bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thioamide‐Bridged Nucleic Acid (thioAmNA) Containing Thymine or 2‐Thiothymine: Duplex‐Forming Ability, Base Discrimination, and Enzymatic Stability
Authors: Habuchi Takaki , Yamaguchi Takao , Obika Satoshi 
Published: December 2018

AbstractOligonucleotides containing bridged nucleic acids (BNAs) show high duplex‐forming ability towards target single‐stranded RNA, so many BNAs have been developed for antisense applications. Amide‐bridged nucleic acids (AmNAs), which are BNA analogues bearing an amide bond at the bridge, exhibit high duplex‐forming ability, enzymatic stability, and antisense activity; thus, the AmNA motif represents a promising BNA scaffold. The high enzymatic stability of the AmNA motif is presumably attributable to the bulky amide structure, because it inhibits the access of nucleases to the phosphodiester linkage. Here, to improve enzymatic stability further, we designed thioAmNAs: thioamide‐bridged nucleotides that have a bulkier bridge structure than AmNA. The synthesis of thioAmNAs bearing either thymine (thioAmNA‐T) or 2‐thiothymine (thioAmNA‐S2T) bases was successful, and the obtained monomers were introduced into designed oligonucleotides without noticeable by‐product generation. The thioAmNA‐T‐ and thioAmNA‐S2T‐modified oligonucleotides showed strong binding affinity toward complementary single‐stranded RNA, with the thioAmNA‐S2T‐modified oligonucleotide displaying excellent base‐discrimination capability. Moreover, both thioAmNA‐T and thioAmNA‐S2T endowed oligonucleotides with higher resistance to enzymatic degradation than AmNA‐T. These results indicate that thioAmNAs are potentially useful chemical modifications for oligonucleotide‐based therapeutics.
Chirality Dependence of Amyloid β Cellular Uptake and a New Mechanistic Perspective
Authors: Dutta Subrata , Finn Thomas S. , Kuhn Ariel J. , Abrams Benjamin , Raskatov Jevgenij A. 
Published: December 2018

AbstractAmyloid β is an inherently disordered peptide that can form diverse neurotoxic aggregates, and its 42‐amino‐acid isoform is believed to be the agent responsible for Alzheimer's disease (AD). Cellular uptake of the peptide is a pivotal step for it to be able to exert many of its toxic actions. The cellular uptake process is complex, and numerous competing internalization pathways have been proposed. To date, it remains unclear which of the uptake mechanisms are particularly important for the overall process, and improvement of this understanding is needed, so that better molecular AD therapeutics can be designed. Chirality can be used as a unique tool to study this process, because some of the proposed mechanisms are expected to proceed in stereoselective fashion, whereas others are not. To shed light on this important issue, we synthesized fluorescently labeled enantiomers of amyloid β and quantified their cellular uptake, finding that uptake occurs in stereoselective fashion, with a typical preference for the l stereoisomer of ≈5:1. This suggests that the process is predominantly receptor‐mediated, with likely minor contributions of non‐stereoselective mechanisms.
TiS2 Monolayer as an Emerging Ultrathin Bifunctional Catalyst: Influence of Defects and Functionalization
Authors: Das Tisita , Chakraborty Sudip , Ahuja Rajeev , Das Gour P. 
Published: December 2018

AbstractWe have envisaged the hydrogen evolution and oxygen evolution reactions (HER and OER) on a two‐dimensional (2D) noble‐metal‐free titanium disulfide (TiS2) monolayer, which belongs to the exciting family of transition metal dichalcogenides (TMDCs). Our theoretical investigation to probe the HER and OER on both the H and T phases of 2D TiS2 is based on electronic‐structure calculations witihin the framework of density functional theory (DFT). Since TiS2 is the lightest compound among the group‐IV TMDCs, it is worth exploring the catalytic activity of a TiS2 monolayer through the functionalization at the anion (S) site, substituting with P, N, and C dopants as well as by incorporating single sulfur vacancy defects. We have investigated the effect of functionalization and vacancy defects on the structural, electronic, and optical response of a TiS2 monolayer by determining the density of states, work‐function, and optical absorption spectra. We have determined the HER and OER activities for the functionalized and defective TiS2 monolayers based on the reaction coordinate, which can be constructed from the adsorption free energies of the intermediates (H*, O*, OH* and OOH*, where * denotes the adosrbed state) in the HER and OER mechanisms. Finally, we have shown that TiS2 monolayers are emerging as a promising material for the HER and OER mechanisms under the influence of functionalization and defects.
First‐Principles Study of Aziridinium Lead Iodide Perovskite for Photovoltaics
Authors: Teng Qiang , Shi Tingting , Zhao Yu‐Jun 
Published: December 2018

