Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Performance of Cell Life Span and Cell Transit Models for Describing Erythropoietic Drug Effects

Prolonged time delay in response to drug action is a common feature of hematological responses to pharmacotherapy such as erythropoiesis. The objective of this study was to compare the performance of two competing modeling approaches for delayed drug effects, mechanistic cell life span models, and semi-mechanistic cell transit models. The comparison was performed with an experimental dataset from multiple dose administrations of an erythropoietin mimetic to Cynomolgus monkeys. Comparative performance measures include visual predictive checks, goodness-of-fit plots, model estimation time, estimation status, and estimation error. The analysis revealed that both models resulted in a similarly good description of the erythropoietic drug effect, with precision and bias of the model-based predictions of red blood cell counts of less than 11%. The cell transit model needed slightly longer time to converge compared to the cell life span model. The system and drug effect parameters were similar in both models indicating that the models can be interchangeably used to describe the current data. Thus, model selection would be dependent on the purpose of the modeling exercise, the available data, and the time allocated for model development.
Early Impairment of Gut Function and Gut Flora Supporting a Role for Alteration of Gastrointestinal Mucosa in Human Immunodeficiency Virus Pathogenesis

ABSTRACT Our results show that impairment of the gastrointestinal tracts in human immunodeficiency virus (HIV)-positive patients is present in the early phases of HIV disease. This impairment is associated with alterations in gut microbiota and intestinal inflammatory parameters. These findings support the hypothesis that alterations at the gastrointestinal-tract level are a key factor in HIV pathogenesis.
Quercetin offers cardioprotection against progression of experimental autoimmune myocarditis by suppression of oxidative and endoplasmic reticulum stress via endothelin-1/MAPK signalling

In order to test the hypothesis that treatment with quercetin at a dose of 10 mg/kg protects from the progression of experimental autoimmune myocarditis (EAM) to dilated cardiomyopathy (DCM), we have used the rat model of EAM induced by porcine cardiac myosin. Our results identified that the post-myocarditis rats suffered from elevated endoplasmic reticulum (ER) stress and adverse cardiac remodelling in the form of myocardial fibrosis, whereas the rats treated with quercetin have been protected from these changes as evidenced by the decreased myocardial levels of ER stress and fibrosis markers when compared with the vehicle-treated DCM rats. In addition, the myocardial dimensions and cardiac function were preserved significantly in the quercetin-treated rats in comparison with the DCM rats treated with vehicle alone. Interestingly, the rats treated with quercetin showed significant suppression of the myocardial endothelin-1 and also the mitogen activated protein kinases (MAPK) suggesting that the protection offered by quercetin treatment against progression of EAM involves the modulation of MAPK signalling cascade. Collectively, the present study provides data to support the role of quercetin in protecting the hearts of the rats with post myocarditis DCM.
Consensus reaching in multi-agent packet-switched networks with non-linear coupling

An important task for multi-agent systems (MAS) is to reach a consensus, e.g. to align their velocity vectors. Recent results propose appropriate consensus protocols to achieve such tasks, but most of them do not consider the effect of communication constraints such as the presence of time-delays in the exchange of information between the agents. In this article, we provide conditions for a non-linear, locally passive MAS of arbitrary size to reach a consensus, when the agents communicate over a packet-switched network that is characterised by a given topology. Both the cases of constant and switching topologies are considered. The nature of the communication channel imposes constraints that are modelled using stochastic delays of arbitrary distribution. We first embed this model in another, distributed but deterministic delay model and provide conditions for the error introduced by this simplification. In our main result, we provide conditions for the locally passive MAS with distributed delays to reach a consensus. In the case of a fixed topology, the underlying directed graph has to contain a spanning tree. In the case of a switching topology, only the union graph of all graphs that persist over time is required to contain a spanning tree. These conditions are independent of the distribution and the size of the packet delays. To show attractivity of the consensus set, we use an invariance principle for systems described by functional differential equations based on an appropriate Lyapunov–Razumikhin function. This methodological approach is the main contribution of this work and can also be applied to other consensus problems with delays. We illustrate our results by numerical simulations showing synchronisation of non-linear Kuramoto oscillators over a digital network.
Review: formation and properties of amyloid-like fibrils derived from alpha-synuclein and related proteins.

