bluuebunny/crossref_metadata_2025_split huggingface dataset:
HPV self‐sampling acceptability and preferences among women living with HIV in Botswana
Authors: Kohler Racquel E. , Elliott Tamara , Monare Barati , Moshashane Neo , Ramontshonyana Kehumile , Chatterjee Pritha , Ramogola‐Masire Doreen , Morroni Chelsea 
Published: September 2019

AbstractObjectiveTo assess the acceptability and preferences of HPV screening with self‐sampling and mobile phone results delivery among women living with HIV (WLWH) in Botswana, as an alternative to traditional speculum screening.MethodsWLWH aged 25 years or older attending an infectious disease clinic in Gaborone were enrolled in a cross‐sectional study between March and April 2017. Women self‐sampled with a flocked swab, had a speculum exam, and completed an interviewer‐administered questionnaire about screening acceptability, experiences, and preferences.ResultsOf the 104 WLWH recruited, 98 (94%) had a history of traditional screening. Over 90% agreed self‐sampling was easy and comfortable. Ninety‐five percent were willing to self‐sample again; however, only 19% preferred self‐sampling over speculum exam for future screening. Preferences differed by education and residence with self‐sampling being considered more convenient, easier, less embarrassing, and less painful. Speculum exams were preferred because of trust in providers’ skills and women's low self‐efficacy to sample correctly. Almost half (47%) preferred to receive results via mobile phone call. Knowledge of cervical cancer did not affect preferences.ConclusionHPV self‐sampling is acceptable among WLWH in Botswana; however, preferences vary. Although self‐sampling is an important alternative to traditional speculum screening, education and support will be critical to address women's low self‐efficacy to self‐sample correctly.
The critical role of calcineurin/NFAT (C/N) pathways and effective antitumor prospect for colorectal cancers
Authors: Gang Wang , Yu‐Zhu Wang , Yang Yu , Feng Shi , Xing‐Li Fu , Heng Zhang 
Published: September 2019

AbstractTranscription factors (TFs) like a nuclear factor of activated T‐cells (NFAT) and its controller calcineurin are highly expressed in primary intestinal epithelial cells (IECs) due to delamination, damage by tumor‐associated flora and selective activation in the intestinal tract tumor are crucial in the progression and growth of colorectal cancer (CRC). This study sought to summarize the current findings concerning the dysregulated calcineurin/NFAT (C/N) signaling involved in CRC initiation and progression. These signalings include proliferation, T‐cell functions, and glycolysis with high lactate production that remodels the acidosis, which genes in tumor cells provide an evolutionary advantage, or even increased their attack phenotype. Moreover, the relationship between C/N and gut microbiome in CRC, especially role of NFAT and toll‐like receptor signaling in regulating intestinal microbiota are also discussed. Furthermore, this review will discuss the proteins and genes relating to C/N induced acidosis in CRC, which includes ASIC2 regulated C/N1 and TFs associated with the glycolytic by‐product that affect T‐cell functions and CRC cell growth. It is revealed that calcineurin or NFAT targeting to antitumor, selective calcineurin inhibition or targets in NFAT signaling may be useful for clinical treatment of CRC. This can further aid in the identification of specific targets via cancer patient‐personalized approach. Future studies should be focused on targeting to C/N or TLR signaling by the combination of therapeutic agents to regulate T‐cell functions and gut microbiome for activating potent anticancer property with the prospect of potentiating the antitumor therapy for CRC.
miR‐125a‐3p suppresses the growth and progression of papillary thyroid carcinoma cell by targeting MMP11
Authors: Song Min , Wang Na , Li Zhen , Zhang Yanfang , Zheng Yingying , Yi Pengfei , Chen Jing 
Published: September 2019