AbstractThe long‐term stability remains one of the main challenges for the commercialization of the rapidly developing hybrid organic‐inorganic perovskite solar cells. Herein, we investigate the electronic and optical properties of the recently reported hybrid halide perovskite (CH2)2NH2PbI3 (AZPbI3), which exhibits a much better stability than the popular halide perovskites CH3NH3PbI3 and HC(NH2)2PbI3, by using density functional theory (DFT). We find that AZPbI3 possesses a band gap of 1.31 eV, ideal for single‐junction solar cells, and its optical absorption is comparable with those of the popular CH3NH3PbI3 and HC(NH2)2PbI3 materials in the whole visible‐light region. In addition, the conductivity of AZPbI3 can be tuned from efficient p‐type to n‐type, depending on the growth conditions. Besides, the charge‐carrier mobilities and lifetimes are unlikely hampered by deep transition energy levels, which have higher formation energies in AZPbI3 according to our calculations. Overall, we suggest that the perovskite AZPbI3 is an excellent candidate as a stable high‐performance photovoltaic absorber material.
Anxiety and exploratory behavior in the African striped mouse, Rhabdomys, taxa are partially modified by the physical rearing environment
Authors: Mackay Megan K. , Pillay Neville 
Published: December 2018

AbstractThe environment may modulate genetic influences on behavioral expression. We investigated whether the physical rearing environment modulates anxiety and exploratory behavior in four populations, representing three species, of the striped mouse Rhabdomys. One population originated from an arid, open habitat and the others from grassy, covered habitats, and two species occurred in sympatry. We raised captive individuals of all populations in treatments that simulated cover or no cover for two generations and investigated the behavior of resulting adults in an open‐field, light–dark and startle response tests. We expected that, when raised without cover, the arid population would be less anxious and more exploratory than grassland populations, but found the opposite in the open‐field test only. We also expected that all individuals would be anxious and less exploratory when raised under cover, which was the case for anxiety in a light–dark test, but individuals from the no cover treatment were more anxious in the open‐field test. Only one population × treatment interaction was detected in which the arid population was least exploratory. Therefore, the physical rearing environment had less of an influence than phylogeny on the development of anxiety and exploration in Rhabdomys.
Standing geographic variation in eclosion time and the genomics of host race formation inRhagoletis pomonellafruit flies
Authors: Doellman Meredith M. , Egan Scott P. , Ragland Gregory J. , Meyers Peter J. , Hood Glen R. , Powell Thomas H. Q. , Lazorchak Peter , Hahn Daniel A. , Berlocher Stewart H. , Nosil Patrik , Feder Jeffrey L. 
Published: December 2018

AbstractTaxa harboring high levels of standing variation may be more likely to adapt to rapid environmental shifts and experience ecological speciation. Here, we characterize geographic and host‐related differentiation for 10,241 single nucleotide polymorphisms inRhagoletis pomonellafruit flies to infer whether standing genetic variation in adult eclosion time in the ancestral hawthorn (Crataegusspp.)‐infesting host race, as opposed to new mutations, contributed substantially to its recent shift to earlier fruiting apple (Malus domestica). Allele frequency differences associated with early vs. late eclosion time within each host race were significantly related to geographic genetic variation and host race differentiation across four sites, arrayed from north to south along a 430‐km transect, where the host races co‐occur in sympatry in the Midwest United States. Host fruiting phenology is clinal, with both apple and hawthorn trees fruiting earlier in the North and later in the South. Thus, we expected alleles associated with earlier eclosion to be at higher frequencies in northern populations. This pattern was observed in the hawthorn race across all four populations; however, allele frequency patterns in the apple race were more complex. Despite the generally earlier eclosion timing of apple flies and corresponding apple fruiting phenology, alleles on chromosomes 2 and 3 associated with earlier emergence were paradoxically at lower frequency in the apple than hawthorn host race across all four sympatric sites. However, loci on chromosome 1 did show higher frequencies of early eclosion‐associated alleles in the apple than hawthorn host race at the two southern sites, potentially accounting for their earlier eclosion phenotype. Thus, although extensive clinal genetic variation in the ancestral hawthorn race exists and contributed to the host shift to apple, further study is needed to resolve details of how this standing variation was selected to generate earlier eclosing apple fly populations in the North.
Reaction of a polar gravel‐spit system to atmospheric warming and glacier retreat as reflected by morphology and internal sediment geometries (South Shetland Islands, Antarctica)
Authors: Heredia Barión Pablo , Lindhorst Sebastian , Schutter Ilona , Falk Ulrike , Kuhn Gerhard 
Published: December 2018

