Morules and ß-catenin predict POLE mutation status in endometrial cancer: A pathway to more cost-effective diagnostic procedures.

OBJECTIVES: The characterization of DNA polymerase epsilon (POLE) mutations has transformed the classification of endometrial endometrioid carcinomas (EECs), highlighting the need for efficient identification methods. This study aims to examine the relationship between distinct morphologic features-namely, squamous morules and squamous differentiation (SD), as well as ß-catenin expression-and the POLE mutation status in endometrial cancer (EC). METHODS: Our study included 35 POLE-mutated (POLEmut) EC cases and 395 non-POLEmut EEC cases. RESULTS: Notably, we observed no presence of morules in POLEmut cases, while SD was identified in 20% of instances. Conversely, morules and SD were identified in 12.7% and 26.1% of non-POLEmut EC cases, respectively, with morules consistently linked to a POLE wild-type status. The nuclear ß-catenin expression is typically absent in tumors with wild-type POLE (wt-POLE) status. CONCLUSIONS: Our findings suggest that the presence of either morules or nuclear ß-catenin expression in EEC could practically rule out the presence of POLE mutations. These morphologic and immunohistochemical features can be used as preliminary screening tools for POLE mutations, offering significant savings in time and resources and potentially enhancing clinical decision-making and patient management strategies. However, further validation in larger, multi-institutional studies is required to fully understand the implications of these findings on clinical practice.

Merazin hydrate produces rapid antidepressant effects by activating CaMKII to promote neuronal activities and proliferation in hippocampus.

In our previous studies, we demonstrated that merazin hydrate (MH) had rapid antidepressant effects, but the deep mechanism needed to be further investigated. In this study, we used depressive-like model, behavioral tests, molecular biology and pharmacological interventions to reveal the underlying mechanisms of MH's rapid antidepressants. We found that a single administration of MH was able to produce rapid antidepressant effects in chronic unpredictable mild stress (CUMS) exposed mice at 1 day later, similar to ketamine. Moreover, MH could not only significantly up-regulated the expressions of cFOS, but also obviously increased the number of Ki67 positive cells in hippocampal dentate gyrus (DG). Furthermore, we also found that the phosphorylated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) was significantly reduced by CUMS in hippocampus, which was also reversed by MH. In addition, pharmacological inhibition of CaMKII by using KN-93 (a CaMKII antagonist) blocked the MH's up-regulation of cFOS and Ki67 in hippocampal DG. To sum up, this study demonstrated that MH produced rapid antidepressant effects by activating CaMKII to promote neuronal activities and proliferation in hippocampus.

Co-occurrence of organophosphate esters and phosphorus fractions in river sediments: Implications for pollution prediction and environment risk assessment.

Organophosphate esters (OPEs) and phosphorus (P) are widespread pollutants in aquatic ecosystems, presenting potential ecological risks. However, there is still a lack of comprehensive understanding of their relationships in sediments. In this study, we investigated the co-occurrence and behaviors of the OPEs and P in urban river sediments. The results indicated serious OPE and P pollution in the study area, with substantial spatial variations in the contents and compositions. The OPE congeners and P fractions exhibited different correlations, particularly more significant linear relationships (R = 0.455 - 0.816, p < 0.05) were observed between the aryl-OPEs and P fractions, potentially due to the influence from sources, physicochemical properties, and total organic carbon. About 56 to 71% of variability in predicting the concentrations of aryl-OPE can be explained by the multiple linear regression model using the Fe/Al- and Ca-bound P contents. The study regions exhibited greater aryl-OPEs ecological risks were consistent with the regions with more serious Total P pollution levels. This study represents the first report demonstrating the potential of Fe/Al-P and Ca-P contents in predicting aryl-OPE contents in heavily polluted sediments, providing a useful reference to comprehensively assess the occurrence and environmental behaviors of aryl-OPEs in anthropogenic polluted sediments.

Deployment and assessment of a deep learning model for real-time detection of anal precancer with high frame rate high-resolution microendoscopy.

