Accurate Patient-Specific Machine Learning Models of Glioblastoma Invasion Using Transfer Learning.

Background And Purpose: MR imaging-based modeling of tumor cell density can substantially improve targeted treatment of glioblastoma. Unfortunately, interpatient variability limits the predictive ability of many modeling approaches. We present a transfer learning method that generates individualized patient models, grounded in the wealth of population data, while also detecting and adjusting for interpatient variabilities based on each patient's own histologic data.

Measuring luteinising hormone pulsatility with a robotic aptamer-enabled electrochemical reader.

Normal reproductive functioning is critically dependent on pulsatile secretion of luteinising hormone (LH). Assessment of LH pulsatility is important for the clinical diagnosis of reproductive disorders, but current methods are hampered by frequent blood sampling coupled to expensive serial immunochemical analysis. Here, we report the development and application of a Robotic APTamer-enabled Electrochemical Reader (RAPTER) electrochemical analysis system to determine LH pulsatility.

Bone Morphogenetic Protein-6 Attenuates Type 1 Diabetes Mellitus-Associated Bone Loss.

Patients with type 1 diabetes mellitus (T1DM) often suffer from osteopenia or osteoporosis. Although most agree that T1DM-induced hyperglycemia is a risk factor for progressive bone loss, the mechanisms for the link between T1DM and bone loss still remain elusive. In this study, we found that bone marrow-derived mesenchymal stem cells (BMSCs) isolated from T1DM donors were less inducible for osteogenesis than those from non-T1DM donors and further identified a mechanism involving bone morphogenetic protein-6 (BMP6) that was produced significantly less in BMSCs derived from T1DM donors than that in control cells.

Characteristics of High Cardiovascular Risk in 1.7 Million Chinese Adults.

Background: As cardiovascular risk increases in China, interest in strategies to mitigate it is growing. However, national information about the prevalence and treatment of high cardiovascular disease (CVD) risk is limited.

Objective: To assess the prevalence and treatment of high CVD risk as well as variations in risk across population subgroups.

Serum levels of TARC, MDC, IL-10, and soluble CD163 in Hodgkin lymphoma: a SWOG S0816 correlative study.

Serum soluble chemokines/cytokines produced by Hodgkin cells and the tumor microenvironment might be of value as biomarkers in classic Hodgkin lymphoma (cHL). We assessed serum thymus and activation-related chemokine (TARC), macrophage-derived chemokine (MDC), interleukin-10 (IL-10), and soluble CD163 (sCD163) levels at baseline, time of interim fluorodeoxyglucose positron emission tomography (PET), and after therapy in cHL patients treated on S0816, an intergroup phase 2 response-adapted study evaluating escalated therapy for interim PET (PET2)-positive patients (www.clinicaltrials.

Synergistic Myoelectrical Activities of Forearm Muscles Improving Robust Recognition of Multi-Fingered Gestures.

Currently, surface electromyography (sEMG) features of the forearm multi-tendon muscles are widely used in gesture recognition, however, there are few investigations on the inherent physiological mechanism of muscle synergies. We aimed to study whether the muscle synergies could be used for gesture recognition. Five healthy participants executed five gestures of daily life (pinch, fist, open hand, grip, and extension) and the sEMG activity was acquired from six forearm muscles.

[Effect of the Sampling Scale and Number on the Heterogeneity of Soil Respiration in a Mixed Broadleaf-conifer Forest].

By upscaling the observed results at the plot scale, the carbon efflux from soils in a region can be estimated. Therefore, it is very important to investigate the spatial relations of soil respiration () and its environment and to evaluate the effect of the sampling scale and number on the accuracy of measurement at the spatial scale. Based on field observation data for a mixed broadleaf-conifer forest in the Pangquangou Nature Reserve of the Shanxi Province, two analysis methods, that is, traditional statistics and geostatistics, were used to analyze the influence of the soil water content (), soil temperature (), litter mass (), litter moisture content (), soil total carbon (C), total nitrogen (N), and ratio of C/N and sulfur (S) on the heterogeneity at 4, 2, and 1 m sampling scales.

Breast Cancer Resistance Protein and Multidrug Resistance Protein 2 Determine the Disposition of Esculetin-7-O-Glucuronide and 4-Methylesculetin-7-O-Glucuronide.

Esculetin (ET)-7-O-glucuronide (ET-G) and 4-methylesculetin (4-ME)-7-O-glucuronide (4-ME-G) are the main glucuronide of ET and 4-ME, respectively. The disposition mediated by efflux transporters for glucuronide has significant influence on the pharmacokinetic profile and efficacy of bioactive compounds. In the current study, transporter gene knockout mice and Caco-2 cells were used to explore the effects of breast cancer resistance protein (BCRP) and multidrug resistance-associated protein 2 (MRP2) on the disposition of ET-G and 4-ME-G.

Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial.

Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses and can function as bona fide antigens that facilitate tumour rejection. Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load and an immunologically 'cold' tumour microenvironment. We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study.

Morphine Exacerbates Postfracture Nociceptive Sensitization, Functional Impairment, and Microglial Activation in Mice.

Background: Emerging evidence suggests that opioid use immediately after surgery and trauma may worsen outcomes. In these studies, the authors aimed to determine whether morphine administered for a clinically relevant time period (7 days) in a tibia fracture orthopedic surgery model had adverse effects on postoperative recovery.

Methods: Mice were given morphine twice daily for 7 days after unilateral tibial fracture and intramedullary pin fixation to model orthopedic surgery and limb trauma.

Depressed TSH level as a predictor of poststroke fatigue in patients with acute ischemic stroke.

Objective: To investigate whether thyroid function profiles can predict poststroke fatigue (PSF) in patients with acute ischemic stroke.

Methods: Patients with stroke were consecutively recruited within 3 days of onset in Jinling Hospital. Serum levels of thyroid hormones, thyroid antibodies, hematologic indexes, and biochemical indexes were measured on admission.

Synergistic Interaction Between Zinc and Reactive Oxygen Species Amplifies Ischemic Brain Injury in Rats.

Background and Purpose- Although intracellular zinc accumulation has been shown to contribute to neuronal death after cerebral ischemia, the mechanism by which zinc keeps on accumulating to cause severe brain damage remains unclear. Herein the dynamic cause-effect relationships between zinc accumulation and reactive oxygen species (ROS) production during cerebral ischemia/reperfusion are investigated. Methods- Rats were treated with zinc chelator, ROS scavenger, mitochondria-targeted ROS inhibitor, or NADPH oxidase inhibitor during a 90-minute middle cerebral artery occlusion.

Exposure to Maternal Diabetes Mellitus Causes Renal Dopamine D Receptor Dysfunction and Hypertension in Adult Rat Offspring.

Epidemiological and experimental studies suggest that maternal diabetes mellitus programs hypertension that is associated with impaired sodium excretion in the adult offspring. However, the underlying mechanisms are not clear. Because dopamine receptor function is involved in the pathogenesis of hypertension, we hypothesized that impaired renal dopamine D receptor function is also involved in the hypertension in offspring of maternal diabetes mellitus.

Drastic induction of MMP-7 by cortisol in the human amnion: implications for membrane rupture at parturition.

Preterm premature rupture of fetal membranes precedes 30-40% of preterm births. Activation of matrix metalloproteases (MMPs) is the one of the major causes of extracellular matrix (ECM) degradation in membrane rupture. Increased cortisol, regenerated by 11β-hydroxysteroid dehydrogenase 1 in the amnion at parturition, is known to participate in a number of parturition-pertinent events.

Small Molecules Co-targeting CKIα and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models.

CKIα ablation induces p53 activation, and CKIα degradation underlies the therapeutic effect of lenalidomide in a pre-leukemia syndrome. Here we describe the development of CKIα inhibitors, which co-target the transcriptional kinases CDK7 and CDK9, thereby augmenting CKIα-induced p53 activation and its anti-leukemic activity. Oncogene-driving super-enhancers (SEs) are highly sensitive to CDK7/9 inhibition.

Cleavage of the leptin receptor by matrix metalloproteinase-2 promotes leptin resistance and obesity in mice.

Obesity and related morbidities pose a major health threat. Obesity is associated with increased blood concentrations of the anorexigenic hormone leptin; however, obese individuals are resistant to its anorexigenic effects. We examined the phenomenon of reduced leptin signaling in a high-fat diet-induced obesity model in mice.

Exercise Reverses Nociceptive Sensitization, Upregulated Neuropeptide Signaling, Inflammatory Changes, Anxiety, and Memory Impairment in a Mouse Tibia Fracture Model.

What We Already Know About This Topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: This study tested the hypothesis that ad lib running wheel exercise in a tibia fracture model of complex regional pain syndrome can reverse hindlimb nociceptive sensitization and inflammation in mice.

Methods: Three weeks after tibia fracture, the cast was removed and hindlimb von Frey thresholds and unweighting were tested; the mice were then randomized to either ad lib access to a running wheel for 4 weeks or no wheel access. After 4 weeks the behavioral testing was repeated and then skin, sciatic nerve, and spinal cord tissues collected for polymerase chain reaction and enzyme immunoassay measurements of neuropeptide and inflammatory mediator levels.

