bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adapting differential molecular representation with hierarchical prompts for multi-label property prediction
Authors: Kang Linjia , Zhou Songhua , Fang Shuyan , Liu Shichao 
Published: September 2024

Abstract
Accurate prediction of molecular properties is crucial in drug discovery. Traditional methods often overlook that real-world molecules typically exhibit multiple property labels with complex correlations. To this end, we propose a novel framework, HiPM, which stands for Hierarchical Prompted Molecular representation learning framework. HiPM leverages task-aware prompts to enhance the differential expression of tasks in molecular representations and mitigate negative transfer caused by conflicts in individual task information. Our framework comprises two core components: the Molecular Representation Encoder (MRE) and the Task-Aware Prompter (TAP). MRE employs a hierarchical message-passing network architecture to capture molecular features at both the atom and motif levels. Meanwhile, TAP utilizes agglomerative hierarchical clustering algorithm to construct a prompt tree that reflects task affinity and distinctiveness, enabling the model to consider multi-granular correlation information among tasks, thereby effectively handling the complexity of multi-label property prediction. Extensive experiments demonstrate that HiPM achieves state-of-the-art performance across various multi-label datasets, offering a novel perspective on multi-label molecular representation learning.
Uncertainty quantification in high-dimensional linear models incorporating graphical structures with applications to gene set analysis
Authors: Tan Xiangyong , Zhang Xiao , Cui Yuehua , Liu Xu 
Published: September 2024

Abstract

Motivation
The functions of genes in networks are typically correlated due to their functional connectivity. Variable selection methods have been developed to select important genes associated with a trait while incorporating network graphical information. However, no method has been proposed to quantify the uncertainty of individual genes under such settings.

Results
In this paper, we construct confidence intervals (CIs) and provide P-values for parameters of a high-dimensional linear model incorporating graphical structures where the number of variables p diverges with the number of observations. For combining the graphical information, we propose a graph-constrained desparsified LASSO (least absolute shrinkage and selection operator) (GCDL) estimator, which reduces dramatically the influence of high correlation of predictors and enjoys the advantage of faster computation and higher accuracy compared with the desparsified LASSO. Theoretical results show that the GCDL estimator achieves asymptotic normality. The asymptotic property of the uniform convergence is established, with which an explicit expression of the uniform CI can be derived. Extensive numerical results indicate that the GCDL estimator and its (uniform) CI perform well even when predictors are highly correlated.

Availability and implementation
An R package implementing the proposed method is available at https://github.com/XiaoZhangryy/gcdl.
Sensitivity analysis for publication bias in meta-analysis of sparse data based on exact likelihood
Authors: Hu Taojun , Zhou Yi , Hattori Satoshi 
Published: September 2024

ABSTRACT
Meta-analysis is a powerful tool to synthesize findings from multiple studies. The normal–normal random-effects model is widely used to account for between-study heterogeneity. However, meta-analyses of sparse data, which may arise when the event rate is low for binary or count outcomes, pose a challenge to the normal–normal random-effects model in the accuracy and stability in inference since the normal approximation in the within-study model may not be good. To reduce bias arising from data sparsity, the generalized linear mixed model can be used by replacing the approximate normal within-study model with an exact model. Publication bias is one of the most serious threats in meta-analysis. Several quantitative sensitivity analysis methods for evaluating the potential impacts of selective publication are available for the normal–normal random-effects model. We propose a sensitivity analysis method by extending the likelihood-based sensitivity analysis with the $t$-statistic selection function of Copas to several generalized linear mixed-effects models. Through applications of our proposed method to several real-world meta-analyses and simulation studies, the proposed method was proven to outperform the likelihood-based sensitivity analysis based on the normal–normal model. The proposed method would give useful guidance to address publication bias in the meta-analysis of sparse data.
A Bayesian latent-subgroup platform design for dose optimization
Authors: Mu Rongji , Zhan Xiaojiang , Tang Rui (Sammi) , Yuan Ying 
Published: September 2024

