Miracle-dz/UniFAR-FTUs huggingface dataset:
ANIMAL MODELS Improved simple T-cannula technique to facilitate surgery and daily skin care of growing pigs

In order to further increase the stability of the cannula behind the ribs and to facilitate cannula exteriorization in growing pigs, the present study aimed to evaluate whether elongation of the cannula flange could increase the stability of the cannula behind the ribs and to develop a tool to improve the exteriorization of the cannula through the ribs. Moreover, it was assessed whether a special skin protection paste and soft polyurethane foam material used in daily skin care could prevent erythema around the fistula. The feasibility of both, the modified simple T-cannula and daily skin care procedure, was evaluated in a digestibility experiment. Simple T-cannulae were made of high-molecular-weight polyethylene and inserted into the distal ileum of eight growing pigs (average body weight at surgery 30 kg). Modifications in the cannula design included a longer flange (11 cm) that was narrowed from the center to the ends and a bending of the flange to adapt it to the curve of the costal arch. In order to reduce the damage to the thread on the outer cannula barrel during surgery, a special surgical plug in conjunction with a screw thread on the inside of the barrel was developed. With respect to the daily cleaning of the fistula, a special skin protection paste was applied on the skin around the fistula to create a waterproof film that entirely sealed the skin. Additionally, foam material was inserted between the retaining ring and the skin to absorb the leaking digesta. Monitoring of the pigs throughout the trial showed that modifications in cannula design proved to be useful as they facilitated exteriorization of the cannula through the ribs and stability of the cannula behind the ribs. Moreover, the use of the skin protection paste and foam material during postsurgical treatment of growing pigs effectively prevented skin irritation around the flank area. F&R "All rights reserved. For permissions, please e-mail" (CopyrightLine) "^nAll rights reserved. For permissions, please e-mail" (CopyrightLine)
Development and Clinical Validation of a Lateral Flow Assay for Urine Fentanyl Screening in the Emergency Department

Background: Rapid identification of fentanyl at the point-of-care is critical. Urine fentanyl concentrations in overdose cases start at single-digit ng/mL. No fentanyl point-of-care assay with cutoff at single-digit ng/mL is available. Methods: A competitive lateral flow assay (LFA) was developed using gold nanoparticles and optimized for rapid screening of fentanyl in 5 minutes. Urine samples from two cohorts of Emergency Department (ED) patients were tested using the LFA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The two cohorts consisted of 218 consecutive ED patients with urine drug-of-abuse screen orders and 7 ED patients with clinically suspected fentanyl overdose, respectively. Results: The LFA detected fentanyl (≥1 ng/mL) and the major metabolite norfentanyl (≥10 ng/mL) with high precision. There was no cross-reactivity with amphetamine, cocaine, morphine, tetrahydrocannabinol, methadone, buprenorphine, naloxone and acetaminophen at 1000 ng/mL, and 0.03%, 0.4% and 0.05% cross-reactivity with carfentanil, risperidone and 9-hydroxyrisperidone, respectively. In 218 consecutive ED patients, the prevalence of cases with fentanyl ≥1 ng/mL or norfentanyl ≥10 ng/mL was 5.5%. The clinical sensitivity and specificity (95% confidence interval (CI)) of the LFA were 100% (75.8–100%) and 99.5% (97.3–99.9%), respectively. The positive and negative predictive values (95% CI) were 92.3% (66.7–98.6%) and 100% (98.2–100%), respectively. The concordance between the LFA and LC-MS/MS was 100% in the 7 suspected fentanyl overdose cases (5 positive, 2 negative). Conclusions: The LFA can detect fentanyl and norfentanyl with high clinical sensitivity and specificity in the ED population. data indicate the clinical need for screening methods to be able to detect fentanyl in urine samples at below single-digit ng/mL and norfentanyl
Mutational Spectrum in the D7-Sterol Reductase Gene and Genotype- Phenotype Correlation in 84 Patients with Smith-Lemli-Opitz Syndrome

Institute of Medical Biology and Human Genetics and Institute of Biochemical Pharmacology, Innsbruck; Department of Biological Chemistry and Kennedy Krieger Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore; Institut für Arterioskleroseforschung, Münster, Germany; Institute of Human Genetics, University of Essen, Essen, Germany; Department of Neuropediatrics and Metabolic Disease, University of Marburg, Marburg, Germany; and Institute of Child Health and Great Ormond Street Hospital, London
Quantitative Hepatic Fat Quantification in NAFLD using Ultrasound-Based Techniques: A Review of Literature and their Diagnostic Performance

