Understanding the Utility of Endocardial Electrocardiographic Imaging in Epi-Endocardial Mapping of 3D Reentrant Circuits.

Background: Studies of VT mechanisms are largely based on a 2D portrait of reentrant circuits on one surface of the heart. This oversimplifies the 3D circuit that involves the depth of the myocardium. Simultaneous epicardial and endocardial (epi-endo) mapping was shown to facilitate a 3D delineation of VT circuits, which is however difficult via invasive mapping. Objective: This study investigates the capability of noninvasive epicardial-endocardial electrocardiographic imaging (ECGI) to elucidate the 3D construct of VT circuits, emphasizing the differentiation of epicardial, endocardial, and intramural circuits and to determine the proximity of mid-wall exits to the epicardial or endocardial surfaces. Methods: 120-lead ECGs of VT in combination with subject-specific heart-torso geometry are used to compute unipolar electrograms (CEGM) on ventricular epicardium and endocardia. Activation isochrones are constructed, and the percentage of activation within VT cycle length is calculated on each surface. This classifies VT circuits into 2D (surface only), uniform transmural, nonuniform transmural, and mid-myocardial (focal on surfaces). Furthermore, the endocardial breakthrough time was accurately measured using Laplacian eigenmaps, and by correlating the delay time of the epi-endo breakthroughs, the relative distance of a mid-wall exit to the epicardium or the endocardium surfaces was identified. Results: We analyzed 23 simulated and in-vivo VT circuits on post-infarction porcine hearts. In simulated circuits, ECGI classified 21% as 2D and 78% as 3D: 82.6% of these were correctly classified. The relative timing between epicardial and endocardial breakthroughs was correctly captured across all cases. In in-vivo circuits, ECGI classified 25% as 2D and 75% as 3D: in all cases, circuit exits and entrances were consistent with potential critical isthmus delineated from combined LGE-MRI and catheter mapping data. Conclusions: ECGI epi-endo mapping has the potential for fast delineation of 3D VT circuits, which may augment detailed catheter mapping for VT ablation.

Hybrid Neural State-Space Modeling for Supervised and Unsupervised Electrocardiographic Imaging.

State-space modeling (SSM) provides a general framework for many image reconstruction tasks. Error in a priori physiological knowledge of the imaging physics, can bring incorrectness to solutions. Modern deep-learning approaches show great promise but lack interpretability and rely on large amounts of labeled data. In this paper, we present a novel hybrid SSM framework for electrocardiographic imaging (ECGI) to leverage the advantage of state-space formulations in data-driven learning. We first leverage the physics-based forward operator to supervise the learning. We then introduce neural modeling of the transition function and the associated Bayesian filtering strategy. We applied the hybrid SSM framework to reconstruct electrical activity on the heart surface from body-surface potentials. In unsupervised settings of both in-silico and in-vivo data without cardiac electrical activity as the ground truth to supervise the learning, we demonstrated improved ECGI performances of the hybrid SSM framework trained from a small number of ECG observations in comparison to the fixed SSM. We further demonstrated that, when in-silico simulation data becomes available, mixed supervised and unsupervised training of the hybrid SSM achieved a further 40.6% and 45.6% improvements, respectively, in comparison to traditional ECGI baselines and supervised data-driven ECGI baselines for localizing the origin of ventricular activations in real data.

