bluuebunny/crossref_metadata_2025 huggingface dataset:
Standardized terminology systems in cytopathology
Authors: Sundling Kaitlin E. , Kurtycz Daniel F. I.
Published: November 2018

There has been increasing pressure for systemization in cytopathology. Lack of uniformity in categorization, variation in opinion based regional practice, and technologic advancement have created an environment disposed toward creation of more consistent evidence‐based approaches to diagnostic problems. This review provides an overview of the major standardized terminology systems in cytology, with historical perspectives and commentary on current uses of these systems. These systems now include gynecologic, thyroid, pancreaticobiliary, urinary, salivary gland, and breast cytology. We summarize major classification systems supported by national and international professional organizations, outlining the structure and goals of each system. Specific benefits and potential pitfalls in the implementation of each system are given. Finally, we address potential criticisms of standardized terminology systems and proposed future directions to continue the evolution of standardized terminology to improve clinical practice.
Exendin‐4(Lys27PAL)/gastrin/xenin‐8‐Gln: A novel acylated GLP‐1/gastrin/xenin hybrid peptide that improves metabolic status in obese‐diabetic (ob/ob) mice
Authors: Hasib Annie , Ng Ming T. , Tanday Neil , Craig Sarah L. , Gault Victor A. , Flatt Peter R. , Irwin Nigel
Published: November 2018

Background

Therapeutic benefits of peptide‐based drugs is limited by rapid renal elimination.

Methods

Therefore, to prolong the biological action profile of the recently characterized triple‐acting hybrid peptide, exendin‐4/gastrin/xenin‐8‐Gln, a fatty acid (C‐16) has been covalently attached, creating exendin‐4(Lys27PAL)/gastrin/xenin‐8‐Gln. Exendin‐4/gastrin and liraglutide/gastrin/xenin‐8‐Gln were also synthesized as direct comparator peptides.

Results

All hybrid peptides evoked significant concentration‐dependent increases of insulin secretion from isolated murine islets and BRIN‐BD11 cells. Following administration of peptides with glucose to mice, all hybrids significantly reduced the overall glycaemic excursion and increased insulin concentrations. In contrast to other treatments, exendin‐4(Lys27PAL)/gastrin/xenin‐8‐Gln displayed impressive antihyperglycaemic actions even 12 hours after administration, highlighting protracted duration of effects. Exendin‐4/gastrin/xenin‐8‐Gln, exendin‐4/gastrin, and exendin‐4(Lys27PAL)/gastrin/xenin‐8‐Gln were then progressed to a 31‐day twice‐daily treatment regimen in obese‐diabetic ob/ob mice. All treatments decreased nonfasting glucose and HbA1c concentrations, as well as enhancing circulating and pancreatic insulin levels. Exendin‐4/gastrin and exendin‐4/gastrin/xenin‐8‐Gln also decreased food intake. Glucose tolerance was improved by all treatments, but only exendin‐4(Lys27PAL)/gastrin/xenin‐8‐Gln augmented glucose‐induced insulin secretion. Interestingly, treatment regimens that included a xenin component induced clear advantages on the metabolic response to glucose‐dependent insulinotropic polypeptide (GIP) and the glucose‐lowering actions of insulin.

Conclusion

This study emphasizes the therapeutic promise of long‐acting, multi‐targeting hybrid gut peptides for type 2 diabetes.
Optimizing the Reaction Performance of La2Ce2O7‐Based Catalysts for Oxidative Coupling of Methane (OCM) at Lower Temperature by Lattice Doping with Ca Cations
Authors: Xu Junwei , Zhang Yan , Liu Yameng , Fang Xiuzhong , Xu Xianglan , Liu Wenming , Zheng Renyang , Wang Xiang
Published: November 2018

To optimize the reaction performance of La2Ce2O7 for OCM, catalysts with varied La/Ce molar ratios and doped by Ca additive have been synthesized and characterized by different techniques. It is discovered that a La2Ce2O7 compound having a disordered cubic defective fluorite phase is predominantly formed in all the samples. Varying the La/Ce ratio influences the fine crystalline structure of the catalysts. As a result, the abundance of the surface facile oxygen and alkaline sites increase by increasing the La/Ce ratio. Moreover, the Ca additive exists on the surface of Ca0.5La2Ce2O7 and Ca0.5La1.5Ce2O7 as dispersed CaCO3, which covers the active sites and is harmful to the OCM reaction. However, for La2Ce1.5Ca0.5O7, the major part of the Ca additive has entered into the lattice of La2Ce2O7 phase as Ca2+ cations, thus creating more oxygen vacancies and improving the surface alkalinity of the catalyst, which is favorable to the OCM reaction. Both the active surface oxygen and alkaline sites are vital for OCM, and their synergism determines the reactivity. By increasing La/Ce ratio and doping Ca2+ into La2Ce2O7 lattice, the quantities of both kinds of active sites can be significantly improved, thus obtaining catalysts with much improved reaction performance. La2Ce1.5Ca0.5O7 owns the largest amount of both types of active sites, hence depicting the best reaction performance, over which the highest C2 yield of 22.5 % can be achieved even at 750 °C.
High‐Pressure Synthesis and Crystal Structure of the Highly Condensed Yttrium Borate YB7O12
Authors: Fuchs Birgit , Schmitt Martin K. , Wurst Klaus , Huppertz Hubert
Published: November 2018

