bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity of γ-ray and radio variability of bright blazars and implications for γ-ray emission location
Authors: Zhang Hai-Ming , Wang Zhen-Jie , Zhang Jin , Yi Ting-Feng , Chen Liang , Lu Rui-Jing , Liang En-Wei
Published: March 2020

Violent multi-wavelength variabilities are observed in γ-ray-selected blazars. We present an analysis of long-term light curves for eight bright blazars to explore the co-variation pattern in the γ-ray and radio bands. We extract their γ-ray light curves and spectra with data observed by the Fermi Large Area Telescope (LAT) since 2008. We find diverse co-variation patterns between the γ-ray and radio (at 43 GHz) fluxes in these sources. The γ-ray and radio fluxes of 3C 454.3 and PKS 1633+382 are correlated without any time lag, suggesting that they are from the same radiation region. Similar correlation is also observed in 3C 273 and PKS 1222+216, but the radio flux lags behind the γ-ray flux by approximately ∼160 d and ∼290 d, respectively. This likely suggests that their γ-ray emission regions are located the upstream of their radio cores at 43 GHz. The γ-ray and radio fluxes of the other four blazars are not correlated, implying that the γ-ray and radio emission may be from different regions in their jets. The γ-ray light curves of the eight blazars can be decomposed into some components with long-timescale variability and some fast spike flares. We propose that they may be attributed to the central engine activity and the magnetic reconnection process or turbulence in the local emission region, respectively.
Assessing the UK Football Policing Unit Funding of Football Banning Orders in Times of Policing Austerity
Authors: Hester Richard
Published: March 2020

This article examines how austerity measures have affected football policing units in UK, with a specific focus on the use of UK Football Policing Unit (UKFPU) funding for football banning orders. The research utilizes semi-structured interviews with football police officers and examines publicly available Home Office data. Austerity measures were found to be restrictive to operational deployments at football matches, reducing opportunities for early intervention, liaison-based policing, and evidence gathering. The findings offer limited support to previous research into UKFPU funding, in that it is a target driven process. However, new accounts are emerging which show that officers are rejecting the idea of funding for banning orders, and that reform is needed. This could be in the guise of UKFPU funding being utilized for other football policing activities that are aimed at preventing disorder, and engaging supporters into positive behaviour change.
Vasculitis and the peripheral nervous system
Authors: Ginsberg Lionel
Published: March 2020

Peripheral neuropathy is a common feature of systemic vasculitis and can also occur when vessel wall inflammation is confined to the vasa nervorum, as a tissue-specific condition—non-systemic vasculitic neuropathy (NSVN). Typically, the clinical picture in both systemic and non-systemic cases is of a lower limb predominant, distal, asymmetric or multifocal neuropathy, which is painful and subacute in onset. For NSVN, nerve biopsy is required to make the diagnosis, and nerve biopsy also has a role when vasculitic neuropathy is suspected and a systemic process has not yet declared itself. Early recognition of the disorder is important, because it is treatable, and without treatment potentially disabling, or even lethal if part of an undiagnosed systemic process. Treatment is generally with combination therapy (glucocorticoid plus other immunosuppressant), after which motor and sensory recovery are likely to occur, albeit slowly, but the patient may be left with chronic neuropathic pain.
IL-37 inhibits M1-like macrophage activation to ameliorate temporomandibular joint inflammation through the NLRP3 pathway
Authors: Luo Ping , Peng Sisi , Yan Yin , Ji Ping , Xu Jie
Published: March 2020

Objectives

IL-37 has been identified as an important anti-inflammatory and immunosuppressive factor. This study was undertaken to explore how IL-37 affects M1/M2-like macrophage polarization and thus contributes to anti-inflammatory processes in the temporomandibular joint.

Methods

Western blotting, quantitative real-time PCR (qRT-PCR) and immunofluorescence were used to verify the IL-37-induced polarization shift from the M1 phenotype to the M2 phenotype, and the related key pathways were analysed by western blotting. Human chondrocytes were stimulated with M1-conditioned medium (CM) or IL-37-pretreated M1-CM, and inflammatory cytokines were detected. siRNA-IL-1R8 and MCC-950 were used to investigate the mechanism underlying the anti-inflammatory effects of IL-37. Complete Freund’s adjuvant-induced and disc perforation-induced inflammation models were used for in vivo studies. Haematoxylin and eosin, immunohistochemical and safranin-O staining protocols were used to analyse histological changes in the synovium and condyle.

Results

Western blotting, qRT-PCR and immunofluorescence showed that IL-37 inhibited M1 marker expression and upregulated M2 marker expression. Western blotting and qRT-PCR showed that pretreatment with IL-37 suppressed inflammatory cytokine expression in chondrocytes. IL-37 inhibited the expression of NLRP3 and upregulated the expression of IL-1R8. Si-IL-1R8 and MCC-950 further confirmed that the anti-inflammatory properties of IL-37 were dependent on the presence of IL-1R8 and NLRP3. In vivo, IL-37 reduced synovial M1 marker expression and cartilage degeneration and increased M2 marker expression.

