Miracle-dz/UniFAR-FTUs huggingface dataset:
High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers.

Pathophysiological parameters such as vascular density and tissue oxygen pressure can influence tumor malignancy and patient survival. Observations from our group showed that metastatic spread of carcinomas of the uterine cervix and of head and neck cancers was closely correlated with the lactate concentration in the primary lesion. Because these results were obtained in a low number of patients, the present investigation was performed to verify such a correlation in a larger population. Cryobiopsies were taken at first diagnosis of cervical cancer from 34 patients. Tissue concentrations of ATP, glucose, and lactate in viable tumor regions of these biopsies were measured microscopically using the technique of imaging bioluminescence. There was no correlation between stage or grade and any of the metabolic parameters measured. ATP and glucose concentrations were not significantly different in metastatic and nonmetastatic primary tumors (P>0.05). However, lactate concentrations were significantly higher (P = 0.001) in tumors with metastatic spread (mean +/- SD, 10.0+/-2.9 micromol/g; n = 20) compared with malignancies in patients without metastases (6.3+/-2.8 micromol/g; n = 14). The majority of patients who suffered a recurrence of the disease (17 of a total of 22 patients) or died (15 of 20) within the observation period of up to 8 years belonged to the metastatic, i.e., high lactate group. A Kaplan-Meier analysis of the data showed that the overall and disease-free survival probabilities of patients having low tumor lactate values were significantly higher compared with patients with high tumor lactate concentrations (P = 0.015 and 0.014, respectively). We conclude that tumor lactate content may be used as a prognostic parameter in the clinic. Furthermore, these findings are in accordance with data from the literature showing that the presence of hypoxia in cervical tumors is associated with a poorer patient survival.
Changes in the left ventricular outflow tract after transcoronary ablation of septal hypertrophy (TASH) for hypertrophic obstructive cardiomyopathy as assessed by transoesophageal echocardiography and by measuring myocardial glucose utilization and perfusion.

AIMS AND METHODS Transcoronary ablation of septal hypertrophy (TASH) leads to marked clinical and haemodynamic improvement in patients with hypertrophic obstructive cardiomyopathy. In order to obtain more detailed information about changes in the outflow tract after TASH, transoesophageal echocardiography and a repeat invasive investigation were conducted before as well as 2 weeks and 6 months after TASH (n=62). In a subset of patients (n=11), metabolism and perfusion of the myocardium ((18)F-FDG-PET and(99m)Tc-MIBI-SPET) were investigated. RESULTS After TASH there was a typical regional subaortic contraction disorder. It was quantified by a significant decrease in the fractional shortening of the left ventricular end-diastolic diameter, which declined from an average of 40.6% to 18.0%. The end-diastolic diameter increased from an average of 39.1 to 40.6 mm. There was also a significant reduction in septal thickness, which continued for up to 6 months after TASH, from an average of 20.0 mm to 11.1 mm in the region of ablation and from 23. 2 to 21.7 mm outside this region. The decrease in the gradient post TASH corresponded with a concomitant significant increase in the outflow tract area from a mean value of 1.04 cm(2)before the process to a value of 3.0 cm(2)after. In contrast to coronary heart disease, these changes were accompanied by non-diffuse, well demarcated subaortic-septal necrosis verified by(18)F-FDG-PET and(99m)Tc-MIBI-SPET. On average the TASH induced necrotic area comprised 6.6% of the left ventricle and correlated significantly with echocardiographic changes in the outflow tract. CONCLUSIONS Alterations post TASH indicated that this catheter interventional treatment for hypertrophic obstructive cardiomyopathy affects the specific region of obstruction. The changes reflect a 'therapeutic remodelling' of the outflow tract of the left ventricle. They were demonstrable over the entire 6 months investigation period and obviously constituted the basis of post TASH clinical and haemodynamic improvement. Progressive alterations post TASH (post TASH reduction of subaortic septal thickness and an increase in the end-diastolic diameter) need special consideration during long-term follow up.
The importance of social sources of cigarettes to school students

Objective: To discover the importance of social sources of tobacco to young people as opposed to commercial sources; to describe the peer market for cigarettes in schools and the consequences for young people of their involvement in it. Study design: Cross sectional questionnaire survey, one-to-one interviews, and focus groups. Setting: Seven schools in Birmingham, UK. Subjects: All students in two randomly selected classes from each school completed the questionnaire, and never smokers, occasional smokers, and regular smokers were interviewed. Results: Two thirds of occasional smokers and one quarter of regular smokers obtained cigarettes socially, mostly for free. A few smokers regularly bought their cigarettes from others. Among friendship groups, both smokers and non-smokers were involved in the exchange of cigarettes, often for money, which is a common activity. A few young people use the selling of cigarettes to fund their own smoking. Some young people, smokers and non-smokers, are involved in semi-commercial selling of cigarettes. All school students are aware of where to purchase cigarettes from non-friends, which is only used “in emergency” because of the high price. One school had a strong punishment policy for students caught with cigarettes. In this school, more people bought singles from the peer market and the price was higher. Conclusions: The passing and selling of cigarettes in school is a common activity, which from the young persons perspective, ensures that all share cross counter purchases. A few people are prepared to use the peer market for monetary gain and it appears to be responsive to external conditions. The peer market might mean that efforts to control illegal sales of cigarettes are not as effective as hoped.
Cysteine-Sparing CADASIL Mutations in NOTCH3 Show Proaggregatory Properties In Vitro

