bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kimma: flexible linear mixed effects modeling with kinship covariance for RNA-seq data
Authors: Dill-McFarland Kimberly A , Mitchell Kiana , Batchu Sashank , Segnitz Richard Max , Benson Basilin , Janczyk Tomasz , Cox Madison S , Mayanja-Kizza Harriet , Boom William Henry , Benchek Penelope , Stein Catherine M , Hawn Thomas R , Altman Matthew C 
Published: May 2023

Abstract

Motivation
The identification of differentially expressed genes (DEGs) from transcriptomic datasets is a major avenue of research across diverse disciplines. However, current bioinformatic tools do not support covariance matrices in DEG modeling. Here, we introduce kimma (Kinship In Mixed Model Analysis), an open-source R package for flexible linear mixed effects modeling including covariates, weights, random effects, covariance matrices, and fit metrics.

Results
In simulated datasets, kimma detects DEGs with similar specificity, sensitivity, and computational time as limma unpaired and dream paired models. Unlike other software, kimma supports covariance matrices as well as fit metrics like Akaike information criterion (AIC). Utilizing genetic kinship covariance, kimma revealed that kinship impacts model fit and DEG detection in a related cohort. Thus, kimma equals or outcompetes current DEG pipelines in sensitivity, computational time, and model complexity.

Availability and implementation
Kimma is freely available on GitHub https://github.com/BIGslu/kimma with an instructional vignette at https://bigslu.github.io/kimma_vignette/kimma_vignette.html.
ROptimus: a parallel general-purpose adaptive optimization engine
Authors: Johnson Nicholas A G , Tamon Liezel , Liu Xin , Sahakyan Aleksandr B 
Published: May 2023

Summary

Motivation
Various computational biology calculations require a probabilistic optimization protocol to determine the parameters that capture the system at a desired state in the configurational space. Many existing methods excel at certain scenarios, but fail in others due, in part, to an inefficient exploration of the parameter space and easy trapping into local minima. Here, we developed a general-purpose optimization engine in R that can be plugged to any, simple or complex, modelling initiative through a few lucid interfacing functions, to perform a seamless optimization with rigorous parameter sampling.

Results
ROptimus features simulated annealing and replica exchange implementations equipped with adaptive thermoregulation to drive Monte Carlo optimization process in a flexible manner, through constrained acceptance frequency but unconstrained adaptive pseudo temperature regimens. We exemplify the applicability of our R optimizer to a diverse set of problems spanning data analyses and computational biology tasks.

Availability and implementation
ROptimus is written and implemented in R, and is freely available from CRAN (http://cran.r-project.org/web/packages/ROptimus/index.html) and GitHub (http://github.com/SahakyanLab/ROptimus).
Metapaths: similarity search in heterogeneous knowledge graphs via meta-paths
Authors: Noori Ayush , Li Michelle M , Tan Amelia L M , Zitnik Marinka 
Published: May 2023

Abstract

Summary
Heterogeneous knowledge graphs (KGs) have enabled the modeling of complex systems, from genetic interaction graphs and protein-protein interaction networks to networks representing drugs, diseases, proteins, and side effects. Analytical methods for KGs rely on quantifying similarities between entities, such as nodes, in the graph. However, such methods must consider the diversity of node and edge types contained within the KG via, for example, defined sequences of entity types known as meta-paths. We present metapaths, the first R software package to implement meta-paths and perform meta-path-based similarity search in heterogeneous KGs. The metapaths package offers various built-in similarity metrics for node pair comparison by querying KGs represented as either edge or adjacency lists, as well as auxiliary aggregation methods to measure set-level relationships. Indeed, evaluation of these methods on an open-source biomedical KG recovered meaningful drug and disease-associated relationships, including those in Alzheimer’s disease. The metapaths framework facilitates the scalable and flexible modeling of network similarities in KGs with applications across KG learning.

