Effects of Academic Detailing, Panel Management and Mailed Multi-Target Stool-DNA Testing on Colorectal Cancer Screening.

INTRODUCTION: Academic detailing, patient-panel management, and mailed, stool-based testing have each been utilized to increase colorectal cancer (CRC) screening in rural clinics. The effectiveness of combining these interventions to increase CRC screening during COVID-19 restrictions was unclear. METHODS: We explored the effects of a multi-component intervention including academic detailing, active patient panel management, and mailed MT-sDNA testing on colorectal cancer screening in our rural family medicine clinic. Baseline interventions included EMR-based provider alerts and mailed patient reminders. Our intervention (March-May 2020) and follow-up periods (June-August 2020) coincided with the initial COVID-19 surge, giving us the opportunity to observe the effects of our intervention during COVID-19 restrictions. RESULTS: A total of 407 patients were eligible and overdue for colorectal cancer screening. Our clinic's CRC screening rate increased significantly after intervention (69.7%) as compared with before (64.3%) (P = <0.01; 95%CI = 5.39-5.4). Our clinic's CRC screening rates increased significantly during the initial 3 months of the COVID-19 surge (67.8%) compared with the same period the prior year. (62.3%) (P = .003; 95%CI = 3.4-7.6). Our CRC screening rates increased after intervention (69.7%) compared with our regional health system (67%) (P = <0.01; 95%CI = 2.6-2.77). Our weekly stool-based CRC screening increased (94% increase) compared with other health systems nationally (61 to 83% decrease). DISCUSSION: A multi-component intervention, including academic detailing, panel management, and mailed MT-sDNA testing, can lead to significant increases in CRC screening in a rural family medicine clinic, empowering providers to maintain an effective CRC screening outreach during COVID-19 related restrictions.

Quantifying GFAP immunohistochemistry in the brain - Introduction of the Reactivity score (R-score) and how it compares to other methodologies.

BACKGROUND: Immunohistochemical upregulation of glial fibrillary acidic protein (GFAP) is commonly used to detect astrogliosis in tissue sections and includes measurement of intensity and/or distribution of staining. There remains a lack of standard objective measures when diagnosing astrogliosis and its severity. NEW METHOD: Aim was to test a novel semi-quantitative assessment of GFAP which we term reactivity (R)-score, on its reproducibility and sensitivity to measure astrogliosis. The R-score, which is based on the proportion of astrocytes seen at each level of reactivity, was compared to 3 other commonly employed quantification methods in research: (1) thresholding, (2) point-counting, and (3) qualitative grading. Sub-regions of the hippocampus, medulla, and cerebellum were studied in piglet, and 4 human cases with clinically reported astrogliosis. Intra-assay coefficient of variation (CV) and percentage agreement cut-offs of ≤ 20% and ≥ 75% were used respectively to compare amongst the methods, with outcome measures being reproducibility across serial and non-serial sections, resilience to changes in experimental conditions, and inter- and intra-rater concordance. RESULTS: Averaged across 3 brain regions, the intra-assay coefficient of variation (CV) was 5% for R-score, with inter and intra-rater kappa scores being 0.99 and 0.95 respectively. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: Based on CV values, the R-score was superior to thresholding (CV of 51%) and point-counting (CV of 16%), with the qualitative grade being found to be on par (percentage agreement 95%). Given the ease, reproducibility and selectivity of the R-score, we propose its validity in future research purposes and clinical application.

f-Block reactions of metal cations with carbon dioxide studied by inductively coupled plasma tandem mass spectrometry.

f-Block chemistry offers an opportunity to test current knowledge of chemical reactivity. The energy dependence of lanthanide cation (Ln+ = Ce+, Pr+, Nd+-Eu+) and actinide cation (An+ = Th+, U+-Am+) oxidation reactions by CO2, was observed by inductively coupled plasma tandem mass spectrometry. This reaction is commonly spin-unallowed because the neutral reactant (CO2, 1Σ+g) and product (CO, 1Σ+) require the metal and metal oxide cations to have the same spin state. Correlation of the promotion energy (Ep) to the first state with two free d-electrons with the reaction efficiency indicates that spin conservation is not a primary factor in the reaction rate. The Ep likely influences the reaction rate by partially setting the crossing between the ground and reactive states. Comparison of Ln+ and An+ congener reactivity indicates that the 5f-orbitals play a small role in the An+ reactions.

