A structure--activity study of seven new water soluble nitrosoureas.

The in vitro alkylating activity, carbamoylating activity, decomposition rates and octanol-water partition coefficients (Log P) of seven water soluble chloroethylnitrosourea antitumor agents and a reference lipid soluble analog were correlated with their biological activities in mice. The alkylating activity of each compound demonstrated a significant inverse linear correlation with both the decomposition rate in 0.1 M sodium phosphate buffer. pH7.4 (r = -0.92,P< 0.01), and the molar ld₁₀ dose (r = 0.87, P< 0.01). A direct relationship was found between the Log P values and both the alkylating activity (r = -0.86. P< 0.01) and the molar ld₁₀ dose (r = 0.77, P< 0.025). However, the addition of the variable. Log P, in multiple regression analysis did not contribute significantly to any of the direct correlations of chemical parameters with biological variables. In comparison, carbamoylating activity did not function as an independent variable for the relative myelotoxicity or lethality of each compound. All water soluble drugs except for chlorozotocin and 1-(2 chloroethyl)-3-(β-d-glucopyranosyl)-1-nitrosourea, the two analogs with glucose carriers, produced a significant reduction in circulating neutrophils at their respective ld₁₀ doses. There was no correlation between relative myelotoxicity and alkylating activity, carbamoylating activity or Log P. The glucose moiety appears to function as an independent variable for reducing nitrosourea cytotoxicity to bone marrow cells without significantly altering antitumor activity.     

Deep-Learning Language-Modeling Approach for Automated,Personalized, and Iterative Radiology-Pathology Correlation

PurposeRadiology-pathology correlation has long been foundational to continuing education, peer learning, quality assurance, and multidisciplinary patient care. The objective of this study was to determine whether modern deep-learning language-modeling techniques could reliably match pathology reports to pertinent radiology reports.MethodsThe recently proposed Universal Language Model Fine-Tuning for Text Classification methodology was used. Two hundred thousand radiology and pathology reports were used for adaptation to the radiology-pathology space. One hundred thousand candidate radiology-pathology pairs, evenly split into match and no-match categories, were used for training the final binary classification model. Matches were defined by a previous-generation artificial intelligence anatomic concept radiology-pathology correlation system.ResultsThe language model rapidly adapted very closely to the prior anatomic concept-matching approach, with 100% specificity, 65.1% sensitivity, and 73.7% accuracy. For comparison, the previous methodology, which was intentionally designed to be specific at the expense of sensitivity, had 98.0% specificity, 65.1% sensitivity, and 73.2% accuracy.ConclusionsModern deep-learning language-modeling approaches are promising for radiology-pathology correlation. Because of their rapid adaptation to underlying training labels, these models advance previous artificial intelligence work in that they can be continuously improved and tuned to improve performance and adjust to user and site-level preference.     

Stochastic nonlinear time series forecasting using time-delay reservoir computers: Performance and universality

Reservoir computing is a recently introduced machine learning paradigm that has already shown excellent performances in the processing of empirical data. We study a particular kind of reservoir computers called time-delay reservoirs that are constructed out of the sampling of the solution of a time-delay differential equation and show their good performance in the forecasting of the conditional covariances associated to multivariate discrete-time nonlinear stochastic processes of VEC-GARCH type as well as in the prediction of factual daily market realized volatilities computed with intraday quotes, using as training input daily log-return series of moderate size. We tackle some problems associated to the lack of task-universality for individually operating reservoirs and propose a solution based on the use of parallel arrays of time-delay reservoirs.     

Looking in apes as a source of human pathogens

Because of the close genetic relatedness between apes and humans, apes are susceptible to many human infectious agents and can serve as carriers of these pathogens. Consequently, they present a serious health hazard to humans. Moreover, many emerging infectious diseases originate in wildlife and continue to threaten human populations, especially vector-borne diseases described in great apes, such as malaria and rickettsiosis. These wild primates may be permanent reservoirs and important sources of human pathogens. In this special issue, we report that apes, including chimpanzees (Pan troglodytes), bonobos (Pan paniscus), gorillas (Gorilla gorilla and Gorilla beringei), orangutans (Pongo pygmaeus and Pongo abelii), gibbons (Hylobates spp., Hoolock spp. and Nomascus spp) and siamangs (Symphalangus syndactylus syndactylus and Symphalangus continentis), have many bacterial, viral, fungal and parasitic species that are capable of infecting humans. Serious measures should be adopted in tropical forests and sub-tropical areas where habitat overlaps are frequent to survey and prevent infectious diseases from spreading from apes to people.     

