bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective, longitudinal study of rheumatoid arthritis treatment patterns with Janus kinase inhibitors and other disease-modifying antirheumatic drugs in Japan
Authors: Kaneko Yuko , Sakurai Masaya , Snijder Robert , Kokubo Satoshi , Kato Daisuke 
Published: May 2022

ABSTRACT

Objectives
There is limited information on the clinical use of Janus kinase inhibitors (JAKis) for rheumatoid arthritis treatment in Japan. The aim of this study was to identify disease-modifying antirheumatic drug (DMARD) treatment patterns in Japan.

Methods
This retrospective, longitudinal study extracted data from the Japan Medical Data Center database. Patients with rheumatoid arthritis diagnosis were enrolled 2016–19, during which patients had a first prescription of a major DMARD, split into six mutually exclusive classes: methotrexate (MTX); other conventional synthetic DMARDs; tumour necrosis factor alpha inhibitors; cytotoxic T-lymphocyte-associated antigen-4-immunoglobulin; anti-interleukin-6 receptor therapies; and JAKis. The primary objective was to describe DMARD treatment patterns, especially for JAKis.

Results
Overall, 10,399 patients were included in the analysis. The most common treatments were MTX, other conventional synthetic DMARDs, and tumour necrosis factor alpha inhibitors. The total number of JAKi prescriptions increased approximately 8-fold during 2016–19. Most (61.1%) patients who received JAKis had prior MTX or tumour necrosis factor alpha inhibitor treatment. The duration of JAKi treatment was longer than for biologics and other conventional synthetic DMARDs and comparable to that of MTX.

Conclusions
The sequence of drug class prescriptions for rheumatoid arthritis in Japan during 2016–19 followed clinical guidelines. Over this period, JAKis were increasingly used as a second-line treatment following MTX.
Efficacy of canakinumab in a patient with adult-onset glucocorticoid-resistant periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome
Authors: Sopeña Bernardo , Araújo Olga , Freire Mayka , Barrera-López Lucía , Hernández-Rodríguez José 
Published: May 2022

ABSTRACT
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, a polygenic or multifactorial condition, is the most frequent autoinflammatory disease in children. There is increasing evidence that some patients may have a disease onset during adulthood. With regard to PFAPA syndrome treatment, single medium-to-high doses of glucocorticoids during flares constitute the therapy of choice in children and adults, colchicine may be useful in some patients, and tonsillectomy has been reported of utility mainly in paediatric patients. Interleukin-1 (IL-1) blockers have been sporadically used with good response in glucocorticoid-resistant cases. We report a patient with an adult onset of glucocorticoid-resistant PFAPA syndrome and inconsistent response to colchicine and anakinra, who later achieved a complete and sustained response to canakinumab. Although canakinumab seems to be a good therapeutic option in paediatric and adult patients with refractory PFAPA syndrome, the best anti-IL-1 agent and the sequence of administration have to be still determined in well-designed clinical trials.
A case of septic arthritis of the elbow joint in rheumatoid arthritis diagnosed by arthroscopic synovectomy
Authors: Hayashibara Masako , Hagino Hiroshi , Hayashi Ikuta , Nagira Keita , Takasu Yuta , Mukunoki Daichi , Nagashima Hideki 
Published: May 2022

ABSTRACT
We report a case of methicillin-resistant Staphylococcus aureus (MRSA) septic arthritis of the elbow detected by arthroscopic synovectomy in an 81-year-old woman with rheumatoid arthritis (RA) who was initially diagnosed with a rheumatoid arthritis flare-up. The patient was administered abatacept, an antirheumatic biological agent, as the synovial fluid culture was negative. Destruction of the joint progressed despite medication, and the patient underwent arthroscopic synovectomy. MRSA was detected in the culture of the synovium that was collected intraoperatively, and septic arthritis was diagnosed. The infection subsided with anti-MRSA antibiotics, but the patient continued to experience moderate pain and limited motion. In RA patients, it might be difficult to differentiate minor findings from infection. Arthroscopic synovectomy is one of the selectable procedures that should be actively considered when infection is suspected.
EHF is a novel regulator of cellular redox metabolism and predicts patient prognosis in HNSCC
Authors: Oyelakin Akinsola , Nayak Kasturi Bala , Glathar Alexandra Ruth , Gluck Christian , Wrynn Theresa , Tugores Antonio , Romano Rose-Anne , Sinha Satrajit 
Published: May 2022

