Miracle-dz/UniFAR-FTUs huggingface dataset:
Matrix stiffening promotes a tumor vasculature phenotype

Significance Dysregulation of both vascular architecture and function is a hallmark of numerous diseases, including cancer. This dysregulation is currently largely attributed to up-regulated proangiogenic growth factors. Here, we show that the stiffness of the underlying extracellular matrix also plays a central role in promoting angiogenesis and a characteristic tumor-like vasculature both in vitro and in vivo. The matrix stiffness-mediated angiogenesis is dependent on increased matrix metalloprotease activity. In addition, increased matrix cross-linking disrupts endothelial cell–cell junctional integrity and results in leakier vasculature. These results suggest that altered tissue mechanics, which are characteristic of solid tumors, directly influence vascular phenotype and, subsequently, may impair therapeutic delivery and efficacy. Tumor microvasculature tends to be malformed, more permeable, and more tortuous than vessels in healthy tissue, effects that have been largely attributed to up-regulated VEGF expression. However, tumor tissue tends to stiffen during solid tumor progression, and tissue stiffness is known to alter cell behaviors including proliferation, migration, and cell–cell adhesion, which are all requisite for angiogenesis. Using in vitro, in vivo, and ex ovo models, we investigated the effects of matrix stiffness on vessel growth and integrity during angiogenesis. Our data indicate that angiogenic outgrowth, invasion, and neovessel branching increase with matrix cross-linking. These effects are caused by increased matrix stiffness independent of matrix density, because increased matrix density results in decreased angiogenesis. Notably, matrix stiffness up-regulates matrix metalloproteinase (MMP) activity, and inhibiting MMPs significantly reduces angiogenic outgrowth in stiffer cross-linked gels. To investigate the functional significance of altered endothelial cell behavior in response to matrix stiffness, we measured endothelial cell barrier function on substrates mimicking the stiffness of healthy and tumor tissue. Our data indicate that barrier function is impaired and the localization of vascular endothelial cadherin is altered as function of matrix stiffness. These results demonstrate that matrix stiffness, separately from matrix density, can alter vascular growth and integrity, mimicking the changes that exist in tumor vasculature. These data suggest that therapeutically targeting tumor stiffness or the endothelial cell response to tumor stiffening may help restore vessel structure, minimize metastasis, and aid in drug delivery.
Modelling glioblastoma tumour-host cell interactions using adult brain organotypic slice co-culture

ABSTRACT Glioblastoma multiforme (GBM) is an aggressive incurable brain cancer. The cells that fuel the growth of tumours resemble neural stem cells found in the developing and adult mammalian forebrain. These are referred to as glioma stem cells (GSCs). Similar to neural stem cells, GSCs exhibit a variety of phenotypic states: dormant, quiescent, proliferative and differentiating. How environmental cues within the brain influence these distinct states is not well understood. Laboratory models of GBM can be generated using either genetically engineered mouse models, or via intracranial transplantation of cultured tumour initiating cells (mouse or human). Unfortunately, these approaches are expensive, time-consuming, low-throughput and ill-suited for monitoring live cell behaviours. Here, we explored whole adult brain coronal organotypic slices as an alternative model. Mouse adult brain slices remain viable in a serum-free basal medium for several weeks. GSCs can be easily microinjected into specific anatomical sites ex vivo, and we demonstrate distinct responses of engrafted GSCs to diverse microenvironments in the brain tissue. Within the subependymal zone – one of the adult neural stem cell niches – injected tumour cells could effectively engraft and respond to endothelial niche signals. Tumour-transplanted slices were treated with the antimitotic drug temozolomide as proof of principle of the utility in modelling responses to existing treatments. Engraftment of mouse or human GSCs onto whole brain coronal organotypic brain slices therefore provides a simplified, yet flexible, experimental model. This will help to increase the precision and throughput of modelling GSC-host brain interactions and complements ongoing in vivo studies. This article has an associated First Person interview with the first author of the paper. Editor's choice: A new ex vivo experimental approach to explore how glioblastoma stem cells interact with distinct brain microenvironments, with potential use a as preclinical model using new anticancer agents.
Patients with anorexia nervosa demonstrate deficiencies of selected essential fatty acids, compensatory changes in nonessential fatty acids and decreased fluidity of plasma lipids.

