In vivo xenograft, nude mice results showed that overexpression of MIR503HG suppressed the tumor growth and tumor metastasis. In conclusion, our results identified a novel lncRNA MIR503HG that exhibited significant antiproliferation, antimigration/invasion effects on bladder cancer cells both in vitro and in vivo, which may hold a therapeutic promise to treat bladder cancer.
Solvent‐free synthesis of rotaxanes
Authors: Inthasot Alex , Tai Tzu‐Yi , Chiu Sheng‐Hsien
Published: January 2019

Rotaxane‐type (macro)molecules are important materials in various fields of research, with many approaches for their synthesis having been developed over the past 30 years or so. When prepared in solution, the efficiency of interlocking pseudorotaxane complexes into the corresponding rotaxanes relies, to a great extent, on the affinity between the host and guest components; these interactions are not always sufficiently strong to overcome the deleterious effects of high reaction temperatures, competitive solvents, and low concentrations. Upon evaporating the solvent, however, the concentrations of the host and guest species increase significantly and, ultimately, their corresponding pseudorotaxanes can be generated with high efficiency in the solvent‐free residue. Furthermore, in the absence of the solvent, the influence of any disrupting byproducts (generated during the interlocking process) on the complexation equilibrium can also be largely reduced. Therefore, high synthetic efficiency and low consumption of solvents and energy can be expected when synthesizing rotaxanes under solvent‐free conditions. This mini‐review covers the main publications dealing with the solvent‐free syntheses of rotaxanes – those in which the interlocking step involves no solvent (or only a trace of it).
Changes in mindfulness facets in a dialectical behaviour therapy skills training group program for borderline personality disorder
Authors: Mitchell Roberta , Roberts Rachel , Bartsch Dianna , Sullivan Thomas
Published: January 2019

Objective

We examined the relationship between mindfulness skills acquisition and symptom reduction.

Method

Participants were adults (n = 35) with a diagnosis of borderline personality disorder (BPD) who completed a 20‐week dialectical behaviour therapy (DBT) skills training group program in a community mental health setting. We used the Five Facet Mindfulness Questionnaire, which measures five dimensions of mindfulness: observing, describing, acting with awareness, nonjudging of inner experience, and nonreactivity to inner experience.

Results

Linear mixed model results suggested that increases in some mindfulness facets, especially in acting with awareness and nonjudging of inner experience were more strongly related to changes during treatment including reductions in BPD symptomology, depression, and distress with increases in nonjudging also predicting a reduction in the hospital use.

Conclusions

These results suggest the usefulness of emphasising mindfulness skills that develop awareness and encourage a nonjudgmental stance.
Increased long noncoding RNA LASP1‐AS is critical for hepatocellular carcinoma tumorigenesis via upregulating LASP1
Authors: Yin Ling , Chen Yihong , Zhou You , Deng Ganlu , Han Ying , Guo Cao , Li Yiyi , Zeng Shan , Shen Hong
Published: January 2019

Aberrant long noncoding RNAs (lncRNA) have been proved to be associated with the many types of malignant tumors (including hepatocellular carcinoma [HCC]). In this study, a lncRNAs and mRNAs microarray analysis was performed in three pairs of HCC patitents’ tumor. We found lncRNA LIM and SH3 protein 1 antisense (LASP1‐AS) and its sense‐cognate gene LIM and SH3 protein 1 (LASP1) were upregulated in HCC and both are correlated with poorer prognosis and lower survival of HCC patients. Meanwhile, the expression of LASP1‐AS correlated positively with LASP1 expression in HCC tissues. LASP1‐AS promoted the proliferation, migration, and invasion abilities of HCC in vitro and vivo by enhancing LASP1 expression. Our study explored lncRNA LASP1‐AS as an oncogene in HCC and promoted proliferation and metastasis capabilities of HCC via increasing the expression of its sense‐cognate gene LASP1. LncRNA LASP1‐AS might be a potential valuable prognostic biomarker and potential therapeutic target of HCC.
Characterization of Cre recombinase  mouse lines enabling cell type‐specific targeting of postnatal intervertebral discs
Authors: Zheng Yixin , Fu Xuejie , Liu Qingbai , Guan Shengqi , Liu Cunchang , Xiu Chunmei , Gong Tingting , Jin Hongting , Saijilafu  , Zhang Zunyi , Chen Di , Chen Jianquan
Published: January 2019

