Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognosticators and the relationship of depression and quality of life in head and neck cancer.

BACKGROUND AND PURPOSE To evaluate the relationship of emotional status and health-related quality of life (HRQOL) in disease-free head and neck cancer (HNC) patients post treatment and to explore their predictive factors. MATERIALS AND METHODS Seventy-three HNC patients, post treatment at least 1 year, were recruited to complete three questionnaires, EORTC QLQ-C30, EORTC-H&N35 cancer module, and the Beck Depression Inventory-II (BDI-II). RESULTS Patients with depression demonstrated significantly poor global health status/QoL (score 41.7 vs. 71.9, P<0.001) and almost all functioning, except for role functioning. Besides, depressive patients presented statistically significant worse symptoms in all QLQ-C30 items, except constipation and financial problems, and in all QLQ-H&N35 symptoms except for teeth and coughing problems. Depression was significantly negative correlated with all functional scales and global health status/QoL (r = -0.341 to -0.750, all P<0.05), and was significantly positive correlated with symptom scales (r = 0.348 to 0.793, all P<0.05), except for constipation. Stepwise multiple linear regression analyses showed that physical functioning and physical distressful symptoms play an important role in the perception of HRQOL (total 46% explained). Global health status and impaired social functioning could explain depression in addition to emotional functioning (total 64% explained). CONCLUSIONS HNC patients with depression were noted to have poorer HRQOL in almost every functioning symptom. HNC patients may get benefit from early interventions to improve HRQOL, emotional status, or both by a more rapid and friendly questionnaire to earlier identify patients with poor HRQOL or depressive status.
TCP in presence of bursty losses

We analyze in this paper the performance of TCP/IP-like congestion control in the presence of random losses. The input rate in the control scheme that we consider has a linear growth rate; whenever a loss occurs, the input rate is halved. This approximates the performance of several versions of TCP/IP that divide their congestion window by two whatever is the cause of the loss. We propose a mathematical model that allows to account for burstiness as well as for correlation in the loss process. Our aim is to study the impact of burstiness on the throughput of the connection. We compute the expected instantaneous input rate and its moments at some potential loss instants, and provide for a useful implicit expression for the Laplace Stieltjis Transform. This allows us to compute explicitly the average throughput and its moments. We show that the average throughput is indeed sensitive to the distribution of the loss process, and not just to the average loss rate: for a given average loss rate, we show that the throughput increases with the burstiness of the loss process. We finally examine the impact of burstiness of losses on the throughput variability.
Next-Generation Probiotics Targeting Clostridium difficile through Precursor-Directed Antimicrobial Biosynthesis

ABSTRACT Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials.
Ethanol facilitates hepatitis C virus replication via up‐regulation of GW182 and heat shock protein 90 in human hepatoma cells

Alcohol use and hepatitis C virus (HCV) infection synergize to cause liver damage, and microRNA‐122 (miR‐122) appears to play a key role in this process. Argonaute 2 (Ago2), a key component of the RNA‐induced silencing complex (RISC), has been shown to be important in modulating miR‐122 function during HCV infection. However, GW182, a critical component of processing bodies (GW bodies) that is recruited by Ago2 to target messenger RNA (mRNA), has not been assessed in HCV infection. To characterize the role of GW182 in the pathogenesis of HCV infection, we determined its transcription and protein expression in an HCV J6/JFH1 culture system. Transcript and protein levels of GW182 as well as HCV RNA and protein expression increased with alcohol exposure. Specific silencing of mRNA expression by small interfering RNA against GW182 significantly decreased HCV RNA and protein expression. Overexpression of GW182 significantly increased HCV RNA and protein expression in HCV J6/JFH1 infected Huh7.5 cells. Furthermore, GW182 colocalized and coimmunoprecipitated with heat shock protein 90 (HSP90), which increased upon alcohol exposure with and without HCV infection and enhanced HCV gene expression. The use of an HSP90 inhibitor or knockdown of HSP90 decreased GW182 and miR‐122 expression and significantly reduced HCV replication. Conclusion: Overall, our results suggest that GW182 protein that is linked to miR‐122 biogenesis and HSP90, which has been shown to stabilize the RISC, are novel host proteins that regulate HCV infection during alcohol abuse. (HEPATOLOGY 2013)
Influence of fluvoxamine on plasma interleukin-6 or clinical improvement in patients with major depressive disorder