Geographical origin identification of mandarin fruits by analyzing fingerprint signatures based on multielemental composition.

Given rising traders and consumers concerns, the global food industry is increasingly demanding authentic and traceable products. Consequently, there is a heightened focus on verifying geographical authenticity as food quality assurance. In this work, we assessed pattern recognition approaches based on elemental predictors to discern the provenance of mandarin juices from three distinct citrus-producing zones located in the Northeast region of Argentina. A total of 202 samples originating from two cultivars were prepared through microwave-assisted acid digestion and analyzed by microwave plasma atomic emission spectroscopy (MP-AES). Later, we applied linear discriminant analysis (LDA), k-nearest neighbor (k-NN), support vector machine (SVM), and random forest (RF) to the element data obtained. SVM accomplished the best classification performance with a 95.1% success rate, for which it was selected for citrus samples authentication. The proposed method highlights the capability of mineral profiles in accurately identifying the genuine origin of mandarin juices. By implementing this model in the food supply chain, it can prevent mislabeling fraud, thereby contributing to consumer protection.

Fatal Human Neurologic Infection Caused by Pigeon Avian Paramyxovirus-1, Australia.

Avian paramyxovirus type 1 (APMV-1) is a virus of birds that results in a range of outcomes, from asymptomatic infections to outbreaks of systemic respiratory and neurologic disease, depending on the virus strain and the avian species affected. Humans are rarely affected; those who are predominantly experience mild conjunctivitis. We report a fatal case of neurologic disease in a 2-year-old immunocompromised child in Australia. Metagenomic sequencing and histopathology identified the causative agent as the pigeon variant of APMV-1. This diagnosis should be considered in neurologic conditions of undefined etiologies. Agnostic metagenomic sequencing methods are useful in such settings to direct diagnostic and therapeutic efforts.

Bokashi fermentation of brewery's spent grains positively affects larval performance of the black soldier fly Hermetia illucens while reducing gaseous nitrogen losses.

Digestion of waste feedstocks by larvae of the black soldier fly Hermetia illucens (Diptera: Stratiomyidae) (BSF) results in proteins for animal feed and organic fertilizer with a reduced environmental footprint, but it can still have negative environmental effects through greenhouse gas (GHG) and ammonia (NH3) emissions. Both biomass conversion by BSF larvae and associated GHG and NH3 emissions can depend on substrate properties that may be optimized through microbial inoculation pre-treatments, such as bokashi fermentation. Here, we quantified the effects of bokashi fermentation of brewery's spent grains on BSF rearing metrics and associated GHG and NH3 emissions at benchtop scale. We found that bokashi fermentation increased larval biomass by 40% and shortened development time by over two days on average, compared with unfermented spent grains. In line with increased larval growth, CO2 emissions in BSF larvae treatments were 31.0 and 79.0% higher in the bokashi fermented spent grains and Gainesville substrates, respectively, compared to the unfermented spent grains. Adding BSF larvae to the spent grains increased cumulative N2O emissions up to 64.0 mg N2O kg substratedry-1 but there were essentially no N2O emissions when larvae were added to fermented spent grains. Bokashi fermentation also reduced NH3 fluxes from the volatilization of substrate nitrogen in the BSF larvae treatment by 83.7-85.8% during days 7 and 9, possibly by increasing N assimilation by larvae or by reducing the transformation of substrate NH4+ to NH3. Therefore, bokashi fermentation may be applied to improve performance of BSF larvae on a common industrial waste stream and reduce associated emissions.

On the path to predicting immune responses in the lung: Modeling the pulmonary innate immune system at the air-liquid interface (ALI).

