Miracle-dz/UniFAR-FTUs huggingface dataset:
Wound recurrences following laparoscopic-assisted colectomy for cancer.

OBJECTIVES To determine the incidence and clinical relevance of wound recurrences (WRs) following laparoscopic-assisted colectomy for cancer; to analyze the most recent experimental studies examining possible pathogenic mechanisms; and to delineate possible prevention strategies. DATA SOURCES A MEDLINE search was conducted using the words "colectomy," "laparoscopy," and "recurrence, local. " Additional articles were retrieved by cross-referencing. STUDY SELECTION All clinical and experimental studies retrieved were reviewed and subjectively selected according to their relevance for clinical practice. DATA EXTRACTION Clinical data from 1990 to 2000 with series analyzing 50 or more patients were preferentially considered. Experimental data were considered based on the most rigorous study designs and the potential impact of experimental findings on clinical practice. DATA SYNTHESIS The incidence of WRs in large series and based on current techniques is comparable to what has been reported for WR following open colectomy. While the pathogenesis of early WR occurrences remains unclear, experience and appropriate training in laparoscopic-assisted colectomy are essential to minimize the incidence of WRs. Results from experimental studies are still controversial, and available data from prospective randomized clinical trials are still limited. CONCLUSIONS Results from prospective randomized trials are needed to provide definitive answers regarding the incidence and survival impact of WRs. Until then, WR may be considered a technical complication following laparoscopic-assisted colectomy.
Development and Stem Cells Research Article

INTRODUCTION The development of complex organisms with specialized cell types, tissues and organs requires tight coordination between cell division and differentiation. This is achieved in part through asymmetric cell divisions that segregate the potential to proliferate and the commitment to differentiate to different daughter cells (Galli and van den Heuvel, 2008; Gonczy, 2008; Knoblich, 2008). For example, asymmetric divisions allow adult stem and precursor cells to self-renew and simultaneously produce daughter cells that will go on to differentiate. By contrast, proliferative (or symmetric) cell divisions generate two essentially identical daughter cells and promote exponential increases in cell number. The proper balance between proliferative and asymmetric cell divisions is crucial in stem cell maintenance and tissue homeostasis. Differences between daughter cells may arise during division or after completion of division (Horvitz and Herskowitz, 1992). The first mode of division is considered intrinsically asymmetric and applies, for instance, to the C. elegans zygote and to During intrinsically asymmetric division, cell-fate determinants become unequally localized according to the polarity of the cell or tissue, and the mitotic spindle aligns along the polarity axis. Consequently, cell cleavage, which takes place perpendicular to the spindle, generates two daughter cells with different constituents. As an alternative mode of asymmetric division, external signals (e.g. from a stem cell niche) may instruct the fate of daughter cells
Hyperschematia after right brain damage: a meaningful entity?

In recent years we reported three right-brain-damaged patients, who exhibited a left-sided disprortionate expansion of drawings, both by copying and from memory, contralateral to the side of the hemispheric lesion (Neurology, 67: 1801, 2006, Neurocase 14: 369, 2008). We proposed the term “hyperschematia” for such an expansion, with reference to an interpretation in terms of a lateral leftward distortion of the representation of extra-personal space, with a leftward anisometric expansion (relaxation) of the spatial medium. The symptom-complex shown by right-brain-damaged patients with “hyperschematia” includes: (1) a disproportionate leftward expansion of drawings (with possible addition of details), by copy and from memory (also in clay modeling, in one patient); (2) an overestimation of left lateral extent, when a leftward movement is required, associated in some patients with a perceptual underestimation; (3) unawareness of the disorder; (4) no unilateral spatial neglect. In most right-brain-damaged patients, left “hyperschematia” involves extra-personal space. In one patient the deficit was confined to a body part (left half-face: personal “hyperschematia”). The neural underpinnings of the disorder include damage to the fronto-temporo-parietal cortices, and subcortical structures in the right cerebral hemisphere, in the vascular territory of the middle cerebral artery. Here, four novel additional patients are reported. Finally, “hypeschematia” is reconsidered, in its clinical components, the underlying pathological mechanisms, as well as its neural underpinnings.
IL-7/Anti-IL-7 mAb Complexes Restore T Cell Development and Induce Homeostatic T Cell Expansion without Lymphopenia1

