Miracle-dz/UniFAR-FTUs huggingface dataset:
[Value of individualized rehabilitation at the ventilatory threshold level in moderately severe chronic obstructive pulmonary disease].

In order to study the efficiency of individual training programs at the ventilatory threshold level, twenty COPD patients were randomized into two groups and studied over a two-month period. At the start, during, and at the end of the study all subjects performed incremental exercise tests. The trained group (59.60 SEM +/- 2.75 years) walked four times a week at the heart rate corresponding to the metabolic level of ventilatory threshold. The other group served as controls (58.2 +/- 1.80 years). A marked increase in the symptom-limited oxygen consumption (+/- 25%) (p < 0.01), the maximal ventilation (+20%) (p < 0.01), and the ventilatory threshold (+19%) (p < 0.05) was found in the trained group. No modification was recorded in the control group. The ventilatory pattern at submaximal intensities expressed in percentage of the initial oxygen consumption showed significant differences between groups, the trained-group ventilation decreased at 50% and 75% VO2 sl (p < 0.05). The breathing frequency also decreased at 50% and 75% VO2 sl (p > 0.05). Moreover, we observed an increase in the oxygen pulse at 50% VO2 sl (p < 0.05). In conclusion, this study demonstrates that individualized training at the ventilatory threshold level increases exercise tolerance and produces better ventilatory comfort in COPD patients.
Protective Role of the Capsule and Impact of Serotype 4 Switching on Streptococcus mitis

ABSTRACT The polysaccharide capsule surrounding Streptococcus pneumoniae is essential for virulence. Recently, Streptococcus mitis, a human commensal and a close relative of S. pneumoniae, was also shown to have a capsule. In this study, the S. mitis type strain switched capsule by acquisition of the serotype 4 capsule locus of S. pneumoniae TIGR4, following induction of competence for natural transformation. Comparison of the wild type with the capsule-switching mutant and with a capsule deletion mutant showed that the capsule protected S. mitis against phagocytosis by RAW 264.7 macrophages. This effect was enhanced in the S. mitis strain expressing the S. pneumoniae capsule, which showed, in addition, increased resistance against early clearance in a mouse model of lung infection. Expression of both capsules also favored survival in human blood, and the effect was again more pronounced for the capsule-switching mutant. S. mitis survival in horse blood or in a mouse model of bacteremia was not significantly different between the wild type and the mutant strains. In all models, S. pneumoniae TIGR4 showed higher rates of survival than the S. mitis type strain or the capsule-switching mutant, except in the lung model, in which significant differences between S. pneumoniae TIGR4 and the capsule-switching mutant were not observed. Thus, we identified conditions that showed a protective function for the capsule in S. mitis. Under such conditions, S. mitis resistance to clearance could be enhanced by capsule switching to serotype 4, but it was enhanced to levels lower than those for the virulent strain S. pneumoniae TIGR4.
Identification of a panel of ten cell surface protein antigens associated with immunotargeting of leukemias and lymphomas by peripheral blood γδ T cells

Background Vγ9Vδ2 T lymphocytes are regarded as promising mediators of cancer immunotherapy due to their capacity to eliminate multiple experimental tumors, particularly within those of hematopoietic origin. However, Vγ9Vδ2 T-cell based lymphoma clinical trials have suffered from the lack of biomarkers that can be used as prognostic of therapeutic success. Design and Methods We have conducted a comprehensive study of gene expression in acute lymphoblastic leukemias and non-Hodgkin’s lymphomas, aimed at identifying markers of susceptibility versus resistance to Vγ9Vδ2 T cell-mediated cytotoxicity. We employed cDNA microarrays and quantitative real-time PCR to screen 20 leukemia and lymphoma cell lines, and 23 primary hematopoietic tumor samples. These data were analyzed using state-of-the-art bioinformatics, and gene expression patterns were correlated with susceptibility to Vγ9Vδ2 T cell mediated cytolysis in vitro. Results We identified a panel of 10 genes encoding cell surface proteins that were statistically differentially expressed between “γδ-susceptible” and “γδ-resistant” hematopoietic tumors. Within this panel, 3 genes (ULBP1, TFR2 and IFITM1) were associated with increased susceptibility to Vγ9Vδ2 T-cell cytotoxicity, whereas the other 7 (CLEC2D, NRP2, SELL, PKD2, KCNK12, ITGA6 and SLAMF1) were enriched in resistant tumors. Furthermore, some of these candidates displayed a striking variance of expression among primary follicular lymphomas and T-cell acute lymphoblastic leukemias. Conclusions Our results suggest that hematopoietic tumors display a highly variable repertoire of surface proteins that can impact on Vγ9Vδ2 cell-mediated immunotargeting. The prognostic value of the proposed markers can now be evaluated in upcoming Vγ9Vδ2 T cell-based lymphoma/leukemia clinical trials.
Evaluation on lung cancer patients’ adaptive planning of TomoTherapy utilising radiobiological measures and Planned Adaptive module

