bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between the frequency of number‐puzzle use and baseline cognitive function in a large online sample of adults aged 50 and over
Authors: Brooker Helen , Wesnes Keith A. , Ballard Clive , Hampshire Adam , Aarsland Dag , Khan Zunera , Stenton Rob , Megalogeni Maria , Corbett Anne 
Published: February 2019

ObjectiveEstablishing affordable lifestyle interventions that might preserve cognitive function in the aging population and subsequent generations is a growing area of research focus. Data from the PROTECT study has been utilised to examine whether number‐puzzle use is related to cognitive function in older adults.MethodsData from 19 078 healthy volunteers aged 50 to 93 years old enrolled on the online PROTECT study were evaluated for self‐reported frequency of performing number puzzles. Two cognitive‐test batteries were employed to assess core aspects of cognitive function including reasoning, focussed and sustained attention, information processing, executive function, working memory, and episodic memory. Analysis of covariance was used to establish the differences between the six frequency groups.ResultsHighly statistically significant main effects of the frequency of performing number puzzles were seen on all 14 cognitive measures, with P values of less than 0.0004. Interestingly, participants who reported engaging in number puzzles more than once a day had superior cognitive performance on 10 core measures compared with all other frequency groups, although not all were statistically significant.ConclusionsThis study has identified a close relationship between frequency of number‐puzzle use and the quality of cognitive function in adults aged 50 to 93 years old. In order to determine the value of these findings as a potential intervention, further research should explore the type and difficulty of the number puzzles. These findings further contribute to the growing evidence that engaging in mentally stimulating activities could benefit the brain function of the ageing population.
The hippocampal code for space in Mongolian gerbils
Authors: Mankin Emily A. , Thurley Kay , Chenani Alireza , Haas Olivia V. , Debs Luca , Henke Josephine , Galinato Melissa , Leutgeb Jill K. , Leutgeb Stefan , Leibold Christian 
Published: February 2019

AbstractLarge parts of our knowledge about the physiology of the hippocampus in the intact brain are derived from studies in rats and mice. While many of those findings fit well to the limited data available from humans and primates, there are also marked differences, for example, in hippocampal oscillation frequencies and in the persistence of theta oscillations. To test whether the distinct sensory specializations of the visual and auditory system of primates play a key role in explaining these differences, we recorded basic hippocampal physiological properties in Mongolian gerbils, a rodent species with high visual acuity, and good low‐frequency hearing, similar to humans. We found that gerbils show only minor differences to rats regarding hippocampal place field activity, theta properties (frequency, persistence, phase precession, theta compression), and sharp wave ripple events. The only major difference between rats and gerbils was a considerably higher degree of head direction selectivity of gerbil place fields, which may be explained by their visual system being able to better resolve distant cues. Thus, differences in sensory specializations between rodent species only affect hippocampal circuit dynamics to a minor extent, which implies that differences to other mammalian lineages, such as bats and primates, cannot be solely explained by specialization in the auditory or visual system.
[2.2.2.2](2,7)‐1‐Bromonaphthalenophane from a Desymmetrized Building Block Bearing Electrophilic and Masked Nucleophilic Functionalities
Authors: Cai Guangke , Chatterjee Shreyam , Hisaki Ichiro , Tobe Yoshito 
Published: February 2019

AbstractIn search of 2,7‐ethylene‐bridged naphthalenophanes with desymmetrized naphthalene cores as inherently chiral cyclophanes, nucleophilic substitution of 1‐bromo‐7‐(bromomethyl)‐2‐[(trimethylsilyl)methyl]naphthalene, a desymmetrized building block bearing an electrophilic group (CH2Br) and a masked nucleophilic functionality (CH2TMS) which can be activated by fluoride anion, was examined. As a result, in contrast to the case of parent naphthalenophanes wherein the smallest [2.2]naphthalenophane was obtained as the major product, only [2.2.2.2](2,7)‐1‐bromonaphthalenophane was obtained albeit in low yields, whereas the corresponding [2.2]‐ or [2.2.2]naphthalenophanes were not obtained. Though the [2.2.2.2]‐1‐bromonaphthalenophane can adopt four idealized geometries of different symmetry, among which three are inherently chiral, theoretical calculations predict that three conformers have almost equal energy and may equilibrate in solution. The X‐ray crystallographic study shows that it adopts a C2 conformation with anti,anti,anti orientation of the C−Br bonds at least as a major component in crystal.
MicroRNA‐365 promotes the contractile phenotype of venous smooth muscle cells and inhibits neointimal formation in rat vein grafts
Authors: Cao Bo‐Jun , Zhu Lei , Wang Xiao‐Wen , Zou Rong‐Jiang , Lu Zhi‐Qian 
Published: February 2019

