The contribution of cumulative blood pressure load to dementia, cognitive function and mortality in older adults.

BACKGROUND: Few studies evaluated the contribution of long-term elevated blood pressure (BP) towards dementia and deaths. We examined the association between cumulative BP (cBP) load and dementia, cognitive decline, all-cause and cardiovascular deaths in older Australians. We also explored whether seated versus standing BP were associated with these outcomes. METHODS: The Sydney Memory and Aging Study included 1037 community-dwelling individuals aged 70-90 years, recruited from Sydney, Australia. Baseline data was collected in 2005-2007 and the cohort was followed for seven waves until 2021. cSBP load was calculated as the area under the curve (AUC) for SBP ≥140 mmHg divided by the AUC for all SBP values. Cumulative diastolic BP (cDBP) and pulse pressure (cPP) load were calculated using thresholds of 90 mmHg and 60 mmHg. Cox and mixed linear models were used to assess associations. RESULTS: Of 527 participants with both seated and standing BP data (47.7% men, median age 77), 152 (28.8%) developed dementia over a mean follow-up of 10.5 years. Higher cPP load was associated with a higher risk of all-cause deaths, and cSBP load was associated with a higher risk of cardiovascular deaths in multivariate models (P for trend < 0.05). Associations between cPP load, dementia and cognitive decline lost statistical significance after adjustment for age. Differences between sitting and standing BP load were not associated with the outcomes. CONCLUSION: Long-term cPP load was associated with a higher risk of all-cause deaths and cSBP load associated with a higher risk of cardiovascular deaths in older Australians.

Self-care behaviours of first-generation Chinese immigrants living with cardiovascular disease: A qualitative study.

AIM: To identify and describe self-care behaviours performed by Chinese immigrants living with cardiovascular disease in Australia, and factors perceived as barriers and facilitators to evidence-based cardiac self-care. DESIGN: A qualitative descriptive design. METHODS: Individual semi-structured phone interviews were conducted among participants meeting the following criteria: (1) first-generation Chinese immigrants to Australia, born in Mainland China, Hong Kong, Macao or Taiwan; (2) Australian permanent residents or citizens; (3) self-reported or medically diagnosed with coronary heart disease, stroke or heart failure; (4) able to speak English or Mandarin; (5) able to provide informed consent, excluding those with history or evidence of impaired cognition such as dementia. Participants were recruited via social media, Chinese community associations and medical centres from September 2021 to June 2022. Data were analysed using inductive and deductive thematic analysis, guided by the Middle-Range Theory of Self-Care of Chronic Illness. The study was reported in line with the COREQ checklist. RESULTS: Twenty participants were interviewed, 60% female, mean age 69.9 years. Most migrated to Australia at older age following their retirement in China; most had limited English proficiency. Many practiced adequate self-care for their CVD in self-care maintenance and monitoring. Variously, they adopted heart-healthy diets, developed exercise routines, attended medical services and closely monitored their body signs and symptoms. However, self-adjusting medications, taking Traditional Chinese Medicine and self-administering health supplements were prevalent practices and first-response management of acute cardiac symptoms was suboptimal. Linguistic and cultural barriers to obtaining mainstream heart health information meant most participants resorted to informal, anecdotal and mainland Chinese sources. CONCLUSION: Diverse factors were held responsible for sub-optimal self-care behaviours but lack of access to linguistically and culturally appropriate heart health information was widely blamed. Linguistically and culturally appropriate community-based heart health education programmes are urgently needed, targeting healthy lifestyle modification, medication literacy and cardiac symptom management. IMPACT: Study findings can be used to improve cardiac nurses' cultural sensitivity and practices targeting Chinese immigrants. Partnering with Chinese community associations offers health service providers and policymakers an innovative route to co-design and deliver targeted heart health education interventions and support for this population. PUBLIC CONTRIBUTION: Chinese community centre managers contributed to data collection by supporting participant recruitment.

