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International universities often promote inclusive learning environments to aid their sojourners' social integration and improve their well-being. However, little is known about how social experiences with inclusion and integration (SEII) unfold for international PhD candidates in Dutch research universities (DRUs). This study uses the narratives of twenty IPCs to understand the factors that play a role in their SEII in a DRU. Findings suggest that nine factors may define SEII among the participants. Two factors--prior experiences in an ILE and identity in PhD role--played a role in participants' early SEII, while seven factors played a role in participants' early and later SEII. These included IPCs' social participation level, intercultural interaction dynamics, shared language adaptation, cultural events, university's international campus climate, social support, and perceived prejudice and stereotypes. IPCs and their international universities should align expectations to promote an inclusive social climate to foster social integration of IPCs.

A significant number of individuals with tuberous sclerosis complex (TSC) exhibit language difficulties. Here, we examined the language-related brain morphometry in 59 participants (7 participants with TSC and comorbid autism spectrum disorder (ASD) (TSC + ASD), 13 with TSC but no ASD (TSC-ASD), 10 with ASD-only (ASD), and 29 typically developing (TD) controls). A hemispheric asymmetry was noted in surface area and gray matter volume of several cortical language areas in TD, ASD, and TSC-ASD groups, but not in TSC + ASD group. TSC + ASD group demonstrated increased cortical thickness and curvature values in multiple language regions for both hemispheres, compared to other groups. After controlling for tuber load in the TSC groups, within-group differences stayed the same but the differences between TSC-ASD and TSC + ASD were no longer statistically significant. These preliminary findings suggest that comorbid ASD in TSC as well as tuber load in TSC is associated with changes in the morphometry of language regions. Future studies with larger sample sizes will be needed to confirm these findings.

Soil water movement is energy-dependent and is influenced by various management practices. It can be understood by measuring the soil water potential (SWP); however, the influence of cover crops (CCs) on SWP is not currently well understood. The objective of this study was to assess the effects of CCs on SWP before and after termination in order to understand their effects on soil water availability for the subsequent cash crop. The experimental design was a completely randomized design with two levels of CCs (CCs vs. no cover crop [NC]) with three replicates. The SWP sensors were buried at 0–10, 10–20, and 20–30 cm depths before CCs were planted. Additionally, soil samples were collected at the aforementioned depths just before CC termination for soil organic carbon (SOC), bulk density (BD), and saturated hydraulic conductivity (Ksat) analysis. Results showed that CCs increased SOC and Ksat, and significantly lowered BD compared with NC management. Before termination, CC plots had significantly lower SWP values compared with NC management, suggesting that the transpirational needs of the CCs can lead to lower water content. After termination, CC management also resulted in lower SWP, suggesting that CCs can increase water-use efficiency by improving soil health parameters. However, effective planning is required for CC implementation, especially in semiarid and arid regions.

Background: Literature is sparse on COVID-19-associated cystitis (CAC), a novel condition comprising frequency, urgency, and nocturia after COVID-19 infection. Objective: To determine the incidence of CAC and correlation with SARS-CoV-2 antibody levels. Design, setting, and participants: This was a retrospective study in which urinary symptoms were scored using the International Consultation on Incontinence Questionnaire-overactive bladder (ICIQ-OAB) at three time points: before the pandemic (January 2020), 2 mo after COVID-19 infection (if applicable), and at the time of the study (May 2021). The setting was a regional health care system. The 18 785 healthcare employees who took part in the BLAST COVID study group were invited to participate, of whom 1895 responded. Outcome measurements and statistical analysis: The outcome measured was the percentage of COVID-positive patients with a significant change on ICIQ-OAB over time. Pearson’s χ2 test was used for comparison of categorical data, and one-way analysis of variance for continuous data and multivariate analysis. A sample size of 618 was calculated for power of 80% and α = 0.05. Results and limitations: Of the 1895 participants, 31.9% (n = 605) were positive for COVID-19 according to positive serology or a polymerase chain reaction (PCR) test. Of these, 492 were PCR-positive and had 2-mo postinfection data, with 36.4% (179/492) reporting an increase of ≥1 point on the ICIQ-OAB compared to baseline (before the pandemic), with de novo OAB in 22% of these cases (40/179). Comparison of symptoms between baseline and the study time revealed that 27.4% (31/113) of those with positive serology only (asymptomatic COVID) and 37.8% (186/492) of those with PCR positivity (symptomatic COVID) had an increase of ≥1 point on the ICIQ-OAB, compared to 15.8% (n = 204) of uninfected patients, with odds ratios of 2.013 (95% confidence interval [CI] 1.294–3.138; p = 0.0015) and 3.236 (95% CI 2.548–4.080; p