Background and Purpose— Mutations in NOTCH3 cause cerebral autosomal–dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common monogenic cause of stroke and vascular dementia. Misfolding and aggregation of NOTCH3 proteins triggered by cysteine-affecting mutations are considered to be the key disease mechanisms. However, the significance of cysteine-sparing mutations is still debated. Methods— We studied a family with inherited small vessel disease by standardized medical history, clinical examination, MRI, ultrastructural analysis of skin biopsies, and Sanger sequencing of all NOTCH3 exons. In addition, we performed in vitro characterization of NOTCH3 variants using recombinant protein fragments and a single-particle aggregation assay. Results— We identified a novel cysteine-sparing NOTCH3 mutation (D80G) in 4 family members, which was absent in a healthy sibling. All mutation carriers exhibited a CADASIL typical brain imaging and clinical phenotype, whereas skin biopsy showed inconsistent results. In vitro aggregation behavior of the D80G mutant was similar compared with cysteine-affecting mutations. This was reproduced with cysteine-sparing mutations from previously reported families having a phenotype consistent with CADASIL. Conclusions— Our findings support the view that cysteine-sparing mutations, such as D80G, might cause CADASIL with a phenotype largely indistinguishable from cysteine mutations. The in vitro aggregation analysis of atypical NOTCH3 mutations offers novel insights into pathomechanisms and might represent a tool for estimating their clinical significance.
A review of the literature

in this work. This electronic representation of RAND intellectual property is provided for non-commercial use only. Unauthorized posting of RAND PDFs to a non-RAND Web site is prohibited. RAND PDFs are protected under copyright law. Permission is required from RAND to reproduce, or reuse in another form, any of our research documents for commercial use. For information on reprint and linking permissions, please see RAND Permissions. Limited Electronic Distribution Rights This PDF document was made available from www.rand. org as a public service of the RAND Corporation.
Detecting the Sybil Attack in Mobile Ad hoc Networks

Mobility is often a problem for providing security services in ad hoc networks. In this paper, we show that mobility can be used to enhance security. Specifically, we show that nodes that passively monitor traffic in the network can detect a Sybil attacker that uses a number of network identities simultaneously. We show through simulation that this detection can be done by a single node, or that multiple trusted nodes can join to improve the accuracy of detection. We then show that although the detection mechanism will falsely identify groups of nodes traveling together as a Sybil attacker, we can extend the protocol to monitor collisions at the MAC level to differentiate between a single attacker spoofing many addresses and a group of nodes traveling in close proximity
Transposable Elements as Stress Adaptive Capacitors Induce Genomic Instability in Fungal Pathogen Magnaporthe oryzae

A fundamental problem in fungal pathogenesis is to elucidate the evolutionary forces responsible for genomic rearrangements leading to races with fitter genotypes. Understanding the adaptive evolutionary mechanisms requires identification of genomic components and environmental factors reshaping the genome of fungal pathogens to adapt. Herein, Magnaporthe oryzae, a model fungal plant pathogen is used to demonstrate the impact of environmental cues on transposable elements (TE) based genome dynamics. For heat shock and copper stress exposed samples, eight TEs belonging to class I and II family were employed to obtain DNA profiles. Stress induced mutant bands showed a positive correlation with dose/duration of stress and provided evidences of TEs role in stress adaptiveness. Further, we demonstrate that genome dynamics differ for the type/family of TEs upon stress exposition and previous reports of stress induced MAGGY transposition has underestimated the role of TEs in M. oryzae. Here, we identified Pyret, MAGGY, Pot3, MINE, Mg-SINE, Grasshopper and MGLR3 as contributors of high genomic instability in M. oryzae in respective order. Sequencing of mutated bands led to the identification of LTR-retrotransposon sequences within regulatory regions of psuedogenes. DNA transposon Pot3 was identified in the coding regions of chromatin remodelling protein containing tyrosinase copper-binding and PWWP domains. LTR-retrotransposons Pyret and MAGGY are identified as key components responsible for the high genomic instability and perhaps these TEs are utilized by M. oryzae for its acclimatization to adverse environmental conditions. Our results demonstrate how common field stresses change genome dynamics of pathogen and provide perspective to explore the role of TEs in genome adaptability, signalling network and its impact on the virulence of fungal pathogens.
Clock drawing from the occupational therapy adult perceptual screening test: its correlation with demographic and clinical factors in the stroke population.

