bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the gravitational-wave sky with LISA: a Bayesian spherical harmonic approach
Authors: Banagiri Sharan , Criswell Alexander , Kuan Tommy , Mandic Vuk , Romano Joseph D , Taylor Stephen R 
Published: September 2021

ABSTRACT
The millihertz gravitational-wave frequency band is expected to contain a rich symphony of signals with sources ranging from Galactic white dwarf binaries to extreme mass ratio inspirals. Many of these gravitational-wave signals will not be individually resolvable. Instead, they will incoherently add to produce stochastic gravitational-wave confusion noise whose frequency content will be governed by the dynamics of the sources. The angular structure of the power of the confusion noise will be modulated by the distribution of the sources across the sky. Measurement of this structure can yield important information about the distribution of sources on Galactic and extragalactic scales, their astrophysics and their evolution over cosmic time-scales. Moreover, since the confusion noise is part of the noise budget of Laser Interferometer Space Antenna (LISA), mapping it will also be essential for studying resolvable signals. In this paper, we present a Bayesian algorithm to probe the angular distribution of the stochastic gravitational-wave confusion noise with LISA using a spherical harmonic basis. We develop a technique based on Clebsch–Gordan coefficients to mathematically constrain the spherical harmonics to yield a non-negative distribution, making them optimal for expanding the gravitational-wave power and amenable to Bayesian inference. We demonstrate these techniques using a series of simulations and analyses, including recovery of simulated distributed and localized sources of gravitational-wave power. We also apply this method to map the gravitational-wave foreground from Galactic white dwarfs using a simplified model of the Galactic white dwarf distribution.
Reciprocal stabilization of transcription factor binding integrates two signaling pathways to regulate fission yeastfbp1transcription
Authors: Koda Wakana , Senmatsu Satoshi , Abe Takuya , Hoffman Charles S , Hirota Kouji 
Published: September 2021

AbstractTranscriptional regulation, a pivotal biological process by which cells adapt to environmental fluctuations, is achieved by the binding of transcription factors to target sequences in a sequence-specific manner. However, how transcription factors recognize the correct target from amongst the numerous candidates in a genome has not been fully elucidated. We here show that, in the fission-yeast fbp1 gene, when transcription factors bind to target sequences in close proximity, their binding is reciprocally stabilized, thereby integrating distinct signal transduction pathways. The fbp1 gene is massively induced upon glucose starvation by the activation of two transcription factors, Atf1 and Rst2, mediated via distinct signal transduction pathways. Atf1 and Rst2 bind to the upstream-activating sequence 1 region, carrying two binding sites located 45 bp apart. Their binding is reciprocally stabilized due to the close proximity of the two target sites, which destabilizes the independent binding of Atf1 or Rst2. Tup11/12 (Tup-family co-repressors) suppress independent binding. These data demonstrate a previously unappreciated mechanism by which two transcription-factor binding sites, in close proximity, integrate two independent-signal pathways, thereby behaving as a hub for signal integration.
A novel PLK1 inhibitor onvansertib effectively sensitizes MYC-driven medulloblastoma to radiotherapy
Authors: Wang Dong , Veo Bethany , Pierce Angela , Fosmire Susan , Madhavan Krishna , Balakrishnan Ilango , Donson Andrew , Alimova Irina , Sullivan Kelly D , Joshi Molishree , Erlander Mark , Ridinger Maya , Foreman Nicholas K , Venkataraman Sujatha , Vibhakar Rajeev 
Published: September 2021

Abstract

Background
Group 3 medulloblastoma (MB) is often accompanied by MYC amplification. PLK1 is an oncogenic kinase that controls cell cycle and proliferation and has been preclinically validated as a cancer therapeutic target. Onvansertib (PCM-075) is a novel, orally available PLK1 inhibitor, which shows tumor growth inhibition in various types of cancer. We aim to explore the effect of onvansertib on MYC-driven medulloblastoma as a monotherapy or in combination with radiation.

Methods
Crisper-Cas9 screen was used to discover essential genes for MB tumor growth. Microarray and immunohistochemistry on pediatric patient samples were performed to examine the expression of PLK1. The effect of onvansertib in vitro was measure by cell viability, colony-forming assays, extreme limiting dilution assay, and RNA-Seq. ALDH activity, cell-cycle distribution, and apoptosis were analyzed by flow cytometry. DNA damage was assessed by immunofluorescence staining. Medulloblastoma xenografts were generated to explore the monotherapy or radio-sensitizing effect.

