Miracle-dz/UniFAR-FTUs huggingface dataset:
Lack of influence of human immunodeficiency virus infection status in the response to therapy and survival of adult patients with mature B-cell lymphoma or leukemia. Results of the PETHEMA-LAL3/97 study.

BACKGROUND AND OBJECTIVES Short, intensive multiagent chemotherapy has resulted in significant progress in Burkitt's lymphoma and leukemia. A protocol was designed to treat all adult patients with mature B-cell lymphoma or leukemia with the aims of comparing the response to therapy and survival with regards to their HIV infection status. DESIGN AND METHODS Fifty-three adult patients with advanced stage Burkitt's lymphoma or Burkitt's leukemia were treated. Response to therapy, survival and toxicity were evaluated according to their HIV infection status. RESULTS The median age of the patients was 53 years (range 15-74). There were no differences in CR rates between HIV-negative (77%) and HIV-positive patients (71%). Only age > 60 years was associated with a lower CR rate (OR 0.18, 95%CI 0.04-0.81, p=0.026). The 2-year overall survival (OS) probability was 51% (95%CI, 38%-64%) for the 53 patients. The OS of HIV-negative and HIV-positive patients did not significantly differ. Only age > 60 years was associated with a shorter OS (OR 5.1, 95%CI 2.0-12.7, p=0.001). The 2-year disease free survival (DFS) for the 40 patients achieving CR was 60% (95%CI, 45%-75%). Age > 60 years was the only identified factor associated with a shorter DFS (OR 5.2, 95%CI 1.4-20, p=0.015). INTERPRETATION AND CONCLUSIONS This study confirms the effectiveness of intensive strategies in adult patients with advanced stage Burkitt's lymphoma or leukemia. It also shows the feasibility of these strategies in individuals with HIV infection with comparable results. Advanced age proved to be the main adverse prognostic factor for response to therapy and survival.
Structural determinant of TRPV1 desensitization interacts with calmodulin

The capsaicin receptor, TRPV1 (VR1), is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. Extracellular Ca2+-dependent desensitization of TRPV1 observed in patch–clamp experiments when using both heterologous expression systems and native sensory ganglia is thought to be one mechanism underlying the paradoxical effectiveness of capsaicin as an analgesic therapy. Here, we show that the Ca2+-binding protein calmodulin binds to a 35-aa segment in the C terminus of TRPV1, and that disruption of the calmodulin-binding segment prevents TRPV1 desensitization. Compounds that interfere with the 35-aa segment could therefore prove useful in the treatment of pain.
Ageing does not influence the sleep-related decrease in the hypercapnic ventilatory response

In young people, a sleep-related reduction in the gain of the ventilatory chemoreflex feedback loop occurs; in the elderly, it has been reported that no sleep-related reduction occurs. A relatively high loop gain could contribute to periodic breathing and central sleep apnoea in the elderly. This study tested the hypothesis that ageing is associated with a reduction in the magnitude of the sleep-related decrease in the hypercapnic ventilatory response (HCVR). The HCVR was measured using a steady state method, awake and asleep, in groups (n=10) of elderly (66–81 yrs) and young (23–35 yrs) nonapnoeics. Upper airway resistance was maintained close to wakefulness levels using continuous positive airway pressure (mean sleep-related increase in resistance: elderly 1.6±1.2 cmH2O·L·s−1, young 1.2±0.8 cmH2O·L·s−1). The sleep-related decrease in the HCVR was similar in the elderly and young groups (elderly: wake 0.14±0.06 and sleep 0.06±0.02 L·min−1·kPa and young, wake 0.19±0.07 and sleep 0.10±0.04 L·min−1·kPa). Ageing per se was shown not to change the magnitude of the sleep-related decrease in hypercapnic ventilatory response. The authors speculate that age-related changes in the hypercapnic ventilatory response are unlikely to contribute to the increased prevalence of central sleep apnoea in the elderly.
Rheology of Leukocytes a

