Miracle-dz/UniFAR-FTUs huggingface dataset:
Positive pre-resection pleural lavage cytology is associated with increased risk of lung cancer recurrence in patients undergoing surgical resection: a meta-analysis of 4450 patients

Introduction The value of pleural lavage cytology (PLC) in assessing the prognosis of early stage lung cancer is still controversial. No systematic review has investigated the relationship between PLC and lung cancer recurrence. Our primary goal was to investigate the association between positive pre-resection PLC and pleural, distant and overall tumour recurrence in patients undergoing surgical resection. Methods Medline, EMBASE and Google Scholar databases were searched up to 2011. All studies reporting relevant outcomes in both patient groups were included. Data were extracted for the following outcomes of interest: overall, local and distant recurrence; and freedom from death (survival—overall and patients with stage I disease only). Random effects meta-analysis was used to aggregate the data. Sensitivity and heterogeneity analysis were performed. Results A meta-analysis of eight studies at maximum follow-up demonstrated a significant association between positive pre-resection PLC and increased risk of post-resection overall recurrence (OR 4.82, 95% CI 2.45 to 9.51), pleural recurrence (OR 9.89, 95% CI 5.95 to 16.44) and distant cancer recurrence (OR 3.18, 95% CI 1.57 to 6.46). Furthermore, a meta-analysis of 17 studies suggested that positive pre-resection PLC was also associated with unfavourable survival (HR 2.08, 95% CI 1.71 to 2.52). These findings were supported by sensitivity analysis. Discussion Positive pre-resection PLC is associated with higher overall, distant and local tumour recurrence and unfavourable patient survival outcomes. This technique may therefore act as a predictor of tumour recurrence and adverse survival. Furthermore, its role in including adjuvant chemotherapy to the management protocol should be investigated within randomised controlled trials.
CovRS-Regulated Transcriptome Analysis of a Hypervirulent M23 Strain of Group A Streptococcus pyogenes Provides New Insights into Virulence Determinants

ABSTRACT The two-component control of virulence (Cov) regulator (R)-sensor (S) (CovRS) regulates the virulence of Streptococcus pyogenes (group A Streptococcus [GAS]). Inactivation of CovS during infection switches the pathogenicity of GAS to a more invasive form by regulating transcription of diverse virulence genes via CovR. However, the manner in which CovRS controls virulence through expression of extended gene families has not been fully determined. In the current study, the CovS-regulated gene expression profiles of a hypervirulent emm23 GAS strain (M23ND/CovS negative [M23ND/CovS−]) and a noninvasive isogenic strain (M23ND/CovS+), under different growth conditions, were investigated. RNA sequencing identified altered expression of ∼349 genes (18% of the chromosome). The data demonstrated that M23ND/CovS− achieved hypervirulence by allowing enhanced expression of genes responsible for antiphagocytosis (e.g., hasABC), by abrogating expression of toxin genes (e.g., speB), and by compromising gene products with dispensable functions (e.g., sfb1). Among these genes, several (e.g., parE and parC) were not previously reported to be regulated by CovRS. Furthermore, the study revealed that CovS also modulated the expression of a broad spectrum of metabolic genes that maximized nutrient utilization and energy metabolism during growth and dissemination, where the bacteria encounter large variations in available nutrients, thus restructuring metabolism of GAS for adaption to diverse growth environments. From constructing a genome-scale metabolic model, we identified 16 nonredundant metabolic gene modules that constitute unique nutrient sources. These genes were proposed to be essential for pathogen growth and are likely associated with GAS virulence. The genome-wide prediction of genes associated with virulence identifies new candidate genes that potentially contribute to GAS virulence. IMPORTANCE The CovRS system modulates transcription of ∼18% of the genes in the Streptococcus pyogenes genome. Mutations that inactivate CovR or CovS enhance the virulence of this bacterium. We determined complete transcriptomes of a naturally CovS-inactivated invasive deep tissue isolate of an emm23 strain of S. pyogenes (M23ND) and its complemented avirulent variant (CovS+). We identified diverse virulence genes whose altered expression revealed a genetic switching of a nonvirulent form of M23ND to a highly virulent strain. Furthermore, we also systematically uncovered for the first time the comparative levels of expression of a broad spectrum of metabolic genes, which reflected different metabolic needs of the bacterium as it invaded deeper tissue of the human host.
THE EXCITATION OF THALAMIC NEURONES BY ACETYLCHOLINE.