IL-7, a member of the common γ-chain family of cytokines, is essential for B and T lymphocyte development and homeostasis of mature T cell subsets. Thus, naive and memory T cells are both dependent on IL-7 for survival and homeostatic proliferation under lymphopenic conditions. In line with prior findings with IL-2, we show in this study that the biological activity of IL-7 in vivo is greatly increased by association with anti-IL-7 mAb. Under in vivo conditions, IL-7/mAb complexes displayed 50- to 100-fold higher activity than free IL-7 and induced massive expansion of pre-B cells. IL-7/mAb complexes also increased thymopoiesis in normal mice and restored thymopoeisis in IL-7-deficient mice. For mature T cells, IL-7/mAb complexes induced marked homeostatic proliferation of both naive and memory CD4+ and CD8+ cell subsets even under normal T cell-replete conditions. Finally, IL-7/mAb complexes were able to enhance the magnitude of the primary response of Ag-specific naive CD8+ cells. The strong stimulatory activity of IL-7/mAb complexes could be useful for treatment of immunodeficiency and cancer.
Plan-based reward shaping for reinforcement learning

Reinforcement learning, while being a highly popular learning technique for agents and multi-agent systems, has so far encountered difficulties when applying it to more complex domains due to scaling-up problems. This paper focuses on the use of domain knowledge to improve the convergence speed and optimality of various RL techniques. Specifically, we propose the use of high-level STRIPS operator knowledge in reward shaping to focus the search for the optimal policy. Empirical results show that the plan-based reward shaping approach outperforms other RL techniques, including alternative manual and MDP-based reward shaping when it is used in its basic form. We show that MDP-based reward shaping may fail and successful experiments with STRIPS-based shaping suggest modifications which can overcome encountered problems. The STRIPS-based method we propose allows expressing the same domain knowledge in a different way and the domain expert can choose whether to define an MDP or STRIPS planning task. We also evaluate the robustness of the proposed STRIPS-based technique to errors in the plan knowledge.
Indirect Reduction of Ear Molds and Associated Mycotoxins in Bacillus thuringiensis Corn Under Controlled and Open Field Conditions: Utility and Limitations

Abstract In 1995, ears of a experimental inbred (CG59-2) containing asynthetic Bacillus thuringiensis Cry IA(b) gene driven byPEPC, pith and pollen promoters and artificially infested withOstrinia nubilalis (Hübner) larvae in small plotstudies were free from insect damage, whereas 40–50% of thecorresponding non-Bt inbred ears were damaged. Bt inbred ears that wereinoculated with Aspergillus flavus Link and Fusariumproliferatum T. Matsushima (Nirenberg) or exposed to natural moldinoculum after infestation with O. nubilalis were free ofvisible signs of mold, as compared with ≈30–40% of the non-Bt earssimilarly treated. Results in 1996 using the same inbred with a singleallele dose of the Bt gene showed similar trends. Mean total fumonisinlevels for non-Bt versus Bt inbred ears were not significantlydifferent (2.8 versus 0.8 ppm, respectively) in 1996. In paired hybridstudies run in 0.4-ha (1-acre) fields, an event 176 Bt hybrid hadsignificantly lower amounts of damage and signs of Fusariumspp. mold, but not fumonisin, compared with a corresponding non-Bthybrid from 1996 to 1998. However, two hybrid pairs that containedeither MON810 or Bt11 constructs examined in similar fields at the samesite had lower levels of fumonisin in both 1997 (30- to 40-fold) and1998. High intrafield variability in insect infestation and presence ofHelicoverpa zea (Boddie) in Bt hybrids was apparentlyresponsible for fewer significant differences in fumonisin levels in1998. Similar trends for all three hybrid pairs were noted in smallplot trials at another site. Incidence of other ear pests or insectpredators varied as much among non-Bt hybrids as they did for Bt/non-Bthybrid pairs.
Lyme borreliosis: a review of data on transmission time after tick attachment