The objective of this study was to assess the essential fatty acid status of patients with anorexia nervosa. Blood was collected from eight fasting female anorexia nervosa patients with a mean of 81% ideal body weight. Fatty acid composition of phospholipids, nonesterified fatty acids, triglycerides and cholesteryl esters of plasma were determined by capillary gas chromatography to indicate polyunsaturated fatty acids status compared with 19 healthy female adults < 25 y old. Subjects with anorexia nervosa showed polyunsaturated fatty acid deficiencies in plasma phospholipids different from simple nutritional essential fatty acid deficiency or chronic malnutrition. The phospholipid profile showed significantly lower (n-6) and (n-3) elongation and desaturation products, and elevated short-chain saturated, short-chain monounsaturated, branched-chain and odd-chain fatty acids. These elevations indicate enhancement of biosynthesis of alternative fatty acids that only partially compensated for the loss of polyunsaturated fatty acids in providing membrane "fluidity. " Calculated mean melting point of the fatty acids of phospholipids in patients with anorexia nervosa was elevated 7.7 degrees C above normal values. These results demonstrate that patients with anorexia nervosa have deficiencies of selected essential fatty acids, compensatory changes in nonessential fatty acids and decreased fluidity of plasma lipids.
Perioperative Management of Adult Patients With External Ventricular and Lumbar Drains: Guidelines From the Society for Neuroscience in Anesthesiology and Critical Care

External ventricular drains and lumbar drains are commonly used to divert cerebrospinal fluid and to measure cerebrospinal fluid pressure. Although commonly encountered in the perioperative setting and critical for the care of neurosurgical patients, there are no guidelines regarding their management in the perioperative period. To address this gap in the literature, The Society for Neuroscience in Anesthesiology & Critical Care tasked an expert group to generate evidence-based guidelines. The document generated targets clinicians involved in perioperative care of patients with indwelling external ventricular and lumbar drains.
Development of microsatellite markers and detection of genetic variation between Goniozus wasp populations

Abstract Molecular genetic markers reveal differences between genotypes according to the presence of alleles (the same or different) at target loci. Microsatellite markers are especially useful codominant markers that have been used in a wide range of studies to elucidate the population structure and dynamics of a range of organisms, including agriculturally beneficial insects such as parasitic wasps (parasitoids). In the present study, twelve primer pairs were designed for the south Asian , Goniozus nephantidis (Muesebeck) (Hymenoptera: Bethylidae), and 24 for its New World congener, Goniozus legneri Gordh, parasitoids of the larvae of the lepidopteran coconut pest Opisina arenosella Walker (Lepidoptera: Crytophasidae) and other lepidopteran pests, respectively, in order to investigate polymorphism within and between populations. The wasps fingerprinted were a total of 85 G. nephantidis and G. legneri, including individuals belonging to three putatively different strains of G. legneri. Annealing gradient tests (50–65°C) were conducted to study the quality of the PCR amplification across an annealing temperature gradient using a mixed genotype DNA template from each species separately. Seven primer pairs, which amplified clear products of approximately the expected size of G. nephantidis and 18 of G. legneri, were then selected for capillary analysis for fragment size determination on a Beckmann CEQ 8000. Neither G. nephantidis nor G. legneri were polymorphic within populations. However, there were six primer pairs that did show polymorphism between G. legneri populations that originated from different geographical areas within South America (Uruguay and Chile). Furthermore, one primer pair revealed diversity between the two strains collected within Chile. One of the markers was subsequently used to provide unbiased assessment of primary sex ratio in G. legneri.
Hyperbaric Oxygen Therapy After Acute Thoracic Spinal Cord Injury: Improvement of Locomotor Recovery in Rats

Study Design. A controlled laboratory study. Objective. The aim of this study was to analyze the effectiveness of hyperbaric therapy (HT) using mild and moderate models of spinal cord injury (SCI). Summary of Background Data. SCI can cause permanent impairment with socioeconomic consequences. The motor deficit occurs by two mechanisms: destruction of neuronal cells and local inflammatory response, resulting in hypoxia. HT acts by increasing oxygen in the injured area. Methods. Thoracic laminectomy was performed in 72 female Wistar rats. The MASCIS impactor was used at 12.5 mm (n = 35) and 25 mm (n = 35) of height to perform, respectively, mild and moderate SCI. Muscle strength was assessed through the Basso, Beattie, and Bresnahan scale (BBB) on days 1, 7, 14, 21, and 28 after SCI. The animals were randomized into five subgroups with seven animals each: (1) control group had SCI without HT; (2) HT 30 minutes after SCI; (3) HT 30 minutes after SCI and daily for 7 days; (4) HT 12 hours after SCI; and (5) HT 12 hours after SCI and daily for 7 days. HT was performed at 2.5 atm for 1 hour. Results. There was a linear relationship between injury severity and motor deficit until day 21, with similar BBB scores on day 28. A pattern of uniform lesions was observed in the mild SCI, with lower variation of BBB when compared with moderate SCI. All animals that underwent HT had significant improvement in motor function and histology when compared with control group. Regardless of the injury model, animals submitted to 7-day protocols had an early improvement in motor function and a smaller area of histological injury. Conclusion. The present study reported that the sooner HT is begun after mild and moderate SCI and the larger the number of sessions, the greater and earlier is the motor recovery and smaller is the tissue injury. Level of Evidence: N/A
A Causal And-Or Graph Model for Visibility Fluent Reasoning in Tracking Interacting Objects

