Miracle-dz/UniFAR-FTUs huggingface dataset:
Highlight article: Respiratory mechanics evaluation of mice submitted to intravenous methacholine: Bolus vs. continuous infusion

The application of a bronchoconstrictor, usually Methacholine (MCh), in respiratory mechanics studies is usually accompanied by the assessment of respiratory mechanics in a dose–response curve. The MCh used in the dose–response curve can be inhaled (i.h.) and intravenous (i.v.) and there are studies comparing i.v. bolus and i.h. MCh in both mice and rats. However, MCh i.v. can be injected at short time interval (bolus) or in continuous infusion. This comparison is relevant since the way MCh is applied influences the mathematical model. We chose an aging process scenario to compare both protocols. This study aims to compare respiratory mechanics of 3-, 6-, and 10-month SAMR1 mice and how both administration methods (continuous infusion and bolus) impact respiratory mechanics evaluation. Both protocols were capable of assessing the difference among ages and doses in: peak or plateau; and area under the curve analysis. The respiratory mechanics parameters were Rn, G, and H (two-way analysis of variance: groups and doses with a P < 0.05 for all). Also, the infusion protocol presented a higher sensitivity to dose increment. In conclusion, both protocols were able to discriminate intragroup and intergroup differences. In the bolus protocol, the highest value of each curve dose may not correspond to the highest real value, and the loss of this point may be a problematic factor in the sample size. These factors are not present in the infusion protocol. Additionally, at this lineage and age screening, the infusion protocol appeared to be more sensitive to differences among ages when compared to the bolus protocol. Impact statement Respiratory mechanics studies are associated with fundamental research and translational studies; the present work thus investigates this particular matter. Our current research describes differences and similarities between two different ways of administrating a very prevalent bronchoconstrictor (methacholine) in an aging process scenario. The core issue of our work is related with troubles we find with the bolus protocol and the application of the mathematical model used to assess the respiratory mechanics. Our findings reveal the continuous infusion as an alternative to these problems and we hope to provide the proper foundations to a more reliable assessment in the respiratory field.
Leisure Choices and Employee Well-Being: Comparing Need Fulfillment and Well-Being during TV and Other Leisure Activities.

BACKGROUND Working adults spend most of their leisure time watching TV. In this paper, we seek to clarify how experiences of psychological need fulfillment and well-being differ when watching TV and engaging in other leisure activities. We suggest that, compared to other leisure activities, watching TV is equally conducive to fulfilling needs for: (a) relaxation and detachment from stress and (b) autonomy, but is less conducive to fulfilling needs for (c) meaning, (d) mastery, and (e) affiliation and thus also less conducive to promoting subjective wellbeing. METHODS We tested our predictions in two day reconstruction studies and a daily diary study. RESULTS People experienced similar levels of detachment and relaxation when watching TV and engaging in other types of leisure. However, they experienced less fulfillment of other needs, and lower levels of satisfaction and some aspects of affective well-being, when watching TV compared to other activities. Further, unlike time spent watching TV, daily time spent in physical activities was positively associated with positive activated affect. CONCLUSIONS Given that watching TV tends to be associated with lower levels of need fulfillment and well-being than other leisure activities, leisure choices may be an important target for improving employee well-being.
Comprehensive analysis on orthopedic drilling: A state-of-the-art review

Bone drilling is a well-known internal fixation procedure to drill a hole, fixing the bone fragments to reduce the susceptibility of permanent paralysis. The success of bone drilling is evaluated based on the extent of osteonecrosis in terms of heat generation, tissue damage, quality of hole, and drilling forces. The appropriate control of cutting conditions, drill geometric parameters, and bone-specific parameters offer bone drilling a viable solution through conventional and non-conventional drilling techniques. The majority of the published research work considers only limited parameters and tries to optimize the drilling parameters and performance measures. However, bone drilling involves numerous conventional and non-conventional drilling parameters and technologies. In order to develop a better understanding of all the studied parameters and performance measures, there is a dire need to develop a framework. The key objective of this review study is to establish a hierarchy of the framework by collecting almost all the parameters studied until now and addressed the relationship between parameters and performance measures to diminish the controversies in the published literature. Therefore, this framework is novel in nature, organizing all the parameters, performance measures, logical comparisons, and limitations of studies. This holistic review can help medical surgeons and design engineers to understand the complicated relationship among parameters and performance measures associated with this state-of-art technologies. Also, modeling, simulations, and optimization techniques are included to explore the application of such techniques in recent advancements in orthopedic drilling.
Diabetes-associated genetic variation in TCF7L2 alters pulsatile insulin secretion in humans.

