bluuebunny/crossref_metadata_2025 huggingface dataset:
OzDES reverberation mapping program: Lag recovery reliability for 6-yr C iv analysis
Authors: Penton A , Malik U , Davis T M , Martini P , Yu Z , Sharp R , Lidman C , Tucker B E , Hoormann J K , Aguena M , Allam S , Annis J , Asorey J , Bacon D , Bertin E , Bhargava S , Brooks D , Calcino J , Carnero Rosell A , Carollo D , Carrasco Kind M , Carretero J , Costanzi M , da Costa L N , Pereira M E S , De Vicente J , Diehl H T , Eifler T F , Everett S , Ferrero I , Fosalba P , Frieman J , García-Bellido J , Gaztanaga E , Gerdes D W , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kim A G , Kuehn K , Kuropatkin N , Maia M A G , Marshall J L , Menanteau F , Miquel R , Morgan R , Möller A , Palmese A , Paz-Chinchón F , Plazas A A , Romer A K , Sanchez E , Scarpine V , Scolnic D , Serrano S , Smith M , Suchyta E , Swanson M E C , Tarle G , To C , Uddin S A , Varga T N , Wester W , Wilkinson R D , Lewis G ,   (DES Collaboration)
Published: October 2021

We present the statistical methods that have been developed to analyse the OzDES reverberation mapping sample. To perform this statistical analysis we have created a suite of customizable simulations that mimic the characteristics of each source in the OzDES sample. These characteristics include: the variability in the photometric and spectroscopic light curves, the measurement uncertainties, and the observational cadence. By simulating the sources in the OzDES sample that contain the C iv emission line, we developed a set of criteria that rank the reliability of a recovered time-lag depending on the agreement between different recovery methods, the magnitude of the uncertainties, and the rate at which false positives were found in the simulations. These criteria were applied to simulated light curves and these results used to estimate the quality of the resulting Radius–Luminosity relation. We grade the results using three quality levels (gold, silver, and bronze). The input slope of the R–L relation was recovered within 1σ for each of the three quality samples, with the gold standard having the lowest dispersion with a recovered a R–L relation slope of 0.454 ± 0.016 with an input slope of 0.47. Future work will apply these methods to the entire OzDES sample of 771 AGN.
Characterizing the PAH emission in the Orion Bar
Authors: Knight C , Peeters E , Tielens A G G M , Vacca W D
Published: October 2021

We present 5–14 $\mu$m spectra at two different positions across the Orion Bar photodissociation region (PDR) obtained with the Infrared Spectrograph onboard the Spitzer Space Telescope and 3.3 $\mu$m PAH observations obtained with the Stratospheric Observatory for Infrared Astronomy (SOFIA). We aim to characterize emission from Polycyclic Aromatic Hydrocarbon (PAH), dust, atomic and molecular hydrogen, argon, sulfur, and neon as a function of distance from the primary illuminating source. We find that all the major PAH bands peak between the ionization front and the PDR front, as traced by H2, while variations between these bands become more pronounced moving away from this peak into the face-on PDRs behind the PDR front and at the backside of the H ii region. While the relative PAH intensities are consistent with established PAH characteristics, we report unusual behaviours and attribute these to the PDR viewing angle and the strength of the FUV radiation field impinging on the PDRs. We determine the average PAH size which varies across the Orion Bar. We discuss subtle differences seen between the cationic PAH bands and highlight the photochemical evolution of carbonaceous species in this PDR environment. We find that PAHs are a good tracer of environmental properties such as the strength of the FUV radiation field and the PAH ionization parameter.
The search for the farthest quasar: consequences for black hole growth and seed models
Authors: Pacucci Fabio , Loeb Abraham
Published: October 2021

The quest for high-redshift quasars has led to a series of record-breaking sources, with the current record holder at z = 7.642. Here, we show how future detections of z > 8 quasars impact the constraints on the parameters for black hole growth and seed models. Using broad flat priors on the growth parameters (Eddington ratio $\, {f_{\rm Edd}}$, duty cycle ${\cal D}$, seed mass M•,seed, and radiative efficiency ϵ), we show that the large uncertainties in their determination decrease by a factor ∼5 when a quasar’s detection redshift goes from z = 9 to z = 12. In this high-redshift regime, ϵ tends to the lowest value allowed, and the distribution for M•,seed peaks well inside the heavy seed domain. Remarkably, two quasars detected at z > 7 with low accretion rates (J1243+0100 and J0313–1806) already tighten the available parameter space, requiring $M_{\rm \bullet , seed} \gt 10^{3.5} \, {\rm M_\odot }$ and ϵ < 0.1. The radiative efficiency is a crucial unknown, with factor ∼2 changes able to modify the predicted mass by ∼3 orders of magnitude already at z ∼ 9. The competing roles of inefficient accretion (decreasing ϵ) and black hole spin-up (increasing ϵ) significantly impact growth models. Finally, we suggest that yields currently predicted by upcoming quasar surveys (e.g. Euclid) will be instrumental for determining the most-likely seed mass regime. For example, assuming thin-disc accretion, a detection of a quasar with $M_\bullet \sim 10^{10} \, {\rm M_\odot }$ by z ∼ 9–10 would exclude the entire parameter space available for light seeds and dramatically reduce the one for heavy seeds.
Immunogenicity of sarilumab and impact on safety and efficacy in Japanese patients with rheumatoid arthritis: analysis of two Phase 3 randomised clinical trials
Authors: Tanaka Yoshiya , Takahashi Toshiya , Sumi Mariko , Hagino Owen , Van Hoogstraten Hubert , Xu Christine , Kato Naoto , Kameda Hideto
Published: October 2021

Objectives

To describe the immunogenicity profile of sarilumab in Japanese patients with rheumatoid arthritis (RA).

