bluuebunny/crossref_metadata_2025_split huggingface dataset:
The number of the CTCF binding sites of the H19/IGF2:IG-DMR correlates with DNA methylation and expression imprinting in a humanized mouse model
Authors: Freschi Andrea , Del Prete Rosita , Pignata Laura , Cecere Francesco , Manfrevola Francesco , Mattia Monica , Cobellis Gilda , Sparago Angela , Bartolomei Marisa S , Riccio Andrea , Cerrato Flavia 
Published: April 2021

Abstract
The reciprocal parent of origin-specific expression of H19 and IGF2 is controlled by the H19/IGF2:IG-DMR (IC1), whose maternal allele is unmethylated and acts as a CTCF-dependent insulator. In humans, internal IC1 deletions are associated with Beckwith–Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS), depending on their parental origin. These genetic mutations result in aberrant DNA methylation, deregulation of IGF2/H19 and disease with incomplete penetrance. However, the mechanism linking the microdeletions to altered molecular and clinical phenotypes remains unclear. To address this issue, we have previously generated and characterized two knock-in mouse lines with the human wild-type (hIC1wt) or mutant (hIC1∆2.2) IC1 allele replacing the endogenous mouse IC1 (mIC1). Here, we report an additional knock-in line carrying a mutant hIC1 allele with an internal 1.8 kb deletion (hIC1∆1.8). The phenotype of these mice is different from that of the hIC1∆2.2-carrying mice, partially resembling hIC1wt animals. Indeed, proper H19 and Igf2 imprinting and normal growth phenotype were evident in the mice with maternal transmission of hIC1Δ1.8, while low DNA methylation and non-viable phenotype characterize its paternal transmission. In contrast to hIC1wt, E15.5 embryos that paternally inherit hIC1Δ1.8 displayed variegated hIC1 methylation. In addition, increased Igf2 expression, correlating with increased body weight, was found in one third of these mice. Chromatin immunoprecipitation experiments in mouse embryonic stem cells carrying the three different hIC1 alleles demonstrate that the number of CTCF target sites influences its binding to hIC1, indicating that in the mouse, CTCF binding is key to determining hIC1 methylation and Igf2 expression.
Proteomic analysis identifies key differences in the cardiac interactomes of dystrophin and micro-dystrophin
Authors: Wang Hong , Marrosu Elena , Brayson Daniel , Wasala Nalinda B , Johnson Eric K , Scott Charlotte S , Yue Yongping , Hau Kwan-Leong , Trask Aaron J , Froehner Stan C , Adams Marvin E , Zhang Liwen , Duan Dongsheng , Montanaro Federica 
Published: April 2021

AbstractΔR4-R23/ΔCT micro-dystrophin (μDys) is a miniaturized version of dystrophin currently evaluated in a Duchenne muscular dystrophy (DMD) gene therapy trial to treat skeletal and cardiac muscle disease. In pre-clinical studies, μDys efficiently rescues cardiac histopathology, but only partially normalizes cardiac function. To gain insights into factors that may impact the cardiac therapeutic efficacy of μDys, we compared by mass spectrometry the composition of purified dystrophin and μDys protein complexes in the mouse heart. We report that compared to dystrophin, μDys has altered associations with α1- and β2-syntrophins, as well as cavins, a group of caveolae-associated signaling proteins. In particular, we found that membrane localization of cavin-1 and cavin-4 in cardiomyocytes requires dystrophin and is profoundly disrupted in the heart of mdx5cv mice, a model of DMD. Following cardiac stress/damage, membrane-associated cavin-4 recruits the signaling molecule ERK to caveolae, which activates key cardio-protective responses. Evaluation of ERK signaling revealed a profound inhibition, below physiological baseline, in the mdx5cv mouse heart. Expression of μDys in mdx5cv mice prevented the development of cardiac histopathology but did not rescue membrane localization of cavins nor did it normalize ERK signaling. Our study provides the first comparative analysis of purified protein complexes assembled in vivo by full-length dystrophin and a therapeutic micro-dystrophin construct. This has revealed disruptions in cavins and ERK signaling that may contribute to DMD cardiomyopathy. This new knowledge is important for ongoing efforts to prevent and treat heart disease in DMD patients.
Tail Base Deflection but not Tail Curvature Varies with Speed in Lizards: Results from an Automated Tracking Analysis Pipeline
Authors: Schultz Johanna T , Cieri Robert L , Proost Tasmin , Pilai Rishab , Hodgson Mitchell , Plum Fabian , Clemente Christofer J 
Published: April 2021

