Deoxybouvardin targets EGFR, MET, and AKT signaling to suppress non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) remains a significant challenge, as it is one of the leading causes of cancer-related deaths, and the development of resistance to anticancer therapy makes it difficult to treat. In this study, we investigated the anticancer mechanism of deoxybouvardin (DB), a cyclic hexapeptide, in gefitinib (GEF)-sensitive and -resistant NSCLC HCC827 cells. DB inhibited the viability and growth of HCC827 cells in a concentration- and time-dependent manner. In vitro kinase assay showed DB inhibited epidermal growth factor receptor (EGFR), mesenchymal-epithelial transition (MET), and AKT, and their phosphorylation was suppressed in HCC827 cells treated with DB. A molecular docking model suggested that DB interacts with these kinases in the ATP-binding pockets. DB induces ROS generation and cell cycle arrest. DB treatment of HCC827 cells leads to mitochondrial membrane depolarization. The induction of apoptosis through caspase activation was confirmed by Z-VAD-FMK treatment. Taken together, DB inhibited the growth of both GEF-sensitive and GEF-resistant NSCLC cells by targeting EGFR, MET, and AKT and inducing ROS generation and caspase activation. Further studies on DB can improve the treatment of chemotherapy-resistant NSCLC through the development of effective DB-based anticancer agents.

Genomic epidemiology and longitudinal sampling of ward wastewater environments and patients reveals complexity of the transmission dynamics of bla KPC-carbapenemase-producing Enterobacterales in a hospital setting.

Background: Healthcare-associated wastewater and asymptomatic patient reservoirs colonized by carbapenemase-producing Enterobacterales (CPE) contribute to nosocomial CPE dissemination, but the characteristics and dynamics of this remain unclear. Methods: We systematically sampled wastewater sites (n = 4488 samples; 349 sites) and patients (n = 1247) across six wards over 6-12 months to understand blaKPC-associated CPE (KPC-E) diversity within these reservoirs and transmission in a healthcare setting. Up to five KPC-E-positive isolates per sample were sequenced (Illumina). Recombination-adjusted phylogenies were used to define genetically related strains; assembly and mapping-based approaches were used to characterize antimicrobial resistance genes, insertion sequences (ISs) and Tn4401 types/target site sequences. The accessory genome was evaluated in some of the largest clusters, and those crossing reservoirs. Results: Wastewater site KPC-E-positivity was substantial [101/349 sites (28.9%); 228/5601 (4.1%) patients cultured]. Thirteen KPC-E species and 109 strains were identified using genomics, and 24% of wastewater and 26% of patient KPC-E-positive samples harboured one or more strains. Most diversity was explained by the individual niche, suggesting localized factors are important in selection and spread. Tn4401 + flanking target site sequence diversity was greater in wastewater sites (P < 0.001), which might favour Tn4401-associated transposition/evolution. Shower/bath- and sluice/mop-associated sites were more likely to be KPC-E-positive (adjusted OR = 2.69; 95% CI: 1.44-5.01; P = 0.0019; and adjusted OR = 2.60; 95% CI: 1.04-6.52; P = 0.0410, respectively). Different strains had different blaKPC dissemination dynamics. Conclusions: We identified substantial and diverse KPC-E colonization of wastewater sites and patients in this hospital setting. Reservoir and niche-specific factors (e.g. microbial interactions, selection pressures), and different strains and mobile genetic elements likely affect transmission dynamics. This should be considered in surveillance and control strategies.

Status and barriers to circular bio-based building material adoption in developed economies: The case of Flanders, Belgium.