AbstractThe dysregulation of miR‐125a‐3p has been observed in multiple tumor types. Nevertheless, the function of miR‐125a‐3p in papillary thyroid carcinoma (PTC) is yet to be explored. Herein, we find that miR‐125a‐3p is markedly downregulated in PTC tissues, and its level is inversely related to the histological grade of PTC. Upregulation of miR‐125a‐3p suppresses the pulmonary metastatic ability as well as the tumor growth of PTC cell in vivo. Consistently, the colony formation ability and other metastasis‐related traits of PTC cell are inhibited by miR‐125a‐3p transfection in vitro. In addition, we identify that matrix metalloprotease 11 (MMP11) is the direct target gene of miR‐125a‐3p, and that miR‐125a‐3p inhibits cell viability, migration, and invasiveness of PTC cell by reducing MMP11 expression in vitro. Together, these data testify that the miR‐125a‐3p/MMP11 axis plays vital roles in the growth and progression of human PTC cells.
ShRNA‐mediated matrix metalloproteinase‐2 gene silencing protects normal cells and sensitizes cancer cells against ionizing‐radiation induced damage
Authors: Shailender Gugalavath , Patanla Kiranmayi , Malla Rama Rao 
Published: September 2019

AbstractIntroductionIonizing radiation (IR) affects healthy tissues during the treatment of cancer radiation therapy and other nuclear and radiological accidents. Some natural compounds showed nonspecific radioprotective activity with severe side effects. The present study is aimed to develop potent and specific radioprotective short hairpin RNA (shRNA), which selectively protects normal cells from IR by specifically targeting matrix metalloproteinases (MMP‐2).ResultsIR reduced the viability of human normal dermal fibroblasts (HDFs) in a dose‐response manner. It enhanced the expression of MMP‐2 at 10 Gy. Plasmid MMP‐2shRNA (pMMP‐2) reduced the IR (10 Gy) induced cytotoxicity analyzed by lactate dehydrogenase (LDH) assay, normalized IR induced cellular and morphological changes with enhanced the clonogenicity in 48 hours at 2 µg/mL. It reduced the ROS generation, released HDFs from G2/M arrest and rescued from apoptosis analyzed by DCFDA dye, cell cycle analysis by PI stain and annexin V assay, respectively. pMMP‐2 also modulates the expression of EGFR and reduced IR induced expression of DNA damage response protein, ATM and increased the expression of repair proteins, KU70/KU80, and RAD51. In addition, decreased the expression of cell cycle regulatory proteins cyclin‐dependent kinases (CDK1) and Cyclin B as well as proapoptotic proteins BAX, caspase‐3, and Cytochrome‐C and increased the expression of survival protein, Bcl‐2. In contrary pMMP‐2 decreased the LDH activity, survival fraction and blocked G2/M phase of cell cycle and increased apoptosis in MCF‐7 cells. In addition, decreased the expression of EGFR, proapoptotic BAX and DNA repair proteins ATM, KU70/80 and RAD51, increased expression of cyclinB as well as CDK1.ConclusionResults conclude that pMMP‐2 protected HDFs from IR and sensitized the MCF‐7 cells. Therefore, pMMP‐2 can be employed for better treatment of radiation accidents and during the treatment of radiotherapy.
Tackling endothelium remodeling in cardiovascular disease
Authors: Guľašová Zuzana , Guerreiro Susana G. , Link Rene , Soares Raquel , Tomečková Vladimíra 
Published: September 2019

