AI-supported modified risk staging for multiple myeloma cancer useful in real-world scenario

Introduction: An efficient readily employable risk prognostication method is desirable for MM in settings where genomics tests cannot be performed owing to geographical/economical constraints. In this work, a new Modified Risk Staging (MRS) has been proposed for newly diagnosed Multiple Myeloma (NDMM) that exploits six easy-to-acquire clinical parameters i.e. age, albumin, β2-microglobulin (β2M), calcium, estimated glomerular filtration rate (eGFR) and hemoglobin.Materials and Methods: MRS was designed using a training cohort of 716 NDMM patients of our inhouse MM Indian (MMIn) cohort and validated on MMIn (n=354) cohort and MMRF (n=900) cohort. K-adaptive partitioning (KAP) was used to find new thresholds for the parameters. Risk staging rules, obtained via training a J48 classifier, were used to build MRS.Results: New thresholds were identified for albumin (3.6 g/dL), β2M (4.8 mg/L), calcium (11.13 mg/dL), eGFR (48.1 mL/min), and hemoglobin (12.3 g/dL) using KAP on the MMIn dataset. On the MMIn dataset, MRS outperformed ISS for OS prediction in terms of C-index, hazard ratios, and its corresponding p-values, but performs comparable in prediction of PFS. On both MMIn and MMRF datasets, MRS performed better than RISS in terms of C-index and p-values. A simple online tool was also designed to allow automated calculation of MRS based on the values of the parameters.Discussion: Our proposed ML-derived yet simple staging system, MRS, although does not employ genetic features, outperforms RISS as confirmed by better separability in KM survival curves and higher values of C-index on both MMIn and MMRF datasets.Funding: Grant: BT/MED/30/SP11006/2015 (Department of Biotechnology, Govt. of India), Grant: DST/ICPS/CPS-Individual/2018/279(G) (Department of Science and Technology, Govt. of India), UGC-Senior Research Fellowship.     

健康信念模式对无症状高尿酸血症病人危险行为的护理干预

目的:研究健康信念模式对无症状高尿酸血症人群的干预效果,为控制高尿酸血症寻求有效途径,从而预防冠心病、脑卒中及Ⅱ型糖尿病的发生.方法:采用随机实验组对照组实验设计,实验组以健康信念模式进行护理干预,一年后检测相关知识及生理指标,并进行统计学分析.结果:干预后实验组相关知识掌握显著优于对照组,血尿酸显著下降(P＜0.01),血脂、体重指数的差异有统计学意义(P＜0.05),血压、血糖的差异无统计学意义(P＞0.05).结论:健康信念可激发无症状高尿酸血症人群的内在动机,减少危险行为,保持最佳的健康状态.     

血清AIb、PA、NLR水平在直肠癌术后发生吻合口瘘评估中的应用

摘要 目的：探讨血清白蛋白（AIb）、前白蛋白（PA）、中性粒细胞与淋巴细胞比值（NLR）水平在直肠癌术后发生吻合口瘘评估中的应用。方法：选择2018年6月至2019年12月于我院进行直肠癌手术患者90例患者进行研究,其中38例发生术后吻合口瘘,设为研究组, 52例未发生吻合口瘘作为对照组。分析患者术后血清AIb、PA、NLR水平变化情况,采用受试者工作特征曲线分析血清AIb、PA、NLR对术后发生吻合口瘘的评估作用。结果：研究组血清AIb、PA水平显著低于对照组,NLR水平显著高于对照组,差异显著（P＜0.05）;造口组术后血清AIb、PA水平显著高于未造口组,NLR水平显著低于未造口组,差异显著（P＜0.05）;ROC结果显示,血清AIb预测术后吻合口瘘的AUC为0.967,灵敏度为81.25%,特异度为90.14%,截断值为33.06 g/L;血清PA预测术后吻合口瘘的AUC为0.772,灵敏度为80.36%,特异度为89.56%,截断值为119.04 mg/L;血清NLR预测术后吻合口瘘的AUC为0.991,灵敏度为85.62%,特异度为93.23%,截断值为6.86。结论：监测血清AIb、PA、NLR水平有助早期发现直肠癌患者术后吻合口瘘。     

