An assessment of compositional methods for the analysis of DNA methylation-based deconvolution estimates.

DNA methylation (DNAm)-based deconvolution estimates contain relative data, forming a composition, that standard methods (testing directly on cell proportions) are ill-suited to handle. In this study we examined the performance of an alternative method, analysis of compositions of microbiomes (ANCOM), for the analysis of DNAm-based deconvolution estimates. We performed two different simulation studies comparing ANCOM to a standard approach (two sample t-test performed directly on cell proportions) and analyzed a real-world data from the Women's Health Initiative to evaluate the applicability of ANCOM to DNAm-based deconvolution estimates. Our findings indicate that ANCOM can effectively account for the compositional nature of DNAm-based deconvolution estimates. ANCOM adequately controls the false discovery rate while maintaining statistical power comparable to that of standard methods.

DNA methylation (DNAm)-based deconvolution provides highly accurate estimates of the proportion of each cell type in a mixed-cell type biological sample (e.g., whole-blood). These estimates can be used for examining the association between cell type proportions and biological or clinical end points; for example, comparing the estimated neutrophil proportion in whole blood between smokers and non-smokers. Cell proportion data has unique features which present challenges for traditional and widely used statistical methods. In response to this issue, our work presents two simulation studies and a real-world analysis that benchmark the performance of current standard statistical methods against an alternative method called analysis composition of microbes (ANCOM), which was originally developed for the analysis of microbiome data. In our real-world analysis we used DNAm data collected from Women's Health Initiative Long Life Study I and compared the results of each method against a gold-standard that is typically not available for these analyses. In each of our simulation studies, ANCOM was able to detect true differences in cell proportions between the groups being compared but had a much lower rate of false discovery compared with the standard statistical methods. Our real-world analysis demonstrated similar findings. Overall, our study highlights the potential of ANCOM as a powerful and robust method for analyzing DNAm-derived deconvolution estimates when the interest is comparisons of cell type proportions and biological or clinical end points. ANCOM's ability to minimize false discovery while maintaining robust statistical power positions it as a valuable addition to the epigenomic analysis toolkit.

Proportion and factors influencing healthcare-seeking behavior among older people in Motta town, East Gojjam: a community-based cross-sectional study, Ethiopia, 2023.

BACKGROUND: In resource-limited countries, older people who are at risk and face numerous health problems, often receive insufficient attention regarding their healthcare-seeking behavior. Assessing the proportion of healthcare-seeking behavior and associated factors among older people in Motta town, was the aim of the study. METHOD: A community-based cross-sectional study was carried out from April 22 to May 22, 2023. The study subjects were chosen using a systematic random sampling technique. To identify candidate variables for multivariable analysis, a bivariable logistic regression analysis was performed. Variables having a P-value of < 0.05 were considered statistically significant. RESULTS: From the total, 161 (39.3%) of respondents had good healthcare-seeking behavior with 95% CI [35%, 44%]. Secondary school [AOR = 2.69, 95% CI = 1.27, 5.68], Education college and above [AOR = 4.6, 95% CI = 2.27, 9.33], Family support during their illness [AOR = 1.39, 95% CI = 1.05, 3.09], Members of CBHI [AOR = 2.02, 95% CI = 1.21, 3.36], and presence of chronic illness [AOR = 2.55, 95%, CI = 1.64, 3.97] were significantly associated with good healthcare-seeking behavior. CONCLUSION AND RECOMMENDATION: This study found that good healthcare-seeking behavior among older people is significantly associated with higher education, strong family support, Community-Based Health Insurance (CBHI) membership, and chronic illnesses. Improving health literacy through education, strengthening family support systems, expanding CBHI participation for better healthcare access, and developing targeted chronic disease management programs to enhance this behavior is recommended. These strategies can collectively improve healthcare utilization and outcomes for older people.

There Is no Universal Standard of Beauty.

