Category: Statistics

Ecol Appl. 2023 Jun 19:e2900. doi: 10.1002/eap.2900. Online ahead of print.

ABSTRACT

Exposure to pesticides can profoundly alter community dynamics. It is expected that dominance patterns will be enhanced or reduced depending on whether the dominant species is less or more sensitive to the pesticide than the subdominant species. Community dynamics are, however, also determined by processes linked to population growth as well as competition at carrying capacity. Here, we used a mesocosm experiment to quantify the effect of chlorpyrifos exposure on the population dynamics of four cladoceran species (Daphnia magna, D. pulicaria, D. galeata and Scapholeberis mucronata) in mixed cultures, testing for direct effects of chlorpyrifos and indirect effects mediated by interactions with other species on timing of population growth and dominance at carrying capacity. We also quantified whether the pesticide-induced changes in community dynamics affect top-down control of phytoplankton. By adding a treatment in which we used different genotype combinations of each species, we also tested to what extent genetic composition affects community responses to pesticide exposure. Immobilization tests showed that D. magna is the least sensitive to chlorpyrifos of the tested species. Chlorpyrifos exposure first lead to a reduction in the abundance of D. galeata to the benefit of D. pulicaria, and subsequently to a reduction in densities of D. pulicaria to the benefit of D. magna. This resulted in D. magna being more dominant in the pesticide than in the control treatment by the end of the experiment. There was no effect of genotypic differences on community patterns, and top-down control of phytoplankton was high in all treatments. Our results suggest that in this community dominance patterns are enhanced in line with the observed among-species differences in sensitivity to the pesticide. Our results also show that the development of the community in the pesticide treatment is a complex interaction between direct and indirect effects of the pesticide.

PMID:37335538 | DOI:10.1002/eap.2900

BJOG. 2023 Jun 19. doi: 10.1111/1471-0528.17558. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the effect of treatment with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS), versus primary debulking surgery (PDS), on quality of life (QoL) in patients with advanced epithelial ovarian cancer (EOC).

DESIGN: Randomised trial conducted in a single institution.

SETTING: Division of Gynaecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

SAMPLE: Patients with stage-IIIC/IV EOC and high tumour load.

METHODS: Patients were randomised (1:1) to undergo either PDS (PDS group) or NACT followed by IDS (NACT/IDS group).

MAIN OUTCOME MEASURES: Quality-of-life (QoL) data, assessed using the European Organization for Research and Treatment of Cancer core QoL questionnaire (QLQ-C30) and ovarian cancer module (OV28); co-primary outcomes were the QLQ-C30 global health score at 12 months (cross-sectional analysis) and the difference in mean QLQ-C30 global health score over time between treatment groups (longitudinal analysis).

RESULTS: From October 2011 to May 2016, 171 patients were enrolled (PDS = 84; NACT/IDS = 87). We observed no clinical or statistically significant difference between treatment groups in any of the QoL functioning scales at 12 months, including QLQ-C30 global health score (NACT/IDS group vs PDS group, mean difference 4.7, 95% CI -4.99 to 14.4, p = 0.340). Over time, we found lower global health scores for those undergoing PDS than for those receiving NACT (difference in mean score 6.27, 95% CI 0.440-12.11, p = 0.035), albeit this was not clinically relevant.

CONCLUSIONS: We found no difference in global QoL related to treatment approach at 12 months, even though patients in the NACT/IDS group reported better global health scores across the 12-month period compared with the PDS group; these findings further confirm that NACT/IDS might be a feasible option for patients unsuitable for PDS.

PMID:37334772 | DOI:10.1111/1471-0528.17558

Microsc Res Tech. 2023 Jun 19. doi: 10.1002/jemt.24369. Online ahead of print.