Cancer-associated fibroblasts reprogram cysteine metabolism to increase tumor resistance to ferroptosis in pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an insidious, rapidly progressing malignancy of the gastrointestinal tract. Due to its dense fibrous stroma and complex tumor microenvironment, neither of which is sensitive to radiotherapy, pancreatic adenocarcinoma is one of the malignancies with the poorest prognosis. Therefore, detailed elucidation of the inhibitory microenvironment of PDAC is essential for the development of novel therapeutic strategies. Methods: We analyzed the association between cancer-associated fibroblasts (CAFs) and resistance to ferroptosis in PDAC using conditioned CAF medium and co-culture of pancreatic cancer cells. Abnormal cysteine metabolism was observed in CAFs using non-targeted metabolomics analysis with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The regulatory effects of cysteine were investigated in PDAC cells through measurement of cell cloning, cell death, cell function, and EdU assays. The effects of exogenous cysteine intake were examined in a mouse xenograft model and the effects of the cysteine pathway on ferroptosis in PDAC were investigated by western blotting, measurement of glutathione and reactive oxygen species levels, among others. Results: It was found that CAFs played a critical role in PDAC metabolism by secreting cysteine, which could increase tumor resistance to ferroptosis. A previously unrecognized function of the sulfur transfer pathway in CAFs was identified, which increased the extracellular supply of cysteine to support glutathione synthesis and thus inducing ferroptosis resistance. Cysteine secretion by CAFs was found to be mediated by the TGF-ß/SMAD3/ATF4 signaling axis. Conclusion: Taken together, the findings demonstrate a novel metabolic relationship between CAFs and cancer cells, in which cysteine generated by CAFs acts as a substrate in the prevention of oxidative damage in PDAC and thus suggests new therapeutic targets for PDAC.

Quantifying the impact of cascade inequalities: a modelling study on the prevention impacts of antiretroviral therapy scale-up in Eswatini.

Background: Inequalities in the antiretroviral therapy (ART) cascade across subpopulations remain an ongoing challenge in the global HIV response. Eswatini achieved the UNAIDS 95-95-95 targets by 2020, with differentiated programs to minimize inequalities across subpopulations, including for female sex workers (FSW) and their clients. We sought to estimate additional HIV infections expected in Eswatini if cascade scale-up had not been equal, and under which epidemic conditions these inequalities could have the largest influence. Methods: Drawing on population-level and FSW-specific surveys in Eswatini, we developed a compartmental model of heterosexual HIV transmission which included eight subpopulations and four sexual partnership types. We calibrated the model to stratified HIV prevalence, incidence, and ART cascade data. Taking observed cascade scale-up in Eswatini as the base-case-reaching 95-95-95 in the overall population by 2020-we defined four counterfactual scenarios in which the population overall reached 80-80-90 by 2020, but where FSW, clients, both, or neither were disproportionately left behind, reaching only 60-40-80. We quantified relative additional cumulative HIV infections by 2030 in counterfactual vs base-case scenarios. We further estimated linear effects of viral suppression gap among FSW and clients on additional infections by 2030, plus effect modification by FSW/client population sizes, rates of turnover, and HIV prevalence ratios. Results: Compared with the base-case scenario, leaving behind neither FSW nor their clients led to the fewest additional infections by 2030: median (95% credible interval) 14.9 (10.4, 18.4)% vs 26.3 (19.7, 33.0)% if both were left behind-a 73 (40, 149)% increase. The effect of lower cascade on additional infections was larger for clients vs FSW, and both effects increased with population size and relative HIV incidence. Conclusions: Inequalities in the ART cascade across subpopulations can undermine the anticipated prevention impacts of cascade scale-up. As Eswatini has shown, addressing inequalities in the ART cascade, particularly those that intersect with high transmission risk, could maximize incidence reductions from cascade scale-up.

Characteristics of the Sexual Networks of Men Who Have Sex With Men in Montréal, Toronto, and Vancouver: Insights from Canada's 2022 Mpox Outbreak.

