Miracle-dz/UniFAR-FTUs huggingface dataset:
Correction: Interstitial Fluid Flow and Drug Delivery in Vascularized Tumors: A Computational Model

Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider–with the help of a theoretical model–the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy’s law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intraand extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various strategies to increase drug exposure time of tumor cells. Citation: Welter M, Rieger H (2013) Interstitial Fluid Flow and Drug Delivery in Vascularized Tumors: A Computational Model. PLoS ONE 8(8): e70395. doi:10.1371/ journal.pone. 0070395 Editor: Timothy W. Secomb, University of Arizona, United States of America Received January 28, 2013; Accepted June 18, 2013; Published August 5, 2013 Copyright: 2013 Welter, Rieger. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Funding: University, Deutsche Forschungsgemeinschaft. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: h.rieger@mx.uni-saarland.de
DESIGNERDRINKS UND MODEGETRAENKE

Designerdrinks sind stark gesuesste und aromatisierte kohlensaeurehaltige alkoholische Getraenke. Seit 1995 werden sie vornehmlich ausgehend von Grossbritannien in Form alkoholhaltiger Limonaden (Alcopops), stark gesuesster Cider (Apfelweine) oder Mischgetraenke auf den Markt gebracht. Aufmachung und Geschmack sind fuer Kinder und Jugendliche besonders attraktiv. Auch bei anderen Getraenken wie Bieren ist zu beobachten, dass man versucht, durch Namen, Symbole oder Inhaltsstoffe einen Bezug zu bestimmten Gruppen herzustellen. Da diese Getraenke auch forensisch von Interesse sind, wurden die Begleitstoffgehalte verschiedener neuerer Getraenke bestimmt. Bemerkenswert ist der hohe 2-Propanolgehalt einiger Getraenke aus britischer Produktion. Eine Erklaerung fuer diese Beobachtung konnte bislang nicht gefunden werden, da groessere 2-Propanolmengen bei der alkoholischen Gaerung nur dann gebildet werden, wenn eine bakterielle Infektion vorliegt. Dabei entstehen ebenfalls groessere Mengen an 2-Butanol und n-Propanol. Diese waren in den Getraenken nicht nachweisbar. Die Konzentrationen an 2-Propanol sind teilweise so hoch, dass bereits bei Blutalkoholspiegeln um 0,5 Promille im Blut 2-Propanol- und Acetonspiegel entstehen, die man sonst bei Alkoholmissbrauch findet. (A) Titel in Englisch: Designer drinks and fashionable beverages.
Clinical Presentation of Prodromal Frontotemporal Dementia

Background. Misrecognition of symptoms in the early stages of frontotemporal dementia (FTD) frequently contributes to diagnostic delay. Three frameworks have been proposed for the clinical identification of prodromal FTD: (1) cognitive profiling, (2) the presence of behavioral/psychiatric symptoms in the absence of memory complaints, and (3) a combined approach of cognitive, behavioral, and neuroimaging features. Objective. To evaluate current conceptual frameworks for the clinical recognition of prodromal FTD with current empirical evidence. Method. We performed a comprehensive PsychINFO and MEDLINE database search to identify articles investigating the prodromal symptoms of FTD. Conclusions. The 3 frameworks capture important aspects of the clinical picture of prodromal FTD but require further refinement. The prodromal stage of FTD is characterized by both cognitive and behavioral features. Diagnostic accuracy will likely be improved by considering a combination of cognitive and behavioral features, because some features overlap with prodromes for Alzheimer's disease and vascular dementia.
Collective force generated by multiple biofilaments can exceed the sum of forces due to individual ones

