bluuebunny/crossref_metadata_2025_split huggingface dataset:
emPDBA: protein-DNA binding affinity prediction by combining features from binding partners and interface learned with ensemble regression model
Authors: Yang Shuang , Gong Weikang , Zhou Tong , Sun Xiaohan , Chen Lei , Zhou Wenxue , Li Chunhua 
Published: May 2023

Abstract
Protein–deoxyribonucleic acid (DNA) interactions are important in a variety of biological processes. Accurately predicting protein-DNA binding affinity has been one of the most attractive and challenging issues in computational biology. However, the existing approaches still have much room for improvement. In this work, we propose an ensemble model for Protein-DNA Binding Affinity prediction (emPDBA), which combines six base models with one meta-model. The complexes are classified into four types based on the DNA structure (double-stranded or other forms) and the percentage of interface residues. For each type, emPDBA is trained with the sequence-based, structure-based and energy features from binding partners and complex structures. Through feature selection by the sequential forward selection method, it is found that there do exist considerable differences in the key factors contributing to intermolecular binding affinity. The complex classification is beneficial for the important feature extraction for binding affinity prediction. The performance comparison of our method with other peer ones on the independent testing dataset shows that emPDBA outperforms the state-of-the-art methods with the Pearson correlation coefficient of 0.53 and the mean absolute error of 1.11 kcal/mol. The comprehensive results demonstrate that our method has a good performance for protein-DNA binding affinity prediction.
Availability and implementation: The source code is available at https://github.com/ChunhuaLiLab/emPDBA/.
Cation leak: a common functional defect causing HCN1 developmental and epileptic encephalopathy
Authors: McKenzie Chaseley E , Forster Ian C , Soh Ming S , Phillips A Marie , Bleakley Lauren E , Russ-Hall Sophie J , Myers Kenneth A , Scheffer Ingrid E , Reid Christopher A 
Published: May 2023

Abstract
Pathogenic variants in HCN1 are an established cause of developmental and epileptic encephalopathy (DEE). To date, the stratification of patients with HCN1-DEE based on the biophysical consequence on channel function of a given variant has not been possible. Here, we analysed data from eleven patients carrying seven different de novo HCN1 pathogenic variants located in the transmembrane domains of the protein. All patients were diagnosed with severe disease including epilepsy and intellectual disability. The functional properties of the seven HCN1 pathogenic variants were assessed using two-electrode voltage-clamp recordings in Xenopus oocytes. All seven variants showed a significantly larger instantaneous current consistent with cation leak. The impact of each variant on other biophysical properties was variable, including changes in the half activation voltage and activation and deactivation kinetics. These data suggest that cation leak is an important pathogenic mechanism in HCN1-DEE. Furthermore, published mouse model and clinical case reports suggest that seizures are exacerbated by sodium channel blockers in patients with HCN1 variants that cause cation leak. Stratification of patients based on their ‘cation leak’ biophysical phenotype may therefore provide key information to guide clinical management of individuals with HCN1-DEE.
Integrated ACMG-approved genes and ICD codes for the translational research and precision medicine
Authors: Wable Raghunandan , Nair Achuth Suresh , Pappu Anirudh , Pierre-Louis Widnie , Abdelhalim Habiba , Patel Khushbu , Mendhe Dinesh , Bolla Shreyas , Mittal Sahil , Ahmed Zeeshan 
Published: May 2023

Abstract
A timely understanding of the biological secrets of complex diseases will ultimately benefit millions of individuals by reducing the high risks for mortality and improving the quality of life with personalized diagnoses and treatments. Due to the advancements in sequencing technologies and reduced cost, genomics data are developing at an unmatched pace and levels to foster translational research and precision medicine. Over 10 million genomics datasets have been produced and publicly shared in 2022. Diverse and high-volume genomics and clinical data have the potential to broaden the scope of biological discoveries and insights by extracting, analyzing and interpreting the hidden information. However, the current and still unresolved challenges include the integration of genomic profiles of the patients with their medical records. The definition of disease in genomics medicine is simplified, whereas in the clinical world, diseases are classified, identified and adopted with their International Classification of Diseases (ICD) codes, which are maintained by the World Health Organization. Several biological databases have been produced, which include information about human genes and related diseases. However, still, there is no database that exists, which can precisely link clinical codes with relevant genes and variants to support genomic and clinical data integration for clinical and translational medicine. In this project, we focused on the development of an annotated gene–disease–code database, which is accessible through an online, cross-platform and user-friendly application, i.e. PROMIS-APP-SUITE-Gene-Disease-Code. However, our scope is limited to the integration of ICD-9 and ICD-10 codes with the list of genes approved by the American College of Medical Genetics and Genomics. The results include over 17 000 diseases and 4000 ICD codes, and over 11 000 gene–disease–code combinations.
Database URL https://promis.rutgers.edu/pas/
The quality of paediatric asthma guidelines: evidence underpinning diagnostic test recommendations from a meta-epidemiological study
Authors: Thomas Elizabeth T , Thomas Sarah T , Perera Rafael , Gill Peter J , Moloney Susan , Heneghan Carl J 
Published: May 2023

