Screening System Research Articles

Deciphering domain structures of Aspergillus and Streptomyces GH3-β-Glucosidases: a screening system for enzyme engineering and biotechnological applications

The glycoside hydrolase family 3 (GH3) β-glucosidases from filamentous fungi are crucial industrial enzymes facilitating the complete degradation of lignocellulose, by converting cello-oligosaccharides and cellobiose into glucose. Understanding the diverse domain organization is essential for elucidating their biological roles and potential biotechnological applications. This research delves into the variability of domain organization within GH3 β-glucosidases. Two distinct configurations were identified in fungal GH3 β-glucosidases, one comprising solely the GH3 catalytic domain, and another incorporating the GH3 domain with a C-terminal fibronectin type III (Fn3) domain. Notably, Streptomyces filamentous bacteria showcased a separate clade of GH3 proteins linking the GH3 domain to a carbohydrate binding module from family 2 (CBM2). As a first step to be able to explore the role of accessory domains in β-glucosidase activity, a screening system utilizing the well-characterised Aspergillus niger β-glucosidase gene (bglA) in bglA deletion mutant host was developed. Based on this screening system, reintroducing the native GH3-Fn3 gene successfully expressed the gene allowing detection of the protein using different enzymatic assays. Further investigation into the role of the accessory domains in GH3 family proteins, including those from Streptomyces, will be required to design improved chimeric β-glucosidases enzymes for industrial application.

Explainable artificial intelligence-driven prostate cancer screening using exosomal multi-marker based dual-gate FET biosensor

Prostate Imaging Reporting and Data System (PI-RADS) score, a reporting system of prostate MRI cases, has become a standard prostate cancer (PCa) screening method due to exceptional diagnosis performance. However, PI-RADS 3 lesions are an unmet medical need because PI-RADS provides diagnosis accuracy of only 30–40% at most, accompanied by a high false-positive rate. Here, we propose an explainable artificial intelligence (XAI) based PCa screening system integrating a highly sensitive dual-gate field-effect transistor (DGFET) based multi-marker biosensor for ambiguous lesions identification. This system produces interpretable results by analyzing sensing patterns of three urinary exosomal biomarkers, providing a possibility of an evidence-based prediction from clinicians. In our results, XAI-based PCa screening system showed a high accuracy with an AUC of 0.93 using 102 blinded samples with the non-invasive method. Remarkably, the PCa diagnosis accuracy of patients with PI-RADS 3 was more than twice that of conventional PI-RADS scoring. Our system also provided a reasonable explanation of its decision that TMEM256 biomarker is the leading factor for screening those with PI-RADS 3. Our study implies that XAI can facilitate informed decisions, guided by insights into the significance of visualized multi-biomarkers and clinical factors. The XAI-based sensor system can assist healthcare professionals in providing practical and evidence-based PCa diagnoses.

Screening Teachers Effectively Across Roles and Classrooms

A growing literature points to the conclusion that information collected while screening applicants has the potential to improve teacher hiring decisions. However, this work sheds little light on the extent to which the predictive validity of screening assessments varies across teacher types or teaching contexts. The author uses information on applicant teachers’ performance on prehire screening assessments in the Los Angeles Unified School District to see whether the relationship between performance on specific screening assessments and the outcomes of hired teachers varies across teacher types or student characteristics. The author finds little evidence that the predictive validity of screening instruments varies between elementary or single-subject teachers, or when teachers serve larger proportions of low-income students or English learners. However, the author finds suggestive evidence that screening instruments predict teachers’ outcomes somewhat differently in special education contexts. Taken as a whole, these results suggest teacher screening systems do not need to be highly differentiated to be useful or can be adapted relatively easily. This bolsters the case for using prehire screening to improve teacher quality and may also indicate the skills and attributes that define teacher quality are largely similar across roles and contexts.

The burden of chronic kidney disease in Asia region: a review of the evidence, current challenges, and future directions.