Conclusion

IL-37 shifting of the polarization of macrophages from the pro-inflammatory M1 phenotype to the beneficial anti-inflammatory M2 phenotype seems to be a promising therapeutic strategy for treating temporomandibular joint inflammation.
Genetic Diversity of Nine Non-Recombinant Potato virus Y Isolates From Three Biological Strain Groups: Historical and Geographical Insights
Authors: Green Kelsie J. , Quintero-Ferrer Arturo , Chikh-Ali Mohamad , Jones Roger A. C. , Karasev Alexander V.
Published: March 2020

Potato virus Y (PVY) isolates from potato currently exist as a complex of six biologically defined strain groups all containing nonrecombinant isolates and at least 14 recombinant minor phylogroups. Recent studies on eight historical UK potato PVY isolates preserved since 1984 found only nonrecombinants. Here, four of five PVY isolates from cultivated potato or wild Solanum spp. collected recently in Australia, Mexico, and the U.S.A. were typed by inoculation to tobacco plants and/or serological testing using monoclonal antibodies. Next, these five modern isolates and four additional historical UK isolates belonging to biological strain groups PVYC, PVYZ, or PVYN obtained from cultivated potato in 1943 to 1984 were sequenced. None of the nine complete PVY genomes obtained were recombinants. Phylogenetic analysis revealed that the four historical UK isolates were in minor phylogroups PVYC1 (YC-R), PVYO-O (YZ-CM1), PVYNA-N (YN-M), or PVYEu-N (YN-RM), Australian isolate YO-BL2 was in minor phylogroup PVYO-O5, and both Mexican isolate YN-Mex43 and U.S.A. isolates YN-MT12_Oth288, YN-MT12_Oth295, and YN-WWAA150131G42 were in minor phylogroup PVYEu-N. When combined, these new findings and those from the eight historical UK isolates sequenced earlier provide important historical insights concerning the diversity of early PVY populations in Europe and the appearance of recombinants in that part of the world. They and four recent Australian isolates sequenced earlier also provide geographical insights about the geographical distribution and diversity of PVY populations in Australia and North America.
Advanced Non–Small Cell Lung Cancer Patients With Low Tumor Mutation Burden Might Derive Benefit From Immunotherapy
Authors: Nie Wei , Xu Mi-Die , Gan Lu , Zhang Yi , Qian Jie , Gu Kai , Zhang Xue-Yan , Wang Hui-Min , Yan Bo , Gu Ping , Zhang Bo , Wang Shu-Yuan , Hu Fang , Li Chang-Hui , Zhong Hua , Han Bao-Hui
Published: March 2020

The aim of this study is to investigate the association between tumor mutation burden (TMB) and survival in non–small cell lung cancer (NSCLC) patients with anti-programmed cell death protein 1 and anti-programmed death-ligand 1 blockade. Two retrospective cohorts and The Cancer Genome Atlas NSCLC data set were included in this study. The restricted cubic spline analysis was used to explore the association between TMB and survival. The cutoff values for TMB were determined by X-tile software. Primary outcomes were overall survival (OS). The associations between TMB and intratumor heterogeneity, number of segments, fraction of genome alterations, aneuploidy score, and T-cell populations were also investigated. In the restricted cubic spline plots, TMB showed an inverted U-shaped curve with OS. The median OS in the low TMB group was significantly longer than those in the medium TMB group. In The Cancer Genome Atlas NSCLC data set, low TMB was also associated with longer OS in comparison with medium TMB. Furthermore, NSCLC patients with low TMB had significantly lower intratumor heterogeneity, number of segments, fraction of genome alterations, aneuploidy score, T-helper type 2 (Th2) cells, and CD8+ T cells, but higher levels of Th1 and Th17 cells. Low TMB might be a prognostic factor for NSCLC patients receiving anti-programmed cell death protein 1/programmed death-ligand 1 immunotherapy.
Lung Transplantation Using a Hybrid Extracorporeal Membrane Oxygenation Circuit
Authors: Thomas Mathew , Martin Archer K. , Allen Wesley L. , Makey Ian A. , Renew J. Ross , Rodrigues Eduardo S. , Mordecai Monica M. , Brown Thomas E , Foeks Jeremy J. , Johnson James L. , Landolfo Kevin L. , Pham Si M.
Published: March 2020

Extracorporeal circulation (ECC) support using intraoperative extracorporeal membrane oxygenation (ECMO) during lung transplantation (LTx) is now a routine practice for many high volume centers. Circuits that are dedicated to ECMO alone can be expensive and do not allow full cardiopulmonary bypass (CPB) to be performed. We describe our technique of instituting venoarterial ECMO during LTx using a less-expensive hybrid circuit that facilitates easy and immediate conversion to full CPB if needed, without interruption of ECC.
Hip fracture care—Latin America
Authors: Rojas Luis Gerardo Padilla , Hernández Sergio Quintero , Ávila José María Jiménez , Cervantes Roberto Enrique López , Enghelmayer Rafael Amadei , Pesciallo Cesar , Garabano German , Mackechnie Madeline C. , Quintero José Eduardo , Kojima Kodi E.
Published: March 2020

Incidence rates of hip fractures in Latin America continue to rise. These fractures are associated with factors such as health, education, and socioeconomic status. Although there are many well-developed public and private healthcare systems available, the quality and consistency in the management of patients with hip fractures varies substantially.

