Canonical WNT/ß-catenin signaling upregulates aerobic glycolysis in diverse cancer types.

Despite many efforts, a comprehensive understanding and clarification of the intricate connections within cancer cell metabolism remain elusive. This might pertain to intracellular dynamics and the complex interplay between cancer cells, and cells with the tumor stroma. Almost a century ago, Otto Warburg found that cancer cells exhibit a glycolytic phenotype, which continues to be a subject of thorough investigation. Past and ongoing investigations have demonstrated intricate mechanisms by which tumors modulate their functionality by utilizing extracellular glucose as a substrate, thereby sustaining the essential proliferation of cancer cells. This concept of "aerobic glycolysis," where cancer cells (even in the presence of enough oxygen) metabolize glucose to produce lactate plays a critical role in cancer progression and is regulated by various signaling pathways. Recent research has revealed that the canonical wingless-related integrated site (WNT) pathway promotes aerobic glycolysis, directly and indirectly, thereby influencing cancer development and progression. The present review seeks to gather knowledge about how the WNT/ß-catenin pathway influences aerobic glycolysis, referring to relevant studies in different types of cancer. Furthermore, we propose the concept of impeding the glycolytic phenotype of tumors by employing specific inhibitors that target WNT/ß-catenin signaling.

Enhancing customer retention in telecom industry with machine learning driven churn prediction.

Customer churn remains a critical concern for businesses, highlighting the significance of retaining existing customers over acquiring new ones. Effective prediction of potential churners aids in devising robust retention policies and efficient customer management strategies. This study dives into the realm of machine learning algorithms for predictive analysis in churn prediction, addressing the inherent challenge posed by diverse and imbalanced customer churn data distributions. This paper introduces a novel approach-the Ratio-based data balancing technique, which addresses data skewness as a pre-processing step, ensuring improved accuracy in predictive modelling. This study fills gaps in existing literature by highlighting the effectiveness of ensemble algorithms and the critical role of data balancing techniques in optimizing churn prediction models. While our research contributes a novel approach, there remain avenues for further exploration. This work evaluates several machine learning algorithms-Perceptron, Multi-Layer Perceptron, Naive Bayes, Logistic Regression, K-Nearest Neighbour, Decision Tree, alongside Ensemble techniques such as Gradient Boosting and Extreme Gradient Boosting (XGBoost)-on balanced datasets achieved through our proposed Ratio-based data balancing technique and the commonly used Data Resampling. Results reveal that our proposed Ratio-based data balancing technique notably outperforms traditional Over-Sampling and Under-Sampling methods in churn prediction accuracy. Additionally, using combined algorithms like Gradient Boosting and XGBoost showed better results than using single methods. Our study looked at different aspects like Accuracy, Precision, Recall, and F-Score, finding that these combined methods are better for predicting customer churn. Specifically, when we used a 75:25 ratio with the XGBoost method, we got the most promising results for our analysis which are presented in this work.

