Tag: pubmed

JMIR Res Protoc. 2024 Nov 14;13:e56649. doi: 10.2196/56649.

ABSTRACT

BACKGROUND: Mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A syndrome, is a rare lysosomal storage disease characterized by autosomal recessive inheritance of mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. This leads to a deficiency of the GALNS enzyme, causing the accumulation of glycosaminoglycans in tissues. Morquio A syndrome primarily affects the skeletal system and joints but can also impact various organs, resulting in symptoms such as hearing and vision loss, respiratory issues, spinal cord compression, heart diseases, and hepatomegaly. The genotype-phenotype relationship is diverse, with studies highlighting variants associated with classic, nonclassic, or intermediate phenotypes. Understanding these genetic factors is crucial for predicting disease prognosis and tailoring effective treatment strategies for individuals with Morquio A syndrome.

OBJECTIVE: The aim of this meta-analysis is to comprehend the relationship between the severity of the phenotype and the genotype of patients with MPS IVA, considering factors such as the type of variant and its location in the different domains of the protein.

METHODS: This meta-analysis will include articles featuring participants of all genders and age groups who have a molecular diagnosis of MPS IVA and a description of the phenotype. Literature published in English, Spanish, and Portuguese will be considered. Exclusion criteria will encompass studies lacking full-text availability and those involving patients with an MPS IVA diagnosis but without phenotype information. The databases to be searched include PubMed, MEDLINE, ScienceDirect, and Scopus. The screening of literature, paper selection, and data extraction will involve 2 independent reviewers, who will conduct the process blindly. In the event of disagreements between the 2 reviewers at any stage, resolution will be sought through discussion or with the involvement of an additional reviewer. The final selection of manuscripts will be based on consensus. The results of the review will be presented using descriptive statistics, and the information will be organized in either diagrammatic or tabular formats, following the guidelines provided by the Joanna Briggs Institute. Genotype-phenotype relationships will be analyzed using IBM SPSS Statistics, using chi-square tests, Fisher exact tests, and regression analysis to interpret the data.

RESULTS: A literature search conducted in January 2024 produced 760 results. The review is expected to be completed by the end of 2024.

CONCLUSIONS: This meta-analysis will gather and analyze information on the phenotype-genotype relationship in patients diagnosed with MPS IVA. The data collection and resulting analyses will make a substantial contribution to understanding the underlying mechanism of the disease, enabling the prediction of the syndrome’s progression and severity.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56649.

PMID:39541578 | DOI:10.2196/56649

Microsc Microanal. 2024 Nov 14:ozae112. doi: 10.1093/mam/ozae112. Online ahead of print.

ABSTRACT

The production of plutonium-238 through irradiation of neptunium-237 (237Np) target materials for the use in radioisotope thermoelectric generators is paramount for continued deep space exploration. This work employs scanning electron microscopy to analyze 237Np materials coupled with a well-developed image analysis framework (Morphological Analysis for Material Attribution, or MAMA) to determine the degree of micron-scale homogeneity in the materials. This work demonstrated how the quantification of particle characteristics can validate production materials and affirm the qualitative similarities observed in micrographs. The 237Np oxide particle analysis determined that the materials from five production runs were quantitatively homogenous (significant at α = 0.05) in particle area, circularity, equivalent circular diameter, and ellipse aspect ratio, with two of the sampling dates having statistically significant different means for one of the four characteristics. These metrics not only confirm general homogeneity of the material but also expand the application of MAMA workflows to 237Np materials, demonstrating the utility of MAMA analysis for a wider breadth of nuclear materials than previously reported. In the open literature, this study is the first time that these microanalytical techniques were applied to 237Np materials to this degree.

PMID:39541565 | DOI:10.1093/mam/ozae112

JCO Glob Oncol. 2024 Nov;10:e2400059. doi: 10.1200/GO.24.00059. Epub 2024 Nov 14.

ABSTRACT

PURPOSE: Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer, with approximately 225,419 new cases with over 125,000 deaths annually in India. This trial compared the efficacy and safety of biosimilar cetuximab versus innovator cetuximab (IC) in combination with platinum-based chemotherapy in patients with recurrent locoregional or metastatic SCCHN.