This article provides a summary review of national hip fracture care guidelines in 4 of the largest countries in Latin America (Mexico, Colombia, Brazil, and Argentina), describing national guidelines, audits, standard treatment approaches in each country and regional policies; with the goal of understanding and comparing the different guidelines, identifying the main problems in each country, learning from the policies of the other countries, and developing improvement projects.
Hip Fracture Management
Authors: Miclau Theodore
Published: March 2020

Hip fractures, among the most common geriatric injuries, are associated with adverse patient outcomes and significant costs. The incidence of these fractures continues to rise with an aging population worldwide. While many factors that negatively impact patient outcomes are nonmodifiable, others, which include pre- and postoperative medical management, timing of surgical stabilization, and fracture fixation methods, are modifiable and have been shown to affect outcomes. Treatment pathways are dependent upon available resources and established systems, and comparative guidelines from different regions and countries are not well documented. This special issue seeks to highlight regional differences in hip fracture care globally and represents a collaborative work of member societies of the International Orthopaedic Trauma Association, an international association of orthopaedic societies dedicated to the promotion of musculoskeletal trauma care through advancements in patient care, research, and education. The expectation is that better understanding these differences will aid efforts to better understand, improve, and standardize existing approaches to hip fracture management worldwide.
The top three unanswered questions in the management of open fractures
Authors: Atwan Yousif , Schemitsch Emil H.
Published: March 2020

Despite improvements in treatment strategies and emphasis on preventative measures, the management of open fractures continues to be a challenging endeavor for orthopaedic surgeons. Deep infections, delayed healing, and nonunion continue to be problematic complications associated with these devastating injuries. There remain many unanswered clinical questions regarding the management of these injuries and how the various aspects of care can be further optimized. There continues to be a paucity of evidence regarding how infection can best be treated and prevented, how to reliability predict bone healing/nonunion, and how bone healing can be best augmented in the setting of open fractures and their potential nonunions. This review aims to assess the current literature on these top unanswered questions and discuss the gaps in evidence that may be filled with future studies.
Hip fracture care and national systems
Authors: Swenning Todd , Leighton Jennifer , Nentwig Michelle , Dart Bradley
Published: March 2020

While it is widely understood that management of hip fractures not only represents clinical decision making dilemmas for the individual orthopaedist, these increasingly common injuries present economic burdens to local and national systems as well. This supplement article looks at current clinical trends, as well as systems-based issues in the United States and Canada.
RE-AIM Evaluation Plan for Washington State Innovation Models Project
Authors: Grembowski David , Conrad Douglas A. , Naranjo Diana , Wood Suzanne , Coe Norma B. , Kwan-Gett Tao , Baseman Janet
Published: March 2020

The State of Washington received a State Innovation Models (SIM) $65 million award from the federal Centers for Medicare & Medicaid Services to improve population health and quality of care and reduce the growth of health care costs in the entire state, which has over 7 million residents. SIM is a “complex intervention” that implements several interacting components in a complex, decentralized health system to achieve goals, which poses challenges for evaluation. Our purpose is to present the state-level evaluation methods for Washington's SIM, a 3-year intervention (2016-2018). We apply the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) evaluation framework to structure our evaluation. We create a conceptual model and a plan to use multiple and mixed methods to study SIM performance in the RE-AIM components from a statewide, population-based perspective.
Shared Decision-Making Measures: A Systematic Review
Authors: Ahmad Muayyad , Abu Tabar Nazih , Othman Elham H. , Abdelrahim Zakaria
Published: March 2020

Background and Objectives:

This review used the recent COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) rating system, which gives the reader the ability to find appropriate instruments in a simple way. Shared decision-making (SDM) is part of health professionals', nurses', and patients' interaction about fundamental and special nursing care issues. The objective of this study was to critically appraise instruments that measure SDM in health care–related decisions according to the COSMIN criteria.

Methods:

This review was reported in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guideline. A thorough search identified SMD measures via PubMed, Cochrane Library, MEDLINE, EBSCO Host, Ovid journals, SAGE journals, and Google Scholar search engine through November 2018 and updated on March 24, 2019. A rating system with “very good,” “adequate,” “doubtful,” or “inadequate” for COSMIN was used.

Results:

The 17 instruments reported in this review are varied in the measured perspectives; observer-based viewpoint, patient questionnaires, provider questionnaires, and physician questionnaires, or even mixed perspectives. Only one instrument (OPTION 12 Scale) received an excellent rating across all 5 COSMIN validity rating sections in content, structural, and criterion validity.

Conclusion:

Most of the instruments scored poorly on the COSMIN checklist. Despite the vast number of instruments measuring SDM, researchers must undertake critical appraisal before selecting an acceptable instrument that meets the specific research goal, as well as the quality requirements.
Fully Automated Segmentation of Connective Tissue Compartments for CT-Based Body Composition Analysis
Authors: Nowak Sebastian , Faron Anton , Luetkens Julian A. , Geißler Helena L. , Praktiknjo Michael , Block Wolfgang , Thomas Daniel , Sprinkart Alois M.
Published: March 2020

Objective

Body composition comprises prognostic information in patients with various malignancies and can be opportunistically determined from routine computed tomography (CT) scans. However, accurate assessment of patients with alterations, for example, due to ascites or anasarca, and accurate identification of intermuscular fat remain challenging. In this study, we aimed to develop a fully automated and highly accurate segmentation tool for connective tissue compartments from abdominal CT scans using the open-source Convolutional Neural Network (CNN) DeepMedic.

Materials and Methods

In this retrospective study, a CNN was developed using data of 1143 consecutive patients undergoing either preinterventional CT for transcatheter aortic valve implantation (TAVI) (82%) or diagnostic CT for liver cirrhosis with portosystemic shunting (PTSS) (18%). All analyses were performed on single-slice images at the L3/L4 level. The data were subdivided into subsets of training (70%), validation (15%), and test data (15%), balanced for TAVI and PTSS patients. To demonstrate the generalizability of the applied method with respect to nonspecific clinical routine data, the model with the highest performance in TAVI and PTSS patients was further tested on 100 randomly selected patients who underwent CT for routine diagnostic purposes at a hospital of maximum care, including critically ill patients. The applicability of the method to native CT examinations was additionally tested on 50 patients.