Lyme borreliosis is increasing rapidly in many parts of the world and is the most commonly occurring vector-borne disease in Europe and the USA. The disease is transmitted by ticks of the genus Ixodes. They require a blood meal at each stage of their life cycle and feed on a wide variety of wild and domestic animals as well as birds and reptiles. Transmission to humans is incidental and can occur during visits to a vector habitat, when host mammals and their associated ticks migrate into the urban environment, or when companion animals bring ticks into areas of human habitation. It is frequently stated that the risk of infection is very low if the tick is removed within 24–48 hours, with some claims that there is no risk if an attached tick is removed within 24 hours or 48 hours. A literature review has determined that in animal models, transmission can occur in <16 hours, and the minimum attachment time for transmission of infection has never been established. Mechanisms for early transmission of spirochetes have been proposed based on their presence in different organs of the tick. Studies have found systemic infection and the presence of spirochetes in the tick salivary glands prior to feeding, which could result in cases of rapid transmission. Also, there is evidence that spirochete transmission times and virulence depend upon the tick and Borrelia species. These factors support anecdotal evidence that Borrelia infection can occur in humans within a short time after tick attachment.
Regulation of CXCR4-Mediated Nuclear Translocation of Extracellular Signal-Related Kinases 1 and 2

Activation of the chemokine receptor CXCR4 by its agonist stromal cell-derived factor 1 (SDF-1) has been associated with cell migration and proliferation in many cell types, but the intracellular signaling cascades are incompletely defined. Here we show that CXCR4-dependent extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation was mediated through the Ras/Raf pathway, as demonstrated with a dominant-negative Ras mutant and pharmacological inhibitors. The Src inhibitor 4-amino-5-methylphenyl-7-(t-butyl)pyrazolo[3,4-d] pyrimidine (PP1) and the Rho-kinase (ROCK) inhibitor N-(4-pyridyl)-4-(1-aminoethyl)cyclohexanecarboxamide dihydrochloride (Y27632) also attenuated SDF-1-induced ERK1/2 phosphorylation. Involvement of Src could furthermore be demonstrated by Src phosphorylation and by the shortened ERK1/2 phosphorylation in SYF cells, which are Src/Yes/Fyn-deficient compared with Src-reconstituted Src++ cells. Membrane translocation of RhoA could be detected similarly. A large portion of the SDF-1-mediated ERK phosphorylation was detected in the nucleus, as shown by Western blotting and confocal microscopy, and resulted in the phosphorylation of the transcription factor Elk. It is interesting that the nuclear accumulation of ERK1/2 and Elk phosphorylation was completely blocked by dominant-negative Rho, Y27632, PP1, and latrunculin B, indicating that the Rho/ROCK pathway, Src kinase, and the actin cytoskeleton were required in this process. In accordance, neither nuclear ERK phosphorylation nor Elk phosphorylation were observed in SYF cells stimulated with SDF-1 but were reconstituted in Src++ cells. In summary, these results demonstrate that Src, Rho/ROCK, and an intact cytoskeleton contribute to overall ERK1/2 activation in SDF-1-stimulated cells and are indispensable for nuclear translocation of ERK1/2 and activation of transcription factors.
A Simple Model System Enabling Human CD34+ Cells to Undertake Differentiation Towards T Cells

