Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis.

OBJECTIVE Juvenile idiopathic arthritis (JIA) can persist through adolescence and adulthood, resulting in significant disability. The use of low-dose oral methotrexate (MTX) for persistent polyarthritis has been shown to be effective by the USA/USSR collaborative study group. However, 2 of the most disabling subgroups of JIA, systemic and extended oligoarthritis, were underrepresented in that study. The present study was therefore conducted to investigate the efficacy of MTX in these 2 subgroups. METHODS Patients under the age of 16 years who fulfilled the International League of Associations for Rheumatology criteria for systemic or extended oligoarticular arthritis were eligible for this multicenter, double-blind, placebo-controlled crossover trial. Forty-five patients with systemic and 43 with extended oligoarticular arthritis were enrolled. The dosage of MTX or placebo was 15 mg/m2, which could be increased to 20 mg/m2 after 2 months. Core outcome variables were considered as primary measures, giving a final score of "improved" or "not improved. " Secondary measures included scores of systemic features and biochemical laboratory measures. Assessment of function was not included since there were no validated functional measures at the start of this trial in 1991. RESULTS In the extended oligoarticular arthritis group, MTX treatment produced significant improvement in 3 of 5 core variables (erythrocyte sedimentation rate, physician's global assessment of disease activity, and parent's global assessment of disease activity). By the primary improvement criteria, there was significant overall improvement during MTX treatment. In the systemic arthritis group, only 2 of 5 core variables were significantly improved (physician's and parent's global assessment of disease activity). Systemic features were not part of the core variables, but the systemic feature score was not significantly different between MTX and placebo treatment. There was no significant overall improvement in this group during MTX treatment. However, no significant interaction between disease subgroup and treatment effect was demonstrated. When the data from both disease subgroups were combined, there was significant clinical improvement during MTX treatment (P = 0.006). CONCLUSION MTX 15-20 mg/m2 given orally once a week was found to be an effective treatment for both extended oligoarticular and systemic JIA in this shortterm trial. Long-term efficacy needs to be addressed in future studies.
Randomized placebo-controlled crossover trial of continuous positive airway pressure for mild sleep Apnea/Hypopnea syndrome.

The minimal disease severity at which patients with the sleep apnea/hypopnea syndrome (SAHS) gain benefit from treatment is not well characterized, although a pilot study of continuous positive airway pressure (CPAP) therapy showed daytime improvements in patients with 5 to 15 apneas + hypopneas per hour slept (AHI). We have thus performed a second, larger, randomized, placebo- controlled study in a prospective series of 34 patients (13 female) with mild SAHS (AHI 5 to 15) and daytime sleepiness. Patients spent 4 wk on CPAP treatment and 4 wk on an oral placebo, with randomization of treatment order, and daytime assessments on the last day of each treatment. Effective CPAP use averaged 2.8 +/- 2.1 h (mean +/- SD) per night. Compared with placebo, CPAP improved symptom score (p < 0.01), subjective (Epworth; p < 0.01) but not objective (maintenance of wakefulness test; p > 0.2) sleepiness, performances on 2 of 7 cognitive tasks (p < 0.02), depression score (p < 0.01), and five subscales of the SF-36 health/functional status questionnaire (p </= 0.03). Fourteen of 34 patients preferred CPAP. In 14 patients with AHI in the range 5 to 10, symptoms, cognitive function, psychological well-being and quality of life were improved. These results confirm benefits for daytime function after CPAP treatment for mild SAHS, but highlight unacceptability of CPAP in many such patients.
Event-triggered variable structure control

ABSTRACT This paper presents a novel variable structure control (VSC) algorithm of event-triggered (ET) type, capable of dealing with a class of nonlinear uncertain systems. By virtue of its ET nature, the algorithm can be used as the kernel of a robust networked control system. The design objective is indeed to reduce the number of transmissions over the network. The proposed ET-VSC also guarantees appropriate robustness properties, even in the presence of delayed transmissions. It is theoretically analysed, proving that the sliding variable associated with the controlled system results in being ultimately confined into a boundary layer of prescribed amplitude. As a consequence, it is proved that the state of the considered uncertain nonlinear system is ultimately bounded as well. Moreover, a lower bound for the time elapsed between consecutive triggering events is provided, which excludes the notorious Zeno behaviour. Finally, the designed ET-VSC control scheme is satisfactorily assessed in simulation.
MTS 1338 , a small Mycobacterium tuberculosis RNA , regulates 1 transcriptional shifts consistent with bacterial adaptation for 2 entering into dormancy and survival within host macrophages 3