Electrophoretically administered acetylcholine (ACh) excited neurones located within the ventro-basal thalamic complex of cats anesthetised with pentobarbital. All ACh sensitive neurones were fired synaptically by volleys in cutaneous nerve fibres; thalamic relay neurones which were fired antidromically from the primary sensory cortex were more sensitive than thalamic interneurones. In comparison with Renshaw cells the excitatory action of ACh was of slow onset and prolonged duration; the spontaneous spindle activity of some cells was depressed prior to excitation. Possible explanations of these time differences between the excitant of ACh upon thalamic and Renshaw cells are discussed.
Molecular characterization of rock microbial communities from the Mars analogue MDRS

Several rock samples have been collected as part of a Mars field analogue campaign (NASA DOMEXILEWG EuroMoonMars) at Mars Desert Research StationMDRS area (Utah Desert, USA). This report details the microbial diversity derived from cultureindependent techniques, such as polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) analysis.
Labelled Dependencies in Machine Translation Evaluation

We present a method for evaluating the quality of Machine Translation (MT) output, using labelled dependencies produced by a Lexical-Functional Grammar (LFG) parser. Our dependency-based method, in contrast to most popular string-based evaluation metrics, does not unfairly penalize perfectly valid syntactic variations in the translation, and the addition of WordNet provides a way to accommodate lexical variation. In comparison with other metrics on 16,800 sentences of Chinese-English newswire text, our method reaches high correlation with human scores.
An analytical approach for scanning probe microscope-tip electrostatic field distribution accounting for dead layer and domain wall

We have proposed a new theoretical approach for the determination of the electric field distribution in the ferroelectric/dielectric system with the presence of the SPM tip. The initial statement of the model has only a numerical solution. To find an analytical solution of the problem, some assumptions are introduced: the domain wall thickness can be considered to be much smaller than the domain size, and we use a high ferroelectric dielectric permittivity. The developed approach allows us to obtain explicit formulas for the polarization and electric field intensity. We have calculated and then analyzed the tip capacitance as a function of the distance from the ferroelectric interface. Additionally, different forms of the SPM tip are considered. It is demonstrated that in the presence of charges at the domain, the results differ from those obtained with the widely used dielectric model by 30%.
Multiscale Mechanics of Fibrin Polymer: Gel Stretching with Protein Unfolding and Loss of Water

<< Focusing on Fibrin Vascular injury initiates biochemical reactions that cause the blood protein, fibrin, to polymerize and help to stop bleeding and support wound healing. Fibrin can also be a scaffold for thrombi that lead to cardiovascular diseases. To maintain homeostasis, fibrin clots must be stiff, plastic, and, so that the network can be decompsed, permeable. Brown et al. (p. 741) investigated the behavior of fibrin clots at the macroscopic, single-fiber, and molecular scale. At relatively low strains, fibers aligned and formed bundles, and at higher strains, protein unfolding occurred. An integrated model provides a molecular basis for fibrin elasticity and extensibility. Protein unfolding in stretched fibrin blood clots creates porous gels that can withstand high strains. Blood clots and thrombi consist primarily of a mesh of branched fibers made of the protein fibrin. We propose a molecular basis for the marked extensibility and negative compressibility of fibrin gels based on the structural and mechanical properties of clots at the network, fiber, and molecular levels. The force required to stretch a clot initially rises linearly and is accompanied by a dramatic decrease in clot volume and a peak in compressibility. These macroscopic transitions are accompanied by fiber alignment and bundling after forced protein unfolding. Constitutive models are developed to integrate observations at spatial scales that span six orders of magnitude and indicate that gel extensibility and expulsion of water are both manifestations of protein unfolding, which is not apparent in other matrix proteins such as collagen.
Does Antihypertensive Drug Class Affect Day‐to‐Day Variability of Self‐Measured Home Blood Pressure? The HOMED‐BP Study