Circular bio-based building materials (CBBMs) provide a potential solution to reduce the climate impacts of buildings and offer opportunities to transition the construction industry to a circular model. Promoting the use of these materials can also bring economic, environmental, and social benefits from valorising biowaste and by-products from other sectors. Despite their potential, CBBMs have not received sufficient attention globally, and their adoption is hindered by various barriers. However, it is unclear what the CBBMs' use status is, what adoption barriers exist, how these barriers interact, and what should be done to address them. This study addresses these knowledge gaps through a systematic study using mixed methods to investigate the adoption status and barriers to these materials in developed economies by using a specific case analysis in Flanders. The data analysis results show that hemp-based, cork-based, and straw-based materials are the most used, while the market for CBBMs is very limited in the region. Twenty-three potential adoption barriers were identified and selected from the existing literature, then ranked based on their mean scores. The t-test analysis helps to identify 13 critical barriers, which are grouped into five categories, including cost and risk-related barriers, technical and cultural-related barriers, the government's role-related barriers, information and quality-related barriers, and market-related barriers. Among them, cost and risk-related barriers, including "concern about the high initial cost", "risks and uncertainties involved in adopting new materials", and "perception of the extra cost being incurred", are the three most critical barriers to CBBM adoption in Flanders. Kendall's W test shows good consensus among the two expert groups-with and without hands-on experience in utilising CBBMs-in their rankings of the barriers. Meanwhile, the Mann-Whitney U test indicates no statistically significant differences in the ranks of barriers between the two expert groups. The interview results confirm almost all survey results and provide deeper insights into the status and barriers to adopting these materials. Practical and policy implications are discussed based on these findings to inform policy deliberations on promoting CBBMs. This study may also be a good reference for scholars and industry practitioners to better understand issues impacting decision-making towards the adoption of CBBMs in the construction industry.

Chemoreactive 2,5-Diketopiperazines from a Penicillium sp., Structure Revision of Reported Analogues and Proposed Facile Transformation Pathways.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (1) and E2 (2), were isolated from a Penicillium fungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of 1 and 2 were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey's reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable 1 and 2 underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2 in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7 and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2 to 7 and 8 was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.

Development and Validation of UPLC-MS/MS Analysis for Sphingolipids Isolated from Velvet Antlers of Cervus elaphus.

Deer velvet antlers, known as tonics, have created a large market as dietary supplements and have been consumed worldwide. Despite the high consumption of velvet antlers as dietary supplements, analytical methods for their identification and standardization remain limited. Quantitative analysis for gangliosides, considered quality indexes for velvet antlers, was developed to indirectly analyze the sialic acid obtained from chemical degradation. Owing to the complex and time-consuming chemical derivatization of gangliosides, a simple and rapid quality evaluation method for velvet antlers must be developed. For the first time, this study reports the isolation and structural elucidation of two new sphingomyelins (1 and 2), two known sphingomyelins (3 and 4), and four ceramides (5-8) as chemical markers from the velvet antlers of Cervus elaphus. To expedite and simplify the quality control of velvet antlers, advanced quantitative analysis of sphingolipids has been developed using ultra-performance liquid chromatography-mass spectroscopy.

Sustainability assessment methods for circular bio-based building materials: A literature review.

Using circular bio-based building materials is considered a promising solution to reduce the environmental impacts of the construction industry. To identify the pros and cons of these materials, it is essential to investigate their sustainability performance. However, the previous sustainability assessment studies are heterogeneous regarding the assessment methods and objectives, highlighting the need for a review to identify and analyse these aspects. Moreover, there is still a lack of studies reviewing the methodological issues and implications of the assessment methods, as well as the current end-of-life scenarios and circularity options for these materials. To address these gaps, this study conducts a systematic and critical review of a sample of 97 articles. The results indicate that Life Cycle Assessment (LCA) is the most frequently applied method, yet most studies are cradle-to-gate analyses of materials. Otherwise, very few studies consider the end-of-life phase, and most of the end-of-life scenarios analysed are unsustainable and have low circularity levels. The analysis also highlights the methodological issues of the assessment methods used, with a particular focus on LCA, such as a lack of consensus on system boundaries, functional units, and databases for facilitating sustainability assessments associated with the use of circular bio-based building materials. Two primary recommendations emerge from the analysis. Firstly, for LCA studies, it is recommended to increase transparency and harmonisation in assessments to improve the comparability of results. Besides, to overcome data availability issues, it is recommended to use data from multiple sources and conduct sensitivity and uncertainty analyses. Secondly, more sustainability assessments (including the three pillars) considering the whole life cycle with more sustainable end-of-life scenarios and circularity options for these materials should be conducted.