Results

Compared with the ground truth of the test data, the presented method achieved highly accurate segmentation results (subcutaneous adipose tissue [SAT], Dice score [DSC]: 0.98 ± 0.01; visceral adipose tissue [VAT], DSC: 0.96 ± 0.04; skeletal muscles [SM], DSC: 0.95 ± 0.02) and showed excellent generalizability on the routine CT diagnostic patients (SAT, DSC: 0.97 ± 0.04; VAT, DSC: 0.95 ± 0.05; SM, DSC: 0.95 ± 0.04) and also on native CT scans (SAT, DSC: 0.99 ± 0.01; VAT, DSC: 0.97 ± 0.03; SM, DSC: 0.97 ± 0.02).

Conclusions

Fully automated determination of body composition based on CT can be performed with excellent results using the open-source CNN DeepMedic. The trained model is made usable for research by a deployable and sharable application.
Healthy Sleep Leads to Improved Nutrition and Exercise in College Females
Authors: Adams Sue K. , Dimond Elizabeth , Delmonico Matthew J. , Sylvester Emily , Accetta Chelsea , Domos Carly , Lofgren Ingrid E.
Published: March 2020

Diet, sleep quality, and exercise are important determinants of physical, mental, and emotional health. College students are particularly vulnerable to impaired health, as they experience multiple unique stressors associated with college life that impact their ability to engage in healthy sleep, diet, and exercise habits. Our results found that exercise significantly mediated the association between sleep quality and diet. Improved sleep habits may increase a young woman's ability and desire to exercise, thus impacting her diet and nutrition. Findings suggest that clinicians can use a person's motivation in any one domain, or multiple domains, to impact other health domains.
Time–energy uncertainty principle for irreversible heat engines
Authors: Hanel Rudolf , Jizba Petr
Published: March 2020

Even though irreversibility is one of the major hallmarks of any real-life process, an actual understanding of irreversible processes remains still mostly semi-empirical. In this paper, we formulate a thermodynamic uncertainty principle for irreversible heat engines operating with an ideal gas as a working medium. In particular, we show that the time needed to run through such an irreversible cycle multiplied by the irreversible work lost in the cycle is bounded from below by an irreducible and process-dependent constant that has the dimension of an action. The constant in question depends on a typical scale of the process and becomes comparable to Planck’s constant at the length scale of the order Bohr radius, i.e. the scale that corresponds to the smallest distance on which the ideal gas paradigm realistically applies.

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
Phenomenological quantum thermodynamics resource theory for closed bipartite Schottky systems
Authors: Muschik Wolfgang
Published: March 2020

How to introduce thermodynamics to quantum mechanics? From numerous possibilities of solving this task, the simple choice is here: the conventional von Neumann equation deals with a density operator whose probability weights are time-independent. Because there is no reason apart from the reversible quantum mechanics that these weights have to be time-independent, this constraint is waived, which allows one to introduce thermodynamical concepts to quantum mechanics. This procedure is similar to that of Lindblad’s equation, but different in principle. But beyond this simple starting point, the applied thermodynamical concepts of discrete systems may perform a ‘source theory’ for other versions of phenomenological quantum thermodynamics.

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
Nonequilibrium thermodynamics: emergent and fundamental
Authors: Ván P.
Published: March 2020

How can we derive the evolution equations of dissipative systems? What is the relation between the different approaches? How much do we understand the fundamental aspects of a second law based framework? Is there a hierarchy of dissipative and ideal theories at all? How far can we reach with the new methods of nonequilibrium thermodynamics?

This article is part of the theme issue ‘Fundamental aspects of nonequilibrium thermodynamics’.
Micromonospora pelagivivens sp. nov., a new species of the genus Micromonospora isolated from deep-sea sediment in Japan
Authors: Intra Bungonsiri , Panbangred Watanalai , Inahashi Yuki , Také Akira , Mori Mihoko , Ōmura Satoshi , Matsumoto Atsuko
Published: March 2020

A novel marine actinomycete, designated strain KJ-029T, was isolated from a marine sediment sample (water depth of 226 m) in Kagoshima, Japan. 16S rRNA gene sequence analysis revealed that the new isolate was most closely related to

Micromonospora craniellae

LHW 63014T (99.3 % similarity). Phylogenetic analyses of the genus

Micromonospora

based on 16S rRNA gene sequences showed that strain KJ-029T was clustered with

Micromonospora craniellae

LHW 63014T and

Micromonospora endophytica

202201T. However, digital DNA–DNA hybridization analyses presented low levels of relatedness in the range of 24.8–32.9 % between strain KJ-029T and the above closely related strains. The novel strain contained meso-diaminopimelic acid and 3-OH-diaminopimelic acid, d-glutamic acid, glycine and d-alanine in the cell-wall peptidoglycan. The acyl type of the peptidoglycan was glycolyl and mycolic acids were absent. The major menaquinone was MK-9(H4). The whole-cell sugars consisted of glucose, mannose, xylose and ribose. Phosphatidylethanolamine was detected as the major phospholipid and corresponded to phospholipid type II. The predominant cellular fatty acid was iso-C16 : 0. The DNA G+C content of the genomic DNA was 71.5 mol%. Based on the present polyphasic study, strain KJ-029T represents a novel species of the genus

Micromonospora

, for which the name Micromonospora pelagivivens sp. nov. is proposed. The type strain is KJ-029T (=NBRC 113519T=TBRC 9233T).
Prevalence and Factors Associated with Depression and Anxiety of Hospitalized Patients with COVID-19
Authors: Kong Xiangyu , Zheng Kailian , Tang Min , Kong Fanyang , Zhou Jiahuan , Diao Le , Wu Shouxin , Jiao Piqi , Su Tong , Dong Yuchao
Published: March 2020

Objective

The 2019 coronavirus disease (COVID-19) epidemic has raised international concern. Mental health is becoming an issue that cannot be ignored in our fight against it. This study aimed to explore the prevalence and factors linked to anxiety and depression in hospitalized patients with COVID-19.

