bluuebunny/crossref_metadata_2025 huggingface dataset:
How stars formed in warps settle into (and contaminate) thick discs
Authors: Khachaturyants Tigran , Beraldo e Silva Leandro , Debattista Victor P
Published: September 2021

In recent years star formation has been discovered in the Milky Way’s warp. These stars formed in the warp (warp stars) must eventually settle into the plane of the disc. We use an N-body+smooth particle hydrodynamics model of a warped galaxy to study how warp stars settle into the disc. By following warp stars in angular momentum space, we show that they first tilt to partially align with the main disc in a time-scale of ${\sim} 1\mbox{$\, {\rm Gyr}$}$. Then, once differential precession halts this process, they phase mix into an axisymmetric distribution on a time-scale of ${\sim} 6 \mbox{$\, {\rm Gyr}$}$. The warp stars end up contaminating the geometric thick disc. Because the warp in our fiducial simulation is growing, the warp stars settle to a distribution with a negative vertical age gradient as younger stars settle further from the mid-plane. While vertically extended, warp star orbits are still nearly circular and they are therefore subject to radial migration, with a net movement inwards. As a result warp stars can be found throughout the disc. The density distribution of a given population of warp stars evolves from a torus to an increasingly centrally filled-in density distribution. Therefore we argue that, in the Milky Way, warp stars should be found in the Solar Neighbourhood. Moreover, settled warp stars may constitute part of the young flaring population seen in the Milky Way’s outskirts.
Measuring sloshing, merging, and feedback velocities in the Virgo cluster
Authors: Gatuzz Efrain , Sanders J S , Dennerl K , Pinto C , Fabian A C , Tamura T , Walker S A , ZuHone J
Published: September 2021

We present a detailed analysis of the velocity structure of the Virgo cluster using XMM–Newton observations. Using a novel technique which uses the Cu K α instrumental line to calibrate the EPIC-pn energy scale, we are able to obtain velocity measurements with uncertainties down to Δv ∼ 100 km s−1. We created 2D projected maps for the velocity, temperature, metallicity, density, pressure, and entropy with an spatial resolution of 0.25 arcmin. We have found that in the innermost gas there is a high velocity structure, most likely indicating the presence of an outflow from the AGN while our analysis of the cluster cool core using RGS data indicates that the velocity of the gas agrees with the M87 optical redshift. An overall gradient in the velocity is seen, with larger values as we move away from the cluster core. The hot gas located within the western radio flow is redshifted, moving with a velocity ∼331 km s−1 while the hot gas located within the eastern radio flow is blueshifted, with a velocity ∼258 km s−1, suggesting the presence of backflows. Our results reveal the effects of both AGN outflows and gas sloshing, in the complex velocity field of the Virgo cluster.
An accurate comprehensive approach to substructure – I. Accreted subhaloes
Authors: Salvador-Solé Eduard , Manrique Alberto , Botella Ignacio
Published: September 2021

This is the first of a series of three papers devoted to the study of halo substructure in hierarchical cosmologies by means of the CUSP formalism. In the present paper, we derive the properties of subhaloes and diffuse dark matter (dDM) accreted on to haloes and their progenitors. Specifically, we relate the dDM present at any time in the inter-halo medium of the real Universe or a cosmological simulation with the corresponding free-streaming mass or the halo resolution mass, respectively, and establish the link between subhaloes and their seeds in the initial density field. By monitoring the collapse and virialization of haloes, we derive from first principles and with no single free parameter the abundance and radial distribution of dDM and subhaloes accreted on to them. Our predictions are in excellent agreement with the results of simulations, but for the predicted fraction of accreted dDM, which is larger than reported in previous works as they only count the dDM accreted on to the final halo, not on to its progenitors. The derivation pursued here clarifies the origin of some key features of substructure. Overall, our results demonstrate that CUSP is a powerful tool for understanding halo substructure and extending the results of simulations to haloes with arbitrary masses, redshifts, and formation times in any hierarchical cosmology endowed with random Gaussian density perturbations.
Cockayne syndrome group A and ferrochelatase finely tune ribosomal gene transcription and its response to UV irradiation
Authors: Lanzafame Manuela , Branca Giulia , Landi Claudia , Qiang Mingyue , Vaz Bruno , Nardo Tiziana , Ferri Debora , Mura Manuela , Iben Sebastian , Stefanini Miria , Peverali Fiorenzo A , Bini Luca , Orioli Donata
Published: September 2021

CSA and CSB proteins are key players in transcription-coupled nucleotide excision repair (TC-NER) pathway that removes UV-induced DNA lesions from the transcribed strands of expressed genes. Additionally, CS proteins play relevant but still elusive roles in other cellular pathways whose alteration may explain neurodegeneration and progeroid features in Cockayne syndrome (CS). Here we identify a CS-containing chromatin-associated protein complex that modulates rRNA transcription. Besides RNA polymerase I (RNAP1) and specific ribosomal proteins (RPs), the complex includes ferrochelatase (FECH), a well-known mitochondrial enzyme whose deficiency causes erythropoietic protoporphyria (EPP). Impairment of either CSA or FECH functionality leads to reduced RNAP1 occupancy on rDNA promoter that is associated to reduced 47S pre-rRNA transcription. In addition, reduced FECH expression leads to an abnormal accumulation of 18S rRNA that in primary dermal fibroblasts from CS and EPP patients results in opposed rRNA amounts. After cell irradiation with UV light, CSA triggers the dissociation of the CSA–FECH–CSB–RNAP1–RPs complex from the chromatin while it stabilizes its binding to FECH. Besides disclosing a function for FECH within nucleoli, this study sheds light on the still unknown mechanisms through which CSA modulates rRNA transcription.
huARdb: human Antigen Receptor database for interactive clonotype-transcriptome analysis at the single-cell level
Authors: Wu Lize , Xue Ziwei , Jin Siqian , Zhang Jinchun , Guo Yixin , Bai Yadan , Jin Xuexiao , Wang Chaochen , Wang Lie , Liu Zuozhu , Wang James Q , Lu Linrong , Liu Wanlu
Published: September 2021