AbstractThe high rate of autologous vein graft failure caused by neointimal hyperplasia remains an unresolved issue in the field of cardiovascular surgery; therefore, it is important to explore new methods for protecting against neointimal hyperplasia. MicroRNA‐365 has been reported to inhibit the proliferation of vascular smooth muscle cells (SMCs). This study aimed to test whether adenovirus‐mediated miR‐365 was able to attenuate neointimal formation in rat vein grafts. We found that miR‐365 expression was substantially reduced in vein grafts following engraftment. In vitro, overexpression of miR‐365 promoted smooth muscle‐specific gene expression and inhibited venous SMC proliferation and migration. Consistent with this, overexpression of miR‐365 in a rat vein graft model significantly reduced grafting‐induced neointimal formation and effectively improved the hemodynamics of the vein grafts. Mechanistically, we identified that cyclin D1 as a potential downstream target of miR‐365 in vein grafts. Specially, to increase the efficiency of miR‐365 gene transfection, a 30% poloxamer F‐127 gel containing 0.25% trypsin was mixed with adenovirus and spread around the vein grafts to increase the adenovirus contact time and penetration. We showed that adenovirus‐mediated miR‐365 attenuated venous SMC proliferation and migration in vitro and effectively inhibited neointimal formation in rat vein grafts. Restoring expression of miR‐365 is a potential therapeutic approach for the treatment of vein graft failure. © 2019 IUBMB Life, 2019
Effect of chronic exposure to inorganic arsenic on intestinal cells
Authors: Chiocchetti Gabriela M. , Vélez Dinoraz , Devesa Vicenta 
Published: February 2019

AbstractChronic exposure to inorganic arsenic (As)—As(III) + As(V)—is associated with type 2 diabetes, vascular diseases and various types of cancer. Although the oral route is the main way of exposure to inorganic As, the adverse gastrointestinal effects produced by chronic exposure are not well documented. The aim of the present study is to evaluate the effect of chronic exposure to As(III) on the intestinal epithelium. For this purpose, NCM460 cells, non‐transformed epithelial cells from the human colon, were exposed to As(III) (0.01‐0.2 mg/L) for 6 months and monitored for acquisition of a tumor‐like phenotype. Secretion of matrix metalloproteinases, histone modifications (H3 acetylation), hyperproliferation capacity, formation of floating spheres, anchorage‐independent growth, release of cytokine interleukin‐8 and expression of relevant genes in colon tumorigenesis were assessed. The results show a maintained proinflammatory response from the beginning, with an increase in interleukin‐8 secretion (≤570%). Downregulation of CDX1 and CDX2 was also observed. After 14 weeks of exposure, cells presented marked increases in matrix metalloproteinase‐2 secretion and histone modifications. As(III)‐treated cells were hyperproliferative, grew in low‐serum media and were able to form free‐floating spheres. Overall, these data suggest that exposure of human colon epithelial cells to As(III) facilitates acquisition of transformed cell characteristics.
Improved chondrogenic response of mesenchymal stem cells to a polyethersulfone/polyaniline blended nanofibrous scaffold
Authors: Hosseini Fatemeh Sadat , Saburi Ehsan , Enderami Seyed Ehsan , Ardeshirylajimi Abdolreza , Bagherabad Matineh Barati , Marzouni Hadi Zare , Ghoraeian Pegah , Soleimanifar Fatemeh 
Published: February 2019

