bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient Cytoplasmic Delivery of Antisense Probes Assisted by Cyclized‐Peptide‐Mediated Photoinduced Endosomal Escape
Authors: Tan Xiaohong , Bruchez Marcel P. , Armitage Bruce A. 
Published: November 2018

AbstractIntracellular delivery and endosomal release of antisense oligonucleotides remain a significant challenge in the development of gene‐targeted therapeutics. Previously, noncovalently cyclized TAT peptide (Cyc‐TAT), in which the final ring‐closing step is accomplished by hybridization of two short complementary γPNA segments, has been proven more efficient than its linear analogues at entering cells. As Cyc‐TAT also readily accommodates a binding site, that is, an overhanging γPNA sequence, for codelivery of functional nucleic acid probes into cells, we were able to demonstrate that the overhang‐Cyc‐TAT penetrated into A549 cells when carrying an anti‐telomerase γPNA that specifically reduced telomerase activity by over 97 %. Herein, we report that the cyclized TAT(FAM) can escape endosomes much more efficiently than the linear TAT(FAM) after LED illumination (490 nm). Based on this observation, the endosomal release of overhang‐Cyc‐TAT(FAM)/anti‐telomerase γPNA complex can be greatly enhanced by photoactivation, thus shortening cell treatment time from 60 to 3 h, while keeping the same high efficiency in inhibiting telomerase activity inside A549 cells.
miR‐381 overcomes cisplatin resistance in breast cancer by targeting MDR1
Authors: Yi Dandan , Xu Lei , Wang Ru , Lu Xingyi , Sang Jianfeng 
Published: November 2018

AbstractIncreasing evidence suggests the involvement of microRNA‐381 (miR‐381) in chemoresistance of cancer treatment. However, its function and molecular mechanisms in breast cancer chemoresistance are still not well elucidated. In the present study, we aimed to investigate the functional role of miR‐381 in cisplatin (DDP) resistance of breast cancer and discover the underlying molecular mechanism. The expression levels of miR‐381 and MDR1 were detected by quantitative real‐time PCR (qRT‐PCR) and Western blot analysis in breast cancer tissues and cell lines. The DDP sensitivity and cell apoptosis of breast cancer cells were determined by MTT assay and flow cytometric analysis, respectively. The relationship between miR‐381 and MDR1 was explored by target prediction and luciferase reporter analysis. miR‐381 was decreased in DDP‐resistant breast cancer tissues and cell lines. Low miR‐381 expression was correlated with poor prognosis of breast cancer patients. miR‐381 overexpression improved DDP sensitivity of MCF‐7/DDP and MDA‐MB‐231/DDP cells. Conversely, miR‐381 inhibition lowered the response of MCF‐7 and MDA‐MB‐231 to DPP. Moreover, miR‐381 could directly suppress multidrug resistance 1 (MDR1) expression. MDR1 knockdown could overcome DDP resistance in MCF‐7/DDP and MDA‐MB‐231/DDP cells, while MDR1 overexpression led to DDP resistance in MCF‐7 and MDA‐MB‐231 cells. Notably, MDR1 overexpression counteracted the inductive effect of miR‐381 mimics on DDP sensitivity of MCF‐7/DDP and MDA‐MB‐231/DDP cells. On the contrary, miR‐381 inhibition‐mediated DDP resistance in MCF‐7 and MDA‐MB‐231 cells was reversed by MDR1 knockdown. In summary, miR‐381 could overcome DDP resistance of breast cancer by directly targeting MDR1, providing a novel therapeutic target for breast cancer chemoresistance.
A novel user‐friendly transcatheter edge‐to‐edge mitral valve repair device in a porcine model
Authors: Pan Wenzhi , Pan Cuizhen , Jilaihawi Hasan , Wei Lai , Tang Yue , Zhou Daxin , Ge Junbo 
Published: November 2018