Abstract Adaptive radiation therapy is a promising concept that allows individualised, dynamic treatment planning based on feedback of measurements. The TomoTherapy Planned Adaptive application, integrated to the helical TomoTherapy planning system, enables calculation of actual dose delivered to the patient for each treatment fraction according to the pretreatment megavoltage computed tomography (MVCT) scan and image registration. As a result, new fractionation treatment plans are available if correction is necessary. In order to evaluate the real clinical effect, biological dose is preferred to physical dose. A biological parameter, biologically effective uniform dose ($\overline{\overline D}$), has the advantages of not only reporting delivered dose but also facilitating the analysis of dose–response relations, which link radiation dose to the clinical effect. Therefore, in this study, four lung patients’ adaptive plans were evaluated using the $\overline{\overline D}$ in addition to physical doses estimated from the TomoTherapy Planned Adaptive module. Higher complication-free tumour control probability (P+) (of about 8%) was observed in patients treated with larger dose-per-fraction by using the $\overline{\overline D}$ in addition to the physical dose. Moreover, a significant increase of 13.2% in the P+ for the adaptive TomoTherapy plan in one of the lung cancer patients was also observed, which indicates the clinical benefit of adaptive TomoTherapy.
The Effect of Increasing Consumption of Pulses and Wholegrains in Obese People: A Randomized Controlled Trial

Background: Wholegrain intake is inversely related to weight gain over time, but little information is available on the role of pulses in weight control. Objective: To compare weight loss, metabolic outcomes, and nutrient intakes in obese people assigned to a diet rich in pulses and wholegrains or a control diet. Methods: Randomized controlled study of 18 months with 113 volunteers (body mass index [BMI] ≥ 28 kg/m2). Diets were based on guidelines published by the National Heart Foundation of New Zealand. The intervention group was advised to consume 2 serves of pulses and 4 serves of wholegrain foods per day as substitutions for more refined carbohydrates. Results: Fiber intakes were higher, intakes of several vitamins and minerals were better maintained, and dietary glycemic index was lower in the intervention compared with the control group. Mean (standard error [SE]) weight loss at 6 months was 6.0 (0.7) kg and 6.3 (0.6) kg in the control and intervention groups, respectively, and was not different between groups (p > 0.05). Blood pressure, triglycerides, and glycemic load were lowered in both groups compared with baseline. Waist circumference was decreased at 18 months in the intervention compared with the control group (−2.8 cm; 95% confidence interval [CI]: −0.4, −5.1). Conclusions: Incorporation of pulses and wholegrain foods into a weight loss program resulted in a greater reduction in waist circumference compared with the group consuming a control diet, although no difference in weight loss was noted between groups. Retention of several nutrients was better with the pulse and wholegrain diet.
Ontogeny of tyrosine hydroxylase mRNA expression in mid‐ and forebrain: Neuromeric pattern and novel positive regions

