bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting siRNA in colorectal cancer therapy: Nanotechnology comes into view
Authors: Aghamiri Shahin , Jafarpour Ali , Malekshahi Ziba Veisi , Mahmoudi Gomari Mohammad , Negahdari Babak 
Published: March 2019

AbstractColorectal cancer (CRC) is known as one of the most important causes of death and mortality worldwide. Although several efforts have been made for finding new therapies, no achievements have been made in this area. Multidrug resistance (MDR) mechanisms are one of the key factors that could lead to the failure of chemotherapy. Moreover, it has been shown that various chemotherapy drugs are associated with several side effects. Hence, it seems that finding new drugs or new therapeutic platforms is required. Among different therapeutic approaches, utilization of nanoparticles (NPs) for targeting a variety of molecules such as siRNAs are associated with good results for the treatment of CRC. Targeting siRNA‐mediated NPs could turn off the effects of oncogenes and MDR‐related genes. In the current study, we summarized various siRNAs targeted by NPs which could be used for the treatment of CRC. Moreover, we highlighted other routes such as liposome for targeting siRNAs in CRC therapy.
Dexmedetomidine ameliorates lipopolysaccharide‐induced acute kidney injury in rats by inhibiting inflammation and oxidative stress via the GSK‐3β/Nrf2 signaling pathway
Authors: Feng Xiujing , Guan Wei , Zhao Yuan , Wang Chaoran , Song Manyu , Yao Yujie , Yang Tianyuan , Fan Honggang 
Published: March 2019

AbstractAcute kidney injury (AKI) is a frequent and serious complication of sepsis; however, there are currently no effective therapies. Inflammation and oxidative stress are the major mechanisms implicated in lipopolysaccharide (LPS)‐induced AKI. Dexmedetomidine (DEX) has been reported to have remarkable anti‐inflammatory and antioxidant effects. Here, we examined the renoprotective effects of DEX and potential underlying mechanisms in rats with LPS‐induced AKI. We analyzed renal function and structure; serum inflammatory cytokine; renal oxidant and antioxidant levels; and renal expression of glycogen synthase kinase‐3β (GSK‐3β)/nuclear factor erythroid 2‐related factor 2 (Nrf2) pathway‐related proteins in rats 4 hr after administration of LPS. Pretreatment with DEX improved renal function and significantly reduced the levels of inflammatory cytokines and oxidative stress markers. Treatment with DEX and the GSK‐3β inhibitor SB216367 promoted phosphorylation of GSK‐3β, induced Nrf2 nuclear translocation, and increased transcription of the Nrf2 target genes heme oxygenase‐1 and NAD(P)H quinone oxidoreductase‐1, primarily in renal tubules. Alpha‐2‐adrenergic receptor (α2‐AR) antagonist atipamezole and imidazoline I
2 receptor (I
2R) antagonist idazoxan reversed the effects of DEX. These results suggest that the renoprotective effects of DEX are mediated via α2‐AR and I
2R‐dependent pathways that reduce inflammation and oxidative stress through GSK‐3β/Nrf2 signaling.
Recent developments in the field of cachexia, sarcopenia, and muscle wasting: highlights from the 11th Cachexia Conference
Authors: Ebner Nicole , Anker Stefan D. , von Haehling Stephan 
Published: March 2019

AbstractThis article highlights the updates from preclinical and clinical studies into the field of wasting disorders that were presented at the 11th Cachexia Conference held in Maastricht, the Netherlands, in December 2018. Herein, we summarize the biological and clinical significance of different markers and new diagnostic tools and cut‐offs for the detection of skeletal muscle wasting, including micro‐RNAs, siRNAs, epigenetic targets, the ubiquitin–proteasome system, mammalian target of rapamycin signalling, news in body composition analysis including the D3‐creatine dilution method, and electrocardiography that was modified to enable segmental impedance spectroscopy. Of particular interest were the beneficial effects of BIO101 on muscle cell differentiation, hypertrophy of myofibers associated with mammalian target of rapamycin pathways activation, and the effect of metal ion transporter ZIP14 loss that reduces cancer‐induced cachexia. The potential of anti‐ZIP14 antibodies and zinc chelation as anti‐cachexia therapy should be tested in patients with cancer cachexia. Big randomized studies were presented such as RePOWER (observational study of patients with primary mitochondrial myopathy), STRAMBO (influence of physical performance assessed as score and clinical testing), MMPOWER (treatment of elamipretide in subjects with primary mitochondrial myopathy), FORCE (examined differences in relative dose intensity and moderate and severe chemotherapy‐associated toxicities between a strength training intervention and a control group), and SPRINTT (effectiveness of exercise training in healthy aging). Effective treatments were urothelin A, rapamycin analogue treatment, epigenetic factor BRD 4 and epigenetic protein BET, and the gut pathobiont Klebsiella oxytoca. Clinical studies that investigated novel approaches, including urolithin A, the role of gut microbiota, metal ion transporter ZIP14, lysophosphatidylcholine and lysophosphatidylethanolamine, and BIO101, were described. It remains a fact, however, that effective treatments of cachexia and wasting disorders are urgently needed in order to improve patients' quality of life and their survival.
Hypertension and diabetes control along the HIV care cascade in rural South Africa
Authors: Manne‐Goehler Jennifer , Siedner Mark J , Montana Livia , Harling Guy , Geldsetzer Pascal , Rohr Julia , Gómez‐Olivé F Xavier , Goehler Alexander , Wade Alisha , Gaziano Thomas , Kahn Kathleen , Davies Justine I , Tollman Stephen , Bärnighausen Till W 
Published: March 2019

