Miracle-dz/UniFAR-FTUs huggingface dataset:
The antioxidant and anti‐inflammatory effects of astaxanthin supplementation on the expression of miR‐146a and miR‐126 in patients with type 2 diabetes mellitus: A randomised, double‐blind, placebo‐controlled clinical trial

The pathogenesis of type 2 diabetes mellitus (T2DM) is associated with chronic oxidative stress and inflammation. It is well known that the expression of some miRNAs such as miRNA‐146a is upregulated in diabetic and hyperglycaemic patients, whereas circulating miRNA‐126 is reduced. Therefore, we aimed to determine the effects of astaxanthin (AST) supplementation on the circulating malondialdehyde (MDA) and interleukin 6 (IL‐6) levels, and the expression of miR‐146a and miR‐126 in patients with T2DM.
A Bayesian Network Decision Support Tool for Low Back Pain Using a RAND Appropriateness Procedure: Proposal and Internal Pilot Study

Background Low back pain (LBP) is an increasingly burdensome condition for patients and health professionals alike, with consistent demonstration of increasing persistent pain and disability. Previous decision support tools for LBP management have focused on a subset of factors owing to time constraints and ease of use for the clinician. With the explosion of interest in machine learning tools and the commitment from Western governments to introduce this technology, there are opportunities to develop intelligent decision support tools. We will do this for LBP using a Bayesian network, which will entail constructing a clinical reasoning model elicited from experts. Objective This paper proposes a method for conducting a modified RAND appropriateness procedure to elicit the knowledge required to construct a Bayesian network from a group of domain experts in LBP, and reports the lessons learned from the internal pilot of the procedure. Methods We propose to recruit expert clinicians with a special interest in LBP from across a range of medical specialties, such as orthopedics, rheumatology, and sports medicine. The procedure will consist of four stages. Stage 1 is an online elicitation of variables to be considered by the model, followed by a face-to-face workshop. Stage 2 is an online elicitation of the structure of the model, followed by a face-to-face workshop. Stage 3 consists of an online phase to elicit probabilities to populate the Bayesian network. Stage 4 is a rudimentary validation of the Bayesian network. Results Ethical approval has been obtained from the Research Ethics Committee at Queen Mary University of London. An internal pilot of the procedure has been run with clinical colleagues from the research team. This showed that an alternating process of three remote activities and two in-person meetings was required to complete the elicitation without overburdening participants. Lessons learned have included the need for a bespoke online elicitation tool to run between face-to-face meetings and for careful operational definition of descriptive terms, even if widely clinically used. Further, tools are required to remotely deliver training about self-identification of various forms of cognitive bias and explain the underlying principles of a Bayesian network. The use of the internal pilot was recognized as being a methodological necessity. Conclusions We have proposed a method to construct Bayesian networks that are representative of expert clinical reasoning for a musculoskeletal condition in this case. We have tested the method with an internal pilot to refine the process prior to deployment, which indicates the process can be successful. The internal pilot has also revealed the software support requirements for the elicitation process to model clinical reasoning for a range of conditions. International Registered Report Identifier (IRRID) DERR1-10.2196/21804
Automation of Infectious Focus Assay for Determination of Filovirus Titers and Direct Comparison to Plaque and TCID50 Assays

Ongoing efforts to develop effective therapies against filoviruses rely, to different extents, on quantifying the amount of viable virus in samples by plaque, TCID50, and focus assays. Unfortunately, these techniques have inherent variance, and laboratory-specific preferences make direct comparison of data difficult. Additionally, human errors such as operator errors and subjective bias can further compound the differences in outcomes. To overcome these biases, we developed a computer-based automated image-processing method for a focus assay based on the open-source CellProfiler software platform, which enables high-throughput screening of many treatment samples at one time. We compared virus titers calculated using this platform to plaque and TCID50 assays using common stocks of virus for 3 major Filovirus species, Zaire ebolavirus, Sudan ebolavirus, and Marburg marburgvirus with each assay performed by multiple operators on multiple days. We show that plaque assays give comparable findings that differ by less than 3-fold. Focus-forming unit (FFU) and TCID50 assays differ by 10-fold or less from the plaque assays due a higher (FFU) and lower (TCID50) sensitivity. However, reproducibility and accuracy of each assay differs significantly with Neutral Red Agarose Overlay plaque assays and TCID50 with the lowest reproducibility due to subjective analysis and operator error. Both crystal violet methylcellulose overlay plaque assay and focus assays perform best for accuracy and the focus assay performs best for speed and throughput.
Endoscopic Cyanoacrylate Injection Versus Balloon‐Occluded Retrograde Transvenous Obliteration for Prevention of Gastric Variceal Bleeding: A Randomized Controlled Trial