Desilification of phytolith exacerbates the release of arsenic from rice straw.

Arsenic (As) turnover in rice paddy agro-ecosystems has received much attention because As can enter the food chain through its accumulation in rice, thereby affecting human health. Returning straw to soil is a common practice to retain nutrients for soil and crops, but it also cycles As within the rice paddy field ecosystems. However, there is still a lack of detailed understanding of the fate of As in rice straw, and how or to what extent it is recycled back into the soil environment. This study aims to elucidate the relationship between the microstructure of rice straw and the release of As during rice straw decomposition. The microstructure of rice straw was found to comprise both organic and silica (phytolith) components. These two constituents are inter-embedded to form a composite-like structure that contains up to 6.48 mg As Kg-1. The 30-day batch experiments revealed that the biochemical release of As simultaneously depends upon the decomposition of the organic component and the desilicification of the silica component. Accompanying the release of As was the release of other elements such as Fe, Al, P and S. These elements can further interact with As to form less mobile compounds. The introduction of either Trichoderma harzianum or Bacillus velezensis was expected to accelerate the decomposition of rice straw, and enhance the silica dissolution, hence contributing to an increase in the As release. Despite these expectations, our observations showed the opposite effects. Microorganisms presumably have facilitated the change in solution chemistry or the inclusion of As into the newly-formed precipitates. The biochemical decomposition process can reduce straw particle size, while the negatively-charge surface will involve microsized straw particles in the electrostatic interaction, thereby favoring the dispersibility state. Therefore, the co-transport of micro-sized straw particles with As under field conditions should not be neglected.

Development and validation of the Baseline Recurrence Risk in Cellulitis (BRRISC) score.

OBJECTIVES: Cellulitis is often treated with antibiotics for longer than recommended by guidelines. Prolonged therapy may reduce recurrence in certain patients, but it is not known which patients are at greatest risk. Our objective was to develop and temporally validate a risk prediction score to identify patients attending hospital with cellulitis at highest risk of recurrence. METHODS: We included UK adult patients with cellulitis attending hospital in an electronic health records (EHR) study to identify demographic, comorbid, physiological, and laboratory factors predicting recurrence (before death) within 90 days, using multivariable logistic regression with backwards elimination in complete cases. A points-based risk score integerised model coefficients for selected predictors. Performance was assessed using the C-index in development and temporal validation samples. RESULTS: The final model included 4938 patients treated for median 8 days (IQR 6-11); 8.8% (n = 436) experienced hospitalisation-associated recurrence. A risk score using eight variables (age, heart rate, urea, platelets, albumin, previous cellulitis, venous insufficiency, and liver disease) ranged from 0-15, with C-index = 0.65 (95%CI: 0.63-0.68). Categorising as low (score 0-1), medium (2-5) and high (6-15) risk, recurrence increased fourfold; 3.2% (95%CI: 2.3-4.4%), 9.7% (8.7-10.8%), and 16.6% (13.3-20.4%). Performance was maintained in the validation sample (C-index = 0.63 (95%CI: 0.58-0.67)). Among patients at high risk, four distinct clinical phenotypes were identified using hierarchical clustering 1) young, acutely unwell with liver disease; 2) comorbid with previous cellulitis and venous insufficiency; 3) chronic renal disease with severe renal impairment; and 4) acute severe illness, with substantial inflammatory responses. CONCLUSIONS: Risk of cellulitis recurrence varies markedly according to individual patient factors captured in the Baseline Recurrence Risk in Cellulitis (BRRISC) score. Further work is needed to optimise the score, considering baseline and treatment response variables not captured in EHR data, and establish the utility of risk-based approaches to guide optimal antibiotic duration.

