bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carrier re-sequencing reveals rare but benign variants in recessive deafness genes
Authors: He Longxia , Pang Xiuhong , Chen Penghui , Wang Xiaowen , Yang Tao , Wu Hao 
Published: September 2017

AbstractFor recessive Mendelian disorders, determining the pathogenicity of rare, non-synonymous variants in known causative genes can be challenging without expanded pedigrees and/or functional analysis. In this study, we proposed to establish a database of rare but benign variants in recessive deafness genes by systematic carrier re-sequencing. As a pilot study, 30 heterozygous carriers of pathogenic variants for deafness were identified from unaffected family members of 18 deaf probands. The entire coding regions of the corresponding genes were re-sequenced in those carriers by targeted next-generation sequencing or Sanger sequencing. A total of 32 non-synonymous variants were identified in the normal-hearing carriers in trans with the pathogenic variant and therefore were classified as benign. Among them were five rare (minor allele frequencies less than 0.005) variants that had previously undefined, disputable or even misclassified function: p.A434T (c.1300 G > A) in SLC26A4, p.R266Q (c.797 G > A) in LOXHD1, p.K96Q (c.286 A > C) in MYO15A, p.T123N (c.368 C > A) in GJB2 and p.V1299I (c.797 G > A) in CDH23. Our results suggested that large scale carrier re-sequencing may be warranted to establish a database of rare but benign variants in causative genes in order to reduce false positive genetic diagnosis of recessive Mendelian disorders.
Survivin and XIAP – two potential biological targets in follicular thyroid carcinoma
Authors: Werner Thomas A. , Dizdar Levent , Nolten Inga , Riemer Jasmin C. , Mersch Sabrina , Schütte Sina C. , Driemel Christiane , Verde Pablo E. , Raba Katharina , Topp Stefan A. , Schott Matthias , Knoefel Wolfram T. , Krieg Andreas 
Published: September 2017

AbstractFollicular thyroid carcinoma’s (FTC) overall good prognosis deteriorates if the tumour fails to retain radioactive iodine. Therefore, new druggable targets are in high demand for this subset of patients. Here, we investigated the prognostic and biological role of survivin and XIAP in FTC. Survivin and XIAP expression was investigated in 44 FTC and corresponding non-neoplastic thyroid specimens using tissue microarrays. Inhibition of both inhibitor of apoptosis proteins (IAP) was induced by shRNAs or specific small molecule antagonists and functional changes were investigated in vitro and in vivo. Survivin and XIAP were solely expressed in FTC tissue. Survivin expression correlated with an advanced tumour stage and recurrent disease. In addition, survivin proved to be an independent negative prognostic marker. Survivin or XIAP knockdown caused a significant reduction in cell viability and proliferation, activated caspase3/7 and was associated with a reduced tumour growth in vivo. IAP-targeting compounds induced a decrease of cell viability, proliferation and cell cycle activity accompanied by an increase in apoptosis. Additionally, YM155 a small molecule inhibitor of survivin expression significantly inhibited tumour growth in vivo. Both IAPs demonstrate significant functional implications in the oncogenesis of FTCs and thus prove to be viable targets in patients with advanced FTC.
Computational Cell Cycle Profiling of Cancer Cells for Prioritizing FDA-Approved Drugs with Repurposing Potential
Authors: Lo Yu-Chen , Senese Silvia , France Bryan , Gholkar Ankur A. , Damoiseaux Robert , Torres Jorge Z. 
Published: September 2017

AbstractDiscovery of first-in-class medicines for treating cancer is limited by concerns with their toxicity and safety profiles, while repurposing known drugs for new anticancer indications has become a viable alternative. Here, we have developed a new approach that utilizes cell cycle arresting patterns as unique molecular signatures for prioritizing FDA-approved drugs with repurposing potential. As proof-of-principle, we conducted large-scale cell cycle profiling of 884 FDA-approved drugs. Using cell cycle indexes that measure changes in cell cycle profile patterns upon chemical perturbation, we identified 36 compounds that inhibited cancer cell viability including 6 compounds that were previously undescribed. Further cell cycle fingerprint analysis and 3D chemical structural similarity clustering identified unexpected FDA-approved drugs that induced DNA damage, including clinically relevant microtubule destabilizers, which was confirmed experimentally via cell-based assays. Our study shows that computational cell cycle profiling can be used as an approach for prioritizing FDA-approved drugs with repurposing potential, which could aid the development of cancer therapeutics.
Broadband biphoton generation and statistics of quantum light in the UV-visible range in an AlGaN microring resonator
Authors: De Leonardis Francesco , Soref Richard A. , Soltani Mohammad , Passaro Vittorio M. N. 
Published: September 2017

