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Canan Bayraktar,1,* Alisan Kayabolen,1,* Arda Odabas,1 Aysegul Durgun,1 Ipek Kok,1 Kenan Sevinc,1 Aroon Supramaniam,2 Adi Idris,2,3 Tugba Bagci-Onder1 1Koç University Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey; 2Menzies Health Institute Queensland, School of Medical Science Griffith University, Gold Coast Campus, Brisbane, QLD, Australia; 3Centre for Immunology and Infection Control, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia*These authors contributed equally to this workCorrespondence: Tugba Bagci-Onder; Alisan Kayabolen, Email tuonder@ku.edu.tr; akayabol@mit.eduPurpose: Over the past three years, extensive research has been dedicated to understanding and combating COVID-19. Targeting the interaction between the SARS-CoV-2 Spike protein and the ACE2 receptor has emerged as a promising therapeutic strategy against SARS-CoV-2. This study aimed to develop ACE2-coated virus-like particles (ACE2-VLPs), which can be utilized to prevent viral entry into host cells and efficiently neutralize the virus.Methods: Virus-like particles were generated through the utilization of a packaging plasmid in conjunction with a plasmid containing the ACE2 envelope sequence. Subsequently, ACE2-VLPs and ACE2-EVs were purified via ultracentrifugation. The quantification of VLPs was validated through multiple methods, including Nanosight 3000, TEM imaging, and Western blot analysis. Various packaging systems were explored to optimize the ACE2-VLP configuration for enhanced neutralization capabilities. The evaluation of neutralization effectiveness was conducted using pseudoviruses bearing different spike protein variants. Furthermore, the study assessed the neutralization potential against the Omicron BA.1 variant in Vero E6 cells.Results: ACE2-VLPs showed a high neutralization capacity even at low doses and demonstrated superior efficacy in in vitro pseudoviral assays compared to extracellular vesicles carrying ACE2. ACE2-VLPs remained stable under various environmental temperatures and effectively blocked all tested variants of concern in vitro. Notably, they exhibited significant neutralization against Omicron BA.1 variant in Vero E6 cells. Given their superior efficacy compared to extracellular vesicles and proven success against live virus, ACE2-VLPs stand out as crucial candidates for treating SARS-CoV-2 infections.Conclusion: This novel therapeutic approach of coating VLPs with receptor particles provides a proof-of-concept for designing effective neutralization strategies for other viral diseases in the future.Keywords: ACE2, virus like particles, SARS-CoV-2, neutralization, VLP, neutralization, escape mutations, spike protein

Background: The aim of this study was to determine attitude of Dutch midwifes, gynecologists and general practitioners (GPs) towards involvement in antenatal cervical cancer screening (CCS) in the Netherlands. Methods: In 2021, Dutch midwives, gynecologists, and GPs were offered a single digital questionnaire assessing perceived feasibility, benefits, and harms of antenatal CCS. Results: A total of 6943 Questionnaires were send and response rate was 18% (N = 1260). Of all respondents, 78% considered antenatal CCS via obstetric care providers feasible. Most respondents (85%) agreed that offering CCS in person can increase motivation to attend. Most midwives (93%) considered that women would feel less encumbered if cervical sampling would be performed by obstetric care providers, rather than by GPs. Conclusion: Results indicate that introduction of antenatal CCS is considered feasible by a majority of Dutch midwifes, gynecologists, and GPs. Considered benefits include improved motivation to attend and reduced test related barriers. [ABSTRACT FROM AUTHOR]

Objectives: To examine families' experiences, including motivation and barriers to undergoing tooth autotransplantation (AT), and their perceptions of associated esthetic and functional outcomes., Methods: Semi-structured, in-depth-interviews (IDIs) were conducted in person with families who had children that underwent the AT procedure. Interviews were audio recorded and transcribed. Transcripts were coded and thematically analyzed both deductively and inductively. A facilitators and barriers matrix and journey maps were created to draw inferences on patterns arising from main themes., Results: Twenty families selecting AT as a solution for a missing maxillary incisor were recruited and interviewed. Overall, all families interviewed had a positive experience with the AT procedure. Motivating factors for undergoing the AT procedure included wanting an earlier intervention for the missing incisor, wishing to mitigate negative psychosocial effects, and the anticipated positive outcomes that would last into adulthood. Barriers to uptake of the AT procedure included the