bluuebunny/crossref_metadata_2025_split huggingface dataset:
PyCoM: a python library for large-scale analysis of residue–residue coevolution data
Authors: Bibik Philipp , Alibai Sabriyeh , Pandini Alessandro , Dantu Sarath Chandra 
Published: March 2024

Abstract

Motivation
Computational methods to detect correlated amino acid positions in proteins have become a valuable tool to predict intra- and inter-residue protein contacts, protein structures, and effects of mutation on protein stability and function. While there are many tools and webservers to compute coevolution scoring matrices, there is no central repository of alignments and coevolution matrices for large-scale studies and pattern detection leveraging on biological and structural annotations already available in UniProt.

Results
We present a Python library, PyCoM, which enables users to query and analyze coevolution matrices and sequence alignments of 457 622 proteins, selected from UniProtKB/Swiss-Prot database (length ≤ 500 residues), from a precompiled coevolution matrix database (PyCoMdb). PyCoM facilitates the development of statistical analyses of residue coevolution patterns using filters on biological and structural annotations from UniProtKB/Swiss-Prot, with simple access to PyCoMdb for both novice and advanced users, supporting Jupyter Notebooks, Python scripts, and a web API access. The resource is open source and will help in generating data-driven computational models and methods to study and understand protein structures, stability, function, and design.

Availability and implementation
PyCoM code is freely available from https://github.com/scdantu/pycom and PyCoMdb and the Jupyter Notebook tutorials are freely available from https://pycom.brunel.ac.uk.
The spatial ecology of Mojave rattlesnakes (Crotalus scutulatus), prairie rattlesnakes (Crotalus viridis), and their hybrids in southwestern New Mexico
Authors: Maag Dylan W , Francioli Yannick Z , Castoe Todd A , Schuett Gordon W , Clark Rulon W 
Published: March 2024

Abstract
Hybridization between species provides unique opportunities to understand evolutionary processes that are linked to reproductive isolation and, ultimately, speciation. However, the extrinsic factors that limit hybridization are poorly understood for most animal systems. Although the spatial ecology of individuals in natural habitats is fundamental to shaping reproductive success and survival, analyses of the spatial ecology of hybrids and their parental groups are rarely reported. Here, we used radiotelemetry to monitor wild rattlesnakes across an interspecific hybrid zone (Crotalus scutulatus and Crotalus viridis) and measured movement parameters and space use (utilization distributions) of individuals to evaluate the hypothesis that hybridization resulted in transgressive or atypical movement patterns. Unexpectedly, of the spatial metrics we investigated, we found that hybrids were very similar to parental individuals. Nonetheless, hybrids did show increased patchiness of core utilization distributions, but this result is likely to be driven by increased habitat patchiness in the hybrid zone. Overall, we did not find evidence for overt extrinsic barriers to hybridization associated with spatial ecology; thus, we suggest that the close evolutionary history between the two parental species and their ecological and behavioural similarities are likely to increase the probability of hybridization events in this unique region of New Mexico.
Lesion network of oculogyric crises maps to brain dopaminergic transcriptomic signature
Authors: Al-Fatly Bassam , Neudorfer Clemens , Kaski Diego , Lang Anthony E , Kühn Andrea A , Fox Michael D , Horn Andreas , Ganos Christos 
Published: March 2024

Abstract
Oculogyric crises are acute episodes of sustained, typically upward, conjugate deviation of the eyes. Oculogyric crises usually occur as the result of acute D2-dopamine receptor blockade, but the brain areas causally involved in generating this symptom remain elusive. Here, we used data from 14 previously reported cases of lesion-induced oculogyric crises and employed lesion network mapping to identify their shared connections throughout the brain. This analysis yielded a common network that included basal ganglia, thalamic, and brainstem nuclei, as well as the cerebellum. Comparison of this network with gene expression profiles associated with the dopamine system revealed spatial overlap specifically with the gene coding for dopamine receptor type 2 (DRD2) as defined by a large-scale transcriptomic database of the human brain. Furthermore, spatial overlap with DRD2 and DRD3 gene expression was specific to brain lesions associated with oculogyric crises when contrasted to lesions that led to other movement disorders. Our findings identify a common neural network causally involved in the occurrence of oculogyric crises and provide a pathophysiological link between lesion locations causing this syndrome and its most common pharmacological cause, namely DRD2 blockade.
Messenger RNA-encoded antibody approach for targeting extracellular and intracellular tau
Authors: Wongsodirdjo Patricia , Caruso Alayna C , Yong Alicia K , Lester Madeleine A , Vella Laura J , Hung Ya Hui , Nisbet Rebecca M 
Published: March 2024