Chronic respiratory diseases and infections are among the largest contributors to death globally, many of which still have no cure, including chronic obstructive pulmonary disorder, idiopathic pulmonary fibrosis, and respiratory syncytial virus among others. Pulmonary therapeutics afford untapped potential for treating lung infection and disease through direct delivery to the site of action. However, the ability to innovate new therapeutic paradigms for respiratory diseases will rely on modeling the human lung microenvironment and including key cellular interactions that drive disease. One key feature of the lung microenvironment is the air-liquid interface (ALI). ALI interface modeling techniques, using cell-culture inserts, organoids, microfluidics, and precision lung slices (PCLS), are rapidly developing; however, one major component of these models is lacking-innate immune cell populations. Macrophages, neutrophils, and dendritic cells, among others, represent key lung cell populations, acting as the first responders during lung infection or injury. Innate immune cells respond to and modulate stromal cells and bridge the gap between the innate and adaptive immune system, controlling the bodies response to foreign pathogens and debris. In this article, we review the current state of ALI culture systems with a focus on innate immune cells and suggest ways to build on current models to add complexity and relevant immune cell populations.

Measuring trace element fingerprinting for cereal bar authentication based on type and principal ingredient.

This paper introduces a method for determining the authenticity of commercial cereal bars based on trace element fingerprints. In this regard, 120 cereal bars were prepared using microwave-assisted acid digestion and the concentrations of Al, Ba, Bi, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Rb, Se, Sn, Sr, V, and Zn were later measured by ICP-MS. Results confirmed the suitability of the analyzed samples for human consumption. Multielemental data underwent autoscaling preprocessing for then applying PCA, CART, and LDA to input data set. LDA model accomplished the highest classification modeling performance with a success rate of 92%, making it the suitable model for reliable cereal bar prediction. The proposed method demonstrates the potential of trace element fingerprints in distinguishing cereal bar samples according to their type (conventional and gluten-free) and principal ingredient (fruit, yogurt, chocolate), thereby contributing to global efforts for food authentication.

CDKN2A/B Homozygous Deletions in Astrocytomas: A Literature Review.

Genomic alterations of CDKN2A and CDKN2B in astrocytomas have been an evolving area of study for decades. Most recently, there has been considerable interest in the effect of CDKN2A and/or CDKN2B (CDKN2A/B) homozygous deletions (HD) on the prognosis of isocitrate dehydrogenase (IDH)-mutant astrocytomas. This is highlighted by the adoption of CDKN2A/B HD as an essential criterion for astrocytoma and IDH-mutant central nervous system (CNS) WHO grade 4 in the fifth edition of the World Health Organisation (WHO) Classification of Central Nervous System Tumours (2021). The CDKN2A and CDKN2B genes are located on the short arm of chromosome 9. CDKN2A encodes for two proteins, p14 and p16, and CDKN2B encodes for p15. These proteins regulate cell growth and angiogenesis. Interpreting the impact of CDKN2A/B alterations on astrocytoma prognosis is complicated by recent changes in tumour classification and a lack of uniform standards for testing CDKN2A/B. While the prognostic impact of CDKN2A/B HD is established, the role of different CDKN2A/B alterations-heterozygous deletions (HeD), point mutations, and promoter methylation-is less clear. Consequently, how these alternations should be incorporated into patient management remains controversial. To this end, we reviewed the literature on different CDKN2A/B alterations in IDH-mutant astrocytomas and their impact on diagnosis and management. We also provided a historical review of the changing impact of CDKN2A/B alterations as glioma classification has evolved over time. Through this historical context, we demonstrate that CDKN2A/B HD is an important negative prognostic marker in IDH-mutant astrocytomas; however, the historical data is challenging to interpret given changes in tumour classification over time, variation in the quality of evidence, and variations in the techniques used to identify CDKN2A/B deletions. Therefore, future prospective studies using uniform classification and detection techniques are required to improve the clinical interpretation of this molecular marker.

Implementation of DNA Methylation Array Profiling in Pediatric Central Nervous System Tumors: The AIM BRAIN Project: An Australian and New Zealand Children's Haematology/Oncology Group Study.