The yttrium borate YB7O12 was obtained in a high‐pressure/high‐temperature experiment at 10 GPa and 1573 K. The crystal structure was clarified by X‐ray single‐crystal diffraction, where the compound was found to crystallize in the orthorhombic space group Pccn (no. 56) with the lattice parameters a = 11.985(2), b = 6.717(6), c = 7.867(7) Å, and a volume of V = 633.0(1) Å3. Built up exclusively from BO4 tetrahedra, YB7O12 features an exceptionally high degree of condensation, which originates from the finding that every tetrahedron contains two threefold‐coordinated oxygen atoms. The compound was further characterized by X‐ray powder diffraction.
Synthesis of Benzimidazole‐Fused Medium‐Sized N,S‐Heterocycles via Palladium‐Catalyzed Cyclizations
Authors: Lopes Alexandra Basilio , Wagner Patrick , Gulea Mihaela
Published: November 2018

The synthesis of unprecedented benzimidazole‐fused thiazocines, thiazonines, and thiazecines having an exocyclic double bond is reported. The process proceeds through an 8‐, 9‐, or 10‐exo‐dig cyclocarbopalladation followed by reduction. The scope and limitations were established and showed the importance of the precursor structure for the success of the reaction. A competition between the exo‐dig and the endo‐dig cyclization was observed for two substrates bearing an N‐homopropargyl chain, the endo‐cyclization leading to rarely encountered 10‐ and 11‐membered N,S‐heterocycles with a trans‐endocyclic double bond. X‐ray structures of three products were obtained by co‐crystallization with fumaric acid and show the twisted structures of these molecules.
Catalytic Enantioselective Synthesis of 3,4,5‐Trisubstituted Isoxazoline N‐Oxides and Regioselective Synthesis of 3,4,5‐Trisubstituted Isoxazoles
Authors: Sahoo Subas Chandra , Pan Subhas Chandra
Published: November 2018

An efficient catalytic asymmetric synthesis of 3,4,5‐trisubstituted isoxazoline N‐oxides and regioselective synthesis of 3,4,5‐trisubstituted isoxazoles has been described. α‐Nitrocinnamates and α‐nitrobenzophenones were utilized as Michael acceptors respectively. Hydroquinine derived thiourea in combination with cesium carbonate was effective for the synthesis of isoxazoline N‐oxides whereas stoichiometric di‐isopropylethylamine (DIPEA) was the best choice for isoxazole synthesis. In both cases a range of aryl and heteroaromatic groups was tolerated.
Effects of Acute Fluorene‐9‐Bisphenol Exposure on Mouse Oocyte in vitro Maturation and Its Possible Mechanisms
Authors: Jiao Xiao‐Fei , Liang Qiu‐Man , Wu Di , Ding Zhi‐Ming , Zhang Jia‐Yu , Chen Fan , Wang Yong‐Sheng , Zhang Shou‐Xin , Miao Yi‐Liang , Huo Li‐Jun
Published: November 2018

Fluorene‐9‐bisphenol (BHPF), a substitute of bisphenol A (BPA) used in the production of the so‐called “BPA‐free” plastics, has now been shown to be released from commercial plastic bottles into drinking water and has strong anti‐estrogenic activity in mice, which suggests that BHPF is also an environmental toxin. However, whether BHPF exposure has effects on mouse oocyte development is unknown. In this study, the influence of acute exposure to BHPF (50–150 μM, 12 hr) on mouse oocyte maturation and its possible mechanisms were investigated. Of note, 50‐μM BHPF had no effects on the maturation of mouse oocytes, whereas 100‐ and 150‐μM BHPF significantly blocked germinal vesicle breakdown and led to the failure of first polar body extrusion. Particularly, 100‐μM BHPF exposure severely decreased the cellular adenosine triphosphate in a time‐dependent manner, which finally brought out the loss of spindles. In addition, the actin cytoskeleton was also impaired. The defective mitochondrial dynamics and decreased mitochondrial DNA implied the damage of mitochondria in BHPF‐treated oocytes. Increased PINK1, Beclin1, and LC3B protein level and decreased TOMM20 and TOMM17A protein level illustrated that mitophagy was induced, which also confirmed that BHPF exposure impaired the cellular mitochondria. Moreover, BHPF induced reactive oxygen species accumulation and early apoptosis. Oocyte quality was also impaired by BHPF exposure through altering histone modifications evidenced by increased H3K9me3 and H3K27me3 levels. Collectively, our results indicated that BHPF exposure disrupted mouse oocyte maturation and reduced oocyte quality through affecting cytoskeleton architecture, mitochondrial function, oxidative stress, apoptosis, and histone modifications. Environ. Mol. Mutagen. 60:243–253, 2019. © 2018 Wiley Periodicals, Inc.
Gene flow improves fitness at a range edge under climate change
Authors: Bontrager Megan , Angert Amy L.
Published: November 2018

