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.

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.

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.

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.

Intranasal therapeutic vaccine containing HBsAg and HBcAg for patients with chronic hepatitis B; 18 months follow-up results of phase IIa clinical study.

AIMS: HBsAg loss with anti-HBs acquisition is considered a functional cure and ideal treatment goal for patients with CHB. Our group have reported the efficacy of therapeutic vaccine with HBsAg and HBcAg (NASVAC) by intranasal and subcutaneous injection. In this study, we investigated the safety and efficacy of newly developed CVP-NASVAC, which contained NASVAC with mucoadhesive carboxyl vinyl polymer (CVP) in the dedicated device. METHODS: A single dose, open-label, phase IIa clinical trial of CVP-NASVAC was conducted. Patients with CHB treated with nucleoside/nucleotide analogs (NAs) and HBV carriers not undergoing anti-HBV treatment were enrolled. CVP-NASVAC was injected through the nose for, in total, 10 times. Participants were followed-up for 18 months, and their HBsAg reduction and anti-HBs induction assessed as endpoints. RESULTS: Among the patients with CHB treated with NAs (n = 27) and HBV carriers without NAs (n = 36), 74.1% and 75.0% exhibited reductions in their baseline HBsAg, and the mean reductions were -0.1454 log10  IU/ml (p < 0.05) and -0.2677 log10  IU/ml (p < 0.05), respectively. Anti-HBs antibody was detected in 40.7% and 58.3% of patients treated with and without NAs, respectively. Six of 71 (9.5%) patients were functionally cured after the CVP-NASVAC treatment. CONCLUSIONS: Anti-HBs induction and HBsAg reduction was observed after CVP-NASVAC treatment in some patients with CHB. The CVP-NASVAC is a safe treatment, which might expect to achieve functional cure for patients with CHB.

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.

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.

Quercetin Impairs HuR-Driven Progression and Migration of Triple Negative Breast Cancer (TNBC) Cells.

In the present study, we have explored the prognostic value of HuR gene as well as protein in breast cancers. Furthermore, we have also investigated the HuR therapeutic relevance in TNBCs, which is an aggressive breast cancer subtype. Using an online meta-analysis tool, we found that HuR protein overexpression positively correlates with reduced overall survival of TNBC patients (p = 0.028). Furthermore, we demonstrated that the TNBC breast cancer cell lines i.e., MDA-MB-231 and MDA-MB-468 are good model systems to study HuR protein, as they both exhibit a significant amount of cytoplasmic HuR (active form). Quercetin treatment significantly inhibited the cytoplasmic HuR in both TNBC cell lines. By using specific HuR siRNA, we established that quercetin-mediated inhibition of adhesion and migration of TNBC cells is dependent on HuR. Upon analyzing adhesion proteins i.e., ß-catenin and CD44, we found that quercetin mediated effect on TNBC adhesion and migration was through the HuR-ß-catenin axis and CD44, independently. Overall, the present results demonstrate that elevated HuR levels are associated with TNBC progression and relapse, and the ability of quercetin to inhibit cytoplasmic HuR protein provides a rationale for using it as an anticancer agent for the treatment of aggressive TNBCs.Supplemental data for this article is available online at at 10.1080/01635581.2021.1952628.

Safety and efficacy of laparoscopic sleeve gastrectomy in patients with portal hypertension with liver function of Childs A.