Non-alcoholic fatty liver disease (NAFLD) is a condition that is characterized by the presence of >5% fat in the liver and affects over one billion people worldwide. If adequate and early precautions are not taken, NAFLD can progress to cirrhosis and death. The current reference standard for detecting hepatic steatosis is a liver biopsy. However, due to the potential morbidity associated with liver biopsies, non-invasive imaging biomarkers have been extensively investigated. Magnetic resonance imaging (MRI)-based methods have proven accuracy in quantifying liver steatosis; however, these techniques are costly and have limited availability. Ultrasound-based quantitative imaging techniques are increasingly utilized because of their widespread availability, ease of use, and relative cost-effectiveness. Several ultrasound-based liver fat quantification techniques have been investigated, including techniques that measure changes in the acoustic properties of the liver due to the presence of fat. In this review, we will focus on quantitative ultrasound approaches and their diagnostic performance in the realm of NAFLD.
Habitual Physical Activity and Plasma Metabolomic Patterns Distinguish Individuals with Low vs. High Weight Loss during Controlled Energy Restriction 1–4

Background: Total weight loss induced by energy restriction is highly variable even under tightly controlled conditions. Identifyingweight-lossdiscriminantswouldprovideavaluableweightmanagementtoolandinsightsintobodyweightregulation. Objective: This study characterized responsiveness to energy restriction in adults from variables including the plasma metabolome, endocrine and inﬂammatory markers, clinical indices, body composition, diet, and physical activity. Methods: Data were derived from a controlled feeding trial investigating the effect of 3–4 dairy product servings in an energy-restricted diet (2092 kJ/d reduction) over 12 wk. Partial least squares regression was used to identify weight-loss discriminants in 67 overweight and obese adults. Linear mixed models were developed to identify discriminant variable differences in high- vs. low-weight–loss responders. Results: Both pre- and postintervention variables ( n = 127) were identiﬁed as weight-loss discriminants (root mean squared error of prediction = 1.85 kg; Q 2 = 0.43). Compared with low-responders (LR), high-responders (HR) had greater decreases in bodyweight (LR: 2.7 6 1.6 kg; HR: 9.4 6 1.8 kg, P < 0.01), BMI (in kg/m 2 ; LR: 1.0 6 0.6; HR: 3.3 6 0.5, P < 0.01), and total fat (LR: 2.2 6 1.1 kg; HR: 8.0 6 2.1 kg, P < 0.01). Signiﬁcant group effects unaffected by the intervention were determined for the respiratory exchange ratio (LR: 0.86 6 0.05; HR: 0.82 6 0.03, P < 0.01), moderate physical activity (LR: 127 6 52 min; HR: 167 6 68 min, P = 0.02), sedentary activity (LR: 1090 6 99 min; HR: 1017 6 110 min, P = 0.02), and plasma stearate [LR: 102,000 6 21,000 quantiﬁer ion peak height (QIPH); HR: 116,000 6 24,000 QIPH, P = 0.01]. Conclusions: Overweight and obese individuals highly responsive to energy restriction had accelerated reductions in adiposity, likely supported in part by higher lipid mobilization and combustion. A novel observation was that person-to-person differencesinhabitualphysicalactivityandmagnitudeofweightlosswereaccompaniedbyuniquebloodmetabolitesignatures. This trial was registered at clinicaltrials.gov as NCT00858312. J Nutr 2015;145:681–90.
Original Contribution Associations Between Midlife (but Not Late-Life) Elevated Coronary Heart Disease Risk and Lower Cognitive Performance: Results From the Framingham Offspring Study

