Wastewater-based surveillance of SARS-CoV-2: Short-term projection (forecasting), smoothing and outlier identification using Bayesian smoothing.

BACKGROUND: Day-to-day variation in the measurement of SARS-CoV-2 in wastewater can challenge public health interpretation. We assessed a Bayesian smoothing and forecasting method previously used for surveillance and short-term projection of COVID-19 cases, hospitalizations, and deaths. METHODS: SARS-CoV-2 viral measurement from the sewershed in Ottawa, Canada, sampled at the municipal wastewater treatment plant from July 1, 2020, to February 15, 2022, was used to assess and internally validate measurement averaging and prediction. External validation was performed using viral measurement data from influent wastewater samples from 15 wastewater treatment plants and municipalities across Ontario. RESULTS: Plots of SARS-CoV-2 viral measurement over time using Bayesian smoothing visually represented distinct COVID-19 "waves" described by case and hospitalization data in both initial (Ottawa) and external validation in 15 Ontario communities. The time-varying growth rate of viral measurement in wastewater samples approximated the growth rate observed for cases and hospitalization. One-week predicted viral measurement approximated the observed viral measurement throughout the assessment period from December 23, 2020, to August 8, 2022. An uncalibrated model showed underprediction during rapid increases in viral measurement (positive growth) and overprediction during rapid decreases. After recalibration, the model showed a close approximation between observed and predicted estimates. CONCLUSION: Bayesian smoothing of wastewater surveillance data of SARS-CoV-2 allows for accurate estimates of COVID-19 growth rates and one- and two-week forecasting of SARS-CoV-2 in wastewater for 16 municipalities in Ontario, Canada. Further assessment is warranted in other communities representing different sewersheds and environmental conditions.

Ensuring accountability for consideration of sex as a biological variable in research.

The National Institute of Health (NIH) policy, Consideration of Sex as a Biological Variable (SABV) in NIH-funded Research (2015), focuses on the expectation that researchers account for the influence of SABV in vertebrate animal and human studies and provide a strong justification for single-sex investigations. When SABV is considered in the research design, data analyses, and reporting, the rigor and reproducibility of the research are elevated and inform best practices and precision health for all people. Additional recommendations include the appropriate use of terminology, integration into curricula, intersection with social determinants of health, and application of sex and gender equity guidelines when disseminating research. This paper is a "call to action" for nurse researchers to lean into and apply this policy's principles and our recommendations, from the bench to the bedside, to advance the equity and health of all people.

Human plasma-like medium (HPLM) induces Cryptococcus neoformans in vivo cell morphologies.

The fungal pathogen Cryptococcus neoformans (C. neoformans) forms yeast cells of different sizes and morphological characteristics during infection. These features are usually not seen in standard laboratory in vitro conditions. Here, we describe in vivo cell morphologies when C. neoformans is grown in human plasma-like medium at 37°C, 5% CO2. We observed mixed-size populations of cells less than 1 µm up to 16.8 µm in cell diameter, increased capsule size, high chitin, and DNA content in larger cells. Our findings show that serum is not required for human plasma-like medium (HPLM)-induced C. neoformans cellular heterogeneity. Thus, this new method offers an opportunity to investigate factors of C. neoformans that mediate pathogenesis or host-pathogen interactions in a physiologically relevant setting.IMPORTANCEWe provide a description of new in vitro culture condition using the human plasma-like medium that supports the formation of the full range of in vivo cell morphologies of C. neoformans.

Preceptor Boot Camp: Basic Training for Novice Preceptors.