170 words) 20 Small non-coding RNAs play a significant role in bacterial adaptation to changing 21 environmental conditions. We investigated the dynamics of expression of MTS1338, a small 22 non-coding RNA of Mycobacterium tuberculosis, in the mouse model in vivo, regulation of 23 its expression in the ex vivo infected macrophages, and the consequences of its 24 overexpression in bacterial cultures. Here we demonstrate that MTS1338 significantly 25 contributes to host-pathogen interactions. Activation of the host immune system triggered 26 NO-inducible up-regulation of MTS1338 in macrophage-engulfed mycobacteria. Constitutive 27 overexpression of MTS1338 in cultured mycobacteria improved their survival in vitro under 28 low pH conditions. MTS1338 up-regulation launched a spectrum of shifts in the 29 transcriptome profile similar to those reported for M. tuberculosis adaptation to hostile intra30 macrophage environment. Using the RNA-seq approach, we demonstrate that gene 31 expression changes accompanying MTS1338 overexpression indicate reduction in 32 translational activity and bacterial growth, which is consistent with entering the dormant 33 state. Taken together, our results suggest a direct involvement on this sRNA in the interplay 34 between mycobacteria and the host immune system during infectious process. 35
Simian Immunodeﬁciency Virus Infection Induces Expansion of (cid:1) 4 (cid:2) 7 (cid:3) and Cytotoxic CD56 (cid:3) NK Cells (cid:1)

Herein we demonstrate that chronic simian immunodeﬁciency virus (SIV) infection induces signiﬁcant upregulation of the gut-homing marker (cid:1) 4 (cid:2) 7 on macaque NK cells, coupled with downregulation of the lymph node-trafﬁcking marker, CCR7. Interestingly, in naïve animals, (cid:1) 4 (cid:2) 7 expression was associated with increased NK cell activation and, on CD16 (cid:3) NK cells, delineated a unique dual-function cytotoxic-CD107a (cid:3) /gamma interferon (IFN- (cid:4) )-secreting population. However, while SIV infection increased CD107a expression on stimulated CD56 (cid:3) NK cells, (cid:1) 4 (cid:2) 7 (cid:3) and (cid:1) 4 (cid:2) 7 (cid:5) NK cells were affected similarly. These ﬁndings suggest that SIV infection redirects NK cells away from the lymph nodes to the gut mucosae but alters NK cell function independent of trafﬁcking repertoires.
High-Throughput Translational Profiling with riboPLATE-seq

Protein synthesis is dysregulated in many diseases, but we lack a systems-level picture of how signaling molecules and RNA binding proteins interact with the translational machinery, largely due to technological limitations. Here we present riboPLATE-seq, a scalable method for generating paired libraries of ribosome-associated and total mRNA. As an extension of the PLATE-seq protocol, riboPLATE-seq utilizes barcoded primers for pooled library preparation, but additionally leverages rRNA immunoprecipitation on whole polysomes to measure ribosome association (RA). We demonstrate the performance of riboPLATE-seq and its utility in detecting translational alterations induced by inhibition of protein kinases.
Discrepancies of mineral volumes predicted by thermodynamic databases