Methods

Patients enrolled in the KAKEHASI and HARUKA studies were included in our analysis. In these studies, patients received sarilumab 150 mg or 200 mg every 2 weeks for 52 or 28 weeks in combination with methotrexate (MTX) (KAKEHASI), or for 52 weeks as monotherapy or in combination with non-MTX conventional synthetic disease-modifying anti-rheumatic drugs (HARUKA). Anti-drug antibodies (ADAs) and neutralising antibodies (NAbs) were assessed in the pooled population.

Results

Positive ADA assay responses occurred in 10/149 (7.1%) patients treated with sarilumab 150 mg and 13/185 (7.0%) patients treated with sarilumab 200 mg, with persistent responses in 2 (1.4%) and 4 (2.2%) patients, respectively. Peak ADA titre was 30. No patients treated with the 150 mg dose and one patient (0.5%) treated with the 200 mg dose exhibited NAbs. There was no evidence of an association between ADA formation and hypersensitivity reactions or reduced efficacy.

Conclusions

ADAs, which occurred at a low frequency and titre, did not affect the safety or efficacy of sarilumab 150 or 200 mg administered as monotherapy or combination therapy in Japanese patients with RA in the KAKEHASI or HARUKA studies.
Evolutionary repair reveals an unexpected role of the tRNA modification m1G37 in aminoacylation
Authors: Clifton Ben E , Fariz Muhammad A , Uechi Gen-Ichiro , Laurino Paola
Published: October 2021

The tRNA modification m1G37, introduced by the tRNA methyltransferase TrmD, is thought to be essential for growth in bacteria because it suppresses translational frameshift errors at proline codons. However, because bacteria can tolerate high levels of mistranslation, it is unclear why loss of m1G37 is not tolerated. Here, we addressed this question through experimental evolution of trmD mutant strains of Escherichia coli. Surprisingly, trmD mutant strains were viable even if the m1G37 modification was completely abolished, and showed rapid recovery of growth rate, mainly via duplication or mutation of the proline-tRNA ligase gene proS. Growth assays and in vitro aminoacylation assays showed that G37-unmodified tRNAPro is aminoacylated less efficiently than m1G37-modified tRNAPro, and that growth of trmD mutant strains can be largely restored by single mutations in proS that restore aminoacylation of G37-unmodified tRNAPro. These results show that inefficient aminoacylation of tRNAPro is the main reason for growth defects observed in trmD mutant strains and that proS may act as a gatekeeper of translational accuracy, preventing the use of error-prone unmodified tRNAPro in translation. Our work shows the utility of experimental evolution for uncovering the hidden functions of essential genes and has implications for the development of antibiotics targeting TrmD.
Chromatin loading of MCM hexamers is associated with di-/tri-methylation of histone H4K20 toward S phase entry
Authors: Hayashi-Takanaka Yoko , Hayashi Yuichiro , Hirano Yasuhiro , Miyawaki-Kuwakado Atsuko , Ohkawa Yasuyuki , Obuse Chikashi , Kimura Hiroshi , Haraguchi Tokuko , Hiraoka Yasushi
Published: October 2021

DNA replication is a key step in initiating cell proliferation. Loading hexameric complexes of minichromosome maintenance (MCM) helicase onto DNA replication origins during the G1 phase is essential for initiating DNA replication. Here, we examined MCM hexamer states during the cell cycle in human hTERT-RPE1 cells using multicolor immunofluorescence-based, single-cell plot analysis, and biochemical size fractionation. Experiments involving cell-cycle arrest at the G1 phase and release from the arrest revealed that a double MCM hexamer was formed via a single hexamer during G1 progression. A single MCM hexamer was recruited to chromatin in the early G1 phase. Another single hexamer was recruited to form a double hexamer in the late G1 phase. We further examined relationship between the MCM hexamer states and the methylation levels at lysine 20 of histone H4 (H4K20) and found that the double MCM hexamer state was correlated with di/trimethyl-H4K20 (H4K20me2/3). Inhibiting the conversion from monomethyl-H4K20 (H4K20me1) to H4K20me2/3 retained the cells in the single MCM hexamer state. Non-proliferative cells, including confluent cells or Cdk4/6 inhibitor-treated cells, also remained halted in the single MCM hexamer state. We propose that the single MCM hexamer state is a halting step in the determination of cell cycle progression.
Probing the stability of the SpCas9–DNA complex after cleavage
Authors: Aldag Pierre , Welzel Fabian , Jakob Leonhard , Schmidbauer Andreas , Rutkauskas Marius , Fettes Fergus , Grohmann Dina , Seidel Ralf
Published: October 2021