Winter plant phenology in the alpine meadow on the eastern Qinghai-Tibetan Plateau.

Background And Aims: There is no knowledge of winter plant phenology and its controlling factors on the Qinghai-Tibetan Plateau (QTP). Thus, we conducted a 4 year winter phenology and growth dynamics study in the alpine meadow on the eastern QTP.

Methods: From November 2013 to March 2017, the phenology of the 'winter-growth' and 'winter-green' species was recorded every 5 d.

Stroke and Cardiovascular Outcomes in Patients With Carotid Disease Undergoing Transcatheter Aortic Valve Replacement.

Background: Stroke is a serious complication of both transcatheter aortic valve replacement (TAVR) and carotid artery disease (CD). The implications of CD in patients undergoing TAVR are unclear.

Methods And Results: The Society of Thoracic Surgeons and American College of Cardiology Transcatheter Valve Therapies Registry, consisting of data from consecutive US TAVR cases during the years 2013 to 2015, was linked to Medicare claims data to ascertain 30-day and 1-year cumulative incidence rates of stroke and all-cause mortality.

Neighborhood Socioeconomic Disadvantage and Care After Myocardial Infarction in the National Cardiovascular Data Registry.

Background: Patients living in disadvantaged neighborhoods are at high risk for adverse outcomes after acute myocardial infarction (MI). Whether residential socioeconomic status (SES) is associated with quality of in-hospital care among patients presenting with MI is unclear.

Methods And Results: Multivariable logistic regression was used to examine the relationship between SES, quality of care, and in-hospital cardiovascular outcomes among patients with MI from diverse SES neighborhoods from July 2008 to December 2013, at 586 participating hospitals in the Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines quality improvement program.

Enhanced Cardiomyocyte NLRP3 Inflammasome Signaling Promotes Atrial Fibrillation.

Background: Atrial fibrillation (AF) is frequently associated with enhanced inflammatory response. The NLRP3 (NACHT, LRR, and PYD domain containing protein 3) inflammasome mediates caspase-1 activation and interleukin-1β release in immune cells but is not known to play a role in cardiomyocytes (CMs). Here, we assessed the role of CM NLRP3 inflammasome in AF.

Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys.

In nonhuman primates we tested a new set of behavioral categories for observable sedative effects using pediatric anesthesiology classifications as a basis. Using quantitative behavioral observation techniques in rhesus monkeys, we examined the effects of alprazolam and diazepam (nonselective benzodiazepines), zolpidem (preferential binding to 1 subunit-containing GABA receptors), HZ-166 (8-ethynyl-6-(2'-pyridine)-4-2,5,10b-triaza-benzo[]azulene-3-carboxylic acid ethyl ester; functionally selective with relatively high intrinsic efficacy for 2 and 3 subunit-containing GABA receptors), MRK-696 [7-cyclobutyl-6-(2-methyl-2-1,2,4-triazol-2-ylmethoxy)-3-(2-flurophenyl)-1,2,4-triazolo(4,3-)pyridazine; no selectivity but partial intrinsic activity], and TPA023B 6,2'-diflouro-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile; partial intrinsic efficacy and selectivity for 2, 3, 5 subunit-containing GABA receptors]. We further examined the role of 1 subunit-containing GABA receptors in benzodiazepine-induced sedative effects by pretreating animals with the 1 subunit-preferring antagonist -carboline-3-carboxylate--butyl ester (CCT).

Three polypeptides screened from phage display random peptide library may be the receptor polypeptide of Mycoplasma genitalium adhesion protein.

Mycoplasma genitalium adhesion protein (MgPa) is a major adhesin of M. genitalium, a human pathogen associated with a series of genitourinary tract diseases. MgPa plays a very important role in M.

Bottom-up Formation of Carbon-Based Structures with Multilevel Hierarchy from MOF-Guest Polyhedra.

Three-dimensional carbon-based structures have proven useful for tailoring material properties in structural mechanical and energy storage applications. One approach to obtain them has been by carbonization of selected metal-organic frameworks (MOFs) with catalytic metals, but this is not applicable to most common MOF structures. Here, we present a strategy to transform common MOFs, by guest inclusions and high-temperature MOF-guest interactions, into complex carbon-based, diatom-like, hierarchical structures (named for the morphological similarities with the naturally existing diatomaceous species).

Regulation of Blood Pressure by Targeting Ca1.2-Galectin-1 Protein Interaction.

Background: L-type Ca1.2 channels play crucial roles in the regulation of blood pressure. Galectin-1 (Gal-1) has been reported to bind to the I-II loop of Ca1.