Cre/loxP technology is an important tool for studying cell type‐specific gene functions. Cre recombinase mouse lines, including Agc1‐CreERT2, Col2a1‐Cre; Col2a1‐CreERT2, Shh‐Cre, Shh‐CreERT2, and Osx‐Cre, have been proven to be valuable tools to elucidate the biology of long bones, yet the information for their activity in postnatal intervertebral disc (IVD) tissues was very limited. In this study, we used R26‐mTmG fluorescent reporter to systematically analyze cell specificity and targeting efficiency of these six mouse lines in IVD tissues at postnatal growing and adult stages. We found that Agc1‐CreERT2 is effective to direct recombination in all components of IVDs, including annulus fibrosus (AF), nucleus pulposus (NP), and cartilaginous endplate (CEP), upon tamoxifen induction at either 2 weeks or 2 months of ages. Moreover, Col2a1‐Cre targets most of the cells in IVDs, except for some cells in the outer AF (OAF) and NP. In contrast, the activity of Col2a1‐CreERT2 is mainly limited to the IAF of IVD tissues at either stage of tamoxifen injection. Similarly, Shh‐Cre directs recombination specifically in all NP cells, whereas Shh‐CreERT2 is active only in a few NP cells when tamoxifen is administered at either stage. Finally, Osx‐Cre targets cells in the CEP, but not in the NP or AF of IVDs tissues at these two stages. Thus, our data demonstrated that all these Cre lines can direct recombination in IVD tissues at postnatal stages with different cell type specificity and/or targeting efficiency, and can, therefore, serve as valuable tools to dissect cell type‐specific gene functions in IVD development and homeostasis.
Comparison of phenotypic markers and neural differentiation potential of human bone marrow stromal cells from the cranial bone and iliac crest
Authors: Ma Yuyuan , Ma Jie , Zhao Yuanyuan , Yang Kaichuang , Zhou Jia , Gao Faliang , Pan Ruolang , Lu Gang
Published: January 2019

Cellular therapies represent a new frontier in the treatment of neurological diseases. Accumulating evidence from preclinical studies of animal models suggests that mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, are an effective therapy for neurological diseases. In this study, we established human MSC lines from both cranial bone marrow (cBMMSCs) and iliac crest bone marrow (iBMMSCs) from the same donors and found that cBMMSCs show higher expression of neural crest‐associated genes than iBMMSCs. Moreover, as observed in both mRNA and protein assays, neurogenic‐induced cells from cBMMSCs expressed significantly higher levels of neural markers, such as NESTIN, SLUG, SOX9, and TWIST, than those from iBMMSCs. Thus, cBMMSCs showed a greater tendency than iBMMSCs to differentiate into neuron‐like cells.
Efficient l‐lactic acid production from purified sweet sorghum juice coupled with soybean hydrolysate as nitrogen source by Lactobacillus thermophilus A69 strain
Authors: Tian Xue‐jiao , Jiang Ai‐lian , Mao Yan‐qin , Wu Bo , He Ming‐xiong , Hu Wei , Chen Ji‐hong , Li Wen‐jian
Published: January 2019

BACKGROUND

High‐efficiency utilization of sweet sorghum juice can bring significant economic feasibility of l‐lactic acid production. However, an expensive nitrogen source increases the capital cost, and the complex composition of sweet sorghum juice could limit the yield.

RESULTS

In the present study, a bioprocess was developed to enhance the efficiency of l‐lactic acid production using purified sweet sorghum juice and cheap nitrogen supply strategies. It was first demonstrated that cheaper soybean hydrolysate could be used as a low‐cost nitrogen source for efficient l‐lactic acid production by Lactobacillus thermophilus A69, the optimal soybean hydrolysate concentration being 25 g L−1. It was then proved that the efficiency of l‐lactic acid production was significantly boosted using sweet sorghum juice purified via clarification treatment. Finally, on combining the cheap nitrogen source and the clarification strategy, 114.6 g L−1 l‐lactic acid with a productivity of 2.61 g L−1 h−1 was produced by A69 strain in a 5 L bioreactor.

CONCLUSION

This study provides a simple, practical and economic approach to promote l‐lactic acid production using sweet sorghum juice as feedstock. © 2019 Society of Chemical Industry
Instrumental variable estimation of reinforcer effects
Authors: Jensen Greg
Published: January 2019

