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NGS and the design of an optimized phage display workflow for peptide discovery
No full textPhage display is a powerful technology that has demonstrated great potential in identifying peptides with high binding affinity and specificity toward a broad spectrum of biological targets. The undesired enrichment of nonspecific binders remains a major challenge in phage display selection. The integration of next-generation sequencing (NGS) into phage display has expanded the horizons of ligand discovery by significantly enhancing our ability to interrogate the massive sequence space of combinatorial phage display libraries and providing quantitative information about their composition and evolution during biopanning. NGS findings have provided strong support for the notion that the selection output still contains a large number of nonspecifically enriched peptide sequences that could not be removed or identified by traditional strategies for biopanning optimization. Despite its great potential for increasing the strength of peptide discovery, the routine NGS-based phage display workflow, which relies on analyzing the biopanning output, fails to effectively distinguish thousands of nonspecific peptides from specific target-binding sequences. By incorporating precise control experiments—including the NGS characterization of the unamplified and amplified naïve libraries and the outputs of targetless and replicate selections—alongside the thoughtful data analysis and interpretation, we propose an optimized workflow of NGS-based phage display that would be capable of distinguishing many target-specific peptides from the overwhelming background of nonspecific binders. Applying such a systematic approach will not only advance fundamental research for peptide discovery but also hold promise for the clinic, where these peptides can serve as the foundation for next-generation diagnostic and therapeutic platforms in precision medicine.</p
Cleaning in place of plate heat exchangers – Removal behavior of whey protein fouling
No full textMaintaining hygiene is critical in food manufacturing, and Cleaning-in-Place (CIP) is the standard method used. In this study we examine the CIP process to remove whey protein fouling in plate heat exchangers (PHEs). Fouling layers, representative for typical manufacturing processes, were generated through a controlled fouling process. The effects of temperature, velocity, pH, and amount of fouling on the cleaning process were assessed by measuring protein mass in the CIP effluent. Regardless of the cleaning conditions, removing the last 2 % of fouling mass takes up almost 50 % of the total cleaning time. To further investigate this slow second stage, the cleaning process was paused, and PHE channels were disassembled to quantify the residual fouling distribution on the plates. The cleaning solution (80 °C of 0.5 wt% NaOH at velocity 27.5 cm·s−1) formed preferential pathways through the PHE channel rather than following the plate's liquid-distribution pattern, thus limiting contact with the residual fouling layer. The subsequent fouling removal was primarily driven by NaOH diffusion. A cleaning mathematical model was developed and validated against experimental data, effectively estimating the cleaning process in two distinct PHE systems.</p
KU-professor: Nye evalueringskriterier bliver ikke mere end et sympatisk initiativ, hvis ikke kulturen følger med
No full textEffect of Edible Cricket Enriched Complementary Porridge and Nutrition Education on Linear Growth of Children 6-14 Months in Siaya County, Kenya:A Randomized 2 x 2 Factorial Trial
No full textEdible crickets are commonly farmed insects containing high-quality protein and micronutrients. They can potentially replace common animal source protein in complementary food (CF). We evaluated the effect of edible cricket-enriched CF on linear growth in a 2 x 2 factorial randomized control trial based on Cricket treatment (+/-CR) and Nutrition Education treatment (+/-ED). We enrolled 284 eligible mother-infant dyads with infants from 6 months having a middle upper arm circumference (MUAC) > 11.5 cm at Rwambwa Sub-County Hospital, Siaya County, Kenya. Participants were randomized to treatment arms with intervention foods issued monthly as a take-home food ration adjusted for age, were offered +ED sessions monthly as personalized audio-visual sessions where education messages and reminders were sent to the mother's mobile phones. Monthly infant anthropometry, feeding practices and child health data were collected. A significant contrast (Z = -0.28 (95% CI: 0.03, 0.53) [p = 0.03]) in length-for-age Z-score (LAZ) between -CR and +CR was observed. By MUAC, girls were significantly 1.98 (1.15, 3.41) (p = 0.01) times likely to be undernourished. Increased illness episodes significantly increased the child's risk to undernutrition, with those experiencing three episodes being 4.30 (95% CI: 1.21, 15.37) times likely to suffer undernutrition, while those with above five episodes were almost six times as likely to be malnourished. Consuming either of the intervention foods resulted in a similar growth rate irrespective of nutrition education treatment offered. Nutrition education improved weight-for-length, irrespective of CF consumed. The similarity in growth rate across study arms signifies the potential of edible cricket protein in growth of infants' comparative to the super cereal.Trial registration: https://clinicaltrials.gov NCT0600262
Clinical Application of Guideline-Directed Medical Therapy in TAVR Patients With Heart Failure and Reduced Ejection Fraction
No full textBackgroundThere are limited data concerning the impact of heart failure (HF) guideline-directed medical therapy (GDMT) in patients with HF with reduced ejection fraction (HFrEF) who undergo transcatheter aortic valve replacement (TAVR).ObjectivesThe aims of this study were to determine whether TAVR patients with HFrEF receive optimal HF-GDMT and to investigate the prognostic significance of HF-GDMT in this setting.MethodsIn a prospective registry, consecutive TAVR patients with HFrEF were stratified into 4 groups (quadruple, triple, double, or single or no therapy) according to prescription of HF-GDMT at discharge post-TAVR and after a 3-month GDMT optimization period. Major adverse cardiovascular events (MACE) were defined as a composite of cardiovascular mortality or hospitalization for heart failure. The median follow-up time was 699 days (Q1-Q3: 510-961 days).ResultsAmong 336 TAVR patients with HFrEF, the rates of quadruple, triple, double, and single or no HF-GDMT were 15%, 19%, 28%, and 38% at discharge and 27%, 21%, 21%, and 27% at 3 months postprocedure, respectively. Among 280 patients (83.3%) eligible for quadruple HF-GDMT, only 27% (n = 76) received this combination at 3 months post-TAVR. Following a 3-month HF-GDMT optimization period, 2-year MACE rates were lower in patients taking quadruple (15.0%; 95% CI: 5.2%-24.8%) compared with triple (22.6%; 95% CI: 10.4%-34.8%), double (24.2%; 95% CI: 13.8%-34.6%), and single or no therapy (43.6%; 95% CI: 31.8%-55.4%; log-rank P < 0.001).ConclusionsHF-GDMT is underused in patients with HFrEF who undergo TAVR, and suboptimal HF-GDMT is associated with increased MACE in this setting. Strategies to improve the initiation and up-titration of HF-GDMT in TAVR patients with HFrEF are needed.Background There are limited data concerning the impact of heart failure (HF) guideline-directed medical therapy (GDMT) in patients with HF with reduced ejection fraction (HFrEF) who undergo transcatheter aortic valve replacement (TAVR). Objectives The aims of this study were to determine whether TAVR patients with HFrEF receive optimal HF-GDMT and to investigate the prognostic significance of HF-GDMT in this setting. Methods In a prospective registry, consecutive TAVR patients with HFrEF were stratified into 4 groups (quadruple, triple, double, or single or no therapy) according to prescription of HF-GDMT at discharge post-TAVR and after a 3-month GDMT optimization period. Major adverse cardiovascular events (MACE) were defined as a composite of cardiovascular mortality or hospitalization for heart failure. The median follow-up time was 699 days (Q1-Q3: 510-961 days). Results Among 336 TAVR patients with HFrEF, the rates of quadruple, triple, double, and single or no HF-GDMT were 15%, 19%, 28%, and 38% at discharge and 27%, 21%, 21%, and 27% at 3 months postprocedure, respectively. Among 280 patients (83.3%) eligible for quadruple HF-GDMT, only 27% (n = 76) received this combination at 3 months post-TAVR. Following a 3-month HF-GDMT optimization period, 2-year MACE rates were lower in patients taking quadruple (15.0%; 95% CI: 5.2%-24.8%) compared with triple (22.6%; 95% CI: 10.4%-34.8%), double (24.2%; 95% CI: 13.8%-34.6%), and single or no therapy (43.6%; 95% CI: 31.8%-55.4%; log-rank P < 0.001). Conclusions HF-GDMT is underused in patients with HFrEF who undergo TAVR, and suboptimal HF-GDMT is associated with increased MACE in this setting. Strategies to improve the initiation and up-titration of HF-GDMT in TAVR patients with HFrEF are needed.</p
Digital biomarkers in early Alzheimer's disease from wearable or portable technology:A scoping review
