Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma LOX-Products and Monocyte Signaling Is Reduced by Adjunctive Cyclooxygenase-2 Inhibitor in a Phase I Clinical Trial of Tuberculosis Patients

Introduction Eicosanoids and intracellular signaling pathways are potential targets for host-directed therapy (HDT) in tuberculosis (TB). We have explored the effect of cyclooxygenase 2 inhibitor (COX-2i) treatment on eicosanoid levels and signaling pathways in monocytes. Methods Peripheral blood mononuclear cells isolated from TB patients included in a randomized phase I clinical trial of standard TB treatment with (n=21) or without (n=18) adjunctive COX-2i (etoricoxib) were analyzed at baseline, day 14 and day 56. Plasma eicosanoids were analyzed by ELISA and liquid chromatography-mass spectrometry (LC-MS), plasma cytokines by multiplex, and monocyte signaling by phospho-flow with a defined set of phospho-specific antibodies. Results Lipoxygenase (LOX)-derived products (LXA4 and 12-HETE) and pro-inflammatory cytokines were associated with TB disease severity and were reduced during TB therapy, possibly accelerated by adjunctive COX-2i. Phosphorylation of p38 MAPK, NFkB, Erk1/2, and Akt in monocytes as well as plasma levels of MIG/CXCL9 and procalcitonin were reduced in the COX-2i group compared to controls. Conclusion COX-2i may reduce excess inflammation in TB via the LOX-pathway in addition to modulation of phosphorylation patterns in monocytes. Immunomodulatory effects of adjunctive COX-2i in TB should be further investigated before recommended for use as a HDT strategy.
Vaccines and Senior Travellers

Background: International tourist travel has been increasingly steadily in recent years, and looks set to reach unprecedented levels in the coming decades. Among these travellers, an increasing proportion is aged over 60 years, and is healthy and wealthy enough to be able to travel. However, senior travellers have specific risks linked to their age, health and travel patterns, as compared to their younger counterparts. Methods: We review here the risk of major vaccine-preventable travel-associated infectious diseases, and forms and efficacy of vaccination for these diseases. Results: Routine vaccinations are recommended for older persons, regardless of whether they travel or not (e.g., influenza, pneumococcal vaccines). Older individuals should be advised about the vaccines that are recommended for their age group in the framework of the national vaccination schedule. Travel-specific vaccines must be discussed in detail on a case-by-case basis, and the risk associated with the vaccine should be carefully weighed against the risk of contracting the disease during travel. Travel-specific vaccines reviewed here include yellow fever, hepatitis, meningococcal meningitis, typhoid fever, cholera, poliomyelitis, rabies, Japanese encephalitis, tick-borne encephalitis and dengue. Conclusion: The number of older people who have the good health and financial resources to travel is rising dramatically. Older travellers should be advised appropriately about routine and travel-specific vaccines, taking into account the destination, duration and purpose of the trip, the activities planned, the type of accommodation, as well as patient-specific characteristics, such as health status and current medications.
Peripheral Nerve Focused Ultrasound Lesioning—Visualization and Assessment Using Diffusion Weighted Imaging

