bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward a Theological Reading of Saint John Henry NewmanThe Oxford Handbook of John Henry Newman, Frederick D.Aquino and Benjamin J.King (eds), Oxford University Press, 2018 (ISBN 978‐0‐19‐871828‐4), xvi + 608 pp., hb £110John Henry Newman: A Portrait in Letters, RoderickStrange (ed.), Oxford University Press, 2015 (ISBN 978‐01996‐0414‐2), 608 pp., hb £32.99Essays Critical and Historical: Volume I, John HenryNewman, Gracewing, 2019 (ISBN 978‐0‐85244‐457‐3), lxii + 574 pp., hb £35
Authors: O'Leary Joseph S.
Published: June 2020

John Henry Newman has reached a new pinnacle of his career with his canonization by Pope Francis on October 13, 2019. These books allow us to see how Newman cultivated “the beauty of holiness” from his early youth in steady, intense theological reflection, putting his own personality and biography at the center of his evangelical effort, and eventually becoming a radiant icon for the Church of England and for the Roman Catholic world. A key moment was the publication of the Apologia in 1864, which established him as a beloved, serene Eminent Victorian, dispelling the mockery of the failing “muscular Christians” and the hostility of many former coreligionists he had bruised on his path to Rome. The Oxford Handbook shows how deeply his holiness was indebted to the Evangelical sources his mature church identity covered over: the letters show that sanctity is compatible with thorniness in family and collegial relationships, and Gracewing's annotated reeditions of his works show how sedulously he retrieved and rewrote his earlier literary output. Together they offer a repristinated image of Newman, illuminating in depth his place in intellectual and ecumenical history. Above all, they may herald a new emergence of Newman as theologian, released from the excessive focus on his biography.
Two novel alleles HLA‐DQB1*03:01:01:23 and DQB1*03:01:01:24 in a Konyak Naga individual from North‐East India
Authors: Keppen Chenole , Sharma Akanksha , Khamo Vinotsole , Medhi Subhash , Kanga Uma
Published: June 2020

HLA‐DQB1*03:01:01:07, intron 1 [1217(A→G)] and intron 2 [2138 (T→C)] substitutions generate HLA‐DQB1*03:01:01:23 and HLA‐DQB1*03:01:01:24, respectively.
Arabic Vocabulary Mastery of Politics and Economic among First Year Student in Public University/ Penguasaan Kosa Kata Bahasa Arab dalam Bidang Politik dan Ekonomi dalam Kalangan Pelajar Tahun Satu di Universiti Awam
Authors: Zumrah Asmuni , Mat Shaid@Md. Said Nazipah , Samah Rosni
Published: June 2020

Arabic language learning requires vocabulary mastery to understand reading texts. The lack of mastery may impede understanding and make it difficult for students to understand certain texts in certain fields. This study aims to analyze the words mastered by students in politics and economics. It also aims to analyze the vocabulary mastery of both fields among students. This study uses quantitative method by distributing test questions to students. The results showed that vocabulary mastery of politics and economics among students was very weak. It also showed the number of words mastered in both fields is limited. Therefore, it is proposed that the texts of political and economic fields should be included in the Arabic language syllabus as their use today is deemed necessary.
The Influence of Predictor Factors on Entrepreneurship Career Inclination: Benefit of Entrepreneurship Career as a Mediator/ Pengaruh Faktor Peramal Terhadap Kecenderungan Kerjaya Keusahawanan: Kebaikan Pekerjaan Keusahawanan Sebagai Pengantara
Authors: Wan Nawang Wan Mohd Zaifurin , Mamat Ibrahim
Published: June 2020