DNA methylation array profiling for classifying pediatric central nervous system (CNS) tumors is a valuable adjunct to histopathology. However, unbiased prospective and interlaboratory validation studies have been lacking. The AIM BRAIN diagnostic trial involving 11 pediatric cancer centers in Australia and New Zealand was designed to test the feasibility of routine clinical testing and ran in parallel with the Molecular Neuropathology 2.0 (MNP2.0) study at Deutsches Krebsforschungszentrum (German Cancer Research Center). CNS tumors from 269 pediatric patients were prospectively tested on Illumina EPIC arrays, including 104 cases co-enrolled on MNP2.0. Using MNP classifier versions 11b4 and 12.5, we report classifications with a probability score ≥0.90 in 176 of 265 (66.4%) and 213 of 269 (79.2%) cases, respectively. Significant diagnostic information was obtained in 130 of 176 (74%) for 11b4, and 12 of 174 (7%) classifications were discordant with histopathology. Cases prospectively co-enrolled on MNP2.0 gave concordant classifications (99%) and score thresholds (93%), demonstrating excellent test reproducibility and sensitivity. Overall, DNA methylation profiling is a robust single workflow technique with an acceptable diagnostic yield that is considerably enhanced by the extensive subgroup and copy number profile information generated by the platform. The platform has excellent test reproducibility and sensitivity and contributes significantly to CNS tumor diagnosis.

RNAi screening for modulators of an osmo-sensitive gene response to extracellular matrix damage reveals negative feedback and interactions with translation inhibition.

In epidermal tissues, extracellular matrices (ECMs) function as barriers between the organism and environment. Despite being at the interface with the environment, little is known about the role of animal barrier ECMs in sensing stress and communicating with cytoprotective gene pathways in neighboring cells. We and others have identified a putative damage sensor in the C. elegans cuticle that regulates osmotic, detoxification, and innate immune response genes. This pathway is associated with circumferential collagen bands called annular furrows; mutation or loss of furrow collagens causes constitutive activation of osmotic, detoxification, and innate immune response genes. Here, we performed a genome-wide RNAi screen for modulators of osmotic stress response gene gpdh-1 in a furrow collagen mutant strain. RNAi of six genes identified in this screen were tested under other conditions and for effects on other stress responses. The functions of these genes suggest negative feedback within osmolyte accumulation pathways and interactions with ATP homeostasis and protein synthesis. Loss of these gpdh-1 modulators had distinct effects on canonical detoxification and innate immune response genes.

Enhancing Visible Light Photocatalytic Degradation of Bisphenol A Using BiOI/Bi2MoO6 Heterostructures.

With the growing population, access to clean water is one of the 21st-century world's challenges. For this reason, different strategies to reduce pollutants in water using renewable energy sources should be exploited. Photocatalysts with extended visible light harvesting are an interesting route to degrade harmful molecules utilized in plastics, as is the case of Bisphenol A (BPA). This work uses a microwave-assisted route for the synthesis of two photocatalysts (BiOI and Bi2MoO6). Then, BiOI/Bi2MoO6 heterostructures of varied ratios were produced using the same synthetic routes. The BiOI/Bi2MoO6 with a flower-like shape exhibited high photocatalytic activity for BPA degradation compared to the individual BiOI and Bi2MoO6. The high photocatalytic activity was attributed to the matching electronic band structures and the interfacial contact between BiOI and Bi2MoO6, which could enhance the separation of photo-generated charges. Electrochemical, optical, structural, and chemical characterization demonstrated that it forms a BiOI/Bi2MoO6 p-n heterojunction. The free radical scavenging studies showed that superoxide radicals (O2•-) and holes (h+) were the main reactive species, while hydroxyl radical (•OH) generation was negligible during the photocatalytic degradation of BPA. The results can potentiate the application of the microwave synthesis of photocatalytic materials.

Aerosol pulmonary immune engineering.