Availability and implementation
The metapaths R package is available via GitHub at https://github.com/ayushnoori/metapaths and is released under MPL 2.0 (Zenodo DOI: 10.5281/zenodo.7047209). Package documentation and usage examples are available at https://www.ayushnoori.com/metapaths.
HAMPLE: deciphering TF-DNA binding mechanism in different cellular environments by characterizing higher-order nucleotide dependency
Authors: Wang Zixuan , Xiong Shuwen , Yu Yun , Zhou Jiliu , Zhang Yongqing 
Published: May 2023

AbstractMotivationTranscription factor (TF) binds to conservative DNA binding sites in different cellular environments and development stages by physical interaction with interdependent nucleotides. However, systematic computational characterization of the relationship between higher-order nucleotide dependency and TF-DNA binding mechanism in diverse cell types remains challenging.ResultsHere, we propose a novel multi-task learning framework HAMPLE to simultaneously predict TF binding sites (TFBS) in distinct cell types by characterizing higher-order nucleotide dependencies. Specifically, HAMPLE first represents a DNA sequence through three higher-order nucleotide dependencies, including k-mer encoding, DNA shape and histone modification. Then, HAMPLE uses the customized gate control and the channel attention convolutional architecture to further capture cell-type-specific and cell-type-shared DNA binding motifs and epigenomic languages. Finally, HAMPLE exploits the joint loss function to optimize the TFBS prediction for different cell types in an end-to-end manner. Extensive experimental results on seven datasets demonstrate that HAMPLE significantly outperforms the state-of-the-art approaches in terms of auROC. In addition, feature importance analysis illustrates that k-mer encoding, DNA shape, and histone modification have predictive power for TF-DNA binding in different cellular environments and are complementary to each other. Furthermore, ablation study, and interpretable analysis validate the effectiveness of the customized gate control and the channel attention convolutional architecture in characterizing higher-order nucleotide dependencies.Availability and implementationThe source code is available at https://github.com/ZhangLab312/Hample.
ppBAM: ProteinPaint BAM track for read alignment visualization and variant genotyping
Authors: Paul Robin , Wang Jian , Reilly Colleen , Sioson Edgar , Patel Jaimin , Matt Gavriel , Acić Aleksandar , Zhou Xin 
Published: May 2023

Abstract

Summary
ProteinPaint BAM track (ppBAM) is designed to assist variant review for cancer research and clinical genomics. With performant server-side computing and rendering, ppBAM supports on-the-fly variant genotyping of thousands of reads using Smith–Waterman alignment. To better visualize support for complex variants, reads are realigned against the mutated reference sequence using ClustalO. ppBAM also supports the BAM slicing API of the NCI Genomic Data Commons (GDC) portal, letting researchers conveniently examine genomic details of vast amounts of cancer sequencing data and reinterpret variant calls.

Availability and implementation
BAM track examples, tutorial, and GDC file access links are available at https://proteinpaint.stjude.org/bam/. Source code is available at https://github.com/stjude/proteinpaint.
Multisite thalamic recordings to characterize seizure propagation in the human brain
Authors: Wu Teresa Q , Kaboodvand Neda , McGinn Ryan J , Veit Mike , Davey Zachary , Datta Anjali , Graber Kevin D , Meador Kimford J , Fisher Robert , Buch Vivek , Parvizi Josef 
Published: May 2023

Abstract
Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in a subset of patients with refractory focal epilepsy. One important uncertainty is to what extent thalamic subregions other than the ANT could be recruited more prominently in the propagation of focal onset seizures. We designed the current study to simultaneously monitor the engagement of the ANT, mediodorsal (MD) and pulvinar (PUL) nuclei during seizures in patients who could be candidates for thalamic neuromodulation.
We studied 11 patients with clinical manifestations of presumed temporal lobe epilepsy (TLE) undergoing invasive stereo-encephalography (sEEG) monitoring to confirm the source of their seizures. We extended cortical electrodes to reach the ANT, MD and PUL nuclei of the thalamus. More than one thalamic subdivision was simultaneously interrogated in nine patients. We recorded seizures with implanted electrodes across various regions of the brain and documented seizure onset zones (SOZ) in each recorded seizure. We visually identified the first thalamic subregion to be involved in seizure propagation. Additionally, in eight patients, we applied repeated single pulse electrical stimulation in each SOZ and recorded the time and prominence of evoked responses across the implanted thalamic regions.
Our approach for multisite thalamic sampling was safe and caused no adverse events. Intracranial EEG recordings confirmed SOZ in medial temporal lobe, insula, orbitofrontal and temporal neocortical sites, highlighting the importance of invasive monitoring for accurate localization of SOZs. In all patients, seizures with the same propagation network and originating from the same SOZ involved the same thalamic subregion, with a stereotyped thalamic EEG signature. Qualitative visual reviews of ictal EEGs were largely consistent with the quantitative analysis of the corticothalamic evoked potentials, and both documented that thalamic nuclei other than ANT could have the earliest participation in seizure propagation. Specifically, pulvinar nuclei were involved earlier and more prominently than ANT in more than half of the patients. However, which specific thalamic subregion first demonstrated ictal activity could not be reliably predicted based on clinical semiology or lobar localization of SOZs.
Our findings document the feasibility and safety of bilateral multisite sampling from the human thalamus. This may allow more personalized thalamic targets to be identified for neuromodulation. Future studies are needed to determine if a personalized thalamic neuromodulation leads to greater improvements in clinical outcome.
Efficacy and safety of supramolecular active zinc in the treatment of scalp psoriasis: a multicentre, randomized, observed-blind, parallel-group, placebo- and active-controlled noninferiority trial
Authors: Yu Chen , Yu Nan , Jiang Xian , Gao Xinghua , Lv Shichao , Wang Gang 
Published: May 2023