Methods

A total of 144 patients diagnosed with COVID-19 were included in this study. We assessed depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS), and social support using the Perceived Social Support Scale (PSSS) among patients at admission. Multivariate linear regression analyses were performed to identify factors associated with symptoms of anxiety and depression.

Results

Of the 144 participants, 34.72% and 28.47% patients with COVID-19 had symptoms of anxiety or depression, respectively. The bivariate correlations showed that less social support was correlated with more anxious (r=-0.196, p<0.05) and depressive (r=-0.360,p<0.05) symptoms among patients with COVID-19. The multiple linear regression analysis showed that gender (β=1.446, p=0.034), age (β=0.074, p=0.003), oxygen saturation (β =-2.140, p=0.049), and social support (β =-1.545, p=0.017) were associated with anxiety for COVID-19 patients. Moreover, age (β=0.084, p=0.001), family infection with SARS-CoV-2 (β =1.515, p=0.027) and social support (β =-2.236, p<0.001) were the factors associated with depression.

Conclusion

Hospitalized patients with COVID-19 presented features of anxiety and depression. Mental concern and appropriate intervention are essential parts of clinical care for those who are at risk.
Disruption of the topological associated domain at Xp21.2 is related to gonadal dysgenesis: A general mechanism of pathogenesis
Authors: dos Santos Ana Paula , Meinel Jakob A. , Cruz Piveta Cristiane dos Santos , de Andrade Juliana Gabriel Ribeiro , Fabbri-Scallet Helena , Gil-da-Silva-Lopes Vera Lúcia , Guerra-Júnior Gil , Künstner Axel , Kaiser Frank J. , Holterhus Paul-Martin , Hiort Olaf , Busch Hauke , Maciel-Guerra Andréa Trevas , de Mello Maricilda Palandi , Werner Ralf
Published: March 2020

Duplications of dosage sensitive sex-locus Xp21.2 including NR0B1 have been linked to 46,XY gonadal dysgenesis (GD) and their effects are attributed merely to increase gene dosage of NR0B1 (DAX1). Here we present a general mechanism how deletions, duplications, triplications or inversions with or without NR0B1 at Xp21.2 can lead to partial or complete GD by disrupting the cognate topological associated domain (TAD) in the vincinity of NR0B1. Our model is supported by three unrelated patients: two showing a 287kb overlapping duplication at the Xp21.2 locus upstream of NR0B1 containing CXorf21 and GK and one patient having a large new triplication of Xp21.2 as the most likely cause of GD. Whole Genome sequencing uncovered the exact structural rearrangements of the duplications and the triplication. Comparison with a previously published deletion upstream of NR0B1 revealed a common 35kb overlap between the deletion, our newly reported NR0B1 upstream duplications and the triplication as well as all other copy number variations (CNVs) at Xp21.2 reported so far. This overlap contains a strong CCCTC-binding factor (CTCF) binding site representing one boundary of the NR0B1 TAD. All three CNVs at Xp21.2 most likely disrupt this TAD boundary, which isolates NR0B1 from CXorf21 and GK and putatively results in GK and CXorf21 enhancer adoption and ensuing ectopic NR0B1 expression. As a result, the patients’ transcriptomes developed an intermediate expression pattern with both ovarian and testicular features and greatly reduced expression of spermatogenesis-related genes. This model not only allows better diagnosis of GD displaying CNVs at Xp21.2, but also gives deeper insight how spatiotemporal activation of developmental genes can be disrupted by reorganized TADs also in other rare diseases.
Framing the potential of public frameshift peptides as immunotherapy targets in colon cancer
Authors: Spaanderman Ide T. , Peters Fleur S. , Jongejan Aldo , Redeker Egbert J.W. , Punt Cornelis J.A. , Bins Adriaan D.
Published: March 2020

Approximately 15% of Colon Cancers are Microsatellite Instable (MSI). Frameshift Peptides (FPs) formed in MSI Colon Cancer are potential targets for immunotherapeutic strategies. Here we comprehensively characterize the mutational landscape of 71 MSI Colon Cancer patients from the cancer genome atlas (TCGA-COAD). We confirm that the mutations in MSI Colon Cancers are frequently frameshift deletions (23% in MSI; 1% in microsatellite stable), We find that these mutations cluster at specific locations in the genome which are mutated in up to 41% of the patients. We filter these for an adequate variant allele frequency, a sufficient mean mRNA level and the formation of a Super Neo Open Reading Frame (SNORF). Finally, we check the influence of Nonsense Mediated Decay by comparing RNA and DNA sequencing results. Thereby we identify a set of 20 NMD-escaping Public FPs (PFPs) that cover over 90% of MSI Colon Cancer patients and 3 out of 4 Lynch patients in the TCGA-COAD. This underlines the potential for PFP directed immunotherapy, both in a therapeutic and a prophylactic setting.
Task-related motor response inflates confidence
Authors: Siedlecka Marta , Paulewicz Borysław , Koculak Marcin
Published: March 2020