Obtained reinforcement (whether measured as counts or as rates) is frequently used as a predictor in regression analyses of behavior. This approach, however, often contradicts the strict requirement that predictors in a regression be statistically independent of behavior. Indeed, by definition, reinforcement in operant scenarios depends on behavior, creating a causal feedback loop. The consequence of this feedback loop is bias in the estimation of regression parameters. This manuscript describes the technique of instrumental variable estimation (IVE), which allows unbiased regression parameters to be obtained through the use of “instruments,” variables that are known a priori to be independent of both compromised predictors and of regression outcomes. Instruments also allow the strength of the bias to be assessed. Two examples of this technique are provided (one relying on real data and one relying on simulation) in the context of regression models of generalized matching.
Morphological tools to evaluate the digestory apparatus in rocky cavy (Kerodon rupestris)
Authors: de Aro Marian Mazeto , dos Santos Amilton Cesar , da Silveira Erick Eduardo , da Silva Lisboa Neto Antônio Francisco , de Oliveira Moacir Franco , de Assis Neto Antônio Chaves
Published: January 2019

This research describes for the first time the complete morphology of the digestive apparatus of rock cavies. Dissection, light microscopy, and scanning electron microscopy were performed. The oral cavity has: the hard palate without palatine wrinkles and the soft palate; the tongue composed by striated musculature, with presence of vallate, foliated, and fungiform papillae with taste buds and filiform papillae with mechanical function; and, 20 teeth of the hypsodonts type. Esophagus, stomach, small intestine (duodenum, jejunum, and ileum), and the large intestine (cecum, colon, and rectum) are found. The anus is present at the end of the alimentary channel. Organs of digestive tube are composed by four tunics: mucosa, submucosa, muscular, and serosa. The duodenum, jejunum and ileum have villi. Jejunum, ileum and cecum present Lieberkühn crypts. The cecum has mucous glands. Colon and rectum are folded and have goblet cells. Anus presents sebaceous glands. As associated glands it is found the liver with six lobes and gallbladder; a lobulated pancreas; and a pair of each major salivary gland (parotid, mandibular, and sublingual). Parotid glands have serous acini and mandibular and sublingual glands have mucous acini. Pancreas has adenomers. The liver has hepatocytes and portal vein, hepatic artery, and bile duct (portal triad), separated by sinusoids. It is concluded that the digestive apparatus of the rock cavy has variations in the dentition, lingual papillae, and acini of the salivary glands when compared to other rodents. Other variations refer to the well‐developed cecum characteristic of herbivorous behavior.
Association of distant recurrence‐free survival with algorithmically extracted MRI characteristics in breast cancer
Authors: Mazurowski Maciej A. , Saha Ashirbani , Harowicz Michael R. , Cain Elizabeth Hope , Marks Jeffrey R. , Marcom P. Kelly
Published: January 2019

Background

While important in diagnosis of breast cancer, the scientific assessment of the role of imaging in prognosis of outcomes and treatment planning is limited.

Purpose: To evaluate the potential of using quantitative imaging variables for stratifying risk of distant recurrence in breast cancer patients.

Study Type

Retrospective.

Population

In all, 892 female invasive breast cancer patients.

Sequence

Dynamic contrast‐enhanced MRI with field strength 1.5 T and 3 T.

Assessment

Computer vision algorithms were applied to extract a comprehensive set of 529 imaging features quantifying size, shape, enhancement patterns, and heterogeneity of the tumors and the surrounding tissue. Using a development set with 446 cases, we selected 20 imaging features with high prognostic value.

Statistical Tests

We evaluated the imaging features using an independent test set with 446 cases. The principal statistical measure was a concordance index between individual imaging features and patient distant recurrence‐free survival (DRFS).

Results

The strongest association with DRFS that persisted after controlling for known prognostic clinical and pathology variables was found for signal enhancement ratio (SER) partial tumor volume (concordance index [C] = 0.768, 95% confidence interval [CI]: 0.679–0.856), tumor major axis length (C = 0.742, 95% CI: 0.650–0.834), kurtosis of the SER map within tumor (C = 0.640, 95% CI: 0.521–0.760), tumor cluster shade (C = 0.313, 95% CI: 0.216–0.410), and washin rate information measure of correlation (C = 0.702, 95% CI: 0.601–0.803).

Data Conclusion

Quantitative assessment of breast cancer features seen in a routine breast MRI might be able to be used for assessment of risk of distant recurrence.