Early Alteration of Right Ventricle-Pulmonary Artery Coupling in Experimental Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Pulmonary hypertension and right ventricular (RV) dysfunction are major prognostic determinants in patients with heart failure with preserved ejection fraction (HFpEF). The underlying pathomechanisms remain unknown. In this context, we sought to study the pathogenesis of pulmonary hypertension and RV dysfunction in a rat model of obesity-associated HFpEF. METHODS AND RESULTS: HFpEF was induced in obesity-prone rats fed a high-fat diet (n=13) and compared with obesity-resistant rats fed with standard chow (n=9). After 12 months, the animals underwent echocardiographic and hemodynamic evaluation followed by tissue sampling for pathobiological assessment. HFpEF rats presented mild RV pressure overload (with increased RV systolic pressure and pulmonary vascular resistance). No changes in pulmonary artery medial thickness and ex vivo vasoreactivity (to acetylcholine and endothelin-1) were observed and RNA sequencing analysis failed to identify gene clustering in HFpEF lungs. However, released nitric oxide levels were decreased in HFpEF pulmonary artery, while lung expression of preproendothelin-1 was increased. In HFpEF rats, RV structure and function were altered, with RV enlargement, decreased RV fractional area change and free wall longitudinal fractional shortening, together with altered right ventricle-pulmonary artery coupling (estimated by tricuspid annular plane systolic excursion/systolic pulmonary artery pressure). Hypertrophy and apoptosis (evaluated by transferase biotin- dUTP nick-end labeling staining) were increased in right and left ventricles of HFpEF rats. There was an inverse correlation between tricuspid annular plane systolic excursion/systolic pulmonary artery pressure and RV apoptotic rate. Plasma levels of soluble suppression of tumorigenicity-2, interleukin-1ß, -6 and -17A were increased in HFpEF rats. CONCLUSIONS: Obesity-associated HFpEF in rats spontaneously evolves to pulmonary hypertension-HFpEF associated with impaired right ventricle-pulmonary artery coupling that appears disproportionate to a slight increase in RV afterload.

7-amino carboxycoumarin 2 inhibits lactate induced epithelial-to-mesenchymal transition via MPC1 in oral and breast cancer cells.

Lactate is an oncometabolite that play important role in tumor aggressiveness. Lactate from the tumor microenvironment (TME) is taken up by cancer cells as an energy resource via mitochondrial oxidative phosphorylation (or OXPHOS). In the present study, by using an online meta-analysis tool we demonstrated that in oral squamous cancer cells (OSCCs) glycolytic and OXPHOS governing genes are overexpressed, like in breast cancer. For experimental demonstration, we treated the OSCC cell line (SCC4) and breast cancer cells (MDA-MB-231) with sodium L-lactate and analyzed its effects on changes in EMT and migration. For the therapeutic intervention of lactate metabolism, we used AZD3965 (an MCT1 inhibitor), and 7ACC2 (an MPC inhibitor). Like breast cancer, oral cancer tissues showed increased transcripts of 12 genes that were previously shown to be associated with glycolysis and OXPHOS. We experimentally demonstrated that L-lactate treatment induced mesenchymal markers and migration of cancer cells, which was significantly neutralized by MPC inhibitor that is, 7ACC2. Such an effect on EMT status was not observed with AZD3965. Furthermore, we showed that lactate treatment increases the MPC1 expression in both cancer cells, and this might be the reason why cancer cells in the high lactate environment are more sensitive to 7ACC2. Overall, our present findings demonstrate that extracellular lactate positively regulates the MPC1 protein expression in cancer cells, thereby putting forward the notion of using 7ACC2 as a potential therapeutic alternative to inhibit malignant oxidative cancers. Future preclinical studies are warranted to validate the present findings.

Evaluating ChatGPT's Accuracy in Responding to Patient Education Questions on Acute Kidney Injury and Continuous Renal Replacement Therapy.

INTRODUCTION: Acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) are critical areas in nephrology. The effectiveness of ChatGPT in simpler, patient education-oriented questions has not been thoroughly assessed. This study evaluates the proficiency of ChatGPT 4.0 in responding to such questions, subjected to various linguistic alterations. METHODS: Eighty-nine questions were sourced from the Mayo Clinic Handbook for educating patients on AKI and CRRT. These questions were categorized as original, paraphrased with different interrogative adverbs, paraphrased resulting in incomplete sentences, and paraphrased containing misspelled words. Two nephrologists verified the questions for medical accuracy. A χ2 test was conducted to ascertain notable discrepancies in ChatGPT 4.0's performance across these formats. RESULTS: ChatGPT provided notable accuracy in handling a variety of question formats for patient education in AKI and CRRT. Across all question types, ChatGPT demonstrated an accuracy of 97% for both original and adverb-altered questions and 98% for questions with incomplete sentences or misspellings. Specifically for AKI-related questions, the accuracy was consistently maintained at 97% for all versions. In the subset of CRRT-related questions, the tool achieved a 96% accuracy for original and adverb-altered questions, and this increased to 98% for questions with incomplete sentences or misspellings. The statistical analysis revealed no significant difference in performance across these varied question types (p value: 1.00 for AKI and 1.00 for CRRT), and there was no notable disparity between the artificial intelligence (AI)'s responses to AKI and CRRT questions (p value: 0.71). CONCLUSION: ChatGPT 4.0 demonstrates consistent and high accuracy in interpreting and responding to queries related to AKI and CRRT, irrespective of linguistic modifications. These findings suggest that ChatGPT 4.0 has the potential to be a reliable support tool in the delivery of patient education, by accurately providing information across a range of question formats. Further research is needed to explore the direct impact of AI-generated responses on patient understanding and education outcomes.