Tyrosine hydroxylase (TH) is the rate‐limiting enzyme in the synthesis of catecholamines and, thus, critical in determining the catecholaminergic phenotype. In this study, we have examined the expression of TH mRNA by in situ hybridization in the embryonic mouse forebrain and midbrain and have mapped its localization according to the neuromeric pattern. We find that early in embryonic development, 10 to 12 days post coitum (dpc), TH mRNA is expressed in ample continuous regions of the neuroepithelium, extending across several neuromeres. However, from 12.5 dpc onward, the expression becomes restricted to discrete regions, which correspond to the dopaminergic nuclei (A8 to A15). In addition to these nuclei previously described, TH mRNA is also observed in regions that do not express this enzyme according to immunohistochemical studies. This difference in relation to protein expression pattern is consequent with the known posttranscriptional regulation of TH expression. The most representative example of a novel positive region is the conspicuous mRNA expression in both medial and lateral ganglionic eminences. This result agrees with reports describing the capacity of striatal stem cells (that is, located at the lateral ganglionic eminence) to become dopaminergic in vitro. Other regions include the isthmic mantle layer and the early floor plate of the midbrain–caudal forebrain. On the whole, the expression map we have obtained opens new perspectives for evolutionary/comparative studies, as well as for therapeutic approaches looking for potentially dopaminergic cells. Developmental Dynamics 234:709–717, 2005. © 2005 Wiley‐Liss, Inc.
Impact of hepatitis C on health related quality of life: A systematic review and quantitative assessment

Hepatitis C virus (HCV) diminishes health related quality of life (HRQOL), and it is now common to measure HRQOL in clinical trials. We sought to summarize the HRQOL data in HCV, and to establish the minimally clinically important difference (MCID) in HRQOL scores in HCV. We performed a systematic review to identify relevant studies, and converted HRQOL data from each study into clinically interpretable statistics. An expert panel used a modified Delphi technique to estimate the MCID in HCV. We found that patients with HCV scored lower than controls across all scales of the SF‐36. Patients achieving sustained virological response (SVR) scored higher across all scales versus patients without SVR, especially in the physical health domains. HRQOL differences did not correspond with differences in liver histology or ALT levels. Based upon the published data, the expert panel concluded that the SF‐36 vitality scale was most relevant in patients with HCV, and generated a mean MCID of 4.2 points on this scale. In conclusion, patients with HCV have a clinically significant decrement in HRQOL versus controls, and physical HRQOL improves in patients achieving SVR but not in those without SVR. The data further suggest that traditional outcomes fail to capture the full spectrum of illness related to chronic HCV. A difference of 4.2 points on the SF‐36 vitality scale can be used as an estimate of the MCID in HCV, and this value may be used as the basis for power calculations in clinical trials evaluating HRQOL. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270‐9139/suppmat/index.html). (HEPATOLOGY 2005;41:790–800.)
Inactivation of the SecA2 protein export pathway in Listeria monocytogenes promotes cell aggregation, impacts biofilm architecture and induces biofilm formation in environmental condition.

Listeria monocytogenes has a dichotomous lifestyle, existing as an ubiquitous saprophytic species and as an opportunistic intracellular pathogen. Besides its capacity to grow in a wide range of environmental and stressful conditions, L. monocytogenes has the ability to adhere to and colonize surfaces. Morphotype variation to elongated cells forming rough colonies has been reported for different clinical and environmental isolates, including biofilms. This cell differentiation is mainly attributed to the reduced secretion of two SecA2-dependent cell-wall hydrolases, CwhA and MurA. SecA2 is a non-essential SecA paralogue forming an alternative translocase with the primary Sec translocon. Following investigation at temperatures relevant to its ecological niches, i.e. infection (37°C) and environmental (20°C) conditions, inactivation of this SecA2-only protein export pathway led, despite reduced adhesion, to the formation of filamentous biofilm with aerial structures. Compared to the wild type strain, inactivation of the SecA2 pathway promoted extensive cell aggregation and sedimentation. At ambient temperature, this effect was combined with the abrogation of cell motility resulting in elongated sedimented cells, which got knotted and entangled together in the course of filamentous-biofilm development. Such a cell differentiation provides a decisive advantage for listerial surface colonization under environmental condition. As further discussed, this morphotypic conversion has strong implication on listerial physiology and is also of potential significance for asymptomatic human/animal carriage.
B-Mode ultrasonography of the paranasal sinuses compared with CT findings

