bluuebunny/crossref_metadata_2025_split huggingface dataset:
PARP1 and CHK1 coordinate PLK1 enzymatic activity during the DNA damage response to promote homologous recombination-mediated repair
Authors: Peng Bin , Shi Ruifeng , Bian Jing , Li Yuwei , Wang Peipei , Wang Hailong , Liao Ji , Zhu Wei-Guo , Xu Xingzhi 
Published: June 2021

Abstract
Polo-like kinase 1 (PLK1) is a master kinase that regulates cell cycle progression. How its enzymatic activity is regulated in response to DNA damage is not fully understood. We show that PLK1 is enriched at double strand breaks (DSBs) within seconds of UV laser irradiation in a PARP-1-dependent manner and then disperses within 10 min in a PARG-dependent manner. Poly(ADP-)ribose (PAR) chains directly bind to PLK1 in vitro and inhibit its enzymatic activity. CHK1-mediated PLK1 phosphorylation at S137 prevents its binding to PAR and recruitment to DSBs but ensures PLK1 phosphorylation at T210 and its enzymatic activity toward RAD51 at S14. This subsequent phosphorylation event at S14 primes RAD51 for CHK1-mediated phosphorylation at T309, which is essential for full RAD51 activation. This CHK1–PLK1–RAD51 axis ultimately promotes homologous recombination (HR)-mediated repair and ensures chromosome stability and cellular radiosensitivity. These findings provide biological insight for combined cancer therapy using inhibitors of PARG and CHK1.
Circular L-RNA aptamer promotes target recognition and controls gene activity
Authors: Ji Danyang , Lyu Kaixin , Zhao Haizhou , Kwok Chun Kit 
Published: June 2021

AbstractRational design of aptamers to incorporate unnatural nucleotides and special chemical moieties can expand their functional complexity and diversity. Spiegelmer (L-RNA aptamer) is a unique class of aptamer that is composed of unnatural L-RNA nucleotides, and so far there are limited L-RNA aptamer candidates and applications being reported. Moreover, the target binding properties of current L-RNA aptamers require significant improvement. Here, using L-Apt.4-1c as an example, we develop a simple and robust strategy to generate the first circular L-RNA aptamer, cycL-Apt.4-1c, quantitatively, demonstrate substantial enhancement in binding affinity and selectivity toward its target, and notably report novel applications of circular L-RNA aptamer in controlling RNA–protein interaction, and gene activity including telomerase activity and gene expression. Our approach and findings will be applicable to any L-RNA aptamers and open up a new avenue for diverse applications.
ANANSE: an enhancer network-based computational approach for predicting key transcription factors in cell fate determination
Authors: Xu Quan , Georgiou Georgios , Frölich Siebren , van der Sande Maarten , Veenstra Gert Jan C , Zhou Huiqing , van Heeringen Simon J 
Published: June 2021

AbstractProper cell fate determination is largely orchestrated by complex gene regulatory networks centered around transcription factors. However, experimental elucidation of key transcription factors that drive cellular identity is currently often intractable. Here, we present ANANSE (ANalysis Algorithm for Networks Specified by Enhancers), a network-based method that exploits enhancer-encoded regulatory information to identify the key transcription factors in cell fate determination. As cell type-specific transcription factors predominantly bind to enhancers, we use regulatory networks based on enhancer properties to prioritize transcription factors. First, we predict genome-wide binding profiles of transcription factors in various cell types using enhancer activity and transcription factor binding motifs. Subsequently, applying these inferred binding profiles, we construct cell type-specific gene regulatory networks, and then predict key transcription factors controlling cell fate transitions using differential networks between cell types. This method outperforms existing approaches in correctly predicting major transcription factors previously identified to be sufficient for trans-differentiation. Finally, we apply ANANSE to define an atlas of key transcription factors in 18 normal human tissues. In conclusion, we present a ready-to-implement computational tool for efficient prediction of transcription factors in cell fate determination and to study transcription factor-mediated regulatory mechanisms. ANANSE is freely available at https://github.com/vanheeringen-lab/ANANSE.
The Impact of Interhospital Competition on Treatment Strategy and Outcomes for Unruptured Intracranial Aneurysms
Authors: Tang Oliver Y , Yoon James S , Durand Wesley M , Ahmed Shaan A , Lawton Michael T 
Published: June 2021

Abstract

BACKGROUND
Interhospital competition has been shown to affect surgical outcomes and expenditures. However, interhospital competition's impact on neurosurgery is poorly characterized.

