julilili42/papers huggingface dataset:
Experimental and Computational Aspects of Electrochemical Reflection Anisotropy Spectroscopy: A Review
2023-03-22

Abstract Electrode/electrolyte interfaces play a crucial role in many electrochemical energy conversion and storage technologies. Hence, a deep understanding of the interfacial structure, energetic alignment and processes is of high relevance and has triggered the development of a number of in situ and operando techniques. One approach for gaining information about the change in surface chemistry and structure on an atomic scale is reflection anisotropy spectroscopy (RAS). This review presents and discusses the continuing effort to develop RAS as an in situ optical probe for solid‐liquid interfaces under applied potentials. Experimental and computational basic principles are presented and key challenges of electrochemical RAS are highlighted. Furthermore, we exemplarily demonstrate the potential of the method for spectroelectrochemistry, focusing on indium phosphide‐ and gold‐aqueous electrolyte interfaces as exemplary case studies, and outline research directions for battery systems.
World tuberculosis day 2023 – Reflections on the spread of drug-resistant tuberculosis by travellers and reducing risk in forcibly displaced populations
2023-03-22

World Tuberculosis (TB) Day, March 24th, 2023, will commemorate the day in 1882 when Professor Robert Koch announced his discovery of Mycobacterium tuberculosis (Mtb) when TB ravaged Europe. Over a century later, in 1993, the World Health Organization (WHO) declared TB a global health emergency. Since then, there have been 60 million deaths due to TB. The tragic state of affairs reflects a great paradox – that, despite affordable and effective TB treatment being available for the past seven decades, the latest 2022 WHO Annual Global Tuberculosis Report highlights that TB remains a leading cause of ill health and death from an infectious disease worldwide [1]. In 2021, the WHO estimated that 10.6 million people fell sick with TB worldwide: six million men, 3.4 million women and 1.2 million children. Multidrug-resistant TB (MDR-TB) remains a threat to global health security. Only one in three people with drug-resistant TB can access treatment; many remain undiagnosed and untreated. TB today occurs in every part of the world. An estimated 1 billion people have latent Mtb infection (LTBI), where the mycobacteria do not cause clinical disease but serve as a reservoir and can re-activate at any time under conditions of stress, malnutrition, poor housing, co-infections and co-morbidities, among other [35]
Deceleration capacity of heart rate predicts 1‐year mortality in patients undergoing transcatheter edge‐to‐edge mitral valve repair
2023-03-22

Abstract Background Risk stratification for transcatheter procedures in patients with severe mitral regurgitation is challenging. Deceleration capacity (DC) has already proven to be a reliable risk predictor in patients undergoing transcatheter aortic valve implantation. We hypothesized, that DC provides prognostic value in patients undergoing transcatheter edge‐to‐edge mitral valve repair (TEER). Methods We retrospectively analyzed electrocardiogram signals from 106 patients undergoing TEER at the University Hospital of Tübingen. All patients received continuous heart‐rate monitoring to assess DC following the procedure. One‐year all‐cause mortality was defined as the primary end point. Results Sixteen patients (15.1%) died within 1 year. The DC in nonsurvivors was significantly reduced compared to survivors (5.1 ± 3.0 vs. 3.0 ± 1.6 ms, p = 0.002). A higher EuroSCORE II and impaired left ventricular function were furthermore associated with poor outcome. In Cox regression analyses, a DC &lt; 4.5 ms was found a strong predictor of 1‐year mortality (hazard ratio: 0.10, 95% confidence interval: 0.13–0.79, p = 0.029). Finally, a significant negative correlation was found between DC and residual mitral regurgitation after TEER ( r = −0.41, p &lt; 0.001). Conclusion In patients with severe mitral regurgitation undergoing TEER, DC may serve as a new predictor of follow‐up mortality.
FOMSy: 3D-printed flexible open-source microfluidic system and flow synthesis of PET-tracer
2023-03-22