INTRODUCTION: Advanced liver disease and portal hypertension (PH) are seen as a relative contraindication for bariatric and metabolic surgery. Several studies have shown significant improvement in liver function and liver histology after bariatric surgery. There are very few studies describing bariatric surgery in patients with PH. The purpose of this retrospective study is to evaluate the feasibility and results of laparoscopic sleeve gastrectomy (SG) in patients with PH. MATERIAL AND METHODS: We present our experience of performing laparoscopic SG in 15 patients with evidence of PH. All the patients were Childs Pugh Criteria A. PH was confirmed by the presence of dilated esophageal varices on endoscopy. RESULTS: The mean operative time was 77.33 ± 15.22 min and mean blood loss was 80.67 ± 37.12 ml. The mean length of stay was 2.73 ± 0.59 days. There were no intraoperative or immediate postoperative complications. None of the patients required blood transfusion in the postoperative period. The weight, BMI, Excess body weight loss% (EBWL%), Total weight loss (TWL) and TWL% at 1 year were 86.05 ± 14.40 kg, 31.16 kg/m2 ± 3.82, 63.84% ± 15.24, 31.49 ± 9.54 kg and 26.50 ± 5.42%, respectively. Diabetes and hypertension resolution at 1 year was 80% and 72.72%, respectively. All the patients were followed up for mean 3 ± 1.5 years. There were no immediate or long-term morbidity and mortality noted. CONCLUSION: SG is a feasible and safe option for the treatment of obesity in carefully selected patients with PH with good weight loss and comorbidity resolution.

Probiotics as Prophylaxis for Postoperative Infections of Under-five Children Following Gastrointestinal Surgery.

Purpose: Evaluation of the efficacy of use of probiotics as prophylaxis for postoperative wound infection in under-five children following gastrointestinal surgery. Materials and Methods: This randomized control trial was conducted over a period of 2 years in the pediatric surgery units of a tertiary level hospital in Dhaka, Bangladesh. A total of 60 patients undergoing gastrointestinal surgery under the age of 5 years were included in the study and randomly assigned to two groups - probiotics group (n = 30) and nonprobiotics group (n = 30). Patients in the probiotics group received probiotics in the preoperative (3 days) and postoperative period (7 days) along with traditional gut preparation (antibiotics and mechanical bowel wash). Patients in the nonprobiotic group got only antibiotics and traditional gut preparation. Outcome variables were surgical site infection, fever, c-reactive protein (CRP), total white blood cell (WBC) count, and neutrophil count. Results: Postoperative wound infection was less in the probiotic group (n = 2) compared to the nonprobiotic group (n = 3), but the difference was not statistically significant (P = 0.640). Postoperative CRP level was significantly lower in the probiotics group (P = 0.020). There was more decline in total count of WBCs in postoperative period in the probiotic group. No statistical difference was seen between the groups in postoperative pyrexia, the total count of WBC, and neutrophil count. Conclusion: Use of probiotics along with traditional gut preparation as prophylaxis for postoperative infection in children showed no added benefit in comparison to the use of traditional gut preparation only.

Prognostic and therapeutic relevance of phosphofructokinase platelet-type (PFKP) in breast cancer.

In the present study, we have explored the prognostic value of the Phosphofructokinase Platelet-type (PFKP) expression and its therapeutic relevance in metastatic breast cancer. PFKP immunohistochemistry was performed on Invasive ductal carcinomas (IDCs; n = 87) of breast, and its association with clinicopathological parameters were evaluated. Using online meta-analysis tools, PFKP's prognostic value was investigated in overall breast cancer as well as in triple negative subtype (TNBCs). For in vitro analysis, MDA-MB-231 cells model was used in order to elucidate mechanisms behind PFKP regulated glycolysis and its impact on cancer cell physiology. Therapeutic relevance of PFKP was further evaluated using PFKP siRNA and Quercetin. PFKP protein expression was found to be positively associated with nodal invasion (p = 0.009), receptor (ER & PR) negative status (p = 0.005 & p = 0.028) and reduced overall survival in breast cancer patients (p = 0.014). In MDA-MB-231 cells, quercetin treatment impaired PFKP-LDHA signaling axis thereby inhibiting aerobic glycolysis mediated increased migration of cancer cells. Our present study demonstrates that elevated PFKP levels are associated with basal cells/TNBC subtypes and might serve as prognostic indicator for TNBC patients. Ability of quercetin to inhibit aerobic glycolysis, cell migration and clonogenic potential of malignant breast cancer cells advocates possibility of quercetin in aggressive breast cancer treatment.

