Opioid Therapy for Cancer Pain in Vietnam: Knowledge, Attitudes, and Perceived Barriers Among Health Care Professionals, Policymakers, and Regulators.

PURPOSE: We aimed to assess knowledge, attitudes, and perceived barriers among health care professionals (HCPs), policymakers, and regulators in Vietnam related to opioid therapy for cancer pain. METHODS: We conducted a cross-sectional study in Vietnam from June to August 2022. Participants completed a questionnaire on their demographic characteristics, knowledge and attitudes toward opioid therapy, and barriers to accessing opioids for cancer pain. RESULTS: Two hundred seven HCPs and 15 policymakers/regulators completed the questionnaire. Poor knowledge about opioids in cancer pain was found in 63.3% of HCPs and 80.0% of policymakers/regulators. Poor knowledge was associated with a lack of training in cancer pain management or palliative care (PC; prevalence ratio [PR], 1.14 [95% CI, 1.04 to 1.24]). Negative attitudes toward opioid therapy in cancer pain were held by 64.7% of HCPs and 80.0% of policymakers/regulators. Negative attitudes were associated with the unavailability of oral morphine in the workplace (PR, 1.10 [95% CI, 1.01 to 1.20]). The most common major barriers reported were the absence of national policy on pain management and PC (34.7%), inadequate training in opioid use for cancer pain (33.8%), lockdown of health facilities during the COVID-19 pandemic (32.4%), limited opioid availability in local health facilities (32.4%), and excessively restrictive regulation of opioid dispensing in pharmacies (32.4%). CONCLUSION: This study found a knowledge deficit and negative attitudes toward opioid therapy for cancer pain among HCPs and policymakers/regulators. Improving education and training in opioid therapy is essential. Recognizing major barriers can guide strategies to enhance safe opioid accessibility for cancer pain management in Vietnam.

Optimizing Green Synthesis of Hydrotalcite - Silver Nanoparticles using Syzygium Nervosum based Reducing Agent.

This work aimed to assess the effect of Syzygium nervosum leaf extract as a reducing agent for green synthesis of AgNPs on HT through an optimizing process using response surface methodology (RSM) and the Box-Benken model. The optimal conditions for synthesis of AgNPs on HT include reaction time of 6.15 hours, reaction temperature of 50 oC and the ratio of diluted Syzygium nervosum leaf extract to reduce AgNO3 of 50.37 mL/mg. Under the optimal conditions, the yield of reduction reaction reached 77.54 %, close to the theoretical value of 76.97 %. Besides, the morphology, density, and characteristics of AgNPs on the surface of HT layers have been determined by using Ultraviolet-visible spectroscopy, Field emission scanning electron microscopy, High resolution transmission electron microscopy, selected area diffraction, X-ray diffraction, Dynamic light scattering, Infrared spectroscopy, Fluorescence emission spectroscopy, Brunauer-Emmett-Teller  methods. The spherical AgNPs were synthesized successfully on the surface of HT with the average particle size of 13.0 ± 1.1 nm. Interestingly, HT-Ag hybrid materials can inhibit strongly the growth of E. coli, S. aureus as well as two antibiotic resistance bacterial strains, P. stutzeri B27 and antibiotic resistance E. coli. Overall, the HT-Ag hybrid materials are very promising for application in practice.

Novel Inhibitors to MmpL3 Transporter of Mycobacterium tuberculosis by Structure-Based High-Throughput Virtual Screening and Molecular Dynamics Simulations.