BACKGROUND Metabolic disorders such as type 2 diabetes have been associated with a decrease in insulin pulse frequency and amplitude. We hypothesized that the T-allele at rs7903146 in TCF7L2, previously associated with β-cell dysfunction, would be associated with changes in these insulin pulse characteristics. METHODS 29 nondiabetic subjects (age = 46 ± 2, BMI = 28 ± 1 Kg/M2) participated in this study. Of these, 16 were homozygous for the C allele at rs7903146 and 13 were homozygous for the T allele. Deconvolution of peripheral C-peptide concentrations allowed the reconstruction of portal insulin secretion over time. This data was used for subsequent analyses. Pulse orderliness was assessed by Approximate Entropy (ApEn) and the dispersion of insulin pulses was measured by a Frequency Dispersion Index (FDI) applied to a Fourier Transform of individual insulin secretion rates. RESULTS During fasting conditions, the CC genotype group exhibited decreased pulse disorderliness compared to the TT genotype group (1.10 ± 0.03 vs. 1.19 ± 0.04, p = 0.03). FDI decreased in response to hyperglycemia in the CC genotype group, perhaps reflecting less entrainment of insulin secretion during fasting. CONCLUSION Diabetes-associated variation in TCF7L2 is associated with decreased orderliness and pulse dispersion unchanged by hyperglycemia. Quantification of ApEn and FDI could represent novel markers of β-cell health.
Conducting Polymer Mediated Electrical Stimulation Induces Multilineage Differentiation with Robust Neuronal Fate Determination of Human Induced Pluripotent Stem Cells

Electrical stimulation is increasingly being used to modulate human cell behaviour for biotechnological research and therapeutics. Electrically conductive polymers (CPs) such as polypyrrole (PPy) are amenable to in vitro and in vivo cell stimulation, being easy to synthesise with different counter ions (dopants) to augment biocompatibility and cell-effects. Extending our earlier work, which showed that CP-mediated electrical stimulation promotes human neural stem cell differentiation, here we report using electroactive PPy containing the anionic dopant dodecylbenzenesulfonate (DBS) to modulate the fate determination of human induced pluripotent stem cells (iPSCs). Remarkably, the stimulation without conventional chemical inducers resulted in the iPSCs differentiating to cells of the three germ lineages—endoderm, ectoderm, and mesoderm. The unstimulated iPSC controls remained undifferentiated. Phenotypic characterisation further showed a robust induction to neuronal fate with electrical stimulation, again without customary chemical inducers. Our findings add to the growing body of evidence supporting the use of electrical stimulation to augment stem cell differentiation, more specifically, pluripotent stem cell differentiation, and especially neuronal induction. Moreover, we have shown the versatility of electroactive PPy as a cell-compatible platform for advanced stem cell research and translation, including identifying novel mechanisms of fate regulation, tissue development, electroceuticals, and regenerative medicine.
Tai Chi Training Evokes Significant Changes in Brain White Matter Network in Older Women