ABSTRACT
The US Food and Drug Administration launched Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development, calling for the paradigm shift from finding the maximum tolerated dose to the identification of optimal biological dose (OBD). Motivated by a real-world drug development program, we propose a master-protocol-based platform trial design to simultaneously identify OBDs of a new drug, combined with standards of care or other novel agents, in multiple indications. We propose a Bayesian latent subgroup model to accommodate the treatment heterogeneity across indications, and employ Bayesian hierarchical models to borrow information within subgroups. At each interim analysis, we update the subgroup membership and dose–toxicity and –efficacy estimates, as well as the estimate of the utility for risk-benefit tradeoff, based on the observed data across treatment arms to inform the arm-specific decision of dose escalation and de-escalation and identify the OBD for each arm of a combination partner and an indication. The simulation study shows that the proposed design has desirable operating characteristics, providing a highly flexible and efficient way for dose optimization. The design has great potential to shorten the drug development timeline, save costs by reducing overlapping infrastructure, and speed up regulatory approval.
On the Addams family of discrete frailty distributions for modeling multivariate case I interval-censored data
Authors: Bardo Maximilian , Hens Niel , Unkel Steffen 
Published: September 2024

Abstract
Random effect models for time-to-event data, also known as frailty models, provide a conceptually appealing way of quantifying association between survival times and of representing heterogeneities resulting from factors which may be difficult or impossible to measure. In the literature, the random effect is usually assumed to have a continuous distribution. However, in some areas of application, discrete frailty distributions may be more appropriate. The present paper is about the implementation and interpretation of the Addams family of discrete frailty distributions. We propose methods of estimation for this family of densities in the context of shared frailty models for the hazard rates for case I interval-censored data. Our optimization framework allows for stratification of random effect distributions by covariates. We highlight interpretational advantages of the Addams family of discrete frailty distributions and theK-point distribution as compared to other frailty distributions. A unique feature of the Addams family and the K-point distribution is that the support of the frailty distribution depends on its parameters. This feature is best exploited by imposing a model on the distributional parameters, resulting in a model with non-homogeneous covariate effects that can be analyzed using standard measures such as the hazard ratio. Our methods are illustrated with applications to multivariate case I interval-censored infection data.
Reflectance confocal microscopy to diagnose malignant melanoma and lentigo maligna in the UK: a single-centre prospective observational trial
Authors: Stevens Howard P , Pellacani Giovanni , Angus Colin , El-Jabbour Joseph N 
Published: September 2024

Abstract

Background
Previous work with reflectance confocal microscopy (RCM) has shown high sensitivity and specificity for malignant melanoma (MM); however, to date, there have been no studies with a UK cohort.

Objectives
To use RCM prospectively to accurately diagnose MM and lentigo maligna (LM) in a private UK secondary care, single-clinician setting; and to assess the potential of RCM to be used as a routine screening procedure.

Methods
In total, 597 patients with a differential clinical diagnosis of MM or LM were consecutively recruited. A sequential record was made of the clinical, dermoscopy and RCM findings by a single dermatologist prior to biopsy. Imaging was done with an arm-mounted confocal microscope unless there was restricted access to a lesion that required a handheld probe. The likelihood of MM was scored for each diagnostic modality, with each diagnosis building on the last. Histology was assessed by a single blinded histopathologist. The trial was registered with ClinicalTrials.gov (NCT03508297).

Results
Altogether, 733 lesions were included in the analysis, including 86 MM and LM (median diameter 7.0 mm). The benign-to-malignant ratio was 3 : 1 (nonmelanocytic malignancies included) and 8.3 : 1 for MM and LM only. The sensitivity and specificity for MM and LM, respectively, was 62.8% [95% confidence interval (CI) 51.7–73.0] and 63.1% (95% CI 59.3–66.8) for clinical examination; 91.9% (95% CI 84.0–96.7) and 42.0% (95% CI 38.1–45.9), respectively, for dermoscopy; and 94.2% (95% CI 87.0–98.1) and 83.0% (95% CI 79.9–85.8), respectively, for RCM. The positive predictive value of RCM in diagnosing MM and LM was 42.4% (95% CI 38.1–46.8) and the negative predictive value was 99.1% (95% CI 97.9–99.6).