The optimal treatment for gastric varices (GVs) is a topic that remains open for study. This study compared the efficacy and safety of endoscopic cyanoacrylate injection and balloon‐occluded retrograde transvenous obliteration (BRTO) to prevent rebleeding in patients with cirrhosis and GVs after primary hemostasis.
Premotor Ramping of Thalamic Neuronal Activity Is Modulated by Nigral Inputs and Contributes to Control the Timing of Action Release

The ventromedial (VM)/ventro-anterior-lateral (VAL) motor thalamus is a key junction within the brain circuits sustaining normal and pathologic motor control functions and decision-making. In this area of thalamus, on one hand, the inhibitory nigro-thalamic pathway provides a main output from the basal ganglia, and, on the other hand, motor thalamo-cortical loops are involved in the maintenance of ramping preparatory activity before goal-directed movements. To better understand the nigral impact on thalamic activity, we recorded electrophysiological responses from VM/VAL neurons while male and female mice were performing a delayed right/left decision licking task. Analysis of correct (corr) and error trials revealed that thalamic ramping activity was stronger for premature licks (impulsive action) and weaker for trials with no licks [omission (omi)] compared with correct trials. Suppressing ramping activity through optogenetic activation of nigral terminals in the motor thalamus during the delay epoch of the task led to a reduced probability of impulsive action and an increased amount of omissions trials. We propose a parsimonious model explaining our data and conclude that a thalamic ramping mechanism contributes to the control of proper timing of action release and that inhibitory nigral inputs are sufficient to interrupt this mechanism and modulate the amount of motor impulsivity in this task. SIGNIFICANCE STATEMENT Coordinated neural activity in motor circuits is essential for correct movement preparation and execution, and even slight imbalances in neural processing can lead to failure in behavioral tasks or motor disorders. Here we focused on how failure to regulate the control of activity balance in the motor thalamus can be implicated in impulsive action release or omissions to act, through an activity ramping mechanism that is required for proper action release. Using optogenetic activation of inhibitory basal ganglia terminals in motor thalamus we show that basal ganglia input is well positioned to control this ramping activity and determine the timing of action initiation.
Diagnosis of Dry Eye Disease Using Principal Component Analysis: A Study in Animal Models of the Disease

ABSTRACT Purpose To evaluate whether principal component analysis (PCA) can assess various diagnostic tests of dry eye disease (DED), providing a simplified, more informative measure of disease status than individual clinical test parameters (ICTP). Materials and Methods ICTP were analyzed using PCA in two groups of normal rabbits (Groups 1 and 2). Group 3, not truly normal, was also assessed. DED was induced in Group 1 by complete dacryoadenectomy; in Groups 2 and 3 by injection of concanavalin A. Tear break up time, tear osmolarity, Schirmer’s tear test and rose bengal staining were the ICTP measured in all groups. Statistical analysis including descriptive statistics, t test, correlation coefficients and PCA was done. PCA using ICTP data from Group 1 generated axes; Group 2 and 3 were plotted over these axes. Results All groups had induction of DED. Correlations for all ICTP were in the correct direction and were strongest for Group 1 and weakest in Group 3. PCA clearly separated DED and normal eyes. Principal component (PC) 1, made up of nearly equal contributions from the four clinical tests, explained 73% of the variation and provided a means to separate normal from DED. PC 1 values under 0.52 can be mathematically defined as DED. Of all pairwise comparisons, PC 1 vs PC 2 and PC 1 vs PC 3 were the most informative providing excellent spatial separation and additional information regarding DED status. Conclusions PCA proved useful for evaluating DED providing a simpler, more comprehensive assessment than ICTP. PC 1 is a valuable, clinically relevant, and informative metric for DED status and severity having superior diagnostic value and statistical strength compared to ICTP. Spatial information on biplots of PC 1 vs PC 3 is also informative. PCA, and specifically PC 1, has the potential to serve as a biomarker for DED.
Psychological, physical, and sleep comorbidities and functional impairment in irritable bowel syndrome: Results from a national survey of U.S. adults

