Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Quality of Life with the Chronic Obstructive Pulmonary Disease Assessment Test in Chronic Obstructive Pulmonary Disease and the Effect of Dyspnea on Disease-Specific Quality of Life in These Patients

Purpose The chronic obstructive pulmonary disease (COPD) assessment test (CAT) was recently introduced for use in assessing disease-specific quality of life and follow-up of patients with COPD. The purpose of this study was to evaluate the effect of the dyspnea on disease-specific quality of life detected by CAT score in patients with COPD. Materials and Methods In this study, 90 stable patients with COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria were included. The level of dyspnea was assessed with the Medical Research Council (MRC) dyspnea scale, and disease-specific quality of life was assessed with CAT score. Results The mean±SD age was 68.5±10.9 (range 41-97) years. A significant relationship was established between CAT score, MRC dyspnea scale score and GOLD stage in patients with COPD. There was also a positive correlation between dyspnea scale scores and GOLD stage in the patients (p<0.001), as well as positive correlation between CAT score and dyspnea scale score (p<0.001). CAT score showed a significant correlation with hospitalization and exacerbations (p<0.05). Conclusion Dyspnea is an important symptom that may impact quality of life in patients with COPD. CAT was shown to be a simple, fast and intelligible measurement of disease-specific quality of life, and was correlated with levels of dyspnea in patients with COPD.
Integrating Continuous and Digital Microfluidics in Electrowetting-on-dielectrics (EWOD) for Heterogeneous Immunoassay

Microfluidic systems have found numerous applications in biomedical research. They rely on channel networks for fluid transport and handling and are generally fabricated in rigid materials, which offers very limited programmability and re-configurability. Digital microfluidics offers the ability to manipulate nanoliters to picoliters of discrete droplets in a programmable fashion. However, complex circuity and signal processing is needed to ensure the precision in sub-micron volume manipulation. In this work, continuous and digital microfluidic functionalities are integrated in a single device for a human IL-6 immunoassay. Precise volume metering for the immunoassay is achieved via an open-loop electrode-based approach without additional hardware, and volume error is decreased by up to 15% as compared with the conventional cylindrical volume estimation. To ensure reliable and reproducible on-chip immunoassay results, sample droplets are precisely and reproducibly dispensed from a continuous electrowetting channel with a volume variance of <3%. In the demonstrated magnetic bead-based immunoassay, sample volume is reduced to ~60 nL, while the continuous channel is used for convenient and rapid sample washing. This strategy allows for a detection limit of 10 pg/mL using colorimetric detection without the need for costly equipment. Ultimately, this approach can be used for improving limits-of-detection or reducing sample volume requirements of immunoassay tests in clinical diagnostics or point-of-care applications.
Normative Three-Dimensional Patellofemoral and Tibiofemoral Kinematics: A Dynamic, in Vivo Study

In order to advance biomechanical modeling, knee joint implant design and clinical treatment of knee joint pathology, accurate in vivo kinematic data of the combined patellofemoral and tibiofemoral joint during volitional activity are critical. For example, one cause of the increased prevalence of anterior knee pain in the female population is hypothesized to be altered tibiofemoral kinematics, resulting in pathological patellofemoral kinematics. Thus, the objectives of this paper were to test the hypothesis that knee joint kinematics vary based on gender and to explore the correlation between the 3-D kinematics of the patellofemoral and tibiofemoral joints. In order to accomplish these goals, a large (n = 34) normative database of combined six degree of freedom patellofemoral and tibiofemoral kinematics, acquired noninvasively during volitional knee extension-flexion using fast-PC (dynamic) magnetic resonance imaging, was established. In this normative database, few correlations between tibiofemoral and patellofemoral kinematics were found. Specifically, tibial external rotation did not predict lateral patellar tilt, as has been stated in previous studies. In general, significant differences could not be found based on gender. Further investigation into these relationships in the presence of pathology is warranted.
Immediate effects of bumetanide on systemic haemodynamics and left ventricular volume in acute and chronic heart failure.

