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Abstract Background Pituitary neuroendocrine tumors (PitNET) are among the most common intracranial tumors. Despite a frequent benign course, aggressive behavior can occur. Tumor behavior is known to be under the influence of the tumor microenvironment (TME). However, the relationship between TME cells and aggressive tumor behavior has not been adequately explored in PitNET. Methods We performed differential expression analysis as well as gene expression program identification based on single-cell RNA sequencing to comparatively characterize the transcriptome of seven gonadotroph and three lactotroph PitNET and correlate it with clinical features using bulk RNA-seq data from an independent cohort of 134 PitNET. Tumor immune infiltration was quantified via immunostaining on tissue sections of gonadotroph and lactotroph PitNET. Results In lactotroph PitNET, we detect a highly proliferative gene profile with significantly increased expression levels in aggressively growing tumors within bulk RNA-seq data of an independent cohort of 134 PitNET samples. We also report high intratumoral heterogeneity in gonadotroph PitNET (GoPN) and lactotroph PitNET (LaPN) and identify signatures of epithelial, endocrine, and immunological gene networks in both subtypes. A comparison of their TME composition shows enrichment of SPP1+ macrophages and CD4+ T cells in GoPN, as well as enrichment of CD4/CD8 double-negative T cells (DN) and natural killer cells (NK) in LaPN. Also notable is the presence of proliferative lymphocytes, the occurrence of which positively correlates with more aggressive tumor behavior in the bulk RNA-seq cohort. However, increased CD8+ T and NK cell abundances correlate significantly with reduced aggressiveness indicating potential anti-tumoral effects. Conclusions Our study expands the knowledge of the differences in cellular composition of gonadotroph and lactotroph PitNET subtypes. It lays the foundation for further studies on the influence of lymphoid cells on the variable aggressive behavior of PitNET. Regarding the treatment of drug-resistant lactotroph PitNET, proliferative lymphocytes, CD8+ T, and NK cells could represent potentially valuable targets for developing new cancer immunotherapies.

Abstract Recent advances in artificial intelligence (AI) created powerful tools for research, particularly for extracting meaningful insights from extremely large data sets. These developments increase research benefits of big data and risks posed to individual privacy, forcing a re-examination of ethics in research which is of particular importance to the Military Health System. To advance discussion of research ethics in this context, the Forum on Health and National Security: Ethical Use of Big Data for Healthy Communities and a Strong Nation was held in December 2018. The workshop was designed to identify ethical questions relevant to population and health research studies using difficult to access, health-related data in the Department of Defense (DoD). Discussions explored researchers’ ethical obligations to research subjects, particularly in the areas of privacy, trust, and consent, as well as potential methods to improve researchers’ ability to collect, access, and share data while protecting privacy and potential risks to national security. These include creating risk management frameworks and data governance policies, improving education and workplace training, and increasing community involvement in research design and practice. While the workshop was conducted in 2018, the discussion of data ethics is still relevant today. The research agenda of the nation is best served by building ethics into the research ecosystem. There are substantial challenges to fully realizing this goal including commitments of time and funding to address the ethical complexities, train others to understand them, and create appropriate ethical frameworks before research begins.

Abstract Background Streptococcus dysgalactiae subspecies equisimilis (SDSE) is increasingly recognized as an emerging cause of invasive diseases including necrotizing soft tissue infections (NSTIs). In contrast to the closely related Streptococcus pyogenes, SDSE infections mainly affect older and comorbid patients. Biofilm formation has been demonstrated in soft tissue biopsies of S. pyogenes NSTI cases. Results Here, we show that bacterial aggregations indicative of biofilms are also present in SDSE NSTI. Although streptokinase (Ska) activity and biofilm formation did not correlate in a diverse set of clinical SDSE isolates, addition of exogenous Ska at an early time point prevented biofilm formation for selected strains. Deletion of ska in SDSE S118 strain resulted in increased biofilm forming capacity. Ska-deficient mutant strain was characterized by a higher metabolic activity and consequent metabolome profiling of biofilms identified higher deposition of a wide range of metabolites as compared to the wild-type. Conclusions Our results argue that Ska suppresses biofilm formation in SDSE independent of its original plasminogen converting activity. However, the impact of biofilms and its consequences for patient outcomes in streptococcal NSTIs remain to be elucidated.

Aim To determine the antimicrobial activity of the bacteriocin-producing probiotic strains Streptococcus salivarius K12 and Streptococcus salivarius M18 alone or in combination against caries-associated Streptococcus mutans.Methods Antimicrobial activity of S. salivarius K12 and/or S. salivarius M18 against S. mutans ATCC 25175 growth and biofilm formation on hydroxyapatite (HA) discs was determined in a flow chamber model by recording the colony forming units (CFU/ml) after 48 h of co-cultivation. The biofilm was analyzed by scanning electron microscopy (SEM) and by confocal laser scanning microscopy (CLSM). Additionally, the simultaneous antagonism assay was used to assess the inhibitory effect of S. salivarius K12 and/or S. salivarius M18 against S. mutans ATCC 25175 and 21 clinical isolates of S. mutans.Results Co-cultivation of S. mutans and S. salivarius K12 and/or S. salivarius M18 led to the inhibition of S. mutans viability, thereby, preventing its biofilm formation on HA discs. Furthermore, S. salivarius K12 and S. salivarius M18 exhibited antimicrobial activity against most clinical isolates of S. mutans.Conclusion The in vitro flow chamber system used in this study allows the simulation of time-dependent administration of S. salivarius probiotic strains, either alone or in combination, to investigate the prevention of S. mutans biofilm formation in a standardized model.

Mulberry Diels-Alder-type adducts (MDAAs), isolated from Morus alba root bark, exhibit dual activity against viral and bacterial pathogens but show sobering efficacy following oral administration. Inhalation administration may overcome issues with oral bioavailability and improve efficacy for the treatment of respiratory infections. To assess the suitability of MDAAs for inhalation administration, physicochemical (e.g. pH, pKa, logP, pH-dependent solubility) and biopharmaceutical (epithelial cytotoxicity, permeability, and uptake) properties of two bioactive MDAA stereoisomers sanggenon C (SGC) and sanggenon D (SGD) were evaluated as isolated natural compounds and within parent extracts (MA21, MA60). Despite their structural similarity, SGD exhibited a 10-fold higher solubility than SGC across pH 1.2–7.4, with slight increases at neutral pH. Both compounds were more soluble in isolated form than in the parent extracts. The more lipophilic SGC was found to be more cytotoxic when compared to SGD, indicating a better cellular penetration, which was confirmed by uptake studies. Nonetheless, SGC and SGD exhibited no measurable permeability across intact Calu-3 monolayers, highlighting their potential for increased lung retention and improved local anti-infective activity following inhalation administration. Results suggest that SGC and SGD in isolated form, rather than as extracts, are promising candidates for pulmonary drug delivery to treat lung infections.

Abstract This study examines whether premature termination of vocational education and training (VET) is more likely when trainees have to make compromises between their realistic occupational aspirations and the occupation for which they are trained in terms of the occupational dimensions of gender type, prestige, and occupational interests. Specifically, it examines the relative importance of the three compromise dimensions on premature VET termination. The study is based on a sample of 3,241 VET entrants from a cohort of ninth graders in 2010 in the German National Educational Panel Study (NEPS-SC4) in combination with aggregated data on occupational characteristics. Results from discrete hazard rate models indicate a higher risk of premature VET termination for trainees whose VET occupation differs from their realistic occupational aspiration from their school days. While compromises in prestige have no overall effect, both compromises in interests and gender type threaten the stability of VET. The results also indicate that compromises in interests have the strongest effect on the risk of premature VET termination and that the effects of compromises in gender type are partly mediated by the effects of compromises in interests. Furthermore, sensitivity analysis revealed that the main effects of compromises in gender type and prestige are gender specific.

