Publications by authors named "Alex Nielsen"

Background: It has been suggested that neuroborreliosis in children can manifest as psychiatric neurodevelopmental disorders or cause long-term neurodevelopmental sequelae. However, previous studies were limited by size and design.

Methods: We performed a nationwide, population-based, matched cohort study in Denmark between 1995 and 2021.

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Replacing petrochemicals with compounds from bio-based manufacturing processes remains an important part of the global effort to move towards a sustainable future. However, achieving economic viability requires both optimized cell factories and innovative processes. Here, we address this challenge by developing a fermentation platform, which enables two concurrent fermentations in one bioreactor.

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Background: Few studies have investigated the risk of psychiatric neurodevelopmental disorders (PNDD) after childhood meningitis.

Methods: Nationwide population-based cohort study (Denmark, 1995-2021) of children with positive cerebrospinal fluid for bacteria or enterovirus, stratified on age as young infants (0 to <90 days,  = 637) or older children (≥90 days to <17 years,  = 1,218). We constructed a comparison cohort from the general population ( = 18,550), and cohorts of siblings of participants.

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Article Synopsis
  • The study investigated the causes of acute peripheral facial palsy (PFP) in Danish children and examined if neuroborreliosis-related PFP could be diagnosed without lumbar punctures by using clinical symptoms and serum Borrelia burgdorferi (Bb) antibodies.
  • Researchers analyzed data from 326 children who underwent lumbar puncture for PFP between 2019 and 2023, focusing on the diagnostic accuracy of serum Bb IgG compared to a clinical risk scoring system that included additional clinical parameters.
  • Findings revealed that 42% of the patients had neuroborreliosis, with high positive predictive values for both serum Bb IgG (88%) and the risk score (90%), suggesting that in high-endemic
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Objectives: To identify diagnostic opportunities, we investigated healthcare-seeking behaviour among patients with Lyme neuroborreliosis (LNB) within 28 weeks before diagnosis.

Methods: We conducted a population-based, nationwide matched nested case-control study (Denmark, 2009-2021). As cases, we included all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis).

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Bio-based production of fuels, chemicals and materials is needed to replace current fossil fuel based production. However, bio-based production processes are very costly, so the process needs to be as efficient as possible. Developments in synthetic biology tools has made it possible to dynamically modulate cellular metabolism during a fermentation.

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  • The study aimed to examine how often patients with neuroborreliosis receive additional antibiotic treatment after their initial doxycycline therapy due to lingering symptoms.
  • Conducted in Denmark between 2009-2021, the research compared 463 neuroborreliosis patients with 2,315 matched individuals from the general population, focusing on doxycycline and phenoxymethylpenicillin usage.
  • Results showed that neuroborreliosis patients were significantly more likely to receive doxycycline again within one year (38.6 times more) compared to the general population, while there was no difference in phenoxymethylpenicillin prescriptions, indicating a specific need for doxycycline rather than just healthcare-seeking behavior.
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Background: Radicular pain is the most predominant symptom among adults with Lyme neuroborreliosis (LNB) but the duration preceding and following diagnosis remains unknown. We aimed to investigate whether patients with LNB have increased obtainment of analgesics before and after diagnosis and for how long.

Methods: We performed a nationwide, population-based, matched cohort study (2009-2021).

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Natural and pure p-coumaric acid has valuable applications, and it can be produced via bioprocessing. However, fermentation processes have so far been unable to provide sufficient production metrics, while a biocatalytic process decoupling growth and production historically showed much promise. This biocatalytic process is revisited in order to tackle product inhibition of the key enzyme tyrosine ammonia lyase.

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Background: Lyme borreliosis is a tick-borne disease caused by the bacterium Borrelia burgdorferi (Bb) sensu lato complex. Previous studies have suggested an association between Lyme borreliosis and heart failure, which have been suggested to be a possible manifestation of Lyme carditis. We aimed to investigate the risk of heart failure among individuals tested for serum Bb antibodies, and serum Bb seropositive individuals.

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Acetogenic gas fermentation is increasingly studied as a promising technology to upcycle carbon-rich waste gasses. Currently the product range is limited, and production yields, rates and titres for a number of interesting products do not allow for economically viable processes. By pairing process modelling and host-agnostic metabolic modelling, we compare fermentation conditions and various products to optimise the processes.

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Objectives: To investigate the short- and long-term risks of atrioventricular block and other cardiac conduction disorders associated with being tested for Borrelia burgdorferi (Bb) antibodies or Bb seropositivity as measures of confounding by indication and Bb infection, respectively.

Methods: We performed a nationwide population-based matched cohort study (Denmark, 1993-2021). We included 52 200 Bb-seropositive individuals (stratified as only Bb-IgM-seropositive [n = 26 103], only Bb-IgG-seropositive [n = 18 698], and Bb-IgM-and-IgG-seropositive [n = 7399]) and two age- and sex-matched comparison cohorts: 104 400 Bb-seronegative individuals and 261 000 population controls.