This research aimed to study the influence of predictor factors on inclination toward entrepreneurship career involving the benefits of entrepreneurship career as a mediator. The method of the study is quantitative approach using 161 sets of questionnaires distributed by simple random method among the form four students from entrepreneurship club in 16 secondary schools in Terengganu. Data was analysed using Statistical Package for the Social Sciences (SPSS) involving descriptive test, Multiple Regression and Hierarchical Regression. Descriptive test finding found that most of the respondents have entrepreneurship career inclination at the high level. The findings of the Multiple Regression analysis found that predictor factors such as social norm, entrepreneurship skills and role model influenced entrepreneurship career inclination. Meanwhile, Hierarchical Regression analysis found that social norms, entrepreneurship skills and role model could influence the entrepreneurship career inclination through mediator the benefits of entrepreneurship career. The findings from these two analysis found that role model is the most dominant factor in influencing of entrepreneurship career inclination directly or indirectly by using the benefits of entrepreneurship career as a mediator. The findings of this study add value to the existing findings of the predictor factors affecting the inclination and the benefits of entrepreneurship career as mediator.
Rational Choice Hypothesis as X-point of Utility Function and Norm Function
Authors: Kato Takeshi , Kudo Yasuyuki , Miyakoshi Junichi , Otsuka Jun , Saigo Hayato , Karasawa Kaori , Yamaguchi Hiroyuki , Deguchi Yasuo
Published: June 2020

Towards the realization of a sustainable, fair and inclusive society, we proposed a novel decision-making model that incorporates social norms in a rational choice model from the standpoints of deontology and utilitarianism. We proposed a hypothesis that interprets choice of action as the X-point for individual utility function that increases with actions and social norm function that decreases with actions. This hypothesis is based on humans psychologically balancing the value of utility and norms in selecting actions. Using the hypothesis and approximation, we were able to isolate and infer utility function and norm function from real-world measurement data of actions on environmental conditions and elucidate the interaction between the both functions that led from current status to target actions. As examples of collective data that aggregate decision-making of individuals, we looked at the changes in power usage before and after the Great East Japan Earthquake and the correlation between national GDP and CO2 emission in different countries. The first example showed that the perceived benefits of power (i.e., utility of power usage) was stronger than the power usage restrictions imposed by norms after the earthquake, contrary to our expectation. The second example showed that a reduction of CO2 emission in each country was not related to utility derived from GDP but to norms related to CO2 emission. Going forward, we will apply this new X-point model to actual social practices involving normative problems, and design the approaches for the diagnosis, prognosis and intervention of social systems by IT systems.
Nation Dreaming: A Consideration of the American Dream in Poland, the U.S., and among Polish Americans
Authors: Hanson Sandra L. , White John K.
Published: June 2020

This paper examines the cooperation and influences between Poland and the U.S on their respective dreams, including the influence of the American Dream on Polish Americans and their potential distinctness from those who remain in Poland. Attitudes involving the American Dream that are examined include beliefs about freedom, liberty, democracy, getting ahead, status/mobility, and inequality. Although scholars have compared these belief systems across countries, there has been no distinct focus on Poland and the U.S., and those who immigrate between these countries. A conceptual framework that combines the American Dream, American exceptionalism, and beliefs about inequality guides the research. Data from the General Social Survey and the World Values Survey are used to answer the research questions. Findings show that Polish Americans agree with other Americans on a majority of items measuring elements of the American Dream. However, Americans and Poles have significantly different opinions on each of the American Dream items. Usually, (but not always) it is Americans who are more supportive of the American Dream. When considering the three groups, Polish Americans, Americans, and Poles, our conclusions suggest a trend where Polish Americans are a hybrid of other Americans and Poles when it comes to their views on the Dream. However, the differences often run in the direction that Polish Americans’ views are more like other Americans and distinct from Poles. Conclusions and implications are provided within the historical context of the long history of cooperation between the U.S. and Poland in fights for freedom and democracy.
A Framework of U.S. Contemporary Police Training: Select Types of Basic Training and Purpose of Field, Inservice, and Specialized Training
Authors: Martin Richard H.
Published: June 2020

The article illustrates an overview of the various types of police training in the United States. It includes types of mandatory minimum annual training within the states, the purpose, importance, and benefits of various types of police training. The types of training include basic training (e.g., sponsored academy basic training and preservice self-pay basic training), field training officer (FTO), roll-call training (e.g., recent incidents, new updates), inservice training (e.g., legal updates, firearms, community policing, mental health issues, wellness), and specialized training (e.g., SWAT training, traffic enforcement, hostage and barricaded subjects, promotions, dealing with issues in the community). Relevancy of training curriculum and validation of selection criteria are| also addressed.
The effect of two 12 kHz multibeam mapping surveys on the foraging behavior of Cuvier's beaked whales off of southern California
Authors: Kates Varghese Hilary , Miksis-Olds Jennifer , DiMarzio Nancy , Lowell Kim , Linder Ernst , Mayer Larry , Moretti David
Published: June 2020