AbstractEndothelial dysfunction is considered an early marker of atherosclerosis. Herein, we address the molecular mechanisms affecting endothelium remodeling in disease. Vascular calcification is highly prevalent in patients with ischemic cardiovascular disease, cerebrovascular disorder, and renal failure, being a common feature in aging, diabetes, dyslipidemia, abnormal valve biomechanics, end‐stage renal disease and atherosclerosis, a major cause of mortality and morbidity. Oxidative stress promotes calcification of vascular smooth muscle cells (SMC) by increasing osteogenic transcription factors expression and activity in atherosclerotic plaques. Various markers of osteogenic differentiation are expressed by SMC in calcified atherosclerotic lesions. Interestingly, decreased levels of some bone factors and microRNAs accelerate vascular calcification and injured tissue regeneration. Another key player in endothelial remodeling is amino acids metabolism. Branched‐chain amino acids are catabolized in several nonhepatic tissues including cardiac muscle. Immune activation and inflammation in cardiovascular disease patients associate with higher phenylalanine/tyrosine ratios. Understanding the whole process that underlies endothelium dysfunction is of paramount importance for the development of new therapeutic approaches.
Accumulation of sphingomyelin in Niemann‐Pick disease type C cells disrupts Rab9‐dependent vesicular trafficking of cholesterol
Authors: Wanikawa Masahiro , Nakamura Hiroyuki , Emori Shunsuke , Hashimoto Naohiro , Murayama Toshihiko 
Published: September 2019

AbstractNiemann‐Pick disease type C (NPC) is a genetic disorder in which patient cells have endosomal/lysosomal accumulation of cholesterol and sphingolipids. However, the relationship between sphingolipids and cholesterol accumulation in NPC cells has not been established. Here, we investigated the role of sphingomyelin (SM) on the accumulation of cholesterol in NPC cells. Reduction of SM by inhibition of the ceramide transfer protein CERT decreased the cholesterol accumulation in NPC cells. The accumulation of SM in NPC cells inhibited the transport of cholesterol to the endoplasmic reticulum. Overexpression of Rab9 in NPC cells reduced the cholesterol accumulation, which was recovered by treatment with SM. In NPC cells that overexpressed a Rab9 constitutively active mutant, SM treatment did not lead to the cholesterol accumulation. These results indicate that SM negatively regulates the Rab9‐dependent vesicular trafficking of cholesterol, and a reduction in SM levels in NPC cells recovers the Rab9‐dependent vesicular trafficking defect.
Network‐based analysis reveals novel gene signatures in the peripheral blood of patients with sporadic nonsyndromic thoracic aortic aneurysm
Authors: Xu Heng , Chen Shanshan , Zhang Hao , Zou Yanqiang , Zhao Jing , Yu Jizhang , Le Sheng , Cui Jikai , Jiang Lang , Wu Jie , Xia Jiahong 
Published: September 2019

AbstractThoracic aortic aneurysm (TAA), a serious cardiovascular disease that causes morbidity and mortality worldwide. At present, few biomarkers can accurately diagnose the appearance of TAA before dissection or rupture. Our research has the intention to investigate the developing applicable biomarkers for TAA promising clinically diagnostic biomarkers or probable regulatory targets for TAA. In our research, we built correlation networks utilizing the expression profile of peripheral blood mononuclear cell obtained from a public microarray data set (GSE9106). Furthermore, we chose the turquoise module, which has the strongest significance with TAA and was further analyzed. Fourteen genes that overlapped with differentially expressed proteins in the medial aortic layer were obtained. Subsequently, we verified the results applying quantitative polymerase chain reaction (Q‐PCR) to our clinical specimen. In general, the Q‐PCR results coincide with the majority of the expression profile. Fascinatingly, a notable change occurred in CLU, DES, MYH10, and FBLN5. In summary, using weighted gene coexpression analysis, our study indicates that CLU, DES, MYH10, and FBLN5 were identified and validated to be related to TAA and might be candidate biomarkers or therapeutic targets for TAA.
Dysbiotic 1‐carbon metabolism in cardiac muscle remodeling
Authors: George Akash K. , Singh Mahavir , Pushpakumar S. , Homme Rubens P. , Hardin Shanna J. , Tyagi Suresh C. 
Published: September 2019