Earthworms can mobilize soil arsenic through their casts.

The mobilization of arsenic (As) in paddy soil has received much attention because it might accelerate the transfer of As from soil to rice. This study aims to elucidate whether earthworms can mobilize As through their casts. Cast samples were collected from 23 different paddy fields in the Red River delta. We first analysed different forms of As through fractionation and then performed batch experiments under reducing conditions to identify factors that govern the mobility of As in casts. Because the dissociation of casts may induce colloids that carry As, the colloidal properties of cast suspensions were also examined. The median value of As in casts (obtained from aqua regia digestion) was 5.11 mg kg-1, which was lower than that in the surrounding soil (6.7 mg kg-1). Compared with the surrounding soil, casts contain less As, possibly because cast As is more labile and more easily lost due to leaching. Various processes, including the reductive dissolution of Fe oxides, decomposition of organic matter, and sorption competition of soluble anionic substances, such as P, Si and DOC, were found to strongly correlate with the release of As from casts. We propose that earthworms, via their casts, may accelerate the As cycle in paddy soils, potentially intensifying As exposure to human health. The dissociation of cast could release colloids containing As; therefore, the cotransport of As with cast-induced colloids should also be considered in future works.

Penicillin Binding Protein Substitutions Cooccur with Fluoroquinolone Resistance in Epidemic Lineages of Multidrug-Resistant Clostridioides difficile.

Clostridioides difficile remains a key cause of healthcare-associated infection, with multidrug-resistant (MDR) lineages causing high-mortality (≥20%) outbreaks. Cephalosporin treatment is a long-established risk factor, and antimicrobial stewardship is a key control. A mechanism underlying raised cephalosporin MICs has not been identified in C. difficile, but among other species, this is often acquired via amino acid substitutions in cell wall transpeptidases (penicillin binding proteins [PBPs]). Here, we investigated five C. difficile transpeptidases (PBP1 to PBP5) for recent substitutions, associated cephalosporin MICs, and co-occurrence with fluoroquinolone resistance. Previously published genome assemblies (n = 7,096) were obtained, representing 16 geographically widespread lineages, including healthcare-associated ST1(027). Recent amino acid substitutions were found within PBP1 (n = 50) and PBP3 (n = 48), ranging from 1 to 10 substitutions per genome. ß-Lactam MICs were measured for closely related pairs of wild-type and PBP-substituted isolates separated by 20 to 273 single nucleotide polymorphisms (SNPs). Recombination-corrected phylogenies were constructed to date substitution acquisition. Key substitutions such as PBP3 V497L and PBP1 T674I/N/V emerged independently across multiple lineages. They were associated with extremely high cephalosporin MICs; 1 to 4 doubling dilutions >wild-type, up to 1,506 µg/mL. Substitution patterns varied by lineage and clade, showed geographic structure, and occurred post-1990, coincident with the gyrA and/or gyrB substitutions conferring fluoroquinolone resistance. In conclusion, recent PBP1 and PBP3 substitutions are associated with raised cephalosporin MICs in C. difficile. Their co-occurrence with fluoroquinolone resistance hinders attempts to understand the relative importance of these drugs in the dissemination of epidemic lineages. Further controlled studies of cephalosporin and fluoroquinolone stewardship are needed to determine their relative effectiveness in outbreak control. IMPORTANCE Fluoroquinolone and cephalosporin use in healthcare settings has triggered outbreaks of high-mortality, multidrug-resistant C. difficile infection. Here, we identify a mechanism associated with raised cephalosporin MICs in C. difficile comprising amino acid substitutions in two cell wall transpeptidase enzymes (penicillin binding proteins). The higher the number of substitutions, the greater the impact on phenotype. Dated phylogenies revealed that substitutions associated with raised cephalosporin and fluoroquinolone MICs were co-acquired immediately before clinically important outbreak strains emerged. PBP substitutions were geographically structured within genetic lineages, suggesting adaptation to local antimicrobial prescribing. Antimicrobial stewardship of cephalosporins and fluoroquinolones is an effective means of C. difficile outbreak control. Genetic changes associated with raised MIC may impart a "fitness cost" after antibiotic withdrawal. Our study therefore identifies a mechanism that may explain the contribution of cephalosporin stewardship to resolving outbreak conditions. However, due to the co-occurrence of raised cephalosporin MICs and fluoroquinolone resistance, further work is needed to determine the relative importance of each.