The impact of multibeam echosounder (MBES) operations on marine mammals has been less studied compared to military sonars. To contribute to the growing body of MBES knowledge, echolocation clicks of foraging Cuvier's beaked whales were detected on the Southern California Antisubmarine Warfare Range (SOAR) hydrophones during two MBES surveys and assembled into foraging events called group vocal periods (GVPs). Four GVP characteristics were analyzed Before, During, and After 12 kHz MBES surveys at the SOAR in 2017 and 2019 to assess differences in foraging behavior with respect to the mapping activity. The number of GVP per hour increased During and After MBES surveys compared with Before. There were no other differences between non-MBES and MBES periods for the three other characteristics: the number of clicks per GVP, GVP duration, and click rate. These results indicate that there was not a consistent change in foraging behavior during the MBES surveys that would suggest a clear response. The animals did not leave the range nor stop foraging during MBES activity. These results are in stark contrast to those of analogous studies assessing the effect of Naval mid-frequency active sonar on beaked whale foraging, where beaked whales stopped echolocating and left the area.
Coronavirus rips through Dutch mink farms, triggering culls
Authors: Enserink Martin
Published: June 2020

Public concerns rise as two workers catch the disease.
Cascading social-ecological costs and benefits triggered by a recovering keystone predator
Authors: Gregr Edward J. , Christensen Villy , Nichol Linda , Martone Rebecca G. , Markel Russell W. , Watson Jane C. , Harley Christopher D. G. , Pakhomov Evgeny A. , Shurin Jonathan B. , Chan Kai M. A.
Published: June 2020

The benefits of ecosystem restoration

Human activities have fundamentally altered many ecosystems. Recent successful restoration efforts have led to healthier ecosystems, but this has led to a disruption in economies dependent on the altered state of the system. One of the best-known trophic cascades is the sea otter–kelp forest system, wherein recovery of once extirpated sea otters is bringing back biodiverse and healthy kelp forests but reducing the abundance of harvested shellfish. Gregret al.looked at the costs and benefits of this shift and found that for key trade-offs, the value of kelp forest–associated features such as tourism, fin fish fisheries, and carbon capture outweighed the losses to economies (see the Perspective by Estes and Carswell). Thus, ecosystem recovery can benefit both ecosystems and economies.

Science, this issue p.1243; see also p.1178
Very fast CRISPR on demand
Authors: Liu Yang , Zou Roger S. , He Shuaixin , Nihongaki Yuta , Li Xiaoguang , Razavi Shiva , Wu Bin , Ha Taekjip
Published: June 2020

Very fast CRISPR on demand

Numerous efforts have been made to improve the temporal resolution of CRISPR-Cas9–mediated DNA cleavage to the hour time scale. Liu
et al.
developed a Cas9 system that achieved genome-editing manipulation at the second time scale (see the Perspective by Medhi and Jasin). Part of the guide RNA is chemically caged, allowing the Cas9-guide RNA complex to bind at a specific genomic locus without cleavage until activation by light. This fast CRISPR system achieves genome editing at high temporal resolution, enabling the study of early molecular events of DNA repair processes. This system also has high spatial resolution at short time scales, allowing editing of one genomic allele while leaving the other unperturbed.

Science
, this issue p.
1265
; see also p.
1180
A brainwide atlas of synapses across the mouse life span
Authors: Cizeron Mélissa , Qiu Zhen , Koniaris Babis , Gokhale Ragini , Komiyama Noboru H. , Fransén Erik , Grant Seth G. N.
Published: June 2020

Brain synapses through the life span

Excitatory synapses connect neurons in the brain to build the circuits that enable behavior. Cizeron
et al.
surveyed synapses in the mouse brain from birth to old age and present the data as a community resource, the Mouse Lifespan Synaptome Atlas (see the Perspective by Micheva
et al.
). Molecular and morphological features defined 37 subtypes of synapses. Although synapse density generally increased in early development and declined in old age, the details differed in different brain areas.