Objectives: Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive targeted tissue ablation technique that can be applied to the nervous system. Diffusion weighted imaging (DWI) can visualize and evaluate nervous system microstructure. Tractography algorithms can reconstruct fiber bundles which can be used for treatment navigation and diffusion tensor imaging (DTI) metrics permit the quantitative assessment of nerve microstructure in vivo. There is a need for imaging tools to aid in the visualization and quantitative assessment of treatment-related nerve changes in MRgFUS. We present a method of peripheral nerve tract reconstruction and use DTI metrics to evaluate the MRgFUS treatment effect. Materials and Methods: MRgFUS was applied bilaterally to the sciatic nerves in 6 piglets (12 nerves total). T1-weighted and diffusion images were acquired before and after treatment. Tensor-based and constrained spherical deconvolution (CSD) tractography algorithms were used to reconstruct the nerves. DTI metrics of fractional anisotropy (FA), and mean (MD), axial (AD), and radial diffusivities (RD) were measured to assess acute (<1–2 h) treatment effects. Temperature was measured in vivo via MR thermometry. Histological data was collected for lesion assessment. Results: The sciatic nerves were successfully reconstructed in all subjects. Tract disruption was observed after treatment using both CSD and tensor models. DTI metrics in the targeted nerve segments showed significantly decreased FA and increased MD, AD, and RD. Transducer output power was positively correlated with lesion volume and temperature and negatively correlated with MD, AD, and RD. No correlations were observed between FA and other measured parameters. Conclusions: DWI and tractography are effective tools for visualizing peripheral nerve segments for targeting in non-invasive surgical methods and for assessing the microstructural changes that occur following MRgFUS treatment.
Impacts of Electric Road Systems on the German and Swedish Electricity Systems—An Energy System Model Comparison

This study analyses the impacts of electrification of the transport sector, involving both static charging and electric road systems (ERS), on the Swedish and German electricity systems. The impact on the electricity system of large-scale ERS is investigated by comparing the results from two model packages: 1) a modeling package that consists of an electricity system investment model (ELIN) and electricity system dispatch model (EPOD); and 2) an energy system investment and dispatch model (SCOPE). The same set of scenarios are run for both model packages and the results for ERS are compared. The modeling results show that the additional electricity load arising from large-scale implementation of ERS is mainly, depending on model and scenario, met by investments in wind power in Sweden (40–100%) and in both wind (20–75%) and solar power (40–100%) in Germany. This study also concludes that ERS increase the peak power demand (i.e., the net load) in the electricity system. Therefore, when using ERS, there is a need for additional investments in peak power units and storage technologies to meet this new load. A smart integration of other electricity loads than ERS, such as optimization of static charging at the home location of passenger cars, can facilitate efficient use of renewable electricity also with an electricity system including ERS. A comparison between the results from the different models shows that assumptions and methodological choices dictate which types of investments are made (e.g., wind, solar and thermal power plants) to cover the additional demand for electricity arising from the use of ERS. Nonetheless, both modeling packages yield increases in investments in solar power (Germany) and in wind power (Sweden) in all the scenarios, to cover the new electricity demand for ERS.
The Role of Upper Body Biomechanics in Elite Racewalkers

The aim of this study was to analyze the link between the upper and lower body during racewalking. Fifteen male and 16 female racewalkers were recorded in a laboratory as they racewalked at speeds equivalent to their 20-km personal records [men: 1:23:12 (±2:45); women: 1:34:18 (±5:15)]; a single representative trial was chosen from each athlete for analysis and averaged data analyzed. Spatial variables (e.g., stride length) were normalized to stature and referred to as ratios. None of the peak upper body joint angles were associated with speed (p < 0.05) and there were no correlations between pelvic motion and speed, but a medium relationship was observed between peak pelvic external rotation (right pelvis rotated backwards) and stride length ratio (r = 0.37). Greater peak shoulder extension was associated with lower stride frequencies (r = −0.47) and longer swing times (r = 0.41), whereas peak elbow flexion had medium associations with flight time (r = −0.44). Latissimus dorsi was the most active muscle at toe-off during peak shoulder flexion; by contrast, pectoralis major increased in activity just before initial contact, concurrent with peak shoulder extension. Consistent but relatively low rectus abdominis and external oblique activation was present throughout the stride, but increased in preparation for initial contact during late swing. The movements of the pelvic girdle were important for optimizing spatiotemporal variables, showing that this exaggerated movement allows for greater stride lengths. Racewalkers should note however that a larger range of shoulder swing movements was found to be associated with lower stride frequency, and smaller elbow angles with increased flight time, which could be indicative of faster walking but can also lead to visible loss of contact. Coaches should remember that racewalking is an endurance event and development of resistance to fatigue might be more important than strength development.
Preparation of the Endometrium for Frozen Embryo Transfer: A Systematic Review

