Miracle-dz/UniFAR-FTUs huggingface dataset:
Building trust in real world evidence (RWE): moving transparency in RWE towards the randomized controlled trial standard

Abstract The increasing use of RWE in regulatory and reimbursement decision-making indicates the significant progress that has been made in building trust in RWE through greater transparency. This review of the published literature and key online sources was conducted to provide an update on progress towards greater transparency in RWE, based on four key barriers to trust identified in a 2016 paper and applying learnings from transparency initiatives established for RCTs, such as the US FDA Amendments Act (FDAAA) 2007 Final Rule. Multiple initiatives from the US FDA, EMA and organizations such as the ISPOR-ISPE Joint Task Force have yielded new guidance documents and tools that enable greater transparency in RWE study methodology (STaRT-RWE and HARPER templates), data source selection and quality (SPIFD2 framework, REQueST tool), strategy (the Center for Open Science RWE Study Registry), and will therefore improve transparency in RWE study reporting. Programs such as the REPEAT Initiative and RWE DUPLICATE are investigating reproducibility of RWE studies and improving understanding of the circumstances when valid inference on treatment effects can be obtained from RWE studies. Further work is needed to embed and to implement the new tools and guidance that are available, and thus raise standards for RWE transparency towards the levels expected for RCTs.
Waves and longshore currents: Comparison of a numerical model with field data

A two-dimensional numerical model is used to predict the shoaling and breaking of surface gravity waves, and the resulting longshore currents, for 5 days of the Nearshore Sediment Transport Study Santa Barbara experiment. Data with incident waves having narrow-banded frequency and directional spectra are selected for comparison in accord with the model assumptions of unidirectional and monochromatic waves. The rms wave height is used for expressing wave energy in the calculations. The current model includes bottom friction, lateral mixing, and nonliner convective accelerations. The extensive field measurements of waves, including quantitative directional information, and longshore current distributions are used to test the model results. The predicted rms wave heights are consistent with the measurements. By tuning the model with field data of longshore currents, the comparison between the model and data shows good agreement, and the obtained values of free parameters are relatively constant for the five experiment days.
Low-level inflammation, immunity, and brain-gut axis in IBS: unraveling the complex relationships

ABSTRACT Irritable bowel syndrome is a common functional gastrointestinal disorder, and it has been shown that the etiology of irritable bowel syndrome is a multifactorial complex of neurological, inflammatory, and immunological changes. There is growing evidence of low-grade chronic inflammation in irritable bowel patients. The peripheral action response of their intestinal immune factors is integrated into the central nervous system, while the microbiota interacts with the brain-gut axis contributing to the development of low-grade chronic inflammation. The objective of this review is to present a discussion about the impact of immune-brain-gut axis-inflammation interactions on irritable bowel syndrome, its clinical relevance in the course of irritable bowel syndrome disease, and possible therapeutic modalities.
Comparison of optical density-based growth kinetics for pure culture Campylobacter jejuni, coli and lari grown in blood-free Bolton broth

Abstract Campylobacter growth kinetic parameters can be used to refine the sensitivity and efficiency of microbial growth-based methods. Therefore, the aim of this study was to construct growth curves for C. jejuni, C. coli, and C. lari in pure culture and calculate growth kinetics for each Campylobacter species in the same environmental conditions. Campylobacter jejuni, C. coli and C. lari were grown over 48 h and inoculated into 15 mL Hungate tubes (N = 3 trials per species; 5 biological replicates per trial; 3 species; 1 strain per species). Absorbance measurements were taken in 45 min intervals over 24 h. Optical density readings were plotted versus time to calculate growth kinetic parameters. C. jejuni exhibited the longest lag phase (p < 0.001) at 15 h 20 min ± 30 min, versus C. coli at 11 h 15 min ± 17 min, and C. lari at 9 h 27 min ± 15 min. The exponential phase duration was no longer than 5 h for all species, and doubling times were all less than 1h 30 min. The variation in growth kinetics for the three species of Campylobacter illustrates the importance of determining individual Campylobacter spp. growth responses for optimizing detection based on low bacterial levels. This study provides kinetics and estimates to define enrichment times necessary for low concentration Campylobacter detection.
Haploid androgenetic development of bovine embryos reveals imbalanced WNT signaling and impaired cell fate differentiation