Anti-plasticizing effect of water on prilocaine and lidocaine - the role of the hydrogen bonding pattern.

It is generally accepted that water, as an effective plasticizer, decreases the glass transition temperatures (Tgs) of amorphous drugs, potentially resulting in physical instabilities. However, recent studies suggest that water can also increase the Tgs of the amorphous forms of the drugs prilocaine (PRL) and lidocaine (LID), thus acting as an anti-plasticizer. To further understand the nature of the anti-plasticizing effect of water, interactions with different solvents and the resulting structural features of PRL and LID were investigated by Fourier transform infrared spectroscopy (FTIR) and quantum chemical simulations. Heavy water (deuterium oxides) was chosen as a solvent, as the deuterium and hydrogen atoms are electronically identical. It was found that substituting hydrogen with deuterium showed a minimal impact on the anti-plasticization of water on PRL. Ethanol and ethylene glycol were chosen as solvents to compare the hydrogen bonding patterns occurring between the hydroxyl groups of the solvents and PRL and LID. Comparison of the various Tgs showed a weaker anti-plasticizing potential of these two solvents on PRL and LID. The frequency shifts of the amide CO groups of PRL and LID due to the interactions with water, heavy water, ethanol, and ethylene glycol as observed in the FTIR spectra showed a correlation with the binding energies calculated by quantum chemical simulations. Overall, this study showed that the combination of weak hydrogen bonding and strong electrostatic contributions in hydrated PRL and LID could play an important role in inducing the anti-plasticizing effect of water on those drugs.

Amplified Assembly of G-Quadruplex-Decorated DNA Network Nanostructure toward AIE Signaling-Based Sensitive Biosensing.

Aggregation-induced emission (AIE) has offered a promising approach for developing low-background fluorescent methods; however, its applications often suffer from complex probe synthesis and poor biocompatibility. Herein, a novel AIE biosensing method for kanamycin antibiotic assays was developed by utilizing a DNA network nanostructure assembled from an aptamer recognition reaction to capture a large number of tetraphenylethylene fluorogen-labeled signal DNA (DTPE) probes. Due to the excellent hydrophilicity of the oligonucleotides, DTPE exhibited excellent water solubility without obvious background signal emission. Based on an ingenious nucleotide design, an abundance of G-quadruplex blocks neighboring the captured DTPE were formed on the DNA nanostructure. Because of the greatly restricted free motion of DTPE by this unique nanostructure, a strong AIE fluorescence signal response was produced to construct the signal transduction strategy. Together with target recycling and rolling circle amplification-based cascade nucleic acid amplification, this method exhibited a wide linear range from 75 fg mL-1 to 1 ng mL-1 and a detection limit down to 24 fg mL-1. The excellent analytical performance and effective manipulation improvement of the method over previous approaches determine its promising potential for various applications.

Service use and glycaemic control of young people with type 1 diabetes transitioning from paediatric to adult care: a 5-year study.

BACKGROUND: Regular contact with specialist care has been linked to better diabetes outcomes for young people with type 1 diabetes (YPwT1D), but evidence is limited to population-based service usage and outcomes. AIMS: This observational 5-year study sought to capture YPwT1D living in the study catchment area (covering metropolitan, regional and rural Australia) as they transitioned to adult-based diabetes healthcare services and to describe their glycaemic control and complication rates, service usage and associated factors. METHODS: Records between 2010 and 2014 in a public healthcare specialist diabetes database were extracted, care processes and outcomes were described, and associations were sought between episodes of care (EOC) and potentially predictive variables. RESULTS: Annual cohort numbers increased yearly, but without significant differences in demographic characteristics. Each year around 40% had no reported planned specialist care, and the average number of planned EOC decreased significantly year on year. Overall, mean HbA1c levels also reduced significantly, but with higher values recorded for those living in non-metropolitan than metropolitan areas (achieving significance in 3 out of 5 years). Diabetes complication assessments were only reported in 37-46%, indicating one in five with retinopathy and hypertension affecting one in three to five young people. CONCLUSIONS: Findings highlight the importance of investment to address the specific needs of adolescents and young adults and demonstrate the need for better support during these vulnerable early years, particularly for non-metropolitan residents. This will entail changes to funding mechanisms, the health workforce and infrastructure, and new models of care to provide equity of access and quality of specialist care.