Thermodynamic databases are an essential tool to predict complex equilibrium mineral assemblages and mineral properties like mineral volumes. They consist of numerous thermodynamic data of various minerals, extracted from experiments. Each database follows its own methodology in calculating chemical and physical properties. Therefore a direct comparision between different database predictions was avoided, due to the contrasting methodolgies and philosophy. Here, we present a direct comparison between the databases of Berman [1] and Holland & Powell [2][3], focusing on mineral volumes [4]. For this propose, a reevaluation of the equation of states was nesscary. In this context, we identify an error also implemented in common thermodynamic softwares, concerning the calculation of excess volume. Even after treating the excess energy correctly, volumes show significant discrepancies between the different database predictions. These discrepancies impact geodynamic interpretations and geothermobarometrical estimations, due to the fact that the Gibbs free energy and rock density depends on mineral volumes. The imagination that pressure can vary by 4 kbar, temperature by 150 C or rock-density up to 30 %, by changing the thermodynamic database is dramatic. These enormous differences must be considered keeping in mind that calculations were done for well studied minerals (e.g. quartz and forsterite). The results play an important role for studies of geodynamic interpretations extracted from thermobarometric software packages like Perple_X, Theriak-Domino or Thermocalc. It is important to estimate the influence of the thermodynamic database on Gibbs free energy, volume and rock density. Summarizing, more experimental data will lead to a better comprehension of these discrepancies.
Comprehensive Analysis of Expression Pro�le and Prognostic Signi�cance of Interferon Regulatory Factors in Pancreatic Cancer

Background: Pancreatic cancer (PC) is a highly lethal disease and an increasing cause of cancer-associated mortality worldwide. Interferon regulatory factors (IRFs) play vital roles in immune response and tumor cellular biological process. However, the speci�c functions of IRFs in PC and tumor immune response are far from systematically clari�ed. This study aimed to explorer the expression pro�le, prognostic signi�cance, and biological function of IRFs in PC. Results: We observed that the level of IRF3, 6, 7, 8, and 9 were elevated in tumor compared to normal tissues in PC. IRF7 expression was signi�cantly associated with patients’ pathology stage in PC. PC patients with high IRF2, low IRF3, and high IRF6 level had signi�cantly poorer overall survival. High mRNA expression, ampli�cation and deep deletion were the three most common types of genetic alterations of IRFs in PC. Low expression of IRF2, 4, 5, and 8 was resistant to most of the drugs or small molecules from Genomics of Drug Sensitivity in Cancer. Moreover, IRFs were positively correlated with the abundance of tumor in�ltrating immune cells in PC, including B cells, CD8+ T cells, CD4+ T cells, macrophages, Neutrophil, and Dendritic cells. Functional analysis indicated that IRFs were involved in T cell receptor signaling pathway, immune response and Toll-like receptor signaling pathway. Conclusions: Our results indicated that certain IRFs could serve as potential therapeutic targets and prognostic biomarker for PC patients. Further basic and clinical studies are needed to validate our �ndings and generalize the clinical application of IRFs in PC.
L'evolució del conflicte de tasca, el conflicte de relació i el conflicte de procés en equips virtuals: el paper de l'entrenament

EnglishThe main objective of this paper is to study the effects of team self-guided training on the team perception of task conflict, relationship conflict and process conflict along three work sessions in a virtual context. For that purpose, a laboratory study was carried out in which 52 synchronous computer-mediated teams worked during three sessions: 27 teams were randomly assigned to the experimental condition where they had received a team-guided training and the others were assigned to the control condition. Results of repeated measure ANCOVA show that the combination of the training and the acquired experience by the team members during the work sessions makes that perception of relationship conflict decreases in virtual teams, once team member familiarity is controlled for. Our results also indicate that no significant differences exist between trained teams and control teams in the perception of task conflict and process conflict. catalaL’objectiu d’aquest treball es estudiar els efectes de l’entrenament autoguiat en la percepcio dels equips del conflicte de tasca, del conflicte de relacio i del conflicte de proces, al llarg de tres sessions i en un context virtual. Per aixo es va fer un estudi de laboratori en el qual cinquanta-dos equips de comunicacio sincronica a traves d’ordinador van treballar durant tres sessions: vint-i-set d’ells foren assignats a la condicio experimental, en la qual van rebre un entrenament autoguiat, i la resta d’equips van ser assignats a la condicio de control. Els resultats d’ANCOVA (analisi de covariancia) de mesures repetides mostren que l’entrenament, junt amb l’experiencia adquirida pels membres dels equips durant les diferents sessions de treball, fa que es perceba menor conflicte de relacio una vegada controlada la familiaritat dels membres de l’equip. Els nostres resultats tambe mostren que no hi ha diferencies significatives entre els equips entrenats i els equips de control, en la percepcio del conflicte de tasca i del conflicte de proces.
A personalized robot companion? - The role of individual differences on spatial preferences in HRI scenarios