AbstractObjectivesThe present study was performed to evaluate the feasibility and safety of the ValveClamp system for transcatheter edge‐to‐edge mitral valve repair in a porcine model.BackgroundThe ValveClamp system is a novel, transapically delivered edge‐to‐edge mitral valve repair system designed for ease of operation.MethodsThirteen young adult swine were enrolled in the study. The procedure was performed via the transapical approach under epicardial echocardiography guidance.ResultsThe acute procedure success rate was 92.3% (12/13). The catheter manipulation time was just 18.5 ± 8.2 min. Four pigs were explanted on the 14th day after the procedure. One pig died at the 20th day because of pneumonia. The other eight pigs lived to the study endpoint (140 days). No pig had severe mitral valve dysfunction. The gross observation showed that the clamp device was securely attached and created a double‐orifice mitral valve in all pigs except the failed one. In the eight pigs living to the endpoint, the clamp device was noted to be completely endothelialized. None of the 13 pigs developed infective endocarditis, thrombosis, thromboembolism, or valve impairment. In two pigs for which mitral regurgitation (MR) was created, the degree of MR was reduced from severe to trace after the device implantation.ConclusionsIt was feasible and safe to use ValveClamp to perform a catheter‐mediated edge‐to‐edge mitral valve repair in a porcine model. This system is potentially applicable as a novel user‐friendly system for the treatment of MR.
Mn3O4@C Nanoparticles Supported on Porous Carbon as Bifunctional Oxygen Electrodes and their Electrocatalytic Mechanism
Authors: Li Ms. Wanqing , Fu Mr. Hongquan , Cao Yonghai , Wang Hongjuan , Yu Hao , Qiao Zhiwei , Liang Hong , Peng Feng 
Published: November 2018

AbstractMn3O4 nanoparticles encapsulated inside carbon nanospheres supported on a carbon plate (Mn3O4@CS/CP) were designed, their bifunctional electrocatalytic performance for both, the oxygen evolution reaction (OER) at the anode and the oxygen reduction reaction (ORR) at the cathode were studied in alkaline solution. The prepared Mn3O4@CS/CP catalyst exhibits excellent electrocatalytic performance towards ORR, with less negative onset potential and long durability. Combining the results of in‐situ Fourier transform infrared spectroscopy (FTIR) and density functional theory (DFT) calculations, it is revealed that Mn3O4 acts as active site for ORR to promote the transformation of OH* into OH−. In addition, Mn3O4@CS/CP possesses an excellent electrochemical OER performances with the lower overpotential along with prosper Tafel slope and robust durability. DFT calculations show the transformation from O* to OOH* is the rate determining step for OER, and Mn3O4@CS/CP shows the minimum barrier, indicating that graphene sheet on the outer of Mn3O4 improves the transformation from O* to OOH*. The oxygen electrode activity parameter (potential difference between OER at current density of 10 mA/cm2 and ORR at current density of −2 mA/cm2) on Mn3O4@CS/CP is 0.72 V, which is superior to those of most bifunctional electrocatalysts reported to date, predicting a promising application in metal‐air batteries and fuel cells.
Turn On of a Ruthenium(II) Photocatalyst by DNA‐Templated Ligation
Authors: Anzola Marcello , Winssinger Nicolas 
Published: November 2018

AbstractHere, the synthesis of a RuII photocatalyst by light‐directed oligonucleotide‐templated ligation reaction is described. The photocatalyst was found to have tremendous potential for signal amplification with >15000 turnovers measured in 9 hours. A templated reaction was used to turn on the activity of this ruthenium(II) photocatalyst in response to a specific DNA sequence. The photocatalysis of the ruthenium(II) complex was harnessed to uncage a new precipitating dye that is highly fluorescent and photostable in the solid state. This reaction was used to discriminate between different DNA analytes based on localization of the precipitate as well as for in cellulo miRNA detection. Finally, a bipyridine ligand functionalized with two different peptide nucleic acid (PNA) sequences was shown to enable template‐mediated ligation (turn on of the ruthenium(II) photocatalysis) and recruitment of substrate for templated photocatalysis.
Synthesis and Ring Strain of a Benzoborirene‐N‐Heterocyclic Carbene Adduct
Authors: Hahn Jennifer , Keck Constanze , Maichle‐Mössmer Cäcilia , von Grotthuss Esther , Ruth Paul Niklas , Paesch Alexander , Stalke Dietmar , Bettinger Holger F. 
Published: November 2018

AbstractThe reduction of an N‐heterocyclic carbene (1,3‐diisopropyl‐4,5‐dimethylimidazolin‐2‐ylidene, IiPr
) adduct of dichloro(ortho‐bromophenyl)borane by tert‐butyl lithium at low temperature yields the IiPr
adduct A of parent benzoborirene, a highly strained boron‐containing bicyclic compound. A is unstable at room temperature and dimerizes at low temperature to the bis‐IiPr
adduct of 9,10‐dihydro‐9,10‐diboraanthracene, characterized by single‐crystal X‐ray crystallography.
Incarceration of Iodine in a Pyrene‐Based Metal–Organic Framework
Authors: Gładysiak Andrzej , Nguyen Tu N. , Spodaryk Mariana , Lee Jung‐Hoon , Neaton Jeffrey B. , Züttel Andreas , Stylianou Kyriakos C. 
Published: November 2018