Aerosolization of immunotherapies poses incredible potential for manipulating the local mucosal-specific microenvironment, engaging specialized pulmonary cellular defenders, and accessing mucosal associated lymphoid tissue to redirect systemic adaptive and memory responses. In this review, we breakdown key inhalable immunoengineering strategies for chronic, genetic, and infection-based inflammatory pulmonary disorders, encompassing the historic use of immunomodulatory agents, the transition to biological inspired or derived treatments, and novel approaches of complexing these materials into drug delivery vehicles for enhanced release outcomes. Alongside a brief description of key immune targets, fundamentals of aerosol drug delivery, and preclinical pulmonary models for immune response, we survey recent advances of inhaled immunotherapy platforms, ranging from small molecules and biologics to particulates and cell therapies, as well as prophylactic vaccines. In each section, we address the formulation design constraints for aerosol delivery as well as advantages for each platform in driving desirable immune modifications. Finally, prospects of clinical translation and outlook for inhaled immune engineering are discussed.

Immigrants' Enforcement Experiences and Concern about Accessing Public Benefits or Services.

Although exclusionary immigration policies are associated with fear of deportation and avoidance of public benefits, relationships between immigration enforcement policy and public charge policies are largely unknown. Using a California population-based survey of 1103 Asian and Latinx immigrants in 2018, we tested the relationship between immigrants' experiences with law enforcement and their concern about public charge. Direct encounters with various forms of law enforcement, including being asked to show proof of citizenship by law enforcement, staying inside to avoid police or immigration officials, and having known someone who had been deported, were associated with immigrants' avoidance of public benefits due to public charge concerns. Latinx immigrants were more likely to be concerns about public charge than Asians. Intersections among immigration policies deserve further consideration. There is a need to provide accurate and reliable information to immigrant communities about public benefits and advocate for inclusive immigration policies.

New Detection of Locally Acquired Japanese Encephalitis Virus Using Clinical Metagenomics, New South Wales, Australia.

In the context of an emerging Japanese encephalitis outbreak within Australia, we describe a novel locally acquired case in New South Wales. A man in his 70s had rapidly progressive, fatal meningoencephalitis, diagnosed as caused by Japanese encephalitis virus by RNA-based metagenomic next-generation sequencing performed on postmortem brain tissue.

Rice Labeling according to Grain Quality Features Using Laser-Induced Breakdown Spectroscopy.

Rice is an important source of nutrition and energy consumed around the world. Thus, quality inspection is crucial for protecting consumers and increasing the rice's value in the productive chain. Currently, methods for rice labeling depending on grain quality features are based on image and/or visual inspection. These methods have shown subjectivity and inefficiency for large-scale analyses. Laser-induced breakdown spectroscopy (LIBS) is an analytical technique showing attractive features due to how quick the analysis can be carried out and its capability of providing spectra that are true fingerprints of the sample's elemental composition. In this work, LIBS performance was evaluated for labeling rice according to grain quality features. The LIBS spectra of samples with their grain quality numerically described as Type 1, 2, and 3 were measured. Several spectral processing methods were evaluated when modeling a k-nearest neighbors (k-NN) classifier. Variable selection was also carried out by principal component analysis (PCA), and then the optimal k-value was selected. The best result was obtained by applying spectrum smoothing followed by normalization by using the first fifteen principal components (PCs) as input variables and k = 9. Under these conditions, the method showed excellent performance, achieving sample classification with 94% overall prediction accuracy. The sensitivities ranged from 90 to 100%, and specificities were in the range of 92-100%. The proposed method has remarkable characteristics, e.g., analytical speed and analysis guided by chemical responses; therefore, the method is not susceptible to subjectivity errors.

Artificial Intelligence-Assisted Classification of Gliomas Using Whole Slide Images.

