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BackgroundEndoscopic endonasal surgery is an established minimally invasive technique for resecting pituitary adenomas. However, understanding orientation and identifying critical neurovascular structures in this anatomically dense region can be challenging. In clinical practice, commercial navigation systems use a tracked pointer for guidance. Augmented Reality (AR) is an emerging technology used for surgical guidance. It can be tracker based or vision based, but neither is widely used in pituitary surgery.MethodsThis pre-clinical study aims to assess the accuracy of tracker-based navigation systems, including those that allow for AR. Two setups were used to conduct simulations: (1) the standard pointer setup, tracked by an infrared camera; and (2) the endoscope setup that allows for AR, using reflective markers on the end of the endoscope, tracked by infrared cameras. The error sources were estimated by calculating the Euclidean distance between a point’s true location and the point’s location after passing it through the noisy system. A phantom study was then conducted to verify the in-silico simulation results and show a working example of image-based navigation errors in current methodologies.ResultsThe errors of the tracked pointer and tracked endoscope simulations were 1.7 and 2.5 mm respectively. The phantom study showed errors of 2.14 and 3.21 mm for the tracked pointer and tracked endoscope setups respectively.DiscussionIn pituitary surgery, precise neighboring structure identification is crucial for success. However, our simulations reveal that the errors of tracked approaches were too large to meet the fine error margins required for pituitary surgery. In order to achieve the required accuracy, we would need much more accurate tracking, better calibration and improved registration techniques.

Semi-natural mountain grasslands are species-rich and provide a wide range of ecosystem services, such as biomass production for livestock grazing and carbon sequestration. Land abandonment but also habitat destruction are threatening these ecosystems highlighting the need for restoration when degraded. The transfer of plant material containing seed collected at non-degraded reference sites is increasingly used for restoration but the appropriate methods to prepare the transfer and to manage the grassland afterwards are still under debates. This study aims at testing the effects of seed bed preparation by harrowing and livestock grazing on the establishment of transferred targets and community trajectories towards the reference system. In a previous study, first year seedling counts showed a positive effect of seed bed preparation and a marginally significant negative effect of grazing on the seedling recruitment of the transferred species. We asked whether the results on first year seedling densities translate into significant effects on plant cover and whether these effects on plant cover change in the following three years. Both grazing and harrowing effects on species establishment were tested using a full factorial split-plot experimental design on five replicate sites. Data on species richness and vegetation cover for both the whole plant community and the transferred species were analysed during four years after seed transfer. The cover of transferred species increased whereas their species richness remained unchanged. We found a weak positive effect of harrowing on total cover whereas grazing had no effect. Seed bed preparation by harrowing had a clear positive effect on transferred target species cover. The negative effect of grazing on first-year seedling recruitment of transferred target species turned into a positive effect in the fourth year. However, this effect was only apparent in the harrowed plots resulting in a significant grazing-by-harrowing interaction. The similarity of the plant communities to the reference increased from the first to the fourth year and this increase was stronger in grazed and harrowed plots. In conclusion, the results confirmed the positive effect of seed bed preparation on restoration by seed transfer and demonstrated that initial grazing exclusion is not needed in mountain grasslands of our study area.

Lisa Svartdal Normann,1– 3 Mads Haugland Haugen,2 Miriam Ragle Aure,3 Vessela N Kristensen,3 Gunhild Mari Mælandsmo,2,4 Kristine Kleivi Sahlberg1,2 1Department of Research and Innovation, Vestre Viken Hospital Trust, Drammen, Norway; 2Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; 3Department of Medical Genetics, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway; 4Institute for Medical Biology, Faculty of Health Sciences, UiT – The Arctic University of Norway, Tromsø, NorwayCorrespondence: Kristine Kleivi Sahlberg, Department of Research and Innovation, Vestre Viken Hospital Trust, Drammen, Norway, Tel +47 98641229, Email Kristine.Sahlberg@vestreviken.noPurpose: Human epidermal growth factor receptor 2 positive (HER2+) breast cancers responding poorly to targeted therapy need improved treatment options. miR-101-5p has shown tumor-suppressive properties in multiple cancer forms, and we assessed the effect and mechanism of action of this miRNA in HER2+ breast cancer.Methods: Expression levels of miR-101-5p in two clinical datasets, TCGA and METABRIC, were compared between tumor and normal adjacent samples, and across molecular subtypes and HER2 status. The ability of miR-101-5p to sensitize for treatment with lapatinib, tucatinib and trastuzumab was explored in HER2+ breast cancer cells responding poorly to such targeted drugs. Proliferation and apoptosis assays and downstream protein analysis were performed.Results: Expression levels of miR-101-5p were significantly lower in tumor compared to normal adjacent tissue (p < 0.001), and particularly low in HER2+ tumors, both the HER2-enriched subtype (p ≤ 0.037) and clinical HER2-status (p < 0.001). In a HER2+ cell line (KPL4) responding poorly to targeted drugs, miR-101-5p overexpression inhibited proliferation (p < 0.001), and combinatorial treatment with lapatinib and trastuzumab significantly further decreased this inhibition (p = 0.004). Proteomic data and in silico analyses revealed PI3K/Akt- and HER2-pathways among the predicted regulated pathways. miR-101-5p alone (p = 0.018) and in combination with lapatinib and trastuzumab (p < 0.001) induced apoptosis, while the targeted drugs alone did not exert any significant effect neither on proliferation nor apoptosis.Conclusion: miR-101-5p acts as a tumor suppressor by inducing apoptosis in HER2+ breast cancer and sensitizes cells with initially poor response to lapatinib and trastuzumab.Keywords: microRNA, targeted treatment, apoptosis, sensitize