The disease burden of chronic kidney disease (CKD) and its impact on healthcare systems has been poorly studied in Asia, a socioeconomically diverse region with wide variations in availability, access, and quality of CKD care. The high CKD burden in this region is predominantly driven by an increased prevalence of risk factors including diabetes mellitus, hypertension, obesity, and use of traditional medicines and is further aggravated by challenges associated with effective implementation of population-based screening and surveillance systems in early detection and intervention of CKD. The Asian continent mostly comprised of low- and middle-income countries with resource restraints lacks robust population-based CKD registries resulting in a paucity of data on CKD incidence and prevalence, various treatment modalities, uptake of current guidelines, and the overall impact of implementation of developmental programs. There is an urgent need for a collaborative action plan between the healthcare community and governments in this region to detect CKD in its early stages and prevent its complications including kidney failure, cardiovascular disease, and death. Research-based evidence on the impact of early detection, sustainable treatment options, quality of life, delay or avoidance of dialysis, and related cost analysis is the need of the hour. We highlight successful implementation of strategic and policy-sharing programs adopted in a few countries; also, consolidate available region-specific data, quantify estimates of CKD burden and propose strategies with a multidisciplinary approach involving patients, the healthcare community and governmental bodies to combat CKD and its complications.

Tolerance of Triploid Hybrids of White Poplar ‘Beilinxiongzhu 1’ to Genetic Transformation Screening Agents In Vitro

Genetic transformation of forest trees is essential for validating gene functions and breeding new varieties through molecular means. Appropriate selective pressure is critical for creating an effective screening system. ‘Beilinxiongzhu 1’ sensitivity testing showed that the critical tolerance concentrations for hygromycin (Hyg), kanamycin (Kan), and glyphosate (PPT) in leaf explants were 2.0 mg/L, 20 mg/L, and 1.0 mg/L, respectively. Among the physiological indicators, soluble sugar content, soluble protein content, and endogenous hormone levels were identified as key markers of the effects of the different antibiotic treatments. Transcriptome analysis showed that Hyg treatment resulted in a large number of differentially expressed genes (DEGs) involved in leaf cell wall synthesis and glucose metabolism. Under Kan treatment, the DEGs were associated with pathways such as ribosome biosynthesis and histone packaging in eukaryotes. Under PPT treatment, significant DEGs were related to ABC transporters. DEGs common to all three antibiotics were involved in glutathione metabolism pathways. A weighted gene co-expression network analysis identified TRXH2, H3.2, H2B, GST, U71K1, and CHS as key genes in response to antibiotic stress. By elucidating the physiological and molecular mechanisms by which different antibiotics affect leaf sprouting, our study serves as a reference for research into the genetic transformation of poplar leaves.

Artificial Intelligence-Based Screening System for Diabetic Retinopathy in Primary Care.

This study aimed to test an artificial intelligence-based reading system (AIRS) capable of reading retinographies of type 2 diabetic (T2DM) patients and a predictive algorithm (DRPA) that predicts the risk of each patient with T2DM of developing diabetic retinopathy (DR). We tested the ability of the AIRS to read and classify 15,297 retinal photographs from our database of diabetics and 1200 retinal images taken with Messidor-2 into the different DR categories. We tested the DRPA in a sample of 40,129 T2DM patients. The results obtained by the AIRS and the DRPA were then compared with those provided by four retina specialists regarding sensitivity (S), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), accuracy (ACC), and area under the curve (AUC). The results of testing the AIRS for identifying referral DR (RDR) in our database were ACC = 98.6, S = 96.7, SP = 99.8, PPV = 99.0, NPV = 98.0, and AUC = 0.958, and in Messidor-2 were ACC = 96.78%, S = 94.64%, SP = 99.14%, PPV = 90.54%, NPV = 99.53%, and AUC = 0.918. The results of our DRPA when predicting the presence of any type of DR were ACC = 0.97, S = 0.89, SP = 0.98, PPV = 0.79, NPV = 0.98, and AUC = 0.92. The AIRS performed well when reading and classifying the retinographies of T2DM patients with RDR. The DRPA performed well in predicting the absence of DR based on some clinical variables.

