bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paramedics assessing Elders at Risk for Independence Loss (PERIL): Derivation, Reliability and Comparative Effectiveness of a Clinical Prediction Rule
Authors: Lee Jacques S. , Verbeek P. Richard , Schull Michael J. , Calder Lisa , Stiell Ian G. , Trickett John , Morrison Laurie J. , Nolan Michael , Rowe Brian H. , Sookram Sunil , Ryan David , Kiss Alex , Naglie Gary 
Published: March 2016

AbstractObjectivesWe conducted a program of research to derive and test the reliability of a clinical prediction rule to identify high-risk older adults using paramedics’ observations.MethodsWe developed the Paramedics assessing Elders at Risk of Independence Loss (PERIL) checklist of 43 yes or no questions, including the Identifying Seniors at Risk (ISAR) tool items. We trained 1,185 paramedics from three Ontario services to use this checklist, and assessed inter-observer reliability in a convenience sample. The primary outcome, return to the ED, hospitalization, or death within one month was assessed using provincial databases. We derived a prediction rule using multivariable logistic regression.ResultsWe enrolled 1,065 subjects, of which 764 (71.7%) had complete data. Inter-observer reliability was good or excellent for 40/43 questions. We derived a four-item rule: 1) “Problems in the home contributing to adverse outcomes?” (OR 1.43); 2) “Called 911 in the last 30 days?” (OR 1.72); 3) male (OR 1.38) and 4) lacks social support (OR 1.4). The PERIL rule performed better than a proxy measure of clinical judgment (AUC 0.62 vs. 0.56, p=0.02) and adherence was better for PERIL than for ISAR.ConclusionsThe four-item PERIL rule has good inter-observer reliability and adherence, and had advantages compared to a proxy measure of clinical judgment. The ISAR is an acceptable alternative, but adherence may be lower. If future research validates the PERIL rule, it could be used by emergency physicians and paramedic services to target preventative interventions for seniors identified as high-risk.
Prediction of noise from serrated trailing edges
Authors: Lyu B. , Azarpeyvand M. , Sinayoko S. 
Published: March 2016

A new analytical model is developed for the prediction of noise from serrated trailing edges. The model generalizes Amiet’s trailing-edge noise theory to sawtooth trailing edges, resulting in a complicated partial differential equation. The equation is then solved by means of a Fourier expansion technique combined with an iterative procedure. The solution is validated through comparison with the finite element method for a variety of serrations at different Mach numbers. The results obtained using the new model predict noise reduction of up to 10 dB at 90$^{\circ }$ above the trailing edge, which is more realistic than predictions based on Howe’s model and also more consistent with experimental observations. A thorough analytical and numerical analysis of the physical mechanism is carried out and suggests that the noise reduction due to serration originates primarily from interference effects near the trailing edge. A closer inspection of the proposed mathematical model has led to the development of two criteria for the effectiveness of the trailing-edge serrations, consistent but more general than those proposed by Howe. While experimental investigations often focus on noise reduction at 90$^{\circ }$ above the trailing edge, the new analytical model shows that the destructive interference scattering effects due to the serrations cause significant noise reduction at large polar angles, near the leading edge. It has also been observed that serrations can significantly change the directivity characteristics of the aerofoil at high frequencies and even lead to noise increase at high Mach numbers.
A prospective cohort study on the association between coffee drinking and risk of non-gallstone-related acute pancreatitis
Authors: Oskarsson Viktor , Sadr-Azodi Omid , Orsini Nicola , Wolk Alicja 
Published: March 2016