METHODS: This phase III trial is a multicenter, randomized, double-blind and parallel group study performed in Indian patients with recurrent locoregional or metastatic SCCHN. Patients were randomly assigned in 2:1 ratio to receive biosimilar cetuximab and IC in combination with cisplatin and fluorouracil via intravenous infusions. The primary end points were disease control rate (DCR) and overall response rate (ORR) as per response evaluation criteria in solid tumors version 1.1. The secondary end points included pharmacokinetics (PK), immunogenicity, safety, and tolerability.

RESULTS: Of 180 patients enrolled, 120 patients received biosimilar cetuximab and 60 patients received IC treatment. No significant statistical difference was observed in the primary outcomes between two groups. Treatment difference in DCR and ORR response was found to be -5.21 (90% CI, -8.94 to -1.48) and -4.79 (90% CI, -19.42 to 9.84), respectively, indicating noninferiority to reference product. The incidence of treatment-emergent adverse events (AEs; biosimilar cetuximab: 89.2% v IC: 91.7%; P = .8364) and serious AEs (biosimilar cetuximab: 23.3% v IC: 13.3%; P = .0603) and PK parameters were comparable between treatment groups. The immunogenicity findings showed higher incidence of anticetuximab antibodies in the biosimilar cetuximab group compared with the IC group at the end of Study.

CONCLUSION: The findings of this study demonstrated noninferiority along with comparable PK, safety, and immunogenicity of biosimilar cetuximab and IC in patients with recurrent or metastatic SCCHN.

PMID:39541562 | DOI:10.1200/GO.24.00059

JCO Glob Oncol. 2024 Nov;10:e2400281. doi: 10.1200/GO-24-00281. Epub 2024 Nov 14.

ABSTRACT

PURPOSE: Health-related quality of life (HRQoL) is now an important goal of therapy for patients with chronic myeloid leukemia (CML). However, there is paucity of data for patients living in low-income countries (LICs) and on factors associated with their HRQoL profile. The primary objective was to compare the HRQoL of patients with CML living in an LIC (Ethiopia) with that of patients living in a high-income country (HIC).

METHODS: Adult patients with CML treated with tyrosine kinase inhibitors in Ethiopia were considered eligible for this study. To assess their HRQoL and symptom burden, eligible patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the EORTC Quality of Life Questionnaire Chronic Myeloid Leukemia 24 (QLQ-CML24). A matched case-control analysis was applied to compare the HRQoL profile of the herein-recruited Ethiopian cohort with a sample of patients with CML from an HIC (Italy).

RESULTS: Overall, 395 Ethiopian patients were enrolled between February 2021 and June 2021. Except for dyspnea and satisfaction with care, the Ethiopian patients reported lower HRQoL and functioning and higher symptom burden compared with patients with CML living in an HIC. A remarkable proportion of Ethiopian patients (n = 353, 89.4%) reported financial toxicity (FT). Compared with patients without FT, those with FT reported a higher prevalence of clinically important problems and symptoms across all the QLQ-C30 scales. For example, the prevalence of clinically important impairment of social functioning was almost sixfold higher for patients with FT compared with those without FT (41.8%, 7.1%, respectively).

CONCLUSION: Our results indicate that the HRQoL profile of patients with CML living in Ethiopia may be worse across several important functional and symptom domains than that of their peers living in an HIC. In addition, FT is highly prevalent among these patients and it is associated with poorer HRQoL outcomes.

PMID:39541560 | DOI:10.1200/GO-24-00281

JCO Glob Oncol. 2024 Nov;10:e2400031. doi: 10.1200/GO.24.00031. Epub 2024 Nov 14.

ABSTRACT

PURPOSE: Stronger Together is a peer mentoring model that seeks to address the severe lack of mental health and psychosocial support for patients with cancer in many low- and middle-income countries (LMICs). This article presents the results of the Stronger Together pilot study among patients with breast and gynecologic cancer in Viet Nam (VN).