Level of Evidence: 4

Technical Efficacy: Stage 6

J. Magn. Reson. Imaging 2019.
Glycogen distribution in mouse hippocampus
Authors: Hirase Hajime , Akther Sonam , Wang Xiaowen , Oe Yuki
Published: January 2019

The hippocampus is a limbic structure involved in the consolidation of episodic memory. In the recent decade, glycogenolysis in the rodent hippocampus has been shown critical for synaptic plasticity and memory formation. Astrocytes are the primary cells that store glycogen which is subject to degradation in hypoglycemic conditions. Focused microwave application to the brain halts metabolic activities, and therefore preserves brain glycogen. Immunohistochemistry against glycogen on focused microwave‐assisted brain samples is suitable for both macroscopic and microscopic investigation of glycogen distribution. Glycogen immunohistochemistry in the hippocampus showed a characteristic punctate signal pattern that depended on hippocampal layers. In particular, the hilus is the most glycogen‐rich subregion of the hippocampus. Moreover, large glycogen puncta (>0.5 µm in diameter) observed in neuropil areas are organized in a patchy pattern consisting of puncta‐rich and ‐poor astrocytes. These observations are discussed with respect to distinct hippocampal neural activity states observed in live animals.
New‐onset atrial fibrillation in patients with acute coronary syndrome may be associated with worse prognosis and future heart failure
Authors: Nagai Mizuyoshi , Itoh Tomonori , Ishida Masaru , Fusazaki Tetsuya , Komatsu Takashi , Nakamura Motoyuki , Morino Yoshihiro
Published: January 2019

Background

The purpose of this study was to evaluate the prognostic value of atrial fibrillation (AF) in patients with acute coronary syndrome (ACS).

Methods

A total 648 of consecutive ACS patients were divided into non‐AF and all‐AF groups. The all‐AF group was further subdivided into new‐onset AF and pre‐existing AF groups. We compared prognosis among these groups using the Cox regression analysis.

Results

The mean follow‐up period was 1.4 ± 1.2 years. Overall patient numbers were 538 in non‐AF and 110 in all‐AF groups (67 in new‐onset AF and 43 in pre‐existing AF). Seventy‐eight all‐cause deaths and 42 cardiac deaths were observed. New‐onset AF had a worse prognosis than the other groups in the Kaplan‐Meier analysis (P = 0.025) after observation. Cox regression analysis indicated no significant difference for all‐cause death among the three groups. The hazard ratio of congestive heart failure requiring hospitalization was significantly higher in the all‐AF and new‐onset AF group than in the non‐AF group. Multivariate logistic regression analysis revealed that renal dysfunction, peripheral arterial disease, Killip classification ≥2, and left ventricular ejection fraction (LVEF) were independent predictors of all‐cause death. The new‐onset AF group had the highest prevalence of Killip classification ≥2 and the lowest LVEF.

Conclusion

In our study, AF was not an independent predictor of all‐cause death, but new‐onset AF may be associated with worse prognosis and future heart failure.
Recommendations for design and conduct of preclinical in vivo studies of orthopedic device‐related infection
Authors: Moriarty T Fintan , Harris Llinos G. , Mooney Robert A. , Wenke Joseph C. , Riool Martijn , Zaat Sebastian A. J. , Moter Annette , Schaer Thomas P. , Khanna Nina , Kuehl Richard , Alt Volker , Montali Andrea , Liu Jianfeng , Zeiter Stephan , Busscher Henk J. , Grainger David W. , Richards R. Geoff
Published: January 2019

Orthopedic device‐related infection (ODRI), including both fracture‐related infection (FRI) and periprosthetic joint infection (PJI), remain among the most challenging complications in orthopedic and musculoskeletal trauma surgery. ODRI has been convincingly shown to delay healing, worsen functional outcome and incur significant socio‐economic costs. To address this clinical problem, ever more sophisticated technologies targeting the prevention and/or treatment of ODRI are being developed and tested in vitro and in vivo. Among the most commonly described innovations are antimicrobial‐coated orthopedic devices, antimicrobial‐loaded bone cements and void fillers, and dual osteo‐inductive/antimicrobial biomaterials. Unfortunately, translation of these technologies to the clinic has been limited, at least partially due to the challenging and still evolving regulatory environment for antimicrobial drug‐device combination products, and a lack of clarity in the burden of proof required in preclinical studies. Preclinical in vivo testing (i.e. animal studies) represents a critical phase of the multidisciplinary effort to design, produce and reliably test both safety and efficacy of any new antimicrobial device. Nonetheless, current in vivo testing protocols, procedures, models, and assessments are highly disparate, irregularly conducted and reported, and without standardization and validation. The purpose of the present opinion piece is to discuss best practices in preclinical in vivo testing of antimicrobial interventions targeting ODRI. By sharing these experience‐driven views, we aim to aid others in conducting such studies both for fundamental biomedical research, but also for regulatory and clinical evaluation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:271–287, 2019.
GC‐MS profiling of fatty acids in green coffee (Coffea arabica L.) beans and chemometric modeling for tracing geographical origins from Ethiopia
Authors: Mehari Bewketu , Redi‐Abshiro Mesfin , Chandravanshi Bhagwan Singh , Combrinck Sandra , McCrindle Rob , Atlabachew Minaleshewa
Published: January 2019

BACKGROUND

This study was aimed at the development of objective analytical method capable of verifying the production region of the coffee beans. One hundred samples of green coffee (Coffea arabica L.) beans from the major producing regions, comprising various sub‐regional types, were studied for variations in their fatty acid compositions by using gas chromatography coupled with mass spectrometry. Principal component analysis (PCA) was used to visualize data trends. Linear discriminant analysis (LDA) was used to construct classification models.