Abstract Haploid embryos have contributed significantly to our understanding of the role of parental genomes in development and can be applied to important biotechnology for human and animal species. However, development to the blastocyst stage is severely hindered in bovine haploid androgenetic embryos (hAE). To further our understanding of such developmental arrest, we performed a comprehensive comparison of the transcriptomic profile of morula-stage embryos, which were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) of transcripts associated with differentiation in haploid and biparental embryos. Among numerous disturbances, results showed that pluripotency pathways, especially the wingless-related integration site (WNT) signaling, were particularly unbalanced in hAE. Moreover, transcript levels of KLF4, NANOG, POU5F1, SOX2, CDX2, CTNNBL1, AXIN2, and GSK3B were noticeably altered in hAE, suggesting disturbance of pluripotency and canonical WNT pathways. To evaluate the role of WNT on hAE competence, we exposed early Day-5 morula stage embryos to the GSK3B inhibitor CHIR99021. Although no alterations were observed in pluripotency and WNT-related transcripts, exposure to CHIR99021 improved their ability to reach the blastocysts stage, confirming the importance of the WNT pathway in the developmental outcome of bovine hAE. Summary Sentence The importance of the wingless-related integration site pathway on bovine haploid androgenetic development by transcriptomic analysis and identifies pluripotency markers associated with cell fate determination during early development. Graphical Abstract
Effects of Risk Characteristic and Risk Perception on Risk Severity of Natural Disaster

This study was to examine the effects of risk characteristic and risk perception on risk severity of natural disaster. The findings showed that the risk severity of natural disaster were classified into geographical disaster, storm and flood damage, drought damage. Typhoon among storm and flood damage showed high scores on risk severity of natural disaster. Moreover participants showed high scores on unfamiliar, undiscoverable, and unknown by scientific knowledge among risk characteristic of natural disaster. Second, risk characteristic was significantly correlated to risk perception. Third, risk characteristic influenced positively on risk severity of natural disaster. Especially, risk characteristic had great effect on storm and flood damage among natural disaster. Fourth, risk perception influenced positively on risk severity of natural disaster. Especially, risk perception had great effect on storm and flood damage among natural disaster.
Dissolution of K in molten iron at high pressure and temperature

Partitioning of K between molten iron and silicate melt was examined at about 26 GPa and 2600°C using a mixture of pure iron and natural microcline as the starting material. The dissolution of K in molten iron up to about 0.2 wt % was confirmed. The distribution coefficient of K between molten iron and silicate melt was about 3.8×10−2 (atomic ratio). This value suggests the presence of 5 ppm K in the earth's core, yielding 3×1010 W for the present day heat generation by K.
Identifying canonical and replicable multi‐scale intrinsic connectivity networks in 100k+ resting‐state fMRI datasets

Despite the known benefits of data‐driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter‐subject correspondence limits the clinical utility of rsfMRI and its application to single‐subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi‐spatial‐scale canonical intrinsic connectivity network (ICN) templates via the use of multi‐model‐order independent component analysis (ICA). We also study the feasibility of estimating subject‐specific ICNs via spatially constrained ICA. The results show that the subject‐level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. In general, large‐scale ICNs require less data to achieve specific levels of (within‐ and between‐subject) spatial similarity with their templates. Importantly, increasing data length can reduce an ICN's subject‐level specificity, suggesting longer scans may not always be desirable. We also find a positive linear relationship between data length and spatial smoothness (possibly due to averaging over intrinsic dynamics), suggesting studies examining optimized data length should consider spatial smoothness. Finally, consistency in spatial similarity between ICNs estimated using the full data and subsets across different data lengths suggests lower within‐subject spatial similarity in shorter data is not wholly defined by lower reliability in ICN estimates, but may be an indication of meaningful brain dynamics which average out as data length increases.
The use of gravity methods to study the underground structure and impact energy of meteorite craters

Gravity data have been used to calculate the mass deficiency and hence the amount of shattered rock under the Deep Bay, Brent, and Holleford craters. The results show good agreement with the crater model computed by Rottenberg as combined with the depth/diameter ratios of Baldwin for meteorite impact craters. The zone of complete rupture is shown to extend to a depth of approximately one-third of the crater's diameter, and impact energy values, derived from energy of crushing, are 6.5×1023 ergs, 2.1×1024 ergs, and 8.7×1025 ergs for Holleford, Brent, and Deep Bay, respectively.
Improved streambank countermeasures: the Des Moines River (USA) case study