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Infection with BK polyomavirus (BKPyV) is a common opportunistic infection after kidney transplantation (KT) and may affect graft function. We aimed to determine the incidence, risk factors, and clinical outcomes of BKPyV DNAemia in a prospective cohort of 601 KT recipients transplanted from 2012 to 2020. BKPyV PCR on plasma was performed at days 60, 90, 180, 270, and 360 post-KT.

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When two black holes merge, the late stage of gravitational wave emission is a superposition of exponentially damped sinusoids. According to the black hole no-hair theorem, this ringdown spectrum depends only on the mass and angular momentum of the final black hole. An observation of more than one ringdown mode can test this fundamental prediction of general relativity.

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Objectives: We compared characteristics and outcomes of individuals who in the cerebrospinal fluid (CSF) were positive for herpes simplex virus (HSV) or varicella-zoster virus (VZV)-intrathecal antibody index test ([AI]-positive) vs. individuals who were PCR-positive for HSV type 1 (HSV1), type 2 (HSV2), and for VZV.

Methods: Nationwide cohort study of all Danish residents with positive CSF-AI or -PCR for HSV or VZV (1995-2021).

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Objectives: In a nationwide, matched cohort study, we aimed to investigate risks of haematologic cancers among individuals tested for Borrelia burgdorferi (Bb) antibodies, and among serum Bb seropositive individuals.

Methods: We identified all Bb seropositive individuals in Denmark (1993-2020) (n = 52 200) and constructed two age- and sex-matched comparison cohorts: (a) Bb seronegative controls (n = 104 400) and (b) background population controls (n = 261 000). We calculated short-term OR (aOR) (<1 month of study inclusion), and long-term hazard ratios (aHR) (>1 month after study inclusion) adjusted for age and sex.

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Article Synopsis
  • p-Coumaric acid (pCA) can be produced through bioprocessing and is important for creating organic thin film transistors.
  • The study examined variants of the tyrosine ammonia lyase (TAL) enzyme from two bacteria to understand their activity, stability, and how they are affected by product inhibition.
  • Although FjTAL showed promising activity and low affinity for pCA, it still faces challenges from product inhibition and requires engineering improvements for better stability and efficiency in industrial applications.
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Microbial tolerance to toxic compounds formed during biomass pretreatment is a significant challenge to produce bio-based products from lignocellulose cost effectively. Rational engineering can be problematic due to insufficient prerequisite knowledge of tolerance mechanisms. Therefore, adaptive laboratory evolution was applied to obtain 20 tolerant lineages of strains able to utilize Distiller's Dried Grains with Solubles-derived (DDGS) hydrolysate.

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Objective: To estimate the incidence of neonatal herpes simplex virus (HSV) infection and the number of neonates with suspected invasive bacterial infection (IBI) needed to treat (NNT) with acyclovir to ensure prompt treatment of invasive HSV infections.

Design: A nationwide population-based cohort study.

Setting: All neonatal and paediatric emergency departments in Denmark from 1 January 2010 to 31 December 2019.

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Parageobacillus thermoglucosidasius is a thermophilic Gram-positive bacterium, which is a promising host organism for sustainable bio-based production processes. However, to take full advantage of the potential of P. thermoglucosidasius, more efficient tools for genetic engineering are required.

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Aim: Paediatric acute liver failure (P-ALF) is a rare and devastating condition that leads to death or liver transplantation (LTx) in 40%-60% of cases. Determining the aetiology can enable disease-specific treatment, aid in prognostication for hepatic recovery and guide the decision-making for liver transplantation. This study aimed to retrospectively evaluate a systematic diagnostic approach to P-ALF in Denmark and to collect epidemiological nationwide data.

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Although strain tolerance to high product concentrations is a barrier to the economically viable biomanufacturing of industrial chemicals, chemical tolerance mechanisms are often unknown. To reveal tolerance mechanisms, an automated platform was utilized to evolve Escherichia coli to grow optimally in the presence of 11 industrial chemicals (1,2-propanediol, 2,3-butanediol, glutarate, adipate, putrescine, hexamethylenediamine, butanol, isobutyrate, coumarate, octanoate, hexanoate), reaching tolerance at concentrations 60%-400% higher than initial toxic levels. Sequencing genomes of 223 isolates from 89 populations, reverse engineering, and cross-compound tolerance profiling were employed to uncover tolerance mechanisms.

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The expression of correctly folded and functional heterologous proteins is important in many biotechnological production processes, whether it is enzymes, biopharmaceuticals or biosynthetic pathways for production of sustainable chemicals. For industrial applications, bacterial platform organisms, such as E. coli, are still broadly used due to the availability of tools and proven suitability at industrial scale.

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The group of natural aromatic compounds known as phenylpropanoids has diverse applications, but current methods of production which are largely based on synthesis from petrochemicals or extraction from agricultural biomass are unsustainable. Bioprocessing is a promising alternative, but improvements in production titers and rates are required to make this method profitable. Here the recent advances in genetic engineering and bioprocess concepts for the production of phenylpropanoids are presented for the purpose of identifying successful strategies, including adaptive laboratory evolution, enzyme engineering, in-situ product removal, and biocatalysis.

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