AbstractIntroductionParticipation in antiretroviral therapy (ART) programmes has been associated with greater utilization of care for hypertension and diabetes in rural South Africa. The objective of this study was to assess whether people living with HIV on ART with comorbid hypertension or diabetes also have improved chronic disease management indicators.MethodsThe Health and Aging in Africa: a longitudinal study of an INDEPTH Community in South Africa (HAALSI) is a cohort of 5059 adults >40 years old. Enrollment took place between November 2014 and November 2015. The study collected population‐based data on demographics, healthcare utilization, height, weight, blood pressure (BP) and blood glucose as well as HIV infection, HIV‐1 RNA viral load (VL) and ART exposure. We used regression models to determine whether HIV care cascade stage (HIV‐negative, HIV+ /No ART, ART/Detected HIV VL, and ART/Undetectable VL) was associated with diagnosis or treatment of hypertension or diabetes, and systolic blood pressure and glucose among those with diagnosed hypertension or diabetes. ART use was measured from drug level testing on dried blood spots.Results and discussionCompared to people without HIV, ART/Undetectable VL was associated with greater awareness of hypertension diagnosis (adjusted risk ratio (aRR) 1.18, 95% CI: 1.09 to 1.28) and treatment of hypertension (aRR 1.24, 95% CI: 1.10 to 1.41) among those who met hypertension diagnostic criteria. HIV care cascade stage was not significantly associated with awareness of diagnosis or treatment of diabetes. Among those with diagnosed hypertension or diabetes, ART/Undetectable VL was associated with lower mean systolic blood pressure (5.98 mm Hg, 95% CI: 9.65 to 2.32) and lower mean glucose (3.77 mmol/L, 95% CI: 6.85 to 0.69), compared to being HIV‐negative.ConclusionsParticipants on ART with an undetectable VL had lower systolic blood pressure and blood glucose than the HIV‐negative participants. HIV treatment programmes may provide a platform for health systems strengthening for cardiometabolic disease.
Computational identification of hepatitis E virus‐encoded microRNAs and their targets in human
Authors: Baruah Vargab , Bose Sujoy 
Published: March 2019

AbstractmicroRNAs (miRNAs) are small, noncoding RNAs which regulate eukaryotic gene expression via RNA interference pathway. Recently, miRNAs have been identified in a number of viruses with current evidence suggesting that they regulate gene expression in both virus and host. This makes viral miRNAs potential targets of clinical intervention, with the possibility of inhibiting aberrant host gene expression associated with the disease. In this study, computational approaches were taken to scan the hepatitis E virus (HEV) genome for putative pre‐miRNA molecules, which were then analyzed for the presence of mature miRNAs. The 3′‐untranslated region (3′‐UTR) and 5′‐UTR sequences targeted by these miRNAs were identified using Miranda computational tool, followed by the functional annotation of the associated messenger RNAs (mRNAs) using Gene Ontology terms and Kyoto Encyclopaedia of Genes and Genomes pathway analysis. We identified a total of nine viral encoded miRNAs in HEV. After functional annotation, the majority of the viral miRNA targets were found to be associated with cell cycle, cell differentiation, nitrogen compound metabolism, transmembrane transport, and chromosome organization. This in‐silico study identified putative viral miRNAs encoded by HEV and their potential human mRNAs targets. These viral miRNAs have the potential to affect host gene expression as well as viral life cycle and pathogenesis and can, therefore, serve as potential therapeutic targets during HEV infection.
Regulatory mechanisms and clinical manifestations of musculoskeletal aging
Authors: Grote Caleb , Reinhardt Daniel , Zhang Mingcai , Wang Jinxi 
Published: March 2019