The rheological properties of human leukocytes (WBCs) have been studied by micropipette aspiration and filtration tests. A small aspiration pressure applied via a micropipette (diameter approximately equal to 3 micron) causes the WBC to undergo a rapid elastic deformation followed by a slow creep. The data can be analyzed with a viscoelastic model: an elastic element K1 in parallel with a Maxwell element (elastic element K2 in series with viscous element mu). Neutrophils and B lymphocytes are similar in K1, K2, and mu, but these values are higher for T lymphocytes. Treatment of neutrophils with colchicine decreases K2 and mu without changing K1, whereas cytochalasin B decreases all three coefficients; these results indicate the importance of cytoskeletal microtubules and microfilaments in WBC rheology. In the presence of Ca2+, WBCs form protopods which have increased viscoelastic coefficients. Inhibition of protopod formation with pentoxifylline is associated with an increase in WBC deformability. The ruffled surface of the apparently round WBC provides an area about twice that needed to enclose a smooth sphere of the same volume; this geometric feature plays an important role in whole WBC deformability tested through 4-5 micron filter pores or micropipettes. Because of its larger volume and higher cellular viscosity, each WBC is equivalent to approximately 700 erythrocytes in its tendency to block 5-micron channels. The rheology of WBCs has significant implications in their functional behavior, including flow through the microcirculation and interaction with endothelial cells.
Functional CD8+ T Cell Responses in Lethal Ebola Virus Infection1

Ebola virus (EBOV) causes highly lethal hemorrhagic fever that leads to death in up to 90% of infected humans. Like many other infections, EBOV induces massive lymphocyte apoptosis, which is thought to prevent the development of a functional adaptive immune response. In a lethal mouse model of EBOV infection, we show that there is an increase in expression of the activation/maturation marker CD44 in CD4+ and CD8+ T cells late in infection, preceding a dramatic rebound of lymphocyte numbers in the blood. Furthermore, we observed both lymphoblasts and apoptotic lymphocytes in spleen late in infection, suggesting that there is lymphocyte activation despite substantial bystander apoptosis. To test whether these activated lymphocytes were functional, we performed adoptive transfer studies. Whole splenocytes from moribund day 7 EBOV-infected animals protected naive animals from EBOV, but not Marburgvirus, challenge. In addition, we observed EBOV-specific CD8+ T cell IFN-γ responses in moribund day 7 EBOV-infected mice, and adoptive transfer of CD8+ T cells alone from day 7 mice could confer protection to EBOV-challenged naive mice. Furthermore, CD8+ cells from day 7, but not day 0, mice proliferated after transfer to infected recipients. Therefore, despite significant lymphocyte apoptosis, a functional and specific, albeit insufficient, adaptive immune response is made in lethal EBOV infection and is protective upon transfer to naive infected recipients. These findings should cause a change in the current view of the ‘impaired’ immune response to EBOV challenge and may help spark new therapeutic strategies to control lethal filovirus disease.
CISR-ODE, A C++ Framework with ODE Solver for Code Based System Dynamics Simulation

Ordinary differential equations are used for modelling a wide range of dynamic systems. Even though there are many graphical software applications for this purpose, a fully customised solution for all problems is code-level programming of the model and solver. In this project, a free and open source C++ framework is designed to facilitate modelling in native code environment and fulfill the common simulation needs of control and many other engineering and science applications. The solvers of this project are obtained from ODEINT and specialised for Armadillo matrix library to provide an easy syntax and a fast execution. The solver code is minimised and its modification for users have become easier. There are several features added to the solvers such as controlling maximum step size, informing the solver about sudden input change and forcing custom times into the results and calling a custom method at these points. The comfort of the model designer, code readability, extendibility and model isolation have been considered in the structure of this framework. The application manages the output results, exporting and plotting them. Modifying the model has become more practical and a portion of corresponding codes are updated automatically. A set of libraries is provided for generation of output figures, matrix hashing, control system functions, profiling, etc. In this paper, an example of using this framework for a classical washout filter model is explained.
Combined parasitic and phased array reconfigurable antenna

This paper presents the development of a novel phased array antenna which is integrated with a series of parasitics to improve the beam steering resolution of the array. The array is based on a circular microstrip element. With the use of the parasitics, a steering range of ±15° is achieved for a specific phased array direction. This introduces a dual means of beam steering, namely wide angle steering using the phased array approach and fine angle steering using parasitics.
Telomere length, oxidative damage, antioxidants and breast cancer risk

