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This paper addresses the analysis of sentence fragments, specifically the English negative polar response item no. Two main types of synchronic analysis have been proposed for present-day English – one in which yes and no are syntactically inert particles which substitute for a clause, the other in which they are the initial element of an elided clause. Using diachronic data from 15th- to 17th-century English, we argue that the emergence of a novel other-speaker question pattern involving no demonstrates that speakers of early English analysed interrogative polar no as the initial element of a clause with TP-ellipsis. This novel pattern has received little attention in the literature, yet this grammatical innovation is interesting because its emergence demonstrates how diachronic change can be used as a diagnostic for underlying grammatical structure.

IntroductionDerivatives from Saccharomyces cerevisiae yeast including yeast extracts and yeast cell walls are sustainable sources of valuable nutrients, including dietary fibers and proteins. Previous studies have shown that certain components from these yeast derivatives can inhibit the growth of harmful intestinal bacteria and promote the growth of beneficial bacteria. However, the effects of yeast derivatives on oral health have not yet been investigated.MethodsAn in vitro oral biofilm model was employed to examine the impacts of yeast derivatives on the oral microbiota and their potential benefits for maintaining oral homeostasis. The model incorporated dental plaque donor material from both healthy and periodontitis diagnosed individuals. Biofilm formation, density, and microbial composition were quantified. Additionally, the production of short-chain fatty acids in the biofilm supernatants was measured.ResultsYeast extracts had only minor effects on oral biofilm formation. In contrast, yeast cell wall derivatives, which are rich in polysaccharides such as beta-glucans and mannans, significantly reduced the density of the oral biofilms in vitro. This reduction in biofilm density was associated with an overall shift in the bacterial community composition, including an increase in beneficial bacteria and a decrease in the abundance of Tannerella forsythia, an important species involved in bacterial coaggregation and the development and maturation of the oral biofilm. Furthermore, the yeast cell wall derivatives decreased the production of short-chain fatty acids, including acetic and butyric acid. These findings were consistent across both healthy and periodontitis microbiomes.ConclusionThis study has demonstrated the potential of yeast cell wall derivatives to positively impact oral health by significantly reducing biofilm density, modulating the oral microbial composition, and decreasing the production of short-chain fatty acids. The observed effects highlight the promising applications of these yeast-based compounds as an approach to managing oral diseases. Further research is needed to fully elucidate the mechanisms of action and explore the clinical potential of yeast cell wall derivatives in promoting and maintaining oral health.

Creativity is important for school performance. As several brain mechanisms involved in creativity are stimulated by low-intensity physical activity, standing might influence creativity. Few studies on the relationship between standing and creativity have been executed, and none among vocational education and training (VET) students. Therefore, the aim of this study was to investigate whether standing influences creativity in VET students. In a randomized crossover study, 192 VET students were randomly allocated to standing or sitting (i.e., control) for 30 min. After 15 min, they performed two creativity tests: Guilford's Alternative Uses Test (divergent thinking) and Remote Associates Test (convergent thinking). Subsequently, conditions were switched, and the procedure was repeated. Multilevel analyses showed no significant effect of standing on divergent or convergent thinking test performance. Our results show that 30 min of standing does not affect creativity in VET students.

Prebiotics can modulate the gut microbial community composition and function for improved (gut) health and increase resilience against infections. In vitro models of the gut facilitate the study of intervention effects on the gut microbial community relevant to health. The mucosa-associated gut microbiota, which thrives in close contact with the host plays a pivotal role in colonization resistance and health. Therefore, we here introduce the Mi-screen, an experimental approach implementing a 96-well plate equipped with a mucus agar layer for the additional culturing of mucosa-associated microbiota in vitro. In this study, we screened the effects of 2’-Fucosyllactose (2’-FL), fructooligosaccharides (FOS), and inulin within a complex microbiota without and with infection with the C. difficile strains ATCC 43599 (Ribotype 001) or ATCC BAA-1870 (Ribotype 027). We analyzed the microbial community composition and short-chain fatty acid levels after 48 h of incubation. The inclusion of an additional substrate and surface in the form of the mucus agar layer allowed us to culture a microbial richness ranging between 100–160 in Chao index, with Shannon indices of 5–6 across culture conditions, indicative of a microbial diversity of physiological relevance. The mucus agar layer stimulated the growth of characteristic mucosa-associated bacteria such as Roseburia inulinovorans. The prebiotic interventions affected luminal and mucosal microbial communities cultured in vitro and stimulated short-chain fatty acid production. FOS, inulin and 2’-FL promoted the growth of Bifidobacterium adolescentis within the mucosa-associated microbiota cultured in vitro. When spiking the untreated conditions with pathogenic C. difficile, the strains thrived within the luminal and the mucosal sample types, whereas prebiotic treatments exhibited inhibitory effects on C. difficile growth and prevented colonization. In conclusion, the Mi-screen facilitates the screening of luminal and mucosa-associated gut microbial community dynamics in vitro and therefore fills an important gap in the field of in vitro modeling.