Anal cancer incidence is significantly higher in people living with HIV as HIV increases the oncogenic potential of human papillomavirus. The incidence of anal cancer in the United States has recently increased, with diagnosis and treatment hampered by high loss-to-follow-up rates. Novel methods for the automated, real-time diagnosis of AIN 2+ could enable "see and treat" strategies, reducing loss-to-follow-up rates. A previous retrospective study demonstrated that the accuracy of a high-resolution microendoscope (HRME) coupled with a deep learning model was comparable to expert clinical impression for diagnosis of AIN 2+ (sensitivity 0.92 [P = 0.68] and specificity 0.60 [P = 0.48]). However, motion artifacts and noise led to many images failing quality control (17%). Here, we present a high frame rate HRME (HF-HRME) with improved image quality, deployed in the clinic alongside a deep learning model and evaluated prospectively for detection of AIN 2+ in real-time. The HF-HRME reduced the fraction of images failing quality control to 4.6% by employing a high frame rate camera that enhances contrast and limits motion artifacts. The HF-HRME outperformed the previous HRME (P < 0.001) and clinical impression (P < 0.0001) in the detection of histopathologically confirmed AIN 2+ with a sensitivity of 0.91 and specificity of 0.87.

Factors associated with the incidence and the expenditure of self-medication among middle-aged and older adults in China: A cross-sectional study.

Background: With the accelerated ageing of population and the growing prevalence of various chronic diseases in China, self-medication plays an increasingly important role in complementing the health care system due to its convenience and economy. Objective: This study aimed to investigate the incidence of self-medication and the amount of self-medication expenditure among middle-aged and older adults in China, and to explore factors associated with them. Methods: A total of 10,841 respondents aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS) wave 4 which conducted in 2018 were included as the sample of this study. The two-part model was adopted to identify the association between the incidence of self-medication and the amount of self-medication expenditure and specific factors, respectively. Results: The incidence of self-medication among Chinese middle-aged and older adults was 62.30%, and the average total and out-of-pocket (OOP) pharmaceutical expenditure of self-medication of the self-medicated individuals were 290.50 and 264.38 Chinese yuan (CNY) respectively. Participants who took traditional Chinese medicine (TCM), self-reported fair, and poor health status, suffered from one and multiple chronic diseases had strongly higher incidence of self-medication. Older age and multiple chronic diseases were strongly associated with higher expenditure of self-medication. Those who took TCM had more self-medication expenditure, while those who drank alcohol had less. Conclusion: Our study demonstrated the great prevalence of self-medication among middle-aged and older adults in China and the large pharmaceutical expenditure that come with it, especially in the high-risk groups of self-medication identified in this paper. These findings enhanced our understanding of self-medication behaviors among Chinese middle-aged and older adults and may contribute to the formulation of targeted public health policy.

Bitstream-based Perceptual Quality Assessment of Compressed 3D Point Clouds.

With the increasing demand of compressing and streaming 3D point clouds under constrained bandwidth, it has become ever more important to accurately and efficiently determine the quality of compressed point clouds, so as to assess and optimize the quality-of-experience (QoE) of end users. Here we make one of the first attempts developing a bitstream-based no-reference (NR) model for perceptual quality assessment of point clouds without resorting to full decoding of the compressed data stream. Specifically, we first establish a relationship between texture complexity and the bitrate and texture quantization parameters based on an empirical rate-distortion model. We then construct a texture distortion assessment model upon texture complexity and quantization parameters. By combining this texture distortion model with a geometric distortion model derived from Trisoup geometry encoding parameters, we obtain an overall bitstream-based NR point cloud quality model named streamPCQ. Experimental results show that the proposed streamPCQ model demonstrates highly competitive performance when compared with existing classic full-reference (FR) and reduced-reference (RR) point cloud quality assessment methods with a fraction of computational cost.

On offer to Ontario consumers three years after legalization: A profile of cannabis products, cannabinoid content, plant type, and prices.

