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It is often difficult to obtain valid estimates of comparative treatment effectiveness and safety owing to differences across patient populations taking different medications in the real world. One approach for assessing comparability between treatment groups in effectiveness studies is to use negative control outcomes (NCOs). NCOs share similar sources of bias with the primary outcomes but have no plausible causal relationship to the treatment of interest. Observing differences in the risk of NCOs thus provides evidence for residual confounding between groups. This retrospective study assessed the comparability of postmenopausal women, treated with osteoporosis medications with various mechanisms of action such as denosumab (receptor activator of nuclear factor κB ligand [RANKL] inhibitor), zoledronic acid (bisphosphonate derivative), or oral bisphosphonates including alendronate. Administrative claims data were extracted from the US Centers for Medicare and Medicaid Services' Chronic Condition Warehouse database (May 2010-December 2016). Propensity scores were used to match denosumab patients 1:1 to comparators. Four nonfracture NCOs and three early fracture NCOs (before substantial biologic effects of treatment would be expected) were assessed over 1-year and 3-month follow-up periods, respectively. According to comparability decision rules established a priori, patients initiating denosumab were comparable to those initiating zoledronic acid or alendronate, irrespective of prior osteoporosis treatment experience. Among new users, new switchers, and in the historical fracture subgroup, no meaningful differences were observed in the cumulative incidence of the seven NCOs comparing denosumab to zoledronic acid. This empirical examination can assist in the selection of appropriate comparator groups for future comparability research using real-world data. [ABSTRACT FROM AUTHOR]

Background: Evidence on simultaneous resection for elderly patients (age ≥ 70 years) with colorectal liver metastasis (CRLM) is lacking. Methods: Four hundred and eighty- two CRLM patients treated by simultaneous resection were categorised into young group (age < 70 years) and elderly group (age ≥ 70 years). Propensity score matching (PSM1) was performed to adjust for differences in baseline characteristics and compare short-term outcomes. An additional propensity score matching (PSM2) including short- term outcomes was performed to analyse survival. Subgroup analysis was performed in patients stratified by the Clinical Risk Score (CRS). Results: After PSM1, 87 young group patients were matched to 50 elderly group patients. Patients in the elderly group had a significantly higher rate of overall post- operative complications (68.0% vs. 46.0%, p = 0.013). After PSM2, 89 young group patients were matched to 47 elderly group patients. Progression- free survival (PFS) was comparable between the two groups (median 11.0 months vs. 9.8 months, p = 0.346). Age ≥ 70 independently predicted worse overall survival (OS) (Hazard ratio, HR = 2.57, 95% confidence interval, CI 1.37-4.82) in multivariate analysis. In the subgroup multivariate analysis of patients with CRS score 3-5, age ≥ 70 was independently associated with worse PFS (HR = 1.62, 95% CI 1.01-2.62) and OS (HR = 2.34, 95% CI 1.26-4.35). Conclusions: Simultaneous resection for elderly CRLM patients is acceptable. Further studies are required to determine the optimal treatment for elderly CRLM patients with high CRS scores. [ABSTRACT FROM AUTHOR]

Ultra-low-frequency (ULF) waves are known to radially diffuse hundreds-keV to few-MeV electrons in the magnetosphere, as the range of drift frequencies of such electrons overlaps with the frequencies of the waves, leading to resonant interactions. The theoretical framework for this process is described by analytic expressions of the resonant interactions between electrons and toroidal and poloidal ULF wave modes in a background magnetic field. However, most expressions estimate the radial diffusion rates based on estimates of the power of ULF waves that are obtained either from spacecraft close to the equatorial plane or from the ground. In this study, using multiyear measurements from the THEMIS and Arase missions, we present a statistical analysis of the distribution of ULF wave power in magnetic latitude and local time and show that the wave power of the radial and azimuthal components of the magnetic field increases away from the magnetic equator. Our result could have significant implications for the radial diffusion rates as currently estimated. [ABSTRACT FROM AUTHOR]

Introduction: Geriatric patients with dementia incur higher healthcare costs and longer hospital stays than other geriatric patients. We aimed to identify risk factors for hospitalization outcomes that could be mitigated early to improve outcomes and impact overall quality of life. Methods: We identified risk factors, that is, demographics, hospital complications, pre-admission, and post-admission risk factors including medical history and comorbidities, affecting hospitalization outcomes determined by hospital stays and discharge dispositions. Over 150 clinical and demographic factors of 15,678 encounters (8407 patients) were retrieved from our institution's data warehouse. We further narrowed themdownto twenty factors through feature selection engineering by using analysis of variance (ANOVA) and Glmnet. We developed an explainable machine-learning model to predict hospitalization outcomes among geriatric patients with dementia. Results: Our model is based on stacking ensemble learning and achieved accuracy of 95.6% and area under the curve (AUC) of 0.757. It outperformed prevalent methods of risk assessment for encounters of patients with Alzheimer's disease dementia (ADD) (4993), vascular dementia (VD) (4173), Parkinson's disease with dementia (PDD) (3735), and other unspecified dementias (OUD) (2777). Top identified hospitalization outcome risk factors, mostly from medical history, include encephalopathy, number of medical problems at admission, pressure ulcers, urinary tract infections, falls, admission source, age, race, anemia, etc., with several overlaps in multi-dementia groups. Discussion: Our model identified several predictive factors that can be modified or intervened so that efforts can be made to prevent recurrence ormitigate their adverse effects. Knowledge of the modifiable risk factors would help guide early interventions for patients at high risk for poor hospitalization outcome as defined by hospital stays longer than seven days, undesirable discharge disposition, or both. The interventions include starting specific protocols on modifiable risk factors like encephalopathy, falls, and infections, where non-existent or not routine, to improve hospitalization outcomes of geriatric patients with dementia. [ABSTRACT FROM AUTHOR]