1 The haemodynamic and radionuclide effects of i.v. bumetanide (25 micrograms kg-1) were prospectively studied in 24 patients with angiographically documented coronary artery disease and either acute exercise-induced (Group I, n = 12) or chronic (Group II, n = 12) heart failure. 2 Bumetanide at rest increased systemic arterial blood pressure and vascular resistance index; cardiac index and pulmonary artery occluded pressure (PAOP) were reduced at an unchanged heart rate in all patients. The left ventricular ejection fraction fell in patients with normal resting left ventricular filling pressure without change in those with chronic heart failure. The cardiac volumes were unchanged in either group. 3 During constant-load supine bicycle exercise, there were similar effects on systemic arterial pressures, vascular resistance index and PAOP; however the cardiac index was maintained at a reduced left ventricular filling pressure and unchanged ejection fraction and volumes. 4 These data demonstrate immediate mild pressor and vasoconstrictor actions of bumetanide which appear independent of the state of cardiac function; they suggest that any immediate improvement in patient symptomatology following bumetanide may be consequent on the reduction in PAOP; short-term reductions in volume may not occur.
Adolescents’ exposure to tobacco and alcohol content in YouTube music videos

Abstract Aims To quantify tobacco and alcohol content, including branding, in popular contemporary YouTube music videos; and measure adolescent exposure to such content. Design Ten‐second interval content analysis of alcohol, tobacco or electronic cigarette imagery in all UK Top 40 YouTube music videos during a 12‐week period in 2013/14; on‐line national survey of adolescent viewing of the 32 most popular high‐content videos. Setting Great Britain. Participants A total of 2068 adolescents aged 11–18 years who completed an on‐line survey. Measurements Occurrence of alcohol, tobacco and electronic cigarette use, implied use, paraphernalia or branding in music videos and proportions and estimated numbers of adolescents who had watched sampled videos. Findings Alcohol imagery appeared in 45% [95% confidence interval (CI) = 33–51%] of all videos, tobacco in 22% (95% CI = 13–27%) and electronic cigarettes in 2% (95% CI = 0–4%). Alcohol branding appeared in 7% (95% CI = 2–11%) of videos, tobacco branding in 4% (95% CI = 0–7%) and electronic cigarettes in 1% (95% CI = 0–3%). The most frequently observed alcohol, tobacco and electronic cigarette brands were, respectively, Absolut Tune, Marlboro and E‐Lites. At least one of the 32 most popular music videos containing alcohol or tobacco content had been seen by 81% (95% CI = 79%, 83%) of adolescents surveyed, and of these 87% (95% CI = 85%, 89%) had re‐watched at least one video. The average number of videos seen was 7.1 (95% CI = 6.8, 7.4). Girls were more likely to watch and also re‐watch the videos than boys, P < 0.001. Conclusions Popular YouTube music videos watched by a large number of British adolescents, particularly girls, include significant tobacco and alcohol content, including branding.
Clinical aspects and relevance of molecular diagnosis in late mucocutaneous leishmaniasis patients in Paraná, Brazil

ABSTRACT The aim of the present work was to study the clinical aspects and relevance of molecular diagnosis in late mucocutaneous leishmaniasis patients in Parana, Brazil. Twenty one suspected cases of mucocutaneous leishmaniasis (MCL) in patients from the endemic areas of leishmaniasis were assessed. Different methods used in diagnosing the disease and the polymerase chain reaction (PCR) technique were compared in order to establish the sensitivity of each method. Out of the 21 patients analyzed, 14.3% presented other etiologies such as vasculitis, syphilis, and paracoccidioidomycosis, with all tests negative for leishmaniasis. Out of the remaining 15 patients, 6.7% cases were confirmed for leishmaniasis by direct examination; 46.67% were positive for culture, which allowed isolating and identifying the parasite and – with the PCR technique - it was possible to diagnose 100% MCL patients for all the three repetitions of exams. The PCR optimized for the present work proved to be an auxiliary method for diagnosing leishmaniasis applicable in the patients carrying MCL due to Leishmania (Viannia) braziliensis and did not need culture to be performed, resulting in a faster diagnosis. Key words: Mucocutaneous leishmaniasis, molecular diagnosis, Leishmania (Viannia) braziliensis
The 4-1BB Costimulation Augments the Proliferation of CD4+CD25+ Regulatory T Cells1