Impact of COVID-19 on risks and deaths of non-communicable diseases in the Western Pacific region.

Countries and areas in the Western Pacific region (WPR) experienced the COVID-19 pandemic and took various preventive measures, which affected non-communicable diseases (NCDs) risks and mortality. Due to differences in COVID-19 prevention measures and other characteristics such as culture, religions, political systems, socioeconomic development, lifestyles, and health care systems, the effects of COVID-19 on NCDs varied greatly among WPR countries. Most countries had an increased all-cause and NCDs mortality during the pandemic, but some developed countries, including New Zealand, Singapore and Australia reported decreased mortality. The pandemic and the preventive measures increased NCD risk factors including unhealthy diet, lack of physical activity and sleep disorders. The effects varied by socioeconomic status and health conditions. COVID-19 related stress, food shortages, and confined lifestyle had immediate detrimental effects on NCDs, and also affected pregnancy outcomes with long-term effects on NCDs risks in coming years.

[Advances in the role and mechanism of NK cell immune response mediated by NKG2A-HLA-E axis in viral infectious diseases].

Natural killer (NK) cells directly lysis the virus-infected cells through rapidly releasing cytotoxic mediators and cytokines. The balance between inhibitory and activated receptors on the surface of NK cells, as well as the corresponding ligands expressed on target cells are involved in the regulation of the cytotoxic function of NK cells. NKG2A is one of the highly anticipated inhibitory receptors expressed on NK cells, which can inhibit the cytotoxicity of NK cells to autologous normal tissue cells through interacting with the ligand HLA-E. The studies have shown that HLA-E is overexpressed on virus-infected cells and forms a complex with peptides derived from viral proteins. The interaction of HLA-E and NKG2A can regulate the functions of NK cells, participateing the pathogenesis process of virus infectious diseases. This review outlines the characteristics of the molecular interaction between NKG2A and HLA-E, as well as the mechanisms of NKG2A-HLA-E axis in regulating NK cell responses.

Long-Term Consumption of 6 Different Beverages and Cardiovascular Disease-Related Mortality: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

The relationship between beverage consumption and risk of cardiovascular disease has been extensively examined in cross-sectional studies. However, limited studies have investigated beverage consumption as a longer-term habitual behavior, which is important owing to potential cumulative harmful or beneficial cardiovascular effects. We examined the association between the long-term consumption of 6 types of beverages (sugar-sweetened or artificially sweetened beverages, tea, coffee, fruit juice, energy drinks, and alcohol) and cardiovascular mortality, by considering sex differences. We conducted a systematic search of MEDLINE, EMBASE, CINAHL, Web of Science, and Scopus databases from 2010 to December 2023. Of 8049 studies identified, 20 studies were included for meta-analysis. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with the use of a random-effects model. We found that long-term coffee consumption was related to reduced cardiovascular disease-related mortality in males (pooled HR: 0.63; 95% CI: 0.46, 0.87; P = 0.005) but not in females (HR: 0.78; 95% CI: 0.60, 1.02; P = 0.07). Long-term higher intake of tea was associated with lower risk of cardiovascular disease-related mortality in all adults (pooled HR: 0.81; 95% CI: 0.72, 0.92; P ≤ 0.001). Higher alcohol intake was linked to higher stroke in both males (pooled HR: 1.44; 95% CI: 1.06, 1.94; P = 0.02) and females (pooled HR: 2.26; 95% CI: 1.34, 3.81; P = 0.002). Higher sugar-sweetened beverage intake was in relation to higher cardiovascular disease-related mortality (pooled HR: 1.31; 95% CI: 1.16, 1.46; P ≤ 0.0001). We concluded that long-term habitual coffee consumption is beneficial for males, and tea consumption is beneficial for all adults. Long-term high alcohol and sugar-sweetened beverage consumption increased risk of cardiovascular disease-related mortality for both males and females. However, we were unable to draw conclusions on the potential benefit or harm of the long-term consumption of fruit juice and energy drinks on cardiovascular disease-related mortality owing to the limited number of studies available. This review was registered at PROSPERO as CRD42020214679.