Subduction initiation processes, such as those evidenced in the Izu-Bonin-Mariana (IBM) forearc crust are a key feature of modern-style plate tectonics. However, the evidence for this process in the Precambrian is limited, due to the scarcity of ophiolite suites and in particular a lack of typical complete ophiolitic sequences similar to those observed in Phanerozoic ophiolites. Mineral analyses of olivine, orthopyroxene, and chrome spinel from the harzburgite and two types of clinopyroxene from the cumulate gabbro of the Fuchuan ophiolite, South China suggest formation in a Neoproterozoic subduction system similar to the IBM. High temperature (1,000-1,200°C), low pressure along with a high degree of melt extraction (>18%) have been recorded in the harzburgite. This evidence, in conjunction with magma evolution from forearc basalt to boninite to hydrous calc-alkaline magmatism, recorded in the crustal section of the Fuchuan ophiolite indicates a transition from initial to mature subduction in a forearc setting. Statistical analysis of global ophiolites through time suggests that IBM-like subduction systems may have successfully operated since at least the latest Neoproterozoic (ca. 1,000 Ma) and be pervasive on Earth from ca. 850 Ma. Additional evidence for Neoproterozoic ophiolites from India, Siberia, and Arabian-Nubian Shield, which are also similar to the IBM forearc ophiolite, suggests that cold and deep subduction became much more common in the Neoproterozoic (ca. 850 Ma) around the periphery of the Rodinia supercontinent. This IBM-like subduction system may have acted as the geodynamic trigger for the break-up of Rodinia. [ABSTRACT FROM AUTHOR]

A radial diffusion model directly driven by the solar wind is developed to reproduce MeV electron variations between L = 2-12 (L is L* in this study) from October 2012 to April 2015. The radial diffusion coefficient, internal source rate, quick loss due to EMIC waves, and slow loss due to hiss waves are all expressed in terms of the solar wind speed, dynamic pressure, and interplanetary magnetic field (IMF). The model achieves a prediction efficiency (PE) of 0.45 at L = 5 and 0.51 at L = 4 after converting the electron phase space densities to differential fluxes and comparing with Van Allen Probes measurements of 2 and 3 MeV electrons at L = 5 and L = 4, respectively. Machine learning techniques are used to tune parameters to get higher PE. By tuning parameters for every 60-day period, the model obtains PE values of 0.58 and 0.82 at L = 5 and L = 4, respectively. Inspired by these results, we divide the solar wind activity into three categories based on the condition of solar wind speed, IMF Bz, and dynamic pressure, and then tune these three sets of parameters to obtain the highest PE. This experiment confirms that the solar wind speed has the greatest influence on the electron flux variations, particularly at higher L, while the dynamic pressure has more influence at lower L. Also, the PE at L = 4 is mostly higher than those at L = 5, suggesting that the electron loss due to the magnetopause shadowing combined with the outward radial diffusion is not well captured in the model. [ABSTRACT FROM AUTHOR]

Electron flux oscillations are often observed in electron energy channels in the range of 10 keV to 100 keV. They are observed in the form of flux fluctuations with periods corresponding to the drift periods of electrons around the Earth and can be produced in the magnetosphere as a result of drift resonant interactions in association with broadband ultra-low frequency (ULF) waves. They are observed in particular during quiet times and are indicators of ongoing drift-resonant processes and resulting radial transport caused by ULF waves. In this study we investigate the association of the appearance of such flux oscillations with the local phase space density. In particular, it is shown that flux oscillations appear when nonzero phase space density gradients are present and furthermore that the observed amplitude of flux oscillations is dependent on radial phase space density gradients, with steeper gradients enabling the observation of flux oscillations with higher-amplitude. Via statistical observations from the Van Allen probes twin-spacecraft mission while at apogee at L* ~5 to ~5.6 it is found that, during quiet times, electron flux oscillations are more likely to diminish for electron energy of ~400 keV, and associated phase space density is more likely to be zero for the corresponding first adiabatic invariant values of ~300 MeV/G. It is also concluded that flux oscillations could be used as indicators of phase space density gradients. [ABSTRACT FROM AUTHOR]

Radiation belt electrons have a complicated relationship with geomagnetic activity. We select electron measurements from 7 years of DEMETER and 6 years of Van Allen Probes data during geomagnetic storms to conduct statistical analysis focusing on the correlation between electron flux and Dst index. We report, for the first time, an upper limit of electron fluxes observed by both satellites throughout the inner and outer belts across a wide energy range from ~100s keV to multi-MeV. The upper flux limit is determined at different L's and energies, for example, 1.9 X 107/cm²-s-sr-MeV at 470 keV at L = 1.5 and 3.6 X 105/cm²-s-sr-MeV at 3.4 MeV at L = 4 (Van Allen Probes). We present the energy spectra of the electron flux upper limit at different L shells and find the measured upper flux limit to be at least three times higher than the predicted flux from the AE8/AE9 models, although the spectral shape is remarkably similar. We show that the average flux with an applied time lag is better correlated with the Dst index and that the time lag optimizing the correlation coefficient is larger at lower L and at higher energies. These findings present the underlying challenges to model the dynamic variation of relativistic electrons in the inner magnetosphere and are important information for space weather considerations. [ABSTRACT FROM AUTHOR]