AbstractOwing to the fact that the cartilage tissue is not able to repair itself, the treatment of the joint damages is very difficult by current methods. Induction of tissue repair requires suitable cell and extracellular matrix. Providing these two parts can only be done using tissue engineering. In the present study, polyethersulfone (PES) and polyaniline (PANI) blend was electrospined for nanofibrous scaffold fabrication. Mesenchymal stem cells were isolated from human adipose tissue (AT‐MSCs), and after characterization cultured on the PES‐PANI scaffold and culture plate. Electron microscopic and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) colorimetric assays were used for biocompatibility evaluation of the scaffold and the chondrogenic differentiation potential of AT‐MSCs were investigated by staining of proteoglycans and gene and protein expression evaluation. Alcian blue staining, real‐time reverse‐transcriptase polymerase chain reaction and Western blot results showed that chondrogenic differentiation potential of AT‐MSCs was significantly increased when grown on PES‐PANI nanofibers and was compared to the one grown on a culture plate. According to the results, PES‐PANI has a promising potential to be used as a biomedical implant in patients with joints lesion, such as arthritis and osteoarthritis.
Downregulation of miroRNA‐141 mediates acquired resistance to trastuzumab and is associated with poor outcome in breast cancer by upregulating the expression of ERBB4
Authors: Han Guodong , Qiu Ni , Luo Kai , Liang Hongling , Li Hongsheng 
Published: February 2019

AbstractBackgroundmicroRNAs are involved in the control of cell growth and apoptosis; they also play an essential role in resistance towards trastuzumab, in breast cancer. The objective of this study was to identify differentially expressed microRNA(s) and explore its therapeutic role in treatment of the disease.MethodsReal‐time polymerase chain reaction (RT‐PCR) was performed to identify the virtual microRNA (miRNA) involved in breast cancer cells resistant to trastuzumab. RT‐PCR and Western blot analysis were carried out to study the effects of microRNA‐141 (miR‐141) on ERBB2, ERBB4 and AKT production. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenylterazolium bromide assay and flow cytometry analysis was carried out to examine the effect of miR‐141 on cell proliferation and apoptosis via ERBB4.ResultAccording to RT‐PCR results, only miR‐141 and miR‐375 among miR‐141, miR‐375, miR‐16, miR‐155, miR‐217 and miR‐205 were downregulated in trastuzumab‐resistant cells. Trastuzumab‐resistant cells displayed higher levels of ERBB4 and p‐AKT as well as showing a higher growth rate and a lower apoptosis rate. Online software programs were used, which identified ERBB4 as a gene targeted by miR‐141 with a highly conserved binding site for miR‐141 located within the ERBB4 3′‐untranslated region. In trastuzumab‐resistant cells, miR‐141 and shERBB4 reduced ERBB4 and p‐AKT levels; ERBB2 and total AKT levels in miR‐141 and shERBB4 groups showed no significant difference. Anti‐miR‐141 was upregulated ERBB4 and p‐AKT levels in parental cell and had no obvious effect on ERBB2 and total AKT levels. Finally, miR‐141 upregulated viability of the cells, which was restored by shERBB4, miR‐141 and shERBB4 inhibited proliferation, and enhanced apoptosis of trastuzumab‐resistant cells. miR‐141 inhibitor caused an evident increase in proliferation and an obvious decrease in apoptosis of parental cells.ConclusionKnockdown of miR‐141 causes overexpression of ERBB4, which is involved in trastuzumab resistance in breast cancer cells. This study has implications that miR‐141 as well as its target, ERBB4, as a potential target for treating trastuzumab‐resistant breast cancers.
Myricetin relieves LPS‐induced mastitis by inhibiting inflammatory response and repairing the blood–milk barrier
Authors: Kan Xingchi , Liu Bingrun , Guo Wenjin , Wei Libin , Lin Yuanqing , Guo Yingcheng , Gong Qian , Li Yanwei , Xu Dianwen , Cao Yu , Huang Bingxu , Dong Aiwen , Ma He , Fu Shoupeng , Liu Juxiong 
Published: February 2019