Populations at the margins of a species' geographic range are often thought to be poorly adapted to their environment. According to theoretical predictions, gene flow can inhibit these range edge populations if it disrupts adaptation to local conditions. Alternatively, if range edge populations are small or isolated, gene flow can provide beneficial genetic variation and may facilitate adaptation to environmental change. We tested these competing predictions in the annual wildflower Clarkia pulchella using greenhouse crosses to simulate gene flow from sources across the geographic range into two populations at the northern range margin. We planted these between-population hybrids in common gardens at the range edge and evaluated how genetic differentiation and climatic differences between edge populations and gene flow sources affected lifetime fitness. During an anomalously warm study year, gene flow from populations occupying historically warm sites improved fitness at the range edge and plants with one or both parents from warm populations performed best. The effects of the temperature provenance of gene flow sources were most apparent at early life history stages, but precipitation provenance also affected reproduction. We also found benefits of gene flow that were independent of climate: after climate was controlled for, plants with parents from different populations performed better at later lifestages than those with parents from the same population, indicating that gene flow may improve fitness via relieving homozygosity. Further supporting this result, we found that increasing genetic differentiation of parental populations had positive effects on fitness of hybrid seeds. Gene flow from warmer populations, when it occurs, is likely to contribute adaptive genetic variation to populations at the northern range edge as the climate warms. On heterogeneous landscapes, climate of origin may be a better predictor of gene flow effects than geographic proximity.
Activated T cells induce proliferation of oligodendrocyte progenitor cells via release of vascular endothelial cell growth factor‐A
Authors: Choi Elliot H. , Xu Yadi , Medynets Marie , Monaco Maria Chiara G. , Major Eugene O. , Nath Avindra , Wang Tongguang
Published: November 2018

Neuroinflammatory diseases such as multiple sclerosis are characterized by infiltration of lymphocytes into the central nervous system followed by demyelination and axonal degeneration. While evidence suggests that activated T lymphocytes induce neurotoxicity and impair function of neural stem cells, the effect of T cells on oligodendrocyte progenitor cells (OPCs) is still uncertain, partly due to the difficulty in obtaining human OPCs. Here we studied the effect of activated T cells on OPCs using OPCs derived from human hematopoietic stem cells or from human fetal brain. OPCs were exposed to supernatants (sups) from activated T cells. Cell proliferation was determined by EdU incorporation and CellQuanti‐Blue assays. Surprisingly, we found that sups from activated T cells induced OPC proliferation by regulating cell cycle progression. Vascular endothelial growth factor A (VEGF‐A) transcripts were increased in T cells after activation. Immunodepletion of VEGF‐A from activated T cell sups significantly attenuated its effect on OPC proliferation. Furthermore, VEGF receptor 2 (VEGFR2) was expressed on OPCs and its inhibition also attenuated activated T cell‐induced OPC proliferation. Thus, activated T cells have a trophic role by promoting OPC proliferation via the VEGFR2 pathway.
Metal wear particles in hematopoietic marrow of the axial skeleton in patients with prior revision for mechanical failure of a hip or knee arthroplasty
Authors: Hall Deborah J. , Pourzal Robin , Jacobs Joshua J. , Urban Robert M.
Published: November 2018

Wear particles generated by hip and knee arthroplasties disseminate to the liver and spleen with the highest concentrations observed in subjects who have had a failed arthroplasty. We asked to what extent metallic particles could also disseminate to remote hematopoietic bone marrow. Cored samples of red marrow from the axial skeleton and proximal humerus were obtained postmortem from four males and two females aged 79–92 years. Seven to seventeen years prior to their demise, each subject had undergone successful revision of their arthroplasty for mechanical failure in which an unintended wear condition had generated a large volume of metal particles. The marrow samples were analyzed using stained histological sections and energy dispersive X‐ray analysis. Intracellular metal alloy particles were detected in the bone marrow of the cranium, proximal humerus, sternum, ribs, lumbar vertebrae, and the iliac crest. The components previously revised for mechanical failure were confirmed to be the predominant source of the disseminated wear debris. Particles of either Ti, Ti6Al4V, CoCrMo, FeCrNi alloys, or BaSO4 were identified in 24 of the 25 marrow samples examined. The particles ranged in size from 50 nm (the limit of resolution of our technique) to 6 μm. Metallic wear particles generated by hip and knee arthroplasties can disseminate widely to hematopoietic bone marrow throughout the axial skeleton and proximal humerus, especially in cases with a history of severe wear. The hematopoietic microenvironment is potentially sensitive to metallic degradation products. However, actual medical sequelae from disseminated wear debris is a rare occurrence. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1930–1936, 2019.
PDGF Modulates BMP2‐Induced Osteogenesis in Periosteal Progenitor Cells
Authors: Wang Xi , Matthews Brya G , Yu Jungeun , Novak Sanja , Grcevic Danka , Sanjay Archana , Kalajzic Ivo
Published: November 2018

BMPs are used in various clinical applications to promote bone formation. The limited success of the BMPs in clinical settings and supraphysiological doses required for their effects prompted us to evaluate the influence of other signaling molecules, specifically platelet‐derived growth factor (PDGF) on BMP2‐induced osteogenesis. Periosteal cells make a major contribution to fracture healing. We detected broad expression of PDGF receptor beta (PDGFRβ) within the intact periosteum and healing callus during fracture repair. In vitro, periosteum‐derived progenitor cells were highly responsive to PDGF as demonstrated by increased proliferation and decreased apoptosis. However, PDGF blocked BMP2‐induced osteogenesis by inhibiting the canonical BMP2/Smad pathway and downstream target gene expression. This effect is mediated via PDGFRβ and involves ERK1/2 MAPK and PI3K/AKT signaling pathways. Therapeutic targeting of the PDGFRβ pathway in periosteum‐mediated bone repair might have profound implications in the treatment of bone disease in the future. © 2018 The Authors JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Overexpression of FOXS1 in gastric cancer cell lines inhibits proliferation, metastasis, and epithelial‐mesenchymal transition of tumor through downregulating wnt/β‐catenin pathway
Authors: Lu Qiyu , Ma Xudong , Li Yijun , Song Wanhong , Zhang Lingshu , Shu Yixiong , Wan Baosheng
Published: November 2018

Background

Expression of forkhead box (FOX) superfamily members has been shown to be decreased in cancer, which was linked to poor prognosis of patients. The aim of this study was to investigate the expression of a new FOX superfamily member, FOXS1, in gastric cancer, and the influence of FOXS1 overexpression on the tumorigenesis of gastric cancer cells. The underlying molecular mechanism was also investigated.