Electrons in the Earth's radiation belts can be categorized into three populations: precipitating, quasi-trapped, and trapped. We use data from the Detection of Electro-Magnetic Emissions Transmitted from Earthquake Regions (DEMETER) and Solar, Anomalous, and Magnetospheric Particle Explorer satellite (SAMPEX) missions and from ground-based neutron monitors (NM) and sunspot observations to investigate the long-term variation of quasi-trapped and trapped sub-MeV electrons on different L shells in the inner belt. DEMETER and SAMPEX measurements span over 17 years and show that at L 1.14 the electron flux is anticorrelated with sunspot number, but proportional to the cosmic ray intensity represented byNMcount rates, which suggests that electrons at the inner edge of the inner belt are produced by Cosmic Ray Albedo Neutron Decay (CRAND). The solar cycle variation of cosmic rays increased the electron flux at L 1.14 by a factor of 2 from solar maximum at 2001 to solar minimum at 2009. At L 1.2, both quasi-trapped and trapped electrons are enhanced during geomagnetic storms and decay to a background level during extended quiet times. At L > 2, quasi-trapped electrons resemble trapped electrons, with correlation coefficients as high as 0.97, indicating that pitch angle scattering is the dominant process in this region. [ABSTRACT FROM AUTHOR]

Earth's slot region, lying between the outer and inner radiation belts, has been identified as due to a balance between inward radial diffusion and pitch angle (PA) scattering induced by waves. However, recent satellite observations and modeling studies indicate that cosmic ray albedo neutron decay (CRAND) may also play a significant role in energetic electron dynamics in the slot region. In this study, using a drift-diffusion-source model, we investigate the relative contribution of all significant waves and CRAND to the dynamics of energetic electrons in the slot region during July 2014, an extended period of quiet geomagnetic activity. The bounce-averaged PA diffusion coefficients from three types of waves (hiss, lightning-generated whistlers [LGW], and very low frequency [VLF] transmitters) are calculated based on quasi-linear theory, while the CRAND source follows the results in Xiang et al. (2019, https://doi.org/10.1029/2018GL081730). The simulation results indicate that both LGW and VLF transmitter waves can enhance loss and weaken the top hat PA distribution induced by hiss waves. For 470 keV electrons at L 2.5, simulation results without CRAND show a much quicker decrease than observations from the Van Allen Probes. After including CRAND, simulated electron flux variations reproduce satellite observations, suggesting that CRAND is an important source for hundreds of keV electrons in the slot region during quiet times. The balance between the CRAND source and loss due to wave-particle interactions provides a lower limit to relativistic electron fluxes in the slot region, which can act as an important reference point for instrument calibration when a true background level is warranted. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the most common malignancy involving the kidneys and a major cause of cancer mortality. The involvement of microRNA (miRNA) expression in the tumorigenesis and progression of RCC has been previously highlighted. Therefore, we conducted this study to investigate whether microRNA‐363 (miR‐363) affects the development of RCC via the Janus tyrosine kinases (JAK2)–signal transducers and activators of transcription (STAT) axis by targeting the growth hormone receptor (GHR), by observing the changes that occurred in the RCC and the normal adjacent tissues of patients with RCC. RCC cells were transfected with a series of miR‐363 mimic, miR‐363 inhibitor, or small interfering RNA against GHR to determine the influence of miR‐363 on the expression of GHR and JAK2–STAT3 axis‐related genes with the use of reverse transcription quantitative polymerase chain reaction and Western blot analysis. The angiogenesis, viability, invasion, and migration of cells were evaluated by means of in vitro angiogenesis, 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐phenytetrazoliumromide (MTT), wound‐healing, and Transwell assays. The results revealed reduced miR‐363 expression and elevated GHR expression in RCC. It was also found that miR‐363 altered the activation of the JAK2–STAT3 axis through the inhibition of GHR. Cells treated with the miR‐363 inhibitor presented with increased capillary vessels, cell viability, invasion, and migration, whereas it was on the contrary in the RCC cells with overexpressed miR‐363. These results implicated that the overexpression of miR‐363 could specifically bind to GHR to downregulate the expression of GHR, which, in turn, inactivates the JAK2–STAT3 axis, thereby influencing the angiogenesis, cell invasion, and migration abilities in RCC. The overexpression of microRNA‐363 (miR‐363) could specifically bind to the growth hormone receptor (GHR) to downregulate the expression of GHR, which, in turn, inactivates the Janus tyrosine kinases (JAK2)–signal transducers and activators of transcription (STAT) axis, thereby influencing the angiogenesis, cell invasion, and migration abilities in renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Neoadjuvant therapy has become increasingly common in human epidermal growth factor receptor-2 (HER2)-positive breast cancer. In this study, we examined the impact of different clinicopathological characteristics on pathological complete response (pCR) in patients treated with anti-HER2 agents. The PubMed and Embase databases were searched from inception through April 2017 to identify studies that met pre-specified criteria. The odds ratios (ORs) and 95% confidence intervals (CIs) were extracted directly or were calculated with other available information. Eleven randomized controlled trials (RCTs) that involved 3,269 HER2-positive women were included in this meta-analysis. Patients with hormone receptor (HR)-negative breast cancer benefited more from anti-HER2 therapy than did patients with HR-positive tumours (OR, 2.25; 95% CI, 1.93-2.62). Furthermore, this improvement in pCR was independent of anti-HER2 agents, phase, combined chemotherapy, neoadjuvant duration, year the trials started and region where the trials were conducted. Patients with small tumours achieved greater benefits than patients with large tumours (OR, 1.25; 95% CI, 1.00-1.55). Age did not predict an additional benefit from anti-HER2 neoadjuvant treatment (OR, 1.02; 95% CI, 0.73-1.45). The impact of nodal status on pCR was dependent on the anti-HER2 agents. In conclusion, for HER2-targeted neoadjuvant treatment in breast cancer, greater benefits were achieved in patients with small HR-negative tumours compared with patients with large HR-positive tumours. These results may improve drug development and treatment strategies, economic analyses and the design and interpretation of clinical trials. [ABSTRACT FROM AUTHOR]