Studies on confidence in decision-making tasks have repeatedly shown correlations between confidence and the characteristics of motor responses. Here, we show the results of two experiments in which we manipulated the type of motor response that precedes confidence rating. Participants decided which box, left or right, contained more dots and then reported their confidence in this decision. In Experiment 1, prior to confidence rating, participants were required to follow a motor cue. Cued-response type was manipulated in two dimensions: task-compatibility (the relation between response set and task-relevant decision alternatives), and stimulus-congruence (spatial correspondence between response key and the location of the stimulus that should be chosen). In Experiment 2, a decision-related response set was randomly varied in each trial, being either vertical (task incompatible) or horizontal (task-compatible, spatially congruent and incongruent). The main results showed that choice confidence increased following task-compatible responses, i.e. responses related to the alternatives of the choice in which confidence was reported. Moreover, confidence was higher in these conditions, independently of response accuracy and spatial congruence with the ‘correct’ stimuli. We interpret these results as suggesting that action appropriate in the context of a given task is an indicator of successful completion of the decision-related process. Such an action, even a spurious one, inflates decisional confidence.
Comparative performance of four nucleic acid amplification tests for SARS-CoV-2 virus
Authors: Xiong Yujuan , Li Zhen-Zhen , Zhuang Qi-Zhen , Chao Yan , Li Fei , Ge Yi-Yuan , Wang Yi , Ke Pei-Feng , Huang Xian-Zhang
Published: March 2020

Coronavirus disease 2019 (COVID-19) can be screened and diagnosed through the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time reverse transcription polymerase chain reaction. SARS-CoV-2 nucleic acid amplification tests (NAATs) have been rapidly developed and quickly applied to clinical testing during the pandemic. However, studies evaluating the performance of these NAAT assays are limited. We evaluated the performance of four NAATs, which were marked by the Conformité Européenne and widely used in China during the pandemic. Results showed that the analytical sensitivity of the four assays was significantly lower than that claimed by the NAAT manufacturers. The limit of detection (LOD) of Daan, Sansure, and Hybribio NAATs was 3000 copies/mL, whereas the LOD of Bioperfectus NAATs was 4000 copies/mL. The results of the consistency test using 46 samples showed that Daan, Sansure, and Hybribio NAATs could detect the samples with a specificity of 100% (30/30) and a sensitivity of 100% (16 /16), whereas Bioperfectus NAAT detected the samples with a specificity of 100% (30/30) and a sensitivity 81.25% (13/16). The sensitivity of Bioperfectus NAAT was lower than that of the three other NAATs; this finding was consistent with the result that Bioperfectus NAAT had a higher LOD than the three other kinds of NAATs. The four above mentioned reagents presented high specificity; however, for the detection of the samples with low virus concentration, Bioperfectus reagent had the risk of missing detection. Therefore, the LOD should be considered in the selection of SARS-CoV-2 NAATs.
Mining Twitter to Assess the Determinants of Health Behavior towards Palliative Care in the United States
Authors: Zhao Yunpeng , Zhang Hansi , Huo Jinhai , Guo Yi , Wu Yonghui , Prosperi Mattia , Bian Jiang
Published: March 2020

Palliative care is a specialized service with proven efficacy in improving patients’ quality-of-life. Nevertheless, lack of awareness and misunderstanding limits its adoption. Research is urgently needed to understand the determinants (e.g., knowledge) related to its adoption. Traditionally, these determinants are measured with questionnaires. In this study, we explored Twitter to reveal these determinants guided by the Integrated Behavioral Model. A secondary goal is to assess the feasibility of extracting user demographics from Twitter data—a significant shortcoming in existing studies that limits our ability to explore more fine-grained research questions (e.g., gender difference). Thus, we collected, preprocessed, and geocoded palliative care-related tweets from 2013 to 2019 and then built classifiers to:1) categorize tweets into promotional vs. consumer discussions, and 2) extract user gender. Using topic modeling, we explored whether the topics learned from tweets are comparable to responses of palliative care-related questions in the Health Information National Trends Survey.
Clinical features and outcomes of 197 adult discharged patients with COVID-19 in Yichang, Hubei
Authors: Zhou Fating , Yu Xiaogang , Tong Xiaowei , Zhang Rong
Published: March 2020

Purpose

To investigate the epidemiology and clinical features of discharged adult patients with coronavirus infection disease 2019 (COVID-19) in Yichang.

Method

The retrospective study recruited 197 cases of COVID-19 discharged from Yichang Central People’s Hospital and Yichang Third People’s Hospital from Jan 17 to Feb 26, 2020. All cases were confirmed by real-time RT-PCR or chest computer tomography (CT). The survivors were followed up until March 4,2020. Clinical data, including demographic characteristic, presentation, underlying illness, exposure history, laboratory examination, radiology and prognosis were enrolled and analyzed by SPSS 19.0 software.

Results

There were 197 adult discharged patients with COVID-19 in this study. Statistical analysis indicated that the average age was 55.94 years, and female patients were 99(50.3%).Those patients mainly resided in urban with exposure history in 2 weeks, while 7 medical staffs were infected. Fever (77.6%%), cough (43.6%) and weakness (14.7%) were the common symptoms. Leukocytes were mainly normal or decreased in 185 patients (92.9%), both lymphocytes and eosinophils were below normal range, the ratios were 56.9% and 50.3%, respectively. On the contrary, lactate dehydrogenases raised in 65 patients. C-reactive protein (72.4%) elevated in the most of patients. The sensitivity of RT-PCR was 63.5%. Chest CT indicated that bilateral patchy shadows (69.0%) were the most common imaging manifestations.169(85.8%) patients recovered and transferred to a designated hospital for observation, and the others (14.2%) turned worst and died of acute respiratory failure.