Abstract In the Midwestern USA, bank erosion is a common hazard due to the high erodibility of the bank soils. In this paper, an improved methodology aimed at identifying the optimal countermeasures to control bank erosion was developed and applied in two sites of the Des Moines River (USA). In situ flow measurements, bed bathymetry and soil properties were collected for providing boundary conditions and parameters of the two-dimensional, depth-averaged hydrodynamic finite element surface water modeling system (FESWMS) model. The model was used to compare the hydraulic performances of four streambank countermeasures: riprap lining (referred to as S1); a series of barbs (S2); alternating barbs and spurs (S3); and the combination of barbs with lining (S4). A key feature of FESWMS was its ability to simulate the wetting/drying conditions of mesh elements, which allowed the simulations of unsubmerged or partially submerged structures for different hydraulic conditions. This research showed that the combination of alternating barbs and spurs (S3) was the only design which provided protection during overbank flows at a competitive cost compared to the other designs analysed. The uniqueness of this methodology is found in the coupling of field measurements and theoretical approaches for depth-averaged velocity profiles to calibrate and validate a hydrodynamic model; and in the proposed design to protect streambanks from severe erosion.
Characteristic seismic activity in the subducting plate boundary zone off Kamaishi, northeastern Japan, revealed by precise hypocenter distribution analysis using ocean‐bottom seismometers

High seismic activity prevails along the plate boundary to the east of northeastern Japan. To understand how this seismic activity is related to subduction process, hypocenter locations are re‐determined using data obtained over 6 years by fiber‐cabled permanent ocean bottom seismometers off Kamaishi. The double‐difference method is adopted to obtain the relative location in more detail. As a result of this analysis, a number of seismic clusters including small repeating earthquakes are identified along the plate boundary. This observation supports the hypothesis that seismic coupling is very low in this region and there only small asperities are distributed along the plate boundary off Kamaishi. A number of events with down‐dip compressional focal mechanisms are identified, corresponding to the upper plane seismicity of the double seismic zone in this area. Although most of these events are located in the crust of the subducting Pacific Plate, some are located in the mantle of the slab.
Slowing of EEG waves correlates with striatal [18F]fluorodopa PET/CT uptake and executive dysfunction in Parkinson's disease

Parkinson's disease (PD) research on specific neuroimaging and neurophysiological biomarkers revealing executive dysfunction mechanisms is limited, necessitating validation. Thus, our study aimed to assess associations between electroencephalographic power spectral density (PSD‐EEG), striatal [18F]Fluorodopa uptake and neuropsychological executive function (EF) testing parameters in PD, while also estimating their diagnostic accuracy. We compared resting PSD‐EEG, striatal [18F]Fluorodopa uptake ratios based on positron emission computed tomography ([18F]FDOPA PET/CT) and neuropsychological EF tests outcomes [Trail Making Test (TMT) and Stroop Test (ST)] between PD patients and healthy controls (HCO) and then calculated correlations among these measures separately for each group. Additionally, we estimated PD diagnostic accuracy of the PSD‐EEG and [18F]FDOPA PET/CT parameters. In PD patients, we observed the following: (i) slower EEG waves, reflected in increased power of the EEG theta and lower‐alpha bands in frontal lobe areas; (ii) reduced [18F]FDOPA PET/CT uptake in the putaminal and caudate nuclei, along with a decreased putamen‐to‐caudate ratio ([18F]FDOPA PET/CT PCR); and (iii) longer performance times evident in nearly all EF tests' parameters. Slower EEG waves correlated negatively with [18F]FDOPA PET/CT PCR and positively with most of the EF test parameters. Furthermore, we found negative correlations between [18F]FDOPA PET/CT PCR and certain EF measures related to ST. [18F]FDOPA PET/CT ratios and several PSD‐EEG parameters, particularly those from the prefrontal cortex, demonstrated clinically reasonable diagnostic accuracy for PD. In conclusion, EEG waves slowing in the frontal lobe were correlated with striatal dopaminergic deficiency and impaired executive function in mild PD patients and showed promise as a biomarker of PD‐related executive dysfunction.
Evaluation of Fourier transform-infrared spectroscopy (FT-IR) as a control measure for nosocomial outbreak investigations