BACKGROUND: A clinical preceptor (CP) provides the vital link to apply didactic learning in clinical practice for nurse practitioner (NP) students. A nationwide shortage of CPs continues. The goal of this pilot project was to evaluate a model for developing preceptors from the school of nursing alumni that addressed modifiable academic barriers to precepting. METHOD: Six NP alumni from the school of nursing participated in a comprehensive novice CP training program based on Kolb's experiential learning theory and unparalleled faculty support through regularly scheduled contact. Pre- and posttests, site visits, and focus groups were used to assess the participants' progress. RESULTS: Participants' self-reported ability to teach and manage time when working with NP students improved, and 83.9% showed improved knowledge of precepting skills. CONCLUSION: Foundational skills and communication are essential elements to support novice CPs. This support may enhance both student and CP experience as well as increase retention of CPs. [J Contin Educ Nurs. 2024;55(6):283-288.].

Superior detection rate of plasma cell FISH using FACS-FISH.

OBJECTIVES: Fluorescence in situ hybridization (FISH) for plasma cell neoplasms (PCNs) requires plasma cell (PC) identification or purification strategies to optimize results. We compared the efficacy of cytoplasmic immunoglobulin FISH (cIg-FISH) and fluorescence-activated cell sorting FISH (FACS-FISH) in a clinical laboratory setting. METHODS: The FISH analysis results of 14,855 samples from individuals with a suspected PCN subjected to cytogenetic evaluation between 2019 and 2022 with cIg-FISH (n = 6917) or FACS-FISH (n = 7938) testing were analyzed. RESULTS: Fluorescence-activated cell sorting-FISH increased the detection rate of abnormalities in comparison with cIg-FISH, with abnormal results documented in 54% vs 50% of cases, respectively (P < .001). It improved the detection of IGH::CCND1 (P < .001), IGH::MAF (P < .001), IGH::MAFB (P < .001), other IGH rearrangements (P < .001), and gains/amplifications of 1q (P < .001), whereas the detection rates of IGH::FGFR3 fusions (P = .3), loss of 17p (P = .3), and other abnormalities, including hyperdiploidy (P = .5), were similar. Insufficient PC yield for FISH analysis was decreased between cIg-FISH and FACS-FISH (22% and 3% respectively, P < .001). Flow cytometry allowed establishment of ploidy status in 91% of cases. In addition, FACS-FISH decreased analysis times, workload efforts, and operating costs. CONCLUSIONS: Fluorescence-activated cell sorting-FISH is an efficient PC purification strategy that affords significant improvement in diagnostic yield and decreases workflow requirements in comparison with cIg-FISH.

Improved Performance of Air-Processed Perovskite Solar Cells via the Combination of Chlorine Precursors and Potassium Thiocyanate.

Due to their low cost and high efficiency, hybrid perovskite solar cells (PSCs) have shown the most outstanding competitiveness among third-generation photovoltaic (PV) devices. However, several challenges remain unresolved, among which the limited stability is arguably the main. Chlorine (Cl) has been widely employed to yield PV performances, but the Cl-doping mechanism and its role in mixed-halide PSCs are not entirely understood. Here, we investigate the effect of Cl-doping using different precursors such as formamidinium chloride (FACl), cesium chloride (CsCl), and lead chloride (PbCl2), which lead to the incorporation of Cl at different sites of the perovskite crystal. We demonstrate that the stability and efficiency of air-processed PSCs are strongly affected by Cl bonding into the cationic chloride precursor. Furthermore, adding potassium thiocyanate (KSCN) leads to the maximum efficiency of 18.1%, improving the operational stability with only 18% PCE loss after 520 h, stored under ambient conditions. Incorporating CsCl and KSCN presents an effective approach to further boost the performance and thermal stability of PSCs by tailoring the composition of the perovskite's composition. Finally, we used the slot-die method to demonstrate that our strategy is scalable for large-area devices that have shown similar performance. Our results show that fully air-processed and stable PSCs with high efficiency for large production and commercialization are achievable.

Detailed characterisation of invasive aspergillosis in a murine model of X-linked chronic granulomatous disease shows new insights in infections caused by Aspergillus fumigatus versus Aspergillus nidulans.

