bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digitally quantified CD8+ cells: the best candidate marker for an immune cell score in non-small cell lung cancer?
Authors: Kilvaer Thomas K , Paulsen Erna-Elise , Andersen Sigve , Rakaee Mehrdad , Bremnes Roy M , Busund Lill-Tove Rasmussen , Donnem Tom 
Published: October 2020

Abstract
The TNM classification is well established as a state-of-the-art prognostic and treatment-decision-making tool for non-small cell lung cancer (NSCLC) patients. However, incorporation of biological data may hone the TNM system. This article focuses on choosing and incorporating subsets of tissue-infiltrating lymphocyte (TIL), detected by specific immunohistochemistry and automatically quantified by open source software, into a TNM-Immune cell score (TNM-I) for NSCLC. We use common markers (CD3, CD4, CD8, CD20 and CD45RO) of TILs to identify TIL subsets in tissue micro-arrays comprising tumor tissue from 553 patients resected for primary NSCLC. The number of TILs is automatically quantified using open source software (QuPath). Their prognostic efficacy, alone and within a TNM-I model, is evaluated in all patients and histological subgroups. Compared with previous manual semi-quantitative scoring of TILs in the same cohort, the present digital quantification proved superior. As a proof-of-concept, we construct a TNM-I, using TNM categories and the CD8+ TIL density. The TNM-I is an independent prognosticator of favorable diagnosis in both the overall cohort and in the main histological subgroups. In conclusion, CD8+ TIL density is the most promising candidate marker for a TNM-I in NSCLC. The prognostic efficacy of the CD8+ TIL density is strongest in lung squamous cell carcinomas, whereas both CD8+ TILs and CD20+ TILs, or a combination of these, may be candidates for a TNM-I in lung adenocarcinoma. Furthermore, based on the presented results, digital quantification is the preferred method for scoring TILs in the future.
Gaining Back What Is Lost: Recovering the Sense of Smell in Mild to Moderate Patients After COVID-19
Authors: Iannuzzi Lucia , Salzo Anna Eugenia , Angarano Gioacchino , Palmieri Vincenzo Ostilio , Portincasa Piero , Saracino Annalisa , Gelardi Matteo , Dibattista Michele , Quaranta Nicola 
Published: October 2020

Abstract
The purpose of our cohort study was to quantify olfactory deficits in Coronavirus disease 2019 (COVID-19) patients using Sniffin’ Sticks and a pre-post design to evaluate olfactory recovery. Thirty adult patients with laboratory-confirmed mild to moderate forms of COVID-19 underwent a quantitative olfactory test performed with the Sniffin’ Sticks test (SST; Burghardt, Wedel, Germany), considering olfactory threshold (T), odor discrimination (D), and odor identification (I). Results were presented as a composite TDI score (range 1–48) that used to define functional anosmia (TDI ≤ 16.5), hyposmia (16.5 &lt; TDI &lt; 30.5), or functionally normal ability to smell (TDI ≥ 30.5). Patients also self-evaluated their olfactory function by rating their ability to smell on a visual analogue scale (Visual Analog Scale rating) and answering a validated Italian questionnaire (Hyposmia Rating Scale). Patients were tested during hospitalization and about 2 months after symptoms onset. During the hospitalization, the overall TDI score indicated that our cohort had impairments in their olfactory ability (10% was diagnosed with anosmia and more than 50% were hyposmic). Almost all patients showed a significant improvement at around 1 month following the first test and for all the parts of the SST except for odor identification. None of the subjects at 1 month was still diagnosed with anosmia. We also quantified the improvement in the TDI score based on initial diagnosis. Anosmic subjects showed a greater improvement than hyposmic and normosmic subjects. In conclusion, within a month time window and 2 months after symptoms’ onset, in our cohort of patients we observed a substantial improvement in the olfactory abilities.
In Vitro Activity of Imipenem/Relebactam Against Enterobacteriaceae Isolates Obtained from Intra-abdominal, Respiratory Tract, and Urinary Tract Infections in China: Study for Monitoring Antimicrobial Resistance Trends (SMART), 2015–2018
Authors: Yang Qiwen , Zhang Hui , Yu Yunsong , Kong Haishen , Duan Qiong , Wang Yong , Zhang Shufang , Sun Ziyong , Liao Kang , Gu Li , Jiang Xiaofeng , Wu Anhua , Huang Wenxiang , Shan Bin , Kang Mei , Hu Fupin , Yu Hua , Zhang Weijuan , Xu Yingchun 
Published: October 2020