ABSTRACT Whole-genome sequencing (WGS) provides greater resolution than other molecular epidemiology strategies and is emerging as a new gold standard approach for microbial strain typing. The Bruker IR Biotyper is designed as a screening tool to identify bacterial isolates that require WGS to establish accurate relationships, but its performance and utility in nosocomial outbreak investigations have not been thoroughly investigated. Here, we evaluated the IR Biotyper by retrospectively examining isolates tested by WGS during investigations of potential nosocomial transmission events or outbreaks. Ninety-eight clinical isolates from 14 different outbreak investigations were examined: three collections of Acinetobacter baumannii (n = 2, n = 9, n = 5 isolates in each collection), one of Escherichia coli (n = 16), two of Pseudomonas aeruginosa (n = 2 and n = 5), two of Serratia marcescens (n = 9 and n = 7), five of Staphylococcus aureus (n = 8, n = 4, n = 3, n = 3, n = 17), and one of Stenotrophomonas maltophilia (n = 8). Linear regression demonstrated a weak, positive correlation between the number of pairwise genome-wide single-nucleotide polymorphisms (SNPs) and IR Biotyper spectral distance values for Gram-positive (r = 0.43, P ≤ 0.0001), Gram-negative (r = 0.1554, P = 0.0639), and all organisms combined (r = 0.342, P ≤ 0.0001). Overall, the IR Biotyper had a positive predictive value (PPV) of 55.81% for identifying strains that were closely related by genomic identity, but a negative predictive value (NPV) of 86.79% for identifying unrelated isolates. When experimentally adjusted cut-offs were applied to A. baumannii, P. aeruginosa, and E. coli, the PPV was 62% for identifying strains that were closely related and the NPV was 100% for identifying unrelated isolates. Implementation of the IR Biotyper as a screening tool in this cohort would have reduced the number of Gram-negative isolates requiring further WGS analysis by 50% and would reduce the number of S. aureus isolates needing WGS resolution by 48%.
Assessment of the Effects of Tidal Mixing in the Kuril Straits on the Formation of the North Pacific Intermediate Water

Abstract To assess accurately the effect of tidal mixing in the Kuril Straits on the formation of the North Pacific Intermediate Water (NPIW), the spatial distribution of diapycnal diffusivity recently obtained by the present authors is incorporated into an eddy-permitting OGCM. It is shown that the NPIW is successfully reproduced, although the diapycnal diffusivity averaged over the entire Kuril Straits is an order of magnitude less than has previously been assumed as a tuning parameter to reproduce the NPIW in low-resolution OGCMs. This strongly suggests that the effect of tidal mixing in the Kuril Straits on the formation of the NPIW is relatively minor and that the physical processes omitted by the low-resolution OGCMs, such as isopycnal mixing along the Kuroshio Extension region, are much more important. This suggestion gives warning of the danger that some misleading conclusions might be derived from OGCMs that employ diapycnal diffusivity just as a tuning parameter to reproduce the observed features.
Seasonal variation of cloud-to-ground lightning flash characteristics in the coastal area of the Sea of Japan

Cloud-to-ground lightning flashes in a coastal area of the Sea of Japan have been observed for a few years by a magnetic direction-finding system for lightning return strokes. Through the operational evaluation of the system, the data obtained so far have been carefully analyzed and corrected. In winter the activity of lightning does not move inland farther than 20–30 km from the coastline, and most of the flashes are detected on the sea. Seasonal variations are also found in polarities and magnetic signal strengths of lightning return strokes.
Maternal and fetal health outcomes in systemic lupus erythematosus pregnancies in the Emirati population: A comparative study