AbstractOnly one previous study has examined the association between coffee consumption and risk of acute pancreatitis, and it found a reduced risk for alcohol-related episodes among high consumers of coffee. Therefore, we examined (1) the association between coffee consumption and risk of non-gallstone-related acute pancreatitis and (2) whether this association was modified by alcohol intake. Data were obtained from two prospective cohorts, the Cohort of Swedish Men and the Swedish Mammography Cohort, including 76 731 men and women (born 1914–1952). Coffee consumption was assessed at baseline with a FFQ, and the cohorts were followed up between 1998 and 2012 via linkage to national health registries. Hazard ratios were estimated using Cox models, with adjustment for potential confounding factors. During 1 035 881 person-years of total follow-up, 383 cases (246 in men and 137 in women) of incident non-gallstone-related acute pancreatitis were identified. Overall, and irrespective of whether a categorical or a continuous exposure model was used, we observed no association between coffee consumption and risk of non-gallstone-related acute pancreatitis (e.g. the multivariable-adjusted hazard ratio for each 1 cup/d increase in coffee consumption was 0·97; 95 % CI 0·92, 1·03). There was no evidence of effect modification by alcohol intake (Pinteraction=0·77). In conclusion, coffee consumption was not associated with risk of non-gallstone-related acute pancreatitis in this large prospective cohort study. Because of the limited number of epidemiological studies and their conflicting results, further research is needed to elucidate this potential association.
Associations of serum n-3 and n-6 PUFA and hair mercury with the risk of incident stroke in men: the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD)
Authors: Daneshmand Roya , Kurl Sudhir , Tuomainen Tomi-Pekka , Virtanen Jyrki K. 
Published: March 2016

AbstractPUFA have been associated with lower risk of CVD, but less is known about their association with stroke risk. Fish, a major source of n-3 PUFA, may also contain methylmercury, which has been associated with higher risk of CVD and attenuation of the benefits of long-chain n-3 PUFA. We investigated the associations of serum n-3 and n-6 PUFA and hair Hg with risk of stroke in men. A total of 1828 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42–60 years and free of CVD at baseline in 1984–1989 were studied. Cox regression models were used for the analyses. During the mean follow-up of 21·2 years, 202 stroke cases occurred, of which 153 were ischaemic strokes. After adjustment for age and examination year, the only statistically significant association among the n-3 and n-6 PUFA was observed between the n-3 PUFA α-linolenic acid and risk of haemorrhagic stroke (hazard ratio in the highest v. the lowest quartile 0·33; 95 % CI 0·13, 0·86; Ptrend=0·03). However, further adjustments attenuated the association to statistically non-significant. Hair Hg was not associated with stroke risk, but among those with hair Hg above the median level, higher serum long-chain n-3 PUFA concentrations were associated with a higher risk of ischaemic stroke. In our cohort of men, serum n-3 or n-6 PUFA or hair Hg were not associated with stroke risk; however, the interaction between Hg and long-chain n-3 PUFA with regard to ischaemic stroke risk warrants further investigation.
Comparison of Carina active middle-ear implant with conventional hearing aids for mixed hearing loss
Authors: Savaş V A , Gündüz B , Karamert R , Cevizci R , Düzlü M , Tutar H , Bayazit Y A 
Published: March 2016

AbstractObjective:To compare the auditory outcomes of Carina middle-ear implants with those of conventional hearing aids in patients with moderate-to-severe mixed hearing loss.Methods:The study comprised nine patients (six males, three females) who underwent middle-ear implantation with Carina fully implantable active middle-ear implants to treat bilateral moderate-to-severe mixed hearing loss. The patients initially used conventional hearing aids and subsequently received the Carina implants. The hearing thresholds with implants and hearing aids were compared.Results:There were no significant differences between: the pre-operative and post-operative air and bone conduction thresholds (p> 0.05), the thresholds with hearing aids and Carina implants (p> 0.05), or the pre-operative (mean, 72.8 ± 19 per cent) and post-operative (mean, 69.9 ± 24 per cent) speech discrimination scores (p> 0.05). One of the patients suffered total sensorineural hearing loss three months following implantation despite an initial 38 dB functional gain. All except one patient showed clinical improvements after implantation according to quality of life questionnaire (Glasgow Benefit Inventory) scores.Conclusion:Acceptance of Carina implants is better than with conventional hearing aids in patients with mixed hearing loss, although both yield similar hearing amplification. Cosmetic reasons appear to be critical for patient acceptance.
Facial emotion recognition and its relationship to cognition and depressive symptoms in patients with Parkinson's disease
Authors: Pietschnig J. , Schröder L. , Ratheiser I. , Kryspin-Exner I. , Pflüger M. , Moser D. , Auff E. , Pirker W. , Pusswald G. , Lehrner J. 
Published: March 2016