Longitudinal Median Nerve Ultrasound Changes in Individuals With Spinal Cord Injury and an Age- and Sex-Matched Nondisabled Cohort.

Objectives: To assess the natural history for development of carpal tunnel syndrome (CTS) in persons with acute spinal cord injury (SCI) at 1 year postdischarge from initial rehabilitation and to assess baseline median nerve (MN) cross-sectional area (CSA) above/below 10 mm2 correlates with any longitudinal changes in quantitative ultrasound (US) of the MN. Design: A prospective cohort study of persons with acute SCI evaluated for CTS using quantitative US and compared to a group without SCI (non-SCI). Setting: Academic medical center. Participants: N=69 total (N=34 SCI, N=35 non-SCI). The average age in both groups was 28 and the SCI group included 30 males and 2 females and the non-SCI group included 30 males and 3 females. Interventions: Not applicable. Main Outcome Measures: The primary outcome was the change in quantitative US parameters of the MN, including CSA and grayscale, from baseline to 1-year follow-up in those with SCI and those without SCI. CTS symptomatology and physical exam sum score and US measures for dominant and nondominant arms were considered secondary outcomes. Results: The SCI had darker nerves at baseline (P=.036, nondominant), greater CTS symptoms at follow-up (P≤.036, bilateral), and no differences in all change scores (all P≥.056). Individuals with smaller nerves at baseline had larger increases in nerve size (P=.029, nondominant) vs those with larger nerves. Change in CTS symptoms CSA (nondominant) and nerve echogenicity (dominant) were inversely associated with their respective baseline values (all P≤.045). Conclusions: We observed few differences between the SCI group and the non-SCI control group and between those with smaller vs larger MN. In general, MN pathology changes (CTS symptoms and US variables) over 1 year were more common in the nondominant arm and appear to be a function of MN pathology at enrollment. Individuals with SCI may experience increased CTS symptoms as soon as 1 year after injury.

Photochemical Dimerization of Plakinidine B Leads to Potent Inhibition of the E3 Ubiquitin-Protein Ligase CBL-B.

A new dimeric alkaloid plakoramine A [(±)-1] was identified from a marine sponge Plakortis sp. Chiral-phase HPLC separation of (±)-1 led to the purified enantiomers (+)-1 and (-)-1 which both potently inhibited CBL-B E3 ubiquitin ligase activities. The absolute configurations of the enantiomers were determined by quantum chemical calculations. Scrutinization of the purification conditions revealed a previously undescribed, nonenzymatic route to form (±)-1 via photochemical conversion of its naturally occurring monomeric counterpart, plakinidine B (2).

Creating Computer Vision Models for Respiratory Status Detection.

This study aims to use computers to detect and recognize ventilation objects (masks and tubes) and their positions on the patient's face. We created two models: the You Only Look Once (YOLO) and the Transfer Learning (TL) models, to perform this computer vision task. The development processes and comparison of performance will be described in this paper. The TL model had a better performance (93%) compared to the YOLO model (93%). Clinical Relevance- Healthcare providers and researchers interested in the field of computer vision applied in medicine, specifically automatic object detection using video streams or real-time video streaming may benefit from findings reported.

Genome-wide fetalization of enhancer architecture in heart disease.