Abstract
Tail movement is an important component of vertebrate locomotion and likely contributes to dynamic stability during steady-state locomotion. Previous results suggest that the tail plays a significant role in lizard locomotion, but little data are available on tail motion during locomotion and how it differs with morphological, ecological, and phylogenetic parameters. We collected high-speed vertical climbing and horizontal locomotion video data from 43 lizard species from four taxonomic groups (Agamidae, Gekkota, Scincidae, and Varanidae) across four habitats. We introduce a new semi-automated and generalizable analysis pipeline for tail and spine motion analysis including markerless pose-estimation, semi-automated kinematic recognition, and muti-species data analysis. We found that step length relative to snout-vent length (SVL) increased with tail length relative to SVL. Examining spine cycles agnostic to limb stride phase, we found that ranges of inter-tail bending compared with inter-spine bending increased with relative tail length, while ranges of tail deflection relative to spine deflection increased with relative speed. Considering stepwise strides, we found the angular velocity and acceleration of the tail center of mass increased with relative speed. These results will provide general insights into the biomechanics of tails in sprawling locomotion enabling biomimetic applications in robotics, and a better understanding of vertebrate form and function. We look forward to adding more species, behaviors, and locomotor speeds to our analysis pipeline through collaboration with other research groups.
HIV, Placental Pathology, and Birth Outcomes—a Brief Overview
Authors: Bruce-Brand Cassandra , Wright Colleen A , Schubert Pawel T 
Published: April 2021

Abstract
The spectrum of placental pathology in human immunodeficiency virus (HIV) is vast. Features observed are not only limited to the effects of the virus itself but may include that of coinfections such as tuberculosis and syphilis. The presence of other comorbidities and changes as a result of antiretroviral therapy may further confound the histologic findings. There is a paucity of unbiased information of the effects of maternal HIV on the placenta and how these changes relate to birth outcomes. Antiretroviral therapy, now in widespread use, has altered the course of maternal HIV disease and it is unknown whether this has altered the pathophysiology of HIV on the placenta. HIV-associated placental findings that have been most well described include acute chorioamnionitis, low placental weight, and maternal vascular malperfusion, with a tendency towards lower rates of chronic villitis.
Improved time-delay lens modelling and H0 inference with transient sources
Authors: Ding Xuheng , Liao Kai , Birrer Simon , Shajib Anowar J , Treu Tommaso , Yang Lilan 
Published: April 2021

ABSTRACT
Strongly lensed explosive transients such as supernovae, gamma-ray bursts, fast radio bursts, and gravitational waves are very promising tools to determine the Hubble constant (H0) in the near future in addition to strongly lensed quasars. In this work, we show that the transient nature of the point source provides an advantage over quasars: The lensed host galaxy can be observed before or after the transient’s appearance. Therefore, the lens model can be derived from images free of contamination from bright point sources. We quantify this advantage by comparing the precision of a lens model obtained from the same lenses with and without point sources. Based on Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3) observations with the same sets of lensing parameters, we simulate realistic mock data sets of 48 quasar lensing systems (i.e. adding AGN in the galaxy centre) and 48 galaxy–galaxy lensing systems (assuming the transient source is not visible but the time delay and image positions have been or will be measured). We then model the images and compare the inferences of the lens model parameters and H0. We find that the precision of the lens models (in terms of the deflector mass slope) is better by a factor of 4.1 for the sample without lensed point sources, resulting in an increase of H0 precision by a factor of 2.9. The opportunity to observe the lens systems without the transient point sources provides an additional advantage for time-delay cosmography over lensed quasars. It facilitates the determination of higher signal-to-noise stellar kinematics of the main deflector, and thus its mass density profile, which, in turn plays a key role in breaking the mass-sheet degeneracy and constraining H0.
The influence of the spiral arm parameters on radial migration in late-type-like galaxies
Authors: Martínez-Bautista Gerardo , Velázquez Héctor , Pérez-Villegas Angeles , Moreno Edmundo 
Published: April 2021