Organoids as an in vitro model to study human tumors and bacteria.

Organoids faithfully replicate the morphological structure, physiological functions, stable phenotype of the source tissue. Recent research indicates that bacteria can significantly influence the initiation, advancement, and treatment of tumors. This article provides a comprehensive review of the applications of organoid technology in tumor research, the relationship between bacteria and the genesis and development of tumors, and the exploration of the impact of bacteria on tumors and their applications in research.

The contribution of raised blood pressure to all-cause and cardiovascular deaths and disability-adjusted life-years (DALYs) in Australia: Analysis of global burden of disease study from 1990 to 2019.

AIMS: In a high-income country, Australia, it is unclear how raised systolic blood pressure (SBP) ranks among other risk factors regarding the overall and cardiovascular disease (CVD) burden, and whether the situation has changed over time. METHODS: We analysed the 2019 Global Burden of Disease (GBD) data, with focus on Australia. We assessed ten leading risk factors for all-cause and CVD deaths and disability-adjusted life-years (DALYs) and compared findings with the Australian Burden of Diseases Study. RESULTS: From 1990 to 2019, raised SBP remained the leading risk factor for attributable all-cause deaths (followed by dietary risks and tobacco use), accounting for 29,056/75,235 (95% Uncertainty Interval (UI) [24,863 to 32,915]) deaths in 1990; 21,845/76,893 [17,678 to 26,044] in 2010; and 25,498/90,393 [20,152 to 30,851] in 2019. Contributions of raised SBP to cardiovascular deaths for both sexes were 54.0% [45.8 to 61.5] in 1990, 44.0% [36.7 to 51.3] in 2010 and 43.7% [36.2 to 51.6] in 2019, respectively. The contribution of raised SBP to cardiovascular deaths declined between 1990 and 2010 but exhibited an increase in males from 2010 onwards, with figures of 52.6% [44.7 to 60.0] in 1990, 43.1% [36.0 to 50.5] in 2010 and 43.5% [35.7 to 51.4] in 2019. The contribution of raised SBP to stroke deaths and DALYs in males aged 25-49 years were higher than other age groups, in excess of 60% and increasing steeply between 2010 and 2019. CONCLUSION: Raised SBP continues to be the leading risk factor for all-cause and cardiovascular deaths in Australia. We urge cross-disciplinary stakeholder engagement to implement effective strategies to detect, treat and control raised blood pressure as a central priority to mitigate the CVD burden.

The state of health professions students' self-directed learning ability during online study and the factors that influence it.

BACKGROUND: Universities have widely switched from traditional face-to-face classes to online instruction as a result of the epidemic. Self-directed learning is becoming the new norm for university students' learning styles. The ability of health professions students to learn independently during online study directly impacts the effectiveness of online medical education. The ability to learn on their own initiative may be affected by health professions students' professional identities, defined as their positive perceptions, evaluations, emotional experiences, and identity as professionals related to medicine. This study aimed to look into the current status and the factors that influence health professions students' self-directed learning ability (SDLA) during online study and its relationship with professional identity. METHODS: This study was conducted from September to November 2022 at a medical school in East China. An online questionnaire was used to collect participants' status of online learning, self-directed learning ability (SDLA), and professional identity. RESULTS: One thousand two hundred ninety-eight health professions students demonstrated intermediate self-directed learning ability during online study. In terms of teacher-student interaction (F = 14.778, P < 0.001), student-student interaction (F = 15.713, P < 0.001), and learning concentration (F = 13.424, P < 0.001), there were significant differences in health professions students' self-directed learning ability. Professional identity and self-directed learning ability positively correlated (r = 0.589-0.802, P < 0.01). Academic atmosphere and professional identity were significant predictors. CONCLUSIONS: The self-directed learning ability of health professions students while receiving instruction online is at an intermediate level and is influenced by several factors. Developing health professions students' professional identities can enhance their ability for self-directed learning.