Background/Aims Patients with irritable bowel syndrome (IBS) in referral practice commonly report mental disorders and functional impairment. Our aim was to determine the prevalence of mental, physical and sleep-related comorbidities in a nationally representative sample of IBS patients and their impact on functional impairment. Methods IBS was defined by modified Rome Criteria based on responses to the chronic conditions section of the National Comorbidity Survey-Replication. Associations between IBS and mental, physical and sleep disorders and 30-day functional impairment were examined using logistic regression models. Results Of 5,650 eligible responders, 186 met criteria for IBS {weighted prevalence 2.5% (SE = 0.3)}. Age >60 years was associated with decreased odds (OR = 0.3; 95% CI:.1-.6); low family income (OR = 2.4; 95% CI:1.2–4.9) and unemployed status (OR = 2.3; 95% CI:1.2–4.2) were associated with increased odds of IBS. IBS was significantly associated with anxiety, behavior, mood disorders (ORs 1.8–2.4), but not eating or substance use disorders. Among physical conditions, IBS was associated with increased odds of headache, chronic pain, diabetes mellitus and both insomnia and hypersomnolence related symptoms (ORs 1.9–4.0). While the association between IBS and patients’ role impairment persisted after adjusting for mental disorders (OR = 2.4, 95% CI 1.5–3.7), associations with impairment in self-care, cognition, and social interaction in unadjusted models (ORs 2.5–4.2) were no longer significant after adjustment for mental disorders. Conclusion IBS is associated with socioeconomic disadvantage, comorbidity with mood, anxiety and sleep disorders, and role impairment. Other aspects of functional impairment appear to be moderated by presence of comorbid mental disorders.
Predictive equations for resting metabolic rate are not appropriate to use in Brazilian male adolescent football athletes

High accuracy in estimating energy expenditure is essential for enhancing sports performance. The resting metabolic rate (RMR), as a primary component of total energy expenditure (TEE), is commonly estimated using predictive equations. However, these references may not be applicable to adolescent athletes. The purpose of this cross-sectional study was to analyse the differences between predicted RMR in relation to energy expenditure measured by indirect calorimetry (IC) among 45 Brazilian male adolescent football athletes. Indirect calorimetry (IC) and anthropometric (bioimpedance) measurements were recorded at a single visit to the laboratory after fasting overnight. The mean age was 15.6 ± 1.14 years, body mass was 63.05 ± 7.8 kg, and height was 172 ± 7.5 cm. The RMR values predicted by equations proposed by the Food and Agriculture Organization (FAO) (United Nations), Henry and Rees (HR), Harris Benedict (HB), and Cunningham (CUN) were compared with IC RMR values, by correlation analysis. The FAO and HR predictive equations yielded different values from IC (IC: 1716.26 ± 202.58, HR: 1864.87 ± 147.78, FAO: 1854.28 ± 130.19, p = 0.001). A moderate correlation of 0.504 was found between the results of HB and IC. In the survival-agreement model, the CUN equation showed low disagreement with the IC RMR, with error values between 200 and 300 kcal/day. The results showed that HB and CUN yielded similar values as IC, with the CUN equation showing low disagreement with IC; hence, adolescent athletes should undergo evaluation with precise laboratory methods to ensure that accurate information about RMR is recorded.
Effects of an “Active-Workstation” Cluster RCT on Daily Waking Physical Behaviors