This article discusses the various factors that contribute to facial beauty and the different contexts in which they are significant. The authors examine the roles of the golden ratio, ideal proportions, symmetry, and specific facial features in what constitutes an attractive face. They also investigate the influence of cultural and evolutionary perspectives on facial beauty and the impact of social media on our perception of beauty. The article provides a comprehensive overview of the topic and emphasises the significance of facial beauty and its impact on our lives. The authors acknowledge that the concept of beauty is difficult to define with absolute precision, and that the objective-subjective argument regarding facial beauty remains unsolved. However, they argue that physical attributes undoubtedly influence perceptions of attractiveness, but beauty extends beyond surface-level features. They also suggest that embracing diversity in beauty standards fosters a more inclusive society that celebrates the unique qualities of every person.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PD-L1 expression as a predictive biomarker in patients with recurrent or metastatic salivary gland carcinoma treated with pembrolizumab.

Although immune checkpoint inhibitors (ICIs) are effective in some patients with salivary gland carcinoma (SGC), biomarkers which predict the efficacy and prognosis of SGC patients treated with pembrolizumab have not been identified. We conducted a multi-institutional retrospective cohort study to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with recurrent and/or metastatic SGC and to determine optimal cut-off values of the combined positive score (CPS) and tumor proportion score (TPS) as numerical expression levels of programmed death-ligand 1 (PD-L1), which predict the efficacy of pembrolizumab. Furthermore, we investigated the association of patient characteristics and hematological markers with clinical outcomes, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). From 2016 to 2021, 27 patients were included in the analysis. ORR of SGC was 25.9%. Optimal cut-off values of CPS and TPS were 15 and 25%, respectively. ORRs of CPS-high and TPS-high were 55.6 and 75.0%, respectively, and significantly higher than those of CPS-low and TPS-low. Furthermore, patients with a low platelet-lymphocyte ratio (PLR) had a significantly longer PFS. No grade 4 or greater adverse events were observed. This study demonstrated the efficacy and safety of pembrolizumab monotherapy and identified optimal cut-off values of CPS and TPS.

Distributions of trace elements with Long-term grazing exclusion in a semi-arid grassland of Inner Mongolia.

Trace elements are the essential mineral nutrients in grassland, however, we still know little about the distributions of trace elements in grassland with long-term grazing exclusion. The contents, stocks, and proportions of iron (Fe), aluminum (Al), manganese (Mn), and boron (B) in green plant-litter-root-soil were evaluated by enclosing for 18, and 39 years inside the fence (F18 and F39) and grazing outside the fence (F0) in Inner Mongolia grassland. The results showed that F18 and F39 decreased the stocks of Fe, Al, and Mn in green plant and root compared to F0 (p < .05), while increased the stocks of them in litter (p < .05). The stock of Fe, Al, and Mn in green plant at F39 was 28.6%, 13.9%, and 39.2% higher than that at F18. The stocks of four trace elements in first layer litter at F39 were increased by 12.7%-52.2% compared to F18, whereas the stocks of them in third layer litter were decreased by 32.2%-42.5%. The F18 obviously increased the stocks of Fe and Mn in soil, especially B (p < .05). While the stocks of these trace elements in soil at F39 were 9.1%-28.0% lower than that at F18, especially B (p < .05). In conclusion, the trace elements were mainly shifted from green plant and root to soil and third layer litter with 18-year grazing exclusion. Compared to 18-year grazing exclusion, the trace elements were shifted from third layer litter and soil to root with 39-year grazing exclusion.

Evaluation of Adherence and Persistence to Triple Therapy in Patients with COPD: A German Claims Data Study.

Purpose: Triple therapy (long-acting muscarinic antagonist/long-acting ß2-agonist/inhaled corticosteroid) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. Multiple-inhaler triple therapy (MITT) is associated with poor adherence and persistence. This study assessed comparative adherence and persistence to single-inhaler triple therapy (SITT) versus MITT among patients with COPD in a real-world setting in Germany. Patients and Methods: This retrospective analysis using the WIG2 benchmark database identified patients with COPD newly initiating triple therapy with MITT or SITT (fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or formoterol/beclomethasone/glycopyrronium bromide [FOR/BDP/GLY]) November 2017-June 2019. Eligible patients were ≥35 years with 1 year's continual insurance prior to triple therapy initiation and no previous record of triple therapy. Inverse probability of treatment weighting was used to balance baseline characteristics. Adherence was measured using proportion of days covered (PDC) at 6, 12, and 18 months post-treatment initiation; persistence (time until treatment discontinuation) was measured at 6, 12, and 18 months, with a gap of >30 days used to define non-persistence. Results: Of 5710 patients included in the analysis (mean age 66 years), 71.4% initiated MITT and 28.6% initiated SITT (FF/UMEC/VI: 41.4%; FOR/BDP/GLY: 58.6%). Mean PDC was higher among SITT versus MITT users at all time points; at each time point, mean PDC was highest among FF/UMEC/VI users. During the first 6 months following treatment initiation, higher adherence was exhibited by FF/UMEC/VI (29%) and FOR/BDP/GLY (19%) users versus MITT users. Over the entire observation period, FF/UMEC/VI users had the highest proportion of persistent patients; at 18 months, 16.5% of FF/UMEC/VI users were persistent versus 2.3% of MITT users. Conclusion: Patients initiating SITT in Germany had significantly higher adherence and persistence compared with patients initiating MITT over 6 to 18 months following treatment initiation. Among SITT, FF/UMEC/VI users had the highest proportion of adherence and persistence.