Heart disease is associated with re-expression of key transcription factors normally active only during prenatal development of the heart. However, the impact of this reactivation on the regulatory landscape in heart disease is unclear. Here, we use RNA-seq and ChIP-seq targeting a histone modification associated with active transcriptional enhancers to generate genome-wide enhancer maps from left ventricle tissue from up to 26 healthy controls, 18 individuals with idiopathic dilated cardiomyopathy (DCM), and five fetal hearts. Healthy individuals have a highly reproducible epigenomic landscape, consisting of more than 33,000 predicted heart enhancers. In contrast, we observe reproducible disease-associated changes in activity at 6,850 predicted heart enhancers. Combined analysis of adult and fetal samples reveals that the heart disease epigenome and transcriptome both acquire fetal-like characteristics, with 3,400 individual enhancers sharing fetal regulatory properties. We also provide a comprehensive data resource (http://heart.lbl.gov) for the mechanistic exploration of DCM etiology.

The effectiveness of Paraffin oil and Mineral oil for day-5 embryo culture in couples undergoing in vitro fertilisation.

OBJECTIVE: This study evaluated the effectiveness of Paraffin oil versus Mineral oil for day-5 embryo culture in couples undergoing assisted reproductive technology (ART). METHODS: We performed a multi-centre, retrospective cohort study at IVFMD (My Duc Hospital) and IVFMD Phu Nhuan (My Duc Phu Nhuan Hospital) from January 2019 to September 2019. We studied couples treated by intracytoplasmic sperm injection (ICSI), using fresh, ejaculated semen and undergoing day-5 embryo transfer. Couples who underwent in vitro maturation (IVM) or oocyte donation cycles or couples where the woman had uterine abnormalities were excluded. From January 2019 to May 2019, we used Mineral oil (LiteOil, LifeGlobal) while Paraffin oil (Liquid Paraffin, Origio) was used from June 2019 to September 2019. The primary outcome was live birth rate after the first transfer, either from a fresh transfer or frozen embryo transfer. RESULTS: Between 1st January 2019 to 30th September 2019, there were 2,312 couples undergoing ART in both centres, of which 762 (377 in the Paraffin group and 385 in the Mineral group) eligible couples were included in the study. Baseline characteristics of couples were comparable between the two groups, with mean female age 31.5 ± 4.3 versus 31.9 ± 4.7 in the Paraffin and Mineral group. Live birth after the first transfer occurred in 153 (40.6%) couples in the Paraffin group, compared to 152 (39.5%) couples in the Mineral group (risk ratio 1.02, 95% confidence interval 0.91 - 1.14). Other secondary outcomes were comparable between the two groups. CONCLUSION: In day-5 embryo culture, Paraffin and Mineral oil resulted in a comparable live birth rate.

A Community-Based Model of Care During the Fourth Wave of the COVID-19 Outbreak in Ho Chi Minh City, Vietnam.

In response to a call for help during a surge in coronavirus disease-19 (COVID-19) cases in Ho Chi Minh City in July 2021, the University of Medicine and Pharmacy at Ho Chi Minh City developed and implemented a community care model for the management of patients with COVID-19. This was based on three main principles: home care; providing monitoring and care at a distance; and providing timely emergency care if needed. One team supported patients at home with frequent contacts and remote monitoring, while a second team transferred and cared for patients requiring treatment at field emergency care facilities. COVID-19-related mortality rates at the two districts where this approach was implemented (0.43% and 0.57%) were substantially lower than the overall rate in Ho Chi Minh City over the same period (4.95%). Thus, utilization of a community care model can increase the number of patients with COVID-19 who can be effectively managed from home, and use of field emergency care facilities limited the number of patients that had to be referred for tertiary care. Importantly, the community care model also markedly reduced the mortality rate compared with traditional methods of COVID-19 patient management.

Detection of African swine fever virus in neonatal piglets with congenital tremors.