Collective dynamics and force generation by cytoskeletal filaments are crucial in many cellular processes. Investigating growth dynamics of a bundle of N independent cytoskeletal filaments pushing against a wall, we show that chemical switching (ATP/GTP hydrolysis) leads to a collective phenomenon that is currently unknown. Obtaining force-velocity relations for different models that capture chemical switching, we show, analytically and numerically, that the collective stall force of N filaments is greater than N times the stall force of a single filament. Employing an exactly solvable toy model, we analytically prove the above result for N = 2. We, further, numerically show the existence of this collective phenomenon, for N ⩾ 2 ? > , in realistic models (with random and sequential hydrolysis) that simulate actin and microtubule bundle growth. We make quantitative predictions for the excess forces, and argue that this collective effect is related to the non-equilibrium nature of chemical switching.
Vaccination against chlamydial and mycobacterial infections Ph

We studied the role of isocitrate lyase in the interaction between Mycobacterium bovis BCG and mice. ApoB100-only LDLR (B6;129S-ApoBLdlr/ J) mice were inoculated with M. bovis BCG harbouring plasmids carrying the gene for isocitrate lyase. The presence of *29 times more copies of this gene resulted in a higher bacterial yield in the spleens and lungs of the infected mice. The spleen was 3–4 times heavier, and in the spleen the bacteria survived over 10 days longer than did the bacteria with the control plasmid. Propionate was less toxic for bacteria carrying icl plasmids in vitro. This recombinant BCG can be a possible vaccine candidate.
Forward-Backward Probability Hypothesis Density Smoothing

A forward-backward probability hypothesis density (PHD) smoother involving forward filtering followed by backward smoothing is proposed. The forward filtering is performed by Mahler's PHD recursion. The PHD backward smoothing recursion is derived using finite set statistics (FISST) and standard point process theory. Unlike the forward PHD recursion, the proposed backward PHD recursion is exact and does not require the previous iterate to be Poisson. In addition, assuming the previous iterate is Poisson, the cardinality distribution and all moments of the backward-smoothed multi-target density are derived. It is also shown that PHD smoothing alone does not necessarily improve cardinality estimation. Using an appropriate particle implementation we present a number of experiments to investigate the ability of the proposed multi-target smoother to correct state as well as cardinality errors.
Laryngoscope decontamination techniques: A survey

Background and Aims: India is a vast country with variable, nonuniform healthcare practices. A laryngoscope is an important tool during general anesthesia and resuscitation. The study aimed to determine the current practices of laryngoscope decontamination in India. Material and Methods: An online survey was conducted amongst 100 anesthesiologists to determine the common methods of laryngoscope decontamination adopted in their settings. The survey was done over 6 months after validating the questionnaire. Results: A total of 73 responses were received out of 100. The result of the survey revealed that there is no uniform technique of laryngoscope decontamination. There is marked variability in techniques followed not only among different institutions, but also within the same institution. Conclusion: There are no fixed protocols adopted for laryngoscope decontamination. Thus, there is a need to develop definitive guidelines on this subject, which can be implemented in India.
Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression

Background: Reduced hippocampal volume and increased prevalence of subcortical white matter lesions are associated with both recurrent early onset depression (EOD) and late onset depression (LOD). It is not clear whether these two factors differentially affect the age of onset of first depression. Therefore, we wished to investigate the relationship between age of first depression onset and hippocampal volume, with adjustment for subcortical white matter lesions. Methods: MRI brain scans were used to compare hippocampal volumes and white matter lesions between age matched female patients (>60 years) with recurrent EOD and LOD and healthy controls. Results: When comparing the three groups and adjusting for age, the Mini-Mental State Examination score, total brain volume and total hippocampal volume were significantly smaller in patients with EOD compared with controls (5.6 vs 6.1 ml; p = 0.04). The prevalence of larger subcortical white matter lesions was higher in patients with LOD compared with patients with EOD (47% vs 8%; p = 0.002). Patients with LOD did not differ in hippocampal volume from patients with EOD or from controls. Conclusions: In late life depression, age of first depression onset may distinguish between different independent neuropathological mechanisms. A small hippocampus volume may be a neuranatomical marker of EOD depression and larger subcortical white matter lesions could be an intermediate between cerebrovascular disease and LOD.
Bradykinin antagonists HOE‐440 and CP‐0597 diminish microcirculatory injury after ischaemia‐reperfusion of the pancreas in rats