Background: Cognitive decline is age relevant and it can start as early as middle age. The decline becomes more obvious among older adults, which is highly associated with increased risk of developing dementia (e.g., Alzheimer’s disease). White matter damage was found to be related to cognitive decline through aging. The purpose of the current study was to compare the effects of Tai Chi (TC) versus walking on the brain white matter network among Chinese elderly women. Methods: A cross-sectional study was conducted where 42 healthy elderly women were included. Tai Chi practitioners (20 females, average age: 62.9 ± 2.38 years, education level 9.05 ± 1.8 years) and the matched walking participants (22 females, average age: 63.27 ± 3.58 years, educational level: 8.86 ± 2.74 years) underwent resting-state functional magnetic resonance imaging (rsfMRI) scans. Diffusion tensor imaging (DTI) and graph theory were employed to study the data, construct the white matter matrix, and compare the brain network attributes between the two groups. Results: Results from graph-based analyses showed that the small-world attributes were higher for the TC group than for the walking group (p < 0.05, Cohen’s d = 1.534). Some effects were significant (p < 0.001) with very large effect sizes. Meanwhile, the aggregation coefficient and local efficiency attributes were also higher for the TC group than for the walking group (p > 0.05). However, no significant difference was found between the two groups in node attributes and edge analysis. Conclusion: Regular TC training is more conducive to optimize the brain functioning and networking of the elderly. The results of the current study help to identify the mechanisms underlying the cognitive protective effects of TC.
Effects of Feed per Tooth and Radial Depth of Cut on Amplitude Parameters and Power Spectral Density of a Machined Surface

Surface topography and roughness significantly affect the functional properties of engineering parts. In this study, a mathematical model simulating the surface topography in end milling is presented and verified by milling experiments. The three dimensional (3D) surface amplitude parameters (arithmetic average deviation Sba and root mean square deviation Sq) of the milled surface were calculated by using the model and the effects of the product (p) and ratio (r) of radial depth of cut ae and feed per tooth fz on amplitude parameters were researched. To evaluate the lateral characteristics of the milled surface, one dimensional (1D) power spectral densities (PSD) along both feed and step-over direction were calculated and investigated. It was found that fz affects 1D PSD along both directions, whereas ae affects 1D PSD along the step-over direction. An angular spectrum, derived from the area power spectral density (APSD), was employed to research the spatial distribution of spectral energy on the milled surface. Furthermore, the influences of p and r on the PSD properties were researched. It was found that r is the significant factor that influences the direction of surface energy spectrum distribution.
Number of Electroconvulsive Therapy Sessions required for Thai Psychiatric Patients: a Retrospective Study

Objective To study predictors of the number of electroconvulsive therapy (ECT) sessions required for symptom remission in psychiatric patients. Patients and Methods We conducted chart reviews for 95 patients whose condition remitted following inpatient ECT. We analyzed the clinical characteristics of the patients and compared the number of ECT sessions between adult (age 18–59 years) and elderly (age ≥ 60 years) patients. Results The overall mean ± SD of the number of ECT sessions was 11.8 ± 4.7 (range: 6–24). By diagnosis, it was 13.3 ± 5.5 for individuals with schizophrenia, 10.1 ± 2.7 for schizoaffective disorder, 14.4 ± 5.6 for bipolar depression, 9.4 ± 1.9 for bipolar mania, 10.9 ± 4.3 for major depressive disorder (MDD), and 11.8 ± 4.3 for those with other diagnoses. For MDD, the number of ECT sessions in elderly patients (13.4 ± 4.6) was statistically greater than that in adult patients (9 ± 2.9) (p = 0.008). Conclusion The number of ECT sessions varied by age and diagnosis. The number of ECT sessions in elderly MDD patients was higher than that in adult MDD patients.
The implication of the SUMOylation pathway in breast cancer pathogenesis and treatment

Abstract Breast cancer is the most commonly diagnosed malignancy in woman worldwide, and is the second most common cause of death in developed countries. The transformation of a normal cell into a malignant derivate requires the acquisition of diverse genomic and proteomic changes, including enzymatic post-translational modifications (PTMs) on key proteins encompassing critical cell signaling events. PTMs occur on proteins after translation, and regulate several aspects of proteins activity, including their localization, activation and turnover. Deregulation of PTMs can potentially lead to tumorigenesis, and several de-regulated PTM pathways contribute to abnormal cell proliferation during breast tumorigenesis. SUMOylation is a PTM that plays a pivotal role in numerous aspects of cell physiology, including cell cycle regulation, protein trafficking and turnover, and DNA damage repair. Consistently with this, the deregulation of the SUMO pathway is observed in different human pathologies, including breast cancer. In this review we will describe the role of SUMOylation in breast tumorigenesis and its implication for breast cancer therapy.
Tuning the Polymorphism of the Anti-VEGF G-rich V7t1 Aptamer by Covalent Dimeric Constructs