lack of dental practitioner awareness of AT as a potential solution and a large number of appointments and travel. Families were also initially concerned over potential complications that could arise from their child undergoing this procedure. The cost of the procedure was both a barrier and a facilitator for treatment., Conclusions: The study results demonstrate that the overall AT is favorably considered by the families of growing children for the replacement of maxillary incisors and highlight factors that may act as motivators or barriers to its uptake., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Decision-analytic models assessing the value of emerging Alzheimer's disease (AD) treatments are challenged by limited evidence on short-term trial outcomes and uncertainty in extrapolating long-term patient-relevant outcomes. To improve understanding and foster transparency and credibility in modeling methods, we cross-compared AD decision models in a hypothetical context of disease-modifying treatment for mild cognitive impairment (MCI) due to AD., Methods: A benchmark scenario (US setting) was used with target population MCI due to AD and a set of synthetically generated hypothetical trial efficacy estimates. Treatment costs were excluded. Model predictions (10-year horizon) were assessed and discussed during a 2-day workshop., Results: Nine modeling groups provided model predictions. Implementation of treatment effectiveness varied across models based on trial efficacy outcome selection (clinical dementia rating - sum of boxes, clinical dementia rating - global, mini-mental state examination, functional activities questionnaire) and analysis method (observed severity transitions, change from baseline, progression hazard ratio, or calibration to these). Predicted mean time in MCI ranged from 2.6 to 5.2 years for control strategy and from 0.1 to 1.0 years for difference between intervention and control strategies. Predicted quality-adjusted life-year gains ranged from 0.0 to 0.6 and incremental costs (excluding treatment costs) from -US$66 897 to US$11 896., Conclusions: Trial data can be implemented in different ways across health-economic models leading to large variation in model predictions. We recommend (1) addressing the choice of outcome measure and treatment effectiveness assumptions in sensitivity analysis, (2) a standardized reporting table for model predictions, and (3) exploring the use of registries for future AD treatments measuring long-term disease progression to reduce uncertainty of extrapolating short-term trial results by health-economic models., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Statement of Problem: Though computer-aided design and computer-aided manufactured (CAD-CAM) denture bases have become popular, evidence on the ability of C. albicans cells to adhere to these denture bases is lacking., Purpose: The purpose of this in vitro study was to evaluate the adherence of Candida albicans to differently manufactured acrylic resin denture bases., Material and Methods: Acrylic resin disks were fabricated using a total of 6 different fabrication methods (compression molding, injection molding, CAD-CAM milling, and rapid prototyping on 3 different printers with 3 different resins). Each material was evaluated for adherence of C. albicans using 2 different experimental methods - suspension in inoculated tryptic soy broth (TSB) or placed onto a uniform lawn of C. albicans on tryptone soya agar (TSA) with 5% sheep's blood. Attached cells were quantified by spiral plating and then used to re-inoculate sterile plates. Logarithmic transformation was completed to normalize data. For the broth suspension, the Kruskal-Wallis test was used to identify any differences between the 6 specimen types in terms of recovery, and the Dunn test was used for post hoc analysis. For the microbial lawn experiment, 1-way analysis of variance (ANOVA) and then the Tukey Honestly Significant Difference (HSD) post hoc test were used., Results: Statistically significant differences were found between the numbers of adherent cells based on manufacturing method and between experimental designs (P<.05). All resins demonstrated growth with re-inoculation., Conclusions: Though statistical significance was noted, neither experimental technique demonstrated what is likely a clinically significant preferential binding to any particular resin surface. Attached Candida cells are effective carriers of pathogens to uninfected surfaces. Further studies are indicated for potential virulence factors and differences in printed resins., (Copyright © 2024 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Objectives: Organisation of a screening programme influences programme resilience to a disruption as COVID-19. Due to COVID-19, the Dutch human papillomavirus-based cervical screening programme was