Ultrasound as a diagnostic aid In the evaluation of the sinuses has been a controversial Issue. Sensitivities have been reported from 29% to 100% and specificities from 55% to 99%. These wide variations in results from previous studies may have resulted from technical differences. However, the “gold standard” most often used for comparison has been a Water's view radiograph, which has been shown to correlate poorly with intraoperative and CT scan findings. To our knowledge, no one In the English language literature has evaluated sonography of the sinuses with computed tomography as the gold standard. In addition, evaluation of the ethmoid sinus has been neglected by previous studies that have primarily assessed the maxillary sinus. We report the results of a blinded, prospective trial comprised of 41 patients examined by B-mode ultrasound with comparison to computed tomography. Frontal and maxillary sinuses were examined with traditional sonographic techniques and the ethmoid sinuses were scanned with a transglobe technique not previously evaluated in the English language literature. Excluding Isolated mucous retention cysts and focal minimal mucosal thickening (defined as <4 mm), sensitivities for ultrasound of the maxillary, frontal, and ethmoid sinuses were 100% each. Specificities were 98% for the maxillary sinus, 100% for the frontal sinus, and 94% for the ethmoid sinus. Technical aspects and implications of this and previous reports will be discussed.
The Impact of Visibility on Teamwork, Collaborative Communication, and Security in Emergency Departments: An Exploratory Study

The aim of this study was to examine the influence of visibility on teamwork, collaborative communication, and security issues in emergency departments (EDs). This research explored whether with high visibility in EDs, teamwork and collaborative communication can be improved while the security issues will be reduced. Visibility has been regarded as a critical design consideration and can be directly and considerably impacted by ED’s physical design. Teamwork is one of the major related operational outcomes of visibility and involves nurses, support staff, and physicians. The collaborative communication in an ED is another important factor in the process of care delivery and affects efficiency and safety. Furthermore, security is a behavioral factor in ED designs, which includes all types of safety including staff safety, patient safety, and the safety of visitors and family members. This qualitative study investigated the impact of visibility on teamwork, collaborative communication, and security issues in the ED. One-on-one interviews and on-site observation sessions were conducted in a community hospital. Corresponding data analysis was implemented by using computer plan analysis, observation and interview content, and theme analyses. The findings of this exploratory study provided a framework to identify visibility as an influential factor in ED design. High levels of visibility impact productivity and efficiency of teamwork and communication and improve the chance of lowering security issues. The findings of this study also contribute to the general body of knowledge about the effect of physical design on teamwork, collaborative communication, and security.
A measurement-based simulation model of a web cluster representing system and application level dynamics

We present a simulation model of a Web cluster which includes important aspects of the hardware, operating and communication systems as well as the application layer for realistic performance evaluations. We formulate the model in UML taking into account both architectural and behavioral aspects and apply detailed system-level measurements at low loads for determining parameters. Measured one-way delays are used to characterize the load on the network. We apply advanced input modeling techniques including multi-modal distributions, multiple phases, and Bézier curves for unconventional shapes to represent all quantities. We also propose a new model based on differences between successive delays for modeling the autocorrelations observed during the measurements. Several internal characteristics of the cluster which significantly affect the behavior at higher loads, including buffering, resource contention, and transport layer mechanisms, are modeled in detail in our UML simulation. The model is able to predict the quantiles of the overall delay for HTTP responses of different configurations beyond the laboratory setup. Replacing all distributions with exponential ones with same means leads to significant deviations, demonstrating the need for serious input modeling.
Longitudinal Sequence and Functional Evolution within Glycoprotein E2 in Hepatitis C Virus Genotype 3a Infection