Novel and effective screening system for recombinant protein production in CHO cells

At present, biopharmaceuticals have received extensive attention from the society, among which recombinant proteins have a good growth trend and a large market share. Chinese hamster ovary (CHO) cells are the preferred mammalian system to produce glycosylated recombinant protein drugs. A highly efficient and stable cell screening method needs to be developed to obtain more and useful recombinant proteins. Limited dilution method, cell sorting, and semi-solid medium screening are currently the commonly used cell cloning methods. These methods are time-consuming and labor-intensive, and they have the disadvantage of low clone survival rate. Here, a method based on semi-solid medium was developed to screen out high-yielding and stable cell line within 3 weeks to improve the screening efficiency. The semi-solid medium was combined with an expression vector containing red fluorescent protein (RFP) for early cell line development. In accordance with the fluorescence intensity of RFP, the expression of upstream target gene could be indicated, and the fluorescence intensity was in direct proportion to the expression of upstream target gene. In conclusion, semi-solid medium combined with bicistronic expression vector provides an efficient method for screening stable and highly expressed cell lines.

Implementation of Artificial Intelligence-Based Diabetic Retinopathy Screening in a Tertiary Care Hospital in Quebec: Prospective Validation Study.

Diabetic retinopathy (DR) affects about 25% of people with diabetes in Canada. Early detection of DR is essential for preventing vision loss. We evaluated the real-world performance of an artificial intelligence (AI) system that analyzes fundus images for DR screening in a Quebec tertiary care center. We prospectively recruited adult patients with diabetes at the Centre hospitalier de l'Université de Montréal (CHUM) in Montreal, Quebec, Canada. Patients underwent dual-pathway screening: first by the Computer Assisted Retinal Analysis (CARA) AI system (index test), then by standard ophthalmological examination (reference standard). We measured the AI system's sensitivity and specificity for detecting referable disease at the patient level, along with its performance for detecting any retinopathy and diabetic macular edema (DME) at the eye level, and potential cost savings. This study included 115 patients. CARA demonstrated a sensitivity of 87.5% (95% CI 71.9-95.0) and specificity of 66.2% (95% CI 54.3-76.3) for detecting referable disease at the patient level. For any retinopathy detection at the eye level, CARA showed 88.2% sensitivity (95% CI 76.6-94.5) and 71.4% specificity (95% CI 63.7-78.1). For DME detection, CARA had 100% sensitivity (95% CI 64.6-100) and 81.9% specificity (95% CI 75.6-86.8). Potential yearly savings from implementing CARA at the CHUM were estimated at CAD $245,635 (US $177,643.23, as of July 26, 2024) considering 5000 patients with diabetes. Our study indicates that integrating a semiautomated AI system for DR screening demonstrates high sensitivity for detecting referable disease in a real-world setting. This system has the potential to improve screening efficiency and reduce costs at the CHUM, but more work is needed to validate it.

Comparison of Inter-Rater and Intra-Rater Reliability of Raters with Different Levels of Experience When Using Landing Error Scoring System (LESS) in Field-Based Screening of Professional Football Players.

