Miracle-dz/UniFAR-FTUs huggingface dataset:
Preemptive pregabalin for postoperative analgesia during minimally invasive hysterectomy: a systematic review and meta-analysis of randomized controlled trials

We aimed to perform a systematic review and meta-analysis of all randomized placebo-controlled trials (RCTs) that examined the analgesic benefits of preemptive pregabalin among patients undergoing minimally invasive hysterectomy. Five major databases were systematically screened from inception until August 29, 2021 Relevant studies were evaluated for risk of bias. Endpoints were analyzed using the random-effects model and pooled as the mean difference or risk ratio with a 95% confidence interval. Four studies with seven treatment arms met the inclusion criteria. The total sample size was 304 patients: 193 and 111 patients were allocated to the pregabalin and placebo groups, respectively. Overall, the included studies revealed a low risk of bias. The summary results revealed that the mean postoperative pain scores at rest were significantly lower in the pregabalin group than in the control group at 0, 2, 4, 6, 12, and 24 hours. Moreover, the mean postoperative pain scores on movement/coughing were significantly lower in the pregabalin group than in the control group at 12 and 24 hours. The rate of patients who were opioid-free postoperatively was significantly higher in the pregabalin group than in the control group. There was no significant difference between the groups in terms of the mean postoperative time to first rescue analgesic and the rates of adverse events. Compared with placebo, preemptive pregabalin was largely safe, and was correlated with superior analgesic effects in terms of lower postoperative pain scores and higher opioid-sparing effects. Additional RCTs are needed to confirm these findings.
The Impact of the Covid-19 Pandemic on Cleft Lip and Palate Service Delivery for New Families in the United Kingdom: Medical and Community Service Provider Perspectives

Objectives Professionals in the United Kingdom providing care to new families affected by cleft lip and/or palate (CL/P) had to adapt to ensure families’ needs were met during a time of uncertainty due to Covid-19. The aims of this study were to explore the impacts of the pandemic on CL/P care provision for new families from the perspectives of professionals working in medical and community settings along with any personal impact on professionals and their reflections on the future of CL/P care. Design Semistructured interviews (n = 27) were completed about experiences from March 2020 to October 2020 with consultant cleft surgeons (n = 15), lead clinical nurse specialists (n = 8), and staff working at the Cleft Lip and Palate Association (n = 4). Transcripts were analyzed using inductive thematic analysis. Results Three themes were identified: (1) the impact of Covid-19 on the provision of cleft care in the United Kingdom, including working conditions, delays to treatment, and Covid-19 policies; (2) the impact of the pandemic on professionals’ mental health, including personal distress and concerns about Covid-19 exposure; and (3) reflections on the future of CL/P care, whereby professionals expressed both hope and concern about the Covid-19 recovery effort. Conclusions The ongoing Covid-19 pandemic has impacted CL/P service delivery for new families significantly, warranting recommendations for cohesive psychological support for families in addition to a safe and resourced recovery effort. Support for professionals is also suggested, following existing evidence-based models for providers’ needs that address the difficulties of working throughout challenging times.
Polydopamine-coated polycaprolactone/carbon nanotube fibrous scaffolds loaded with brain-derived neurotrophic factor for peripheral nerve regeneration

Carbon nanotubes (CNTs) have attracted increasing attention in the field of peripheral nerve tissue engineering due to their unique structural and physical characteristics. In this study, a novel type of aligned conductive scaffolds composed of polycaprolactone (PCL) and CNTs were fabricated via electrospinning. Utilizing mussel-inspired polydopamine (PDA) surface modification, brain-derived neurotrophic factor (BDNF) was loaded onto PCL/CNT fibrous scaffolds to obtain PCL/CNT-PDA-BDNF fibrous scaffolds capable of the sustained release of BDNF over 28 d. Schwann cells were cultured on these scaffolds, and the effect of the scaffolds on peripheral nerve regeneration in vitro was assessed by studying cell proliferation, morphology and the expressions of myelination-related genes S100, P0 and myelin basic protein. Furthermore, the effect of these scaffolds on peripheral nerve regeneration in vivo was investigated using a 10 mm rat sciatic nerve defect model. Both the in vitro and in vivo results indicate that PCL/CNT-PDA-BDNF fibrous scaffolds effectively promote sciatic nerve regeneration and functional recovery. Therefore, PCL/CNT-PDA-BDNF fibrous scaffolds have great potential for peripheral nerve restoration.
Neural alterations in working memory of mild‐moderate TBI: An fMRI study in Malaysia