BACKGROUND: The 2022-2023 global mpox outbreak disproportionately affected gay, bisexual, and other men who have sex with men (GBM). We investigated differences in GBM's sexual partner distributions across Canada's 3 largest cities and over time, and how they shaped transmission. METHODS: The Engage Cohort Study (2017-2023) recruited GBM via respondent-driven sampling in Montréal, Toronto, and Vancouver (n = 2449). We compared reported sexual partner distributions across cities and periods: before COVID-19 (2017-2019), pandemic (2020-2021), and after lifting of restrictions (2021-2023). We used Bayesian regression and poststratification to model partner distributions. We estimated mpox's basic reproduction number (R0) using a risk-stratified compartmental model. RESULTS: Pre-COVID-19 pandemic distributions were comparable: fitted average partners (past 6 months) were 10.4 (95% credible interval: 9.4-11.5) in Montréal, 13.1 (11.3-15.1) in Toronto, and 10.7 (9.5-12.1) in Vancouver. Sexual activity decreased during the pandemic and increased after lifting of restrictions, but remained below prepandemic levels. Based on reported cases, we estimated R0 of 2.4 to 2.7 and similar cumulative incidences (0.7%-0.9%) across cities. CONCLUSIONS: Similar sexual partner distributions may explain comparable R0 and cumulative incidence across cities. With potential for further recovery in sexual activity, mpox vaccination and surveillance strategies should be maintained.

Colorectal cancer histopathology image analysis: A comparative study of prognostic values of automatically extracted morphometric nuclear features in multispectral and red-blue-green imagery.

OBJECTIVES: Multispectral imaging (MSI) has been utilized to predict the prognosis of colorectal cancer (CRC) patients, however, our understanding of the prognostic value of nuclear morphological parameters of bright-field MSI in CRC is still limited. This study was designed to compare the efficiency of MSI and standard red-green-blue (RGB) images in predicting the prognosis of CRC. METHODS: We compared the efficiency of MS and conventional RGB images on the quantitative assessment of hematoxylin-eosin (HE) stained histopathology images. A pipeline was developed using a pixel-wise support vector machine (SVM) classifier for gland-stroma segmentation, and a marker-controlled watershed algorithm was used for nuclei segmentation. The correlation between extracted morphological parameters and the five-year disease-free survival (5-DFS) was analyzed. RESULTS: Forty-seven nuclear morphological parameters were extracted in total. Based on Kaplan-Meier analysis, eight features derived from MS images and seven featured derived from RGB images were significantly associated with 5-DFS, respectively. Compared with RGB images, MSI showed higher accuracy, precision, and Dice index in nuclei segmentation. Multivariate analysis indicated that both integrated parameters 1 (factors negatively correlated with CRC prognosis including nuclear number, circularity, eccentricity, major axis length) and 2 (factors positively correlated with CRC prognosis including nuclear average area, area perimeter, total area/total perimeter ratio, average area/perimeter ratio) in MS images were independent prognostic factors of 5-DFS, in contrast with only integrated parameter 1 (P<0.001) in RGB images. More importantly, the quantification of HE-stained MS images displayed higher accuracy in predicting 5-DFS compared with RGB images (76.9% vs 70.9%). CONCLUSIONS: Quantitative evaluation of HE-stained MS images could yield more information and better predictive performance for CRC prognosis than conventional RGB images, thereby contributing to precision oncology.

Research on ultrasonic bone cutting mechanism based on extended finite element method.

The research on the crack propagation mechanism of bone has important research significance and clinical medical value for the selection of cutting parameters and the development of new surgical tools. In this paper, an extended finite element method (X-FEM) model of ultrasonic bone cutting considering microstructure was developed to further study the ultrasonic bone cutting mechanism and to quantitatively analyze the effects of cutting direction, ultrasonic parameters, and cutting parameters on the mechanism of ultrasonic bone cutting crack propagation. The results show that ultrasonic bone cutting is essentially a controlled crack propagation process, in which brittle crack and fatigue crack are the main crack propagation mechanisms. In order to improve the efficiency of ultrasonic bone cutting, large amplitude and high-frequency ultrasonic vibration are preferred. Compared with the other two cutting directions, the crack propagation deflection angle in the transverse cutting direction is the largest, resulting in the worst cutting surface. Therefore, in the path planning of orthopedic surgical robots, the transverse cutting direction should be avoided as much as possible. Frequency only has a significant effect on the crack propagation rate and has a positive correlation. There is a positive correlation between the deflection angle, propagation length, propagation rate, and amplitude, which provides the possibility to control the direction and length of crack propagation by controlling the amplitude of ultrasonic. The feed speed is much lower than the ultrasonic vibration speed, which makes the influence of ultrasonic vibration speed on the crack propagation characteristics dominant. The X-FEM model of ultrasonic bone cutting provides an effective method for selecting reasonable machining parameters of orthopedic robot and optimize the design of ultrasonic osteotome.