ABSTRACT
We performed test-particle simulations of a spiral late-type-like galaxy to study the radial migration in a steady potential. Our model includes a bulge, a disc, a dark matter halo, and spiral arms represented by a cosine potential. We varied the structural and dynamical parameters of the spiral arms to study the influence of each configuration on the stellar orbits, such as the pitch angle, the radial scale length, and the pattern speed. We analysed the changes in the z component of the angular momentum (Lz), radius (R), and eccentricity of individual stars at different times. We found that the stellar orbits are affected by radial migration in all cases. Also, we found that the most relevant parameter to the radial migration phenomenon, in co-rotation, is the radial scale length of the spiral arms.
Parameter estimation of hairy Kerr black holes from its shadow and constraints from M87*
Authors: Afrin Misba , Kumar Rahul , Ghosh Sushant G 
Published: April 2021

ABSTRACT
The recently obtained hairy Kerr black holes, due to additional sources or surrounding fluid, like dark matter, with conserved energy-momentum tensor, have a deviation α and primary hair l0, apart from rotation parameter a and mass M. In the wake of the Event Horizon Telescope (EHT) observations of the supermassive black hole M87*, a recent surge in interest in black hole shadows suggests comparing the black holes in general relativity and modified theories of gravity to assess these models’ differences. Motivated by this, we take on an extensive study of the rotating hairy Kerr black holes, which encompasses, in particular cases, the Kerr black hole (α = 0). We investigate ergosphere and shadows of the black holes to infer that their size and shape are affected due to the l0 and are found to harbour a richer chaotic structure. In particular, the hairy Kerr black holes possess smaller size but more distorted shadows when compared with Kerr black holes. We also estimate the parameters l0 and a associated with hairy Kerr black holes using the shadow observables. The inferred circularity deviation ΔC ≤ 0.1 for the M87* black hole is satisfied, whereas shadow angular diameter θd = 42 ± 3μas, within 1σ region, for a given choice of α, places bounds on the parameters a and l0. Interestingly, the shadow axial ratio obeying 1 &lt; Dx ≲ 4/3 is in agreement with the EHT results and thus eventuates in the hairy Kerr black holes being suitable candidates for astrophysical black holes.
Virial shocks are suppressed in cosmic ray-dominated galaxy haloes
Authors: Ji Suoqing , Kereš Dušan , Chan T K , Stern Jonathan , Hummels Cameron B , Hopkins Philip F , Quataert Eliot , Faucher-Giguère Claude-André 
Published: April 2021

ABSTRACT
We study the impact of cosmic rays (CRs) on the structure of virial shocks, using a large suite of high-resolution cosmological FIRE-2 simulations accounting for CR injection by supernovae. In Milky Way-mass, low-redshift (z ≲ 1−2) haloes, which are expected to form ‘hot haloes’ with slowly cooling gas in quasi-hydrostatic equilibrium (with a stable virial shock), our simulations without CRs do exhibit clear virial shocks. The cooler phase condensing out from inflows becomes pressure confined to overdense clumps, embedded in low-density, volume-filling hot gas with volume-weighted cooling time longer than inflow time. The gas thus transitions sharply from cool free-falling inflow, to hot and thermal-pressure supported at approximately the virial radius (≈Rvir), and the shock is quasi-spherical. With CRs, we previously argued that haloes in this particular mass and redshift range build up CR-pressure-dominated gaseous haloes. Here, we show that when CR pressure dominates over thermal pressure, there is no significant virial shock. Instead, inflowing gas is gradually decelerated by the CR pressure gradient and the gas is relatively subsonic out to and even beyond Rvir. Rapid cooling also maintains subvirial temperatures in the inflowing gas within ∼Rvir.
NSrp70 is a lymphocyte-essential splicing factor that controls thymocyte development
Authors: Kim Chang-Hyun , Park Sang-Moo , Lee Sun-jae , Kim Young-Dae , Jang Se-Hwan , Woo Seon-Min , Kwon Taeg-Kyu , Park Zee-Yong , Chung Ik-Joo , Kim Hye-Ran , Jun Chang-Duk 
Published: April 2021