No full textBackgroundThe pursuit of accurate biomarkers for early detection and disease monitoring of Alzheimer's disease (AD) has driven a growing interest in digital biomarkers. We aimed to map the research landscape of digital biomarkers in early AD obtained with wearable or portable digital health technologies (DHTs).MethodsIn our scoping review, we included original research on portable or wearable DHTs where digital biomarkers were measured in populations of early AD (mild cognitive impairment (MCI) or mild dementia). We searched MEDLINE, Web of Science and EMBASE with a wide search strategy with independent review and data extraction by two review team members. We charted data in tabular/graphical form.ResultsAfter deduplication and screening of 8893 records, we included 109 studies describing a wide array of wearable or portable DHTs that obtained digital biomarkers. The study population consisted of 3019 individuals with MCI due to AD (54 % female, weighted mean age 73 years), and 1942 individuals with mild AD (55 % female, weighted mean age 73 years). The most studied biomarkers were rest/activity (39 %), speech (17 %), and gait (14 %), with most studies focusing on one domain. Few studies reported outcomes associated with diagnosis (16 %) and prognosis (3 %).ConclusionWe identified a growing evidence base investigating digital biomarkers in early AD. There is a paucity of studies examining diagnostic and prognostic properties, representing a knowledge gap. This overview may help to guide future research efforts to bridge the gap between the development and clinical implementation of digital biomarkers in early Alzheimer's disease.BACKGROUND: The pursuit of accurate biomarkers for early detection and disease monitoring of Alzheimer's disease (AD) has driven a growing interest in digital biomarkers. We aimed to map the research landscape of digital biomarkers in early AD obtained with wearable or portable digital health technologies (DHTs).METHODS: In our scoping review, we included original research on portable or wearable DHTs where digital biomarkers were measured in populations of early AD (mild cognitive impairment (MCI) or mild dementia). We searched MEDLINE, Web of Science and EMBASE with a wide search strategy with independent review and data extraction by two review team members. We charted data in tabular/graphical form.RESULTS: After deduplication and screening of 8893 records, we included 109 studies describing a wide array of wearable or portable DHTs that obtained digital biomarkers. The study population consisted of 3019 individuals with MCI due to AD (54 % female, weighted mean age 73 years), and 1942 individuals with mild AD (55 % female, weighted mean age 73 years). The most studied biomarkers were rest/activity (39 %), speech (17 %), and gait (14 %), with most studies focusing on one domain. Few studies reported outcomes associated with diagnosis (16 %) and prognosis (3 %).CONCLUSION: We identified a growing evidence base investigating digital biomarkers in early AD. There is a paucity of studies examining diagnostic and prognostic properties, representing a knowledge gap. This overview may help to guide future research efforts to bridge the gap between the development and clinical implementation of digital biomarkers in early Alzheimer's disease.</p
Impact of molecular subtypes on postoperative hydrocephalus following resection of posterior fossa medulloblastoma and ependymoma in children:A systematic review and meta-analysis
No full textOBJECTIVE: The objective of this systematic review was to investigate the possible impact of tumor molecular subtype on the risk of postoperative hydrocephalus following resection of posterior fossa ependymomas and medulloblastomas in children.METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline based systematic literature review and meta-analysis was performed using the PubMed and Embase databases. The final searches were conducted on February 1st, 2025. Predetermined eligibility criteria were based on the Population, Intervention, Comparison and Study design framework. A risk of bias analysis was performed using the Risk of Bias In Non-randomized Studies of Exposures tool. Count data was pooled across the included studies with the addition of a 10-year nationwide cohort from Denmark (DK cohort). Extracted data from medulloblastoma studies were compared using chi-squared tests and calculations of relative risks.RESULTS: A total of four studies were included, three of which pertained to medulloblastoma (MB). In total, postoperative hydrocephalus was reported in 22.4% (68/304) of children with MB. The lowest rate was observed for MBWNT (7.9%), and the highest for MBGrp3 (29.7%), however the difference across molecular subtypes was not statistically significant (p = 0.08, chi-squared). The relative risk of postoperative hydrocephalus was significantly lower for MBWNT when compared to non-MBWNT (RR of 0.32 [95% CI, 0.11-0.98]), and significantly higher for MBGrp3 when directly compared to MBWNT (RR of 3.76 [95% CI, 1.19-11.87]). Only one of the four included studies pertained to children with posterior fossa ependymomas (EPN). For EPN, postoperative hydrocephalus was reported in 26.5% (22/83) after pooling with the DK cohort data (n = 14), with similar rates for Posterior Fossa Type A (PFA-EPN) (27.0%) and Posterior Fossa Type B (PFB-EPN) (22.2%).CONCLUSIONS: In this systematic literature review, we investigated the potential association between tumor molecular subtype in children with posterior fossa EPN and MB and postoperative hydrocephalus. Here, we show that the rate of postoperative hydrocephalus is significantly lower for MBWNT when compared to non-MBWNT and significantly higher for MBGrp3 when compared to MBWNT selectively. No clear difference was observed across PFA-EPN and PFB-EPN, possibly due to the limited number of patients. Improving our understanding of cerebrospinal fluid disturbances associated with posterior fossa tumors holds potential to further optimize the treatment of hydrocephalus in these children in the future.</p
Sildenafil provokes headache but not migraine in men with migraine without aura:a randomized, placebo-controlled crossover trial
No full textBACKGROUND: Cyclic guanosine monophosphate (cGMP)-mediated mechanisms plays a role in migraine pathophysiology. Sildenafil, a phosphodiesterase type 5 inhibitor, increases intracellular cGMP and can reliably induce migraine attacks in women. However, its migraine-inducing potential in men remains largely unknown.METHODS: In this randomized, double-blind, placebo-controlled crossover trial, 12 men with migraine without aura received sildenafil (100 mg) and placebo in separate sessions ≥ 7 days apart. An open-label parallel cohort of 15 women with migraine received sildenafil (100 mg) under similar experimental conditions. The primary endpoints were (i) the incidence of migraine-like attacks after sildenafil compared with placebo in men, and (ii) the incidence of migraine-like attacks after sildenafil in men and women.RESULTS: In men, sildenafil induced headache more frequently than placebo (83% vs. 25%, p = 0.033), whereas the incidence of migraine-like attacks did not differ between sildenafil and placebo (25% vs. 17%, p = 0.500). In women, sildenafil induced headache in all participants and migraine-like attacks in 67%, a significantly higher proportion than in men (67% vs. 25%, p = 0.038). Adverse events were more frequent after sildenafil than placebo, most commonly flushing and nasal congestion.CONCLUSIONS: Sildenafil provoked headache but not migraine in men with migraine without aura, whereas women showed a markedly greater susceptibility to migraine induction. These findings suggest that cGMP-mediated mechanisms contribute less prominently to migraine generation in men.GRAPHICAL ABSTRACT: [Image: see text]SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10194-025-02262-2.</p
The coupling between hydrology, the development of the active layer and the chemical signature of surface water in a periglacial catchment in West Greenland
No full textAn important factor for controlling the chemical signature of surface water is the interactions with soil particles and groundwater. In permafrost landscapes, ground ice restricts groundwater flow, which implies a limited influence of processes such as weathering on the chemical signature of the runoff. The aim of this study was to examine how freeze-thaw processes, hydrology and water age interact to shape the chemical and stable hydrogen and oxygen isotopic signature of surface water in a catchment in West Greenland. Measuring runoff in remote catchments is challenging, and therefore we used a validated hydrological model to estimate daily runoff over multiple years. We also applied a particle tracking simulation to determine groundwater ages and used data on stable isotopic and chemical composition from various water types - including surface water, groundwater, lake water and precipitation - spanning from early snowmelt to the end of the thawed season. Our results show that groundwater age generally is less than one year and rarely exceeds four years, total runoff is dominated by groundwater, and overland flow is restricted to the snowmelt period and after heavy rain events. Monitoring of thaw rates in the active layer indicates a rapid thawing in connection with running water, and meltwater from ground ice quickly becomes an important fraction of the runoff. Taken together, our data suggest that even in continuous permafrost landscapes with thin active layers and an absence of truly old and mobile groundwater, soil processes exert a strong influence on the chemical and stable isotopic signature of runoff, i.e., similar to what has been observed in other climatic settings