Molecular interactions of hydrated co-amorphous systems of prilocaine and lidocaine.

It is generally accepted that water as a plasticizer can decrease the glass transition temperatures (Tgs) of amorphous drugs and drug excipient systems. However, previous studies suggest that water, as an anti-plasticizer, can increase the Tgs of co-amorphous systems of prilocaine (PRL) and lidocaine (LID). In order to investigate the intermolecular interactions between water and co-amorphous PRL-LID systems, Fourier transform infrared spectroscopy (FTIR) and principal component analysis (PCA) were conducted. Water was found to bind with the carbonyl groups of PRL and LID molecularly evenly in the hydrated co-amorphous PRL-LID systems. Quantum chemical simulations visually confirmed the interactions between water and co-amorphous PRL-LID systems. Furthermore, the physical stability of hydrated co-amorphous PRL-LID systems was improved due to the anti-plasticizing effect of water, compared with the anhydrous samples. The preference of water to interact with the carbonyl groups of PRL and LID as binding sites could be associated with the anti-plasticizing effect of water on the co-amorphous PRL-LID systems.

Potassium-Enriched Salt Substitutes: A Review of Recommendations in Clinical Management Guidelines.

Excess dietary sodium intake and insufficient dietary potassium intake are both well-established risk factors for hypertension. Despite some successful initiatives, efforts to control hypertension by improving dietary intake have largely failed because the changes required are mostly too hard to implement. Consistent recent data from randomized controlled trials show that potassium-enriched, sodium-reduced salt substitutes are an effective option for improving consumption levels and reducing blood pressure and the rates of cardiovascular events and deaths. Yet, salt substitutes are inconsistently recommended and rarely used. We sought to define the extent to which evidence about the likely benefits and harms of potassium-enriched salt substitutes has been incorporated into clinical management by systematically searching guidelines for the management of hypertension or chronic kidney disease. We found incomplete and inconsistent recommendations about the use of potassium-enriched salt substitutes in the 32 hypertension and 14 kidney guidelines that we reviewed. Discussion among the authors identified the possibility of updating clinical guidelines to provide consistent advice about the use of potassium-enriched salt for hypertension control. Draft wording was chosen to commence debate and progress consensus building: strong recommendation for patients with hypertension-potassium-enriched salt with a composition of 75% sodium chloride and 25% potassium chloride should be recommended to all patients with hypertension, unless they have advanced kidney disease, are using a potassium supplement, are using a potassium-sparing diuretic, or have another contraindication. We strongly encourage clinical guideline bodies to review their recommendations about the use of potassium-enriched salt substitutes at the earliest opportunity.

Impact of Fruit and Fruit Juice on Death and Disease Incidence: A Sex-Specific Longitudinal Analysis of 18 603 Adults.