BACKGROUND/AIM The aim of this study was to explore the relationships between clock drawing ability following stroke, and key clinical variables including cognition, functional independence, side and type of stroke, educational level and age. METHODS One hundred and ninety-seven people with stroke were recruited from 12 hospital and rehabilitation facilities. The participants' scores from the Clock Drawing Test in the Occupational Therapy Adult Perceptual Screening Test were the dependent variables and were entered into logistic regression with Functional Independence Measure motor scores, side of stroke, Oxfordshire Classification System of Stroke, educational level and age as independent variables. Correlation with the Mini-Mental State Examination was analysed independently, due to its strong correlation with other variables. RESULTS The Mini-Mental State Examination correlated significantly with the Clock Drawing Test ( Exp (B) = 0.826, P < 0.001). In the multivariate analysis, a significant relationship was found with age (Exp ( B) = 1.052, P < 0.001), Functional Independence Measure - motor (Exp (B) = 0.984, P = 0.030) and side of stroke (Exp (B) = 0.384, P = 0.003). Age demonstrated the strongest correlation with the Clock Drawing Test ability and the greatest decline was from approximately 70 years of age. CONCLUSIONS The Clock Drawing Test may be a useful and quick screen of cognitive impairments following stroke. Age-related decline must be considered and it is essential that clinicians use this only as a strategy to determine whether a more comprehensive assessment is required.
Effect of DHU001, a Polyherbal Formula, on Dinitrofluorobenzene-induced Contact Dermatitis (Type I allergy)

The effect of DHU001, a mixed herbal formula consisted of 7 types aqueous extracts for various respiratory disorders were evaluated on 2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis, type I allergic model. Contact dermatitis was induced by sensitization with dinitrophenyl-derivatized ovalbumin (DNP-OVA) and DNFB challenge as antigen. Two different dosages of DHU001 (300 and 150 mg/kg) were orally administered to DNP-OVA sensitization mice once a day for 7 days with reference material, dexamethasone (15 mg/kg, intraperitoneal treatment). End of 7 days oral administration of DHU001 extracts or intraperitoneal treatment of dexamethasone, the changes on the edematous changes and scratching behavior were measured. Immediate after DNFB challenge on ear or paw of DNP-OVA sensitized mice, increases of ear and paw thicknesses and weights were detected with anterior ear skin (dermis to epidermis) thickness and paw scratching behavior increases. However, these contact dermatitis signs induced by DNFB treatment were reduced by treatment of the both different dosages of DHU001 and dexamethasone, respectively. The results obtained in this study suggest that oral treatment of DHU001 extracts also has relatively favorable effects on contact dermatitis.
Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

Bone metastases, often a consequence of breast, prostate, and lung carcinomas, are characterized by an increased bone turnover, which can be visualized by positron emission tomography (PET), as well as single-photon emission computed tomography (SPECT). Bisphosphonate complexes of 99mTc are predominantly used as SPECT tracers. In contrast to SPECT, PET offers a higher spatial resolution and, owing to the 68Ge/68Ga generator, an analog to the established 99mTc generator exists. Complexation of Ga(III) requires the use of chelators. Therefore, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), NOTA (1,4,7-triazacyclododecane-1,4,7-triacetic acid), and their derivatives, are often used. The combination of these macrocyclic chelators and bisphosphonates is currently studied worldwide. The use of DOTA offers the possibility of a therapeutic application by complexing the β-emitter 177Lu. This overview describes the possibility of diagnosing bone metastases using [68Ga]Ga-BPAMD (68Ga-labeled (4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid) as well as the successful application of [177Lu]Lu-BPAMD for therapy and the development of new diagnostic and therapeutic tools based on this structure. Improvements concerning both the chelator and the bisphosphonate structure are illustrated providing new 68Ga- and 177Lu-labeled bisphosphonates offering improved pharmacological properties.
Polaronic mass renormalization of impurities in Bose-Einstein condensates: Correlated Gaussian-wave-function approach

We propose a class of variational Gaussian wavefunctions to describe Fr\"ohlich polarons at finite momenta. Our wavefunctions give polaron energies that are in excellent agreement with the existing Monte Carlo results for a broad range of interactions. We calculate the effective mass of polarons and find smooth crossover between weak and intermediate impurity-bosons coupling. Effective masses that we obtain are considerably larger than those predicted by the mean-field method. A novel prediction based on our variational wavefunctions is a special pattern of correlations between host atoms that can be measured in time-of-flight experiments. We discuss atomic mixtures in systems of ultracold atoms in which our results can be tested with current experimental technology.
Development and Function of Myeloid‐Derived Suppressor Cells Generated From Mouse Embryonic and Hematopoietic Stem Cells