Abstract

Background
Asthma is one of the most frequent reasons children visit a general practitioner (GP). The diagnosis of childhood asthma is challenging, and a variety of diagnostic tests for asthma exist. GPs may refer to clinical practice guidelines when deciding which tests, if any, are appropriate, but the quality of these guidelines is unknown.

Objectives
To determine (i) the methodological quality and reporting of paediatric guidelines for the diagnosis of childhood asthma in primary care, and (ii) the strength of evidence supporting diagnostic test recommendations.

Design
Meta-epidemiological study of English-language guidelines from the United Kingdom and other high-income countries with comparable primary care systems including diagnostic testing recommendations for childhood asthma in primary care. The AGREE-II tool was used to assess the quality and reporting of the guidelines. The quality of the evidence was assessed using GRADE.

Results
Eleven guidelines met the eligibility criteria. The methodology and reporting quality varied across the AGREE II domains (median score 4.5 out of 7, range 2–6). The quality of evidence supporting diagnostic recommendations was generally of very low quality. All guidelines recommended the use of spirometry and reversibility testing for children aged ≥5 years, however, the recommended spirometry thresholds for diagnosis differed across guidelines. There were disagreements in testing recommendations for 3 of the 7 included tests.

Conclusions
The variable quality of guidelines, lack of good quality evidence, and inconsistent recommendations for diagnostic tests may contribute to poor clinician adherence to guidelines and variation in testing for diagnosing childhood asthma.
Trolls without borders: a comparative analysis of six foreign countries’ online propaganda campaigns
Authors: Walter Dror , Ophir Yotam 
Published: May 2023

Abstract
Despite the existence of multiple propaganda campaigns from around the globe, most scholarly attention has been primarily given to those operated by Russia. This focus on a single country has limited the scope of propaganda research. We offer a systematic comparison of six campaigns, examining the issues they engaged with, and their deployment strategies. Using a computational analysis of more than 9.5 million tweets released by the Twitter Moderation Research Consortium, we show differences across campaigns. Some operations were massive in scale while others were modest. Some focused on US domestic affairs, while others emphasized global issues. While some campaigns showed high levels of sophistication in terms of persona crafting and account deployment, others did not participate in pre-propaganda. We conclude by discussing the practical and theoretical implications of these findings.
An Effective Criterion for Nielsen–Schreier Varieties
Authors: Dotsenko Vladimir , Umirbaev Ualbai 
Published: May 2023

Abstract
To the memory of V. A. Artamonov (1946–2021) All algebras of a certain type are said to form a Nielsen–Schreier variety if every subalgebra of a free algebra is free. This property has been perceived as extremely rare; in particular, only six Nielsen–Schreier varieties of algebras with one binary operation have been discovered in prior work on this topic. We propose an effective combinatorial criterion for the Nielsen–Schreier property in the case of algebras over a field of zero characteristic; in our approach, operads play a crucial role. Using this criterion, we show that the well-known varieties of all pre-Lie algebras and of all Lie-admissible algebras are Nielsen–Schreier, and, quite surprisingly, that there are already infinitely many non-equivalent Nielsen–Schreier varieties of algebras with one binary operation and identities of degree four.
Cohomology of (, Γ)-Modules Over Pseudorigid Spaces
Authors: Bellovin Rebecca 
Published: May 2023