Background Channelling the development of haematopoietic progenitor cells into T lymphocytes is dependent upon a series of extrinsic prompts whose temporal and spatial sequence is critical for a productive outcome. Simple models of human progenitor cells development depend in the main on the use of xenogeneic systems which may provide some limitations to development. Methods and Findings Here we provide evidence that a simple model system which utilises both human keratinocyte and fibroblast cell lines arrayed on a synthetic tantalum coated matrix provides a permissive environment for the development of human CD34⁺ haematopoietic cells into mature CD4⁺ or CD8⁺ T lymphocytes in the presence of Interleukin 7 (IL-7), Interleukin 15 (IL-15) and the Fms-like tyrosine kinase 3 ligand (Flt-3L). This system was used to compare the ability of CD34+ cells to produce mature thymocytes and showed that whilst these cells derived from cord blood were able to productively differentiate into thymocytes the system was not permissive for the development of CD34+ cells from adult peripheral blood. Conclusions/Significance Our study provides direct evidence for the capacity of human cord blood CD34+ cells to differentiate along the T lineage in a simple human model system. Productive commitment of the CD34⁺ cells to generate T cells was found to be dependent on a three-dimensional matrix which induced the up-regulation of the Notch delta-like ligand 4 (Dll-4) by epithelial cells.
Elucidation of Hepatitis C Virus Transmission and Early Diversification by Single Genome Sequencing

A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures.
Set-Asides and Subsidies in Auctions

Set-asides and subsidies are used extensively in government procurement and natural resource sales. We analyze these policies in an empirical model of U.S. Forest Service timber auctions. The model fits the data well both within the sample of unrestricted sales where we estimate the model, and when we predict (out of sample) bidder entry and prices for small business set-asides. Our estimates suggest that restricting entry to small businesses substantially reduces efficiency and revenue, although it does increase small business participation. An alternative policy of subsidizing small bidders would increase revenue and small bidder profit, while eliminating almost all of the efficiency loss of set-asides, and only slightly decreasing the profit of larger firms. We explain these findings by connecting to the theory of optimal auction design.
Protective Effects of Astaxanthin from Paracoccus carotinifaciens on Murine Gastric Ulcer Models

The purpose of this study was to investigate the effect of astaxanthin extracted from Paracoccus carotinifaciens on gastric mucosal damage in murine gastric ulcer models. Mice were pretreated with astaxanthin for 1 h before ulcer induction. Gastric ulcers were induced in mice by oral administration of hydrochloride (HCl)/ethanol or acidified aspirin. The effect of astaxanthin on lipid peroxidation in murine stomach homogenates was also evaluated by measuring the level of thiobarbituric acid reactive substance (TBARS). The free radical scavenging activities of astaxanthin were also measured by electron spin resonance (ESR) measurements. Astaxanthin significantly decreased the extent of HCl/ethanol‐ and acidified aspirin‐induced gastric ulcers. Astaxanthin also decreased the level of TBARS. The ESR measurement showed that astaxanthin had radical scavenging activities against the 1,1‐diphenyl‐2‐picrylhydrazyl radical and the superoxide anion radical. These results suggest that astaxanthin has antioxidant properties and exerts a protective effect against ulcer formation in murine models. Copyright © 2011 John Wiley & Sons, Ltd.
The mammalian tRNA ligase complex mediates splicing of XBP1 mRNA and controls antibody secretion in plasma cells

The unfolded protein response (UPR) is a conserved stress‐signaling pathway activated after accumulation of unfolded proteins within the endoplasmic reticulum (ER). Active UPR signaling leads to unconventional, enzymatic splicing of XBP1 mRNA enabling expression of the transcription factor XBP1s to control ER homeostasis. While IRE1 has been identified as the endoribonuclease required for cleavage of this mRNA, the corresponding ligase in mammalian cells has remained elusive. Here, we report that RTCB, the catalytic subunit of the tRNA ligase complex, and its co‐factor archease mediate XBP1 mRNA splicing both in vitro and in vivo. Depletion of RTCB in plasma cells of Rtcbfl/fl Cd23‐Cre mice prevents XBP1s expression, which normally is strongly induced during plasma cell development. RTCB‐depleted plasma cells show reduced and disorganized ER structures as well as severe defects in antibody secretion. Targeting RTCB and/or archease thus represents a promising strategy for the treatment of a growing number of diseases associated with elevated expression of XBP1s.
Boceprevir and personalized medicine in hepatitis C virus infection