Introduction: Cannabis was legalized in Canada in October 2018, regulating the production, distribution, sale, and possession of dried cannabis and cannabis oils. Additional products were legalized 1 year later, including edibles, concentrates, and topicals, with new lines of commercial products coming to market. Ontario is the most populous province in Canada and has the largest cannabis market with the highest number of in-person retail stores and the most cannabis products available online. This study aims to create a profile of products available to consumers three years after legalization by summarizing types of products, THC and CBD potency, plant type, and prices of product sub-categories. Methods: We extracted data from the website of the Ontario Cannabis Store (OCS)-the public agency overseeing the only online store and sole wholesaler to all authorized in-person stores-in the first quarter of 2022 (January 19-March 23). We used descriptive analyses to summarize the data. A total of 1,771 available products were mapped by route of administration into inhalation (smoking, vaping, and concentrates), ingestible (edibles, beverages, oils, and capsules) and topical. Results: Most inhalation products included ≥20%/g THC (dried flower: 94%; cartridges: 96%; resin: 100%) while ingestible products had similar proportions of THC and CBD content. Indica-dominant products tend to be more prominent in inhalation products while sativa-dominant products tend to be more prominent in ingestible products. The average sale price of cannabis was 9.30 $/g for dried flower, 5.79 $/0.1g for cartridges, 54.82 $/g for resin, 3.21 $/unit for soft chews, 1.37 $/ml for drops, 1.52 $/unit for capsules, and 39.94 $/product for topicals. Discussion: In summary, a wide variety of cannabis products were available to Ontarians for different routes of administration and provides numerous indica-dominant, sativa-dominant, and hybrid/blend options. The current market for inhalation products however is geared towards the commercialization of high-THC products.

To establish a model for the prediction of initial standard and maintenance doses of warfarin for the Han Chinese population based on gene polymorphism: a multicenter study.

PURPOSE: The purpose of this paper is to study the correlation between demographic and clinical factors and warfarin dose of patients in Chinese Han population taking warfarin and study gene polymorphisms impact of related gene loci (CYP2C9*3, VKORC1-1639G > A) on warfarin doses, to establish a model to predict initial standard dose and maintenance dose based on CYP2C9*3, VKORC1-1639G > A genotype. METHODS: The study collects the data of patients in our hospital and other subcenters which incorporates 2160 patients to establish the initial dose model and 1698 patients for the stable dose model, and sequences 26 multigene sites in 451 patients. Based on the patient's dosage, clinical data, and demographic characteristics, the genetic and non-genetic effects on the initial dose and stable dose of warfarin are calculated by using statistical methods, and the prediction model of initial standard dose and maintenance dose can be established via multiple linear regression. RESULTS: The initial dose of warfarin (mg/day) was calculated as (1.346 + 0.350 × (VKORC1-1639G > A) - 0.273 × (CYP2C9*3) + 0.245 × (body surface area) - 0.003 × (age) - 0.036 × (amine-iodine) + 0.021 × (sex))2. This model incorporated seven factors and explained 55.3% of the individualization differences of the warfarin drug dose. The maintenance dose of warfarin (mg/day) was calculated as (1.336 + 0.299 × (VKORC1-1639G > A) + 0.480 × (body surface area) - 0.214 × (CYP2C9*3) - 0.074 × (amine-iodine) - 0.003 × (age) - 0.077 × (statins) - 0.002 × (height))2. This model incorporated six factors and explained 42.4% of the individualization differences in the warfarin drug dose. CONCLUSION: The genetic and non-genetic factors affecting warfarin dose in Chinese Han population were studied systematically in this study. The pharmacogenomic dose prediction model constructed in this study can predict anticoagulant efficacy of warfarin and has potential application value in clinical practice.

Implementing a Fee-for-Service Cervical Cancer Screening and Treatment Program in Cameroon: Challenges and Opportunities.