Despite the worldwide increase in frozen embryo transfer, the search for the best protocol to prime endometrium continues. Well-designed trials comparing various frozen embryo transfer protocols in terms of live birth rates, maternal, obstetric and neonatal outcome are urgently required. Currently, low-quality evidence indicates that, natural cycle, either true natural cycle or modified natural cycle, is superior to hormone replacement treatment protocol. Regarding warmed blastocyst transfer and frozen embryo transfer timing, the evidence suggests the 6th day of progesterone start, LH surge+6 day and hCG+7 day in hormone replacement treatment, true natural cycle and modified natural cycle protocols, respectively. Time corrections, due to inter-personal differences in the window of implantation or day of vitrification (day 5 or 6), should be explored further. Recently available evidence clearly indicates that, in hormone replacement treatment and natural cycles, there might be marked inter-personal variation in serum progesterone levels with an impact on reproductive outcomes, despite the use of the same dose and route of progesterone administration. The place of progesterone rescue protocols in patients with low serum progesterone levels one day prior to warmed blastocyst transfer in hormone replacement treatment and natural cycles is likely to be intensively explored in near future.
Online Learning and Memory of Neural Trajectory Replays for Prefrontal Persistent and Dynamic Representations in the Irregular Asynchronous State

In the prefrontal cortex (PFC), higher-order cognitive functions and adaptive flexible behaviors rely on continuous dynamical sequences of spiking activity that constitute neural trajectories in the state space of activity. Neural trajectories subserve diverse representations, from explicit mappings in physical spaces to generalized mappings in the task space, and up to complex abstract transformations such as working memory, decision-making and behavioral planning. Computational models have separately assessed learning and replay of neural trajectories, often using unrealistic learning rules or decoupling simulations for learning from replay. Hence, the question remains open of how neural trajectories are learned, memorized and replayed online, with permanently acting biological plasticity rules. The asynchronous irregular regime characterizing cortical dynamics in awake conditions exerts a major source of disorder that may jeopardize plasticity and replay of locally ordered activity. Here, we show that a recurrent model of local PFC circuitry endowed with realistic synaptic spike timing-dependent plasticity and scaling processes can learn, memorize and replay large-size neural trajectories online under asynchronous irregular dynamics, at regular or fast (sped-up) timescale. Presented trajectories are quickly learned (within seconds) as synaptic engrams in the network, and the model is able to chunk overlapping trajectories presented separately. These trajectory engrams last long-term (dozen hours) and trajectory replays can be triggered over an hour. In turn, we show the conditions under which trajectory engrams and replays preserve asynchronous irregular dynamics in the network. Functionally, spiking activity during trajectory replays at regular timescale accounts for both dynamical coding with temporal tuning in individual neurons, persistent activity at the population level, and large levels of variability consistent with observed cognitive-related PFC dynamics. Together, these results offer a consistent theoretical framework accounting for how neural trajectories can be learned, memorized and replayed in PFC networks circuits to subserve flexible dynamic representations and adaptive behaviors.
The Impact of Naturalistic Age Stereotype Activation