Development and validation of a sensitive liquid chromatography-tandem mass spectrometry method for the assay of 12 substances in rat plasma and its application to rat pharmacokinetics of Epimedium and Psoraleae Fructus herb pair after oral administration.

Epimedium (EM) and Psoraleae Fructus (PF) are a traditional herb combination often used as a fixed form to treat osteoporosis disease in the clinic. However, the intricate interactions of this pair remain unknown. In our study, we undertook a comprehensive examination of their compatibility behaviors. Concurrently, a precise and sensitive quantitation method was successfully developed and validated using liquid chromatography-tandem mass spectrometry for the determination of 12 components. This method was applied in analyzing herbal extracts and biological samples (both in the portal vein and systemic plasma), which was also used to study the pharmacokinetics of the herb pair. The results indicated that the combination of EM and PF enhanced the dissolution of chemical components from PF in extracts, but it had a negligible influence on the contents of the components from EM. On the contrary, the in vivo exposure of the lowly exposed EM flavonoids significantly increased following the combination of EM and PF, whereas the highly exposed psoralen and isopsoralen were greatly reduced. These interactions might be crucial for the synergy and toxicity reduction of the herbal pair in disease treatment, which pave the way for further exploration into the clinical application and pharmacological mechanisms of EM and PF.

Identification and characterization of TOR in Macrobrachium rosenbergii and its role in muscle protein and lipid production.

The recent scarcity of fishmeal and other resources means that studies on the intrinsic mechanisms of nutrients in the growth and development of aquatic animals at the molecular level have received widespread attention. The target of rapamycin (TOR) pathway has been reported to receive signals from nutrients and environmental stresses, and regulates cellular anabolism and catabolism to achieve precise regulation of cell growth and physiological activities. In this study, we cloned and characterized the full-length cDNA sequence of the TOR gene of Macrobrachium rosenbergii (MrTOR). MrTOR was expressed in all tissues, with higher expression in heart and muscle tissues. In situ hybridization also indicated that MrTOR was expressed in muscle, mainly around the nucleus. RNA interference decreased the expression levels of MrTOR and downstream protein synthesis-related genes (S6K, eIF4E, and eIF4B) (P < 0.05) and the expression and enzyme activity of the lipid synthesis-related enzyme, fatty acid synthase (FAS), and increased enzyme activity of the lipolysis-related enzyme, lipase (LPS). In addition, amino acid injection significantly increased the transcript levels of MrTOR and downstream related genes (S6K, eIF4E, eIF4B, and FAS), as well as triglyceride and total cholesterol tissue levels and FAS activity. Starvation significantly increased transcript levels and enzyme activities of adenylate-activated protein kinase and LPS and decreased transcript levels and enzyme activities of FAS, as well as transcript levels of MrTOR and its downstream genes (P < 0.05), whereas amino acid injection alleviated the starvation-induced decreases in transcript levels of these genes. These results suggested that arginine and leucine activated the TOR signaling pathway, promoted protein and lipid syntheses, and alleviated the pathway changes induced by starvation.

Trends and projections of inflammatory bowel disease at the global, regional and national levels, 1990-2050: a bayesian age-period-cohort modeling study.

BACKGROUND: Inflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and treatment strategies. METHODS: Using data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD. RESULTS: In 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36-1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were - 0.60 (95% UI - 0.73 to - 0.48), - 0.69 (95% UI - 0.81 to - 0.57), and - 1.04 (95% UI - 1.06 to - 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data. CONCLUSION: Increasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts.