Abstract In this work, we introduce a low-cost open-source flow system that includes a dual syringe pump with implemented pressure sensor and back pressure regulator. The entire system can be built for around 500 €. Commercially available flow systems can be very expensive with equipment starting at, but often greatly exceeding, 10,000 €. This high price of entry makes such technology prohibitively expensive for many research groups. Such systems stand to benefit the emerging academic pharmaceutical field by providing the experience and availability of reliable and affordable solutions. To implement accessible flow chemistry at research facilities, the systems must be made affordable. In addition, space in research laboratories is usually limited and commercially available flow systems can be very bulky. Having a compact and individually adjustable system is thus beneficial, with 3D printing technology offering the solution. Our compact 3D-printed system meets the needs of many applications in flow chemistry research as well as educational requirements for universities. As a proof of concept, we conceptualized, developed, and tested a custom flow system that can be used to synthesize [ 18 F]2-fluoro-2-desoxy-d-glucose ([ 18 F]FDG), the most commonly used PET-tracer. This system was designed to perform the typical functions and operations required in radiotracer production i.e. radiofluorination, dilution, SPE-trapping, deprotection, and SPE-elution. With this proof-of-concept in hand, the system can be easily customized to produce other radiopharmaceuticals. Graphical Abstract
Molecular characterisation of a rabbit Hepatitis E Virus strain detected in a chronically HEV-infected individual from Germany
2023-03-22

In immunocompromised individuals persisting viremia frequently leads to a chronic hepatitis E virus (HEV) infection. Zoonotic transmission of HEV from pigs and wild boar to humans is proven and sporadic infections with rabbit HEV (raHEV) have recently been reported. Here, the molecular characterisation of a raHEV strain isolated from an immunocompromised, chronically HEV-infected, heart-transplanted patient is described. After successful ribavirin (RBV) treatment of a HEV infection in 2019, the patient was again tested HEV positive in 2021 and received a second RBV therapy cycle. Full-length HEV genome amplification and next generation sequencing was performed on a plasma sample taken between first and second cycle of RBV therapy and a stool sample taken two months after starting the second cycle. The sequence of plasma (raHEV-83) and stool (raHEV-99) derived virus showed the highest nucleotide sequence identity to a Chinese raHEV and a phylogenetic relationship to a raHEV strain isolated from a French patient. Furthermore, sequence analysis revealed the presence of RBV-associated substitutions V1479I and G1634K in the HEV sequences from plasma and additionally K1398R from stool. The results underline the role of rabbits as putative sources of HEV infection and emphasize the need of a one health concept for a better understanding of HEV epidemiology and to develop tools for prevention and control of HEV infection.
Axonal damage and astrocytosis are biological correlates of grey matter network integrity loss: a cohort study in autosomal dominant Alzheimer disease
2023-03-22

Abstract Brain development and maturation leads to grey matter networks that can be measured using magnetic resonance imaging. Network integrity is an indicator of information processing capacity which declines in neurodegenerative disorders such as Alzheimer disease (AD). The biological mechanisms causing this loss of network integrity remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and network integrity in mutation carriers (N=219) and noncarriers (N=136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Aβ, Tau, synaptic (SNAP-25, neurogranin) and neuronal calcium-sensor protein (VILIP-1) preceded grey matter network disruptions by several years, while inflammation related (YKL-40) and axonal injury (NfL) abnormalities co-occurred and correlated with network integrity. This suggests that axonal loss and inflammation play a role in structural grey matter network changes. Key points - Abnormal levels of fluid markers for neuronal damage and inflammatory processes in CSF are associated with grey matter network disruptions. - The strongest association was with NfL, suggesting that axonal loss may contribute to disrupted network organization as observed in AD. - Tracking biomarker trajectories over the disease course, changes in CSF biomarkers generally precede changes in brain networks by several years.
Fever-like temperature impacts onStaphylococcus aureusandPseudomonas aeruginosainteraction, physiology, and virulence bothin vitroandin vivo
2023-03-22