ABSTRACTBackground:Impairments in facial emotion recognition (FER) have been detected in patients with Parkinson disease (PD). Presently, we aim at assessing differences in emotion recognition performance in PD patient groups with and without mild forms of cognitive impairment (MCI) compared to healthy controls.Methods:Performance on a concise emotion recognition test battery (VERT-K) of three groups of 97 PD patients was compared with an age-equivalent sample of 168 healthy controls. Patients were categorized into groups according to two well-established classifications of MCI according to Petersen's (cognitively intact vs. amnestic MCI, aMCI, vs. non-amnestic MCI, non-aMCI) and Litvan's (cognitively intact vs. single-domain MCI, sMCI, vs. multi-domain MCI, mMCI) criteria. Patients and controls underwent individual assessments using a comprehensive neuropsychological test battery examining attention, executive functioning, language, and memory (Neuropsychological Test Battery Vienna, NTBV), the Beck Depression Inventory, and a measure of premorbid IQ (WST).Results:Cognitively intact PD patients and patients with MCI in PD (PD-MCI) showed significantly worse emotion recognition performance when compared to healthy controls. Between-groups effect sizes were substantial, showing non-trivial effects in all comparisons (Cohen's ds from 0.31 to 1.22). Moreover, emotion recognition performance was higher in women, positively associated with premorbid IQ and negatively associated with age. Depressive symptoms were not related to FER.Conclusions:The present investigation yields further evidence for impaired FER in PD. Interestingly, our data suggest FER deficits even in cognitively intact PD patients indicating FER dysfunction prior to the development of overt cognitive dysfunction. Age showed a negative association whereas IQ showed a positive association with FER.
miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia
Authors: Navarro A , Pairet S , Álvarez-Larrán A , Pons A , Ferrer G , Longarón R , Fernández-Rodríguez C , Camacho L , Monzó M , Besses C , Bellosillo B 
Published: March 2016

AbstractThe biological basis of essential thrombocythemia (ET) patients lacking known mutations is still unknown. MicroRNAs (miRNA) regulate hematopoietic differentiation and are deregulated in several hematopoietic malignancies. However, miRNA expression in ET patients has been poorly explored. We performed miRNA profiling in platelets from 19 ET patients and 10 healthy controls. Hierarchical cluster analysis showed two well-separated clusters between patients and controls, indicating that ET platelets had a characteristic 70-miRNA signature (P<0.0001), 68 of which were downregulated. According to the mutational status, three differentially expressed miRNAs, miR-15a (P=0.045), miR-150 (P=0.001) and miR-519a (P=0.036), were identified. A 40-miRNA signature was identified characterizing JAK2V617F-positive ET patients. Eight genes, whose interaction with the miRNAs could activate the JAK/STAT pathway were identified. An inverse correlation was observed between miRNAs expression and their target genes for SOCS1 and miR-221, SOCS3 and miR-221, SOCS3 and miR-203, and PTPN11 and miR-23a. All three miRNAs were upregulated in JAK2V617F-negative ET patients. SOCS1 and SOCS3 were validated as targets of miR-221 and miR-203, respectively. In summary, our study shows that platelets from JAK2V617F-negative ET patients harbor a specific miRNA signature that can participate in the modulation of the JAK/STAT pathway through regulation of key genes as SOCS1 and SOCS3.
A conserved motif in JNK/p38-specific MAPK phosphatases as a determinant for JNK1 recognition and inactivation
Authors: Liu Xin , Zhang Chen-Song , Lu Chang , Lin Sheng-Cai , Wu Jia-Wei , Wang Zhi-Xin 
Published: March 2016

AbstractMitogen-activated protein kinases (MAPKs), important in a large array of signalling pathways, are tightly controlled by a cascade of protein kinases and by MAPK phosphatases (MKPs). MAPK signalling efficiency and specificity is modulated by protein–protein interactions between individual MAPKs and the docking motifs in cognate binding partners. Two types of docking interactions have been identified: D-motif-mediated interaction and FXF-docking interaction. Here we report the crystal structure of JNK1 bound to the catalytic domain of MKP7 at 2.4-Å resolution, providing high-resolution structural insight into the FXF-docking interaction. The 285FNFL288 segment in MKP7 directly binds to a hydrophobic site on JNK1 that is near the MAPK insertion and helix αG. Biochemical studies further reveal that this highly conserved structural motif is present in all members of the MKP family, and the interaction mode is universal and critical for the MKP-MAPK recognition and biological function.
Regulation at a distance of biomolecular interactions using a DNA origami nanoactuator
Authors: Ke Yonggang , Meyer Travis , Shih William M. , Bellot Gaetan 
Published: March 2016