Introduction: Invasive aspergillosis (IA) is the most prevalent infectious complication in patients with chronic granulomatous disease (CGD). Yet, understanding of fungal pathogenesis in the CGD host remains limited, particularly with regards to A. nidulans infection. Methods: We have used a murine model of X-linked CGD to investigate how the pathogenesis of IA varies between A. fumigatus and A. nidulans, comparing infection in both X-linked CGD (gp91-/-) mice and their parent C57BL/6 (WT) mice. A 14-colour flow cytometry panel was used to assess the cell dynamics over the course of infection, with parallel assessment of pulmonary cytokine production and lung histology. Results: We observed a lack of association between pulmonary pathology and infection outcome in gp91-/- mice, with no significant mortality in A. nidulans infected mice. An overwhelming and persistent neutrophil recruitment and IL-1 release in gp91-/- mice following both A. fumigatus and A. nidulans infection was observed, with divergent macrophage, dendritic cell and eosinophil responses and distinct cytokine profiles between the two infections. Conclusion: We have provided an in-depth characterisation of the immune response to pulmonary aspergillosis in an X-linked CGD murine model. This provides the first description of distinct pulmonary inflammatory environments in A. fumigatus and A. nidulans infection in X-linked CGD and identifies several new avenues for further research.

Unmasking a fungal fire.

Immune checkpoint inhibitor (ICI) therapy represents a breakthrough cancer treatment by stimulating dysfunctional T cells in the tumour environment to kill cancer cells. Beyond effects on anticancer immunity, ICI therapy may be associated with increased susceptibility to or more rapid resolution of chronic infections, particularly those caused by human fungal pathogens. In this concise review, we summarise recent observations and findings that implicate immune checkpoint blockade in fungal infection outcomes.

Cell type-specific changes identified by single-cell transcriptomics in Alzheimer's disease.

The rapid advancement of single-cell transcriptomics in neurology has allowed for profiling of post-mortem human brain tissue across multiple diseases. Over the past 3 years, several studies have examined tissue from donors with and without diagnoses of Alzheimer's disease, highlighting key changes in cell type composition and molecular signatures associated with pathology and, in some cases, cognitive decline. Although all of these studies have generated single-cell/nucleus RNA-seq or ATAC-seq data from the full array of major cell classes in the brain, they have each focused on changes in specific cell types. Here, we synthesize the main findings from these studies and contextualize them in the overall space of large-scale omics studies of Alzheimer's disease. Finally, we touch upon new horizons in the field, in particular advancements in high-resolution spatial interrogation of tissue and multi-modal efforts-and how they are likely to further advance mechanistic and target-selection studies on Alzheimer's disease.

Impact of changes at the Candida albicans cell surface upon immunogenicity and colonisation in the gastrointestinal tract.

The immunogenicity of Candida albicans cells is influenced by changes in the exposure of microbe-associated molecular patterns (MAMPs) on the fungal cell surface. Previously, the degree of exposure on the C. albicans cell surface of the immunoinflammatory MAMP ß-(1,3)-glucan was shown to correlate inversely with colonisation levels in the gastrointestinal (GI) tract. This is important because life-threatening systemic candidiasis in critically ill patients often arises from translocation of C. albicans strains present in the patient's GI tract. Therefore, using a murine model, we have examined the impact of gut-related factors upon ß-glucan exposure and colonisation levels in the GI tract. The degree of ß-glucan exposure was examined by imaging flow cytometry of C. albicans cells taken directly from GI compartments, and compared with colonisation levels. Fungal ß-glucan exposure was lower in the cecum than the small intestine, and fungal burdens were correspondingly higher in the cecum. This inverse correlation did not hold for the large intestine. The gut fermentation acid, lactate, triggers ß-glucan masking in vitro, leading to attenuated anti-Candida immune responses. Additional fermentation acids are present in the GI tract, including acetate, propionate, and butyrate. We show that these acids also influence ß-glucan exposure on C. albicans cells in vitro and, like lactate, they influence ß-glucan exposure via Gpr1/Gpa2-mediated signalling. Significantly, C. albicans gpr1Δ gpa2Δ cells displayed elevated ß-glucan exposure in the large intestine and a corresponding decrease in fungal burden, consistent with the idea that Gpr1/Gpa2-mediated ß-glucan masking influences colonisation of this GI compartment. Finally, extracts from the murine gut and culture supernatants from the mannan grazing gut anaerobe Bacteroides thetaiotaomicron promote ß-glucan exposure at the C. albicans cell surface. Therefore, the local microbiota influences ß-glucan exposure levels directly (via mannan grazing) and indirectly (via fermentation acids), whilst ß-glucan masking appears to promote C. albicans colonisation of the murine large intestine.