Abstract This article draws on different strands of existing scholarship to provide an analytical framework for understanding the barriers to achieving a well-being economy. It explores the interplay between agential and structural power, where some actor-coalitions can reproduce or transform pre-existing structures. Conversely, these structures are strategically selective, favouring some actors, interests, and strategies over others. Making sense of this interplay between agential and structural power, the article introduces the notion of power complex e s—time-space-specific actor-coalitions with common industry-related interests and the power to reproduce or transform structures in a given conjuncture. To understand the historical “becoming” of today’s political-economic terrain, the article provides a regulationist-inspired history of the rise, fall, and re-emergence of four power complexes: the financial, fossil, livestock-agribusiness, and digital. They pose significant threats to pillars of a wellbeing economy such as ecological sustainability, equ(al)ity, and democracy. Subsequently, today’s structural context is scrutinised in more detail to understand why certain actors dominate strategic calculations in contemporary power complexes. This reveals strategic selectivities that favour multi- and transnational corporate actors over civil society, labour movements, and public bureaucracies. The article then examines firm-to-state lobbying as a strategy employed by corporate actors within today’s structural context to assert their interests. It presents illustrative cases of Blackstone, BP, Bayer, and Alphabet. Finally, it explores implications and challenges for realising a wellbeing economy based on post-/degrowth visions. It emphasises the double challenge faced by such a wellbeing-economy actor-coalition. On one hand, it has to navigate within contemporary modes of regulation that favour corporate strategies of capital accumulation while, on the other, it must confront the self-expanding and extractive logic of capital. In this context, three key challenges are outlined: the need to form unconventional strategic alliances, operate on various spatial dimensions simultaneously, and institutionalise alternatives to firm-to-state lobbying to influence policymaking.

Reducing anastomotic leak rates after bowel resection is a priority among patients undergoing gynecologic oncology surgery. While near-infrared (NIR) angiography has been investigated in the colorectal literature, more recent work has demonstrated promising results when used in gynecologic cancer surgery. It has been repeatedly shown to be a safe intervention that can offer real time assessment of bowel perfusion, offering the surgeon the opportunity to act on the results in the hopes of decreasing the risk of complications.

Japanese encephalitis virus (JEV) is a zoonotic mosquito-transmitted Flavivirus circulating in birds and pigs. In humans, JEV can cause severe viral encephalitis with high mortality. Considering that vector-free direct virus transmission was observed in experimentally infected pigs, JEV introduction into an immunologically naïve pig population could result in a series of direct transmissions disrupting the alternating host cycling between vertebrates and mosquitoes. To assess the potential consequences of such a realistic scenario, we passaged JEV ten times in pigs. This resulted in higher in vivo viral replication, increased shedding, and stronger innate immune responses in pigs. Nevertheless, the viral tissue tropism remained similar, and frequency of direct transmission was not enhanced. Next generation sequencing showed single nucleotide deviations in 10% of the genome during passaging. In total, 25 point mutations were selected to reach a frequency of at least 35% in one of the passages. From these, six mutations resulted in amino acid changes located in the precursor of membrane, the envelope, the non-structural 3 and the non-structural 5 proteins. In a competition experiment with two lines of passaging, the mutation M374L in the envelope protein and N275D in the non-structural protein 5 showed a fitness advantage in pigs. Altogether, the interruption of the alternating host cycle of JEV caused a prominent selection of viral quasispecies as well as selection of de novo mutations associated with fitness gains in pigs, albeit without enhancing direct transmission frequency.

During May 2022–April 2023, dengue virus serotype 3 was identified among 601 travel-associated and 61 locally acquired dengue cases in Florida, USA. All 203 sequenced genomes belonged to the same genotype III lineage and revealed potential transmission chains in which most locally acquired cases occurred shortly after introduction, with little sustained transmission.

Abstract Background Streptococcus pyogenes (group A streptococcus, GAS) causes a variety of diseases ranging from mild superficial infections of the throat and skin to severe invasive infections, such as necrotizing soft tissue infections (NSTIs). Tissue passage of GAS often results in mutations within the genes encoding for control of virulence (Cov)R/S two component system leading to a hyper-virulent phenotype. Dendritic cells (DCs) are innate immune sentinels specialized in antigen uptake and subsequent T cell priming. This study aimed to analyze cytokine release by DCs and other cells of monocytic origin in response to wild-type and natural covR/S mutant infections. Methods Human primary monocyte-derived (mo)DCs were used. DC maturation and release of pro-inflammatory cytokines in response to infections with wild-type and covR/S mutants were assessed via flow cytometry. Global proteome changes were assessed via mass spectrometry. As a proof-of-principle, cytokine release by human primary monocytes and macrophages was determined. Results In vitro infections of moDCs and other monocytic cells with natural GAS covR/S mutants resulted in reduced secretion of IL-8 and IL-18 as compared to wild-type infections. In contrast, moDC maturation remained unaffected. Inhibition of caspase-8 restored secretion of both molecules. Knock-out of streptolysin O in GAS strain with unaffected CovR/S even further elevated the IL-18 secretion by moDCs. Of 67 fully sequenced NSTI GAS isolates, 28 harbored mutations resulting in dysfunctional CovR/S. However, analyses of plasma IL-8 and IL-18 levels did not correlate with presence or absence of such mutations. Conclusions Our data demonstrate that strains, which harbor covR/S mutations, interfere with IL-18 and IL-8 responses in monocytic cells by utilizing the caspase-8 axis. Future experiments aim to identify the underlying mechanism and consequences for NSTI patients.

Background: Polymerization shrinkage of composite resins affects the marginal closure of direct dental restorations. It is responsible for developing secondary caries and indirectly affects the survival rate of restorations. This study aims to investigate the null hypothesis, which states that there are no significant differences in the marginal microleakage of Class II restorations when examined in vitro using different dental adhesives, whether the restoration material used is a composite with glass fiber reinforcement or not. Methods: Class II cavities were prepared on both proximal surfaces of thirty-six extracted human molars. A single-component (Universal VivaPen) and a two-component (Futurabond DC) self-etch adhesive system were used for the restorations in the control group (Charisma Classic) and the experimental group (Charisma Classic with Interlig glass fiber strip). An oblique layering technique and a 40-s soft-start light-curing polymerization were used. After selective pre-isolation, the specimens were placed in a 0.2% methylene blue solution and incubated at 37 °C for 24 h. The teeth were sectioned in the mesiodistal direction, and two examiners examined and graded the extent of dye penetration. Statistical analysis was conducted using the Mann–Whitney U and chi-square tests (p < 0.05). Results: All the composite restorations reinforced with glass fiber showed significantly reduced dye infiltration compared to the control group (p < 0.05). A significant difference (p < 0.05) was also observed between the two adhesives. Conclusions: The null hypothesis was rejected. Glass fiber strips significantly reduced composite restoration microleakage regardless of the adhesive. The marginal fit of the restoration was also influenced by the adhesive system used.

Fisheries science draws on morphometric data for stock assessments. Length–weight relationships are essential for estimating body weight from length measurements taken either underwater (in situ) or out of the water (ex situ). We examined morphometric models for the high-valued sea cucumber, Holothuria lessoni. From 77 specimens captured in 2024 (mean weight ± SD: 1774 ± 372 g), we measured body length and width in situ and ex situ, then weighed the animals ex situ. We compared morphometric models using four biometric parameters. The fitted relationships were more statistically significant (p < 0.001) when using in situ measurements compared to ex situ measurements. The length–weight relationship from our study was compared with those from two previous studies on the same species at the same location. Each study generated significantly (p < 0.001) different length–weight relationships. These findings suggest that length–weight relationships should be re-evaluated at regular intervals, as they may evolve over time. Our study indicates that estimation of body weight from length (and width) must rely on established relationships corresponding to whether the measurements are made in situ or ex situ. Our results suggest that in situ measurements could provide more reliable data for length–weight relationships in certain holothuroids.