Evaluating ChatGPT's efficacy in assessing the safety of non-prescription medications and supplements in patients with kidney disease.

Background: This study investigated the efficacy of ChatGPT-3.5 and ChatGPT-4 in assessing drug safety for patients with kidney diseases, comparing their performance to Micromedex, a well-established drug information source. Despite the perception of non-prescription medications and supplements as safe, risks exist, especially for those with kidney issues. The study's goal was to evaluate ChatGPT's versions for their potential in clinical decision-making regarding kidney disease patients. Method: The research involved analyzing 124 common non-prescription medications and supplements using ChatGPT-3.5 and ChatGPT-4 with queries about their safety for people with kidney disease. The AI responses were categorized as "generally safe," "potentially harmful," or "unknown toxicity." Simultaneously, these medications and supplements were assessed in Micromedex using similar categories, allowing for a comparison of the concordance between the two resources. Results: Micromedex identified 85 (68.5%) medications as generally safe, 35 (28.2%) as potentially harmful, and 4 (3.2%) of unknown toxicity. ChatGPT-3.5 identified 89 (71.8%) as generally safe, 11 (8.9%) as potentially harmful, and 24 (19.3%) of unknown toxicity. GPT-4 identified 82 (66.1%) as generally safe, 29 (23.4%) as potentially harmful, and 13 (10.5%) of unknown toxicity. The overall agreement between Micromedex and ChatGPT-3.5 was 64.5% and ChatGPT-4 demonstrated a higher agreement at 81.4%. Notably, ChatGPT-3.5's suboptimal performance was primarily influenced by a lower concordance rate among supplements, standing at 60.3%. This discrepancy could be attributed to the limited data on supplements within ChatGPT-3.5, with supplements constituting 80% of medications identified as unknown. Conclusion: ChatGPT's capabilities in evaluating the safety of non-prescription drugs and supplements for kidney disease patients are modest compared to established drug information resources. Neither ChatGPT-3.5 nor ChatGPT-4 can be currently recommended as reliable drug information sources for this demographic. The results highlight the need for further improvements in the model's accuracy and reliability in the medical domain.

A Neutral PCNHCP Co(I)-Me Pincer Complex as a Catalyst for N-Allylic Isomerization with a Broad Substrate Scope.

Earth-abundant-metal catalyzed double bond transposition offers a sustainable and atom-economical route toward the synthesis of internal alkenes. With an emphasis specifically on internal olefins and ethers, the isomerization of allylic amines has been particularly under represented in the literature. Herein, we report an efficient methodology for the selective isomerization of N-allylic organic compounds, including amines, amides, and imines. The reaction is catalyzed by a neutral PCNHCP cobalt(I) pincer complex and proceeds via a π-allyl mechanism. The isomerization occurs readily at 80-90 °C, and it is compatible with a wide variety of functional groups. The in situ formed enamines could additionally be used for a one-pot inverse-electron-demand Diels-Alder reaction to furnish a series of diversely substituted heterobiaryls, which is further discussed in this report.