Synucleinsare small proteins that are highly expressed in brain tissue and are localised at presynaptic terminals in neurons. alpha-Synuclein has been identified as a component of intracellular fibrillar protein deposits in several neurodegenerative diseases, and two mutant forms of alpha-synuclein have been associated with autosomal-dominant Parkinson's Disease. A fragment of alpha-synuclein has also been identified as the non-Abeta component of Alzheimer's Disease amyloid. In this review we describe some structural properties of alpha-synuclein and the two mutant forms, as well as alpha-synuclein fragments, with particular emphasis on their ability to form beta-sheet on ageing and aggregate to form amyloid-like fibrils. Differences in the rates of aggregation and morphologies of the fibrils formed by alpha-synuclein and the two mutant proteins are highlighted. Interactions between alpha-synuclein and other proteins, especially those that are components of amyloid or Lewy bodies, are considered. The toxicity of alpha-synuclein and related peptides towards neurons is also discussing in relation to the aetiology of neurodegenerative diseases.
Iron monitoring and supplementation: how do we achieve the best results?

A number of factors have been shown to limit the response to recombinant human erythropoietin (r-HuEPO). One major factor appears to be an inadequate iron supply to the bone marrow. Erythropoiesis is dependent upon a continuous supply of iron to the bone marrow. The rate at which iron can be drawn from existing stores may easily limit the rate of delivery for haemoglobin synthesis. This results in 'functional iron deficiency' which is distinct from 'absolute iron deficiency' caused by depletion of iron stores. At present there are three main parameters available to clinicians wishing to monitor iron status in their patients: serum ferritin and transferrin saturation (TFS), which are indirect measurements, and the percentage of hypochromic red cells, which directly reflects marrow iron status. Ferritin levels should be measured before starting r-HuEPO therapy to ensure adequate iron stores (>200 microg/l), and when patients move from the correction phase to the maintenance phase of therapy (have stores become depleted during the correction phase? ). In addition, ferritin levels can give an indication of iron overload following excess parenteral iron administration. The TFS represents a balance between iron supply by stores and demand by bone marrow. A saturation below 20% probably indicates iron-deficient erythropoiesis. However, this is an indirect measure of marrow iron supply and wide fluctuations have been observed when determined at different time points. The percentage of hypochromic red blood cells is measured by flow cytometry and a hypochromic subpopulation of more than 10% (normal percentage <2.5%) indicates iron-deficient erythropoiesis. However, not all departments may have access to the required equipment. The aim of iron supplementation is to provide sufficient iron for the correction phase and to replace iron losses (1500-2000 mg/year in haemodialysis patients) during the maintenance phase of r-HuEPO therapy. This amounts to a daily iron need in the range of 5 7 mg, which is well above the normal dietary intake and absorptive capacity of the human intestine. Therefore, there is a need for intravenous iron, in particular when the patient has absolute or functional iron deficiency, is intolerant of oral iron, or is not complying well with the oral regimen.
Integrating Spirituality into a Group Psychotherapy Program for Women Surviving from Breast Cancer

Background In spite of a significant relation between spirituality and hope, happiness and life satisfaction, the effectiveness of spiritual interventions in the mentioned mental strengths has been less dealt with. The present study is conducted in order to determine the effectiveness of spiritual group intervention on the increase of hope, life satisfaction and happiness in women surviving from breast cancer. Methods Sixty women surviving from Breast Cancer were voluntarily assigned in to case and control groups, and were assessed before and after Islamic perspective spiritual intervention by spiritual experience, hope, happiness and life satisfaction questionnaires. Statistical analysis of data was performed using descriptive and inferential statistics through covariance. Results The spiritual intervention resulted in significant increase of hope, happiness and life satisfaction (P < 0.05). Conclusion Spiritual intervention appears to be a potentially beneficial intervention for increasing mental strengths among those suffering from breast cancer. Therefore, it seems necessary to consider it as an important element incomprehensive treatment, plans, and in palliative and supportive care.
Lightweight emulation to study peer-to-peer systems

The current methods used to test and study peer-to-peer systems (namely modeling, simulation, or execution on real testbeds) often show limits regarding scalability, realism and accuracy. This paper describes and evaluates P2PLab, our framework to study peer-to-peer systems by combining emulation (use of the real studied application within a configured synthetic environment) and visualization. P2PLab is scalable (it uses a distributed network model) and has good visualization characteristics (many virtual nodes can be executed on the same physical node by using process-level visualization). Experiments with the BitTorrent file-sharing system complete this paper and demonstrate the usefulness of this platform.
The molecular dimension of microbial species: 2. Synechococcus strains representative of putative ecotypes inhabiting different depths in the Mushroom Spring microbial mat exhibit different adaptive and acclimative responses to light