AbstractBackgroundConsidering the increasing incidence of carbapenem-resistant Enterobacteriaceae in China, this study aimed to establish the in vitro effectiveness of imipenem/relebactam (IMI/REL) on clinical Enterobacteriaceae isolates derived from intra-abdominal infections (IAIs), respiratory tract infections (RTIs), and urinary tract infections (UTIs) in China between 2015 and 2018.MethodsIn total, 8781 Enterobacteriaceae isolates from IAI, RTI, and UTI samples were collected from 22 hospitals across 7 geographic regions of China. Susceptibility to antimicrobial drugs was tested using the Clinical and Laboratory Standards Institute broth microdilution and breakpoints, and IMI/REL activity was assessed using United States Food and Drug Administration guidelines.ResultsIn 2015–2018, the most frequently identified Enterobacteriaceae species was Escherichia coli (n = 4676 [53.3%]), followed by Klebsiella pneumoniae (n = 2949 [33.6%]) and Enterobacter cloacae (n = 542 [6.2%]). The Enterobacteriaceae isolates showed 95.2% overall susceptibility to IMI/REL, of which the susceptibility rates in isolates from IAI, RTI, and UTI were 95.8%, 91.4%, and 96.6%, respectively. Overall, the susceptibilities of both intensive care unit (ICU) and non-ICU Enterobacteriaceae isolates to colistin were 92.9%, followed by IMI/REL (90.7% [95.9%]) and amikacin (83.3% [92.3%]). In addition, IMI/REL restored 66.3% susceptibility in imipenem-nonsusceptible Enterobacteriaceae.ConclusionsGiven their high in vitro susceptibility, Enterobacteriaceae infections in China should be considered for IMI/REL treatment, especially with isolates that are not susceptible to carbapenems.
Uneven geographies of economic recovery and the stickiness of individual displacement
Authors: Monastiriotis Vassilis , Gordon Ian R , Laliotis Ioannis 
Published: October 2020

AbstractHow far do economic recoveries help those whose employment potential was most affected in times of crisis to clamber back—and under what regional conditions? We examine this issue drawing on individuals’ employment histories from the UK Household Longitudinal Study. We find that—with the notable exception of the London economy—loss of occupational status is ‘sticky’, with evidence of limited ‘bouncing back’ for those ‘bumped down’ the occupational ladder during the crisis. London’s exceptionalism is consistent with expected metropolitan advantages (denser/larger labour markets), but we find no evidence of a broader North–South divide, while comparisons across regions outside London reveal no significant associations with general indicators of the form/intensity of economic recovery.
Esophageal defect repair by artificial scaffolds: a systematic review of experimental studies and proportional meta-analysis
Authors: Schizas Dimitrios , Frountzas Maximos , Sgouromallis Emmanouil , Spartalis Eleftherios , Mylonas Konstantinos S , Papaioannou Theodore G , Dimitroulis Dimitrios , Nikiteas Nikolaos 
Published: October 2020

Abstract

Background
The traditional technique of gastrointestinal reconstruction of the esophagus after esophagectomy presents plenty of complications. Hence, tissue engineering has been introduced as an effective artificial alternative with potentially fewer complications. Three types of esophageal scaffolds have been used in experimental studies so far. The aim of our meta-analysis is to present the postoperative outcomes after esophageal replacement with artificial scaffolds and the investigation of possible factors that affect these outcomes.

Methods
The present proportional meta-analysis was designed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and A MeaSurement Tool to Assess systematic Reviews guidelines. We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, and Google Scholar databases from inception until February 2020.

