bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemopreventive effects of Strobilanthes crispus leaf extract on azoxymethane-induced aberrant crypt foci in rat colon
Authors: Al-Henhena Nawal , Khalifa Shaden A. M. , Ying Rozaida Poh Yuen , Hassandarvish Pouya , Rouhollahi Elham , Al-Wajeeh Nahla Saeed , Ali Habibah Mohd , Abdulla Mahmood Ameen , El-Seedi Hesham R. 
Published: August 2015

AbstractIn this work, microscopic and histological studies suggest that Strobilanthes crispus ethanol extract reduce azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. S. crispus is considered a traditional medicine and used as an antioxidant. Its leaf contains a large amount of phenolic compounds to which its radical scavenging role is attributed and enhance its ability to eradicate oxidative stress reactions. The study was designed to determine the chemopreventive effect of S. crispus ethanol extract in vivo and in vitro by elucidating the effect of the extract on intermediate biomarkers which can be used as effective predictors of colon cancer. S. crispus was analyzed for DPPH free radical scavenging, nitric oxide (NO) and ferric acid reduction. The results indicated that S. crispus oral administration significantly inhibited colorectal carcinogenesis induced by AOM as revealed by the reduction in the number of ACF. S. crispus down-regulated the expression of PCNA, Bcl2 and β-catenin. Additionally, it exerted a pronounced inhibitory effect on MDA and NO levels and stimulatory effect on CAT and GPx activities. These results demonstrate that S. crispus is a chemopreventive agent for colorectal cancer through the suppression of early and intermediate carcinogenic phases that may be related to its flavonoid content.
Tailoring the Two Dimensional Electron Gas at Polar ABO3/SrTiO3 Interfaces for Oxide Electronics
Authors: Li Changjian , Liu Zhiqi , Lü Weiming , Wang Xiao Renshaw , Annadi Anil , Huang Zhen , Zeng Shengwei , Ariando  , Venkatesan T. 
Published: August 2015

AbstractThe 2D electron gas at the polar/non-polar oxide interface has become an important platform for several novel oxide electronic devices. In this paper, the transport properties of a wide range of polar perovskite oxide ABO3/SrTiO3 (STO) interfaces, where ABO3 includes LaAlO3, PrAlO3, NdAlO3, NdGaO3 and LaGaO3 in both crystalline and amorphous forms, were investigated. A robust 4 unit cell (uc) critical thickness for metal insulator transition was observed for crystalline polar layer/STO interface while the critical thickness for amorphous ones was strongly dependent on the B site atom and its oxygen affinity. For the crystalline interfaces, a sharp transition to the metallic state (i.e. polarization catastrophe induced 2D electron gas only) occurs at a growth temperature of 515 °C which corresponds to a critical relative crystallinity of ~70 ± 10% of the LaAlO3 overlayer. This temperature is generally lower than the metal silicide formation temperature and thus offers a route to integrate oxide heterojunction based devices on silicon.
MSIseq: Software for Assessing Microsatellite Instability from Catalogs of Somatic Mutations
Authors: Ni Huang Mi , McPherson John R. , Cutcutache Ioana , Teh Bin Tean , Tan Patrick , Rozen Steven G. 
Published: August 2015

AbstractMicrosatellite instability (MSI) is a form of hypermutation that occurs in some tumors due to defects in cellular DNA mismatch repair. MSI is characterized by frequent somatic mutations (i.e., cancer-specific mutations) that change the length of simple repeats (e.g., AAAAA…., GATAGATAGATA...). Clinical MSI tests evaluate the lengths of a handful of simple repeat sites, while next-generation sequencing can assay many more sites and offers a much more complete view of their somatic mutation frequencies. Using somatic mutation data from the exomes of a 361-tumor training set, we developed classifiers to determine MSI status based on four machine-learning frameworks. All frameworks had high accuracy and after choosing one we determined that it had >98% concordance with clinical tests in a separate 163-tumor test set. Furthermore, this classifier retained high concordance even when classifying tumors based on subsets of whole-exome data. We have released a CRAN R package, MSIseq, based on this classifier. MSIseq is faster and simpler to use than software that requires large files of aligned sequenced reads. MSIseq will be useful for genomic studies in which clinical MSI test results are unavailable and for detecting possible misclassifications by clinical tests.
A distinct three-helix centipede toxin SSD609 inhibits Iks channels by interacting with the KCNE1 auxiliary subunit
Authors: Sun Peibei , Wu Fangming , Wen Ming , Yang Xingwang , Wang Chenyang , Li Yiming , He Shufang , Zhang Longhua , Zhang Yun , Tian Changlin 
Published: August 2015