Abstract
Monoclonal antibodies have emerged as a leading therapeutic agent for the treatment of disease, including Alzheimer’s disease. In the last year, two anti-amyloid monoclonal antibodies, lecanemab and aducanumab, have been approved in the USA for the treatment of Alzheimer’s disease, whilst several tau-targeting monoclonal antibodies are currently in clinical trials. Such antibodies, however, are expensive and timely to produce and require frequent dosing regimens to ensure disease-modifying effects. Synthetic in vitro-transcribed messenger RNA encoding antibodies for endogenous protein expression holds the potential to overcome many of the limitations associated with protein antibody production. Here, we have generated synthetic in vitro-transcribed messenger RNA encoding a tau-specific antibody as a full-sized immunoglobulin and as a single-chain variable fragment. In vitro transfection of human neuroblastoma SH-SY5Y cells demonstrated the ability of the synthetic messenger RNA to be translated into a functional tau-specific antibody. Furthermore, we show that the translation of the tau-specific single-chain variable fragment as an intrabody results in the specific engagement of intracellular tau. This work highlights the utility of messenger RNA for the delivery of antibody therapeutics, including intrabodies, for the targeting of tau in Alzheimer’s disease and other tauopathies.
Maintained renin–angiotensin–aldosterone system inhibitor therapy with sodium zirconium cyclosilicate following a hyperkalaemia episode: a multicountry cohort study
Authors: Rastogi Anjay , Pollack Charles V , Sánchez Lázaro Ignacio José , Lesén Eva , Arnold Matthew , Franzén Stefan , Allum Alaster , Hernández Ignacio , Murohara Toyoaki , Kanda Eiichiro 
Published: March 2024

ABSTRACT

Background
This observational cohort study compared the likelihood of maintained (stabilized/up-titrated) renin–angiotensin–aldosterone system inhibitor (RAASi) therapy at 6 months following hyperkalaemia in patients with chronic kidney disease (CKD) and/or heart failure (HF) from the USA, Japan and Spain who received sodium zirconium cyclosilicate (SZC) for at least 120 days, relative to those with no prescription for a potassium (K+) binder.

Methods
Using health registers and hospital medical records, patients with CKD and/or HF receiving RAASi therapy who experienced a hyperkalaemia episode were identified. Propensity score (PS) matching (1:4) was applied to balance the SZC cohort to the no K+ binder cohort on baseline characteristics. Logistic regression analysis was performed to compare the odds of maintained RAASi therapy at 6 months in the SZC versus no K+ binder cohorts.

Results
The PS-matched SZC cohort included 565 (USA), 776 (Japan) and 56 (Spain) patients; the no K+ binder cohort included 2068, 2629 and 203 patients, respectively. At 6 months, 68.9% (USA), 79.9% (Japan) and 69.6% (Spain) in the SZC cohorts versus 53.1% (USA), 56.0% (Japan) and 48.3% (Spain) in the no K+ binder cohorts had maintained RAASi therapy. Meta-analysed across countries, the odds ratio of maintained RAASi therapy in the SZC cohort versus no K+ binder cohort was 2.56 (95% confidence interval 1.92–3.41; P &lt; .0001).

