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Abstract Aim If surgical guide fabrication is introduced in a dental education program, a digital and conventional workflow can be used. This study evaluated operator preference, perceived difficulty and effectiveness and operating time of both fabrication methods. Materials and Methods Forty participants in a university setting (students, n = 20; dentists, n = 20) with varying levels of dental experience, but no experience in surgical guide fabrication, were randomly assigned to consecutively fabricate surgical guides on a standardized training model, with either the digital or conventional workflow first. The operating time was measured, and operator preference and the perception of difficulty and effectiveness were assessed with a questionnaire. T tests were used for statistical analysis (α = .05). Result Of the students, 95% preferred the digital workflow and of the dentists 70%. The perceived difficulty of the digital workflow was significantly lower than the conventional workflow in the student group. Both groups perceived the digital workflow to be more effective. The mean operating time (mm:ss) amounted 12:34 ± 2:24 (students) and 18:07 ± 6:03 (dentists) for the digital, and 22:20 ± 3:59 (students) and 20:16 ± 4:03 (dentists) for the conventional workflow. Conclusion Both students and dentists prefer the digital workflow for surgical guide fabrication. Students perceive the digital workflow as less difficult and more effective than the conventional workflow. The operating time for surgical guide fabrication is shorter with a digital workflow. This study indicates that digital fabrication techniques for surgical guides are preferred to be incorporated into the dental curriculum to teach students about treatment planning in implant dentistry.

Pseudoinvasion (PI) is a benign lesion in which cancer is mimicked in the colon by misplacement of dysplastic glands in the submucosa. Although there are morphological clues, the discrimination of PI from true invasion can be a challenge during pathological evaluation of colon adenomas. Both overdiagnosis and underdiagnosis can result in inadequate clinical decisions. This calls for novel tools to aid in cases where conventional methods do not suffice. We performed mass spectrometry imaging (MSI)-based spatial glycomics analysis on a cohort of formalin-fixed paraffin-embedded tissue (FFPE) material from 16 patients who underwent polypectomy. We used this spatial glycomic data to reconstruct the molecular histology of the tissue section using spatial segmentation based on uniform manifold approximation and projection for dimension reduction (UMAP). We first showed that the spatial glycomic phenotypes of the different morphological entities separated as distinct clusters in colon tissues, we separated true invasion from the other morphological entities. Then, we found that the glycomic phenotype in areas with suspected PI in the submucosa was strongly correlating with the corresponding glycomic phenotype of the adenomatous colon epithelium from the same tissue section (Pearson correlation distance average = 0.18). These findings suggest that using spatial glycomics, we can distinguish PI as having a molecular phenotype similar to the corresponding surface epithelium and true invasion as having a different phenotype even when compared to high-grade dysplasia. Therefore, when a novel molecular phenotype is found in the deepest submucosal region, this may be used as an argument in favor of true invasion.

This paper analyses the effects of product innovations introduced by firms in upstream and downstream sectors and firms in the same sector on firm employment. To this end, we extend the Harrison et al. (2014. "Does Innovation Stimulate Employment? A Firm-Level Analysis Using Comparable Micro-Data from Four European Countries." International Journal of Industrial Organization 35 (1): 29–43) model and analyse the relationship between firm innovation and employment to account for innovation in the same and related sectors. We employ panel data for the innovation activities of Spanish firms together with input–output data. The results show that product innovation by firms in the same sector harms the firm's employment. We also find a negative effect on employment for the introduction of new products in upstream sectors, which results in the reduction of labour in the focal firm. The type of labour that is negatively affected by innovations introduced by both same-sector and upstream firms is low-skilled. No significant effects are found for innovations introduced in downstream industries. [ABSTRACT FROM AUTHOR]