Results
Overall, 32 studies were included that recruited 587 animals. The pooled morbidity after esophageal scaffold implantation was 53.4% (95% CI = 36.6–70.0%). The pooled survival interval was 111.1 days (95% CI = 65.5–156.8 days). Graft stenosis (46%), postoperative dysphagia (15%), and anastomotic leak (12%) were the most common complications after esophageal scaffold implantation. Animals that underwent an implantation of an artificial scaffold in the thoracic part of their esophagus presented higher survival rates than animals that underwent scaffold implantation in the cervical or abdominal part of their esophagus (P &lt; 0.001 and P = 0.011, respectively).

Conclusion
Tissue engineering seems to offer an effective alternative for the repair of esophageal defects in animal models. Nevertheless, issues like graft stenosis and lack of motility of the esophageal scaffolds need to be addressed in future experimental studies before scaffolds can be tested in human trials.
How to approach adult patients with asymptomatic esophageal eosinophilia
Authors: Schreiner Philipp , Biedermann Luc , Greuter Thomas , Wright Benjamin L , Straumann Alex 
Published: October 2020

Summary
As the awareness among gastroenterologists regarding endoscopic features suggesting eosinophilic esophagitis is increasing, individuals without symptoms of esophageal dysfunction are increasingly being found to have esophageal eosinophilia on biopsies performed during upper gastrointestinal endoscopies. However, the course of disease and the management of these asymptomatic individuals with esophageal eosinophilia remain elusive.
In this review, we propose a definition of asymptomatic individuals with esophageal eosinophilia and discuss the prevalence, risk factors, and course of disease of this specific patient group. Furthermore, we have established a diagnostic and therapeutic pathway based on the most recent available data.
Prevalence and Outcomes of COVID-19 Among Patients With Inflammatory Bowel Disease—A Danish Prospective Population-based Cohort Study
Authors: Attauabi Mohamed , Poulsen Anja , Theede Klaus , Pedersen Natalia , Larsen Lone , Jess Tine , Rosager Hansen Malte , Verner-Andersen Marianne Kajbæk , V Haderslev Kent , Berg Lødrup Anders , Molazahi Akbar , Neumann Anders , Wase Abdel , Seidelin Jakob Benedict , Burisch Johan 
Published: October 2020

Abstract

Background and Aims
As no population-based study has investigated the susceptibility and disease course of COVID-19 among patients with inflammatory bowel diseases [IBD], we aimed to investigate this topic in a population-based setting.

Methods
Two cohorts were investigated. First, a nationwide cohort of all IBD patients diagnosed with COVID-19 was prospectively followed to investigate the disease courses of both diseases. Second, within a population-based cohort of 2.6 million Danish citizens, we identified all individuals tested for SARS-CoV-2 to determine the occurrence of COVID-19 among patients with and without IBD and other immune-mediated inflammatory diseases [IMIDs].

Results
Between January 28, 2020 and June 2, 2020, a total of 76 IBD patients with COVID-19 were identified in the national cohort and prospectively followed for 35 days (interquartile range [IQR]: 25–51). A large proportion [n = 19: 25%] required a COVID-19-related hospitalisation for 7 days [IQR: 2–8.5] which was associated with being 65 years or older (odds ratio [OR] = 23].80, 95% confidence interval [CI] 6.32–89.63, p &lt;0.01) and presence of any non-IMID comorbidity [OR = 8.12, 95% CI 2.55–25.87, p &lt;0.01], but not use of immunomodulators [p = 0.52] or biologic therapies [p = 0.14]. In the population-based study, 8476 of 231 601 [3.7%] residents tested positive for SARS-CoV-2; however, the occurrence was significantly lower among patients with IBD [62 of the 2486 patients = 2.5%, p &lt;0.01] and other IMIDs [531 of 16 492 patients = 3.2%, p &lt;0.01] as compared with patients without IMIDs.