Continuous and discrete proportion elicit different cognitive strategies.

Despite proportional information being ubiquitous, there is not a standard account of proportional reasoning. Part of the difficulty is that there are several apparent contradictions: in some contexts, proportion is easy and privileged, while in others it is difficult and ignored. One possibility is that although we see similarities across tasks requiring proportional reasoning, people approach them with different strategies. We test this hypothesis by implementing strategies computationally and quantitatively comparing them with Bayesian tools, using data from continuous (e.g., pie chart) and discrete (e.g., dots) stimuli and preschoolers, 2nd and 5th graders, and adults. Overall, people's comparisons of highly regular and continuous proportion are better fit by proportion strategy models, but comparisons of discrete proportion are better fit by a numerator comparison model. These systematic differences in strategies suggest that there is not a single, simple explanation for behavior in terms of success or failure, but rather a variety of possible strategies that may be chosen in different contexts.

Simulation analyses of the evolution of intra-inflorescence flowering patterns assuming selection on anthesis interval among individual flowers.

What conditions select flowering patterns within inflorescences, or variation in the anthesis interval within inflorescences among plants? Under what conditions are gradual blooming and simultaneous blooming, both traits related to floral display size, advantageous? We constructed a simulation model in which the opening times and longevities of individual flowers within inflorescences, the sizes of attractive structures of individual flowers, and the numbers of ovules and pollen grains produced by individual flowers evolve. Individual plants in the population compete for pollinators, and plants are selected by pollinators according to their floral display sizes and amounts of resources allocated to attractive structures. We found that, if the proportion of pollen on a pollinator deposited on a stigma was low, gradual blooming did not evolve even if inbreeding depression was greater than 0.5. This is because the amount of outcross-pollen on pollinators decreased at a low rate during flower visits within a single inflorescence, and the selfing rate was suppressed to a low level even if the floral display size was large. On the other hand, if the proportion of pollen deposition was high, gradual blooming evolved even if inbreeding depression was smaller than 0.5. This may be because gradual blooming can enhance pollen delivery to other plants by reducing the loss of self-pollen by geitonogamy. On the other hand, allocation ratios among floral organs (female and male organs and attractive structures) were independent of the degree of simultaneous and gradual blooming within inflorescences. We concluded that the evolution of gradual blooming is more strongly affected by the proportion of pollen on a pollinator deposited on a stigma than by inbreeding depression.

Integration of miRNA expression analysis of purified leukocytes and whole blood reveals blood-borne candidate biomarkers for lung cancer.

Changes in leukocyte populations may confound the disease-associated miRNA signals in the blood of cancer patients. We aimed to develop a method to detect differentially expressed miRNAs from lung cancer whole blood samples that are not influenced by variations in leukocyte proportions. The Ref-miREO method identifies differential miRNAs unaffected by changes in leukocyte populations by comparing the within-sample relative expression orderings (REOs) of miRNAs from healthy leukocyte subtypes and those from lung cancer blood samples. Over 77% of the differential miRNAs observed between lung cancer and healthy blood samples overlapped with those between myeloid-derived and lymphoid-derived leukocytes, suggesting the potential impact of changes in leukocyte populations on miRNA profile. Ref-miREO identified 16 differential miRNAs that target 19 lung adenocarcinoma-related genes previously linked to leukocytes. These miRNAs showed enrichment in cancer-related pathways and demonstrated high potential as diagnostic biomarkers, with the LASSO regression models effectively distinguishing between healthy and lung cancer blood or serum samples (all AUC > 0.85). Additionally, 12 of these miRNAs exhibited significant prognostic correlations. The Ref-miREO method offers valuable candidates for circulating biomarker detection in cancer that are not affected by changes in leukocyte populations.