CRISPR–Cas9 is a ribonucleoprotein complex that sequence-specifically binds and cleaves double-stranded DNA. Wildtype Cas9 and its nickase and cleavage-incompetent mutants have been used in various biological techniques due to their versatility and programmable specificity. Cas9 has been shown to bind very stably to DNA even after cleavage of the individual DNA strands, inhibiting further turnovers and considerably slowing down in-vivo repair processes. This poses an obstacle in genome editing applications. Here, we employed single-molecule magnetic tweezers to investigate the binding stability of different Streptococcus pyogenes Cas9 variants after cleavage by challenging them with supercoiling. We find that different release mechanisms occur depending on which DNA strand is cleaved. After initial target strand cleavage, supercoils are only removed after the collapse of the R-loop. We identified several states with different stabilities of the R-loop. Most importantly, we find that the post-cleavage state of Cas9 exhibits a higher stability than the pre-cleavage state. After non-target strand cleavage, supercoils are immediately but slowly released by swiveling of the non-target strand around Cas9 bound to the target strand. Consequently, Cas9 and its non-target strand nicking mutant stay stably bound to the DNA for many hours even at elevated torsional stress.
Discovery of highly reactive self-splicing group II introns within the mitochondrial genomes of human pathogenic fungi
Authors: Liu Tianshuo , Pyle Anna M
Published: October 2021

Fungal pathogens represent an expanding global health threat for which treatment options are limited. Self-splicing group II introns have emerged as promising drug targets, but their development has been limited by a lack of information on their distribution and architecture in pathogenic fungi. To meet this challenge, we developed a bioinformatic workflow for scanning sequence data to identify unique RNA structural signatures within group II introns. Using this approach, we discovered a set of ubiquitous introns within thermally dimorphic fungi (genera of Blastomyces, Coccidioides and Histoplasma). These introns are the most biochemically reactive group II introns ever reported, and they self-splice rapidly under near-physiological conditions without protein cofactors. Moreover, we demonstrated the small molecule targetability of these introns by showing that they can be inhibited by the FDA-approved drug mitoxantrone in vitro. Taken together, our results highlight the utility of structure-based informatic searches for identifying riboregulatory elements in pathogens, revealing a striking diversity of reactive self-splicing introns with great promise as antifungal drug targets.
PharmacoDB 2.0: improving scalability and transparency of in vitro pharmacogenomics analysis
Authors: Feizi Nikta , Nair Sisira Kadambat , Smirnov Petr , Beri Gangesh , Eeles Christopher , Esfahani Parinaz Nasr , Nakano Minoru , Tkachuk Denis , Mammoliti Anthony , Gorobets Evgeniya , Mer Arvind Singh , Lin Eva , Yu Yihong , Martin Scott , Hafner Marc , Haibe-Kains Benjamin
Published: October 2021

Cancer pharmacogenomics studies provide valuable insights into disease progression and associations between genomic features and drug response. PharmacoDB integrates multiple cancer pharmacogenomics datasets profiling approved and investigational drugs across cell lines from diverse tissue types. The web-application enables users to efficiently navigate across datasets, view and compare drug dose–response data for a specific drug-cell line pair. In the new version of PharmacoDB (version 2.0, https://pharmacodb.ca/), we present (i) new datasets such as NCI-60, the Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) dataset, as well as updated data from the Genomics of Drug Sensitivity in Cancer (GDSC) and the Genentech Cell Line Screening Initiative (gCSI); (ii) implementation of FAIR data pipelines using ORCESTRA and PharmacoDI; (iii) enhancements to drug–response analysis such as tissue distribution of dose–response metrics and biomarker analysis; and (iv) improved connectivity to drug and cell line databases in the community. The web interface has been rewritten using a modern technology stack to ensure scalability and standardization to accommodate growing pharmacogenomics datasets. PharmacoDB 2.0 is a valuable tool for mining pharmacogenomics datasets, comparing and assessing drug–response phenotypes of cancer models.
msRepDB: a comprehensive repetitive sequence database of over 80 000 species
Authors: Liao Xingyu , Hu Kang , Salhi Adil , Zou You , Wang Jianxin , Gao Xin
Published: October 2021

Repeats are prevalent in the genomes of all bacteria, plants and animals, and they cover nearly half of the Human genome, which play indispensable roles in the evolution, inheritance, variation and genomic instability, and serve as substrates for chromosomal rearrangements that include disease-causing deletions, inversions, and translocations. Comprehensive identification, classification and annotation of repeats in genomes can provide accurate and targeted solutions towards understanding and diagnosis of complex diseases, optimization of plant properties and development of new drugs. RepBase and Dfam are two most frequently used repeat databases, but they are not sufficiently complete. Due to the lack of a comprehensive repeat database of multiple species, the current research in this field is far from being satisfactory. LongRepMarker is a new framework developed recently by our group for comprehensive identification of genomic repeats. We here propose msRepDB based on LongRepMarker, which is currently the most comprehensive multi-species repeat database, covering >80 000 species. Comprehensive evaluations show that msRepDB contains more species, and more complete repeats and families than RepBase and Dfam databases. (https://msrepdb.cbrc.kaust.edu.sa/pages/msRepDB/index.html).
Genomicus in 2022: comparative tools for thousands of genomes and reconstructed ancestors
Authors: Nguyen Nga Thi Thuy , Vincens Pierre , Dufayard Jean François , Roest Crollius Hugues , Louis Alexandra
Published: October 2021