Serum- and glucocorticoid-inducible kinase 3 (SGK3) is a downstream mediator of PI3K, which is essential for maintaining the functional integrity of podocytes. However, little is known about the role of SGK3 in podocyte function. Herein, we demonstrated that SGK3 contributes to the maintenance of podocyte integrity. Conditionally immortalized mouse podocyte cells (MPCs) were treated with puromycin aminonucleoside (PAN). PAN treatment inhibited the activity of SGK3 and the expression of podocin. Short hairpin RNA (shRNA)-mediated knockdown of SGK3 also reduced podocin expression in the absence of PAN. Adriamycin (ADR)-treated mice developed proteinuria and had decreased renal glomerular SGK3 expression in comparison to control mice. Consistent with a role for SGK3 in the ADR effect, SGK3 knockout (KO) mice had markedly reduced kidney podocin expression and significantly elevated proteinuria compared with wild-type mice. Electron microscopy revealed that SGK3 KO mice displayed partial effacement of podocyte foot processes. Further, a SGK3 target protein, glycogen synthase kinase-3 (GSK3), was discovered to be dramatically activated in PAN and SGK3 shRNA-treated MPCs and in SGK3 KO mice. Taken together, these data strongly suggest that SGK3 plays a significant role in regulating podocyte function, likely by controlling the expression and activity of GSK3. [ABSTRACT FROM AUTHOR]

Melilotus albus Medik. is a legume species with potential to be used as a forage or conserved fodder in Northwest China. Breeding M. albus as a forage crop is focused on simultaneously improving forage yield and reducing coumarin (Cou) content. The goal of the present study was to estimate genotypic variation for several key agronomic traits and to evaluate the impact of single-trait selection and Smith--Hazel-index-based multitrait selection for herbage dry weight (DW), plant height (PH), stem number (SN), and leaf area (LA). A quantitative genetic analysis was conducted on trait measurements from 25 half-sib (HS) families evaluated at Yuzhong and Linze, in China. Significant (P < 0.05) genotypic variation among the HS families for all traits was observed. There was also significant (P < 0.05) genotype x environment interaction for all traits except for LA. The predicted genetic gain, based on estimated genotypic variance, for single-trait selection varied from 2.3 to 30.3% per selection cycle. Pattern analysis of the HS family ´ multitrait best linear unbiased prediction matrix provided a graphical summary of the association among the traits, as well as the four HS family groups generated from clustering. Some members within Group 1 could be crossed to generate a breeding population to be used in recurrent selection for M. albus cultivar development in Northwest China. The applicability of a Smith--Hazel selection index to increase expression of the traits DW, PH, and SN and reduce LA, indirectly reducing Cou content, was confirmed. This index enabled identification of families for increasing key biomass traits and decreasing Cou production. [ABSTRACT FROM AUTHOR]

Amino acid content and composition are important nutritional components of wheat (Triticum aestivum L.) grain. Field experiments were conducted with six high-protein and four lowprotein cultivars (HPCs and LPCs), grown under four N application rates (0, 120, 225, and 330 kg ha-1) at two sites to understand the variations of amino acid composition in wheat grain and its responses to N fertilizer management. Amino acid composition was significantly influenced by site, cultivar, N rates, and their interactions. Planting site had the greatest effects on lysine, threonine, isoleucine, histidine, and total essential amino acids (EAA), while N fertilizer had the greatest effects on leucine, phenylalanine, total amino acid (TAA) and essential amino acids index (EAAI). In contrast, cultivars displayed relative low but stable effects on amino acid composition. High-protein cultivars always obtained greater content of EAA compositions, while LPCs had higher N use efficiencies for EAA and lysine contents. Applied N significantly increased grain yield and contents of protein, EAA, TAA, and lysine at both sites, while it significantly decreased EAAI and protein digestibility- corrected amino acid score (PDCAAS) at Xinyang. The greater yield and lysine, EAA, and TAA content were optimized with the application of N rates of 225 kg ha-1 at Nanyang (wheat-maize [Zea mays L.] rotation system) and 120 to 225 kg ha-1 at Xinyang (wheat-rice [Oryza sativa L.] rotation system). It indicated that under rainfed and temperate environmental conditions, improving lysine, EAA, and TAA in wheat production could be achieved through combinations of cultivar selection and adoption of sitespecific nutrient management practices. [ABSTRACT FROM AUTHOR]

Straw incorporation (SI) is considered a valid agricultural measure for ameliorating soil quality and sequestrating soil C. This study aimed to quantitatively summarize the response of cereal yield to SI management. Our results showed that compared with straw removal, SI could significantly enhance cereal yield by 7% over all of China across the 9-yr period. In all regions, SI in coarse-textured soils increased yields more than in fine-textured soils. Straw incorporation resulted in greater yield increases for upland crops compared with rice (Oryza sativa L.) cropping, and for rotary tillage compared with plowing and no tillage. Overall, SI-induced cereal yield increases were greater in areas with a lack of soil nutrients and soil water. The SI-induced increases of 1 t ha-1 of soil organic C (SOC) storage could increase cereal yield by 44 kg ha-1. If half or full amounts of cereal straw is returned across all of China's agricultural regions, cereal yields would increase by an average of 2.84 and 5.07 Tg yr-1, respectively, which would contribute to achieving the increasing yield requirements of China. [ABSTRACT FROM AUTHOR]