Working memory (WM) encompasses crucial cognitive processes or abilities to retain and manipulate temporary information for immediate execution of complex cognitive tasks in daily functioning such as reasoning and decision‐making. The WM of individuals sustaining traumatic brain injury (TBI) was commonly compromised, especially in the domain of WM. The current study investigated the brain responses of WM in a group of participants with mild–moderate TBI compared to their healthy counterparts employing functional magnetic resonance imaging. All consented participants (healthy: n = 26 and TBI: n = 15) performed two variations of the n‐back WM task with four load conditions (0‐, 1‐, 2‐, and 3‐back). The respective within‐group effects showed a right hemisphere‐dominance activation and slower reaction in performance for the TBI group. Random‐effects analysis revealed activation difference between the two groups in the right occipital lobe in the guided n‐back with cues, and in the bilateral occipital lobe, superior parietal region, and cingulate cortices in the n‐back without cues. The left middle frontal gyrus was implicated in the load‐dependent processing of WM in both groups. Further group analysis identified that the notable activation changes in the frontal gyri and anterior cingulate cortex are according to low and high loads. Though relatively smaller in scale, this study was eminent as it clarified the neural alterations in WM in the mild–moderate TBI group compared to healthy controls. It confirmed the robustness of the phenomenon in TBI with the reproducibility of the results in a heterogeneous non‐Western sample.
Probing Fluorinated Motifs onto Dual AChE-MAO B Inhibitors: Rational Design, Synthesis, Biological Evaluation, and Early-ADME Studies.

Bioisosteric H/F or CH2OH/CF2H replacement was introduced in coumarin derivatives previously characterized as dual AChE-MAO B inhibitors to probe the effects on both inhibitory potency and drug-likeness. Along with in vitro screening, we investigated early-ADME parameters related to solubility and lipophilicity (Sol7.4, CHI7.4, log D7.4), oral bioavailability and central nervous system (CNS) penetration (PAMPA-HDM and PAMPA-blood-brain barrier (BBB) assays, Caco-2 bidirectional transport study), and metabolic liability (half-lives and clearance in microsomes, inhibition of CYP3A4). Both specific and nonspecific tissue toxicities were determined in SH-SY5Y and HepG2 lines, respectively. Compound 15 bearing a -CF2H motif emerged as a water-soluble, orally bioavailable CNS-permeant potent inhibitor of both human AChE (IC50 = 550 nM) and MAO B (IC50 = 8.2 nM, B/A selectivity > 1200). Moreover, 15 behaved as a safe and metabolically stable neuroprotective agent, devoid of cytochrome liability.
Exploring The Rooms with Lykta Creating Immersive Gaming Experiences through Projected Augmented Reality

The immersive gaming capabilities of projected augmented reality using a prototype system, Lykta, are investigated. To accomplish this a horror game is designed and implemented, drawing design methods from the fields of game design and interaction design. An approach with two design iterations is used, followed by a playtest in which interviews and questionnaires are used to gauge the immersiveness of the experience provided by the game. Throughout the process, improvements are made to the prototype system. The result is a game played in a dark room. The experiences provides the players with the illusion of exploring the game world using just a flashlight, which in reality is a projector projecting out the game. The results from the playtest are compared to several different kinds of immersion, with findings showing that the players had at least to some degree experienced several different kinds of immersion. Future evaluations of a more quantitative and comparative nature are suitable for determining the immersive aspects of projected augmented reality in more detail, but tentative results suggest that a new type of immersion, spatial immersion, might be a relevant addition to other immersion models.
Enhanced performance of organic solar cell doped with gold nanorods into hole transporting layer