Abstract
Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous disease with relatively high morbidity and mortality rates. The lack of effective therapies, high recurrence rates and drug resistance driven in part, by tumor heterogeneity, contribute to the poor prognosis for patients diagnosed with this cancer. This problem is further exacerbated by the fact that key regulatory factors contributing to the disease diversity remains largely elusive. Here, we have identified EHF as an important member of the ETS family of transcription factors that is highly expressed in normal oral tissues, but lost during HNSCC progression. Interestingly, HNSCC tumors and cell lines exhibited a dichotomy of high and low EHF expression, and patients whose tumors retained EHF expression showed significantly better prognosis, suggesting a potential tumor suppressive role for EHF. To address this, we have performed gain and loss of function studies and leveraged bulk and single-cell cancer genomic datasets to identify global EHF targets by RNA-sequencing (RNA-seq) and Chromatin Immunoprecipitation and next generation sequencing (ChIP-seq) experiments of HNSCC cell lines. These mechanistic studies have revealed that EHF, acts as a regulator of a broad spectrum of metabolic processes, specifically targeting regulators of redox homeostasis such as NRF2 and SOX2. Our immunostaining results confirm the mutually exclusive expression patterns of EHF and SOX2 in HNSCC tumors and suggest a possible role for these two factors in establishing discrete metabolic states within the tumor microenvironment. Taken together, EHF may serve as a novel prognostic marker for classifying HNSCC patients for actionable and targeted therapeutic intervention.
ePeak: from replicated chromatin profiling data to epigenomic dynamics
Authors: Daunesse Maëlle , Legendre Rachel , Varet Hugo , Pain Adrien , Chica Claudia 
Published: May 2022

Abstract
We present ePeak, a Snakemake-based pipeline for the identification and quantification of reproducible peaks from raw ChIP-seq, CUT&RUN and CUT&Tag epigenomic profiling techniques. It also includes a statistical module to perform tailored differential marking and binding analysis with state of the art methods. ePeak streamlines critical steps like the quality assessment of the immunoprecipitation, spike-in calibration and the selection of reproducible peaks between replicates for both narrow and broad peaks. It generates complete reports for data quality control assessment and optimal interpretation of the results. We advocate for a differential analysis that accounts for the biological dynamics of each chromatin factor. Thus, ePeak provides linear and nonlinear methods for normalisation as well as conservative and stringent models for variance estimation and significance testing of the observed marking/binding differences. Using a published ChIP-seq dataset, we show that distinct populations of differentially marked/bound peaks can be identified. We study their dynamics in terms of read coverage and summit position, as well as the expression of the neighbouring genes. We propose that ePeak can be used to measure the richness of the epigenomic landscape underlying a biological process by identifying diverse regulatory regimes.
Automated brain tumor identification using magnetic resonance imaging: A systematic review and meta-analysis
Authors: Kouli Omar , Hassane Ahmed , Badran Dania , Kouli Tasnim , Hossain-Ibrahim Kismet , Steele J Douglas 
Published: May 2022

Abstract

Background
Automated brain tumor identification facilitates diagnosis and treatment planning. We evaluate the performance of traditional machine learning (TML) and deep learning (DL) in brain tumor detection and segmentation, using MRI.

Methods
A systematic literature search from January 2000 to May 8, 2021 was conducted. Study quality was assessed using the Checklist for Artificial Intelligence in Medical Imaging (CLAIM). Detection meta-analysis was performed using a unified hierarchical model. Segmentation studies were evaluated using a random effects model. Sensitivity analysis was performed for externally validated studies.

