Tag: statistics

J Clin Oncol. 2023 Apr 27:JCO2201153. doi: 10.1200/JCO.22.01153. Online ahead of print.

ABSTRACT

PURPOSE: Artificial intelligence (AI) algorithms improve breast cancer detection on mammography, but their contribution to long-term risk prediction for advanced and interval cancers is unknown.

METHODS: We identified 2,412 women with invasive breast cancer and 4,995 controls matched on age, race, and date of mammogram, from two US mammography cohorts, who had two-dimensional full-field digital mammograms performed 2-5.5 years before cancer diagnosis. We assessed Breast Imaging Reporting and Data System density, an AI malignancy score (1-10), and volumetric density measures. We used conditional logistic regression to estimate odds ratios (ORs), 95% CIs, adjusted for age and BMI, and C-statistics (AUC) to describe the association of AI score with invasive cancer and its contribution to models with breast density measures. Likelihood ratio tests (LRTs) and bootstrapping methods were used to compare model performance.

RESULTS: On mammograms between 2-5.5 years prior to cancer, a one unit increase in AI score was associated with 20% greater odds of invasive breast cancer (OR, 1.20; 95% CI, 1.17 to 1.22; AUC, 0.63; 95% CI, 0.62 to 0.64) and was similarly predictive of interval (OR, 1.20; 95% CI, 1.13 to 1.27; AUC, 0.63) and advanced cancers (OR, 1.23; 95% CI, 1.16 to 1.31; AUC, 0.64) and in dense (OR, 1.18; 95% CI, 1.15 to 1.22; AUC, 0.66) breasts. AI score improved prediction of all cancer types in models with density measures (P_LRT values < .001); discrimination improved for advanced cancer (ie, AUC for dense volume increased from 0.624 to 0.679, Δ AUC 0.065, P = .01) but did not reach statistical significance for interval cancer.

CONCLUSION: AI imaging algorithms coupled with breast density independently contribute to long-term risk prediction of invasive breast cancers, in particular, advanced cancer.

PMID:37104728 | DOI:10.1200/JCO.22.01153

J Chem Inf Model. 2023 Apr 27. doi: 10.1021/acs.jcim.3c00187. Online ahead of print.

ABSTRACT

In this work, we show that the apparent pK_a measured by standard titration experiments is an insufficient measure of acidity or basicity of organic functional groups in multiprotic compounds─a frequent aspect of lead optimization in pharmaceutical research. We show that the use of the apparent pK_a in this context may result in costly mistakes. To properly represent the group’s true acidity/basicity, we propose pK₅₀─a single-proton midpoint measure derived from a statistical thermodynamics treatment of multiprotic ionization. We show that pK₅₀, which may be directly measured in specialized NMR titration experiments, is superior in tracking the functional group’s acidity/basicity across congeneric series of related compounds and converges to the well familiar ionization constant in the monoprotic case.

PMID:37104727 | DOI:10.1021/acs.jcim.3c00187

J Clin Oncol. 2023 Apr 27:JCO2202389. doi: 10.1200/JCO.22.02389. Online ahead of print.

ABSTRACT

PURPOSE: To report patient-reported outcomes (PROs) of a phase III trial evaluating total androgen suppression (TAS) combined with dose-escalated radiation therapy (RT) for patients with intermediate-risk prostate cancer.

METHODS: Patients with intermediate-risk prostate cancer were randomly assigned to dose-escalated RT alone (arm 1) or RT plus TAS (arm 2) consisting of luteinizing hormone-releasing hormone agonist/antagonist with oral antiandrogen for 6 months. The primary PRO was the validated Expanded Prostate Cancer Index Composite (EPIC-50). Secondary PROs included Patient-Reported Outcome Measurement Information System (PROMIS)-fatigue and EuroQOL five-dimensions scale questionnaire (EQ-5D). PRO change scores, calculated for each patient as the follow-up score minus baseline score (at the end of RT and at 6, 12, and 60 months), were compared between treatment arms using a two-sample t test. An effect size of 0.50 standard deviation was considered clinically meaningful.