ABSTRACT

Medicinal plants are richest source of chemical compounds that can be used to evolve novel drugs. According to World Health Organization (WHO), in developing countries more than 3.5 billion people relay on herbal drugs for their primary health care. In the present study, an attempt was carried out to authenticate some selected medicinal plants (Fagonia cretica L., Peganum harmala L., Tribulus terrestris L., Chrozophora tinctoria L. Raf. and Ricinus communis L.) from family Zygophyllaceae and Euphorbiaceae using light and scanning electron macroscopic techniques. Macroscopic evaluation and comparative anatomy (Light Microscopy) of the root and fruits revealed great diversity in macro and microscopic features. Scanning electron microscopy (SEM) of root powder showed non-glandular trichomes, stellate trichomes, parenchyma cells and vessels. Fruits SEM exhibited non-glandular trichomes, glandular trichomes, stellate trichomes, peltate trichomes and mesocarp cells. Both macroscopic and microscopic evaluation plays a crucial role in the correct substantiation and validation of novel sources. These findings can serve as an essential source of information to accomplish the authenticity and to appraise the quality and purity of the herbal drugs in accordance to WHO guidelines. These parameters can be used to distinguish the selected plants from their commonly used adulterants. RESEARCH HIGHLIGHTS: In the current work, five plants (Fagonia cretica L., Peganum harmala L., Tribulus terrestris L., Chrozophora tinctoria L. Raf. and Ricinus communis L.) from Zygophyllaceae and Euphorbiaceae were investigated for macroscopy and microscopy (LM & SEM) for the first time. Macroscopic and microscopic evaluation disclosed great diversity in morphology and histology. Microscopy is the backbone of standardization process. Current study helped in correct identification and quality assurance of the plant materials. Their statistical investigation may possess great potency for plant taxonomists to further appraise the vegetative growth and tissue development which is requisite especially for fruit to enhance the yield of herbal drugs and their formulation. Further molecular studies, compounds isolation and characterization are required to deepen the knowledge of these herbal drugs.

PMID:37334760 | DOI:10.1002/jemt.24369

J Appl Clin Med Phys. 2023 Jun 19:e14065. doi: 10.1002/acm2.14065. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study is to investigate the use of a deep learning architecture for automated treatment planning for proton pencil beam scanning (PBS).

METHODS: A 3-dimensional (3D) U-Net model has been implemented in a commercial treatment planning system (TPS) that uses contoured regions of interest (ROI) binary masks as model inputs with a predicted dose distribution as the model output. Predicted dose distributions were converted to deliverable PBS treatment plans using a voxel-wise robust dose mimicking optimization algorithm. This model was leveraged to generate machine learning (ML) optimized plans for patients receiving proton PBS irradiation of the chest wall. Model training was carried out on a retrospective set of 48 previously-treated chest wall patient treatment plans. Model evaluation was carried out by generating ML-optimized plans on a hold-out set of 12 contoured chest wall patient CT datasets from previously treated patients. Clinical goal criteria and gamma analysis were used to compare dose distributions of the ML-optimized plans against the clinically approved plans across the test patients.

RESULTS: Statistical analysis of mean clinical goal criteria indicates that compared to the clinical plans, the ML optimization workflow generated robust plans with similar dose to the heart, lungs, and esophagus while achieving superior dosimetric coverage to the PTV chest wall (clinical mean V95 = 97.6% vs. ML mean V95 = 99.1%, p < 0.001) across the 12 test patients.

CONCLUSIONS: ML-based automated treatment plan optimization using the 3D U-Net model can generate treatment plans of similar clinical quality compared to human-driven optimization.

PMID:37334746 | DOI:10.1002/acm2.14065

J Clin Hypertens (Greenwich). 2023 Jun 19. doi: 10.1111/jch.14687. Online ahead of print.

ABSTRACT

To compare the predictive value of mortality between left ventricular hypertrophy (LVH) defined by Chinese thresholds and defined by international guidelines in hypertension individuals and investigate better indexation methods for LVH in Chinese population. We included 2454 community hypertensive patients with Left ventricular mass (LVM) and relative wall thickness. LVM was indexed to body surface area (BSA), height^{2 7} and height ^{1 7} . The outcomes were all-cause and cardiovascular mortality. Cox proportional hazards models were used to explore the association between LVH and the outcomes. C-statistics and time-dependent receiver operating characteristic curve (ROC) was used to evaluate the value of those indicators. During a median follow-up of 49 months (interquartile range 2-54 months), 174 participants (7.1%) died from any cause (n = 174), with 71 died of cardiovascular disease. LVM/BSA defined by the Chinese thresholds was significantly associated with cardiovascular mortality (HR: 1.63; 95%CI: 1.00-2.64). LVM/BSA was significantly associated with all-cause mortality using Chinese thresholds (HR: 1.56; 95%CI: 1.14-2.14) and using Guideline thresholds (HR: 1.52; 95%CI: 1.08-2.15). LVM/Height^1.7 was significantly associated with all-cause mortality using Chinese thresholds (HR: 1.60; 95%CI: 1.17-2.20) and using Guideline thresholds (HR: 1.54; 95%CI: 1.04-2.27). LVM/Height^2.7 was not significantly associated with all-cause mortality. C-statistics indicated that LVM/BSA and LVM/Height^1.7 by Chinese thresholds had better predictive ability for mortality. Time-ROC indicated that only LVM/Height^1.7 defined by Chinese threshold had incremental value for predicting mortality. We found that in community hypertensive populations, race-specific thresholds should be used to classify LV hypertrophy related to mortality risk stratification. LVM/BSA and LVM/Height^1.7 are acceptable normalization method in Chinese hypertension.