Background Recent literature suggests that blood pressure variability (BPV) predicts outcome beyond blood pressure level (BPL) and that antihypertensive drug classes differentially influence BPV. We compared calcium channel blockers, angiotensin‐converting enzyme inhibitors, and angiotensin receptor blockade for effects on changes in self‐measured home BPL and BPV and for their prognostic significance in newly treated hypertensive patients. Methods and Results We enrolled 2484 patients randomly allocated to first‐line treatment with a calcium channel blocker (n=833), an angiotensin‐converting enzyme inhibitor (n=821), or angiotensin receptor blockade (n=830). Home blood pressures in the morning and evening were measured for 5 days off treatment before randomization and for 5 days after 2 to 4 weeks of randomized drug treatment. We assessed BPL and BPV changes as estimated by variability independent of the mean and compared cardiovascular outcomes. Home BPL response in each group was significant (P≤0.0001) but small in the angiotensin‐converting enzyme inhibitor group (systolic/diastolic: 4.6/2.8 mm Hg) compared with the groups treated with a calcium channel blocker (systolic/diastolic: 8.3/3.9 mm Hg) and angiotensin receptor blockade (systolic/diastolic: 8.2/4.5 mm Hg). In multivariable adjusted analyses, changes in home variability independent of the mean did not differ among the 3 drug classes (P≥0.054). Evening variability independent of the mean before treatment significantly predicted hard cardiovascular events independent of the corresponding home BPL (P≤0.022), whereas BPV did not predict any cardiovascular outcome based on the morning measurement (P≥0.056). Home BPV captured after monotherapy had no predictive power for cardiovascular outcome (P≥0.22). Conclusions Self‐measured home evening BPV estimated by variability independent of the mean had prognostic significance, whereas antihypertensive drug classes had no significant impact on BPV changes. Home BPL should remain the primary focus for risk stratification and treatment. Clinical Trial Registration URL: http://www.umin. ac.jp/ctr/index.htm. Unique identifier: C000000137.
Advances in Children’s Speech Recognition within an Interactive Literacy Tutor

In this paper we present recent advances in acoustic and language modeling that improve recognition performance when children read out loud within digital books. First we extend previous work by incorporating cross-utterance word history information and dynamic n-gram language modeling. By additionally incorporating Vocal Tract Length Normalization (VTLN), Speaker-Adaptive Training (SAT) and iterative unsupervised structural maximum a posteriori linear regression (SMAPLR) adaptation we demonstrate a 54% reduction in word error rate. Next, we show how data from children's read-aloud sessions can be utilized to improve accuracy in a spontaneous story summarization task. An error reduction of 15% over previous published results is shown. Finally we describe a novel real-time implementation of our research system that incorporates time-adaptive acoustic and language modeling.
Exploring Shared-Memory Optimizations for an Unstructured Mesh CFD Application on Modern Parallel Systems

In this work, we revisit the 1999 Gordon Bell Prize winning PETSc-FUN3D aerodynamics code, extending it with highly-tuned shared-memory parallelization and detailed performance analysis on modern highly parallel architectures. An unstructured-grid implicit flow solver, which forms the backbone of computational aerodynamics, poses particular challenges due to its large irregular working sets, unstructured memory accesses, and variable/limited amount of parallelism. This code, based on a domain decomposition approach, exposes tradeoffs between the number of threads assigned to each MPI-rank sub domain, and the total number of domains. By applying several algorithm- and architecture-aware optimization techniques for unstructured grids, we show a 6.9X speed-up in performance on a single-node Intel® XeonTM1 E5 2690 v2 processor relative to the out-of-the-box compilation. Our scaling studies on TACC Stampede supercomputer show that our optimizations continue to provide performance benefits over baseline implementation as we scale up to 256 nodes.
Design of a Passive and Portable DMFC Operating in All Orientations

