bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catecholaminergic axon innervation and morphology in flat‐mounts of atria and ventricles of mice
Authors: Bizanti Ariege , Zhang Yuanyuan , Harden Scott W. , Chen Jin , Hoover Donald B. , Gozal David , Shivkumar Kalyanam , Cheng Zixi Jack 
Published: January 2023

AbstractSympathetic efferent axons regulate cardiac functions. However, the topographical distribution and morphology of cardiac sympathetic efferent axons remain insufficiently characterized due to the technical challenges involved in immunohistochemical labeling of the thick walls of the whole heart. In this study, flat‐mounts of the left and right atria and ventricles of FVB mice were immunolabeled for tyrosine hydroxylase (TH), a marker of sympathetic nerves. Atrial and ventricular flat‐mounts were scanned using a confocal microscope to construct montages. We found (1) In the atria: A few large TH‐immunoreactive (IR) axon bundles entered both atria, branched into small bundles and then single axons that eventually formed very dense terminal networks in the epicardium, myocardium and inlet regions of great vessels to the atria. Varicose TH‐IR axons formed close contact with cardiomyocytes, vessels, and adipocytes. Multiple intrinsic cardiac ganglia (ICG) were identified in the epicardium of both atria, and a subpopulation of the neurons in the ICG were TH‐IR. Most TH‐IR axons in bundles traveled through ICG before forming dense varicose terminal networks in cardiomyocytes. We did not observe varicose TH‐IR terminals encircling ICG neurons. (2) In the left and right ventricles and interventricular septum: TH‐IR axons formed dense terminal networks in the epicardium, myocardium, and vasculature. Collectively, TH labeling is achievable in flat‐mounts of thick cardiac walls, enabling detailed mapping of catecholaminergic axons and terminal structures in the whole heart at single‐cell/axon/varicosity scale. This approach provides a foundation for future quantification of the topographical organization of the cardiac sympathetic innervation in different pathological conditions.
Defining cardiac fibrosis complexity and regulation towards therapeutic development
Authors: Claridge Bethany , Drack Auriane , Pinto Alexander R. , Greening David W. 
Published: January 2023

AbstractCardiac fibrosis is insidious, accelerating cardiovascular diseases, heart failure, and death. With a notable lack of effective therapies, advances in both understanding and targeted treatment of fibrosis are urgently needed. Remodelling of the extracellular matrix alters the biomechanical and biochemical cardiac structure and function, disrupting cell‐matrix interactions and exacerbating pathogenesis to ultimately impair cardiac function. Attempts at clinical fibrotic reduction have been fruitless, constrained by an understanding which severely underestimates its dynamic complexity and regulation. Integration of single‐cell sequencing and quantitative proteomics has provided new insights into cardiac fibrosis, including reparative or maladaptive processes, spatiotemporal changes and fibroblast heterogeneity. Further studies have revealed microenvironmental and intercellular signalling mechanisms (including soluble mediators and extracellular vesicles), and intracellular regulators including post‐translational/epigenetic modifications, RNA binding proteins, and non‐coding RNAs. This understanding of novel disease processes and molecular targets has supported the development of innovative therapeutic strategies. Indeed, targeted modulation of cellular heterogeneity, microenvironmental signalling, and intracellular regulation offer promising pre‐clinical therapeutic leads. Clinical development will require further advances in our mechanistic understanding of cardiac fibrosis and dissection of the molecular basis for fibrotic remodelling. This review provides an overview of the complexities of cardiac fibrosis, emerging regulatory mechanisms and therapeutic strategies, and highlights knowledge gaps and opportunities for further investigation towards therapeutic/clinical translation.
Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome
Authors: Augustin Aisha , Guennec Adrien Le , Umamahesan Chianna , Kendler‐Rhodes Aidan , Tucker Rosalind M. , Chekmeneva Elena , Takis Panteleimon , Lewis Matthew , Balasubramanian Karthik , DeSouza Neville , Mullish Benjamin H , Taylor David , Ryan Suzanne , Whelan Kevin , Ma Yun , Ibrahim Mohammad A. A. , Bjarnason Ingvar , Hayee Bu’ Hussain , Charlett André , Dobbs Sylvia M. , Dobbs R. John , Weller Clive 
Published: January 2023