Telomeres play a critical role in maintaining the integrity and stability of the genome, and are susceptible to oxidative damage after telomere shortening to a critical length. In the present study, we explored the role of white blood cell DNA telomere length on breast cancer risk, and examined whether urinary 15‐F2‐isoprostanes (15‐F2t‐IsoP) and 8‐oxo‐7,8‐dihydrodeoxyguanosine (8‐oxodG) or dietary antioxidant intake modified the relationship between telomere length and breast cancer risk. A population‐based case–control study—the Long Island Breast Cancer Study Project—was conducted among 1,067 cases and 1,110 controls. Telomere length was assessed by quantitative PCR. Overall, the mean levels of telomere length (T/S ratio), 15‐F2t‐IsoP and 8‐oxodG were not significantly different between cases and controls. Among premenopausal women only, carrying shorter telomeres (Q3 and Q4), as compared with the longest (Q1), was associated with significantly increased breast cancer risk. Age‐adjusted OR and 95% CI were 1.71 (1.10–2.67) and 1.61 (1.05–2.45). The 5‐F2t‐IsoP and 8‐oxodG biomarkers did not modify the telomere–breast cancer association. A moderate increase in breast cancer risk was observed among women with the shortest telomeres (Q4) and lower dietary and supplemental intake of β‐carotene, vitamin C or E intake [OR (95% CI) = 1.48 (1.08–2.03), 1.39 (1.01–1.92) and 1.57 (1.14–2.18), respectively], although the trend test exhibited statistical significance only within the lower vitamin E intake subgroup (ptrend = 0.01). These results provided the strongest evidence to date that breast cancer risk may be affected by telomere length among premenopausal women or women with low dietary intake of antioxidants or antioxidant supplements. © 2008 Wiley‐Liss, Inc.
GSK2374697, a long duration glucagon‐like peptide‐1 (GLP‐1) receptor agonist, reduces postprandial circulating endogenous total GLP‐1 and peptide YY in healthy subjects

We investigated the effects of a long‐duration glucagon‐like peptide‐1 (GLP‐1) receptor agonist, GSK2374697, on postprandial endogenous total GLP‐1 and peptide YY (PYY). Two cohorts of healthy subjects, one normal/overweight and one obese, were randomized to receive GSK2374697 2 mg (n = 8 each) or placebo (n = 4 and n = 2) subcutaneously on days 1, 4 and 7. Samples for plasma endogenous GLP‐1 and PYY were collected after breakfast on days −1 and 12. Weighted mean area under the curve (0–4 h) of total GLP‐1 and PYY in treated subjects was reduced compared with placebo. The least squares mean difference for change from baseline was −1.24 pmol/l [95% confidence interval (CI) −2.33, −0.16] and −4.47 pmol/l (95% CI −8.74, −0.20) for total GLP‐1 and PYY, respectively, in normal/overweight subjects (p < 0.05 for both), and −1.56 (95% CI −2.95, −0.16) and −3.02 (95% CI −8.58, 2.55), respectively, in obese subjects (p < 0.05 for GLP‐1). In healthy subjects, GSK2374697 reduced postprandial total GLP‐1 and PYY levels, suggesting feedback suppression of enteroendocrine L‐cell secretion of these peptides.
In Vivo Evaluation of the Potential of High-Frequency Ultrasound for Arthroscopic Examination of the Shoulder Joint

Objective Accurate arthroscopic evaluation of cartilage lesions could significantly improve the outcome of repair surgery. In this study, we investigated for the first time the potential of intra-articular ultrasound as an arthroscopic tool for grading cartilage defects in the human shoulder joint in vivo and compared the outcome to results from arthroscopic evaluation and magnetic resonance imaging findings. Design A total of 26 sites from 9 patients undergoing routine shoulder arthroscopy were quantitatively evaluated with a clinical intravascular (40MHz) ultrasound imaging system, using the regular arthroscopy portals. Reflection coefficient (R), integrated reflection coefficient (IRC), apparent integrated backscattering (AIB), and ultrasound roughness index (URI) were calculated, and high-resolution ultrasound images were obtained per site. Each site was visually graded according to the International Cartilage Repair Society (ICRS) system. “Ultrasound scores” corresponding to the ICRS system were determined from the ultrasound images. Magnetic resonance imaging was conducted and cartilage integrity at each site was classified into 5 grades (0 = normal, 4 = severely abnormal) by a radiologist. Results R and IRC were lower at sites with damaged cartilage surface (P = 0.033 and P = 0.043, respectively) and correlated with arthroscopic ICRS grades (rs = −0.444, P = 0.023 and rs = −0.426, P = 0.03, respectively). Arthroscopic ICRS grades and ultrasound scores were significantly correlated (rs = 0.472, P = 0.015), but no significant correlation was found between magnetic resonance imaging data and other parameters. Conclusion The results suggest that ultrasound arthroscopy could facilitate quantitative clinical appraisal of articular cartilage integrity in the shoulder joint and provide information on cartilage lesion depth and severity for quantitative diagnostics in surgery.
Health, wellbeing and community involvement of older people in rural Scotland

