Tag: nevin manimala

Clin Cancer Res. 2023 Nov 8. doi: 10.1158/1078-0432.CCR-23-0561. Online ahead of print.

ABSTRACT

BACKGROUND: The MONALEESA-2, -3, -7 trials demonstrated statistically significant and clinically meaningful progression-free survival (PFS) and overall survival (OS) benefits with ribociclib + endocrine therapy (ET) vs ET alone in hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Understanding the association of intrinsic subtypes with survival outcomes could potentially guide treatment decisions. Here, we evaluated the association of intrinsic subtypes with OS in MONALEESA-2, -3, -7.

PATIENTS AND METHODS: Tumor samples from MONALEESA-2, -3, -7 underwent PAM50-based subtyping. The relationship between subtypes and OS was assessed using univariable and multivariable Cox proportional hazards models. Multivariable models were adjusted for clinical prognostic factors.

RESULTS: Overall, 990 tumors (among 2066 patients) from ribociclib (n=580) and placebo (n=410) arms were profiled. Subtype distribution was luminal A, 54.5%; luminal B, 28.0%; HER2E, 14.6%; basal-like, 2.8%; and was consistent across treatment arms. The luminal A subtype had the best OS outcomes in both arms, while basal-like had the worst. Patients with HER2E (HR, 0.60; P=.018), luminal B (HR, 0.69; P=.023), and luminal A (HR, 0.75; P=.021) subtypes derived OS benefit with ribociclib. Patients with basal-like subtype did not derive benefit from ribociclib (HR, 1.92; P=.137); however, patient numbers were small (n=28).

CONCLUSION: The prognostic value of intrinsic subtypes for OS was confirmed in this pooled analysis of the MONALEESA trials (largest data set in HR+/HER2- ABC). While basal-like subtype did not benefit, a consistent OS benefit was observed with ribociclib added to ET across luminal and HER2E subtypes.

PMID:37939142 | DOI:10.1158/1078-0432.CCR-23-0561

PLoS Comput Biol. 2023 Nov 8;19(11):e1011607. doi: 10.1371/journal.pcbi.1011607. Online ahead of print.

ABSTRACT

Ecological interactions are fundamental at the cellular scale, addressing the possibility of a description of cellular systems that uses language and principles of ecology. In this work, we use a minimal ecological approach that encompasses growth, adaptation and survival of cell populations to model cell metabolisms and competition under energetic constraints. As a proof-of-concept, we apply this general formulation to study the dynamics of the onset of a specific blood cancer-called Multiple Myeloma. We show that a minimal model describing antagonist cell populations competing for limited resources, as regulated by microenvironmental factors and internal cellular structures, reproduces patterns of Multiple Myeloma evolution, due to the uncontrolled proliferation of cancerous plasma cells within the bone marrow. The model is characterized by a class of regime shifts to more dissipative states for selectively advantaged malignant plasma cells, reflecting a breakdown of self-regulation in the bone marrow. The transition times obtained from the simulations range from years to decades consistently with clinical observations of survival times of patients. This irreversible dynamical behavior represents a possible description of the incurable nature of myelomas based on the ecological interactions between plasma cells and the microenvironment, embedded in a larger complex system. The use of ATP equivalent energy units in defining stocks and flows is a key to constructing an ecological model which reproduces the onset of myelomas as transitions between states of a system which reflects the energetics of plasma cells. This work provides a basis to construct more complex models representing myelomas, which can be compared with model ecosystems.

PMID:37939139 | DOI:10.1371/journal.pcbi.1011607

Clin Cancer Res. 2023 Nov 8. doi: 10.1158/1078-0432.CCR-23-1889. Online ahead of print.

ABSTRACT

PURPOSE: Evidence suggests that MAPK pathway activation, as measured by ERK1/2 phosphorylation (p-ERK), predicts overall survival (OS) in recurrent glioblastoma patients receiving anti-PD-1 therapy. We aimed to validate these findings in independent cohorts.