Abstract
Alternative pre-mRNA splicing is a critical step to generate multiple transcripts, thereby dramatically enlarging the proteomic diversity. Thus, a common feature of most alternative splicing factor knockout models is lethality. However, little is known about lineage-specific alternative splicing regulators in a physiological setting. Here, we report that NSrp70 is selectively expressed in developing thymocytes, highest at the double-positive (DP) stage. Global splicing and transcriptional profiling revealed that NSrp70 regulates the cell cycle and survival of thymocytes by controlling the alternative processing of various RNA splicing factors, including the oncogenic splicing factor SRSF1. A conditional-knockout of Nsrp1 (NSrp70-cKO) using CD4Cre developed severe defects in T cell maturation to single-positive thymocytes, due to insufficient T cell receptor (TCR) signaling and uncontrolled cell growth and death. Mice displayed severe peripheral lymphopenia and could not optimally control tumor growth. This study establishes a model to address the function of lymphoid-lineage-specific alternative splicing factor NSrp70 in a thymic T cell developmental pathway.
Twitter Surveillance at the Intersection of the Triangulum
Authors: Majmundar Anuja , Allem Jon-Patrick , Cruz Tess Boley , Unger Jennifer B , Pentz Mary Ann 
Published: April 2021

Abstract

Introduction
A holistic public health surveillance approach can help capture the public’s tobacco and marijuana-related attitudes and behaviors. Using publicly available data from Twitter, this is one of the first studies to describe key topics of discussions related to each intersection (e-cigarette, combustible tobacco, and marijuana) of the Triangulum framework.

Aims and Methods
Twitter posts (n = 999 447) containing marijuana, e-cigarette, and combustible tobacco terms were collected from January 1, 2018 to December 23, 2019. Posts to Twitter with co-occurring mentions of keywords associated with the Triangulum were defined as an intersection (e-cigarettes and combustible tobacco, combustible tobacco and marijuana, e-cigarettes and marijuana, and marijuana, e-cigarettes and combustible tobacco). Text classifiers and unsupervised machine learning were used to identify predominant topics in posts.

Results
Product Features and Cartridges were commonly referenced at the intersection of e-cigarette and marijuana-related conversations. Blunts and Cigars and Drugs and Alcohol were commonly referenced at the intersection of combustible tobacco and marijuana-related discussions. Flavors and Health Risks were discussed at the intersection of e-cigarette and combustible-related conversations, while discussions about Illicit products and Health risks were key topics of discussion when e-cigarettes, combustible tobacco, and marijuana were referenced all together in a single post.

Conclusion
By examining intersections of marijuana and tobacco products, this study offers inputs for designing comprehensive FDA regulations including regulating product features associated with appeal, improving enforcement to curb sales of illicit products, and informing the FDA’s product review and standards procedures for tobacco products that can be used with marijuana.

Implications
This study is the first to leverage the Triangulum framework and Twitter data to describe key topics of discussions at the intersection of e-cigarette, combustible tobacco, and marijuana. Real-time health communication interventions can identify Twitter users posting in the context of e-cigarettes, combustible tobacco, and marijuana by automated methods and deliver tailored messages. This study also demonstrates the utility of Twitter data for surveillance of complex and evolving health behaviors.
A Combined Microsurgical and Endovascular Approach to Giant Paraclinoid Aneurysm: 2-Dimensional Operative Video
Authors: Pojskić Mirza , Arnautović Kenan I , Ibn Essayed Walid , Al-Mefty Ossama 
Published: April 2021

Abstract
Giant paraclinoid aneurysm remains a treatment challenge because of their complex anatomy and surgical difficulties stems frequently from a calcified or atherosclerotic aneurysmal neck and compression of the optic pathways.1–9
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9
To improve exposure, facilitate the dissection of the aneurysm, assure vascular control, reduce brain retraction and temporary occlusion time, and enable simultaneous treatment of possible associated aneurysms, we combined the cranio-orbital zygomatic (COZ) approach
9
with endovascular balloon occlusion of the internal carotid artery (ICA) and suction decompression of the aneurysm.
4