Bovine viral diarrhea virus (BVDV), a pestivirus in the family Flaviviridae, is a major livestock pathogen. Horizontal transmission leads to acute transient infections via the oronasal route, whereas vertical transmission might lead to the birth of immunotolerant, persistently infected animals. In both cases, BVDV exerts an immunosuppressive effect, predisposing infected animals to secondary infections. Erns, an immunomodulatory viral protein, is present on the envelope of the virus and is released as a soluble protein. In this form, it is taken up by cells and, with its RNase activity, degrades single- and double-stranded (ds) RNA, thus preventing activation of the host’s interferon system. Here, we show that Erns of the pestiviruses BVDV and Bungowannah virus effectively inhibit dsRNA-induced IFN synthesis in well-differentiated airway epithelial cells cultured at the air–liquid interface. This activity was observed independently of the side of entry, apical or basolateral, of the pseudostratified, polarized cell layer. Virus infection was successful from both surfaces but was inefficient, requiring several days of incubation. Virus release was almost exclusively restricted to the apical side. This confirms that primary, well-differentiated respiratory epithelial cells cultured at the air–liquid interface are an appropriate model to study viral infection and innate immunotolerance in the bovine respiratory tract. Furthermore, evidence is presented that Erns might contribute to the immunosuppressive effect observed after BVDV infections, especially in persistently infected animals.

Neurobehavioral studies have provided evidence for the effectiveness of anodal tDCS on language production, by stimulation of the left Inferior Frontal Gyrus (IFG) or of left Temporo-Parietal Junction (TPJ). However, tDCS is currently not used in clinical practice outside of trials, because behavioral effects have been inconsistent and underlying neural effects unclear. Here, we propose to elucidate the neural correlates of verb and noun learning and to determine if they can be modulated with anodal high-definition (HD) tDCS stimulation. Thirty-six neurotypical participants were randomly allocated to anodal HD-tDCS over either the left IFG, the left TPJ, or sham stimulation. On day one, participants performed a naming task (pre-test). On day two, participants underwent a new-word learning task with rare nouns and verbs concurrently to HD-tDCS for 20 min. The third day consisted of a post-test of naming performance. EEG was recorded at rest and during naming on each day. Verb learning was significantly facilitated by left IFG stimulation. HD-tDCS over the left IFG enhanced functional connectivity between the left IFG and TPJ and this correlated with improved learning. HD-tDCS over the left TPJ enabled stronger local activation of the stimulated area (as indexed by greater alpha and beta-band power decrease) during naming, but this did not translate into better learning. Thus, tDCS can induce local activation or modulation of network interactions. Only the enhancement of network interactions, but not the increase in local activation, leads to robust improvement of word learning. This emphasizes the need to develop new neuromodulation methods influencing network interactions. Our study suggests that this may be achieved through behavioral activation of one area and concomitant activation of another area with HD-tDCS.

Genomic prediction has mostly been used in single environment contexts, largely ignoring genotype x environment interaction, which greatly affects the performance of plants. However, in the last decade, prediction models including marker x environment (MxE) interaction have been developed. We evaluated the potential of genomic prediction in red clover (Trifolium pratense L.) using field trial data from five European locations, obtained in the Horizon 2020 EUCLEG project. Three models were compared: (1) single environment (SingleEnv), (2) across environment (AcrossEnv), (3) marker x environment interaction (MxE). Annual dry matter yield (DMY) gave the highest predictive ability (PA). Joint analyses of DMY from years 1 and 2 from each location varied from 0.87 in Britain and Switzerland in year 1, to 0.40 in Serbia in year 2. Overall, crude protein (CP) was predicted poorly. PAs for date of flowering (DOF), however ranged from 0.87 to 0.67 for Britain and Switzerland, respectively. Across the three traits, the MxE model performed best and the AcrossEnv worst, demonstrating that including marker x environment effects can improve genomic prediction in red clover. Leaving out accessions from specific regions or from specific breeders’ material in the cross validation tended to reduce PA, but the magnitude of reduction depended on trait, region and breeders’ material, indicating that population structure contributed to the high PAs observed for DMY and DOF. Testing the genomic estimated breeding values on new phenotypic data from Sweden showed that DMY training data from Britain gave high PAs in both years (0.43–0.76), while DMY training data from Switzerland gave high PAs only for year 1 (0.70–0.87). The genomic predictions we report here underline the potential benefits of incorporating MxE interaction in multi-environment trials and could have perspectives for identifying markers with effects that are stable across environments, and markers with environment-specific effects.

IntroductionThe use of virtual environments in rehabilitation has been growing. The current systematic review aimed to evaluate how and where virtual technologies are combined with music in rehabilitation.MethodsA literature search was conducted in seven databases (ACM Digital Library, CINAHL Complete, Cochrane Library, Computer Science database, Medline, Nursing & Allied Health database, and Scopus). It included articles published from 2006 to February 2023. The search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for study selection. Twelve studies with 160 participants were included in the review. In addition, a descriptive approach was used to gather data from the studies for the areas of interest.ResultsVirtual Reality (VR) and Augmented Reality were most familiar and used in rehabilitation, but Mixed Reality, and Extended Reality were less studied. It became evident that equipment, diverse applications, assessment metrics, training environments, and methodologies were highly varied. Most of the studies were pilots, the overall quality of included studies was rated moderate, and the risk of bias was high in the included studies. The studies on motor rehabilitation after stroke showed a clinical improvement in hand functions, specifically fractionation. Furthermore, studies that included motivation, adherence, and mental health, slightly supported the idea that VR technologies with music have the potential to promote motivation and exercise adherence, increase positive emotions, and decrease anxiety. In addition, user experience and feasibility studies presented technologies combined with music to be safe and acceptable in rehabilitation.DiscussionIn light of these findings, it can be inferred that virtual technologies with music offer promising avenues for future rehabilitation research. However, some confusion was obtained related to the included studies’ definitions of technologies and management terms. Furthermore, it is important to note the limited number of studies and participants, the heterogeneity among participants, and the overall quality of the studies that restrict the generalizability of these results to a larger population. Therefore, future researchers should define concepts and terms, delve deeper into this area to uncover the potential benefits, and clarify the specific mechanisms through which virtual technologies with music can positively impact rehabilitation outcomes.

Livestock grazing, a widespread land use in semi-arid systems, is often placed in opposition to the perpetuation of biological soil crusts (“biocrusts”: lichens, mosses, and algal crusts including cyanobacteria) that live on the soil surface and provide ecosystem functions. The composition of biocrusts and vascular plants varies with climate, soils, and disturbance. In general, ruderal mosses and light algal crusts make up greater proportions of biocrusts in the presence of disturbance, although morphogroups of biocrusts respond differently to various disturbances. It is unknown if there are scenarios under which grazing can occur and ruderal components of biocrust could be maintained. We examine the hypothesis that soil surface texture-moisture interactions influence the ability of biocrusts to withstand trampling, reasoning that finer-textured soils are firmer (therefore serving as a better substrate for biocrusts) when dry and that coarser-textured are firmer when wet. We test these relationships within Birds of Prey, National Conservation Area (Boise, Idaho, USA). Results demonstrate two associations of biocrusts, dependent on season of grazing: one dominated by light algal crusts and lichens that frequently occurs with wet season grazing, and a second dominated by tall mosses and cup lichens that frequently occurs with dry season grazing. High cover of the invasive annual grass, Bromus tectorum (L.) was observed on sites with coarse-textured soils, and high sand content, that are grazed at relatively high intensities, creating unstable surfaces, and likely putting biocrusts at greater susceptibility to trampling. Results suggest that livestock management that accounts for soil texture and moisture could be used to maintain cover of ruderal biocrusts on fine-textured soils, that are grazed in the dry season, at low intensity. We discuss our findings in the context of managing for species of interest. Our findings are timely as varying the season of grazing is increasingly discussed as a means of favoring desirable native perennial grasses. Although ruderal morphogroups of biocrusts are not interpreted as having equivalent ecosystem functions compared to intact biocrusts, their contributions to soil stability, fertility, hydrology, and weed abatement could increase if they were more intentionally targeted by management.