Tuberculosis (TB)-causing bacterium Mycobacterium tuberculosis (Mtb) utilizes mycolic acids for building the mycobacterial cell wall, which is critical in providing defense against external factors and resisting antibiotic action. MmpL3 is a secondary resistance nodulation division transporter that facilitates the coupled transport of mycolic acid precursor into the periplasm using the proton motive force, thus making it an attractive drug target for TB infection. In 2019, X-ray crystal structures of MmpL3 from M. smegmatis were solved with a promising inhibitor SQ109, which showed promise against drug-resistant TB in Phase II clinical trials. Still, there is a pressing need to discover more effective MmpL3 inhibitors to counteract rising antibiotic resistance. In this study, structure-based high-throughput virtual screening combined with molecular dynamics (MD) simulations identified potential novel MmpL3 inhibitors. Approximately 17 million compounds from the ZINC15 database were screened against the SQ109 binding site on the MmpL3 protein using drug property filters and glide XP docking scores. From this, the top nine compounds and the MmpL3-SQ109 crystal complex structure each underwent 2 × 200 ns MD simulations to probe the inhibitor binding energetics to MmpL3. Four of the nine compounds exhibited stable binding properties and favorable drug properties, suggesting these four compounds could be potential novel inhibitors of MmpL3 for M. tuberculosis.

Comtrifosides A and B, two new triterpenoid saponins from the leaves of Combretum trifoliatum.

The phytochemical composition of the Combretum trifoliatum leaves was studied for the first time. Two new triterpenoid saponins, named comtrifoside A (1) and comtrifoside B (2), together with two other saponins (3-4) were purified by variously chromatographic techniques. For the first time, compound 3 was informed from the Combretum genus, as well as all of the isolated compounds (1-4) were reported from C. trifoliatum. The chemical structures of them were clearly characterised using extensive UV-VIS, IR, HRMS-ESI, and NMR experimental data. The in vitro anti-inflammatory activities of 1 & 2 were examined against NO overproduction in LPS activation of RAW264.7.

Prenatal opioid use as a predictor of postpartum suicide attempts among reproductive-age women enrolled in Oregon Medicaid.

BACKGROUND: The rates of suicide and opioid use disorder (OUD) among pregnant and postpartum women continue to increase. This research characterized OUD and suicide attempts among Medicaid-enrolled perinatal women and examined prenatal OUD diagnosis as a marker for postpartum suicide attempts. METHODS: Data from Oregon birth certificates, Medicaid eligibility and claims files, and hospital discharge records were linked and analyzed. The sample included Oregon Medicaid women aged 15-44 who became pregnant and gave live births between January 2008 and January 2016 (N = 61,481). Key measures included indicators of suicide attempts (separately for any means and opioid poisoning) and OUD diagnosis, separately assessed during pregnancy and the one-year postpartum period. Probit regression was used to examine the overall relationship between prenatal OUD diagnosis and postpartum suicide attempts. A simultaneous equations model was employed to explore the link between prenatal OUD diagnosis and postpartum suicide attempts, mediated by postpartum OUD diagnosis. RESULTS: Thirty-three prenatal suicide attempts by any means were identified. Postpartum suicide attempts were more frequent with 58 attempts, corresponding to a rate of 94.3 attempts per 100,000. Of these attempts, 79% (46 attempts) involved opioid poisoning. A total of 1,799 unique women (4.6% of the sample) were diagnosed with OUD either during pregnancy or one-year postpartum with 53% receiving the diagnosis postpartum. Postpartum suicide attempts by opioid poisoning increased from 55.5 per 100,000 in 2009 to 105.1 per 100,000 in 2016. The rate of prenatal OUD also almost doubled over the same period. Prenatal OUD diagnosis was associated with a 0.15%-point increase in the probability of suicide attempts by opioid poisoning within the first year postpartum. This increase reflects a three-fold increase compared to the rate for women without a prenatal OUD diagnosis. A prenatal OUD diagnosis was significantly associated with an elevated risk of postpartum suicide attempts by opioid poisoning via a postpartum OUD diagnosis. CONCLUSIONS: The risk of suicide attempt by opioid poisoning is elevated for Medicaid-enrolled reproductive-age women during pregnancy and postpartum. Women diagnosed with prenatal OUD may face an increased risk of postpartum suicides attempts involving opioid poisoning.

Developing an Online Health Community Platform for Facilitating Empowerment in Chronic Disease Prevention and Health Promotion.

