Nevin Manimala

Clin Lymphoma Myeloma Leuk. 2022 Jun 30:S2152-2650(22)00217-8. doi: 10.1016/j.clml.2022.06.013. Online ahead of print.

ABSTRACT

BACKGROUND: Managing double-expressor lymphomas (DEL) is controversial given the dearth of data and lack of standardized guidelines on this high-risk subset of lymphomas. No prospective and few retrospective studies limited by either their sample size or short follow-up address the question of initial treatment of choice for DEL. We performed the largest analysis to date exploring R-CHOP vs DA-EPOCH-R in DEL.

METHODS: Adults with DEL diagnosed from 6/2012-2/2021 at 4 unique sites were retrospectively analyzed. Progression-free survival (PFS) was the primary endpoint. Key secondary endpoints include overall survival (OS), overall and complete response rates (ORR and CRR), cumulative incidence of relapse, and autologous hematopoietic cell transplantation (autoHCT) utilization.

RESULTS: 155 patients were included, 61 treated with R-CHOP and 94 with DA-EPOCH-R. 3-year PFS and OS were similar between R-CHOP and DA-EPOCH-R, 33.2% vs 57.2%,(P = .063), and 72.2% vs 71.6% (P = .43) after median follow-up times of 2.43 and 2.89 years, respectively. Patients <65 had improved PFS with DA-EPOCH-R, hazard ratio 0.41 (P = .01). CRR and ORR rates were also similar. Relapse rates were not statistically different, 51.9% vs 28.6% (P = .069). AutoHCT utilization was higher with R-CHOP vs DA-EPOCH-R, 23.0% vs 8.5% (P = .017).

CONCLUSIONS: Our findings do not support the use of DA-EPOCH-R over R-CHOP for DEL. Patients <65 years may experience longer PFS with DA-EPOCH-R, but limitations to the analysis make this interpretation difficult.

PMID:35858904 | DOI:10.1016/j.clml.2022.06.013

World J Surg Oncol. 2022 Jul 20;20(1):238. doi: 10.1186/s12957-022-02699-8.

ABSTRACT

BACKGROUND: Signet-ring cell carcinoma of the stomach (SRCC) is a particular gastric cancer entity. Its incidence is increasing. Its diagnosis is pathological; it corresponds to adenocarcinoma with a majority of signet-ring cells component (> 50%). These histological features give it its aggressiveness characteristics. This has repercussions on the prognostic level and implications for the alternatives of therapy, especially since some authors suggest a potential chemoresistance. This survey aimed to identify the epidemiological, pathological, therapeutic, and prognostic characteristics of SRCC as a separate disease entity.

METHODS: This was a retrospective study of 123 patients admitted for gastric adenocarcinoma to Habib Thameur Hospital in Tunis over 11 years from January 2006 to December 2016. A comparative study was performed between 2 groups: the SRCC group with 62 patients and the non-SRCC (non-signet-ring cell carcinoma of the stomach) with 61 patients.

RESULTS: The prevalence of SRCC in our series was 50%. SRCC affected significantly younger patients (55 vs 62 years; p = 0.004). The infiltrative character was more common in SRCC tumors (30.6 vs 14.8%; p = 0.060), whereas the budding character was more often noted in non-SRCC tumors (78.7 vs 58.1%; p = 0.039). There was no significant difference in tumor localization between both groups. Linitis plastica was noted in 14 patients with SRCC against a single patient with non-SRCC (p = 0.001). The tumor size was more important in the non-SRCC group (6.84 vs 6.39 cm; p = 0.551). Peritoneal carcinomatosis was noted in 4.3% of cases in the SRCC group versus 2.2% of cases in the NSRCC group (p = 0.570). Total gastrectomy was more often performed in the SRCC group (87 vs 56%; p = 0.001). Resection was more often curative in the non-SRCC group (84.4 vs 78.3%; p = 0.063). Postoperative chemotherapy was more commonly indicated in the SRCC group (67.4 vs 53.3%; p = 0.339). Tumor recurrence was more common in the non-SRCC group (35.7 vs 32%; p = 0.776). The most common type of recurrence was peritoneal carcinomatosis in the SRCC group (62.5%) and hepatic metastasis in the non-SRCC group (60%; p = 0.096). The overall 5-year survival in the SRCC group was lower than in the non-SRCC group, with no statistically significant difference (47.1 vs 51.5%; p = 0.715). The overall survival was more important for SRCC in early cancer (100 vs 80%; p = 0.408), whereas it was higher for non-SRCC in advanced cancer (48.1 vs 41.9%; p = 0.635).

CONCLUSION: Apart from its epidemiological and pathological features, SRCC seems to have a worse prognosis. Indeed, it is diagnosed at a more advanced stage and has a worse prognosis in advanced cancer than non-SRCC. It is therefore to be considered as a particular entity of gastric adenocarcinoma requiring a specific therapeutic protocol where the place of chemotherapy remains to be more investigated.