Frequency of antimicrobial-resistant bloodstream infections in 111 hospitals in Thailand, 2022.

OBJECTIVES: To evaluate the frequency of antimicrobial-resistant bloodstream infections (AMR BSI) in Thailand. METHODS: We analyzed data from 2022, generated by 111 public hospitals in health regions 1 to 12, using the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), and submitted to the Ministry of Public Health, Thailand. Multilevel Poisson regression models were used. RESULTS: The most common cause of community-origin AMR BSI was third-generation cephalosporin-resistant Escherichia coli (3GCREC, 65.6%; 5101/7773 patients) and of hospital-origin AMR BSI was carbapenem-resistant Acinetobacter baumannii (CRAB, 51.2%, 4968/9747 patients). The percentage of patients tested for BSI was negatively associated with the frequency of community-origin 3GCREC BSI and hospital-origin CRAB BSI (per 100,000 tested patients). Hospitals in health regions 4 (lower central region) had the highest frequency of community-origin 3GCREC BSI (adjusted incidence rate ratio, 2.06; 95% confidence interval: 1.52-2.97). Health regions were not associated with the frequency of hospital-origin CRAB BSI, and between-hospital variation was high, even adjusting for hospital level and size. CONCLUSION: The high between-hospital variation of hospital-origin CRAB BSI suggests the importance of hospital-specific factors. Our approach and findings highlight health regions and hospitals where actions against AMR infection, including antimicrobial stewardship and infection control, should be prioritized.

A Retrospective Review on HIV Pre-Exposure Prophylaxis in Davao City.

Objectives: Evaluating the adherence to HIV Pre-Exposure Prophylaxis (PrEP) is essential for increasing its utilization and decreasing the risk of HIV transmission among Davao City's vulnerable groups. Methods: The research method utilized in the study is a quantitative, retrospective, descriptive research design. This method was employed to retrospectively review the de-identified data, which involved the fill and refill dates of PrEP and tablets supplied, to calculate the Proportion of Days Covered (PDC) among individuals in Davao City from January 2021 to December 2023. The study also included some demographic characteristics such as age and gender. Results: From 178 data entries collected, the age group of 25 to 34 years old was found to have the highest HIV PrEP use (52.25%), followed by those between 18 to 24 (30.90%), 35 to 44 (13.48%), and 45 years old and older (3.37%). Out of 178, only 2 clients were female. Furthermore, 73.60% of the 178 entries in the pharmacy records were identified to be taking PrEP daily. Descriptive statistics showed that the frequency of adherent clients across the years were 36.36%, 44.74% and 38.46%, respectively. Furthermore, the average PDC through the years was found to be 70.13%, 80.48%, and 72.8%. Age did not significantly affect adherence to PrEP during the years investigated (p-values > 0.05). Conclusion: Adherence to PrEP improved consistently in 2022 but declined in 2023, showing erratic adherence rates. Furthermore, adherence to HIV PrEP in Davao City was found to be suboptimal and while there are clients who are adherent, many are not. The results emphasize the need for targeted interventions and suggest that other socio-behavioral factors may play a role in this. To improve adherence and prevent HIV contractions, both short-term actions like public education campaigns about HIV PrEP and long-term plans like incorporating PrEP into the community pharmacies can be contributive.

Domain-specific control for cognitive and emotional conflict: Evidence from the transfer of proportion congruency effects.

There is ongoing debate about whether control-related processing related to cognitive conflict and emotional conflict operate independently. This study manipulated the proportion of congruent to incongruent trials to determine the domain specificity or generality of these two types of conflict control. Two experiments were conducted in which spatial Simon conflict was combined with emotional face-word conflict. In Experiment 1, the proportion congruency (PC) of spatial conflict was manipulated, and in Experiment 2, the PC of emotional conflict was manipulated. The aim was to determine whether control-related processes elicited by cognitive or emotional conflict show domain-specific (within cognitive or within emotional control-related effects) or domain-general effects, where control elicited by cognitive conflict benefits emotional control processes and vice versa. Behavioral findings indicated that spatial and emotional conflict exhibited within-domain PC effects. For event-related brain potential (ERP) activity, PC effects were primarily reflected in a late slow potential, rather than an early negativity, suggesting that control-related adjustments impacted conflict resolution rather than conflict detection. Furthermore, the results did not show evidence of PC effects across domains for behavioral or ERP data, indicating that proactive control elicited by PC manipulation does not transfer across cognitive and emotional conflict. This study supports the modular nature of proactive control for processes related to cognitive and emotional control.