May Measurement Month 2019: an analysis of blood pressure screening results from Bangladesh.

According to the Non-communicable disease Risk Factors Survey of 2018, more than one-fifth (21.0%) of adults aged 25 years or older have hypertension and one-third of the adults did not have their blood pressure (BP) measured in their lifetime in Bangladesh. The National Heart Foundation of Bangladesh participated in May Measurement Month (MMM) 2017 and 2018 as well as this 2019 as a part of a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. This opportunistic screening of voluntary participants aged ≥18 years was carried out from May to July 2019. Data were collected from 100 screening sites in 16 districts in Bangladesh. BP measurement, the definition of hypertension, and statistical analysis followed the MMM protocol. Data on 24 941 individuals were analysed. Among the participants, 12 658 (50.8%) were female. After multiple imputation, 6990 (28.0%) had hypertension. Among the 6990 participants with hypertension, 5007 (71.6%) were on antihypertensive medication and 5331 (76.3%) were aware of having hypertension. Among 6990 participants with hypertension, 3217 (46.0%) had controlled BP (<140/90 mmHg) and among the participants with hypertension and on antihypertensive medication, 64.2% had controlled BP. Opportunistic BP screening can identify significant numbers of people with raised BP and thus assist in the prevention of cardiovascular diseases.

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

Hepatitis B Core-related Antigen: An Alternative to Hepatitis B Virus DNA to Assess Treatment Eligibility in Africa.

BACKGROUND: To eliminate hepatitis B virus (HBV) infection, it is essential to scale up testing and treatment. However, conventional tools to assess treatment eligibility, particularly nucleic acid testing (NAT) to quantify HBV DNA, are hardly available and affordable in resource-limited countries. We therefore assessed the performance of a novel immunoassay, hepatitis B core-related antigen (HBcrAg), as an inexpensive (US$ <15/assay) alternative to NAT to diagnose clinically important HBV DNA thresholds (≥2000, ≥20 000, and ≥200 000 IU/mL) and to select patients for antiviral therapy in Africa. METHODS: Using a well-characterized cohort of treatment-naive patients with chronic HBV infection in The Gambia, we evaluated the accuracy of serum HBcrAg to diagnose HBV DNA levels and to indicate treatment eligibility determined by the American Association for the Study of Liver Diseases, based on reference tests (HBV DNA, hepatitis B e antigen, alanine aminotransferase, liver histopathology, and/or FibroScan). RESULTS: A total of 284 treatment-naive patients were included in the analysis. The area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of serum HBcrAg were 0.88 (95% confidence interval [CI], .82-.93), 83.3%, and 83.9%, respectively, to diagnose HBV DNA ≥2000 IU/mL; and 0.94 (95% CI, .88-.99), 91.4%, and 93.2% for ≥200 000 IU/mL. A simplified treatment algorithm using HBcrAg without HBV DNA showed high AUROC (0.91 [95% CI, .88-.95]) with a sensitivity of 96.6% and specificity of 85.8%. CONCLUSIONS: HBcrAg might be an accurate alternative to HBV DNA quantification as a simple and inexpensive tool to identify HBV-infected patients in need of antiviral therapy in low- and middle-income countries.

In-silico assessment of the effects of right ventricular assist device on pulmonary arterial hypertension using an image based biventricular modeling framework.

Pulmonary arterial hypertension (PAH) is a heart disease that is characterized by an abnormally high pressure in the pulmonary artery (PA). While right ventricular assist device (RVAD) has been considered recently as a treatment option for the end-stage PAH patients, its effects on biventricular mechanics are, however, largely unknown. To address this issue, we developed an image-based modeling framework consisting of a biventricular finite element (FE) model that is coupled to a lumped model describing the pulmonary and systemic circulations in a closed-loop system. The biventricular geometry was reconstructed from the magnetic resonance images of two PAH patients showing different degree of RV remodeling and a normal subject. The framework was calibrated to match patient-specific measurements of the left ventricular (LV) and RV volume and pressure waveforms. An RVAD model was incorporated into the calibrated framework and simulations were performed with different pump speeds. Results showed that RVAD unloads the RV, improves cardiac output and increases septum curvature, which are more pronounced in the PAH patient with severe RV remodeling. These improvements, however, are also accompanied by an adverse increase in the PA pressure. These results suggest that the RVAD implantation may need to be optimized depending on disease progression.