ABSTRACTAging is the strongest risk factor for degenerative bone and joint diseases. Clinical therapies for age‐related musculoskeletal disorders face significant challenges as their pathogenic mechanisms remain largely unclear. This review article focuses on the recent advances in the understanding of regulatory mechanisms of musculoskeletal aging and their clinical relevance. We begin with the prevalence and socioeconomic impacts of major age‐related musculoskeletal disorders such as sarcopenia, osteoporosis, osteoarthritis, and degenerative tendinopathy. The current understanding of responsible biological mechanisms involved in general aging is then summarized. Proposed molecular, cellular, and biomechanical mechanisms relevant to the clinical manifestations of aging in the musculoskeletal system are discussed in detail, with a focus on the disorders affecting muscle, bone, articular cartilage, and tendon. Although musculoskeletal aging processes share many common pathways with the aging of other body systems, unique molecular and cellular mechanisms may be involved in the aging processes of musculoskeletal tissues. Advancements in the understanding of regulatory mechanisms of musculoskeletal aging may promote the development of novel treatments for age‐related musculoskeletal disorders. Finally, future research directions for major musculoskeletal tissues including functional interaction between the tissues and their clinical relevance to age‐related musculoskeletal disorders are highlighted in the Future Prospects section. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1475–1488, 2019.
Short‐ and long‐term survival has improved after radical cystectomy for bladder cancer in Québec during the years 2000‐2015
Authors: Wissing Michel D. , Santos Fabiano , Zakaria Ahmed S. , O'Flaherty Ana , Tanguay Simon , Kassouf Wassim , Aprikian Armen G. 
Published: March 2019

AbstractBackground and ObjectivesWe evaluated the short‐ and long‐term outcome in bladder cancer (BC) patients treated with radical cystectomy (RC) in Québec (Canada).MethodsData were collected from provincial registries on all BC patients who underwent RC in Québec province in 2000‐2015. Outcomes were hospitalization rates and survival. Survival analyses were conducted using log‐rank tests and Cox proportional hazards models.ResultsIn total, 4450 patients were included in our analysis. RC was increasingly conducted by higher‐volume surgeons in larger, higher‐volume, academic hospitals. Comparing patients treated in 2010‐2015 to 2000‐2009, recently treated patients had shorter postoperative hospital stays (absolute difference, 0.9 days,P < 0.001) but also a higher readmission rate (25.0% vs 21.1% in the 30 days following discharge,P = 0.003). Overall (5‐year rates 50.9% vs 42.7%,P < 0.001) and BC‐specific survival (61.3% vs 55.5%,P < 0.001) had significantly improved. In multivariable analyses, overall survival was significantly better in recently treated patients (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.60‐0.73), younger patients (HR, 1.16; 95% CI, 1.14‐1.19), patients residing closer to the hospital (HR, 1.03; 95% CI, 1.01‐1.06), and patients treated by high‐volume surgeons (HR, 0.88; 95% CI, 0.82‐0.94).ConclusionsSurvival in BC patients after RC has improved in recent years. Other predictors for survival are younger age, shorter distance between patients' residences and hospitals, and higher surgeon's RC loads.
Visible Light Rewritable and Long‐Lived Colors in Cholesteric Liquid Crystals: A Facile Co‐Doping Strategy
Authors: Zhao Dongxu , Zhao Xiaoyu , Wang Jing , Peng Haiyan , Liao Yonggui , Xie Xiaolin , Smalyukh Ivan I. , Yu Yanlei 
Published: March 2019

AbstractPhotoresponsive cholesteric liquid crystals (CLCs) are able to selectively reflect colors upon light exposure. Yet, it still remains a formidable challenge to realize simultaneous rewriting and long‐life color in CLCs using visible light. Herein, guided by time dependent density functional theory (TD‐DFT) computation, an octafluorinated binaphthyl azobenzene is synthesized to achieve the fast response and long‐life color upon visible light exposure. Subsequently, based on the solubility parameter, uniform CLCs are formulated through a facile co‐doping strategy. Interestingly, the CLCs change reflection colors from blue to green, red, and then into the near infrared region in seconds upon 550 nm light illumination. The completely reversible process is readily accessable upon 450 nm irradiation. More importantly, each color is independently stable for ≈24 h in the dark.
Molecular evidence supporting the precursor nature of atypical adenomatous hyperplasia of the prostate
Authors: Cheng Liang , Montironi Rodolfo , Davidson Darrell D. , Wang Mingsheng , Lopez‐Beltran Antonio , Zhang Shaobo 
Published: March 2019