A microfluidic layout concept for passive and portable Direct Methanol fuel Cells (DMFCs) is presented. We proofed this concept by developing a DMFC that continuously runs for 40 hours in all orientations without the need for any active components such as pumps or valves. In contrast to our previous work [1], the system now is truly portable. In any orientation of the DMFC, a bubble driven self regulating supply mechanism safely removes carbon dioxide and transports at least 3.5 times more methanol to the anode than critically needed to sustain DMFC operation. On the cathode, diffusive oxygen supply and the transport of the reaction product water along a capillary gradient out of the DMFC ensures a stable performance. Compared to our previous work [1], the power output was increased by a factor of 2.5 and reached p = 5.5 mW cm-2. A stable power output for 40 hours of p = 4 mW cm-2 was achieved for the preferred vertical position with bubbles moving against buoyancy forces. In the most challenging horizontal position with the anode facing downwards, a power output of at least p = 3.1 mW cm-2 was reached for the same period of time.
Is Sovereign Wealth Fund Investment Destabilizing?

We investigate whether accusations by the popular press regarding the potential destabilizing force of sovereign wealth fund (SWF) investment have merit. SWF investments are associated with a reduction in the compensation of risk over the five-year term examined. Firm volatility decomposition suggests that it is mainly idiosyncratic risk that drives these impacts. Granger causality results suggest that SWFs are poorly informed in their investments (compared to the market) or they have nonfinancial motivations. There is no evidence that the media coverage precedes the poor performance. These findings suggest that SWF investment could be potentially destabilizing.
Therapeutic drug monitoring of cancer chemotherapy

Therapeutic drug monitoring is not routinely used for chemotherapy agents. There are Several reasons, but one major drawback is the lack of established therapeutic Concentration ranges. Combination chemotherapy makes the establishment of Therapeutic ranges for individual drugs difficult, the concentration-effect relationship for a single drug may not be the same as when that drug is used in a drug combination. Pharmacokinetic optimization protocols for many classes of cytotoxic compounds exist in specialized centers, and some of these protocols are now part of large multicentre trials. Nonetheless, TDM clearly has the potential to improve the clinical use of chemotherapy gents, most of which have very narrow therapeutic indices and highly variable pharmacokinetics. A substantial body of literature accumulating during the past 15 years demonstrates relationships between systemic exposure to various chemotherapy agents and their toxic or therapeutic effects. This article reviews TDM concepts in addition to tools based on pharmacokinetic modeling of chemotherapy agents. The administered dose of chemotherapy agents is sometimes adjusted individually using either a priori or a posteriori methods. These models can only be applied by using the same dose and schedule as the original study. Bayesian estimation offers more flexibility in blood sampling times and, owing to its precision and to the amount of information provided is the method of choice for ensuring that a given patient benefits from the desired systemic exposure. Moreover, the role and application of Pharmacogenetics as a tool for individualizing chemotherapy is discussed highlighting the agents and mechanisms that have been well studied and defined and their relevance to clinical practice. Finally, this paper address issues critical to the optimal use of TDM in a clinical setting, and the role of clinical pharmacist in this regard. In addition, it discusses future developments in this field that can contribute to improving cancer chemotherapy In terms of patient outcome and survival. J Oncol Pharm Practice (2007) 13: 207—221.
Rheumatic immune-related adverse events of checkpoint therapy for cancer: case series of a new nosological entity