It is unclear how coronary heart disease (CHD) risk across the adult life span affects late-life cognition. We estimated associations of midlife and late-life elevated CHD risk with cognitive trajectories (general cognitive performance, processing speed/executive function, memory) in later life (after age 55 years or age 70 years) among 2,892 Framingham Offspring Study participants who had completed CHD risk assessments approximately every 4 years since 1971 and had undergone neuropsychological testing between 1999 and 2014. We stratified analyses by apolipoprotein E gene (APOE) ε4 allele carrier status. Using linear mixed-effects models, elevated CHD risk in midlife (age 55 years) was associated with lower levels of general cognitive performance (β = −0.560 standard deviation (SD) units, 95% confidence interval (CI): −0.874, −0.246), executive function (β = −0.624 SD units, 95% CI: −0.916, −0.332), and memory (β = −0.560 SD units, 95% CI: −0.907, −0.213) at age 70 years but not with rates of cognitive change. Late-life (age 70 years) elevated CHD risk, however, was associated with somewhat better levels of general cognitive performance and memory. There were associations between duration of elevated CHD risk during midlife and levels (but not trajectories) of later-life cognitive outcomes. Associations were not modified by APOE-ε4 status. These findings suggest that midlife elevated CHD risk is associated with lower cognition, independently of APOE-ε4 status, suggesting that risk of vascular disease may not contribute a “second hit” to AD risk.
The functional importance of structural differences between the mannitol-specific IIA and the regulatory IIA nitrogen

The three-dimensional structures of the IIA domain of the mannitol-specific phosphoenol-pyruvate dependent phosphotransferase system (PTS) of Escherichia coli and the regulatory IIA"" enzyme have been compared. The enzymes are 20% identical in sequence and contain the sequence motif specific for IIA proteins belonging to the mannitol-fructose family of the PTS. The fold of the enzymes is nearly identical, which confirms their evolution from a common ancestor. Moreover, the phosphorylation site of IIA"'" (His65) and one of the observed conformations of the active site Arg49 are extremely similar to their equivalents (His73 and Arg57) in IIAnt'. In contrast, Hisl20, the equivalent of the second active site His 11 1 of IIA"'", is not located in the active site of IIAnt' but points into the solvent on the other side of the molecule. The different position of His120 makes it unlikely that this residue assists in phosphoryl transfer in the regulatory 1IA""s. As His120 is conserved in all IIA"" enzymes, it could have an essential role in the recognition of the target protein of IIA"".
Current Concepts Review Arti ﬁ cial Intelligence and Orthopaedics An Introduction for Clinicians

(cid:1) Arti ﬁ cial intelligence (AI) provides machines with the ability to perform tasks using algorithms governed by pattern recognition and self-correction on large amounts of data to narrow options in order to avoid errors. (cid:1) The 4 things necessary for AI in medicine include big data sets, powerful computers, cloud computing
Pathogen proﬁle Ralstonia solanacearum , a widespread bacterial plant pathogen in the post-genomic era

NEMO PEETERS* , ALICE GUIDOT, FABIENNE VAILLEAU AND MARC VALLS INRA UMR441 Laboratoire des Interactions Plantes Micro-organismes (LIPM), 24 chemin de Borde Rouge—Auzeville CS 52627, 31326 Castanet Tolosan Cedex, France CNRS UMR2594 Laboratoire des Interactions Plantes Micro-organismes (LIPM), 24 chemin de Borde Rouge—Auzeville CS 52627, 31326 Castanet Tolosan Cedex, France Université de Toulouse, INP, ENSAT, 18 chemin de Borde Rouge, 31326 Castanet Tolosan, France Department of Genetics, University of Barcelona and Centre for Research in Agricultural Genomics (CRAG), Edifici CRAG, Campus UAB, 08193 Bellaterra, Spain
Perspective Of Mice and Men: Impacts of Calorie Restriction on Metabolomics of the Cerebellum

The main purpose of research in mice is to explore metabolic changes in animal models and then predict or propose potential translational benefits in humans. Although some researchers in the brain research field have mentioned that the mouse experiments results still lack the complex neuroanatomy of humans, caution is required to interpret the findings. In mice, we observed in article seventeenth of the series of the effects of graded levels of calorie restriction, metabolomic changes in the cerebellum indicated activation of hypothalamocerebellar connections driven by hunger responses. Therefore, the purpose of the current perspective is to set this latest paper into a wider context of the physiological, behavioral, and molecular changes seen in these mice and to compare and contrast them with previous human studies.
Improvement of Gut Diversity and Composition After Direct-Acting Antivirals in Hepatitis C Virus–Infected Patients With or Without Human Immunodeficiency Virus Coinfection