In the optimization process of nucleic acid aptamers, increased affinity and/or activity are generally searched by exploring structural analogues of the lead compound. In many cases, promising results have been obtained by dimerization of the starting aptamer. Here we studied a focused set of covalent dimers of the G-quadruplex (G4) forming anti-Vascular Endothelial Growth Factor (VEGF) V7t1 aptamer with the aim of identifying derivatives with improved properties. In the design of these covalent dimers, connecting linkers of different chemical nature, maintaining the same polarity along the strand or inverting it, have been introduced. These dimeric aptamers have been investigated using several biophysical techniques to disclose the conformational behavior, molecularity and thermal stability of the structures formed in different buffers. This in-depth biophysical characterization revealed the formation of stable G4 structures, however in some cases accompanied by alternative tridimensional arrangements. When tested for their VEGF165 binding and antiproliferative activity in comparison with V7t1, these covalent dimers showed slightly lower binding ability to the target protein but similar if not slightly higher antiproliferative activity on human breast adenocarcinoma MCF-7 cells. These results provide useful information for the design of improved dimeric aptamers based on further optimization of the linker joining the two consecutive V7t1 sequences.
Prednisone for Acute Complex Regional Pain Syndrome: A Retrospective Cohort Study

Objective The objective of this study was to evaluate prednisone effectiveness on complex regional pain syndrome (CRPS) features in a community-based outpatient rehabilitation setting. Design A single-centre, retrospective inception cohort design was used. Inclusion criteria were CRPS diagnosis according to the Budapest criteria, involvement of multiple joints, treatment with prednisone, and duration of symptoms less than one year. Typical prednisone treatment was 28-day taper regimen with 60 mg. Patient symptoms and signs were compared before and after treatment. Results There were 39 patients who met inclusion criteria for analysis. Duration of symptoms before treatment was 80.8 ± 67.7 days. Following treatment, 19 (48.7%) patients reported complete pain resolution, 19 (48.7%) patients reported decreased pain permitting functional use, and 1 (2.6%) patient reported no improvement. All symptoms and signs decreased significantly following oral prednisone treatment (p < 0.001). Range of motion (ROM) deficits persisted in 19 (49%) patients. However, 17 of these patients reported functional ROM recovery. Degree of ROM recovery and time-to-treatment had low positive correlation (r = 0.354, p < 0.001). Range of motion (ROM) deficits persisted in 19 (49%) patients. However, 17 of these patients reported functional ROM recovery. Degree of ROM recovery and time-to-treatment had low positive correlation ( Conclusions These data support short-course prednisone treatment for acute and subacute CRPS with multijoint involvement in a community rehabilitation setting. The association between time-to-treatment and ROM recovery suggests earlier treatment may result in improved ROM outcomes.
Doubling the Accuracy of Indoor Positioning: Frequency Diversity

Determination of indoor position based on fine time measurement (FTM) of the round trip time (RTT) of a signal between an initiator (smartphone) and a responder (Wi-Fi access point) enables a number of applications. However, the accuracy currently attainable—standard deviations of 1–2 m in distance measurement under favorable circumstances—limits the range of possible applications. An emergency worker, for example, may not be able to unequivocally determine on which floor someone in need of help is in a multi-story building. The error in position depends on several factors, including the bandwidth of the RF signal, delay of the signal due to the high relative permittivity of construction materials, and the geometry-dependent “noise gain” of position determination. Errors in distance measurements have unusal properties that are exposed here. Improvements in accuracy depend on understanding all of these error sources. This paper introduces “frequency diversity,” a method for doubling the accuracy of indoor position determination using weighted averages of measurements with uncorrelated errors obtained in different channels. The properties of this method are verified experimentally with a range of responders. Finally, different ways of using the distance measurements to determine indoor position are discussed and the Bayesian grid update method shown to be more useful than others, given the non-Gaussian nature of the measurement errors.
Cannabinoids, Blood–Brain Barrier, and Brain Disposition