Objective This research was conducted to evaluate the effects of citrus fiber (CF) as a natural alternative to sodium tripolyphosphate (STPP) in marinated broiler boneless chicken breast and inside beef skirt on overall retention rate, shear force, and consumer sensory attributes. Methods Five different marinade formulations were targeted to include 0.9% salt, either 0.25% or 0.50% STPP or CF and water on a finished product basis. Water and salt only were considered the negative control (CON). Chicken breasts (n = 14) and inside beef skirt (n = 14) were randomly assigned to a treatment, raw weights recorded and then placed in a vacuum tumbler. Marinated weights were recorded, individually packed, and randomly assigned to either retail display for 10-day retention rate, shear force analysis, cook loss, or consumer sensory panel. Results Pickup percentage, and overall retention was similar among treatments for chicken breast and inside beef skirt. Citrus fiber treatments resulted in higher cooking loss compared to the CON in chicken breast; though, CF050 resulted in similar cooking loss compared to STPP025 in inside beef skirt. No differences were found in sensory attributes for chicken breast, however, WBSF data showed CF025 was tougher than CF050, STPP050, and CON. Inside beef skirt with CF050 were least liked overall by the consumer panel. Conclusion Citrus fiber included in marinades at a lower percentage rate can produce similar texture characteristics, and sensory properties compared with those marinated with STPP.

Background and Aims: The prevalence of inflammatory bowel disease (IBD) is increasing globally. In this context, identifying risk factors for severe disease is important. We examined how race/ethnicity and immigration status influence IBD manifestations, treatments, and outcomes in a diverse, tertiary-care safety-net hospital. Methods: We conducted a single-center retrospective review of all IBD inpatients and outpatients treated from 1997–2017. Using logistic regression modeling, we compared disease onset, treatment, and outcomes by race (White, Black, Hispanic, or Asian) and immigration status (US-born vs foreign-born). Results: A total of 577 patients were identified, of which 29.8% were White, 27.4% were Hispanic, 21.7% were Black, and 13.0% were Asian. Compared to Whites, Asians were more likely to be male (odds ratio [OR] 2.63, 95% confidence interval [CI]: 1.45, 5.00), whereas Blacks were more likely to be diagnosed with Crohn’s disease (OR 1.75, 95% CI: 1.10, 2.77) and more likely to undergo IBD-related intestinal resection (OR 2.49, 95% CI: 1.40, 4.50). Compared to US-born patients, foreign-born patients were more likely to be diagnosed with ulcerative colitis (OR 1.77, 95% CI: 1.04, 3.02). They were also less likely to be diagnosed before 16 years of age (OR 0.19, 95% CI: 0.08, 0.41), to have undergone intestinal resections (OR 0.39, 95% CI: 0.19, 0.83), to have received biologics (OR 0.43, 95% CI: 0.25, 0.76), or to have had dermatologic manifestations (OR 0.12, 95% CI: 0.03, 0.41). Conclusion: IBD phenotype varies by race, although foreign-born patients of all races show evidence of later-onset and milder disease. These findings may aid in disease prognostication and clinical management and, furthermore, may provide insight into intrinsic and environmental influences on IBD pathogenesis.

Jealousy and mate retention have received attention in research over the last few decades. Despite this, most of the research has examined male jealousy and male mate retention, emphasizing cost-inflicting behavior due to its role in relationships and domestic violence. The aim of this study was to investigate the relationship between jealousy and all mate retention strategies in romantic relationships among women during the COVID-19 pandemic. The sample consisted of 772 Croatian women aged 19 to 40 who were in a heterosexual relationship at the time. This study was conducted online, and the participants completed the Multidimensional Jealousy Scale and Mate Retention Inventory. The results showed that cognitive, emotional, and behavioral jealousy were positively correlated with all mate retention strategies, which indicates that a stronger experience of jealousy can be expected to result in more frequent use of all partner retention strategies. We also found that all three dimensions of jealousy and relationship length positively predicted both cost-inflicting and benefit-provisioning mate retention behavior, whereas age was a negative predictor of benefit-provisioning behavior only. The findings of this study suggest that, although jealousy can substantially explain interpersonally risky and damaging behavior in relationships, it can also explain affectionate and attentive behavior, to some extent.

Abstract N‐acetyl glutamate synthase (NAGS) deficiency (OMIM #: 237310) is a rare urea cycle disorder that usually presents early in life with hyperammonemia. NAGS catalyzes the synthesis of N‐acetyl glutamate (NAG) which functions as an activator of the carbamoyl phosphate synthetase‐1 mediated conversion of ammonia to carbamoyl phosphate. The absence of NAG results in a proximal urea cycle disorder which can result in severe neurologic sequelae secondary to hyperammonemia and even death. Unlike the other urea cycle disorders, a specific pharmacological treatment for NAGS deficiency exists in the form of carglumic acid, an analog of NAG. Here we present a 29‐year‐old previously healthy female who presented with hyperammonemia and obtundation just after the birth of her first child. Exome sequencing revealed two novel variants in the NAGS gene, and plasma metabolomics revealed extremely low levels of NAG. Carglumic acid treatment led to prompt resolution of her biochemical abnormalities and symptoms. She tolerated two subsequent pregnancies, 2 years and 6 years after her initial presentation, while taking carglumic acid, and breastfed her third child, all without complications in the mother or children. This case report emphasizes the importance of considering urea cycle disorders in previously‐healthy adults presenting with neurological symptoms during periods of metabolic stress, including the postpartum period. It also highlights the efficacious and safe use of carglumic acid during pregnancy and while breastfeeding.

Abstract Mycoparasitism is a key feature of Trichoderma (Hypocreales, Ascomycota) biocontrol agents. Recent studies of intracellular signal transduction pathways of the potent mycoparasite Trichoderma atroviride revealed the involvement of Tmk1, a mitogen-activated protein kinase (MAPK), in triggering the mycoparasitic response. We previously showed that mutants missing Tmk1 exhibit reduced mycoparasitic activity against several plant pathogenic fungi. In this study, we identified the most robustly regulated targets that were governed by Tmk1 during mycoparasitism using transcriptome and proteome profiling. Tmk1 mainly exerts a stimulating function for T. atroviride during its mycoparasitic interaction with the fungal plant pathogen Rhizoctonia solani, as reflected by 89% of strongly differently responding genes in the ∆tmk1 mutant compared to the wild type. Specifically, 54% of these genes showed strong downregulation in the response with a deletion of the tmk1 gene, whereas in the wild type the same genes were strongly upregulated during the interaction with the fungal host. These included the gene encoding the mycoparasitism-related proteinase Prb1; genes involved in signal transduction pathways such as a candidate coding for a conserved 14-3-3 protein, and a gene coding for Tmk2, the T. atroviride cell-wall integrity MAP kinase; genes encoding a specific siderophore synthetase, and multiple FAD-dependent oxidoreductases and aminotransferases. Due to the phosphorylating activity of Tmk1, different (phospho-)proteomics approaches were applied and identified proteins associated with cellular metabolism, energy production, protein synthesis and fate, and cell organization. Members of FAD- and NAD/NADP-binding-domain proteins, vesicular trafficking of molecules between cellular organelles, fungal translational, as well as protein folding apparatus were among others found to be phosphorylated by Tmk1 during mycoparasitism. Outstanding downregulation in the response of the ∆tmk1 mutant to the fungal host compared to the wild type at both the transcriptome and the proteome levels was observed for nitrilase, indicating that its defense and detoxification functions might be greatly dependent on Tmk1 during T. atroviride mycoparasitism. An intersection network analysis between the identified transcripts and proteins revealed a strong involvement of Tmk1 in molecular functions with GTPase and oxidoreductase activity. These data suggest that during T. atroviride mycoparasitism this MAPK mainly governs processes regulating cell responses to extracellular signals and those involved in reactive oxygen stress.