PMID:35858903 | DOI:10.1186/s12957-022-02699-8

Sci Rep. 2022 Jul 20;12(1):12380. doi: 10.1038/s41598-022-15983-0.

ABSTRACT

This research aims to contribute in developing a mathematical model for the composite probabilistic energy emissions dispatch (CPEED) with renewable energy systems, and it proposes a novel framework, based on an existing astute black widow optimization (ABWO) algorithm. Renewable energy power generation technology has contributed to pollution reduction and sustainable development. Therefore, this research aims to explore the CPEED problem in the context of renewable energy generation systems to enhance the energy and climate benefits of the power systems. Five benchmark test systems, combined with conventional thermal power plants and renewable energy sources such as wind and solar, are considered herein to obtain the optimum solution for cost and pollutant emission by using the ABWO approach. The ascendancy is not limited to environmental impacts, but it also provides the diversification of energy supply and reduction of reliance on imported fuels. As a result, the research findings contribute in lowering the cost of fuel and pollutant emissions, correlated with electricity generation systems, while increasing the renewable energy usage and penetration. Finally, the performance and efficacy of the designed scheme have been fully validated by comprehensive experimental results and statistical analyses.

PMID:35858895 | DOI:10.1038/s41598-022-15983-0

BMC Public Health. 2022 Jul 20;22(1):1391. doi: 10.1186/s12889-022-13796-4.

ABSTRACT

BACKGROUND: The present study aimed to apply the theory of planned behavior (TPB) to identify predictors of adults’ intentions to improve oral health behaviors.

METHODS: This cross-sectional study was conducted with 1,328 adults living in the Jeddah city, Saudi Arabia. A 64-item questionnaire that evaluated behavioral intention, oral health knowledge (OHK) and TPB constructs (attitudes, perceived behavioral control, and subjective norms) was distributed. Descriptive statistics and structural equation modeling (SEM) were used to describe the data and examine the associations among the variables. A p-value of < 0.05 was considered significant.

RESULTS: The analysis revealed that the TPB model explained 72% of the variance in oral health behavioral intentions (OHBI), indicating a good model fit. The TPB constructs of attitudes (β = 0.299), subjective norms (β = 0.035), and perceived behavioral control (β = 0.144) were significant predictors of OHBI, whereas OHK was not. Attitude was the strongest predictor of intentions to improve oral health behaviors.

CONCLUSIONS: The findings suggest that this model could be a helpful framework for designing oral health promotion and intervention programs. Such programs should focus on changing adults’ attitudes, positive influences from close relationships, and improving self-efficacy of OHB to improve their oral health behavior.

PMID:35858885 | DOI:10.1186/s12889-022-13796-4

BMC Geriatr. 2022 Jul 21;22(1):605. doi: 10.1186/s12877-022-03239-5.

ABSTRACT

BACKGROUND: The potential decrease in daily physical activity associated with the COVID-19 pandemic lockdowns may have a negative impact on people living with dementia. Given the limited literature around the effects of home confinement in people living with dementia, this study investigated changes in physical exercise levels of participants in the intervention arm of the Promoting Activity, Independence and Stability in Early Dementia (PrAISED) Randomised Controlled Trial during the first COVID-19 national lockdown. It hypothesised that participants would maintain physical exercise levels.

METHODS: A repeated measure (three time points) study involving 30 participants (mean age = 78.0 years, 15 male and 15 female, 22 (73.0%) living with their primary caregiver), from four regions in England receiving the PrAISED intervention. PrAISED is an individually tailored intervention of physical exercises and functional activities. Trained therapists deliver therapy sessions over a period of 52 weeks. Study participants received therapy sessions via phone or video calling during the COVID-19 lockdown. This study investigated self-reported minutes of physical exercise recorded on study calendars for the months of February (i.e., baseline – pre-lockdown), May (i.e., T1 – during lockdown), and August (i.e., T2-post-lockdown) 2020.

RESULTS: Participants reported a statistically significant increase in activity levels between February and May (Wilcoxon Z = -2.013, p = 0.044) and a statistically significant decrease between May and August (Wilcoxon Z = -2.726, p = 0.004). No significant difference was found in the physical activity levels from pre- to post-lockdown (Wilcoxon Z = 0.485, p = 0.620).

CONCLUSION: Despite concerns that the restrictions associated with the COVID-19 pandemic might lead to reductions in physical exercise, participants in receipt of the PrAISED intervention increased their amount of physical exercise during lockdown. Our findings support the potential of remote support for people living with dementia to help them maintain physical exercise levels in circumstances where face-to-face service provision is not possible.

TRIAL REGISTRATION: The PrAISED trial and process evaluation have received ethical approval number 18/YH/0059 from the Bradford/Leeds Ethics Committee. The Clinical Trial Identifier for PrAISED is: ISRCTN15320670 ( https://doi.org/10.1186/ISRCTN15320670 ). Registration was made on 04/09/2018.