It is essential for physical sports therapists to use reliable field-based tests to identify potential injury risk factors in athletes. The purpose of this study was to compare the inter- and intra-rater reliability of experienced and novice raters during use of the Landing Error Scoring System (LESS) in a field-based examination of professional football athletes. Thirty-seven male football athletes underwent pre-season LESS assessment. Two raters independently evaluated the recorded landing techniques at two separate intervals, two months apart, following the LESS standard protocol. Inter-and intra-rater values were calculated for the LESS total scores and individual scoring items. The overall LESS scores had excellent intra-rater reliability values for both the experienced (interclass correlation coefficient (ICC) = 0.95, 95% CI, 0.89-0.97; p < 0.001) and novice rater (ICC = 0.95, 95% CI, 0.90-0.97; p < 0.001), and very good to excellent inter-rater values for the first (ICC = 0.90, 95% CI, 0.77-0.95; p < 0.001) and second (ICC = 0.86, 95% CI, 0.71-0.93; p < 0.001) evaluation. Most of the individual scoring items ranged from moderate to perfect agreement. In conclusion, sports physical therapists, regardless of experience, can reliably use the LESS's total score, through video analysis of the regime. Individual scoring items can inform clinicians about impairments in the landing mechanism but data should be interpreted cautiously.

Separation and utilization of iron, cerium, and other rare earth elements from rare earth waste by chlorination

Due to the lack of effective screening systems in the rare earth waste recycling industry, the composition of rare earth elements in rare earth waste is complex and difficult to separate. In response to such problems, by studying the reaction behavior between various elements in rare earth waste and cobalt chloride, we propose a process path for the separation and recovery of iron, cerium and other rare earth elements using cobalt chloride roasting. The experiments on simulated wastes show that the leaching rates of the Nd, Sm, Gd, Pr can reach 98.31%, 94.5%, 93.87% and 72.05% under the optimal process conditions, respectively. Ce and iron remain in the leaching residue in the form of CeO2 and CoFe2O4, respectively. And through a simple magnetic separation process, CeO2 and CoFe2O4 can be enriched in non-magnetic leaching residue and magnetic leaching residue, respectively. The cerium content in the leaching residue composed of cobalt ferrite is only 1.95%. Therefore, this method is beneficial to the separation and high-value utilization of iron, cerium, and other rare earth elements in the waste system. The research results can provide theoretical reference for the low-cost and high-value recovery of rare earth secondary resources.

The Impact of the COVID-19 Pandemic on Tele-ophthalmology-Based Retinal Screening.

This study reports our experiences with systematic retinal screening in Denmark through optometrists with access to tele-ophthalmological services before, during, and after the COVID-19 pandemic. We evaluated an optometrist-based retinal screening system with a referral option for tele-ophthalmological service by a consultant ophthalmologist within the time period of August1, 2018 to September30, 2023. The optometrist collected patient history, refraction, best-corrected visual acuity, intraocular pressure, basic slit-lamp examination, 4-in-1 visual field report, and retinal imaging using color fundus 45° photography. Tele-ophthalmological services were provided by consultant ophthalmologists. Within pre-defined periods of pre-COVID-19, COVID-19, and post-COVID-19, we evaluated the rate of referrals to the tele-ophthalmological service, diagnoses made, and referrals to the public healthcare system. A total of 1,142,028 unique individuals, which corresponded to 19.1% of the entire population of Denmark, underwent screening by the optometrists; 50,612 (4.4%) of these individuals were referred to the tele-ophthalmological examination by consultant ophthalmologists. A referral for further ophthalmic examination, either at hospital or at an ophthalmic practice, was made for 10,300 individuals (20.4% of those referred for tele-ophthalmology, corresponding to 0.9% of the population screened). The referral rate from the screening to the tele-ophthalmological service increased from before COVID-19 (3.4%) to during COVID-19 (4.3%) and further after COVID-19 (6.4%). This increase coincided with an increasing prevalence of conditions seen in the tele-ophthalmological service. During a period of 5years, 19.1% of the entire population of Denmark underwent retinal screening. This provided an adjunctive health service during a period of severe strain on the public healthcare system, while limiting the number of excessive referrals to the public healthcare system. Temporal trends illustrated an increased pattern of use of a large-scale tele-ophthalmological system.

In Situ Raman Hyperspectral Analysis of Microbial Colonies for Secondary Metabolites Screening.