Genomicus is a database and web-server dedicated to comparative genomics in eukaryotes. Its main functionality is to graphically represent the conservation of genomic blocks between multiple genomes, locally around a specific gene of interest or genome-wide through karyotype comparisons. Since 2010 and its first release, Genomicus has synchronized with 60 Ensembl releases and seen the addition of functions that have expanded the type of analyses that users can perform. Today, five public instances of Genomicus are supporting a total number of 1029 extant genomes and 621 ancestral reconstructions from all eukaryotes kingdoms available in Ensembl and Ensembl Genomes databases complemented with four additional instances specific to taxonomic groups of interest. New visualization and query tools are described in this manuscript. Genomicus is freely available at http://www.genomicus.bio.ens.psl.eu/genomicus.
MLL1 is regulated by KSHV LANA and is important for virus latency
Authors: Tan Min , Li Shijun , Juillard Franceline , Chitas Rute , Custódio Tânia F , Xue Han , Szymula Agnieszka , Sun Qiming , Liu Bing , Álvarez Ángel L , Chen She , Huang Jing , Simas J Pedro , McVey Colin E , Kaye Kenneth M
Published: October 2021

Mixed lineage leukemia 1 (MLL1) is a histone methyltransferase. Kaposi's sarcoma-associated herpesvirus (KSHV) is a leading cause of malignancy in AIDS. KSHV latently infects tumor cells and its genome is decorated with epigenetic marks. Here, we show that KSHV latency-associated nuclear antigen (LANA) recruits MLL1 to viral DNA where it establishes H3K4me3 modifications at the extensive KSHV terminal repeat elements during primary infection. LANA interacts with MLL1 complex members, including WDR5, integrates into the MLL1 complex, and regulates MLL1 activity. We describe the 1.5-Å crystal structure of N-terminal LANA peptide complexed with MLL1 complex member WDR5, which reveals a potential regulatory mechanism. Disruption of MLL1 expression rendered KSHV latency establishment highly deficient. This deficiency was rescued by MLL1 but not by catalytically inactive MLL1. Therefore, MLL1 is LANA regulable and exerts a central role in virus infection. These results suggest broad potential for MLL1 regulation, including by non-host factors.
EWAS Open Platform: integrated data, knowledge and toolkit for epigenome-wide association study
Authors: Xiong Zhuang , Yang Fei , Li Mengwei , Ma Yingke , Zhao Wei , Wang Guoliang , Li Zhaohua , Zheng Xinchang , Zou Dong , Zong Wenting , Kang Hongen , Jia Yaokai , Li Rujiao , Zhang Zhang , Bao Yiming
Published: October 2021

Epigenome-Wide Association Study (EWAS) has become a standard strategy to discover DNA methylation variation of different phenotypes. Since 2018, we have developed EWAS Atlas and EWAS Data Hub to integrate a growing volume of EWAS knowledge and data, respectively. Here, we present EWAS Open Platform (https://ngdc.cncb.ac.cn/ewas) that includes EWAS Atlas, EWAS Data Hub and the newly developed EWAS Toolkit. In the current implementation, EWAS Open Platform integrates 617 018 high-quality EWAS associations from 910 publications, covering 51 phenotypes, 275 diseases and 104 environmental factors. It also provides well-normalized DNA methylation array data and the corresponding metadata from 115 852 samples, which involve 707 tissues, 218 cell lines and 528 diseases. Taking advantage of integrated knowledge and data in EWAS Atlas and EWAS Data Hub, EWAS Open Platform equips with EWAS Toolkit, a powerful one-stop site for EWAS enrichment, annotation, and knowledge network construction and visualization. Collectively, EWAS Open Platform provides open access to EWAS knowledge, data and toolkit and thus bears great utility for a broader range of relevant research.
Palmaris brevis spasm syndrome in manual workers using vibratory tools
Authors: Cooke R
Published: October 2021

Palmaris brevis spasm syndrome (PBSS) appears to reflect benign muscle hyperactivity, with unprovoked recurrent spasm of the muscle and consequent dimpling of the hypothenar eminence. Two cases are reported, being the first known report of the condition among manual workers or those using vibratory tools. Each was diagnosed during routine health surveillance for hand–arm vibration syndrome. With hand cramps being a frequent report among vibration-exposed workers, this condition should be considered in such cases, although the lack of reports means that the frequency of the condition is unknown. One of the employees described more frequent episodes of spasm during periods of increased manual work. Diagnosis is possible by witnessing the characteristic spasm, or by viewing photographs of it. Functional impairment is not usual, except for the brief duration of an attack. There is no consensus regarding appropriate treatment.
Underascertainment of COVID-19 cases among first responders: a seroepidemiological study
Authors: Backhaus I , Hermsen D , Timm J , Boege F , Lübke N , Göbels K , von der Lieth D , Dragano N
Published: October 2021

Background

Providing frontline support places first responders at a high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Aims

This study was aimed to determine the anti-SARS-CoV-2 seroprevalence in a cohort of first responders (i.e. firefighters/paramedics), to detect the underascertainment rate and to assess risk factors associated with seropositivity.

Methods

We conducted a serological survey among 745 first responders in Germany during 27 November and 4 December 2020 to determine the anti-SARS-CoV-2 seroprevalence using Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics, Mannheim, Germany). As part of the examination, participants were asked to provide information on coronavirus disease 2019 (COVID-19)-like-symptoms, information on sociodemographic characteristics and workplace risk factors for a SARS-CoV-2 infection and any prior COVID-19 infection. Descriptive statistics and logistic regression analysis were performed and seroprevalence estimates were adjusted for test sensitivity and specificity.