Optimization of supraclavicular lymph node clinical target volume delineation in high-risk breast cancer: a single center experience and recommendation.

BACKGROUND: Prophylactic irradiation of supraclavicular lymph node drainage areas can improve the regional control rate of lymph node-positive or lymph node-negative disease but a locally-advanced stage breast cancer, and it can reduce breast cancer-related mortality. However, many controversies exist in the clinical target volume delineation of supraclavicular lymph node drainage in patients with breast cancer. METHODS: We retrospectively analyzed 42 patients with breast cancer and supraclavicular lymph node metastasis at our hospital between January 2017 and December 2021. Among these cases, 32 were locally advanced and 10 were stage IV at initial treatment. A patient with breast cancer who did not undergo dissection of the supraclavicular and infraclavicular lymph nodes at our hospital was selected as a standard patient. A contrast-enhanced computed tomography (CT) scan for positioning was used as a template image, and blood vessels, muscles, and bony landmarks were used as references for positioning. The metastatic supraclavicular lymph nodes were identified in all enrolled patients and projected into the template CT images. RESULTS: The metastastic pattern of supraclavicular lymph node in breast cancer was proposed: distribution along the posterolateral border of the internal jugular vein (medial supraclavicular group) and along the transverse jugular vein (lateral supraclavicular group). We theorized that the lateral and posterior borders of the clinical target volume in the supraclavicular region should include the lymph nodes in the posterior triangle of the neck (level V) in high-risk individuals. If the metastatic axillary lymph node is extensive, then the superior border of the supraclavicular region should be moved upward appropriately. CONCLUSIONS: This study analyzed patients with breast cancer and supraclavicular lymph node metastasis at initial treatment, explored the metastastic pattern of supraclavicular lymph node, and applied anatomical knowledge to further optimize the target volume delineation of supraclavicular lymph node drainage area in high-risk breast cancer.

Electrochemical selenium-catalyzed para-amination of N-aryloxyamides: access to polysubstituted aminophenols.

Aminophenols are a class of important compounds with various pharmacological activities such as anticancer, anti-inflammatory, antimalarial, and antibacterial activities. Herein, we introduce a mild and efficient electrochemical selenium-catalyzed strategy to synthesize polysubstituted aminophenols. High atom efficiency and transition metal-free and oxidant-free conditions are the striking features of this protocol. By merging electrochemical and organoselenium-catalyzed processes, the intramolecular rearrangement of N-aryloxyamides produces para-amination products at room temperature in a simple undivided cell.

Identification of monocyte-associated biomarkers in systemic lupus erythematosus and their pan-cancer analysis.

Immune dysregulation is not only a pathogenic mechanism in systemic lupus erythematosus (SLE) but also a potential cause of the link between SLE and cancer. The current understanding of SLE monocyte-associated biomarkers is limited, and the precise mechanism behind the link between SLE and cancer is uncertain. By using WGCNA and immune infiltration to analyze the GSE72326 dataset, we determined the most pertinent modules for monocytes and discovered eight candidate hub genes from them. The limma software was used to find genes that were differently expressed in SLE. The genes that overlapped between the two were chosen using a Venn diagram as the essential genes related to monocytes in SLE, and the essential genes were verified by several datasets. Correlation analysis and GSEA analysis were used to examine the probable immunological pathways connected to key genes. We examined the expression of hub genes in cancer and their interaction with monocytes using the GEPIA and TIMER databases to understand the significance of essential genes in tumorigenesis. In addition, we performed transcription factor identification. We discovered three biomarkers (IFI30, BLVRA, and RIN2) that are mostly involved in interferon-related signaling pathways and are associated with monocyte-mediated immune responses in SLE. The three important genes are also strongly expressed in a number of malignancies and have a relationship with monocytes. As a result, IFI30, BLVRA, and RIN2 may act as SLE-associated biomarkers of monocytes and as a bridge between SLE and tumors. We proposed that interferon-related signaling pathways might function as possible mediators of cancer risk in SLE.

