Search

Abstract Background Although plastic pollution is increasing worldwide, very little is known about the microbial processes that take place once plastic debris is incorporated into the soil matrix. In this study, we conducted the first metatranscriptome analysis of polyethylene (PE)-associated biofilm communities in highly polluted landfill soil and compared their gene expression to that of a forest soil community within a 53-day period. Results Our findings indicate that the microbial population present in soil contaminated with plastic debris is predisposed to both inhabit and degrade plastic surfaces. Surprisingly, the microbial community from undisturbed forest soil contained a diverse array of plastic-associated genes (PETase, alkB, etc.), indicating the presence of an enzymatic machinery capable of plastic degradation. Plastic-degrading taxa were upregulated in the early stages of biofilm formation. During the maturation of the biofilm, the alkB1/alkM transcripts, which encode PE-degrading enzymes, and transporters such as fadL, livG, livF, livH, and livM were upregulated, along with transcripts associated with the fatty acid β-oxidation pathway. Conclusions In this study, we address the underlying patterns of gene expression during biofilm development in a PE-associated plastisphere in soil and address the pressing question of whether natural microbial communities have the potential to biodegrade petrochemical-based plastic in the soil environment.

Abstract Background Despite the growing interest in the use of human genomic data for drug target identification and validation, the extent to which the spectrum of human disease has been addressed by genome-wide association studies (GWAS), or by drug development, and the degree to which these efforts overlap remain unclear. Methods In this study we harmonize and integrate different data sources to create a sample space of all the human drug targets and diseases and identify points of convergence or divergence of GWAS and drug development efforts. Results We show that only 612 of 11,158 diseases listed in Human Disease Ontology have an approved drug treatment in at least one region of the world. Of the 1414 diseases that are the subject of preclinical or clinical phase drug development, only 666 have been investigated in GWAS. Conversely, of the 1914 human diseases that have been the subject of GWAS, 1121 have yet to be investigated in drug development. Conclusions We produce target-disease indication lists to help the pharmaceutical industry to prioritize future drug development efforts based on genetic evidence, academia to prioritize future GWAS for diseases without effective treatments, and both sectors to harness genetic evidence to expand the indications for licensed drugs or to identify repurposing opportunities for clinical candidates that failed in their originally intended indication.

This study investigated the impact of a course-based community asset mapping (CAM) project on undergraduate students' capacity for identifying and understanding assets within communities surrounding specific schools. The mapping project was grounded in the literature on culturally sustaining pedagogy and experiential education and involved teacher education students (n = 45) collaborating to complete and report on an analysis of local community assets. Findings indicated participants gained improved knowledge and competence regarding CAM, were able to provide more accurate and detailed explanations of assets and the asset mapping process, and were able to identify various assets available to PK-12 students and families in particular communities within the local school district. The discussion highlights participants' success in inventorying physical, tangible assets, and notes where they fell short of recognizing other assets. We also discuss how coursework could have better supported the project and could have allowed the potential of CAM to be more fully realized. The conclusion addresses implications for teacher preparation, particularly for connecting candidates with communities and for the implementation of assignments similar to the community asset mapping project studied herein.

The current pilot study tested the feasibility and preliminary efficacy of a combined group cognitive behavioral therapy and exercise intervention (CBT+E), as compared to treatment as usual (TAU) for managing anxiety and mood symptoms in university students. Participants were 16 undergraduate students with at least mild anxiety, depression, or stress symptoms. Participants were randomly assigned to group CBT+E or TAU. CBT+E ran for seven weeks with group sessions held twice weekly. The first weekly session consisted of group CBT followed by 30 minutes of running and the second weekly session consisted of only group running. Findings suggest that the group CBT+E intervention is feasible in terms of retention and participation, but that recruitment strategies need to be improved. Suggestions to improve recruitment in future research are provided. Preliminary efficacy data show positive trends suggesting further pursuit of this type of intervention is important.