RESULTS: For the primary PRO instrument (EPIC), the completion rates were ≥86% through the first year of follow-up and 70%-75% at 5 years. For the EPIC hormonal and sexual domains, there were clinically meaningful (P < .0001) deficits in the RT + TAS arm. However, there were no clinically meaningful differences by 1 year between arms. There were also no clinically meaningful differences at any time points between arms for PROMIS-fatigue, EQ-5D, and EPIC bowel/urinary scores.

CONCLUSION: Compared with dose-escalated RT alone, adding TAS demonstrated clinically meaningful declines only in EPIC hormonal and sexual domains. However, even these PRO differences were transient, and there were no clinically meaningful differences between arms by 1 year.

PMID:37104723 | DOI:10.1200/JCO.22.02389

J Am Chem Soc. 2023 Apr 27. doi: 10.1021/jacs.3c01095. Online ahead of print.

ABSTRACT

Conformational changes underpin function and encode complex biomolecular mechanisms. Gaining atomic-level detail of how such changes occur has the potential to reveal these mechanisms and is of critical importance in identifying drug targets, facilitating rational drug design, and enabling bioengineering applications. While the past two decades have brought Markov state model techniques to the point where practitioners can regularly use them to glimpse the long-time dynamics of slow conformations in complex systems, many systems are still beyond their reach. In this Perspective, we discuss how including memory (i.e., non-Markovian effects) can reduce the computational cost to predict the long-time dynamics in these complex systems by orders of magnitude and with greater accuracy and resolution than state-of-the-art Markov state models. We illustrate how memory lies at the heart of successful and promising techniques, ranging from the Fokker-Planck and generalized Langevin equations to deep-learning recurrent neural networks and generalized master equations. We delineate how these techniques work, identify insights that they can offer in biomolecular systems, and discuss their advantages and disadvantages in practical settings. We show how generalized master equations can enable the investigation of, for example, the gate-opening process in RNA polymerase II and demonstrate how our recent advances tame the deleterious influence of statistical underconvergence of the molecular dynamics simulations used to parameterize these techniques. This represents a significant leap forward that will enable our memory-based techniques to interrogate systems that are currently beyond the reach of even the best Markov state models. We conclude by discussing some current challenges and future prospects for how exploiting memory will open the door to many exciting opportunities.

PMID:37104720 | DOI:10.1021/jacs.3c01095

Clin J Pain. 2023 Apr 24. doi: 10.1097/AJP.0000000000001116. Online ahead of print.

ABSTRACT

OBJECTIVE: Determine the relative effectiveness and safety profiles of percutaneous and minimally invasive interventions for chronic low back pain.

METHODS: A systematic search was performed for randomized controlled trials (RCTs) published in the past 20 years reporting on radiofrequency (RF) ablation of the basivertebral, disc annulus and facet nerve structures, steroid injection of the disc, facet joint and medial branch, biologic therapies, and multifidus muscle stimulation. Outcomes evaluated included Visual Analog Scale (VAS) pain scores, Oswestry Disability Index (ODI) scores, quality of life (SF-36 and EQ-5D) scores and serious adverse event (SAE) rates. Basivertebral nerve (BVN) ablation was chosen as the subject of comparison to all other therapies using a random-effects meta-analysis.

RESULTS: Twenty-seven studies were included. BVN ablation was found to provide significant improvements in VAS and ODI scores for 6-, 12- and 24-months follow-up (P≤0.05). Biologic therapy and multifidus muscle stimulation were the only two treatments with both VAS and ODI outcomes not significantly different from BVN ablation at 6-, 12- and 24-months follow-up. All outcomes found to be statistically significant represented inferior results to those of BVN ablation. Insufficient data precluded meaningful comparisons of SF-36 and EQ-5D scores. The SAE rates for all therapies and all reported time points were not significantly different from BVN ablation except for biologic therapy and multifidus muscle stimulation at 6-months follow- up.