Personalized Medicine Transformed: ChatGPT's Contribution to Continuous Renal Replacement Therapy Alarm Management in Intensive Care Units.

The accurate interpretation of CRRT machine alarms is crucial in the intensive care setting. ChatGPT, with its advanced natural language processing capabilities, has emerged as a tool that is evolving and advancing in its ability to assist with healthcare information. This study is designed to evaluate the accuracy of the ChatGPT-3.5 and ChatGPT-4 models in addressing queries related to CRRT alarm troubleshooting. This study consisted of two rounds of ChatGPT-3.5 and ChatGPT-4 responses to address 50 CRRT machine alarm questions that were carefully selected by two nephrologists in intensive care. Accuracy was determined by comparing the model responses to predetermined answer keys provided by critical care nephrologists, and consistency was determined by comparing outcomes across the two rounds. The accuracy rate of ChatGPT-3.5 was 86% and 84%, while the accuracy rate of ChatGPT-4 was 90% and 94% in the first and second rounds, respectively. The agreement between the first and second rounds of ChatGPT-3.5 was 84% with a Kappa statistic of 0.78, while the agreement of ChatGPT-4 was 92% with a Kappa statistic of 0.88. Although ChatGPT-4 tended to provide more accurate and consistent responses than ChatGPT-3.5, there was no statistically significant difference between the accuracy and agreement rate between ChatGPT-3.5 and -4. ChatGPT-4 had higher accuracy and consistency but did not achieve statistical significance. While these findings are encouraging, there is still potential for further development to achieve even greater reliability. This advancement is essential for ensuring the highest-quality patient care and safety standards in managing CRRT machine-related issues.

Comprehensive analysis of antigenic variations and genomic properties of hepatitis B virus in clinical samples in the mid-north east region of Bangladesh.

This investigation delineates an exhaustive analysis of the clinical, immunological, and genomic landscapes of hepatitis B virus (HBV) infection across a cohort of 22 verified patients. The demographic analysis unveiled a pronounced male bias (77.27%), with patient ages spanning 20 to 85 years and durations of illness ranging from 10 days to 4 years. Predominant clinical manifestations included fever, fatigue, anorexia, abdominal discomfort, and arthralgia, alongside observed co-morbidities such as chronic renal disorders and hepatocellular carcinoma. Antigenic profiling of the HBV envelope proteins elucidated significant heterogeneity among the infected subjects, particularly highlighted by discordances in the detection capabilities of small and large HBsAg assays, suggesting antigenic diversity. Quantitative assessment of viral loads unveiled a broad spectrum, accompanied by atypical HBeAg reactivity patterns, challenging the reliability of existing serological markers. Correlative studies between viral burden and antigenicity of the envelope proteins unearthed phenomena indicative of diagnostic evasion. Notably, samples demonstrating robust viral replication were paradoxically undetectable by the large HBsAg ELISA kit, advocating for more sophisticated diagnostic methodologies. Genotypic examination of three HBV isolates classified them as genotype D (D2), with phylogenetic alignment to strains from various global origins. Mutational profiling identified pivotal mutations within the basic core promoter and preS2/S1 regions, associated with an augmented risk of hepatocellular carcinoma. Further, mutations discerned in the small HBsAg and RT/overlap regions were recognized as contributors to vaccine and/or diagnostic escape mechanisms. In summation, this scholarly discourse elucidates the intricate interplay of clinical presentations, antigenic diversity, and genomic attributes in HBV infection, accentuating the imperative for ongoing investigative endeavors to refine diagnostic and therapeutic modalities.

Commonly consumed processed packaged foods in Bangladesh are unhealthy and their nutrient contents are not in conformity with the label declaration.