This study investigated the relationship between individual differences and proxemic behaviour in an HRI setting involving a robot approaching a person. In total 33 participants took part in three different scenarios; verbal interaction, physical interaction and no interaction. Participant control over the robot, and approach direction was also varied. Measurements of the preferred robot approach distance was obtained, and analysed along with the participants' demographic and personality data. The results indicate differences in approach direction preferences based on gender. Also, results show that the participants' personality traits of extraversion and conscientiousness are associated with changes in approach distance preferences according to robot autonomy. The results are discussed in light of relevant literature from the social sciences.
Targeting acetyl-CoA metabolism attenuates the formation of fear memories through reduced activity-dependent histone acetylation

Histone acetylation is a key component in the consolidation of long-term fear memories. Epigenetic enzymes involved in histone acetylation, including histone acetyltransferases and deacetylases, have been put forward as potential pharmacological targets in the treatment of pathological fear memories, such as those that underlie post-traumatic stress disorder (PTSD). However, these enzymes typically play a ubiquitous role in gene regulation, which precludes the clinical use of systemic manipulations. Recently, we have found that a nuclear-localized metabolic enzyme, Acetyl-coA synthetase 2 (Acss2), modulates histone acetylation during learning and memory. Loss of Acss2 is well-tolerated in mice, with no impact on general health or baseline behavior. Here, we show that an Acss2 null mouse model shows reduced acquisition of long-term fear memories in assays of contextual and cued fear conditioning. We find that loss of Acss2 leads to consolidation-specific reductions in both histone acetylation and the expression of critical learning and memory-related genes in the dorsal hippocampus. Further, we show that systemic administration of blood-brain-barrier (BBB)-permeable Acss2 inhibitors during the consolidation window reduces fear memory formation in mice and rats, and also reduces anxiety in a predator-scent-stress (PSS) paradigm. Our findings suggest that Acss2 plays a critical role in the formation of fear memories, and represents a potential pharmacological target in the treatment of PTSD.
use of laryngeal mask versus tracheal tube. Anes-

Sir,—We thank Dr Brain and colleagues for their interest in our paper [1] and for their comments. We shall take their points in order. (1) We confirm that a No. 3 LMA was used in female patients (60%) in our study. The study reflects common practice in anaesthesia. Standard practice in this hospital, as in many others at the time the study was carried out (1992), was to use a No. 3 LMA for adult female and a No. 4 LMA for adult male patients. While we agree that inadequate mask surface area may be a cause of malpositioning, the No. 5 LMA only became available very recently and hence was not used in our study. We cannot speculate as to what the results might have been using different mask sizes. (2) A standard dose of vecuronium was used (0.1 mg kg~')j all operations took 30-40 min and neuromuscular block was monitored with a peripheral nerve stimulator using the train-offour method. Antagonism of neuromuscular block was affected simultaneously with discontinuing volatile agent. A difference in the depth of anaesthesia between the two groups is unlikely. We do not know of any well validated means of measuring depth of anaesthesia, but we were unaware of any clinical disparity. There is no evidence that our patients were partially antagonized. We accept that a Relaxograph would give more quantitative information and further work is indicated to clarify the relationship between degree of neuromuscular block and oesophageal pH. Whatever the physiological explanation of the phenomena, the two groups were treated identically and a significant difference was observed. It is fallacious to argue that the two groups should have been treated differently for the purposes of the study. (3) It would seem unlikely that an oesophageal probe measuring less than 1.5 mm in diameter would have a significant effect on the upper oesophageal sphincter although the theoretical risk exists. We are not sure what methodological modification Brain and colleagues would suggest. For the LMA to even partially rely on the competence of a weak physiological sphincter is a cause for concern. (4) Our LMA placement was by standard insertion technique. (5) We agree there may have been theoretical differences in the ventilatory variables between groups. This may be important where high peak flow rates are used in small radius tubes. We are not aware of clinically significant pressure gradients in tracheal tubes of larger diameters at low flow rates. Though inventive, this explanation does not account for our results; rather one would expect it to obscure the inter-group difference we observed. In our original article, we commented on the final remarks in the letter of Brain and colleagues. Aspiration has been described by several authors [2, 3]. There remains considerable doubt as to the safety of ventilation via the LMA.
Predicting the impact of pneumococcal conjugate vaccine programme options in Vietnam: a dynamic transmission model