CONCLUSIONS: BVN ablation, biologic therapy and multifidus stimulation all provide significant, durable improvements in both pain and disability compared to other interventions, which provided only short-term pain relief. Studies on BVN ablation reported no SAEs, a significantly better result than for studies of biologic therapy and multifidus stimulation.

PMID:37104694 | DOI:10.1097/AJP.0000000000001116

J Infus Nurs. 2023 May-Jun 01;46(3):149-156. doi: 10.1097/NAN.0000000000000503.

ABSTRACT

Caregiver/patient fall injury risks increase when medical tubing drapes on floors. The objective of this research was to examine the value of a novel carriage system that organizes and elevates medical and intravenous (IV) tubing. Using a prospective, multicenter, cohort design, value of the IV carriage system was assessed using a valid, reliable survey that provided the total score and scores of 3 involvement factors: personal relevance, attitude, and importance. The survey was scored on a 0-100 scale, and questions about tubing elevation, patient mobility, and ease of use were rated on 0-10 scales. Participants were adult and pediatric inpatient caregivers (n = 131). In adult intensive care environments (n = 61), carriage system value scores were higher in the quaternary care site compared to 4 enterprise adult intensive care sites (median [Q1, Q3]: 90.0 [69.2, 97.5] vs 72.5 [52.5, 78.3], respectively; P = .008). Compared to nurses working in adult environments (n = 58), pediatric nurses (n = 40) had higher value scores (median [Q1, Q3]: 89.2 [68.3, 97.5] vs 97.5 [85.8, 100.0], respectively; P = .007). High median score ratings (9-10) were given for tubing elevation, patient mobility, and ease of use. In conclusion, the IV carriage system was valued by nurses as an important tool in clinical practice.

PMID:37104690 | DOI:10.1097/NAN.0000000000000503

J Infus Nurs. 2023 May-Jun 01;46(3):139-148. doi: 10.1097/NAN.0000000000000504.

ABSTRACT

Central vascular access devices (CVADs) are standard for the treatment of leukemia. The objectives of this study were to examine predictors for central line-associated bloodstream infection (CLABSI) and causative microorganisms. A retrospective case/control design was used to examine electronic health records (EHRs) of patients with acute leukemia, a CVAD, and neutropenia. Variables were examined for differences between those who developed bacteremia (cases: n = 10) and those who did not (controls: n = 13). Variables included conditions of health (eg, patient history, laboratory results at the time of nadir, nutritional intake during hospitalization, and CVAD care practices). Fisher exact and Mann-Whitney U tests were used for comparison. Nine organisms were identified, including viridans group streptococci (20%) and Escherichia coli (20%). No statistical differences in variables were found between groups. However, over 50% of the nutritional intake data was missing due to lack of documentation. These findings indicate that further study is needed to examine barriers for electronic documentation. The data collection site found opportunities to improve patient care that included education regarding the daily care of CVADs, collaboration with nutritional services to ensure accurate assessments, and coordination with clinical information systems to improve clinical documentation compliance.

PMID:37104689 | DOI:10.1097/NAN.0000000000000504

Methods Protoc. 2023 Mar 28;6(2):35. doi: 10.3390/mps6020035.

ABSTRACT

Increasing evidence strongly supports the key role of the tumour microenvironment in response to systemic therapy, particularly immune checkpoint inhibitors (ICIs). The tumour microenvironment is a complex tapestry of immune cells, some of which can suppress T-cell immunity to negatively impact ICI therapy. The immune component of the tumour microenvironment, although poorly understood, has the potential to reveal novel insights that can impact the efficacy and safety of ICI therapy. Successful identification and validation of these factors using cutting-edge spatial and single-cell technologies may enable the development of broad acting adjunct therapies as well as personalised cancer immunotherapies in the near future. In this paper we describe a protocol built upon Visium (10x Genomics) spatial transcriptomics to map and characterise the tumour-infiltrating immune microenvironment in malignant pleural mesothelioma. Using ImSig tumour-specific immune cell gene signatures and BayesSpace Bayesian statistical methodology, we were able to significantly improve immune cell identification and spatial resolution, respectively, improving our ability to analyse immune cell interactions within the tumour microenvironment.