Immunotherapy of cancer with checkpoint inhibitors has been associated with a spectrum of autoimmune and systemic inflammatory reactions known as immune-related adverse events (irAEs). Rheumatic irAEs are infrequently reported and extensively described. Here, we report our experience over an 18-month period with 15 patients evaluated in the rheumatology department for rheumatic irAEs. We identified 13 patients without pre-existing autoimmune disease (AID) who subsequently developed rheumatic irAEs, and two with established AID referred pre-emptively. irAEs encountered included: inflammatory arthritis, sicca syndrome, polymyalgia rheumatica-like symptoms and myositis. All cases required glucocorticoids, and three required a biological agent. Rheumatic irAEs led to temporary or permanent cessation of immunotherapy in all but five patients. One patient with pre-existing AID experienced a flare after starting immunotherapy. Our findings underscore that rheumatic irAEs are complex, at times require additional immunosuppressive therapy, and may influence ongoing immunotherapy regimens for the primary disease. Similar irAEs will be increasingly seen as checkpoint inhibitors adopted as standard of care in the community.
Phasic activity in the human erector spinae during repetitive hand movements

1 Phasic activity in the human back muscle erector spinae (ES) was studied during repetitive hand movements. The hand movements were elicited voluntarily by the subject or induced passively by the experimenter through a servomotor or through cyclical electrical stimulation of muscles acting about the wrist. The aim of the study was to determine whether the rhythmical activation of ES was of supraspinal, intersegmental or segmental origin. 2 When voluntary rhythmical hand movements were performed as fast as possible, cyclical ES EMG bursts occurred at the same frequency. This frequency was significantly higher than that reached when the task was to contract the back muscles as rapidly as possible. This suggests that the ES activity during the fast hand movements was not generated by direct commands descending to the ES muscles from the motor area of the cerebral cortex responsible for voluntary back muscle activation. 3 During imposed rhythmical hand movements, ES EMG bursts remained entrained to the hand movements, even when movement frequencies far exceeded those attainable voluntarily either for the hand or the back. This showed that ES EMG responses could be evoked by the hand movements even when these were not generated by descending neural commands. Two alternative mechanisms of ES activation were considered: (a) propriospinal transmission of afferent input entering the spinal cord from the upper extremity; (b) afferent input from ES and other trunk muscles, responding to local oscillations transmitted mechanically from the hand to the lower back. 4 Activation of ES via proprioceptive signals from the forearm was unlikely since (a) simultaneous electrical stimulation of wrist extensor and wrist flexor muscles did not result in repetitive ES EMG bursting; (b) cyclical vibration of the wrist extensors did not evoke ES EMG bursting; (c) when the forearm was constrained and the hand was moved passively, the lower trunk accelerations and cyclical ES EMG both occurred at a harmonic of the hand movement frequency. 5 We conclude that the repetitive ES EMG bursting during hand movements was probably due to a local segmental reflex rather than to descending commands. Remote mechanical oscillations of the trunk caused by hand movements evidently elicited proprioceptive reflexes in ES that presumably contributed to trunk stabilization.
Disorganization of Equilibrium Directional Interactions in the Brain Motor Network of Parkinson's disease: New Insight of Resting State Analysis Using Granger Causality and Graphical Approach

Parkinson's disease (PD) is a progressive neurological disorder characterized by tremor, rigidity, and slowness of movements. Particular changes related to various pathological attacks in PD could result in causal interactions of the brain network from resting state functional magnetic resonance imaging (rs-fMRI) data. In this paper, we aimed to disclose the network structure of the directed influences over the brain using multivariate Granger causality analysis and graph theory in patients with PD as compared with control group. rs-fMRI at rest from 10 PD patients and 10 controls were analyzed. Topological properties of the networks showed that information flow in PD is smaller than that in healthy individuals. We found that there is a balanced local network in healthy control group, including positive pair-wise cross connections between caudate and cerebellum and reciprocal connections between motor cortex and caudate in the left and right hemispheres. The results showed that this local network is disrupted in PD due to disturbance of the interactions in the motor networks. These findings suggested alteration of the functional organization of the brain in the resting state that affects the information transmission from and to other brain regions related to both primary dysfunctions and higher-level cognition impairments in PD. Furthermore, we showed that regions with high degree values could be detected as betweenness centrality nodes. Our results demonstrate that properties of small-world connectivity could also recognize and quantify the characteristics of directed influence brain networks in PD.