AbstractAtypical adenomatous hyperplasia (AAH) of the prostate is characterized by lobular proliferation of closely packed small acini. It is hypothesized that AAH is a precursor lesion for low‐grade prostate cancer arising from the transition zone. Telomere dysfunction is common during malignant transformation of epithelia. In this study, we investigate telomere shortening in AAH (n = 93), high‐grade prostatic intraepithelial neoplasia (HGPIN) (
n = 68), and prostatic adenocarcinoma (PCA) (
n = 70) using quantitative fluorescence in situ hybridization. Twenty percent (19 of 93) of AAH specimens, 68% (46 of 68) of HGPIN, and 83% (58 of 70) of PCA showed significant telomere shortening. Thirty‐two percent of AAH lesions had α‐methylacyl‐CoA racemase (AMACR) expression, a sensitive and specific marker for HGPIN and PCA. AMACR expression in AAH was seen more frequently in AAH foci with telomere shortening or coexisting PCA. Our findings indicate that a subset of AAH lesions have telomere shortening and AMACR expression, suggesting that these foci may be precursors for PCA.
Class of tight bounds on the Q‐function with closed‐form upper bound on relative error
Authors: Perić Zoran H. , Nikolić Jelena R. , Petković Marko D. 
Published: March 2019

In this paper, we propose a novel class of parametric bounds on the Q‐function, which are lower bounds for 1 ≤ a < 3 and x > xt = (a (a‐1) / (3‐a))1/2, and upper bound for a = 3. We prove that the lower and upper bounds on the Q‐function can have the same analytical form that is asymptotically equal, which is a unique feature of our class of tight bounds. For the novel class of bounds and for each particular bound from this class, we derive the beneficial closed‐form expression for the upper bound on the relative error. By comparing the bound tightness for moderate and large argument values not only numerically, but also analytically, we demonstrate that our bounds are tighter compared with the previously reported bounds of similar analytical form complexity.
Effect of Different Cereal Peptides on the Development of Type 1 Diabetes is Associated with Their Anti‐inflammatory Ability: In Vitro and In Vivo Studies
Authors: Sun Suling , Zhang Hao , Shan Kai , Sun Tianjun , Lin Mengyuan , Jia Lingling , Chen Yong Q. 
Published: March 2019

ScopeThe aim of the study is to explore which properties of selected peptides will positively predict their antidiabetic activity in vitro and in vivo.Methods and resultsStreptozotocin‐induced diabetic C57BL/6J mice are administered with soybean peptide (SP), mung bean peptide (MP), corn peptide (CP), and wheat peptide (WP) (500 mg kg–1 d–1) for 10 weeks. CP and WP improve hyperglycemia homeostasis in streptozotocin‐induced diabetic mice. Female nonobese diabetic (NOD) mice are treated with CP, WP, fractions C1 and C2 (isolated from CP), and W1 and W2 (isolated from WP) beginning at 3 weeks of age. CP, C2, and W2 delay the initiation of diabetes and decrease serum IL‐6 levels in NOD mice. CP also reduces insulitis and increases the β‐cell area in NOD mice. MIN‐6 cells are incubated with the selected peptides. CP, C2, and W2 result in the reduced expression of LPS‐induced IL‐6 mRNA in MIN‐6 cells. CP inhibits signaling pathways related to apoptosis and inflammation. The antioxidative, hydrophobic, and proliferative properties of the selected peptides are analyzed. The hypoglycemic effects of cereal peptides are not associated with their antioxidant activity, hydrophobicity, or proliferative ability.ConclusionFindings suggest that the effect of cereal peptides on the development of T1D is associated with their anti‐inflammatory ability.
Intermittently tagged real‐time MRI reveals internal tongue motion during speech production
Authors: Chen Weiyi , Byrd Dani , Narayanan Shrikanth , Nayak Krishna S. 
Published: March 2019