Abstract Background Staphylococcus aureus and Pseudomonas aeruginosa cause a wide variety of bacterial infections and coinfections, showing a complex interaction that involves the production of different metabolites and metabolic changes. Temperature is a key factor for bacterial survival and virulence and within the host, bacteria could be exposed to an increment in temperature during fever development. We analyzed the previously unexplored effect of fever-like temperatures (39°C) on S. aureus USA300 and P. aeruginosa PAO1 microaerobic mono- and co-cultures compared with 37°C, by using RNAseq and physiological assays including in-vivo experiments. Results In general terms both temperature and co-culturing had a strong impact on both PA and SA with the exception of the temperature response of monocultured PA. We studied metabolic and virulence changes on both species. Altered metabolic features at 39°C included arginine biosynthesis and the periplasmic glucose oxidation in S. aureus and P. aeruginosa monocultures respectively. When PA co-cultures were exposed at 39°C they upregulated ethanol oxidation related genes along with an increment in organic acid accumulation. Regarding virulence factors, monocultured SA showed an increase in the mRNA expression of the agr operon and hld, pmsα and pmsβ genes at 39°C. Supported by mRNA data, we performed physiological experiments and detected and increment in hemolysis, staphylxantin production and a decrease in biofilm formation at 39°C. On the side of PA monocultures, we observed increase in extracellular lipase and protease and biofilm formation at 39°C along with a decrease in motility in correlation with changes observed at mRNA abundance. Additionally, we assessed host-pathogen interaction both in-vitro and in-vivo . S. aureus monocultured at 39°C showed a decrease in cellular invasion and an increase in IL-8 -but not in IL-6- production by A549 cell line. PA also decreased its cellular invasion when monocultured at 39°C and did not induce any change in IL-8 or IL-6 production. PA strongly increased cellular invasion when co-cultured at 37°C and 39°C. Finally, we observed increased lethality in mice intranasally inoculated with S. aureus monocultures pre-incubated at 39°C and even higher levels when inoculated with co-cultures. The bacterial burden for P. aeruginosa was higher in liver when the mice were infected with co-cultures previously incubated at 39°C comparing with 37°C. Conclusion Our results highlight a relevant change in the virulence of bacterial opportunistic pathogens exposed to fever-like temperatures in presence of competitors, opening new questions related to bacteria-bacteria and host-pathogen interactions and coevolution.
International Mediation, Identity Construction, and Normative Change
2023-03-22

Abstract In this article, I argue the following: mediation can operate as an arena in which identities are reconstructed while the very occurrence of mediation can trigger and fuel processes of identity reconstruction. More precisely, the norms promoted through mediation can serve to reconstruct the identities of the conflict parties. I will make this claim by examining two contemporary instances of mediation in Syria and Yemen, cases which diverge in the third-party peacemaking approach taken. I investigate these cases by gathering and thematically analyzing an original qualitative dataset comprising 74 semi-structured interviews, 50 press conferences, and 110 official documents. My analysis challenges existing literature concerning the intertwinement of norms, identity, and mediation; contributes to our understanding of how identities in Syria and Yemen were transformed following the revolutions of 2011; and interrogates traditional understandings of the purpose and effects of mediation.
Complications of Intravenous Tenecteplase Versus Alteplase for the Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
2023-03-23