Ischaemia‐reperfusion of the pancreas was performed in 35′ anaesthetized Sprague‐Dawley rats. The effects of two bradykinin antagonists, HOE‐140 (13 μg kg−1 intravenous bolus injection, n = 7) and CP‐0597 (18 μg kg−lh−1intravenous infusion, n = 7) on pancreatic microvascular perfusion and leucocyte‐endothelium interaction were quantitatively analysed by intravital fluorescence microscopy. Three further groups underwent sham operation (n = 7), ischaemia of 2 h without treatment (n = 7), and ischaemia of 2 h with infusion of phosphate buffer (n = 7). Functional capillary density was significantly greater in animals treated with HOE‐140 or CP‐0597 than in sham‐treated animals, and was decreased to only 60 per cent. Adherence of leucocytes to the endothelium of postcapillary venules was significantly reduced when compared with ischaemia without antagonist. These results demonstrate a positive effect of the two bradykinin antagonists HOE‐140 and CP‐0597 on microvascular perfusion failure after ischaemia‐reperfusion of the pancreas.
Cyberknife radiosurgery for breast cancer spine metastases

There are few options for breast cancer patients with spinal metastases recurrent within a previous radiation treatment field. CyberKnife radiosurgery has been used in our institution to treat such patients. To evaluate their outcomes, as there are no comparable radiation treatment options, the outcomes were compared between 18 patients with spinal metastases from breast cancer treated with CyberKnife stereotactic radiosurgery, 17 of which had prior radiotherapy to the involved spinal region and were progressing, and 18 matched patients who received conventional external beam radiotherapy (CRT) up‐front for spinal metastases.
Adhesion of sickle red blood cells and damage to interleukin-1 beta stimulated endothelial cells under flow in vitro.

Two factors that are hypothesized to contribute to vasoocclusive crises in sickle cell anemia are increased sickle red blood cell-endothelial cell interactions and damage to endothelium. Despite considerable study, the mechanisms by which erythrocyte-endothelial interactions occur and the role of endothelial damage have not yet been fully elucidated. In this report, we demonstrate that adhesion and damage may be related in a model of vasoocclusion in sickle cell anemia. Phase contrast microscopy coupled to digital image processing was used to determine the adhesion of sickle red blood cells to 1-, 4-, and 24-hour interleukin-I beta (IL-1 beta) stimulated endothelial calls in a parallel plate flow chamber. Morphological alterations to activated endothelial cells after the perfusion of sickle erythrocytes were also identified. Pretreatment of monolayers with 50 pg/mL of IL-1 beta for 1, 4, and 24 hours caused approximately 16-fold increases in adhesion of sickle cells to activated endothelium at all time points. Results with an Arginine-glycine aspartic acid (RGD) peptide and monoclonal antibodies indicated a role for three different endothelial cell receptors: alpha v beta 3 after 1 hour of IL-1 beta stimulation; E-selectin after 4 hours of IL-1 beta stimulation; and vascular cell adhesion molecule-1 after prolonged exposure to cytokines. Perfusion of sickle, but not normal, erythrocytes resulted in alteration of endothelial morphology. Approximately 6% to 8% damage was observed on 4- and 24-hour IL-1 beta stimulated endothelial cells after the perfusion of sickle cells. Damage to 24-hour activated endothelial cells showed a positive correlation (r = .899) with the number of adherent sickle erythrocytes.
Polyphenols benefits of olive leaf (Olea europaea L) to human health.

INTRODUCTION The phenolic compounds present in olive leaves (Olea europaea L.) confer benefits to the human health. OBJECTIVES To review the scientific literature about the benefits of the polyphenols of olive leaves to human health. METHOD Literature review in the LILACS-BIREME, SciELO and MEDLINE databases for publications in English, Portuguese and Spanish with the descriptors "Olea europaea", "olive leaves", "olive leaf", "olive leaves extracts", "olive leaf extracts", "phenolic compounds", "polyphenols", "oleuropein", "chemical composition", and "health". There were identified 92 articles, but only 38 related to the objectives of the study and 9 articles cited in the works were included due to their relevance. RESULTS AND DISCUSSION The phenolic compounds present in olive leaves, especially the oleuropein, are associated to antioxidant, antihypertensive, hypoglycemic, hypocholesterolemic and cardioprotective activity. Furthermore, studies associate the oleuropein to an anti-inflammatory effect in trauma of the bone marrow and as a support in the treatment of obesity.
Marked increase in veno-occlusive disease of the liver associated with methotrexate use for graft-versus-host disease prophylaxis in patients receiving busulfan/cyclophosphamide.