ABSTRACTBackgroundGut‐brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease‐modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide.MethodsWe characterised 77 participants with diagnosed‐PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time. Complete‐linkage hierarchical cluster analysis of metabolites discriminant for PD‐status was performed.ResultsLonger colonic transit was linked to deficits in faecal short‐chain‐fatty acids outside PD, to a ‘tryptophan‐containing metabolite cluster’ overall. Phenotypic cluster analysis aggregated colonic transit with brady/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan‐cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole‐ring compound (anti‐fungals) and vitamin B3 (anti‐inflammatory) and with higher serum CCL20 (chemotactic for lymphocytes/dendritic cells towards mucosal epithelium). The faster pulse in PD was irrespective of postural hypotension. The benzoic acid‐cluster deficit was linked to (well‐recognised) lower caffeine and alcohol intakes, tryptophan‐cluster deficit to higher maltose intake. Free‐sugar intake was increased in PD, maltose intake being 63% higher (p = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [p = .001, adjusted for proton‐pump inhibitors (p = .001)], with 16% of PD‐probands exceeding a cut‐point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut‐point.ConclusionsEmerging picture is of (i) clinical phenotype being described by deficits in microbial metabolites essential to gut health; (ii) intestinal inflammation; (iii) a systemic inflammatory response syndrome.
Synthesis of Functionalized Proline‐Derived Azabicycloalkane Amino Acids and Their Applications in Drug Discovery: Recent Advances
Authors: Serra Massimo , Terreni Marco , Bernardi Eric , Colombo Lino 
Published: January 2023

AbstractAfter the first synthesis reported in 1994, azabicycloalkane amino acids have raised increasing interest, becoming one of the most important classes of constrained dipeptide mimics. Their incorporation into peptidomimetic structures allowed the obtainment of a wide range of biologically active compounds. Over the years, different research groups have worked at the development of synthetic strategies to gain these rigid dipeptide surrogates, nevertheless, methods affording functionalized and “easy‐to‐functionalize” derivatives are quite less described. The presence of a derivatizable azabicycloalkanone core could allow the introduction of chemical modifications aimed to improve the pharmaceutical properties of a biologically active compound without the need for redesigning its chemical synthesis. This account has collected and critically surveyed relevant approaches to the synthesis of functionalized azabicycloalkane amino acids, focusing the attention on the period of 2010 to the present. Moreover, recent applications of these compounds in drug discovery will be discussed.
Status of epilepsy in the tropics: An overlooked perspective
Authors: Liu Jiaqi , Zhang Peng , Zou Qin , Liang Jiantang , Chen Yongmin , Cai Yi , Li Shichuo , Li Jinmei , Su Jing , Li Qifu 
Published: January 2023

AbstractEpilepsy is one of the most common serious chronic neurological diseases affecting people of all ages globally. It is characterized by recurrent seizures. About 50 million people worldwide have epilepsy. Indubitably, people with epilepsy (PWE) may be without access to appropriate treatment. Many studies have examined the molecular mechanisms and clinical aspects of epilepsy; nonetheless, the treatment gap exists in some special areas. In the tropics, the specific geographical and ecological conditions and a lack of medical resources result in neglect or delay of diagnosis for PWE. Herein, we summarized the epidemiology of epilepsy in the tropics and discussed the disease burden and existing problems, aiming to offer a medical environment for patients in need and highlight the importance of reducing the epileptic disease burden in tropical countries.
Settling of superparamagnetic silica encapsulated DNA microparticles in river water
Authors: Tang Yuchen , Zhang Fengbo , Bogaard Thom , Chassagne Claire , Ali Zeeshan , Bandyopadhyay Sulalit , Foppen Jan Willem 
Published: January 2023