AbstractKCNE1 is a single-span transmembrane auxiliary protein that modulates the voltage-gated potassium channel KCNQ1. The KCNQ1/KCNE1 complex in cardiomyocytes exhibited slow activated potassium (Iks) currents. Recently, a novel 47-residue polypeptide toxin SSD609 was purified from Scolopendra subspinipes dehaani venom and showed Iks current inhibition. Here, chemically synthesized SSD609 was shown to exert Iks inhibition in extracted guinea pig cardiomyocytes and KCNQ1/KCNE1 current attenuation in CHO cells. The K+ current attenuation of SSD609 showed decent selectivity among different auxiliary subunits. Solution nuclear magnetic resonance analysis of SSD609 revealed a distinctive three-helix conformation that was stabilized by a new disulfide bonding pattern as well as segregated surface charge distribution. Structure-activity studies demonstrated that negatively charged Glu19 in the amphipathic extracellular helix of KCNE1 was the key residue that interacted with SSD609. The distinctive three-helix centipede toxin SSD609 is known to be the first polypeptide toxin acting on channel auxiliary subunit KCNE1, which suggests a new type of pharmacological regulation for ion channels in cardiomyocytes.
The exosome controls alternative splicing by mediating the gene expression and assembly of the spliceosome complex
Authors: Zhang Lin , Wan Yufeng , Huang Guobin , Wang Dongni , Yu Xinyang , Huang Guocun , Guo Jinhu 
Published: August 2015

AbstractThe exosome is a complex with exoribonuclease activity that regulates RNA surveillance and turnover. The exosome also plays a role in regulating the degradation of precursor mRNAs to maintain the expression of splicing variants. InNeurospora, the silencing ofrrp44, which encodes the catalytic subunit of the exosome, changed the expression of a set of spliceosomal snRNA, snRNP genes and SR protein related genes. The knockdown ofrrp44also affected the assembly of the spliceosome. RNA-seq analysis revealed a global change in bulk splicing events. Exosome-mediated splicing may regulate alternative splicing of NCU05290, NCU07421 and the circadian clock genefrequency(frq). The knockdown ofrrp44led to an increased ratio of splicing variants without intron 6 (I-6) and shorter protein isoform small FRQ (s-FRQ) as a consequence. These findings suggest that the exosome controls splicing events by regulating the degradation of precursor mRNAs and the gene expression, assembly and function of the spliceosome.
A novel olfactory pathway is essential for fast and efficient blood-feeding in mosquitoes
Authors: Won Jung Je , Baeck Seung-Jae , Perumalsamy Haribalan , Hansson Bill S. , Ahn Young-Joon , Kwon Hyung Wook 
Published: August 2015

AbstractIn mosquitoes, precise and efficient finding of a host animal is crucial for survival. One of the poorly understood aspects of mosquito blood-feeding behavior is how these insects target an optimal site in order to penetrate the skin and blood vessels without alerting the host animal. Here we provide new findings that a piercing structure of the mouthpart of the mosquitoes, the stylet, is an essential apparatus for the stage in blood feeding. Indeed, the stylet possesses a number of sensory hairs located at the tip of the stylet. These hairs house olfactory receptor neurons that express two conventional olfactory receptors ofAedes aegypti(AaOrs), AaOr8 and AaOr49, together with the odorant co-receptor (AaOrco).In vivocalcium imaging using transfected cell lines demonstrated that AaOr8 and AaOr49 were activated by volatile compounds present in blood. Inhibition of gene expression of these AaOrs delayed blood feeding behaviors of the mosquito. Taken together, we identified olfactory receptor neurons in the stylet involved in mosquito blood feeding behaviors, which in turn indicates that olfactory perception in the stylet is necessary and sufficient for mosquitoes to find host blood in order to rapidly acquire blood meals from a host animal.
Long noncoding RNA FER1L4 suppresses cancer cell growth by acting as a competing endogenous RNA and regulating PTEN expression
Authors: Xia Tian , Chen Shengcan , Jiang Zhen , Shao Yongfu , Jiang Xiaoming , Li Peifei , Xiao Bingxiu , Guo Junming 
Published: August 2015