Almost self-fulfilling, commonly held negative stereotypes about old age and memory can impair older adults’ episodic memory performance, due to age-based stereotype threat or self-stereotyping effects. Research studies demonstrating detrimental impacts of age stereotypes on memory performance are generally conducted in research laboratories or medical settings, which often underestimate memory abilities of older adults. To better understand the “real world” impact of negative age and memory stereotypes on episodic memory, the present research tested story recall performance of late middle-aged and older adults (N = 51) following a naturalistic age stereotype manipulation, wherein every day, newspaper-style materials (comics and puzzles) were either embedded with negative age and memory stereotype stimuli (stereotype group) or neutral stimuli (control group). Furthermore, all participants were tested in favorable, familiar environments. Potential moderators of the stereotype effects, e.g., metamemory beliefs, were assessed at baseline. Current memory evaluation and subjective age, as well as perceived stereotype threat and task-related anxiety, were assessed following the stereotype manipulation as potential mechanisms of the expected stereotype effects. Results suggested a contrast effect, as the stereotype group demonstrated superior story recall performance compared to the control group. Marginally significant moderation effects by age and perceived stereotype threat indicated that stereotype rejection was present for late middle-aged adults but not older adults, indicative of stereotype lift, and for individuals who reported low and average, but not high, levels of perceived stereotype threat. Additionally, a trend suggested more positive memory evaluation for those in the stereotype group who reported awareness of the stereotype stimuli than those who did not notice the stimuli. These results are consistent with other research demonstrating benefits to memory performance in adulthood based on motivational and contextual factors, such as using relevant memory materials and testing in favorable conditions. Moreover, the results of this study contribute to our understanding of individuals’ responses to different types of stereotype stimuli, and the differential impact of stereotype manipulations that are subtle versus blatant. Individuals were motivated to counteract negative stereotype effects when conditions were supportive, stereotype presentations were naturalistic, and personal beliefs were positive.
Oceanic Diel Vertical Movement Patterns of Blue Sharks Vary With Water Temperature and Productivity to Change Vulnerability to Fishing

In the pelagic environment diel vertical movements (DVM) are widespread across taxa, from zooplankton ascending from day-time depths into surface layers at night to avoid visual predators, to apex predators following prey movements to maximise foraging opportunities. The drivers of DVM in large predators such as pelagic sharks have only recently begun to be investigated in detail with the advent of sophisticated archival tags and high-resolution oceanographic datasets. In this study, we satellite tagged adult [>180 cm fork length, (FL)] blue sharks (Prionace glauca) in the North Atlantic Ocean to examine behavioural changes in response to the encountered environment, and therefore, to determine potential risks of capture using pelagic longline fisheries data. Although blue sharks recurrently use surface waters, cyclic diel behaviours were observed, with >95% of night-time spent above 250 m depth and variable day-time depth use. Hence, three different diel behaviours were identified during the tracking period: (i) regular normal DVM (nDVM) (dawn descent – dusk ascent, with over 90% of nighttime spent above 250 m, and between 5 and 50% of the day below this threshold); (ii) surface-oriented behaviour (occupation of surface waters both day and night), and (iii) deep depth-oriented nDVM [dawn descent – dusk ascent, with the majority (>50%) of daytime spent at depth]. Importantly, diel behaviours generally occurred in different ocean regions with nDVM frequently observed in high latitudes, associated with cold, highly productive waters (e.g., North Atlantic Current/Labrador Current convergence zone, West African upwelling area), while depth-oriented nDVM was observed in warm, oligotrophic areas. Thus, day-time occupation of shallow waters significantly increased with lower water temperature at depth (100 m), and with increasing concentration (and decreasing depth) of the chlorophyll a maximum. During nights of full moon blue sharks spent significantly more time in the depth range of longline hooks, while fishing effort and catches were also higher. We demonstrate that increased occupancy of surface layers driven by highly productive, cold waters and greater lunar illumination lead to higher capture risk. Understanding habitat-specific vulnerability to fishing in a commercially important pelagic shark species is essential for improving management and conservation measures.
Swedish and Norwegian Police Interviewers' Goals, Tactics, and Emotions When Interviewing Suspects of Child Sexual Abuse