Abstract

Background
Controlling the relapses of scalp psoriasis is a clinical issue.

Objectives
To evaluate the efficacy and safety of a supramolecular active zinc antidandruff hair conditioner in managing scalp psoriasis (SP).

Methods
This multicentre randomized, observed-blind, parallel-group, placebo- and active-controlled noninferiority trial enrolled 211 patients with SP between October 2018 and June 2019. The participants were randomized 1 : 1 : 1 to the experimental (supramolecular active zinc antidandruff hair conditioner), placebo (supramolecular hydrogel) or positive control (calcipotriol ointment) group. The primary efficacy endpoint was the disease control rate at the end of the fourth week of treatment, measured using the Investigator’s Global Assessment score.

Results
This study included 70, 70 and 71 participants in the experiment, control and placebo groups, respectively. The disease control rates of SP at the end of week 4 of treatment in the full-analysis set (FAS) were 39%, 25% and 37% in the experimental, placebo and control groups. The margin of superiority between the experimental and placebo groups was &gt; 0 [96% confidence interval (CI) 13.22% (0.43% to ∞)] in the FAS. The experimental group was superior to the placebo group. The noninferiority margin between the experiment and control groups was &gt; –15% [96% CI –1.43% (–14.91% to ∞)] in the FAS. The experimental group was not inferior to the control group.

Conclusions
Supramolecular active zinc antidandruff hair conditioner was helpful for the treatment of SP, and it has good clinical efficacy in maintaining therapeutic effect and assisting in preventing the recurrence of psoriasis.
Primary cutaneous lymphomas: exploration of 10-year data from supraregional mutlidisciplinary team meetings in Glasgow, UK
Authors: McCusker Sarah , Ngu Ivy 
Published: May 2023

Abstract
Primary cutaneous lymphomas (PCLs) are non-Hodgkin lymphomas, presenting in the skin. They are classified into cutaneous B-cell lymphomas (CBCLs) or cutaneous T-cell lymphomas (CTCLs). The most common CTCL subtypes are mycosis fungoides (MF) and Sézary syndrome (SS). All patient’s cases should be discussed at a specialist multidisciplinary team (MDT) meeting. This is the first published review, to our knowledge, of PCL MDT case discussion in the UK. Patient cases between 2008 and 2019 were reviewed to assess: frequency of PCL subtype, documentation of CTCL staging and management of MF/SS. Of 356, 103 (29%) were CBCLs and the majority (n = 200, 56%) were CTCLs. MF/SS was the diagnosis in 120 (34%). Staging was documented in 44% (n = 53) of patients with MF/SS. Management largely followed guidelines for MF/SS, topical corticosteroids were the most common treatment (n = 93, 78%). Frequency of PCL subtype is largely comparable with previously published data. Documentation of CTCL staging is low, but higher than other reports. Our work begins to address the gap in real-world data on CTCLs. A standardized approach to data collection would inform clinical practice.
Rites of Resistance: Urban Liturgy and the Crowd in the Patarine Revolt of Milan, c.1057–75
Authors: Norrie James 
Published: May 2023