Fecal calprotectin (FC), chitinase 3-like-1 protein (CHI3L1), S100A12 and osteoprotegerin (OPG) are biomarkers of intestinal inflammation. This cross-sectional study aimed to evaluate these biomarkers in a cohort of children with Crohn’s disease (CD) and compare them with other measures of disease activity. Stool samples from children with CD were used to measure FC, CHI3L1, S100A12 and OPG by enzyme-linked immunosorbent assay. Serum inflammatory markers were measured and pediatric CD disease activity index (PCDAI) scores calculated. The simple endoscopic score for CD (SES-CD) was reported for a subgroup who underwent ileocolonoscopy corresponding with the stool samples. Sixty-five children were recruited. Children in clinical remission had lower FC and CHI3L1 levels than those with active disease (FC: 277 vs. 1648 µg/g, p = 0.012; CHI3L1: 23 vs. 227 ng/g, p = 0.013). FC levels differed between patients with clinically active or inactive isolated ileal CD. Although FC and CHI3L1 levels correlated strongly (r = 0.83), none of the fecal markers correlated well with serum markers. Only FC and OPG correlated with SES-CD scores (r = 0.57 and r = 0.48, respectively). In conclusion, FC correlated with both endoscopic and clinical disease activity and was the only biomarker that differentiated between active and inactive ileal CD. CHI3L1 also predicted clinical disease activity and correlated highly with FC. Further investigation of the role of CHI3L1 is required.

Many diseases are caused by disruptions to the network of biochemical reactions that allow cells to respond to external signals. Here Nilsson et al develop a method to simulate cellular signaling using artificial neural networks to predict cellular responses and activities of signaling molecules.

Abstract The formation of aggregates and biofilms enhances bacterial colonisation and infection progression by affording protection from antibiotics and host immune factors. Despite these advantages there is a trade-off, whereby bacterial dissemination is reduced. As such, biofilm development needs to be controlled to suit adaptation to different environments. Here we investigate members from one of largest groups of bacterial adhesins, the autotransporters, for their critical role in the assembly of bacterial aggregates and biofilms. We describe the structural and functional characterisation of autotransporter Ag43 variants from different Escherichia coli pathotypes. We show that specific interactions between amino acids on the contacting interfaces of adjacent Ag43 proteins drives a common mode of trans-association that leads to cell clumping. Furthermore, subtle variation of these interactions alters aggregation kinetics and the degree of compacting within cell clusters. Together, our structure–function investigation reveals an underlying molecular basis for variations in the density of bacterial communities.

Abstract Background Continuous monitoring using wireless wearable sensors is a promising solution for use in clinical practice and in the home setting. It is important to involve nurses to ensure successful implementation. This paper aims to provide an overview of 1) factors affecting implementation of continuous monitoring using wireless wearable sensors by evaluating nurses’ experiences with its use on the nursing ward, and 2) nurses’ expectations for use in the home setting. Methods Semi-structured interviews were conducted with 16 nurses from three teaching hospitals in the Netherlands, covering constructs from the Consolidated Framework for Implementation Research (CFIR). A deductive approach of directed content analysis was applied. One additional factor was added using the Unified Theory for Acceptance of Technology (UTAUT). The quotes and domains were rated on valence (positive, neutral, negative) and strength (strong: − 2, + 2, neutral 0, and weak: − 1, + 1). Results Data was collected on 27 CFIR constructs and 1 UTAUT construct. In the experience of at least 8 nurses, five constructs had a strong positive influence on implementation on the nursing ward, including relative advantage (e.g., early detection of deterioration), patient needs and resources (e.g. feeling safe), networks and communications (e.g. execute tasks together), personal attributes (e.g. experience with intervention), and implementation leaders (e.g., project leader). Five constructs had a strong negative influence: evidence strength and quality (e.g. lack of evidence from practical experience), complexity (e.g. number of process steps), design quality and packaging (e.g., bad sensor quality), compatibility (e.g, change in work) and facilitating conditions (e.g, Wi-Fi connection). Nurses expected continuous monitoring in the home setting to be hindered by compatibility with work processes and to be facilitated by staff’s access to information. Technical facilitating conditions (e.g. interoperability) were suggested to be beneficial for further development. Conclusions This paper provides an overview, of factors influencing implementation of continuous monitoring including relative importance, based on nurses’ experiences with use on nursing wards, and their perspectives for use in the home setting. Implementation of continuous monitoring is affected by a wide range of factors. This overview may be used as a guideline for future implementations.