The impacts and implications of an intensifying fire regime on Alaskan boreal forest composition and albedo

Climate warming and drying are modifying the fire dynamics of many boreal forests, moving them towards a regime with a higher frequency of extreme fire years characterized by large burns of high severity. Plot‐scale studies indicate that increased burn severity favors the recruitment of deciduous trees in the initial years following fire. Consequently, a set of biophysical effects of burn severity on postfire boreal successional trajectories at decadal timescales have been hypothesized. Prominent among these are a greater cover of deciduous tree species in intermediately aged stands after more severe burning, with associated implications for carbon and energy balances. Here we investigate whether the current vegetation composition of interior Alaska supports this hypothesis. A chronosequence of six decades of vegetation regrowth following fire was created using a database of burn scars, an existing forest biomass map, and maps of albedo and the deciduous fraction of vegetation that we derived from Moderate Resolution Imaging Spectroradiometer (MODIS) satellite imagery. The deciduous fraction map depicted the proportion of aboveground biomass in deciduous vegetation, derived using a RandomForest algorithm trained with field data sets (n=69, 71% variance explained). Analysis of the difference Normalized Burn Ratio, a remotely sensed index commonly used as an indicator of burn severity, indicated that burn size and ignition date can provide a proxy of burn severity for historical fires. LIDAR remote sensing and a bioclimatic model of evergreen forest distribution were used to further refine the stratification of the current landscape by burn severity. Our results show that since the 1950s, more severely burned areas in interior Alaska have produced a vegetation cohort that is characterized by greater deciduous biomass. We discuss the importance of this shift in vegetation composition due to climate‐induced changes in fire severity for carbon sequestration in forest biomass and surface reflectance (albedo), among other feedbacks to climate.     

Economical challenges to microbial producers of butanol: feedstock, butanol ratio and titer

Butanol is an important solvent and transport fuel additive, and can be produced by microbial fermentation. Attempts to generate a superior microbial producer of butanol have been made through different metabolic engineering strategies. However, to date, butanol bio-production is still not economically competitive compared to petrochemical-derived production because of its major drawbacks, such as, high cost of the feedstocks, low butanol concentration in the fermentation broth and the co-production of low-value by-products acetone and ethanol. Here we analyze the main bottlenecks in microbial butanol production and summarize relevant advances from recently reported studies. Further needs and directions for developing real industrially applicable strains in butanol production are also discussed.     

Control of DNA Replication by the Nucleus/Cytoplasm Ratio in Xenopus

The nucleus/cytoplasm (N/C) ratio controls S phase dynamics in many biological systems, most notably the abrupt remodeling of the cell cycle that occurs at the midblastula transition in early Xenopus laevis embryos. After an initial series of rapid cleavage cycles consisting only of S and M phases, a critical N/C ratio is reached, which causes a sharp increase in the length of S phase as the cell cycle is reconfigured to resemble somatic cell cycles. How the N/C ratio determines the length of S phase has been a longstanding problem in developmental biology. Using Xenopus egg extracts, we show that DNA replication at high N/C ratio is restricted by one or more limiting substances. We report here that the protein phosphatase PP2A, in conjunction with its B55α regulatory subunit, becomes limiting for replication origin firing at high N/C ratio, and this in turn leads to reduced origin activation and an increase in the time required to complete S phase. Increasing the levels of PP2A catalytic subunit or B55α experimentally restores rapid DNA synthesis at high N/C ratio. Inversely, reduction of PP2A or B55α levels sharply extends S phase even in low N/C extracts. These results identify PP2A-B55α as a link between DNA replication and N/C ratio in egg extracts and suggest a mechanism that may influence the onset of the midblastula transition in vivo.     