Abstract
This essay uses an unexploited liturgical source, a twelfth-century order book by the Milanese cleric Beroldo, to illuminate how processions shaped the practice of the largest and most radical popular movement of the central Middle Ages, the Pataria of Milan, during a pivotal moment of urban change. Religious processions had the power to project episcopal authority across a rapidly expanding urban population. They also sanctioned the redistribution of wealth and resources to city churches. At the same time, they provided a possible grammar of resistance to those who rose up against urban elites. The Pataria struggled at the pulpit and on the streets for the sexual and economic purity of the clergy. It first erupted in the city on 10 May 1057—during a liturgical parade. The conflict between supporters of religious reform on the one hand, and the archbishop’s aristocratic court and clergy on the other, persisted until the movement’s defeat in 1075. Until then, Patarine violence continually disrupted liturgical time, tearing priests from their altars and overturning solemn processions.
The article introduces Beroldo and other Milanese liturgical sources in context, and their value as witnesses to later eleventh-century history. It surveys how episcopal processions responded to urban expansion and developed a growing but unstable social and political importance. With a picture of the urban and liturgical landscape in place, it then investigates how Patarine violence contested the ways that processions, on days such as Easter baptism or the Three Day Litanies, created civic community and communicated relations of power.
Pre-treatment bicarbonate levels and decongestion by acetazolamide: the ADVOR trial
Authors: Martens Pieter , Verbrugge Frederik H , Dauw Jeroen , Nijst Petra , Meekers Evelyne , Augusto Silvio Nunes , Ter Maaten Jozine M , Heylen Line , Damman Kevin , Mebazaa Alexandre , Filippatos Gerasimos , Ruschitzka Frank , Tang Wai Hong Wilson , Dupont Matthias , Mullens Wilfried 
Published: May 2023

Abstract

Aims
Acetazolamide inhibits proximal tubular sodium and bicarbonate re-absorption and improved decongestive response in acute heart failure in the ADVOR trial. It is unknown whether bicarbonate levels alter the decongestive response to acetazolamide.

Methods and results
This is a sub-analysis of the randomized, double-blind, placebo-controlled ADVOR trial that randomized 519 patients with acute heart failure and volume overload in a 1:1 ratio to intravenous acetazolamide (500 mg/day) or matching placebo on top of standardized intravenous loop diuretics (dose equivalent of twice oral maintenance dose). The primary endpoint was complete decongestion after 3 days of treatment (morning of day 4). Impact of baseline HCO3 levels on the treatment effect of acetazolamide was assessed. : Of the 519 enrolled patients, 516 (99.4%) had a baseline HCO3 measurement. Continuous HCO3 modelling illustrated a higher proportional treatment effect for acetazolamide if baseline HCO3 ≥ 27 mmol/l. A total of 234 (45%) had a baseline HCO3 ≥ 27 mmol/l. Randomization towards acetazolamide improved decongestive response over the entire range of baseline HCO3− levels (P = 0.004); however, patients with elevated baseline HCO3 exhibited a significant higher response to acetazolamide [primary endpoint: no vs. elevated HCO3; OR 1.37 (0.79–2.37) vs. OR 2.39 (1.35–4.22), P-interaction = 0.065), with higher proportional diuretic and natriuretic response (both P-interaction &lt; 0.001), greater reduction in congestion score on consecutive days (treatment × time by HCO3-interaction &lt;0.001) and length of stay (P-interaction = 0.019). The larger proportional treatment effect was mainly explained by the development of diminished decongestive response in the placebo arm (loop diuretics only), both with regard to reaching the primary endpoint of decongestion as well as reduction in congestion score. Development of elevated HCO3 further worsened decongestive response in the placebo arm (P-interaction = 0.041). A loop diuretic only strategy was associated with an increase in the HCO3 during the treatment phase which was prevented by acetazolamide (day 3: placebo 74.8% vs. acetazolamide 41.3%, P &lt; 0.001).