PD-L1 Expression in Paired Samples of Rectal Cancer.

Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to tumour proportion (TPS), immune cell (ICS), and the combined positive score (CPS). Eighty-three patients were included. At diagnosis, PD-L1 expression ≥1%/≥5% was observed in 15.4%/0%, 80.7%/37.4%, and 69.2%/25.6% of patients based on TPS, ICS, and CPS, respectively. At surgery, the respective figures were 4.6%/1.5%, 60.2%/32.5%, and 50.7%/26.2%. Using the 1% cut-off and regardless of the scoring system, PD-L1 was less expressed in surgery than biopsy samples (p ≤ 0.04). In paired specimens, PD-L1-ICS reduction was especially observed following neoadjuvant long-course (chemo)radiotherapy (p = 0.03). PD-L1-ICS of ≥5% in surgical samples (HR: 0.17; p = 0.02), and a biopsy-to-surgery increase in PD-L1-ICS (HR: 0.19; p = 0.04) was predictive for longer disease-free survival, while the PD-L1-ICS of either ≥1% (HR 0.28; p = 0.04) or ≥5% (HR 0.19; p = 0.03) in surgical samples and the biopsy-to-surgery increase in PD-L1-ICS (HR: 0.20; p = 0.04) were associated with better overall survival. Our study suggests that PD-L1 expression in RC is largely reflective of immune cell infiltration, and its presence/increase in surgical samples predicts better outcomes.

Rare incompatible stimuli evoke visual mismatch negativity in a flanker task.

In the flanker task, the behavioral performance for incompatible stimuli is worse in the mostly compatible (rare) condition than in the equiprobable condition. Furthermore, incompatible stimuli evoke visual mismatch negativity (VMMN) when comparing the rare and equiprobable conditions. Compatible and incompatible stimuli differ in terms of their shape and type. This study aimed to examine whether VMMN evoked by rare incompatible stimuli were associated with the shape or type of the stimulus. In a modified version of the flanker task, stimuli were manipulated by two shapes (typical or peculiar) and two types (compatible or incompatible): typical compatible stimuli (< < < < < and > > > > >), typical incompatible stimuli (> > < > > and < < > < <), peculiar compatible stimuli (+ < < < + and + > > > +), and peculiar incompatible stimuli (+ > < > + and + < > < +). In the rare condition, typical incompatible, peculiar compatible, and peculiar incompatible stimuli were presented with a probability of 10%, whereas all the stimuli were presented equally in the equiprobable condition. Right posterior negativity from 200 to 250 ms was significantly more negative in the rare condition than in the equiprobable condition for typical and peculiar incompatible stimuli; however, this difference was not observed for peculiar compatible stimuli. VMMN was significantly more negative for typical and peculiar incompatible stimuli than for peculiar compatible stimuli, and was not significantly different between typical and peculiar incompatible stimuli. These findings suggest that VMMN for incompatible stimuli is associated with the type rather than the shape of the stimulus.

Developing the Additive Systems of Stand Basal Area Model for Broad-Leaved Mixed Forests.

Stand basal area (SBA) is an important variable in the prediction of forest growth and harvest yield. However, achieving the additivity of SBA models for multiple tree species in the complex structure of broad-leaved mixed forests is an urgent scientific issue in the study of accurately predicting the SBA of mixed forests. This study used data from 58 sample plots (30 m × 30 m) for Populus davidiana × Betula platyphylla broad-leaved mixed forests to construct the SBA basic model based on nonlinear least squares regression (NLS). Adjustment in proportion (AP) and nonlinear seemingly unrelated regression (NSUR) were used to construct a multi-species additive basal area prediction model. The results identified the Richards model (M6) and Korf model (M1) as optimal for predicting the SBA of P. davidiana and B. platyphylla, respectively. The SBA models incorporate site quality, stand density index, and age at 1.3 m above ground level, which improves the prediction accuracy of basal area. Compared to AP, NSUR is an effective method for addressing the additivity of basal area in multi-species mixed forests. The results of this study can provide a scientific basis for optimizing stand structure and accurately predicting SBA in multi-species mixed forests.