The thymus-derived CD4+CD25+ T cells belong to a subset of regulatory T cells potentially capable of suppressing the proliferation of pathogenic effector T cells. Intriguingly, these suppressor cells are themselves anergic, proliferating poorly to mitogenic stimulation in culture. In this study, we find that the 4-1BB costimulator receptor, best known for promoting the proliferation and survival of CD8+ T cells, also induces the proliferation of the CD4+CD25+ regulatory T cells both in culture and in vivo. The proliferating CD4+CD25+ T cells produce no detectable IL-2, suggesting that 4-1BB costimulation of these cells does not involve IL-2 production. The 4-1BB-expanded CD4+CD25+ T cells are functional, as they remain suppressive to other T cells in coculture. These results support the notion that the peripheral expansion of the CD4+CD25+ T cells is controlled in part by costimulation.
Study of the impact of the T877A mutation on ligand‐induced helix‐12 positioning of the androgen receptor resulted in design and synthesis of novel antiandrogens

Antiandrogen flutamide, an antagonist of the wild‐type androgen receptor (AR), is used in the clinics for treating metastatic prostate cancer. However, the T877A mutated AR is paradoxically activated by hydroxyflutamide, an active form of flutamide. Despite of crystallographic studies, how the T877A mutation results in antagonist‐agonist conversion of hydroxyflutamide remains a puzzle. Here, started from a structural model of the apo form of AR ligand‐binding domain (AR‐LBD), we have investigated the impact of the T877A mutation on ligand‐induced helix‐12 positioning by replica‐exchange molecular dynamics (REMD) simulations with an unique protocol, which is capable of simulating the H12 dynamics and keeping the main body of AR‐LBD unchanged. Specifically, (i) we have computationally demonstrated that on the binding of hydroxyflutamide, the apo form of H12 rearranges into the agonistic form in the T877A mutant, but into the antagonistic forms in the wild‐type receptor, shedding light on hydroxyflutamide agonism/antagonism; (ii) By REMD simulations, we have predicted antiandrogen SC184 is a non‐agonist of the T877A mutant. This was confirmed by luciferase assays; and (iii) on the basis of the binding modes of hydroxyflutamide and SC184 from the simulations, we designed a novel flutamide derivative called SC333, which was subsequently predicted to be a pure antagonist of the T877A mutant. We then synthesized and experimentally confirmed SC333 is a pan‐antiandrogen effective against the wild‐type and the T877A and W741C mutated ARs, showing low micromolar cytotoxicity in LNCaP cells. Importantly, we demonstrated that distribution of the H12 conformations from REMD simulations is correlated with ligand agonist/antagonist activity. Proteins 2010. © 2009 Wiley‐Liss, Inc.
OldGen: mobile phone personalization for older adults

Mobile devices are currently difficult to customize for the usability needs of elderly users. The elderly are instead referred to specially designed "senior phones" or software add-ons. These tend to compromise in functionality as they attempt to solve many disabilities in a single solution. We present OldGen, a prototype framework where a novel concept enables accessibility features on generic mobile devices, by decoupling the software user interface from the phone's physical form factor. This opens up for better customization of the user interface, its functionality and behavior, and makes it possible to adapt it to the specific needs of each individual. OldGen makes the user interface portable, such that it could be moved between different phone hardware, regardless of model and brand. Preliminary observations and evaluations with elderly users indicate that this concept could address individual user interface related accessibility issues on general-purpose devices.
Hierarchical decision processes that operate over distinct timescales underlie choice and changes in strategy