Conclusions
This study demonstrates that RCM can reliably diagnose MM and is fast enough to be integrated into UK pigmented lesion clinics by dermatologists trained in RCM. The number needed to treat decreased from 3.86 with clinical examination to 2.96 with dermoscopy to 1.30 with RCM.
Chronic kidney disease–associated pruritus and quality of life with difelikefalin treatment: a post hoc analysis of phase 3 data using the Skindex-10 questionnaire
Authors: Ständer Sonja , Fishbane Steven , Schaufler Thilo , Ruessmann Despina , Morin Isabelle , Menzaghi Frédérique , Wen Warren , Kalantar-Zadeh Kamyar 
Published: September 2024

ABSTRACT

Background
Pruritus is a common condition in chronic kidney disease (CKD), especially for patients receiving haemodialysis. CKD-associated pruritus (CKD-aP) can be distressing and have a negative impact on quality of life (QoL). This post hoc analysis aimed to assess the relationship between pruritus relief and QoL.

Methods
Data from phase 3 trials [(NCT03422653, NCT03636269 grouped), and NCT03998163] of the novel antipruritic difelikefalin (N = 914) were used to assess the relationship between reductions in pruritus intensity at Week 12 (24-h Worst Itching Intensity Numeric Rating Scale; WI-NRS), perceived improvement in itch (Patient Global Impression of Change, PGI-C) and pruritus-related QoL (Skindex-10 questionnaire).

Results
Patients receiving difelikefalin had greater improvements in Skindex-10 total scores than those receiving placebo [LS mean treatment difference –3.4; 95% confidence interval (CI) –5.5, –1.3; P = .002] and greater improvements across Skindex-10 domains (disease, mood and social functioning) at Week 12. In patients receiving difelikefalin, those with clinically meaningful improvements in pruritus (≥3-point reduction in WI-NRS score) at Week 12 had a greater improvement in Skindex-10 total score (mean difference 14.2; 95% CI 11.0, 17.3; P &lt; .001) and Skindex-10 domains than those with a &lt;3-point reduction in WI-NRS score. Improvements in Skindex-10 total scores correlated with PGI-C.

Conclusions
Improvements in pruritus intensity following 12 weeks of treatment with difelikefalin were associated with improvements in QoL. Larger improvements in Skindex-10 scores were seen in patients with a greater reduction in pruritus intensity, indicating that improvements in pruritus are associated with a range of factors, such as mood and social functioning, that affect pruritus-related QoL.
Interactive tools for functional annotation of bacterial genomes
Authors: Price Morgan N , Arkin Adam P 
Published: September 2024

Abstract
Automated annotations of protein functions are error-prone because of our lack of knowledge of protein functions. For example, it is often impossible to predict the correct substrate for an enzyme or a transporter. Furthermore, much of the knowledge that we do have about the functions of proteins is missing from the underlying databases. We discuss how to use interactive tools to quickly find different kinds of information relevant to a protein’s function. Many of these tools are available via PaperBLAST (http://papers.genomics.lbl.gov). Combining these tools often allows us to infer a protein’s function. Ideally, accurate annotations would allow us to predict a bacterium’s capabilities from its genome sequence, but in practice, this remains challenging. We describe interactive tools that infer potential capabilities from a genome sequence or that search a genome to find proteins that might perform a specific function of interest.
Database URL: http://papers.genomics.lbl.gov
Comparing right- versus left-first implantation in off-pump sequential double-lung transplantation: an observational cohort study
Authors: Van Slambrouck Jan , Decaluwé Herbert , Vanluyten Cedric , Vandervelde Christelle M , Orlitová Michaela , Beeckmans Hanne , Schoenaers Charlotte , Jin Xin , Makarian Roza S , De Leyn Paul , Van Veer Hans , Depypere Lieven , Belmans Ann , Vanaudenaerde Bart M , Vos Robin , Van Raemdonck Dirk , Ceulemans Laurens J 
Published: September 2024