A route to enhancing the efficiency of organic solar cells (OSCs) is the incorporation of gold (Au) nanoparticles into the hole transport layer poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). The improved performance of OSCs after incorporation of gold nanorods (AuNRs) into the PEDOT:PSS layer has been investigated both experimentally and theoretically. The results reveal that the role of the optical properties of AuNRs has been proven to be minor compared to their electrical properties in the improvement of the power conversion efficiency (PCE) of OSCs. The work-function of AuNRs along with the increased interfacial area between the active layer/PEDOT:PSS after doping is an important factor in enhancing the PCE of OSCs. Simulation of two dimensional electric field distributions using the finite difference time domain (FDTD) method shows a small increment in the absorption spectrum of the active layer after incorporation of AuNRs. An improvement in recombination resistance from impedance spectroscopy study and a reduced ideality factor from the dark current-voltage characteristics of AuNR-doped OSCs demonstrate the progress in efficient internal charge transfer and reduction in recombination mechanism. The overall impact of doping primarily enhances the fill factor of OSCs, which leads to an improvement in efficiency from 1.76 to 2.73%.
Disentangling the last 1,000 years of human–environment interactions along the eastern side of the southern Andes (34–52°S lat.)

Significance Understanding how people have shaped landscapes requires detailed information on past changes in climate, vegetation, fire, and land use. The environmental and human history of four sites along the eastern Andes of southern South America (34–52°S) shows the changing influence of people and climate on landscape development over the last millennia. Initially, burning by hunter-gatherers and climate variability shaped forest, shrubland, and grassland mosaics. Widespread alteration of fire regimes and vegetation ∼400 y ago is attributed to increased Native American pastoralism prior to extensive Euro-American settlement. Late-19th century ranching and logging led to broadscale changes in fire activity and vegetation across the region. These high-resolution, landscape-scale reconstructions reveal complex human–environment interactions that are often overlooked in regional-to-global syntheses.
Be brave, BE-FIT! A pilot investigation of an ACT-informed exposure intervention to reduce exercise fear-avoidance in older adults

ABSTRACT Exercise sensitivity, fear of physical sensations of exertion, is particularly elevated in individuals with cardiovascular disease and can promote fear-avoidance of physical activity. We developed an ACT-informed exposure intervention to target exercise sensitivity, called Behavioral Exposure For Interoceptive Tolerance (BE-FIT). In this Stage I pilot trial, we developed and evaluated the feasibility, safety, and initial efficacy of BE-FIT in low active patients with elevated exercise sensitivity enrolled in outpatient cardiac rehabilitation. BE-FIT is a 6-session, manualized, program-adjunctive treatment delivered during the initial weeks of cardiac rehabilitation and involves exposure to feared bodily sensations and exercise situations, bolstered by acceptance and values-focused processes. Patients (Mage = 70.7 years) were assigned to BE-FIT (n = 12) or an activity monitoring-only control (n = 7). Patients in the BE-FIT condition reported high satisfaction, completed 100% of sessions, and 86.3% (SD = 16.4%) of homework exposures. There were no adverse events reported. BE-FIT produced large-sized effects on reductions in exercise sensitivity and increases in both average steps/day and moderate-to-vigorous physical activity (MVPA) mins/day, from baseline to end-of-treatment. In contrast, the monitoring-only cohort evidenced small-sized reductions in exercise sensitivity and no change in average steps/day or MVPA mins/day. BE-FIT is safe, feasible, acceptable with promising findings from this Stage I trial.
Curing inflammatory diseases using phosphorous dendrimers.

Different types of water-soluble phosphorous dendrimers have been synthesized and display many different biological properties. It has been shown in particular that phosphorous dendrimers of first generation functionalized with azabisphosphonate terminal functions are able to stimulate the human immune system ex vivo. These dendrimers are internalized by monocytes within a few seconds, and induce their anti-inflammatory activation. The presence of the dendrimers induces also the inhibition of the differentiation of monocytes into osteoclasts, the maturation of dendritic cells, and inhibits the proliferation of the proinflammatory CD4+ T lymphocytes. Finally, after 2-3 weeks of culture of peripheral blood mononuclear cells, amplifications by several tens of natural killer cells is observed. In view of all these properties, the influence of these azabisphosphonate-dendrimers has been tested in vivo with several animal models, against different chronic or acute inflammatory diseases, such as multiple sclerosis, rheumatoid arthritis, uveitis, and psoriasis, but also against myeloid leukemia, a hematological cancer. The hematological safety has been demonstrated in mice, as there is no platelet aggregation, no hemolysis, and no disturbance in the hematological formula. The safety of the azabisphosphonate-dendrimer has been assessed also with non-human primates (cynomolgus monkeys) which received repeated injections, as a de-risking pre-clinical test. Biochemical, hematological, and all immunological parameters in peripheral blood remained within a normal physiological range throughout the study, and all survived well. Other phosphorous dendrimers also display anti-inflammatory properties in vivo, in particular dendrimers functionalized with mannose derivatives, which prevent acute lung diseases when given orally (per os) to mice. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.
Acute aerobic exercise reveals that FAHFAs distinguish the metabolomes of overweight and normal-weight runners