Significance Decisions are guided by available information and strategies that link information to action. Following a bad outcome, two potential sources of error—flawed strategy and poor information—must be distinguished to improve future performance. In a direction discrimination task where subjects decide by accumulating sensory evidence to a bound, we show that humans disambiguate sources of error by integrating expected accuracy and outcome over multiple choices. The strategy switches when the integral reaches a threshold. A hierarchy of decision processes in which lower levels integrate sensory evidence over short timescales, and higher levels interact with lower levels over longer timescales, quantitatively explains the behavior. Expected accuracy links these two levels and enables adaptive changes of decision strategy. Decision-making in a natural environment depends on a hierarchy of interacting decision processes. A high-level strategy guides ongoing choices, and the outcomes of those choices determine whether or not the strategy should change. When the right decision strategy is uncertain, as in most natural settings, feedback becomes ambiguous because negative outcomes may be due to limited information or bad strategy. Disambiguating the cause of feedback requires active inference and is key to updating the strategy. We hypothesize that the expected accuracy of a choice plays a crucial rule in this inference, and setting the strategy depends on integration of outcome and expectations across choices. We test this hypothesis with a task in which subjects report the net direction of random dot kinematograms with varying difficulty while the correct stimulus−response association undergoes invisible and unpredictable switches every few trials. We show that subjects treat negative feedback as evidence for a switch but weigh it with their expected accuracy. Subjects accumulate switch evidence (in units of log-likelihood ratio) across trials and update their response strategy when accumulated evidence reaches a bound. A computational framework based on these principles quantitatively explains all aspects of the behavior, providing a plausible neural mechanism for the implementation of hierarchical multiscale decision processes. We suggest that a similar neural computation—bounded accumulation of evidence—underlies both the choice and switches in the strategy that govern the choice, and that expected accuracy of a choice represents a key link between the levels of the decision-making hierarchy.
Review Article: Stem Cells in Human Reproduction

The derivation of human embryonic stem (hES) cells heralds a new era in stem cell research, generating excitement for their therapeutic potential in regenerative medicine. Pioneering work of embryologists, developmental biologists, and reproductive medicine practitioners in in vitro fertilization clinics has facilitated hES cell research. This review summarizes current research focused on optimizing hES cell culture conditions for good manufacturing practice, directing hES cell differentiation toward trophectoderm and germ cells, and approaches used to reprogram cells for pluripotent cell derivation. The identification of germ stem cells in the testis and the recent controversy over their existence in the ovary raise the possibility of harnessing them for treating young cancer survivors. There is also the potential to harvest fetal stem cells with pluripotent cell—like properties from discarded placental tissues. The recent identification of adult stem/progenitor cell activity in the human endometrium offers a new understanding of common gynecological diseases. Discoveries resulting from research into embryonic, germ, fetal, and adult stem cells are highly relevant to human reproduction
Long-term sequelae of subclinical depressive symptoms in early adolescence

Abstract The long-term sequelae of adolescent depressive symptoms were examined in a multimethod, multireporter study of a diverse community sample of 179 adolescents followed from age 14 to 24. Mild to moderate levels of early adolescent depressive symptoms were found to predict lower maternal relationship quality, less positive interactions with romantic partners, and greater loneliness in adulthood even after accounting for prior levels of social functioning and for concurrent levels of adult depressive symptoms. Predictions were partially mediated via late adolescent avoidance of social interactions and poor maternal relationship quality. Results are interpreted as suggesting the potential impact of depressive symptoms on adolescent social development and the need to consider treatment for even mild symptoms and their social concomitants.
Prediction and modeling of pre-analytical sampling errors as a strategy to improve plasma NMR metabolomics data

Motivation Biobanks are important infrastructures for life science research. Optimal sample handling regarding e.g. collection and processing of biological samples is highly complex, with many variables that could alter sample integrity and even more complex when considering multiple study centers or using legacy samples with limited documentation on sample management. Novel means to understand and take into account such variability would enable high‐quality research on archived samples. Results This study investigated whether pre‐analytical sample variability could be predicted and reduced by modeling alterations in the plasma metabolome, measured by NMR, as a function of pre‐centrifugation conditions (1‐36 h pre‐centrifugation delay time at 4 °C and 22 °C) in 16 individuals. Pre‐centrifugation temperature and delay times were predicted using random forest modeling and performance was validated on independent samples. Alterations in the metabolome were modeled at each temperature using a cluster‐based approach, revealing reproducible effects of delay time on energy metabolism intermediates at both temperatures, but more pronounced at 22 °C. Moreover, pre‐centrifugation delay at 4 °C resulted in large, specific variability at 3 h, predominantly of lipids. Pre‐analytical sample handling error correction resulted in significant improvement of data quality, particularly at 22 °C. This approach offers the possibility to predict pre‐centrifugation delay temperature and time in biobanked samples before use in costly downstream applications. Moreover, the results suggest potential to decrease the impact of undesired, delay‐induced variability. However, these findings need to be validated in multiple, large sample sets and with analytical techniques covering a wider range of the metabolome, such as LC‐MS. Availability and implementation The sampleDrift R package is available at https://gitlab.com/CarlBrunius/sampleDrift. Contact carl.brunius@chalmers.se Supplementary information Supplementary data are available at Bioinformatics online.
Disruption of Poly(ADP-ribosyl)ation Mechanisms Alters Responses of Arabidopsis to Biotic Stress1[C][W][OA]

