Category: Statistics

BMC Nephrol. 2023 Jul 28;24(1):224. doi: 10.1186/s12882-023-03280-5.

ABSTRACT

PURPOSE: Osteoporosis is a systemic disease characterized by decreased bone strength and an increased risk of fracture in old age. Age and pathologic renal failure are independent risk factors for osteoporosis. However, it is not determined whether age-related decreased renal function, in the context of senescence, can be considered as an independent risk factor for osteoporosis. Therefore, this study was conducted to evaluate the effect of senescence-induced renal failure on bone quality and trabecular bone score.

METHODS: This study used a cross-sectional design and was carried out based on data collected during the Bushehr Elderly Health (BEH) program, Phase II. A total of 2,125 elderly participants aged over 60 years old entered the study after meeting the inclusion criteria and providing informed consent. They underwent examinations for weight, height, abdominal and hip circumference, as well as blood pressure measurement. All participants also underwent DXA to assess bone mass density (BMD). Trabecular bone score (TBS) was calculated using the DXA apparatus software output. Univariate and adjusted multivariate linear regression analyses were used to evaluate the associations.

RESULTS: In the univariate linear regression analysis, there was a direct correlation between age-related renal failure and TBS (β = 0.038, p < 0.0001), neck of femur BMD (β = 0.047, p < 0.0001), and lumbar BMD (β = 0.055, p < 0.0001). However, after adjusting for BMI, age, sex, smoking, and physical activity, no significant association was observed for these variables.

CONCLUSION: It is hypothesized that age-related renal failure cannot be considered as an independent risk factor for osteoporosis in elderly individuals aged over 60 years old.

PMID:37507659 | DOI:10.1186/s12882-023-03280-5

BMC Cancer. 2023 Jul 28;23(1):708. doi: 10.1186/s12885-023-11153-1.

ABSTRACT

BACKGROUND: In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab.

METHODS: Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor β receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors. Phase II evaluated the safety of galunisertib with nivolumab in NSCLC patients who had received prior platinum-based treatment but were immuno-oncology agent-naive.

RESULTS: This trial was conducted between October 2015 and August 2020. No dose-limiting toxicities were observed in phase I. In the phase II NSCLC cohort (n = 25), patients received 150 mg twice daily galunisertib (14 days on/14 days off dosing schedule for all phases) plus nivolumab at 3 mg/kg (intravenously every 2 weeks). In this phase, the most frequent treatment-related adverse events (AEs) were pruritus (n = 9, 36%), fatigue (n = 8, 32%), and decreased appetite (n = 7, 28%). No grade 4 or 5 treatment-related AEs were observed. Six (24%) patients had confirmed partial response (PR) and 4 (16%) had stable disease; 1 additional patient had confirmed PR after initial pseudo-progression. The median duration of response was 7.43 months (95% confidence interval [CI]: 3.75, NR). Among the 7 responders, including the delayed responder, 1 had high PD-L1 expression (≥ 50%). The median progression-free survival was 5.26 months (95% CI: 1.77, 9.20) and the median overall survival was 11.99 months (95% CI: 8.15, NR). Interferon gamma response genes were induced post-treatment and cell adhesion genes were repressed, although the association of these observations with tumor response and clinical outcomes was not statistically powered due to limited samples available.

CONCLUSIONS: The study met its primary endpoint as galunisertib combined with nivolumab was well tolerated. Preliminary efficacy was observed in a subset of patients in the Phase 2 NSCLC cohort.

TRIAL REGISTRATION: Trial registered with ClinicalTrials.gov (NCT02423343; 22.04.2015).

PMID:37507657 | DOI:10.1186/s12885-023-11153-1

Behav Res Methods. 2023 Jul 28. doi: 10.3758/s13428-023-02187-1. Online ahead of print.