Background: Chronic liver diseases such as hepatic tumors can affect the brain through the liver–brain axis, leading to neurotransmitter dysregulation and behavioral changes. Cancer patients suffer from fatigue, which can be associated with sleep disturbances. Sleep is regulated via two interlocked mechanisms: homeostatic regulation and the circadian system. In mammals, the hypothalamic suprachiasmatic nucleus (SCN) is the key component of the circadian system. It generates circadian rhythms in physiology and behavior and controls their entrainment to the surrounding light/dark cycle. Neuron–glia interactions are crucial for the functional integrity of the SCN. Under pathological conditions, oxidative stress can compromise these interactions and thus circadian timekeeping and entrainment. To date, little is known about the impact of peripheral pathologies such as hepatocellular carcinoma (HCC) on SCN. Materials and Methods: In this study, HCC was induced in adult male mice. The key neuropeptides (vasoactive intestinal peptide: VIP, arginine vasopressin: AVP), an essential component of the molecular clockwork (Bmal1), markers for activity of neurons (c-Fos), astrocytes (GFAP), microglia (IBA1), as well as oxidative stress (8-OHdG) in the SCN were analyzed by immunohistochemistry at four different time points in HCC-bearing compared to control mice. Results: The immunoreactions for VIP, Bmal1, GFAP, IBA1, and 8-OHdG were increased in HCC mice compared to control mice, especially during the activity phase. In contrast, c-Fos was decreased in HCC mice, especially during the late inactive phase. Conclusions: Our data suggest that HCC affects the circadian system at the level of SCN. This involves an alteration of neuropeptides, neuronal activity, Bmal1, activation of glia cells, and oxidative stress in the SCN.

We report a dengue outbreak in Key Largo, Florida, USA, from February through August 2020, during the COVID-19 pandemic. Successful community engagement resulted in 61% of case-patients self-reporting. We also describe COVID-19 pandemic effects on the dengue outbreak investigation and the need to increase clinician awareness of dengue testing recommendations.

BackgroundThe acquisition of handwriting skills is essential for a child’s academic success, self-confidence, and general school performance. Nevertheless, an estimated 5% to 27% of children face handwriting challenges, where the ability to modulate pressure on the pencil and lead on the paper is a key motor component. ObjectiveWe aimed to investigate the experience with and usability of the SensoGrip system, a pressure-measuring pen system with personalized real-time feedback about pressure modulation, in a clinical setting with children and occupational therapists (OTs). MethodsA multimethods study was conducted, incorporating qualitative interviews and questionnaires with children, user diaries, focus group discussions, and a usability questionnaire with OTs, along with a questionnaire for parents. ResultsThe study involved OTs (n=8), children with handwriting difficulties (n=16), and their parents (n=16), each of whom used the SensoGrip system in up to 5 therapy sessions. OTs reported that the SensoGrip system helped to focus the child’s awareness on handwriting pressure and to measure it objectively. The system received high acceptance and usability ratings from the OTs—usefulness: median score of 4 out of 7; ease of use and ease of learning: median score of 6 out of 7; and satisfaction: median score of 6 out of 7. Participants appreciated that it fosters pressure awareness and motivation to draw and write. ConclusionsThe SensoGrip pressure-sensing system with real-time feedback is a promising tool for pediatric occupational therapy. It supports children with handwriting difficulties to adjust their pressure application during the task. In the future, controlled quantitative trials are warranted to further examine the system’s impact.

BackgroundThe COVID-19 pandemic has highlighted the growing relevance of telehealth in health care. Assessing health care and nursing students’ telehealth competencies is crucial for its successful integration into education and practice. ObjectiveWe aimed to assess students’ perceived telehealth knowledge, skills, attitudes, and experiences. In addition, we aimed to examine students’ preferences for telehealth content and teaching methods within their curricula. MethodsWe conducted a cross-sectional web-based study in May 2022. A project-specific questionnaire, developed and refined through iterative feedback and face-validity testing, addressed topics such as demographics, personal perceptions, and professional experience with telehealth and solicited input on potential telehealth course content. Statistical analyses were conducted on surveys with at least a 50% completion rate, including descriptive statistics of categorical variables, graphical representation of results, and Kruskal Wallis tests for central tendencies in subgroup analyses. ResultsA total of 261 students from 7 bachelor’s and 4 master’s health care and nursing programs participated in the study. Most students expressed interest in telehealth (180/261, 69% very or rather interested) and recognized its importance in their education (215/261, 82.4% very or rather important). However, most participants reported limited knowledge of telehealth applications concerning their profession (only 7/261, 2.7% stated profound knowledge) and limited active telehealth experience with various telehealth applications (between 18/261, 6.9% and 63/261, 24.1%). Statistically significant differences were found between study programs regarding telehealth interest (P=.005), knowledge (P

Abstract Background Streptococcus pyogenes (group A streptococci; GAS) is the main causative pathogen of monomicrobial necrotizing soft tissue infections (NSTIs). To resist immuno-clearance, GAS adapt their genetic information and/or phenotype to the surrounding environment. Hyper-virulent streptococcal pyrogenic exotoxin B (SpeB) negative variants caused by covRS mutations are enriched during infection. A key driving force for this process is the bacterial Sda1 DNase. Methods Bacterial infiltration, immune cell influx, tissue necrosis and inflammation in patient´s biopsies were determined using immunohistochemistry. SpeB secretion and activity by GAS post infections or challenges with reactive agents were determined via Western blot or casein agar and proteolytic activity assays, respectively. Proteome of GAS single colonies and neutrophil secretome were profiled, using mass spectrometry. Results Here, we identify another strategy resulting in SpeB-negative variants, namely reversible abrogation of SpeB secretion triggered by neutrophil effector molecules. Analysis of NSTI patient tissue biopsies revealed that tissue inflammation, neutrophil influx, and degranulation positively correlate with increasing frequency of SpeB-negative GAS clones. Using single colony proteomics, we show that GAS isolated directly from tissue express but do not secrete SpeB. Once the tissue pressure is lifted, GAS regain SpeB secreting function. Neutrophils were identified as the main immune cells responsible for the observed phenotype. Subsequent analyses identified hydrogen peroxide and hypochlorous acid as reactive agents driving this phenotypic GAS adaptation to the tissue environment. SpeB-negative GAS show improved survival within neutrophils and induce increased degranulation. Conclusions Our findings provide new information about GAS fitness and heterogeneity in the soft tissue milieu and provide new potential targets for therapeutic intervention in NSTIs.

ObjectiveMentalization is discussed as a mechanism of change in psychotherapy due to its positive effects on psychological functioning. In order to specifically apply mentalization-based interventions, a better understanding of the relationship between interventions and in-session mentalization is needed. The study aimed to explore the association between interventions and effective mentalizing.MethodFifteen therapy sessions of three therapies with male adolescents with conduct disorder were transcribed and rated with the Reflective Functioning (RF) Scale and a newly developed Mentalization-based Treatment (MBT) intervention coding manual. The coded interventions were categorized into intervention levels according to the MBT manual. Fisher’s exact tests were performed to test differences in frequencies of interventions in high-RF sequences (RF score ≥ 4) compared with remaining therapy sequences (RF score ≤ 3).ResultsSpecific MBT interventions such as demand questions, affectelaboration, empathic validation, change of subject, challenge, patienttherapist relation and mentalizing for the patient were related to effective mentalizing. Moreover, intervention levels such as supportive & empathic, basic- mentalizing & affect mode and relational mentalizing were positively associated with effective mentalizing.ConclusionMBT interventions seem to promote effective mentalizing at various intervention levels. Interventions that enhance effective mentalizing seem to be patient specific. In line with MBT theory, their effect on effective mentalizing might depend on various variables, such as the patients’ arousal and pre-mentalizing mode.