RESULTS

Twenty‐one different fatty acids were detected in all of the samples. The total fatty acid content varied from 83 to 204 g kg−1 across the regions. Oleic, linoleic, palmitic, stearic and arachidic acids were identified as the most discriminating compounds among the production regions. The recognition and prediction abilities of the LDA model for classification at regional level were 95% and 92%, respectively, and 92% and 85%, respectively, at sub‐regional level.

CONCLUSION

Fatty acids contain adequate information for use as descriptors of the cultivation region of coffee beans. Chemometric methods based on fatty acid composition can be used to detect fraudulently labeled coffees, with regard to the production region. These can benefit the coffee production market by providing consumers with products of the expected quality. © 2019 Society of Chemical Industry
Posttraumatic Stress Trajectories in World Trade Center Tower Survivors: Hyperarousal and Emotional Numbing Predict Symptom Change
Authors: Adams Shane W. , Allwood Maureen A. , Bowler Rosemarie M.
Published: January 2019

There is a paucity of knowledge concerning the underlying symptomatology of heterogeneous posttraumatic stress symptom (PTSS) trajectories following mass trauma, such as a terrorist attack. This study examined longitudinal PTSS trajectories using latent growth mixture modeling in 2,355 World Trade Center (WTC) tower survivors surveyed by the WTC Health Registry an average of 2.5, 5.5, and 10.5 years after the September 11, 2001 terrorist attacks. Covariates included sociodemographic characteristics, WTC‐related exposure, and other traumas/stressors. Four curvilinear PTSS trajectories were identified: low symptom (74.9%), recovering (8.0%), worsening (6.7%), and chronic (10.4%). The majority of WTC survivors (85.3%) maintained stable symptom trajectories over time, with PTSS changes occurring less often. Although WTC‐related exposure was associated with initial PTSS severity, exposure was not associated with chronicity or change of PTSS over time. Male gender and a higher number of post‐WTC disaster life‐stressors were associated with worsening symptom severity over time. Individuals with more severe hyperarousal symptoms at Wave 1, particularly of anxious arousal, were more likely to have PTSS that worsened over time, adjusted odds ratio (aOR) = 1.55. Less severe emotional numbing symptoms, particularly of dysphoria, at Wave 1, were marginally significantly associated with subsequent PTSS recovery, aOR = 0.75. Interventions that target hyperarousal and emotional numbing symptoms may mitigate a worsening of symptoms and facilitate posttraumatic recovery following future mass traumas, such as terrorist attacks. Further clinical implications are discussed.
Bring the facts, bust the myths
Authors: Plume Andrew
Published: January 2019

Question everything and seek answers
Harnessing Polyisobutylene by Rotaxanation with γ‐Cyclodextrin: Opportunities for Making Smart Molecular Necklaces
Authors: Przybylski Cédric , Ramoul Hassen , Bonnet Véronique , Abad Mathilde , Jarroux Nathalie
Published: January 2019

A new type of polyrotaxane based on the threading of γ‐cyclodextrins (γ‐CDs) along a highly hydrophobic polymer, polyisobutylene (PIB), is successfully prepared and finely characterized. The used radical coupling associated with tuned reaction time and temperature leads to a fast and controlled necklace synthesis with low reagent consumption. Synthesis exhibits appealing conversion and threading rates with almost 100% and 62–73%, respectively. A combination of well‐established SEC and NMR techniques, with a more forefront MALDI‐TOF MS approach, provides details on the original PIB and the resulting polyrotaxanes (M
w, M
n, PDI, and average number of γ‐CD threaded). Interestingly, tetramethylguanidinium‐2‐(4‐hydroxyphenylazo)benzoate in DMF for MALDI analysis is revealed as a suitable matrix to overcome solubility troubles widely observed with PIB. Moreover, rotaxanation appears as an alternative to the grafting of polar groups to modify/handle hydrophobic polymers. Such an approach offers new opportunities to achieve the synthesis, with unambiguous evidence, of new supramolecular necklaces based on highly hydrophobic polymers.
Porous Polymers Derived from Octavinylsilsesquioxane by Cationic Polymerization
Authors: Du Yajing , Ge Mingtao , Liu Hongzhi
Published: January 2019