Conclusions
In routine clinical practice across three countries, patients treated with SZC were substantially more likely to maintain guideline-concordant RAASi therapy at 6 months following hyperkalaemia relative to patients with no K+ binder treatment.
High-resolution free-breathing automated quantitative myocardial perfusion by cardiovascular magnetic resonance for the detection of functionally significant coronary artery disease
Authors: Crawley R , Kunze K P , Milidonis X , Highton J , McElroy S , Frey S M , Hoefler D , Karamanli C , Wong N C K , Backhaus S J , Alskaf E , Neji R , Scannell C M , Plein S , Chiribiri A 
Published: March 2024

Abstract

Aims
Current assessment of myocardial ischaemia from stress perfusion cardiovascular magnetic resonance (SP-CMR) largely relies on visual interpretation. This study investigated the use of high-resolution free-breathing SP-CMR with automated quantitative mapping in the diagnosis of coronary artery disease (CAD). Diagnostic performance was evaluated against invasive coronary angiography (ICA) with fractional flow reserve (FFR) measurement.

Methods and results
Seven hundred and three patients were recruited for SP-CMR using the research sequence at 3 Tesla. Of those receiving ICA within 6 months, 80 patients had either FFR measurement or identification of a chronic total occlusion (CTO) with inducible perfusion defects seen on SP-CMR. Myocardial blood flow (MBF) maps were automatically generated in-line on the scanner following image acquisition at hyperaemic stress and rest, allowing myocardial perfusion reserve (MPR) calculation. Seventy-five coronary vessels assessed by FFR and 28 vessels with CTO were evaluated at both segmental and coronary territory level. Coronary territory stress MBF and MPR were reduced in FFR-positive (≤0.80) regions [median stress MBF: 1.74 (0.90–2.17) mL/min/g; MPR: 1.67 (1.10–1.89)] compared with FFR-negative regions [stress MBF: 2.50 (2.15–2.95) mL/min/g; MPR 2.35 (2.06–2.54) P &lt; 0.001 for both]. Stress MBF ≤ 1.94 mL/min/g and MPR ≤ 1.97 accurately detected FFR-positive CAD on a per-vessel basis (area under the curve: 0.85 and 0.96, respectively; P &lt; 0.001 for both).

Conclusion
A novel scanner-integrated high-resolution free-breathing SP-CMR sequence with automated in-line perfusion mapping is presented which accurately detects functionally significant CAD.
Mutation Rate and Effective Population Size of the Model Cooperative Bacterium Myxococcus xanthus
Authors: Wielgoss Sébastien , Van Dyken James David , Velicer Gregory J 
Published: March 2024

Abstract
Intrinsic rates of genetic mutation have diverged greatly across taxa and exhibit statistical associations with several other parameters and features. These include effective population size (Ne), genome size, and gametic multicellularity, with the latter being associated with both increased mutation rates and decreased effective population sizes. However, data sufficient to test for possible relationships between microbial multicellularity and mutation rate (µ) are lacking. Here, we report estimates of two key population-genetic parameters, Ne and µ, for Myxococcus xanthus, a bacterial model organism for the study of aggregative multicellular development, predation, and social swarming. To estimate µ, we conducted an ∼400-day mutation accumulation experiment with 46 lineages subjected to regular single colony bottlenecks prior to clonal regrowth. Upon conclusion, we sequenced one clonal-isolate genome per lineage. Given collective evolution for 85,323 generations across all lines, we calculate a per base-pair mutation rate of ∼5.5 × 10−10 per site per generation, one of the highest mutation rates among free-living eubacteria. Given our estimate of µ, we derived Ne at ∼107 from neutral diversity at four-fold degenerate sites across two dozen M. xanthus natural isolates. This estimate is below average for eubacteria and strengthens an already clear negative correlation between µ and Ne in prokaryotes. The higher and lower than average mutation rate and Ne for M. xanthus, respectively, amplify the question of whether any features of its multicellular life cycle—such as group-size reduction during fruiting-body development—or its highly structured spatial distribution have significantly influenced how these parameters have evolved.
Partisanship with Rightist and Leftist Parties in Central America: A Test of Four Hypotheses
Authors: Perelló Lucas , Navia Patricio 
Published: March 2024