PMID:37334744 | DOI:10.1111/jch.14687

CNS Neurosci Ther. 2023 Jun 19. doi: 10.1111/cns.14316. Online ahead of print.

ABSTRACT

BACKGROUND: The systematic molecular associations between the peripheral blood cells and brain in Alzheimer’s disease (AD) remains unclear, which hinders our understanding of AD pathological mechanisms and the exploration of new diagnostic biomarkers.

METHODS: Here, we performed an integrated analysis of the brain and peripheral blood cells transcriptomics to establish peripheral biomarkers of AD. By employing multiple statistical analyses plus machine learning, we identified and validated multiple regulated central and peripheral network in patients with AD.

RESULTS: By bioinformatics analysis, a total of 243 genes were differentially expressed in the central and peripheral systems, mainly enriched in three modules: immune response, glucose metabolism and lysosome. In addition, lysosome related gene ATP6V1E1 and immune response related genes (IL2RG, OSM, EVI2B TNFRSF1A, CXCR4, STAT5A) were significantly correlated with Aβ or Tau pathology. Finally, receiver operating characteristic (ROC) analysis revealed that ATP6V1E1 showed high-diagnostic potential for AD.

CONCLUSION: Taken together, our data identified the main pathological pathways in AD progression, particularly the systemic dysregulation of the immune response, and provided peripheral biomarkers for AD diagnosis.

PMID:37334737 | DOI:10.1111/cns.14316

Ann Surg. 2023 Jun 19. doi: 10.1097/SLA.0000000000005958. Online ahead of print.

ABSTRACT

OBJECTIVE: We sought to evaluate symptomatic adverse event (AE) rates among patients with pancreatic cancer receiving neoadjuvant therapy on clinical trial (A021501) using the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE).

SUMMARY BACKGROUND DATA: To date, pancreatic cancer clinical trials have measured AEs using standard physician reporting (CTCAE). Patient-reported symptomatic AEs have been incompletely characterized.

METHODS: A021501 (Dec 31, 2016-Jan 1, 2019) randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX + hypofractionated radiotherapy (Arm 2), followed by pancreatectomy and adjuvant FOLFOX6. Patients completed PRO-CTCAE assessments at baseline, on day 1 of each chemotherapy cycle, and daily during radiotherapy.

RESULTS: Of 126 patients, 96 (76%) initiated treatment and completed a baseline plus at least 1 post-baseline PRO-CTCAE assessment. Diarrhea and fatigue were the only symptomatic grade 3 or higher AEs identified in at least 10% of patients using CTCAE. At least 10% of all patients reported an adjusted PRO-CTCAE composite grade 3 AE during neoadjuvant treatment for 10 of 15 items: anxiety (10%), bloating of abdomen (16%), decreased appetite (18%), diarrhea (13%), dry mouth (21%), fatigue (36%), nausea (18%), generalized pain (16%), abdominal pain (21%), and problems tasting (32%). Decreased appetite was higher in Arm 2 than in Arm 1 (P=0.0497); no other differences between study arms were observed.

CONCLUSIONS: Symptomatic AEs during neoadjuvant therapy were common and were reported more frequently by patients using PRO-CTCAE than were recorded by clinicians using standard CTCAE.

PMID:37334719 | DOI:10.1097/SLA.0000000000005958

Teach Learn Med. 2023 Jun 19:1-8. doi: 10.1080/10401334.2023.2224789. Online ahead of print.