T-cell receptors (TCRs) and B-cell receptors (BCRs) are critical in recognizing antigens and activating the adaptive immune response. Stochastic V(D)J recombination generates massive TCR/BCR repertoire diversity. Single-cell immune profiling with transcriptome analysis allows the high-throughput study of individual TCR/BCR clonotypes and functions under both normal and pathological settings. However, a comprehensive database linking these data is not yet readily available. Here, we present the human Antigen Receptor database (huARdb), a large-scale human single-cell immune profiling database that contains 444 794 high confidence T or B cells (hcT/B cells) with full-length TCR/BCR sequence and transcriptomes from 215 datasets. All datasets were processed in a uniform workflow, including sequence alignment, cell subtype prediction, unsupervised cell clustering, and clonotype definition. We also developed a multi-functional and user-friendly web interface that provides interactive visualization modules for biologists to analyze the transcriptome and TCR/BCR features at the single-cell level. HuARdb is freely available at https://huarc.net/database with functions for data querying, browsing, downloading, and depositing. In conclusion, huARdb is a comprehensive and multi-perspective atlas for human antigen receptors.
“Craniotomy Within Craniotomy” Technique for Safe Resection of an Intracranial Arteriovenous Malformation With Frontal Bony Erosion: 2-Dimensional Operative Video
Authors: Khorasanizadeh MirHojjat , Ravina Kristine , Filippidis Aristotelis , Ogilvy Christopher S
Published: September 2021

Surgical resection is one option in the treatment of large high-grade brain arteriovenous malformations (AVMs). Resection of AVMs with skull-eroding components can be challenging due to the risk of excessive bleeding from these components during craniotomy and bone flap removal. We present a case of a 25-yr-old woman who presented with an acute onset right-sided frontal headache. She was found to have a large, frontal Spetzler-Martin grade IV AVM with an associated dural AVM. The AVM had caused focal erosions of the right frontal bone by a venous varix traversing the region of the calvarial defect. An elective staged endovascular embolization followed by surgical resection was recommended considering the patient's young age and the large size of the AVM located in a noneloquent area. Given the high risk of intraoperative hemorrhage during the craniotomy portion of the procedure, a “craniotomy within craniotomy” approach was planned. During this approach, a small rectangle of bone, including the portion eroded by the venous varix, was left in place, while the larger bone flap surrounding it was removed for an initial approach to the AVM. The small bony piece was safely removed at later stages of resection once the arterial feeders had been reasonably obliterated. Immediate postoperative catheter angiogram demonstrated good filling of the intracranial vascular territories with no residual AVM. The patient developed mild left facial and left hand weakness postoperatively, which resolved after 2 wk of follow-up. The patient remained neurologically intact on further follow-up.
Technique for Treatment of a Symptomatic Intracranial Stenosis With Balloon Angioplasty and Wingspan Stent Placement: 3-Dimensional Operative Video
Authors: Cotton Patrick C , Kan Peter
Published: September 2021

Intracranial angioplasty and stenting is an increasingly common modality to treat intracranial atherosclerosis, which accounts for 80 000 strokes annually. Early trials showed there to be a high complication rate
1,2
associated with stenting but with improved technique this complication rate has dramatically decreased.
3
The following video details the procedure of intracranial balloon angioplasty and stenting for a high-grade stenosis of the right internal carotid artery. The risks and benefits of the procedure were discussed with the patient and they consented to the procedure.
Clipping of Multiple Cerebral Aneurysms Through Cranioorbital Zygomatic Approach: 2-Dimensional Operative Video
Authors: Almefty Rami O , Ibn Essayed Walid , Al-Mefty Ossama
Published: September 2021

Ruptured cerebral aneurysm is a grave disease, with a high morbidity and mortality, mandating securing the aneurysm to eliminate fatal rebleeding.
1
Multiple aneurysms are frequent and may occur in approximately 20% of the cases with female prominence.
2
The risk of subarachnoid hemorrhage in unruptured aneurysms is higher in patients who had prior ruptured aneurysms.
3
Hence, there is an indication of treating all concomitant aneurysms when one is ruptured. We present the case of clipping of 3 aneurysms via a cranioobritozygomatic (COZ) approach including a middle cerebral artery, anterior choroidal artery, and superior cerebellar artery in a patient presenting with subarachnoid hemorrhage and multiple aneurysms with suboptimal morphology for endovascular coiling. We highlight the advantages of the COZ in the clipping of complex posterior circulation aneurysms and the advantage of mobilization of neural structures to gain wider exposure.
4-6
The temporal fossa space provided by zygomatic osteotomy allows the outward mobilization of the temporal lobe after freeing it by splitting the Sylvian fissure. The falciform ligament is opened overlying the optic nerve, allowing for safe dissection within the opticocarotid window. The oculomotor nerve is detethered from the dura surrounding its entry into the cavernous sinus. These maneuvers allow for mobilization of the critical neurovascular structures, which widens the operative corridor without undue traction or retraction. The COZ with clinoidectomy shortens and widens the operative field, allows for enhanced maneuverability, improved visualization, and exposure of the clinoidal carotid, and facilitates the release and mobilization of the optic and third nerve. The patient consented to surgery.

