bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison ofSpathaspora passalidarumand recombinantSaccharomyces cerevisiaefor integration of first- and second-generation ethanol production
Authors: Pereira Isabela de Oliveira , dos Santos Ângela Alves , Gonçalves Davi L , Purificação Marcela , Guimarães Nick Candiotto , Tramontina Robson , Coutouné Natalia , Zanella Eduardo , Matsushika Akinori , Stambuk Boris U , Ienczak Jaciane Lutz
Published: September 2021

First-generation ethanol (E1G) is based on the fermentation of sugars released from saccharine or starch sources, while second-generation ethanol (E2G) is focused on the fermentation of sugars released from lignocellulosic feedstocks. During the fractionation process to release sugars from hemicelluloses (mainly xylose), some inhibitor compounds are released hindering fermentation. Thus, the biggest challenge of using hemicellulosic hydrolysate is selecting strains and processes able to efficiently ferment xylose and tolerate inhibitors. With the aim of diluting inhibitors, sugarcane molasses (80% of sucrose content) can be mixed to hemicellulosic hydrolysate in an integrated E1G–E2G process. Cofermentations of xylose and sucrose were evaluated for the native xylose consumer Spathaspora passalidarum and a recombinant Saccharomyces cerevisiae strain. The industrial S. cerevisiae strain CAT-1 was modified to overexpress the XYL1, XYL2 and XKS1 genes and a mutant ([4–59Δ]HXT1) version of the low-affinity HXT1 permease, generating strain MP-C5H1. Although S. passalidarum showed better results for xylose fermentation, this yeast showed intracellular sucrose hydrolysis and low sucrose consumption in microaerobic conditions. Recombinant S. cerevisiae showed the best performance for cofermentation, and a batch strategy at high cell density in bioreactor achieved unprecedented results of ethanol yield, titer and volumetric productivity in E1G–E2G production process.
Globalization/deglobalization: lessons from liberal monetary orders
Authors: Brawley Mark R
Published: September 2021

Economic globalization never proceeded in a smooth steady trajectory. The current international economy, organized around liberal principles, faces potential problems unleashed by the COVID-19 pandemic. Two popular theoretical approaches offer varying reasons for the survivability of the contemporary order. One stresses the benefits associated with participating in liberal international orders, claiming such arrangements are essentially self-sustaining. The rival view emphasizes the uneven distribution of gains, emphasizing the role of leadership, especially for dampening crises. To examine the support for each argument, I examine the evolution of international monetary arrangements. International monetary orders lie at the heart of liberal international economies; no prior liberal monetary order has proven self-sustaining. Liberal international monetary sub-orders depend upon leadership as much as cooperation for their survival—leaders exert efforts to shape followers' actions so long as the leader draws sufficient benefits to make such efforts worthwhile. The economic disruption caused by the COVID-19 pandemic provides the latest illustration of this point, though these arguments also suggest experiences across issue-areas will vary.
Emerging middle powers and the liberal international order
Authors: Aydin Umut
Published: September 2021

In the post-Cold War era, a number of middle powers rose to prominence thanks to domestic reforms and a favourable international environment of economic and political globalization. These countries began to pursue middle power foreign policies, working actively in international organizations, engaging in areas such as conflict mediation, humanitarian assistance and the promotion of human rights, and helping to diffuse democracy and market reforms in their neighbourhoods. In this way, they contributed to the stability and expansion of the liberal international order in the post-Cold War period. Nonetheless, recent democratic and economic backsliding in these middle powers raises concerns. Focusing on the cases of Turkey and Mexico, this article explores how reversals in democratic and market reforms, exacerbated by recent trends towards deglobalization, influence emerging middle powers' foreign policies and their potential contributions to the liberal international order. I argue that whereas their rise had helped reinforce and expand the liberal international order, emerging middle powers' illiberal turn may have a destabilizing effect on this order.
How ‘making the world in its own liberal image’ made the West less liberal
Authors: Miller Benjamin
Published: September 2021

How did the attempt to make the world more liberal end up making the West less liberal? Following the end of the Cold War the US tried to promote liberalism in various parts of the world. This promotion took place under the liberal belief in its universality. A few of these attempts succeeded, most notably the integration of China into the global economy. Many other liberalizing endeavours failed, notably democracy-promotion in China, Russia and the Middle East. Yet, both the successes and the failures resulted in the rise of illiberal elements in the West as reflected in Brexit and Trumpism. The article shows how the outcomes of the attempts at liberalization—both the failures and the successes—generated these populist forces. The Chinese economic success took place at least partly because of the US-led integration of China into the international order. Yet, this success produced adverse economic effects in the West. Such outcomes led to the rise of economic populism. The American liberal interventions in the Middle East affected the rise of terrorism and of Muslim migration to the West. These developments influenced the rise of cultural populism in the West, which advances resentment of foreigners, migrants and minorities.
Donor Love Will Tear Us Apart: How Complexity and Learning Marginalize Accountability in Peacebuilding Interventions
Authors: Bächtold Stefan
Published: September 2021