Since the discovery of penicillin, a vast array of microbial antibiotics has been identified and applied in the medical field. Globally, the search for drug candidates via microbial screening is ongoing. Traditional screening methods, however, are time-consuming and require labor-intensive sample processing, significantly reducing throughput. This research introduces a Raman spectroscopy-based screening system tailored to the in situ analysis of microbial colonies on solid culture media. Employing multivariate curve resolution-alternating least-squares (MCR-ALS) for spectral decomposition, our approach reveals the production of secondary metabolites at the single colony level. We enhanced the microbial culture method, enabling direct, high signal-to-noise (S/N) ratio Raman spectroscopic measurements of colonies of Escherichia coli and actinomycetes species. Through semisupervised MCR analysis using the known spectra of actinorhodin and undecylprodigiosin as references, we accurately assessed the production of these compounds by Streptomyces coelicolor A3(2). Furthermore, we herein successfully detected the production of amphotericin B by Streptomyces nodosus, even in the absence of prior spectral information. This demonstrates the potential of our technique in the discovery of secondary metabolites. In addition to enabling the detection of the above-mentioned compounds, this analysis revealed the heterogeneity of the spatial distribution of their production in each colony. Our technique makes a significant contribution to the advancement of microbial screening, offering a rapid, efficient alternative to conventional methods and opening avenues for secondary metabolites discovery.

Health economic evaluation of an artificial intelligence (AI)-based rapid nutritional diagnostic system for hospitalised patients: A multicentre, randomised controlled trial

Background & aimsMalnutrition is prevalent among hospitalised patients, and increases the morbidity, mortality, and medical costs; yet nutritional assessments on admission are not routine. This study assessed the clinical and economic benefits of using an artificial intelligence (AI)-based rapid nutritional diagnostic system for routine nutritional screening of hospitalised patients. MethodsA nationwide multicentre randomised controlled trial was conducted at 11 centres in 10 provinces. Hospitalised patients were randomised to either receive an assessment using an AI-based rapid nutritional diagnostic system as part of routine care (experimental group), or not (control group). The overall medical resource costs were calculated for each participant and a decision-tree was generated based on an intention-to-treat analysis to analyse the cost-effectiveness of various treatment modalities. Subgroup analyses were performed according to clinical characteristics and a probabilistic sensitivity analysis was performed to evaluate the influence of parameter variations on the incremental cost-effectiveness ratio (ICER). ResultsIn total, 5763 patients participated in the study, 2830 in the experimental arm and 2933 in the control arm. The experimental arm had a significantly higher cure rate than the control arm (23.24% versus 20.18%; p = 0.005). The experimental arm incurred an incremental cost of 276.52 CNY, leading to an additional 3.06 cures, yielding an ICER of 90.37 CNY. Sensitivity analysis revealed that the decision-tree model was relatively stable. ConclusionThe integration of the AI-based rapid nutritional diagnostic system into routine inpatient care substantially enhanced the cure rate among hospitalised patients and was cost-effective. RegistrationNCT04776070 (https://clinicaltrials.gov/study/NCT04776070)

ITPK1 Sensitizes Tumor Cells to IgA-dependent Neutrophil Killing InVivo.

Neutrophils can efficiently trigger cytotoxicity toward tumor cells and other target cells upon engagement of the IgA receptor CD89. However, the cell-intrinsic factors that influence the induction of cell death upon exposure to neutrophil effector mechanisms invivo remain largely unknown. To uncover genetic regulators that influence target cell sensitivity to IgA-induced neutrophil-mediated killing, we used a human CD89 (hCD89) transgenic mouse model in which IgA-mediated killing of Her2-positive CD47-deficient murine target cells is mediated by neutrophils. Using a genome-wide invivo screening approach, we demonstrate that deletion of the gene encoding inositol-tetrakisphosphate 1 kinase (ITPK1) increases survival of target cells in anti-Her2 IgA-treated mice. Moreover, we show that this effect depends on neutrophil activity and on the ITPK1 kinase domain. Notably, ITPK1 deficiency did not measurably impact survival of IgA-opsonized target cells in invitro systems, underscoring the importance of invivo screening systems to uncover physiologically relevant regulators of neutrophil killing.