Background: People with an acquired brain injury (ABI) find it challenging to use social media due to changes in their cognition and communication skills. Using social media can provide opportunities for positive connection, but there is a lack of interventions specifically designed to support safe and successful social media use after ABI. Aims: To investigate the outcomes of completing a social media skills intervention and identify barriers and facilitators for future implementation. Methods & Procedures: The study used a mixed-methods, pre-post-intervention design. A total of 17 adults with an ABI were recruited. Participants completed an intervention that included a short self-guided course about social media skills (social-ABI-lity course), and then participated in a private, moderated Facebook group over a 12-week period (social-ABI-lity Facebook group). Data were collected over this period through observation of group activity and weekly surveys. They were also collected on social media use and quality of life at pre-intervention, post-intervention and after 3 months. Participants provided feedback on the experience of participating in the programme via a post-intervention interview. Outcomes & Results: At post-intervention, there were significant improvements in confidence in using Facebook (p = 0.002) and enjoyment of using Facebook to connect with others (p = 0.013). There was no significant change in reported quality of life, although participants described the multiple benefits of connection they perceived from involvement in the group. Observational data and feedback interviews were informative about the feasibility and acceptability of the intervention. Conclusions & Implications: This pilot study provided preliminary evidence that an intervention comprising a short, self-guided training course and a private, moderated Facebook group improved outcomes for people with ABI. Key recommendations for future implementation include embedding active peer moderators within groups and taking an individualized approach to delivery of the intervention.

BACKGROUND: Bladder cancer poses a significant public health burden, with high recurrence and progression rates in patients with non-muscle-invasive bladder cancer (NMIBC). Current treatment options include bladder-sparing therapies (BST) and radical cystectomy, both with associated risks and benefits. However, evidence supporting optimal management decisions for patients with recurrent high-grade NMIBC remains limited, leading to uncertainty for patients and clinicians. The CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options) Study aims to address this critical knowledge gap by comparing outcomes between patients undergoing BST and radical cystectomy. METHODS: The CISTO Study is a pragmatic, prospective observational cohort trial across 36 academic and community urology practices in the US. The study will enroll 572 patients with a diagnosis of recurrent high-grade NMIBC who select management with either BST or radical cystectomy. The primary outcome is health-related quality of life (QOL) at 12 months as measured with the EORTC-QLQ-C30. Secondary outcomes include bladder cancer-specific QOL, progression-free survival, cancer-specific survival, and financial toxicity. The study will also assess patient preferences for treatment outcomes. Statistical analyses will employ targeted maximum likelihood estimation (TMLE) to address treatment selection bias and confounding by indication. DISCUSSION: The CISTO Study is powered to detect clinically important differences in QOL and cancer-specific survival between the two treatment approaches. By including a diverse patient population, the study also aims to assess outcomes across the following patient characteristics: age, gender, race, burden of comorbid health conditions, cancer severity, caregiver status, social determinants of health, and rurality. Treatment outcomes may also vary by patient preferences, health literacy, and baseline QOL. The CISTO Study will fill a crucial evidence gap in the management of recurrent high-grade NMIBC, providing evidence-based guidance for patients and clinicians in choosing between BST and radical cystectomy. The CISTO study will provide an evidence-based approach to identifying the right treatment for the right patient at the right time in the challenging clinical setting of recurrent high-grade NMIBC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03933826. Registered on May 1, 2019.

In the medical diagnostics domain, pathology and histology are pivotal for the precise identification of diseases. Digital histopathology, enhanced by automation, facilitates the efficient analysis of massive amount of biopsy images produced on a daily basis, streamlining the evaluation process. This study focuses in Stain Color Normalization (SCN) within a Whole-Slide Image (WSI) cohort, aiming to reduce batch biases. Building on published graphical method, this research demonstrates a mathematical population or data-driven method that optimizes the dependency on the number of reference WSIs and corresponding aggregate sums, thereby increasing SCN process efficiency. This method expedites the analysis of color convergence 50-fold by using stain vector Euclidean distance analysis, slashing the requirement for reference WSIs by more than half. The approach is validated through a tripartite methodology: 1) Stain vector euclidean distances analysis, 2) Distance computation timing, and 3) Qualitative and quantitative assessments of SCN across cancer tumors regions of interest. The results validate the performance of data-driven SCN method, thus potential to enhance the precision and reliability of computational pathology analyses. This advancement is poised to enhance diagnostic processes, therapeutic strategies, and patient prognosis.