 Image at 1:40 reprinted with permission from Al-Mefty O, Operative Atlas of Meningiomas. Vol 1, © LWW, 1998.
Giant Ossified Clival Chondrosarcoma Resection: 2-Dimensional Operative Video
Authors: Ibn Essayed Walid , Al-Mefty Ossama
Published: September 2021

Chondrosarcomas are a spectrum of tumors with variable clinical behavior, histologically classified as grades I, II, and III.
1
Maximal surgical resection with adjuvant radiation is the gold standard for grade III malignant tumors.
2,3
Lower-grade skull base chondrosarcomas have a slow progressive local growth pattern with an overall benign profile.
1,4
In these grade I and II tumors, radical resection can be sufficient in achieving long-term control of the disease without the need for adjuvant therapy, thus avoiding the long-term side effects of irradiation in relatively young patients.
4,5
As a slow-growing tumor, skull base chondrosarcoma might reach a giant size with progressive neurological deficits prior to diagnosis. In these cases, to achieve maximal resection, skull base approaches tailored to the patient's anatomy are essential.
4,6
Cranial approach is frequently needed due to the calcified nature of part of the tumor that is not amenable to resection through the endonasal approach. The endoscope is extremely helpful combined with the microscopic resection. We demonstrate these techniques through in the surgery of a 39-yr-old female who presented with progressive neurological deficits from a giant ossified chondrosarcoma and underwent a combined petrosal approach for the resection of her tumor. A postoperative small enhancement remained stable on the 4-yr follow-up exam. The pathology confirmed grade II chondrosarcoma, with the patient recovering from her neurological deficit except the third nerve. The patient consented to the surgery and publication of images.

 Image at 1:36 reprinted with permission from Al-Mefty O, Operative Atlas of Meningiomas. Vol 1, ©LWW, 1998.
Neural rhythmic underpinnings of intergroup bias: implications for peace-building attitudes and dialogue
Authors: Levy Jonathan , Goldstein Abraham , Influs Moran , Masalha Shafiq , Feldman Ruth
Published: September 2021

Intergroup bias is a ubiquitous socio-cognitive phenomenon that, while sustaining human dependence on group living, often leads to prejudice, inequity, and violence; yet, its neural underpinnings remain unclear. Framed within the Israeli–Palestinian conflict and targeting youth, this study utilized magnetoencephalography to describe intrinsic neural oscillatory processes that represent the intergroup bias and may link with engagement in peacemaking in order to shed further light on the neural mechanisms underpinning intergroup conflict. Across the oscillatory spectrum, from very low to very high frequency bands, the only rhythm found to underlie the intergroup bias was the alpha rhythm. Alpha rhythm was continuously activated across the task and integrated a rapid perceptual component in the occipital cortex with a top-down cognitive-control component in the medial cingulate cortex. These components were distinctly associated with the real-life intergroup dialogue style and expressed attitudes that promote active engagement in peacemaking. Our findings suggest that the cortical alpha rhythm plays a crucial role in sustaining intergroup bias and addresses its impact on concrete intergroup experiences. The results highlight the need to provide opportunities for active peace-building dialogue to youth reared amidst intractable conflicts.
CE: Hypertensive Emergencies: A Review
Authors: Mathews Essie P. , Newton Faith , Sharma Kartavya
Published: September 2021

While acute blood pressure elevations are commonly seen in the ED, not all require emergency treatment. True hypertensive emergencies are characterized by a rapid elevation in blood pressure to a level above 180/120 mmHg and are associated with acute target organ damage, which requires immediate hospitalization for close hemodynamic monitoring and IV pharmacotherapy. Recognizing the clinical signs and symptoms of hypertensive emergency, which may vary widely depending on the target organ involved, is critical. High blood pressure levels that produce no signs or symptoms of target organ damage may be treated without hospitalization through an increase in or reestablishment of previously prescribed oral antihypertensive medication. However, all patients presenting with blood pressure this high should undergo evaluation to confirm or rule out impending target organ damage, which differentiates hypertensive emergency from other hypertensive crises and is vital in facilitating appropriate emergency treatment. Drug therapy for hypertensive emergency is influenced by end-organ involvement, pharmacokinetics, potential adverse drug effects, and patient comorbidities. Frequent nursing intervention and close monitoring are crucial to recuperation. Here, the authors define the spectrum of uncontrolled hypertension; discuss the importance of distinguishing hypertensive emergencies from hypertensive urgencies; and describe the pathophysiology, clinical manifestations, and management of hypertensive emergencies.
A Low-threshold Comprehensive Shared Medical Appointment Program for Perinatal Substance Use in an Underserved Population
Authors: Ganetsky Valerie S. , Heil Jessica , Yates Brianna , Jones Iris , Hunter Krystal , Rivera Brandon , Wilson Lindsay , Salzman Matthew , Baston Kaitlan E.
Published: September 2021

Objectives

We describe retention in care, medication for opioid use disorder (MOUD) prescribing, and urine toxicology outcomes of a comprehensive perinatal shared medical appointment model that combined medication, group-based counseling, and recovery supports.