Abstract Background Anxiety disorders are prevalent and disabling conditions involving excessive worry and tension. Generalized anxiety disorder (GAD), the most common anxiety disorder, affects 5% of individuals from high-income countries and many individuals report that treatment options are not accessible, effective, or tolerable. Clinical evidence suggests that nutrition interventions, based on the Mediterranean diet and supplementation of omega-3 fatty acids, can significantly improve symptoms of depression; however, the effect of nutrition interventions on anxiety symptoms has not been studied in a clinical population. The primary objective of the present study is to assess the feasibility and acceptability of a dietary counselling and omega-3 fatty acid supplementation intervention delivered to adult women with GAD. The secondary objectives include assessing changes in anxiety symptom severity, assessing changes in quality of life, assessing changes in biomarkers, and evaluating the components of the program. Methods This study is a randomized, wait-list controlled pilot trial delivering a 12-week, dietary counselling intervention and omega-3 supplementation to 50 adult women with GAD. Participants will complete seven individual counselling sessions which include education, personalized recommendations, mindful eating techniques, motivational interviewing, and goal setting. They will be provided with recipes, instructional videos, and food items. The intervention is designed based on the Social Cognitive Theory and previous research that has been done by the author team to identify dietary constituents with the most evidence to support their use in the treatment of anxiety disorders. Questionnaires and blood work will be completed at baseline, after the waiting period (for those in the waitlist group), and after the intervention. Discussion Results from this study will lay the foundation for future large-scale studies in this area and may provide preliminary evidence of the role of diet counselling and omega-3 supplementation in the management of GAD. Research on the role of nutrition in psychiatric care has been identified as a priority by a number of international organizations. The present trial directly addresses the call for the research that is most needed to advance the field. Trial registration This protocol was registered at ClinicalTrials.gov on October 10, 2022; NCT05573672 . Trial sponsor: The Canadian College of Naturopathic Medicine, 1255 Sheppard Ave E, Toronto, ON M2K 1E2, 416–498-1255. Steering committee: Composed of MA, LL, KC, IvdW, SM, UN, AJ. The committee meets monthly to oversee the trial. Protocol identifier: CCNM_EASe-GADCT_2201v4.

BackgroundThe role of the vulvar microbiome in the development of (pre)malignant vulvar disease is scarcely investigated. The aim of this exploratory study was to analyze vulvar microbiome composition in lichen sclerosus (LS) and vulvar high-grade squamous intraepithelial lesions (HSIL) compared to healthy controls.MethodsWomen with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements.ResultsHealthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043).ConclusionThis study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.

Radio wave treatment is considered as an alternative for steam treatment of soil in glasshouse horticulture for pathogen suppression. In principle, radio wave treatment can be selectively focused on localized infestations, as well as accommodate renewable energy sources. It may therefore help to significantly reduce fossil fuel consumption for soil treatment in greenhouse horticulture. A prototype treatment system has been developed prior to this study. Following this system's development, the next step is to develop optimum treatment strategies for its application. To this end, this study presents the development of an experimental method to perform quantified experimentation at laboratory scale on pathogen infested soil samples. The study is an interdisciplinary approach that merges respective contributions from microwave engineering, control engineering, and phytopathology. The design requirements for the experimental system are outlined. The design of the layout of the apparatus, computer simulations to optimize its geometry, and the design of power and temperature control are discussed. The study is finalized by reporting a demonstration of the experimental method. [ABSTRACT FROM AUTHOR]

Abstract Aim In order to evaluate the role of MMP-14 in ovarian cancer, a systematic review was conducted. Methods In March 2020, a search in Pubmed was performed with MMP-14 and ovarian cancer as search terms. After exclusion of the references not on MMP-14 or ovarian cancer or not in English, the studies found were classified into two categories: basic research and clinicopathological research. Results In total, 94 references were found of which 33 were excluded. Two additional articles were found in the reference lists of the included studies. Based on the full texts, another 4 were excluded. Eventually, 59 studies were included in the review, 32 on basic research and 19 on clinicopathological research. 8 studies fell in both categories. The basic research studies show that MMP-14 plays an important role in ovarian cancer in the processes of proliferation, invasion, angiogenesis and metastasis. In clinocopathological research, MMP-14 expression is found in most tumours with characteristics of poor prognosis but this immunohistochemical MMP-14 determination does not seem to be an independent predictor of prognosis. Conclusions From this systematic review of the literature concerning MMP-14 in ovarian cancer it becomes clear that MMP-14 plays various important roles in the pathophysiology of ovarian cancer. The exact translation of these roles in the pathophysiology to the importance of MMP-14 in clinicopathological research in ovarian cancer and possible therapeutic role of anti-MMP-14 agents needs further elucidation.