METHODS: Eligible participants comprised women age 25 years or older with a diagnosis of breast or gynecologic cancers and receiving treatment at four participating hospitals. Participants were asked whether they wanted to proceed with usual care or be matched with a trained and supervised peer mentor (a cancer survivor). Surveys were administered at baseline (0) and 2, 4, and 6 months and assessed depression, anxiety, stress, mental health and physical health components of quality of life (QOL), self-efficacy, and social support. We computed and compared 2-, 4-, and 6-month changes in scores from baseline and conducted difference-in-difference analyses to estimate the intervention effect at 6 months.

RESULTS: The sample size included N = 186 participants. Mentees (n = 91) exhibited improvements in depression, anxiety, stress, and mental health QOL across all time points, whereas usual care participants (n = 95) experienced these improvements at later periods (4 and 6 months). Compared with usual care participants, mentees reported greater improvements in depression at 2 and 4 months, mental health QOL at all time points, and self-efficacy and social support at 4 and 6 months. Greater improvements in stress were also seen in the breast cancer subsample.

CONCLUSION: Stronger Together is a promising model to improve mental health and psychosocial outcomes among patients with breast and gynecologic cancer in VN and can help fill gaps in cancer peer support interventions in many LMICs.

PMID:39541553 | DOI:10.1200/GO.24.00031

J Psychopathol Clin Sci. 2024 Nov 14. doi: 10.1037/abn0000960. Online ahead of print.

ABSTRACT

Substance use relapse is difficult to define, and previous work has used one-size-fits-all ad hoc definitions. Researchers have called for a dynamic and personalized understanding of relapse as a concept and model, necessitating novel statistical tools. We aimed to develop and validate a novel statistical model of latent relapse processes: the double-well potential model (DWPM). This model describes posttreatment substance use in terms of a dynamical system with stable equilibria of abstinence and relapse, person-specific dominant equilibria (tilt), the ease of changing between equilibria (steepness), and an overall relapse risk (RR). Using timeline follow-back data from N = 139 adults with a substance use disorder transitioning back to the community after residential treatment, we examined individual differences and the criterion-related validity of DWPM parameters to determine the clinical utility of the double-well model. While nonuse was the predominant stable state across participants, we found significant between-subjects variability steepness and RR. These individual differences were predictable via demographics, baseline psychopathology, treatment history, and treatment condition. Steepness and RR also predicted long-term outcomes, including life satisfaction and criminal behavior, above and beyond traditional metrics of relapse (proportion of days used and time to first use). Thus, the DWPM is a strong theoretical and statistical representation of the underlying relapse processes. Moreover, the parameters show criterion-related validity and may be useful in precision medicine. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PMID:39541537 | DOI:10.1037/abn0000960

Psychol Methods. 2024 Nov 14. doi: 10.1037/met0000695. Online ahead of print.

ABSTRACT

Simulation studies are widely used for evaluating the performance of statistical methods in psychology. However, the quality of simulation studies can vary widely in terms of their design, execution, and reporting. In order to assess the quality of typical simulation studies in psychology, we reviewed 321 articles published in Psychological Methods, Behavior Research Methods, and Multivariate Behavioral Research in 2021 and 2022, among which 100/321 = 31.2% report a simulation study. We find that many articles do not provide complete and transparent information about key aspects of the study, such as justifications for the number of simulation repetitions, Monte Carlo uncertainty estimates, or code and data to reproduce the simulation studies. To address this problem, we provide a summary of the ADEMP (aims, data-generating mechanism, estimands and other targets, methods, performance measures) design and reporting framework from Morris et al. (2019) adapted to simulation studies in psychology. Based on this framework, we provide ADEMP-PreReg, a step-by-step template for researchers to use when designing, potentially preregistering, and reporting their simulation studies. We give formulae for estimating common performance measures, their Monte Carlo standard errors, and for calculating the number of simulation repetitions to achieve a desired Monte Carlo standard error. Finally, we give a detailed tutorial on how to apply the ADEMP framework in practice using an example simulation study on the evaluation of methods for the analysis of pre-post measurement experiments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PMID:39541533 | DOI:10.1037/met0000695

J Chem Theory Comput. 2024 Nov 14. doi: 10.1021/acs.jctc.4c01112. Online ahead of print.