This study aimed to develop an online health community platform for facilitating the empowerment of people with chronic diseases dwelling in the community regarding disease prevention and health promotion. The user-centered design approach included four main steps: (1) identifying the health problems and needs of target users, (2) developing the content of the platform, (3) constructing the platform, and (4) pilot testing, refinement, and finalization. An online health community platform available both in a mobile application and a Web-enabled application has been launched to facilitate empowerment and self-management by people with chronic conditions. The main components of the application comprised (1) screening for chronic diseases and health problems, (2) setting personal goals for health promotion and action planning to achieve the goals themselves, (3) offering an online health community with shared group goals that help users engage with their peers to attain their goals, and (4) creating one's own online health community and inviting others to participate. The platform has the potential to encourage people with chronic conditions to proactively engage in their own health promotion. Future studies are needed to determine the impact of the application on self-management and empowerment for its users.

Discovery of novel inhibitors of histone deacetylase 6: Structure-based virtual screening, molecular dynamics simulation, enzyme inhibition and cell viability assays.

Histone deacetylase 6 (HDAC6) contributes to cancer metastasis in several cancers, including triple-negative breast cancer (TNBC)-the most lethal form that lacks effective therapy. Although several efforts have been invested to develop selective HDAC6 inhibitors, none have been approved by the FDA. Toward this goal, existing computational studies used smaller compound libraries and shorter MD simulations. Here, we conducted a structure-based virtual screening of ZINC "Druglike" library containing 17,900,742 compounds using a Glide virtual screening protocol comprising various filters with increasing accuracy. The top 20 hits were subjected to molecular dynamics simulation, MM-GBSA binding energy calculations, and further ADMET prediction. Furthermore, enzyme inhibition assay and cell viability assay were performed on six available compounds from the identified hits. C4 (ZINC000077541942) with a good profile of predicted drug properties was found to inhibit HDAC6 (IC50: 4.7 ± 11.6 µM) with comparative affinity to that of the known HDAC6 selective inhibitor Tubacin (TA) in our experiments. C4 also demonstrated cytotoxic effects against triple-negative breast cancer (TNBC) cell line MDA-MB-231 with EC50 of 40.6 ± 12.7 µM comparable to that of TA (2-20 µM). Therefore, this compound, with pharmacophore features comprising a non-hydroxamic acid zinc-binding group, heteroaromatic linker, and cap group, is proposed as a novel HDAC6 inhibitor.

EGCG-like non-competitive inhibitor of DYRK1A rescues cognitive defect in a down syndrome model.

Overexpression of the chromosome 21 DYRK1A gene induces morphological defects and cognitive impairments in individuals with Down syndrome (DS) and in DS mice models. Aging neurons of specific brain regions of patients with Alzheimer's disease, DS and Pick's disease have increased DYRK1A immunoreactivity suggesting a possible association of DYRK1A with neurofibrillary tangle pathology. Epigallocatechin-3-gallate (EGCG) displays appreciable inhibition of DYRK1A activity and, contrary to all other published inhibitors, EGCG is a non-competitive inhibitor of DYRK1A. Prenatal exposure to green tea polyphenols containing EGCG protects from brain defects induced by overexpression of DYRK1A. In order to produce more robust and possibly more active analogues of the natural compound EGCG, here we synthetized new EGCG-like molecules with several structural modifications to the EGCG skeleton. We replaced the ester boun of EGCG with a more resistant amide bond. We also replaced the oxygen ring by a methylene group. And finally, we positioned a nitrogen atom within this ring. The selected compound was shown to maintain the non-competitive property of EGCG and to correct biochemical and behavioral defects present in a DS mouse model. In addition it showed high stability and specificity.

Hospital Capabilities Associated With Behavioral Health Integration Within Emergency Departments.