A positive association has been found between physical activity (PA) and student mental wellbeing (SMW). This association has been mainly explored in secondary school and university students. Studies in vocational education and training (VET) are lacking, while VET students could especially benefit from exploring this association since research shows that VET students, who often come from low socioeconomic status (SES) households, are prone to low SMW. Low SMW can result in higher school dropout rates and long-term negative effects, such as unemployment, social exclusion, and impoverishment. The aim of the current study was to explore the association between total PA and different physical activity behaviors {PABs, i.e., moderate to vigorous physical activity (MVPA), light physical activity (LPA), and sedentary behavior (SB)}, and SMW in the VET setting. In this cross-sectional observational study, students wore an ActivPAL3™ accelerometer for 7 consecutive days to measure PAB. SMW was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Rosenberg self-esteem questionnaire (RSE). Complete data for the analyses were obtained from 85 students. Multiple regression analyses showed a significant positive association between total PA and self-esteem and a significant negative association between total PA and depressive symptoms. Taking different PA intensities into account, there was a significant positive association between LPA and self-esteem and a significant negative association between LPA and depressive symptoms. No significant associations were found between MVPA and the outcome measures, although the associations were aligned with the findings for LPA. High levels of SB were significantly associated with low self-esteem; however, the association between SB and depressive symptoms was not significant. The significant positive associations between LPA and SMW and the negative association between SB and self-esteem indicate that decreasing SB and increasing LPA could contribute to improve SMW. Future research should determine if these are causal relationships.

Research suggests that sedentary behavior (SB) is negatively associated with cognitive outcomes. Interrupting prolonged sitting has been shown to improve cognitive functions, including executive functioning (EF), which is important for academic performance. No research has been conducted on the effect of standing on EF in VET students, who make up a large proportion of the adolescent population and who are known to sit more than other students of this age. In this study, we investigated the acute effects of reducing SB by short time standing on EF in vocational education and training (VET) students. In a randomized crossover study, 165 VET students were first taught for 15 min in seated position. After this, they performed while seated the Letter Memory Test for updating, and the Color Shape Test for shifting and inhibition. Students were randomly assigned to a sitting or standing condition. All students were taught again for 15 min and then took the same tests in the condition they were allocated to, respectively, standing or seated. After 1 week, the test procedure was repeated, in which students switched conditions. Mixed model analyses showed no significant effect of sitting or standing on updating, shifting, or inhibition. Also, no significant differences were found for the order of condition on updating, shifting, or inhibition. Our results suggest that 40 min of standing does not significantly influence EF among VET students.

Abstract Background In the military, insufficient postural stability is a risk factor for developing lower extremity injuries. Postural stability training programs are effective in preventing these injuries. However, an objective method for the measurement of postural stability in servicemen is lacking. The primary objective of this study was to assess the influence of the number of repetitions, different foot positions and real-time visual feedback on postural stability, as well as their effects on the intrasession reliability of postural stability measurements in servicemen. The secondary objective was to assess the concurrent validity of the measurements. Methods Twenty healthy servicemen between 20 and 50 years of age and in active duty were eligible for this quantitative, cross-sectional study. The measurements took place on a force plate, measuring the mean velocity of the center of pressure. The participants were asked to stand as still as possible in three different foot positions (wide stance, small stance, and on one leg), five times each for 45 s each time, and the measurements were performed with and without real-time visual feedback. Results We observed a significant main effect of foot position (P

Abstract Background This study examines the relationship between coping strategies and symptoms of anxiety or depression among Dutch servicemembers deployed to Afghanistan. Methods Coping strategies were assessed in 33 battlefield casualties (BCs) and the control group (CTRLs) of 33 uninjured servicemembers from the same combat units using the Cognitive Emotion Regulation Questionnaire. A factor analysis was performed, and two clusters of coping strategies were derived, namely, adaptive and maladaptive coping. Symptoms of anxiety and depression were evaluated using the depression and anxiety subscales of the Symptom Checklist-90-Revised. Correlations between coping and symptoms of anxiety and between coping and symptoms of depression were calculated, and a logistic regression was performed. Results A moderate correlation was observed between maladaptive coping and symptoms of anxiety in the BC group (r = 0.42) and among the CTRLs (r = 0.56). A moderate correlation was observed between maladaptive coping and symptoms of depression in both groups (r = 0.55). The statistical analysis for the total sample (BCs and CTRLs) demonstrated no association between coping and symptoms of anxiety or depression. Conclusions A correlation but no association was observed between maladaptive coping and mental health disorders in deployed Dutch servicemembers. Further research should focus on constructing cluster profiles of coping strategies and associating them with mental health outcomes and reintegration into society.