AbstractThe creation of nanometre-sized structures that exhibit controllable motions and functions is a critical step towards building nanomachines. Recent developments in the field of DNA nanotechnology have begun to address these goals, demonstrating complex static or dynamic nanostructures made of DNA. Here we have designed and constructed a rhombus-shaped DNA origami ‘nanoactuator’ that uses mechanical linkages to copy distance changes induced on one half (‘the driver’) to be propagated to the other half (‘the mirror’). By combining this nanoactuator with split enhanced green fluorescent protein (eGFP), we have constructed a DNA–protein hybrid nanostructure that demonstrates tunable fluorescent behaviours via long-range allosteric regulation. In addition, the nanoactuator can be used as a sensor that responds to specific stimuli, including changes in buffer composition and the presence of restriction enzymes or specific nucleic acids.
Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus
Authors: Ji Quanjiang , Chen Peter J. , Qin Guangrong , Deng Xin , Hao Ziyang , Wawrzak Zdzislaw , Yeo Won-Sik , Quang Jenny Winjing , Cho Hoonsik , Luo Guan-Zheng , Weng Xiaocheng , You Qiancheng , Luan Chi-Hao , Yang Xiaojing , Bae Taeok , Yu Kunqian , Jiang Hualiang , He Chuan 
Published: March 2016

AbstractMost low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase ‘WalK’ (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resulted in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. The molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.
A CEP215–HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer
Authors: Chavali Pavithra L. , Chandrasekaran Gayathri , Barr Alexis R. , Tátrai Péter , Taylor Chris , Papachristou Evaggelia K. , Woods C. Geoffrey , Chavali Sreenivas , Gergely Fanni 
Published: March 2016

AbstractNumerical centrosome aberrations underlie certain developmental abnormalities and may promote cancer. A cell maintains normal centrosome numbers by coupling centrosome duplication with segregation, which is achieved through sustained association of each centrosome with a mitotic spindle pole. Although the microcephaly- and primordial dwarfism-linked centrosomal protein CEP215 has been implicated in this process, the molecular mechanism responsible remains unclear. Here, using proteomic profiling, we identify the minus end-directed microtubule motor protein HSET as a direct binding partner of CEP215. Targeted deletion of the HSET-binding domain of CEP215 in vertebrate cells causes centrosome detachment and results in HSET depletion at centrosomes, a phenotype also observed in CEP215-deficient patient-derived cells. Moreover, in cancer cells with centrosome amplification, the CEP215–HSET complex promotes the clustering of extra centrosomes into pseudo-bipolar spindles, thereby ensuring viable cell division. Therefore, stabilization of the centrosome–spindle pole interface by the CEP215–HSET complex could promote survival of cancer cells containing supernumerary centrosomes.
Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance
Authors: Kabe Yasuaki , Nakane Takanori , Koike Ikko , Yamamoto Tatsuya , Sugiura Yuki , Harada Erisa , Sugase Kenji , Shimamura Tatsuro , Ohmura Mitsuyo , Muraoka Kazumi , Yamamoto Ayumi , Uchida Takeshi , Iwata So , Yamaguchi Yuki , Krayukhina Elena , Noda Masanori , Handa Hiroshi , Ishimori Koichiro , Uchiyama Susumu , Kobayashi Takuya , Suematsu Makoto 
Published: March 2016

AbstractProgesterone-receptor membrane component 1 (PGRMC1/Sigma-2 receptor) is a haem-containing protein that interacts with epidermal growth factor receptor (EGFR) and cytochromes P450 to regulate cancer proliferation and chemoresistance; its structural basis remains unknown. Here crystallographic analyses of the PGRMC1 cytosolic domain at 1.95 Å resolution reveal that it forms a stable dimer through stacking interactions of two protruding haem molecules. The haem iron is five-coordinated by Tyr113, and the open surface of the haem mediates dimerization. Carbon monoxide (CO) interferes with PGRMC1 dimerization by binding to the sixth coordination site of the haem. Haem-mediated PGRMC1 dimerization is required for interactions with EGFR and cytochromes P450, cancer proliferation and chemoresistance against anti-cancer drugs; these events are attenuated by either CO or haem deprivation in cancer cells. This study demonstrates protein dimerization via haem–haem stacking, which has not been seen in eukaryotes, and provides insights into its functional significance in cancer.
Versatile protein tagging in cells with split fluorescent protein
Authors: Kamiyama Daichi , Sekine Sayaka , Barsi-Rhyne Benjamin , Hu Jeffrey , Chen Baohui , Gilbert Luke A. , Ishikawa Hiroaki , Leonetti Manuel D. , Marshall Wallace F. , Weissman Jonathan S. , Huang Bo 
Published: March 2016