Methods

We conducted a retrospective study of program retention between 11/1/16 and 3/31/20 in pregnant and postpartum women with substance dependence or use disorder. Disengagement reasons, MOUD prescribing, and urine toxicology were abstracted from medical records. A Cox proportional hazards model was used to evaluate risk factors for program disengagement.

Results

Approximately 87% of patients had OUD and 80% were pregnant at the initial visit (N = 140). Retention at 3 months, 6 months, 1 year, and 2 years was approximately 86%, 78%, 66%, and 48%, respectively. Over 97% of patients were prescribed MOUD and 88% of all urine toxicology results were negative for non-prescribed opioids. Patients enrolled after initiation of wraparound services (HR 0.52, 95% CI 0.28 – 0.96) and those attending more shared medical appointments (HR 0.90, 95% CI 0.87 – 0.93) had a lower hazard of disengagement after controlling for other covariates. Loss to follow-up was the most common disengagement reason.

Conclusions

A low-threshold, comprehensive perinatal shared medical appointment program had high retention rates, increased access to evidence-based MOUD, and high rates of opioid-negative urine toxicology. Participants enrolled after wraparound services began had a lower hazard of disengagement. Future research in perinatal substance use should evaluate the most optimal and cost-effective components of comprehensive programs to inform standard of care.
Subtrochanteric Femur Fractures Treated With Femoral Nail: The Effect of Cerclage Wire Augmentation on Complications, Fracture Union, and Reduction: A Systematic Review and Meta-Analysis of Comparative Studies
Authors: Hoskins Wayne , McDonald Laura , Spelman Tim , Bingham Roger
Published: September 2021

Objective:

To perform a systematic review and meta-analysis of subtrochanteric femur fractures treated with an intramedullary nail, augmented with or without cerclage wiring, comparing the risk of reoperation, nonunion, loss of fixation, and implant failure; fracture reduction and time to union.

Data Source:

A systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed through MEDLINE, EMBASE, PubMed, Web of Science, and Scopus databases using a combination of controlled vocabulary and keywords on September 30, 2020.

Study Selection:

All comparative (prospective and retrospective) studies of subtrochanteric fractures managed with intramedullary nail, that compared the addition of cerclage wire to without in patients 16 years of age or older were included. Pathological, atypical bisphosphonate, and segmental fractures were excluded, as were non-English literature.

Data Extraction:

Data from each study were independently recorded by 2 investigators.

Data Synthesis:

Agreement was obtained on 18 studies (all retrospective) for final inclusion, with 378 patients receiving cerclage wire and 911 without. A random-effects meta-analysis was used to analyze the pooled aggregate data.

Conclusions:

There is no statistically significant advantage in using cerclage wire with femoral intramedullary nail when treating subtrochanteric femur fractures regarding risk of reoperation, nonunion, loss of fixation, and implant failure or time to union. An advantage favoring cerclage wire was seen for accuracy of fracture reduction. Cerclage wiring was used more often in cases associated with high-energy trauma. Given the relatively small number of events available to be modelled, a clinical benefit for cerclage wiring may still exist for certain fracture types.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Applied Anatomy of the Quadriceps Tendon Related to the Technique of Harvesting the Quadriceps Tendon Graft
Authors: Thi Cao , Ha Nguyen Dang Phu
Published: September 2021

Introduction:

The quadriceps tendon (QT) is a common autologous graft for anterior cruciate ligament reconstruction. However, the best way to harvest it is still undefined. This study aims to determine the QT’s anatomical structures as a graft for anterior cruciate ligament reconstruction and the ideal harvest site.

Methods:

Thirty fresh frozen knees from 15 cadavers were dissected, and the QT was analyzed. The length, depth, and width of the QT were measured in a standardized manner for each cadaver.

Results:

The QT superficial morphology showed 2 distinct peaks, with the maximum length correlating with the real lateral peak. The full length of the tendon was located at 64.3%±5.4% of the width from the medial border of the insertion. The maximum length of the QT was 79.4±4.5 mm. The mean width at its insertion onto the patella was 36.0±4.3 mm. The thickness at its maximum length on patella insertion was 7.2±0.4 mm. The mean diameter of the QT graft was 8.5±0.5 mm, with a mean cross-sectional area of 64.7±4.1 mm2.

Conclusion:

QT graft harvest should begin by locating the apex (maximum length) of the tendon (64.3% of the distance from the patella’s medial edge). The surgeon should then harvest a 10 mm wide graft medially to the maximum length, harvesting 70 mm long and full-thickness tendon.
A review of research progress on mechanisms and overcoming strategies of acquired osimertinib resistance
Authors: Qu Fanjie , Zhou Yi , Yu Weiwei
Published: September 2021

Targeted therapy with epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) is the standard first-line treatment for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Third-generation EGFR-TKIs, represented by osimertinib, have been approved to overcome the EGFR T790M mutation in patients who are resistant to first- or second-generation TKIs, which brings more survival benefits for patients with advanced NSCLC. However, resistance to the third generation of EGFR-TKIs is still inevitable. Acquired drug resistance is the main reason for limiting the long-term effectiveness of targeted therapy in EGFR-mutated NSCLC patients. The mechanism of EGFR-TKI resistance of the third generation has become a focus of research in the field of targeted therapy. In this review, we summarize the research progress in resistance mechanisms of advanced NSCLC to osimertinib and the potential overcoming strategies and hope to provide a clinical basis and ideas for precision treatment of NSCLC.
Perspectives of Canadian Rural Consultant Pediatricians on Diagnosing Autism Spectrum Disorder: A Qualitative Study
Authors: Das Jennifer , Hartman Laura , King Gillian , Jones-Stokreef Nicola , Moore Hepburn Charlotte , Penner Melanie
Published: September 2021

Background:

Consultant pediatricians represent a potential resource for increasing autism spectrum disorder (ASD) diagnostic capacity; however, little is known about how they perceive their roles in ASD diagnosis.