temporarily suspended. Afterwards, multiple measures have been taken to catch-up participation. This study aimed to investigate programme resilience by examining the effect of COVID-19 and programme measures taken on participation in cervical screening., Study Design: Observational cohort study., Methods: Data from the national screening registry and Dutch nationwide pathology databank (Palga) were used on invitations and follow-up in 2018/2019 (pre-COVID) and 2020 (COVID). Sending invitations, reminders and self-sampling kits were suspended from March to July 2020. Main outcome measures include distribution of participant characteristics (age, region and screening history), participation rates by age and region, time between invitation and participation (i.e. response time) and self-sampling use per month., Results: Participation rate was significantly lower in 2020 (49.8%) compared to 2018/19 (56.8%, P < 0.001), in all ages and regions. Compared to 2018/19, participation rates decreased most in women invited from January to March 2020 (-6.7%, -9.1% and -10.4%, respectively). From August, participation rates started to recover (difference between -0.8% and -2.7%). Median response time was longer in February and March (2020: 143 and 173 days; 2018/19: 53 and 55 days) and comparable from July onwards (median difference 0-6 days). Self-sampling use was higher in 2020 (16.3%) compared to 2018/19 (7.6%)., Conclusions: The pandemic impacted participation rates in the Dutch cervical screening programme, especially of women invited before the programme pause. Implementation of self-sampling in national cervical screening programmes could increase participation rates and could serve as an alternative screening method in times of exceptional health care circumstances, such as a pandemic. Due to the well-organised programme and measures taken to catch-up participation, the impact of COVID-19 on the screening programme remained small., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study evaluated the effects of inoculating corn silage and/or feeding a direct-fed microbial (PRO) on performance and nutrient digestibility of lactating dairy cows. At harvesting, corn silage was treated either with water (culated or not [CON]) or Lactococcus lactis and Lentilactobacillus buchneri (INC; SiloSolve FC) at 1.5 × 10 5 cfu/g of corn silage. Ten mini silos and one farm-scale silo bunker per treatment were prepared for the laboratory and the lactating dairy cow trial, respectively. Five mini silos per treatment were opened on days 2 or 90 post-ensiling for pH measurement, as well as chemical analysis and aerobic stability, respectively. The farm-scale silo bunkers were opened 77 d post-ensiling for the beginning of the lactating cow trial. Eighty lactating Holstein cows were assigned in a 2 × 2 factorial design to: (1) CON silage without PRO (CON-CON; n  = 20), (2) CON silage with PRO at 14 g/head/d (CON-PRO; n  = 20), (3) INC silage without PRO (INC-CON; n  = 20), and (4) INC silage with PRO at 14 g/head/d (INC-PRO; n  = 20). Concurrently with the feeding trial, eight cows per treatment were chosen for nutrient digestibility. The pH of the corn silage was not affected by the silage inoculant ( P  ≥ 0.29), but INC yielded greater concentration of acetic acid and longer aerobic stability ( P  < 0.01). Dairy cows fed INC had a lower mean total dry matter intake (DMI), milk protein content, and somatic cell counts vs. CON ( P  ≤ 0.02). On the other hand, milk and fat- and protein-corrected milk (FPCM) production efficiency, milk urea-N, DM, crude protein, and starch digestibility were greater for INC-fed cows ( P  ≤ 0.03). Feeding direct-fed microbials (DFM) improved mean body weight, milk yield, and FPCM, as well as milk protein and lactose yield ( P  ≤ 0.05), but reduced milk fat and protein content ( P  = 0.02). A silage inoculant × DFM interaction was observed for milk production efficiency, milk protein and lactose content, and somatic cell count ( P  ≤ 0.05). Dairy cows fed INC-CON had a greater milk production efficiency and milk lactose content ( P  ≤ 0.04), but INC-PRO had lower milk protein content and SCC ( P  ≤ 0.03). In summary, inoculating L. lactis and L. buchneri increased acetic acid content and aerobic stability of corn silage, reduced DMI, but improved milk production efficiency and nutrient digestibility of lactating Holstein dairy cows. On the other hand, feeding PRO improved milk, protein, and lactose yield. Additionally, combining the feeding of an inoculated corn silage with PRO reduced milk somatic cell count., Competing Interests: G. Copani, K. A. Bryan, K. L. M. Witt, R. C. do Amaral, and B. I. Cappellozza are employees of Chr. Hansen. I. Kok and W. M. van Straalen are employees of Schothorst Feed Research and declare no further conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science.)