AbstractUnless there is a genetic defect/mutation/deletion in a gene, the causation of a given disease is chronic dysregulation of gut metabolism. Most of the time, if not always, starts within the gut; that is what we eat. Recent research shows that the imbalance between good versus bad microbial population, especially in the gut, causes systemic diseases. Thus, an appropriate balance of the gut microbiota (eubiosis over dysbiosis) needs to be maintained for normal health (Veeranki and Tyagi, 2017, Journal of Cellular Physiology, 232, 2929–2930). However, during various diseases such as metabolic syndrome, inflammatory bowel disease, diabetes, obesity, and hypertension the dysbiotic gut environment tends to prevail. Our research focuses on homocysteine (Hcy) metabolism that occupies a center‐stage in many biochemically relevant epigenetic mechanisms. For example, dysbiotic bacteria methylate promoters to inhibit gene activities. Interestingly, the product of the 1‐carbon metabolism is Hcy, unequivocally. Emerging studies show that host resistance to various antibiotics occurs due to inverton promoter inhibition, presumably because of promoter methylation. This results from modification of host promoters by bacterial products leading to loss of host's ability to drug compatibility and system sensitivity. In this study, we focus on the role of high methionine diet (HMD), an ingredient rich in red meat and measure the effects of a probiotic on cardiac muscle remodeling and its functions. We employed wild type (WT) and cystathionine beta‐synthase heterozygote knockout (CBS+/−) mice with and without HMD and with and without a probiotic; PB (Lactobacillus) in drinking water for 16 weeks. Results indicate that matrix metalloproteinase‐2 (MMP‐2) activity was robust in CBS+/− fed with HMD and that it was successfully attenuated by the PB treatment. Cardiomyocyte contractility and ECHO data revealed mitigation of the cardiac dysfunction in CBS+/− + HMD mice treated with PB. In conclusion, our data suggest that probiotics can potentially reverse the Hcy‐meditated cardiac dysfunction.
Physiologically Based Pharmacokinetic Models to Predict Maternal Pharmacokinetics and Fetal Exposure to Emtricitabine and Acyclovir
Authors: Liu Xiaomei I. , Momper Jeremiah D. , Rakhmanina Natella , van den Anker John N. , Green Dionna J. , Burckart Gilbert J. , Best Brookie M. , Mirochnick Mark , Capparelli Edmund V. , Dallmann André 
Published: September 2019

AbstractPregnancy is associated with physiological changes that may impact drug pharmacokinetics (PK). The goals of this study were to build maternal‐fetal physiologically based pharmacokinetic (PBPK) models for acyclovir and emtricitabine, 2 anti(retro)viral drugs with active renal net secretion, and to (1) evaluate the predicted maternal PK at different stages of pregnancy; (2) predict the changes in PK target parameters following the current dosing regimen of these drugs throughout pregnancy; (3) evaluate the predicted concentrations of these drugs in the umbilical vein at delivery; (4) compare the model performance for predicting maternal PK of emtricitabine in the third trimester with that of previously published PBPK models; and (5) compare different previously published approaches for estimating the placental permeability of these 2 drugs. Results showed that the pregnancy PBPK model for acyclovir predicted all maternal concentrations within a 2‐fold error range, whereas the model for emtricitabine predicted 79% of the maternal concentrations values within that range. Extrapolation of these models to earlier stages of pregnancy indicated that the change in the median PK target parameters remained well above the target threshold. Concentrations of acyclovir and emtricitabine in the umbilical vein were overall adequately predicted. The comparison of different emtricitabine PBPK models suggested an overall similar predictive performance in the third trimester, but the comparison of different approaches for estimating placental drug permeability revealed large differences. These models can enhance the understanding of the PK behavior of renally excreted drugs, which may ultimately inform pharmacotherapeutic decision making in pregnant women and their fetuses.
Population Pharmacokinetics of Talazoparib in Patients With Advanced Cancer
Authors: Yu Yanke , Durairaj Chandrasekar , Shi Haihong , Wang Diane D. 
Published: September 2019

