bluuebunny/crossref_metadata_2025_split huggingface dataset:
New mechanism for optical super-resolution via anisotropic near-zero index metamaterials
Authors: Wu Qiannan , Wang Jianyang , Sun Baoyin , Fu Yangyang , Xu Yadong 
Published: March 2021

Abstract
In this paper, we propose a new mechanism for obtaining optical super-resolution based on anisotropic near-zero index metamaterials (AZIMs). It is found that AZIMs can not only achieve perfect transmission of electromagnetic energy but also realize a super-resolution lens. Moreover, we find the performance of super-resolution imaging is not sensitive to the loss and impedance mismatching, as analytically and numerically demonstrated. Our findings provide a new way to explore high-resolution optical imaging.
Emergent physics-informed design of deep learning for microscopy
Authors: Wijesinghe Philip , Dholakia Kishan 
Published: March 2021

Abstract
Deep learning has revolutionised microscopy, enabling automated means for image classification, tracking and transformation. Beyond machine vision, deep learning has recently emerged as a universal and powerful tool to address challenging and previously untractable inverse image recovery problems. In seeking accurate, learned means of inversion, these advances have transformed conventional deep learning methods to those cognisant of the underlying physics of image formation, enabling robust, efficient and accurate recovery even in severely ill-posed conditions. In this perspective, we explore the emergence of physics-informed deep learning that will enable universal and accessible computational microscopy.
Systems pharmacology: a combination strategy for improving efficacy of PD-1/PD-L1 blockade
Authors: Zheng Chunli , Xiao Yue , Chen Chuang , Zhu Jinglin , Yang Ruijie , Yan Jiangna , Huang Ruifei , Xiao Wei , Wang Yonghua , Huang Chao 
Published: March 2021

Abstract
Targeting tumor microenvironment (TME), such as immune checkpoint blockade (ICB), has achieved increased overall response rates in many advanced cancers, such as non-small cell lung cancer (NSCLC), however, only in a fraction of patients. To improve the overall and durable response rates, combining other therapeutics, such as natural products, with ICB therapy is under investigation. Unfortunately, due to the lack of systematic methods to characterize the relationship between TME and ICB, development of rational immune-combination therapy is a critical challenge. Here, we proposed a systems pharmacology strategy to identify resistance regulators of PD-1/PD-L1 blockade and develop its combinatorial drug by integrating multidimensional omics and pharmacological methods. First, a high-resolution TME cell atlas was inferred from bulk sequencing data by referring to a high-resolution single-cell data and was used to predict potential resistance regulators of PD-1/PD-L1 blockade through TME stratification analysis. Second, to explore the drug targeting the resistance regulator, we carried out the large-scale target fishing and the network analysis between multi-target drug and the resistance regulator. Finally, we predicted and verified that oxymatrine significantly enhances the infiltration of CD8+ T cells into TME and is a powerful combination agent to enhance the therapeutic effect of anti-PD-L1 in a mouse model of lung adenocarcinoma. Overall, the systems pharmacology strategy offers a paradigm to identify combinatorial drugs for ICB therapy with a systems biology perspective of drug-target-pathway-TME phenotype-ICB combination.
Effect of remote ischaemic preconditioning on mortality and morbidity after non-cardiac surgery: meta-analysis
Authors: Wahlstrøm K L , Bjerrum E , Gögenur I , Burcharth J , Ekeloef S 
Published: March 2021

AbstractBackgroundRemote ischaemic preconditioning (RIPC) has been shown to have a protective role on vital organs exposed to reperfusion injury. The aim of this systematic review was to evaluate the effects of non-invasive RIPC on clinical and biochemical outcomes in patients undergoing non-cardiac surgeryMethodsA systematic literature search of PubMed, EMBASE, Scopus, and Cochrane databases was carried out in February 2020. RCTs investigating the effect of non-invasive RIPC in adults undergoing non-cardiac surgery were included. Meta-analyses and trial sequential analyses (TSAs) were performed on cardiovascular events, acute kidney injury, and short- and long-term mortality.ResultsSome 43 RCTs including 3660 patients were included. The surgical areas comprised orthopaedic, vascular, abdominal, pulmonary, neurological, and urological surgery. Meta-analysis showed RIPC to be associated with fewer cardiovascular events in non-cardiac surgery (13 trials, 1968 patients, 421 events; odds ratio (OR) 0.68, 95 per cent c.i. 0.47 to 0.96; P = 0.03). Meta-analyses of the effect of RIPC on acute kidney injury (12 trials, 1208 patients, 211 events; OR 1.14, 0.78 to 1.69; P = 0.50; I2 = 9 per cent), short-term mortality (7 trials, 1239 patients, 65 events; OR 0.65, 0.37 to 1.12; P = 0.12; I2 = 0 per cent), and long-term mortality (4 trials, 1167 patients, 9 events; OR 0.67, 0.18 to 2.55; P = 0.56; I2 = 0 per cent) showed no significant differences for RIPC compared with standard perioperative care in non-cardiac surgery. However, TSAs showed that the required information sizes have not yet been reached.ConclusionApplication of RIPC to non-cardiac surgery might reduce cardiovascular events, but not acute kidney injury or all-cause mortality, but currently available data are inadequate to confirm or reject an assumed intervention effect.
The impact of progesterone receptor negativity on oncological outcomes in oestrogen-receptor-positive breast cancer
Authors: Davey M G , Ryan É J , Folan P J , O’Halloran N , Boland M R , Barry M K , Sweeney K J , Malone C M , McLaughlin R J , Kerin M J , Lowery A J 
Published: March 2021