Abstract Active grassland restoration has gained importance in mitigating the dramatic decline of farmnland biodiversity. While there is evidence that such operations are generally effective in promoting plant diversity, little is known about the effectiveness of the different methods applied. Restoration methods can differ in intensity of seed bed preparation, seed source and method of seed application. In this systematic literature search and meta‐analysis, we screened the literature for studies of the restoration of mesic grasslands in temperate Europe. We focused on active restoration experiments that included a treatment and lasted for more than 3 years. We evaluated the influence of restoration factors on plant species richness relative to non‐restored controls. We found 187 articles that investigated the outcome of operations aimed at actively restoring mesic temperate grasslands. Most articles focused on plants, with only 9.6% dealing with other organisms (e.g. beetles, pollinating insects). Many papers had to be excluded due to incomplete data, too short study duration and/or lack of an adequate control. This resulted in 13 articles fulfilling our criteria for inclusion, yielding a total of 56 data points for the meta‐analysis. Restoration actions increased plant species richness by, on average, 17.4%, compared to controls. The seed source explained a significant amount of variation in plant species richness: seeds originating from a speciose donor grassland had a positive effect. This effect was even enhanced when combined with a commercial seed mix, whereas commercial seed mixes alone had no significant effect. We did not observe any effect of other factors, such as the type of seed bed preparation or the seed application method. A seed‐source obtained from species‐rich grasslands seems to be key to efficient grassland restoration in mesic grasslands of temperate Europe. Even though seeds from a speciose donor grassland should be preferred over commercial seeds, associating natural and commercial seed mixes increases plant species richness. This systematic literature search further revealed two major research gaps in grassland restoration ecology: a deficit in long‐term investigations as well as a deficit in studies focusing on non‐plant organisms.

This study offers an integrated evaluation methodology for construction project delay causes viewed as a multicriteria sorting (MCS) problem. Time, cost, and quality were the three project management factors considered as criteria to evaluate 38 identified delay causes. The priority weights were extracted using the integration of Weighted Influence Non-linear Gauge Systems (WINGS) and Level-Based Weight Assessment (LBWA) to capture the inherent interdependencies of the criteria. The sorting of 38 delay causes was performed using FlowSort. To handle the uncertainty and vagueness of the judgments of the decision makers in the evaluation process, q-rung fuzzy orthopair fuzzy sets (q-ROFS) were integrated within the proposed computational framework. The proposed novel q-ROF–WINGS–LBWA–FlowSort method was applied in an actual case study in residential construction projects. The delay causes were categorized under three categories of construction firm vulnerability into four levels of impact. In highly vulnerable construction firms, thirty-five delay causes have a high impact, two have a moderate impact, and one has the least impact. In moderately vulnerable and least-vulnerable construction firms, 32 and 28 delay causes have a medium impact, respectively. The results may provide insights for decision makers in highly vulnerable construction firms, i.e., small companies with limited resources and networks. Layers of sensitivity and comparative analyses were put forward to test the robustness of the approach.