Abstract The impact of preterm babies’ admission at the Neonatal Intensive Care (NICU) on the mental health of mothers is a global challenge. However, the prevalence and predictors of Common Mental Disorders (CMDs) among this population remain underexplored. This study assessed the predictors of CMDs among mothers of preterm infants in the NICUs in the Upper East Region of Ghana. A cross-sectional study was conducted, targeting mothers of preterm babies in two hospitals in the Upper East Region. The Self-Report Questionnaire (SRQ-20) was used to collect data from 375 mothers of preterm babies admitted to the NICUs. Statistical analyses were done using SPSS version 20. The study found a prevalence of 40.9% for CMDs among mothers of preterm babies admitted to the two NICUs. The predictors of CMDs were unemployment (aOR 2.925, 95% CI 1.465, 5.840), lower levels of education (aOR 5.582, 95% CI 1.316, 23.670), antenatal anxiety (aOR 3.606, 95% CI 1.870, 6.952), and assisted delivery (aOR 2.144, 95% CI 1.083, 4.246). Conversely, urban residence (aOR 0.390, 95% CI 0.200, 0.760), age range between 25 and 31 (aOR 0.238, 95% CI 0.060, 0.953), and having a supportive partner (aOR 0.095, 95% CI 0.015, 0.593) emerged as protective factors. This study emphasizes the imperative of addressing maternal mental health within the NICU setting for preterm births.

Achieving carbon neutrality by 2050 requires unprecedented technological, economic, and sociological changes. With time as a scarce resource, it is crucial to base decisions on relevant facts and information to avoid misdirection. This study aims to help decision makers quickly find relevant information related to companies and organizations in the renewable energy sector. In this study, we propose fine-tuning five RNN and transformer models trained for French on a new category, “TECH”. This category is used to classify technological domains and new products. In addition, as the model is fine-tuned on news related to startups, we note an improvement in the detection of startup and company names in the “ORG” category. We further explore the capacities of the most effective model to accurately predict entities using a small amount of training data. We show the progression of the model from being trained on several hundred to several thousand annotations. This analysis allows us to demonstrate the potential of these models to extract insights without large corpora, allowing us to reduce the long process of annotating custom training data. This approach is used to automatically extract new company mentions as well as to extract technologies and technology domains that are currently being discussed in the news in order to better analyze industry trends. This approach further allows to group together mentions of specific energy domains with the companies that are actively developing new technologies in the field.

Abstract Background Fruit consumption has been associated with a lower cardiovascular disease (CVD) risk but the underlying mechanisms are unclear. We investigated the cross-sectional and prospective associations of fruit consumption with markers of adiposity, blood pressure, lipids, low-grade inflammation, glycaemia, and oxidative stress. Methods The main analyses included 365 534 middle-aged adults from the UK Biobank at baseline, of whom 11 510, and 38 988 were included in the first and second follow-up respectively, free from CVD and cancer at baseline. Fruit consumption frequency at baseline was assessed using a questionnaire. We assessed the cross-sectional and prospective associations of fruit with adiposity (body mass index, waist circumference and %body fat), systolic and diastolic blood pressure, lipids (low-density and high-density lipoproteins, triglycerides and apolipoprotein B), glycaemia (haemoglobin A1c), low-grade inflammation (C-reactive protein) and oxidative stress (gamma-glutamyl-transferase) using linear regression models adjusted for socioeconomic and lifestyle factors. Analyses were repeated in a subset with two to five complete 24-h dietary assessments (n = 26 596) allowing for adjustment for total energy intake. Results Fruit consumption at baseline generally showed weak inverse associations with adiposity and biomarkers at baseline. Most of these relationships did not persist through follow-up, except for inverse associations with diastolic blood pressure, C-reactive protein, gamma-glutamyl transferase and adiposity. However, for most mechanisms, mean levels varied by less than 0.1 standard deviations (SD) between high and low fruit consumption (> 3 vs

In 2019, the European Union banned Triton X-100, a detergent widely used in laboratory diagnostics, including the Viral PCR Sample Solution (VPSS), and urged manufacturers to find environmentally sustainable alternatives. Tergitol 15-S-9 (VPSS2) has been proposed as an alternative surfactant. This multicenter study evaluated the effectiveness of VPSS2, a Tergitol-based viral solution, as a replacement for VPSS. Our results show the equivalent performance of VPSS2 to VPSS for nucleic acid extraction and viral stability over time at different temperatures. The new VPSS formulation was also tested against external quality assurance panels and clinical samples. The results of this work support adopting this modified viral PCR sample solution to replace Triton X-100-containing viral transport solutions.