The present study was undertaken to identify the major nutrient content in processed foods commonly consumed in Bangladesh, their label conformity healthiness, and percent daily nutrient contribution. Twenty-four nationally representative composite samples were analyzed using AOAC and other standard methods. Results were compared with label information using a restrictive approach and EU tolerance guidelines. The healthiness of the products was evaluated in terms of the Health Star Rating (HSR) scheme and the UK traffic light labeling system. Among the analyzed samples, fried pulse, chanachur, lozenge, and fried peas had the highest amount of protein, fat, carbohydrates, and dietary fiber, respectively. Biscuits and milk chocolate had high levels of trans fatty acids (TFA) and saturated fatty acids (SFA). It was observed that around half of the products lacked information about saturated fatty acid (46%), followed by total dietary fiber and trans-fat (38% each). Other information was missing in one-fifth of the products, namely protein (17%), total fat (17%), available carbohydrate (17%), energy (17%), sugar (21%), and salt (21%). Label compliance analysis according to the restrictive approach revealed that none of the products accurately reported the salt, sugar, saturated fat, and trans fat content on the label. According to the EU tolerance guideline, approximately half of the products had protein (58%), fat (54%), and carbohydrate (42%) levels that fell within the EU tolerance limit. However, only around one-third of the samples had sugar (21%), salt (38%), and saturated fat (33%) levels that met the EU tolerance limit. In terms of healthiness analysis, according to the HSR, the range of stars was between 0.5 and 2.5 of the foods where fried peas got the highest rating (2.5 stars), while in terms of the UK traffic light system, none of the samples got all green signals. The lozenge got green lights for fat, SFA, and salt contents. It was also found that consumption of 100 g of fried peas or pulse would exceed the acceptable daily limit of salt, sugar, and SFA compared to the daily maximum allowable intake for the 2000 kcal diet recommended by the WHO. However, according to the serving size, biscuits were major contributors of TFA, sugar, and SFA, whereas fried pulse was a key contributor of sodium/salt. Proper regulatory actions should be introduced to promote healthy processed foods with user-friendly front-of-the-pack labeling and monitor their quality to prevent non-communicable diseases (NCDs).

Morphometric features, seminal profile and diluters effect on post-thaw semen quality of Munshiganj cattle in Bangladesh.

The study investigates morphometric features, seminal profile and post-thaw semen quality of Munshiganj cattle. Morphometric features were measured using measuring tape from 20 Munshiganj cattle while coat color was measured by observing in naked eye. Fresh and post thaw semen quality parameters were analyzed using Computer Assisted semen analyzer (CASA). Coat color of Munshiganj male cattle were creamy white to dull pinkish and female were white to creamy. The mean body weight, body length, hearth girth, height at wither, head length, head width, ear length, ear width, fore leg length, hind leg length, tail length, tail doc circumference, horn length, horn diameter and mouth circumference were 362.80 kg, 137.31 cm, 160.66 cm, 135.21 cm, 50.97 cm, 20.58 cm, 19.75 cm, 9.88 cm, 73.02 cm, 74.84 cm, 106.10 cm, 20.75 cm, 13.60 cm, 16.12 cm and 43.00 cm, respectively. There was significant difference (p < 0.05) between male and female in terms of body weight (418.00 vs 307.60 kg), heart girth (173.74 vs 147.57 cm), head width (22.50 vs 18.67 cm), horn diameter (18.58 vs 13.66 cm) and mouth circumference (46.60 vs 39.40 cm). Average scrotal length was 16.76 cm while scrotal circumference was 32.70 cm. Age had significant effect (p < 0.05) on morphometric characteristics of Munshiganj male and female cattle. On the other hand, season had no significant effect on semen quality. Mean semen volume, sperm concentration, total motile, progressive, static, slow and live spermatozoa were 5.83 ± 0.88 ml, 1510.27 ± 844.07 million/ml, 91.9 ± 2.17 %, 63.80 ± 12.53 %, 8.10 ± 2.17 %, 0.10 ± 0.10 %, 91.38 ± 0.25 %, respectively. On the other hand, sperm head length and width, sperm tail length of Munshiganj cattle were 10.39 ± 0.16 µm, 4.26 ± 0.07 µm, 21.5 ± 0.52 µm, respectively. Individual breeding bull had a significant (p < 0.05) effect on post-thawed motile sperm percentage. Four different diluters (Triladyl, Steridyl, Tris-egg yolk-Citrate and Andromed) were used to compare the effects of diluter on post-thaw semen quality of Munshiganj cattle and found that diluter had no significant effect (p > 0.05) on post thaw semen quality except slow motility and proximal droplet percentages. Munshiganj cattle had a distinctive phenotypic feature with standard quality semen and had no effect of egg yolk free and egg yolk based diluters on post thaw semen quality.