ABSTRACT

Phenomenon: Existing literature, as well as anecdotal evidence, suggests that tiered clinical grading systems may display systematic demographic biases. This study aimed to investigate these potential inequities in-depth. Specifically, this study attempted to address the following gaps in the literature: (1) studying grades actually assigned to students (as opposed to self-reported ones), (2) using longitudinal data over an 8-year period, providing stability of data, (3) analyzing three important, potentially confounding covariates, (4) using a comprehensive multivariate statistical design, and (5) investigating not just the main effects of gender and race, but also their potential interaction. Approach: Participants included 1,905 graduates (985 women, 51.7%) who received the Doctor of Medicine degree between 2014 and 2021. Most of the participants were white (n = 1,310, 68.8%) and about one-fifth were nonwhite (n = 397, 20.8%). There were no reported race data for 10.4% (n = 198). To explore potential differential grading, a two-way multivariate analysis of covariance was employed to examine the impact of race and gender on grades in eight required clerkships, adjusting for prior academic performance. Findings: There were two significant main effects, race and gender, but no interaction effect between gender and race. Women received higher grades on average on all eight clerkships, and white students received higher grades on average on four of the eight clerkships (Medicine, Pediatrics, Surgery, Obstetrics/Gynecology). These relationships held even when accounting for prior performance covariates. Insights: These findings provide additional evidence that tiered grading systems may be subject to systematic demographic biases. It is difficult to tease apart the contributions of various factors to the observed differences in gender and race on clerkship grades, and the interactions that produce these biases may be quite complex. The simplest solution to cut through the tangled web of grading biases may be to move away from a tiered grading system altogether.

PMID:37334710 | DOI:10.1080/10401334.2023.2224789

J Biomol Struct Dyn. 2023 Jun 19:1-13. doi: 10.1080/07391102.2023.2225007. Online ahead of print.

ABSTRACT

The in silico evaluation of 27 p-aminosalicylic acid derivatives, also referred to as neuraminidase inhibitors was the focus of the current study. To search and predict new potential neuraminidase inhibitors, this study was based on the ligand-based pharmacophore modeling, 3D QSAR, molecular docking, ADMET and MD simulation studies. The data was generated from recently reported inhibitors and divided into two groups, one of these group has 17 compounds for training and the second group has 10 compounds for testing purpose. The generated pharmacophore has known as ADDPR_4 was found statistically significant 3D-QSAR model owing the high trust scores (R² = 0.974, Q² = 0.905, RMSE = 0.23). Morever external validation was also employed to evaluate the prediction capacity of the built pharmacophore model (R²_pred = 0.905). In addition, in silico ADMET, analyses were employed to evaluate the obtained hits for drug likeness properties. The stability of formed complexes was further evaluated using molecular dynamics. Top two hits showed stable complexes with Neuraminidase based on calculated total binding energy by MM-PBSA.Communicated by Ramaswamy H. Sarma.

PMID:37334701 | DOI:10.1080/07391102.2023.2225007

Ann Surg. 2023 Jun 19. doi: 10.1097/SLA.0000000000005942. Online ahead of print.

ABSTRACT

OBJECTIVE: This proof-of-concept explores the use of an episode grouper to more accurately identify the complete set of surgical services typically provided in a surgical episode of care and the corresponding range of prices, using colectomy for cancer as the example.

SUMMARY /BACKGROUND DATA: Price transparency is an important policy issue that will require surgeons to better understand the components and cost of care.

METHODS: This study uses the Episode Grouper for Medicare (EGM) business logic to construct colectomy surgical episodes of care for cancer using Medicare claims data for the Boston Hospital Referral Region (HRR) from 2012-2015. Descriptive statistics show the mean reimbursement based on patient severity and stage of surgery along with the number of unique clinicians billing for care and the mix of services provided.

RESULTS: The EGM episode grouper identified 3,182 colectomies in Boston between 2012 and 2015 with 1,607 done for cancer. The mean Medicare allowed amount per case is $29,954 and varies from $26,605 to $36,850 as you move from low to high severity cases. The intra-facility stage is the most expensive ($23,175 on average) compared to the pre ($780) and post ($6,479) facility stages. There is tremendous heterogeneity in service mix.

CONCLUSION: Episode groupers are a potentially valuable tool for identifying variation in service mix and teaming patterns that correlate with total price. By looking at patient care holistically, stakeholders can identify opportunities for price transparency and care redesign that have heretofore been hidden.

PMID:37334700 | DOI:10.1097/SLA.0000000000005942