Abstract Birdshot chorioretinopathy is an inflammatory eye condition strongly associated with MHC-I allele HLA-A29. The striking association with MHC-I suggests involvement of T cells, whereas natural killer (NK) cell involvement remains largely unstudied. Here we show that HLA-A29-positive birdshot chorioretinopathy patients have a skewed NK cell pool containing expanded CD16 positive NK cells which produce more proinflammatory cytokines. These NK cells contain populations that express CD8A which is involved in MHC-I recognition on target cells, display gene signatures indicative of high cytotoxic activity (GZMB, PRF1 and ISG15), and signaling through NK cell receptor CD244 (SH2D1B). Long-term monitoring of a cohort of birdshot chorioretinopathy patients with active disease identifies a population of CD8bright CD244bright NK cells, which rapidly declines to normal levels upon clinical remission following successful treatment. Collectively, these studies implicate CD8bright CD244bright NK cells in birdshot chorioretinopathy.

PURPOSE: While the T2-FLAIR mismatch sign is highly specific for isocitrate dehydrogenase (IDH)-mutant, 1p/19q-noncodeleted astrocytomas among lower-grade gliomas, its utility in WHO grade 4 gliomas is not well-studied. We derived the partial T2-FLAIR mismatch sign as an imaging biomarker for IDH mutation in WHO grade 4 gliomas. METHODS: Preoperative MRI scans of adult WHO grade 4 glioma patients (n = 2165) from the multi-institutional ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium were analyzed. Diagnostic performance of the partial T2-FLAIR mismatch sign was evaluated. Subset analyses were performed to assess associations of imaging markers with overall survival (OS). RESULTS: One hundred twenty-one (5.6%) of 2165 grade 4 gliomas were IDH-mutant. Partial T2-FLAIR mismatch was present in 40 (1.8%) cases, 32 of which were IDH-mutant, yielding 26.4% sensitivity, 99.6% specificity, 80.0% positive predictive value, and 95.8% negative predictive value. Multivariate logistic regression demonstrated IDH mutation was significantly associated with partial T2-FLAIR mismatch (odds ratio [OR] 5.715, 95% CI [1.896, 17.221], p = 0.002), younger age (OR 0.911 [0.895, 0.927], p

Mammalian organs exhibit distinct physiology, disease susceptibility, and injury responses between the sexes. In the mouse kidney, sexually dimorphic gene activity maps predominantly to proximal tubule (PT) segments. Bulk RNA sequencing (RNA-seq) data demonstrated that sex differences were established from 4 and 8 weeks after birth under gonadal control. Hormone injection studies and genetic removal of androgen and estrogen receptors demonstrated androgen receptor (AR)-mediated regulation of gene activity in PT cells as the regulatory mechanism. Interestingly, caloric restriction feminizes the male kidney. Single-nuclear multiomic analysis identified putative cis-regulatory regions and cooperating factors mediating PT responses to AR activity in the mouse kidney. In the human kidney, a limited set of genes showed conserved sex-linked regulation, whereas analysis of the mouse liver underscored organ-specific differences in the regulation of sexually dimorphic gene expression. These findings raise interesting questions on the evolution, physiological significance, disease, and metabolic linkage of sexually dimorphic gene activity.

The rate model of basal ganglia function predicts that muscle activity in dystonia is due to disinhibition of thalamus resulting from decreased inhibitory input from pallidum. We seek to test this hypothesis in children with dyskinetic cerebral palsy undergoing evaluation for deep brain stimulation (DBS) to analyze movement-related activity in different brain regions. The results revealed prominent beta-band frequency peaks in the globus pallidus interna (GPi), ventral oralis anterior/posterior (VoaVop) subnuclei of the thalamus, and subthalamic nucleus (STN) during movement but not at rest. Connectivity analysis indicated stronger coupling between STN-VoaVop and STN-GPi compared to GPi-STN. These findings contradict the hypothesis of decreased thalamic inhibition in dystonia, suggesting that abnormal patterns of inhibition and disinhibition, rather than reduced GPi activity, contribute to the disorder. Additionally, the study implies that correcting abnormalities in GPi function may explain the effectiveness of DBS targeting the STN and GPi in treating dystonia.