Abstract

Background
Oestrogen receptor (ER) status provides invaluable prognostic and therapeutic information in breast cancer (BC). When clinical decision making is driven by ER status, the value of progesterone receptor (PgR) status is less certain. The aim of this study was to describe clinicopathological features of ER-positive (ER+)/PgR-negative (PgR-) BC and to determine the effect of PgR negativity in ER+ disease.

Methods
Consecutive female patients with ER+ BC from a single institution were included. Factors associated with PgR- disease were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan–Meier and Cox regression analysis.

Results
In total, 2660 patients were included with a mean(s.d.) age of 59.6(13.3) years (range 21–99 years). Median follow-up was 97.2 months (range 3.0–181.2). Some 2208 cases were PgR+ (83.0 per cent) and 452 were PgR- (17.0 per cent). Being postmenopausal (odds ratio (OR) 1.66, 95 per cent c.i. 1.25 to 2.20, P &lt; 0.001), presenting with symptoms (OR 1.71, 95 per cent c.i. 1.30 to 2.25, P &lt; 0.001), ductal subtype (OR 1.51, 95 per cent c.i. 1.17 to 1.97, P = 0.002) and grade 3 tumours (OR 2.20, 95 per cent c.i. 1.68 to 2.87, P &lt; 0.001) were all associated with PgR negativity. In those receiving neoadjuvant chemotherapy (308 patients), pathological complete response rates were 10.1 per cent (25 of 247 patients) in patients with PgR+ disease versus 18.0 per cent in PgR- disease (11 of 61) (P = 0.050). PgR negativity independently predicted worse disease-free (hazard ratio (HR) 1.632, 95 per cent c.i. 1.209 to 2.204, P = 0.001) and overall survival (HR 1.774, 95 per cent c.i. 1.324 to 2.375, P &lt; 0.001), as well as worse overall survival in ER+/HER2- disease (P = 0.004).

Conclusions
In ER+ disease, PgR- tumours have more aggressive clinicopathological features and worse oncological outcomes. Neoadjuvant and adjuvant therapeutic strategies should be tailored according to PgR status.
Opioid Use Associated With Higher Costs Among Patients With Inflammatory Bowel Disease
Authors: Szigethy Eva M , Murphy Sean M , Ehrlich Orna G , Heller Caren A , Engel-Nitz Nicole M , Meadows Perry , Allen John I 
Published: March 2021

Abstract

Background
Opioid use by patients with inflammatory bowel disease (IBD) has been associated with poorer health outcomes. This study describes socioeconomic characteristics; health utilization trends; and costs of patients with IBD and either no opioid prescriptions, or in 1 of 3 opioid duration categories based on Center for Disease Control guidelines: acute (0–30 days), moderate (31–90 days), or chronic (&gt;90 days). We utilized the Cost of IBD Care Optum research database results for this study.

Methods
The Optum Research Database from years 2007 to 2016 including IBD patients with commercial or Medicare Advantage insurance in the United States was used. Additional inclusion criteria included continuous enrollment with medical and pharmacy benefit coverage for at least 24 months (12 months before and 12 months after the index date of IBD diagnosis). The association between costs and patient characteristics were assessed across a no opioid use group during this period and the 3 opioid duration groups.