OBJECTIVES: To identify hospital capabilities associated with behavioral health (BH) processes in emergency departments (EDs). RESEARCH DESIGN: Six hundred two hospital responses to the 2017/2018 National Survey of Healthcare Organizations and Systems were linked to 2017 American Hospital Association Annual Survey data. Separate multivariable regressions estimated how hospital capabilities (the use of quality improvement methods, approaches to disseminate best patient-care practices, barriers to using care delivery innovations, and inpatient beds for psychiatric or substance use) were associated with each of 4 ED-based BH processes: mental health and substance use disorder screening, team-based approaches to BH, telepsychiatry, and direct referrals to community-based BH clinicians. Models controlled for hospital structural characteristics and area-level socioeconomic factors. RESULTS: Most hospitals screened for BH conditions and provided direct referrals to community-based BH clinicians. Approximately half of the hospitals used a team approach to BH. A minority had implemented telepsychiatry. Each additional process used to disseminate best patient-care practices was associated with more screening for BH conditions (an increase of 4.07 points on the screening index, P <0.01) and greater likelihood of using a team approach to BH [4.41 percentage point ( P <0.01) increase]. Hospitals reporting more barriers to the use of care delivery innovations reported less screening and use of a team approach [a decrease of 0.15 points on the screening index ( P <0.01) and 0.28 percentage points reduction in likelihood of team approach use ( P <0.001) for 1-point increase in the barrier index]. CONCLUSIONS: Research and interventions focused on removing innovation barriers or adding processes to disseminate best practices offer a path to accelerate BH integration in hospital EDs.

Coronary flow capacity and survival prediction after revascularization: physiological basis and clinical implications.

BACKGROUND AND AIMS: Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization. METHODS: Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0. RESULTS: Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025). CONCLUSIONS: Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization.

Structural and enzymatic evidence for the methylation of the ACK1 tyrosine kinase by the histone lysine methyltransferase SETD2.

SETD2 (SET-domain containing protein 2) is a histone methyltransferase (HMT) of the SET family responsible for the trimethylation of K36 of histone H3, thus producing the epigenetic mark H3K36me3. Recent studies have shown that certain SET family HMTs, such as SMYD2, SMYD3 or SETDB1 can also methylate protein kinases and therefore be involved in signaling pathways. Here we provide structural and enzymatic evidence showing that SETD2 methylates the protein tyrosine kinase ACK1 in vitro. ACK1 is recognized as a major integrator of signaling from various receptor tyrosine kinases. Using ACK1 peptides and recombinant proteins, we show that SETD2 methylates the K514 residue of ACK1 generating K514 mono, di or tri-methylation. Interestingly, K514 is found in a "H3K36-like" motif of ACK1 which is known to be post-translationally modified and to be involved in protein-protein interaction. The crystal structure of SETD2 catalytic domain in complex with an ACK1 peptide further provides the structural basis for the methylation of ACK1 K514 by SETD2. Our work therefore strongly suggests that ACK1 could be a novel non-histone substrate of SETD2 and further supports that SET HMTs, such as SETD2, could be involved in both epigenetic regulations and cell signaling.

Data-driven prediction of the shear capacity of ETS-FRP-strengthened beams in the hybrid 2PKT-ML approach.

A new approach that combines analytical two-parameter kinematic theory (2PKT) with machine learning (ML) models for estimating the shear capacity of embedded through-section (ETS)-strengthened reinforced concrete (RC) beams is proposed. The 2PKT was first developed to validate its representativeness and confidence against the available experimental data of ETS-retrofitted RC beams. Given the deficiency of the test data, the developed 2PKT was utilized to generate a large data pool with 2643 samples. The aim was to optimize the ML algorithms, namely, the random forest, extreme gradient boosting (XGBoost), light gradient boosting machine, and artificial neural network (ANN) algorithm. The optimized ANN model exhibited the highest accuracy in predicting the total shear strength of ETS-strengthened beams and ETS shear contribution. In terms of predicting the total shear strength of ETS-strengthened beams, the ANN model achieved R2 values of 0.99, 0.98, and 0.96 for the training, validation, and testing data, respectively. By contrast, the ANN model could predict ETS shear contribution with high accuracy, with R2 values of 0.99, 0.99, and 0.97 for the training, validation, and testing data, respectively. Then, the effects of all design variables on the shear capacity of the ETS-strengthened beams were investigated using the hybrid 2PKT-ML. The obtained trends could well appraise the reasonability of the proposed approach.

Dietaryindex: A User-Friendly and Versatile R Package for Standardizing Dietary Pattern Analysis in Epidemiological and Clinical Studies.