A chemical approach to extend flower longevity of Japanese morning glory via inhibition of master senescence regulator EPHEMERAL1.

Petal senescence in flowering plants is a type of programmed cell death with highly regulated onset and progression. A NAM/ATAF1,2/CUC2 transcription factor, EPHEMERAL1 (EPH1), has been identified as a key regulator of petal senescence in Japanese morning glory (Ipomoea nil). Here we used a novel chemical approach to delay petal senescence in Japanese morning glory by inhibiting the DNA-binding activity of EPH1. A cell-free high-throughput screening system and subsequent bioassays found two tetrafluorophthalimide-based compounds, Everlastin1 and Everlastin2, that inhibited the EPH1-DNA interaction and delayed petal senescence. The inhibitory mechanism was due to the suppression of EPH1 dimerization. RNA-sequencing analysis revealed that the chemical treatment strongly suppressed the expression of programmed cell death- and autophagy-related genes. These results suggest that a chemical approach targeting a transcription factor can regulate petal senescence.

Development of an in vitro compound screening system that replicate the in vivo spine phenotype of idiopathic ASD model mice.

Autism Spectrum Disorder (ASD) is a developmental condition characterized by core symptoms including social difficulties, repetitive behaviors, and sensory abnormalities. Aberrant morphology of dendritic spines within the cortex has been documented in genetic disorders associated with ASD and ASD-like traits. We hypothesized that compounds that ameliorate abnormalities in spine dynamics might have the potential to ameliorate core symptoms of ASD. Because the morphology of the spine is influenced by signal inputs from other neurons and various molecular interactions, conventional single-molecule targeted drug discovery methods may not suffice in identifying compounds capable of ameliorating spine morphology abnormalities. In this study, we focused on spine phenotypes in the cortex using BTBR T + Itpr3 tf /J (BTBR) mice, which have been used as a model for idiopathic ASD in various studies. We established an in vitro compound screening system using primary cultured neurons from BTBR mice to faithfully represent the spine phenotype. The compound library mainly comprised substances with known target molecules and established safety profiles, including those approved or validated through human safety studies. Following screening of this specialized library containing 181 compounds, we identified 15 confirmed hit compounds. The molecular targets of these hit compounds were largely focused on the 5-hydroxytryptamine receptor (5-HTR). Furthermore, both 5-HT1AR agonist and 5-HT3R antagonist were common functional profiles in hit compounds. Vortioxetine, possessing dual attributes as a 5-HT1AR agonist and 5-HT3R antagonist, was administered to BTBR mice once daily for a period of 7days. This intervention not only ameliorated their spine phenotype but also alleviated their social behavior abnormality. These results of vortioxetine supports the usefulness of a spine phenotype-based assay system as a potent drug discovery platform targeting ASD core symptoms.

Identification and Characterization of Novel Small-Molecule Enhancers of the CUL3LZTR1 E3 Ligase KRAS Complex.