Abstract Background Powered wheelchairs are an essential technology to support mobility, yet their use is associated with a high level of sedentarism that can have negative health effects for their users. People with Duchenne muscular dystrophy (DMD) start using a powered wheelchair in their early teens due to the loss of strength in their legs and arms. There is evidence that low-intensity exercise can help preserve the functional abilities of people with DMD, but options for exercise when sitting in a powered wheelchair are limited. Methods In this paper, we present the design and the feasibility study of a new version of the MOVit device that allows powered-wheelchair users to exercise while driving the chair. Instead of using a joystick to drive the wheelchair, users move their arms through a cyclical motion using two powered, mobile arm supports that provide controller inputs to the chair. The feasibility study was carried out with a group of five individuals with DMD and five unimpaired individuals. Participants performed a series of driving tasks in a wheelchair simulator and on a real driving course with a standard joystick and with the MOVit 2.0 device. Results We found that driving speed and accuracy were significantly lowered for both groups when driving with MOVit compared to the joystick, but the decreases were small (speed was 0.26 m/s less and maximum path error was 0.1 m greater). Driving with MOVit produced a significant increase in heart rate (7.5 bpm) compared to the joystick condition. Individuals with DMD reported a high level of satisfaction with their performance and comfort in using MOVit. Conclusions These results show for the first time that individuals with DMD can easily transition to driving a powered wheelchair using cyclical arm motions, achieving a reasonable driving performance with a short period of training. Driving in this way elicits cardiopulmonary exercise at an intensity found previously to produce health-related benefits in DMD.

Estimating turnover in a population provides information on population dynamics, such as dispersal and mortality. Dispersal increases genetic diversity and affects the genetic structure. Golden eagles are monogamous, tend to mate for life, and have strong nest site fidelity, which suggests low turnover rates. Here, we first studied genetic diversity and population structure in the Finnish golden eagle population using 11 microsatellite loci and a fragment of a mitochondrial DNA control region. We found no notable changes in genetic diversity during the 15-year study period and did not discover any population structure. Then, we examined the turnover rate using chick genotypes (N = 935) by estimating relatedness between chicks born in the same territory in different years. The results showed a turnover rate of 23%, which correlated with the breeding success of the previous year. Similarly, in the absence of turnover, the pair changed nest sites within a territory after an unsuccessful breeding. In addition, our dataset also revealed natal dispersal of ten individuals. Natal dispersal distance was 110 km on average (median 98 km); however, the distance seemed to vary depending on geographical location, being greater in Northern Finland than in Southern Finland.

Ophthalmic examination is essential in the avian triage process in order to apply prompt therapeutic plans and evaluate rehabilitation potential. Fundoscopy is traditionally performed by direct or indirect ophthalmoscopy. Recent technological developments have enabled the design of a small-sized and affordable retinal imaging system to examine the fundus. We investigate the use of a smartphone-based device to realize fundus examination through a prospective cross-sectional observational study. Seventy-seven eyes of 39 birds of 15 different species were evaluated using the smartphone-based device in a rescue wildlife center. Pupil dilation was achieved prior to examination via rocuronium topical application. Assessment of fundus by the smartphone was classified as satisfactory, moderately satisfactory, and unsatisfactory. Fundus examination was also performed with a 20D, 30D, or 78D lens for comparison. Pupillary dilation was satisfactory, moderately satisfactory, or absent in 17, 32, and 28 eyes, respectively. Fundus examination with the smartphone-based device was satisfactory, moderately satisfactory, or unsatisfactory in 44, 15, and 18 eyes, respectively. The feasibility of the fundus examination was affected by the form of the globe; by the quality of pupil dilation; by the color of the iris (images could not be obtained from species with an orange, bright iris); and by the species, with owls (Strigiformes) being the easiest to observe. Based on these findings, fundus examination was feasible in most bird species examined in this study.

Integral membrane proteins (MP) exhibit specific tridimensional conformation and topology that define their various functions. Pathogen surface antigens, encompassing many MP, are at the forefront of the viral strategy which is broadly targeted by the host immune response. These antigens are present in equilibrium under different oligomeric forms with distinctive epitopes, and to obtain them in a soluble form and/or stable constitutes a real risk. The solubilization of a full-length MP directly from a pathogen to rapidly obtain a native antigen mimicking the original conformation of the MP at the pathogen surface is the process development reported in this work. Rabies virus (RABV) was used as a model for this demonstration and its full-length glycoprotein (G) was stabilized in amphiphatic polymers (A8-35 amphipols). The stability of the soluble RABV-G was evaluated under various stress conditions (temperatures, agitation and light exposures) and a long-term stable RABV-G formulation, suitable for the freeze-drying process, was defined using a design of experiment approach. RABV-G/A8-35 in liquid form was shown to be antigenically stable at 5 °C and 25 °C for one month, and a dedicated kinetic model predicted its stability up to 1 year at 5 °C. To mitigate the RABV-G/A8-35 sensitivity to mechanical stress, a solid form of RABV-G/A8-35 and a freeze-drying process were considered, resulting in a 2-year thermally stable product at 5 °C, 25 °C and 37 °C. To the best of our knowledge, this is the first time that a natural full-length MP, extracted from a virus and trapped in amphipols, was kept antigenically stable in the long term, in a defined freeze-dried form out of any refrigerated storage conditions. These results described an easy process to obtain a pure, well conformed native-like antigen of interest, from a circulating pathogen which is of concern for diagnostic (quantification/characterization assays), therapeutic and vaccine strategies. After the physical characterization of the protein, the identification of RABV G/A8-35 neutralizing epitopes has been underway before in vivo testing.