OBJECTIVE
To assess how interhospital competition is associated with treatment strategy and outcomes for unruptured intracranial aneurysms (UIAs).

METHODS
We identified all elective UIA admissions in the National Inpatient Sample from 2002 to 2011. Competitive intensity of each hospital market was quantified using the validated Herfindahl-Hirschman Index (HHI), with lower values denoting higher competition. We then obtained nationwide HHI values for 2012 to 2016 from the Health Care Cost Project. Outcomes included treatment modality (clipping, coiling, or nonoperative management), inpatient mortality, disposition, complications, length of stay (LOS), and costs. Multivariate regression assessed the association between HHI and outcomes, controlling for patient demographics, severity metrics, hospital characteristics, and treatment.

RESULTS
We studied 157 979 elective UIA admissions at 1435 hospitals from 2002 to 2011, with an increase in coiling admissions (13.4% to 33.7%) and decrease in clipping admissions (30.9% to 17.6%). Mean hospital HHI was 0.11 (range = 0.001-0.97). Competition decreased for 61.8% of hospitals from 2002 to 2011 and 68.1% of metropolitan localities from 2012 to 2016. Admissions in more competitive hospital markets exhibited increased odds of undergoing surgery (odds ratio [OR] = 1.37, P < .001), with preference toward coiling over clipping (OR = 1.27, P < .001). HHI was not associated with mortality, disposition, or LOS. However, increased interhospital competition was associated with more complications (OR = 1.09, P = .001) and greater hospital costs (β-coefficient = 1.06, P < .001).

CONCLUSION
For UIA patients, admission to hospitals in more competitive geographies was associated with increased rates of surgical intervention, coiling utilization, complications, and hospitalization costs.
ArabidopsisSSB1, a Mitochondrial Single-Stranded DNA-Binding Protein, is Involved in ABA Response and Mitochondrial RNA Splicing
Authors: Qian Jie , Li Meng , Zheng Min , Hsu Yi-Feng 
Published: June 2021

AbstractA mitochondrion is a semiautonomous organelle that provides energy for life activities and balances plant growth and stress responses. Abscisic acid (ABA) regulates multiple physiological processes, including seed maturation, seed dormancy, stomatal closure and various abiotic stress responses. However, the relationship between mitochondrial activity and the ABA response is unclear. In this study, an Arabidopsis mutant, ssb1-1, was isolated because of its hypersensitivity toward ABA. Assessment results showed that ABA negatively regulates the expression of Arabidopsis SSB1. Mutations in ABA-insensitive 4 (ABI4) and ABI5, genes of key transcription factors involved in ABA-dependent seed dormancy, attenuated the ABA sensitivity of ssb1-1 during germination, suggesting that Arabidopsis SSB1 may act as a regulator in ABA response. Inhibition of endogenous ABA biosynthesis reversed the NaCl-sensitive phenotype of the ssb1-1 mutant, indicating that enhanced ABA biosynthesis is critical for the salinity stress response of ssb1-1. Moreover, compared to that of the wild type, ssb1-1 accumulated more reactive oxygen species (ROS) and exhibited increased sensitivity to the application of exogenous H2O2 during seed germination. SSB1 is also required for mitochondrial RNA splicing, as indicated by the result showing that SSB1 loss of function led to a decreased splicing efficiency of nad1 intron1 and nad2 intron1. Taken together, our data reported here provide insights into a novel role of Arabidopsis SSB1 in ABA signaling and mitochondrial RNA splicing.
Quantum phase transition and resurgence: Lessons from three-dimensional $\mathcal{N}=4$ supersymmetric quantum electrodynamics
Authors: Fujimori Toshiaki , Honda Masazumi , Kamata Syo , Misumi Tatsuhiro , Sakai Norisuke , Yoda Takuya 
Published: June 2021