ABSTRACT

Estimating absolute binding free energies from molecular simulations is a key step in computer-aided drug design pipelines, but the agreement between computational results and experiments is still very inconsistent. Both the accuracy of the computational model and the quality of the statistical sampling contribute to this discrepancy, yet disentangling the two remains a challenge. In this study, we present an automated protocol based on OneOPES, an enhanced sampling method that exploits replica exchange and can accelerate several collective variables to address the sampling problem. We apply this protocol to 37 host-guest systems. The simplicity of setting up the simulations and producing well-converged binding free energy estimates without the need to optimize simulation parameters provides a reliable solution to the sampling problem. This, in turn, allows for a systematic force field comparison and ranking according to the correlation between simulations and experiments, which can inform the selection of an appropriate model. The protocol can be readily adapted to test more force field combinations and study more complex protein-ligand systems, where the choice of an appropriate physical model is often based on heuristic considerations rather than systematic optimization.

PMID:39541508 | DOI:10.1021/acs.jctc.4c01112

J Nanobiotechnology. 2024 Nov 13;22(1):704. doi: 10.1186/s12951-024-02907-5.

ABSTRACT

As novel multifunctional materials that merge enzyme-like capabilities with the distinctive traits of nanomaterials, nanozymes have made significant strides in interdisciplinary research areas spanning materials science, bioscience, and beyond. This article, for the first time, employed bibliometric methods to conduct an in-depth statistical analysis of the global nanozymes research and demonstrate research progress, hotspots and trends. Drawing on data from the Web of Science Core Collection database, we comprehensively retrieved the publications from 2004 to 2024. The burgeoning interest in nanozymes research across various nations indicated a growing and widespread trend. This article further systematically elaborated the enzyme-like activities, matrix, multifunctional properties, catalytic mechanisms and various applications of nanozymes, and the field encounters challenges. Despite notable progress, and requires deeper exploration guide the future research directions. This field harbors broad potential for future developments, promising to impact various aspects of technology and society.

PMID:39538291 | DOI:10.1186/s12951-024-02907-5

BMC Cancer. 2024 Nov 13;24(1):1399. doi: 10.1186/s12885-024-13145-1.

ABSTRACT

BACKGROUND: Breast cancer is the most prevalent cancer worldwide. Belgium shows high age-standardized incidence rates, but also high survival rates. Like many health outcomes, breast cancer has been associated with multiple factors of socioeconomic status. This paper aims to (a) map educational differences in breast cancer incidence, mortality and death rates within 5 years of diagnosis, (b) update earlier trends in breast cancer mortality rates in Belgium for the 2004-2013 period and (c) investigate the role of fertility indicators as mediating factors in the association between education and breast cancer outcomes.

METHODS: Data consisted of a linkage between the 2001 Belgian Census, register data on mortality and cancer incidence data (2004-2013) from the Belgian Cancer Registry. We calculated age standardized rates, rate ratios (Poisson regression) and hazard ratios (Cox regression) and furthermore also applied the method of Excess Portion Eliminated (EPE) in a mediation analysis of the fertility indicators. We stratified our analysis by age: younger than 50 (premenopausal) and 50 or older (postmenopausal).

RESULTS: We observed striking differences in breast cancer incidence, all-cause and cause-specific death rates 5-years after diagnosis by educational level. Higher educated women had higher breast cancer incidence, but also lower all-cause and lower cause-specific death rates; adding up to zero differences in breast cancer mortality in the postmenopausal group and lower breast cancer mortality in the premenopausal group.

CONCLUSION: A notable shift in the social gradient occurred since the 1990’s, favouring higher-educated women in recent years. Especially, with regards to survival after diagnosis there is potential for policy intervention. Stage at diagnosis played a crucial role, but differences between socioeconomic groups remained significant after including this parameter. While fertility indicators played a role, the impact was less pronounced than expected.

PMID:39538280 | DOI:10.1186/s12885-024-13145-1