Background: Few standardized and open-source tools exist for calculating dietary pattern indexes from dietary intake data in epidemiological and clinical studies. Miscalculations of dietary indexes, with suspected erroneous findings, are occasionally noted in the literature. Objective: The primary aim is to develop and validate dietaryindex, a user-friendly and versatile R package that standardizes the calculation of dietary indexes. Methods: Dietaryindex utilizes a two-step process: an initial calculation of serving size for each food and nutrient category, followed by the calculation of individual dietary indexes. It includes generic functions that accept any preprocessed serving sizes of food groups and nutrients, with the standard serving sizes defined according to the methodologies used in well-known prospective cohort studies. For ease of use, dietaryindex also offers one-step functions that directly reference common datasets and tools, including the National Health and Nutrition Examination Survey (NHANES) and Block Food Frequency Questionnaire, eliminating the need for data preprocessing. At least two independent researchers validated the serving size definitions and scoring algorithms of dietaryindex. Results: Dietaryindex can calculate multiple dietary indexes of high interest in research, including Healthy Eating Index (HEI) - 2020, Alternative Healthy Eating Index 2010, Dietary Approaches to Stop Hypertension Index, Alternate Mediterranean Diet Score, Dietary Inflammatory Index, American Cancer Society 2020 dietary index, and Planetary Health Diet Index from the EAT-Lancet Commission. In our validation process, dietaryindex demonstrated full accuracy (100%) in all generic functions with two-decimal rounding precision in comparison to hand-calculated results. Similarly, using NHANES 2017-2018 data and ASA24 and DHQ3 example data, the HEI2015 outputs from dietaryindex aligned (99.95%-100%) with results using the SAS codes from the National Cancer Institute. Conclusions: Dietaryindex is a user-friendly, versatile, and validated informatics tool for standardized dietary index calculations. We have open-sourced all the validation files and codes with detailed tutorials on GitHub (https://github.com/jamesjiadazhan/dietaryindex).

Prevalence of obesity and abdominal obesity and their association with metabolic-related conditions in Vietnamese adults: an analysis of Vietnam STEPS survey 2009 and 2015.

Background: The abdominal obesity trends and prevalence are important contributing factors to significant rise of many noncommunicable diseases in Vietnam but have not been well-documented in the literature. This study aimed to describe the prevalence and trends of obesity and abdominal obesity in Vietnam from 2009 to 2015 and evaluate how different definitions of obesity and abdominal obesity are associated with metabolic-related conditions. Methods: We conducted a secondary analysis based on the Vietnam STEPS (STEPwise approach to Surveillance) cross-sectional Survey 2009 and 2015. Obesity and abdominal obesity were defined using the body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) cut-offs from the World Health Organization (WHO) and International Diabetes Federation (IDF). Findings: Depending on the specific cut-offs, from 2009 to 2015, obesity prevalence increased from 0.8%-10% to 1.7%-16.4% in women and from 0.8%-10.3% to 1.7%-15% in men; abdominal obesity prevalence increased from 3%-31.3% to 8%-41.7% in women and from 0.3%-19.3% to 0.4%-25% in men. Abdominal obesity using WC-IDF and WHR-WHO definitions had noticeably higher sensitivity and lower specificity for metabolic-related conditions compared to the other four criteria. All anthropometric measurements were statistically correlated with biomarkers/blood pressure in 2009 and 2015 except for fasting glucose. Only WC-IDF and WHR-WHO definitions showed consistent association with all reported metabolic-related conditions regardless of sex and survey years. Interpretation: The prevalence of obesity and abdominal obesity in Vietnam is increasing rapidly, especially abdominal obesity in women regardless of the criteria used. More studies are needed to investigate how using different diagnostic criteria for obesity and abdominal obesity could better identify metabolic-related conditions. Funding: Authors received no funding for this study.

A Ceratopteris EXCESS MICROSPOROCYTES1 suppresses reproductive transition in the fern vegetative leaves.