Materials and Methods

FOXS1 expression levels were firstly measured in 15 paired gastric cancer and peritumor tissue using quantitative polymerase chain reaction or immunohistochemistry. Secondly, FOXS1 overexpression models were established in two gastric cancer cell lines (SNU‐216 and AGS) and FOXS1 knockdown model was established in SNU‐638 gastric cancer cell line. Markers for cell proliferation, metastasis, cell cycle status, and wnt/β‐catenin pathway were evaluated. Influence of FOXS1 overexpression on tumorigenesis was further evaluated in xenograft model.

Results

Expression of FOXS1 was significantly decreased in gastric cancer tissue in both messenger RNA and protein levels, compared with peritumor tissue. Our results showed that compared to cell lines transfected with negative control, gastric cancer cell lines with FOXS1 overexpression showed suppressed cell proliferation, metastasis, and increased ratio of G0/G1 phase. Xenograft model also showed suppressed tumor growth in FOXS1 overexpression group. Epithelial‐mesenchymal transition was also inhibited when FOXS1 was overexpressed, which was indicated by an increase of E‐cadherin expression and decrease in vimentin expression. Further investigation showed that expression of β‐catenin was decreased, together with decreased expression in downstream signaling factors, c‐Myc and cyclin‐D1 in FOXS1 overexpression cell lines. On the other hand, knockdown of FOXS1 showed opposite trends in the changes of those markers for cell proliferation, metastasis, cell cycle status, and wnt/β‐catenin pathway, compared with FOXS1 overexpression.

Conclusion

In conclusion, the present study showed that FOXS1 expression is downregulated in most GC cases in our cohort, and this loss of expression may promote cell proliferation and metastasis through upregulation of wnt/β‐catenin pathway.
miR‐146b overexpression ameliorates lipopolysaccharide‐induced acute lung injury in vivo and in vitro
Authors: He Ruoxi , Li Ying , Zhou Li , Su Xiaoli , Li Yuanyuan , Pan Pinhua , Hu Chengping
Published: November 2018

Acute respiratory distress syndrome (ARDS) is a type of acute lung injury (ALI), which causes high morbidity and mortality. So far, effective clinical treatment of ARDS is still limited. Recently, miR‐146b has been reported to play a key role in inflammation. In the present study, we evaluated the functional role of miR‐146b in ARDS using the murine model of lipopolysaccharide (LPS)‐induced ALI. The miR‐146b expression could be induced by LPS stimulation, and miR‐146b overexpression was required in the maintenance of body weight and survival of ALI mice; after miR‐146b overexpression, LPS‐induced lung injury, pulmonary inflammation, total cell and neutrophil counts, proinflammatory cytokines, and chemokines in bronchial alveolar lavage (BAL) fluid were significantly reduced. The promotive effect of LPS on lung permeability through increasing total protein, albumin and IgM in BAL fluid could be partially reversed by miR‐146b overexpression. Moreover, in murine alveolar macrophages, miR‐146b overexpression reduced LPS‐induced TNF‐α and interleukin (IL)‐1β releasing. Taken together, we demonstrated that miR‐146b overexpression could effectively improve the LPS‐induced ALI; miR‐146b is a promising target in ARDS treatment.
Nobiletin suppresses high‐glucose–induced inflammation and ECM accumulation in human mesangial cells through STAT3/NF‐κB pathway
Authors: Liu Zhenzhou , Han Yanru , Zhao Fucheng , Zhao Zhenxia , Tian Junlei , Jia Kui
Published: November 2018

Diabetic nephropathy (DN) is a complication of chronic diabetes and the main cause of end‐stage renal disease all over the world. Inflammation and extracellular matrix (ECM) accumulation play important roles in the pathogenesis of DN. Evidence suggested that nobiletin acts anti‐inflammatory role and plays a critical role in diabetes; however, its role in DN remains unclear. In the current study, we promulgated the nobiletin involved in high‐glucose–induced glomerular mesangial cell inflammation and ECM accumulation. Nobiletin treatment significantly abrogated high‐glucose–induced glomerular mesangial cell proliferation. Nobiletin treatment markedly suppressed inflammation cytokine secretion, including interleukin (IL)‐1β, IL‐6, tumor necrosis factor α, and monocyte chemoattractant protein 1 in high‐glucose–induced glomerular mesangial cell. Also, exposed nobiletin to high‐glucose–induced glomerular mesangial cell considerably reduced ECM accumulation through inhibited ECM‐associated protein type 4 collagen and fibronectin expression. Furthermore, nobiletin treatment abolished nuclear factor κB (NF‐κB) pathway activation through signal transducer and activator of transcription 3 (STAT3) inhibition. Overexpression STAT3 reversed the effects of nobiletin on high‐glucose–induced glomerular mesangial cell proliferation, inflammation, ECM accumulation, and NF‐κB pathway activation. Hence, our results suggest that nobiletin play roles in high‐glucose‐induced glomerular mesangial cells through inhibiting inflammation and ECM accumulation, and the STAT3/NF‐κB pathway was involved in the function of nobiletin.
Self‐stigma and the mediating impact of the “why try” effect on depression
Authors: Corrigan Patrick W. , Nieweglowski Katherine , Sayer Janis
Published: November 2018