Results
PLK1 is overexpressed in Group 3 MB. The IC50 concentrations of onvansertib in Group 3 MB cell lines were in a low nanomolar range. Onvansertib reduced colony formation, cell proliferation, stem cell renewal and induced G2/M arrest in vitro. Moreover, onvansertib in combination with radiation increased DNA damage and apoptosis compared with radiation treatment alone. The combination radiotherapy resulted in marked tumor regression in xenografts.

Conclusions
These findings demonstrate the efficacy of a novel PLK1 inhibitor onvansertib in vitro and in xenografts of Group 3 MB, which suggests onvansertib is an effective strategy as monotherapy or in combination with radiotherapy in MB.
Machine learning approach to differentiation of peripheral schwannomas and neurofibromas: A multi-center study
Authors: Zhang Michael , Tong Elizabeth , Wong Sam , Hamrick Forrest , Mohammadzadeh Maryam , Rao Vaishnavi , Pendleton Courtney , Smith Brandon W , Hug Nicholas F , Biswal Sandip , Seekins Jayne , Napel Sandy , Spinner Robert J , Mahan Mark A , Yeom Kristen W , Wilson Thomas J 
Published: September 2021

Abstract

Background
Non-invasive differentiation between schwannomas and neurofibromas is important for appropriate management, preoperative counseling, and surgical planning, but has proven difficult using conventional imaging. The objective of this study was to develop and evaluate machine learning approaches for differentiating peripheral schwannomas from neurofibromas.

Methods
We assembled a cohort of schwannomas and neurofibromas from 3 independent institutions and extracted high-dimensional radiomic features from gadolinium-enhanced, T1-weighted MRI using the PyRadiomics package on Quantitative Imaging Feature Pipeline. Age, sex, neurogenetic syndrome, spontaneous pain, and motor deficit were recorded. We evaluated the performance of 6 radiomics-based classifier models with and without clinical features and compared model performance against human expert evaluators.

Results
One hundred and seven schwannomas and 59 neurofibromas were included. The primary models included both clinical and imaging data. The accuracy of the human evaluators (0.765) did not significantly exceed the no-information rate (NIR), whereas the Support Vector Machine (0.929), Logistic Regression (0.929), and Random Forest (0.905) classifiers exceeded the NIR. Using the method of DeLong, the AUCs for the Logistic Regression (AUC = 0.923) and K Nearest Neighbor (AUC = 0.923) classifiers were significantly greater than the human evaluators (AUC = 0.766; p = 0.041).

Conclusions
The radiomics-based classifiers developed here proved to be more accurate and had a higher AUC on the ROC curve than expert human evaluators. This demonstrates that radiomics using routine MRI sequences and clinical features can aid in differentiation of peripheral schwannomas and neurofibromas.
Primary Care Associated With Follow Up Viral Load Testing in Patients Cured of Hepatitis C Infection With Direct Acting Antivirals at a Multidisciplinary Addiction Treatment Program: Insights From a Real-World Setting
Authors: Haque Lamia Y. , Butner Jenna L. , Shi Julia M. , Henry Susan , Deng Yanhong , Ciarleglio Maria M. , Madden Lynn M. , Tetrault Jeanette M. 
Published: September 2021

Objectives
Treatment of hepatitis C virus infection (HCV) with direct acting antiviral therapy is encouraged regardless of substance use status. Patients with substance use disorder are at risk of HCV reinfection after cure. Follow up viral load testing (FUVL) with HCV RNA is recommended. We investigated factors associated with adoption of FUVL in real-world clinical settings.

Methods
Medical records of all patients with SUD who achieved HCV cure with direct acting antivirals at a multidisciplinary addiction treatment program between 2014 and 2019 were reviewed as part of a quality improvement initiative. Demographic and clinical characteristics including SUD treatment, urine toxicology results, and medical service use were collected. Factors associated with FUVL were analyzed and the rate of HCV reinfection was determined.