BACKGROUND: The health benefits of fruits are well established, but fruit juice has been more controversial. Fruit and juice are often ingested with other foods, which prompted our investigation to determine whether fruit consumed as juice may negate the beneficial effects of consuming whole fruit in people with cardiovascular disease. METHODS AND RESULTS: We retrospectively analyzed data from a population-based study in Australia (the 45 and Up Study) linked with hospitalization and mortality data up to September 2018. Kaplan-Meier survival estimates and Cox proportional hazards models were used to examine effects of fruit, fruit juice, and the combination of fruit and fruit juice in relation to death and disease incidence among men and women living with cardiovascular disease. A total of 7308 deaths occurred among 18 603 participants diagnosed with cardiovascular disease over a 13-year follow-up. After multivariable adjustment, inadequate fruit intake (hazard ratio [HR], 1.12 [95% CI, 1.01-1.24]) and high fruit juice intake (HR, 1.26 [95% CI, 1.12-1.41]) predicted all-cause mortality in women. Also, high fruit juice intake plus either adequate fruit intake (HR, 1.18 [95% CI, 1.02-1.37]) or inadequate fruit intake (HR, 1.43 [95% CI, 1.21-1.69]) predicted mortality in women. No relationships were found in men after multivariable adjustments. Also, we found no prognostic value for fruit and fruit juice intake on disease incidence. CONCLUSIONS: In adults with cardiovascular disease, we found that fruit juice (in combination with adequate or inadequate fruit intake) predicted mortality in women but not in men. These effects became less clear when focusing on disease incidence.

A Positioning and Navigation Method Combining Multimotion Features Dead Reckoning with Acoustic Localization.

Accurate location information can offer huge commercial and social value and has become a key research topic. Acoustic-based positioning has high positioning accuracy, although some anomalies that affect the positioning performance arise. Inertia-assisted positioning has excellent autonomous characteristics, but its localization errors accumulate over time. To address these issues, we propose a novel positioning navigation system that integrates acoustic estimation and dead reckoning with a novel step-length model. First, the features that include acceleration peak-to-valley amplitude difference, walk frequency, variance of acceleration, mean acceleration, peak median, and valley median are extracted from the collected motion data. The previous three steps and the maximum and minimum values of the acceleration measurement at the current step are extracted to predict step length. Then, the LASSO regularization spatial constraint under the extracted features optimizes and solves for the accurate step length. The acoustic estimation is determined by a hybrid CHAN-Taylor algorithm. Finally, the location is determined using an extended Kalman filter (EKF) merged with the improved pedestrian dead reckoning (PDR) estimation and acoustic estimation. We conducted some comparative experiments in two different scenarios using two heterogeneous devices. The experimental results show that the proposed fusion positioning navigation method achieves 8~56.28 cm localization accuracy. The proposed method can significantly migrate the cumulative error of PDR and high-robustness localization under different experimental conditions.

Tenacibaculum tangerinum sp. nov., isolated from a tidal flat sediment.

An orange-coloured bacterium, designated as strain GRR-S3-23T, was isolated from a tidal flat sediment collected from Garorim Bay, Chuncheongbuk-do, Republic of Korea. Cells of GRR-S3-23T were aerobic, Gram-stain-negative, rod-shaped and motile. GRR-S3-23T grew at 18-40 °C (optimum, 30 °C), pH 7.0-9.0 (optimum, pH 7.0) and with 2-4 % NaCl (optimum, 2-3 % w/v). Results of 16S rRNA gene sequence analysis indicated that GRR-S3-23T was closely related to Tenacibaculum aiptasiae a4T (97.6 %), followed by Tenacibaculum aestuarii SMK-4T (97.5 %), Tenacibaculum mesophilum MBIC 1140T (97.4 %), Tenacibaculum singaporense TLL-A2T (97.3 %), Tenacibaculum crassostreae JO-1T (97.2 %),and Tenacibaculum sediminilitoris YKTF-3T (97.1 %). The average amino acid identity values between GRR-S3-23T and the related strains were 86.8-72.8 %, the average nucleotide identity values were 83.3-74.1 %, and the digital DNA-DNA hybridization values were 27.0-19.6 %. GRR-S3-23T possessed menaquinone-6 (MK-6) as major respiratory quinone and had summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c, 20.6 %) and iso-C15 : 1G (10.8 %) as major fatty acids (>10.0 %). The polar lipid profiles of GRR-S3-23T contained phosphatidylethanolamine, one unidentified aminolipid, one unidentified aminophospholipid, three unidentified lipids, one unidentified glycolipid and four unidentified phospholipids. The DNA G+C content of GRR-S3-23T was 33.7%. On the basis of the results of the polyphasic analysis involving phylogenetic, phylogenomic, physiological and chemotaxonomic analyses described in this study, GRR-S3-23T is considered to represent a novel species within the genus Tenacibaculum, for which the name Tenacibaculum tangerinum is proposed. The type strain is GRR-S3-23T (=KCTC 102029T=KACC 23271T=JCM 36353T).

