Tag: nevin manimala

Cell Death Dis. 2023 Jun 10;14(6):357. doi: 10.1038/s41419-023-05870-5.

ABSTRACT

Pediatric Acute Myeloid Leukemia (AML) is a rare and heterogeneous disease characterized by a high prevalence of gene fusions as driver mutations. Despite the improvement of survival in the last years, about 50% of patients still experience a relapse. It is not possible to improve prognosis only with further intensification of chemotherapy, as come with a severe cost to the health of patients, often resulting in treatment-related death or long-term sequels. To design more effective and less toxic therapies we need a better understanding of pediatric AML biology. The NUP98-KDM5A chimeric protein is exclusively found in a particular subgroup of young pediatric AML patients with complex karyotypes and poor prognosis. In this study, we investigated the impact of NUP98-KDM5A expression on cellular processes in human Pluripotent Stem Cell models and a patient-derived cell line. We found that NUP98-KDM5A generates genomic instability through two complementary mechanisms that involve accumulation of DNA damage and direct interference of RAE1 activity during mitosis. Overall, our data support that NUP98-KDM5A promotes genomic instability and likely contributes to malignant transformation.

PMID:37301844 | DOI:10.1038/s41419-023-05870-5

BMC Cancer. 2023 Jun 10;23(1):532. doi: 10.1186/s12885-023-10919-x.

ABSTRACT

BACKGROUND: Cancer patients with newly created ostomies face complications that reduce quality of life (QOL) and increase morbidity and mortality. This proof-of-concept study examined the feasibility, usability, acceptability, and initial efficacy of an eHealth program titled the “Patient Reported Outcomes-Informed Symptom Management System” (PRISMS) during post-ostomy creation care transition.

METHODS: We conducted a 2-arm pilot randomized controlled trial among 23 patients who received surgical treatment with curative intent for bladder and colorectal cancer and their caregivers. After assessing QOL, general symptoms, and caregiver burden at baseline, participants were randomly assigned to PRISMS (n = 16 dyads) or usual care (UC) (n = 7 dyads). After a 60-day intervention period, participants completed a follow-up survey and post-exit interview. We used descriptive statistics and t-tests to analyze the data.

RESULTS: We achieved an 86.21% recruitment rate and a 73.91% retention rate. Among the PRISMS participants who used the system and biometric devices (n = 14, 87.50%), 46.43% used the devices for ≥ 50 days during the study period. Participants reported PRISMS as useful and acceptable. Compared to their UC counterparts, PRISMS patient social well-being scores decreased over time and had an increased trend of physical and emotional well-being; PRISMS caregivers experienced a greater decrease in caregiver burden.

CONCLUSIONS: PRISMS recruitment and retention rates were comparable to existing family-based intervention studies. PRISMS is a useful and acceptable multilevel intervention with the potential to improve the health outcomes of cancer patients needing ostomy care and their caregivers during post-surgery care transition. A sufficiently powered RCT is needed to test its effects.

TRIAL REGISTRATION: ClinicalTrial.gov ID: NCT04492007. Registration date: 30/07/2020.

PMID:37301841 | DOI:10.1186/s12885-023-10919-x

BMC Genomics. 2023 Jun 10;24(1):312. doi: 10.1186/s12864-023-09420-3.

ABSTRACT

BACKGROUND: The emergence and rapid spread of new severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) variants have challenged the control of the COVID-19 pandemic globally. Burundi was not spared by that pandemic, but the genetic diversity, evolution, and epidemiology of those variants in the country remained poorly understood. The present study sought to investigate the role of different SARS-COV-2 variants in the successive COVID-19 waves experienced in Burundi and the impact of their evolution on the course of that pandemic. We conducted a cross-sectional descriptive study using positive SARS-COV-2 samples for genomic sequencing. Subsequently, we performed statistical and bioinformatics analyses of the genome sequences in light of available metadata.

RESULTS: In total, we documented 27 PANGO lineages of which BA.1, B.1.617.2, AY.46, AY.122, and BA.1.1, all VOCs, accounted for 83.15% of all the genomes isolated in Burundi from May 2021 to January 2022. Delta (B.1.617.2) and its descendants predominated the peak observed in July-October 2021. It replaced the previously predominant B.1.351 lineage. It was itself subsequently replaced by Omicron (B.1.1.529, BA.1, and BA.1.1). Furthermore, we identified amino acid mutations including E484K, D614G, and L452R known to increase infectivity and immune escape in the spike proteins of Delta and Omicron variants isolated in Burundi. The SARS-COV-2 genomes from imported and community-detected cases were genetically closely related.

CONCLUSION: The global emergence of SARS-COV-2 VOCs and their subsequent introductions in Burundi was accompanied by new peaks (waves) of COVID-19. The relaxation of travel restrictions and the mutations occurring in the virus genome played an important role in the introduction and the spread of new SARS-COV-2 variants in the country. It is of utmost importance to strengthen the genomic surveillance of SARS-COV-2, enhance the protection by increasing the SARS-COV-2 vaccine coverage, and adjust the public health and social measures ahead of the emergence or introduction of new SARS-COV-2 VOCs in the country.