Bayesian variable selection using Knockoffs with applications to genomics.

Given the costliness of HIV drug therapy research, it is important not only to maximize true positive rate (TPR) by identifying which genetic markers are related to drug resistance, but also to minimize false discovery rate (FDR) by reducing the number of incorrect markers unrelated to drug resistance. In this study, we propose a multiple testing procedure that unifies key concepts in computational statistics, namely Model-free Knockoffs, Bayesian variable selection, and the local false discovery rate. We develop an algorithm that utilizes the augmented data-Knockoff matrix and implement Bayesian Lasso. We then identify signals using test statistics based on Markov Chain Monte Carlo outputs and local false discovery rate. We test our proposed methods against non-bayesian methods such as Benjamini-Hochberg (BHq) and Lasso regression in terms TPR and FDR. Using numerical studies, we show the proposed method yields lower FDR compared to BHq and Lasso for certain cases, such as for low and equi-dimensional cases. We also discuss an application to an HIV-1 data set, which aims to be applied analyzing genetic markers linked to drug resistant HIV in the Philippines in future work.

Transforming Clinical Education During a Global Pandemic: Building New Approaches to Clinical Education.

ABSTRACT: The sudden and severe impact of COVID-19 on nursing education brought about many challenges and opportunities. The Community of Inquiry model and Online Collaborative Learning theory provided a guiding framework for preparing faculty to develop curriculum and deliver online/virtual synchronous clinical and laboratory experiences for junior and senior nursing students, overcome identified challenges, and evaluate the experiences. The swift change to virtual clinical education required careful reflection about how we teach, evaluate learning, and move forward with precision while establishing new best practices.

Implications of the COVID-19 pandemic: Virtual nursing education for delirium care.

BACKGROUND: Technology is increasingly used in nursing education, particularly during the SARS-CoV-2 (COVID-19) pandemic. COVID-19 also brought new challenges to patient care and limited access to in-person clinical experiences for nursing students. Pivoting to virtual simulation (VS) for clinical was necessary during the height of the pandemic. With students' return to clinical settings, VS experiences continue to be needed, due to quarantine of clinical settings and/or shortage of available clinical sites. VS clinical experiences have been successfully utilized over the past decade; however, the literature lacks resources on the use of VS for delirium care of patients. METHOD: In this article, the authors describe the creation and provision of a VS clinical day using interactive computer-based technology to educate nursing students to prevent, recognize, and manage delirium. The VS clinical was in conjunction with a Behavioral Health course. RESULTS: Evaluation of students demonstrated attainment of objectives. Students reported satisfaction with the VS experience. CONCLUSION: Technology in nursing education and use of VS clinical provide effective strategies for clinical learning when in-person clinical experiences are unavailable, either due to access limitations or lack of patients with specific health needs.

Vision Evaluation Tools for Adults With Acquired Brain Injury: A Scoping Review.