Background Responses of the metabolome to acute aerobic exercise may predict maximum oxygen consumption (VO2max) and longer-term outcomes, including the development of diabetes and its complications. Methods Serum samples were collected from overweight/obese trained (OWT) and normal-weight trained (NWT) runners prior to and immediately after a supervised 90-minute treadmill run at 60% VO2max (NWT = 14, OWT = 11) in a cross-sectional study. We applied a liquid chromatography high-resolution–mass spectrometry–based untargeted metabolomics platform to evaluate the effect of acute aerobic exercise on the serum metabolome. Results NWT and OWT metabolic profiles shared increased circulating acylcarnitines and free fatty acids (FFAs) with exercise, while intermediates of adenine metabolism, inosine, and hypoxanthine were strongly correlated with body fat percentage and VO2max. Untargeted metabolomics-guided follow-up quantitative lipidomic analysis revealed that baseline levels of fatty acid esters of hydroxy fatty acids (FAHFAs) were generally diminished in the OWT group. FAHFAs negatively correlated with visceral fat mass and HOMA-IR. Strikingly, a 4-fold decrease in FAHFAs was provoked by acute aerobic running in NWT participants, an effect that negatively correlated with circulating IL-6; these effects were not observed in the OWT group. Machine learning models based on a preexercise metabolite profile that included FAHFAs, FFAs, and adenine intermediates predicted VO2max. Conclusion These findings in overweight human participants and healthy controls indicate that exercise-provoked changes in FAHFAs distinguish normal-weight from overweight participants and could predict VO2max. These results support the notion that FAHFAs could modulate the inflammatory response, fuel utilization, and insulin resistance. Trial registration ClinicalTrials.gov, NCT02150889. Funding NIH DK091538, AG069781, DK098203, TR000114, UL1TR002494.
Type‐2 diabetes mellitus and recovery of rocuronium‐induced neuromuscular blockade

Type-2 diabetes mellitus is highly prevalent among surgical patients, including an estimated 10% prevalence of undiagnosed diabetes [1]. In these patients, the response to neuromuscular blocking drugs could be affected by altered nerve conduction and pathophysiological changes at the neuromuscular junction, especially at the pre-synaptic membrane [2]. Only two studies have tested the influence of type-2 diabetes on the recovery of neuromuscular blockade after a standard dose of rocuronium, and they showed conflicting results [3, 4]. We aimed to conduct a descriptive observational study comparing spontaneous recovery after a dose of rocuronium 1.2 mg.kg (the rapid sequence induction dose) in patients with and without type-2 diabetes. After such a high dose, it is important to assess any possible prolongation in the time required to recover to a moderate degree of blockade (train-of-four count 1–3), since this time guides further dosage of rocuronium, as well as the reversal strategy in short procedures. Written consent was obtained from all study participants. We included patients with type-2 diabetes without neuropathy or nephropathy and patients without diabetes. Those in both groups were aged > 45 y, BMI between 18.5 and 30 kg.m, ASA physical status 1–3 and scheduled for elective surgery of an expected duration of >120 min. Monitoring was carried out through acceleromyography using the TOF-WATCH-SX (Organon Ltd, Dublin, Ireland) following guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking drugs [5]. Sevoflurane was used for the maintenance of anaesthesia. The following variables were recorded: blockade onset time (95% amplitude reduction in singletwitch-response); time to appearance of post-tetanic count (deep blockade onset time); and time until detection of the first (moderate blockade onset time), second and third twitches of the train-of-four. Train-of-four stimulation was performed every 15 s, and while the train-of-four count was zero, the intensity of blockade was assessed with a post-tetanic count every 15 min. Sample size was calculated assuming an a of 0.05 and a b of 0.2 in a twosided test and considering a common SD of 20 min, based on our own preliminary data. A minimum of 52 patients were needed per study group in order to detect a statistically significant difference > 10 min in the appearance of moderate blockade. Data were analysed using the unpaired t-test for continuous variables and the Chi-square test for differences in proportions. We recruited 116 patients between January 2019 and October 2021 (58 in each group). Nine patients did not achieve recovery of the second twitch of the train-of-four and 11 did not reach recovery of the third twitch, either
Current Medication Practices and Preferences Among Patients With Psoriatic Arthritis