Complexity theory and systems thinking are increasingly popular in both academic and practitioner discourses to “improve” peacebuilding. Recently, they have also been considered to make peacebuilding interventions more bottom-up and less exclusive. Contributing to the debate in international political sociology on the role of (professional) knowledge in shaping interventions, I examine this claim with an analysis of professional peacebuilding discourse. Drawing on an extensive corpus of operational guidance, policy documents, and interview material, I situate the emerging uses of concepts of complexity in peacebuilding against the backdrop of the power struggles of its actors and institutions. Against the introduction of measures of managerial control, professional peacebuilding discourse has cast its interventions as exceptional and in need of different methods. Thus, learning replaces donors’ standardized measures of accountability. However, the peculiar conflation of accountability as learning that emerges from these struggles legitimizes self-referential expert rule and learning, and marginalizes debates on peacebuilders’ accountability. Rather than “de-colonizing” or making peacebuilding more inclusive, the way complexity concepts have emerged in peacebuilding discourse reproduces—rather than questions—the power structures of international interventions, and denies the people targeted by interventions the status of subjects to be accountable to.
Toward a Radical IR: Transformation, Praxis, and Critique in a (Neo)Liberal World Order
Authors: Tatum Dillon Stone
Published: September 2021

Can there be a “radical IR?” Scholars have given little attention to the question of the following: where is radicalism in the discipline? I argue that not only is it possible to think about radical international theory, but that it is necessary in the contemporary world. International theorists have to grapple with developments of fundamental change, including the so-described decline of the (neo)liberal international order, transformations in global capital, and an upsurge in populist political movements that advocate for fundamental political change. In approaching the question of radicalism in IR, the article develops a working definition of radicalism as an approach to politics that focuses on the International as a whole, uses theoretical tools from the humanistic sciences to engage in an active politics of fundamental transformation, and deploys methods that are historicist, genealogical, and oriented toward “getting to the root of things.” Additionally, the paper illustrates the virtues and promises of a radical IR by using the case of (neo)liberal world order arguments to show how a radical IR could change the trajectory of these engagements.
The Dynamics of Social Capital: Examining the Reciprocity between Network Features and Social Support
Authors: Xu Shan , Li Wenbo , Zhang Weiwu
Published: September 2021

An essential tenet of social capital is that it is a reciprocal process: social networks produce desirable outcomes, and the resulting outcomes can then feed back into influencing networks. The current study is among the first to examine a dynamic, reciprocal process of social capital, using within-person measures from 2,065 reports of offline and online daily social interactions from 66 participants over a 1-week period. Results show that online and offline social interactions, characterized by tie strength and communication diversity, generate different levels of emotional, practical, and informational support, which, in turn, exerts differential influence on tie strength and diversity of subsequent interactions. Results also reveal a mismatch between the resulting social support and subsequent motivated social interactions. Importantly, social support reinforces subsequent tie strength but reduces communication diversity.
Landscape Anthropization Affects Mosquito Diversity in a Deciduous Forest in Southeastern Mexico
Authors: Barrientos-Roldán Maggi Janelly , Abella-Medrano Carlos Antonio , Ibáñez-Bernal Sergio , Sandoval-Ruiz César Antonio
Published: September 2021

Mosquitoes (Diptera: Culicidae) are considered the group of insects that most impacts human health. Land use change, conversion of conserved sites into agricultural environments, urbanization, defaunation, and introduction of domestic animals can affect mosquito diversity positively or negatively, increasing the risk of transmission of zoonotic diseases. Here, we describe the diversity of adult mosquitoes in two environments (deciduous forest and anthropized zone) over 2 yr (2014–2016), using eight CDC traps at each site in three climatic seasons (rainy, cold, and dry). We captured 795 individuals belonging to 22 species. We constructed rank-abundance curves to determine spatial and temporal changes in the mosquito communities. We measured alpha diversity using the Shannon index (H′), Shannon exponential (eH) and Simpson dominance (Ds), and beta diversity using Jaccard’s coefficient of similarity (Ij). The most abundant species were Culex quinquefasciatus (40.5%), Culex coronator (18.3%), and Anopheles pseudopunctipennis (12.4%). The highest mosquito diversity was in the deciduous forest during the rainy season. Beta diversity analysis showed that species overlap varied among climatic seasons, with the sites sharing 65% species during the rainy season, but only 33% of species during the dry season. We found differences in the diversity of mosquitoes at the two sites, and the mosquito assemblage of the anthropized zone was significantly different from that of the deciduous forest.
Unsettling Entitlement and ‘Ginx’s Baby’
Authors: Cohen Monica F
Published: September 2021