Results
Among 51,178 IBD patients, 33,229 (64.93%) were part of the no opioid use group, while 13,635 (26.64%) were in acute, 1698 (3.32%) were in moderate, and 2616 (5.11%) were in chronic use groups, as determined by pharmacy claims data. Patients in the chronic group were more likely to be white (75.38%) compared to all the other groups (no opioid use, acute, and moderate), have attained less education (only high school diploma), have had lower incomes, and have had Medicare instead of commercial insurance. Patients across all opioid prescription groups were more likely to have had diagnoses associated with pain in the prior year, with rates increasing by the length of opioid prescription (63.68%, 80.17%, and 86.11% for acute, moderate, and chronic groups). Compared to the no-use group, the acute group had more ambulatory (outpatient) visits, while the chronic group had fewer. Emergency department visits and inpatient hospitalizations were higher in all 3 opioid groups compared to the no opioid use group. Ambulatory, emergency department, inpatient, and total (medical + pharmacy) costs were higher in all 3 opioid groups, compared to the no opioid use group, even after adjusting for demographic and clinical patient characteristics.

Conclusions
Among patients with IBD, increasing opioid use was associated with higher healthcare resource utilization and, concomitantly, higher healthcare costs during this period.
Impact of coronary calcium score and lesion characteristics on the diagnostic performance of machine-learning-based computed tomography-derived fractional flow reserve
Authors: Koo Hyun Jung , Kang Joon-Won , Kang Soo-Jin , Kweon Jihoon , Lee June-Goo , Ahn Jung-Min , Park Duk-Woo , Lee Seung Whan , Lee Cheol Whan , Park Seong-Wook , Park Seung-Jung , Kim Young-Hak , Yang Dong Hyun 
Published: March 2021

Abstract

Aims
To evaluate the impact of coronary artery calcium (CAC) score, minimal lumen area (MLA), and length of coronary artery stenosis on the diagnostic performance of the machine-learning-based computed tomography-derived fractional flow reserve (ML-FFR).

Methods and results
In 471 patients with coronary artery disease, computed tomography angiography (CTA) and invasive coronary angiography were performed with fractional flow reserve (FFR) in 557 lesions at a single centre. Diagnostic performances of ML-FFR, computational fluid dynamics-based CT-FFR (CFD-FFR), MLA, quantitative coronary angiography (QCA), and visual stenosis grading were evaluated using invasive FFR as a reference standard. Diagnostic performances were analysed according to lesion characteristics including the MLA, length of stenosis, CAC score, and stenosis degree. ML-FFR was obtained by automated feature selection and model building from quantitative CTA. A total of 272 lesions showed significant ischaemia, defined by invasive FFR ≤0.80. There was a significant correlation between CFD-FFR and ML-FFR (r = 0.99, P &lt; 0.001). ML-FFR showed moderate sensitivity and specificity in the per-patient analysis. Diagnostic performances of CFD-FFR and ML-FFR did not decline in patients with high CAC scores (CAC &gt; 400). Sensitivities of CFD-FFR and ML-FFR showed a downward trend along with the increase in lesion length and decrease in MLA. The area under the curve (AUC) of ML-FFR (0.73) was higher than those of QCA and visual grading (AUC = 0.65 for both, P &lt; 0.001) and comparable to those of MLA (AUC = 0.71, P = 0.21) and CFD-FFR (AUC = 0.73, P = 0.86).

Conclusion
ML-FFR showed comparable results to MLA and CFD-FFR for the prediction of lesion-specific ischaemia. Specificities and accuracies of CFD-FFR and ML-FFR decreased with smaller MLA and long lesion length.
Structural change in the job matching process in the United States, 1923–1932
Authors: Lee Woong , Yoon Yeo Joon 
Published: March 2021

Abstract
This paper explores the structural change in the job matching process in the United States from 1923 to 1932. Bai–Perron test is employed with data from public employment offices. The result shows that there are two structural changes, July 1928 and August 1930. The first breakpoint corresponds to approximately a year before the stock market crash, implying that there was a sign of downturn in the labor market when the economy was still in a period of expansion. The second break point is related to the Great Contraction when the entire economy was going in a downward spiral.
MultiPhATE2: code for functional annotation and comparison of phage genomes
Authors: Ecale Zhou Carol L , Kimbrel Jeffrey , Edwards Robert , McNair Katelyn , Souza Brian A , Malfatti Stephanie 
Published: March 2021