After the eruption of volcanoes around the world, monitoring of the dispersion of ash in the atmosphere is an important task for satellite remote sensing since ash represents a threat to air traffic. In this work we present a novel method, tailored for Eyjafjallajökull ash but applicable to other eruptions as well, that uses thermal observations of the SEVIRI imager aboard the geostationary Meteosat Second Generation satellite to detect ash clouds and determine their mass column concentration and top height during the day and night. This approach requires the compilation of an extensive data set of synthetic SEVIRI observations to train an artificial neural network. This is done by means of the RTSIM tool that combines atmospheric, surface and ash properties and runs automatically a large number of radiative transfer calculations for the entire SEVIRI disk. The resulting algorithm is called “VADUGS” (Volcanic Ash Detection Using Geostationary Satellites) and has been evaluated against independent radiative transfer simulations. VADUGS detects ash-contaminated pixels with a probability of detection of 0.84 and a false-alarm rate of 0.05. Ash column concentrations are provided by VADUGS with correlations up to 0.5, a scatter up to 0.6 g m−2 for concentrations smaller than 2.0 g m−2 and small overestimations in the range 5 %–50 % for moderate viewing angles 35–65∘, but up to 300 % for satellite viewing zenith angles close to 90 or 0∘. Ash top heights are mainly underestimated, with the smallest underestimation of −9 % for viewing zenith angles between 40 and 50∘. Absolute errors are smaller than 70 % and with high correlation coefficients of up to 0.7 for ash clouds with high mass column concentrations. A comparison with spaceborne lidar observations by CALIPSO/CALIOP confirms these results: For six overpasses over the ash cloud from the Puyehue-Cordón Caulle volcano in June 2011, VADUGS shows similar features as the corresponding lidar data, with a correlation coefficient of 0.49 and an overestimation of ash column concentration by 55 %, although still in the range of uncertainty of CALIOP. A comparison with another ash algorithm shows that both retrievals provide plausible detection results, with VADUGS being able to detect ash further away from the Eyjafjallajökull volcano, but sometimes missing the thick ash clouds close to the vent. VADUGS is run operationally at the German Weather Service and this application is also presented.

This is a report of a women who failed 2 surgical repairs of vesicovaginal fistula secondary to refractory bladder spasms.After each surgical procedure – the hysterectomy and subsequent fistula repairs – the patient reported severe bladder spasms refractory to medical management.Our treatment was intradetrusor onabotuliniumtoxinA injections 4 weeks prior to a planned surgical fistula repair. The patient had successful vaginal approach fistula repair and has not required any subsequent overactive bladder (OAB) treatment.

Abstract Several observational studies suggested that gut microbiome-affecting-medication impairs the effectiveness of immunotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). We postulated that if the effectiveness of immunotherapy is affected by drug-related changes of the microbiome, a stronger association between the use of co-medication and overall survival (OS) will be observed in patients treated with immunotherapy as compared to patients treated with chemotherapy. In a retrospective matched cohort study, immunotherapy patients were matched (1:1) to patients treated with chemotherapy in the pre immunotherapy era. The association between the use of antibiotics, opioids, proton pump inhibitors, metformin and other antidiabetics on OS was assessed with multivariable cox-regression analyses. Interaction tests were applied to investigate whether the association differs between patients treated with immuno- or chemotherapy. A total of 442 patients were studied. The use of antibiotics was associated with worse OS (adjusted Hazard Ratio (aHR) 1.39, p = 0.02) independent of the type of therapy (chemotherapy or immunotherapy). The use of opioids was also associated with worse OS (aHR 1.33, p = 0.01). The other drugs studied showed no association with OS. Interaction term testing showed no effect modification by immuno- or chemotherapy for the association of antibiotics and opioids with OS. The use of antibiotics and opioids is similarly associated with worse outcomes in both chemotherapy and immunotherapy treated NSCLC patients. This suggests that the association is likely to be a consequence of confounding rather than disturbing the composition of the microbiome.

Post orgasmic illness syndrome (POIS) is increasingly being recognized as a debilitating cause of sexual dysfunction in males. It is often misdiagnosed due to its unfamiliarity to providers, resulting in numerous potentially unnecessary tests and treatments. Currently, there is no known single most effective treatment, but several case reports suggest desensitization, hormonal therapy, and other treatment modalities may be useful. However, these treatments are experimental in nature and have not been evaluated in placebo-controlled trials. We report on the use of a simple over-the-counter antihistamine in the management of POIS.