Emerging evidence suggests that myeloid‐derived suppressor cells (MDSCs) have great potential as a novel immune intervention modality in the fields of transplantation and autoimmune diseases. Thus far, efforts to develop MDSC‐based therapeutic strategies have been hampered by the lack of a reliable source of MDSCs. Here we show that functional MDSCs can be efficiently generated from mouse embryonic stem (ES) cells and bone marrow hematopoietic stem (HS) cells. In vitro‐derived MDSCs encompass two homogenous subpopulations: CD115+Ly‐6C+ and CD115+Ly‐6C− cells. The CD115+Ly‐6C+ subset is equivalent to the monocytic Gr‐1+CD115+F4/80+ MDSCs found in tumor‐bearing mice. In contrast, the CD115+Ly‐6C− cells, a previously unreported population of MDSCs, resemble the granulocyte/macrophage progenitors developmentally. In vitro, ES‐ and HS‐MDSCs exhibit robust suppression against T‐cell proliferation induced by polyclonal stimuli or alloantigens via multiple mechanisms involving nitric oxide synthase‐mediated NO production and interleukin (IL)‐10. Impressively, they display even stronger suppressive activity and significantly enhance ability to induce CD4+CD25+Foxp3+ regulatory T‐cell development compared with tumor‐derived MDSCs. Furthermore, adoptive transfer of ES‐MDSCs can effectively prevent alloreactive T‐cell‐mediated lethal graft‐versus‐host disease, leading to nearly 82% long‐term survival among treated mice. The successful in vitro generation of MDSCs may represent a critical step toward potential clinical application of MDSCs. STEM CELLS 2010;28:620–632
Microstructural characterisation of double pulse resistance spot welded advanced high strength steel

The effects of single and double pulse resistance spot welding on the microstructures of an advanced high strength automotive steel are presented in this work. The double pulse welding schemes partially remelt the primary weld nugget and anneal the area at the fusion boundary of the nugget. The effects of the annealing treatment on the segregation and the microstructure have been studied by electron probe microanalysis (EPMA) in combination with electron backscatter diffraction (EBSD). Results show that phosphorus has been redistributed at the primary weld nugget edge of the double pulse welds, while the mean block width and ellipticity of the prior austenite grains were smaller in welds subjected to double pulsing compared with single pulse weld. A favourable failure mode was obtained for the double pulse welds although behaviour did not correlate with the measured grain size.
Worst-Case Analysis for Split Delivery Vehicle Routing Problems

In the vehicle routing problem (VRP) the objective is to construct a minimum cost set of routes serving all customers where the demand of each customer is less than or equal to the vehicle capacity and where each customer is visited once. In the split delivery vehicle routing problem (SDVRP) the restriction that each customer is visited once is removed. We show that the cost savings that can be realized by allowing split deliveries is at most 50. We also study the variant of the VRP in which the demand of a customer may be larger than the vehicle capacity, but where each customer has to be visited a minimum number of times. We show that the cost savings that can be realized by allowing more than the minimum number of required visits is again at most 50. Furthermore, we analyze the performance of simple heuristics that handle customers with demands larger than the vehicle capacity by employing full load out-and-back trips to these customers until the demands become less than or equal to the vehicle capacity. Finally, we investigate situations in which demands are discrete and vehicle capacities are small.
Bowel dysfunction in patients with cauda equina lesions

Despite their serious sequels on bowel function, lesions of the cauda equina have not been previously systematically studied in larger patient populations. This was the aim of the present report. From the registrars of a diagnostic and rehabilitation centres 67 patients with clinical, electrodiagnostic and radiological findings supportive of the cauda equina lesions were recruited. The Slovene versions of the standard questionnaires for anal incontinence and constipation were used. The responses were scored, impairments categorized and previous treatments noted. Neurological examination, electromyography (EMG) of lumbo‐sacral myotomes, quantitative anal sphincter EMG and electromyographic evaluation of the sacral reflex were performed. Severe anal incontinence/constipation was reported by 18%/0%, moderate by 36%/33%, and slight by 28%/43% of our patients. Twenty‐one per cent of patients wore pads continuously and 14% occasionally. More than half of the patients (60%) reported changes in their lifestyle due to anal incontinence. No patient had completely normal findings on neurological examination. Perianal sensory loss correlated (P < 0.05) with anal incontinence and gender with constipation (women >men). Only two patients had received medical attention for bowel dysfunction. Study thus demonstrated significant bowel impairment in patients with lesions of the cauda equina, which has received insufficient medical attention.