Results
Among 149 patients, 58.4% received FUVL. Receipt of FUVL was associated with engagement in ongoing primary medical care after cure (AOR 4.39, 95% CI [1.67, 11.49]). The HCV reinfection rate among those who received FUVL was 1.95 per 100 person-years of follow up (95% CI [0.64, 5.98]). There was no significant difference in the percentage of negative urine toxicology results before and after cure.

Conclusions
Over half of a cohort of patients with substance use disorder cured of HCV received FUVL. The relationship between FUVL and engagement in primary medical and substance use treatment highlights the importance of integrated systems in providing longitudinal care for patients cured of HCV. Standardized interventions that facilitate FUVL testing and management of infectious complications of SUD in addiction treatment settings are needed.
An Updated Systematic Review and Meta-analysis of Duloxetine for Knee Osteoarthritis Pain
Authors: Chen Bo , Duan Jingrui , Wen Shengyue , Pang Jian , Zhang Min , Zhan Hongsheng , Zheng Yuxin 
Published: September 2021

Objective:
We conducted the updated systematic review and meta-analysis of the best available quantitative and qualitative evidence to evaluate the effects and safety of duloxetine for the treatment of knee osteoarthritis (OA) pain.

Methods:
A comprehensive literature search used 3 English and 4 Chinese biomedical databases from inception through July 10, 2020. We included randomized controlled trials of duloxetine with intervention duration of 2 weeks or longer for knee OA. The primary outcome was pain intensity measured by Brief Pain Inventory and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcome measurements included 36-Item Short Form Health Survey, Patient’s Global Impression of Improvement, Clinical Global Impressions of Severity, and adverse events (AEs). The quality of all included studies was evaluated using the Cochrane risk-of-bias criteria. The review was registered in the PROSPERO (CRD 42020194072).

Results:
Six studies totaling 2059 patients met the eligibility criteria. Duloxetine had significant reductions in Brief Pain Inventory 24 hours average pain (mean difference [MD]=−0.74; 95% confidence interval [CI], −0.92 to −0.57; P<0.00001; I
2=13%; 5 trials; 1695 patients); patient general activity (MD=−0.76; 95% CI, −0.96 to −0.56; P<0.00001; I
2=0%; 5 trials; 1694 patients) WOMAC physical function subscale (MD=−4.22; 95% CI, −5.14 to −3.30; P<0.00001; I
2=26%; 5 trials; 1986 patients); Patient’s Global Impression of Improvement (MD=−0.48; 95% CI, −0.58 to −0.37; P<0.00001; I
2=29%; 5 trials; 1741 patients); and Clinical Global Impressions of Severity (MD=−0.34; 95% CI, −0.44 to −0.24; P<0.00001; I
2=0%; 4 trials; 1178 patients) compared with placebo control. However, no difference on WOMAC pain subscale (standard mean difference=−1.68; 95% CI, −3.45 to 0.08; P=0.06; I
2=100%; 3 trials; 1104 patients) and in serious AEs (risk ratio=0.92; 95% CI, 0.40-2.11; P=0.84; I
2=0%; 5 trials; 1762 patients) between duloxetine and placebo. Furthermore, duloxetine failed to show superior effects for improving the life quality and demonstrated more treatment-emergent AEs.

Conclusion:
Duloxetine may be an effective treatment option for knee OA patients but further rigorously designed and well-controlled randomized trials are warranted.
The Activity Patterns Scale
Authors: López-Roig Sofía , Peñacoba Cecilia , Martínez-Zaragoza Fermín , Abad Esther , Catalá Patricia , Suso-Ribera Carlos , Pastor-Mira María-Ángeles 
Published: September 2021

Objectives:
Avoidance, persistence, and pacing are activity patterns that have different adaptive effects in chronic pain patients. Some inconsistent findings have been explained from a contextual perspective that underlines the purpose of the activity. In this way, avoidance, persistence, and pacing are multidimensional constructs, nuanced by their goals. This multidimensionality has been supported with a new instrument, the Activity Patterns Scale, in heterogeneous chronic pain samples. Owing to the clinical implications of this conceptualization, the complexity of the activity patterns and their relationships with health outcomes in fibromyalgia (FM), our aim was to explore the construct validity of this scale in this pain problem, testing its internal structure and the relationships with other constructs.

Materials and Methods:
The sample included 702 women with diagnosis of FM from tertiary (53.3%) and community settings (46.7%). Confirmatory factor analysis was conducted to test different factor structures of the activity patterns and Pearson correlation to explore the relationships with health outcomes and psychosocial variables.