As in-feed antibiotics are phased out of swine production, producers are seeking alternatives to facilitate improvements in growth typically seen from this previously common feed additive. Kazachstania slooffiae is a prominent commensal fungus in the swine gut that peaks in relative abundance shortly after weaning and has beneficial interactions with other bacteriome members important for piglet health. In this study, piglets were supplemented with K. slooffiae to characterize responses in piglet health as well as fungal and bacterial components of the microbiome both spatially (along the entire gastrointestinal tract and feces) and temporally (before, during, and after weaning). Litters were assigned to one of four treatments: no K. slooffiae (CONT); one dose of K. slooffiae 7 days before weaning (day 14; PRE); one dose of K. slooffiae at weaning (day 21; POST); or one dose of K. slooffiae 7 days before weaning and one dose at weaning (PREPOST). The bacteriome and mycobiome were analyzed from fecal samples collected from all piglets at day 14, day 21, and day 49, and from organ samples along the gastrointestinal (GI) tract at day 21 and day 49. Blood samples were taken at day 14 and day 49 for cytokine analysis, and fecal samples were assayed for antimicrobial resistance. While some regional shifts were seen in response to K. slooffiae administration in the mycobiome of the GI tract, no remarkable changes in weight gain or health of the animals were observed, and changes were more likely due to sow and the environment. Ultimately, the combined microbiome changed most considerably following the transition from suckling to nursery diets. This work describes the mycobiome along the piglet GI tract through the weaning transition for the first time. Based on these findings, K. slooffiae administered at this concentration may not be an effective tool to hasten colonization of K. slooffiae in the piglet GI tract around the weaning transition nor support piglet growth, microbial gut health, or immunity. However, diet and environment greatly influence microbial community development.

Mentalizing describes the ability to imagine mental states underlying behavior. Furthermore, mentalizing allows one to identify, reflect on, and make sense of one's emotional state as well as to communicate one's emotions to oneself and others. In existing self-report measures, the process of mentalizing emotions in oneself and others was not captured. Therefore, the Mentalizing Emotions Questionnaire (MEQ; current version in German) was developed. In Study 1 (N = 510), we explored the factor structure of the MEQ with an Exploratory Factor Analysis. The factor analysis identified one principal (R2 = .65) and three subfactors: the overall factor was mentalizing emotions, the three subdimensions were self, communicating and other. In Study 2 (N = 509), we tested and confirmed the factor structure of the 16-items MEQ in a Confirmatory Factor Analysis (CFI = .959, RMSEA = .078, SRMR = .04) and evaluated its psychometric properties, which showed excellent internal consistency (α = .92 - .95) and good validity. The MEQ is a valid and reliable instrument which assesses the ability to mentalize emotions provides incremental validity to related constructs such as empathy that goes beyond other mentalization questionnaires.

Anxiety is a common comorbidity for individuals with ASD, and there is some preliminary data about the efficacy of physical exercise to alleviate anxiety. However, we are not aware of any studies that have compared the effects of a physical exercise program on anxiety in underserved children with ASD using a randomized controlled research design. This paper describes a method to evaluate and compare the efficacy of an 8-week physical exercise intervention with a sedentary play intervention to alleviate anxiety in young children with autism spectrum disorders (ASD) from underserved backgrounds. We assessed anxiety and its physical symptoms using the parent-rated Child Behavior Checklist DSM-5 anxiety (CBCL DSM-5) subscale, the child-rated Screen for Childhood Anxiety Related Emotional Disorder (SCARED), the parent-rated Child's Sleep Habits Questionnaire (CSHQ), and salivary cortisol. We also utilized the Physical Activity Questionnaire for Older Children (PAQ-C) to assess physical activity level and identify compounds. Unique components of this study include: • Implementation of novel physical exercise and sedentary play interventions that have been designed for children with ASD. • Recruitment of predominantly underserved and non-English speaking families.

Epistemic stance, comprising epistemic trust, mistrust, and credulity, and the closely related construct of mentalizing have been related to paranoid ideation and conspiracy mentality. All phenomena are common in the general population and may become clinically and societally relevant at an extreme expression by influencing an individual’s positioning towards socially transmitted information possibly as far as complete social detachment or attachment to extremist views. Herein, an individual’s experienced distress may play an important role, which has however largely been neglected in empirical research. Thus, this study aims to empirically investigate the effect of epistemic stance on a clinically relevant aspect of paranoid ideation, namely paranoid distress. We assume that epistemic stance will be associated with paranoid distress, but that this association will be mediated by mentalizing. Moreover, we assume that epistemic stance will be indirectly associated with conspiracy thinking via paranoid distress. Data of 595 participants (mean age = 43.05; SD = 13.87; female = 48.32%, male = 51.18%, diverse = 0.51%) were collected via self-report questionnaires through an online-based cross-sectional study. Structural equation modeling was performed for data analysis. As expected, epistemic mistrust was associated with paranoid distress via mentalizing deficits. Unexpectedly, epistemic trust was associated with more paranoid distress. Indirectly, epistemic trust was associated with conspiracy mentality via paranoid distress. Findings partially confirmed the hypothesized associations. Mentalizing may be a target for reducing distress associated with a distrusting epistemic stance. Epistemically trusting individuals with high paranoid distress may turn to conspiracy theories for regulation.

The first comprehensive programme in the Croatian language in the Republic of Serbia started in 2002, and the status of the Croatian community as a national minority was recognized, but teaching took place in very challenging circumstances, considering the numerous obstacles in hiring teachers, difficulties with textbooks, the decreasing number of Croats and the perception of the typologically related Serbian language as the mother tongue among Croats. The aim of this research is to get an insight into the experiences of teachers who work within the Croatian Teaching Abroad (CTA) programme in the Republic of Serbia. Only teachers from the Republic of Croatia selected by the Ministry of Science and Education participated in the research. The research was conducted through an anonymous survey that examined: 1) teacher education for work through the analysis of specific and general competencies and the suitability of available textbooks in the Croatian language, 2) the teachers’ ability to deliver content related to the cultural and historical heritage of Croatia and 3) the teachers’ qualifications for teaching Croatian as a heritage language. The results show that: 1) the teachers need additional intercultural competencies that they did not acquire during formal education, 2) the existing textbooks are not fully suitable for teaching language and literature, 3) the teachers need further training and practice in teaching the Croatian language before teaching Croatian abroad, especially in the area of acquiring Croatian as a heritage language, which is primarily due to the lack of programmes for the education of teachers of Croatian as a foreign or heritage language at the formal level. Moreover, the teachers note the problem of students’ prior knowledge and motivation, as well as that of differentiating between the Croatian and Serbian languages, as great challenges.

ABSTRACT: Energy and nutrient deficiency in dairy cows in early lactation is considered to contribute to their increased susceptibility to mastitis. We have tested the hypothesis that feeding diets with high contents of either nitrogenic, glucogenic, or lipogenic components in early lactation affects both the endocrine and metabolic status, as well as the mammary immune competence. After calving, cows were fed increasing amounts of concentrate up to 10 kg/d rich in crude protein (nitrogenic, n = 10), glucogenic precursors (glucogenic, n = 11), or lipids (lipogenic, n = 11). In wk 3, one udder quarter was challenged with lipopolysaccharide (LPS) from Escherichia coli. Blood and milk were sampled on the day before LPS challenge (d −1), and on d 0, 1, 2, 3, and 9 after LPS challenge. On the day of LPS challenge additional samples were taken hourly for quarter milk and every 3 h for blood. Urea concentrations were higher in plasma and milk of cows fed the nitrogenic diet. However, plasma concentrations of glucose, cholesterol, triglycerides, β-hydroxybutyrate, nonesterified fatty acids, as well as insulin, glucagon, and insulin-like growth factor-1 were not affected by the different diets. The mammary immune challenge induced a substantial increase of somatic cell count (SCC) in the treated quarter, and a transient decrease of total milk yield and white blood cells similar in all diet groups for one day. The absolute phagocytosis of blood leukocytes was decreased; however, the phagocytosis per cell was increased in glucogenic-fed cows at 6 h after LPS challenge. During mammary inflammation an insulin resistance, shown by increased plasma glucose, insulin, and glucagon, developed similarly in all diet groups. β-hydroxybutyrate and nonesterified fatty acids were decreased at 1 d after LPS challenge in glucogenic-fed cows only. Cholesterol did not change, and triglycerides only decreased significantly in lipogenic-fed cows 6 h after challenge. On d 9 after LPS challenge, SCC and milk yield and metabolic factors were recovered in all groups. In conclusion, the endocrine and metabolic situation, and the immune response to intramammary LPS of dairy cows during early lactation was not substantially influenced by the elevated supply of nitrogenic, glucogenic, or lipogenic components due to the provided feed in this study.