The RAS family of GTPases is among the most frequently mutated proteins in human cancer, creating a high clinical demand for therapies that counteract their signaling activity. An important layer of regulation that could be therapeutically exploited is the proteostatic regulation of the main RAS GTPases KRAS, NRAS, and HRAS, as well as the closely related members, MRAS and RIT1, by the leucine zipper-like transcriptional regulator 1 cullin 3 RING E3 ubiquitin ligase complex (CUL3LZTR1). Genetic inactivation of LZTR1, as observed in different cancer entities and Noonan syndrome leads to enhanced RAS GTPase abundance and altered MAPK pathway activation state. Novel therapeutic approaches to interfere with hyperactive RAS signaling, thereby complementing existing treatments, are highly sought after. Motivated by the growing arsenal of molecular glue degraders, we report the identification of novel chemical fragments that enhance the protein-protein interaction (PPI) of the KRAS-LZTR1 complex. We established a split-luciferase-based reporter assay that monitors the RAS GTPase-LZTR1 interaction in a scalable format, capable of capturing chemical, as well as mutational perturbations. Using this screening system, in combination with a small fragment library, we identified two fragments, C53 and Z86, that enhance the interaction of the KRAS-LZTR1 complex in a dose-dependent manner. Further orthogonal validation experiments using proximity biotinylation (BioID), thermal shift assays, and NMR spectroscopy demonstrated fragment-dependent enhanced recruitment of endogenous LZTR1 and physical engagement of KRAS. The two fragments, which potentiate the KRAS-LZTR1 interaction, serve as starting points for fragment-based drug discovery. Additionally, the assay we introduced is amenable to high-throughput screening to further explore the pharmacological modulation of the CUL3LZTR1-RAS GTPase complex.

Efficiency of a technology-assisted nutritional screening system: A retrospective analysis of 11,722 admissions in a tertiary hospital

Background and AimNutritional screening is essential for addressing malnutrition and its consequences. However, routine implementation in large hospitals faces several challenges. To overcome these obstacles, the Clinical Nutrition Service of a tertiary hospital developed a technology-assisted nutritional screening system. This study evaluates the system's efficiency in detecting and assessing patients at nutritional risk upon hospital admission. It also examines the association between nutritional risk, clinical outcomes, and sociodemographic characteristics. MethodsThis retrospective, analytical, observational study examined 11,722 hospital admissions of adult patients in 2019, each with a minimum hospital stay of 48 hours in a tertiary hospital. Rates and timing for the detection, referral, and assessment of patients at nutritional risk were calculated. Participants were divided into low (Malnutrition Screening Tool [MST] < 2 points) and moderate/high (MST ≥ 2) nutritional risk groups to evaluate the relationship between nutritional risk and clinical and demographic variables. ResultsWe found that 91% of patients underwent nutritional screening within the first hours of admission, with a median time of 9 hours from admission to screening (interquartile range [IQR] 3-19). The prevalence of nutritional risk (MST ≥ 2) was 21%. All patients identified as being at nutritional risk were immediately referred for a nutritional assessment once identified, with a median referral time of 0 hours (IQR 0-0). This assessment was carried out by a nutritionist for 98% of these patients, with a median time of 19 hours from referral to assessment (IQR 6-24). Compared to the low-risk group, patients with nutritional risk were older, had higher rates of mortality and admission to the intensive care unit (ICU), longer hospital stays, and a higher proportion of men and cancer diagnoses (p=0.00 for all comparisons). After adjusting for age and sex, nutritional risk was significantly associated with a higher probability of ICU admission (Odds Ratio [OR] 1.13; 95% CI 1.02-1.24) and in-hospital mortality (OR 2.32; 95% CI 1.97-2.73). ConclusionThe integration of technology into nutritional screening was highly efficient for early detection and assessment of at-risk patients upon hospital admission. Features of this system could guide other hospitals. The association found between nutritional risk and clinical outcomes emphasizes the importance of prompt and appropriate nutritional interventions.

Enzyme-Mediated Duplex Exponential Amplification: A New Platform for Rapid Screening of &amp;lt;i&amp;gt;Hylurgus ligniperda&amp;lt;/i&amp;gt;