AbstractParticle tracers are sometimes used to track sources and sinks of riverine particulate and contaminant transport. A potentially new particle tracer is ~200 nm sized superparamagnetic silica encapsulated DNA (SiDNAFe). The main objective of this research was to understand and quantify the settling and aggregation behaviour of SiDNAFe in river waters based on laboratory settling experiments. Our results indicated, that in quiescent conditions, more than 60% of SiDNAFe settled within 30 h, starting with a rapid settling phase followed by an exponential‐like slow settling phase in the three river waters we used (Meuse, Merkske, and Strijbeek) plus MilliQ water. In suspensions of 1000× higher particle concentrations, the hydrodynamic diameter (Dh‐DLS) of SiDNAFe increased over time, with its polydispersity index (PDI) positively correlated with particle size. From these observations, we inferred that the rapid SiDNAFe settling was mainly due to homo‐aggregation and not due to hetero‐aggregation (e.g., with particulate matter present in river water). Incorporating a first‐order mass loss term which mimics the exponential phase of the settling in quiescent conditions seems to be an adequate step forward when modelling the transport of SiDNAFe in river injection experiments. Furthermore, we validated the applicability of magnetic separation and up‐concentration of SiDNAFe in real river waters, which is an important advantage for carrying out field‐scale SiDNAFe tracing experiments.
Global iterative optimization framework for predicting cognitive function statuses of patients with end‐stage renal disease
Authors: Sheng Quan , Zhang Yutao , Shi Haifeng , Jiao Zhuqing 
Published: January 2023

AbstractThe existing methods to determine the cognitive function level of end‐stage renal disease (ESRD) are not only inaccurate but also susceptible to the influence of the patient's education level, emotional state, and examination environment. We proposed a global iterative optimization framework (GIO) to accurately predict cognitive function statuses of ESRD patients without being affected by the above factors. First, the functional magnetic resonance imaging (fMRI) data preprocessed and the time series were extracted to construct brain functional networks. Secondly, the areas under curve (AUC) of topological attribute parameters in the brain functional networks were extracted as features. After statistical analysis, the global efficiency, the characteristic path length, and the shortest path length in the small‐world network were selected as features for linear fusion. Finally, the support vector regression (SVR) was used as the basis of GIO framework, and the global iterative search strategy was introduced to find out the most appropriate penalty factor and radial basis function parameters. Achieving the objective of accurately predicting the cognitive function status of patients with end‐stage renal disease. Since this framework uses SVR which has special advantages in processing small sample data, and introduces appropriate parameter selection method, the prediction ability of GIO framework has been significantly improved. Experimental results demonstrate that the final prediction accuracy of the proposed framework is significantly better than those of SVR, LSSVR, GMO‐SVR, GMO‐LSSVR, and PSO‐SVR. The mean absolute error (MAE) and the mean absolute percentage error (MAPE) of the proposed framework are 0.55% and 2.58%, respectively. It is suggested that this framework is more convenient to determine the current level of cognitive function in ESRD patients and is conducive to the early prevention of cognitive dysfunction in ESRD patients.
Impact of ultraviolet radiation nearly overrides the effects of elevated pCO2 on a prominent nitrogen‐fixing cyanobacterium
Authors: Yi Xiangqi , Gao Kunshan 
Published: January 2023