AbstractMastitis, an inflammation of mammary gland, is a serious disease that affects the health of dairy cows around the world. Myricetin, a flavonoid from Bayberry, has been reported to suppress various inflammatory response. The aim of this study was to evaluate the effect of myricetin on lipopolysaccharide (LPS)‐induced in vivo and in vitro mastitis model and clarify the underlying mechanism. In vivo experiments, myricetin attenuated the severity of inflammatory lesion and neutrophil infiltration. Moreover, myricetin pretreatment induced a significant decrease in the activity of myeloperoxidase (MPO) and the production of TNF‐α, IL‐6, and IL‐1β triggered by LPS. Myricetin pretreatment could also increase the integrity of the blood–milk barrier and upregulate the tight junction proteins in LPS‐induced mice mastitis. In vitro, myricetin inhibited LPS‐induced inflammatory response in mice mammary epithelial cells (mMECs). In the further mechanism studies, we found that the anti‐inflammatory effect of myricetin was mediated by inhibiting LPS‐induced phosphorylation of AKT, IKK‐α, IκB‐α, and P65 in vivo and in vitro. Collectively, these data suggested that myricetin effectively ameliorated the inflammatory response by inhibiting the AKT/IKK/NF‐κB signaling pathway and repairing the integrity of blood–milk barrier in LPS‐induced mice mastitis.
The effect of anodal/cathodal biphasic electrical stimulation on insulin release
Authors: Siegel David , Baca Serapio M. , Thompson David C. , Huntsman Molly M. , Mower Morton M. , Ross David 
Published: February 2019

AbstractWe studied the effects of electrical stimulation on insulin release from rat insulinoma (INS‐1) cells. The anodal/cathodal biphasic stimulation (ACBPS) electrical waveform resulted in a voltage‐ and stimulation duration‐dependent increase in insulin release. ACBPS elicited insulin release both in the presence and absence of glucose. Basal and ACBPS‐induced insulin secretion could be inhibited by mitochondrial poisons and calcium channel blockers, indicating that insulin release was dependent on adenosine triphosphate (ATP) and the influx of calcium. ACBPS parameters that released insulin caused no detectable plasma membrane damage or cytotoxicity, although temporary morphological changes could be observed immediately after ACBPS. ACBPS did not alter the plasma membrane transmembrane potential but did cause pronounced uptake of MitoTracker Red into the mitochondrial membrane, indicating an increased mitochondrial membrane potential. While the ATP:ADP ratio after ACBPS did not change, the guanosine triphosphate (GTP) levels increased and increased GTP levels have previously been associated with insulin release in INS‐1 cells. These results provide evidence that ACBPS can have significant biological effects on cells. In the case of INS‐1 cells, ACBPS promotes insulin release without causing cytotoxicity.
Anti‐inflammatory effects of resolvins in diabetic nephropathy: Mechanistic pathways
Authors: Yaribeygi Habib , Atkin Stephen L. , Simental‐Mendía Luis E. , Barreto George E. , Sahebkar Amirhossein 
Published: February 2019

AbstractThe incidence of diabetes mellitus is growing rapidly. The exact pathophysiology of diabetes is unclear, but there is increasing evidence of the role of the inflammatory response in both developing diabetes as well as its complications. Resolvins are naturally occurring polyunsaturated fatty acids that are found in fish oil and sea food that have been shown to possess anti‐inflammatory actions in several tissues including the kidneys. The pathways by which resolvins exert this anti‐inflammatory effect are unclear. In this review we discuss the evidence showing that resolvins can suppress inflammatory responses via at least five molecular mechanisms through inhibition of the nucleotide‐binding oligomerization domain protein 3 inflammasome, inhibition of nuclear factor κB molecular pathways, improvement of oxidative stress, modulation of nitric oxide synthesis/release and prevention of local and systemic leukocytosis. Complete understanding of these molecular pathways is important as this may lead to the development of new effective therapeutic strategies for diabetes and diabetic nephropathy.
4β‐Hydroxycholesterol as an Endogenous Biomarker for CYP3A Activity: Literature Review and Critical Evaluation
Authors: Penzak Scott R. , Rojas‐Fernandez Carlos 
Published: February 2019