Background: Prior systematic reviews have compared the efficacy of intravenous tenecteplase and alteplase in acute ischemic stroke, assigning their relative complications as a secondary objective. The objective of the present study is to determine whether the risk of treatment complications differs between patients treated with either agent. Methods: We performed a systematic review including interventional studies and prospective and retrospective, observational studies enrolling adult patients treated with intravenous tenecteplase for ischemic stroke (both comparative and noncomparative with alteplase). We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and the www.ClinicalTrials.gov registry from inception through June 3, 2022. The primary outcome was symptomatic intracranial hemorrhage, and secondary outcomes included any intracranial hemorrhage, angioedema, gastrointestinal hemorrhage, other extracranial hemorrhage, and mortality. We performed random effects meta-analyses where appropriate. Evidence was synthesized as relative risks, comparing risks in patients exposed to tenecteplase versus alteplase and absolute risks in patients treated with tenecteplase. Results: Of 2226 records identified, 25 full-text articles (reporting 26 studies of 7913 patients) were included. Sixteen studies included alteplase as a comparator, and 10 were noncomparative. The relative risk of symptomatic intracranial hemorrhage in patients treated with tenecteplase compared with alteplase in the 16 comparative studies was 0.89 ([95% CI, 0.65–1.23]; I 2 =0%). Among patients treated with low dose (&lt;0.2 mg/kg; 4 studies), medium dose (0.2–0.39 mg/kg; 13 studies), and high dose (≥0.4 mg/kg; 3 studies) tenecteplase, the RRs of symptomatic intracranial hemorrhage were 0.78 ([95% CI, 0.22–2.82]; I 2 =0%), 0.77 ([95% CI, 0.53–1.14]; I 2 =0%), and 2.31 ([95% CI, 0.69–7.75]; I 2 =40%), respectively. The pooled risk of symptomatic intracranial hemorrhage in tenecteplase-treated patients, including comparative and noncomparative studies, was 0.99% ([95% CI, 0%–3.49%]; I 2 =0%, 7 studies), 1.69% ([95% CI, 1.14%–2.32%]; I 2 =1%, 23 studies), and 4.19% ([95% CI, 1.92%–7.11%]; I 2 =52%, 5 studies) within the low-, medium-, and high-dose groups. The risks of any intracranial hemorrhage, mortality, and other studied outcomes were comparable between the 2 agents. Conclusions: Across medium- and low-dose tiers, the risks of complications were generally comparable between those treated with tenecteplase versus alteplase for acute ischemic stroke.
Gamification of an n-back working memory task – Is it worth the effort? An EEG and eye-tracking study
2023-03-23

Gamification of cognitive tasks might positively affect emotional-motivational factors (emotional design perspective) or negatively affect cognitive factors like working memory load (minimalistic design perspective). The current study examined the effects of gamification in a spatial n-back working memory task on task performance, task load (i.e., working memory load and effort), and subjective task experience. Task load was assessed by the physiological process measures pupil dilation and EEG theta (4-6 Hz) and alpha (8-13 Hz) frequency band power. Gamification was achieved by elements of emotional design (i.e., the visual screen design using, e.g., color, cartoon figures as n-back stimuli, and a narrative embedding of the task). While EEG and eye-tracking were recorded, participants conducted gamified and non-gamified 1-back and 2-back load levels. The gamification resulted in positive effects on subjective task experience and affect. Despite these effects, gamification did not affect task performance and task load. However, exploratory analyses revealed increased EEG theta power at right-parietal electrodes for gamified task versions compared to non-gamified ones. Potentially, this effect might indicate participants' increased effort or concentration in the gamified n-back task. In line with an emotional design perspective, gamification positively altered subjective task experience and affect without hampering task performance and therefore justify the extra effort of implementing game elements.
New workflow predicts drug targets against SARS-CoV-2 via metabolic changes in infected cells
2023-03-23

COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and PREDICATE to create tissue-specific metabolic models, construct viral biomass functions and predict host-based antiviral targets from more than one genome. We observed that pymCADRE reduces the computational time of flux variability analysis for internal optimizations. We applied these tools to create a new metabolic network of primary bronchial epithelial cells infected with SARS-CoV-2 and identified enzymatic reactions with inhibitory effects. The most promising reported targets were from the purine metabolism, while targeting the pyrimidine and carbohydrate metabolisms seemed to be promising approaches to enhance viral inhibition. Finally, we computationally tested the robustness of our targets in all known variants of concern, verifying our targets’ inhibitory effects. Since laboratory tests are time-consuming and involve complex readouts to track processes, our workflow focuses on metabolic fluxes within infected cells and is applicable for rapid hypothesis-driven identification of potentially exploitable antivirals concerning various viruses and host cell types.
Low-grade inflammation during the glucocorticoid withdrawal phase in patients with Cushing's syndrome
2023-03-23