PMID:37104017 | DOI:10.3390/mps6020035

Noncoding RNA. 2023 Mar 30;9(2):22. doi: 10.3390/ncrna9020022.

ABSTRACT

Long non-coding RNAs (lncRNAs) play important roles in the maintenance of metabolic homeostasis. Recently, many studies have suggested that lncRNAs, such as Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and Imprinted Maternally Expressed Transcript (H19), might participate in the pathogenesis of metabolic disorders such as obesity. We conducted a case-control study with 150 Russian children and adolescents aged between 5 and 17 years old in order to assess the statistical association between the single nucleotide polymorphisms (SNPs) rs3200401 in MALAT1 and rs217727 in H19, and the risk of developing obesity in this population. We further explored the possible association of rs3200401 and rs217727 with BMI Z-score and insulin resistance. The MALAT1 rs3200401 and H19 rs217727 SNPs were genotyped using Taqman SNP genotyping assay. The MALAT1 rs3200401 SNP was identified as a risk factor for childhood obesity (p < 0.05) under the dominant and allelic models, and the CT heterozygous genotype was associated with the risk of increased BMI and with insulin resistance. The H19 rs217727 SNP had no significant association with obesity risk (all p > 0.05). Our findings thus suggest that MALAT1 SNP rs3200401 is a potential indicator of obesity susceptibility and pathogenesis in children and adolescents.

PMID:37104004 | DOI:10.3390/ncrna9020022

JMIR Form Res. 2023 Apr 27;7:e44857. doi: 10.2196/44857.

ABSTRACT

BACKGROUND: Social skills training by human trainers is a well-established method of teaching appropriate social and communication skills and strengthening social self-efficacy. Specifically, human social skills training is a fundamental approach to teaching and learning the rules of social interaction. However, it is cost-ineffective and offers low accessibility, since the number of professional trainers is limited. A conversational agent is a system that can communicate with a human being in a natural language. We proposed to overcome the limitations of current social skills training with conversational agents. Our system is capable of speech recognition, response selection, and speech synthesis and can also generate nonverbal behaviors. We developed a system that incorporated automated social skills training that completely adheres to the training model of Bellack et al through a conversational agent.

OBJECTIVE: This study aimed to validate the training effect of a conversational agent-based social skills training system in members of the general population during a 4-week training session. We compare 2 groups (with and without training) and hypothesize that the trained group’s social skills will improve. Furthermore, this study sought to clarify the effect size for future larger-scale evaluations, including a much larger group of different social pathological phenomena.

METHODS: For the experiment, 26 healthy Japanese participants were separated into 2 groups, where we hypothesized that group 1 (system trained) will make greater improvement than group 2 (nontrained). System training was done as a 4-week intervention where the participants visit the examination room every week. Each training session included social skills training with a conversational agent for 3 basic skills. We evaluated the training effect using questionnaires in pre- and posttraining evaluations. In addition to the questionnaires, we conducted a performance test that required the social cognition and expression of participants in new role-play scenarios. Blind ratings by third-party trainers were made by watching recorded role-play videos. A nonparametric Wilcoxson Rank Sum test was performed for each variable. Improvement between pre- and posttraining evaluations was used to compare the 2 groups. Moreover, we compared the statistical significance from the questionnaires and ratings between the 2 groups.

RESULTS: Of the 26 recruited participants, 18 completed this experiment: 9 in group 1 and 9 in group 2. Those in group 1 achieved significant improvement in generalized self-efficacy (P=.02; effect size r=0.53). We also found a significant decrease in state anxiety presence (P=.04; r=0.49), measured by the State-Trait Anxiety Inventory (STAI). For ratings by third-party trainers, speech clarity was significantly strengthened in group 1 (P=.03; r=0.30).

CONCLUSIONS: Our findings reveal the usefulness of the automated social skills training after a 4-week training period. This study confirms a large effect size between groups on generalized self-efficacy, state anxiety presence, and speech clarity.

PMID:37103996 | DOI:10.2196/44857