AbstractTo address a need for improved tools for annotation and comparative genomics of bacteriophage genomes, we developed multiPhATE2. As an extension of multiPhATE, a functional annotation code released previously, multiPhATE2 performs gene finding using multiple algorithms, compares the results of the algorithms, performs functional annotation of coding sequences, and incorporates additional search algorithms and databases to extend the search space of the original code. MultiPhATE2 performs gene matching among sets of closely related bacteriophage genomes, and uses multiprocessing to speed computations. MultiPhATE2 can be re-started at multiple points within the workflow to allow the user to examine intermediate results and adjust the subsequent computations accordingly. In addition, multiPhATE2 accommodates custom gene calls and sequence databases, again adding flexibility. MultiPhATE2 was implemented in Python 3.7 and runs as a command-line code under Linux or MAC operating systems. Full documentation is provided as a README file and a Wiki website.
A high-quality, chromosome-level genome assembly of the Black Soldier Fly (Hermetia illucens L.)
Authors: Generalovic Tomas N , McCarthy Shane A , Warren Ian A , Wood Jonathan M D , Torrance James , Sims Ying , Quail Michael , Howe Kerstin , Pipan Miha , Durbin Richard , Jiggins Chris D 
Published: March 2021

Abstract
Hermetia illucens L. (Diptera: Stratiomyidae), the Black Soldier Fly (BSF) is an increasingly important species for bioconversion of organic material into animal feed. We generated a high-quality chromosome-scale genome assembly of the BSF using Pacific Bioscience, 10X Genomics linked read and high-throughput chromosome conformation capture sequencing technology. Scaffolding the final assembly with Hi-C data produced a highly contiguous 1.01 Gb genome with 99.75% of scaffolds assembled into pseudochromosomes representing seven chromosomes with 16.01 Mb contig and 180.46 Mb scaffold N50 values. The highly complete genome obtained a Benchmarking Universal Single-Copy Orthologs (BUSCO) completeness of 98.6%. We masked 67.32% of the genome as repetitive sequences and annotated a total of 16,478 protein-coding genes using the BRAKER2 pipeline. We analyzed an established lab population to investigate the genomic variation and architecture of the BSF revealing six autosomes and an X chromosome. Additionally, we estimated the inbreeding coefficient (1.9%) of the lab population by assessing runs of homozygosity. This provided evidence for inbreeding events including long runs of homozygosity on chromosome 5. The release of this novel chromosome-scale BSF genome assembly will provide an improved resource for further genomic studies, functional characterization of genes of interest and genetic modification of this economically important species.
Non-Governmental Organisations and National Human Rights Institutions monitoring the execution of Strasbourg Judgments: An Empirical Perspective on Rule 9 Communications
Authors: Erken Elif 
Published: March 2021

Abstract
This article considers a scarcely explored perspective in relation to the execution of judgments of the ECtHR, notably, the formal involvement of NGOs and NHRIs. Rule 9(2) of the Committee of Minister Rules’ allows NGOs and NHRIs to participate in the supervision process for the execution of the Court’s judgments by submitting reports (Communications) in which these actors review and assess domestic authorities’ performance with respect to judgment execution. On the basis of interviews with important stakeholders, this article provides an all-round user-based perspective of this Rule 9 mechanism and its perceived impact. Doing so elucidates whether the Rule 9 procedure allows NGOs and NHRIs to engage in the important cycle of reporting and pressuring for change, the conclusions of which are important in assessing if and how Rule 9 works to advance the execution of judgments of the ECtHR.
The cap-specific m6A methyltransferase, PCIF1/CAPAM, is dynamically recruited to the gene promoter in a transcription-dependent manner
Authors: Sugita Ai , Kuruma Soichiro , Yanagisawa Natsuki , Ishiguro Hiroyasu , Kano Ryoya , Ohkuma Yoshiaki , Hirose Yutaka 
Published: March 2021

Abstract
N 6-methyladenosine (m6A), the most abundant modification in eukaryotic mRNAs, plays an important role in mRNA metabolism and functions. When adenosine is transcribed as the first cap-adjacent nucleotide, it is methylated at the ribose 2′-O and N6 positions, thus generating N6, 2′-O-dimethyladenosine (m6Am). Phosphorylated C-terminal domain (CTD)-interacting factor 1 (PCIF1) is a novel cap-specific adenine N6-methyltransferase responsible for m6Am formation. As PCIF1 specifically interacts with the Ser5-phosphorylated CTD of RNA polymerase II (Pol II), which is a marker for the early phase of transcription, PCIF1 is speculated to be recruited to the early elongating Pol II. In this study, subcellular fractionation and immunofluorescence microscopy demonstrated that PCIF1 is mainly localized to the transcriptionally active chromatin regions in HeLa cells. Chromatin immunoprecipitation (ChIP) revealed that PCIF1 was predominantly localized to the promoter of a broad range of Pol II-transcribed genes, including several protein-coding genes and non-coding RNA genes. Moreover, PCIF1 accumulation on these promoters depended entirely on transcriptional activity and Ser5 phosphorylation of the CTD. These results suggest that PCIF1 dynamically localizes to the Pol II early in transcription and may efficiently catalyze N6-methylation of the first adenosine residue of nascent mRNAs cotranscriptionally.
Sequential conformational changes in transmembrane domains of presenilin 1 in Aβ42 downregulation
Authors: Cai Tetsuo , Tomita Taisuke 
Published: March 2021