Tri-model classifiers for EEG based mental task classification: hybrid optimization assisted framework.

The commercial adoption of BCI technologies for both clinical and non-clinical applications is drawing scientists to the creation of wearable devices for daily living. Emotions are essential to human existence and have a significant impact on thinking. Emotion is frequently linked to rational decision-making, perception, interpersonal interaction, and even basic human intellect. The requirement for trustworthy and implementable methods for the detection of individual emotional responses is needed with rising attention of the scientific community towards the establishment of some significant emotional connections among people and computers. This work introduces EEG recognition model, where the input signal is pre-processed using band pass filter. Then, the features like discrete wavelet transform (DWT), band power, spectral flatness, and improved Entropy are extracted. Further, for recognition, tri-classifiers like long short term memory (LSTM), improved deep belief network (DBN) and recurrent neural network (RNN) are used. Also to enhance tri-model classifier performance, the weights of LSTM, improved DBN, and RNN are tuned by model named as shark smell updated BES optimization (SSU-BES). Finally, the perfection of SSU-BES is demonstrated over diverse metrics.

Spatial variation in livelihood security among livestock-based agricultural farming systems in climatically vulnerable Indian Sundarbans.

Farm households in the UNESCO World Heritage site Sundarbans face serious problems, including increased soil salinity, frequent extreme weather events, seawater intrusion and flood damage, all of which cause distress to the livelihoods of the farm families. Policymakers commonly acknowledge livestock as a crucial resource for mitigating economic losses caused by crop failures due to extreme weather events. Despite Sundarbans' vulnerability to extreme weather events, smallholder farmers' livelihoods vary across the region. Identifying spatial livelihood variations aids in targeted strategies to address climate extremes. We chose the highest cow- and buffalo-populated blocks among the 19 blocks in the Sundarbans to assess variations in livelihood dimensions, including nutritional, economic, social and infrastructural security. We used dummy variable regression models to examine the differences in livelihood security dimensions among households living in different locations. The study found that Namkhana had the highest livelihood security score among the blocks studied, while Gosaba had the lowest score because it's in a remote area with limited infrastructure. The study found a significant difference in the overall livelihood security score among the blocks we examined, indicating the need for a location-specific, cluster-based approach for the overall development of the Sundarbans. The study can shape a policy framework for socio-economic development in the Indian Sundarbans through its findings on location-specific livelihood security. For securing smallholder farmers' livelihoods in the vulnerable Sundarbans region, policymakers must give priority to improving infrastructure, viz., roads, marketing facilities and animal healthcare centers.

Performance of ChatGPT on Nephrology Test Questions.