Land plant sexual reproduction involves the transition of cells from somatic to reproductive identity during post-embryonic development. In Arabidopsis, the leucine-rich repeat receptor-like kinase EXCESS MICROSPOROCYTES1 (EXS/EMS1) restricts the number of sporogenous cells during the transition from diploid tissue to haploid spore production by promoting the formation of the tapetum cell layer within the anther. Although all land plants studied contain EMS1 genes, its function is unknown beyond a few angiosperms. In the model fern Ceratopteris (Ceratopteris richardii), we discovered an EMS1 homolog (CrEMS1) that functions to suppress formation of reproductive structures on vegetative leaves of the fern sporophyte, a role not found in angiosperms. Suppression of CrEMS1 by RNAi did not affect sporogenesis on reproductive leaves but did affect antheridium production of the fern gametophyte. Expression patterns of CrEMS1 across developmental stages suggest threshold levels of CrEMS1 control the specification of reproductive organs during both generations of the fern. Additional EMS1 homologs present in the fern genome suggest a dynamic role of EMS1 receptors in the evolution of reproductive development in vascular plants.

Rational design of an acidic erythritol (ACER) medium for the enhanced isolation of the environmental pathogen Burkholderia pseudomallei from soil samples.

The soil bacterium Burkholderia pseudomallei causes melioidosis, a potentially fatal and greatly underdiagnosed tropical disease. Detection of B. pseudomallei in the environment is important to trace the source of infections, define risk areas for melioidosis and increase the clinical awareness. Although B. pseudomallei polymerase chain reaction (PCR)-based environmental detection provides important information, the culture of the pathogen remains essential but is still a methodological challenge. B. pseudomallei can catabolize erythritol, a metabolic pathway, which is otherwise rarely encountered among bacteria. We recently demonstrated that replacing threonine with erythritol as a single carbon source in the pH-neutral threonine-basal salt solution (TBSS-C50) historically used improved the isolation of B. pseudomallei from rice paddy soils. However, further culture medium parameters for an optimized recovery of B. pseudomallei strains from soils are still ill-defined. We, therefore, aimed to design a new erythritol-based medium by systematically optimizing parameters such as pH, buffer capacity, salt and nutrient composition. A key finding of our study is the enhanced erythritol-based growth of B. pseudomallei under acidic medium conditions. Our experiments with B. pseudomallei strains from different geographical origin led to the development of a phosphate-buffered acidic erythritol (ACER) medium with a pH of 6.3, higher erythritol concentration of 1.2%, supplemented vitamins and nitrate. This highly selective medium composition shortened the lag phase of B. pseudomallei cultures and greatly increased growth densities compared to TBSS-C50 and TBSS-C50-based erythritol medium. The ACER medium led to the highest enrichments of B. pseudomallei as determined from culture supernatants by quantitative PCR in a comparative validation with soil samples from the central part of Vietnam. Consequently, the median recovery of B. pseudomallei colony forming units on Ashdown's agar from ACER subcultures was 5.4 times higher compared to TBSS-C50-based erythritol medium (p = 0.005) and 30.7 times higher than TBSS-C50 (p < 0.001). In conclusion, our newly developed ACER medium significantly improves the isolation of viable B. pseudomallei from soils and, thereby, has the potential to reduce the rate of false-negative environmental cultures in melioidosis risk areas.

Postpartum Medicaid coverage and outpatient care utilization among low-income birthing individuals in Oregon: impact of Medicaid expansion.

Objective: This study examined the effect of Medicaid expansion in Oregon on duration of Medicaid enrollment and outpatient care utilization for low-income individuals during the postpartum period. Methods: We linked Oregon birth certificates, Medicaid enrollment files, and claims to identify postpartum individuals (N = 73,669) who gave birth between 2011 and 2015. We created one pre-Medicaid expansion (2011-2012) and two post-expansion (2014-2015) cohorts (i.e., previously covered and newly covered by Medicaid). We used ordinary least squares and negative binomial regression models to examine changes in postpartum coverage duration and number of outpatient visits within a year of delivery for the post-expansion cohorts compared to the pre-expansion cohort. We examined monthly and overall changes in outpatient utilization during 0-2 months, 3-6 months, and 7-12 months after delivery. Results: Postpartum coverage duration increased by 3.14 months and 2.78 months for the post-Medicaid expansion previously enrolled and newly enrolled cohorts (p < 0.001), respectively. Overall outpatient care utilization increased by 0.06, 0.19, and 0.34 visits per person for the previously covered cohort and 0.12, 0.13, and 0.26 visits per person for newly covered cohort during 0-2 months, 3-6 months, and 7-12 months, respectively. Monthly change in utilization increased by 0.006 (0-2 months) and 0.004 (3-6 months) visits per person for post-Medicaid previously enrolled cohort and decreased by 0.003 (0-2 months) and 0.02 (7-12 months) visits per person among newly enrolled cohort. Conclusion: Medicaid expansion increased insurance coverage duration and outpatient care utilization during postpartum period in Oregon, potentially contributing to reductions in pregnancy-related mortality and morbidities among birthing individuals.