Abstract
Alzheimer disease (AD) is the most common neurodegenerative disease worldwide. AD is pathologically characterized by the deposition of senile plaques in the brain, which are composed of an amyloid-β peptide (Aβ) that is produced through the multistep cleavage of amyloid precursor protein (APP) by γ-secretase. γ-Secretase is a membrane protein complex, which includes its catalytic subunit presenilin 1 (PS1). However, much about the structural dynamics of this enzyme remain unclear. We have previously demonstrated that movements of the transmembrane domain (TMD) 1 and TMD3 of PS1 are strongly associated with decreased production of the Aβ peptide ending at the 42nd residue (i.e. Aβ42), which is the aggregation-prone, toxic species. However, the association between these movements as well as the sequence of these TMDs remains unclear. In this study, we raised the possibility that the vertical movement of TMD1 is a prerequisite for expansion of the catalytic cavity around TMD3 of PS1, resulting in reduced Aβ42 production. Our results shed light on the association between the conformational changes of TMDs and the regulation of γ-secretase activity.
Identifying Optimal Program Models and Clinical Tools for Follow-Up Care
Authors: Gilmore Katherine R , Rodriguez M Alma 
Published: March 2021

AbstractFifteen years ago, the Institute of Medicine (IOM) issued a report that defined Survivorship Care as a distinct phase of the cancer care continuum. The required domains to meet the health needs of cancer survivors were outlined in the report: cancer surveillance and screening, cancer prevention and lifestyle counseling, management of treatment related persistent or late effects, coordination of care, and psychosocial support services. In response to that report, The University of Texas MD Anderson Cancer Center implemented a tiered survivorship care model that is risk based. The core principle is that cancer survivors’ health needs will depend on the cancer treatment and disease-specific risks. We here describe this model for low-, intermediate-, and high-risk cancer survivors, in which comanagement between oncology and primary care providers is risk dependent. Our clinical model defines transition as appropriate when there is a minimal risk of primary cancer relapse, which is specific to each cancer type and disease stage. This model is embedded into disease-specific clinical practice algorithms, aligned with the IOM domains of care. Over the past 10 years, we have successfully transitioned nearly 25 000 patients to disease-specific survivorship clinics, providing care based on the IOM domains. We have learned from our process that expansion of survivorship care into established clinical settings requires engagement of champions and key clinical stakeholders. Future directions for survivorship care should explore the application and potential benefits of telemedicine as a care delivery system to meet the needs of cancer survivors.
Ganoderma lucidum ameliorates the diabetic nephropathy via down-regulatory effect on TGFβ-1 and TLR-4/NFκB signalling pathways
Authors: Hassan Hanan M , Mahran Yasmen F , Ghanim Amal M H 
Published: March 2021

Abstract

Objectives
Diabetic nephropathy (DN) is one of the most important complications of diabetes mellitus and it is considered as a principal cause for end-stage renal failure. Ganoderma lucidum (GL) has been studied for its reno-protective effect against different kidney injury models. The aim of our study is to investigate the mechanisms by which GL can improve kidney injury and consequent renal inflammation and fibrosis.

Methods
GL either in a low dose (250 mg/kg, i.p.) or high dose (500 mg/kg, i.p.) was administered to DN rat model, and nephropathy indices were investigated.

Key findings
GL treatment significantly down-regulated kidney injury molecule-1 (KIM-1) gene expression and inhibited TLR-4 (Toll-like receptor-4)/NFκB (nuclear factor kappa B) signalling pathway. As well, GL treatment significantly decreased the pro-inflammatory mediator; IL-1β (interleukin-1 beta) level and fibrosis-associated growth factors; FGF-23 (fibroblast growth factor-23) and TGFβ-1 (transforming growth factor beta-1) levels. In addition, GL remarkably inhibited (Bax) the pro-apoptotic protein and induced (Bcl-2) the anti-apoptotic protein expression in kidneys. Moreover, GL treatment significantly alleviates kidney injury indicated by correcting the deteriorated kidney function and improving oxidative stress status in DN rats.

Conclusions
GL significantly improved renal function indices through dose-dependent kidney function restoration, oxidative stress reduction, down-regulation of gene expression of KIM-1 and TLR4/NFκB signalling pathway blockage with subsequent alleviation of renal inflammation and fibrosis.