AbstractAberrantly expressed long noncoding RNAs (lncRNAs) are associated with various cancers. However, the roles of lncRNAs in the pathogenesis of most cancers are unclear. Here, we report that the lncRNA FER1L4 (fer-1-like family member 4, pseudogene) acts as a competing endogenous RNA (ceRNA) to regulate the expression of PTEN (a well-known tumor suppressor gene) by taking up miR-106a-5p in gastric cancer. We observed that FER1L4 was downregulated in gastric cancer and that its level corresponded with that of PTEN mRNA. Both FER1L4 and PTEN mRNA were targets of miR-106a-5p. Further experiments demonstrated that FER1L4 downregulation liberates miR-106a-5p and decreases the abundances of PTEN mRNA and protein. More importantly, FER1L4 downregulation accelerated cell proliferation by promoting the G0/G1 to S phase transition. We conclude that one mechanism by which lncRNAs function in in tumorigenesis is as ceRNAs for tumor suppressor mRNAs.
Identification of gene mutation in patients with osteogenesis imperfect using high resolution melting analysis
Authors: Wang Jianhai , Ren Xiuzhi , Bai Xue , Zhang Tianke , Wang Yi , Li Keqiu , Li Guang 
Published: August 2015

AbstractOsteogenesis imperfecta (OI), a congenital bone disorder, is caused by mutations in COL1A1 and COL1A2 genes, leading to deficiency of type I collagen. The high resolution melting (HRM) analysis has been used for detecting mutations, polymorphisms and epigenetic alteration in double-stranded DNAs. This study was to evaluate the potential application of HRM analysis for identifying gene mutations in patients with OI. This study included four children with OI and their parents and fifty normal people as controls. Blood samples were collected for HRM analysis of PCR-amplified exons and flanking DNA sequences of COL1A1 and COL1A2 genes. Direct gene sequencing was performed to validate HRM-identified gene mutations. As compared to controls, HRM analysis of samples form children with OI showed abnormal melting curves in exons 11 and 33–34 of the COL1A1 gene and exons 19 and 48 of the COL1A2 gene, which indicates the presence of heterozygous mutations in COL1A1 and COL1A2 genes. In addition to two known mutations in the COL1A2 gene, c.982G > A and c.3197G > T, sequencing analysis identified two novel mutations in the COL1A1 gene, c.2321delC and c.768dupC mutations, which function as premature stop codons. These results support future studies of applying HRM analysis as a diagnostic approach for OI.
Rational Design of Highly Potent and Slow-Binding Cytochrome bc1 Inhibitor as Fungicide by Computational Substitution Optimization
Authors: Hao Ge-Fei , Yang Sheng-Gang , Huang Wei , Wang Le , Shen Yan-Qing , Tu Wen-Long , Li Hui , Huang Li-Shar , Wu Jia-Wei , Berry Edward A. , Yang Guang-Fu 
Published: August 2015

AbstractHit to lead (H2L) optimization is a key step for drug and agrochemical discovery. A critical challenge for H2L optimization is the low efficiency due to the lack of predictive method with high accuracy. We described a new computational method called Computational Substitution Optimization (CSO) that has allowed us to rapidly identify compounds with cytochrome bc1 complex inhibitory activity in the nanomolar and subnanomolar range. The comprehensively optimized candidate has proved to be a slow binding inhibitor of bc1 complex, ~73-fold more potent (Ki = 4.1 nM) than the best commercial fungicide azoxystrobin (AZ; Ki = 297.6 nM) and shows excellent in vivo fungicidal activity against downy mildew and powdery mildew disease. The excellent correlation between experimental and calculated binding free-energy shifts together with further crystallographic analysis confirmed the prediction accuracy of CSO method. To the best of our knowledge, CSO is a new computational approach to substitution-scanning mutagenesis of ligand and could be used as a general strategy of H2L optimisation in drug and agrochemical design.
The Neuraminidase Stalk Deletion Serves as Major Virulence Determinant of H5N1 Highly Pathogenic Avian Influenza Viruses in Chicken
Authors: Stech Olga , Veits Jutta , Abdelwhab El-Sayed M. , Wessels Ute , Mettenleiter Thomas C. , Stech Jürgen 
Published: August 2015