AbstractAlthough the marine N2‐fixers Trichodesmium spp. are affected by increasing pCO2 and by ultraviolet radiation (UVR) in their habitats, little is known on their potential responses to future ocean acidification in the presence of UVR. We grew Trichodesmium at two pCO2 levels (410 and 1000 μatm) under natural sunlight, documented the filament length, growth, and chlorophyll content after its acclimation to the pCO2 treatments, and measured its carbon and N2 fixation rates under different solar radiation treatments with or without UVR. We showed that the elevated pCO2 did not significantly alter the diazotroph's growth, filament length, or pigment content, and its photosynthetic rate was only affected by solar radiation treatments rather than the pCO2 levels. The presence of UV‐A and UV‐B inhibited photosynthesis by 10–22% and 17–21%, respectively. Inhibition of N2 fixation by UV‐B was proportional to its intensity, whereas UV‐A stimulated N2 fixation at low, but inhibited it at high, intensities. Elevated pCO2 only stimulated N2 fixation under moderate levels of solar radiation. The simulated depth profile of N2 fixation in the water column showed that UV‐induced inhibition dominated the combined effects of elevated pCO2 and UVR at 0–30 m depth and the combination of these factors enhanced N2 fixation at 30–60 m depth, but this effect diminished in deeper water. Our results suggest that Trichodesmium could be influenced more by UVR than by pCO2 and their combined action result in negative effects on N2 fixation under high solar radiation, but positive effects under low to moderate solar radiation.
Imaging through Random Media Using Coherent Averaging
Authors: Hwang Byungjae , Woo Taeseong , Ahn Cheolwoo , Park Jung‐Hoon 
Published: January 2023

AbstractA new phase retrieval method for imaging through random media is proposed and demonstrated. Although methods to recover the Fourier amplitude through random distortions are well established, recovery of the Fourier phase has been a more difficult problem and is still a very active and important research area. Here, it is shown that by simply ensemble averaging shift‐corrected images, the Fourier phase of an object obscured by random distortions can be accurately retrieved up to the diffraction limit. The method is simple, fast, does not have any optimization parameters, and does not require prior knowledge or assumptions about the sample. The feasibility and robustness of the method are demonstrated by realizing all computational diffraction‐limited imaging through atmospheric turbulence as well as imaging through multiple scattering media.
Neuromelanin‐Sensitive Magnetic Resonance Imaging Changes in the Locus Coeruleus/Subcoeruleus Complex in Patients with Typical and Atypical Parkinsonism
Authors: Nobileau Alexis , Gaurav Rahul , Chougar Lydia , Faucher Alice , Valabrègue Romain , Mangone Graziella , Leu‐Semenescu Smaranda , Lejeune François‐Xavier , Corvol Jean‐Christophe , Arnulf Isabelle , Vidailhet Marie , Grabli David , Degos Bertrand , Lehéricy Stéphane 
Published: January 2023

AbstractBackgroundThe locus coeruleus/subcoeruleus complex (LC/LsC) is a structure comprising melanized noradrenergic neurons.ObjectiveTo study the LC/LsC damage across Parkinson's disease (PD) and atypical parkinsonism in a large group of subjects.MethodsWe studied 98 healthy control subjects, 47 patients with isolated rapid eye movement sleep behavior disorder (RBD), 75 patients with PD plus RBD, 142 patients with PD without RBD, 19 patients with progressive supranuclear palsy (PSP), and 19 patients with multiple system atrophy (MSA). Twelve patients with MSA had proven RBD. LC/LsC signal intensity was derived from neuromelanin magnetic resonance imaging using automated software.ResultsThe signal intensity was reduced in all parkinsonian syndromes compared with healthy control subjects, except in PD without RBD. The signal intensity decreased as age increased. Moreover, the signal intensity was lower in MSA than in isolated RBD and PD without RBD groups. In PD, the signal intensity correlated negatively with the percentage of REM sleep without atonia. There were no differences in signal intensity between PD plus RBD, PSP, and MSA.ConclusionsNeuromelanin signal intensity was reduced in all parkinsonian disorders, except in PD without RBD. The presence of RBD in parkinsonian disorders appears to be associated with lower neuromelanin signal intensity. Furthermore, lower LC/LsC signal changes in PSP could be partly caused by the effect of age. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
The surface‐reconstruction virtual‐region mesh update method for problems with topology changes
Authors: González Felipe A. , Elgeti Stefanie , Behr Marek 
Published: January 2023