This story traces the many adventures of a title, from Edward Jenkins’s 1870 novel, Ginx’s Baby, through colonial resistance to imperial copyright law in Canada, to the photograph of a distressed baby that Charles Darwin featured in The Expression of Emotions in Man and Animals and that the art photographer Oscar Rejlander reproduced as popular cartes de visites. The reiterative use of the title across genres and oceans conjures an image of Victorian popular culture as an unregulated bazaar affording the surprising emergence of unintended creators. Copyright history, frame analysis, and name theory help explain how the title of a popular novel could lend itself to so many unrelated creative objects.
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

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

Transcriptional 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

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

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.
Perioperative Care of Patients Undergoing Major Complex Spinal Instrumentation Surgery: Clinical Practice Guidelines From the Society for Neuroscience in Anesthesiology and Critical Care
Authors: Blacker Samuel N. , Vincent Anita , Burbridge Mark , Bustillo Maria , Hazard Sprague W. , Heller Benjamin J. , Nadler Jacob W. , Sullo Elaine , Lele Abhijit V. ,   On Behalf of the Society for Neuroscience in Anesthesiology and Critical Care
Published: September 2021

Evidence-based standardization of the perioperative management of patients undergoing complex spine surgery can improve outcomes such as enhanced patient satisfaction, reduced intensive care and hospital length of stay, and reduced costs. The Society for Neuroscience in Anesthesiology and Critical Care (SNACC) tasked an expert group to review existing evidence and generate recommendations for the perioperative management of patients undergoing complex spine surgery, defined as surgery on 2 or more thoracic and/or lumbar spine levels. Institutional clinical management protocols can be constructed based on the elements included in these clinical practice guidelines, and the evidence presented.
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.

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.
Clinicopathological significance and prognostic value of P27 expression in gastric cancer patients: a meta-analysis
Authors: Feng Hui , Zhang Hongmei , Yan Zongting
Published: September 2021

Loss of P27 expression correlates with clinical progression in a variety of human cancers. However, the correlation between P27 expression and gastric cancer remains controversial. In this meta-analysis, we performed an electronic search based on six databases to select a sufficient number of studies. Pooled hazard ratio (HR) was used as estimates to investigate the association between P27 expression and prognosis of patients with gastric cancer. We identified 19 studies with 2387 gastric cancer patients, ranging between 50 and 316 samples per study. Q and I
2 tests demonstrated that the homogeneity among 19 studies (I
2 = 47%, P = 0.0004), thus we applied a fixed-effects model to calculate the pooled HR of P27expression and overall survival (OS) of gastric cancer patients was 0.68, and 95% confidence interval (CI) was 0.60–0.78. Next, we conducted a subgroup meta-analysis and found that patients with low P27 expression in Asians (HR = 0.69, 95% CI: 0.58–0.82) and non-Asians (HR = 0.57, 95% CI: 0.41–0.79) had poor prognosis. In addition, we found the publication bias results of OS in the final included 19 studies showed that this funnel plot presented incomplete symmetry, and then removed three literatures with larger HRs bias, and found that the remaining 16 literatures were homogeneity (I
2 = 0%, P = 0.47), the pooled HR was 0.52 with 95% CI of 0.43-0.62, and the publication bias disappeared. These results suggested a strong association between P27 underexpression and poorer prognosis of gastric cancer in patients. P27 may be a tumor suppressor for predicting survival outcome of gastric cancer patients.
Arsenic sulfide inhibits the progression of gastric cancer through regulating the circRNA_ASAP2/Wnt/β-catenin pathway
Authors: Hu Jing , Hu Bin , Deng Li , Cheng Lin , Fan Qunhong , Lu Caibao
Published: September 2021