The E2 glycoprotein of Hepatitis C virus (HCV) is a major target of the neutralizing antibody (NAb) response with the majority of epitopes located within its receptor binding domain (RBD; 384–661). Within E2 are three variable regions located at the N-terminus (HVR1; 384–411), and internally at 460–480 (HVR2) and 570–580 [intergenotypic variable region (igVR)], all of which lie outside a conserved core domain that contains the CD81 binding site, essential for attachment of virions to host cells and a major target of NAbs. In this study, we examined the evolution of the E1 and E2 region in two patients infected with genotype 3a virus. Whereas one patient was able to clear the acute infection, the other developed a chronic infection. Mutations accumulated at multiple positions within the N-terminal HVR1 as well as within the igVR in both patients over time, whereas mutations in HVR2 were observed only in the chronically infected patient. Mutations within or adjacent to the CD81 contact site were observed in both patients but were less frequent and more conservative in the patient that cleared his/her infection. The evolution of CD81 binding function and antigenicity was examined with longitudinal E2 RBD sequences. The ability of the RBD to bind CD81 was completely lost by week 108 in the patient that developed chronic HCV. In the second patient, the ability of the week 36 RBD, just prior to viral clearance, to bind CD81 was reduced ~50% relative to RBD sequences obtained earlier. The binding of a NAb specific to a conserved epitope located within E2 residues 411–428 was significantly reduced by week 108 despite complete conservation of its epitope suggesting that E2 antigenicity is allosterically modulated. The exposure of non-neutralizing antibody epitopes was similarly explored and we observed that the epitope of 3 out of 4 non-NAbs were significantly more exposed in the RBDs representing the late timepoints in the chronic patient. By contrast, the exposure of non-neutralizing epitopes was reduced in the patient that cleared his/her infection and could in part be attributed to sequence changes in the igVR. These studies reveal that during HCV infection, the exposure of the CD81 binding site on E2 becomes increasingly occluded, and the antigenicity of the E2 RBD towards both neutralizing and non-neutralizing antibodies is modulated via allosteric mechanisms.
Overexpression of PIP5KL1 suppresses the growth of human cervical cancer cells in vitro and in vivo

PIP5KL1 (phosphatidylinositol‐4‐phosphate 5‐kinase‐like 1), the fourth member of PIP5Ks (phosphatidylinositol‐4‐phosphate 5‐kinases) type I, acts as a scaffold for localization and activation of PIP5Ks, which in turn regulate numerous cellular processes. However, the role of PIP5KL1 in the development of human cancer is poorly studied. In this study, we established a stable clone of PIP5KL1 overexpressing human cervical cancer HeLa cells. RT‐PCR (reverse transcription‐polymerase chain reaction) and Western immunoblot analysis were performed to testify the mRNA and protein levels of PIP5KL1 in HeLa cells. The effect of PIP5KL1 overexpression on in vitro cell growth was assessed by measuring cell proliferation and migration. The athymic nude mouse model was used to examine the effects of PIP5KL1 on tumour growth in vivo. Stable transfection of PIP5KL1 induced a significant increase in expression of both mRNA and protein levels and consequent robust inhibition of proliferation (P<0.05) and migration (P<0.05) of HeLa cells. Overexpression of PIP5KL1 significantly suppressed the growth of HeLa xenograft tumours in the flanks of nude mice. Taken together, these studies indicate a functional negative correlation between elevated levels of PIP5KL1 and the development of human cervical cancer, suggesting that PIP5KL1 overexpression may suppress cervical cancer formation.
A shorter form health survey: can the SF-12 replicate results from the SF-36 in longitudinal studies?

BACKGROUND The SF-36 is a generic health status measure which has gained popularity as a measure of outcome in a wide variety of patient groups and social surveys. However, there is a need for even shorter measures, which reduce respondent burden. The developers of the SF-36 have consequently suggested that a 12-item sub-set of the items may accurately reproduce the two summary component scores which can be derived from the SF-36 [the Physical Component Summary Score (PCS) and Mental Health Component Summary Score (MCS)]. In this paper, we adopt scoring algorithms for the UK SF-36 and SF-12 summary scores to evaluate the picture of change gained in various treatment groups. METHODS The SF-36 was administered in three treatment groups (ACE inhibitors for congestive heart failure, continuous positive airways therapy for sleep apnoea, and open vs laparoscopic surgery for inguinal hernia). RESULTS PCS and MCS scores calculated from the SF-36 or a sub-set of 12 items (the 'SF-12') were virtually identical, and indicated the same magnitude of ill-health and degree of change over time. CONCLUSION The results suggest that where two summary scores of health status are adequate than the SF-12 may be the instrument of choice.