Results:
A 6-factor structure showed acceptable fit indices (standardized root mean square residual=0.062; root mean-square error of approximation=0.066; comparative fit index=0.908). The highest significant relationships for health outcomes was between activity avoidance and FM impact (r=0.36) and excessive persistence and negative affect (r=0.41).

Discussion:
Avoidance and persistence activity patterns are shown as multidimensional constructs but not pacing. The ongoing pain in these women may make it difficult to regulate their activity taking into account other goals not contingent on pain fluctuations.
Differential diagnosis of necrotizing myopathy
Authors: Selva-O’Callaghan Albert , Trallero-Araguás Ernesto , Milisenda Jose C. , Grau-Junyent Josep M. 
Published: September 2021

Purpose of review
Necrotizing myopathy is a broad term. It includes patients with the recently described immune-mediated necrotizing myopathies (IMNM) who have specific antibodies, such as anti-hydroxy-3-methylglutaryl-CoA reductase or anti-signal recognition particle, seronegative phenotypes that can be associated with cancer, and other types of myositis and connective tissue diseases involving necrotic muscle fibers as a characteristic pathologic feature. Necrotizing myopathies that are not immune-mediated, such as those caused by drugs, dystrophies, infections, or even hypothyroidism are also included. The purpose of this review is to address the differential diagnosis of these disorders.

Recent findings
New IMNM have been described over the last few years, some of them related with checkpoint inhibitors, drugs that are being increasingly used in cancer treatment. Necrotizing myopathy has also been reported in association with specific phenotypes and autoantibodies (e.g. anti-Mi2 dermatomyositis, antisynthetase syndrome, and myositis associated with antimitochondrial antibodies). Rarer cases associated with graft-versus-host disease and severe acute respiratory syndrome coronavirus 2 infection are also emerging.

Summary
Differentiation between patients with IMNM and those without the superimposed autoimmune phenomena helps clinicians determine the best individualized approach to use and the appropriate immunosuppressive therapy, whenever needed.
Outcomes of Anterior Decompression and Anterior Instrumentation in Thoracolumbar Burst Fractures—A Prospective Observational Study With Mid-Term Follow-up
Authors: Mittal Samarth , Rana Arvind , Ahuja Kaustubh , Ifthekar Syed , Yadav Gagandeep , Sudhakar Pudipeddi Venkata , Sinha Shivendra K. , Kar Santanu , Sarkar Bhaskar , Kandwal Pankaj , Farooque Kamran 
Published: September 2021

Objective:
To analyze the functional, neurological, and radiological outcomes after anterior surgery in thoracolumbar burst fractures.

Design:
Prospective observational study.

Setting:
Tertiary care hospital.

Patients:
Thirty-six patients with thoracolumbar burst fractures (T11-L2).

Intervention:
Anterior decompression, anterior column reconstruction with mesh cage, and instrumented stabilization.

Outcome:
Functional (Visual Analog Score, Oswestry Disability Index, and Spinal Cord Independence Measure), neurological (ASIA Impairment Scale), and radiological (kyphosis, anterior vertebral height loss, canal encroachment %) parameters.

Results:
Patients were prospectively followed for a mean duration of 5.9 ± 3.2 years (2.4–10 years). Statistically significant improvement was noted in functional outcomes from preop values (P-value < 0.001). 29 patients (80.5%) had improvement in neurology after surgery at the final follow-up with a positive correlation with % change in canal encroachment (r = 0.64, P −0.018). The mean preoperative kyphosis of 29.1 ± 11.9 degrees got corrected to 9.4 ± 3.8 degrees in immediate postop and 15.7 ± 11.8 at the final follow-up(P < 0.001). Preoperative mean canal encroachment of 58.5 ± 15.7% was reduced to 6.5 ± 3.2% postoperatively (P < 0.001). Two patients developed neurological complications (subacute progressive ascending myelopathy), and 5 patients developed pulmonary complications. No pseudarthrosis, implant loosening, or cage migration was noted in any patient.