In our paper, the effects of As4S4 treatments on the growth and migration of gastric cancer (GC) cells were explored, and the potential underlying molecular mechanisms were also identified. Cell viability was evaluated by cell counting kit 8 assay. The expression of Ki-67 was examined using immunofluorescence staining. Cell apoptosis was assessed by flow cytometry. The migratory and invasion abilities of cells were determined using Transwell assay. The mRNA and protein levels of related gene were examined by RT-qPCR and western blotting, respectively. CircRNAs chip was performed to identify the differentiated expression of circRNAs in GC cells following the treatment with As4S4. Our results revealed that the proliferation, migration and invasion of GC cells were remarkably suppressed by the treatment with As4S4, while cell apoptosis was promoted. Furthermore, circRNA_ASAP2 was a novel target of As4S4 in GC, and it is involved in As4S4-modulated biological behavior alterations in GC cells. In addition, the activities of the Wnt/β-catenin signaling in GC cells were affected by the overexpression circRNA_ASAP2 and the treatment with As4S4. Moreover, the behavior changes in GC cells caused by the knockdown of circRNA_ASAP2 were reversed by the treatment with Wnt agonist SKL2001. In summary, As4S4 could function as an antitumor agent in GC through regulating the circRNA_ASAP2/Wnt/β-catenin pathway, which in turn influences the growth and metastasis of GC cells.
Skin Cancer Incidence in Organ Transplant Recipients Referred for Benign Skin Conditions
Authors: Chundydyal Sakil , Cheng Joyce Y. , Wang Mike , Li Fang-Yong , Colegio Oscar R.
Published: September 2021

BACKGROUND

Solid organ transplant recipients (SOTRs) are at ∼100-fold increased risk for developing skin cancers compared with the general population, with increased morbidity and mortality. These patients are closely followed by dermatology; however, it is unclear how referral reasons from nondermatologic providers affect care in these patients.

OBJECTIVE

This study examines the reason SOTRs are referred to dermatologic care by nondermatologic providers as a potential predictor of nonmelanoma skin cancer (NMSC) outcomes.

MATERIALS AND METHODS

A retrospective case–control study was conducted with the records of 353 adult SOTRs referred to a specialized transplant dermatology clinic within an academic tertiary care center between 2007 and mid-2012.

RESULTS

Eighty-one patients were diagnosed with 491 total premalignant and malignant skin lesions. A considerable proportion of patients diagnosed with NMSC were referred for benign skin conditions such as rash or acne.

CONCLUSION

These results indicate that some SOTRs referred to dermatology for benign skin disorders are incidentally diagnosed with cutaneous malignancies; this is concerning given that referrals for benign skin conditions may delay appropriate care for cutaneous malignancies and preventative care. Better risk stratification, improved interdisciplinary collaboration, and prompt referrals for dermatologic care are needed in the care of SOTRs.
Observed Versus Expected COVID-19 Infections Among National Football League Players During the 2020 Season
Authors: Lopez Michael J. , Mack Christina , Bliss Thompson , Wasserman Erin B. , Myers Emily , Solomon Gary , Lynch John , Casolaro Anthony , Osterholm Michael , Hanfling Dan , Mayer Thom , Sills Allen K.
Published: September 2021

Background:

The National Football League (NFL) and National Football League Players Association implemented a set of strict protocols for the 2020 season with the intent to mitigate COVID-19 risk among players and staff. In that timeframe, the league’s 32 teams completed 256 regular season games and several thousand meetings and practices. In parallel, community cases of COVID-19 were highly prevalent. We assess the risk of holding a 2020 NFL season by comparing community and player COVID-19 infections.

Methods:

We used county-level COVID-19 test data from each team to establish baseline distributions of infection rates expected to occur in a population similar in age and sex to NFL players. We used a binomial distribution to simulate expected infections in each community cohort and compared these findings with observed COVID-19 infections in players.

Results:

Over a 5-month period (1 August 2020 to 2 January 2021), positive NFL player infections (n = 256) were 55.7% lower than expected when compared with simulations from NFL community cohorts. For 30 of 32 teams (94%), observed counts fell at or below expectation, including 28 teams (88%) for which rates were lower. Two teams fell above baseline expectation.