Objectives The etiology of depression remains unknown. There is, however, a growing body of evidence that cytokines are involved in the pathophysiology of depression. The aim of this study is to investigate the effects of fluvoxamine on plasma interleukin-6 (IL-6) levels and on clinical improvement of the depressive state. Subjects and methods Thirty patients who met the DSM-IV criteria for major depressive disorder (MDD) were enrolled in the study. Thirteen were male and 17 were female, and their ages ranged from 26 to 70 years (mean ± standard deviation 45.0±14.2). The patients were treated with fluvoxamine for 8 weeks. The dosages of fluvoxamine varied among the patients and, based on ethical considerations, were not fixed. Results The fluvoxamine doses were positively related to plasma fluvoxamine levels (r =0.8798, P<0.001). A significant correlation was observed between the patients’ plasma IL-6 levels and their 17-item Hamilton Rating Scale for Depression (HAMD17) scores (r =0.4555, P=0.0010). A positive correlation was found between the delta plasma IL-6 (week 0–week 8) and the delta HAMD17 (week 0–week 8) (r =0.5226, P=0.002). Conclusion Effect of fluvoxamine on IL-6 is partially associated with its clinical efficacy for MDD.
Effects of morphine and alcohol on functional brain connectivity during “resting state”:A placebo‐controlled crossover study in healthy young men

A major challenge in central nervous system (CNS) drug research is to develop a generally applicable methodology for repeated measurements of drug effects on the entire CNS, without task‐related interactions and a priori models. For this reason, data‐driven resting‐state fMRI methods are promising for pharmacological research. This study aimed to investigate whether different psychoactive substances cause drug‐specific effects in functional brain connectivity during resting‐state. In this double blind placebo‐controlled (double dummy) crossover study, seven resting‐state fMRI scans were obtained in 12 healthy young men in three different drug sessions (placebo, morphine and alcohol; randomized). Drugs were administered intravenously based on validated pharmacokinetic protocols to minimize the inter‐ and intra‐subject variance in plasma drug concentrations. Dual‐regression was used to estimate whole‐brain resting‐state connectivity in relation to eight well‐characterized resting‐state networks, for each data set. A mixed effects analysis of drug by time interactions revealed dissociable changes in both pharmacodynamics and functional connectivity resulting from alcohol and morphine. Post hoc analysis of regions of interest revealed adaptive network interactions in relation to pharmacokinetic and pharmacodynamic curves. Our results illustrate the applicability of resting‐state functional brain connectivity in CNS drug research. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Endothelial Progenitor Cells During Cerebrovascular Disease

Background and Purpose— Endothelial progenitor cells (EPCs) are associated with endothelial repair after ischemia in cardiac or peripheral circulation. There are no reports of EPCs with cerebrovascular disease. We present our experience with EPCs in patients with cerebrovascular disease. Summary of Report— EPC counts differed significantly (P<0.001) between stroke patients (acute stroke: median 4.75 and range 0 to 33; stable stroke: median 7.25 and range 0 to 43) and control subjects (median 15.5 and range 4.3 to 50), independent of age. The level of EPCs was significantly correlated with the Framingham coronary risk score (FCRS) (&rgr;=−0.349; P=0.002). Conclusions— Similar to cardiac experience, the low EPC levels may play a role in the pathophysiology of cerebrovascular disease.
Impact of workplace based assessment on doctors’ education and performance: a systematic review

Objective To investigate the literature for evidence that workplace based assessment affects doctors’ education and performance. Design Systematic review. Data sources The primary data sources were the databases Journals@Ovid, Medline, Embase, CINAHL, PsycINFO, and ERIC. Evidence based reviews (Bandolier, Cochrane Library, DARE, HTA Database, and NHS EED) were accessed and searched via the Health Information Resources website. Reference lists of relevant studies and bibliographies of review articles were also searched. Review methods Studies of any design that attempted to evaluate either the educational impact of workplace based assessment, or the effect of workplace based assessment on doctors’ performance, were included. Studies were excluded if the sampled population was non-medical or the study was performed with medical students. Review articles, commentaries, and letters were also excluded. The final exclusion criterion was the use of simulated patients or models rather than real life clinical encounters. Results Sixteen studies were included. Fifteen of these were non-comparative descriptive or observational studies; the other was a randomised controlled trial. Study quality was mixed. Eight studies examined multisource feedback with mixed results; most doctors felt that multisource feedback had educational value, although the evidence for practice change was conflicting. Some junior doctors and surgeons displayed little willingness to change in response to multisource feedback, whereas family physicians might be more prepared to initiate change. Performance changes were more likely to occur when feedback was credible and accurate or when coaching was provided to help subjects identify their strengths and weaknesses. Four studies examined the mini-clinical evaluation exercise, one looked at direct observation of procedural skills, and three were concerned with multiple assessment methods: all these studies reported positive results for the educational impact of workplace based assessment tools. However, there was no objective evidence of improved performance with these tools. Conclusions Considering the emphasis placed on workplace based assessment as a method of formative performance assessment, there are few published articles exploring its impact on doctors’ education and performance. This review shows that multisource feedback can lead to performance improvement, although individual factors, the context of the feedback, and the presence of facilitation have a profound effect on the response. There is no evidence that alternative workplace based assessment tools (mini-clinical evaluation exercise, direct observation of procedural skills, and case based discussion) lead to improvement in performance, although subjective reports on their educational impact are positive.
Deterministic Extractors for Independent-Symbol Sources