Supplemental digital content is available in the text. ABSTRACT Purpose This study aimed to evaluate the effects of sit-to-stand and treadmill desks on sedentary behavior during a 12-month, cluster-randomized multicomponent intervention with an intent-to-treat design in overweight office workers. Methods Sixty-six office workers were cluster-randomized into a control (n = 21; 8 clusters), sit-to-stand desk (n = 23; 9 clusters), or treadmill desk (n = 22; 7 clusters) group. Participants wore an activPAL™ accelerometer for 7 d at baseline, month 3, month 6, and month 12 and received periodic feedback on their physical behaviors. The primary outcome was total daily sedentary time. Exploratory outcomes included total daily and workplace sedentary, standing and stepping time, and the number of total daily and workplace sedentary, standing, and stepping bouts. Intervention effects were analyzed using random-intercept mixed linear models accounting for repeated measures and clustering effects. Results Total daily sedentary time did not significantly differ between or within groups after 12 months. Month 3 gains were observed in total daily and workplace standing time in both intervention groups (sit-to-stand desk: mean Δ ± SD, 1.03 ± 1.9 h·d−1 and 1.10 ± 1.87 h at work; treadmill desk: mean Δ ± SD, 1.23 ± 2.25 h·d−1 and 1.44 ± 2.54 h at work). At month 3, the treadmill desk users stepped more at the workplace than the control group (mean Δ ± SD, 0.69 ± 0.87 h). Month 6 gains in total daily stepping were observed within the sit-to-stand desk group (mean Δ ± SD, 0.82 ± 1.62 h·d−1), and month 3 gains in stepping at the workplace were observed for the treadmill desk group (mean Δ ± SD, 0.77 ± 0.83 h). These trends were sustained through month 12 in only the sit-to-stand desk group. Conclusions Active-workstation interventions may cause short-term improvements in daily standing and stepping. Treadmill desk users engaged in fewer sedentary bouts, but sit-to-stand desks resulted in more frequent transitions to upright physical behaviors.
Deposition of carbon, deuterium, and metals on the wall and limiters of the Tokamak Fusion Test Reactor

Following a two‐year operational period the Tokamak Fusion Test Reactor (TFTR) graphite fixed bumper limiter has been examined by a variety of methods. The areal density of metals was mapped in situ by beta backscattering. Several tiles were examined in detail by nuclear‐reaction analysis, Rutherford backscattering, and proton‐induced x‐ray emission to measure areal densities of deuterium and impurities. Some areas of the limiter were found to be covered by deposited material several microns thick. Other areas where the incident plasma flux is higher were much cleaner. Long‐term collection coupons were also examined to characterize deposition on the wall. From these results the total amount of deuterium on the limiter and wall in TFTR is estimated to be ∼1.3×1024 atoms. The implications of this for wall‐pumping effects and future tritium inventory are discussed.
Reconstruction of Orbital Exenteration Defects with Cheek Rotation Flaps: Indications, Technique, Complications, Rehabilitation, and Survival

Abstract The objective of this study was to examine the role of cheek rotation flaps in the reconstruction of orbital defects after exenteration. From January 2000 to August 2018, patients undergoing orbital exenteration and reconstruction with cheek rotation flaps were enrolled in this retrospective study. All patients were evaluated for wound complications, orbital rehabilitation, tumor relapse, and survival. Thirty patients completed the study. Fourteen complications allocated to 11 patients were assessed. The most common complications were seroma (13%), temporary facial nerve weakness (13%), and partial necrosis of the flap (10%). A major complication occurred in a total of two patients (7%), so that surgical correction was necessary. Eleven patients had a relapse; 15 patients died as part of the follow-up. Fifteen patients were treated with facial prostheses. The overall survival rate was 61% after 1 year and 42% after 5 years. Follow-up periods ranged from 6 to 95 months. Cheek rotation flap reconstruction after exenteration is a reliable method with a low rate of major complications. It is indicated when an approach to the parotid gland or the neck region is necessary because of suspected lymph node metastasis and in elderly patients because of their skin's laxity. It can be performed as primary or secondary reconstruction. Good esthetic results can be achieved, especially after endosseous implantation.
Assessing the relationship between monoallelic PRKN mutations and Parkinson’s risk