Science
this issue p.
270
; see also p.
253
Disordered proteins follow diverse transition paths as they fold and bind to a partner
Authors: Kim Jae-Yeol , Chung Hoi Sung
Published: June 2020

Shedding light on disordered proteins

Disordered proteins often fold as they bind to a partner protein. There could be many different molecular trajectories between the unbound proteins and the bound complex. Most methods to measure transition paths rely on monitoring a single distance, making it difficult to resolve complex pathways. Kim and Chung used fast three-color single-molecule Foster resonance energy transfer (FRET) to simultaneously probe distance changes between the two ends of an unfolded protein and between each end and a probe on the partner protein. They show that binding can be initiated by diverse conformations and that the molecules are held together by non-native interactions as the disordered protein folds. This allows the association to be diffusion limited because most collisions lead to binding.

Science
, this issue p.
1253
A biodiversity target based on species extinctions
Authors: Rounsevell Mark D. A. , Harfoot Mike , Harrison Paula A. , Newbold Tim , Gregory Richard D. , Mace Georgina M.
Published: June 2020

A single target comparable to the 2°C climate target may help galvanize biodiversity policy
Cell position fates and collective fountain flow in bacterial biofilms revealed by light-sheet microscopy
Authors: Qin Boyang , Fei Chenyi , Bridges Andrew A. , Mashruwala Ameya A. , Stone Howard A. , Wingreen Ned S. , Bassler Bonnie L.
Published: June 2020

Biofilm formation from cell fountains

Bacteria form three-dimensional communities called biofilms that are ubiquitous in nature and underlie human infections. Medically, biofilms are problematic because they protect resident cells from antibiotics. Although biofilms have been intensively studied, we do not understand how they develop cell by cell. Micron-sized bacteria are densely packed within biofilms, making it exceptionally challenging to track their movements. Qin
et al.
studied biofilm formation in the pathogen and model biofilm former
Vibrio cholerae
(see the Perspective by Dal Co and Brenner). The authors combined light-sheet microscopy with cell labeling to map the trajectories of a biofilm founder cell and its descendants in space and time as they built a biofilm. The findings revealed that as the bacteria reproduce, a bacterial “fountain” drives biofilm expansion and dictates the final positions of the offspring.

Science
, this issue p.
71
; see also p.
30
Costs and benefits of living with predators
Authors: Estes James A. , Carswell Lilian P.
Published: June 2020

Integrating ecology and economics reveals a net monetary benefit from sea otters
COVID-19 and flu, a perfect storm
Authors: Belongia Edward A. , Osterholm Michael T.
Published: June 2020

The world is in uncharted waters for the 2020 respiratory virus season. For the first time in modern history, the Northern Hemisphere faces the prospect of the coronavirus disease 2019 (COVID-19) pandemic and a simultaneous epidemic of seasonal influenza. Each causes life-threatening illness and death, especially in older adults, people with chronic diseases, and other vulnerable populations. How can we prepare for this convergence?
Efficacy of Guanabenz Combination Therapy against Chronic Toxoplasmosis across Multiple Mouse Strains
Authors: Martynowicz Jennifer , Doggett J. Stone , Sullivan William J.
Published: June 2020

Toxoplasma gondii
, an obligate intracellular parasite that can cause life-threatening acute disease, differentiates into a quiescent cyst stage to establish lifelong chronic infections in animal hosts, including humans. This tissue cyst reservoir, which can reactivate into an acute infection, is currently refractory to clinically available therapeutics. Recently, we and others have discovered drugs capable of significantly reducing the brain cyst burden in latently infected mice, but not to undetectable levels.
Metformin Suppresses Development of the Echinococcus multilocularis Larval Stage by Targeting the TOR Pathway
Authors: Loos Julia A. , Dávila Valeria A. , Brehm Klaus , Cumino Andrea C.
Published: June 2020