Abstract Background Magnetic resonance imaging (MRI) is being used extensively in the search for pathoanatomical factors contributing to low back pain (LBP) such as Modic changes (MC). However, it remains unclear whether clinical findings can identify patients with MC. The purpose of this explorative study was to assess the predictive value of six clinical tests and three questionnaires commonly used with patients with low-back pain (LBP) on the presence of Modic changes (MC). Methods A retrospective cohort study was performed using data from Dutch military personnel in the period between April 2013 and July 2016. Questionnaires included the Roland Morris Disability Questionnaire, Numeric Pain Rating Scale, and Pain Self-Efficacy Questionnaire. The clinical examination included (i) range of motion, (ii) presence of pain during flexion and extension, (iii) Prone Instability Test, and (iv) straight leg raise. Backward stepwise regression was used to estimate predictive value for the presence of MC and the type of MC. The exploration of clinical tests was performed by univariable logistic regression models. Results Two hundred eighty-six patients were allocated for the study, and 112 cases with medical records and MRI scans were available; 60 cases with MC and 52 without MC. Age was significantly higher in the MC group. The univariate regression analysis showed a significantly increased odds ratio for pain during flexion movement (2.57 [95% confidence interval (CI): 1.08–6.08]) in the group with MC. Multivariable logistic regression of all clinical symptoms and signs showed no significant association for any of the variables. The diagnostic value of the clinical tests expressed by sensitivity, specificity, positive predictive, and negative predictive values showed, for all the combinations, a low area under the curve (AUC) score, ranging from 0.41 to 0.53. Single-test sensitivity was the highest for pain in flexion: 60% (95% CI: 48.3–70.4). Conclusion No model to predict the presence of MC, based on clinical tests, could be demonstrated. It is therefore not likely that LBP patients with MC are very different from other LBP patients and that they form a specific subgroup. However, the study only explored a limited number of clinical findings and it is possible that larger samples allowing for more variables would conclude differently.

BACKGROUND:Bayesian networks (BNs) are machine-learning-based computational models that visualize causal relationships and provide insight into the processes underlying disease progression, closely resembling clinical decision-making. Preoperative identification of patients at risk for lymph node metastasis (LNM) is challenging in endometrial cancer, and although several biomarkers are related to LNM, none of them are incorporated in clinical practice. The aim of this study was to develop and externally validate a preoperative BN to predict LNM and outcome in endometrial cancer patients. METHODS AND FINDINGS:Within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), we performed a retrospective multicenter cohort study including 763 patients, median age 65 years (interquartile range [IQR] 58-71), surgically treated for endometrial cancer between February 1995 and August 2013 at one of the 10 participating European hospitals. A BN was developed using score-based machine learning in addition to expert knowledge. Our main outcome measures were LNM and 5-year disease-specific survival (DSS). Preoperative clinical, histopathological, and molecular biomarkers were included in the network. External validation was performed using 2 prospective study cohorts: the Molecular Markers in Treatment in Endometrial Cancer (MoMaTEC) study cohort, including 446 Norwegian patients, median age 64 years (IQR 59-74), treated between May 2001 and 2010; and the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study cohort, including 384 Dutch patients, median age 66 years (IQR 60-73), treated between September 2011 and December 2013. A BN called ENDORISK (preoperative risk stratification in endometrial cancer) was developed including the following predictors: preoperative tumor grade; immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), p53, and L1 cell adhesion molecule (L1CAM); cancer antigen 125 serum level; thrombocyte count; imaging results on lymphadenopathy; and cervical cytology. In the MoMaTEC cohort, the area under the curve (AUC) was 0.82 (95% confidence interval [CI] 0.76-0.88) for LNM and 0.82 (95% CI 0.77-0.87) for 5-year DSS. In the PIPENDO cohort, the AUC for 5-year DSS was 0.84 (95% CI 0.78-0.90). The network was well-calibrated. In the MoMaTEC cohort, 249 patients (55.8%) were classified with