Tracking humans that are interacting with the other subjects or environment remains unsolved in visual tracking, because the visibility of the human of interests in videos is unknown and might vary over time. In particular, it is still difficult for state-of-the-art human trackers to recover complete human trajectories in crowded scenes with frequent human interactions. In this work, we consider the visibility status of a subject as a fluent variable, whose change is mostly attributed to the subject's interaction with the surrounding, e.g., crossing behind another object, entering a building, or getting into a vehicle, etc. We introduce a Causal And-Or Graph (C-AOG) to represent the causal-effect relations between an object's visibility fluent and its activities, and develop a probabilistic graph model to jointly reason the visibility fluent change (e.g., from visible to invisible) and track humans in videos. We formulate this joint task as an iterative search of a feasible causal graph structure that enables fast search algorithm, e.g., dynamic programming method. We apply the proposed method on challenging video sequences to evaluate its capabilities of estimating visibility fluent changes of subjects and tracking subjects of interests over time. Results with comparisons demonstrate that our method outperforms the alternative trackers and can recover complete trajectories of humans in complicated scenarios with frequent human interactions.
A Risk Stratification Model for Lung Cancer Based on Gene Coexpression Network and Deep Learning

Risk stratification model for lung cancer with gene expression profile is of great interest. Instead of previous models based on individual prognostic genes, we aimed to develop a novel system-level risk stratification model for lung adenocarcinoma based on gene coexpression network. Using multiple microarray, gene coexpression network analysis was performed to identify survival-related networks. A deep learning based risk stratification model was constructed with representative genes of these networks. The model was validated in two test sets. Survival analysis was performed using the output of the model to evaluate whether it could predict patients' survival independent of clinicopathological variables. Five networks were significantly associated with patients' survival. Considering prognostic significance and representativeness, genes of the two survival-related networks were selected for input of the model. The output of the model was significantly associated with patients' survival in two test sets and training set (p < 0.00001, p < 0.0001 and p = 0.02 for training and test sets 1 and 2, resp.). In multivariate analyses, the model was associated with patients' prognosis independent of other clinicopathological features. Our study presents a new perspective on incorporating gene coexpression networks into the gene expression signature and clinical application of deep learning in genomic data science for prognosis prediction.
Resting State EEG-based biometrics for individual identification using convolutional neural networks

Biometrics is a growing field, which permits identification of individuals by means of unique physical features. Electroencephalography (EEG)-based biometrics utilizes the small intra-personal differences and large inter-personal differences between individuals' brainwave patterns. In the past, such methods have used features derived from manually-designed procedures for this purpose. Another possibility is to use convolutional neural networks (CNN) to automatically extract an individual's best and most unique neural features and conduct classification, using EEG data derived from both Resting State with Open Eyes (REO) and Resting State with Closed Eyes (REC). Results indicate that this CNN-based joint-optimized EEG-based Biometric System yields a high degree of accuracy of identification (88%) for 10-class classification. Furthermore, rich inter-personal difference can be found using a very low frequency band (0-2Hz). Additionally, results suggest that the temporal portions over which subjects can be individualized is less than 200 ms.
A New Target-specific Object Proposal Generation Method for Visual Tracking

Object proposal generation methods have been widely applied to many computer vision tasks. However, existing object proposal generation methods often suffer from the problems of motion blur, low contrast, deformation, etc., when they are applied to video related tasks. In this paper, we propose an effective and highly accurate target-specific object proposal generation (TOPG) method, which takes full advantage of the context information of a video to alleviate these problems. Specifically, we propose to generate target-specific object proposals by integrating the information of two important objectness cues: colors and edges, which are complementary to each other for different challenging environments in the process of generating object proposals. As a result, the recall of the proposed TOPG method is significantly increased. Furthermore, we propose an object proposal ranking strategy to increase the rank accuracy of the generated object proposals. The proposed TOPG method has yielded significant recall gain (about 20%-60% higher) compared with several state-of-the-art object proposal methods on several challenging visual tracking datasets. Then, we apply the proposed TOPG method to the task of visual tracking and propose a TOPG-based tracker (called as TOPGT), where TOPG is used as a sample selection strategy to select a small number of high-quality target candidates from the generated object proposals. Since the object proposals generated by the proposed TOPG cover many hard negative samples and positive samples, these object proposals can not only be used for training an effective classifier, but also be used as target candidates for visual tracking. Experimental results show the superior performance of TOPGT for visual tracking compared with several other state-of-the-art visual trackers (about 3%-11% higher than the winner of the VOT2015 challenge in term of distance precision).
A causal role for right frontopolar cortex in directed, but not random, exploration