Pharmacokinetic and metabolite profile of orally administered anemoside B4 in rats with an improved exposure in formulations of rectal suppository.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla chinensis (Bunge) Regel is a traditional Chinese herbal medicine used to treat intestinal amebiasis, malaria, vaginal trichomoniasis, and bacterial infections. Anemoside B4 (AB4), a pentacyclic triterpenoid saponin, is one of the primary bioactive substances in Pulsatilla chinensis (Bunge) Regel, and gavage administration of AB4 to animals has been demonstrated to exhibit anticancer, anti-inflammatory, and antiviral actions. However, AB4 exposure in plasma is very low after oral administration, and the biotransformation of AB4 in vivo after oral administration remains unknown. AIM OF THE STUDY: The reason for conducting this research was to explore at the metabolite profile of AB4 in rats following oral administration. Additionally, we aimed to develop an appropriate extravascular formulation to increase the exposure and duration of AB4 in vivo. MATERIALS AND METHODS: A well-validated HPLC-QQQ-MS/MS method was used for the quantification of AB4 in plasma and was further applied to evaluate and compare the pharmacokinetic properties of AB4 dissolved in a saline solution and AB4 formulations in a rectal suppository or enteric capsule. Reliable UHPLC coupled to Q-Exactive Plus high-resolution MS was used to identify the metabolites in rat plasma, bile, urine, and faeces. RESULTS: AB4 was extensively metabolized, and a total of 29 metabolites were identified. The primary metabolic routes included deglycosylation, oxidation, dehydrogenation, reduction, sulfation, hydration, acetylation, and glucuronidation. The pharmacokinetic comparison showed that both the rectal suppository and enteric capsule increased the exposures of AB4 and one of its active metabolites, 23-hydroxybetulinic acid (23-HA). Notably, rectal suppositories increased systemic AB4 exposure (AUC0-∞) by approximately 49 and 28 times higher than that of the AB4 saline solution and enteric capsules, respectively. The t1/2 of AB4 was extended to approximately 7 h after rectal administration compared to 2 h after oral administration. CONCLUSION: Overall, our study demonstrated that the mismatched exposure-response relationship of AB4 could result from extensive metabolism in the gastrointestinal and circulatory systems. Thus, a rectal suppository could be an alternative formulation of AB4 to obtain both higher and longer exposure.

Three-Component Electrochemical Aminoselenation of 1,3-Dienes.

Azoles and organoselenium compounds are pharmacologically important scaffolds in medicinal chemistry and natural products. We developed an efficient regioselective electrochemical aminoselenation reaction of 1,3-dienes, azoles, and diselenide derivatives to access selenium-containing allylazoles skeletons. This protocol is more economical and environmentally friendly and features a broad substrate scope; pyrazole, triazole, and tetrazolium were all tolerated under the standard conditions, which could be applied to the expedient synthesis of bioactive molecules and in the pharmaceutical industry.

Tumor immune microenvironment components and the other markers can predict the efficacy of neoadjuvant chemotherapy for breast cancer.

Breast cancer is an epithelial malignant tumor that occurs in the terminal ducts of the breast. Neoadjuvant chemotherapy (NACT) is an important part of breast cancer treatment. Its purpose is to use systemic treatment for some locally advanced breast cancer patients, to decrease the tumor size and clinical stage so that non-operable breast cancer patients can have a chance to access surgical treatment, or patients who are not suitable for breast-conserving surgery can get the opportunity of breast-conserving. However, some patients who do not respond to NACT will lead deterioration in their condition. Therefore, prediction of NACT efficacy in breast cancer is vital for precision therapy. The tumor microenvironment (TME) has a crucial role in the carcinogenesis and therapeutic response of breast cancer. In this review, we summarized the immune cells, immune checkpoints, and other biomarkers in the TME that can evaluate the efficacy of NACT in treating breast cancer. We believe that the detection and evaluation of the TME components in breast cancer are helpful to predict the efficacy of NACT, and the prediction methods are in the prospect. In addition, we also summarized other predictive factors of NACT, such as imaging examination, biochemical markers, and multigene/multiprotein profiling.