Abstract
Although scholars have made substantial progress in the debate on party systems in Latin America, many questions about partisanship in the region remain unaddressed. This article explores how the determinants of partisanship identified in the literature navigate in Central America, a region commonly overlooked by scholars. We examine a decade of public opinion surveys by the Latin American Public Opinion Project (LAPOP) from 2008 to 2018 to explore the individual-level determinants of partisan attachments with sixty-six leftist and rightist parties in six Central American countries to test four hypotheses. While differences across countries exist, self-placement on the left-right ideological scale, engagement in societal organizations, and protest participation help portray partisan attachments.
Development of a Reversed-Phase UPLC Method for Assay of Fipronil Including Determination of Its Related Substances in Bulk Batches of Fipronil Drug Substance
Authors: Berger Shane N , Rustum Abu M 
Published: March 2024

Abstract

Background
Fipronil is a commonly used pesticide in the agricultural and animal health industries for the protection of crops and control of fleas, ticks, and chewing lice. It is difficult to obtain reproducible retention time and relative retention time (RRT) for a common hydrolytic degradation product of fipronil with the current European Pharmacopeia (EP) monograph for assay and estimation of related substances of fipronil. This situation causes misidentification, mislabeling, and/or false out-of-specification results for this hydrolytic degradation product of fipronil in bulk commercial batches during batch release and/or in the stability samples during the shelf life of a released batch.

Objective
This study aimed to develop a reversed-phase ultra performance liquid chromatography (UPLC) method for assay and identification of fipronil including identification and estimation of its related substances in bulk drug substance batches of fipronil and provide consistent retention time of the hydrolytic degradation product.

Methods
Fipronil and its related substances were separated by gradient elution on a Halo C18 column (50 mm × 2.1 mm id, 2.0 µm particle size) maintained at 40°C with 0.1% H3PO4 in H2O as mobile phase-A and acetonitrile–methanol (50 + 50, v/v) as mobile phase-B. Fipronil and its related substances were detected and quantified at 280 nm with a quantitation limit of 0.05% of the target (analytical) concentration.

Results
The UPLC method was able to separate all analytes of interest by gradient elution with a total run time of 7 min (approximately 40% faster than EP).

Conclusion
In this paper, we report the development and validation of a fast, stability-indicating reversed-phase UPLC method for assay and estimation of related substances of fipronil in stability samples and bulk batches of fipronil.

Highlights
The new UPLC method is approximately 40% faster than the current Ph. Eur. monograph for fipronil assay and the new method provides reproducible retention of a common hydrolytic degradation product of fipronil.
Building an ethical research culture: Scholars of refugee background researching refugee-related issues
Authors: Albtran Ahmad , Aksu Pinar , Al-Fakir Zuhair , Al-Hashimi Heidar , Baillot Helen , Izzeddin Azad , Yohannes Hyab Teklehaimanot , Kirkwood Steve , Mfaco Bulelani , Nicole Tandy , Ní Raghallaigh Muireann , Ogutu Gordon , O’Reilly Zoë , Younes Angham 
Published: March 2024

Abstract
Recent scholarship on the need to decolonize refugee research, and migration research more generally, points to the urgency of challenging ongoing colonial power structures inherent in such research. Increased involvement of scholars with lived experience is one way to challenge and remake unequal and colonial power relations. Through discussions with researchers of forced migration, we aimed to explore the challenges, barriers, and supports related to involvement in such research, and to identify how research practices and structures could be improved to increase and facilitate the involvement of scholars with refugee backgrounds. In this field reflection, we highlight key points and suggestions for better research practice that emerged from these discussions. In doing so, we are endeavouring to contribute to the important ongoing conversation about ethics and decolonizing research. We build on existing ethical guidelines by opening up some of the complexities of ethical practice and offering concrete actions that can be taken to work through these.
Identification of causal diffusion effects using placebo outcomes under structural stationarity
Authors: Egami Naoki 
Published: March 2024