In this paper, we consider the task of deterministically extracting randomness from sources consisting of a sequence of <i>n</i> independent symbols from {0,1}<i>d</i>. The only randomness guarantee on such a source is that the whole source has min-entropy <i>k</i> . We give an explicit deterministic extractor which extract Ω(log<i>k</i>-loglog(1/ ε)) bits with error ε , for any <i>n</i>, <i>d</i>, <i>k</i> ∈ \BBN and ε ∈ (0,1). For sources with a larger min-entropy, we can extract even more randomness. When <i>k</i> ≥ <i>n</i><sup>1/2+γ</sup>, for any constant γ ∈ (0,1/2), we can extract <i>m</i>=<i>k</i>-<i>O</i>(<i>d</i> log(1/ ε)) bits with any error ε ≥ 2<sup>-Ω(</sup><i>n</i><sup>γ</sup>). When <i>k</i> ≥ log<i>cn</i> , for some constant <i>c</i> > 0, we can extract <i>m</i>=<i>k</i>-(1/ ε)<i>O</i>(1) bits with any error ε ≥ <i>k</i><sup>-Ω(1)</sup>. Our results generalize those of Kamp and Zuckerman and Gabizon which only work for bit-fixing sources (with <i>d</i>=1 and each bit of the source being either fixed or perfectly random). Moreover, we show the existence of a nonexplicit deterministic extractor which can extract <i>m</i>=<i>k</i>-<i>O</i>(log(1/ ε)) bits whenever <i>k</i>=ω(<i>d</i>+log(<i>n</i>/ ε)) . Finally, we show that even to extract from bit-fixing sources, any extractor, seeded or not, must suffer an entropy loss <i>k</i>-<i>m</i>=Ω(log(1/ ε)). This generalizes a lower bound of Radhakrishnan and Ta-Shma on extracting from general sources.
Gene-Expression Profile Changes Correlated with Tumor Progression and Lymph Node Metastasis in Esophageal Cancer

Purpose: The purpose of this research was to identify molecular clues to tumor progression and lymph node metastasis in esophageal cancer and to test their value as predictive markers. Experimental Design: We explored the gene expression profiles in cDNA array data of a 36-tissue training set of esophageal squamous cell carcinoma (ESCC) by using generalized linear model-based regression analysis and a feature subset selection algorithm. By applying the identified optimal feature sets (predictive gene sets), we trained and developed ensemble classifiers consisting of multiple probabilistic neural networks combined with AdaBoosting to predict tumor stages and lymph node metastasis. We validated the classifier abilities with 18 independent cases of ESCC. Results: We identified 71 genes of 1289 cancer-related genes of which the expression correlated with tumor stages. Of the 71 genes, 47 significantly differed between the Tumor-Node-Metastasis pT1/2 and pT3/4 stages. Cell cycle regulators and transcriptional factors possibly promoting the growth of tumor cells were highly expressed in the early stages of ESCC, whereas adhesion molecules and extracellular matrix-related molecules possibly promoting invasiveness increased in the later stages. For lymph node metastasis, we identified 44 genes with predictive values, which included cell adhesion molecules and cell membrane receptors showing higher expression in node-positive cases and cell cycle regulators and intracellular signaling molecules showing higher expression in node-negative cases. The ensemble classifiers trained with the selected features predicted tumor stage and lymph node metastasis in the 18 validation cases with respective accuracies of 94.4% and 88.9%. This demonstrated the reproducibility and predictive value of the identified features. Conclusion: We suggest that these characteristic genes will provide useful information for understanding the malignant nature of ESCC as well as information useful for personalizing the treatments.
Analysis and development of new materials for polymer laser sintering