Objectives To evaluate adverse pregnancy outcomes in patients with systemic lupus erythematosus (SLE), compare their maternal and fetal outcomes with those of age-matched pregnant women without SLE, and identify factors linked to increased risks of adverse outcomes. Methods Medical records from Tawam Hospital were reviewed retrospectively to identify patients with SLE and a history of pregnancy. Demographics, clinical variables, and maternal and fetal outcomes were obtained. A one-to-one age-matched healthy control group was randomly selected. The outcomes and odd ratios of women with and without SLE were compared, and factors associated with adverse pregnancy outcomes were examined. Results The outcomes of 78 SLE pregnancies in 39 women were analyzed. Adverse maternal outcomes, such as gestational diabetes mellitus (GDM), occurred in 32% of pregnancies, whereas adverse fetal outcomes, such as low-birth weight and preterm deliveries, occurred in 51% of pregnancies. Pregnant women with SLE had a 5-fold higher risk of GDM, had higher odds of maternal hypertension, and were more likely to deliver through cesarean section than those without SLE. Preterm deliveries and low-birth weight were also more common in SLE pregnancies. Steroid use during pregnancy was significantly associated with an increased risk of GDM development. Lupus nephritis, maternal hypertension, pre-eclampsia, and GDM were linked to preterm deliveries. Conclusion Pregnant women with SLE were at a higher risk for adverse maternal and fetal outcomes than age-matched pregnant women without SLE. These findings can guide clinical management and emphasize the need for close monitoring of SLE pregnancies.
Protein dose requirements to maximize skeletal muscle protein synthesis after repeated bouts of resistance exercise in young trained women

Studies examining the effect of protein (PRO) feeding on post resistance exercise (RE) muscle protein synthesis (MPS) have primarily been performed in men, and little evidence is available regarding the quantity of PRO required to maximally stimulate MPS in trained women following repeated bouts of RE. We therefore quantified acute (4 h and 8 h) and extended (24 h) effects of two bouts of resistance exercise, alongside protein‐feeding, in women, and the PRO requirement to maximize MPS. Twenty‐four RE trained women (26.6 ± 0.7 years, mean ± SEM) performed two bouts of whole‐body RE (3 × 8 repetitions/maneuver at 75% 1‐repetition maximum) 4 h apart, with post‐exercise ingestion of 15 g, 30 g, or 60 g whey PRO (n = 8/group). Saliva, venous blood, and a vastus lateralis muscle biopsy were taken at 0 h, 4 h, 8 h, and 24 h post‐exercise. Plasma leucine and branched chain amino acids were quantified using gas chromatography mass spectrometry (GC–MS) after ingestion of D2O. Fifteen grams PRO did not alter plasma leucine concentration or myofibrillar synthetic rate (MyoFSR). Thirty and sixty grams PRO increased plasma leucine concentration above baseline (105.5 ± 5.3 μM; 120.2 ± 7.4 μM, respectively) at 4 h (151.5 ± 8.2 μM, p < 0.01; 224.8 ± 16.0 μM, p < 0.001, respectively) and 8 h (176.0 ± 7.3 μM, p < 0.001; 281.7 ± 21.6 μM, p < 0.001, respectively). Ingestion of 30 g PRO increased MyoFSR above baseline (0.068 ± 0.005%/h) from 0 to 4 h (0.140 ± 0.021%/h, p < 0.05), 0 to 8 h (0.121 ± 0.012%/h, p < 0.001), and 0 to 24 h (0.099 ± 0.011%/h, p < 0.01). Ingestion of 60 g PRO increased MyoFSR above baseline (0.063 ± 0.003%/h) from 0 to 4 h (0.109 ± 0.011%/h, p < 0.01), 0 to 8 h (0.093 ± 0.008%/h, p < 0.01), and 0 to 24 h (0.086 ± 0.006%/h, p < 0.01). Post‐exercise ingestion of 30 g or 60 g PRO, but not 15 g, acutely increased MyoFSR following two consecutive bouts of RE and extended the anabolic window over 24 h. There was no difference between the 30 g and 60 g responses.
Characterisation of the effects of time on the shaft friction of displacement piles in sand

This paper describes a new approach to represent the effects of time on the shaft friction of displacement piles in sand. The proposal is based on the findings from pile test programmes performed at a test bed site in Western Australia in addition to data from well-documented full-scale pile tests. The investigation reveals a significant influence of installation disturbance on the subsequent gain in capacity (set-up) of shaft friction. Set-up is viewed as a recovery process, rather than a capacity gain, following the disturbance induced by pile installation. Gains in capacity in the medium and longer term tend to vary with the logarithm of time, while capacity changes shortly after installation are seen to be relatively small. A new expression is proposed to represent this ageing characteristic, which also incorporates a limiting (or maximum available) shaft friction.