Abstract
We study a resurgence structure of a quantum field theory with a phase transition to uncover relations between resurgence and phase transitions. In particular, we focus on three-dimensional $\mathcal{N}=4$ supersymmetric quantum electrodynamics (SQED) with multiple hypermultiplets, where a second-order quantum phase transition has recently been proposed in the large-flavor limit. We provide interpretations of the phase transition from the viewpoints of Lefschetz thimbles and resurgence. For this purpose, we study the Lefschetz thimble structure and properties of the large-flavor expansion for the partition function obtained by the supersymmetric localization. We show that the second-order phase transition is understood as a phenomenon where a Stokes and an anti-Stokes phenomenon occur simultaneously. The order of the phase transition is determined by how saddles collide at the critical point. In addition, the phase transition accompanies an infinite number of Stokes phenomena due to the supersymmetry. These features are appropriately mapped to the Borel plane structures as the resurgence theory expects. Given the lessons from SQED, we provide a more general discussion on the relationship between the resurgence and phase transitions. In particular, we show how the information on the phase transition is decoded from the Borel resummation technique.
Neuromuscular Electrical Stimulation Improves Muscle Strength, Biomechanics of Movement, and Functional Mobility in Children With Chronic Neurological Disorders: A Systematic Review and Meta-Analysis
Authors: Cobo-Vicente Fernando , San Juan Alejandro F , Larumbe-Zabala Eneko , Estévez-González Agustín Jesús , Donadio Márcio Vinícius Fagundes , Pérez-Ruiz Margarita 
Published: June 2021

Abstract

Objective
Chronic neurological disorders (CNDs) generally produce deleterious effects on the musculoskeletal system and can affect physical activity and increase sedentary behavior in children, hindering the execution of training programs and the attainment of a correct dose of exercise. The purpose of this systematic review was to analyze the effect of neuromuscular electrical stimulation (NMES) on skeletal muscle and then on biomechanics of movement, functional mobility, strength, spasticity, muscle architecture, and body composition of children and adolescents with CNDs and chronic diseases.

Methods
The search was conducted in April 2020 in PubMed, MEDLINE, Scopus, the Cochrane Library, and Web of Science, without publication period restriction. Publications investigating the effect of NMES on children and adolescents with CNDs and other chronic diseases were independently selected by 2 researchers. One author independently extracted data from the studies selected, and a second author cross-checked.

Results
Eighteen studies with 595 participants aged between 3 and 14 years were included. Quality assessment showed that 50% of the studies presented a low risk of bias. The pooled effect of NMES on gross motor functional measure, calculated as a standardized mean difference using a random effects model, was 0.41 (95% CI = 0.19–0.64).

Conclusion
The use of NMES programs for children diagnosed with cerebral palsy, spinal muscular atrophy, and obstetric injury of the brachial plexus was effective in improving muscle strength, biomechanics of movement, and functional mobility.

Impact
NMES can be a useful tool to prevent the reduction of mobility that results from CNDs.
Political Determinants of Competition in the Mobile Telecommunication Industry
Authors: Faccio Mara , Zingales Luigi 
Published: June 2021

Abstract
We study the relationship between the presence of politicians on mobile service operators’ boards and the regulation of the mobile telecommunication sector. In countries in which mobile operators have deeper connections with local politicians, we find that rules promote competition less, even after we control for country fixed effects and a country’s level of corruption. Rules that promote competition are associated with lower concentration and lower prices. There is no evidence that procompetition rules are associated with worse quality, lower investments, less employment, or lower wages. Thus, all the evidence points to political connections being a form of rent-seeking.
Implementation and Assessment of a Proning Protocol for Nonintubated Patients With COVID-19
Authors: D'Souza Felicia R. , Murray John P. , Tummala Sandeep , Puello Frances , Pavkovich David S. , Ash Daniel , Kelly Stephanie B. H. , Tyker Albina , Anderson Daniela , Francisco Mary A. , Pierce Nicole L. , Cerasale Matthew T. 
Published: June 2021

ABSTRACT

Introduction:
The COVID-19 pandemic has caused over 1,250,000 deaths worldwide. With limited therapeutic options, proning nonintubated patients emerged as a safe and affordable intervention to manage hypoxemia.