PMID:37301830 | DOI:10.1186/s12864-023-09420-3

Lipids Health Dis. 2023 Jun 10;22(1):71. doi: 10.1186/s12944-023-01838-8.

ABSTRACT

OBJECTIVES: Eicosapentaenoic acid in its ethyl ester form is the single active component of icosapent ethyl (IPE). This study was a phase III, multi-center trial assessing the safety and efficiency of IPE for treating very high triglyceride (TG) in a Chinese cohort.

METHODS: Patients having TG levels (5.6-22.6 mmol/L) were enrolled and randomly assigned to receive a treatment of oral intake of 4 g or 2 g/day of IPE, or placebo. Before and after 12 weeks of treatment, TG levels were assessed and the median was calculated to determine the change between the baseline and week 12. In addition to examining TG levels, the impact of such treatments on other lipid changes was also investigated. The official Drug Clinical Trial Information Management Platform has registered this study (CTR20170362).

RESULTS: Random assignments were performed on 373 patients (mean age 48.9 years; 75.1% male). IPE (4 g/day) lowered TG levels by an average of 28.4% from baseline and by an average of 19.9% after correction for placebo (95% CI: 29.8%-10.0%, P < 0.001). In addition, plasma concentration of non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein (VLDL) cholesterol, and VLDL-TG remarkedly reduced after IPE (4 g/day) treatment by a median of 14.6%, 27.9%, and 25.2%, respectively compared with participants in placebo group. Compared to the placebo, neither 4 nor 2 g of IPE daily elevated LDL-C levels with statistical significance. IPE was well tolerated by all the treatment groups.

CONCLUSIONS: IPE at 4 g/day dramatically lowered other atherogenic lipids without a noticeable increase in LDL-C, thereby decreasing TG levels in an exceptionally high-TG Chinese population.

PMID:37301827 | DOI:10.1186/s12944-023-01838-8

BioData Min. 2023 Jun 10;16(1):17. doi: 10.1186/s13040-023-00333-1.

ABSTRACT

Single-cell RNA-sequencing (scRNA-seq) data can serve as a good indicator of cell-to-cell heterogeneity and can aid in the study of cell growth by identifying cell types. Recently, advances in Variational Autoencoder (VAE) have demonstrated their ability to learn robust feature representations for scRNA-seq. However, it has been observed that VAEs tend to ignore the latent variables when combined with a decoding distribution that is too flexible. In this paper, we introduce ScInfoVAE, a dimensional reduction method based on the mutual information variational autoencoder (InfoVAE), which can more effectively identify various cell types in scRNA-seq data of complex tissues. A joint InfoVAE deep model and zero-inflated negative binomial distributed model design based on ScInfoVAE reconstructs the objective function to noise scRNA-seq data and learn an efficient low-dimensional representation of it. We use ScInfoVAE to analyze the clustering performance of 15 real scRNA-seq datasets and demonstrate that our method provides high clustering performance. In addition, we use simulated data to investigate the interpretability of feature extraction, and visualization results show that the low-dimensional representation learned by ScInfoVAE retains local and global neighborhood structure data well. In addition, our model can significantly improve the quality of the variational posterior.

PMID:37301826 | DOI:10.1186/s13040-023-00333-1

Environ Sci Pollut Res Int. 2023 Jun 10. doi: 10.1007/s11356-023-27883-5. Online ahead of print.

ABSTRACT

Taxis pose a higher threat to global climate change and human health through air emissions. However, the evidence on this topic is scarce, especially, in developing countries. Therefore, this study conducted estimation of fuel consumption (FC) and emission inventories on Tabriz taxi fleet (TTF), Iran. A structured questionnaire to obtain operational data of TTF, municipality organizations, and literature review were used as data sources. Then modeling was used to estimate fuel consumption ratio (FCR), emission factors (EFs), annual FC, and emissions of TTF using uncertainty analysis. Also, the impact of COVID-19 pandemic period was considered on the studied parameters. The results showed that TTF have high FCRs of 18.68 L/100 km (95% CI=17.67-19.69 L/100 km), which are not affected by age or mileage of taxis, significantly. The estimated EFs for TTF are higher than Euro standards, but the differences are not significant. However, it is critical as can be an indication of inefficiency of periodic regulatory technical inspection tests for TTF. COVID-19 pandemic caused significant decrease in annual total FC and emissions (9.03-15.6%), but significant increase in EFs of per-passenger-kilometer traveled (47.9-57.3%). Annual vehicle-kilometer-traveled by TTF and the estimated EFs for gasoline-compressed natural gas bi-fueled TTF are the main influential parameters in the variability of annual FC and emission levels. More studies on sustainable FC and emissions mitigation strategies are needed for TTF.

PMID:37301810 | DOI:10.1007/s11356-023-27883-5

Clin Transl Oncol. 2023 Jun 10. doi: 10.1007/s12094-023-03233-2. Online ahead of print.