As the world&amp;apos;s second largest timber importer, wood demand in China has been growing extremely rapidly, leading to an increase of 163% from 2009 to 2018. The plant quarantine pest &amp;lt;i&amp;gt;H. ligniperda Fabricius, 1787&amp;lt;/i&amp;gt; is an invasive species frequently intercepted at ports. &amp;lt;i&amp;gt;H. ligniperda&amp;lt;/i&amp;gt; causes damage mainly to pine and spruce. To improve the efficiency of on-site inspection and the efficacy of early detection, tight quarantine in ports, time-effective identification, and a national surveillance program for high-risk invasive bark beetles are in urgent need. In this study, a simple, fast and accurate classification method for &amp;lt;i&amp;gt;H. ligniperda &amp;lt;/i&amp;gt;is established based on the enzyme-mediated duplex exponential amplification (EmDEA) technique. Partial region from &amp;lt;i&amp;gt;inhibitor of apoptosis 2&amp;lt;/i&amp;gt; (&amp;lt;I&amp;gt;IAP2)&amp;lt;/I&amp;gt; gene was selected as the target and 6 primer/probe combinations were designed. Through selection, the combination of 3-HY-F3, 3-HY-R2 and 3-HY-RNA5 was chosen as the final primer-probe set, as it showed the lowest Ct with highest final fluorescence signal. Method validation and specificity test using 6 other beetle species living on coniferous wood showed that this method is result reliable and specific. Through parameter analysis with positive plasmid, the detection limit was calculated to be 13.6 copies/μL (9×10&amp;lt;sup&amp;gt;-7&amp;lt;/sup&amp;gt; ng DNA/ reaction), much higher than conventional molecular methods such as PCR. The whole process including isothermal amplification, data analysis, and result output can be finished in 30 min, which is highly time-effective. Besides, the operation is simple and little training is needed for non-professionals. The application prospects of this rapid screening system include customs screening in ports, wild survey in non-lab situations and early warning system development. The new analysis platform EmDEA, can also be implemented in rapid detection and identification of other forestry pests.

Factors influencing fidelity to guideline implementation strategies for improving pain care at cancer centres: a qualitative sub-study of the Stop Cancer PAIN Trial

BackgroundThe Stop Cancer PAIN Trial was a phase III pragmatic stepped wedge cluster randomised controlled trial which compared effectiveness of screening and guidelines with or without implementation strategies for improving pain in adults with cancer attending six Australian outpatient comprehensive cancer centres (n = 688). A system for pain screening was introduced before observation of a ‘control’ phase. Implementation strategies introduced in the ‘intervention’ phase included: (1) audit of adherence to guideline recommendations, with feedback to clinical teams; (2) health professional education via an email-administered ‘spaced education’ module; and (3) a patient education booklet and self-management resource. Selection of strategies was informed by the Capability, Opportunity and Motivation Behaviour (COM-B) Model (Michie et al., 2011) and evidence for each strategy’s stand-alone effectiveness. A consultant physician at each centre supported the intervention as a ‘clinical champion’. However, fidelity to the intervention was limited, and the Trial did not demonstrate effectiveness. This paper reports a sub-study of the Trial which aimed to identify factors inhibiting or enabling fidelity to inform future guideline implementation initiatives.MethodsThe qualitative sub-study enabled in-depth exploration of factors from the perspectives of personnel at each centre. Clinical champions, clinicians and clinic receptionists were invited to participate in semi-structured interviews. Analysis used a framework method and a largely deductive approach based on the COM-B Model.ResultsTwenty-four people participated, including 15 physicians, 8 nurses and 1 clinic receptionist. Coding against the COM-B Model identified ‘capability’ to be the most influential component, with ‘opportunity’ and ‘motivation’ playing largely subsidiary roles. Findings suggest that fidelity could have been improved by: considering the readiness for change of each clinical setting; better articulating the intervention’s value proposition; defining clinician roles and responsibilities, addressing perceptions that pain care falls beyond oncology clinicians’ scopes of practice; integrating the intervention within existing systems and processes; promoting patient-clinician partnerships; investing in clinical champions among senior nursing and junior medical personnel, supported by medical leaders; and planning for slow incremental change rather than rapid uptake.ConclusionsFuture guideline implementation interventions may require a ‘meta-implementation’ approach based on complex systems theory to successfully integrate multiple strategies.Trial registrationRegistry: Australian New Zealand Clinical Trials Registry; number: ACTRN 12615000064505; data: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspxid=367236&isReview=true.