A new rapid and efficient approach is developed for the preparation of porous materials via cationic polymerization of octavinylsilsesquioxane (OVS). The reaction proceeds rapidly and efficiently at room temperature, forming a predominantly covalent porous network polymer. A series of experiments are conducted to clarify the effects of reaction time, temperature, and solvent on the polymerization process. The results show that all the products possess a nanoporous structure with surface areas of approximately 300 – 620 m2 g−1 and a pore volume of 0.15 – 0.54 cm3 g−1. The porosity of these polymers can be readily tailored by changing the reaction conditions. The post functionalization of the materials is further investigated by epoxidation and the application of these polymers as carbon dioxide adsorbents (up to 0.98 mmol g−1) is also explored. The work has general implications in understanding the reactive nature of the cationic polymerization of OVS and is very promising for promoting the application of porous materials.
Identification of epithelial‐specific ETS‐1 (ESE‐1) as a tumor suppressor and molecular target of green tea compound, EGCG
Authors: Ha Taekyu , Lee Jihye , Lou Zhiyuan , Lee Bok‐Soon , Kim Chul‐Ho , Lee Seong‐Ho
Published: January 2019

Epithelial specific ETS‐1 (ESE‐1) belongs to the E26 transformation‐specific transcription factor superfamily and is of great interest as a potential target for managing several types of cancer. Despite its clinical significance, the documented effects of ESE‐1 on cancer development and progression are contradictory and its underlying biological mechanism of action remains elusive. The objectives of this study are to investigate whether ESE‐1 is a tumor suppressor and to identify dietary anti‐cancer compound to activate ESE‐1 expression in human colon cancer model. ESE‐1 knockout and xenograft mouse models were used to examine the effect of ESE‐1 in colon tumorigenesis. Stable human colon cancer cell lines were used for in vitro mechanistic studies. ESE‐1 knockout in mice increased azoxymethane (AOM)‐induced and dextran sulfate sodium (DSS)‐promoted formation of aberrant crypt foci (ACF). Conversely, overexpression of ESE‐1 suppressed tumorigenicity in a xenograft mouse study, and repressed anchorage‐independent growth and migration/invasion in human colon cancer cells. Full length ESE‐1 localized abundantly in the nucleus, and internal deletion of nuclear localization sequence 2 (NLS2) reduced nuclear ESE‐1. Three lysine residues (318KKK320) in the NLS2 determine its nuclear localization. We identified epigallocatechin‐3‐gallate (EGCG) that acts as a transcriptional activator of ESE‐1 in human colon cancer cells. These findings propose a novel and promising molecular target of dietary anti‐cancer compounds for prevention of colon cancer.
Tardive dyskinesia is associated with altered putamen Akt/GSK‐3β signaling in nonhuman primates
Authors: Hernandez Giovanni , Mahmoudi Souha , Cyr Michel , Diaz Jorge , Blanchet Pierre J. , Lévesque Daniel
Published: January 2019

Background

Tardive dyskinesia is a delayed and potentially irreversible motor complication arising from chronic exposure to antipsychotic drugs. Interaction of antipsychotic drugs with G protein‐coupled receptors triggers multiple intracellular events. Nevertheless, signaling pathways that might be associated with chronic unwanted effects of antipsychotic drugs remain elusive. In this study, we aimed to better understand kinase signaling associated with the expression of tardive dyskinesia in nonhuman primates.

Methods

We exposed capuchin monkeys to prolonged haloperidol (n = 10) or clozapine (n = 6) treatments. Untreated animals were used as controls (n = 6). Half of haloperidol‐treated animals (5) developed mild tardive dyskinesia similar to that found in humans. Using Western blots and immunochemistry, we measured putamen total and phosphorylated protein kinase levels associated with canonical and noncanonical signaling cascades of G protein‐coupled receptors.

Results

Antipsychotic drugs enhanced pDARPP‐32 and pERK1/2, but no difference ws observed in phosphoprotein kinase levels between dyskinetic and nondyskinetic monkeys. On the other hand, comparison of kinase levels between haloperidol‐treated dyskinetic and nondyskinetic monkeys indicated that dyskinetic animals had lower GRK6 and β‐arrestin2 levels. Levels of pAkt and pGSK‐3β were also reduced, but only haloperidol‐treated monkeys that developed tardive dyskinesia had reduced pGSK‐3β levels, whereas pAkt levels in dyskinetic animals positively correlated with dyskinetic scores. Interestingly, double immunofluorescence labeling showed that putamen dopamine D3 receptor levels were upregulated and that D3/pAkt colocalization was enriched in haloperidol‐treated animals displaying tardive dyskinesia.