Background. Unrecognized visual deficits (VDs) following an acquired brain injury (ABI) may impact clients' rehabilitation. Little is known about evaluation tools used in vision rehabilitation. Purpose. To systematically explore the literature describing evaluation tools used for VD on adults with ABI. Method. Using a scoping review methodology, we searched in MEDLINE(Ovid), Embase, CINAHL, PsycINFO, and the grey literature from inception to 2020. Quantitative and thematic analyses were performed. Findings. Of the 83 studies reporting on 86 evaluation tools, 47% used multiple tools to assess VD. Tools were mostly used by occupational therapists and psychologists to evaluate intermediate, intermediate to high, and high-level visual skills. Clinicians tend to select specific tools that focus on different levels of the hierarchy of visual skills. Implications. Future research should investigate the optimal timeframe for assessment of VD and the psychometric properties of tools to ensure comprehensive VD evaluation.

Introducing the American Society for Bone and Mineral Research multistakeholder group secondary fracture prevention recommendations: Nurse practitioners play an important role.

ABSTRACT: Sequelae after an osteoporosis-related fracture include significant morbidity and mortality. Preventing repeat fractures is an important aspect of mitigating these sequelae. As highlighted in the American Society for Bone and Mineral Research multistakeholder coalition's Secondary Fracture Prevention: Consensus Clinical Recommendations, nurse practitioners play an important role in secondary fracture prevention. With a focus on education, longitudinal relationships with patients, and expertise in coordinating and managing care, nurse practitioners are uniquely qualified to run Fracture Liaison Services and help close the gap to care in secondary fracture prevention.

MelLec Exacerbates the Pathogenesis of Aspergillus fumigatus-Induced Allergic Inflammation in Mice.

Environmental factors, particularly fungi, influence the pathogenesis of allergic airway inflammation, but the mechanisms underlying these effects are still unclear. Melanin is one fungal component which is thought to modulate pulmonary inflammation. We recently identified a novel C-type lectin receptor, MelLec (Clec1a), which recognizes fungal 1,8-dihydroxynaphthalene (DHN)-melanin and is able to regulate inflammatory responses. Here we show that MelLec promotes pulmonary allergic inflammation and drives the development of Th17 T-cells in response to spores of Aspergillus fumigatus. Unexpectedly, we found that MelLec deficiency was protective, with MelLec-/- animals showing normal weight gain and significantly reduced pulmonary inflammation in our allergic model. The lungs of treated MelLec-/- mice displayed significantly reduced inflammatory foci and reduced bronchial wall thickening, which correlated with a reduced cellular influx (particularly neutrophils and inflammatory monocytes) and levels of inflammatory cytokines and chemokines. Notably, fungal burdens were increased in MelLec-/- animals, without apparent adverse effects, and there were no alterations in the survival of these mice. Characterization of the pulmonary T-cell populations, revealed a significant reduction in Th17 cells, and no alterations in Th2, Th1 or Treg cells. Thus, our data reveal that while MelLec is required to control pulmonary fungal burden, the inflammatory responses mediated by this receptor negatively impact the animal welfare in this allergic model.

The Rab32/BLOC-3-dependent pathway mediates host defense against different pathogens in human macrophages.

Macrophages provide a first line of defense against microorganisms, and while some mechanisms to kill pathogens such as the oxidative burst are well described, others are still undefined or unknown. Here, we report that the Rab32 guanosine triphosphatase and its guanine nucleotide exchange factor BLOC-3 (biogenesis of lysosome-related organelles complex-3) are central components of a trafficking pathway that controls both bacterial and fungal intracellular pathogens. This host-defense mechanism is active in both human and murine macrophages and is independent of well-known antimicrobial mechanisms such as the NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)-dependent oxidative burst, production of nitric oxide, and antimicrobial peptides. To survive in human macrophages, Salmonella Typhi actively counteracts the Rab32/BLOC-3 pathway through its Salmonella pathogenicity island-1-encoded type III secretion system. These findings demonstrate that the Rab32/BLOC-3 pathway is a novel and universal host-defense pathway and protects mammalian species from various pathogens.