ABSTRACT Many bacterial species typically live in complex three-dimensional biofilms, yet much remains unknown about differences in essential processes between nonbiofilm and biofilm lifestyles. Here, we created a CRISPR interference (CRISPRi) library of knockdown strains covering all known essential genes in the biofilm-forming Bacillus subtilis strain NCIB 3610 and investigated growth, biofilm colony wrinkling, and sporulation phenotypes of the knockdown library. First, we showed that gene essentiality is largely conserved between liquid and surface growth and between two media. Second, we quantified biofilm colony wrinkling using a custom image analysis algorithm and found that fatty acid synthesis and DNA gyrase knockdown strains exhibited increased wrinkling independent of biofilm matrix gene expression. Third, we designed a high-throughput screen to quantify sporulation efficiency after essential gene knockdown; we found that partial knockdowns of essential genes remained competent for sporulation in a sporulation-inducing medium, but knockdown of essential genes involved in fatty acid synthesis exhibited reduced sporulation efficiency in LB, a medium with generally lower levels of sporulation. We conclude that a subset of essential genes are particularly important for biofilm structure and sporulation/germination and suggest a previously unappreciated and multifaceted role for fatty acid synthesis in bacterial lifestyles and developmental processes. IMPORTANCE For many bacteria, life typically involves growth in dense, three-dimensional communities called biofilms that contain cells with differentiated roles held together by extracellular matrix. To examine how essential gene function varies between vegetative growth and the developmental states of biofilm formation and sporulation, we created and screened a comprehensive library of strains using CRISPRi to knockdown expression of each essential gene in the biofilm-capable Bacillus subtilis strain 3610. High-throughput assays and computational algorithms identified a subset of essential genes involved in biofilm wrinkling and sporulation and indicated that fatty acid synthesis plays important and multifaceted roles in bacterial development.

Regenerating islet-derived protein (REG) 1A (aka pancreatic stone protein) and REG3A (aka pancreatitis-associated protein) are upregulated in humans with sepsis, pancreatitis, and gastrointestinal diseases, but little is known about this protein family in dogs. Our aim was to identify REG1 and REG3 family members in dogs. REG-family genes were computationally annotated in the canine genome and proteome, with verification of gene expression using publicly available RNA-seq data. The presence of the protein in canine pancreatic tissue and plasma was investigated with Western blot and immunohistochemistry, using anti-human REG1A and REG3A antibodies. Protein identity was confirmed with mass spectrometry. Two members of the REG3 subfamily were found in the canine genome, REG3E1 and REG3E2, both encoding for the same 176 AA protein, subsequently named REG3E. Anti-human REG3A antibodies demonstrated cross-reactivity with the canine REG3E protein in pancreas homogenates. In canine plasma, a protein band of approximately 17 kDa was apparent. Mass spectrometry confirmed this protein to be the product of the two annotated REG3E genes. Strong immunoreactivity to anti-human REG3A antibodies was found in sections of canine pancreas affected with acute pancreatitis, but it was weak in healthy pancreatic tissue. Recombinant canine REG3E protein underwent a selective trypsin digestion as described in other species. No evidence for the presence of a homolog of REG1A in dogs was found in any of the investigations. In conclusion, dogs express REG3E in the pancreas, whose role as biomarker merits further investigations. Homologs to human REG1A are not likely to exist in dogs.

Abstract Background Delirium occurs frequently following cardiothoracic surgery, and infectious disease is an important risk factor for delirium. Surgery and cardiopulmonary bypass induce suppression of the immune response known as immunoparalysis. We aimed to investigate whether delirious patients had more pronounced immunoparalysis following cardiothoracic surgery than patients without delirium, to explain this delirium-infection association. Methods A prospective matched case–control study was performed in two university hospitals. Cytokine production (tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and IL-10) of ex vivo lipopolysaccharide (LPS)-stimulated whole blood was analyzed in on-pump cardiothoracic surgery patients preoperatively, and at 5 timepoints up to 3 days after cardiothoracic surgery. Delirium was assessed by trained staff using two validated delirium scales and chart review. Results A total of 89 patients were screened of whom 14 delirious and 52 non-delirious patients were included. Ex vivo-stimulated production of TNF-α, IL-6, IL-8, and IL-10 was severely suppressed following cardiothoracic surgery compared to pre-surgery. Postoperative release of cytokines in non-delirious patients was attenuated by 84% [IQR: 13–93] for TNF-α, 95% [IQR: 78–98] for IL-6, and 69% [IQR: 55–81] for IL-10. The attenuation in ex vivo-stimulated production of these cytokines was not significantly different in patients with delirium compared to non-delirious patients (p > 0.10 for all cytokines). Conclusions The post-operative attenuation of ex vivo-stimulated production of pro- and anti-inflammatory cytokines was comparable between patients that developed delirium and those who remained delirium-free after on-pump cardiothoracic surgery. This finding suggests that immunoparalysis is not more common in cardiothoracic surgery patients with delirium compared to those without.