Objective:

The objective of this study was to examine the perspectives of rural consultant pediatricians regarding their perceived roles, facilitators, and barriers in ASD diagnosis.

Methods:

We performed a qualitative study using thematic analysis. Consultant pediatricians from 3 small-sized and medium-sized Ontario communities were recruited. Semistructured interviews were conducted, transcribed, coded, and analyzed.

Results:

Fourteen pediatricians participated in this study. Participants all considered ASD diagnosis to be in their scope of practice. The major theme identified was the process of diagnosing ASD, which occurred in 3 stages: preassessment (gathering information before the first clinic visit), diagnosis, and service access. All these stages are influenced by ecological factors consisting of characteristics of the child, family, individual physician, pediatric group practice, and the broader system of ASD care.

Conclusion:

Consultant pediatricians practicing in nonurban Ontario communities see ASD diagnosis as part of their scope of practice and collaboratively work within groups to address the needs of their communities. Strategies aimed at increasing diagnostic capacity should target salaried group practices and improve the efficiency of assessments through preclinic information gathering.
Developmental and Behavioral Problems of Preschool-Age Children with Chronic Rheumatic Diseases
Authors: Çelen Yoldaş Tuba , Özdel Semanur , Karakaya Jale , Bülbül Mehmet
Published: September 2021

Objective:

Juvenile idiopathic arthritis (JIA) is the most common autoimmune and familial Mediterranean fever (FMF) the most common autoinflammatory chronic rheumatic disease in childhood. We aimed first to identify developmental and behavioral problems of preschool-age children with common chronic rheumatic diseases, second to compare the diagnostic categories, and third to elucidate the associated factors with these difficulties.

Method:

Of the 91 participants included in this study, 46 were children with rheumatic diseases (27 with JIA and 19 with FMF) and 45 were healthy children. The general developmental and emotional/behavioral problems of each child were evaluated by the Ages and Stages Questionnaire and Child Behavior Checklist-1½-5, respectively. The State-Trait Anxiety Inventory and Beck Depression Inventory were used for maternal well-being.

Results:

Internalizing problem scores were increased, and the percentage of children who failed at least 1 developmental domain and experienced delays in fine motor and problem-solving domains were higher in children with chronic rheumatic diseases when compared with healthy children. Being in the group of rheumatic diseases, fewer maternal education years and higher screen time were found to be independent risk factors significantly associated with any developmental delay in the multivariable model. Maternal trait anxiety scores were positively associated with internalizing and total problems only in FMF.

Conclusion:

Preschool-age children with a diagnosis of chronic rheumatic diseases were more vulnerable for developmental and behavioral problems compared with healthy children. The management of chronic rheumatic diseases in the early years should include the screening of developmental and behavioral problems.
Mesenchymal Stem Cell Therapy for Osteogenesis Imperfecta
Authors: Götherström Cecilia , David Anna L. , Walther-Jallow Lilian , Åström Eva , Westgren Magnus
Published: September 2021

The aim of this study was to provide a brief overview on the background and rationale on treating fetuses and children suffering from osteogenesis imperfecta (OI) with mesenchymal stem cells (MSCs). MSCs ability to migrate, engraft, and differentiate into bone cells and to act via paracrine effects on the recipient’s tissues makes these cells promising candidates as a clinical therapy for OI. Animal work and limited clinical studies in humans support the use of MSC in treating OI. Off-the-shelf MSC have a good safety profile and exhibit multilineage differentiation potential and a low immunogenic profile and thereby may enable this potential therapy to become widely available. MSC transplantation before and after birth to treat OI is an experimental therapy that is currently tested in the international multicentre phase I/II clinical trial BOOSTB4 that aims to assess the safety and efficacy of fetal MSC transplantation for the treatment of severe types of OI.
Joint Environmental Radiation Survey by JAEA and KAERI Around the Fukushima Daiichi Nuclear Power Plant: Performance of Mobile Gamma-Ray Spectrometry Using Backpack and Carborne Survey Platforms
Authors: Ji Young-Yong , Ochi Kotaro , Hong Sang Bum , Nakama Shigeo , Sanada Yukihisa , Mikami Satoshi
Published: September 2021