The use of cyclosporine-A/methotrexate (CyA/MTX) for graft-versus-host disease (GVHD) prophylaxis is safe and effective for patients undergoing allogeneic bone marrow transplantation after preparation with cyclophosphamide and total body irradiation. We report 87 patients prepared for allogeneic transplant with busulfan 4 mg/kg/d orally for 4 days, followed by cyclophosphamide 60 mg/kg/d intravenously for 2 days (Bu4Cy2). A marked increase in hepatotoxicity was observed in 20 patients administered CyA/MTX, compared with 67 historical control patients who received CyA/methylprednisolone (CyA/MP) for GVHD prophylaxis with all other treatment and support variables remaining constant. The incidence of hyperbilirubinemia (bilirubin greater than or equal to 2 mg/dL) increased from 48% to 80% (P = .02), and the mean maximal bilirubin increased from 4.67 +/- 7.27 to 8.72 +/- 8.73 mg/dL (P = .04), when CyA/MTX was used in place of CyA/MP for GVHD prophylaxis. In addition, the incidence of veno-occlusive disease (VOD) increased from 18% to 70% (P = .0001), and death caused by VOD increased from 4.5% to 25% (P = .02). Survival was not significantly different for the two groups because of a higher non-VOD death rate in patients receiving CyA/MP for GVHD prophylaxis (P = .77). We suggest caution when using Bu4Cy2 in combination with CyA/MTX for GVHD prophylaxis.
Sequential Versus Continual Purified Urinary FSH/hCG in Men With Idiopathic Hypogonadotropic Hypogonadism.

CONTEXT Gonadotropin therapy using a human chorionic gonadotropin (hCG) and FSH preparation is an effective regimen in inducing masculinization and spermatogenesis in men with idiopathic hypogonadotropic hypogonadism (IHH). However, the high cost of medication and frequent injections affect compliance. OBJECTIVE The aim of this study was to determine the efficacy of sequential use of highly purified urinary FSH (uFSH)/hCG in men with IHH. DESIGN AND SETTING A randomized, open-label, prospective, controlled noninferiority trial with an 18-month follow-up was conducted in 9 tertiary hospitals. PATIENTS AND INTERVENTION A total of 67 Chinese men with IHH were randomly allocated into group A receiving continual uFSH (75 U, 3 times a week) and hCG (2000 U, twice a week) injection and group B receiving sequential uFSH (75 U, 3 times a week every other 3 months) and hCG (2000 U, twice a week) injection. MAIN OUTCOME MEASURE The primary outcome was the proportion of subjects with a sperm concentration of ≥ 1.0 × 10(6)/mL during the 18 months. The efficacy between groups A and B was compared for noninferiority. RESULTS Of the patients, 17/33 (51.5%) receiving continual uFSH/hCG and 19/34 (55.9%) receiving sequential uFSH/hCG achieved sperm concentrations of ≥ 1.0 × 10(6)/mL. The efficacy in the sequential uFSH/hCG group was not inferior to that in the continual uFSH/hCG group (noninferiority, P = .008) by intention-to-treat analysis. CONCLUSIONS The efficacy of the sequential uFSH/hCG regimen is not inferior to that of the continual uFSH/hCG regimen in inducing spermatogenesis and masculinization of patients with IHH.
Lipoprotein(a) is associated with left ventricular systolic dysfunction in a Chinese population of patients with hypertension and without coronary artery disease