Results

The test-adjusted seroprevalence was 4% (95% CI 3.1–6.2) and the underascertainment rate was 2.3. Of those tested SARS-CoV-2 antibody positive, 41% were aware that they had been infected in the past. Seropositivity was elevated among paramedics who worked in the emergency rescue team providing first level of pre-hospital emergency care (6% [95% CI 3.4–8.6]) and those directly exposed to a COVID-19 case (5% [95% CI 3.5–8.1]). Overall, the seroprevalence and the underascertainment rate were higher among first responders than among the general population.

Conclusions

The high seroprevalence and underascertainment rate highlight the need to mitigate potential transmission within and between first responders and patients. Workplace control measures such as increased and regular COVID-19-testing and the prompt vaccination of all personnel are necessary.
Changes in Pain Self-Efficacy, Coping Skills, and Fear-Avoidance Beliefs in a Randomized Controlled Trial of Yoga, Physical Therapy, and Education for Chronic Low Back Pain
Authors: Marshall Allison , Joyce Christopher T , Tseng Bryan , Gerlovin Hanna , Yeh Gloria Y , Sherman Karen J , Saper Robert B , Roseen Eric J
Published: October 2021

Objective

We evaluated exercise interventions for cognitive appraisal of chronic low back pain (cLBP) in an underserved population.

Methods

We conducted a secondary analysis of the Back to Health Trial, showing yoga to be noninferior to physical therapy (PT) for pain and function outcomes among adults with cLBP (n = 320) recruited from primary care clinics with predominantly low-income patients. Participants were randomized to 12 weeks of yoga, PT, or education. Cognitive appraisal was assessed with the Pain Self-Efficacy Questionnaire (PSEQ), Coping Strategies Questionnaire (CSQ), and Fear-Avoidance Beliefs Questionnaire (FABQ). Using multiple imputation and linear regression, we estimated within- and between-group changes in cognitive appraisal at 12 and 52 weeks, with baseline and the education group as references.

Results

Participants (mean age = 46 years) were majority female (64%) and majority Black (57%), and 54% had an annual household income <$30,000. All three groups showed improvements in PSEQ (range 0–60) at 12 weeks (yoga, mean difference [MD] = 7.0, 95% confidence interval [CI]: 4.9, 9.0; PT, MD = 6.9, 95% CI: 4.7 to 9.1; and education, MD = 3.4, 95% CI: 0.54 to 6.3), with yoga and PT improvements being clinically meaningful. At 12 weeks, improvements in catastrophizing (CSQ, range 0–36) were largest in the yoga and PT groups (MD = –3.0, 95% CI: –4.4 to –1.6; MD = –2.7, 95% CI: –4.2 to –1.2, respectively). Changes in FABQ were small. No statistically significant between-group differences were observed on PSEQ, CSQ, or FABQ at either time point. Many of the changes observed at 12 weeks were sustained at 52 weeks.

Conclusion

All three interventions were associated with improvements in self-efficacy and catastrophizing among low-income, racially diverse adults with cLBP.

Trial registration

ClinicalTrials.gov identifier NCT01343927.
Using a Learning Health System to Improve Physical Therapy Care for Patients With Intermittent Claudication: Lessons Learned From the ClaudicatioNet Quality System
Authors: Sinnige Anneroos , Spruijt Steffie , Saes Mickey , Van der Wees Philip J , Hoogeboom Thomas J , Teijink Joep A W
Published: October 2021

Absrtact

 

Routinely collected outcomes data can be used to improve physical therapy care through benchmarking, personalization, continued education, and treatment optimization. This article describes how a nationwide infrastructure to routinely collect data from daily practice was created and how these data were used through a support system (called the ClaudicatioNet Quality system) to improve physical therapy care for patients with intermittent claudication in the Netherlands. ClaudicatioNet is a nationwide network of 2100 specialized physical therapists, providing high-quality supervised exercise therapy in combination with lifestyle counseling. The ClaudicatioNet Quality system uses a large national registry in which specific relevant health outcomes have been routinely collected since 2015. These data have then been used in turn to assess quality of care and provide transparency to therapists and other stakeholders. The Quality system is intended to serve as a learning health system, to support continuous learning at the therapist, practice, and network level. In this approach, individual patients and physical therapists are provided with opportunities to personalize, benchmark, and evaluate (and possibly alter) a treatment plan using routinely collected data from historical patients. The Quality system is described based on the essential elements of a learning health system. The challenges and lessons learned in developing the Quality system also are described.