African swine fever virus (ASF) has circulated in Vietnam since 2018, causing significant losses to the pig industry. Quick, accurate diagnosis of African swine fever virus (ASFV) infection is crucial for controlling the disease. The detection of the virus in piglets with congenital tremors is described in this paper. ASFV was detected in brain tissues by polymerase chain reaction (PCR) and immunohistochemistry. Classical swine fever virus, porcine parvovirus, porcine reproductive and respiratory syndrome virus, and pseudorabies virus were not detected by PCR, suggesting that the ASFV was the cause of these neurological signs.

Health record hiccups-5,526 real-world time series with change points labelled by crowdsourced visual inspection.

BACKGROUND: Large routinely collected data such as electronic health records (EHRs) are increasingly used in research, but the statistical methods and processes used to check such data for temporal data quality issues have not moved beyond manual, ad hoc production and visual inspection of graphs. With the prospect of EHR data being used for disease surveillance via automated pipelines and public-facing dashboards, automation of data quality checks will become increasingly valuable. FINDINGS: We generated 5,526 time series from 8 different EHR datasets and engaged >2,000 citizen-science volunteers to label the locations of all suspicious-looking change points in the resulting graphs. Consensus labels were produced using density-based clustering with noise, with validation conducted using 956 images containing labels produced by an experienced data scientist. Parameter tuning was done against 670 images and performance calculated against 286 images, resulting in a final sensitivity of 80.4% (95% CI, 77.1%-83.3%), specificity of 99.8% (99.7%-99.8%), positive predictive value of 84.5% (81.4%-87.2%), and negative predictive value of 99.7% (99.6%-99.7%). In total, 12,745 change points were found within 3,687 of the time series. CONCLUSIONS: This large collection of labelled EHR time series can be used to validate automated methods for change point detection in real-world settings, encouraging the development of methods that can successfully be applied in practice. It is particularly valuable since change point detection methods are typically validated using synthetic data, so their performance in real-world settings cannot be assumed to be comparable. While the dataset focusses on EHRs and data quality, it should also be applicable in other fields.

Antimicrobial resistance in commensal opportunistic pathogens isolated from non-sterile sites can be an effective proxy for surveillance in bloodstream infections.

Antimicrobial resistance (AMR) surveillance in bloodstream infections (BSIs) is challenging in low/middle-income countries (LMICs) given limited laboratory capacity. Other specimens are easier to collect and process and are more likely to be culture-positive. In 8102 E. coli BSIs, 322,087 E. coli urinary tract infections, 6952 S. aureus BSIs and 112,074 S. aureus non-sterile site cultures from Oxfordshire (1998-2018), and other (55,296 isolates) rarer commensal opportunistic pathogens, antibiotic resistance trends over time in blood were strongly associated with those in other specimens (maximum cross-correlation per drug 0.51-0.99). Resistance prevalence was congruent across drug-years for each species (276/312 (88%) species-drug-years with prevalence within ± 10% between blood/other isolates). Results were similar across multiple countries in high/middle/low income-settings in the independent ATLAS dataset (103,559 isolates, 2004-2017) and three further LMIC hospitals/programmes (6154 isolates, 2008-2019). AMR in commensal opportunistic pathogens cultured from BSIs is strongly associated with AMR in commensal opportunistic pathogens cultured from non-sterile sites over calendar time, suggesting the latter could be used as an effective proxy for AMR surveillance in BSIs.

Classification of Respiratory Conditions using Auscultation Sound.

Management of respiratory conditions relies on timely diagnosis and institution of appropriate management. Computerized analysis and classification of breath sounds has a potential to enhance reliability and accuracy of diagnostic modality while making it suitable for remote monitoring, personalized uses, and self-management uses. In this paper, we describe and compare sound recognition models aimed at automatic diagnostic differentiation of healthy persons vs patients with COPD vs patients with pneumonia using deep learning approaches such as Multi-layer Perceptron Classifier (MLPClassifier) and Convolutional Neural Networks (CNN).Clinical Relevance-Healthcare providers and researchers interested in the field of medical sound analysis, specifically automatic detection/classification of auscultation sound and early diagnosis of respiratory conditions may benefit from this paper.