This study presents a hierarchical background modelling and subtraction approach for real-time detection of moving objects. At the first level, a novel pixel-wise background modelling method is proposed for coarse detection. The method can dynamically assign the optimal number of components for each pixel with the borrow-lend strategy. And a flexible learning rate which is variable and different for each component is presented to adapt to scene changes. Additionally, a new mechanism using a framework of finite state machine is introduced to maintain and update the background models. At the second level, in order to deal with sudden illumination changes, a block-wise foreground validation approach is adopted for refined detection. The authors compare the proposed approach with state-of-the-art methods and experimental results under various scenes demonstrate the robustness and effectiveness of the proposed approach. [ABSTRACT FROM AUTHOR]

This study reports on self-regulated learning ( SRL) of Chinese distance learners by using a structured SRL scale. SRL of adult and lifelong learners is a well-researched area, though its application within distance education is a new area of investigation. Open and distance learning lean heavily on self-learning and self-learning resources, though interaction at designated learning centers and online learning platforms is occasionally offered. In China, there is still persistence of the age-old teacher-centric model of teaching-learning; and, within distance education offered largely by the radio and television universities, there is insistence for regular tuition classes at designated branch schools. At the backdrop of understanding and enhancing SRL of Chinese distance learners, the authors took up this research to find out the elements and levels of SRL ability among Chinese distance learners. Based on factor analysis (on 357 students for item analysis and on 600 distance learners for structural validity of the initial 117-item scale), a standardized 54-item Self-regulated Learning Ability Scale was finalized and administered on a random sample of 2738 undergraduate learners (1630 males and 1108 females) from the Open Distance Education Centre of Beijing Normal University, P. R. China, doing an online course during 2009-10. The sample came from either senior high school (grade 12) or junior college (grade 14). Data on four dimensions of SRL-planning, control, regulating and evaluation-were analyzed using ' t' test for variables of gender, level of education and age. Results indicated that all the participants had above-average levels of SRL in all the four dimensions of planning, control, regulating and evaluation. In so far as gender was concerned, male distance learners were better in SRL than female distance learners, especially in control (ie, content and resources) and all the evaluation dimensions. Though no age difference was found, students from junior colleges had better planning, regulating and evaluating abilities than those who came from senior high schools. These results have been discussed in the context of current changes in Chinese distance/online education and also in relation to the age-old Chinese culture of learning. The results will also have implications for designing distance and online learning generally. [ABSTRACT FROM AUTHOR]

Relay cropping timing has been frequently reported to influence flue-cured tobacco (Nicotiana tabacum L.) production. However, the optimal planting time for a relay corn (Zea mays L.) crop on flue-cured tobacco fields is unknown in terms of tobacco health, yield, quality, and economic value. A field experiment was conducted with 10, 17, 24, and 31 d after flue-cured tobacco apex excision as the relay cropping timings of corn, and tobacco monoculture as the control at Chuxiong, Yunnan, China in 2010 and 2011. The five treatments were repeated three times in a randomized complete block design. The occurrence of brown spot (Alternaria alternata), plant biomass, plant N and K nutrition, yield, chemical composition, smoking quality, and economic value of flue-cured tobacco were affected by year. Relay cropping 17 d after tobacco apex excision resulted in better chemical composition and smoking quality. The incidence and severity index of brown spot, plant biomass, plant N and K nutrition, yield, chemical composition, smoking quality, and economic value of tobacco were not significantly affected by the relay cropping timing of corn, indicating that relay cropping of corn at a later growth stage of flue-cured tobacco has no negative effect on tobacco production while the relay corn crop may bring additional income to tobacco growers. In conclusion, if the production of relay corn is profitable, relay cropping of corn after flue-cured tobacco apex excision could become a recommended cropping system in Yunnan and other regions with similar environmental conditions. [ABSTRACT FROM AUTHOR]

Objectives To evaluate renorrhaphy techniques and to analyze surgical outcomes in retroperitoneal laparoscopic partial nephrectomy. Methods A retrospective study from January 2008 to December 2011 analyzed 526 patients with renal tumors in whom renorrhaphy was changed from one layer, interrupted, figure-of-eight ( n = 228) suture to two layers, continuous, unknotted ( n = 298) suture. All procedures were carried out by the same laparoscopic surgeon ( XZ). Patient demographics, tumor characteristics, operative outcomes and perioperative renal function were compared. Results Median follow up for one layer, interrupted, figure-of-eight suture and two layers, continuous, unknotted suture was 31 and 28 months, respectively. The two layers, continuous, unknotted suture group had shorter warm ischemia time ( P = 0.021), faster removal of Jackson- Pratt drains ( P = 0.029) and shorter hospital stay ( P = 0.037) than the one layer, interrupted, figure-of-eight suture group. There was a trend towards a better preservation of glomerular filtration rates in the two layers, continuous, unknotted suture group ( P = 0.045). In a multivariable model, the two layers, continuous, unknotted suture technique was a statistically significant independent predictor of warm ischemia time ( P = 0.01), hospital stay ( P = 0.001) and estimated glomerular filtration rates ( P = 0.043). Conclusions Two layers, continuous, unknotted suture renorrhaphy allows better outcomes than one layer, interrupted, figure-of-eight suture renorrhaphy in retroperitoneal laparoscopic partial nephrectomy. A longer clinical follow-up evaluation is warranted. [ABSTRACT FROM AUTHOR]