Alveolar echinococcosis (AE) is a severe disease caused by the larval stage of the tapeworm
Echinococcus multilocularis
. Current chemotherapeutic treatment options based on benzimidazoles are of limited effectiveness, which underlines the need to find new antiechinococcosis drugs. Metformin is an antihyperglycemic and antiproliferative agent that shows activity against the related parasite
Echinococcus granulosus
. Hence, we assessed the
in vitro
and
in vivo
effects of the drug on
E. multilocularis
.
Comparative Pathogenesis of Bovine and Porcine Respiratory Coronaviruses in the Animal Host Species and SARS-CoV-2 in Humans
Authors: Saif Linda J. , Jung Kwonil
Published: June 2020

Discovery of bats with severe acute respiratory syndrome (SARS)-related coronaviruses (CoVs) raised the specter of potential future outbreaks of zoonotic SARS-CoV-like disease in humans, which largely went unheeded. Nevertheless, the novel SARS-CoV-2 of bat ancestral origin emerged to infect humans in Wuhan, China, in late 2019 and then became a global pandemic. Less than 5 months after its emergence, millions of people worldwide have been infected asymptomatically or symptomatically and at least 360,000 have died.
Microaneurysms visualisation using five different optical coherence tomography
angiography devices compared to fluorescein angiography
Authors: Parrulli Salvatore , Corvi Federico , Cozzi Mariano , Monteduro Davide , Zicarelli Federico , Staurenghi Giovanni
Published: June 2020

Background

To compare fluorescein angiography (FA) and five different optical
coherence tomography angiography (OCTA) devices and to test their
reproducibility in the evaluation of retinal microaneurysms (MAs) secondary to
diabetic retinopathy (DR).

Methods

On the same day, patients with DR were imaged with FA and five OCTA
devices: prototype Spectralis OCTA, prototype PlexElite, RTVue XR Avanti,
AngioPlex and DRI OCT Triton. For all OCTA devices, a 3×3 volume scan pattern
was performed. MAs were evaluated for the superficial capillary plexus (SCP)
and deep capillary plexus (DCP).

Results

Twenty eyes of 15 patients with DR were included. FA counted a
significantly higher number of MAs compared to OCTA devices. Spectralis OCTA
obtained a significantly higher number of MAs compared to PlexElite, RTVue XR
Avanti, AngioPlex and DRI OCT Triton (p<0.0001). PlexElite and AngioPlex
showed a greater number of MAs in the SCP, Spectralis OCTA, RTVue XR Avanti and
DRI OCT Triton in the DCP. Higher sensitivity (43.3%) but lowest specificity
(54.4%) was observed for Spectralis OCTA compared to other devices. The higher
specificity (78.5%) and positive predictive value (83.3%) were observed for DRI
OCT Triton.

Conclusions

FA remains the best imaging modality to visualise retinal MAs. Spectralis
OCTA was able to detect more MAs compared to other devices, likely due to the
higher number of B-scans in the scanned area as well as due to the higher
number of repeated B-scans. The high variability between OCTA devices should be
taken into account for future clinical trials as in clinical practice.
Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) Study: design of lifestyle intervention
Authors: Dagogo-Jack Samuel , Brewer Amy A , Owei Ibiye , French Lindsey , Umekwe Nkiru , Rosenthal Renate , Wan Jim
Published: June 2020

Introduction

Intensive lifestyle intervention (ILI) prevents progression from prediabetes to type 2 diabetes (T2D) but reversal of prediabetes is less well studied.

Research design and methods

The overall objectives of the Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) Study (ClinicalTrials.gov ID:NCT02027571) are to determine the natural history and reversibility of prediabetes. The study tests specific hypotheses on the patterns of progression to prediabetes among normoglycemic African-American (AA) and European-American (EA) offspring of parents with T2D; emergence of microvascular and macrovascular complications during transition from normal to impaired glucose regulation; significance of the ‘metabolically healthy’ obese phenotype; and effect of duration of the prediabetic state on its reversibility with lifestyle intervention. Participants who developed incident prediabetes were offered ILI and evaluated quarterly for 5 years. The primary outcome was restoration of normal glucose regulation (fasting plasma glucose <100 mg/dL and two-hour plasma glucose (2hrPG)<140 mg/dL).