According to the implementing arrangement between the Japan Atomic Energy Agency (JAEA) and the Korea Atomic Energy Research Institute (KAERI) in the field of radiation protection and environmental radiation monitoring, a joint survey program was performed to assess ground deposition of radioactive cesium in areas surrounding the Fukushima Daiichi Nuclear Power Plants. The purpose of this joint survey was to evaluate the field applications of the developed survey systems and methodologies. Understanding the performance of each system within a cesium-deposited contaminated zone is important for ensuring an appropriate response following a nuclear accident. The results of the measured ambient dose rates determined using each survey method were compared. Two kinds of survey system were used in the mobile gamma-ray spectrometry, which were MARK-M1 (Monitoring of Ambient Radiation of KAERI—the 1st Multipurpose system) based on two LaBr3(Ce) detectors of KAERI and KURAMA-II (Kyoto University Radiation Mapping - II) system with one CsI(Tl) detector of JAEA. First, mobile gamma-ray spectrometry using a backpack survey platform was conducted to assess the distribution of dose rates around specific survey sites, which were expected to be slightly contaminated by radioactive cesium in Minamisoma and Tomioka. A carborne survey using two gamma-ray spectrometers loaded inside a vehicle was successfully conducted to compare the measured dose rates in routes from site to site and verify evaluation methods, including attenuation correction.
MULTISCALE CORRELATION OF MICROVASCULAR CHANGES ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY WITH RETINAL SENSITIVITY IN DIABETIC RETINOPATHY
Authors: Levine Emily S. , Moult Eric M. , Greig Eugenia Custo , Zhao Yi , Pramil Varsha , Gendelman Isaac , Alibhai Agha Y. , Baumal Caroline R. , Witkin Andre J. , Duker Jay S. , Fujimoto James G. , Waheed Nadia K.
Published: September 2021

Purpose:

To assess global, zonal, and local correlations between vessel density changes measured by optical coherence tomography angiography and retinal sensitivity measured by microperimetry across diabetic retinopathy severity.

Methods:

Diabetic patients and nondiabetic controls underwent optical coherence tomography angiography imaging and microperimetry testing. Pearson's correlation was used to assess associations between average sensitivity and skeletonized vessel density (SVD) or foveal avascular zone area centrally. Linear mixed effects modeling was used to assess relationships between local SVD measurements and their spatially corresponding retinal sensitivity measurements.

Results:

Thirty-nine eyes from 39 participants were imaged. In all slabs, there was a statistically significant positive correlation between retinal sensitivities and SVDs on both global and zonal scales. No statistically significant correlation was found between central retinal sensitivities and the foveal avascular zone areas. Assessment of 1,136 spatially paired retinal sensitivity and SVD measurements revealed a statistically significant local relationship; this seemed to be driven by eyes with proliferative diabetic retinopathy that had reduced retinal sensitivities.

Conclusion:

This study supports positive correlations between SVD and retinal sensitivity at global and zonal spatial scales in diabetic eyes. However, our analysis did not find evidence of statistically significant correlations between retinal sensitivity and SVD on a local scale until advanced diabetic retinopathy.
EN-FACE IMAGING OF ATYPICAL EPIRETINAL TISSUE IN LAMELLAR MACULAR HOLE
Authors: Eun Jun Soo , Choi Young Joo , Kang Se Woong , Choi Kyung Jun , Kim Sang Jin , Roh Hyeon Cheol
Published: September 2021

Purpose:

To elucidate the significance of en-face optical coherence tomography imaging of atypical epiretinal tissue (AET) in the lamellar macular hole (LMH).

Methods:

This study involved 29 eyes of 29 patients who underwent surgical treatment for LMH with AET. Best-corrected visual acuity, metamorphopsia assessment (M-score), and optical coherence tomography were evaluated before and 6 months after surgery. The novel en-face optical coherence tomography parameters, such as the area of AET and hyperreflective fringe, were correlated with clinical factors before and after LMH surgery.

Results:

Preoperatively, hyperreflective fringe was noted in 25 (86.2%) patients. The splitting of the inner retina, disruption of the ellipsoid zone, the extent of foveal cavitation, symptom duration, and change in best-corrected visual acuity were correlated with the area of AET (all P < 0.05). Multivariate regression analysis revealed that a larger area of AET was associated with longer symptom duration and less improvement in postoperative vision (all P < 0.05).

Conclusion:

The area of AET may represent the chronicity of LMH and is significantly associated with visual outcomes after LMH surgery. This novel en-face optical coherence tomography parameter can be used as a predictive factor for surgical outcomes in LMH with AET.
Neural and behavioral correlates of human pain avoidance in participants with and without episodic migraine
Authors: Gandhi Wiebke , de Vos Cecile C. , Becker Susanne , Hoge Richard D. , Hoeppli Marie-Eve , Schweinhardt Petra
Published: September 2021

The innate motivation to avoid pain can be disrupted when individuals experience uncontrollable stress, such as pain. This can lead to maladaptive behaviors, including passivity, and negative affect. Despite its importance, motivational aspects of pain avoidance are understudied in humans and their neural mechanisms vastly unknown. Rodent models suggest an important role of the periaqueductal gray, but it is unknown whether it subserves a similar role in humans. Furthermore, it is unclear whether pain avoidance is associated with individual differences in pain coping. Using functional magnetic resonance imaging, networks underlying pain avoidance behavior were examined in 32 participants with and without episodic migraine. Pain avoidance behavior was assessed using an adaptation of the incentive delay task. In each trial of the task, participants tried to avoid a painful stimulus and receive a nonpainful one instead while the difficulty to succeed varied across trials (3 difficulty levels: safe, easy, and difficult). After unsuccessful pain avoidance on the preceding trial, participants showed reduced pain avoidance behavior, especially in the difficult condition. This reduction in behavior was associated with higher helplessness scores only in participants with migraine. Higher helplessness in participants with migraine was further correlated with a stronger decrease in activation of cortical areas associated with motor behavior, attention, and memory after unsuccessful pain avoidance. Of these areas, specifically posterior parietal cortex activation predicted individual's pain avoidance behavior on the next trial. The results link individual pain coping capacity to patterns of neural activation associated with altered pain avoidance in patients with migraine.
Long-term Hearing Preservation and Speech Perception Performance Outcomes With the Slim Modiolar Electrode
Authors: Shew Matthew A. , Walia Amit , Durakovic Nedim , Valenzuela Carla , Wick Cameron C. , McJunkin Jonathan L. , Buchman Craig A. , Herzog Jacques A.
Published: September 2021

Objective:

Describe audiologic outcomes in hearing preservation (HP) cochlear implant candidates using a slim modiolar electrode (SME).