Abstract Importance Endogenous Cushing's syndrome (CS) leads to profound immunosuppression. Successful surgery induces biochemical remission and reversal of immunosuppression, which is characterized by clinical signs of glucocorticoid withdrawal and associated with increased susceptibility to infections and thromboembolic complications. Objective We hypothesized that the glucocorticoid withdrawal phase is characterized by low-grade inflammation that may be related to patient-relevant outcomes. Setting In this retrospective observational study, we analyzed longitudinal data from 80 patients with CS prospectively enrolled in the German Cushing's registry between 2012 and 2021. All enrolled patients underwent successful surgery. In a second step, a case–control study was performed in 25 of the patients with age-, gender-, and body mass index–matched control patients in whom hypercortisolism was excluded. Analyses included the inflammatory markers C-reactive protein and interleukin-6, as well as body composition, muscle function testing, and quality-of-life questionnaires. The patients were studied during active CS and in the postoperative remission phase 1, 3, 6, 12, and 24 months after surgery. Results Compared with the preoperative phase and matched controls, patients with CS had increased systemic inflammatory markers in the early remission phase. One month following surgery, median (interquartile range) C-reactive protein was 0.48 mg dL−1 (0.14-0.90) vs 0.10 mg dL−1 (0.06-0.39) during active CS (P ≤ .001). Similarly, interleukin-6 1 month after surgery was 7.2 pg mL−1 (3.3-11.7) vs 1.7 pg mL−1 (1.5-2.5) during active CS (P ≤ .001). Obesity and hemoglobin A1c (HbA1c) were associated with increased inflammation levels. This proinflammatory state lasted until 1 year following surgery. Moreover, inflammatory markers during early remission showed an inverse correlation with long-term muscle function. Conclusions The glucocorticoid withdrawal phase is associated with a low-grade inflammatory state, which is particularly pronounced in obese and hyperglycemic patients and related to lower muscle function.
standard-GEM: standardization of open-source genome-scale metabolic models
2023-03-23

ABSTRACT The field of metabolic modelling at the genomescale continues to grow with more models being created and curated. This comes with an increasing demand for adopting common principles regarding transparency and versioning, in addition to standardisation efforts regarding file formats, annotation and testing. Here, we present a standardised template for git-based and GitHub-hosted genome-scale metabolic models (GEMs) supporting both new models and curated ones, following FAIR principles (findability, accessibility, interoperability, and reusability), and incorporating bestpractices. standard-GEM facilitates the reuse of GEMs across web services and platforms in the metabolic modelling field and enables automatic validation of GEMs. The use of this template for new models, and its adoption for existing ones, paves the way for increasing model quality, openness, and accessibility with minimal effort. Availability standard-GEM is available from github.com/MetabolicAtlas/standard-GEM under the conditions of the CC BY 4.0 licence along with additional supporting material.
Optimization of FK-506 production in Streptomyces tsukubaensis by modulation of Crp-mediated regulation
2023-03-23

Abstract FK-506 is a potent immunosuppressive macrocyclic polyketide with growing pharmaceutical interest, produced by Streptomyces tsukubaensis . However, due to low levels synthesized by the wild-type strain, biotechnological production of FK-506 is rather limited. Optimization strategies to enhance the productivity of S. tsukubaensis by means of genetic engineering have been established. In this work primarily global regulatory aspects with respect to the FK-506 biosynthesis have been investigated with the focus on the global Crp (cAMP receptor protein) regulator. In expression analyses and protein-DNA interaction studies, the role of Crp during FK-506 biosynthesis was elucidated. Overexpression of Crp resulted in two-fold enhancement of FK-506 production in S. tsukubaensis under laboratory conditions. Further optimizations using fermentors proved that the strategy described in this study can be transferred to industrial scale, presenting a new approach for biotechnological FK-506 production. Key Points • The role of the global Crp (cAMP receptor protein) regulator for FK-506 biosynthesis in S. tsukubaensis was demonstrated • Crp overexpression in S. tsukubaensis was applied as an optimization strategy to enhance FK-506 and FK-520 production resulting in two-fold yield increase