Conclusion
Acetazolamide improves decongestive response over the entire range of HCO3− levels; however, the treatment response is magnified in patients with baseline or loop diuretic-induced elevated HCO3 (marker of proximal nephron NaHCO3 retention) by specifically counteracting this component of diuretic resistance.
Regional disparity on patient characteristics and perceptions after implantable cardioverter-defibrillator implantation: results from an EHRA patient survey
Authors: Januszkiewicz Łukasz , Barra Sérgio , Providencia Rui , Chun Julian K R , Conte Giulio , Farkowski Michał M , Guerra Jose M , Marijon Eloi , de Asmundis Carlo , Boveda Serge 
Published: May 2023

Abstract

Aims
The aim of this study was to identify potential regional disparities in characteristics of implantable cardioverter-defibrillator (ICD) recipients, patient perceptions and perspectives after implantation and level of information provided to patients.

Methods and results
The prospective, multicentre, and multinational European Heart Rhythm Association patient Survey ‘Living with an ICD’ included patients already implanted with an ICD (median ICD dwell time – 5 years, interquartile range 2–10). An online questionnaire was filled-in by patients invited from 10 European countries. A total of 1809 patients (the majority in their 40s to 70s, 65.5% men) were enrolled, with 877 (48.5%) from Western Europe (group 1), followed by 563 from Central/Eastern Europe (group 2, 31.1%), and 369 from Southern Europe (group 3, 20.4%). A total of 52.9% of Central/Eastern Europe patients reported increased satisfaction after ICD placement compared with 46.6% from Western and 33.1% from Southern Europe (1 vs. 2 P = 0.047, 1 vs. 3 P &lt; 0.001, 2 vs. 3 P &lt; 0.001). About 79.2% of Central/Eastern and 76.0% of Southern Europe patients felt optimally informed at the time of device implantation compared with just 64.6% from Western Europe (1 vs. 2 P &lt; 0.001, 1 vs. 3 P &lt; 0.001, 2 vs. 3 P = ns).

Conclusions
While physicians in Southern Europe should address the patients’ concerns about the impact of the ICD on quality of life, physicians from Western Europe should focus on improving the quality of information provided to their prospective ICD patients. Novel strategies to address regional differences in patients’ quality of life and provision of information are warranted.
National policies on physical activity from 64 countries with different economies: a scoping review with thematic analysis
Authors: Minatto Giseli , Silva Kelly Samara , Bandeira Alexsandra da Silva , dos Santos Priscila Cristina , Sandreschi Paula Fabricio , Manta Sofia Wolker , da Silva Juliana Rezende Melo , Parente Raphael Câmara Medeiros , Barbosa Filho Valter Cordeiro 
Published: May 2023

Abstract
In 2018, the World Health Organization (WHO) launched a Global Action Plan on Physical Activity (PA), which included 20 policy actions for creating active societies, environments, people and systems. The objective of this scoping review was to summarize the themes/contents of national PA policies/plans conforming to the WHO’s proposals and the country’s economy. This review followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines for scoping reviews. A systematic search of electronic databases (Web of Science, Medline/PubMed, LILACS, PsycINFO, Scopus and SPORTDiscus) and 441 government documents/websites from 215 countries/territories was conducted (February 2021). Documents on national-level policies, published in English, Spanish and Portuguese since 2000, were eligible. The information on content and structure was systematically extracted and summarized into dimensions proposed by the WHO: active societies, environments, people and systems. The search identified 888 article references and 586 potentially relevant documents. After the screening, 84 policy documents from 64 countries were eligible. Most documents (n = 46) provided detailed PA policies/plans amid other health topics (e.g. non-communicable diseases, named ‘general documents’), and 38 were PA-specific. The content analysis merged 54 visions, 65 missions, 108 principles, 119 objectives, 53 priorities, 105 targets, 126 indicators and 1780 actions/strategies from 38 PA-specific and 46 general documents. Among the PA-specific documents, the active system’s dimension was the most contemplated in the principles (n = 43), priorities (n = 51) and action/strategies (n = 530) elements. At the same time, the objectives (n = 39), targets (n = 52) and indicators (n = 58) presented contents more frequently related to the active people dimension. For the general documents, all principles (n = 4), objectives (n = 14) and priorities (n = 7) were related to the dimension of active people, while target (n = 51), indicator (n = 53) and actions/strategies (n = 292) elements presented content related to all dimensions. The increase in countries with national PA policies/plans should be followed by improving the current ones because important dimensions seem to be not considered in these documents. This will facilitate a global PA agenda that considers the complexity and multidimensionality of PA promotion.