EXPERIMENTAL DESIGN: In a 24-patient clinical trial on recurrent glioblastoma and high-grade gliomas, we examined the link between p-ERK levels and overall survival (OS). Patients received intravenous nivolumab, followed by maximal safe resection and an intracerebral injection of either ipilimumab alone or combined with nivolumab. Bi-weekly adjuvant nivolumab was then administered up to five times (NCT03233152). Using REMARK criteria, we conducted independent analyses for p-ERK quantification and statistical evaluations. Additional comparative analysis included prior cohorts, totaling 65 patients. Cox proportional hazards models and meta-analysis were employed to assess p-ERK as a predictive biomarker post-immunotherapy.

RESULTS: Lower median p-ERK+ cell density was observed compared to prior studies, likely due to tissue handling variances. Nonetheless, high p-ERK was associated with prolonged OS, particularly in IDH wild-type glioblastomas (P=0.036). Median OS for high and low p-ERK patients were 55.6 and 30 weeks, respectively. Multivariable analysis reinforced p-ERK’s significance in survival prediction (P=0.011). Meta-analysis across three cohorts (n=65) supported the survival benefit of elevated tumor p-ERK levels (P=0.0424).

CONCLUSIONS: This study strengthens the role of p-ERK as a predictive biomarker for OS in glioblastoma patients on immune checkpoint blockade. Future research should focus on further validation in prospective trials and the standardization of preanalytical variables influencing p-ERK quantification.

PMID:37939133 | DOI:10.1158/1078-0432.CCR-23-1889

PLoS Biol. 2023 Nov 8;21(11):e3002373. doi: 10.1371/journal.pbio.3002373. Online ahead of print.

ABSTRACT

Corrective feedback received on perceptual decisions is crucial for adjusting decision-making strategies to improve future choices. However, its complex interaction with other decision components, such as previous stimuli and choices, challenges a principled account of how it shapes subsequent decisions. One popular approach, based on animal behavior and extended to human perceptual decision-making, employs “reinforcement learning,” a principle proven successful in reward-based decision-making. The core idea behind this approach is that decision-makers, although engaged in a perceptual task, treat corrective feedback as rewards from which they learn choice values. Here, we explore an alternative idea, which is that humans consider corrective feedback on perceptual decisions as evidence of the actual state of the world rather than as rewards for their choices. By implementing these “feedback-as-reward” and “feedback-as-evidence” hypotheses on a shared learning platform, we show that the latter outperforms the former in explaining how corrective feedback adjusts the decision-making strategy along with past stimuli and choices. Our work suggests that humans learn about what has happened in their environment rather than the values of their own choices through corrective feedback during perceptual decision-making.

PMID:37939126 | DOI:10.1371/journal.pbio.3002373

PLoS One. 2023 Nov 8;18(11):e0293948. doi: 10.1371/journal.pone.0293948. eCollection 2023.

ABSTRACT

INTRODUCTION: Telemonitoring involves the transmission of clinical information through digital means, including internet-connected devices such as smartphones, health tracking apps and video conferencing platforms. This strategy could provide a viable alternative to facilitate follow-up in several conditions, including cancer.

OBJECTIVES: To synthesise the available evidence on the effectiveness of internet-based telemonitoring platforms amongst oncological patients. Relevant endpoints include overall quality of life, the ability to detect postoperative complications, severe toxicity reactions attributable to chemotherapy, reducing the frequency of hospitalisations, emergency department visits and mortality.

METHODS: A systematic review of published and unpublished randomised and controlled studies will be carried out. Iterative searches in PubMED/MEDLINE, EMBASE, Epistemonikos, LILACS, and Cochrane CENTRAL repositories from January 2000 to January 2023 will be conducted. Grey literature repositories, such as Clinicaltrials, BioRxiv and MedRxiv will be searched as well. The Cochrane risk of bias tool will be used to assess the quality of the eligible studies. If possible, a meta-analysis based on the random-effects model will be conducted to evaluate changes in any of the aforementioned outcomes. Heterogeneity will be assessed with Cochrane’s Q and I2 statistics. Its exploration will be carried out using subgroup and sensitivity analyses. Relevant subgroups include the proportion of elderly patients in each study, characteristics of each platform, study type, type of funding and moment of conduction (i.e. before or after the COVID-19 pandemic). Publication bias will be assessed using funnel plots and Egger’s test.

REGISTRATION: This systematic review protocol is registered in PROSPERO. Its registration number is CRD42023412705.