Conclusions
Patients with IMIDs, including IBD, had a significantly lower susceptibility to COVID-19 than patients without IMIDs, and neither immunosuppressive therapies nor IBD activity were associated with the disease course of COVID-19.
Radiofrequency ablation: technological trends, challenges, and opportunities
Authors: Habibi Mohammadali , Berger Ronald D , Calkins Hugh 
Published: October 2020

Abstract
More than three decades have passed since utilization of radiofrequency (RF) ablation in the treatment of cardiac arrhythmias. Although several limitations and challenges still exist, with improvements in catheter designs and delivery of energy the way we do RF ablation now is much safer and more efficient. This review article aims to give an overview on historical advances on RF ablation and challenges in performing safe and efficient ablation.
High-degree atrioventricular block in COVID-19 hospitalized patients
Authors: Dagher Lilas , Wanna Bassam , Mikdadi Ghiath , Young Monique , Sohns Christian , Marrouche Nassir F 
Published: October 2020

Abstract

Aims
The novel coronavirus SARS-CoV-2 has shown the potential to significantly affect the cardiovascular system. Cardiac arrhythmias are commonly reported complications in COVID-19 hospitalized patients.

Methods and results
While tachyarrhythmias seem most common, we describe four cases of COVID-19 patients who developed a transient high-degree atrioventricular (AV) block during the course of their hospitalization. All four patients who developed a high-degree AV block during their hospitalization with COVID-19 did not require permanent pacing.

Conclusion
Similarly to most AV blocks associated with infectious organisms and given its transient nature, this case series suggests that conservative management strategies should be preferred in COVID-19 patients who develop complete heart block.
Antidepressant Use Partially Mediates the Association Between Depression and Risk of Falls and Fall Injuries Among Older Adults
Authors: Lohman Matthew C , Fairchild Amanda J , Merchant Anwar T 
Published: October 2020

Abstract

Background
The association between depression and fall risk in older adults is recognized, yet the mechanisms underlying this association are unclear. This study estimated the mediating role of antidepressant use in the association between depression and falls and fall injuries.

Methods
Longitudinal data from the Health and Retirement Study (2004–2006) were linked with medication data from the Prescription Drug Study (2005). The sample included community-dwelling adults aged ≥65 with data on depression and medication use (n = 3565). Depression was measured using 2 independent survey tools: Composite International Diagnostic Interview for depression short form and an 8-item version of the Center for Epidemiological Studies-Depression scale. We used causal mediation analysis to estimate and compare the direct and indirect (mediated by antidepressant use) effects of depression on falls and fall injuries.

Results
Individuals with major depressive disorder were significantly more likely to experience a fall (OR: 1.92; 95% CI: 1.41, 2.62) and a fall injury (OR: 1.67; 95% CI: 1.09, 2.55) over 2 years. Indirect effect estimates showed that antidepressant medication use accounted for approximately 19% and 18% of the association between major depressive disorder and falls and fall injuries, respectively. Results were similar when using an alternative depression measure and when considering only selective serotonin reuptake inhibitor antidepressants.

Conclusions
Antidepressant use explains a significant proportion, but not a majority, of the association between depression and greater fall risk. Treatment benefits of antidepressants should be considered with, and may outweigh, concerns about increased risk of falls associated with antidepressant use.
Structural evidence for a proline-specific glycopeptide recognition domain in an O-glycopeptidase
Authors: Noach Ilit , Boraston Alisdair B 
Published: October 2020

AbstractThe glycosylation of proteins is typically considered as a stabilizing modification, including resistance to proteolysis. A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition. IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction. IMPa, however, is a relatively large multidomain protein and how its additional domains may contribute to its function remains unknown. Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline. The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions. This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
Black Lives Matter in health promotion: moving from unspoken to outspoken
Authors: Leitch Stephanie , Corbin J Hope , Boston-Fisher Nikita , Ayele Christa , Delobelle Peter , Gwanzura Ottemöller Fungisai , Matenga Tulani Francis L , Mweemba Oliver , Pederson Ann , Wicker Josette 
Published: October 2020