Abstract
We study the cohomology of families of $(\varphi ,\Gamma )$-modules with coefficients in pseudoaffinoid algebras. We prove that they have finite cohomology, and we deduce an Euler characteristic formula and Tate local duality. We classify rank-$1$$(\varphi ,\Gamma )$-modules and deduce that triangulations of pseudorigid families of $(\varphi ,\Gamma )$-modules can be interpolated, extending a result of [29]. We then apply this to study extended eigenvarieties at the boundary of weight space, proving in particular that the eigencurve is proper at the boundary and that Galois representations attached to certain characteristic $p$ points are trianguline.
On the Average of p-Selmer Ranks in Quadratic Twist Families of Elliptic Curves Over Global Function Fields
Authors: Park Sun Woo , Wang Niudun 
Published: May 2023

Abstract
Let $\mathbb{F}_{q}$ be a finite field whose characteristic is relatively prime to $2$ and $3$. Let $p$ be a prime number that is coprime to $q$. Let $E$ be an elliptic curve over the global function field $K = \mathbb{F}_{q}(t)$ such that $\textrm{Gal}(K(E[p])/K)$ contains the special linear group $\textrm{SL}_{2}(\mathbb{F}_{p})$. We show that if the quadratic twist family of $E$ has an element whose Néron model has a multiplicative reduction away from $\infty $, then the average $p$-Selmer rank is $p+1$ in large $q$-limit for almost all primes $p$.
Stabilizing Authoritarian Rule: The Role of International Organizations
Authors: Cottiero Christina , Haggard Stephan 
Published: May 2023

Abstract
Research has demonstrated how membership in more democratic regional intergovernmental organizations (ROs) can strengthen the prospects for democracy. However, a significant number of ROs are dominated by autocratic members who have quite different preferences: to limit democratic contagion and consolidate authoritarian rule against democratic challengers. We outline a menu of mechanisms through which ROs with authoritarian memberships might have pernicious effects on the prospects for democratic rule. We use cross-national quantitative analyses to demonstrate that membership in more deeply authoritarian international organizations is associated with autocratization. We supplement the quantitative results with an analysis of twenty-nine of the most authoritarian ROs and illustrative case studies. The multi-method approach strengthens inference by showing that authoritarian international organizations do in fact engage in behaviors inimical to democratic rule.
Dominated Cosmopolitanism: Consumer Habitus Dynamics among Low-Resource Migrants
Authors: Chytkova Zuzana , Kjeldgaard Dannie 
Published: May 2023

AbstractCosmopolitanism is often cast as an elite cultural orientation and as a privileged disposition to an increasingly globalized marketplace, instigated by, and lived through, mobility. But how does cosmopolitanism evolve among consumers at intersectional subordinate positions of power? This article analyzes the emergence of cosmopolitanism through a 9 year longitudinal extended case study of female migrants with low levels of resources. Through the deployment of a Bourdieusian framework, cosmopolitanism is theorized to evolve through processes set in motion by the experience of mismatch and subsequent alignment between new social contexts and existing socialized dispositions (hysteresis). The experience of hysteresis caused by mobility can lead to a habitus with traits of cosmopolitanism. The emergence of a cosmopolitan habitus can result in a sense of emancipation, but it also engenders new subordinate positions within intersectional systems of power. The outcome of this process is labeled dominated cosmopolitanism, representing a more nuanced version of cosmopolitanism that incorporates various systems of power. The analysis has implications for acculturation studies in consumption contexts characterized by low-resource endowments and provides new insights into the processual nature of the constitution of social systems of power.
Reference genome of an iconic lizard in western North America, Blainville’s horned lizard Phrynosoma blainvillii
Authors: Richmond Jonathan Q , McGuire Jimmy A , Escalona Merly , Marimuthu Mohan P A , Nguyen Oanh , Sacco Samuel , Beraut Eric , Toffelmier Erin , Fisher Robert N , Wang Ian J , Shaffer H Bradley 
Published: May 2023