Results
Of 224 studies included in the systematic review, 46 segmentation and 38 detection studies were eligible for meta-analysis. In detection, DL achieved a lower false positive rate compared to TML; 0.018 (95% CI, 0.011 to 0.028) and 0.048 (0.032 to 0.072) (P &lt; .001), respectively. In segmentation, DL had a higher dice similarity coefficient (DSC), particularly for tumor core (TC); 0.80 (0.77 to 0.83) and 0.63 (0.56 to 0.71) (P &lt; .001), persisting on sensitivity analysis. Both manual and automated whole tumor (WT) segmentation had “good” (DSC ≥ 0.70) performance. Manual TC segmentation was superior to automated; 0.78 (0.69 to 0.86) and 0.64 (0.53 to 0.74) (P = .014), respectively. Only 30% of studies reported external validation.

Conclusions
The comparable performance of automated to manual WT segmentation supports its integration into clinical practice. However, manual outperformance for sub-compartmental segmentation highlights the need for further development of automated methods in this area. Compared to TML, DL provided superior performance for detection and sub-compartmental segmentation. Improvements in the quality and design of studies, including external validation, are required for the interpretability and generalizability of automated models.
Radiomics and radiogenomics in pediatric neuro-oncology: A review
Authors: Madhogarhia Rachel , Haldar Debanjan , Bagheri Sina , Familiar Ariana , Anderson Hannah , Arif Sherjeel , Vossough Arastoo , Storm Phillip , Resnick Adam , Davatzikos Christos , Fathi Kazerooni Anahita , Nabavizadeh Ali 
Published: May 2022

Abstract
The current era of advanced computing has allowed for the development and implementation of the field of radiomics. In pediatric neuro-oncology, radiomics has been applied in determination of tumor histology, identification of disseminated disease, prognostication, and molecular classification of tumors (ie, radiogenomics). The field also comes with many challenges, such as limitations in study sample sizes, class imbalance, generalizability of the methods, and data harmonization across imaging centers. The aim of this review paper is twofold: first, to summarize existing literature in radiomics of pediatric neuro-oncology; second, to distill the themes and challenges of the field and discuss future directions in both a clinical and technical context.
Genomic Surveillance of SARS-CoV-2 in a University Community: Insights Into Tracking Variants, Transmission, and Spread of Gamma (P.1) Variant
Authors: Ciubotariu Ilinca I , Dorman Jack , Perry Nicole M , Gorenstein Lev , Kattoor Jobin J , Fola Abebe A , Zine Amy , Hendrix G Kenitra , Wilkes Rebecca P , Kitchen Andrew , Carpi Giovanna 
Published: May 2022

AbstractBackgroundUsing a combination of data from routine surveillance, genomic sequencing, and phylogeographic analysis, we tracked the spread and introduction events of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focusing on a large university community.MethodsHere, we sequenced and analyzed 677 high-quality SARS-CoV-2 genomes from positive RNA samples collected from Purdue University students, faculty, and staff who tested positive for the virus between January 2021 and May 2021, comprising an average of 32% of weekly cases across the time frame.ResultsOur analysis of circulating SARS-CoV-2 variants over time revealed periods when variants of concern (VOC) Alpha (B.1.1.7) and Iota (B.1.526) reached rapid dominance and documented that VOC Gamma (P.1) was increasing in frequency as campus surveillance was ending. Phylodynamic analysis of Gamma genomes from campus alongside a subsampling of &gt;20 000 previously published P.1 genomes revealed 10 independent introductions of this variant into the Purdue community, predominantly from elsewhere in the United States, with introductions from within the state of Indiana and from Illinois, and possibly Washington and New York, suggesting a degree of domestic spread.ConclusionsWe conclude that a robust and sustained active and passive surveillance program coupled with genomic sequencing during a pandemic offers important insights into the dynamics of pathogen arrival and spread in a campus community and can help guide mitigation measures.
Piercing the Parliamentary Veil against Judicial Review: The Case against Parliamentary Privilege
Authors: Lui Edward 
Published: May 2022