The explore-exploit dilemma occurs anytime we must choose between exploring unknown options for information and exploiting known resources for reward. Previous work suggests that people use two different strategies to solve the explore-exploit dilemma: directed exploration, driven by information seeking, and random exploration, driven by decision noise. Here, we show that these two strategies rely on different neural systems. Using transcranial magnetic stimulation to inhibit the right frontopolar cortex, we were able to selectively inhibit directed exploration while leaving random exploration intact. This suggests a causal role for right frontopolar cortex in directed, but not random, exploration and that directed and random exploration rely on (at least partially) dissociable neural systems.
Temperature-dependent model for hole transport mechanism in a poly(1.8-diaminocarbazole)/Si structure

Abstract To investigate the conduction mechanism in an organic/inorganic heterojunction, poly(1.8-diaminocarbazole) (PDACz) on a p-type silicon substrate in a sandwich configuration were contacted with Al electrodes and temperature-dependent current–voltage measurements performed in the temperature range 280–380 K. It was found that the barrier height decreased and the ideality factor increased with decreasing temperature. Temperature and bias-dependent transition regimes were observed. These anomalies are explained by further analysis of the low- and high-field regions of the current–voltage curves. The trap density Hb and the characteristic trap energy Et were found to be 1.85 × 1017 cm−3 and 25 meV, respectively. Assuming that the trapped carrier density pt is higher than free-carrier density p, it is concluded that hole transport is dominated by space-charge-limited currents.
Identifying Genetic Variants for Heart Rate Variability in the Acetylcholine Pathway

Heart rate variability is an important risk factor for cardiovascular disease and all-cause mortality. The acetylcholine pathway plays a key role in explaining heart rate variability in humans. We assessed whether 443 genotyped and imputed common genetic variants in eight key genes (CHAT, SLC18A3, SLC5A7, CHRNB4, CHRNA3, CHRNA, CHRM2 and ACHE) of the acetylcholine pathway were associated with variation in an established measure of heart rate variability reflecting parasympathetic control of the heart rhythm, the root mean square of successive differences (RMSSD) of normal RR intervals. The association was studied in a two stage design in individuals of European descent. First, analyses were performed in a discovery sample of four cohorts (n = 3429, discovery stage). Second, findings were replicated in three independent cohorts (n = 3311, replication stage), and finally the two stages were combined in a meta-analysis (n = 6740). RMSSD data were obtained under resting conditions. After correction for multiple testing, none of the SNPs showed an association with RMSSD. In conclusion, no common genetic variants for heart rate variability were identified in the largest and most comprehensive candidate gene study on the acetylcholine pathway to date. Future gene finding efforts for RMSSD may want to focus on hypothesis free approaches such as the genome-wide association study.
Knowledge Completion for Generics using Guided Tensor Factorization

Given a knowledge base or KB containing (noisy) facts about common nouns or generics, such as “all trees produce oxygen” or “some animals live in forests”, we consider the problem of inferring additional such facts at a precision similar to that of the starting KB. Such KBs capture general knowledge about the world, and are crucial for various applications such as question answering. Different from commonly studied named entity KBs such as Freebase, generics KBs involve quantification, have more complex underlying regularities, tend to be more incomplete, and violate the commonly used locally closed world assumption (LCWA). We show that existing KB completion methods struggle with this new task, and present the first approach that is successful. Our results demonstrate that external information, such as relation schemas and entity taxonomies, if used appropriately, can be a surprisingly powerful tool in this setting. First, our simple yet effective knowledge guided tensor factorization approach achieves state-of-the-art results on two generics KBs (80% precise) for science, doubling their size at 74%–86% precision. Second, our novel taxonomy guided, submodular, active learning method for collecting annotations about rare entities (e.g., oriole, a bird) is 6x more effective at inferring further new facts about them than multiple active learning baselines.
The Longitudinal Effect of Vertigo and Dizziness Symptoms on Psychological Distress: Symptom-Related Fears and Beliefs as Mediators

Abstract Despite the frequent observation that vertigo and dizziness (VD) disorders may trigger or exacerbate secondary psychiatric comorbidities, there is limited understanding of the mechanisms underlying this development. To address this gap, we investigated whether symptom-related fears and cognitions as indicated by questionnaire-based measures are mediators of the longitudinal effect of VD symptoms on anxiety and depression after 1 year. We analyzed data from a large study with patients of a treatment center specialized in vertigo (N = 210). Simple and multiple parallel mediation models strengthened our hypothesis that fear of bodily sensations and cognitions about these symptoms play a mediating role in the relationship between VD symptoms and psychopathology at follow-up after baseline scores of the outcome were controlled for. Results are discussed within a cognitive theory framework and point to the potential benefits of interventions that modify symptom-related beliefs and fears via cognitive psychotherapy in this therapeutically underserved population.