ABSTRACT

A guideline is proposed that comprises the minimum items to be reported in research studies involving an eye tracker and human or non-human primate participant(s). This guideline was developed over a 3-year period using a consensus-based process via an open invitation to the international eye tracking community. This guideline will be reviewed at maximum intervals of 4 years.

PMID:37507649 | DOI:10.3758/s13428-023-02187-1

Accid Anal Prev. 2023 Jul 26;191:107232. doi: 10.1016/j.aap.2023.107232. Online ahead of print.

ABSTRACT

This paper aims to empirically evaluate the ordered and unordered discrete outcome frameworks to approach riders’ red-light running (RLR) decisions and compare the differences in influencing factors between riders’ risk-taking and opportunistic RLR behaviors. A total of 2057 cyclist samples approaching the intersections during red signals were observed by video in Beijing, China. To better capture the unobserved heterogeneity, apart from the traditional models, three advanced models including the random thresholds random parameters hierarchical ordered logit (RTRPHOL) model, the random parameters logit model with heterogeneity in means and variances (RPLHMV) model, and the correlated random parameters logit model with heterogeneity in means (CRPLHM), are developed. Results show that: 1) the unordered framework statistically outperformed its ordered counterparts, and the RPLHMV and CRPLHM models are statistically better than others. 2) The female and e-bicycle indicators produce a heterogeneity-in-means effect, and the low-volume and left-side indicators produce a heterogeneity-in-variances effect. 3) e-bike riders and riders from the right side are more inclined to have risk-taking behavior than opportunistic behavior, and both RLR behaviors of cyclists are most susceptible to the number of violating individual indicator. Findings illustrate that multilayer unobserved heterogeneity should be adequately considered in developing precise micro-simulation and practical guidance in traffic safety.

PMID:37506407 | DOI:10.1016/j.aap.2023.107232

Photobiomodul Photomed Laser Surg. 2023 Jul 28. doi: 10.1089/photob.2023.0046. Online ahead of print.

ABSTRACT

Objective: This systematic review aimed to assess the influence of antimicrobial photodynamic therapy (aPDT) as an adjunct to mechanical debridement (MD) on peri-implant clinical and radiographic outcomes among cigarette smokers and diabetics with peri-implant mucositis (piM). Methods: Randomized controlled trials, assessing the clinical and radiographic parameters of aPDT versus MD alone among smokers and diabetics with piM, were included in the study. Meta-analyses were conducted to calculate the standard mean difference with a 95% confidence interval. The methodological quality of the included studies was assessed utilizing the modified Jadad quality scale. Results: The meta-analyses found statistically significant differences between the impact of adjunct aPDT and MD alone on the peri-implant plaque index (PI), probing depth (PD), and bleeding on probing among smokers and diabetics with piM at the final follow-up visit. However, no significant differences were found between the impact of adjunct aPDT and MD alone on the peri-implant crestal bone loss among smokers and diabetics with piM at the final follow-up. Conclusions: The application of aPDT as an adjunctive to MD demonstrated improved scores of the peri-implant clinical parameters among smokers and diabetics with piM in comparison with MD alone.

PMID:37506360 | DOI:10.1089/photob.2023.0046

JCO Clin Cancer Inform. 2023 Jul;7:e2300048. doi: 10.1200/CCI.23.00048.

ABSTRACT

PURPOSE: Radiotherapy (RT) toxicities can impair survival and quality of life, yet remain understudied. Real-world evidence holds potential to improve our understanding of toxicities, but toxicity information is often only in clinical notes. We developed natural language processing (NLP) models to identify the presence and severity of esophagitis from notes of patients treated with thoracic RT.