AbstractA pyrene‐based metal‐organic framework (MOF) SION‐8 captured iodine (I2) vapor with a capacity of 460 and 250 mg g−1MOF at room temperature and 75 °C, respectively. Single‐crystal X‐ray diffraction analysis and van‐der‐Waals‐corrected density functional theory calculations confirmed the presence of I2 molecules within the pores of SION‐8 and their interaction with the pyrene‐based ligands. The I2–pyrene interactions in the I2‐loaded SION‐8 led to a 104‐fold increase of its electrical conductivity compared to the bare SION‐8. Upon adsorption, ≥95 % of I2 molecules were incarcerated and could not be washed out, signifying the potential of SION‐8 towards the permanent capture of radioactive I2 at room temperature.
Resurrection and Reactivation of Acetylcholinesterase and Butyrylcholinesterase
Authors: Franjesevic Andrew J. , Sillart Sydney B. , Beck Jeremy M. , Vyas Shubham , Callam Christopher S. , Hadad Christopher M. 
Published: November 2018

AbstractOrganophosphorus (OP) nerve agents and pesticides present significant threats to civilian and military populations. OP compounds include the nefarious G and V chemical nerve agents, but more commonly, civilians are exposed to less toxic OP pesticides, resulting in the same negative toxicological effects and thousands of deaths on an annual basis. After decades of research, no new therapeutics have been realized since the mid‐1900s. Upon phosphylation of the catalytic serine residue, a process known as inhibition, there is an accumulation of acetylcholine (ACh) in the brain synapses and neuromuscular junctions, leading to a cholinergic crisis and eventually death. Oxime nucleophiles can reactivate select OP‐inhibited acetylcholinesterase (AChE). Yet, the fields of reactivation of AChE and butyrylcholinesterase encounter additional challenges as broad‐spectrum reactivation of either enzyme is difficult. Additional problems include the ability to cross the blood brain barrier (BBB) and to provide therapy in the central nervous system. Yet another complication arises in a competitive reaction, known as aging, whereby OP‐inhibited AChE is converted to an inactive form, which until very recently, had been impossible to reverse to an active, functional form. Evaluations of uncharged oximes and other neutral nucleophiles have been made. Non‐oxime reactivators, such as aromatic general bases and Mannich bases, have been developed. The issue of aging, which generates an anionic phosphylated serine residue, has been historically recalcitrant to recovery by any therapeutic approach—that is, until earlier this year. Mannich bases not only serve as reactivators of OP‐inhibited AChE, but this class of compounds can also recover activity from the aged form of AChE, a process referred to as resurrection. This review covers the modern efforts to address all of these issues and notes the complexities of therapeutic development along these different lines of research.
Simply Structured Near‐Infrared Emitters with a Multicyano Linear Acceptor for Solution‐Processed Organic Light‐Emitting Diodes
Authors: Zhao Bingjie , Xie Guohua , Wang Huiqin , Han Chunmiao , Xu Hui 
Published: November 2018

AbstractNear‐infrared (NIR) organic light‐emitting diodes (OLEDs) show great potential in a variety of applications including sensors, night vision, and information security. Despite the superiority of thermally activated delayed fluorescence (TADF) in 100 % exciton harvesting, the development of NIR TADF OLEDs is still a great challenge, especially in terms of solution‐processing technology. In this work, a multicyano acceptor of 2‐dicyanomethylene‐3‐cyano‐4,5,5‐trimethyl‐2,5‐dihydrofurance (TCF) with strong electron‐withdrawing ability was employed to construct solution‐processible NIR emitters, CzTCF and tBCzTCF, with the feature of donor–π–acceptor (D–π–A) structure. The significantly enhanced intermolecular charge transfer effects not only render the deep‐red and NIR emissions of CzTCF and tBCzTCF films, respectively, but also lead to their typical TADF characteristics. Consequently, the nondoped solution‐processed NIR OLED based on tBCzTCF was successfully demonstrated with the peak wavelength of 715 nm, which paves the way for developing NIR emitters without polycyclic aromatic cores and heavy‐metal ions.
H2 Activation by Non‐Transition‐Metal Systems: Hydrogenation of Aldimines and Ketimines with LiN(SiMe3)2
Authors: Elliott Daniel C. , Marti Alex , Mauleón Pablo , Pfaltz Andreas 
Published: November 2018