The “why try” effect, a consequence of self‐stigma, is a sense of behavioral futility that may worsen depression. This study examines the regressive model of self‐stigma, the factor structure of a why try measure, and the pathway through which self‐stigma leads to depression. Data from 291 people self‐identifying with mental illness were collected through an online survey. Participants completed the Why Try Stigma Scale (WTSS) and measures of self‐stigma and depression. Structural equation modeling was used to test the WTSS factor structure and path models. Reducing the WTSS from 12 to 6 items led to good fit. The regressive model of self‐stigma was validated. A good fit was demonstrated for a model in which harm leads to unworthiness, then incapability, and then depression. The regressive model worsens sense of worthiness, which in turn affects personal capability, resulting in increased depression.
Suicide risk and social support in Australian resource sector employees: A cross‐sectional study
Authors: Miller P. , Brook L. , Stomski N.J. , Ditchburn G. , Morrison P.
Published: November 2018

This study examines the association between suicide risk and social support in Australian resource sector employees. We included 150 participants, who completed the Beck Hopelessness Scale and MOS‐Social Support Survey. Data were analyzed using smallest space analysis and multidimensional scalogram analysis. The analysis identified four distinct regions, which were conceptualized as “confiding,” “affection,” “companionship,” and “practical help.” All of these components of social support were associated with hopelessness, which has important clinical implications as hopelessness is related to suicide risk. The results of this study also demonstrated that lower levels of social support, and greater sense of perceived hopelessness tended to lead to Australian resource workers seeking assistance from mental health professionals in the previous year. Attention should turn towards providing interventions that promote social support for employees in Australian resource industry.
Facilitating community connections among people with mental illnesses: Perspectives from grassroots community leaders
Authors: Bromage Billy , Barrenger Stacey L. , Clayton Ashley , Rowe Michael , Williamson Bridgett , Benedict Patricia , Kriegel Liat S.
Published: November 2018

We conducted focus groups comprising 20 grassroots community leaders to identify social and structural elements that affect community engagement among people with serious mental illnesses. Community leaders not affiliated with mental health systems have been mostly left out of the discussions about inclusion and engagement, even though they possess unique information about the places where they live and can be essential partners in making community connections. The findings from the focus groups point to elements that both facilitate and inhibit connections, as well as roles community mental health practitioners may take on, to engage with community leaders and people with mental illness to minimize barriers and foster connections in community settings. Additionally, the focus groups elucidated the interplay between the right to be a member of one's community and a community's responsibility to create a welcoming environment. The current study garnered information regarding the broader needs and implications of community connections, as well as some specific suggestions to enhance community engagement among people with serious mental illness. Hesitation and stigma around engaging individuals with mental illnesses were identified as barriers to inclusion. Further study about how community leaders and groups may be involved in facilitating meaningful community connections is recommended.
microRNA‐186 inhibition of PI3K–AKT pathway via SPP1 inhibits chondrocyte apoptosis in mice with osteoarthritis
Authors: Lin Zeng , Tian Xin‐Yi , Huang Xi‐Xi , He Ling‐Li , Xu Feng
Published: November 2018

Chondrocyte apoptosis has been implicated as a major pathological osteoarthritis (OA) change in humans and experimental animals. We evaluate the ability of miR‐186 on chondrocyte apoptosis and proliferation in OA and elucidate the underlying mechanism concerning the regulation of miR‐186 in OA. Gene expression microarray analysis was performed to screen differentially expressed messenger RNAs (mRNAs) in OA. To validate the effect of miR‐186 on chondrocyte apoptosis, we upregulated or downregulated endogenous miR‐186 using mimics or inhibitors. Next, to better understand the regulatory mechanism for miR‐186 governing SPP1, we suppressed the endogenous expression of SPP1 by small interfering RNA (siRNA) against SPP1 in chondrocytes. We identified SPP1 is highly expressed in OA according to an mRNA microarray data set GSE82107. After intra‐articular injection of papain into mice, the miR‐186 is downregulated while the SPP1 is reciprocal, with dysregulated PI3K–AKT pathway in OA cartilages. Intriguingly, miR‐186 was shown to increase chondrocyte survival, facilitate cell cycle entry in OA chondrocytes, and inhibit chondrocyte apoptosis in vitro by modulation of pro‐ and antiapoptotic factors. The determination of luciferase activity suggested that miR‐186 negatively targets SPP1. Furthermore, we found that the effect of miR‐186 suppression on OA chondrocytes was lost when SPP1 was suppressed by siRNA, suggesting that miR‐186 affected chondrocytes by targeting and depleting SPP1, a regulator of PI3K–AKT pathway. Our findings reveal a novel mechanism by which miR‐186 inhibits chondrocyte apoptosis in OA by interacting with SPP1 and regulating PI3K–AKT pathway. Restoring miR‐186 might be a future therapeutic strategy for OA.
Leukemia therapy by flavonoids: Future and involved mechanisms
Authors: Saraei Raedeh , Marofi Faroogh , Naimi Adel , Talebi Mehdi , Ghaebi Mahnaz , Javan Naser , Salimi Omid , Hassanzadeh Ali
Published: November 2018