AbstractA number of cytochrome P450 (CYP)3A phenotyping probes have been used to characterize the drug interaction potential of new molecular entities; of these, midazolam has emerged as the gold standard. Recently, plasma 4β‐hydroxycholesterol (4β‐OHC), the metabolite of CYP3A‐mediated cholesterol metabolism, has been championed as an endogenous biomarker for CYP3A, particularly during chronic conditions where CYP3A activity is altered by disease and in long‐term treatment studies where midazolam administration is not optimal. Multiple studies in humans have shown that 4β‐OHC can qualitatively differentiate among weak, moderate, and potent CYP3A induction when an inducer, typically rifampin, is administered for up to 2 weeks. Conversely, longer durations of CYP3A inhibitor administration (≥1 month) appear to be necessary to differentiate among weak, moderate, and potent CYP3A inhibitors. A number of studies have reported statistically significant linear relationships between 4β‐OHC plasma concentrations (and 4β‐OHC:cholesterol ratios) and midazolam clearance. However, sufficiently powered studies assessing the ability of 4β‐OHC or 4β‐OHC:cholesterol ratios to measure CYP3A activity (ie, predictive performance) have not been conducted to date. Additional limitations associated with 4β‐OHC phenotyping include inability to detect acute changes in CYP3A activity, uncertainty with regard to its intestinal formation, ambiguity surrounding the role of CYP3A5 in its metabolism, and lack of clarity regarding the role of transporters in its disposition. As such, the data do not support the use of 4β‐OHC or 4β‐OHC:cholesterol ratios as an endogenous biomarker for CYP3A activity.
A case of gastric carcinoma with lymphoid stroma diagnosed by an endoscopic ultrasound‐guided fine‐needle biopsy
Authors: Tanabe Hiroki , Ando Katsuyoshi , Sutoh Daisuke , Ohta Katsuhisa , Ohdaira Hironori , Suzuki Yutaka , Fujiya Mikihiro , Okumura Toshikatsu 
Published: February 2019

AbstractEndoscopic ultrasound‐guided sampling is indicated to achieve an accurate diagnosis of subepithelial lesions of the stomach when a standard biopsy fails. Gastric carcinoma with lymphoid stroma (GCLS) is located under the epithelial layer with dense lymphocytic infiltration, making a pathological diagnosis by a biopsy difficult. We herein report a case of the pathological diagnosis of GCLS using an endoscopic ultrasound‐guided fine‐needle biopsy. The patient underwent distal gastrectomy and was diagnosed with Epstein‐Barr virus‐negative cancer.
ART adherence and viral suppression are high among most non‐pregnant individuals with early‐stage, asymptomatic HIV infection: an observational study from Uganda and South Africa
Authors: Haberer Jessica E , Bwana Bosco M , Orrell Catherine , Asiimwe Stephen , Amanyire Gideon , Musinguzi Nicholas , Siedner Mark J , Matthews Lynn T , Tsai Alexander C , Katz Ingrid T , Bell Kathleen , Kembabazi Annet , Mugisha Stephen , Kibirige Victoria , Cross Anna , Kelly Nicola , Hedt‐Gauthier Bethany , Bangsberg David R 
Published: February 2019

AbstractIntroductionThe success of universal antiretroviral therapy (ART) access and aspirations for an AIDS‐free generation depend on high adherence in individuals initiating ART during early‐stage HIV infection; however, adherence may be difficult in the absence of illness and associated support.MethodsFrom March 2015 to October 2017, we prospectively observed three groups initiating ART in routine care in Uganda and South Africa: men and non‐pregnant women with early‐stage HIV infection (CD4 > 350 cells/μL), pregnant women with early‐stage HIV infection and men and non‐pregnant women with late‐stage HIV infection (CD4 < 200 cells/μL). Socio‐behavioural questionnaires were administered and viral loads were performed at 0, 6 and 12 months. Adherence was monitored electronically.ResultsAdherence data were available for 869 participants: 322 (37%) early/non‐pregnant, 199 (23%) early/pregnant and 348 (40%) late/non‐pregnant participants. In Uganda, median adherence was 89% (interquartile range 74 to 96) and viral suppression was 90% at 12 months; neither differed among groups (p > 0.72). In South Africa, median adherence was higher in early/non‐pregnant versus early/pregnant or late/non‐pregnant participants (76%, 37%, 52%; p < 0.001), with similar trends in viral suppression (86%, 51%, 79%; p < 0.001). Among early/non‐pregnant individuals in Uganda, adherence was higher with increasing age and lower with structural barriers; whereas in South Africa, adherence was higher with regular income, higher perceived stigma and use of other medications, but lower with maladaptive coping and cigarette smoking.DiscussionART adherence among non‐pregnant individuals with early‐stage infection is as high or higher than with late‐stage initiation, supporting universal access to ART. Challenges remain for some pregnant women and individuals with late‐stage infection in South Africa and highlight the need for differentiated care delivery.