AbstractIn recent years, H2 activation at non‐transition‐metal centers has met with increasing attention. Here, a system in which H2 is activated and transferred to aldimines and ketimines using substoichiometric amounts of lithium bis(trimethylsilyl)amide is reported. Notably, the reaction tolerates the presence of acidic protons in the α‐position. Mechanistic investigations indicated that the reaction proceeds via a lithium hydride intermediate as the actual reductant.
The Quest for Stable Silaaldehydes: Synthesis and Reactivity of a Masked Silacarbonyl
Authors: Sarkar Debotra , Nesterov Vitaly , Szilvási Tibor , Altmann Philipp J. , Inoue Shigeyoshi 
Published: November 2018

AbstractThe first donor–acceptor complex of a silaaldehyde, with the general formula (NHC)(Ar)Si(H)OGaCl3(NHC=N‐heterocyclic carbene), was synthesized using the reaction of silyliumylidene–NHC complex [(NHC)2(Ar)Si]Cl with water in the presence of GaCl3. Conversion of this complex to the corresponding silacarboxylate dimer [(NHC)(Ar)SiO2GaCl2]2, free silaacetal ArSi(H)(OR)2, silaacyl chloride (NHC)(Ar)Si(Cl)OGaCl3, and phosphasilene–NHC adduct (NHC)(Ar)Si(H)PTMS unveil its true potential as a synthon in silacarbonyl chemistry.
Are aromatase inhibitors associated with higher myocardial infarction risk in breast cancer patients? A Medicare population‐based study
Authors: Kamaraju Sailaja , Shi Yushu , Smith Elizabeth , Nattinger Ann B. , Laud Purushottam , Neuner Joan 
Published: November 2018

BackgroundTheoretically, the estrogen deprivation induced by aromatase inhibitors (AIs) might cause ischemic heart disease, but empiric studies have shown mixed results. We aimed to compare AIs and tamoxifen with regard to cardiovascular events among older breast cancer patients outside of clinical trials. We hypothesized that AIs increase the risk of myocardial infarction.MethodsWe identified women age ≥67 years diagnosed with breast cancer from June 30, 2006 to June 1, 2008 in the surveillance, epidemiology, and end results (SEER)‐Medicare database, treated with either tamoxifen or an AI, and followed through December 31, 2012. To compare myocardial infarction (MI) risk for the treatment groups of AIs vs tamoxifen, we developed and assigned stabilized probability of treatment weights and used the Fine and Gray model for time to MI with death not related to MI as a competing risk.ResultsOf the cohort of 5648 women, 4690 were treated with AIs and 958 with tamoxifen; a total of 251 patients developed MI, and 22 patients died of MI during the study period while 476 died of other causes. The hazard for MI was not significantly different between AI vs tamoxifen groups (HR = 1.01, 95% CI 0.72‐1.42), after adjusting for the following known MI risk factors at the start of adjuvant therapy: diabetes, ischemic heart disease, congestive heart failure, MI, and peripheral vascular disease.ConclusionsIn this SEER‐Medicare‐based population study, there were no significant differences in the risk of MI between AI and tamoxifen users after adjustment for known risk factors.
Predictors of all‐cause mortality and ischemic events within and beyond 1 year after an acute coronary syndrome: Results from the EPICOR registry
Authors: Rossello Xavier , Bueno Héctor , Pocock Stuart J , Van de Werf Frans , Danchin Nicolas , Annemans Lieven , Medina Jesús , Zeymer Uwe 
Published: November 2018

BackgroundPatients discharged after an acute coronary syndrome (ACS) have substantial risk of recurrent ischemic events or dying.HypothesisA difference may exist in risk predictors for all‐cause mortality and ischemic events between year 1 and 2 of follow‐up post‐ACS.MethodsEPICOR (NCT01171404) was a prospective, international, real‐world cohort study of consecutive patients hospitalized for ACS within 24 hours of symptom onset and surviving to discharge. Total of 10 568 patients were enrolled (555 hospitals; 20 countries) and followed‐up for 2 years. From these, 4943 were admitted with ST‐elevation myocardial infarction (STEMI) and 5625 with non‐ST‐elevation ACS (NSTE‐ACS). Potential baseline predictors of major adverse cardiac and cerebrovascular events (MACCE; death, non‐fatal myocardial infarction [MI], non‐fatal stroke) were evaluated in year 1 and 2 post‐discharge.ResultsMACCE incidence per 100 person‐years at risk within and after 1 year was 5.3 vs 3.6, primarily death (4.1 vs 2.3), with no significant differences for MI or stroke. Older age, lack of coronary revascularization, raised creatinine, low hemoglobin, previous cardiac disease, previous chronic obstructive pulmonary disease, raised glucose, male sex, and geographic region were risk factors for MACCE in both year 1 and 2. By contrast, low ejection fraction, poorer quality of life, low body mass index (BMI) <20 kg/m2, in‐hospital cardiac complications, and Killip class lost predictive power after 1 year.ConclusionWe observed continuous MACCE risk during 2 years of follow‐up after discharge for ACS, with greater mortality within the first year. Specific predictors at discharge for events after 1 year could not be identified.
Prevalence of comorbidities and effect on survival in survivors of human papillomavirus–related and human papillomavirus–unrelated head and neck cancer in the United States
Authors: Eytan Danielle F. , Blackford Amanda L. , Eisele David W. , Fakhry Carole 
Published: November 2018