The effect of a biosynthetic bacterial 6-phytase (PhyG) on the digestibility and excretion of crude protein (CP), phosphorus (P), and phytate-P (PP) in midlactating dairy cows was investigated. Thirty Holstein-Friesians were assigned to three treatments with 10 cows per treatment in a randomized block design. Cows were fed forage (grass and corn silage) provided ad libitum, and a concentrate (without added inorganic phosphate) administered separately in amounts individualized per cow according to milk production, supplemented with phytase according to treatment. The formulated forage-to-concentrate-ratio was ~65%:35%. Dietary treatments comprised the control diet (CON) and CON supplemented with 2,000 (PhyG2,000) or 5,000 (PhyG5,000) phytase units (FTU)/kg DM in the total diet. The experiment comprised an 18-d preperiod for the collection of data to facilitate the allocation of cows to the treatments, followed by a 19-d experimental period comprising a 14-d diet adaptation period and 5 d of twice daily feces collection. Fecal samples were analyzed for the determination of apparent total tract digestibility (ATTD) of chemical constituents in the diet. The ATTD of PP was 92.6% in CON suggesting a high but incomplete degradation of phytate by ruminal microbial phytases. Cows fed PhyG2,000 exhibited increased ATTD of CP and PP [68.4% (2.7% points above CON) and 95.1% (2.5% points above CON), respectively] whilst PhyG5,000 further increased ATTD PP and also increased ATTD P [54.1% (7.8% points above CON)]; ATTD of Ca tended to be increased in PhyG5,000 vs. CON. Linear dose-response relationships were observed for ATTD of DM, CP, P, Ca, and PP. In addition, fecal excretion of P, and PP linearly reduced and that of Ca and CP tended to linearly reduce with increasing PhyG dose level. No difference was observed for DM intake and milk composition was unaffected except for milk protein which tended to be higher in cows fed PhyG5,000 than CON. In summary, the addition of exogenous phytase at 2,000 FTU/kg or higher to diets of lactating dairy cows improved P, PP, Ca, and CP digestibility and reduced fecal excretion of P, PP, and CP in a dose-dependent manner., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Objective: The purpose of this study was to compare the linear and volumetric wear of conventional and milled double-cross-linked polymethyl methacrylate, nano-composite, and nano-ceramic infused resin posterior denture teeth., Methods: Double-cross-linked polymethyl methacrylate (PMMA) premolar teeth were scanned and used to mill denture teeth from a double-cross-linked PMMA resin disc and a nano-composite with nano-ceramic infused resin disc. The specimens (n = 8: conventional double-cross-linked PMMA resin teeth-DCL, milled double-cross-linked PMMA resin teeth-DCL-CAM, conventional nano-composite infused resin teeth with four layers composed of composite and PMMA resin teeth-NC, and milled nano-composite and nano-ceramic infused resin teeth-NC-CAM) underwent chewing simulation in the biaxial fatigue testing machine at 1.53 Hz frequency, thermocycling between 5 and 55°C, and 49 N force against a Ø6mm steatite. After 250,000 cycles, the linear changes on the occlusal surfaces of the specimens were analyzed with pairwise comparison with Bonferroni post hoc test, and the volumetric changes of the specimens were analyzed with a one-way ANOVA with Bonferroni post hoc test (p < 0.05)., Results: The linear wear of the conventional and milled denture teeth was linearly correlated with the number of cycles between 50,000 and 250,000 cycles. After 250,000 cycles, NC had significantly more linear and volumetric wear (0.52 ± 0.10 mm and 4.29 ± 0.94 mm 3 ) than DCL (0.18 ± 0.03 mm and 0.74 ± 0.14 mm 3 ; p < 0.001) and NC-CAM (0.15 ± 0.03 mm and 0.35 ± 0.21 mm 3 ; p < 0.001). DCL-CAM and NC-CAM had linearly and volumetrically equivalent wear to DCL (p > 0.05). NC-CAM had significantly less linear and volumetric wear (0.15 ± 0.03 mm and 0.35 ± 0.21 mm 3 ) than DCL-CAM (0.24 ± 0.07 mm and 1.22 ± 0.61 mm 3 ; p < 0.05)., Conclusions: The conventional NC wore more than DCL, DCL-CAM, and NC-CAM. Both milled denture teeth wore an equivalent amount to conventional DCL. The wear between the conventional and milled DCL was equivalent., Clinical Significance: Denture teeth selection can prolong the retreading process and decrease the occurrences of prosthetic complications. Milled denture teeth are good alternatives to conventional denture teeth with regards to their wear resistance., (© 2022 Wiley Periodicals LLC.)

Visual attention of young children with autism spectrum disorder (ASD) has been well documented in the literature for the past 20 years. In this study, we developed a Decision Support System (DSS) that uses machine learning (ML) techniques to identify young children with ASD from typically developing (TD) children. Study participants included 26 to 36 months old young children with ASD (n = 61) and TD children (n = 72). The results showed that the proposed DSS achieved up to 87.5% success rate in the early assessment of ASD in young children. Findings suggested that visual attention is a unique, promising biomarker for early assessment of ASD. Study results were discussed, and suggestions for future research were provided., (Copyright © 2022 Elsevier B.V. All rights reserved.)