PMID:35858870 | DOI:10.1186/s12877-022-03239-5

J Patient Saf. 2022 Jul 11. doi: 10.1097/PTS.0000000000001066. Online ahead of print.

ABSTRACT

OBJECTIVE: The COVID-19 pandemic prompted labor and delivery units to establish ways to decrease viral exposure to healthcare workers while continuing to deliver optimal patient care. A laborist model was implemented to improve safety at our tertiary care hospital in Long Island. The aim of the study is to determine whether implementation of a laborist model during the COVID-19 pandemic is associated with a change in the frequency of cesarean birth.

METHODS: The retrospective cohort study included patients who delivered at a single tertiary center during March 2019 to May 2019 and March 2020 to May 2020 when our laborist model was initiated. The primary outcome compared the frequency of a cesarean delivery between both models. Secondary outcomes were the frequency of adverse obstetrical complications, which included intensive care unit admission, shoulder dystocia, intra-amniotic infection, hemorrhage, and need for blood transfusion. Statistical analysis included multivariable regression to adjust for potential confounders.

RESULTS: A total of 1506 patients were included. Baseline characteristics were similar between the 2 groups. After adjusting for potential confounders, there was no significant difference in the frequency of cesarean births between both models (37% versus 35%; adjusted odds ratio, 1.003; 95% confidence interval, 0.46-2.89). Similarly, there were no significant differences in adverse outcomes between the study populations (adjusted odds ratio, 1.064; 95% confidence interval, 0.68-1.59).

CONCLUSIONS: A change in practice behavior during a pandemic was not associated with an increase in frequency of cesarean births or adverse obstetrical outcomes.

PMID:35858475 | DOI:10.1097/PTS.0000000000001066

Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2201208119. doi: 10.1073/pnas.2201208119. Epub 2022 Jul 18.

ABSTRACT

Completion of the Lassa virus (LASV) life cycle critically depends on the activities of the virally encoded, RNA-dependent RNA polymerase in replication and transcription of the viral RNA genome in the cytoplasm of infected cells. The contribution of cellular proteins to these processes remains unclear. Here, we applied proximity proteomics to define the interactome of LASV polymerase in cells under conditions that recreate LASV RNA synthesis. We engineered a LASV polymerase-biotin ligase (TurboID) fusion protein that retained polymerase activity and successfully biotinylated the proximal proteome, which allowed the identification of 42 high-confidence LASV polymerase interactors. We subsequently performed a small interfering RNA (siRNA) screen to identify those interactors that have functional roles in authentic LASV infection. As proof of principle, we characterized eukaryotic peptide chain release factor subunit 3a (eRF3a/GSPT1), which we found to be a proviral factor that physically associates with LASV polymerase. Targeted degradation of GSPT1 by a small-molecule drug candidate, CC-90009, resulted in strong inhibition of LASV infection in cultured cells. Our work demonstrates the feasibility of using proximity proteomics to illuminate and characterize yet-to-be-defined host-pathogen interactome, which can reveal new biology and uncover novel targets for the development of antivirals against highly pathogenic RNA viruses.

PMID:35858434 | DOI:10.1073/pnas.2201208119

Proc Natl Acad Sci U S A. 2022 Aug 2;119(31):e2200732119. doi: 10.1073/pnas.2200732119. Epub 2022 Jul 19.

NO ABSTRACT

PMID:35858388 | DOI:10.1073/pnas.2200732119

Proc Natl Acad Sci U S A. 2022 Jul 19;119(29):e2114365119. doi: 10.1073/pnas.2114365119. Epub 2022 Jul 11.

ABSTRACT

Molecular analysis on the single-cell level represents a rapidly growing field in the life sciences. While bulk analysis from a pool of cells provides a general molecular profile, it is blind to heterogeneities between individual cells. This heterogeneity, however, is an inherent property of every cell population. Its analysis is fundamental to understanding the development, function, and role of specific cells of the same genotype that display different phenotypical properties. Single-cell mass spectrometry (MS) aims to provide broad molecular information for a significantly large number of cells to help decipher cellular heterogeneity using statistical analysis. Here, we present a sensitive approach to single-cell MS based on high-resolution MALDI-2-MS imaging in combination with MALDI-compatible staining and use of optical microscopy. Our approach allowed analyzing large amounts of unperturbed cells directly from the growth chamber. Confident coregistration of both modalities enabled a reliable compilation of single-cell mass spectra and a straightforward inclusion of optical as well as mass spectrometric features in the interpretation of data. The resulting multimodal datasets permit the use of various statistical methods like machine learning-driven classification and multivariate analysis based on molecular profile and establish a direct connection of MS data with microscopy information of individual cells. Displaying data in the form of histograms for individual signal intensities helps to investigate heterogeneous expression of specific lipids within the cell culture and to identify subpopulations intuitively. Ultimately, t-MALDI-2-MSI measurements at 2-µm pixel sizes deliver a glimpse of intracellular lipid distributions and reveal molecular profiles for subcellular domains.

PMID:35858333 | DOI:10.1073/pnas.2114365119