Conclusions:

The NFL/NFLPA protocols that governed team facilities, travel, gameday, and activities outside of the workplace were associated with lower infection rates among NFL players compared with the surrounding community. The NFL’s 2020–2021 season are consistent with the hypothesis that robust testing and behavioral protocols support a safe return to sport and work.
Face Mask–Associated Recurrent Corneal Erosion Syndrome and Corneal Infection
Authors: Tang Yi Fan , Chong Elaine W. T.
Published: September 2021

In the current coronavirus disease 2019 (COVID-19) pandemic, important public health measures such as the utilization of face masks has been widely enforced, including community-wide mandatory face mask use. During this period, there have been observations of an increasing number of patients presenting with dry eye symptoms among regular mask users with no history of ocular surface pathology. Individuals have reported being aware of air blowing upward from the mask into their eyes that is likely to increase the evaporation of their tear film leading to ocular irritation. Although face mask use is essential in combatting the COVID-19 pandemic, it is important to recognize the potential effects it may have on ocular health. We report a case of face mask–associated ocular complication. After an initial cornea abrasion from mask use, the patient developed recurrent corneal erosion syndrome that was complicated by microbial keratitis after the enforcement of mandatory mask use in public areas.
Prostaglandin E2 and F2α Alter Expression of Select Cholesteryl Esters and Triacylglycerols Produced by Human Meibomian Gland Epithelial Cells
Authors: Ziemanski Jillian F. , Wilson Landon , Barnes Stephen , Nichols Kelly K.
Published: September 2021

Purpose:

PGF2α analogs are commonly used to treat glaucoma and are associated with higher rates of meibomian gland dysfunction (MGD). The purpose of this study was to evaluate the physiological effects of PGF2α and PGE2 on immortalized human meibomian gland epithelial cells (HMGECs).

Methods:

HMGECs were immunostained for the 4 PGE2 receptors (EP1, EP2, EP3, and EP4) and 1 PGF2α receptor (FP) and imaged. Rosiglitazone-differentiated HMGECs were exposed to PGF2α and PGE2 (10−9 to 10−6 M) for 3 hours. Cell viability was assessed by an adenosine triphosphate–based luminescent assay, and lipid extracts were analyzed for cholesteryl esters (CEs), wax esters (WEs), and triacylglycerols (TAGs) by ESI-MSMSALL in positive ion mode by a Triple TOF 5600 Mass Spectrometer using SCIEX LipidView 1.3.

Results:

HMGECs expressed 3 PGE2 receptors (EP1, EP2, and EP4) and the 1 PGF2α receptor (FP). Neither PGE2 nor PGF2α showed signs of cytotoxicity at any of the concentrations tested. WEs were not detected from any of the samples, but both CEs and TAGs exhibited a diverse and dynamic profile. PGE2 suppressed select CEs (CE 22:1, CE 26:0, CE 28:1, and CE 30:1). PGF2α dose dependently increased several CEs (CE 20:2, CE 20:1, CE 22:1, and CE 24:0) yet decreased others. Both prostaglandins led to nonspecific TAG remodeling.

Conclusions:

PGE2 and PGF2α showed minimal effect on HMGEC viability. PGF2α influences lipid expression greater than PGE2 and may do so by interfering with meibocyte differentiation. This work may provide insight into the mechanism of MGD development in patients with glaucoma treated with PGF2α analogs.
Topical Insulin—Utility and Results in Refractory Neurotrophic Keratopathy in Stages 2 and 3
Authors: Soares Ricardo José dos Santos Machado , Arêde Carlos , Sousa Neves Filipe , da Silva Fernandes Joana , Cunha Ferreira Catarina , Sequeira Joaquim
Published: September 2021

Purpose:

The purpose of this study was to evaluate the clinical outcome of patients with refractory neurotrophic keratopathy (NK) in stages 2 and 3 treated with topical insulin.

Methods:

Retrospective analysis of eyes with NK in stages 2 and 3 refractory to standard medical and/or surgical treatment which were treated with topical insulin (1 unit per mL). This treatment was applied 4 times per day and was continued until the persistent epithelial defect (PED) or ulcer resolved. The primary outcome of the study was the complete reepithelialization of the PED or persistent ulcer. “Best-corrected visual acuity” pretreatment and posttreatment, “days until complete reepithelialization” data, and anterior segment photographs were obtained. Outcome measures were compared before and after treatment in both groups using paired and independent samples t tests.

Results:

Twenty-one eyes were included in this study, and 90% achieved complete reepithelialization of the PED and/or persistent ulcer within 7 to 45 days of follow-up. The mean number of days until complete reepithelialization was significantly lower in NK stage 2 (18 ± 9 days) when compared with NK stage 3 (29 ± 11 days) (P = 0.025). The best-corrected visual acuity improved significantly in both NK stage 2 (P < 0.001) and NK stage 3 (P = 0.004). No side effects were reported during the follow-up.

Conclusions:

Our results suggest that topical insulin drops may be an effective therapeutic in refractory NK. This therapy may prove extremely useful because of its low cost and high accessibility.