AbstractWe present a physical investigation on the generation of correlated photon pairs that are broadly spaced in the ultraviolet (UV) and visible spectrum on a AlGaN/AlN integrated photonic platform which is optically transparent at these wavelengths. Using spontaneous four wave mixing (SFWM) in an AlGaN microring resonator, we show design techniques to satisfy the phase matching condition between the optical pump, the signal, and idler photon pairs, a condition which is essential and is a key hurdle when operating at short wavelength due to the strong normal dispersion of the material. Such UV-visible photon pairs are quite beneficial for interaction with qubit ions that are mostly in this wavelength range, and will enable heralding the photon-ion interaction. As a target application example, we present the systematic AlGaN microresonator design for generating signal and idler photon pairs using a blue wavelength pump, while the signal appears at the transition of ytterbium ion (171Yb+, 369.5 nm) and the idler appears in the far blue or green range. The photon pairs have minimal crosstalk to the pump power due to their broad spacing in spectral wavelength, thereby relaxing the design of on-chip integrated filters for separating pump, signal and idler.
87Sr/86Sr evidence from the epeiric Martin Ridge Basin for enhanced carbonate weathering during the Hirnantian
Authors: Hu Dongping , Zhang Xiaolin , Zhou Lian , Finney Stanley C. , Liu Yongsheng , Shen Danielle , Shen Megan , Huang Wei , Shen Yanan 
Published: September 2017

AbstractA pronounced positive δ13C excursion in the Hirnantian Age has been documented globally, reflecting large perturbations of carbon cycling in the Late Ordovician oceans. Increased organic-carbon burial or enhanced carbonate weathering during glacioeustatic sea-level regression has been proposed to account for this anomalous C-isotope excursion. To test the two competing hypotheses, we measured 87Sr/86Sr and δ13C of carbonates from the Copenhagen Canyon section in Nevada, USA. Our data reveal two rapid negative 87Sr/86Sr shifts that coincide with two prominent positive δ13C excursions and glacial advances. Numerical model simulations suggest that enhanced weathering of carbonates driven by glacio-eustatically controlled sea-level fall is required to produce the observed drops of 87Sr/86Sr and the coeval large positive δ13C excursions, possibly with or without increased organic carbon burial.
Structural insights into the Middle East respiratory syndrome coronavirus 4a protein and its dsRNA binding mechanism
Authors: Batool Maria , Shah Masaud , Patra Mahesh Chandra , Yesudhas Dhanusha , Choi Sangdun 
Published: September 2017

AbstractMiddle East respiratory syndrome coronavirus (MERS-CoV) has evolved to navigate through the sophisticated network of a host’s immune system. The immune evasion mechanism including type 1 interferon and protein kinase R-mediated antiviral stress responses has been recently attributed to the involvement of MERS-CoV protein 4a (p4a) that masks the viral dsRNA. However, the structural mechanism of how p4a recognizes and establishes contacts with dsRNA is not well explained. In this study, we report a dynamic mechanism deployed by p4a to engage the viral dsRNA and make it unavailable to the host immune system. Multiple variants of p4a-dsRNA were created and investigated through extensive molecular dynamics procedures to highlight crucial interfacial residues that may be used as potential pharmacophores for future drug development. The structural analysis revealed that p4a exhibits a typical αβββα fold structure, as found in other dsRNA-binding proteins. The α1 helix and the β1-β2 loop play a crucial role in recognizing and establishing contacts with the minor grooves of dsRNA. Further, mutational and binding free energy analyses suggested that in addition to K63 and K67, two other residues, K27 and W45, might also be crucial for p4a-dsRNA stability.
Deep sequencing reveals the first fabavirus infecting peach
Authors: He Yan , Cai Li , Zhou Lingling , Yang Zuokun , Hong Ni , Wang Guoping , Li Shifang , Xu Wenxing 
Published: September 2017