PMID:37939125 | DOI:10.1371/journal.pone.0293948

PLoS One. 2023 Nov 8;18(11):e0292496. doi: 10.1371/journal.pone.0292496. eCollection 2023.

ABSTRACT

BACKGROUND: Obstetric ultrasound is one of the most important advances in antenatal tests. Despite the importance of knowing the knowledge status of ultrasound and the category of attitude, there is no similar study done in Ethiopia. Thus, this study aimed to assess knowledge and attitude and associated factors toward ultrasound examination at the University of Gondar comprehensive specialized hospital, Northwest Ethiopia.

METHODS: Institutional-based cross-sectional study was conducted at the University of Gondar comprehensive specialized hospital, Northwest Ethiopia from May 15, 2022, to Jun 30, 2022. Data was collected and transferred from the Open data Kit server and analyzed using STATA version 14. The strength of the association, presented using an adjusted odds ratio with a 95% confidence interval and p-value ≤0.05, is considered to declare statistically significant variables.

RESULTS: A total of 422 pregnant women participated, with a response rate of 100%. Of the total pregnant women, only 39% of them are knowledgeable about obstetric ultrasound whereas 52% of them have a favorable attitude. Being a housewife, government employee, and private employee (AOR = 17, 95% CI = 2.12, 151), (AOR = 10, 95% CI = 1.2, 85) and (AOR = (13, 95% CI = 1.5, 115), respectively were associated positively with knowledge about ultrasound. However, residing in a rural (AOR = 0.07; 95%CI = 0.02, 0.21), never been pregnant before (AOR = 0.59 95% CI = 0.38, 0.94), and having information (AOR = 1.7, 95% CI = 1, 2.9) were negatively associated with knowledge about ultrasound. Whereas, attaining primary education (AOR = 2.61; 95%CI = 1.1, 6.4) was positively associated with favorable attitudes while living in rural areas was negatively associated with a favorable attitude (AOR = 0.42; 95%CI = 0.18, 0.97).

CONCLUSION: In this study, knowledge and attitude about ultrasound among pregnant women in Gondar City are low. Residence, occupation, being pregnant before, and having information were significantly associated factors of knowledge. While residence and educational status of the respondents were significant factors of attitude. Therefore, health information about obstetric ultrasound shall be given to women who live in rural areas, women who are students, merchants and farmers, illiterate, and primigravida.

PMID:37939118 | DOI:10.1371/journal.pone.0292496

Int J Surg. 2023 Nov 8. doi: 10.1097/JS9.0000000000000860. Online ahead of print.

ABSTRACT

BACKGROUND: Myofascial pain syndrome (MPS) has an impact on physical health and quality of life for patients, with various non-invasive methods used for relieving myofascial pain. We aimed to compare the effectiveness of different non-invasive therapeutic interventions for MPS.

MATERIALS AND METHODS: We searched PubMed, Embase, CINAHL Complete, Web of Science, Cochrane, and Scopus to identify randomized controlled trials (RCTs) describing the effects of any non-invasive treatments in patients with MPS. The primary outcome was pain intensity, while pressure pain threshold and pain-related disability were secondary outcomes.

RESULTS: The analysis included 40 studies. Manual therapy (MD of pain: -1.60, 95% CI: -2.17 to -1.03; MD of pressure pain threshold: 0.52, 95% CI: 0.19 to 0.86; MD of pain-related disability: -5.34, 95% CI: -8.09 to -2.58), laser therapy (MD of pain: -1.15, 95% CI: -1.83 to -0.46; MD of pressure pain threshold: 1.00, 95% CI: 0.46 to 1.54; MD of pain-related disability: -4.58, 95% CI: -7.80 to -1.36)，extracorporeal shock wave therapy (MD of pain: -1.61, 95% CI:-2.43 to -0.78; MD of pressure pain threshold: 0.84, 95% CI: 0.33 to 1.35; MD of pain-related disability: -5.78, 95% CI: -9.45 to -2.12), and ultrasound therapy (MD of pain: -1.54, 95% CI: -2.24 to -0.84; MD of pressure pain threshold: 0.77, 95% CI: 0.31 to 1.22) were more effective than no treatment.