Abstract Biallelic Parkin (PRKN) mutations cause autosomal recessive Parkinson’s disease (PD); however, the role of monoallelic PRKN mutations as a risk factor for PD remains unclear. We investigated the role of single heterozygous PRKN mutations in three large independent case-control cohorts totalling 10 858 PD cases and 8328 controls. Overall, after exclusion of biallelic carriers, single PRKN mutations were more common in PD than controls conferring a >1.5-fold increase in the risk of PD [P-value (P) = 0.035], with meta-analysis (19 574 PD cases and 468 488 controls) confirming increased risk [Odds ratio (OR) = 1.65, P = 3.69E-07]. Carriers were shown to have significantly younger ages at the onset compared with non-carriers (NeuroX: 56.4 vs. 61.4 years; exome: 38.5 vs. 43.1 years). Stratifying by mutation type, we provide preliminary evidence for a more pathogenic risk profile for single PRKN copy number variant (CNV) carriers compared with single nucleotide variant carriers. Studies that did not assess biallelic PRKN mutations or consist of predominantly early-onset cases may be biasing these estimates, and removal of these resulted in a loss of association (OR = 1.23, P = 0.614; n = 4). Importantly, when we looked for additional CNVs in 30% of PD cases with apparent monoallellic PRKN mutations, we found that 44% had biallelic mutations, suggesting that previous estimates may be influenced by cryptic biallelic mutation status. While this study supports the association of single PRKN mutations with PD, it highlights confounding effects; therefore, caution is needed when interpreting current risk estimates. Together, we demonstrate that comprehensive assessment of biallelic mutation status is essential when elucidating PD risk associated with monoallelic PRKN mutations.
Contribution of small tissue biopsy and flow cytometry to preoperative cytological categorization of salivary gland fine needle aspirates according to the Milan System: Single center experience on 287 cases

Milan system for reporting salivary gland cytopathology (MSRSGC) was proposed to provide a standardized reporting system for salivary gland fine needle aspiration biopsies. Modified Menghini type semi‐automatic aspiration biopsy needles provide small tissue fragments (STFs), as well as cellular smears, and immunohistochemical and molecular studies can be performed using the STFs.
A Novel Measure Inspired by Lyapunov Exponents for the Characterization of Dynamics in State-Transition Networks

The combination of network sciences, nonlinear dynamics and time series analysis provides novel insights and analogies between the different approaches to complex systems. By combining the considerations behind the Lyapunov exponent of dynamical systems and the average entropy of transition probabilities for Markov chains, we introduce a network measure for characterizing the dynamics on state-transition networks with special focus on differentiating between chaotic and cyclic modes. One important property of this Lyapunov measure consists of its non-monotonous dependence on the cylicity of the dynamics. Motivated by providing proper use cases for studying the new measure, we also lay out a method for mapping time series to state transition networks by phase space coarse graining. Using both discrete time and continuous time dynamical systems the Lyapunov measure extracted from the corresponding state-transition networks exhibits similar behavior to that of the Lyapunov exponent. In addition, it demonstrates a strong sensitivity to boundary crisis suggesting applicability in predicting the collapse of chaos.
An Inverse Channel Model for Modeling Contaminant Transport

Recent experimental and theoretical investigations of transport in a fracture indicate that fluid flows preferentially through flow channels in the fracture plane. Several one-dimensional (1D) channel models have been introduced to interpret flow and transport through two-dimensional (2D) fractured media. However, those models are not capable of reproducing a tracer breakthrough curve accurately, and the aperture distributions (i.e., aperture mean and standard deviation) predicted by those models cannot characterize flow channels in the fracture. In this paper, we present a new 1D channel model using an inverse algorithm. At a given breakthrough curve, we divide the time domain into a limited number of intervals based on the principle of superposition and then determine aperture distribution of each channel inversely. The new channel model reproduces the tracer breakthrough curve of a fracture almost exactly at a given pressure drop. In addition, the aperture distributions obtained by the new channel model have good agreement with those of 2D modeling of transport in the fracture. In parameter analyses, we found that flow channeling becomes dominant in fracture flow when the coefficient of variation is > 0.3. Therefore the new channel model can effectively simulate flow and tracer transport in a fracture in that range.