Laser Sintering is an Additive Manufacturing technology that uses digital files to construct 3-dimensional parts by depositing and consolidating layers of powdered material. Application of the technology for metal and ceramic powders is common but the focus of this work was on polymer laser sintering. A significant drawback for polymer laser sintering is the limited selection of materials currently available for use compared with more conventional processes such as injection moulding. This constrains the usefulness of the technology for designers and engineers. A primary reason for this is a lack of detailed understanding of the development process for new materials for laser sintering. This PhD investigation examines some of the key attributes and requirements needed for successfully implementing new polymer-based laser sintering materials. A strategic method for characterizing and identifying new polymer materials was created utilizing thermal measurements, practical and analytical methods to quantify sintering rate, and degradation studies. Validation of this work occurred through the successful integration of a new laser sintering material at industrial project partner Burton Snowboards. Thermal degradation as a result of the laser sintering process was studied in detail and resulted in the creation of a proposed new parameter: Stable Sintering Region (SSR). The term acknowledges and defines the region above the melting point that is the minimum requirement for sintering to occur and an upper limit beyond which polymer deterioration impedes on mechanical properties. A quantitative approach to define the SSR was developed and explored with three different laser sintering materials, two of which were flexible elastomers. The ability to specifically interpret laser sintering process parameters from thermal degradation characterization was created and used to explore the effects of high energy input on tensile properties and molecular weight. The results of these tests showed the potential to identify an Optimum Sintering Range based on maximizing mechanical properties through the control of energy input and molecular weight. This thesis makes a significant contribution to the knowledge and understanding of polymer laser sintering, especially in the context of materials development. Novel concepts such as the Stable Sintering Region were developed using a theoretical approach and practical measurements and were also thoroughly explored for verification. Additionally, a new method to use a powder characterization technique to predict the actual machine parameters of a material in the laser sintering process was quantified. This has several implications for testing new materials for laser sintering and efficiently identifying appropriate processing conditions.
Relationships between Cardiorespiratory and Muscular Fitness with Cardiometabolic Risk in Adolescents

This study examined the independent relationships between cardiorespiratory and muscular fitness with cardiometabolic risk in adolescents. Subjects were 192 adolescents (118 boys), aged 15–17.5 years. The 2 m multi-stage fitness test assessed cardiorespiratory fitness and the counter movement jump assessed muscular fitness. Additional measures included interleukin-6, C-reactive protein, adiponectin, fibrinogen and plasminogen activator inhibitor-1. Regression analysis revealed that cardiorespiratory fitness was negatively related to cardiometabolic risk (β = –0.014, p < 0.001). With additional adjustment for muscular fitness the relationship remained significant (β = –0.015, p < 0.001). Muscular fitness was negatively related to cardiometabolic risk (β = –0.021, p < 0.001) and remained significant after adjustment for cardiorespiratory fitness. Participants in the least-fit quartile for both cardiorespiratory and muscular fitness had significantly poorer cardiometabolic risk scores than those in the other quartiles. Findings revealed that muscular and cardiorespiratory fitness are significantly associated with cardiometabolic risk independently of one another.
Worm Palaeo-Evo-Devo-The ontogeny of Ottoia prolifica from the Burgess Shale

Ottoia prolifica Walcott, 1911 is a 500 million years old fossil cycloneuralian worm from the Burgess Shale, Canada, British Columbia. We report newly observed details of the morphology and ontogeny of this species. Previously unknown details could be observed by applying crossedpolarized light. This approach revealed that the tail end is equipped with six hook-shaped spines and that the scalids in the anterior retractable region, the introvert, are arranged in at least 30 radii. Furthermore, an ontogenetic change could be observed: earlier developmental stages have an elongate worm-shaped trunk, while the trunk of adults is pronouncedly bellied. The newly observed details of Ottoia prolifica raise questions about the taxonomic status of other Cambrian cycloneuralians and about existing homology hypotheses for cycloneuralians.
Purification and Characterization of Protein Nanotubes Assembled from a Single Bacterial Microcompartment Shell Subunit

Dr. C. R. Noël, Prof. C. A. Kerfeld MSU-DOE Plant Research Laboratory Department of Biochemistry Michigan State University 612 Wilson Road , East Lansing , MI 48824 , USA E-mail: ckerfeld@lbl.gov Dr. F. Cai, Prof. C. A. Kerfeld Physical Biosciences Division Lawrence Berkeley Nation Laboratory 1 Cyclotron Road , Berkeley , CA 94720 , USA Prof. C. A. Kerfeld Department of Plant and Microbial Biology UC Berkeley Berkeley, CA 94720 , USA