Background: The influence of direct-acting antivirals (DAAs) on the composition of gut microbiota in hepatitis C virus (HCV)– infected patients with or without human immunodeficiency virus (HIV) is unclear. Methods: We enrolled 62 patients with HCV monoinfection and 24 patients with HCV/HIV coinfection receiving elbasvir-grazoprevir from a clinical trial. Fecal specimens collected before treatment and 12 weeks after treatment were analyzed using amplicon-based 16S ribosomal RNA sequencing. Results: Sustained virological response rates in the monoinfection and coinfection groups were similar (98.4% vs 95.8%). Pretreatment bacterial communities in the patient groups were less diverse and distinct from those of healthy controls. Compared with HCV-monoinfected patients, HCV/HIV-coinfected individuals showed comparable microbial alpha diversity but decreased Firmicutes-Bacteroidetes ratios. The improvement of microbial dysbiosis was observed in responders achieving sustained virological response across fibrosis stages but was not found in nonresponders. Responders with a low degree of fibrosis exhibited a recovery in alpha diversity to levels comparable to those in healthy controls. Reciprocal alterations of increased beneficial bacteria and reduced pathogenic bacteria were also observed in responders. Conclusions: This study indicates a short-term effect of direct-acting antivirals in restoration of microbial dysbiosis. The favor-able changes in gut microbiota profiles after viral eradication might contribute toward the reduction of HCV-related complications among infected individuals.
Conformational Selection in the Recognition of the Snurportin Importin β Binding Domain by Importin β

The structural flexibility of β -karyopherins is critical to mediate the interaction with transport substrates, nucleoporins, and the GTPase Ran. In this paper, we provide structural evidence that the molecular recognition of the transport adaptor snurportin by importin β follows the population selection mechanism. We have captured two drastically different conformations of importin β bound to the snurportin importin β binding domain trapped in the same crystallographic asymmetric unit. We propose the population selection may be a general mechanism used by β karyopherins to recognize transport substrates. Transport factors of the importin β -superfamily (also known as β -karyopherins) include at least 20 different known members in humans (1). β -Karyopherins can function as both import and export receptors, and their interaction with transport cargos is either direct or mediated by adaptors. At the structural level, β -karyopherins share a common helical architecture consisting of 18–21 repeated HEAT repeats (2). During transport, β karyopherins interact simultaneously with import and export cargos and nucleoporins, in a process that is finely regulated by the small GTPase Ran.
Ultra-High-Resolution Ion Mobility Separations Over Extended Path Lengths and Mobility Ranges Achieved using a Multilevel Structures for Lossless Ion Manipulations Module

electrode dimensions; ion funnel dimensions; ion switch schematic; photographs of multilevel SLIM and ion escalator hole; schematics of ion escalator from different views; ion trajectory simulations and associated mobiligrams using other TW speeds; description of SIMION parameters; effect of ion escalator TW amplitude on ion transmission efficiency; effect of guard voltage on ion transmission efficiency; list of heavy-labeled phosphopeptides; and separations of phosphopeptide isomers (PDF) Simulation for ten m/z 602 ions traversing the ion escalator (MP4) Abstract Over the past few years, structures for lossless ion manipulations (SLIM) have used traveling waves (TWs) to move ions over long serpentine paths that can be further lengthened by routing the ions through multiple passages of the same path. Such SLIM “multipass” separations provide unprecedentedly high ion mobility resolving powers but are ultimately limited in their ion mobility range because of the range of mobilities spanned in a single pass; that is, higher mobility ions ultimately “overtake” and “lap” lower mobility ions that have experienced fewer passes, convoluting their arrival time distribution at the detector. To achieve ultrahigh resolution separations over broader mobility ranges, we have developed a new multilevel SLIM possessing multiple stacked serpentine paths. Ions are transferred between SLIM levels through apertures (or ion escalators) in the SLIM surfaces. The initial multilevel SLIM module incorporates four levels and three interlevel ion escalator passages, providing a total path length of 43.2 m. Using the full path length and helium buffer gas, high resolution separations were achieved for Agilent tuning mixture phosphazene ions over a broad mobility range (K 0 ≈ 3.0 to 1.2 cm 2 /(V*s)). High sensitivity was achieved using “in-SLIM” ion accumulation over an extended trapping region of the first SLIM level. High transmission efficiency of ions over a broad mobility range (e.g., K 0 ≈ 3.0 to 1.67 cm 2 /(V*s)) was achieved, with transmission efficiency rolling off for the lower mobility ions (e.g., K 0 ≈ 1.2 cm 2 /(V*s)). Resolving powers of up to ~560 were achieved using all four ion levels to separate reverse peptides (SDGRG 1+ and GRGDS 1+ ). A
Optimization and stability of CD variability in pitch 40 nm contact holes on NXE:3300