Abstract

OBJECTIVES
Historically, the perfusion-guided sequence suggests to first transplant the side with lowest lung perfusion. This sequence is thought to limit right ventricular afterload and prevent acute heart failure after first pneumonectomy. As a paradigm shift, we adopted the right-first implantation sequence, irrespective of lung perfusion. The right donor lung generally accommodates a larger proportion of the cardiac output. We hypothesized that the right-first sequence reduces the likelihood of oedema formation in the firstly transplanted graft during second-lung implantation. Our objective was to compare the perfusion-guided and right-first sequence for intraoperative extracorporeal membrane oxygenation (ECMO) need and primary graft dysfunction (PGD).

METHODS
A retrospective single-centre cohort study (2008–2021) including double-lung transplant cases (N = 696) started without ECMO was performed. Primary end-points were intraoperative ECMO cannulation and PGD grade 3 (PGD3) at 72 h. Secondary end-points were patient and chronic lung allograft dysfunction-free survival. In cases with native left lung perfusion ≤50% propensity score adjusted comparison of the perfusion-guided and right-first sequence was performed.

RESULTS
When left lung perfusion was ≤50%, right-first implantation was done in 219 and left-first in 189 cases. Intraoperative escalation to ECMO support was observed in 10.96% of right-first versus 19.05% of left-first cases (odds ratio 0.448; 95% confidence interval 0.229–0.0.878; P = 0.0193). PGD3 at 72 h was observed in 8.02% of right-first versus 15.64% of left-first cases (0.566; 0.263–1.217; P = 0.1452). Right-first implantation did not affect patient or chronic lung allograft dysfunction-free survival.

CONCLUSIONS
The right-first implantation sequence in off-pump double-lung transplantation reduces need for intraoperative ECMO cannulation with a trend towards less PGD grade 3.
By word of mouth: the case for teacher-to-teacher research dialogue
Authors: Scheffler Paweł , Baranowska Karolina , Loewen Shawn 
Published: September 2024

Abstract
The current study investigated factors that potentially influenced the pedagogic practices of 132 EFL teachers from 28 secondary schools in a large city in Poland. The teachers completed a questionnaire about the factors that impacted their teaching practices. The primary influences on teaching practices turned out to be the course textbook and the secondary school exit exam. The data were further analysed using cluster analysis to identify groups of teachers with similar profiles. The results indicated two main clusters. One cluster was favourable to research-related resources, such as publications, conferences, and workshops. A second cluster was less favourable towards research. We interpret this result as highlighting the importance of within-profession dialogue in which research awareness and useful evidence-based practices are shared among teachers.
Effects of home care and e-mobile training/consultancy on women’s postpartum symptoms and breastfeeding self-efficacy: a randomized clinical trial
Authors: Karaçay Yıkar Seda , Nazik Evşen 
Published: September 2024

Abstract

Background
Most women experience breastfeeding problems and need changes due to postpartum physical symptoms and low breastfeeding self-efficacy.

Methods
Postpartum home care and e-mobile training/consultancy has been introduced to address this issue. This study was conducted as a randomized controlled interventional study. The sample of the study consisted of 75 (home care group = 25, control group = 25, e-mobile training/consultancy group = 25) women who met the sample selection criteria, agreed to participate in the study, and were hospitalized in the postpartum ward of a City Hospital. Data were collected through the Personal Information Form, the Postpartum Physical Symptom Severity Scale and the Breastfeeding Self-Efficacy Scale (BSES).

Results
In all postpartum stages, a statistically significant difference was detected between the home care, e-mobile training/consultancy and control group women in terms of the Postpartum Physical Symptoms Severity Scale and BSES total mean scores (P &lt; .05). Interviews showed that the home care group had the lowest Postpartum Physical Symptom Severity Scale total mean scores and the highest BSES total mean scores (P &lt; .05). Postpartum home visits and e-mobile training/consultancy should be considered a routine part of postpartum care. It is effective in reducing postpartum physical symptoms and increasing breastfeeding self-efficacy.