ABSTRACT

PURPOSE: The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation.

METHODS/PATIENTS: Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification.

RESULTS: 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375).

CONCLUSIONS: The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.

PMID:37301805 | DOI:10.1007/s12094-023-03233-2

Rheumatol Int. 2023 Jun 10. doi: 10.1007/s00296-023-05358-7. Online ahead of print.

ABSTRACT

This systematic review is aimed to evaluate the effects of balneotherapy with thermal mineral water for managing the symptoms and signs of osteoarthritis located at any anatomical site. The systematic review was conducted according to the PRISMA Statement. The following databases were consulted: PubMed, Scopus, Web of Science, Cochrane Library, DOAJ and PEDro. We included clinical trials evaluating the effects of balneotherapy as a treatment for patients with osteoarthritis, published in English and Italian language, led on human subjects. The protocol was registered in PROSPERO. Overall, 17 studies have been included in the review. All of these studies were performed on adults or elderly patients suffering from osteoarthritis localized to knees, hips, hands or lumbar spine. The treatment assessed was always the balneotherapy with thermal mineral water. The outcomes evaluated were pain, palpation/pressure sensibility, articular tenderness, functional ability, quality of life, mobility, deambulation, ability to climb stairs, medical objective and patients’ subjective evaluation, superoxide dismutase enzyme activity, serum levels of interleukin-2 receptors. The results of all the included studies agree and demonstrated an improvement of all the symptoms and signs investigated. In particular, pain and quality of life were the main symptoms evaluated and both improved after the treatment with thermal water in all the studies included in the review. These effects can be attributed to physical and chemical-physical properties of thermal mineral water used. However, the quality of many studies resulted not so high due and, consequently, it is necessary to perform new clinical trial in this field using more correct methods for conducting the study and for processing statistical data.

PMID:37301799 | DOI:10.1007/s00296-023-05358-7

J Math Biol. 2023 Jun 11;87(1):5. doi: 10.1007/s00285-023-01944-2.

ABSTRACT

Dengue is the most rapidly spreading mosquito-borne disease that poses great threats to public health. We propose a compartmental model with primary and secondary infection and targeted vaccination to assess the impact of serostatus-dependent immunization on mitigating the spread of dengue virus. We derive the basic reproduction number and investigate the stability and bifurcations of the disease-free equilibrium and endemic equilibria. The existence of a backward bifurcation is proved and is used to explain the threshold dynamics of the transmission. We also carry out numerical simulations and present bifurcation diagrams to reveal rich dynamics of the model such as bi-stability of the equilibria, limit cycles, and chaos. We prove the uniform persistence and global stability of the model. Sensitivity analysis suggests that mosquito control and protection from mosquito bites are still the key measures of controlling the spread of dengue virus, though serostatus-dependent immunization is implemented. Our findings provide insightful information for public health in mitigating dengue epidemics through vaccination.

PMID:37301798 | DOI:10.1007/s00285-023-01944-2

Glob Chang Biol. 2023 Jun 10. doi: 10.1111/gcb.16801. Online ahead of print.

ABSTRACT

Biodiversity offsetting is a globally influential policy mechanism for reconciling trade-offs between development and biodiversity loss. However, there is little robust evidence of its effectiveness. We evaluated the outcomes of a jurisdictional offsetting policy (Victoria, Australia). Offsets under Victoria’s Native Vegetation Framework (2002-2013) aimed to prevent loss and degradation of remnant vegetation, and generate gains in vegetation extent and quality. We categorised offsets into those with near-complete baseline woody vegetation cover (“avoided loss”, 2702 ha) and with incomplete cover (“regeneration”, 501 ha), and evaluated impacts on woody vegetation extent from 2008 to 2018. We used two approaches to estimate the counterfactual. First, we used statistical matching on biophysical covariates: a common approach in conservation impact evaluation, but which risks ignoring potentially important psychosocial confounders. Second, we compared changes in offsets with changes in sites that were not offsets for the study duration but were later enrolled as offsets, to partially account for self-selection bias (where landholders enrolling land may have shared characteristics affecting how they manage land). Matching on biophysical covariates, we estimated that regeneration offsets increased woody vegetation extent by 1.9%-3.6%/year more than non-offset sites (138-180 ha from 2008 to 2018) but this effect weakened with the second approach (0.3%-1.9%/year more than non-offset sites; 19-97 ha from 2008 to 2018) and disappeared when a single outlier land parcel was removed. Neither approach detected any impact of avoided loss offsets. We cannot conclusively demonstrate whether the policy goal of ‘net gain’ (NG) was achieved because of data limitations. However, given our evidence that the majority of increases in woody vegetation extent were not additional (would have happened without the scheme), a NG outcome seems unlikely. The results highlight the importance of considering self-selection bias in the design and evaluation of regulatory biodiversity offsetting policy, and the challenges of conducting robust impact evaluations of jurisdictional biodiversity offsetting policies.

PMID:37300408 | DOI:10.1111/gcb.16801