Multisequence MRI-based radiomics nomogram for early prediction of osimertinib resistance in patients with non-small cell lung cancer brain metastases.

Background: Osimertinib resistance is a major problem in the course of targeted therapy for non-small cell lung cancer (NSCLC) patients. To develop and validate a multisequence MRI-based radiomics nomogram for early prediction of osimertinib resistance in NSCLC with brain metastases (BM). Methods: Pretreatment brain MRI of 251 NSCLC patients proven with BM were retrospectively enrolled from two centers (training cohort: 196 patients; testing cohort: 55 patients). According to the gene test result of osimertinib resistance, patients were labeled as resistance and non-resistance groups (training cohort: 65 versus 131 patients; testing cohort: 25 versus 30 patients). Radiomics features were extracted from T2WI, T2 fluid-attenuated inversion recovery (T2-FLAIR), diffusion weighted imaging (DWI) and contrast-enhanced T1-weighted imaging (T1-CE) sequences separately and radiomics score (rad-score) were built from the four sequences. Then a multisequence MRI-based nomogram was developed and the predictive ability was evaluated by ROC curves and calibration curves. Results: The rad-scores of the four sequences has significant differences between resistance and non-resistance groups in both training and testing cohorts. The nomogram achieved the highest predictive ability with area under the curve (AUC) of 0.989 (95 % confidence interval, 0.976-1.000) and 0.923 (95 % confidence interval, 0.851-0.995) in the training and testing cohort respectively. The calibration curves showed excellent concordance between the predicted and actual probability of osimertinib resistance using the radiomics nomogram. Conclusions: The multisequence MRI-based radiomics nomogram can be used as a noninvasive auxiliary tool to identify candidates who were resistant to osimertinib, which could guide clinical therapy for NSCLC patients with BM.

Burden of Hypertensive Heart Disease and High Systolic Blood Pressure in Australia from 1990 to 2019: Results From the Global Burden of Diseases Study.

BACKGROUND: There is a dearth of comprehensive studies examining the burden and trends of hypertensive heart disease (HHD) and high systolic blood pressure (SBP) among the Australian population. We aimed to explore the burden of HHD and high SBP, and how they changed over time from 1990 to 2019 in Australia. METHODS: We analysed data from the Global Burden of Disease study in Australia. We assessed the prevalence, mortality, disability-adjusted life-years (DALY), years lived with disability (YLD) and years of life lost (YLL) attributable to HHD and high SBP. Data were presented as point estimates with 95% uncertainty intervals (UI). We compared the burden of HHD and high SBP in Australia with World Bank defined high-income countries and six other comparator countries with similar sociodemographic characteristics and economies. RESULTS: From 1990 to 2019, the burden of HHD and high SBP in Australia reduced. Age standardised prevalence rate of HHD was 119.3 cases per 100,000 people (95% UI 86.6-161.0) in 1990, compared to 80.1 cases (95% UI 57.4-108.1) in 2019. Deaths due to HDD were 3.4 cases per 100,000 population (95% UI 2.6-3.8) in 1990, compared to 2.5 (95% UI 1.9-3.0) in 2019. HHD contributed to 57.2 (95% UI 46.6-64.7) DALYs per 100,000 population in 1990 compared to 38.4 (95% UI 32.0-45.2) in 2019. Death rates per 100,000 population attributable to high SBP declined significantly over time for both sexes from 1990 (155.6 cases; 95% UI 131.2-177.0) to approximately one third in 2019 (53.8 cases; 95% UI 43.4-64.4). Compared to six other countries in 2019, the prevalence of HHD was highest in the USA (274.3%) and lowest in the UK (52.6%), with Australia displaying the third highest prevalence. Australia ranked second in term of lowest rates of deaths and third for lowest DALYs respectively due to high SBP. From 1990-2019, Australia ranked third best for reductions in deaths and DALYs due to HHD and first for reductions in deaths and DALYs due to high SBP. CONCLUSION: Over the past three decades, the burden of HHD in Australia has reduced, but its prevalence remains relatively high. The contribution of high SBP to deaths, DALYs and YLLs also reduced over the three decades.