Involvement in community activities offers a route to achieving one of the five “essential elements” of older people’s wellbeing as identified by McCormick et. al., (2009) – that of “having a role”, i.e. having a sense of purpose, belonging and value within society. This suggests that older people living within remote and rural communities would derive wellbeing benefits from participation in informal helping and volunteering. This chapter uses information from the European Union-funded O4O: Older People for Older People initiative, conducted from 2007-2010, which considered dimensions of older people’s participation in remote, rural communities with the goal of encouraging and studying how older people could help other older people stay living in their own homes and communities for longer. The chapter presents quantitative evidence from a survey of people aged 55 and over in four remote Scottish communities on the relationship between socio-economic characteristics and participation in community activities. Further insights are brought from the analysis of interviews conducted with older people living within the four communities. By taking these communities as case studies, the chapter is able to comment on the relationship between participation and older people’s wellbeing within the rural context.
Fibrinolytic and hemostatic parameter response after resistance exercise.

These experiments were designed to study the effect of resistance exercise on parameters pertinent to the hemostatic and fibrinolytic systems. Seven normal healthy subjects (6 male, 1 female, 25 +/- 3 yr mean SD) were studied under three conditions: control (C) [no exercise], high volume resistance exercise (HVRE), and low volume resistance exercise (LVRE), which were randomized for each subject, with 7 d separating tests. Both HVRE and LVRE trials encompassed the performance of five sets of nine exercises. After establishing one repetition maximum (1 RM), the HVRE involved the performance of moderate resistance, higher repetition, and shorter resting periods, whereas LVRE involved the use of high resistance, lower repetition, and longer resting intervals. Heart rate (HR) was monitored at rest and continuously during trials and venous blood was removed with minimum stasis, before and immediately after HVRE, LVRE, and before and after 38 min of supine rest (C). The blood was enzymatically analyzed for lactic acid (LA) and assayed using chromogenic substrates for the determination of tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), and Factor VIII (FVIII) activities. Global fibrinolysis (GF) was also screened in the fibrin plate and hematocrit ratios were employed to calculate percent plasma volume changes. Values were corrected for changes in plasma volume then data were analyzed using repeated measures ANOVA. There were no significant (P > 0.05) changes in the parameters measured in the resting condition over the three testing occasions and no significant differences (P > 0.05) were observed during the control experiment. (ABSTRACT TRUNCATED AT 250 WORDS)
Increased serum hepatitis C virus RNA levels among alcoholic patients with chronic hepatitis C

Hepatitis viruses and alcohol are major causes of liver disease. This study was aimed at investigating the effect of alcohol intake on the replication of hepatitis C virus and the efficacy of interferon therapy. Fiftythree patients who were histologically proved to have chronic hepatitis C were tested. Of these, 16 were diagnosed as habitual drinkers whose cumulative total consumption of alcohol was more than 100 kg or who had consumed at least 60 gm of ethanol daily for at least 5 yr. The quantities of hepatitis C virus RNA in serum were measured with a competitive assay that combined reverse transcription and polymerase chain reaction. The subjects received a 26‐wk course of interferon‐α therapy. There were no significant differences in age and ALT levels between habitual drinkers and nonhabitual drinkers. The titer of viral RNA (logarithmic transformed copy numbers per milliliter of serum) of habitual drinkers (8.5 ± 0.5) was higher than that of nonhabitual drinkers (7.7 ± 0.8) (p < 0.01). Neopterin levels in serum, a marker for the activation of cellmediated immunity, were lower for habitual drinkers (5.7 ± 1.5 pmol/ml) than for nonhabitual drinkers (8.1 ± 5.0 pmol/ml) (p < 0.01). Eleven of the nonhabitual drinkers (30%) were long‐term responders whose alanine aminotransferase levels remained within normal range during the 24 wk after interferon therapy, whereas only one (6%) of the habitual drinkers was a long‐term responder (p = 0.06). These findings suggest that alcohol intake increases hepatitis C virus RNA levels in serum—at least in part—impairment of cellular immunity, and modulates the efficacy of interferon therapy. (Hepatology 1994;20:1115–1120).
Aquaglyceroporins serve as metabolic gateways in adiposity and insulin resistance control