SummaryRacism is a public health crisis. Black communities (including Africans, the African diaspora and people of African descent) experience worse health outcomes as demonstrated by almost any measure of health and wellbeing—e.g. life expectancy; disease prevalence; maternal mortality rates. While health promotion has its foundation in promoting equity and social justice, it is clear that however well-intended, we are not affecting meaningful change for Black communities quickly enough. Through this article, we outline the intersection of social determinants of health and anti-Black racism. We describe how in the first 8 months of 2020 Black communities around the globe have been disproportionately affected by COVID-19, while also having to respond to new instances of police brutality. We assert that the time has come for health promotion to stop neutralizing the specific needs of Black communities into unspoken ‘good intentions’. Instead, we offer some concrete ways for the field to become outspoken, intentional and honest in acknowledging what it will take to radically shift how we promote health and wellbeing for Black people.
Genomics-based immuno-oncology: bridging the gap between immunology and tumor biology
Authors: DiNatale Renzo G , Hakimi A Ari , Chan Timothy A 
Published: October 2020

Abstract
The first hypotheses about how the immune system affects cancers were proposed in the early 20th century. These early concepts about cancer immunosurveillance were further developed in the decades that followed, but a detailed understanding of cancer immunity remained elusive. It was only recently, through the advent of high-throughput technologies, that scientists gained the ability to profile tumors with a resolution that allowed for granular assessment of both tumor cells and the tumor microenvironment. The advent of immune checkpoint inhibitors (ICIs), which have proven to be effective cancer therapies in many malignancies, has spawned great interest in developing biomarkers for efficacy, an endeavor that highlighted the value of dissecting tumor immunity using large-scale methods. Response to ICI therapy has been shown to be a highly complex process, where the dynamics of tumor and immune cells is key to success. The need to understand the biologic mechanisms at the tumor–immune interface has given rise to the field of cancer immunogenomics, a discipline that aims to bridge the gap between cancer genomics and classical immunology. We provide a broad overview of this emerging branch of translational science, summarizing common platforms used and recent discoveries in the field, which are having direct clinical implications. Our discussion will be centered around the genetic foundations governing tumor immunity and molecular determinants associated with clinical benefit from ICI therapy. We emphasize the importance of molecular diversity as a driver of anti-tumor immunity and discuss how these factors can be probed using genomic approaches.
RNA-Seq profiling of leukocytes reveals a sex-dependent global circular RNA upregulation in multiple sclerosis and 6 candidate biomarkers
Authors: Iparraguirre Leire , Alberro Ainhoa , Sepúlveda Lucía , Osorio-Querejeta Iñaki , Moles Laura , Castillo-Triviño Tamara , Hansen Thomas B , Muñoz-Culla Maider , Otaegui David 
Published: October 2020

Abstract
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, with higher prevalence in women, that leads to neurological disability. The disease course and clinical phenotype are highly variable, and therefore, biomarkers for the diagnosis, classification, monitoring of the disease and treatment assessment are needed. Studies have shown a dysregulation in the coding and non-coding RNAs and proposed some as biomarkers. However, still none of them have reached the clinical practice. Recently, circular RNAs (circRNAs) have emerged as new players in the transcriptome that hold a great potential as biomarkers in several diseases. Leukocytes from 30 MS patients and 20 healthy controls (HCs) were RNA-sequenced to study the linear and circular transcriptome. Differential expression analysis was performed by DESeq, and circRNA candidates were studied in a second cohort (70 MS and 46 HC) by RT-qPCR and in paired samples drawn during the relapse and remission phases (20 patients). Among the differentially expressed circRNAs, 96.1% are upregulated in patients compared with controls, but similar circRNA profiles are found between MS types. The same upregulation trend was observed in females but not in males or in the linear transcriptome. The upregulation of 6 circRNAs was validated, and a change in their expression was found between relapse and remission. The 6 circRNAs showed a good performance to discriminate patients from HC with a combined area under the curve of 0.852. There is global, specific and sex-dependent increase of circRNA expression in MS, and 6 circRNAs are proposed as potential biomarkers.