Phylogenetic Diversity Indices from an Affine and Projective Viewpoint.

Phylogenetic diversity indices are commonly used to rank the elements in a collection of species or populations for conservation purposes. The derivation of these indices is typically based on some quantitative description of the evolutionary history of the species in question, which is often given in terms of a phylogenetic tree. Both rooted and unrooted phylogenetic trees can be employed, and there are close connections between the indices that are derived in these two different ways. In this paper, we introduce more general phylogenetic diversity indices that can be derived from collections of subsets (clusters) and collections of bipartitions (splits) of the given set of species. Such indices could be useful, for example, in case there is some uncertainty in the topology of the tree being used to derive a phylogenetic diversity index. As well as characterizing some of the indices that we introduce in terms of their special properties, we provide a link between cluster-based and split-based phylogenetic diversity indices that uses a discrete analogue of the classical link between affine and projective geometry. This provides a unified framework for many of the various phylogenetic diversity indices used in the literature based on rooted and unrooted phylogenetic trees, generalizations and new proofs for previous results concerning tree-based indices, and a way to define some new phylogenetic diversity indices that naturally arise as affine or projective variants of each other or as generalizations of tree-based indices.

Genetic distance and ancestry proportion modify the association between maternal genetic risk score of type 2 diabetes and fetal growth.

BACKGROUND: Maternal genetic risk of type 2 diabetes (T2D) has been associated with fetal growth, but the influence of genetic ancestry is not yet fully understood. We aimed to investigate the influence of genetic distance (GD) and genetic ancestry proportion (GAP) on the association of maternal genetic risk score of T2D (GRST2D) with fetal weight and birthweight. METHODS: Multi-ancestral pregnant women (n = 1,837) from the NICHD Fetal Growth Studies - Singletons cohort were included in the current analyses. Fetal weight (in grams, g) was estimated from ultrasound measurements of fetal biometry, and birthweight (g) was measured at delivery. GRST2D was calculated using T2D-associated variants identified in the latest trans-ancestral genome-wide association study and was categorized into quartiles. GD and GAP were estimated using genotype data of four reference populations. GD was categorized into closest, middle, and farthest tertiles, and GAP was categorized as highest, medium, and lowest. Linear regression analyses were performed to test the association of GRST2D with fetal weight and birthweight, adjusted for covariates, in each GD and GAP category. RESULTS: Among women with the closest GD from African and Amerindigenous ancestries, the fourth and third GRST2D quartile was significantly associated with 5.18 to 7.48 g (weeks 17-20) and 6.83 to 25.44 g (weeks 19-27) larger fetal weight compared to the first quartile, respectively. Among women with middle GD from European ancestry, the fourth GRST2D quartile was significantly associated with 5.73 to 21.21 g (weeks 18-26) larger fetal weight. Furthermore, among women with middle GD from European and African ancestries, the fourth and second GRST2D quartiles were significantly associated with 117.04 g (95% CI = 23.88-210.20, p = 0.014) and 95.05 g (95% CI = 4.73-185.36, p = 0.039) larger birthweight compared to the first quartile, respectively. The absence of significant association among women with the closest GD from East Asian ancestry was complemented by a positive significant association among women with the highest East Asian GAP. CONCLUSIONS: The association between maternal GRST2D and fetal growth began in early-second trimester and was influenced by GD and GAP. The results suggest the use of genetic GD and GAP could improve the generalizability of GRS.

Combining Partial True Discovery Guarantee Procedures.