AbstractA disease causing smaller and cracked fruit affects peach [Prunus persica (L.) Batsch], resulting in significant decreases in yield and quality. In this study, peach tree leaves showing typical symptoms were subjected to deep sequencing of small RNAs for a complete survey of presumed causal viral pathogens. The results revealed two known viroids (Hop stunt viroid and Peach latent mosaic viroid), two known viruses (Apple chlorotic leaf spot trichovirus and Plum bark necrosis stem pitting-associated virus) and a novel virus provisionally named Peach leaf pitting-associated virus (PLPaV). Phylogenetic analysis based on RNA-dependent RNA polymerase placed PLPaV into a separate cluster under the genus Fabavirus in the family Secoviridae. The genome consists of two positive-sense single-stranded RNAs, i.e., RNA1 [6,357 nt, with a 48-nt poly(A) tail] and RNA2 [3,862 nt, with a 25-nt poly(A) containing two cytosines]. Biological tests of GF305 peach indicator seedlings indicated a leaf-pitting symptom rather than the smaller and cracked fruit symptoms related to virus and viroid infection. To our knowledge, this is the first report of a fabavirus infecting peach. PLPaV presents several new molecular and biological features that are absent in other fabaviruses, contributing to an overall better understanding of fabaviruses.
A novel non prophage(-like) gene-intervening element within gerE that is reconstituted during sporulation in Bacillus cereus ATCC10987
Authors: Abe Kimihiro , Shimizu Shin-ya , Tsuda Shuhei , Sato Tsutomu 
Published: September 2017

AbstractGene rearrangement is a widely-shared phenomenon in spore forming bacteria, in which prophage(-like) elements interrupting sporulation-specific genes are excised from the host genome to reconstitute the intact gene. Here, we report a novel class of gene-intervening elements, named gin, inserted in the 225 bp gerE-coding region of the B. cereus ATCC10987 genome, which generates a sporulation-specific rearrangement. gin has no phage-related genes and possesses three site-specific recombinase genes; girA, girB, and girC. We demonstrated that the gerE rearrangement occurs at the middle stage of sporulation, in which site-specific DNA recombination took place within the 9 bp consensus sequence flanking the disrupted gerE segments. Deletion analysis of gin uncovered that GirC and an additional factor, GirX, are responsible for gerE reconstitution. Involvement of GirC and GirX in DNA recombination was confirmed by an in vitro recombination assay. These results broaden the definition of the sporulation-specific gene rearrangement phenomenon: gene-intervening elements are not limited to phage DNA but may include non-viral genetic elements that carry a developmentally-regulated site-specific recombination system.
Sclerostin induced tumor growth, bone metastasis and osteolysis in breast cancer
Authors: Zhu Menghai , Liu Changzhen , Li Shifei , Zhang Shudong , Yao Qi , Song Qingkun 
Published: September 2017

AbstractBreast cancer is the second leading cause of cancer-related deaths among women worldwide. Many patients suffer from bone metastasis. Sclerostin, a key regulator of normal bone remodeling, is critically involved in osteolytic bone diseases. However, its role in breast cancer bone metastasis remains unknown. Here, we found that sclerostin was overexpressed in breast cancer tumor tissues and cell lines. Inhibition of sclerostin by antibody (Scl-Ab) significantly reduced migration and invasion of MDA-MB-231 and MCF-7 cells in a time- and dose-dependent manner. In xenograft model, sclerostin inhibition improved survival of nude mice and prevented osteolytic lesions resulting from tumor metastasis. Taken together, sclerostin promotes breast cancer cell migration, invasion and bone osteolysis. Inhibition of sclerostin may serve as an efficient strategy for interventions against breast cancer bone metastasis or osteolytic bone diseases.
Recent Advances in the Chemistry of 2-Acylaziridines
Authors: Pankova Alena , Kuznetsov Mikhail 
Published: September 2017

This review highlights recent achievements in the transformations of 2-acylaziridines toward the synthesis of cyclic and acyclic nitrogen-containing compounds. The influence of a carbonyl group on reaction selectivity is discussed.1	Introduction2	Reactions via C–C Bond Cleavage3	Reactions via C–N Bond Cleavage3.1	Reactions Starting with the Aziridine Ring Opening3.2	Reactions Starting at the Carbonyl Group4	Conclusion
Ischemic Conditioning as a Hemostatic Intervention in Surgery and Cardiac Procedures: A Systematic Review
Authors: Krag Andreas , Hvas Anne-Mette 
Published: September 2017