Purpose: This exploratory study innovates the pedagogy of undergraduate business research courses by integrating Generative Artificial Intelligence (GAI) tools, guided by human-centered artificial intelligence, social-emotional learning, and authenticity principles. Design/methodology/approach: An insider case study approach was employed to examine an undergraduate business research course where 72 students utilized GAI for coursework. Thematic analysis was applied to their meta-reflective journals. Findings: Students leverage GAI tools as brainstorming partners, co-writers, and co-readers, enhancing research efficiency and comprehension. They exhibit authenticity and human-centered AI principles in their GAI engagement. GAI integration imparts relevant AI skills to students. Research limitations/implications: Future research could explore how teams collectively interact with GAI tools. Practical implications: Incorporating meta-reflections can promote responsible GAI usage and develop students' self-awareness, critical thinking, and ethical engagement. Social implications: Open discussions about social perceptions and emotional responses surrounding GAI use are necessary. Educators can foster a learning environment that nurtures students' holistic development, preparing them for technological challenges while preserving human learning and growth. Originality/value: This study fills a gap in exploring the delivery and outcomes of AI-integrated undergraduate education, prioritizing student perspectives over the prevalent focus on educators' viewpoints. Additionally, it examines the teaching and application of AI for undergraduate research, diverging from current studies that primarily focus on research applications for academics.

During 2009, pandemic influenza A(H1N1)pdm09 virus affected humans on Réunion Island. Since then, the virus has sustained circulation among local swine herds, raising concerns about the potential for genetic evolution of the virus and possible retransmission back to humans of variants with increased virulence. Continuous surveillance of A(H1N1)pdm09 infection in pigs is recommended.

* Context.--Serology plays a vital role in celiac disease (CD) diagnosis, and the latest European guidelines advocate for biopsy-free diagnoses in patients with [greater than or equal to] 10X the upper limit of normal (ULN) of anti-tissue transglutaminase (tTG) immunoglobulin A (IgA) antibodies. Objective.--To assess performance characteristics of a novel automated particle-based multianalyte technology (Aptiva) for anti-tTG and anti-deamidated gliadin peptide (DGP) antibody detection as compared to the traditional enzyme-linked immunosorbent assay (QUANTA Lite). Performance characteristics of the [greater than or equal to] 10X ULN anti-tTG IgA criteria for serologic diagnosis of CD were also evaluated. Design.--Sera samples from 703 patients were tested for anti-tTG IgA, anti-tTG immunoglobulin G (IgG), antiDGP IgA, and anti-DGP IgG antibodies on both platforms. In total, 127 patients had medical information and were classified as CD-positive (n = 58) and CD-negative (n = 69) based on biopsy results. Clinical performance characteristics were evaluated. Results.--Anti-tTG IgA detection showed equal clinical sensitivity and specificity of 91% sensitivity and 99% specificity on both platforms. Anti-tTG IgG resulted in moderate sensitivity of 69% and 72%, but high specificity of 100% and 94% on Aptiva and QUANTA Lite, respectively. Anti-DGP IgG displayed comparable sensitivity of 90% and 81%, and a specificity of 94% and 99%, on Aptiva and QUANTA Lite, respectively. Anti-DGP IgA demonstrated greater sensitivity on QUANTA Lite (83%) than Aptiva (69%) and similar specificities of 97% and 98% on QUANTA Lite and Aptiva, respectively. At [greater than or equal to] 10X ULN levels for anti-tTG IgA, Aptiva displayed a sensitivity of 72% and a specificity of 100%, and QUANTA Lite showed a sensitivity of 69% and a specificity of 100%. Conclusions.--Aptiva is a reliable method to measure CD biomarkers with reduced hands-on necessity and high-throughput capabilities. This study supports the use of a [greater than or equal to] 10X ULN anti-tTG IgA biopsy-free approach for serologic diagnosis of CD. (Arch Pathol Lab Med. 2023;147:1422-1430; doi: 10.5858/arpa.2022-0385-OA), Celiac disease (CD) is a chronic immune-mediated disease of the small intestine triggered by dietary gluten in genetically predisposed individuals. (1,2) The prevalence of biopsy-confirmed CD is estimated at 0.7% [...]