Conclusion

COVID-19 infection with highly contagious have become a life-threaten public healthy problem, the sensitivity of RT-PCR was limited. Chest CT scan was recommended for the suspected patients. Furthermore, lymphocytopenia and eosinophils declining without leukocytes increasing may be considered as a useful evidence for the diagnosis.
Descriptive and prognostic value of a computational model of metastasis in high-risk neuroblastoma
Authors: Benzekry Sébastien , Sentis Coline , Coze Carole , Tessonnier Laëtitia , André Nicolas
Published: March 2020

High Risk Neuroblastoma (HRNB) is the second most frequent solid tumor in children. Prognosis remains poor despite multimodal therapies. Mathematical models have been developed to describe metastasis, but their prognosis value has yet to be determined and none exists in neuroblastoma.

We established such a model for HRNB relying on two coefficients: α(growth) and μ (dissemination). The model was calibrated using diagnosis values of primary tumor size, lactate dehydrogenase circulating levels (LDH) and the meta-iodo-benzyl-guanidine (mIBG) SIOPEN score from nuclear imaging, using data from 49 metastatic patients treated according to the European HR_NBL1 protocol.

The model was able to accurately describe the data for both total tumor mass (LDH, R2 > 0.99) and number of visible metastasis (SIOPEN, R2 = 0.96). Statistical analysis revealed significant association of LDH with overall survival (OS, p=0.0268). However, clinical variables alone were not able to generate a Cox-based model with sufficient prognosis ability (p=0.507). The parameter μ was found to be independent of the clinical variables and positively significantly associated with OS (p = 0.0175 in multivariate analysis). Critically, addition of this novel computational biomarker to the clinical data drastically improved the performances of predictive algorithms, with a concordance index in cross-validation going from 0.755 to 0.827. The resulting signature had significant prognosis ability of OS (p=0.0353).

Mechanistic modeling was able to describe pathophysiological data of metastatic HRNB and outperformed the predictive value of clinical variables. The physiological substrate underlying these results has yet to be explored, and results should be confirmed in a larger cohort.

Significance

A mechanistic mathematical model of metastasis in high risk neuroblastoma is able to describe clinical data and provides a numerical biomarker with superior predictive power of overall survival than clinical data alone.
Health Worker Practices, Facilitators and Barriers towards the Intensified Case-Finding Tuberculosis Screening Tool in Uganda
Authors: Kakinda Michael , Matovu Joseph K. B , Obuku Ekwaro A.
Published: March 2020

Introduction

Although the Tuberculosis (TB) Intensified Case Finding (ICF) tool was introduced in 2011, only 15.7% of the estimated 35 million people living with HIV were screened for TB in 2013. We explored the facilitators, barriers and health care workers’ practices regarding use of the ICF tool in TB screening.

Methods

We conducted a qualitative study in Jinja, eastern Uganda. We purposively sampled eight (4 private and 4 Government) health facilities (HFs) with the guidance of the District TB and Leprosy Supervisor (DTLS). At each health facility, three health care workers (in-charge TB clinic, a TB focal person & one laboratory technician (total: 24 participants in 8 HFs) were interviewed using a key informant interview guide. Data were collected on how TB was screened and diagnosed in general and when using the ICF tool in particular. Data were audio-recorded, transcribed in verbatim, coded and analyzed using a thematic framework.

Results

The ICF tool was available in all the 8 HFs; however, only half (12/24) the health workers interviewed at these facilities had ever used it for screening TB. The facilitators to ICF use were all levels of health cadres could use it, with simple, close-ended questions and clear, simple instructions. However, several barriers were identified as hindering the use of the ICF tool. The barriers to the use of the ICF tool are segmented according to the Health System building blocks, Leadership and Governance Barriers (concurrent use of other tools, lack of detailed training), Health Workforce Barriers (Lack of awareness of about the tool, perceived increased workload) and Health Information Management System Barriers (Stock-outs of the ICF tools).

Discussion

The ICF tool was found to be simple and easy to use; however, its use remained low due to a variety of perceived barriers by health workers. There is a need to increase the health care workers’ awareness about the ICF tool to improve its utilization in TB screening.
Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial
Authors: Palma David A. , Olson Robert , Harrow Stephen , Gaede Stewart , Louie Alexander V. , Haasbeek Cornelis , Mulroy Liam , Lock Michael , Rodrigues George B. , Yaremko Brian P. , Schellenberg Devin , Ahmad Belal , Senthi Sashendra , Swaminath Anand , Kopek Neil , Liu Mitchell , Moore Karen , Currie Suzanne , Schlijper Roel , Bauman Glenn S. , Laba Joanna , Qu X. Melody , Warner Andrew , Senan Suresh
Published: March 2020

Purpose

The oligometastatic paradigm hypothesizes that patients with a limited number of metastases may achieve long-term disease control, or even cure, if all sites of disease can be ablated. However, long-term randomized data testing this paradigm are lacking.

Methods

We enrolled patients with a controlled primary malignancy and 1-5 metastatic lesions, with all metastases amenable to stereotactic ablative radiotherapy (SABR). We stratified by the number of metastases (1-3 vs. 4-5) and randomized in a 1:2 ratio between palliative standard of care (SOC) treatments (Arm 1) vs. SOC plus SABR (Arm 2). We employed a randomized phase II screening design with a primary endpoint of overall survival (OS), using an alpha of 0.20 (wherein a p-value <0.20 indicates a positive trial). Secondary endpoints included progression-free survival (PFS), toxicity, and quality of life (QOL). Herein we present long-term outcomes from the trial.