AbstractIn addition to the popular method of fluorescent protein fusion, live cell protein imaging has now seen more and more application of epitope tags. The small size of these tags may reduce functional perturbation and enable signal amplification. To address their background issue, we adapt self-complementing split fluorescent proteins as epitope tags for live cell protein labelling. The two tags, GFP11 and sfCherry11 are derived from the eleventh β-strand of super-folder GFP and sfCherry, respectively. The small size of FP11-tags enables a cost-effective and scalable way to insert them into endogenous genomic loci via CRISPR-mediated homology-directed repair. Tandem arrangement FP11-tags allows proportional enhancement of fluorescence signal in tracking intraflagellar transport particles, or reduction of photobleaching for live microtubule imaging. Finally, we show the utility of tandem GFP11-tag in scaffolding protein oligomerization. These experiments illustrate the versatility of FP11-tag as a labelling tool as well as a multimerization-control tool for both imaging and non-imaging applications.
The fertilization-induced zinc spark is a novel biomarker of mouse embryo quality and early development
Authors: Zhang Nan , Duncan Francesca E. , Que Emily L. , O’Halloran Thomas V. , Woodruff Teresa K. 
Published: March 2016

AbstractUpon activation, mammalian eggs release billions of zinc ions in an exocytotic event termed the “zinc spark.” The zinc spark is dependent on and occurs coordinately with intracellular calcium transients, which are tightly associated with embryonic development. Thus, we hypothesized that the zinc spark represents an early extracellular physicochemical marker of the developmental potential of the zygote. To test this hypothesis, we monitored zinc exocytosis in individual mouse eggs following parthenogenetic activation or in vitro fertilization (IVF) and tracked their development. Retrospective analysis of zinc spark profiles revealed that parthenotes and zygotes that developed into blastocysts released more zinc than those that failed to develop. Prospective selection of embryos based on their zinc spark profile significantly improved developmental outcomes and more than doubled the percentage of embryos that reached the blastocyst stage. Moreover, the zinc spark profile was also associated with embryo quality as the total cell number in the resulting morulae and blastocysts positively correlated with the zinc spark amplitude (R = 0.9209). Zinc sparks can thus serve as an early biomarker of zygote quality in mouse model.
Nanoscale precipitates strengthened lanthanum-bearing Mg-3Sn-1Mn alloys through continuous rheo-rolling
Authors: Guan R. G. , Shen Y. F. , Zhao Z. Y. , Misra R. D. K. 
Published: March 2016

AbstractWe elucidate the effect of lanthanum (La) on the microstructure and mechanical properties of Mg-3Sn-1Mn-xLa (wt.%) alloy plates processed through continuous rheo-rolling for the first time. At x = 0.2 wt.%, La dissolved completely in the α-Mg matrix. As the La content was increased to 0.6 wt.%, a new plate-shaped three-phase compound composed of La5Sn3, Mg2Sn and Mg17La2 phases was formed with an average length of 380 ± 10 nm and an average width of 110 ± 5 nm. This compound had a pinning effect on the α-Mg grain boundary and on dislocations. With further increase in La-content to 1.0 wt.%, the length of the plate-shaped compound increased to an average length of 560 ± 10 nm, while the width was reduced to 90 ± 5 nm. The particle size of Mg2Sn decreased from 100 nm to 50 nm with increase in La-content from 0.2 to 1.4 wt.%. At La content of 1.0 wt.%, the tensile strength and elongation of the alloy was maximum, with 29% and 32% increase, respectively, compared to the Mg-3Sn-1Mn (wt.%) alloy, and 37% and 89% increase, in comparison to the Mg-3Sn-1Mn-0.87 Ce (wt.%) alloy.