CONCLUSION: Our findings support that manual therapy, laser therapy, and extracorporeal shock wave therapy could effectively reduce pain intensity, pressure pain threshold, and pain-related disability with statistical significance when compared with placebo. This finding may provide clinicians appropriate therapeutic modalities for patients with myofascial pain syndrome among different scenarios.

PMID:37939115 | DOI:10.1097/JS9.0000000000000860

Am J Epidemiol. 2023 Nov 3:kwad212. doi: 10.1093/aje/kwad212. Online ahead of print.

ABSTRACT

In a recent systematic review, Bastos et al. compared the sensitivities of saliva sampling and nasopharyngeal swabs in the detection of SARS-CoV-2 infection by assuming a composite reference standard defined as positive if either test is positive, and negative if both tests are negative (double negative). Even under a perfect specificity assumption, this approach ignores the double-negative results and risks overestimating the sensitivities due to residual misclassification. In this article, we first illustrate the impact of double-negative results in the estimation of the sensitivities in a single study, and then propose a two-step latent class meta-analysis method to re-evaluate both sensitivities using the same published dataset in Bastos et al. by properly including the observed double-negative results. We also conduct extensive simulation studies to compare the performance of the proposed method and Bastos et al.’s method for varied levels of prevalence and between-study heterogeneity. The results demonstrate that the sensitivities are overestimated noticeably in Bastos et al.’s method, and the proposed method provides a more accurate evaluation with nearly no bias and close to nominal coverage probability. In conclusion, double-negative results can significantly impact the estimated sensitivities when a gold standard is absent, and thus should be properly incorporated.

PMID:37939113 | DOI:10.1093/aje/kwad212

PLoS One. 2023 Nov 8;18(11):e0293305. doi: 10.1371/journal.pone.0293305. eCollection 2023.

ABSTRACT

This study explores the mediating effect of personality traits in the relationship between entrepreneurial intentions and student academic performance. The sample comprised 175 students from a top-ranked Tamil Nadu, India university. Data was collected using a survey questionnaire as the research instrument. A descriptive research design was employed to understand the variables under investigation comprehensively. Partial Least Squares Structural Equation Modeling (PLS-SEM) and SPSS v25 was utilized as the statistical analysis tool. This study used the Theory of Planned Behaviour as a theoretical framework to explore the mediating effect of personality traits in the relationship between entrepreneurial intentions and academic performance among university students. The study’s findings revealed essential insights into the relationship between entrepreneurial intentions, personality traits, and academic performance. The results showed that personality traits significantly mediate the relationship between entrepreneurial intentions and academic performance. This finding suggests that a student’s personality traits influence the impact of entrepreneurial intentions on academic performance. Furthermore, the study found that while entrepreneurial intentions did not have a significant direct effect on academic performance, they did have a substantial indirect effect through personality traits. This indicates that personality traits act as a crucial mechanism through which entrepreneurial intentions can influence academic performance among students.

PMID:37939091 | DOI:10.1371/journal.pone.0293305

Bone Marrow Transplant. 2023 Nov 8. doi: 10.1038/s41409-023-02146-6. Online ahead of print.

ABSTRACT

Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF) and is recommended for patients with higher risk disease. However, there is a risk of early mortality, and optimal timing is unknown. JAK inhibitor (JAKi) therapy may offer durable improvement in symptoms, splenomegaly and quality of life. The aim of this multicentre, retrospective observational study was to compare outcomes of patients aged 70 years or below with MF in chronic phase who received upfront JAKi therapy vs. upfront HCT in dynamic international prognostic scoring system (DIPSS)-stratified categories. For the whole study cohort, median overall survival (OS) was longer for patients who received a JAKi vs. upfront HCT, 69 (95% CI 57-89) vs. 42 (95% CI 20-not reached, NR) months, respectively (p = 0.01). In patients with intermediate-2 and high-risk disease, median OS was 55 (95% CI 36-73) months with JAKi vs. 36 (95% CI 20-NR) months for HCT (p = 0.27). An upfront HCT strategy was associated with early mortality and difference in median OS was not observed in any risk group by 5 years of follow-up. Within the limitations of a retrospective observational study, we did not observe any benefit of a universal upfront HCT approach for higher-risk MF.

PMID:37938736 | DOI:10.1038/s41409-023-02146-6