Results

Between 2012 and 2016, 99 patients were randomized (33 in Arm 1, 66 in Arm 2) at 10 centres internationally. Median age was 68 (range 43-89) and the majority (n=59; 60%) were male. The most common primary tumor types were breast (n=18), lung (n=18), colorectal (n=18), and prostate (n=16). Median follow-up was 51 months. Five-year OS was 17.7% in Arm 1 (95% confidence interval [CI]: 6-34%) vs. 42.3% in Arm 2 (95% CI: 28-56%; stratified log-rank p=0.006). Five-year PFS was ‘not reached’ in Arm 1 (3.2% [95% CI: 0-14%] at 4-years with last patient censored) and was 17.3% (95% CI: 8-30%) in Arm 2 (p=0.001). There were no new grade 2-5 adverse events and no differences in QOL between arms.

Conclusions

With extended follow-up, the impact of SABR on OS was larger in magnitude than in the initial analysis, and durable over time. There were no new safety signals, and SABR had no detrimental impact on QOL. (NCT01446744)

Funding

Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant
A single holiday was the turning point of the COVID-19 policy of Israel
Authors: Klausner Ziv , Fattal Eyal , Hirsch Eitan , Shapira Shmuel C.
Published: March 2020

Background

The impact of COVID-19 has been profound, and the public health challenge seem to be the most serious regarding respiratory viruses since the 1918 H1N1 influenza pandemic. In the absence of effective vaccine or biomedical treatment, the basic rules of public health measures have not changed, namely public distancing.

Methods

We analyzed epidemiological investigation reports during the first month of the outbreak in Israel. In addition, we present a deterministic compartment model and simulations of several scenarios emphasizing quarantine and isolation policies given their efficiency.

Results

We identify an abrupt change from controlled epidemic regime to an exponential growth (R0 = 2.19) in light of the actual policy-makers decisions and public behavior in Israel. Our analysis show that before the abrupt change, the new cases trend was due to returning citizens infected abroad. The abrupt change followed a holiday in which social distancing was clearly inefficient and many public gatherings were held. We further discuss three different modeled scenarios of quarantine efficiency: high-, medium-, and low-efficiency.

Conclusions

Israel early lessons show that there is no allowance to compromise with the directive of social distancing. Even before the onset of the pandemic in Israel, fine-tuned but determined early decisions were taken by policy makers to monitor flight arrivals from Covid-19 affected regions and to limit public gatherings. Our analysis show that one particular holiday has shifted the occurrence curve from controlled regime to exponential growth. Therefore, even a short lapse in public responsiveness can have a dramatic effect.
Early Spread of SARS-Cov-2 in the Icelandic Population
Authors: Gudbjartsson Daniel F , Helgason Agnar , Jonsson Hakon , Magnusson Olafur T , Melsted Pall , Norddahl Gudmundur L , Saemundsdottir Jona , Sigurdsson Asgeir , Sulem Patrick , Agustsdottir Arna B , Eiriksdottir Berglind , Fridriksdottir Run , Gardarsdottir Elisabet E , Georgsson Gudmundur , Gretarsdottir Olafia S , Gudmundsson Kjartan R , Gunnarsdottir Thora R , Gylfason Arnaldur , Holm Hilma , Jensson Brynjar O , Jonasdottir Aslaug , Jonsson Frosti , Josefsdottir Kamilla S , Kristjansson Thordur , Magnusdottir Droplaug N , Roux Louise le , Sigmundsdottir Gudrun , Sveinbjornsson Gardar , Sveinsdottir Kristin E , Sveinsdottir Maney , Thorarensen Emil A , Thorbjornsson Bjarni , Löve Arthur , Masson Gisli , Jonsdottir Ingileif , Moller Alma , Gudnason Thorolfur , Kristinsson Karl G , Thorsteinsdottir Unnur , Stefansson Kari
Published: March 2020

BACKGROUND

Limited data exist on how SARS-CoV-2 enters and spreads in the general population.

METHODS

We used two strategies for SARS-CoV-2 testing: targeted testing of high-risk individuals (n=4,551) and a population screening (n=5,502). We sequenced SARS-CoV-2 from 340 individuals.

RESULTS

On March 22 2020, 528 had tested positive for SARS-CoV-2 in the targeted testing (11.6%) and 50 in the population screening (0.9%); approximately 0.2% of the Icelandic population. Large fractions of positives had travelled outside Iceland (38.4% and 34.0%). Fewer under 10 years old were positive than those older: 2.8% vs. 12.3% for targeted testing (P=1.6e-9) and 0.0% vs. 1.0% for population screening (P=0.031). Fewer females were positive in the targeted testing than males (9.5% vs. 14.6%, P=6.8e-9). SARS-CoV-2 came from eight clades, seven A clades and one B clade. The clade composition differed between the testing groups and changed with time. In the early targeted testing, 65.0% of clades were A2a1 and A2a2 derived from Italian and Austrian skiing areas, but in the later targeted testing went down to 30.6% and were overtaken by A1a and A2a, the most common clades in the population screening.

CONCLUSION

SARS-CoV-2 has spread widely in Iceland outside of the high-risk groups. Several strains cause these infections and their relative contribution changed rapidly. Children and females are less vulnerable than adults and males. To contain the pandemic we must increase the scope of the testing.