Impact

The use of routinely collected health outcomes can, if implemented correctly, facilitate continuous learning among physical therapists and contribute to person-centered care. This example of a learning health system might serve as a blueprint for physical therapists on how to optimally implement and distill meaning from routinely collected clinical data.
Updates in Motor Learning: Implications for Physical Therapist Practice and Education
Authors: Leech Kristan A , Roemmich Ryan T , Gordon James , Reisman Darcy S , Cherry-Allen Kendra M
Published: October 2021

Over the past 3 decades, the volume of human motor learning research has grown enormously. As such, the understanding of motor learning (ie, sustained change in motor behavior) has evolved. It has been learned that there are multiple mechanisms through which motor learning occurs, each with distinctive features. These mechanisms include use-dependent, instructive, reinforcement, and sensorimotor adaptation-based motor learning. It is now understood that these different motor learning mechanisms contribute in parallel or in isolation to drive desired changes in movement, and each mechanism is thought to be governed by distinct neural substrates. This expanded understanding of motor learning mechanisms has important implications for physical therapy. It has the potential to facilitate the development of new, more precise treatment approaches that physical therapists can leverage to improve human movement. This Perspective describes scientific advancements related to human motor learning mechanisms and discusses the practical implications of this work for physical therapist practice and education.
Mild cognitive impairment in patients with systemic sclerosis and features analysis
Authors: Wuriliga  , Xu Dong , He Yang , Xu Dan , Chen Beidi , Li Xue , Zhang Xiaoying , Zhang Jun , Shen Ming , Mu Rong
Published: October 2021

Objective

Nervous system damage in patients with SSc has recently attracted attention. In this study, we aimed to explore mild cognitive impairment (MCI) in SSc patients and the characteristics of these patients.

Methods

A total of 103 SSc patients were consecutively enrolled from July 2018 to May 2019, and 97 matched healthy individuals were also included as controls. Brief cognitive tests, such as the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ), were used to assess the cognitive function of all subjects. We compared the differences in MCI between SSc patients and healthy controls, as well as the differences in demographic and clinical features between SSc patients with and without MCI. Associations of quantitative demographic and clinical features with MoCA-BJ scores in the SSc patients were also evaluated.

Results

The score of MoCA-BJ was lower in the SSc group compared with those in the healthy group [24 (9–30) vs 26 (15–30), P < 0.001]. MCI (MoCA-BJ score ≤ 25) was found in 61.2% (63/103) of the enrolled SSc patients but only in 27.8% (27/97) of the healthy individuals. Other tests evaluating some of the specific domains of cognitive functions showed that the SSc patients had impaired memory, attention and executive ability. Compared with SSc patients without MCI, SSc patients with MCI had lower education level, total serum protein and serum albumin but higher ANA positivity.

Conclusion

MCI is common in patients with SSc and should be drawn to the attention of rheumatologists. Lower education level, malnutrition and higher ANA positivity were closely related to the cognitive dysfunctions in SSc patients, providing directions for further interventions.
COVID-19 infection, admission and death among people with rare autoimmune rheumatic disease in England: results from the RECORDER project
Authors: Rutter Megan , Lanyon Peter C , Grainge Matthew J , Hubbard Richard , Peach Emily , Bythell Mary , Stilwell Peter , Aston Jeanette , Stevens Sarah , Pearce Fiona A
Published: October 2021

Objectives

To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared with the general population.

Methods

We used Hospital Episode Statistics to identify all people alive on 1 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths.

Results

We identified a cohort of 168 680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardized infection rate was 1.54 (95% CI: 1.50, 1.59) times higher than in the general population. A total of 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.41 (2.30–2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population.

Conclusions

During the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared with the general population. These increases were seen despite shielding policies.
Default and control network connectivity dynamics track the stream of affect at multiple timescales
Authors: Lettieri Giada , Handjaras Giacomo , Setti Francesca , Cappello Elisa Morgana , Bruno Valentina , Diano Matteo , Leo Andrea , Ricciardi Emiliano , Pietrini Pietro , Cecchetti Luca
Published: October 2021

In everyday life, the stream of affect results from the interaction between past experiences, expectations and the unfolding of events. How the brain represents the relationship between time and affect has been hardly explored, as it requires modeling the complexity of everyday life in the laboratory setting. Movies condense into hours a multitude of emotional responses, synchronized across subjects and characterized by temporal dynamics alike real-world experiences. Here, we use time-varying intersubject brain synchronization and real-time behavioral reports to test whether connectivity dynamics track changes in affect during movie watching. The results show that polarity and intensity of experiences relate to the connectivity of the default mode and control networks and converge in the right temporoparietal cortex. We validate these results in two experiments including four independent samples, two movies and alternative analysis workflows. Finally, we reveal chronotopic connectivity maps within the temporoparietal and prefrontal cortex, where adjacent areas preferentially encode affect at specific timescales.
Appearance concerns are uniquely associated with LPP amplitude to pictures of oneself
Authors: Jordan Carson D , Stewart Rochelle A , Brush C J , Cougle Jesse R , Hajcak Greg
Published: October 2021

A number of psychiatric disorders, including body dysmorphic disorder (BDD), anorexia nervosa, bulimia nervosa, and social anxiety disorder, are characterized by heightened appearance concerns and increased cognitive and perceptual biases toward one’s own physical appearance. In the present study, we examined individual differences in self-reported appearance anxiety and symptoms of BDD in relation to the late positive potential (LPP)—an index of stimulus significance—in response to pictures of oneself, strangers and objects among 83 female college students. The results indicated that the LPP was larger for pictures of oneself compared to pictures of strangers and objects. Further, the Yale–Brown Obsessive-Compulsive Scale Modified for Body Dysmorphic Disorder and Appearance Anxiety Inventory scales both related to an increased LPP to pictures of oneself but not to strangers or objects. The findings suggest that the LPP elicited by pictures of oneself may function as a neural marker of appearance concerns, which could be leveraged to study the development and maintenance of a range of psychiatric disorders characterized by increased appearance concerns.
New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors
Authors: Aschenbrenner Diane S.
Published: October 2021