METHODS: Our corpus consisted of a gold-labeled data set of 1,524 clinical notes from 124 patients with lung cancer treated with RT, manually annotated for Common Terminology Criteria for Adverse Events (CTCAE) v5.0 esophagitis grade, and a silver-labeled data set of 2,420 notes from 1,832 patients from whom toxicity grades had been collected as structured data during clinical care. We fine-tuned statistical and pretrained Bidirectional Encoder Representations from Transformers-based models for three esophagitis classification tasks: task 1, no esophagitis versus grade 1-3; task 2, grade ≤1 versus >1; and task 3, no esophagitis versus grade 1 versus grade 2-3. Transferability was tested on 345 notes from patients with esophageal cancer undergoing RT.

RESULTS: Fine-tuning of PubMedBERT yielded the best performance. The best macro-F1 was 0.92, 0.82, and 0.74 for tasks 1, 2, and 3, respectively. Selecting the most informative note sections during fine-tuning improved macro-F1 by ≥2% for all tasks. Silver-labeled data improved the macro-F1 by ≥3% across all tasks. For the esophageal cancer notes, the best macro-F1 was 0.73, 0.74, and 0.65 for tasks 1, 2, and 3, respectively, without additional fine-tuning.

CONCLUSION: To our knowledge, this is the first effort to automatically extract esophagitis toxicity severity according to CTCAE guidelines from clinical notes. This provides proof of concept for NLP-based automated detailed toxicity monitoring in expanded domains.

PMID:37506330 | DOI:10.1200/CCI.23.00048

J Clin Oncol. 2023 Jul 28:JCO2202322. doi: 10.1200/JCO.22.02322. Online ahead of print.

ABSTRACT

PURPOSE: In COLUMBUS part 1, patients with advanced BRAF^V600-mutant melanoma were randomly assigned 1:1:1 to encorafenib 450 mg once daily plus binimetinib 45 mg twice a day (COMBO450), vemurafenib 960 mg twice a day, or encorafenib 300 mg once daily (ENCO300). As previously reported, COMBO450 improved progression-free survival (PFS) versus vemurafenib (part 1 primary end point) and ENCO300 (part 1 key secondary end point; not statistically significant). Part 2, requested by the US Food and Drug Administration, evaluated the contribution of binimetinib by maintaining the same encorafenib dosage in the combination (encorafenib 300 mg once daily plus binimetinib 45 mg twice daily [COMBO300]) and ENCO300 arms.

METHODS: In part 2, patients were randomly assigned 3:1 to COMBO300 or ENCO300. ENCO300 (parts 1 and 2) data were combined, per protocol, for PFS analysis (key secondary end point) by a blinded independent review committee (BIRC). Other analyses included overall response rate (ORR), overall survival, and safety.

RESULTS: Two hundred fifty-eight patients received COMBO300, and 86 received ENCO300. Per protocol, ENCO300 arms (parts 1 and 2 combined) were also evaluated (n = 280). The median follow-up for ENCO300 was 40.8 months (part 1) and 57.1 months (part 2). The median PFS (95% CI) was 12.9 months (10.9 to 14.9) for COMBO300 versus 9.2 months (7.4 to 11.1) for ENCO300 (parts 1 and 2) and 7.4 months (5.6 to 9.2) for ENCO300 (part 2). The hazard ratio (95% CI) for COMBO300 was 0.74 (0.60 to 0.92; two-sided P = .003) versus ENCO300 (parts 1 and 2). The ORR by BIRC (95% CI) was 68% (62 to 74) and 51% (45 to 57) for COMBO300 and ENCO300 (parts 1 and 2), respectively. COMBO300 had greater relative dose intensity and fewer grade 3/4 adverse events than ENCO300.

CONCLUSION: COMBO300 improved PFS, ORR, and tolerability compared with ENCO300, confirming the contribution of binimetinib to efficacy and safety.

PMID:37506329 | DOI:10.1200/JCO.22.02322

Environ Sci Technol. 2023 Jul 28. doi: 10.1021/acs.est.3c01121. Online ahead of print.