Two new complexes with 5-methyl-1-(pyridine-3-yl)-1H-1,2,3-triazole-4-carboxylic acid (Hmptc) ligand: [Cd(mptc)2(H2O)4] (1) and [Cu(mptc)4 ⋅ 2H2O]n (2) were prepared and their crystal structures were determined by single crystal X-ray diffraction analyses. In complex 1, the Cd(II) ions coordinates with the pyridyl nitogen atom from the Hmptc ligand, forming a mononuclear Cd(II) compound. Complex 2 exhibits a novel two-dimensional (2D) polymer in which four Hmptc ligands stabilize the Cu(II) atom. And the coordination involves one nitrogen atom of the triazole, one oxygen atom of the carboxylic acid and the pyridyl nitrogen atom. In addition, FT-IR and solid-state fluorescent emission spectroscopy of two compounds have been determined. [ABSTRACT FROM AUTHOR]

The article discusses a clinical investigation through an analysis of 61 cases of retroperitoneoscopic left living donor nephrectomy carried out from March 2008 to June 2010. The study to increase awareness of the variations in anatomy of the posterior lumbar tributaries of the left renal vein was jointly conducted by the Chinese PLA General Hospital and the 309 Hospital of PLA in Beijing, China. Also mentioned are the details of the analysis including the objectives, results and conclusions.

Background. Very few articles have been written about the expression of kallikreins (KLK4 and KLK7) in oral cancers. Therefore, the purpose of this study was to examine and report on their prognostic potential. Methods. Eighty archival blocks of primary oral cancers were sectioned and stained for KLK4 and KLK7 by immunohistochemistry. The percentage and the intensity of malignant keratinocyte staining were correlated with patient survival using Cox regression analysis. Results. Both kallikreins were expressed strongly in the majority of tumor cells in 68 of 80 cases: these were mostly moderately or poorly differentiated neoplasms. Staining was particularly intense at the infiltrating front. Patients with intense staining had significantly shorter overall survival (p < .05). Conclusion. This is the first observation on the patient survival influenced by kallikrein expression in oral carcinoma. The findings are consistent with those for carcinomas at other sites, in particular the prostate and ovary. KLK4 and/or KLK7 mmunohistochemistry seems to have diagnostic and prognostic potential in this disease. [ABSTRACT FROM AUTHOR]

Hepatitis B re-activation is a well-described complication in patients with inactive chronic hepatitis B receiving chemotherapy. Screening for HBV and pre-emptive therapy are recommended. However, the rates of HBV screening, prophylaxis and re-activation during rituximab-containing chemotherapy are unknown. We performed a retrospective study of patients with non-Hodgkin lymphoma (NHL) who received rituximab between August 1997 and September 2009. We evaluated patients for hepatitis B serologies, antiviral prophylaxis and hepatitis B re-activation during or up to 6 months after chemotherapy. One thousand four hundred and twenty-nine patients underwent rituximab-containing chemotherapy for NHL. Hepatitis B serologies were documented in 524 (36.6%) patients. Of these, 20 (3.8%) were HBsAg positive and 10 (50%) experienced HBV re-activation. Only half (5/10) had HBV serology documented before re-activation. Only 3/8 (37.5%) of patients with newly documented HBsAg positivity received antiviral prophylaxis. Virological breakthrough occurred in two of the patients on chronic therapy, in one of three inactive carriers on prophylaxis and in two of five patients not receiving prophylaxis. Re-activation developed in another five patients not screened previously for hepatitis B. One patient developed ALF and died. Re-activation did not occur in 25 patients with isolated positive core antibody. At tertiary care institutions hepatitis B serologies are infrequently assessed before rituximab-based chemotherapy and prophylaxis is uncommon. Greater adherence to recommendations for screening and prophylaxis is necessary. This suboptimal screening rate could be even lower in community hospitals and could result in significant harm to unscreened and unprophylaxed patients. [ABSTRACT FROM AUTHOR]

In searching for new targets for antimalarials we investigated the biosynthesis of hypusine present in eukaryotic initiation factor-5A (eIF-5A) in Plasmodium. Here, we describe the cloning and expression of deoxyhypusine hydroxylase (DOHH), which completes the modification of eIF-5A through hydroxylation of deoxyhypusine. The dohh cDNA sequence revealed an ORF of 1236 bp encoding a protein of 412 amino acids with a calculated molecular mass of 46.45 kDa and an isoelectric point of 4.96. Interestingly, DOHH from Plasmodium has a FASTA SCORE of only 27 compared with its human ortholog and contains several matches similar to E-Z-type HEAT-like repeat proteins (IPR004155 (InterPro), PF03130 (Pfam), SM00567 (SMART) present in the phycocyanin lyase subunits of cyanobacteria. Purified DOHH protein displayed hydroxylase activity in a novel in vitro DOHH assay, but phycocyanin lyase activity was absent. dohh is present as a single-copy gene and is transcribed in the asexual blood stages of the parasite. A signal peptide at the N-terminus might direct the protein to a different cellular compartment. During evolution, Plasmodium falciparum acquired an apicoplast that lost its photosynthetic function. It is possible that plasmodial DOHH arose from an E/F-type phycobilin lyase that gained a new role in hydroxylation. Structured digital abstract • : DHS (uniprotkb: ) enzymaticly reacts ( ) with eIF-5A (uniprotkb: ) by enzymatic studies ( ) • : DOHH (uniprotkb: ) enzymaticly reacts ( ) with eIF-5A (uniprotkb: ) by enzymatic studies ( ) [ABSTRACT FROM AUTHOR]