Study Design:

Retrospective.

Setting:

Tertiary referral center.

Patients:

Two hundred three adult cochlear implant patients with preoperative low-frequency pure-tone average (LFPTA) ≤ 80 dB HL that received the SME.

Intervention:

Implantation with a SME electrode.

Main Outcome Measures:

Primary outcome was postoperative HP, defined as LFPTA ≤80 dB HL. HP status was analyzed at “early” (activation or 3 mo) and “long-term” (6 or 12 mo) time frames using the patient's worst audiogram. Speech perception tests were compared between HP and non-HP cohorts.

Results:

Of the 203 HP candidates, the tip fold-over rate was 7.4%. The mean shifts in LFPTA at the “early” and “long-term” time points were 25.9 ± 16.2 dB HL and 29.6 ± 16.9 dB HL, respectively. Of 117 patients with preoperative LFPTA ≤60 dB HL, the early and long-term mean LFPTA shifts were 19.5 ± 12.3 dB HL and 32.6 ± 17.2 dB HL, respectively; early and long-term HP rates were 61.1% and 50.8%, respectively. For patients with preoperative LFPTA ≤80 dB HL, early and long-term HP rates were 45.5% and 43.7%, respectively. No significant difference was observed in postoperative speech perception performance (CNC, AzBio, HINT) at 3, 6, or 12 months between HP versus non-HP groups.

Conclusions:

HP is feasible using the SME. While electroacoustic stimulation was not studied in this cohort, HP provided no clear advantage in speech perception abilities in this group of patients. The current reporting standard of what constitutes HP candidacy (preoperative LFPTA ≤80 dB HL) should be reconsidered.
Pediatric Primary Tympanoplasty Outcomes With Autologous and Non-autologous Grafts
Authors: Cass Nathan D. , Hebbe Annika L. , Meier Maxene R. , Kaizer Alexander M. , Kalmanson Olivia A. , Stevens Christina , Tholen Kaitlyn E. , Haville Salina , Handley Elyse , Francom Christian R. , Herrmann Brian W.
Published: September 2021

Objective:

To compare rates of successful tympanic membrane (TM) closure in primary pediatric tympanoplasty between various autologous and non-autologous tissues.

Methods:

A retrospective chart review was performed examining all primary pediatric tympanoplasties over a 20-year period at a single institution.

Results:

In 564 pediatric tympanoplasties, no statistically significant difference existed between success rates of autologous and non-autologous grafts (p = 0.083). Compared with fascia, the hazard ratios (and 95% confidence intervals [CI]) for failure for each graft were as follows: human pericardial collagen (HR 0.90, CI 0.54–1.50, p = 0.680), porcine submucosal collagen (HR 1.07, CI 0.56–2.05, p = 0.830), human acellular dermal collagen (HR 1.66, CI 0.95–2.87, p = 0.073), and “multiple grafts” (HR 0.72, CI 0.26–1.98, p = 0.520). Survival curves demonstrated that 75% of graft failures occurred by 6 months after surgery, the rest occurring between 6 and 12 months postoperatively. Larger perforations encompassing more than or equal to 50% of the TM had lower success rates (HR 1.50, CI 1.02–2.21, p = 0.041) than smaller perforations encompassing less than 50% of the TM. Age was not correlated with success (HR 0.98, CI 0.93–1.03, p = 0.390).

Conclusion:

This study found that non-autologous collagen grafts provide equivalent rates of healing when compared with autologous tissue in primary pediatric tympanoplasty. In addition to the potential for reduced operative time and donor site morbidity, these materials provide a viable graft alternative in fascia-depleted ears.

Level of Evidence: Level 4
Intraoperative Electrocochleography Correlates to Outcomes in Transmastoid and Middle Cranial Fossa Superior Semicircular Canal Dehiscence Repair
Authors: Ellsperman Susan E. , Telian Steven A. , Kileny Paul R. , Welch Christopher M.
Published: September 2021

Objective:

To determine the degree to which electrocochleography (ECoG) correlates with auditory and vestibular outcomes after repair of superior semicircular canal dehiscence (SSCD) via transmastoid (TM) and middle cranial fossa (MCF) approaches.

Study Design:

Retrospective review.

Setting:

Academic tertiary referral center.

Patients:

Adults with SSCD who underwent repair between 2005 and 2019.

Intervention:

Pre-, intra-, and postoperative ECoG.

Main Outcome Measures:

Patient-reported vestibular and auditory symptoms; pre-, intra-, and postoperative ECoG measures, dizziness handicap inventory (DHI) scores.

Results:

Forty-six patients underwent SSCD repair (40 unilateral, six bilateral) between 2005 and 2019, including 24 MCF and 28 TM approaches. There were no differences in preoperative, intraoperative, or postrepair ECoG SP/AP values between the MCF and TM groups (p 0.12, 0.77, 0.58). Patients had subjective improvement in vestibular symptoms (or stable vestibular function in patients operated for predominantly auditory manifestations) with both approaches (MCF: 87.5%; TM: 92.3%; p 0.64). A successful outcome correlated with intraoperative SP/AP ratio normalization (p 0.0005). Similarly, DHI scores were similar in both groups preoperatively (p 0.66) and returned to their preoperative baseline postoperatively with both (p 0.52). Reported vestibular symptoms persisted or worsened more often in patients with migraine (66.6% vs. 28.9%, p 0.03), and with persistently abnormal ECoG measures, though the latter was not statistically significant in this population (38% vs. 15%, p 0.10). Patients had subjective improvement or stability in auditory symptoms using either approach (MCF: 96%; TM: 100%; p 0.62), also correlating with SP/AP ratio normalization (p 0.008).