Abstract Background Home visitation services within German Early Childhood Interventions (ECI) for families with a child aged 0–3 are mainly provided by frontline pediatric nurses and family midwifes. Home visitors are often challenged by difficult interactions with families. Mentalizing, the ability to understand mental states of oneself and others, is a key skill for building effective working relationships, which in turn positively affect intervention outcomes. The aim of this study was to investigate if a mentalizing skills training offered to home visitors active in German ECI contributes to continued professional development. We investigated, whether the training positively affected the quality of the working relationships with families as well as home visitors’ empathy, self-efficacy, and mentalizing. Methods To test the effects of a single day mentalizing skills training on the working relationship in N = 73 ECI home visitors, we used a quasi-experimental design with repeated measures (T0, T1, T2, T3) across seven weeks in order to assess immediate change from baseline (T0) after the training (T2) and stability of changes at follow up (T3). A literature-based intervention was implemented before the training to estimate possible repeated measurement and expectational effects (T1). Primary outcome was the quality of the working relationship experienced by the home visitors. Secondary outcome criteria were empathy, work-related self-efficacy, self-reported and observer-rated mentalizing. Results Significant positive change in the working relationship quality was observed at T2 and at T3. Results on the secondary outcomes were less consistent, with data indicating improvement in empathy and increase on some but not all components of mentalizing. Conclusions This study provides preliminary evidence that brief mentalizing skills trainings may be an effective method for continuous professional qualification in frontline ECI home visitors who afterwards, experience better working relationships with families. Thus, training participation may positively impact efficacy and implementation of home visitations in ECI.

Abstract. Influenza A virus and Staphylococcus aureus are common causative agents of pneumonia. Co-infections with these two pathogens frequently occur and are characterized, among others, by higher morbidity and mortality due to hyper-inflammation of the lungs. Here, we aimed to profile systemic and local cytokine composition at early acute stages of pneumonia in a murine model. All mice recovered from single influenza A virus and/or staphylococcal infections. In contrast, co-infections led to a severe clinical outcome. While distinct cytokine patterns were detected in lungs of single-pathogen-infected animals, co-infections combined both virus- and bacteria-driven responses. However, analyses of infected human primary monocytic cells as well as bronchial epithelial cells did not reflect murine profiles. Based on infectious dose, mainly bacteria-driven responses were noted. The impact of single cells to cytokine composition of the lungs and translation of murine studies to humans remains uncertain and warrants further studies.

In this paper, a concept for an anthropomorphic replacement hand cast with silicone with an integrated sensory feedback system is presented. In order to construct the personalized replacement hand, a 3D scan of a healthy hand was used to create a 3D-printed mold using computer-aided design (CAD). To allow for movement of the index and middle fingers, a motorized orthosis was used. Information about the applied force for grasping and the degree of flexion of the fingers is registered using two pressure sensors and one bending sensor in each movable finger. To integrate the sensors and additional cavities for increased flexibility, the fingers were cast in three parts, separately from the rest of the hand. A silicone adhesive (Silpuran 4200) was examined to combine the individual parts afterwards. For this, tests with different geometries were carried out. Furthermore, different test series for the secure integration of the sensors were performed, including measurements of the registered information of the sensors. Based on these findings, skin-toned individual fingers and a replacement hand with integrated sensors were created. Using Silpuran 4200, it was possible to integrate the needed cavities and to place the sensors securely into the hand while retaining full flexion using a motorized orthosis. The measurements during different loadings and while grasping various objects proved that it is possible to realize such a sensory feedback system in a replacement hand. As a result, it can be stated that the cost-effective realization of a personalized, anthropomorphic replacement hand with an integrated sensory feedback system is possible using 3D scanning and 3D printing. By integrating smaller sensors, the risk of damaging the sensors through movement could be decreased.

Background: In Patients with Hirschsprung Disease (HSCR) suffering from obstructive symptoms after their pull-through surgery, a transition zone pull-through (TZPT) was suggested as a causing factor. Current guidelines recommend a reoperation resecting the transition zone in these patients. This present study reports the clinical outcomes in patients with a confirmed TZPT. Methods: A retrospective review of patients who underwent a primary transanal pull-through for recto-sigmoid HSCR at the Children's Hospital Colorado from January 2010 until June 2020 was performed. We included patients with a TZPT confirmed on the definitive histopathological report of the proximal margin's circumference obtained at the time of their pull-through surgery and follow-up at the Children's Hospital Colorado. Demographic data were collected. The primary outcome of interest was fecal control, episodes of Hirschsprung-associated enterocolitis (HAEC), the necessity of bowel management (with either laxatives or enemas), and a redo pull-through. Results: Six patients had a TZPT. Two patients suffered episodes of HAEC. One patient is fecal incontinent. None of them underwent redo pull-through surgery. Medical treatment was successful in all with obstructive symptoms. Conclusion: Patients who underwent a pull-through surgery for HSCR with retained transition zone may suffer from obstructive symptoms, which can be managed conservatively with medical treatment. A TZPT is not necessarily associated with persistent obstructive symptoms. Level of evidence/type of study: Level III, retrospective.

Abstract This study investigates the contamination potential of herbicides to groundwater with the help of numerical modeling (HYDRUS‐1D) and stable carbon isotopes for characterizing biodegradation. Four herbicides, metolachlor, terbuthylazine, prosulfuron, and nicosulfuron, were applied over a period of 4.5 years on two lysimeters located in Wielenbach, Germany, and monitored by lysimeter drainage. These lysimeters contained soil cores dominated by sandy gravel (Ly1) and clayey sandy silt (Ly2) and were both cropped with maize (Zea mays). In the preceding study, we characterized flow within the lysimeters by using stable water isotopes and unsaturated flow models. Building up on these findings, models were extended for describing reactive transport of the herbicides and investigating process contributions. At the end of the experiment, 0.9%–15.9% of the applied herbicides (up to 20.9% if including metabolites) were recovered by lysimeter drainage. Metabolite formation and accumulation was observed, and biodegradation was also indicated by small changes in carbon isotope signals (δ13C) between applied and leached herbicides. Model setups could describe the dynamics of herbicide concentrations in lysimeter drainage well. Concentration peaks in drainage were partly also linked with strong precipitation events, indicating preferential flow influence. The soil core with the coarser texture (Ly1) showed less herbicide leaching than the finer texture (Ly2), which can be explained by a larger mobile phase in Ly1. Overall, our approaches and findings contribute to the understanding of multi‐process herbicide transport in the vadose zone and leaching potentials to groundwater, where δ13C can provide valuable hints for microbial degradation.

Abstract Understanding transport and fate processes in the subsurface is of fundamental importance to identify the leaching potentials of herbicides or other compounds to groundwater resources. HYDRUS‐1D was used to simulate water flow and solute transport in arable land lysimeters. Simulations were compared to observed drainage rates and stable water isotopes (δ18O) in the drainage. Four different model setups were investigated and statistically evaluated for their model performance to identify dominant processes for water flow characterization in the vadose zone under similar cultivation management and climatic conditions. The studied lysimeters contain soil cores dominated by sandy gravel (Ly1) and clayey sandy silt (Ly2), both cropped with maize located in Wielenbach, Germany. First, a single‐porosity setup was chosen. For Ly1, modeling results were satisfactory, but for Ly2, the damping observed in the isotope signature of the drainage could not be fully covered. By considering immobile water with a dual‐porosity setup for Ly2, model performance improved. This could be due to a higher fraction of fine pores in Ly2 available for water storage, leading to mixing processes of isotopically enriched summer precipitation and lighter winter water. Accounting for isotopic evaporation fractionation processes in both model setups did not lead to improved model performance. Consequentially, the difference in soil hydraulic properties between the two lysimeters seems to impact water flow processes. Knowledge of such differences is crucial to prevent contamination and mitigate potential risks to soil and groundwater.