Background Catch-up campaigns (CCs) at the introduction of the pneumococcal conjugate vaccines (PCVs) may accelerate the impact of PCVs. However, limited vaccine supplies may delay vaccine introduction if additional doses are needed for such campaigns. We studied the relative impact of introducing PCV13 with and without catch-up campaign, and the implications of potential introduction delays. Methods We used a dynamic transmission model applied to the population of Nha Trang in Sout central Vietnam. Four strategies were considered: routine vaccination (RV) only, and RV alongside catch-up campaigns among <1y olds (CC1), <2y olds (CC2) and <5y olds (CC5). The model was parameterised with local data on human social contact rates, and was fitted to local carriage data. Post-PCV predictions were based on best estimates of parameters governing post-PCV dynamics, including serotype competition, vaccine efficacy and duration of protection. Results Our model predicts elimination of vaccine-type (VT) carriage across all age groups within 10 years of introduction in all scenarios with near-complete replacement by non-VT. Most of the benefit of CCs is predicted to occur within the first 3 years after introduction, with the highest impact in the first year, when IPD incidence is predicted to be 11% (95%CrI 9 – 14%) lower than RV with CC1, 25% (21 – 30 %) lower with CC2 and 38% (32 – 46%) lower with CC5. However, CCs would only prevent more cases of IPD insofar such campaigns do not delay introduction by more than 31 (95%CrI 30 – 32) weeks with CC1, 58 (53 – 63) weeks with CC2 and 89 (78 – 101) weeks for CC5. Conclusion CCs are predicted to offer a substantial additional reduction in pneumococcal disease burden over RV alone, if their implementation does not result in much introduction delay. Those findings are important to help guide vaccine introduction in countries that have not yet introduced PCV, particularly in Asia.
Allostatic load amplifies the effect of blood lead levels on elevated blood pressure among middle-aged U . S . adults : A cross-sectional study

Background: Scientists and regulators have sought to understand whether and how physiologic dysregulation due to chronic stress exposure may enhance vulnerability to the adverse health effects of toxicant exposures. We conducted a cross-sectional study to determine whether allostatic load (AL), a composite measure of physiologic response to chronic exposure to stress, amplifies the effect of lead exposure on blood pressure among middle-aged adults. Methods: We analyzed associations between blood lead levels and blood pressure in a nationally representative sample of 8,194 U.S. adults (aged 40-65 years) participating in the National Health and Nutritional Examination Survey, 1999--2008. Outcomes were elevated systolic (≥ 140 mm Hg) and diastolic (≥ 90 mm Hg) blood pressure. AL was defined as the aggregate score of seven components, reflecting dysregulation of the cardiovascular, inflammatory, and endocrine systems. Results: Logistic regression models showed a linear dose-response relationship for quintiles of blood lead and elevated systolic blood pressure in the high AL group (p = 0.03) but not the low AL group (p = 0.24). Similarly, the relationship between lead exposure and elevated diastolic blood pressure was stronger among the high AL group than the low AL group. Within the high AL group, the fourth and fifth quintiles had significantly elevated odds of elevated blood pressure compared to lowest quintile [OR = 1.92, (95% CI, 1.07, 3.47) and OR =2.28 (95% CI, 1.33, 3.91), respectively]. In the low AL group, none of the quintile effects were significantly different than the referent group although there was evidence of a linear trend (p =0.03). The lead by AL interaction term was not statistically significant for either systolic or diastolic blood pressure models. Conclusions: Results suggest that higher AL may amplify the adverse effects of lead on blood pressure. Future research should assess the implications of cumulative exposures to environmental and social stressors for regulatory decision-making.