Potential therapeutic actions of the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are based on their activity as analgesics, anti-emetics, anti-inflammatory agents, anti-seizure compounds. THC and CBD lipophilicity and their neurological actions makes them candidates as new medicinal approaches to treat central nervous system (CNS) diseases. However, they show differences about penetrability and disposition in the brain. The present article is an overview about THC and CBD crossing the blood–brain barrier (BBB) and their brain disposition. Several findings indicate that CBD can modify the deleterious effects on BBB caused by inflammatory cytokines and may play a pivotal role in ameliorating BBB dysfunction consequent to ischemia. Thus supporting the therapeutic potential of CBD for the treatment of ischemic and inflammatory diseases of CNS. Cannabinoids positive effects on cognitive function could be also considered through the aspect of protection of BBB cerebrovascular structure and function, indicating that they may purchase substantial benefits through the protection of BBB integrity. Delivery of these cannabinoids in the brain following different routes of administration (subcutaneous, oral, and pulmonary) is illustrated and commented. Finally, the potential role of cannabinoids in drug-resistance in the clinical management of neurological or psychiatric diseases such as epilepsy and schizophrenia is discussed on the light of their crossing the BBB.
The Assessment of Overall Hangover Severity

The aim of this study was to critically evaluate and compare the different methods to assess overall hangover severity. Currently, there are three multi-item hangover scales that are commonly used for this purpose. All of them comprise a number of hangover symptoms for which an average score is calculated. These scales were compared to a single, 1-item scale assessing overall hangover severity. The results showed that the hangover symptom scales significantly underestimate (subjective) hangover severity, as assessed with a 1-item overall hangover severity scale. A possible reason for this could be that overall hangover severity varies, depending on the frequency of occurrence of individual symptoms included in the respective scale. In contrast, it can be assumed that, when completing a 1-item overall hangover scale, the rating includes all possible hangover symptoms and their impact on cognitive and physical functioning and mood, thus better reflecting the actually experienced hangover severity. On the other hand, solely relying on hangover symptom scales may yield false positives in subjects who report not having a hangover. When the average symptom score is greater than zero, this may lead to non-hungover subjects being categorized as having a hangover, as many of the somatic and psychological hangover symptoms may also be experienced without consuming alcohol (e.g., having a headache). Taken together, the current analyses suggest that a 1-item overall hangover score is superior to hangover symptom scales in accurately assessing overall hangover severity. We therefore recommend using a 1-item overall hangover rating as primary endpoint in future hangover studies that aim to assess overall hangover severity.
Accelerometer Triad Calibration for Pole Tilt Compensation Using Variance Based Sensitivity Analysis

In Engineering Geodesy, most coordinate frames are aligned with the local vertical. For many measurement tasks, it is therefore necessary to manually (or arithmetically) align sensors or equipment with the local vertical, which is a common source of errors and it is very time consuming. Alternatively, accelerometer triads as part of inertial measurement units (IMUs) are used in several applications for horizon leveling. In this contribution we analyze and develop a method to use accelerometer triads for pole tilt compensation with total stations. Several triad sensor models are investigated and applied in a calibration routine using an industrial robot arm. Furthermore a calibration routine to determine the orientation of the IMU mounted on the pole is proposed. Using variance based sensitivity analysis we investigate the influence of different model parameters on leveling and pole tilt compensation. Based on this inference the developed calibration routines are adjusted. The final evaluation experiment shows an RMS of 2.4 mm for the tilt compensated measured ground point with tilts up to 50 gon.