Conclusion:
Anterior surgery performed in 36 patients with thoracolumbar burst fractures in our study showed good outcomes. 80.5% of patients improved in neurology after surgery by at least one ASIA Impairment Scale grade. There was statistically significant improvement noted in radiological outcome (Kyphosis and Canal encroachment %) and functional outcome (Visual Analog Score, Oswestry Disability Index, and Spinal Cord Independence Measure score) after surgery in immediate postop and at the final follow-up. Only 13.8% of patients developed pulmonary complications that were managed successfully with chest drain.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Radiographic Templating for Calcaneus Operative Fixation: How Similar Is Side-to-Side Comparison?
Authors: Raji Yazdan , LaTulip Scott M. , Faraji Navid , DeLozier Sarah J. , Vallier Heather A. , Ochenjele George 
Published: September 2021

Objectives:
Calcaneal fractures often require contralateral, uninjured calcaneus radiographs as a template. The purpose of this study was to establish mean values for calcaneal radiographic parameters in an uninjured urban American population and perform side-by-side comparison with respect to age, sex, laterality, and radiograph obliquity (XRO).

Design:
Retrospective analysis of consecutive patients.

Setting:
Fourteen hospitals including Level 1 trauma center.

Patients/Participants:
Retrospective review of >800 uninjured patients with bilateral foot and calcaneus radiographs obtained between June and December 2019 was performed. Inclusion criteria were the following: age 18–89 years without fracture; previous foot surgical procedures; radiographic evidence of arthrosis in ankle, hindfoot, or midfoot; osteomyelitis; tumor; or foot deformities.

Intervention:
The lateral radiographs were independently reviewed by 3 observers, measuring Böhler angle (BA), crucial angle of Gissane (CAG), calcaneal length (CL), calcaneal height (CH), calcaneotalar ratio (CTR), and XRO.

Main Outcome Measurements:
The mean values of BA, CAG, CL, CH, and CTR were established. Side-by-side comparisons were completed with respect to age, sex, laterality, and XRO.

Results:
There were no statistically significant differences in side-by-side measurements of the BA, CAG, CL, or CH. XRO had significant effects on the measurements of BA, CAG, CH, and CTR. Side-by-side comparisons showed greater intersubject variability than within-subject differences.

Conclusions:
We did not observe any differences in commonly measured calcaneal radiographic parameters. CAG is not a reliable parameter for diagnostic and operative planning purposes. We conclude that the use of contralateral calcaneus radiographs as templates for calcaneus fractures is a valid technique.
The Impact of Operative Intervention in Pediatric Lyme Arthritis
Authors: Tout Andrew R. , McClincy Michael , Anderson Alyce , Nowalk Andrew , Campfield Brian T. 
Published: September 2021

Background:
Lyme arthritis often presents as acute monoarticular arthritis challenging to distinguish from septic arthritis. Typical management for Lyme arthritis entails antibiotic therapy, while septic arthritis usually warrants operative debridement. During the period when Western Pennsylvania transitioned to a Lyme-endemic region, many children underwent operative intervention who were ultimately diagnosed with Lyme arthritis due to diagnostic ambiguity. We examined the impact of the operative intervention on pediatric Lyme arthritis outcomes.

Methods:
We conducted a retrospective cohort study of patients admitted to a tertiary care children’s hospital who were diagnosed with Lyme arthritis from 2008 to 2018 using chart review. Inclusion criteria were positive Lyme serology by Centers for Disease Control and Prevention (CDC) definition, clinical arthritis, and negative bacterial cultures. We recorded clinical presentation, laboratory data, details of hospitalization, costs, and outcomes after therapy to compare the impact of antibiotics alone (nonoperative group) versus antibiotics plus operative debridement (operative group).

Results:
A total of 149 patients met the inclusion criteria. Overall, 47 (32%) patients underwent orthopaedic intervention. Operative management was associated with increased length (3.17 vs. 1.40 d) and cost ($27,850 vs. $10,716) of admission. The clinical resolution was documented in 57/58 patients (98%) in the nonoperative group and 41/42 patients (98%) in the operative group. The median duration to resolution was 21 days for both groups.

Conclusions:
Operative management of pediatric patients with Lyme arthritis is associated with increased resource utilization and costs while being similarly efficacious to nonoperative management. As the US Lyme epidemic expands, improved diagnosis and management of acute undifferentiated arthritis may prevent unneeded operative intervention.

Level of Evidence:
Level III—retrospective cohort study.