Poly(ADP-ribosyl)ation is a posttranslational protein modification in which ADP-ribose (ADP-Rib) units derived from NAD+ are attached to proteins by poly(ADP-Rib) polymerase (PARP) enzymes. ADP-Rib groups are removed from these polymer chains by the enzyme poly(ADP-Rib) glycohydrolase (PARG). In animals, poly(ADP-ribosyl)ation is associated with DNA damage responses and programmed cell death. Previously, we hypothesized a role for poly(ADP-ribosyl)ation in plant defense responses when we detected defense-associated expression of the poly(ADP-ribosyl)ation-related genes PARG2 and NUDT7 and observed altered callose deposition in the presence of a chemical PARP inhibitor. The role of poly(ADP-ribosyl)ation in plant defenses was more extensively investigated in this study, using Arabidopsis (Arabidopsis thaliana). Pharmacological inhibition of PARP using 3-aminobenzamide perturbs certain innate immune responses to microbe-associated molecular patterns (flg22 and elf18), including callose deposition, lignin deposition, pigment accumulation, and phenylalanine ammonia lyase activity, but does not disrupt other responses, such as the initial oxidative burst and expression of some early defense-associated genes. Mutant parg1 seedlings exhibit exaggerated seedling growth inhibition and pigment accumulation in response to elf18 and are hypersensitive to the DNA-damaging agent mitomycin C. Both parg1 and parg2 knockout plants show accelerated onset of disease symptoms when infected with Botrytis cinerea. Cellular levels of ADP-Rib polymer increase after infection with avirulent Pseudomonas syringae pv tomato DC3000 avrRpt2+, and pathogen-dependent changes in the poly(ADP-ribosyl)ation of discrete proteins were also observed. We conclude that poly(ADP-ribosyl)ation is a functional component in plant responses to biotic stress.
Hepatic Stellate Cells and microRNAs in Pathogenesis of Liver Fibrosis

microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by either blocking translation or inducing degradation of target mRNA. miRNAs play essential roles in diverse biological and pathological processes, including development of hepatic fibrosis. Hepatic stellate cells (HSCs) play a central role in development of hepatic fibrosis and there are intricate regulatory effects of miRNAs on their activation, proliferation, collagen production, migration, and apoptosis. There are multiple differentially expressed miRNAs in activated HSCs, and in this review we aim to summarize current data on miRNAs that participate in the development of hepatic fibrosis. Based on this review, miRNAs may serve as biomarkers for diagnosis of liver disease, as well as markers of disease progression. Most importantly, dysregulated miRNAs may potentially be targeted by novel therapies to treat and reverse progression of hepatic fibrosis.
Using carbon nanotubes to enhance creep performance of lead free solder

Abstract In the present study, the influence of multiwalled carbon nanotubes (CNTs) on the creep performance of 95·8Sn–3·5Ag–0·7Cu lead free solder is investigated. Composite solders containing varying weight percentages of CNTs were synthesised. Solder joints were fabricated and subjected to a series of tests under testing temperatures ranging from 25 to 125°C and applied stresses ranging from 4 to 18 MPa. Creep results revealed that solders containing CNTs exhibited significantly improved creep resistance and also creep time to failure increased. Stress exponents of composite solders were higher than that of monolithic solder. In general, stress exponent was found to increase with increasing applied stress and with decreasing testing temperature. The range of activation energies of composite solder with 0·01 wt-%CNT addition was found to be comparable to that of monolithic Sn–Ag–Cu. However, as the amount of CNT increased to 0·04 wt-%, the range of activation energies increased accordingly.