Methods:
A proning protocol to identify and prone eligible patients was implemented. Patients were encouraged to self-prone for 2–3 hours, 3 times daily. Investigators created educational materials for nurses and patients and developed a COVID-19–specific proning order within the electronic health record (EHR). Investigators completed an 800-person retrospective chart review to study the implementation of this protocol.

Results:
From March 22, 2020, to June 5, 2020, 586 patients were admitted to the COVID-19 floor. Of these patients, 42.8% were eligible for proning. Common contraindications were lack of hypoxia, altered mental status, and fall risk. The proning protocol led to a significant improvement in provider awareness of patients appropriate for proning, increasing from 12% to 83%, as measured by placement of a proning order into the EHR. There was a significant improvement in all appropriate patients documented as proned, increasing from 18% to 45% of eligible patients.

Conclusions:
The creation of an effective hospital-wide proning protocol to address the exigencies of the COVID-19 pandemic is possible and may be accomplished in a short period of time.
Understanding the Relationship between Breast Reconstruction Subtype and Risk of Financial Toxicity: A Single-Institution Pilot Study
Authors: Bailey Chad M. , Asaad Malke , Boukovalas Stefanos , Lin Yu-Li , Kothamasu Venkata , Kapur Sahil K. , Villa Mark T. , Butler Charles E. , Offodile Anaeze C. 
Published: June 2021

Background:
The impact of breast reconstruction on financial toxicity remains poorly understood despite growing awareness. The authors sought to illustrate the relationship between breast reconstruction subtypes and the risk of financial toxicity.

Methods:
The authors conducted a single-institution cross-sectional survey of all female breast cancer patients undergoing any form of breast reconstruction between January of 2018 and June of 2019. Financial toxicity was measured by means of the validated Comprehensive Score for Financial Toxicity instrument. Demographics, clinical course, and coping strategies were abstracted from a purpose-built survey and electronic medical records. Multivariable linear regression was performed to identify associations with financial toxicity.

Results:
The authors’ analytical sample was 350 patients. One hundred eighty-four (52.6 percent) underwent oncoplastic reconstruction, 126 (36 percent) underwent implant-based reconstruction, and 40 (11.4 percent) underwent autologous reconstruction. Oncoplastic reconstruction recipients were older, had a higher body mass index, and were more likely to have supplemental insurance and receive adjuvant hormonal therapy. No significant differences in the risk of financial toxicity were uncovered across breast reconstruction subtypes (p = 0.53). Protective factors against financial toxicity were use of supplemental insurance (p = 0.0003) and escalating annual household income greater than $40,000 (p < 0.0001). Receipt of radiation therapy was positively associated with worsening financial toxicity (−2.69; 95 CI percent, −5.22 to −0.15). Financial coping strategies were prevalent across breast reconstruction subtypes.

Conclusions:
Breast reconstruction subtype does not differentially impact the risk of financial toxicity. Increasing income and supplemental insurance were found to be protective, whereas receipt of radiation therapy was positively associated with financial toxicity. Prospective, multicenter studies are needed to identify the main drivers of out-of-pocket costs and financial toxicity in breast cancer care.
Carving Out Financial Success: The Power of Insurance Carve-Outs in a Private Plastic Surgery Practice
Authors: Kind Gabriel M. , Davis Matthew J. , Abu-Ghname Amjed , Ochoa Oscar , Hoxworth Ron , Winocour Sebastian , Maricevich Marco , Chrysopoulo Minas 
Published: June 2021

Background:
Since the Patient Protection and Affordable Care Act was signed into law, there has been a push away from fee-for-service payment models. The rise of bundled payments has drastically impacted plastic surgeons’ incomes, especially nonsalaried surgeons in private practice. As a result, physicians must now attempt to optimize contractual reimbursement agreements (carve-outs) with insurance providers. The aim of this article is to explain the economics behind negotiating carve-outs and to offer a how-to guide for plastic surgeons to use in such negotiations.