Conclusions:

Correction of abnormal preoperative ECoG reliably correlates to patient symptom improvement after SSCD repair. No significant differences in postoperative outcomes were noted between patients undergoing TM versus MCF repair. Circumspection regarding the likelihood of an ideal outcome after SSCD repair should be exercised when counseling patients with concomitant migraine.

Define Professional Practice Gap and Educational Need:

It is not certain whether outcomes differ between the two dominant approaches for SSCD repair. Surgeons and patients would benefit from an intraoperative metric that reflects satisfactory plugging of SSCD.

Learning Objective:

To highlight the reliability and unique utility of intraoperative ECoG and demonstrate the correlation between ECoG correction and symptom improvement for SSCD repair.

Desired Result:

To report subjective and objective outcomes following SSCD repair and encourage adoption of intraoperative ECoG monitoring.

Level of Evidence:

Level V.

Indicate IRB or IACUC:

IRB review considers this study exempt (HUM00169949).
The Effect of Supervision in Vestibular Rehabilitation in Patients with Acute or Chronic Unilateral Vestibular Dysfunction: A Systematic Review
Authors: Lilios Andreas , Chimona Theognosia , Nikitas Christos , Papadakis Chariton , Chatziioannou Ioannis , Skoulakis Charalambos
Published: September 2021

Objective:

The investigation of supervised vestibular rehabilitation treatment role for individuals with dizziness and imbalance due to peripheral, unilateral vestibular disorders.

Databases Reviewed:

Cochrane, PubMed, and Physiotherapy Evidence Database (PEDro) were utilized to identify relevant studies.

Methods:

The key search terms used were “Vestibular Rehabilitation and Unilateral Vestibular Hypofunction,” “Vestibular Rehabilitation and Unilateral Vestibular Loss,” and “Vestibular Rehabilitation and Supervision.” A manual search was performed by exploring the references of included articles to identify studies not captured through the computer-based searches. The quality of the studies was assessed according to the PEDro scale. Inclusion criteria were: 1) studies with patients, aged from 18 to 80 years, with acute or chronic dizziness and disequilibrium due to unilateral vestibular dysfunction, 2) randomized control trials (RCTs), 3) studies comparing supervised vestibular rehabilitation program with an unsupervised vestibular rehabilitation program or home-based training or standard care or placebo, and 4) articles written in the English language. Studies reporting cases of vertigo and imbalance due to possible recurrent pathologies, acute benign paroxysmal positional vertigo, or central neurological/orthopedic deficits, were excluded.

Results:

A total of 448 articles were retrieved from the systematic database search strategy. Five of them were included in the systematic review after full-text analysis, plus one more after manual searching of their references. All studies involved supervised vestibular rehabilitation treatment programs compared with unsupervised home training, the performance of daily activities and, standard care. Based on PEDro's scoring system, one study rated as high-quality RCT, three studies were considered of fair quality and one scored as low-quality RCT.

Conclusions:

Although most RCTs report better outcomes with a supervised vestibular rehabilitation treatment program regarding the emotional status, dizziness, and balance improvement, this systematic review failed to provide a strong evidence that supervision is superior to unsupervised protocols in patients with UNH. The self-reported subjective measures used by the included RCTs represent a serious limitation of their results.
Utilizing Single Cell RNA-Sequencing to Implicate Cell Types and Therapeutic Targets for SSNHL in the Adult Cochlea
Authors: Nelson Lacey , Johns J. Dixon , Gu Shoujun , Hoa Michael
Published: September 2021

Objective:

To identify genes implicated in sudden sensorineural hearing loss (SSNHL) and localize their expression in the cochlea to further explore potential pathogenic mechanisms and therapeutic targets.

Study Design:

Systematic literature review and bioinformatics analysis.

Data Sources:

The following sources were searched from inception through July 2, 2020: PubMed-NCBI, MEDLINE, Embase, CINAHL, Cochrane Library, ClinicalTrials.gov, OpenGrey, GreyNet, GreyLiterature Report, and European Union Clinical Trials Registry. PubMed-NCBI and MEDLINE were additionally searched for human temporal bone histopathologic studies related to SSNHL.

Methods:

Literature review of candidate SSNHL genes was conducted according to PRISMA guidelines. Existing temporal bone studies from SSNHL patients were analyzed to identify the most commonly affected inner ear structures. Previously published single-cell and single-nucleus RNA-Seq datasets of the adult mouse stria vascularis, as well as postnatal day 7 and 15 mouse cochlear hair cells and supporting cells, were utilized for localization of the SSNHL-related genes curated through literature review.

Conclusions:

We report 92 unique single nucleotide polymorphisms (SNPs) in 76 different genes that have been investigated in relation to SSNHL in the literature. We demonstrate that a subset of these genes are expressed by cell types in the adult mouse stria vascularis and organ of Corti, consistent with findings from temporal bone studies in human subjects with SSNHL. We highlight several potential genetic targets relevant to current and possible future SSNHL treatments.