Abstract Background Degeneration of shoulder muscle tissues often result in tearing, causing pain, disability and loss of independence. Differential muscle involvement patterns have been reported in tears of shoulder muscles, yet the molecules involved in this pathology are poorly understood. The spatial distribution of biomolecules across the affected tissue can be accurately obtained with matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI). The goal of this pilot study was to decipher the metabolic landscape across shoulder muscle tissues and to identify signatures of degenerated muscles in chronic conditions. Methods Paired biopsies of two rotator cuff muscles, torn infraspinatus and intact teres minor, together with an intact shoulder muscle, the deltoid, were collected during an open tendon transfer surgery. Five patients, average age 65.2 ± 3.8 years, were selected for spatial metabolic profiling using high‐spatial resolution (MALDI‐TOF) and high‐mass resolution (MALDI‐FTICR) MSI in negative or positive ion mode. Metabolic signatures were identified using data‐driven analysis. Verifications of spatial localization for selected metabolic signatures were carried out using antibody immunohistology. Results Data‐driven analysis revealed major metabolic differences between intact and degenerated regions across all muscles. The area of degenerated regions, encompassed of fat, inflammation and fibrosis, significantly increased in both rotator cuff muscles, teres minor (27.9%) and infraspinatus (22.8%), compared with the deltoid (8.7%). The intact regions were characterized by 49 features, among which lipids were recognized. Several of the identified lipids were specifically enriched in certain myofiber types. Degenerated regions were specifically marked by the presence of 37 features. Heme was the most abundant metabolite in degenerated regions, whereas Heme oxygenase‐1 (HO‐1), which catabolizes heme, was found in intact regions. Higher HO‐1 levels correlated with lower heme accumulation. Conclusions Degenerated regions are distinguished from intact regions by their metabolome profile. A muscle‐specific metabolome profile was not identified. The area of tissue degeneration significantly differs between the three examined muscles. Higher HO‐1 levels in intact regions concurred with lower heme levels in degenerated regions. Moreover, HO‐1 levels discriminated between dysfunctional and functional rotator cuff muscles. Additionally, the enrichment of specific lipids in certain myofiber types suggests that lipid metabolism differs between myofiber types. The signature metabolites can open options to develop personalized treatments for chronic shoulder muscles degeneration.

Abstract Background Tackling childhood obesity is complex and requires a community-based approach implemented in multiple environments. It is known from literature that knowledgeable and skilled professionals are essential to implement such an approach successfully. The aim of the present study was to assess the need for training and support among a global network of programme directors implementing a Community-Based Childhood Obesity Intervention (CBCOI) based on the EPODE approach, in order to assist them in optimising the implementation process. Methods An online survey was sent to 40 programme directors representing programmes implementing a CBCOI based on the EPODE approach. The survey consisted of statements on a 5-point Likert scale and multiple-choice questions about attitude towards and usefulness of training and support, and preferences for some predefined training types and training topics. In total, 22 programme directors responded to the survey (55% response rate). Data were analysed using descriptive statistics to describe the need for support in order to improve successful implementation. Results Respondents strongly agreed that continually updating skills and learning how to make their programmes more effective and sustainable at the start and during the implementation was important. On-site training was preferred most at the commencement of a programme, while a 2-day training course was most valued during implementation. Monitoring, measuring and programme evaluation was identified as the most valuable training topic. Conclusions The results indicate a continuing and significant need for support and training among programme directors implementing a CBCOI. The findings give directions regarding topics and types of training and support in order to improve the implementation process.

Introduction: Diabetic nephropathy (DN) and hypertensive nephrosclerosis (HN) represent the most common causes of chronic kidney disease (CKD) and many patients progress to ­end-stage renal disease. Patients are treated primarily through the management of cardiovas­cular risk factors and hypertension; however patients with HN have a more favorable outcome. A noninvasive clinical approach to separate these two entities, especially in hypertensive patients who also have diabetes, would allow for targeted treatment and more appropriate resource allocation to those patients at the highest risk of CKD progression. Meth­ods: In this preliminary study, high-spatial-resolution matrix-assisted laser desorption/ion­ization (MALDI) mass spectrometry imaging (MSI) was integrated with high-mass accuracy MALDI-FTICR-MS and nLC-ESI-MS/MS analysis in order to detect tissue proteins within kidney biopsies to discriminate cases of DN (n = 9) from cases of HN (n = 9). Results: Differences in the tryptic peptide profiles of the 2 groups could clearly be detected, with these becoming even more evident in the more severe histological classes, even if this was not evident with routine histology. In particular, 4 putative proteins were detected and had a higher signal intensity within regions of DN tissue with extensive sclerosis or fibrosis. Among these, 2 proteins (PGRMC1 and CO3) had a signal intensity that increased at the latter stages of the disease and may be associated with progression. Discussion/Conclusion: This preliminary study represents a valuable starting point for a future study employing a larger cohort of patients to develop sensitive and specific protein biomarkers that could reliably differentiate between diabetic and hypertensive causes of CKD to allow for improved diagnosis, fewer biopsy procedures, and refined treatment approaches for clinicians.