AbstractSedimentary architecture and morphogenetic evolution of a polar bay‐mouth gravel‐spit system are revealed based on topographic mapping, sedimentological data, radiocarbon dating and ground‐penetrating radar investigations. Data document variable rates of spit progradation in reaction to atmospheric warming synchronous to the termination of the last glacial re‐advance (LGR, 0.45–0.25 ka BP), the southern hemisphere equivalent of the Little Ice Age cooling period. Results show an interruption of spit progradation that coincides with the proposed onset of accelerated isostatic rebound in reaction to glacier retreat. Spit growth resumed in the late 19th century after the rate of isostatic rebound decreased, and continues until today. The direction of modern spit progradation, however, is rotated northwards compared with the growth axis of the early post‐LGR spit. This is interpreted to reflect the shift and strengthening in the regional wind field during the last century. A new concept for the interplay of polar gravel‐spit progradation and glacio‐isostatic adjustment is presented, allowing for the prediction of future coastal evolution in comparable polar settings. © 2018 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd.
Receptor tyrosine kinase MET as potential target of multi‐kinase inhibitor and radiosensitizer sorafenib in HNSCC
Authors: Beizaei Kaweh , Gleißner Lisa , Hoffer Konstantin , Bußmann Lara , Vu Anh Thu , Steinmeister Leonhard , Laban Simon , Möckelmann Nikolaus , Münscher Adrian , Petersen Cordula , Rothkamm Kai , Kriegs Malte 
Published: December 2018

AbstractBackgroundThe multi‐kinase inhibitor sorafenib displays antitumoral effects in head and neck squamous cell carcinoma (HNSCC); however, the targeted kinases are unknown. Here we aimed to identify those kinases to determine the mechanism of sorafenib‐mediated effects and establish candidate biomarkers for patient stratification.MethodsThe effects of sorafenib and MET inhibitors crizotinib and SU11274 were analyzed using a slide‐based antibody array, Western blotting, proliferation, and survival assays. X‐rays were used for irradiations.ResultsSorafenib inhibited auto‐phosphorylation of epidermal growth factor receptor and MET, which has not been described previously. MET expression in HNSCC cells was not always associated with activity/phosphorylation. Furthermore, sorafenib‐dependent cell kill and radiosensitization was not associated with MET level. Although MET inhibitors blocked proliferation, they caused only mild cytotoxicity and no radiosensitization.ConclusionWe identified MET as a new potential target of sorafenib. However, MET inhibition is not the cause for sorafenib‐mediated cytotoxicity or radiosensitization.
Masticatory function and related factors after oral oncological treatment: A 5‐year prospective study
Authors: de Groot Reilly J. , Wetzels Jan‐Willem , Merkx Matthias A.W. , Rosenberg Antoine J.W.P. , de Haan Anton F.J. , van der Bilt Andries , Abbink Jan H. , Speksnijder Caroline M. 
Published: December 2018

AbstractBackgroundChewing ability is often compromised in patients with oral cancer. The aim of this study was to identify which factors affect masticatory performance in these patients.MethodsPatients with primary oral cancer were assessed for up to 5 years after primary treatment. Healthy controls were assessed once. A mixed‐model analysis was performed, with masticatory performance as outcome measure.ResultsA total of 123 patients were included in the study. Factors positively associated with masticatory performance were number of occlusal units (OU), having functional dentures, and maximum mouth opening (MMO). The impact of tumor location and maximum bite force (MBF) differed per assessment moment. Masticatory performance declined for up to 1 year but recovered at 5 years after treatment.ConclusionMasticatory performance in patients treated for oral cancer is affected by MBF, MMO, number of OU, and dental status. These should be the focus of posttreatment therapy.
Regression of human immunodeficiency virus‐associated oral Kaposi sarcoma with combined antiretroviral therapy: A case report and literature review
Authors: Franco Juliana Bertoldi , Maureira Pena Loreto José , Martins e Martins Fabiana , de Oliveira Marcio Augusto , Ortega Karem L. 
Published: December 2018