Conclusions

Our results suggest that upregulation of putamen dopamine D3 receptor and alterations along the noncanonical GRK6/β‐arrestin2/Akt/GSK‐3β molecular cascade are associated with the development of tardive dyskinesia in nonhuman primates. © 2019 International Parkinson and Movement Disorder Society
Low Mach number limit of global solutions to 3‐D compressible nematic liquid crystal flows with Dirichlet boundary condition
Authors: Zeng Lan , Ni Guoxi , Ai Xiao
Published: January 2019

In this paper, we consider the uniform estimates of strong solutions in the Mach number ϵ and t ∈ [0,∞) for the compressible nematic liquid crystal flows in a 3‐D bounded domain
, provided the initial data are small enough and the density is close to the constant state. Here, we consider the case that the velocity field satisfies the Dirichlet boundary condition. Based on the uniform estimates, we obtain the global convergence of the compressible nematic liquid crystal system to the incompressible nematic liquid crystals system as the Mach number tends to zero.
Diffusion tractography of the rat knee at microscopic resolution
Authors: Wang Nian , Mirando Anthony J. , Cofer Gary , Qi Yi , Hilton Matthew J. , Johnson G. Allan
Published: January 2019

Purpose

To evaluate whole knee joint tractography, including articular cartilage, ligaments, meniscus, and growth plate using diffusion tensor imaging (DTI) at microscopic resolution.

Methods

Three rat knee joints were scanned using a modified 3D diffusion‐weighted spin echo pulse sequence with 90‐ and 45‐μm isotropic spatial resolution at 9.4T. The b values varied from 250 to 1250 s/mm2 with 4 times undersampling in phase directions. Fractional anisotropy (FA) and mean diffusivity (MD) were compared at different spatial resolution and b values. Tractography was evaluated at multiple b values and angular resolutions in different connective tissues, and compared with conventional histology. The mean tract length and tract volume in various types of tissues were also quantified.

Results

DTI metrics (FA and MD) showed consistent quantitative results at 90‐ and 45‐μm isotropic spatial resolutions. Tractography of various connective tissues was found to be sensitive to the spatial resolution, angular resolution, and diffusion weightings. Higher spatial resolution (45 μm) supported tracking the cartilage collagen fiber tracts from the superficial zone to the deep zone, in a continuous and smooth progression in the transitional zone. Fiber length and fiber volume in the growth plate were strongly dependent on angular resolution and b values, whereas tractography in ligaments was found to be less dependent on spatial resolution.

Conclusion

High spatial and angular resolution DTI and diffusion tractography can be valuable for knee joint research because of its visualization capacity for collagen fiber orientations and quantitative evaluation of tissue’s microscopic properties.
Highly Active Catalysis of Cobalt Tetrakis(pentafluorophenyl)porphyrin Promoted by Chitosan for Cyclohexane Oxidation in Response‐Surface‐Methodology‐Optimized Reaction Conditions
Authors: Mo Lin‐Qiang , Huang Xian‐Fei , Huang Guan , Yuan Guang‐Ping , Wei Su‐Juan
Published: January 2019

We aimed at elevating catalytic performances of cobalt tetrakis(pentafluorophenyl)porphyrin (Co TPFPP) through axial coordination, nanocavities, and covalently grafting action. The Co TPFPP was immobilized onto nanoporous and nonporous chitosan, forming Co TPFPP/np‐ and nonp‐CTS catalysts, respectively. The catalysts were characterized by various spectroscopic techniques. The catalytic performances of these catalysts for cyclohexane oxidation under response‐surface‐methodology‐optimized oxidation reaction conditions were estimated and compared. Co TPFPP/np‐CTS was an excellent catalyst at aspect of catalytic activity, exhibiting the considerable potential reusability, 24.2 mol % yields (KA oil : cyclohexanone and cyclohexanol) in average, and total turnover frequencies (TOFs) of 3.25×106 h−1. This is attributed to the structural characteristics of the Co TPFPP/np‐CTS catalyst: the cobalt porphyrin molecules could be highly scattered on CTS, forming the independent active sites, and were not leached. The axial coordination exerted the most important effect on the catalytic activity, and the covalent grafting action had a decisive effect on the increase of the total TOFs and on the reusability of the catalyst.
Diabetes Treatment: Selective Synthetic Receptor for Glucose
Authors: Shirinfar Bahareh , Ahmed Nisar
Published: January 2019