Although without clear scientific rationale, body size- based dosing is often used for administering monoclonal antibodies (mAbs). This simulation study compared the performance of body size-based and fixed dosing in reducing pharmacokinetic (PK) and/or pharmacodynamic (PD) variability in adults for 12 mAbs with published population PK and/or PD models. At the population level, 95th percentile intervals of concentration-time profiles, distribution, and variability of exposure for 1000 subjects after both dosing approaches were examined. At the individual level, the difference between the exposures of patients with extreme body sizes from the typical exposure following both approaches was compared. The results show that the 2 dosing approaches perform similarly across the mAbs investigated with fixed dosing being better for some mAbs and body size-based dosing being better for the others. Based on this finding, we recommend using fixed dosing in first-in-human (FIH) adult studies because it offers other advantages. When sufficient data become available, a full assessment of body size effect on PK/PD should be conducted to determine the optimal dosing approach for phase 3 trials. Other factors that may affect the selection of dosing approach were also discussed. Dosing approach for mAbs in the pediatric population is out of the scope of this study. [ABSTRACT FROM AUTHOR]

The adenylyl cyclase-associated protein (CAP) was first identified in the budding yeast as a protein that functions in cytoskeletal organization and signal transduction. We isolated two CAP homologs from wild-type cotton Gossypium arboreum L. (DPL971) and its natural fuzzless mutant (DPL972). Alignments of 3998-bp genomic and 1425-bp cDNA sequences revealed that the cap genes contain nine introns and an open reading frame (ORF) encoding a 471 amino acid protein. The predicted amino acid sequence shares high identity (~70%) with Arabidopsis thaliana, Medicago truncatula, and Oryza sativa. Expression profiles of the gene were studied from ovule, leaf, hypocotyl, and root tissues, through reverse transcriptase polymerase chain reaction and Northern blotting analysis. The results revealed that the gene was expressed in all tissues tested in wild-type and fuzzless plants. The expression of GaCAP reached the highest level in both wild-type and mutant fibers during 1 to 4 d postanthesis (DPA), then gradually declined in the mutant after 4 DPA. By comparing the predicted amino acid sequences, a polar substitution was observed at a conserved position between wild-type and mutant. At this position, the conserved uncharged unpolar alanine (amino acid 44) of GaCAP was replaced by a polar threonine in GaCAPm. Therefore, our results suggest that GaCAP may play a functional role during early stages of cotton fiber development. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate the association between DNA polymorphisms, including single-nucleotide polymorphisms (SNPs) and insertion/deletion polymorphisms, in exon 1 and promoter of the CDH1 gene, and the risk of transitional cell carcinoma (TCC) of the urinary bladder (TCCB). PATIENTS, SUBJECTS AND METHODS This was a hospital-based case-control study of 180 patients with TCCB and 110 normal controls. Genomic DNA was extracted from blood samples of all participants and genotypes determined using polymerase chain reaction and DNA sequencing techniques. Haplotypes were analysed using appropriate software. RESULTS SNPs were detected at −160A/C, −73A/C and 178C/T; an inserted oligonucleotide of 5′-CCGTGCCCCAGCC-3′ was identified at 234 bp. The −160A allele frequency in the case group was 0.67, statistically higher than in the control group (0.42; P < 0.001), and higher in invasive carcinoma (0.77) than in superficial carcinoma (0.60). For −73C/A and 178C/T SNPs there was no difference among genotypes. The 234 repeat oligonucleotide insertion (2I) frequencies in cases was 0.27, statistically higher than in the control group (0.17; P = 0.01). The most common haplotype in controls was C-A-T-I (28%), the frequency of which was higher than in the TCCB group (6%). The A-A-T-2I was the only variation distribution carrying the −160A allele and was at a statistically higher frequency in the TCCB group (37%, the most common haplotype in cases) than in the control group. CONCLUSION The −160A, 234 2I allele and haplotype A-A-T-2I were risk factors of TCCB. Haplotype C-A-T-I might act as a protective factor for TCCB. [ABSTRACT FROM AUTHOR]

Three new eremophilane sesquiterpenes were isolated from the MeOH extract of the roots of Senecio nemorensis. Their structures were identified as 8α-hydroxy-6β-(isobutanoyloxy)-1-oxoeremophila-7(11),9-dieno-12,8β-lactone (1), 6β,8β-dimethoxy-1-oxoeremophila-7(11),9-dieno-12,8α-lactone (2), and 10α-hydroxy-6β-(isobutanoyloxy)-1-oxoeremophila-7(11),8-dieno-12,8-lactone (3), respectively, based on spectroscopic data, including IR, EI-MS, HR-ESI-MS, and 1D- and 2D-NMR data. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects induced by three different sterilization methods [steam, γ‐radiation, and ethylene oxide (EO)] with different dose or time period of sterilization by means of Fourier transform infrared spectroscopy, X‐ray diffraction, and assessments of molecular weight and degree of deacetylation. The experiment results clearly showed that the steam sterilization greatly darkened the color of chitosan powder; γ‐irradiation strongly depolymerized the chitosan especially at irradiation dose above 10 kGy; and exposure to EO led to minor change in crystallinity and network structure of chitosan powder. Therefore, these three methods have their respective advantages and disadvantages, suggesting that the selection of the sterilization method of chitosan should depend upon the specific requirement of the final application. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 1968–1972, 2007 [ABSTRACT FROM AUTHOR]