Copy number variations of obesity relevant loci associated with body mass index in young Chinese

Obesity is one of the most complex human diseases that are widely concerned and studied. More recently, copy number variations (CNVs) emerge as another important genetic marker to influence various human diseases. To elucidate the relationship between obesity and CNVs, this current study selected obesity-related candidate CNVs and analyzed their association with body mass index (BMI). Results showed that a CNV locus, 8q24.3, was significantly different (P = 0.0070) in CNV frequency between the obese and healthy controls in a young eastern Chinese cohort, while no statistical significance was observed in other seven candidate loci including well reported 10q11.22 and 16p11.2 loci. The association of 8q24.3 CNVs with BMI of the subjects only showed marginal significance, while the copy number (CN) of 5p15.33 had a significant correlation with the BMI of the subject. These results suggested that 8q24.3 CN gains was associated with obesity, and 5p15.33 might also contribute to obesity pathogenesis, highlighting the importance of these CNVs for obesity risks, as well as providing new evidence for CNVs in the pathology of common diseases.     

Human health risk assessment of toxic elements in fish species collected from the river Buriganga,Bangladesh

Abstract

Multielement (48) analysis was carried out of various fish species collected from river Buriganga, the most polluted river in Bangladesh to assess human health risk by toxic elements. Sixteen elements that is, Be, V, Cr, Mn, Ni, Cu, Zn, As, Se, Mo, Cd, Ba, Hg, Pb, Bi, and U, were taken into account due to their toxicities on human health. Results show that concentrations of elements in various fish species were higher in winter than those in monsoon. Among 16 elements, Mn, Cu, Zn, Cd, Ba, Pb were above Food Safety Guideline in some fishes in winter. THQ and TTHQ/HI values were less than 1 for all fishes in monsoon while THQ and TTHW/HI values were more than 1 for most of fishes in winter. These results suggesting non-carcinogenic health hazard through consumption of contaminated fishes. Only As showed low cancer risk while no cancer risk was observed for other toxic elements in monsoon. In winter, Pb showed only moderate cancer risk for Mystus vittatus (site-7) while for other fishes low cancer risk was found by Pb. It can therefore be concluded that there is human health risk in consuming of fishes collected from river Buriganga especially in winter.     

Glucose Metabolism and Regulation in Lactating Mink (Mustela Vison) - Effects of Low Dietary Protein Supply

Eighteen lactating mink raising litters of 6 to 7 kits were fed ad libitum from parturition on diets with 32% of ME derived from protein and decreasing fat:carbohydrate ratios [high fat:low carbohydrate (HFLC): 67:1, medium fat:medium carbohydrate (MFMC): 52:16, low fat:high carbohydrate (LFHC): 37:31]. Four weeks post partum the dams were fitted with a jugular vein catheter, and the experiment started with a 3 hours fasting period, after which the dams were fed 210kJ ME of the experimental diets. Blood samples were collected 10 and 5min before feeding and 30, 60, 90, 120, 150 and 180min postprandially. Two hours postprandially a single dose of 50µCi U-¹⁴C-labelled glucose was administered to each dam and blood samples were collected 5, 10, 20, 30, 45 and 60min after the tracer administration. Plasma concentrations of glucose and insulin 30 to 120min postprandially were higher in dams fed the LFHC diet, than in dams fed the HFLC diet, values for dams fed the MFMC diet being intermediate. Plasma glucagon concentrations were not significantly affected by dietary treatment. The glucagon:insulin ratios decreased postprandially in all dams, the response being significant in dams fed the LFHC diet. Plasma concentrations of urea were not significantly affected by dietary treatment. Plasma FFA concentrations tended to increase postprandially in dams fed the HFLC diet. Glucose turnover rates were approximately 4.0% permin in all dams, irrespective of dietary treatment. However, the daily glucose flux was lower in dams fed the HFLC diet than in dams fed the LFHC diet, and tended to be lower than in dams fed the MFMC diet. In conclusion, a dietary protein supply of 32% of ME simultaneously with a carbohydrate supply of 16% or 31% of ME had no adverse effects on glucose homeostasis or glucose metabolism in lactating mink.     

水环境中耐药菌污染与危害研究进展

细菌在抗菌药选择性压力下产生耐药性并可传代,通过质粒和整合子等可移动基因元件将耐药基因在相同或不同种属中广泛传播,导致细菌多重耐药,并可通过多种途径进入水体,水环境日益成为庞大的耐药基因库,为致病菌及条件致病菌提供获得大量耐药基因的机会,若多重耐药菌再次侵入人体,可能引发严重的公共卫生问题。