Macrophages are essential for skeletal muscle homeostasis, but how their dysregulation contributes to the development of fibrosis in muscle disease remains unclear. Here, we used single-cell transcriptomics to determine the molecular attributes of dystrophic and healthy muscle macrophages. We identified six clusters and unexpectedly found that none corresponded to traditional definitions of M1 or M2 macrophages. Rather, the predominant macrophage signature in dystrophic muscle was characterized by high expression of fibrotic factors, galectin-3 (gal-3) and osteopontin (Spp1). Spatial transcriptomics, computational inferences of intercellular communication, and in vitro assays indicated that macrophage-derived Spp1 regulates stromal progenitor differentiation. Gal-3+ macrophages were chronically activated in dystrophic muscle, and adoptive transfer assays showed that the gal-3+ phenotype was the dominant molecular program induced within the dystrophic milieu. Gal-3+ macrophages were also elevated in multiple human myopathies. These studies advance our understanding of macrophages in muscular dystrophy by defining their transcriptional programs and reveal Spp1 as a major regulator of macrophage and stromal progenitor interactions.

Infecting humans with controlled doses of helminths, such as human hookworm (termed hookworm therapy), is proposed to prevent or treat various intestinal and extraintestinal diseases. However, full-scale clinical trials examining hookworm therapy are limited by the inability to scale-up the production of hookworm larvae to infect sufficient numbers of patients. With the aim of overcoming this challenge, this study infected four healthy individuals with hookworm larvae that had been reanimated from cryopreserved eggs to examine their viability and immunogenicity. We demonstrate that reanimated cryopreserved hookworm larvae establish a viable hookworm infection and elicit a similar immune response to larvae cultured from fresh stool. Furthermore, a refined understanding of the therapeutic mechanisms of hookworm is imperative to determine which diseases to target with hookworm therapy. To investigate potential therapeutic mechanisms, this study assessed changes in the immune cells, microbiome, and plasma metabolome in the four healthy individuals infected with cryopreserved hookworm larvae and another nine individuals infected with larvae cultured from freshly obtained stool. We identified potential immunoregulatory mechanisms by which hookworm may provide a beneficial effect on its host, including increased expression of CTLA-4 on regulatory T cells (Tregs) and upregulation of tryptophan metabolism. Furthermore, we found that a participant’s baseline microbiome predicted the severity of symptoms and intestinal inflammation experienced during a controlled hookworm infection. In summary, our findings demonstrate the feasibility of full-scale clinical trials examining hookworm therapy by minimizing the reliance on human donors and optimizing the culturing process, thereby enabling viable hookworm larvae to be mass-produced and enabling on-demand inoculation of patients. Furthermore, this study provides insights into the complex interactions between helminths and their host, which could inform the development of novel therapeutic strategies.

‘Continuing care’ refers to the provision of co-ordinated care and support overtime. Currently, little is known about continuing care programs for young people who complete alcohol and other drug treatment. This paper analyses data from an interview-based study that aimed to identify the generative mechanisms underpinning an innovative continuing care program for young people. Researchers recruited 11 current and former program clients aged 17 to 25 years and nine program staff. Analysis identified five generative mechanisms of the program that supported participants to manage their substance use over the long term, namely person-centred counselling; relationship stability; safety and inclusion; situated mode of ordering continuing care; and organizational memory. Participants reported that the best continuing care for young people is holistic, includes regular and sustained contact, employs an innovative approach to intervention, establishes links with community services and other support structures, and provides care within a safe, person-centred, and situated framework.

ABSTRACTThere is a need for operational decision-making methodologies applicable at local management scales which are inclusive and enable the integration of plural values, knowledges and perspectives of co-produced ecosystem services. Here we describe a deliberative scenario analysis method using ‘management intervention bundles’ as distinct scenarios to assess the perceived impact of changing management on woodland ecosystem services. We used three hypothetical future management scenarios, Biodiversity Conservation, People Engagement and Austerity, alongside scenarios of the Past, Present and an existing Management Plan. We assessed the perceived impacts of these scenarios on 11 ecosystem services using local expert workshops in six sites across Scotland. The experts were chosen to represent a range of different perspectives, from biodiversity to the local economy, community concerns and recreation. Overall, Management Plan, Biodiversity Conservation and People Engagement scenarios performed significantly better than Past, Present and Austerity scenarios. Further quantitative and in-depth qualitative analysis revealed trade-offs and noteworthy patterns. We explore some of these key trade-offs and patterns and argue that our methodology has potential to be an effective tool for local managers to support local decision-making at management scales for co-produced ecosystem services. Our methodology enabled a diverse group of local experts to express and deliberate a range of values, experiences and viewpoints. This knowledge sharing and collective learning allowed the development of shared values and perspectives, which are thought to be critical in more equitable and inclusive decision-making.