Conclusıon
In line with the results of this study, the use of home care and e-mobile training/consultancy is recommended to decrease physical symptoms and increase breastfeeding self-efficacy.
Do poor psychosocial resources mediate health inequalities in type 2 diabetes mellitus? Findings from the Maastricht study
Authors: Sezer Bengisu , Albers Jeroen , Meisters Rachelle , Schram Miranda T , Köhler Sebastian , Stehouwer Coen D A , Koster Annemarie , Bosma Hans 
Published: September 2024

Abstract
Low socioeconomic position (SEP) has been identified as a risk factor for type 2 diabetes mellitus (T2DM), and psychosocial resources might be on the pathway in this association. We examined two poor psychosocial resources, low control beliefs and inferiority beliefs, that might link low SEP with T2DM. 8292 participants aged 40–75 living in Southern Netherlands participated in The Maastricht Study starting from September 2010 to October 2020 and were followed up to 10 years with annual questionnaires. SEP (education, income, occupation), low control beliefs, inferiority beliefs, and (pre)diabetes by oral glucose tolerance test were measured at baseline. Incident T2DM was self-reported per annum. We analysed the mediating roles of poor psychosocial resources by using counterfactual mediation analysis. People with low SEP had more often prevalent and incident T2DM (e.g. low education: HR = 2.13, 95%CI: 1.53–2.97). Low control beliefs and high inferiority beliefs were more common among people with low SEP. Moreover, low control beliefs and high inferiority beliefs were risk factors for T2DM (e.g. low control beliefs: HR = 1.50, 95%CI: 1.08–2.09). The relationship between SEP and T2DM was partially mediated by control beliefs (8.0–13.6%) and inferiority beliefs (2.2–4.5%). We conclude that poor psychosocial resources are important in socioeconomic inequalities in diabetes. Researchers and practitioners should consider the psychosocial profile of people with lower SEP, as such a profile might interfere with the development, treatment, and prevention of T2DM. Further research should explore how poor psychosocial resources interact with chronic stress in relation to socioeconomic health inequalities.
Enterococcal-host interactions in the gastrointestinal tract and beyond
Authors: Madani Wiam Abdalla Mo , Ramos Yusibeska , Cubillos-Ruiz Juan R , Morales Diana K 
Published: September 2024

Abstract
The gastrointestinal tract (GIT) is typically considered the natural niche of enterococci. However, these bacteria also inhabit extraintestinal tissues, where they can disrupt organ physiology and cause life-threatening infections. Here, we discuss how enterococci, primarily Enterococcus faecalis, interact with the intestine and other host anatomical locations such as the oral cavity, heart, liver, kidney, and vaginal tract. The metabolic flexibility of these bacteria allows them to quickly adapt to new environments, promoting their persistence in diverse tissues. In transitioning from commensals to pathogens, enterococci must overcome harsh conditions such as nutrient competition, exposure to antimicrobials, and immune pressure. Therefore, enterococci have evolved multiple mechanisms to adhere, colonize, persist, and endure these challenges in the host. This review provides a comprehensive overview of how enterococci interact with diverse host cells and tissues across multiple organ systems, highlighting the key molecular pathways that mediate enterococcal adaptation, persistence, and pathogenic behavior.
Flynotyper 2.0: an updated tool for rapid quantitative assessment of Drosophila eye phenotypes
Authors: Ray Johnathan , Banerjee Deepro , Wang Qingyu , Girirajan Santhosh 
Published: September 2024

Abstract
About two-thirds of the genes in the Drosophila melanogaster genome are also involved in its eye development, making the Drosophila eye an ideal system for genetic studies. We previously developed Flynotyper, a software that uses image processing operations to identify and quantify the degree of roughness by measuring disorderliness of ommatidial arrangement in the fly eye. This software has enabled researchers to quantify morphological defects of thousands of eye images caused by genetic perturbations. Here, we present Flynotyper 2.0, a software that has an updated computer vision library, improved performance, and a streamlined pipeline for high-throughput analysis of multiple eye images. We also tested several batches of Drosophila eye images to ensure robustness and reproducibility of the updated Flynotyper 2.0 software.