AbstractIschemic conditioning induced by nonlethal cycles of tissue ischemia and reperfusion attenuates ischemia–reperfusion injury. The objective of this study is to systematically review the effects of local and remote ischemic conditioning on laboratory parameters of hemostasis and the clinical outcomes of thromboembolism or bleeding in patients undergoing surgery or cardiac procedures. PubMed and Embase were searched for relevant human trials published in English between January 1, 1986, and September 7, 2016, and additional studies were identified from reference lists. Data on laboratory parameters of hemostasis, thromboembolism, and bleeding were extracted for qualitative synthesis. In total, 69 studies were included; of these, 53 were randomized controlled trials (RCTs) and 11 were meta-analyses. Local and remote ischemic conditioning reduced platelet activation in patients undergoing cardiac procedures. Local ischemic conditioning did not reduce the thromboembolic risk in patients undergoing surgery or cardiac procedures. Remote ischemic conditioning reduced the incidence of arterial thromboembolism after surgery or cardiac procedures in 3 out of 28 RCTs and 4 out of 5 meta-analyses. Local and remote ischemic conditioning did not increase operative bleeding. In conclusion, ischemic conditioning reduced platelet activity without increasing the risk of bleeding in patients undergoing surgery or cardiac procedures. Limited evidence supports the proposal that ischemic conditioning reduces the incidence of arterial thromboembolism in patients undergoing surgery or cardiac procedures.
Sutureless Microvascular Anastomosis using Intravascular Stenting and Cyanoacrylate Adhesive
Authors: Kuwabara Masahiro , Kubo Satoshi , Domoto Takashi , Aoki Shimpo , Azuma Ryuichi , Kiyosawa Tomoharu , Aizawa Tetsushi 
Published: September 2017

Background Microvascular anastomosis using cyanoacrylate adhesive has a reputation among researchers as an alternative to conventional sutures. However, a degree of ingenuity is required to avoid the collapse of the vascular lumen for the duration of the anastomosis. The aim of this study was to determine the feasibility of intravascular stenting (IVaS) as a temporary stent during sutureless microvascular anastomosis with cyanoacrylate adhesive.
Methods Sixty male Fisher 344 rats were evenly divided into two groups. The right superficial femoral arteries (RSFAs) were transected in each group. Microvascular anastomoses were then performed with the sutureless (SL) method in one group and conventional sutures (CS) in the other group. The diameter of the RSFA, duration of microvascular anastomosis, and the patency of the RSFA were evaluated immediately after anastomosis and 7 days after the surgery. Tissue samples were obtained for pathological consideration.
Results There was no significant difference in the diameter of the RSFAs between the SL and the CS groups. There was no significant difference in the patency rates of the groups. The anastomosis time of the SL group was significantly shorter than that of the CS group, regardless of the experience of the surgeons. A histological analysis showed a comparable level of foreign body reactions in each group.
Conclusion IVaS plays a supportive role in sutureless microvascular anastomosis with cyanoacrylate adhesive. The short-term safety of this technique has now been confirmed at the experimental stage.
Antibiotikabeschichtete Implantate in der Unfallchirurgie
Authors: Haubruck Patrick , Schmidmaier Gerhard 
Published: September 2017

ZusammenfassungPerioperative implantatassoziierte Infektionen stellen eine schwerwiegende Komplikation für betroffene Patienten dar, welche die Therapie prolongiert und große sozioökonomische Auswirkung haben kann. Trotz moderner Therapieoptionen und aufwendigen Bestrebungen, neue Therapien zu etablieren, verbleibt eine Inzidenz zwischen 1% nach Niedrigenergietraumata und bspw. 30% nach komplexen offenen Tibiafrakturen. Insbesondere offene Frakturen stellen ein hohes perioperatives Infektionsrisiko dar. Bis zu 60% dieser Frakturen sind bereits initial bakteriell kontaminiert. Die Therapie implantatassoziierter Infektionen ist häufig schwierig, daher sind effektive Präventionsmaßnahmen sinnvoll. Eine vielversprechende Option stellen hierbei mit Antibiotika beschichtete Implantate dar. In den letzten Jahren konnte erfolgreich eine Poly-D,L-Lactid- und Gentamycinbeschichtung für intramedulläre Implantate entwickelt und in die Klinik eingeführt werden. Erste In-vivo-Studien zeigten eine protektive Wirkung der Beschichtung auf Implantatbesiedelung. Weiterhin zeigten Studien ein vorteilhaftes Freisetzungsprofil des Gentamycins mit hoher initialer Freisetzung und effektiven lokalen Konzentrationen des Wirkstoffs. Die Ergebnisse der tierexperimentellen, In-vitro- und ersten klinischen Studien führten zur Entwicklung der ersten zugelassenen Implantate, die eine Beschichtung mit Antibiotika aufwiesen: Der „Unreamed Tibia Nail“ (UTN) PROtect™ (DepuySynthes, Johnson/Johnson Company, Inc New Jersey, USA), der im August 2005 die CE-Zulassung erhielt, und dessen Nachfolger, der Expert Tibia Nail (ETN) PROtect™, welches das aktuell einzige zur Verfügung stehende mit Antibiotikum beschichtete Implantat in der Frakturversorgung ist. Klinische Studien bestätigten die Effizienz der beschichteten Implantate zur Prävention von implantatassoziierten Infektionen vor allem bei Hochrisikopatienten. Die Verwendung des ETN PROtect sowohl bei frischen Frakturen als auch in Revisionsfällen kann das Auftreten von implantatassoziierten Infektionen und Osteomyelitis verhindern ohne gentamycinassoziierte Nebenwirkungen hervorzurufen. Antimikrobiell beschichtete Implantate stellen daher eine vielversprechende Option dar, implantatassoziierte Infektionen zu verhindern und damit die Komplikationsrate insgesamt zu reduzieren.
Family Functioning, Medical Self-Management, and Health Outcomes Among School-Aged Children With Sickle Cell Disease: A Mediation Model
Authors: Psihogios Alexandra M , Daniel Lauren C , Tarazi Reem , Smith-Whitley Kim , Patterson Chavis A , Barakat Lamia P 
Published: September 2017