Imbalance of Innate and Adaptive Immunity in Esophageal Achalasia.

Background/Aims: Previous studies reveal that immune-mediated neuroinflammation plays a key role in the etiology of esophageal achalasia. However, the understanding of leucocyte phenotype and proportion is limited. This study aim to evaluate the phenotypes of leukocytes and peripheral blood mononuclear cells transcriptomes in esophageal achalasia. Methods: We performed high-dimensional flow cytometry to identified subsets of peripheral leukocytes, and further validated in lower esophageal sphincter histologically. RNA sequencing was applied to investigate the transcriptional changes in peripheral blood mononuclear cells of patients with achalasia. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) was used for estimating the immune cell types. A differential gene expression analysis was performed and the differential expressed genes were subjected to gene ontology, Kyoto Encyclopedia of Genes and Genomes network, protein-protein interaction network construction. Results: An imbalance between innate and adaptive immune cells occurred in achalasia. Specifically, neutrophils and CD8+ T cells increased both in peripheral blood and lower esophageal sphincter in achalasia. Eosinophils decreased in peripheral blood but massively infiltrated in lower esophageal sphincter. CIBERSORT analysis of peripheral blood mononuclear cells RNA sequencing displayed an increased prevalence of CD8+ T cells. 170 dysregulated genes were identified in achalasia, which were enriched in immune cells migration, immune response, etc. Proton pump inhibitor analysis revealed the intersections and gained 7 hub genes in achalasia, which were IL-6, Toll-like receptor 2, IL-1ß, tumor necrosis factor, complement C3, and complement C1q A chain. Conclusion: Patients with achalasia exhibited an imbalance of systematic innate and adaptive immunity, which may play an important role in the development of achalasia.

A single-cell transcriptional landscape of immune cells shows disease-specific changes of T cell and macrophage populations in human achalasia.

Achalasia is a rare motility disorder of the esophagus caused by the gradual degeneration of myenteric neurons. Immune-mediated ganglionitis has been proposed to underlie the loss of myenteric neurons. Here, we measure the immune cell transcriptional profile of paired lower esophageal sphincter (LES) tissue and blood samples in achalasia and controls using single-cell RNA sequencing (scRNA-seq). In achalasia, we identify a pattern of expanded immune cells and a specific transcriptional phenotype, especially in LES tissue. We show C1QC+ macrophages and tissue-resident memory T cells (TRM), especially ZNF683+ CD8+ TRM and XCL1+ CD4+ TRM, are significantly expanded and localized surrounding the myenteric plexus in the LES tissue of achalasia. C1QC+ macrophages are transcriptionally similar to microglia of the central nervous system and have a neurodegenerative dysfunctional phenotype in achalasia. TRM also expresses transcripts of dysregulated immune responses in achalasia. Moreover, inflammation increases with disease progression since immune cells are more activated in type I compared with type II achalasia. Thus, we profile the immune cell transcriptional landscape and identify C1QC+ macrophages and TRM as disease-associated immune cell subsets in achalasia.