Closely related strains of thermophilic Synechococcus were cultivated from the microbial mats found in the eﬄuent channels of Mushroom Spring, Yellowstone National Park (YNP). These strains have identical or nearly identical 16S rRNA sequences but are representative of separate, predicted putative ecotype (PE) populations, which were identified by using the more highly resolving psaA locus and which predominate at different vertical positions within the 1-mm-thick upper-green layer of the mat. Pyrosequencing confirmed that each strain contained a single, predominant psaA genotype. Strains differed in growth rate as a function of irradiance. A strain with a psaA genotype corresponding to a predicted PE that predominates near the mat surface grew fastest at high irradiances, whereas strains with psaA genotypes representative of predominant subsurface populations grew faster at low irradiance and exhibited greater sensitivity to abrupt shifts to high light. The high-light-adapted and low-light-adapted strains also exhibited differences in pigment content and the composition of the photosynthetic apparatus (photosystem ratio) when grown under different light intensities. Cells representative of the different strains had similar morphologies under low-light conditions, but under high-light conditions, cells of low-light-adapted strains became elongated and formed short chains of cells. Collectively, the results presented here are consistent with the hypothesis that closely related, but distinct, ecological species of Synechococcus occupy different light niches in the Mushroom Spring microbial mat and acclimate differently to changing light environments.
Medicaid Enrollment Choice into Managed Care Health Plans

Rural Aid to Families with Dependent Children (AFDC) Medicaid recipients were surveyed to identify factors that influenced their enrollment choice between two managed care health plans and the traditional Medicaid fee-for-service plan. Bivariate and logistic regression analyses provided evidence that the Medicaid institutional information structure directly influenced recipient decision to enroll in managed care plans. Current smokers were more likely to choose a managed care plan in this sample. There was no evidence that health status, health service use patterns, marital status, or ethnicity was related to the enrollment decision. Of those who chose the traditional Medicaid fee-for-service plan, 41 percent reported that they did not understand what managed care was.
Chemotherapy Reduces Para-aortic Node Recurrences in Endometrial Cancer With Positive Pelvic and Unknown Para-aortic Nodes

Objective The objective of this study was to evaluate how the administration of different adjuvant therapies influences the risk for developing recurrences in the para-aortic area in endometrial cancer (EC) with positive pelvic and unknown para-aortic nodes. Methods We retrospectively evaluated the data of 58 patients with EC affected by stage IIIC1 who had undergone pelvic but not para-aortic lymphadenectomy from January 1, 1990 to December 31, 2011. Survival outcomes within the first 5 years after surgery were assessed using the Kaplan-Meier model. Results Chemotherapy plus radiotherapy, chemotherapy only, and external radiotherapy only were administered in 12 (23%), 18 (34%), and 23 (43%) patients, respectively. Five (9%) patients, who were selected to forego adjuvant therapy due to poor performance status, were excluded from the analysis. Disease-free and overall survivals assessed at 5 years were 54%, and 61%, respectively. All para-aortic recurrences were observed among the patients with endometrioid EC, whereas no cases of para-aortic recurrences were found in patients with nonendometrioid histology (5/36 (14%) vs 0/17 (0%); P = 0.16); the latter were more likely to develop distant (hematogenous, peritoneal, and distant lymphatic) recurrences (P = 0.09). Type of adjuvant therapy was the only factor influencing para-aortic failure: chemotherapy (± radiotherapy) reduced the rate of para-aortic node recurrence in comparison with pelvic radiotherapy as a sole modality (P = 0.01). However, adjuvant therapy did not influence the 5-year survival outcomes (P > 0.05). Conclusions In the absence of local treatment (ie, para-aortic lymphadenectomy and radiotherapy), the administration of chemotherapy seems effective in reducing recurrences in the para-aortic area among patients with stage IIIC1 endometrioid EC.
Clinical Significance of Quantitative Assessment of Rectoanal Inhibitory Reflex (RAIR) in Patients With Constipation

Background Rectoanal inhibitory reflex (RAIR) is routinely assessed in anorectal manometry and is of clinical value in the diagnosis of patients with constipation. However, no quantitative analysis is currently available for the assessment of RAIR. The aim of this study was to evaluate the diagnostic value of quantitative assessment of RAIR in patients with constipation. Methods Nine healthy subjects, 22 constipation patients (CO) and 26 fecal incontinence patients (FI) were enrolled in this study. RAIR was solicited by inflating the balloon with various volumes from 10 to 50 mL. The percentage of relaxation was determined on the basis of the rectal resting sphincter pressure and residual pressure with the balloon distention. Results Percentage of internal sphincter relaxation induced by rectal distention in constipation patients was significantly lower with distention of 20, 30, 40, and 50 mL in comparison with that in healthy subjects (Mixed model, P<0.05). The volume of distention required to achieve a relaxation of 50% was significantly higher in patients with CO (37.3±3.1 mL) than that in healthy subjects (27.8±2.6 mL, P<0.03) or FI (26.3±2.3 mL, P<0.05). It was also found that the percentage of relaxation could be used to differentiate the patients with constipation with a specificity of 64% and a sensitivity of 67%. Conclusions Patients with CO have impaired RAIR in comparison with healthy subjects and patients with FI. Quantitative assessment of RAIR is valuable in the diagnosis of patients with CO and may be incorporated in the clinical anorectal manometric test.
An ophthalmic solution of a peroxisome proliferator-activated receptor gamma agonist prevents corneal inflammation in a rat alkali burn model