Flavonoids are a varied family of phytonutrients (plant chemicals) usually are detected in fruits and vegetables. In this big family, there exist more than 10,000 members that is separated into six chief subtypes: isoflavonols, flavonoenes, flavones, flavonols, anthocyanins, and chalcones. The natural compounds, such as fruits, have visible positive effects in regulating of survival involved signaling pathways that performance as the regulator of cell survival, growth, and proliferation. Researchers have established that commonly consumption up flavonoids decreases incidence and development risk of certain cancers, especially leukemia. Flavonoids have been able to induce apoptosis and stimulate cell cycle arrest in cancer cells via different pathways. Similarly, they have antiangiogenesis and antimetastasis capability, which were shown in wide ranges of cancer cells, particularly, leukemia. It seems that flavonoid because of their widespread approval, evident safety and low rate of side effects, have hopeful anticarcinogenic potential for leukemia therapy. Based on the last decade reports, the most important acting mechanisms of these natural compounds in leukemia cells are stimulating of apoptosis pathways by upregulation of caspase 3, 8, 9 and poly ADP‐ribose polymerase (PARP) and proapoptotic proteins, particularly Bax activation. As well, they can induce cell cycle arrest in target cells not only via increasing of activated levels of p21 and p53 but also by inhibition of cyclins and cyclin‐dependent kinases. Furthermore, attenuation of neclear factor‐κB and signal transducer and activator of transcription 3 activation, suppression of signaling pathway and downregulation of intracellular antiapoptotic proteins are other significant antileukemic function mechanism of flavonoids. Overall, it appears that flavonoids are promising and effective compounds in the field of leukemia therapy. In this review, we tried to accumulate and revise most promising flavonoids and finally declared their major working mechanisms in leukemia cells.
IL-4Rα-expressing CD11c+ cells contribute to driving optimal cellular responses during Schistosoma mansoni infection in mice
Authors: Ndlovu Hlumani , Nono Justin Komguep , Nieuwenhuizen Natalie Eva , Brombacher Frank
Published: November 2018

Development of IL-4 receptor alpha (IL-4Rα)-dependent cellular immunity regulates host protection against acute schistosomiasis. In this study, we investigated the importance of IL-4Rα-expressing CD11c+ cells in driving the development of optimal cellular responses to Schistosoma mansoni infection by using CD11ccreIL-4Rα−/lox BALB/c mice, which lacked IL-4Rα expression on dendritic cells and alveolar macrophages. Abrogation of IL-4Rα expression on CD11c+ cells affected activation of CD4+ T cells, resulting in reduced numbers of effector CD4+ T cells and impaired production of Th1 and Th2 cytokines by CD4+ T cells ex vivo. However, secretion of both type 1 and type 2 Ab isotypes was unchanged in infected CD11c-specific IL-4Rα-deficient mice compared to littermate controls. Together, these data demonstrate that IL-4Rα-expressing CD11c+ cells play an important role in maintaining cellular immunity during schistosomiasis in mice.

Review on IL-4Rα-expressing CD11c+ cell contribution to maintaining optimal cellular immunity during acute schistosomiasis in mice.
Mechanical performance of cementless total knee replacements: It is not all about the maximum loads
Authors: Quevedo González Fernando J. , Lipman Joseph D. , Lo Darrick , De Martino Ivan , Sculco Peter K. , Sculco Thomas P. , Catani Fabio , Wright Timothy M.
Published: November 2018

Finite element (FE) models are frequently used to assess mechanical interactions between orthopedic implants and surrounding bone. However, FE studies are often limited by the small number of bones that are modeled; the use of normal bones that do not reflect the altered bone density distributions that result from osteoarthritis (OA); and the application of simplified load cases usually based on peak forces and without consideration of tibiofemoral kinematics. To overcome these limitations, we undertook an integrated approach to determine the most critical scenario for the interaction between an uncemented tibial component and surrounding proximal tibial bone. A cementless component, based on a modern design, was virtually implanted using computed‐tomography scans from 13 patients with knee OA. FE simulations were performed across a demanding activity, stair ascent, by combining in vivo experimental forces from the literature with tibiofemoral kinematics measured from patients who had received the same design of knee component. The worst conditions for the bone–implant interaction, in terms of micromotion and percentage of interfacial bone mass at risk of failure, did not arise from the maximum applied loads. We also found large variability among bones and tibiofemoral kinematics sets. Our results suggest that future FE studies should not focus solely on peak loads as this approach does not consistently correlate to worst‐case scenarios. Moreover, multiple load cases and multiple bones should be considered to best reflect variations in tibiofemoral kinematics, anatomy, and tissue properties. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:350–357, 2019.
Extremely Compressible Hydrogel via Incorporation of Modified Graphitic Carbon Nitride
Authors: Kumru Baris , Molinari Valerio , Dünnebacke Reinhild , Blank Kerstin G. , Schmidt Bernhard V. K. J.
Published: November 2018

Extremely compressible hydrogels are fabricated in one pot via sulfonic‐acid‐modified graphitic carbon nitride (g‐CN‐AHPA) as a visible light photoinitiator and reinforcer. The hydrogels show unusual compressibility upon applied stress up to 12 MPa, presenting temporary physical deformation, and remain undamaged after stress removal despite their high water content (90 wt%). Cyclic compressibility proves the fatigue resistance of the covalently and electrostatically reinforced system that possesses tissue adhesive properties, shock resistance, cut resistance, and little to no toxicity.
Thermal Approaches to Perpendicular Block Copolymer Microdomains in Thin Films: A Review and Appraisal
Authors: Wang Hyun Suk , Kim Ki Hyun , Bang Joona
Published: November 2018