ABSTRACT

Government policies and corporate strategies aimed at reducing methane emissions from the oil and gas sector increasingly rely on measurement-informed, site-level emission inventories, as conventional bottom-up inventories poorly capture temporal variability and the heavy-tailed nature of methane emissions. This work is based on an 11-month methane measurement campaign at oil and gas production sites. We find that operator-level top-down methane measurements are lower during the end-of-project phase than during the baseline phase. However, gaps persist between end-of-project top-down measurements and bottom-up site-level inventories, which we reconcile with high-frequency data from continuous monitoring systems (CMS). Specifically, we use CMS to (i) validate specific snapshot measurements and determine how they relate to the temporal emission profile of a given site and (ii) create a measurement-informed, site-level inventory that can be validated with top-down measurements to update conventional bottom-up inventories. This work presents a real-world demonstration of how to reconcile CMS rate estimates and top-down snapshot measurements jointly with bottom-up inventories at the site level. More broadly, it demonstrates the importance of multiscale measurements when creating measurement-informed, site-level emission inventories, which is a critical aspect of recent regulatory requirements in the Inflation Reduction Act, voluntary methane initiatives such as the Oil and Gas Methane Partnership 2.0, and corporate strategies.

PMID:37506319 | DOI:10.1021/acs.est.3c01121

Genome Biol Evol. 2023 Jul 28:evad132. doi: 10.1093/gbe/evad132. Online ahead of print.

ABSTRACT

Meiotic recombination is both a fundamental biological process required for proper chromosomal segregation during meiosis and an important genomic parameter that shapes major features of the genomic landscape. However, despite the central importance of this phenotype, we lack a clear understanding of the selective pressures that shape its variation in natural populations, including humans. While there is strong evidence of fitness costs of low rates of recombination, the possible fitness costs of high rates of recombination are less defined. To determine whether a single lower fitness bound can explain the variation in recombination rate observed in human populations, we simulated the evolution of recombination rate as a sexually dimorphic quantitative trait. Under each scenario, we statistically compared the resulting trait distribution to the observed distribution of recombination rates from a published study of the Icelandic population. To capture the genetic architecture of recombination rate in humans, we modeled it as a moderately complex trait with modest heritability. For our fitness function, we implemented a hyperbolic tangent curve with several flexible parameters to capture a wide range of existing hypotheses. We found that costs of low rates of recombination alone are likely insufficient to explain current variation in recombination rate in both males and females, supporting the existence of fitness costs of high rates of recombination in humans. With simulations using both upper and lower fitness boundaries, we describe a parameter space for the costs of high recombination rate that produces results consistent with empirical observations.

PMID:37506266 | DOI:10.1093/gbe/evad132

Neurodiagn J. 2023 Jul 28:1-10. doi: 10.1080/21646821.2023.2232709. Online ahead of print.

ABSTRACT

Background: The intensive physical regimen followed by throwers and archers can impose stress on the elbow and hand in particular positions, which may increase the risk of developing peripheral nerve disorders and symptoms like pain and numbness. Purpose: The purpose of the study is to investigate the effect of forearm and elbow joint positions on ulnar nerve conduction velocity in throwers, archers, and non-athletes. Method: Total 34 subjects both males and females were included with body mass index (BMI) between 18.5 and 24.9 kg/m². Nerve conduction study (NeuroStim NS2 EMG/NCV/EP System) was used for measuring ulnar nerve conduction velocity (NCV) across elbow joint at different angles (0° elbow extension, 45°, 90°, and 120° elbow flexion) with different forearm positions. Result: Repeated Measure Analysis of Variance (RMANOVA) revealed that there was a statistically significant difference in mean values of ulnar NCV at different angles, forearm positions & groups (p < .05). Conclusion: The forearm and elbow positions can have a significant impact on ulnar NCV, especially in athletes who perform repetitive upper limb motions. Results showed that the archers had significantly slower NCV than throwers and non-athletes at 90° of elbow flexion and forearm pronation.

PMID:37506256 | DOI:10.1080/21646821.2023.2232709