Purpose We clarified the effects of an ophthalmic solution of a peroxisome proliferator-activated receptor gamma (PPARγ) agonist on corneal inflammation and wound healing after alkali burn injury in rats. Methods After alkali exposure, either an ophthalmic solution with 0.1% pioglitazone hydrochloride (the PPARγ group) or vehicle (the vehicle group) was topically applied to the cornea until day 14. Histological, immunohistochemical, and real-time reverse transcription polymerase chain reaction analysis were performed. Results After alkali injury, PPARγ expression increased, with the infiltration of many inflammatory cells. The infiltration of neutrophils and macrophages started from the corneal limbus within 6 h, and developed in the corneal center by day 7, with associated neovascularization. The accumulation of α-smooth muscle actin-positive myofibroblasts and the deposition of type III collagen were noted on day 14. The histological changes were suppressed significantly by treatment with the ophthalmic solution of the PPARγ agonist. In addition, the number of infiltrating M2 macrophages in the cornea was increased by PPARγ agonist treatment. In real-time reverse transcription polymerase chain reaction analysis, the messenger ribonucleic acid expression levels of interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, transforming growth factor beta 1, and vascular endothelial growth factor-A were decreased in the PPARγ group compared to the vehicle group in the early periods of corneal inflammation. Conclusions The ophthalmic solution of the PPARγ agonist inhibited inflammation, decreased the fibrotic reaction, and prevented neovascularization in the cornea from the early phase after alkali burn injury. The ophthalmic solution of the PPARγ agonist may provide a new treatment strategy with useful clinical applications for corneal inflammation and wound healing.
Intermittent Ischemic Preconditioning Protects Against Hepatic Ischemia-Reperfusion Injury and Extensive Hepatectomy in Steatotic Rat Liver

ABSTRACT Background: Hepatic steatosis causes severe liver damage and has deleterious effects when associated with ischemia-reperfusion mechanisms. Ischemic preconditioning (IPC) protects lean liver against prolonged ischemia by improving micro-circulation and reducing lipid peroxidation. We investigated the effect of intermittent IPC on liver ischemia-reperfusion injury (IRI) and extensive hepatectomy in severe hepatic steatosis. Methods: Severe hepatic steatosis was performed by 12–14 weeks of choline-free diet in 108 Wistar rats. We induced 30-minute ischemia-reperfusion manipulations and extensive hepatectomy with or without prior IPC in steatotic livers and after 6 and 24 hours of reperfusion blood transaminases, and IL6, TNFα, NO and Lactate in blood and liver tissue were measured. Results: Steatotic rats subjected to hepatic ischemia-reperfusion alone after extensive hepatectomy, showed severe liver damage with significantly increased values of AST, ALT, TNFα and Lactate and significantly reduced IL6 and NO, while no one rat survived for more than 29 hours. On the contrary, steatotic rats subjected to intermittent IPC, 24 hours before ischemia-reperfusion, presented increased 30-day survival (67%), lower values of AST, ALT, TNFα and Lactate, and increased IL6 and NO levels. Simple and intermittent IPC manipulations, 1 hour before the IRI and extended hepatectomy, did not prolong survival more than 57 and 98 hours, respectively. Simple IPC, 24 hours before IRI and extended hepatectomy had the lowest possible survival (16.7%). Conclusions: Hepatic steatosis and IRI after major liver surgery largely affect morbidity and mortality. Intermittent IPC, 24 hours before IRI and extensive hepatectomy, presents higher 30-day survival and improved liver function parameters.
Facilitativeness, Conflict, Demand for Approval, Self-Esteem, and Satisfaction With Romantic Relationships

Abstract This study is an examination of the extent to which satisfaction with a main current romantic relationship is associated with negative conflict, demand for approval, self-esteem, and the 3 facilitative conditions of unconditional regard, empathy, and congruence. One or more of these conditions have been proposed as important determinants of relationship satisfaction by various relationship-enhancement approaches such as behavioral marital therapy and cognitive-behavioral marital therapy. College students (86 women and 58 men) completed S. S. Hendrick's (1988) Relationship Satisfaction Scale, a measure of negative conflict formulated by the author, R. G. Jones's (1969) Demand for Approval Scale (modified for a particular relationship), M. Rosenberg's (1965) Self-Esteem Scale, and a shortened modified version of G. T. Barrett-Lennard's (1964) Relationship Inventory. Relationship satisfaction was most strongly related to the level of regard and empathy, which is consistent with approaches to relationships that emphasize empathy training.