Objective The aim of this study was to evaluate real-world psoriatic arthritis (PsA) medication use and patient medication preferences. Methods This is a cross-sectional survey of Classification for Psoriatic Arthritis criteria defined PsA patients recruited from a single-center PsA registry from June to September 2020. Preferences were ranked on a 5-point Likert scale ranging from “not at all important” to “extremely important. ” Results One hundred thirty-seven patients (29%) responded. The median duration (years) of PsA skin and joint symptoms was 19 (interquartile range, 10–34) and 12 (interquartile range, 8–21), respectively. The most common initial immunomodulatory medications were anti–tumor necrosis factor α (35%), methotrexate (19%), and anti–phosphodiesterase 4 (anti-PDE4) (12.4%). At survey administration, the most common immunomodulatory therapies were anti–tumor necrosis factor α (30%), anti–interleukin 17 (IL-17) (20.4%), and methotrexate (10.2%). After 2018, when updated guidelines from the American College of Rheumatology/National Psoriasis Foundation were published, a significantly higher percentage of patients' first medication was an anti–IL-17 compared with 2018 or earlier (30% vs 3.5%, p < 0.001), a pattern also seen with anti-PDE4 (40% vs 11.5%, p < 0.012). Medication preferences most ranked as “extremely” important were prevention of joint damage (80%), ability to perform daily activities (71%), prevention of pain (70.1%), rheumatologist recommendation (63%), and medication adverse effects (62%). Conclusions The significant increase of anti–IL-17 and anti-PDE4 medications as initial treatment after 2018 may reflect their inclusion as potential initial therapy in updated guidelines, along with the importance placed by patients on medication adverse effects. Given the expanding armamentarium of PsA medications, it is increasingly important to align patient preferences and therapeutic options to ensure durable use of effective therapy.
Pre-treatment plasma cytokine levels as potential predictors of short-term remission of depression

Abstract Objectives The response to antidepressants varies significantly among individuals and is difficult to predict before treatment. In this randomised control trial, we explored cytokines that correlate with the therapeutic effect of mirtazapine (MIR) and selective serotonin reuptake inhibitors (SSRIs) and whether they could be predictors of remission for each antidepressant. Methods Plasma cytokines, such as tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were assayed in 95 participants before medication and assayed by the enzyme-linked immunosorbent assay. The Hamilton Rating Scale for Depression assessed depressive symptoms over 4 weeks. Results In the SSRI group, the baseline GM-CSF level was significantly higher in the remission group than in the non-remission group (p = .022). In the MIR group, the baseline level of TNF-α was significantly higher (p = .039) and IL-2 was lower (p = .032) in the remission group than in the non-remission group. In patients prescribed with MIR, the cut-off values of TNF-α (10.035 pg/mL) and IL-2 (1.170 pg/mL) calculated from the receiver operating characteristic curve suggested that the remission rate, which corresponds to a positive predictive value, could be increased from 31.3% to 60.0% and 50.0%, respectively. For those prescribed with SSRIs, the remission rate was 37.0% and using the cut-off value of GM-CSF (0.205 pg/mL), the remission rate could be almost doubled to 70%. Conclusions Our study shows that pre-treatment plasma concentrations of TNF-α, IL-2, and GM-CSF may suggest the predictability of remission by SSRIs or MIR.