AbstractBackgroundKaposi's sarcoma (KS) is the most prevalent malignant neoplasia in human immunodeficiency virus positive (HIV+) patients for which the primary mode of management was chemotherapy.MethodsWe have presented the case of a newly diagnosed HIV+ male patient who was diagnosed with a pedunculated nodule in the anterior region of the hard palate, measuring 3.5 cm in diameter and with 2 months of evolution.ResultsHistopathological examination confirmed the clinical hypothesis of KS. Soon after the diagnosis, the patient started using combined antiretroviral therapy (Biovir and Kaletra), presenting a significant reduction of the lesion after 4 weeks. With 1.5 cm in diameter, the lesion was surgically removed. The patient was followed‐up for 10 years without any recurrence.ConclusionIn antiretroviral‐naive patients with a well‐preserved immune system, the use of cART may be efficient in reducing the progression of the KS lesions, thus avoiding the use of chemotherapeutic agents.
Three prognostic indexes as predictors of response to adjuvant chemoradiotherapy in patients with oral squamous cell carcinoma after radical surgery: A large‐scale prospective study
Authors: Chen Fa , Lin Lisong , Liu Fengqiong , Yan Lingjun , Qiu Yu , Wang Jing , Hu Zhijian , Wu Junfeng , Bao Xiaodan , Lin Liangkun , Wang Rui , Cai Lin , He Baochang 
Published: December 2018

AbstractBackgroundTo develop and validate practical prognostic indexes (PIs) for predicting the prognosis and response to postoperative adjuvant therapy in patients with oral squamous cell carcinoma (OSCC).MethodsA large cohort of 1071 OSCC patients were randomized to either training set (N = 708) or validation set (N = 363). Three types of PIs were developed according to the nomogram scores, β coefficients and excess hazard ratios, respectively. Restricted cubic spline was used to demonstrate the relationship between PIs and the risks of death.ResultsFirst, a nomogram was developed incorporating age at diagnosis, smoking status, clinical stage, tumor differentiation, lymph node status, comorbidity, and neutrophil to lymphocyte ratio levels. Then, three PIs were established with high survival predictive ability, and were superior to AJCC staging system (all P < .05). The risks of death were escalated continuously with the increasing number of PIs. Interestingly, adjuvant chemoradiotherapy was positively associated with poor overall survival in patients with low PIs, but exerted a beneficial effect on patients with high PIs.ConclusionCombined nomogram with further established PIs not only predicts the survival probability of OSCC patients, but also continuously quantifies the risk of death. High PIs could predict a beneficial response to adjuvant chemoradiotherapy, whereas low PIs indicate an unfavorable response.
Radiographic nodal prognostic factors in stage I HPV‐related oropharyngeal squamous cell carcinoma
Authors: Bhattasali Onita , Thompson Lester D. R. , Schumacher Andrew J. , Iganej Shawn 
Published: December 2018

AbstractBackgroundThe updated AJCC Cancer Staging Manual groups all p16‐positive oropharyngeal squamous cell carcinoma (OPSCC) with unilateral nodal involvement within 6 cm into the new clinical N1 classification, consolidating a heterogeneous group of disease with varying radiographic findings.MethodsA central radiological review was conducted identifying 233 patients with stage I node‐positive (cT1‐2N1) disease who underwent definitive concurrent chemoradiation. Factors evaluated included lymph node size, low‐neck lymphadenopathy, retropharyngeal lymphadenopathy, overt radiographic extracapsular extension, and matted lymphadenopathy.ResultsOn multivariate analysis adjusted for age, smoking history, and chemotherapy regimen, low‐neck lymphadenopathy (hazard ratio (HR) = 6.55; P < .001) and retropharyngeal lymphadenopathy (HR = 3.36; P = .009) predicted for inferior progression‐free survival (PFS). low‐neck lymphadenopathy (HR = 6.38; P = .001) and retropharyngeal lymphadenopathy (HR = 3.32; P = .02) also predicted for inferior overall survival (OS). All other radiographic characteristics showed no prognostic impact for PFS or OS.ConclusionsThis analysis suggests that caution should be advised against de‐intensification efforts among patients with stage I node‐positive p16‐positive OPSCC with low‐neck lymphadenopathy or retropharyngeal lymphadenopathy.
Expression of CD44, EGFR, p16, and their mutual combinations in patients with head and neck cancer: Impact on outcomes of intensity‐modulated radiation therapy
Authors: Slavik Marek , Shatokhina Tetiana , Sana Jiri , Ahmad Parwez , Kazda Tomas , Selingerova Iveta , Hermanova Marketa , Cervena Renata , Novotny Tomas , Burkon Petr , Smilek Pavel , Horakova Zuzana , Slampa Pavel , Slaby Ondrej 
Published: December 2018