Current developments towards multipin, dry electrodes in electroencephalography (EEG) are promising for applications in non-laboratory environments. Dry electrodes do not require the application of conductive gel, which mostly confines the use of gel EEG systems to the laboratory environment. The aim of this study is to validate soft, multipin, dry EEG electrodes by comparing their performance to conventional gel EEG electrodes. Fifteen healthy volunteers performed three tasks, with a 32-channel gel EEG system and a 32-channel dry EEG system: the 40 Hz Auditory Steady-State Response (ASSR), the checkerboard paradigm, and an eyes open/closed task. Within-subject analyses were performed to compare the signal quality in the time, frequency, and spatial domains. The results showed strong similarities between the two systems in the time and frequency domains, with strong correlations of the visual (ρ = 0.89) and auditory evoked potential (ρ = 0.81), and moderate to strong correlations for the alpha band during eye closure (ρ = 0.81–0.86) and the 40 Hz-ASSR power (ρ = 0.66–0.72), respectively. However, delta and theta band power was significantly increased, and the signal-to-noise ratio was significantly decreased for the dry EEG system. Topographical distributions were comparable for both systems. Moreover, the application time of the dry EEG system was significantly shorter (8 min). It can be concluded that the soft, multipin dry EEG system can be used in brain activity research with similar accuracy as conventional gel electrodes.

Aim: If surgical guide fabrication is introduced in a dental education program, a digital and conventional workflow can be used. This study evaluated operator preference, perceived difficulty and effectiveness and operating time of both fabrication methods. Materials and Methods: Forty participants in a university setting (students, n = 20; dentists, n = 20) with varying levels of dental experience, but no experience in surgical guide fabrication, were randomly assigned to consecutively fabricate surgical guides on a standardized training model, with either the digital or conventional workflow first. The operating time was measured, and operator preference and the perception of difficulty and effectiveness were assessed with a questionnaire. T tests were used for statistical analysis (α =.05). Result: Of the students, 95% preferred the digital workflow and of the dentists 70%. The perceived difficulty of the digital workflow was significantly lower than the conventional workflow in the student group. Both groups perceived the digital workflow to be more effective. The mean operating time (mm:ss) amounted 12:34 ± 2:24 (students) and 18:07 ± 6:03 (dentists) for the digital, and 22:20 ± 3:59 (students) and 20:16 ± 4:03 (dentists) for the conventional workflow. Conclusion: Both students and dentists prefer the digital workflow for surgical guide fabrication. Students perceive the digital workflow as less difficult and more effective than the conventional workflow. The operating time for surgical guide fabrication is shorter with a digital workflow. This study indicates that digital fabrication techniques for surgical guides are preferred to be incorporated into the dental curriculum to teach students about treatment planning in implant dentistry. [ABSTRACT FROM AUTHOR]

BackgroundThe development of treatments for freezing of gait (FOG) in Parkinson's disease (PD) requires experimental study set-ups in which FOG is likely to occur, and is amenable to therapeutic interventions. We explore whether the 'Auditory Stroop Task' (AST) can be used to increase cognitive load (and thereby elicit FOG), simultaneously with visual cues (as a therapeutic intervention for FOG). We additionally examined how these two contrasting effects might interact in affecting gait and FOG parameters.ObjectivesWe investigated whether: (1) the 'Auditory Stroop Task' (AST) influences gait in healthy elderly and persons with PD who experience FOG, and increases the frequency of FOG events among PD patients; (2) the AST and visual cues interact; and (3) different versions of the AST exert different cognitive loads.MethodsIn 'Experiment 1', 19 healthy elderly subjects performed a walking task while performing a high and low load version of the AST. Walking with a random numbers task, and walking without cognitive load served as control conditions. In 'Experiment 2', 20 PD patients with FOG and 18 healthy controls performed a walking task with the AST, and no additional cognitive load as control condition. Both experiments were performed with and without visual cues. Velocity, cadence, stride length, and stride time were measured in all subjects. FOG severity was measured in patients.ResultsCompared to the control conditions, the AST negatively affected all gait parameters in both patients and controls. The AST did not increase the occurrence of FOG in patients. Visual cues reduced the decline in stride length induced by cognitive load in both groups. Both versions of the AST exerted similar effects on gait parameters in controls.ConclusionsThe AST is well-suited to simulate the effects of cognitive load on gait parameters, but not FOG severity, in gait experiments in persons with PD and FOG.