Abstract
For centuries, parliamentary privilege has stood as a bar against judicial review over the internal affairs of Parliament. The literature surrounding parliamentary privilege has mostly been about the scope of the privilege; few have discussed if the existence of the privilege itself is justified. This article undertakes that task, by examining parliamentary privilege as a defence against judicial review. Three propositions will be made. First, in the context of judicial review, parliamentary privilege is defined by the outer limits of the principle of exclusive cognisance. Article 9 of the Bill of Rights 1689 adds nothing. Second, parliamentary privilege as it relates to judicial review is incompatible with the two prevailing models of the separation of powers. Third, six arguments that may be made in favour of parliamentary privilege will be refuted. Accordingly, parliamentary privilege should no longer provide a defence towards judicial review.
Naive and memory T cells TCR–HLA-binding prediction
Authors: Glazer Neta , Akerman Ofek , Louzoun Yoram 
Published: May 2022

Abstract
T cells recognize antigens through the interaction of their T cell receptor (TCR) with a peptide-major histocompatibility complex (pMHC) molecule. Following thymic-positive selection, TCRs in peripheral naive T cells are expected to bind MHC alleles of the host. Peripheral clonal selection is expected to further increase the frequency of antigen-specific TCRs that bind to the host MHC alleles. To check for a systematic preference for MHC-binding T cells in TCR repertoires, we developed Natural Language Processing-based methods to predict TCR–MHC binding independently of the peptide presented for Class I MHC alleles. We trained a classifier on published TCR–pMHC binding pairs and obtained a high area under curve (AUC) of over 0.90 on the test set. However, when applied to TCR repertoires, the accuracy of the classifier dropped. We thus developed a two-stage prediction model, based on large-scale naive and memory TCR repertoires, denoted TCR HLA-binding predictor (CLAIRE). Since each host carries multiple human leukocyte antigen (HLA) alleles, we first computed whether a TCR on a CD8 T cell binds an MHC from any of the host Class-I HLA alleles. We then performed an iteration, where we predict the binding with the most probable allele from the first round. We show that this classifier is more precise for memory than for naïve cells. Moreover, it can be transferred between datasets. Finally, we developed a CD4–CD8 T cell classifier to apply CLAIRE to unsorted bulk sequencing datasets and showed a high AUC of 0.96 and 0.90 on large datasets. CLAIRE is available through a GitHub at: https://github.com/louzounlab/CLAIRE, and as a server at: https://claire.math.biu.ac.il/Home.
T-LOC: A comprehensive tool to localize and characterize T-DNA integration sites
Authors: Li Shaofang , Wang Chenyang , You Chenjiang , Zhou Xueping , Zhou Huanbin 
Published: May 2022

Abstract
Scientists have developed many approaches based on PCR or next-generation sequencing to localize and characterize integrated T-DNAs in transgenic plants generated by Agrobacterium tumefaciens-mediated T-DNA transfer. However, none of these methods has the robust ability to handle all transgenic plants with diversified T-DNA patterns. Utilizing the valuable information in the whole-genome sequencing data of transgenic plants, we have developed a comprehensive approach (T-LOC) to localize and characterize T-DNA integration sites (TISs). We evaluated the performance of T-LOC on genome sequencing data from 48 transgenic rice (Oryza sativa) plants that provide real and unbiased resources of T-DNA integration patterns. T-LOC discovered 75 full TISs and reported a diversified pattern of T-DNA integration: the ideal single-copy T-DNA between two borders, multiple-copy of T-DNAs in tandem or inverted repeats, truncated partial T-DNAs with or without the selection hygromycin gene, the inclusion of T-DNA backbone, the integration at the genome repeat region, and the concatenation of multiple ideal or partial T-DNAs. In addition, we reported that DNA fragments from the two A. tumefaciens plasmids can be fused with T-DNA and integrated into the plant genome. Besides, T-LOC characterizes the genomic changes at TISs, including deletion, duplication, accurate repair, and chromosomal rearrangement. Moreover, we validated the robustness of T-LOC using PCR, Sanger sequencing, and Nanopore sequencing. In summary, T-LOC is a robust approach to studying the TISs independent of the integration pattern and can recover all types of TISs in transgenic plants.
Three-dimensional-printed polycaprolactone scaffolds with interconnected hollow-pipe structures for enhanced bone regeneration
Authors: Duan Jiahua , Lei Dong , Ling Chen , Wang Yufeng , Cao Zhicheng , Zhang Ming , Zhang Huikang , You Zhengwei , Yao Qingqiang 
Published: May 2022