Aquaglyceroporins (AQP3, AQP7, AQP9 and AQP10) encompass a subfamily of aquaporins that allow the movement of water and other small solutes, especially glycerol, through cell membranes. Adipose tissue constitutes a major source of glycerol via AQP7. We have recently reported that, in addition to the well-known expression of AQP7 in adipose tissue, AQP3 and AQP9 are also expressed in omental and subcutaneous fat depots. Moreover, insulin and leptin act as regulators of aquaglyceroporins through the PI3K/Akt/mTOR pathway. AQP3 and AQP7 appear to facilitate glycerol efflux from adipose tissue while reducing the glycerol influx into hepatocytes via AQP9 to prevent the excessive lipid accumulation and the subsequent aggravation of hyperglycemia in human obesity. This Extra View focuses on the control of glycerol release by aquaglyceroporins in the adipose tissue and briefly discusses the importance of glycerol as a substrate for hepatic gluconeogenesis, pancreatic insulin secretion and cardiac ATP production.
Association between Loss-of-Function Mutations in the Filaggrin Gene and Self-Reported Food Allergy and Alcohol Sensitivity

Background: Loss-of-function mutations of the filaggrin (FLG) gene cause an impaired skin barrier and increase the risk of atopic dermatitis. Interestingly, FLG mutations have also been found to be associated with a high risk of peanut allergy. Objective: We investigated the association of FLG mutations with self-reported food allergy, symptoms of oral allergy syndrome (OAS), and alcohol sensitivity. Methods: A total of 3,471 adults from the general population participated in a health examination. Information on food allergies, OAS and alcohol sensitivity was obtained by questionnaire. FLG mutation carriers were defined as having at least one null mutation allele of R501X or 2282del4. Primary lactose intolerance (PLI) was defined as the C/C genotype of the rs4988235 polymorphism. Results: FLG mutations were associated with a higher risk of self-reported allergy to eggs (OR 3.22 and 95% CI 1.46-7.11), milk (OR 2.10 and 95% CI 1.12-3.92), fish (OR 4.54 and 95% CI 1.88-10.96) and wheat (OR 3.59 and 95% CI 1.61-8.02), but not with symptoms of OAS (OR 1.05 and 95% CI 0.73-1.51). Serum-specific IgE was measured in a subsample and confirmed the association between FLG and IgE to milk. A significant gene-by-gene interaction between FLG and PLI was observed in relation to self-reported allergy to milk. Furthermore, FLG mutations were associated with a higher risk of alcohol sensitivity. Conclusions: We found that loss-of-function mutations in the FLG gene were significantly associated with self-reported food allergy and alcohol sensitivity, but not with OAS. These findings, if confirmed, support the idea that skin barrier functions may be involved in the pathogenesis of food allergy.
Uracil Salvage Pathway in Lactobacillus plantarum: Transcription and Genetic Studies

ABSTRACT The uracil salvage pathway in Lactobacillus plantarum was demonstrated to be dependent on the upp-pyrP gene cluster. PyrP was the only high-affinity uracil transporter since a pyrP mutant no longer incorporated low concentrations of radioactively labeled uracil and had increased resistance to the toxic uracil analogue 5-fluorouracil. The upp gene encoded a uracil phosphoribosyltransferase (UPRT) enzyme catalyzing the conversion of uracil and 5-phosphoribosyl-α-1-pyrophosphate to UMP and pyrophosphate. Analysis of mutants revealed that UPRT is a major cell supplier of UMP synthesized from uracil provided by preformed nucleic acid degradation. In a mutant selection study, seven independent upp mutants were isolated and all were found to excrete low amounts of pyrimidines to the growth medium. Pyrimidine-dependent transcription regulation of the biosynthetic pyrimidine pyrR1-B-C-Aa1-Ab1-D-F-E operon was impaired in the upp mutants. Despite the fact that upp and pyrP are positioned next to each other on the chromosome, they are not cotranscribed. Whereas pyrP is expressed as a monocistronic message, the upp gene is part of the lp_2376-glyA-upp operon. The lp_2376 gene encodes a putative protein that belongs to the conserved protein family of translation modulators such as Sua5, YciO, and YrdC. The glyA gene encodes a putative hydroxymethyltransferase involved in C1 unit charging of tetrahydrofolate, which is required in the biosynthesis of thymidylate, pantothenate, and purines. Unlike upp transcription, pyrP transcription is regulated by exogenous pyrimidine availability, most likely by the same mechanism of transcription attenuation as that of the pyr operon.