AbstractPoly(ADP‐ribose) polymerase (PARP) inhibitors have been developed to treat cancers associated with somatic BRCA mutations and germline genetic aberrations involved in the DNA damage response. The efficacy, tolerability, and pharmacokinetic/pharmacodynamic (PK/PD) profile of talazoparib, a potent small‐molecule PARP inhibitor, was established in 4 clinical studies in cancer patients (2 phase 1 studies PRP‐001 and PRP‐002, the phase 2 ABRAZO trial, and the phase 3 EMBRACA trial). The current study aimed to describe the population PK of talazoparib and identify covariates that affect talazoparib PK in patients with advanced cancers using pooled data from these 4 studies. Talazoparib PK was well characterized by a 2‐compartment model with first‐order absorption and absorption lag time. Based on covariate analysis, no dose adjustment for talazoparib is required based on a patient's age, sex, baseline body weight, Asian race, the presence of mild renal or hepatic impairment, or use of acid‐reducing agents. A reduced 0.75‐mg daily dose is recommended for patients taking a potent P‐glycoprotein inhibitor and those with moderate renal impairment. Insufficient data were available to establish dosing recommendations for patients with severe renal and moderate or severe hepatic impairment. The PK of a single 1‐mg talazoparib capsule is comparable with 4 0.25‐mg capsules. Talazoparib can be taken with or without food. These data provide support for dosing recommendations and labeling information for talazoparib.
The interactions of an algae–fungi symbiotic system influence nutrient removal from synthetic wastewater
Authors: Jiang Mengqi , Li Huimin , Zhou Yanping , Zhang Jibiao 
Published: September 2019

AbstractBACKGROUNDAlgae–bacteria symbiotic system has attracted much attention in the fields of nutrients removal from wastewater. Fungi has also been demonstrated to promote the cultivation of microalgae. However, capability and mechanism of algae–fungi symbiotic system for nutrient removal remains unclear.RESULTSThis study assessed the removal efficiencies of an algae–fungi symbiotic system of Chlorella variabilis NC64A and Ganoderma lucidum for chemical oxygen demand (CODcr), total nitrogen (TN), total phosphorus (TP), and ammonia nitrogen (NH3‐N) from synthetic wastewater. The highest levels of dry cell weight (DCW), chlorophyll‐a (Chl‐a), and enzyme activity in the algae–fungi symbiotic system were obtained at an algae–fungi mass ratio of 1:3. At this ratio, the system on the tenth day removed 75.5%, 76.7%, 74.7%, and 90.0% of CODcr, TN, TP, and NH3‐N, respectively. Maximum values of both DCW (0.89 g L−1) and Chl‐a (2885 mg L−1) were achieved on day 6. Chlorella variabilis NC64A and G. lucidum coexisted as an algae–fungi consortium, in which G. lucidum exerted pressure on C. variabilis NC64A via enzymatic hydrolysis of cellulose in algal cell walls.CONCLUSIONAlgae–fungi interactions have the tendency to establish symbiosis and a fully autotrophic system without the need for an additional carbon source. © 2019 Society of Chemical Industry
Feasibility of the lidocaine injection method during esophageal endoscopic submucosal dissection
Authors: Yoshizaki Tetsuya , Obata Daisuke , Ueda Chise , Katayama Norio , Aoki Yasuhiro , Okamoto Norihiro , Hashimura Hiroki , Matsumoto Masanori , Takagi Megumi , Ikeoka Seitaro , Yoshida Ryutaro , Momose Kenji , Eguchi Takaaki , Yamashita Hiroshi , Okada Akihiko 
Published: September 2019