A new synthetic receptor has selective and strong interactions with glucose, directing towards future diabetes management. These studies pave the way to design future selective receptors that can potentially be modified with combinations of urea walls having multiple H‐binding sites to generate hydrophilic affinities, and the incorporation of promising aromatic systems for hydrophobic π‐interactions with glucose CH.
Stewardship and health systems strengthening: An overview
Authors: Brinkerhoff Derick W. , Cross Harry E. , Sharma Suneeta , Williamson Taylor
Published: January 2019

The World Health Organization (WHO) introduced the concept of stewardship to clarify the practical components of governance in the health sector. For the WHO, stewardship concentrated on how government actors take responsibility for the health system and the wellbeing of the population, fulfill health system functions, assure equity, and coordinate interaction with government and society. This article overviews the contents of this special issue, which offers examples of how health stewards in a variety of countries have addressed issues of health security, primary care expansion, family planning, and quality of care. The contributors' articles draw lessons for policy, programs, and management useful for practitioners and scholars. Our overview identifies several themes emerging from the articles: the foundational role of legal frameworks for effective stewardship, the importance of institutional arrangements as enablers, the influence of regional and global entities on national stewardship, the connection between credible decision‐making structures and stewardship, and pathways to sustainable financing and domestic resource mobilization. The discussion concludes with highlighting several gaps in knowledge and practice related to health stewardship.
Outcome of pediatric non‐Hodgkin lymphoma in Central America: A report of the Association of Pediatric Hematology Oncology of Central America (AHOPCA)
Authors: Peña‐Hernandez Armando , Ortiz Roberta , Garrido Claudia , Gomez‐Garcia Wendy , Fuentes‐Alabi Soad , Martinez Roxana , Metzger Monika L. , Chantada Guillermo L. , Ribeiro Raul C.
Published: January 2019

Background

Treating B–non‐Hodgkin lymphoma (B‐NHL) in lower‐income countries is challenging because of imprecise diagnosis, the increased risk of fatal toxicity associated with advanced disease at presentation, and limited supportive care.

Procedure

Central American patients with newly diagnosed stage I or II B‐NHL received a modified Berlin–Frankfurt–Münster (BFM) regimen including a prephase (prednisone, cyclophosphamide) followed by A/B/A courses (A: cytarabine, dexamethasone, etoposide, ifosfamide, methotrexate, and intrathecal therapy; B: cyclophosphamide, dexamethasone, doxorubicin, methotrexate, and intrathecal therapy). Those with stage III or IV NHL received additional courses (B/A/B), intensified for stage IV disease by additional vincristine and methotrexate doses. Patients in poor condition received a second prephase treatment before their chemotherapy courses.

Results

Between March 2004 and June 2016, of 405 patients with B‐NHL, 386 (109 females) were eligible for treatment. Immunohistochemistry was performed in 177 cases (47.4%) and characterized the disease as mature B‐cell lymphoma. Stage distribution was as follows: I/II, 31 (8.1%); III, 252 (65.3%); IV, 93 (24.1%); 10 (2.6%) not available. The 3‐year overall survival was 70% for the whole group (86% for stages I/II, 75% for stage III, 58% for stage IV). Events included death during induction (34 patients, 8.8%), relapse/progression (46, 11.9%), death in remission (9, 2.3%), second malignancy (1, 0.26%), and death of unknown cause (1, 0.26%). Twenty‐three (6%) patients abandoned or refused therapy.

Conclusions

Approximately 70% of children with B‐NHL from Central America experienced long‐term, disease‐free survival with a modified BFM schedule. Toxic death and relapse/resistant disease were the main reasons for treatment failure.
Shape memory properties and unusual optical behaviour of an interpenetrating network of poly(ethylene oxide) and poly(2‐hydroxyethyl methacrylate)
Authors: Jagtap Siddheshwar , Dalvi Vishal , Sankar Kalleta , Ratna Debdatta
Published: January 2019

An interpenetrating polymer network (IPN) with shape memory properties was prepared by using poly(2‐hydroxyethyl methacrylate) (PHEMA) and poly(ethylene oxide) (PEO). PHEMA acts as a fixed phase and PEO as a switching phase. The switching action of PEO is due to the reversible process of melting and crystallization. It was observed that the shape recovery of the IPN increases with increasing crosslinker concentration up to an optimum value and decreases thereafter. In addition to the shape memory property, the IPNs show a reversible change in optical properties from translucent to opaque. The change in optical properties is quite different from that observed in a semicrystalline polymer system where the transparency increases as a result of the melting of crystals. This behaviour of the IPN is explained in terms of H‐bonding of PEO with PHEMA. Fourier transform infrared spectroscopy was used to study the H‐bonding between PEO and PHEMA. © 2019 Society of Chemical Industry