AbstractBackgroundInformed by the Pediatric Self-Management Model, the present study tested relationships between parent and family functioning, sickle cell disease (SCD) self-management, and health outcomes for children with SCD.Method83 children with SCD and a parent completed baseline data as part of a larger investigation of a family-based, problem-solving intervention for children with SCD (M age = 8.47). Youth and parents completed a measure of child health-related quality of life (HRQOL), and parents completed measures of family efficacy, parenting stress, and SCD self-management. SCD pain episodes and urgent health utilization information over the past year were obtained via medical chart review.ResultsSCD self-management mediated the relationship between parent-reported family efficacy and parent proxy HRQOL, as well as the relationship between parenting stress and child and parent proxy HRQOL. Mediation models were nonsignificant for outcomes beyond HRQOL, including SCD pain episodes and urgent health utilization.ConclusionFostering family efficacy and reducing parenting stress may be meaningful intervention targets for improving SCD self-management and child HRQOL among school-aged children. Although findings were consistent with the Pediatric Self-Management Model in terms of HRQOL, the model was not supported for pain episodes or urgent health utilization, highlighting the need for multi-method, longitudinal research on the SCD self-management behaviors that are linked to preventable health outcomes.
Modelling the ArH+ emission from the Crab nebula
Authors: Priestley F. D. , Barlow M. J. , Viti S. 
Published: September 2017

Abstract
We have performed combined photoionization and photodissociation region (PDR) modelling of a Crab nebula filament subjected to the synchrotron radiation from the central pulsar wind nebula, and to a high flux of charged particles; a greatly enhanced cosmic-ray ionization rate over the standard interstellar value, ζ0, is required to account for the lack of detected [C i] emission in published Herschel SPIRE FTS observations of the Crab nebula. The observed line surface brightness ratios of the OH+ and ArH+ transitions seen in the SPIRE FTS frequency range can only be explained with both a high cosmic-ray ionization rate and a reduced ArH+ dissociative recombination rate compared to that used by previous authors, although consistent with experimental upper limits. We find that the ArH+/OH+ line strengths and the observed H2 vibration–rotation emission can be reproduced by model filaments with nH = 2 × 104 cm−3, ζ = 107ζ0 and visual extinctions within the range found for dusty globules in the Crab nebula, although far-infrared emission from [O i] and [C ii] is higher than the observational constraints. Models with nH = 1900 cm−3 underpredict the H2 surface brightness, but agree with the ArH+ and OH+ surface brightnesses and predict [O i] and [C ii] line ratios consistent with observations. These models predict HeH+ rotational emission above detection thresholds, but consideration of the formation time-scale suggests that the abundance of this molecule in the Crab nebula should be lower than the equilibrium values obtained in our analysis.
Britain and Ireland
Authors: Avis Paul 
Published: September 2017

Abstract
This chapter begins by noting the contribution of British ecumenists to the ecumenical movement and then proceeds to survey the ecumenical scene in Britain and Ireland against the political and constitutional background of the United Kingdom—comprising England, Scotland, Wales, and Northern Ireland—and the separate jurisdiction of the Republic of Ireland. It notes the favourable ecumenical climate in England and Wales and goes on to outline local ecumenical relationships, including Local Ecumenical Partnerships, the ecumenical instruments for each nation and for all four, and various forms of cooperation at the national level. The chapter then turns to examples of theological dialogue, proposals for closer unity, and the problems of their reception and implementation, with a particular focus on the Anglican-Methodist Covenant.