Proposal of an automated tumor-stromal ratio assessment algorithm and a nomogram for prognosis in early-stage invasive breast cancer.

BACKGROUND: The tumor-stromal ratio (TSR) has been verified to be a prognostic factor in many solid tumors. In most studies, it was manually assessed on routinely stained H&E slides. This study aimed to assess the TSR using image analysis algorithms developed by the Qupath software, and integrate the TSR into a nomogram for prediction of the survival in invasive breast cancer (BC) patients. METHODS: A modified TSR assessment algorithm based on the recognition of tumor and stroma tissues was developed using the Qupath software. The TSR of 234 invasive BC specimens in H&E-stained tissue microarrays (TMAs) were assessed with the algorithm and categorized as stroma-low or stroma-high. The consistency of TSR estimation between Qupath prediction and pathologist annotation was analyzed. Univariable and multivariable analyses were applied to select potential risk factors and a nomogram for predicting survival in invasive BC patients was constructed and validated. An extra TMA containing 110 specimens was obtained to validate the conclusion as an independent cohort. RESULTS: In the discovery cohort, stroma-low and stroma-high were identified in 43.6% and 56.4% cases, respectively. Good concordance was observed between the pathologist annotated and Qupath predicted TSR. The Kaplan-Meier curve showed that stroma-high patients were associated with worse 5-DFS compared to stroma-low patients (p = 0.007). Multivariable analysis identified age, T stage, N status, histological grade, ER status, HER-2 gene, and TSR as potential risk predictors, which were included in the nomogram. The nomogram was well calibrated and showed a favorable predictive value for the recurrence of BC. Kaplan-Meier curves showed that the nomogram had a better risk stratification capability than the TNM staging system. In the external validation of the nomogram, the results were further validated. CONCLUSIONS: Based on H&E-stained TMAs, this study successfully developed image analysis algorithms for TSR assessment and constructed a nomogram for predicting survival in invasive BC.

Differential Patterns by Area-Level Social Determinants of Health in Coronavirus Disease 2019 (COVID-19)-Related Mortality and Non-COVID-19 Mortality: A Population-Based Study of 11.8 Million People in Ontario, Canada.

BACKGROUND: Social determinants of health (SDOH) have been associated with coronavirus disease 2019 (COVID-19) outcomes. We examined patterns in COVID-19-related mortality by SDOH and compared these patterns to those for non-COVID-19 mortality. METHODS: Residents of Ontario, Canada, aged ≥20 years were followed from 1 March 2020 to 2 March 2021. COVID-19-related death was defined as death within 30 days following or 7 days prior to a positive COVID-19 test. Area-level SDOH from the 2016 census included median household income; proportion with diploma or higher educational attainment; proportion essential workers, racially minoritized groups, recent immigrants, apartment buildings, and high-density housing; and average household size. We examined associations between SDOH and COVID-19-related mortality, and non-COVID-19 mortality using cause-specific hazard models. RESULTS: Of 11 810 255 individuals, we observed 3880 COVID-19-related deaths and 88 107 non-COVID-19 deaths. After accounting for demographics, baseline health, and other area-level SDOH, the following were associated with increased hazards of COVID-19-related death (hazard ratio [95% confidence interval]: lower income (1.30 [1.04-1.62]), lower educational attainment (1.27 [1.07-1.52]), higher proportions essential workers (1.28 [1.05-1.57]), racially minoritized groups (1.42 [1.08-1.87]), apartment buildings (1.25 [1.07-1.46]), and large vs medium household size (1.30 [1.12-1.50]). Areas with higher proportion racially minoritized groups were associated with a lower hazard of non-COVID-19 mortality (0.88 [0.84-0.92]). CONCLUSIONS: Area-level SDOH are associated with COVID-19-related mortality after accounting for demographic and clinical factors. COVID-19 has reversed patterns of lower non-COVID-19 mortality among racially minoritized groups. Pandemic responses should include strategies to address disproportionate risks and inequitable coverage of preventive interventions associated with SDOH.