The Food and Drug Administration (FDA) has granted accelerated approval to dostarlimab-gxly (Jemperli) for the treatment of adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors.
In Full Bloom
Authors: Fraser Diane
Published: October 2021

A daughter realizes her mother, a former geriatric nurse, is experiencing dementia.
Exploring Social and Demographic Factors as Determinants of Intestinal Inflammation in Very Low Birth-Weight Infants
Authors: Desorcy-Scherer Katelyn , Weaver Michael , Parker Leslie A.
Published: October 2021

Background:

Very low birth-weight (VLBW) infants are disproportionately affected by inflammatory morbidities including necrotizing enterocolitis. Despite the influence of social and demographic factors on infant health outcomes, their relationship with intestinal inflammation is unknown.

Purpose:

To explore the influence of maternal race, maternal socioeconomic status, and infant sex on intestinal inflammation in VLBW infants.

Methods:

This was a secondary analysis of existing data from a randomized controlled trial of 143 infants 32 weeks' gestation or less and weighing 1250 g or less. In the previous study, fecal calprotectin and S100A12 values were collected at weeks 3 and 6. The infant sample was determined on the basis of the availability of these results, which served as intestinal inflammation biomarkers for the present study. General linear mixed models assessed the relationship between biomarkers and social and demographic factors. Gestational age, antibiotic exposure, mother's own milk feeding, acuity, and week of sample collection were used as control variables.

Findings/Results:

The sample included 124 infants. Fifty-two infants (42%) were African American, 86 (69%) had Medicaid coverage, and 65 (53%) were male. Fecal calprotectin levels were higher in African American infants (P= .02) and infants with private insurance coverage (P= .009); no difference was found between sexes. There was no association between S100A12 levels and infant sex, maternal race, or socioeconomic status.

Implications for Practice and Research:

Consideration of social and demographic factors may be important when caring for VLBW infants. Further exploration of factors contributing to associations between social or demographic factors and intestinal inflammation is needed.
Outcomes of patients with malignant esophagogastric junction obstruction receiving metallic stents: A single-center experience
Authors: Pan Yu-Ling , Wu Pei-Shan , Ye Bing-Wei , Li Chung-Pin , Lee I-Cheng , Lee Kuei-Chuan , Huang Yi-Hsiang , Hou Ming-Chih
Published: October 2021

Background:

Malignancies-related esophagogastric junction (EGJ) obstruction is usually diagnosed in inoperable status with poor clinical outcomes. Metallic stent placement at EGJ could improve dysphagia for these patients. However, studies regarding the outcomes in these patients receiving metallic stents are still limited. This study aimed to investigate the outcomes of metallic stent placement in malignant EGJ obstruction.

Methods:

Forty-one patients with inoperable malignant EGJ obstruction receiving metallic stent placement were retrospectively enrolled. The clinical outcomes between different stents and deployment techniques were analyzed.

Results:

The overall technical success rate was 97.6% and clinical success rate was 92.1%. The median overall survival time was 77 (4-893) days, and the patency time was 71 (4-893) days, respectively. Poststent radiotherapy significantly prolonged survival and stent patency. Between patients receiving uncovered or partially covered metal stents, there was no difference in procedure-related complications, survival time, and stent patency time. Moreover, the clinical outcomes in patients receiving duodenal stents for malignant EGJ obstruction are not inferior to those receiving esophageal stents.

Conclusion:

This study provides crucial information for endoscopists to establish individualized stenting strategies for malignant EGJ obstruction.
Infantile Hemangiomas
Authors: Jonak Cory , Martin Kari
Published: October 2021

This is an up-to-date review article on infantile hemangiomas written for nurse practitioners, physician assistants, and nurses working the field of dermatology. The goal of this review is to provide a brief overview of infantile hemangioma diagnostic characteristics, clinical disease course, current treatments, and differential diagnoses to assist healthcare workers in diagnosing, managing, and/or referring their patients affected by infantile hemangiomas.
The Hidradenitis Suppurativa Foundation
Authors: Ezekwe Nneamaka , Parks-Miller Angie , Hamzavi Iltefat
Published: October 2021

The Hidradenitis Suppurativa (HS) Foundation strives to improve the lives of people living with HS. To achieve that mission, the HS Foundation works through advocacy, education, and research. Our vision is to live in a world where no one suffers from HS. Read about what our organization has to offer.
Abnormal monocyte differentiation and function in chronic myelomonocytic leukemia
Authors: Dhawan Abhishek , Padron Eric
Published: October 2021

Purpose of review

Monocytes serve as the phagocytic defense surveillance system of the human body. Although there is comprehensive evidence regarding monocyte development, characterization and function under steady state hematopoietic continuum, the deviations and complexities in the monocyte secretome during myeloid malignancies have not been comprehensively examined and delineated.

Recent findings

This review summarizes the aspects of development, functions, transcriptional and cytokine-mediated regulation of monocytes during steady state hematopoiesis and also contrasts the aberrations observed in myelomonocytic leukemias like chronic myelomonocytic leukemia (CMML). It presents the findings from the major studies highlighting the novel markers for identifying CMML monocytes, altered signaling cascades, roles in disease progression and potential therapeutic interventions to reduce the monocyte mediated inflammatory milieu for disease amelioration.