CONTEXT.­: Glioma is the most common primary brain tumor in adults. The diagnosis and grading of different pathological subtypes of glioma is essential in treatment planning and prognosis. OBJECTIVE.­: To propose a deep learning-based approach for the automated classification of glioma histopathology images. Two classification methods, the ensemble method based on 2 binary classifiers and the multiclass method using a single multiclass classifier, were implemented to classify glioma images into astrocytoma, oligodendroglioma, and glioblastoma, according to the 5th edition of the World Health Organization classification of central nervous system tumors, published in 2021. DESIGN.­: We tested 2 different deep neural network architectures (VGG19 and ResNet50) and extensively validated the proposed approach based on The Cancer Genome Atlas data set (n = 700). We also studied the effects of stain normalization and data augmentation on the glioma classification task. RESULTS.­: With the binary classifiers, our model could distinguish astrocytoma and oligodendroglioma (combined) from glioblastoma with an accuracy of 0.917 (area under the curve [AUC] = 0.976) and astrocytoma from oligodendroglioma (accuracy = 0.821, AUC = 0.865). The multiclass method (accuracy = 0.861, AUC = 0.961) outperformed the ensemble method (accuracy = 0.847, AUC = 0.933) with the best performance displayed by the ResNet50 architecture. CONCLUSIONS.­: With the high performance of our model (>80%), the proposed method can assist pathologists and physicians to support examination and differential diagnosis of glioma histopathology images, with the aim to expedite personalized medical care.

Exploring the potential of paper-based analytical sensors for tea geographical origin authentication.

Tea (Camellia sinensis (L.) Kuntze-surname of German origin) is a popular beverage consumed worldwide due to its health benefits. Its quality depends on measuring features that may discriminate teas from distinct provenances. Protected designation of origin (PDO) is therefore a very useful label for tea quality evaluation. In the present work, antioxidant activity profiles obtained from microfluidic paper-based analytical devices (µPADs) were analyzed by chemometrics to determine the tea geographic origin. Based on the existing literature, we constructed a database containing chemical data from 26 samples and evaluated it by principal component analysis (PCA) coupled to linear discriminant analysis (LDA). Antioxidant activity was an effective LDA predictor for sample discrimination accomplishing accuracies from 75 to 82%. Modeling performance was favored by an external validation method. The best classification model was found using the first nine PCs as input variables. Training samples achieved a perfect success rate, while the test ones were predicted with 83% specificity, 100% sensitivity, and 90% overall accuracy. The modeling robustness was verified by integrating AUC (0.943) from ROC curve. The PCA-LDA approach taken here demonstrated that the teas coming from different countries can be correctly authenticated through µPADs, thus contributing to certificate samples PDO. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05440-1.

Synthesis of ß,ß-Disubstituted Styrenes via Trimethylsilyl Trifluoromethanesulfonate-Promoted Aldehyde-Aldehyde Aldol Coupling-Elimination.

In the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and 2,6-lutidine, α,α-disubstituted aldehydes condense with electron-rich aromatic aldehydes to yield ß,ß-disubstituted styrenes. More electron-rich aromatic aldehydes react more rapidly and in higher yield. Preliminary results suggest that the reaction may proceed via the ionization and formal deformylation of an aldol intermediate.

Sexual dimorphism in Caenorhabditis elegans stress resistance.

Physiological responses to the environment, disease, and aging vary by sex in many animals, but mechanisms of dimorphism have only recently begun to receive careful attention. The genetic model nematode Caenorhabditis elegans has well-defined mechanisms of stress response, aging, and sexual differentiation. C. elegans has males, but the vast majority of research only uses hermaphrodites. We found that males of the standard N2 laboratory strain were more resistant to hyperosmolarity, heat, and a natural pro-oxidant than hermaphrodites when in mixed-sex groups. Resistance to heat and pro-oxidant were also male-biased in three genetically and geographically diverse C. elegans strains consistent with a species-wide dimorphism that is not specific to domestication. N2 males were also more resistant to heat and pro-oxidant when keep individually indicating that differences in resistance do not require interactions between worms. We found that males induce canonical stress response genes by similar degrees and in similar tissues as hermaphrodites suggesting the importance of other mechanisms. We find that resistance to heat and pro-oxidant are influenced by the sex differentiation transcription factor TRA-1 suggesting that downstream organ differentiation pathways establish differences in stress resistance. Environmental stress influences survival in natural environments, degenerative disease, and aging. Understanding mechanisms of stress response dimorphism can therefore provide insights into sex-specific population dynamics, disease, and longevity.