Abstract
Genome assemblies are increasingly being used to identify adaptive genetic variation that can help prioritize the population management of protected species. This approach may be particularly relevant to species like Blainville’s horned lizard, Phrynosoma blainvillii, due to its specialized diet on noxious harvester ants, numerous adaptative traits for avoiding predation (e.g. cranial horns, dorsoventrally compressed body, cryptic coloration, and blood squirting from the orbital sinuses), and status as Species of Special Concern in California. Rangewide decline since the early 20th century, the basis of its conservation status, has been driven mainly by habitat conversion, over-collecting, and invasion of a non-native ant that displaces its native ant prey base. Here, we report on a scaffold-level genome assembly for P. blainvillii as part of the California Conservation Genomics Project (CCGP), produced using Pacific Biosciences HiFi long reads and Hi-C chromatin-proximity sequencing technology. The de novo assembly has 78 scaffolds, a total length of ~2.21 Gb, a scaffold N50 length of ~352 Mb, and BUSCO score of 97.4%. This is the second species of Phrynosoma for which a reference genome has been assembled and represents a considerable improvement in terms of contiguity and completeness. Combined with the landscape genomics data being compiled by the CCGP, this assembly will help strategize efforts to maintain and/or restore local genetic diversity, where interventions like genetic rescue, translocation, and strategic land preservation may be the only means by which P. blainvillii and other low-vagility species can survive in the fragmented habitats of California.
Improving combination therapies: targeting A2B-adenosine receptor to modulate metabolic tumor microenvironment and immunosuppression
Authors: Evans Jason V , Suman Shankar , Goruganthu Mounika Uttam L , Tchekneva Elena E , Guan Shuxiao , Arasada Rajeswara Rao , Antonucci Anneliese , Piao Longzhu , Ilgisonis Irina , Bobko Andrey A , Driesschaert Benoit , Uzhachenko Roman V , Hoyd Rebecca , Samouilov Alexandre , Amann Joseph , Wu Ruohan , Wei Lai , Pallerla Aaditya , Ryzhov Sergey V , Feoktistov Igor , Park Kyungho P , Kikuchi Takefumi , Castro Julio , Ivanova Alla V , Kanagasabai Thanigaivelan , Owen Dwight H , Spakowicz Daniel J , Zweier Jay L , Carbone David P , Novitskiy Sergey V , Khramtsov Valery V , Shanker Anil , Dikov Mikhail M 
Published: May 2023

Abstract

Background
We investigated the role of A2B-adenosine receptor in regulating immunosuppressive metabolic stress in the tumor microenvironment. Novel A2B-adenosine receptor antagonist PBF-1129 was tested for antitumor activity in mice and evaluated for safety and immunologic efficacy in a phase I clinical trial of patients with non-small cell lung cancer.

Methods
The antitumor efficacy of A2B-adenosine receptor antagonists and their impact on the metabolic and immune tumor microenvironment were evaluated in lung, melanoma, colon, breast, and epidermal growth factor receptor–inducible transgenic cancer models. Employing electron paramagnetic resonance, we assessed changes in tumor microenvironment metabolic parameters, including pO2, pH, and inorganic phosphate, during tumor growth and evaluated the immunologic effects of PBF-1129, including its pharmacokinetics, safety, and toxicity, in patients with non-small cell lung cancer.

Results
Levels of metabolic stress correlated with tumor growth, metastasis, and immunosuppression. Tumor interstitial inorganic phosphate emerged as a correlative and cumulative measure of tumor microenvironment stress and immunosuppression. A2B-adenosine receptor inhibition alleviated metabolic stress, downregulated expression of adenosine-generating ectonucleotidases, increased expression of adenosine deaminase, decreased tumor growth and metastasis, increased interferon γ production, and enhanced the efficacy of antitumor therapies following combination regimens in animal models (anti–programmed cell death 1 protein vs anti–programmed cell death 1 protein plus PBF-1129 treatment hazard ratio = 11.74 [95% confidence interval = 3.35 to 41.13], n = 10, P &lt; .001, 2-sided F test). In patients with non-small cell lung cancer, PBF-1129 was well tolerated, with no dose-limiting toxicities; demonstrated pharmacologic efficacy; modulated the adenosine generation system; and improved antitumor immunity.