Under non-inflammatory conditions HLA class II is predominantly expressed on hematopoietic cells. Therefore, donor CD4 T-cells after allogeneic stem cell transplantation (alloSCT) may mediate graft-vs.-leukemia reactivity without graft-vs.-host disease (GVHD). We analyzed immune responses in four patients converting from mixed to full donor chimerism without developing GVHD upon purified CD4 donor lymphocyte infusion (DLI) from their HLA-identical sibling donor after T-cell depleted alloSCT. In vivo activated T-cells were clonally isolated after CD4 DLI. Of the alloreactive T-cell clones, 96% were CD4 positive, illustrating the dominant role of CD4 T-cells in the immune responses. We identified 9 minor histocompatibility antigens (MiHA) as targets for alloreactivity, of which 8 were novel HLA class II restricted MiHA. In all patients, MiHA specific CD4 T-cells were found that were capable to lyse hematopoietic cells and to recognize normal and malignant cells. No GVHD was induced in these patients. Skin fibroblasts forced to express HLA class II, were recognized by only two MiHA specific CD4 T-cell clones. Of the 7 clones that failed to recognize fibroblasts, two targeted MiHA were encoded by genes not expressed in fibroblasts, presentation of one MiHA was dependent on HLA-DO, which is absent in fibroblasts, and T-cells recognizing the remaining 4 MiHA had an avidity that was apparently too low to recognize fibroblasts, despite clear recognition of hematopoietic cells. In conclusion, purified CD4 DLI from HLA-identical sibling donors can induce conversion from mixed to full donor chimerism with graft-vs.-malignancy reactivity, but without GVHD, by targeting HLA class II restricted MiHA.

Este artículo presenta una metodología para configurar los sistemas regionales de innovación (SRI) en Europa. A partir de la técnica estadística del análisis factorial, 35 variables altamente correlacionadas, pero que reflejan distintos aspectos de la actividad innovadora regional, son reducidas a siete variables compuestas o factores, cada una representando aspectos claves o subsistemas de los sistemas de innovación. Esta técnica holística y objetiva permite, a su vez, una serie de aplicaciones, entre ellas, el cálculo de un índice de capacidad tecnológica, la configuración de una tipología de los SRI y la estimación de una función de producción de conocimiento identificando los determinantes de la innovación.

Introduction The curative effect of allogeneic stem cell transplantation (allo-SCT) as a treatment modality for hematological malignancies is based on the capacity of donor T cells to effectively induce graft-versus-leukemia [...], Patients with leukemia who receive a T cell-depleted allogeneic stem cell graft followed by postponed donor lymphocyte infusion (DLI) can experience graft-versus-leukemia (GVL) reactivity, with a lower risk of graft-versus-host disease (GVHD). Here, we have investigated the magnitude, diversity, and specificity of alloreactive CD8 T cells in patients who developed GVL reactivity after DLI in the absence or presence of GVHD. We observed a lower magnitude and diversity of CD8 T cells for minor histocompatibility antigens (MiHAs) in patients with selective GVL reactivity without GVHD. Furthermore, we demonstrated that MiHA-specific T cell clones from patients with selective GVL reactivity showed lower reactivity against nonhematopoietic cells, even when pretreated with inflammatory cytokines. Expression analysis of MiHA-encoding genes showed that similar types of antigens were recognized in both patient groups, but in patients who developed GVHD, T cell reactivity was skewed to target broadly expressed MiHAs. As an inflammatory environment can render nonhematopoietic cells susceptible to T cell recognition, prevention of such circumstances favors induction of selective GVL reactivity without development of GVHD.

Mass spectrometry imaging (MSI) is a molecular imaging technique that maps the distribution of molecules in biological tissues with high spatial resolution. The most widely used MSI modality is matrix-assisted laser desorption/ionization (MALDI), mainly due to the large variety of analyte classes amenable for MALDI analysis. However, the organic matrices used in classical MALDI may impact the quality of the molecular images due to limited lateral resolution and strong background noise in the low mass range, hindering its use in metabolomics. Here we present a matrix-free laser desorption/ionization (LDI) technique based on the deposition of gold nanolayers on tissue sections by means of sputter-coating. This gold coating method is quick, fully automated, reproducible, and allows growing highly controlled gold nanolayers, necessary for high quality and high resolution MS image acquisition. The performance of the developed method has been tested through the acquisition of MS images of brain tissues. The obtained spectra showed a high number of MS peaks in the low mass region (m/z below 1000 Da) with few background peaks, demonstrating the ability of the sputtered gold nanolayers of promoting the desorption/ionization of a wide range of metabolites. These results, together with the reliable MS spectrum calibration using gold peaks, make the developed method a valuable alternative for MSI applications.