PurposeTo demonstrate a tagging method compatible with RT‐MRI for the study of speech production.MethodsTagging is applied as a brief interruption to a continuous real‐time spiral acquisition. Tagging can be initiated manually by the operator, cued to the speech stimulus, or be automatically applied with a fixed frequency. We use a standard 2D 1‐3‐3‐1 binomial SPAtial Modulation of Magnetization (SPAMM) sequence with 1 cm spacing in both in‐plane directions. Tag persistence in tongue muscle is simulated and validated in vivo. The ability to capture internal tongue deformations is tested during speech production of American English diphthongs in native speakers.ResultsWe achieved an imaging window of 650‐800 ms at 1.5T, with imaging signal to noise ratio ≥ 17 and tag contrast to noise ratio ≥ 5 in human tongue, providing 36 frames/s temporal resolution and 2 mm in‐plane spatial resolution with real‐time interactive acquisition and view‐sharing reconstruction. The proposed method was able to capture tongue motion patterns and their relative timing with adequate spatiotemporal resolution during the production of American English diphthongs and consonants.ConclusionIntermittent tagging during real‐time MRI of speech production is able to reveal the internal deformations of the tongue. This capability will allow new investigations of valuable spatiotemporal information on the biomechanics of the lingual subsystems during speech without reliance on binning speech utterance repetition.
Monolithic cut finite element–based approaches for fluid‐structure interaction
Authors: Schott Benedikt , Ager Christoph , Wall Wolfgang A. 
Published: March 2019

SummaryCut finite element method–based approaches toward challenging fluid‐structure interaction (FSI) are proposed. The different considered methods combine the advantages of competing novel Eulerian (fixed grid) and established arbitrary Lagrangian‐Eulerian (moving mesh) finite element formulations for the fluid. The objective is to highlight the benefit of using cut finite element techniques for moving‐domain problems and to demonstrate their high potential with regard to simplified mesh generation, treatment of large structural motions in surrounding flows, capturing boundary layers, their ability to deal with topological changes in the fluid phase, and their general straightforward extensibility to other coupled multiphysics problems. In addition to a pure fixed‐grid FSI method, advanced fluid‐domain decomposition techniques are also considered, leading to highly flexible discretization methods for the FSI problem. All stabilized formulations include Nitsche‐based weak coupling of the phases supported by the ghost penalty technique for the flow field. For the resulting systems, monolithic solution strategies are presented. Various two‐ and three‐dimensional FSI cases of different complexity levels validate the methods and demonstrate their capabilities and limitations in different situations.
Localizing gradient‐enhanced Rousselier model for ductile fracture
Authors: Xu Yanjie , Poh Leong Hien 
Published: March 2019

SummaryNonlocal enhancement is widely adopted to resolve the mesh sensitivity issue in standard continuum damage models. Although it regularizes structural response well, the damage profile is reported to exhibit a spurious damage growth. To remedy this problem, a localizing gradient enhancement is adopted in the Rousselier model to simulate a localized rupture. The localizing gradient enhancement, recently developed in the small deformation framework, is extended in this paper to a large deformation framework, motivated by the strain localization phenomenon during a ductile fracture. The regularization property of the current model is verified with a flat grooved plate test, and the superior performance in damage localization is demonstrated with a uniaxial tensile plate test and a compact tension test on aluminum alloy. Results obtained with the localizing gradient enhancement are consistent with experimental observation, without the nonphysical damage growth in conventional gradient enhancement.
Excitation Energy‐Transfer Processes in the Sensitization Luminescence of Europium in a Highly Luminescent Complex
Authors: Huang Yan‐Jie , Ke Can , Fu Li‐Min , Li Yu , Wang Shu‐Feng , Ma Ying‐Chao , Zhang Jan‐Ping , Wang Yuan 
Published: March 2019

AbstractThe excitation energy transfer (EET) pathways in the sensitization luminescence of EuIII and the excitation energy migration between the different ligands in [Eu(fod)3dpbt] [where fod=6,6,7,7,8,8,8‐heptafluoro‐2,2‐dimethyl‐3,5‐octanedione and dpbt=2‐(N,N‐diethylanilin‐4‐yl)‐4,6‐bis(3,5‐dimethylpyrazol‐1‐yl)‐1,3,5‐triazine], exhibiting well‐separated fluorescence excitation and phosphorescence bands of the different ligands, were investigated by using time‐resolved luminescence spectroscopy for the first time. The data clearly revealed that upon the excitation of dpbt, the sensitization luminescence of EuIII in [Eu(fod)3dpbt] was dominated by the singlet EET pathway, whereas the triplet EET pathway involving T1(dpbt) was inefficient. The energy migration from T1(dpbt) to T1(fod) in [Eu(fod)3dpbt] was not observed. Moreover, upon the excitation of fod, a singlet EET pathway for the sensitization of EuIII luminescence, including the energy migration from S1(fod) to S1(dpbt) was revealed, in addition to the triplet EET pathway involving T1(fod). Under the excitation of dpbt at 410 nm, [Eu(fod)3dpbt] exhibited an absolute quantum yield for EuIII luminescence of 0.59 at 298 K. This work provides a solid and elegant example for the concept that singlet EET pathway could dominate the sensitization luminescence of EuIII in some complexes.