Background and AimEsophageal endoscopic submucosal dissection (ESD) is often technically difficult due to intraoperative body movements. The level of sedation can be increased to suppress body movements, but this may not be successful in all cases. Using local analgesics for submucosal injection during ESD may aid in conscious sedation. This study evaluated the feasibility of the lidocaine injection method (LIM) during esophageal ESD.MethodsTwenty‐nine patients with superficial esophageal cancer were enrolled in this study at Osaka Saiseikai Nakatsu Hospital, and 1% lidocaine + 0.4% hyaluronate sodium was injected into the submucosa underneath the lesion during esophageal ESD. The main outcome was body movements that disturbed the procedure.ResultsMost patients were male (90%), with a median age of 70 years (interquartile range [IQR]: 66–75 years old), and the median lesion size was 17 mm (IQR: 12–21 mm). The median injection volume of lidocaine was 70 mg (IQR: 55–79 mg). All lesions were successfully removed en bloc. In all cases, there were no body movements that disturbed the procedure. Regarding adverse events of sedation, five patients (17%) had hypotension, four patients (14%) had bradycardia, and seven patients (24%) had hypoxemia during ESD. Convulsions or arrhythmia as adverse events associated with lidocaine were not observed.ConclusionsEsophageal ESD with LIM did not cause body movements that disturbed the procedure. LIM may help create a stable conscious sedation method for esophageal ESD.
TLR4 mediates alveolar bone resorption in experimental peri‐implantitis through regulation of CD45+ cell infiltration, RANKL/OPG ratio, and inflammatory cytokine production
Authors: Deng Shu , Hu Yang , Zhou Jing , Wang Yufeng , Wang Yuguang , Li Sicong , Huang Grace , Peng Cheng , Hu Anka , Yu Qing , Han Xiaozhe 
Published: September 2019

AbstractBackgroundThe present study was to determine the role of Toll‐like receptor 4 (TLR4) signaling in inflammation and alveolar bone resorption using a murine model of Porphyromonas gingivalis‐associated ligature‐induced peri‐implantitis.MethodsSmooth surface titanium implants were placed in the left maxilla alveolar bone 6 weeks after extraction of first and second molars in Wild‐type (WT) and TLR4−/− (TLR4 KO) mice. Silk ligatures immersed with P. gingivalis were tied around the implants 4 weeks after the implant placement and confirmation of osteointegration. Two weeks after the ligation, bone resorption, osteoclastogenesis, cellular inflammatory responses, and gingival mRNA expression levels of cytokines were assessed by micro‐computed tomography, tartrate‐resistant acid phosphatase (TRAP) staining, immunobiological examination and Real‐time quantitative polymerase chain reaction, respectively.ResultsIn both WT and TLR4 KO mice, the bone resorption around implants was significantly increased in the P. gingivalis/ligation group compared with control group. In P. gingivalis/ligation group, the levels of bone resorption, TRAP+ cell formation, and gingival CD3+ and CD45+ cell infiltration were significantly decreased in TLR4 KO mice compared with that in WT mice. Receptor activator of nuclear factor‐kappa B ligand /osteoprotegerin (RANKL/OPG) ratio was significantly increased after P. gingivalis/ligation treatment in WT mice not in TLR4 KO mice. When comparing the P. gingivalis/ligation group with the respective control group, gingival mRNA expressions of IL‐1β, IFN‐γ, and 1L‐17 were significantly increased in TLR4 KO mice.ConclusionThis study suggests that TLR4 mediates alveolar bone resorption in P. gingivalis associated ligature‐induced peri‐implantitis through regulation of immune B cell infiltration, RANKL/OPG expression ratio, and differential inflammatory cytokine production.
Social media conflicts during the financial crisis: Managerial implications for retail banks
Authors: Dineva Denitsa , Lu Xiaoming , Breitsohl Jan 
Published: September 2019

AbstractSocial media can be used proactively to disseminate accurate corporate information and address undesirable consumer behaviors online in order to help counteract negativity in the business environment in the wake of a financial crisis. Social media thus has become a popular open forum for financial institutions such as retail banks to engage in corporate dialogue with consumers. We recommend that financial services firms preemptively use their social media‐based online communities in order to disseminate accurate corporate information in times of a financial crisis. Particularly, firms can choose between a range of reactive and proactive strategies to manage social conflict in the wake of a financial crisis.