Closed testing has recently been shown to be optimal for simultaneous true discovery proportion control. It is, however, challenging to construct true discovery guarantee procedures in such a way that it focuses power on some feature sets chosen by users based on their specific interest or expertise. We propose a procedure that allows users to target power on prespecified feature sets, that is, "focus sets." Still, the method also allows inference for feature sets chosen post hoc, that is, "nonfocus sets," for which we deduce a true discovery lower confidence bound by interpolation. Our procedure is built from partial true discovery guarantee procedures combined with Holm's procedure and is a conservative shortcut to the closed testing procedure. A simulation study confirms that the statistical power of our method is relatively high for focus sets, at the cost of power for nonfocus sets, as desired. In addition, we investigate its power property for sets with specific structures, for example, trees and directed acyclic graphs. We also compare our method with AdaFilter in the context of replicability analysis. The application of our method is illustrated with a gene ontology analysis in gene expression data.

Treatment patterns and factors associated with adherence in pulmonary arterial hypertension.

OBJECTIVE: Improving understanding of actual pulmonary hypertension (PH) treatment adherence patterns is crucial to properly treating these patients. We aimed to primarily assess adherence to treatments used for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) specific therapies, identify potential factors related to it and secondly describe its treatment patterns. METHODS: A 6-month observational cross-sectional study in a tertiary care hospital was conducted. Patients with PH-targeted therapy who picked it up in the ambulatory hospital pharmacy and who had been on treatment with the same drug for at least 1 year were included. Adherence was assessed as: 1) Proportion of days covered (PDC); and 2) Simplified Medication Adherence Questionnaire (SMAQ). PDC ≥80% was considered adherent. Statistical analyses were performed to evaluate the study outcomes. Logistic regressions were estimated to identify the association between baseline characteristics and factors associated with adherence. P < 0.05 indicated statistical significance. RESULTS: A total of 63 patients with 127 different treatments were included, 71.4% were females with a mean age (SD) of 59 (15) years. PAH was the most common diagnosis (74.6%). Double therapy was used in 39.7% of patients, being the combination of Macitentan + Tadalafil and Ambrisentan + Tadalafil the most prescribed. Endothelin receptor antagonists were the most used treatment (40.2%). Adherence according to PDC was 93.7%, showing no great differences depending on the targeted drug used, and according to SMAQ 61.9%. The agreement degree of both methods was slight (65.1%; Kappa 0.12). Only female sex (OR: 0.23, 95% CI: 0.06-0.90; p = 0.035) was associated with worse adherence in the SMAQ method but not in the PDC. Adverse events were reported by a 55.6% of participants and the perception of effective treatment was high (95.2%). CONCLUSIONS: Adherence to PH therapy differs depending on the assessment method; PDC showed greater adherence rate than SMAQ. According to SMAQ, female sex may have a negative impact on adherence in this cohort, but PDC revealed no factors influencing it. No notable differences in adherence between treatment types were found and generally patients felt the treatments were effective in controlling their disease.

Analyzing the correlation between low proportion of hobnail features in papillary thyroid carcinoma and clinical aggressiveness risk.

PURPOSE: Hobnail features may enhance the clinical aggressiveness of papillary thyroid carcinoma (PTC). However, whether a low proportion (<30%) of these features contributes to increased PTC aggressiveness remains unclear. This study investigated whether PTC cases with a low proportion hobnail features (<30%) exhibit clinical invasiveness and pathological features of aggressiveness. METHODS: Pathological specimens from patients with postoperatively diagnosed PTC were retrospectively analyzed. Among them, 29 PTC cases with a low proportion of hobnail features (<30%) were compared with 173 consecutive classical PTC (cPTC) cases. Data regarding age at presentation, sex, tumor size, number of tumors, and histological characteristics were obtained by reviewing electronic medical records. Postoperative information was obtained during follow-up visits and telephone interviews. RESULTS: Twenty-nine patients with PTC with a low proportion of hobnail features (<30%) were identified, exhibiting a median age of 34 years. At a median follow-up of 31 (IQR, 23-37) months, two patients had recurrent disease in the PTC with a low proportion of hobnail features (<30%) group, whereas there was no recurrence in the cPTC group. No distant metastasis and postoperative mortality were observed in either group. Compared with the cPTC group, patients with PTC and a low proportion of hobnail features exhibited larger tumor volumes and higher susceptibility to capsular invasion and lymph node metastasis. Tumor size and hobnail features emerged as independent risk factors for lymph node metastasis. CONCLUSION: PTC with a low proportion hobnail features (<30%) and larger tumor volumes are associated with the occurrence of lymph node metastasis. A low proportion of hobnail features (<30%) in PTC may heighten invasiveness, elevating the risk of recurrence.