AbstractBackgroundProgress in radiation treatment of head and neck squamous cell carcinoma (HNSCC) deserves the studies focused on molecular predictors that would help to enhance individually tailored treatment.Methodsp16/epidermal growth factor receptor (EGFR)/cluster of differentiation‐44 (CD44) was immunohistochemically analyzed in 165 HNSCC patients.ResultsIn the entire group and the p16 negative cohort, better 3‐year overall survival and locoregional control correlated with p16 positivity, CD44, and EGFR negativity were observed. Combined analysis revealed the worst results in the CD44+/p16−, EGFR+/p16−, and EGFR+/CD44+ groups and in the EGFR+/CD44+ within p16 negative cohort. Multivariate analysis found tumor stage, Karnofsky index, p16, and CD44 as prognostic factors of overall survival and clinical stage, and p16 as a prognostic factor for locoregional control. Clinical stage and Karnofsky index affected overall survival and tumor stage. EGFR affected locoregional control in the p16 negative subgroup.ConclusionOur study confirmed the negative effect of CD44 and EGFR and the positive effect of p16 on radiotherapy results.
Neonatal McCune‐Albright Syndrome: A Unique Syndromic Profile With an Unfavorable Outcome
Authors: Corsi Alessandro , Cherman Natasha , Donaldson David L , Robey Pamela G , Collins Michael T , Riminucci Mara 
Published: December 2018

ABSTRACTSomatic gain‐of‐function mutations of GNAS cause a spectrum of clinical phenotypes, ranging from McCune‐Albright syndrome (MAS) to isolated disease of bone, endocrine glands, and more rarely, other organs. In MAS, a syndrome classically characterized by polyostotic fibrous dysplasia (FD), café‐au‐lait (CAL) skin spots, and precocious puberty, the heterogenity of organ involvement, age of onset, and clinical severity of the disease are thought to reflect the variable size and the random distribution of the mutated cell clone arising from the postzygotic mutation. We report a case of neonatal MAS with hypercortisolism and cholestatic hepatobiliary dysfunction in which bone changes indirectly emanating from the disease genotype, and distinct from FD, led to a fatal outcome. Pulmonary embolism of marrow and bone fragments secondary to rib fractures was the immediate cause of death. Ribs, and all other skeletal segments, were free of changes of typical FD and fractures appeared to be the result of a mild‐to‐moderate degree of osteopenia. The mutated allele was abundant in the adrenal glands and liver, but not in skin, muscle, and fractured ribs, where it could only be demonstrated using a much more sensitive PNA hybridization probe‐based FRET (Förster resonance energy transfer) technique. Histologically, bilateral adrenal hyperplasia and cholestatic disease matched the abundant disease genotype in the adrenals and liver. Based on this case and other sporadic reports, it appears that gain‐of‐function mutations of GNAS underlie a unique syndromic profile in neonates characterized by CAL skin spots, hypercortisolism, hyperthyroidism, hepatic and cardiac dysfunction, and an absence (or latency) of FD, often with a lethal outcome. Taken together, our and previous cases highlight the phenotypic severity and the diagnostic and therapeutic challenges of MAS in neonates. Furthermore, our case specifically points out how secondary bone changes, unrelated to the direct impact of the mutation, may contribute to the unfavorable outcome of very early‐onset MAS. © 2018 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
The role of lncRNAs in signaling pathway implicated in CC
Authors: Yang Min , Wang Min , Li Xianping , Xie Yixin , Xia Xiaomeng , Tian Jingjing , Zhang Kan , Tang Aiguo 
Published: December 2018

AbstractCervical cancer (CC) is the second most common malignancy in females. Owing to poor diagnosis, resistance to the systemic therapies, and high recurrence rate, patients with CC have a relatively poor prognosis. The role of a signaling pathway in CC has always been the focus among worldwide researchers. As reported before, aberrant expression of proteins associated with signaling pathways, such as phosphatidylinositol 3‐kinase(PI3K), EGF‐R, β‐catenin, and Erk and Bcl‐2 was discovered in CC. Therefore, aberrant molecular signaling pathways are significant parts of cervical carcinogenesis. Recently discovered long noncoding RNAs (lncRNAs) as a new regulator player of molecular biology in CC have always been reported. In this review, we highlighted the role of lncRNA in signaling pathway implicated in CC and outlined the molecular mechanism of lncRNA in it. All of these present an opportunity for developing diagnosis and therapies against CC.