Block copolymer thin films are highly versatile and accessible materials capable of producing nanofeatures in the size regime of a few to hundreds of nanometers by a simple spin‐coating‐and‐anneal process. Unfortunately, this simple protocol usually leads to parallel microdomains, which limits the applicability of such nanofeatures. A great deal of effort has been put into achieving perpendicular microdomains, but those that incorporate thermal annealing are arguably the most practical and reproducible in the lab and industry. This review discusses the recent ongoing efforts on various thermal approaches to achieving perpendicular microdomains in order to provide the readers with a toolbox to work with.
Ethyl gallate as a novel ERK1/2 inhibitor suppresses patient‐derived esophageal tumor growth
Authors: Liu Feifei , Zu Xueyin , Xie Xiaomeng , Liu Kangdong , Chen Hanyong , Wang Ting , Liu Fangfang , Bode Ann M. , Zheng Yan , Dong Zigang , Kim Dong Joon
Published: November 2018

Ethyl gallate (EG) is a phenolic compound that is isolated from walnut kernels, euphorbia fischeriana, and galla rhois. It has been reported to exhibit antioxidant and anticancer activities. However, EG's effects on esophageal cancer have not yet been investigated. In the present study, we report that EG is a novel ERK1/2 inhibitor that suppresses esophageal cancer growth in vitro and in vivo. EG suppressed anchorage‐dependent and ‐independent esophageal cancer cell growth. The results of in vitro kinase assays and cell‐based assays indicated that EG directly binds to and inhibits ERK1 and ERK2 activities and their downstream signaling. Additionally, EG's inhibitory effect on cell growth is resistant to the re‐activation of ERK1/2. EG increased G2/M phase cell cycle by reducing the expression of cyclin A2 and cyclin B1. The compound also stimulated cellular apoptosis through the activation of caspases 3 and 7 and inhibition of BCL2 expression. Notably, EG inhibited patient‐derived esophageal tumor growth in an in vivo mouse model. These results indicate that EG is an ERK1/2 inhibitor that could be useful for treating esophageal cancer.
D‐HMBC versus LR‐HSQMBC: Which experiment provides theoretically and experimentally the best results?
Authors: Bigler Peter , Furrer Julien
Published: November 2018

The long‐range heteronuclear single quantum multiple bond correlation (LR‐HSQMBC) experiment is the experiment of choice for visualizing heteronuclear long‐range coupling interactions nJCH across 4–6‐bonds and is experimentally superior to the decoupled heteronuclear multiple‐bond correlation (D‐HMBC) experiment. Yet, the exact reasons have not been fully understood and established. On the basis of our recent investigation of the nonrefocused variants LR‐HSQC and HMBC, we have extended a JHH′‐dedicated investigation to the D‐HMBC and LR‐HSQMBC experiments. Unlike the nonrefocused variants, the influence of homonuclear couplings JHH′ on the intensity of long‐range nJCH cross‐peaks is not easily predictable and may be summarized as follows: (a) irrespective of the magnitude and number of JHH′ interactions long‐range nJCH cross‐peaks are more intense in D‐HMBC spectra as long as the evolution delay Δ is not too large, because in contrast to LR‐HSQMBC no JHH′‐caused intensity zeroes will occur. (b) If JHH′ is small and Δ large, the intensity of cross peaks in D‐HMBC spectra may be weakened or may even vanish at Δ = (0.25+0.5k)/JHH′, whereas for the LR‐HSQMBC this unwanted effect occurs at Δ = k + 0.5/JHH′. Consequently, when Δ is adjusted to visualize weak nJCH long‐range correlations, our findings corroborate that there are potentially more cross‐peaks expected to show up in a LR‐HSQMBC spectrum compared with a D‐HMBC spectrum. This has been indeed noticed experimentally, even though the intensity of a many long‐range nJCH cross‐peaks may still be higher in the spectra of the D‐HMBC experiment correspondingly adjusted for detecting weak nJCH correlations.
Three‐dimensional finite element analysis of the pelvic organ prolapse: A parametric biomechanical modeling
Authors: Babayi Masumeh , Azghani Mahmood‐Reza , Hajebrahimi Sakineh , Berghmans Bary
Published: November 2018

Aims

To evaluate the role of soft tissue and ligaments damage and level of pelvic muscles activation versus intra‐abdominal pressure, on pelvic organ prolapse.

Methods

This was a computational modeling based on the finite element analysis. Three pelvic muscles, four pelvic ligaments, and three organs (urethra, vagina, and rectum) were simulated. The model was subjected to total 41 472 analysis cases including three intra‐abdominal pressures, two damaging levels for the ligaments, three damaging levels for the muscles, and four intentional levels of activation for muscles.

Results

Increased intra‐abdominal pressures caused significant statistical increase of the pelvic organ prolapse (P = 0.000) up to 10 mm downward. Ligaments’ defect had no statistically‐significant effect on prolapse of the organs (P = 0.981 for rectum, P = 0.423 for urethra, and P = 0.752 for vagina). Damage in the pelvic floor muscles and low intentional level of activation also deteriorated the prolapse (P = 0.000).

Conclusion

Increase of the intra‐abdominal pressure (IAP) as may be existed during pregnancy or physical activity increased the organ prolapse. Damages of the ligaments caused less effects on the prolapse. Loss of the passive properties of the muscles which is probable after delivery or aging moderately deteriorated the prolapse disorder. However, activation of the pelvic floor muscles prevented the prolapse. Different recruitments of the muscles, specifically the pubococcygeus (PCM), could compensate the possible defects in other tissues. Targeted pelvic floor muscle training (PFMT) could also be effective in older adults due to considerable role of the pelvic muscles’ intentional activation.
Bladder management experiences among people living with neurologic disease: A systematic review and meta‐synthesis of qualitative research
Authors: Welk Blayne , McGarry Patrick , Kennelly Michael , Myers Jeremy ,   For the Neurogenic Bladder Research Group
Published: November 2018

Aim

To systematically review the qualitative literature on neurogenic bladder management to better understand the relevant psychosocial issues.