Covalent attachment of phycocyanobilin (PCB) to the α-subunit of C-phycocyanin, CpcA, is catalysed by the heterodimeric PCB : CpcA lyase, CpcE/F [Fairchild CD, Zhao J, Zhou J, Colson SE, Bryant DA & Glazer AN (1992) Proc Natl Acad Sci USA 89, 7017–7021]. CpcE and CpcF of the cyanobacterium, Mastigocladus laminosus PCC 7603, form a 1 : 1 complex. Lyase-mutants were constructed to probe functional domains. When in CpcE (276 residues) the N terminus was truncated beyond the R33YYAAWWL motif, or the C terminus beyond amino acid 237, the enzyme became inactive. Activity decreases to 20% when C-terminal truncations went beyond L275, which is a key residue: the Km of CpcE(L275D) and (L276D) increased by 61% and 700%, kcat/ Km decreased 3- and 83-fold, respectively. The enzyme also lost activity when in CpcF (213 residues) the 20 N-terminal amino acids were truncated; truncation of 53 C-terminal amino acids inhibited complex formation with CpcE, possibly due to misfolding. According to chemical modifications, one accessible arginine and one accessible tryptophan are essential for CpcE activity, and one carboxylate for CpcF. Both subunits bind PCB, as assayed by Ni2+ affinity chromatography, SDS/PAGE and Zn2+-induced fluorescence. The bound PCB could be transferred to CpcA to yield α-CPC. The PCB transfer capacity correlates with the activity of the lyase, indicating that PCB bound to CpcE/F is an intermediate of the enzymatic reaction. A catalytic mechanism is proposed, in which a CpcE/F complex binds PCB and adjusts via a salt bridge the conformation of PCB, which is then transferred to CpcA. [ABSTRACT FROM AUTHOR]

The chemical modification of β-N-acetyl-D-glucosaminidase (EC3.2.1.30) from Turbo cornutus Solander has been first studied. The results demonstrate that the sulfhydryl group of cysteine residues and the hydroxyl group of serine residues are not essential to the enzyme's function. The modification of indole group of tryptophan of the enzyme by N-bromosuccinimide (NBS) can lead to the complete inactivation, accompanying the absorption decreasing at 278 nm and the fluorescence intensity quenching at 335 nm, indicating that tryptophan is essential residue to the enzyme. The modification of amino group of lysine residue by formaldehyde and trinitrobenzenesulfonic acid also inactivates the enzyme completely. The results show that lysine and tryptophan are probably situated in the active site of the enzyme. The modification of the imidazole residue and carboxyl group leads to inactivate incompletely, indicating they are not the composing groups of the enzyme active center, and they are essential for maintaining the enzyme's conformation which is necessary for the catalytic activity of the enzyme. IUBMB Life, 55: 547-552, 2003 [ABSTRACT FROM AUTHOR]

Background: Breath odor is scored by different techniques, each with its own shortcomings. Organoleptic ratings are uncomfortable for the patient, subjective, influenced by external parameters including food and cosmetics, and especially lack international calibration. Portable sulphide monitors are relatively expensive and neglect several major malodorous molecules (e.g., butyric and propionic acids, putrescine, and cadaverine). Gas chromatography necessitates expensive devices and experienced technicians. This pilot study explored the applicability of a new technique (saliva incubation) by comparing its discrimination power, in a morning bad breath inhibition study of antiseptics, to those of hydrogen sulphide (H2S) measurement devices and organoleptic ratings. Methods: After a professional cleaning, 8 periodontally healthy students abstained from all means of mechanical plaque control for 5 experimental periods of 7 days, with intervening washout periods of at least 2 weeks. During each experimental period, the students rinsed only twice daily with different antiseptics. At day 7, morning breath was scored clinically (volatile sulphide compound [VSC] level and organoleptic ratings), and 13 ml of saliva was collected and divided between 3 glass tubes that were sealed and incubated (37°C, anaerobic chamber). Immediately after collection and after 3 and 6 hours of incubation, the headspace air in one of the tubes was examined for VSC production and organoleptic measurements. Results: The investigations of the incubated saliva correlated well with the 7-day intraoral VSC recordings and organoleptic ratings (P ≤0.005). Moreover, evaluations showed a similar inter-product ranking for their efficacy in malodor control. The power analyses indicated a higher discrimination power for the saliva incubation test than for the intraoral registrations. Conclusions: The strong correlation between odor production of incubated saliva and clinical assessments suggests that the saliva incubation test may be used as an indirect method to measure oral malodor and can be employed to investigate the antimalodor effectiveness of oral hygiene products. [ABSTRACT FROM AUTHOR]

Examines the grain growth phenomena in interface region of alpha-alumina bilayer composites. Relation of interfacial microstructure with carbon oxide (CaO)-Silicon Oxide (SiO[sub 2]) doping levels; Identification of grain growth modes in interface region; Impact of impurity levels on CaO-SiO[sub 2].

Key points The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole‐cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)‐Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC‐δ‐ and SOM‐positive CeL neurons. The histamine‐induced effect is mediated by H3 receptors expressed on VGLUT1‐/VGLUT2‐positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC‐δ‐ and SOM‐positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1‐ or VGLUT2‐positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)–CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors. [ABSTRACT FROM AUTHOR]