Methods:
Based on work relative value units, Medicare reimbursement, overhead expenses, physician workload, and desired income, the authors present an approach that allows surgeons to evaluate the reimbursement they receive for various procedures. The authors then review factors that influence whether a carve-out can be pursued. Finally, the authors consider relevant nuances of negotiating with insurance companies.

Results:
Using tissue expander insertion (CPT 19357) as an example, the authors review the mathematics, thought process required, and necessary steps in determining whether a carve-out should be pursued. Strategies for negotiation with insurance companies were identified. The presented approach can be used to potentially negotiate a carve-out for any reconstructive procedure that meets appropriate financial criteria.

Conclusions:
Understanding practice costs will allow plastic surgeons to evaluate the true value of insurance reimbursements and determine whether a carve-out is worth pursuing. Plastic surgeons must be prepared to negotiate adequate reimbursement carve-outs whenever possible. Ultimately, by aligning the best quality patient care with insurance companies’ financial motivations, plastic surgeons have the opportunity to improve reimbursement for some reconstructive procedures.
Convolutional Neural Network Models for Automatic Preoperative Severity Assessment in Unilateral Cleft Lip
Authors: McCullough Meghan , Ly Steven , Auslander Allyn , Yao Caroline , Campbell Alex , Scherer Stefan , Magee William P. 
Published: June 2021

Background:
Despite the wide range of cleft lip morphology, consistent scales to categorize preoperative severity do not exist. Machine learning has been used to increase accuracy and efficiency in detection and rating of multiple conditions, yet it has not been applied to cleft disease. The authors tested a machine learning approach to automatically detect and measure facial landmarks and assign severity grades using preoperative photographs.

Methods:
Preoperative images were collected from 800 unilateral cleft lip patients, manually annotated for cleft-specific landmarks, and rated using a previously validated severity scale by eight expert reviewers. Five convolutional neural network models were trained for landmark detection and severity grade assignment. Mean squared error loss and Pearson correlation coefficient for cleft width ratio, nostril width ratio, and severity grade assignment were calculated.

Results:
All five models performed well in landmark detection and severity grade assignment, with the largest and most complex model, Residual Network, performing best (mean squared error, 24.41; cleft width ratio correlation, 0.943; nostril width ratio correlation, 0.879; severity correlation, 0.892). The mobile device–compatible network, MobileNet, also showed a high degree of accuracy (mean squared error, 36.66; cleft width ratio correlation, 0.901; nostril width ratio correlation, 0.705; severity correlation, 0.860).

Conclusions:
Machine learning models demonstrate the ability to accurately measure facial features and assign severity grades according to validated scales. Such models hold promise for the creation of a simple, automated approach to classifying cleft lip morphology. Further potential exists for a mobile telephone–based application to provide real-time feedback to improve clinical decision making and patient counseling.
Diagnostic Performance of COVID-19 Reporting and Data System Classification Across Residents and Radiologists: A Retrospective Study
Authors: Koşar Tunç Melis , Kış Naciye , İnce Okan , Kurtul Yıldız Hülya , Önder Hakan 
Published: June 2021

Objective
The aim of the study was to evaluate the interobserver agreement and diagnostic accuracy of COVID-19 Reporting and Data System (CO-RADS), in patients suspected COVID-19 pneumonia.

Methods
Two hundred nine nonenhanced chest computed tomography images of patients with clinically suspected COVID-19 pneumonia were included. The images were evaluated by 2 groups of observers, consisting of 2 residents-radiologists, using CO-RADS. Reverse transcriptase–polymerase chain reaction (PCR) was used as a reference standard for diagnosis in this study. Sensitivity, specificity, area under receiver operating characteristic curve (AUC), and intraobserver/interobserver agreement were calculated.

Results
COVID-19 Reporting and Data System was able to distinguish patients with positive PCR results from those with negative PCR results with AUC of 0.796 in the group of residents and AUC of 0.810 in the group of radiologists. There was moderate interobserver agreement between residents and radiologist with κ values of 0.54 and 0.57.

Conclusions
The diagnostic performance of CO-RADS for predicting COVID-19 pneumonia showed moderate interobserver agreement between residents and radiologists.