Introduction Data on relationship between lipoprotein(a) (Lp(a)) and non-ischemic heart dysfunction are limited. This study is aimed to assess the association between Lp(a) and left ventricular systolic dysfunction in a Chinese population of patients with hypertension and without coronary artery disease (CAD). Material and methods This cross-sectional study included 1611 patients with hypertension and without CAD in China. The factors associated with left ventricular ejection fraction (LVEF) were evaluated using univariate and multivariate analysis. Results A higher percentage of hypertensive patients with LVEF < 50% were men, and had lower plasma high-density lipoprotein cholesterol, but higher plasma Lp(a), serum creatinine, and hemoglobin levels than those with LVEF ≥ 50% using univariate analysis. When participants were classified as four groups according to Lp(a) quartiles, LVEF was decreased with increased Lp(a) levels. The prevalence of LVEF < 50% was increased with Lp(a) quartiles. Multiple linear regression analysis indicated that plasma Lp(a) levels, man, and serum creatinine levels were independently correlated with LVEF in hypertensive patients. Multiple logistic regression analysis indicated that plasma Lp(a) levels (OR = 5.566, 95% CI: 1.745–17.758, p = 0.004) or Lp(a) quartiles (quartile 4: OR = 3.234, 95% CI: 1.290–8.105, quartile 1 as reference, p = 0.012) was independently correlated with LVEF < 50% with adjustment for other potential confounders. Ordinal logistic regression analysis demonstrated that Lp(a) (OR = 5.760, 95% CI: 1.831–18.120, p = 0.003) was independently correlated with different LVEF categories (≥ 50%, 35–49%, and < 35%) in hypertensive patients. Conclusions Left ventricular ejection fraction is decreased with increased plasma Lp(a) levels. Lipoprotein(a) is independently correlated with left ventricular systolic dysfunction in patients with hypertension and without CAD.
Gestion des ressources humaines en production cyclique

Nos travaux de recherche portent sur le probleme de prise en compte des contraintes liees aux ressources humaines, en terme d’affectation des operateurs aux machines, dans les problemes d’ordonnancement d’atelier. Ce probleme integrant l’affectation des operateurs aux machines consiste a determiner l’etat d’atelier au cours du temps, et a considerer le probleme d’ordonnancement d’atelier dans sa globalite en prenant en compte l’influence de l’affectation des ressources humaines sur les activites de production. Ceci impose en plus de la gestion de la sequence des travaux, la gestion des affectations des hommes aux postes de travail. Nous avons considere le cas ou les productivites des machines dependant de l’affectation des operateurs. Nous avons suppose que le nombre d’operateurs est inferieur au nombre de machines, un operateur peut superviser simultanement plusieurs machines et que la supervision simultanee de plusieurs machines par un operateur diminue les productivites de ces dernieres. L’originalite de nos travaux de recherche est liee au fait que les durees operatoires des travaux sont variables dans le temps et sont fonction de l’evolution des affectations des operateurs aux machines dans le temps
Wrist injuries in adolescent gymnasts of a Chinese opera school: radiographic survey.

PURPOSE To determine the prevalence of chronic wrist injuries among adolescent gymnasts and the consequences of repetitive stress. MATERIALS AND METHODS Students of a Chinese opera school underwent radiography of both wrists and answered a questionnaire. They were separated into study (n = 261) and control (n = 63) groups according to participation in or abstinence from exercise training, respectively. They were further separated into fused and unfused physis subgroups. The ulnar variance was measured on posteroanterior radiographs. Abnormalities of distal radii were investigated. RESULTS An increase in both mean ulnar variance and frequency of ulnar-plus variance was noted in the study subgroups. Fourteen (8.2%) of 170 wrists of the fused physis study subgroup had an exceedingly large ulnar-plus variance. Sixty-one (17.3%) of 352 wrists had abnormal morphology of the distal radii in the unfused physis study subgroup. Widening of the physis was the most common finding. CONCLUSION Chronic, repetitive stress in the wrists of adolescent gymnasts results in a localized growth disturbance of the distal radius with resultant ulnar-plus variance. Stress injuries of the physis may lead to permanent sequelae, even in asymptomatic individuals.