Percutaneous transluminal coronary angioplasty: Report from the registry of the National Heart, Lung, and Blood Institute

Data have been collected from 34 centers in the United States and Europe performing percutaneous transluminal coronary angioplasty since September 1977. The procedure was carried out in 631 patients, with an average age of 51 years (range 23 to 76), of whom 80 percent had single vessel coronary disease, 17 percent had double or triple vessel disease and 3 percent had stenosis of the left main coronary artery. Coronary angioplasty was successful (greater than 20 percent decrease of coronary stenosis) in 59 percent of the stenosed arteries. The mean degree of stenosis was reduced from 83 to 31 percent. Emergency coronary bypass operation was required in 40 patients (6 percent). Myocardial infarction occurred in 29 patients (4 percent). In-hospital death occurred in six patients (1 percent), three with single vessel and three with multivessel disease. Ninety-one patients have been followed up for at least 1 year after coronary angioplasty. Of the 65 patients with an initially successful angioplasty, 83 percent were in improved condition compared with their status before angioplasty. Thus, the initial satisfactory results obtained in a few centers have now been confirmed in many centers using transluminal coronary angioplasty.     

"Mitral stenosis" secondary to combined "massive" mitral anular calcific deposits and small, hypertrophied left ventricles. Hemodynamic documentation in four patients.

Certain observations are described in four elderly women with massive mitral anular calcific deposits, small thick-walled left ventricles and diastolic gradients between pulmonary artery wedge position (or left atrium) and left ventricle. All four patients had some degree of obstruction to left ventricular outflow. Examination at necropsy (two patients) or at operation (one patient) disclosed only focal fibrous thickening of the mitral leaflets without commissural or chordal fusion. By auscultation, none had mitral opening snaps, only two had loud first heart sounds and only one had a mitral diastolic rumble. Hemodynamic documentation of a diastolic gradient between pulmonary artery wedge position (or left atrium) and left ventricle in the presence of massive mitral anular calcific deposits and in the absence of diffuse disease of the mitral leaflets has not been demonstrated previously. The diastolic gradients are considered to result from the combination of the large mitral anular calcific deposits and the small, thick-walled, noncompliant left ventricles.     

清除人类免疫缺陷病毒感染新策略研究进展

尽管HAART能有效降低HIV感染的发病率和死亡率,但长远影响尚不明确.过去几年关于HIV病毒储存库的特征性描述有利于我们更好地理解成功消除体内HIV的策略,因此清除HIV感染重新受到关注.此文主要描述了达到彻底治愈HIV的目标需要克服的主要障碍以及最新研究策略.     

First report of natural infection in hedgehogs with Leishmania major, a possible reservoir of zoonotic cutaneous leishmaniasis in Algeria

We report here the first known cases of natural infection of hedgehogs with Leishmania major. Cutaneous leishmaniasis is an important public health problem in the area of M'sila, a semi-arid province in Algeria's northern Sahara, where two species of hedgehog live, Atelerix algirus and Paraechinus aethiopicus. The aim of this research was to survey Leishmania infection in these hedgehogs and evaluate whether they were reservoir hosts of Leishmania in an endemic zoonotic focus of leishmaniasis. Serological and molecular methods were used to determine the presence of Leishmania in 24 hedgehogs caught directly by hand and identified at species level as 19 A. algirus and 5 P. aethiopicus. Specific anti-Leishmania antibodies were detected in 29.2% of individuals by Western blot and in 26.3% by ELISA. The real-time PCR performed in spleen, ear and blood samples detected Leishmania spp. DNA in 12.5% of the individuals, one A. algirus and two P. aethiopicus. Three skin and two spleen samples of these animals were found to be parasitized and were identified by molecular test as L. major. Considering our results, it is suggested that hedgehogs have a potential epidemiological role as reservoir hosts of L. major.     

3种保虫宿主日本血吸虫特征性差异表达基因的筛选与验证

目的筛选日本血吸虫3种重要保虫宿主来源虫体的特征性差异表达基因,寻找可以用于鉴别这3种宿主来源虫体的遗传标记。方法日本血吸虫尾蚴人工感染黄牛、水牛和山羊,收集感染后49 d成虫,分别抽提RNA,逆转录成cD NA,体外转录为cRNA并进行片段化;采用定制的血吸虫芯片分别进行杂交,筛选每种宿主来源虫体的特征性差异表达基因。采用实时定量PCR法对所筛选差异表达基因的表达水平做进一步测定,验证芯片数据的结果,并对这些特征性差异表达基因进行验证。结果通过芯片杂交,分析筛选获得实验黄牛组来源虫体特征性差异表达基因3个,水牛组来源虫体4个,山羊组来源虫体7个。其中黄牛组2个、水牛组3个、山羊组5个特征性差异表达基因在另一批次3种宿主来源虫体的重复试验中得到验证。结论芯片杂交筛选出10个3种宿主来源虫体的特征性差异表达基因,这些基因可能可以作为这3种不同宿主来源虫体的遗传标记。