BACKGROUND: ChatGPT is a novel tool that allows people to engage in conversations with an advanced machine learning model. ChatGPT's performance in the US Medical Licensing Examination is comparable with a successful candidate's performance. However, its performance in the nephrology field remains undetermined. This study assessed ChatGPT's capabilities in answering nephrology test questions. METHODS: Questions sourced from Nephrology Self-Assessment Program and Kidney Self-Assessment Program were used, each with multiple-choice single-answer questions. Questions containing visual elements were excluded. Each question bank was run twice using GPT-3.5 and GPT-4. Total accuracy rate, defined as the percentage of correct answers obtained by ChatGPT in either the first or second run, and the total concordance, defined as the percentage of identical answers provided by ChatGPT during both runs, regardless of their correctness, were used to assess its performance. RESULTS: A comprehensive assessment was conducted on a set of 975 questions, comprising 508 questions from Nephrology Self-Assessment Program and 467 from Kidney Self-Assessment Program. GPT-3.5 resulted in a total accuracy rate of 51%. Notably, the employment of Nephrology Self-Assessment Program yielded a higher accuracy rate compared with Kidney Self-Assessment Program (58% versus 44%; P < 0.001). The total concordance rate across all questions was 78%, with correct answers exhibiting a higher concordance rate (84%) compared with incorrect answers (73%) ( P < 0.001). When examining various nephrology subfields, the total accuracy rates were relatively lower in electrolyte and acid-base disorder, glomerular disease, and kidney-related bone and stone disorders. The total accuracy rate of GPT-4's response was 74%, higher than GPT-3.5 ( P < 0.001) but remained below the passing threshold and average scores of nephrology examinees (77%). CONCLUSIONS: ChatGPT exhibited limitations regarding accuracy and repeatability when addressing nephrology-related questions. Variations in performance were evident across various subfields.

Salt Intake Estimation from Urine Samples in South Asian Population: Scoping Review.

The World Health Organization recommended reducing one's salt intake below 5 g/day to prevent disability and death from cardiovascular and other chronic diseases. This review aimed to identify salt estimation at the population level in South Asian countries, namely Afghanistan, Bangladesh, Bhutan, India, Nepal, Pakistan, and Sri Lanka. We searched electronic databases and government websites for the literature and reports published between January 2011 and October 2021 and also consulted key informants for unpublished reports. We included studies that assessed salt intake from urinary sodium excretion, either spot urine or a 24 h urine sample, on a minimum of 100 samples in South Asian countries. We included 12 studies meeting the criteria after screening 2043 studies, out of which five followed nationally representative methods. This review revealed that salt intake in South Asian countries ranges from 6.7-13.3 g/day. The reported lowest level of salt intake was in Bangladesh and India, and the highest one was in Nepal. The estimated salt intake reported in the nationally representative studies were ranging from 8 g/day (in India) to 12.1 g/day (in Afghanistan). Salt consumption in men (8.9-12.5 g/day) was reported higher than in women (7.1-12.5 g/day). Despite the global target of population salt intake reduction, people in South Asian countries consume a much higher amount of salt than the WHO-recommended level.

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.

Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders.

Hepatitis B vaccine induces the production of antibodies against hepatitis B surface antigen (anti-HBs) and prevents hepatitis B virus (HBV) infection. However, 5-10% of individuals cannot develop anti-HBs even after multiple vaccinations (HB vaccine non-responders). We developed an intranasal vaccine containing both HBs antigen (HBsAg) and HB core antigen (HBcAg) and mixed it with a viscosity enhancer, carboxyl vinyl polymer (CVP-NASVAC). Here, we investigated the prophylactic capacity of CVP-NASVAC in HB vaccine non-responders. Thirty-four HB vaccine non-responders were administered three doses of intranasal CVP-NASVAC. The prophylactic capacity of CVP-NASVAC was assessed by evaluating the induction of anti-HBs and anti-HBc (IgA and IgG) production, HBV-neutralization activity of sera, and induction of HBs- and HBc-specific cytotoxic T lymphocytes (CTLs). After CVP-NASVAC administration, anti-HBs and anti-HBc production were induced in 31/34 and 27/34 patients, respectively. IgA anti-HBs and anti-HBc titers significantly increased after CVP-NASVAC vaccination. HBV-neutralizing activity in vitro was confirmed in the sera of 26/29 CVP-NASVAC-administered participants. HBs- and HBc-specific CTL counts substantially increased after the CVP-NASVAC administration. Mild adverse events were observed in 9/34 participants; no serious adverse events were reported. Thus, CVP-NASVAC could be a beneficial vaccine for HB vaccine non-responders.