AbstractHighly pathogenic avian influenza viruses (HPAIV) cause devastating losses in gallinaceous poultry world-wide and raised concerns of a novel pandemic. HPAIV develop from low-pathogenic precursors by acquisition of a polybasic HA cleavage site (HACS), the prime virulence determinant. Beside that HACS, other adaptive changes accumulate in those precursors prior to transformation into an HPAIV. Here, we aimed to unravel such virulence determinants in addition to the HA gene. Stepwise reduction of HPAIV genes revealed that the HPAIV HA and NA form a minimum set of virulence determinants, sufficient for a lethal phenotype in chicken. Abolishing the NA stalk deletion considerably reduced lethality and prevented transmission. Conversely, the analogous stalk deletion reconstructed in the NA of an LPAIV reassortant carrying only the HPAIV HA resulted in 100% lethality both after primary and contact infection. Remarkably, the unmodified LPAIV NA with its long stalk, when exclusively introduced into the H5N1 HPAIV, still enabled high virulence and efficient transmission. Therefore, irrespective of an NA stalk deletion, minor virulence determinants in addition to the essential polybasic HACS contribute to high virulence, whereas the NA stalk deletion alone may serve as major virulence determinant.
Subset of early radial glial progenitors that contribute to the development of callosal neurons is absent from avian brain
Authors: García-Moreno Fernando , Molnár Zoltán 
Published: August 2015

Significance
Understanding development and evolution of the neocortex has important implications. We describe here a major difference between avian and mammalian dorsal pallial progenitors regarding their fate restrictions. In mouse cortex we identified an early population of radial glial cells that are delayed in the generation of neurons. After self-renewal and transit-amplifying mitoses, these murine progenitors become committed to the genesis of upper-layer callosal pyramidal neurons and glia. In the chick embryonic pallium we identified a homologous population of progenitors; however, these have no delayed neurogenesis and their lineage is therefore not segregated from that of the other pallial progenitors. We hypothesize on the relation between the early neurogenic delay of progenitors and the origin of the corpus callosum.
Admissions to Detoxification after Treatment: Does Engagement Make a Difference?
Authors: Acevedo Andrea , Garnick Deborah , Ritter Grant , Lundgren Lena , Horgan Constance 
Published: August 2015

Background Treatment engagement is a well-established performance measure for the treatment of substance use disorders. This study examined whether outpatient treatment engagement is associated with a reduced likelihood of subsequent detoxification admissions. Methods This study used administrative data on treatment services received by clients in specialty treatment facilities licensed in Massachusetts. The sample consisted of 11,591 adult clients who began an outpatient treatment episode in 2006. Treatment engagement was defined as receipt of at least 1 treatment service within 14 days of beginning a new outpatient treatment episode and receipt of at least 2 additional treatment services in the next 30 days. The outcome was a subsequent detoxification admission. Multilevel survival models examined the relationship between engagement and outcomes, with time to detoxification admission as the dependent variable censored at 365 days. Results Only 35% of clients met the outpatient engagement criteria, and 15% of clients had a detoxification admission within a year after beginning their outpatient treatment episode. Controlling for client demographics, insurance type, and substance use severity, clients who met the engagement criteria had a lower hazard of having a detoxification admission during the year following the index outpatient visit than those who did not engage (hazard ratio = 0.87, P < .01). Conclusions Treatment engagement is a useful measure for monitoring quality of care. The findings from this study could help inform providers and policy makers on ways to target care and reduce the likelihood of more intensive services.
Multispecialty Screening, Brief Intervention, and Referral to Treatment (SBIRT) Training in An Academic Medical Center: Resident Training Experience across Specialties
Authors: Clemence A. Jill , Balkoski Victoria I. , Schaefer Bianca M. , Lee Minsun , Bromley Nicole , Maisonneuve Isabelle M. , Hamilton Christopher J. , Lukowitsky Mark R. , Poston John , Hall Schekeva , Pieterse Portia , Antonikowski Angela , Glick Stanley D. 
Published: August 2015

Background The Substance Abuse and Mental Health Services Administration (SAMHSA) has recently begun to fund programs that train medical residents on how to utilize an evidence-based validated system known as screening, brief intervention, and referral to treatment (SBIRT) for providing early detection and brief treatment of unhealthy substance use. This paper investigates training outcomes of multispecialty SBIRT training at one such program at Albany Medical Center (AMC), one of the initial SAMHSA grantees. Methods Training outcomes were measured across 3 domains of learning: trainee satisfaction, acquired knowledge, and perceived usefulness. The authors explored differences in learning experience by postgraduate year and by specialty. Results Overall, residents were highly satisfied with the training, and learning outcomes met objectives. Residents’ ratings of usefulness did not vary by program year. However, the results indicate that relative to residents in other programs, residents in psychiatry and pediatrics found the training components significantly more useful, whereas emergency medicine residents found training components to have less utility. Residents who found the training relevant to their daily work were more satisfied and more receptive to SBIRT training overall, which may help explain difference scores by program. Conclusions Residents were highly satisfied with SBIRT skills training, although ratings of usefulness varied by residency program. Specialization by program and on-site modeling by senior faculty may enhance trainee satisfaction and perceived usefulness.
SODAS: Surveillance of Drugs of Abuse Study
Authors: Lowe David J. , Torrance Hazel J. , Ireland Alastair J. , Bloeck Felix , Stevenson Richard 
Published: August 2015