BACKGROUND: Cervical cancer screening is one of the most effective cancer prevention strategies, but most women in Africa have never been screened. In 2007, the Cameroon Baptist Convention Health Services, a large faith-based health care system in Cameroon, initiated the Women's Health Program (WHP) to address this disparity. The WHP provides fee-for-service cervical cancer screening using visual inspection with acetic acid enhanced by digital cervicography (VIA-DC), prioritizing care for women living with HIV/AIDS. They also provide clinical breast examination, family planning (FP) services, and treatment for reproductive tract infection (RTI). Here, we document the strengths and challenges of the WHP screening program and the unique aspects of the WHP model, including a fee-for-service payment system and the provision of other women's health services. METHODS: We retrospectively reviewed WHP medical records from women who presented for cervical cancer screening from 2007-2014. RESULTS: In 8 years, WHP nurses screened 44,979 women for cervical cancer. The number of women screened increased nearly every year. The WHP is sustained primarily on fees-for-service, with external funding totaling about $20,000 annually. In 2014, of 12,191 women screened for cervical cancer, 99% received clinical breast exams, 19% received FP services, and 4.7% received treatment for RTIs. We document successes, challenges, solutions implemented, and recommendations for optimizing this screening model. CONCLUSION: The WHP's experience using a fee-for-service model for cervical cancer screening demonstrates that in Cameroon VIA-DC is acceptable, feasible, and scalable and can be nearly self-sustaining. Integrating other women's health services enabled women to address additional health care needs. IMPLICATION FOR PRACTICE: The Cameroon Baptist Convention Health Services Women's Health Program successfully implemented a nurse-led, fee-for-service cervical cancer screening program using visual inspection with acetic acid-enhanced by digital cervicography in the setting of a large faith-based health care system in Cameroon. It is potentially replicable in many African countries, where faith-based organizations provide a large portion of health care. The cost-recovery model and concept of offering multiple services in a single clinic rather than stand-alone "silo" cervical cancer screening could provide a model for other low-and-middle-income countries planning to roll out a new, or make an existing, cervical cancer screening services accessible, comprehensive, and sustainable.

A plastic microchip for nucleic acid purification.

A microchip for purifying nucleic acids from bacterial pathogens was designed and fabricated in plastic. The fabricated plastic microchips were tested for their ability to purify nucleic acids from the bacteria Listeria monocytogenes (L. monocytogenes), Escherichia coli (E. coli), and Salmonella typhimurium (S. typhimurium). These chips were constructed using rapid and low-cost plastic fabrication techniques including hot embossing and plastic casting. Silicon molds fabricated by photolithography and dry etching were used for chip prototyping. Zeonor plastic (poly (cycloolefin) resin) and epoxy microchips were fabricated using hot embossing and plastic casting, respectively. A low temperature sputtering technique was used to coat a layer of silicon dioxide onto the channel region for nucleic acid binding in chaotropic salt solutions. The purification channels contain an array of features to increase the surface area for DNA binding and purification. DNA was quantified with PicoGreen fluorescent dye and the quality of the material as a substrate for polymerase chain reaction (PCR) was tested using target specific primers. DNA could be recovered from the microchip and detected using PCR from a minimum of 10(6) of L. monocytogenes, E. coli, and S. typhimurium cells, respectively. With the simplicity of the plastic chip's fabrication and DNA purification, our microchip makes it ideal for a miniaturized DNA testing system.

Metal-oxide-Semiconductor capacitors fabricated by layer-by-layer nanoassembly and microfabrication.

Metal oxide semiconductor (MOS) capacitors were fabricated by electrostatic layer-by-layer self-assembly (LbL-SA) combined with a modified lift-off technique. The MOS capacitors were built on both n-type and p-type silicon substrates. The numbers of silicon dioxide (SiO2) nanoparticle layers were varied to characterize the electrical performance of MOS capacitors. Unlike the conventional process, LbL-SA allows us to deposit the thin films for a semiconductor device with a lower temperature, lower cost, and shorter processing time. The stability of the silica insulation layers was also investigated. Atomic force microscopy (AFM) served to monitor the film quality of the self-assembled thin films.