Improving Generalization by Learning Geometry-Dependent and Physics-Based Reconstruction of Image Sequences.

Deep neural networks have shown promise in image reconstruction tasks, although often on the premise of large amounts of training data. In this paper, we present a new approach to exploit the geometry and physics underlying electrocardiographic imaging (ECGI) to learn efficiently with a relatively small dataset. We first introduce a non-Euclidean encoding-decoding network that allows us to describe the unknown and measurement variables over their respective geometrical domains. We then explicitly model the geometry-dependent physics in between the two domains via a bipartite graph over their graphical embeddings. We applied the resulting network to reconstruct electrical activity on the heart surface from body-surface potentials. In a series of generalization tasks with increasing difficulty, we demonstrated the improved ability of the network to generalize across geometrical changes underlying the data using less than 10% of training data and fewer variations of training geometry in comparison to its Euclidean alternatives. In both simulation and real-data experiments, we further demonstrated its ability to be quickly fine-tuned to new geometry using a modest amount of data.

HIV- and sex work-related stigmas and quality of life of female sex workers living with HIV in South Africa: a cross-sectional study.

BACKGROUND: Environmental quality of life (QoL) assesses individually perceived factors such as physical safety and security, accessibility, quality of healthcare, and physical environment. These factors are particularly relevant in the context of sex work and HIV, where stigma has been identified as an important barrier across several prevention and treatment domains. This study aims to examine the association between different types of HIV- and sex work-related stigmas and environmental QoL among female sex workers (FSW) living with HIV in Durban, South Africa. METHODS: We conducted cross-sectional analyses using baseline data from the Siyaphambili randomized controlled trial. FSW who reported sex work as their primary source of income and had been diagnosed with HIV for ≥ 6 months were enrolled from June 2018-March 2020, in eThekwini, South Africa. We evaluated the association between environmental QoL, dichotomizing the environmental domain score collected by the WHO Quality of Life HIV Brief (WHOQOL-HIV BREF) questionnaire at the median, and stigma using modified robust Poisson regression models. Five stigma subscales were assessed: sex work-related (anticipated, enacted, or internalized stigma) and HIV-related (anticipated or enacted stigma). RESULTS: Among 1373 FSW, the median environmental QoL was 10.5 out of 20 [IQR: 9.0-12.5; range 4.0-19.0], while the median overall QoL was 3 out of 5 [IQR: 2-4; range 1-5]. One-third of FSW (n = 456) fell above the median environmental QoL score, while 67% were above the median overall QoL (n = 917). Reporting anticipated sex work stigma was associated with lower environmental QoL (adjusted prevalence ratio [aPR] 0.74 [95% CI 0.61, 0.90]), as was severe internalized sex work stigma (aPR: 0.64, 95% CI 0.48, 0.86). Reporting enacted HIV stigma versus none was similarly associated with lower environmental QoL (aPR: 0.65, 95% CI 0.49, 0.87). Enacted sex work stigma and anticipated HIV stigma were not statistically associated with environmental QoL. CONCLUSIONS: This study highlights the need to consider the impact of multiple stigmas on FSW's non-HIV related clinical outcomes, including safety and physical well-being. Moreover, these results suggest that addressing underlying structural risks may support the impact of more proximal HIV prevention and treatment interventions. Trial registration NCT03500172 (April 17, 2018).