Boceprevir was the first agent, along with telaprevir, of a novel class of direct-acting antivirals that entered clinical practice for the treatment of chronic hepatitis C. Boceprevir is an antiprotease that directly blocks hepatitis C virus (HCV) replication. Two studies in patients with HCV genotype 1 infection have shown that addition of boceprevir to the standard of care, ie, pegylated interferon-alfa (PEG-IFN-α) and ribavirin, markedly increased the rate of sustained virological response. A sustained virological response was obtained in about 70% of patients who had never been treated, as well as in 69%–75% and 40% of previous relapsers and nonresponders to PEG-IFN-α-ribavirin, respectively. Side effects were observed in almost all treated patients. Anemia, the most frequent adverse event related to administration of boceprevir, occurred in about 50% of patients. The decision to add boceprevir to the standard of care is made on an individual basis, and takes into account the prognosis of the liver disease, the efficacy of therapy, as it could be at best predicted, and the side effects that may arise, taking into account the comorbidities of the patient. Ultimately, the treatment must be accepted by the patient, who should fully understand the benefits and risks. Boceprevir trials were designed with the concept of individualized and response-guided therapy which establishes treatment decisions on how rapidly patients respond to treatment. Individualized therapy for chronic hepatitis C is based on patient and viral characteristics to make the best choice about whether a person will benefit from therapy and to evaluate on-treatment predictors of response to shorten therapy in patients with a rapid response as well as in patients who did not respond sufficiently to expect HCV eradication. This review focuses on the main results obtained so far, their impact on the treatment of patients with chronic hepatitis C, and potential therapeutic perspectives.
Special Issue on Foundations of Social Computing

An unprecedented information wealth produced by online social networks, further augmented by location/collocation data, is currently fragmented across different proprietary services. Combined, it can accurately represent the social world and enable novel socially aware applications. We present Prometheus, a socially aware peer-to-peer service that collects social information from multiple sources into a multigraph managed in a decentralized fashion on user-contributed nodes, and exposes it through an interface implementing nontrivial social inferences while complying with user-defined access policies. Simulations and experiments on PlanetLab with emulated application workloads show the system exhibits good end-to-end response time, low communication overhead, and resilience to malicious attacks.
Evaluation of mouse urinary bladder smooth muscle for diurnal differences in contractile properties

Most physiological systems show daily variations in functional output, entrained to the day–night cycle. Humans exhibit a daily rhythm in urinary voiding (micturition), and disruption of this rhythm (nocturia) has significant clinical impact. However, the underlying mechanisms are not well-understood. Recently, a circadian rhythm in micturition was demonstrated in rodents, correlated with functional changes in urodynamics, providing the opportunity to address this issue in an animal model. Smooth muscle cells from mouse bladder have been proposed to express a functional and autonomous circadian clock at the molecular level. In this study, we addressed whether a semi-intact preparation of mouse urinary bladder smooth muscle (UBSM) exhibited measurable differences in contractility between day and night. UBSM tissue strips were harvested at four time points over the diurnal cycle, and spontaneous (phasic) and nerve-evoked contractions were assessed using isometric tension recordings. During the active period (ZT12-24) when micturition frequency is higher in rodents, UBSM strips had no significant differences in maximal- (high K+) or nerve-evoked contractions compared to strips harvested from the resting period (ZT0-12). However, a diurnal rhythm in phasic contraction was observed, with higher amplitudes at ZT10. Consistent with the enhanced phasic amplitudes, expression of the BK K+ channel, a key suppressor of UBSM excitability, was lower at ZT8. Higher expression of BK at ZT20 was correlated with an enhanced effect of the BK antagonist paxilline (PAX) on phasic amplitude, but PAX had no significant time-of-day dependent effect on phasic frequency or nerve-evoked contractions. Overall, these results identify a diurnal difference for one contractile parameter of bladder muscle. Taken together, the results suggest that autonomous clocks in UBSM make only a limited contribution to the integrated control of diurnal micturition patterns.