Hepatitis C virus (HCV), a major cause of chronic liver disease in humans, is the focus of intense research efforts worldwide. Yet structural data on the viral envelope glycoproteins E1 and E2 are scarce, in spite of their essential role in the viral life cycle. To obtain more information, we developed an efficient production system of recombinant E2 ectodomain (E2e), truncated immediately upstream its trans-membrane (TM) region, using Drosophila melanogaster cells. This system yields a majority of monomeric protein, which can be readily separated chromatographically from contaminating disulfide-linked aggregates. The isolated monomeric E2e reacts with a number of conformation-sensitive monoclonal antibodies, binds the soluble CD81 large external loop and efficiently inhibits infection of Huh7.5 cells by infectious HCV particles (HCVcc) in a dose-dependent manner, suggesting that it adopts a native conformation. These properties of E2e led us to experimentally determine the connectivity of its 9 disulfide bonds, which are strictly conserved across HCV genotypes. Furthermore, circular dichroism combined with infrared spectroscopy analyses revealed the secondary structure contents of E2e, indicating in particular about 28% beta-sheet, in agreement with the consensus secondary structure predictions. The disulfide connectivity pattern, together with data on the CD81 binding site and reported E2 deletion mutants, enabled the threading of the E2e polypeptide chain onto the structural template of class II fusion proteins of related flavi- and alphaviruses. The resulting model of the tertiary organization of E2 gives key information on the antigenicity determinants of the virus, maps the receptor binding site to the interface of domains I and III, and provides insight into the nature of a putative fusogenic conformational change.

BackgroundPowered wheelchairs are an essential technology to support mobility, yet their use is associated with a high level of sedentarism that can have negative health effects for their users. People with Duchenne muscular dystrophy (DMD) start using a powered wheelchair in their early teens due to the loss of strength in their legs and arms. There is evidence that low-intensity exercise can help preserve the functional abilities of people with DMD, but options for exercise when sitting in a powered wheelchair are limited.MethodsIn this paper, we present the design and the feasibility study of a new version of the MOVit device that allows powered-wheelchair users to exercise while driving the chair. Instead of using a joystick to drive the wheelchair, users move their arms through a cyclical motion using two powered, mobile arm supports that provide controller inputs to the chair. The feasibility study was carried out with a group of five individuals with DMD and five unimpaired individuals. Participants performed a series of driving tasks in a wheelchair simulator and on a real driving course with a standard joystick and with the MOVit 2.0 device.ResultsWe found that driving speed and accuracy were significantly lowered for both groups when driving with MOVit compared to the joystick, but the decreases were small (speed was 0.26 m/s less and maximum path error was 0.1 m greater). Driving with MOVit produced a significant increase in heart rate (7.5 bpm) compared to the joystick condition. Individuals with DMD reported a high level of satisfaction with their performance and comfort in using MOVit.ConclusionsThese results show for the first time that individuals with DMD can easily transition to driving a powered wheelchair using cyclical arm motions, achieving a reasonable driving performance with a short period of training. Driving in this way elicits cardiopulmonary exercise at an intensity found previously to produce health-related benefits in DMD.

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1-3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10-18.

Background: Dietary challenges are common among individuals with intellectual disability residing in supervised living in Norway, and this is a major risk factor for health problems. The aim of this study was to explore feasibility of the nutrition tablet app APPetitus, among persons with intellectual disability and their formal caregivers. Method: Joint dyad interviews with residents and caregivers were conducted after five individuals with intellectual disability used APPetitus for eight weeks. Seven formal caregivers and managers participated in subsequent focus group interviews. Thematic analysis informed the data analysis. The study complies with the Consolidated Criteria for Reporting Qualitative Research (COREQ). Results: The findings were mapped into three themes: APPetitus mediating nutritional conversations, residents' strategies to control the conversation and caregiver support as a required prerequisite for overall user comprehension. Conclusions: The study demonstrates that a nutritional app can contribute to and normalize nutritional conversations, and empower residents to participate.