Development of Therapy Based on the Exploration of Biological Events Underlying the Pathogenetic Mechanisms of Chronic Hepatitis B Infection.

According to the World Health Organization (WHO), an estimated 296 million people are chronically infected with hepatitis B virus (HBV). Approximately 15-25% of these people develop complications such as advanced chronic liver diseases (ACLDs). Mortality due to HBV-related complications accounted for an estimated 882,000 deaths in 2019. Potent preventive vaccines have already restricted new HBV infections, and several drugs are available to treat chronic HBV infections. However, the positive impacts of these drugs have been recorded in only a few patients with chronic HBV infection. These drugs do not show long-term efficacy and cannot halt the progression to complications. Thus, more effective and evidence-based therapeutic strategies need to be urgently developed for patients with chronic HBV infection. CHB is a pathological entity induced by HBV that progresses due to impaired host immunity. This indicates the inherent limitations of antiviral-drug-based monotherapy for treating patients with chronic HBV infection. Additionally, commercially available antiviral drugs are not available to patients in developing and resource-constrained countries, posing a challenge to achieving the following WHO goal: "Elimination of Hepatitis by 2030". As such, this review aimed to provide insights regarding evidence-based and effective management strategies for chronic HBV infection.

Combination of 3PO analog PFK15 and siPFKL efficiently suppresses the migration, colony formation ability, and PFK-1 activity of triple-negative breast cancers by reducing the glycolysis.

Among all the subtypes of breast cancer, triple-negative breast cancer (TNBC) has been associated with the worst prognosis. Recently, for many solid tumors (including breast cancer) metabolic reprogramming has appeared as a cancer cell hallmark, and the elevated glycolytic pathway has been linked to their aggressive phenotype. In the present study, we evaluated the prognostic and therapeutic relevance of PFKFB3 (6-phosphofructo-2- kinase/fructose-2,6-bisphosphatase) in TNBCs. Prognostic significance of PFKFB3 expression was evaluated in overall breast cancers as well as in TNBCs. PFKFB3 inhibitor (3PO potent analogue i.e., PFK15) cytotoxicity in TNBC cell lines (MDA-MB-231 and MDA-MB-468) was analyzed using an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cancer cell physiological characteristics like clonogenicity and migration were also investigated after PFK15 treatment. As fructose-2,6-bisphosphate (F-2,6-BP), has been associated with increased PFK-1 activity, the effect of PFKFB3 inhibition by PFK15 was investigated on two major isoforms of phosphofructokinase-1 (PFK-1) in breast cancer, that is, phosphofructokinase-platelet type (PFKP) and phosphofructokinase-liver type (PFKL) (relevant to breast cancer). For PFKL inhibition, the siRNA approach was used. PFKFB3 expression was significantly correlated with inferior overall survival in breast cancer patients including TNBCs. PFK15 treatment in TNBC cells (i.e., MDA-MB-231 and MDA-MB-468) resulted in a decreased PFKP expression, thereby leading to reduced colony formation ability, migration rate, and extracellular lactate levels. However, to our surprise PFK15 treatment in both TNBC cells also resulted in elevated PFKL levels. Our results demonstrated that the combinatorial inhibition of PFK15 with siPFKL was more effective in TNBC cells, as it led to a decrease in colony formation ability, migration rate, extracellular lactate levels, and PFK-1 activity when compared with individual treatments. Using bona fide PFKFB3 inhibitor, that is, AZ67, we further show that AZ67 treatment to TNBC cells has no effect either on the expression of PFKP and PFKL, or on the lactate production. In summary, our present in vitro study demonstrated that 3PO derived PFK15 mechanism of action is totally different from AZ67 in TNBC cells. However, we advocate that the PFK15-mediated inhibition (along with PFKL) on the TNBCs migration, colony formation, and PFK-1 activity can be further explored for the therapeutic advantage of TNBC patients.