AbstractThree-dimensional (3D)-printed scaffolds are widely used in tissue engineering to help regenerate critical-sized bone defects. However, conventional scaffolds possess relatively simple porous structures that limit the delivery of oxygen and nutrients to cells, leading to insufficient bone regeneration. Accordingly, in the present study, perfusable and permeable polycaprolactone scaffolds with highly interconnected hollow-pipe structures that mimic natural micro-vascular networks are prepared by an indirect one-pot 3D-printing method. In vitro experiments demonstrate that hollow-pipe-structured (HPS) scaffolds promote cell attachment, proliferation, osteogenesis and angiogenesis compared to the normal non-hollow-pipe-structured scaffolds. Furthermore, in vivo studies reveal that HPS scaffolds enhance bone regeneration and vascularization in rabbit bone defects, as observed at 8 and 12 weeks, respectively. Thus, the fabricated HPS scaffolds are promising candidates for the repair of critical-sized bone defects.
0049 Screen time and sleep in young adolescents before and across the first year of the COVID-19 pandemic
Authors: Kiss Orsolya , de Zambotti Massimiliano , Schaefer Emil , Durley Ingrid , Kerr Erin , Dulai Teji , Arra Nicole , Obilor Todd , Camacho Leticia , Hsu Carrie , Baker Fiona 
Published: May 2022

Abstract

Introduction
The COVID-19 pandemic has been associated with profound biopsychosocial changes for children, potentially affecting their health and wellbeing. Among these changes are altered sleep patterns and screen time use, however, no work has examined interactions between these two behaviors in the context of the pandemic. Here, we used longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study® to investigate changes in both sleep and screen time, and their relationship, from before and across the first year of the COVID-19 pandemic in young adolescents.

Methods
More than 5000 adolescents (11-14 years; 48% girls) completed digital surveys about their sleep and daily screen time use before the pandemic and across six timepoints during 2020-2021, as part of the ongoing ABCD Study®. Random intercept linear mixed effect models (LMMs) were used to examine longitudinal associations between bedtime, wake-up time, and daily screen time use (social media, gaming), considering age, sex, and school effects.

Results
Adolescents’ wake up time was delayed (R2 = 0.51; ~1.5 hour) during May-August 2020 relative to the pre-pandemic assessment (p&lt;0.01), which was partially related to the summer break (p&lt;0.01), before advancing to earlier times in October 2020. Bedtimes also delayed at all pandemic assessments (R2=0.62; ~1 hour), even after starting the new school year (p&lt;0.01), particularly in older adolescents (p&lt;0.01) and girls (p&lt;0.01). Recreational screen time was dramatically higher across the first year of the pandemic, relative to pre-pandemic (p&lt;0.01; ~45min social media, ~20min video gaming). More time spent with screen related activities was associated with later bedtimes and wake up times (p&lt;0.01), across the pandemic, with effects being evident in male and female adolescents.

Conclusion
Our findings show profound changes in sleep timing and screen time use across the pandemic in young adolescents, and critically, that excessive screen time negatively impacts sleep. As adolescents increasingly turn to more screen usage, these data highlight the need to promote their balanced and informed use of social media platforms, video games, and other digital technology to ensure adequate opportunity to sleep and maintain other healthy behaviors during this critical period of developmental change.

Support (If Any)
NIH U01DA041022