Recent findings provide rationale for the development of therapeutic strategies aimed at disrupting the leukemic initiating cells and malignant monocyte axis.
Casting a NET on cancer: the multiple roles for neutrophil extracellular traps in cancer
Authors: Wolach Ofir , Martinod Kimberly
Published: October 2021

Purpose of review

The role of the innate immune system has become widely appreciated in cancer and cancer-associated disorders. Neutrophils, the most abundant circulating leukocytes, have prognostic value in determining cancer progression and survival. One of the ways by which neutrophils negatively impact outcome is by formation of neutrophil extracellular traps (NETs) which result in release of nuclear chromatin and bioactive proteins into the extracellular space. Here, we review the evidence for NETs contributions to cancer progression, metastasis, and cancer-associated thrombosis (CAT).

Recent findings

NETs are increased across several cancer types and predict progression and adverse outcome. Several preclinical and clinical observations implicate NETs in promoting tumor growth, angiogenesis and metastasis via distinct pathways. Furthermore, NETs are shown to contribute to resistance to immunotherapy. NETs also emerge as key players in the prothrombotic phenotype associated with cancer that can result in potentially life-threatening arterial and venous thrombosis. Recent mechanistic insights expose several potential targets to inhibit NET formation and disrupt the interaction between NETs and tumor cells.

Clinical and translational insights highlight the central role of NETs in cancer progression and metastasis, disease resistance and CAT. Targeting NETs and NET-associated pathways may represent a novel approach to treat cancer.
Effects of a Weight and Pain Management Program in Patients With Rheumatoid Arthritis With Obesity
Authors: Somers Tamara J. , Blumenthal James A. , Dorfman Caroline S. , Huffman Kim M. , Edmond Sara N. , Miller Shannon N. , Wren Anava A. , Caldwell David , Keefe Francis J.
Published: October 2021

Background

Obesity is associated with poor outcomes for patients with rheumatoid arthritis (RA). Effective weight management is imperative. Although traditional lifestyle behavioral weight loss programs have demonstrated efficacy for reducing weight, these interventions do not meet the pain-related weight loss challenges of RA patients with obesity.

Objective

A 12-session group program (90 minutes per session) was developed integrating pain coping skills training into a lifestyle behavioral weight loss intervention. In addition to the weekly group sessions, participants engaged in supervised exercise sessions 3 times per week.

Methods

Through a small, pilot randomized trial, 50 participants were randomized to receive the intervention (n = 29) or standard care of RA (n = 21). Feasibility data (i.e., accrual, attrition, adherence) was examined using descriptive statistics (e.g., percent). We examined patterns of change in study outcomes from baseline to follow-up separately for the intervention and standard care arms using descriptive statistics and paired t tests. Effect sizes are also presented.

Results

Of those randomized to the intervention group,79.3% initiated treatment, with participants attending 74.3% of group skills sessions and 64.2% of exercise sessions. Intervention participants evidenced reductions in weight (mean, −2.28 kg) and waist circumference (mean, −4.76 cm) and improvements in physical functioning, eating behaviors, pain, and self-efficacy for weight control.

Conclusions

Findings suggest that incorporating a combined pain coping skills training and behavioral weight loss intervention into medical management of RA may improve outcomes. Study accrual and attrition, as well as intervention adherence, will inform future, larger randomized efficacy trials of the intervention.

Retrospectively registered: January 29, 2020, NCT04246827
Development of a COVID-19 Vaccine Readiness Kit for Veterans With Rheumatologic Diseases on Immunomodulators
Authors: Kumar Bharat , Fick Benjamin , Seeman Lisa , Levins Lori , Davis Benjamin , Swee Melissa L.
Published: October 2021

Background

The advent of multiple safe and effective vaccines to prevent SARS-CoV-2 infection represents a major step in resolving the COVID-19 global pandemic. Vaccination of individuals with rheumatologic diseases on immunomodulators represents an additional challenge because data suggest that certain immunomodulators may impact vaccine efficacy.

Methods

At a large, predominantly rural Midwestern Veterans Affairs rheumatology clinic, an interprofessional group of investigators conducted a quality improvement project to develop a COVID-19 vaccine readiness kit, consisting of patient education materials and a readiness questionnaire to help guide veteran decision-making. Using a Lean Six Sigma approach and the DMAIC (Define-Measure-Analyze-Improve-Control) framework, the investigators identified customer values, needs, and barriers to participation. Return rates and responses from the questionnaire were tracked over 28 days.

Results

One hundred seventy-nine veterans were identified and mailed kits; 129 (73%) returned the questionnaire within 28 days. Ninety-seven percent of those opted to hold immunomodulators after at least 1 administration of the vaccine; 3.1% were not interested in vaccination. Veterans voiced satisfaction at the simplicity of the process, comprehensibility of materials, and the clarity of communication.

Conclusions

The Lean Six Sigma approach, systematically focusing on identifying the values, needs, and barriers of veterans on immunomodulators, was critical to high participation rates from veterans. This approach is cost-effective for resource-poor settings, audiences without access or familiarity to digital content, and rural settings separated by large geographic distances.