Methods

We used two reviewers to systematically review EMBASE, CINAHL, and PsycINFO for qualitative studies that included a neurogenic bladder patient population and were relevant to bladder management. We used a meta‐ethnography technique to summarize and synthesize the data.

Results

We found 13 studies that were relevant. When choosing a bladder management technique (three studies), there were two major themes (bladder management decision makers, and characteristics and risks) that impacted the process. For studies evaluating life with a urinary catheter (five about intermittent catheters, and five about indwelling catheters), relevant themes could be arranged into three consecutive periods: First, a changed life (the initial stage of selecting and using a catheter: coping, teaching and technical challenges, and control and independence). Second, learning to live with a catheter (the practical skill and knowledge that goes into using a catheter: knowledge, adjustments, and normalization). Third, a new life (the acceptance and integration of a catheter into a person's life: problems and benefits, unpredictability, travel and social activities, intimacy and relationships, and dealing with negative emotions). Themes were generally consistent across studies.

Conclusions Several important themes were identified from the existing qualitative literature; these can provide insight into how neurogenic bladder patients select a bladder management method, and how physicians can optimize their counseling and the long‐term management of these patients.
A finite element approach for analysis and computational modelling of coupled reaction diffusion models
Authors: Yadav Om Prakash , Jiwari Ram
Published: November 2018

In this article, we establish the existence and uniqueness of solutions to the coupled reaction–diffusion models using Banach fixed point theorem. The Galerkin finite element method is used for the approximation of solutions, and an a priori error estimate is derived for such approximations. A scheme is proposed by combining the Crank–Nicolson and the predictor–corrector methods for the time discretization. Some numerical examples are considered to illustrate the accuracy and efficiency of the proposed scheme. It is found that the scheme is second‐order convergent. In addition, nonuniform grids are used in some cases to enhance the accuracy of the scheme.
The biological embedding of neonatal stress exposure: A conceptual model describing the mechanisms of stress‐induced neurodevelopmental impairment in preterm infants
Authors: Nist Marliese Dion , Harrison Tondi M. , Steward Deborah K.
Published: November 2018

The biological embedding of early life stress exposure may result in life‐long neurodevelopmental impairment in preterm infants. Infants hospitalized in the neonatal intensive care unit are exposed to significant experiential, environmental, and physiologic stressors over the course of their extended hospitalization. Stress exposure during the sensitive period of brain development may alter biological processes, including functioning of the immune system, the autonomic nervous system, and the hypothalamic‐pituitary‐adrenal axis as well as gene expression. These alterations may subsequently affect brain structure and function. Changes to these processes may mediate the relationship between neonatal stress exposure and neurodevelopment in preterm infants and represent potential therapeutic targets to improve long‐term outcomes. The purpose of this paper is to introduce a conceptual model, based on published research, that describes the mechanisms mediating stress exposure and neurodevelopment impairment in preterm infants and to provide the theoretical foundation on which to base future descriptive research, intervention studies, and clinical care.
Reframing the conversation about contralateral prophylactic mastectomy: Preparing women for postsurgical realities
Authors: Bloom Diane L. , Chapman Brittany M. , Wheeler Stephanie B. , McGuire Kandace P. , Lee Clara N. , Weinfurt Kevin , Rosenstein Donald L. , Plichta Jennifer K. , Jacobson Vann Julie C. , Hwang E. Shelley
Published: November 2018

Objective

Women with unilateral, early‐stage breast cancer and low genetic risk are increasingly opting for contralateral prophylactic mastectomy (CPM), a concerning trend because CPM offers few clinical benefits while increasing risks of surgical complications. Few qualitative studies have analyzed factors motivating this irreversible decision. Using qualitative methods, this study sought to understand women's decision making and the impact of CPM on self‐confidence, sense of femininity, sexual intimacy, and peace of mind.

Methods

Women who had CPM within the last 10 years were recruited to participate in the study. We conducted a thematic analysis of the data.

Results

Forty‐five women were interviewed. When making the decision for CPM, most had incomplete knowledge of potential negative outcomes. However, all believed CPM had more benefits than harms and would confer the most peace of mind and the fewest regrets should cancer return. They knew their contralateral breast cancer risk was low but were not persuaded by statistics. They wanted to do everything possible to reduce their risk of another breast cancer, even by a minimal amount, but most reported paying an unexpectedly high price for this small reduction in risk. Nevertheless, 41 of 45 reported that they would make the same decision again.

Conclusions

These findings highlight an opportunity for physicians to reframe the conversation to focus on the patient experience of the tradeoffs of CPM rather than statistical odds of future cancers. Our findings suggest that more data may not dissuade women from CPM but may better prepare them for its outcomes.
A Depolarized Dynamic Light Scattering Method to Calculate Translational and Rotational Diffusion Coefficients of Nanorods
Authors: Nixon‐Luke Reece , Bryant Gary
Published: November 2018

A new analysis of depolarized dynamic light scattering data is presented, which allows the unambiguous determination of rotational and translational diffusions coefficients of nanorods in suspension. By visualizing data scaling, purely translational diffusive motions can be isolated from vertically polarized scattering, allowing the unique determination of rotational diffusion from the depolarized scattering. The method is applied to nanorods with four different aspect ratios, and compared with theoretical predictions. Diffusion coefficients obtained show good agreement with calculations based on the direct measurements of rod length and diameter. Where the theories are shown to be valid, the method allows the measurement of statistically meaningful particle sizes and aspect ratios.