An integrated cell atlas of the lung in health and disease.

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1+ profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.

Proportion and number of cancer cases and deaths attributable to behavioral risk factors in Vietnam.

Identifying modifiable risk factors that contribute to cancer is essential in setting up preventive strategies. Therefore, this study aimed to estimate the number and proportion of cancer cases and deaths attributable to five behavior-related risk factors-tobacco smoking, second-hand smoking, alcohol consumption, high body mass index and insufficient physical activity in Vietnam in 2020. Population attributable fractions were calculated for relationships of risk factors and cancer types based on sufficient evidence according to IARC or strong evidence according to WCRF/AICR. Relative risks were retrieved from meta-analyses where possible. Prevalence of risk factors was obtained from the most current available nationally representative population surveys in Vietnam. Cancer cases and deaths were obtained from GLOBOCAN 2020. An estimated 40.5% of all cancer cases in men (39 924 cases) and 7.8% in women (6542 cases) were attributable to these risk factors. The proportions of cancer deaths attributable to these risk factors were 44.0% in men (32 807 cases) and 8.9% in women (4235 cases). Tobacco smoking was the leading cause of cancer cases and deaths in men, followed by alcohol consumption and high BMI. In women, high BMI accounted for the highest proportion of cancer cases and second-hand smoking accounted for the highest proportion of cancer deaths. Lung and upper aerodigestive tract cancer cases and deaths could have been reduced at least by half if these risk factors had been eliminated. To reduce cancer incidence and mortality, preventive actions focusing on tobacco control are likely to have the most significant impact, especially in men.

Computational analysis of drug resistance of taxanes bound to human ß-tubulin mutant (D26E).

The single-point mutation D26E in human ß-tubulin is associated with drug resistance seen with two anti-mitotic taxanes (paclitaxel and docetaxel) when used to treat cancers. The molecular mechanism of this resistance remains elusive. However, docetaxel and a third-generation taxane, cabazitaxel, are thought to overcome this resistance. Here, structural models of both the wildtype (WT) and D26E mutant (MT) human ß-tubulin were constructed based on the crystal structure of pig ß-tubulin in complex with docetaxel (PDB ID: 1TUB). The three taxanes were docked into the WT and MT ß-tubulin, and the resulting complexes were submitted to three independent runs of 200 ns molecular dynamic simulations, which were then averaged. MM/GBSA calculations revealed the binding energy of paclitaxel with WT and MT ß-Tubulin to be -101.5 ± 8.4 and -90.4 ± 8.9 kcal/mol, respectively. The binding energy of docetaxel was estimated to be -104.7 ± 7.0 kcal/mol with the WT and -103.8 ± 5.5 kcal/mol with the MT ß-tubulin. Interestingly, cabazitaxel was found to have a binding energy of -122.8 ± 10.8 kcal/mol against the WT and -106.2 ± 7.0 kcal/mol against the MT ß-tubulin. These results show that paclitaxel and docetaxel bound to the MT less strongly than the WT, suggesting possible drug resistance. Similarly, cabazitaxel displayed a greater binding propensity against WT and MT ß-tubulin than the other two taxanes. Furthermore, the dynamic cross-correlation matrices (DCCM) analysis suggests that the single-point mutation D26E induces a subtle dynamical difference in the ligand-binding domain. Overall, the present study revealed how the single-point mutation D26E may reduce the binding affinity of the taxanes, however, the effect of the mutation does not significantly affect the binding of cabazitaxel.