Objective
Novel psychoactive substance (NPS) as a form of recreational drug use has become increasingly popular. There is a paucity of information with regard to the prevalence and clinical sequelae of these drugs. The aim of this study was to detect NPS in patients presenting to the emergency department with suspected toxicological ingestion.

Patients and methods
The prospective study was performed in a large emergency department in the UK. During a 3-month period 80 patients were identified by clinicians as having potentially ingested a toxicological agent. Urine samples were analysed using liquid chromatography high-resolution mass spectrometry, and basic clinical data was gathered.

Results
Eighty patients with a history of illicit or recreational drug consumption had urine screenings performed. Forty-nine per cent (39) of the patients undergoing a screen had more than one illicit substance detected. Twenty per cent (16) of the patients tested positive for at least one NPS.

Conclusion
Almost half of the presented patients revealed ingestion of multiple substances, which correlated poorly with self-reporting of patients. Developing enhanced strategies to monitor evolving drug trends is crucial to the ability of clinicians to deliver care to this challenging group of patients.
Number of organ dysfunctions predicts mortality in emergency department patients with suspected infection: a multicenter validation study
Authors: Jessen Marie K. , Skibsted Simon , Shapiro Nathan I. 
Published: August 2015

Objectives
The aim of this study was to validate the association between number of organ dysfunctions and mortality in emergency department (ED) patients with suspected infection.

Methods
This study was conducted at two medical care center EDs. The internal validation set was a prospective cohort study conducted in Boston, USA. The external validation set was a retrospective case–control study conducted in Aarhus, Denmark. The study included adult patients (>18 years) with clinically suspected infection. Laboratory results and clinical data were used to assess organ dysfunctions. Inhospital mortality was the outcome measure. Multivariate logistic regression was used to determine the independent mortality odds for number and types of organ dysfunctions.

Results
We enrolled 4952 (internal) and 483 (external) patients. The mortality rate significantly increased with increasing number of organ dysfunctions: internal validation: 0 organ dysfunctions: 0.5% mortality, 1: 3.6%, 2: 9.5%, 3: 17%, and 4 or more: 37%; external validation: 2.2, 6.7, 17, 41, and 57% mortality (both P<0.001 for trend). Age-adjusted and comorbidity-adjusted number of organ dysfunctions remained an independent predictor. The effect of specific types of organ dysfunction on mortality was most pronounced for hematologic [odds ratio (OR) 3.3 (95% confidence interval (CI) 2.0–5.4)], metabolic [OR 3.3 (95% CI 2.4–4.6); internal validation], and cardiovascular dysfunctions [OR 14 (95% CI 3.7–50); external validation].

Conclusion
The number of organ dysfunctions predicts sepsis mortality.
Tranexamic acid in major trauma: implementation and evaluation across South West England
Authors: Paudyal Priyamvada , Smith Jason , Robinson Maria , South Adrian , Higginson Ian , Reuben Adam , Shaffee Julian , Black Sarah , Logan Stuart 
Published: August 2015

Objective
To carry out a prospective evaluation of tranexamic acid (TXA) use in trauma patients.

Patients and methods
TXA was introduced to all emergency ambulances and emergency departments in the South West, UK, on 1 December 2011. We carried out a prospective evaluation of TXA use in trauma patients in the South West Peninsula between December 2011 and December 2012. We collected prehospital and hospital data on TXA administration using the Trauma Audit Research Network database. Data on prehospital administration of TXA were cross-checked with the South Western Ambulance Service Trust. Data were analysed using SPSS (version 20).

Results
Altogether, 82 patients were administered TXA during the study period. The median age of the patients was 49 years (IQR 30, 66), and 72% were men. One-third of the patients arrived at hospital by air ambulance. During the first 3 months, administration of TXA was limited to one patient each month receiving the drug. However, an upward trend was observed after June until October 2012, with the increment being more than 10 fold in July, September and October 2012.

Conclusion
This is the first study to evaluate the use of TXA in civilian practice in the UK. Our study shows that ambulance service personnel and emergency departments can effectively administer TXA.