AbstractIn this work, we introduce a novel boundary‐conforming mesh‐update method that is particularly designed for problems with large boundary displacements and topology changes. This method, which we call the surface‐reconstruction virtual‐region mesh update method, integrates the virtual region approach and a surface reconstruction process to handle complex boundary movements. The virtual region approach allows having an activated and deactivated part of the mesh, where elements can freely enter or leave the activated domain. Furthermore, the surface reconstruction ensures boundary conformity of the activated domain. The robustness of the proposed method is shown in two numerical examples: a variation of the benchmark Poiseuille flow, and the flow simulation during a closing diaphragm valve. In particular, the diaphragm valve simulation includes large boundary movement, complex geometry, and closing motion. For this case, both steady and transient simulation results at different closing conditions are presented.
Pulsatile hemorrhage posterior to the mandibular third molar due to abnormal branching of the inferior alveolar artery: A case report
Authors: Takaoka Shohei , Ishibashi‐Kanno Naomi , Namai Tomono , Yamagata Kenji , Yanagawa Toru , Bukawa Hiroki 
Published: January 2023

AbstractBackgroundThe retromolar canal and foramen posterior to the mandibular third molar are rare anatomical variants through which branches of the inferior alveolar neurovascular bundle may pass.Case PresentationPulsatile hemorrhage occurred when the removal of a mandibular third molar and a surrounding cystic lesion was attempted in a 56‐year‐old woman. On imaging, well‐developed inferior alveolar artery branch was observed in the retromolar canal, and the facial artery could not be identified on the same side.ConclusionClinicians must be aware of this anatomical variant to avoid complications.
Tumor biology, biomarkers, and liquid biopsy in pediatric renal tumors
Authors: Walz Amy L. , Maschietto Mariana , Crompton Brian , Evageliou Nicholas , Dix David , Tytgat Godelieve , Gessler Manfred , Gisselsson David , Daw Najat C. , Wegert Jenny 
Published: January 2023

AbstractThe expansion of knowledge regarding driver mutations for Wilms tumor (WT) and malignant rhabdoid tumor of the kidney (MRT) and various translocations for other pediatric renal tumors opens up new possibilities for diagnosis and treatment. In addition, there are growing data surrounding prognostic factors that can be used to stratify WT treatment to improve outcomes. Here, we review the molecular landscape of WT and other pediatric renal tumors as well as WT prognostic factors. We also review incorporation of circulating tumor DNA/liquid biopsies to leverage this molecular landscape, with potential use in the future for distinguishing renal tumors at the time of diagnosis and elucidating intratumor heterogeneity, which is not well evaluated with standard biopsies. Incorporation of liquid biopsies will require longitudinal collection of multiple biospecimens. Further preclinical research, identification and validation of biomarkers, molecular studies, and data sharing among investigators are crucial to inform therapeutic strategies that improve patient outcomes.
Understanding the experiences and perspectives of prenatal screening among a diverse cohort
Authors: Riches Naomi O. , Johnson Erin P. , Subramaniam Akila , Vora Neeta L. , Hardisty Emily , LaRiviere Kate , Rothwell Erin 
Published: January 2023

AbstractIntroductionRapid advances in prenatal genetic screening technology make it difficult for providers to deliver adequate prenatal counseling. The aim of this study was to understand how prenatal screening educational approaches can meet the needs of patients.MethodsQualitative content analysis was conducted on a diverse population who were interviewed to explore their perceived experiences and preferences for prenatal screening educational delivery.ResultsTwenty‐two women from three US sites were interviewed. Participants were racially/ethnically diverse with 22.7% identifying as Black or African American (n = 5), 40.9% as Hispanic (n = 9), and 4.5% as Pacific Islander (n = 1). Four themes were identified: prenatal screening education, prenatal screening decision‐making, return of results, and suggestions for creating a decision aid. Most results were consistent with previous research not targeting a diverse population.Discussion/ConclusionOur results indicate that learning style preferences vary between patients and that current methods are not consistently satisfying patient's desire for understanding, particularly with ‘high‐risk’ results, suggesting that a standardized tool could improve knowledge and decrease decisional conflict. This diverse cohort suggested a list and description of each of the testing options offered, information about each condition being screened for, a timeline for the testing and return of results, costs associated, and non‐technical language.