The patient is a 50-yr-old female who presented with headache and hemianopsia. MRI, CT, and 4-vessel angiography revealed a giant right ophthalmic paraclinoid partially thrombosed aneurysm. Surgery was performed via right COZ approach with removal of the anterior clinoid. Unroofing the optic canal and opening the falciform ligament and the optic sheath, allowing the dissection and mobilization of the optic nerve from the aneurysm and the origin of ophthalmic artery. The endovascular team placed a deflated, double lumen balloon catheter in the ICA 2 cm above the common carotid bifurcation. Proximal control is achieved by inflating the balloon. Distal control is then gained by temporary clipping just proximal of the origin of PcomA.
4
Retrograde suction decompression through the catheter partially collapses and softens the aneurysm.
1

,

4

,
6–8
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8
Carotid occlusion was applied twice, 2:47 and 2:57 min. Intraoperative angiogram revealed the obliteration of the aneurysm and the patency of the carotid and ophthalmic artery. The patient recovered well, and visual deficit resolved and was neurologically intact. Patient consented for surgery.
Illustrations in video reprinted with minimal modification from Surgical Neurology, vol 50, issue 6, Arnautović KI, Al-Mefty O, Angtuaco E, A combined microsurgical skull-base and endovascular approach to giant and large paraclinoid aneuroysms, 504–518,
4
Copyright 1998, with permission from Elsevier Science Inc.
Putting Our Shoulder to the Wheel: Current Understanding and Gaps in Nerve Ablation for Chronic Shoulder Pain
Authors: Eckmann Maxim S , McCormick Zachary L , Beal Colby , Julia Jonathan , Cheney Cole W , Nagpal Ameet S 
Published: April 2021

Abstract
Shoulder pain is prevalent, burdensome, and functionally limiting, with diverse pathology and associated treatments. This narrative review provides a summary of relevant neuroanatomy, proposed ablation targets, safety and efficacy concerns for ablation targets, and current research gaps. Radiofrequency ablation (RFA) of peripheral sensory nerves is a well-established treatment for chronic joint and spine pain, but it is relatively nascent for shoulder pain. Cadaveric studies demonstrate the shoulder joint is innervated by articular branches of the suprascapular nerve, axillary nerve, lateral pectoral nerve, and upper and lower subscapular nerves. Shoulder articular branch RFA appears to be a safe and effective treatment for chronic shoulder pain, but there are currently no widely accepted protocols for ablation targets. There are also no randomized controlled trials (RCT) assessing safety and efficacy of proposed targets or the prognostic value of articular blocks. Future research studies should prioritize categorical data, use appropriate functional measures as primary endpoints, and would ideally include a large-scale RCT.
ICD-10 Coding of Musculoskeletal Conditions in the Veterans Health Administration
Authors: Coleman Brian C , Goulet Joseph L , Higgins Diana M , Bathulapalli Harini , Kawecki Todd , Ruser Christopher B , Bastian Lori A , Martino Steve , Piette John D , Edmond Sara N , Heapy Alicia A 
Published: April 2021

Abstract

Objective
We describe the most frequently used musculoskeletal diagnoses in Veterans Health Administration care. We report the number of visits and patients associated with common musculoskeletal International Classification of Diseases (ICD)-10 codes and compare trends across primary and specialty care settings.

Design
Secondary analysis of a longitudinal cohort study.

Subjects
Veterans included in the Musculoskeletal Diagnosis Cohort with a musculoskeletal diagnosis from October 1, 2015, through September 30, 2017.

Methods
We obtained counts and proportions of all musculoskeletal diagnosis codes used and the number of unique patients with each musculoskeletal diagnosis. Diagnosis use was compared between primary and specialty care settings.

Results
Of more than 6,400 possible ICD-10 M-codes describing “Diseases of the Musculoskeletal System and Connective Tissue,” 5,723 codes were used at least once. The most frequently used ICD-10 M-code was “Low Back Pain” (18.3%), followed by “Cervicalgia” (3.6%). Collectively, the 100 most frequently used codes accounted for 80% of M-coded visit diagnoses, and 95% of patients had at least one of these diagnoses. The most common diagnoses (spinal pain, joint pain, osteoarthritis) were used similarly in primary and specialty care settings.

Conclusion
A diverse sample of all available musculoskeletal diagnosis codes were used; however, less than 2% of all possible codes accounted for 80% of the diagnoses used. This trend was consistent across primary and specialty care settings. The most frequently used diagnosis codes describe the types of musculoskeletal conditions, among a large pool of potential diagnoses, that prompt veterans to present to the Veterans Health Administration for musculoskeletal care.