Prevalence and risk of hepatitis E virus infection in the HIV population of Nepal.

BACKGROUND: Infection with the hepatitis E virus (HEV) can cause acute hepatitis in endemic areas in immune-competent hosts, as well as chronic infection in immune-compromised subjects in non-endemic areas. Most studies assessing HEV infection in HIV-infected populations have been performed in developed countries that are usually affected by HEV genotype 3. The objective of this study is to measure the prevalence and risk of acquiring HEV among HIV-infected individuals in Nepal. METHODS: We prospectively evaluated 459 Human Immunodeficiency Virus (HIV)-positive individuals from Nepal, an endemic country for HEV, for seroprevalence of HEV and assessed risk factors associated with HEV infection. All individuals were on antiretroviral therapy and healthy blood donors were used as controls. RESULTS: We found a high prevalence of HEV IgG (39.4%) and HEV IgM (15.3%) in HIV-positive subjects when compared to healthy HIV-negative controls: 9.5% and 4.4%, respectively (OR: 6.17, 95% CI 4.42-8.61, p < 0.001 and OR: 3.7, 95% CI 2.35-5.92, p < 0.001, respectively). Individuals residing in the Kathmandu area showed a significantly higher HEV IgG seroprevalance compared to individuals residing outside of Kathmandu (76.8% vs 11.1%, OR: 30.33, 95% CI 18.02-51.04, p = 0.001). Mean CD4 counts, HIV viral load and presence of hepatitis B surface antigen correlated with higher HEV IgM rate, while presence of hepatitis C antibody correlated with higher rate of HEV IgG in serum. Overall, individuals with HEV IgM positivity had higher levels of alanine aminotransferase (ALT) than IgM negative subjects, suggesting active acute infection. However, no specific symptoms for hepatitis were identified. CONCLUSIONS: HIV-positive subjects living in Kathmandu are at higher risk of acquiring HEV infection as compared to the general population and to HIV-positive subjects living outside Kathmandu.

Spectrally and Spatially Multiplexed Serological Array-in-Well Assay Utilizing Two-Color Upconversion Luminescence Imaging.

We demonstrate a simple dual-mode multiplexed array-in-well immunoassay for simultaneous classification and detection of serum IgG and IgM antibodies against influenza A and human adenoviruses based on the color and position of the upconversion luminescence on the array. Biotinylated influenza A/H1N1 and A/H5N1 as well as adenovirus serotype 2 and 5 hexon antigens along with positive and negative controls were printed in an array format onto the bottom of streptavidin-coated microtiter wells. The anti-influenza A and antiadenovirus antibodies present in the sample were captured to the array and detected with antihuman antibody-coated upconverting nanophosphors (UCNPs). The green emitting UCNPs (NaYF4:Yb(3+),Er(3+)) coated with antihuman IgG and blue emitting UCNPs (NaYF4:Yb(3+),Tm(3+)) coated with antihuman IgM were used to detect human IgG and IgM antibodies, respectively. The emission of the bound UCNPs was imaged free of autofluorescence with anti-Stokes photoluminescence microwell imager. No spectral cross-talk was observed between green and blue emitting UCNPs. Also the cross-reactivities between UCNP-conjugates and immobilized human IgG and IgM antibodies were negligible. Position of the signal on the array defined the antigen specificity and the antibody class was defined by the color of the upconversion luminescence. This technology could be used for differentiation between acute infection from past infection and immunity. Additionally, the class of the antibody response can be used for the differentiation between primary and secondary infections, hence, facilitating epidemiological seroprevalence studies.

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.