Controlling the Global and Local CD uniformity (GCDU and LCDU) of Contact Holes (CH) and the associated edge placement errors are important for the implementation of EUV lithography in high-volume production at memory chip manufacturers. The GCDU describes the average CH CD variability within and between the fields on the wafer, while the LCDU comprises the CH-to-CH variation between neighboring CHs. We have experimentally measured these parameters on a representative memory layer to understand the current performance, and suggest possibilities and pathways for future improvement. We report on an extensive experimental imaging study of a 40 nm pitch square CH array use case, using ASML’s NXE:3300 EUV exposure tool at imec. We decompose the GCDU into Intra-Field and Intra-Wafer signatures, and the LCDU into systematic and stochastic components. Through this decomposition, we can assess the contribution of mask, scanner and resist process. A 10-month monitor evaluates the changes over time of these respective components and the relation between GCDU and LCDU. The mask contribution to LCDU was further examined by a CH-to-CH comparison of mask and wafer measurements. LCDU improvements could be obtained by optimizing the source for a better contrast through focus (6% LCDU improvement w.r.t. a Standard Quasar source shape at best focus, up to 30% in defocus) as well as by a resist stack optimization. Optimized resist stacks delivered 15% improvements in a lower LCDU on one hand, or a lower dose-tosize on the other hand. The results of this pitch 40 nm contact hole study lead to a better understanding of the needs for mask and scanner for the memory use case at 0.33 NA EUV lithography.
Drosophila Furrowed/Selectin is a homophilic cell adhesion molecule stabilizing Frizzled and intercellular interactions during PCP establishment

Summary Establishment of planar cell polarity (PCP) in a tissue requires coordination of directional signals from cell to cell. It is thought that this is mediated by the core PCP factors, which include cell adhesion molecules. Here, we demonstrate that furrowed , the Drosophila Selectin, is required for PCP generation. Disruption of PCP in furrowed -deficient flies results from a primary defect in Fz levels and cell adhesion. Furrowed localizes at/near apical junctions, largely co-localizing with Frizzled and Flamingo (Fmi). It physically interacts with and stabilizes Frizzled, and further, it mediates intercellular Frizzled-Van Gogh (Vang)/Strabismus interactions, similarly to Fmi. Furrowed does so through a homophilic cell adhesion role that is distinct from its known carbohydrate-binding function described during vertebrate blood-cell/endothelial cell interactions. Importantly, the carbohydrate function is dispensable for PCP establishment. In vivo studies suggest that Furrowed functions partially redundantly with Fmi, mediating intercellular Frizzled-Vang interactions between neighboring cells. of defects. a Fw the Fz/PCP core proteins. that cell cell adhesion bridges
Blind deconvolution o fb ar codesignals

Bar code reconstruction involves recovering a clean signal from an observed one that is corrupted by convolution with a kernel and additive noise. The precise form of the convolution kernel is also unknown, making reconstruction harder than in the case of standard deblurring. On the other hand, bar codes are functions that have a very special form—this makes reconstruction feasible. We develop and analyse a tota lv ariation based variational model for the solution of this problem. This new technique models systematically the interaction of neighbouring bars in the bar code under convolution with a kernel, as well as th ee stimation of the unknown parameters of th ek ernel from global information contained in the observed signal.
Biomarker Discovery for Lupus Nephritis Through Longitudinal Urine Proteomics

Lupus nephritis is a frequent and serious complication of systemic lupus erythematosus (SLE). Treatment often requires the use of immunosuppression, and may be associated with severe side effects. The ability to predict relapse, relapse severity, and recovery could be used to more effectively implement therapy and reduce toxicity. We postulated that a proteomic analysis of the low-molecular weight urine proteome using serial urine samples obtained before, during, and after SLE nephritis flares would demonstrate potential biomarkers of SLE renal flare. This study was undertaken to test our hypothesis. Urine from 25 flare cycles of 19 WHO Class III, IV, and V SLE nephritis patients was used. Urine samples included a baseline, and pre-flare, flare, and post-flare specimens. The urines were fractionated to remove proteins larger than 30 kDa, and spotted onto weak cation exchanger (CM10) protein chips for analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). differentially-expressed differentially-expressed of pre-flare at