Introduction: Here we report an infant with a 46,XY karyotype and novel de novo PPP1R12A stop-loss variant with a concomitant anorectal malformation (ARM) and difference in sex development (DSD). Case report: This is an infant born with ambiguous genitalia and rectoperineal fistula. Genetic testing confirmed a 46,XY chromosomal complement and whole exome sequencing demonstrated a novel de novo heterozygous PPP1R12A stop-loss variant. The infant underwent tapering jejunoplasty, proximal jejunostomy and mucous fistula creation for jejunal atresia and posterior sagittal anorectoplasty for the ARM. The gonad will be addressed with a biopsy and orchiopexy when the infant reaches six months of age. Conclusion: Although Müllerian anomalies and hypospadias may be common with ARM, a true DSD of this nature is exceedingly rare. Multidisciplinary care with urology, endocrinology, genetics, and colorectal surgery is paramount to providing optimal care for this patient.

Background: Postoperative anal dilations (PAD) are the standard of care for patients after a posterior sagittal anorectoplasty (PSARP) for anorectal malformation (ARM) or a transanal pull-through (TP) procedure for Hirschsprung disease (HD). This study assessed the psychosocial impact of PAD among caregivers of children with ARM or HD, which may inform postoperative care strategies. Methods: Caregivers of patients with ARM and HD who underwent PSARP or TP within five years participated in the online survey. Questions included demographics, patient and caregiver experiences with PAD, and baseline psychosocial functioning. Quantitative results were reported descriptively, while qualitative responses were summarized as major themes. Results: The survey indicated a response rate of 26% caregivers, with most being female (91%) and biological mothers (85%). Patients were mostly male (65%), born with ARM (74%), and were five months old on average when PAD began. Caregivers reported that during PAD, children experienced distress (56%), pain (44%), and fear (41%), while a third noted no negative reactions. Over time, their child’s ability to cope with PAD got easier (38%) or stayed the same (41%). Caregivers reported worry/anxiety (88%), guilt (71%), stress (62%), and frustration (35%), noting that additional coping strategies to manage the emotional and logistical challenges of daily PAD would be helpful. Conclusion: Although PAD is necessary, it can be highly stressful for the patients and their caregivers. Key findings emphasized the need for additional coping strategies and highlighted the importance of integrating psychosocial support into the postoperative care regimen.

In mice, reactivation of neurons that express cFos during fear conditioning induces a behavioural response. Here the authors show that cFos expression in mouse dentate gyrus shifts every day to different neurons, even during highly consistent spatial navigation, and suggest this clock-like selection mechanism may aid the encoding of episodic memories.

Abstract The COVID–19 pandemic has caused considerable interest worldwide in antiviral surfaces, and there has been a dramatic increase in the research and development of innovative material systems to reduce virus transmission in the past few years. The International Organization for Standardization (ISO) norms 18,184 and 21,702 are two standard methods to characterize the antiviral properties of porous and non-porous surfaces. However, during the last years of the pandemic, a need for faster and inexpensive characterization of antiviral material was identified. Therefore, a complementary method based on an Inactivated Virus System (InViS) was developed to facilitate the early-stage development of antiviral technologies and quality surveillance of the production of antiviral materials safely and efficiently. The InViS is loaded with a self-quenched fluorescent dye that produces a measurable increase in fluorescence when the viral envelope disintegrates. In the present work, the sensitivity of InViS to viral disintegration by known antiviral agents is demonstrated and its potential to characterize novel materials and surfaces is explored. Finally, the InViS is used to determine the fate of viral particles within facemasks layers, rendering it an interesting tool to support the development of antiviral surface systems for technical and medical applications.

Abstract Quantitative radiomic and iodine imaging features have been explored for diagnosis and characterization of tumors. In this work, we invistigate combined whole-lesion radiomic and iodine analysis for the differentiation of pulmonary tumors on contrast-enhanced dual-energy CT (DECT) chest images. 100 biopsy-proven solid lung lesions on contrast-enhanced DECT chest exams within 3 months of histopathologic sampling were identified. Lesions were volumetrically segmented using open-source software. Lesion segmentations and iodine density volumes were loaded into a radiomics prototype for quantitative analysis. Univariate analysis was performed to determine differences in volumetric iodine concentration (mean, median, maximum, minimum, 10th percentile, 90th percentile) and first and higher order radiomic features (n = 1212) between pulmonary tumors. Analyses were performed using a 2-sample t test, and filtered for false discoveries using Benjamini–Hochberg method. 100 individuals (mean age 65 ± 13 years; 59 women) with 64 primary and 36 metastatic lung lesions were included. Only one iodine concentration parameter, absolute minimum iodine, significantly differed between primary and metastatic pulmonary tumors (FDR-adjusted p = 0.015, AUC 0.69). 310 (FDR-adjusted p = 0.0008 to p = 0.0491) radiomic features differed between primary and metastatic lung tumors. Of these, 21 features achieved AUC ≥ 0.75. In subset analyses of lesions imaged by non-CTPA protocol (n = 72), 191 features significantly differed between primary and metastatic tumors, 19 of which achieved AUC ≥ 0.75. In subset analysis of tumors without history of prior treatment (n = 59), 40 features significantly differed between primary and metastatic tumors, 11 of which achieved AUC ≥ 0.75. Volumetric radiomic analysis provides differentiating capability beyond iodine quantification. While a high number of radiomic features differentiated primary versus metastatic pulmonary tumors, fewer features demonstrated good individual discriminatory utility.

The Transiting Exoplanet Survey Satellite (TESS) continues to increase dramatically the number of known transiting exoplanets, and is optimal for monitoring bright stars amenable to radial velocity (RV) and atmospheric follow-up observations. TOI-1386 is a solar-type (G5V) star that was detected via TESS photometry to exhibit transit signatures in three sectors with a period of 25.84 days. We conducted follow-up RV observations using Keck/High Resolution Echelle Spectrometer (HIRES) as part of the TESS–Keck Survey, collecting 64 RV measurements of TOI-1386 with the HIRES spectrograph over 2.5 yr. Our combined fit of the TOI-1386 photometry and RV data confirm the planetary nature of the detected TESS signal, and provide a mass and radius for planet b of 0.148 ± 0.019 M _J and 0.540 ± 0.017 R _J , respectively, marking TOI-1386 b as a warm sub-Saturn planet. Our RV data further reveal an additional outer companion, TOI-1386 c, with an estimated orbital period of 227.6 days and a minimum mass of 0.309 ± 0.038 M _J . The dynamical modeling of the system shows that the measured system architecture is long-term stable, although there may be substantial eccentricity oscillations of the inner planet due to the dynamical influence of the outer planet.

The Transiting Exoplanet Survey Satellite (TESS) has discovered hundreds of new worlds, with TESS planet candidates now outnumbering the total number of confirmed planets from Kepler. Owing to differences in survey design, TESS continues to provide planets that are better suited for subsequent follow-up studies, including mass measurement through radial velocity (RV) observations, compared to Kepler targets. In this work, we present the TESS-Keck Survey’s (TKS) Mass Catalog: a uniform analysis of all TKS RV survey data that has resulted in mass constraints for 126 planets and candidate signals. This includes 58 mass measurements that have reached ≥5 σ precision. We confirm or validate 32 new planets from the TESS mission either by significant mass measurement (15) or statistical validation (17), and we find no evidence of likely false positives among our entire sample. This work also serves as a data release for all previously unpublished TKS survey data, including 9,204 RV measurements and associated activity indicators over our three-year survey. We took the opportunity to assess the performance of our survey and found that we achieved many of our goals, including measuring the mass of 38 small (