There are currently screening programmes for breast, cervical and colorectal cancer in many European countries. However, the uptake of cancer screening in general may vary within and between countries. The aim of this study is to assess the inequalities in testing utilization by socio-economic status and whether the amount of inequality varies across European regions. We conducted an analysis based on cross-sectional data from the second wave of the European Health Interview Survey from 2013 to 2015. We analysed the use of breast, cervical, and colorectal cancer testing by socio-economic position (household income, educational level and employment status), socio-demographic factors, self-perceived health and smoking behaviour, by using multinomial logistic models, and inequality measurement based on the Slope index of inequality (SII) and Relative index of inequality (RII). The results show that the utilization of mammography (Odds Ratio (OR) = 0.55, 95% confidence interval (95%CI):0.50-0.61), cervical smear tests (OR = 0.60, 95%CI:0.56-0.65) and colorectal testing (OR = 0.82, 95%CI:0.78-0.86) was overall less likely among individuals within a low household income compared to a high household income. Also, individuals with a non-EU country of birth, low educational level and being unemployed (or retired) were overall less likely to be tested. The income-based inequality in breast (SII = 0.191;RII = 1.260) and colorectal testing utilization (SII = 0.161;RII = 1.487) was the greatest in Southern Europe. For cervical smears, this inequality was greatest in Eastern Europe (SII = 0.122;RII = 1.195). We concluded that there is considerable inequality in the use of cancer tests in Europe, with inequalities associated with household income, educational level, employment status, and country of birth., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Programmed cell death protein 1 (PD-1) antibody treatment is standard of care for melanoma and non-small-cell lung cancer (NSCLC). Accurately predicting which patients will benefit is currently not possible. Tumor uptake and biodistribution of the PD-1 antibody might play a role. Therefore, we carried out a positron emission tomography (PET) imaging study with zirconium-89 ( 89 Zr)-labeled pembrolizumab before PD-1 antibody treatment., Patients and Methods: Patients with advanced or metastatic melanoma or NSCLC received 37 MBq (1 mCi) 89 Zr-pembrolizumab (∼2.5 mg antibody) intravenously plus 2.5 or 7.5 mg unlabeled pembrolizumab. After that, up to three PET scans were carried out on days 2, 4, and 7. Next, PD-1 antibody treatment was initiated. 89 Zr-pembrolizumab tumor uptake was calculated as maximum standardized uptake value (SUV max ) and expressed as geometric mean. Normal organ uptake was calculated as SUV mean and expressed as a mean. Tumor response was assessed according to (i)RECIST v1.1., Results: Eighteen patients, 11 with melanoma and 7 with NSCLC, were included. The optimal dose was 5 mg pembrolizumab, and the optimal time point for PET scanning was day 7. The tumor SUV max did not differ between melanoma and NSCLC (4.9 and 6.5, P = 0.49). Tumor 89 Zr-pembrolizumab uptake correlated with tumor response (P trend = 0.014) and progression-free (P = 0.0025) and overall survival (P = 0.026). 89 Zr-pembrolizumab uptake at 5 mg was highest in the spleen with a mean SUV mean of 5.8 (standard deviation ±1.8). There was also 89 Zr-pembrolizumab uptake in Waldeyer's ring, in normal lymph nodes, and at sites of inflammation., Conclusion: 89 Zr-pembrolizumab uptake in tumor lesions correlated with treatment response and patient survival. 89 Zr-pembrolizumab also showed uptake in lymphoid tissues and at sites of inflammation., Competing Interests: Disclosure MJ reports consultancy fees from AstraZeneca (paid to UMCG). JBH reports consultancy roles for Achilles Therapeutics, BioNTech, BMS, GSK, Immunocore, Instil Bio, Molecular Partners, MSD, Merck Serono, Neogene Therapeutics, Novartis, Pfizer, PokeAcel, Roche/Genentech, Sanofi, T-Knife, and Third Rock Ventures and research grants from Amgen, Asher-Bio, BMS, BioNTech, MSD, Novartis, and Neogene Therapeutics (paid to the Netherlands Cancer Institute). WT reports fees from Merck, Sharp, Dohme, and Bristol-Myers-Squibb (paid to UMCG). EGEdV reports an advisory role at Daiichi Sankyo, NSABP, and Sanofi and research funding from Amgen, AstraZeneca, Bayer, Chugai Pharma, Crescendo, CytomX Therapeutics, G1 Therapeutics, Genentech, Nordic Nanovector, Radius Health, Regeneron, Roche, Servier, and Synthon (paid to UMCG). GAPH reports consulting and advisory role at Amgen, Roche, MSD, BMS, Pfizer, Novartis, and Pierre Fabry and research funding from BMS and Seerave (paid to UMCG). TJNH reports consultancy fees (paid to UMCG) from BMS, MSD, Merck, Boehringer, AstraZeneca, and Roche. AJvdW reports an advisory role at Janssen, Takeda, and Boehringer-Ingelheim (paid to UMCG) and research funding from AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche, and Takeda. MNL-dH reports research funding from Merck, Bayer, and Amgen (paid to UMCG). HJMG reports an advisory role at Eli Lilly, MSD, BMS, and Novartis. All other authors have declared no conflicts of interest., (Copyright © 2021. Published by Elsevier Ltd.)