AbstractBackgroundThe increasing incidence of human papillomavirus (HPV)–related head and neck cancer (HNC) has led to the increasing prevalence of survivors, yet to the best of the authors’ knowledge the prevalence of comorbidities during the survivorship period and their effects on survival are relatively unknown.MethodsIn this retrospective cross‐sectional study, individuals with a first incident primary diagnosis of HNC from 2004 through 2011 from the Surveillance, Epidemiology, and End Results (SEER)–Medicare‐linked databases were included in the analysis and classified as patients with HPV‐related or HPV‐unrelated HNC. The presence of 30 comorbid conditions of interest was identified. Associations between comorbidity and treatment group as well as overall survival were evaluated.ResultsThe study population consisted of 8025 patients with HPV‐unrelated HNC and 2499 patients with HPV‐related HNC. Hypertension, congestive heart failure, cerebrovascular disease, and chronic obstructive pulmonary disease all were found to be highly prevalent at the time of the cancer diagnosis and increased over time for both groups. These comorbidities were found at significantly lower rates in the HPV‐related HNC population, yet were associated with an increased risk of death in both groups. The probabilities of developing cancer‐related comorbidities such as pneumonia, dysphagia, weight loss, malnutrition, and dental issues rose significantly in both groups after treatment but were more likely in patients with HPV‐related HNC. In both groups of patients, the presence of each comorbidity either at the time of diagnosis or during survivorship was associated with a significantly increased risk of death.ConclusionsThere is a large burden of comorbidities in both patients with HPV‐related and HPV‐unrelated HNC, both of which are associated with decreased survival. Oncologic surveillance should not be limited to the evaluation of disease status, but also should include screening for the highly prevalent conditions associated with the risk of death.
Medulloblastoma: Challenges and advances in treatment and research
Authors: Martirosian Vahan , Neman Josh 
Published: November 2018

AbstractBackgroundMedulloblastoma (MB) is a pediatric brain tumor occurring in the posterior fossa. MB is a highly heterogeneous tumor, which can be grouped into four main subgroups: WNT, SHH, Group 3, and Group 4. Each subgroup is different both in its implicated pathways and pathology, as well as how they are treated in the clinic.Recent FindingsStandard protocol for MB treatment consists of maximal safe resection, followed by craniospinal radiation (in patients 3 years and older) and adjuvant chemotherapy. Advances in clinical stratification of this tumor have allowed establishment of treatment de‐escalation trials aimed at reducing long‐term side effects. However, there have been few advances in identifying novel therapeutic strategies for MB patients due to difficulties in creating chemotherapeutics that can bypass the blood‐brain‐barrier—among other factors. On the other hand, with the help of whole genome sequencing technologies, molecular pathways involved in MB pathogenesis have become clearer and have helped drive MB research. Regardless, this advance in research has yet to translate to the clinic, which may be due to the inability of current in vivo and in vitro models to accurately recapitulate this heterogeneous tumor in humans.ConclusionsThere have been significant advances in knowledge and treatment of medulloblastoma over the last few decades. Whole genome sequencing has helped elucidate clear differences between the subgroups of MB, allowing physicians to better tailor treatments to each patient in an effort to reduce long‐term sequelae. However, there are still many more obstacles to overcome, including less cytotoxic therapies in the clinic and better modeling systems to accurately replicate this disease in the laboratory. Scientists and physicians must work in a more cohesive manner to create translatable results from the laboratory to the clinic—helping improve therapies for medulloblastoma patients.
Flow Cytometry Instrumentation – An Overview
Authors: Büscher Martin 
Published: November 2018

AbstractThe term flow cytometry, used since the seventies, describes a technology employed mainly in biology and medicine to measure and classify suspended particles, e.g., cells or microspheres. Measurable cell parameters include: geometric properties, such as cell size (diameter, surface area, volume); physiological properties (membrane potential, integrity, vitality); and quantities of DNA, RNA, cytokines, surface antigens, nuclear antigens, enzymes, and proteins. © 2018 by John Wiley & Sons, Inc.