Conclusions
Data identify A2B-adenosine receptor as a valuable therapeutic target to modify metabolic and immune tumor microenvironment to reduce immunosuppression, enhance the efficacy of immunotherapies, and support clinical application of PBF-1129 in combination therapies.
Professional service firms and the manufacturing of the corporate nobility
Authors: Bühlmann Felix 
Published: May 2023

AbstractGlobal professional service firms (GPSFs) are key actors in contemporary capitalism. They (co-) produce and disseminate new business practices, linking firms, sectors, and countries, integrating them into a global system. We examine a second, less studied function of these firms: underpinning capitalism’s status hierarchies. We ask whether these firms have emerged as producers of a new corporate nobility—as an extension of elite universities, and as a stepping stone in the selection and promotion of top executives. Focusing on the US, we ask: do global professional service firms merely amplify the credentials of elite universities, or can they compensate for an absence of an elite education in the careers of US top managers? and do professional service firms equip future top managers with specific expertise or merely with symbolic capital? Based on a sample of 2,610 top executive managers from leading American firms in 2005 and 2018, we study the role law, consulting, or audit firms played in their careers. Using multinomial regression analyses, we find that the career function of GPSFs varies: consulting firms amplify existing status and enhance the symbolic capital of alumni, aiding their ascent to the most prestigious jobs in US top firms. In contrast, top managers leverage audit firm roles to compensate for a non-elite background, yet then tend to be channelled into narrow, specialist roles in top management. We relate these results to Bourdieu’s state nobility analysis and propose an augmented typology of these firms at the heart of contemporary capitalism.
Effective two-body scatterings around a massive object
Authors: Wang Yihan , Ford Saavik , Perna Rosalba , McKernan Barry , Zhu Zhaohuan , Zhang Bing 
Published: May 2023

ABSTRACT
Two-body scatterings under the potential of a massive object are very common in astrophysics. If the massive body is far enough away that the two small bodies are in their own gravitational sphere of influence, the gravity of the massive body can be temporarily ignored. However, this requires the scattering process to be fast enough that the small objects do not spend too much time at distances near the surface of the sphere of influence. In this paper, we derive the validation criteria for effective two-body scattering and establish a simple analytical solution for this process, which we verify through numerical scattering experiments. We use this solution to study star–black hole scatterings in the discs of active galactic nuclei and planet–planet scatterings in planetary systems, and calculate their one-dimensional cross-section analytically. Our solution will be valuable in reducing computational time when treating two-body scatterings under the potential of a much more massive third body, provided that the problem settings are in the valid parameter space region identified by our study.
A statistical analysis of the structure of the interstellar medium in the disc of the Milky Way
Authors: Bates M L , Whitworth A P 
Published: May 2023

ABSTRACT
We construct Convolutional Neural Networks (CNNs) trained on exponentiated fractional Brownian motion (xfBm) images, and use these CNNs to analyse Hi-GAL images of surface density in the Galactic Plane. The CNNs estimate the Hurst parameter, ${\cal H}$ (a measure of the power spectrum), and the scaling exponent, ${\cal S}$ (a measure of the range of surface densities), for a square patch comprising $[{\cal N}\times {\cal N}]=$ [128 × 128], [64 × 64], or [32 × 32] pixels. The resulting estimates of ${\cal H}$ are more accurate than those obtained using Δ-variance. We stress that statistical measures of structure are inevitably strongly dependent on the range of scales they actually capture, and difficult to interpret when applied to fields that conflate very different lines of sight. The CNNs developed here mitigate this issue by operating effectively on small fields (small ${\cal N}$), and we exploit this property to develop a procedure for constructing detailed maps of ${\cal H}$ and ${\cal S}$. This procedure is then applied to Hi-GAL maps generated with the ppmap procedure. There appears to be a bimodality between sightlines with higher surface density ($\gtrsim 32\, {\rm M}_{_\odot }\, {\rm pc^{-2}}$), which tend to have higher ${\cal H}\, (\gtrsim 0.8)$ and ${\cal S}\, (\gtrsim 1)$; and sightlines intercepting regions of lower surface density ($\lesssim 32\, {\rm M}_{_\odot }\, {\rm pc^{-2}}$), which tend to have lower ${\cal H}\, (\lesssim 0.8)$ and ${\cal S}\, (\lesssim 1)$; unsurprisingly the former sightlines are concentrated towards the Galactic Midplane and the Inner Galaxy. The surface density PDF takes the form dP/dΣ ∝ Σ−3 for $\Sigma \gtrsim 32\, {\rm M}_{_\odot }\, {\rm pc^{-2}}$, and on most sightlines this power-law tail is dominated by dust cooler than $\, \sim 20\, \rm {K}$, which is the median dust temperature in the Galactic Plane.