As the suspect interview is one of the key elements of a police investigation, it has received a great deal of merited attention from the scientific community. However, suspect interviews in child sexual abuse (CSA) investigations is an understudied research area. In the present mixed-methods study, we examine Swedish (n = 126) and Norwegian (n = 52) police interviewers' self-reported goals, tactics, and emotional experiences when conducting interviews with suspected CSA offenders. The quantitative analyses found associations between the interviewers' self-reported goals, tactics, and emotions during these types of suspect interviews. Interviewers who reported experiencing more negative emotions were more likely to employ confrontational tactics. Specifically, anger was positively associated with the goal of obtaining a confession and with aggressive tactics like raising one's voice and emphasizing the seriousness of the crime. Frustration and disgust displayed similar patterns. Somewhat contrasting these quantitative results, the thematic analysis identified a strong consensus that emotions should not and do not affect the police interviewers' work. Furthermore, the police interviewers described a range of strategies for managing emotions during the interview and for processing their emotional reactions afterwards. The present findings highlight the relevance of emotional processes in CSA suspect interviews and provide an initial exploration of the potentially complex relationship between the goals, tactics, and emotional experiences of police interviewers who question CSA suspects.
Global Transcriptomics Uncovers Distinct Contributions From Splicing Regulatory Proteins to the Macrophage Innate Immune Response

Pathogen sensing via pattern recognition receptors triggers massive reprogramming of macrophage gene expression. While the signaling cascades and transcription factors that activate these responses are well-known, the role of post-transcriptional RNA processing in modulating innate immune gene expression remains understudied. Given their crucial role in regulating pre-mRNA splicing and other RNA processing steps, we hypothesized that members of the SR/hnRNP protein families regulate innate immune gene expression in distinct ways. We analyzed steady state gene expression and alternatively spliced isoform production in ten SR/hnRNP knockdown RAW 264.7 macrophage-like cell lines following infection with the bacterial pathogen Salmonella enterica serovar Typhimurium (Salmonella). We identified thousands of transcripts whose abundance is increased or decreased by SR/hnRNP knockdown in macrophages. Notably, we observed that SR and hnRNP proteins influence expression of different genes in uninfected versus Salmonella-infected macrophages, suggesting functionalization of these proteins upon pathogen sensing. Likewise, we found that knockdown of SR/hnRNPs promoted differential isoform usage (DIU) for thousands of macrophage transcripts and that these alternative splicing changes were distinct in uninfected and Salmonella-infected macrophages. Finally, having observed a surprising degree of similarity between the differentially expressed genes (DEGs) and DIUs in hnRNP K and U knockdown macrophages, we found that hnRNP K and U knockdown macrophages are both more restrictive to Vesicular Stomatitis Virus (VSV), while hnRNP K knockdown macrophages are more permissive to Salmonella Typhimurium. Based on these findings, we conclude that many innate immune genes evolved to rely on one or more SR/hnRNPs to ensure the proper magnitude of their induction, supporting a model wherein pre-mRNA splicing is critical for regulating innate immune gene expression and controlling infection outcomes in macrophages ex vivo.
Phenotypic and Genetic Characterization of Temperature-Induced Mutagenesis and Mortality in Cupriavidus metallidurans

Cupriavidus metallidurans strains display a decreased viability when incubated in rich medium at a temperature of 37°C compared to their normal growth temperature of 30°C, a phenomenon coined “temperature-induced mortality and mutagenesis” (TIMM). To scrutinize this aberrant phenotype further, the contributions of specific inducers and protective agents were determined. Different growth media, including lysogeny broth (LB) and Schatz, and components, including casamino acids, in particular amino acids (proline, cysteine, glycine, glutamine, leucine, histidine and phenylalanine) and ammonium, were found to induce TIMM at 37°C. Sorbitol was found to counteract TIMM. Furthermore, although TIMM is well conserved within the C. metallidurans species, multiple and strain-specific TIMM inducers exist. Twenty-nine percent of the TIMM survivors inherited resistance to TIMM. Whole-genome sequencing of two resistant derivatives revealed an important role of an uncharacterized oxidoreductase, indicating putative metabolic poisoning when grown in high-concentration nitrogen-containing media at 37°C.