Abstract
Social and biomedical scientists have long been interested in the process through which ideas and behaviours diffuse. In this article, we study an urgent social problem, the spatial diffusion of hate crimes against refugees in Germany, which has admitted more than 1 million asylum seekers since the 2015 refugee crisis. Despite its importance, identification of causal diffusion effects, also known as peer and contagion effects, remains challenging because the commonly used assumption of no omitted confounders is often untenable due to contextual confounding and homophily bias. To address this long-standing problem, we examine causal identification using placebo outcomes under a new assumption of structural stationarity, which formalizes the underlying diffusion process with a class of nonparametric structural equation models with recursive structure. We show under structural stationarity that a lagged dependent variable is a general, valid placebo outcome for detecting a wide range of biases, including the 2 types mentioned above. We then propose a difference-in-differences style estimator that can directly correct biases under an additional causal assumption. Analysing fine-grained geo-coded hate crime data from Germany, we show when and how the proposed methods can detect and correct unmeasured confounding in spatial causal diffusion analysis.
Comapping Cellular Content and Extracellular Matrix with Hemodynamics in Intact Arterial Tissues Using Scanning Immunofluorescent Multiphoton Microscopy
Authors: Tobe Yasutaka , Robertson Anne M , Ramezanpour Mehdi , Cebral Juan R , Watkins Simon C , Charbel Fady T , Amin-Hanjani Sepideh , Yu Alexander K , Cheng Boyle C , Woo Henry H 
Published: March 2024

Abstract
Deviation of blood flow from an optimal range is known to be associated with the initiation and progression of vascular pathologies. Important open questions remain about how the abnormal flow drives specific wall changes in pathologies such as cerebral aneurysms where the flow is highly heterogeneous and complex. This knowledge gap precludes the clinical use of readily available flow data to predict outcomes and improve treatment of these diseases. As both flow and the pathological wall changes are spatially heterogeneous, a crucial requirement for progress in this area is a methodology for acquiring and comapping local vascular wall biology data with local hemodynamic data. Here, we developed an imaging pipeline to address this pressing need. A protocol that employs scanning multiphoton microscopy was developed to obtain three-dimensional (3D) datasets for smooth muscle actin, collagen, and elastin in intact vascular specimens. A cluster analysis was introduced to objectively categorize the smooth muscle cells (SMC) across the vascular specimen based on SMC actin density. Finally, direct quantitative comparison of local flow and wall biology in 3D intact specimens was achieved by comapping both heterogeneous SMC data and wall thickness to patient-specific hemodynamic results.
Ocular Effects of MEK Inhibitor Therapy: Literature Review, Clinical Presentation, and Best Practices for Mitigation
Authors: Jeng-Miller Karen W , Miller Miles A , Heier Jeffrey S 
Published: March 2024

Abstract
MEK signaling pathway targeting has emerged as a valuable addition to the options available for the treatment of advanced cancers including melanoma and non-small cell lung cancer. Ophthalmologic monitoring of patients taking part in clinical trials of MEK inhibitors has shown that while ocular effects are common, generally emerging during the first days to weeks of treatment, the majority are either asymptomatic or have minimal visual impact and are benign, resolving without intervention or the need to reduce or stop MEK inhibitor therapy. However rare cases of serious, potentially vision-threatening ocular toxicities have been reported during MEK inhibitor therapy. There is currently no recommendation for routine ophthalmologic screening or monitoring of patients with advanced cancer who are initiating MEK inhibitor therapy. However, baseline ophthalmologic examination may be useful for all patients initiating MEK inhibitor therapy to allow the differentiation of preexisting pathology versus the development of MEK inhibitor-associated retinopathy in the event of the emergence of symptomatic ocular events. Regular ophthalmologic examination may be appropriate for patients at increased risk for ocular events, such as patients with a history of ocular inflammation, infection, or underlying macular/retinal disease. All patients reporting visual disturbance should be referred for prompt ophthalmologic review to determine the potential seriousness of any underlying abnormalities and whether there is a need for treatment modification or specific intervention. Understanding the potential consequences of ocular toxicities is of particular importance in the context of decision-making for the continuation of potentially life-prolonging medications such as MEK inhibitors.