Results

Of the 223 subjects enrolled in the PROP-ABC Study, 158 participants with incident prediabetes started ILI. The mean age was 53.3±9.28 years; body mass index 30.6±6.70 kg/m2; 70% were female, 52.4% AA and 47.6% EA. The ILI program used goal setting, weight-based calorie restriction, physical activity (180 min/week), self-monitoring, and meal replacement. Monthly face-to-face (F2F) counseling sessions during the initial 6 months, and quarterly visits thereafter, were supplemented with electronic and postal contacts. Attendance at F2F sessions was highly correlated with weight loss (r=0.98, p<0.0001). Meal replacement induced ~5 kg weight loss within 3 months in participants with recrudescent weight pattern. Self-reported exercise minutes correlated with pedometer step counts (r=0.47, p<0.0001).

Conclusion

The PROP-ABC Study has demonstrated the feasibility of executing an ILI program designed to test reversibility of incident prediabetes in a biracial cohort.
Feasibility study of in vitro drug sensitivity assay of advanced non-small cell lung adenocarcinomas
Authors: Papp Emoke , Steib Anita , Abdelwahab Elhusseiny MM , Meggyes-Rapp Judit , Jakab Laszlo , Smuk Gabor , Schlegl Erzsebet , Moldvay Judit , Sárosi Veronika , Pongracz Judit E
Published: June 2020

Background Despite improved screening techniques, diagnosis of lung cancer is often late and its prognosis is poor. In the present study, in vitro chemosensitivity of solid tumours and pleural effusions of lung adenocarcinomas were analysed and compared with clinical drug response.

Methods Tumour cells were isolated from resected solid tumours or pleural effusions, and cryopreserved. Three-dimensional (3D) tissue aggregate cultures were set up when the oncoteam reached therapy decision for individual patients. The aggregates were then treated with the selected drug or drug combination and in vitro chemosensitivity was tested individually measuring ATP levels. The clinical response to therapy was assessed by standard clinical evaluation over an 18 months period.

Results Based on the data, the in vitro chemosensitivity test results correlate well with clinical treatment response.

Conclusions Such tests if implemented into the clinical decision making process might allow the selection of an even more individualised chemotherapy protocol which could lead to better therapy response.
Outpatient palliative medicine consultations: urgent or routine?
Authors: Alam Sorayya , Pope Ashley , Le Lisa , Al-Awamer Ahmed , Banerjee Subrata , Lau Jenny , Mak Ernie , Zimmermann Camilla , Hannon Breffni
Published: June 2020

Background

Although outpatient palliative care clinics (OPCCs) provide a venue for early, pre-emptive referral to palliative care on a routine basis, some patients will continue to require urgent referrals. The purpose of this study was to characterise these urgent referrals to determine whether they reflect clinical need or convenience.

Methods

We retrospectively compared new patients in an OPCC who were seen urgently versus those seen at routine appointments. Descriptive statistics compared the two groups in terms of clinical characteristics, referring teams, symptoms, performance status and outcomes. Logistic regression was used to identify factors associated with urgent referral to the OPCC. Overall survival was compared using the log-rank test.

Results

Between January 2016 and December 2017, a total of 113 urgent referrals were reviewed in the OPCC; these were compared with a random sample of 217 routine referrals. Patients seen urgently were more likely to be referred by surgical oncology, and to report worse symptom scores for pain (p=0.0007), tiredness (p=0.02), well-being (p=0.001), constipation (p=0.02) and sleep (p=0.01). More patients seen urgently required direct admission to hospital following the visit (17.7% vs 0.9%, p<0.001). Median survival was shorter for patients seen urgently (4.3 months, 95% CI 3.4 to 7.8) versus routinely (8.1 months, 95% CI 7.2 to 9.5).

Conclusions

Compared with routine referrals, new patients seen urgently in the OPCC had higher symptom burden, shorter median survival and a greater chance of direct admission to hospital. Palliative care clinics should consider how best to accommodate urgent referrals.
Identification of PD1-mediated regulation of antitumor antigen response in patients with NSCLC using the trans vivo DTH assay
Authors: Lema Diego A , Jankowska-Gan Ewa , Sethakorn Nan , Burlingham William , Leal Ticiana
Published: June 2020

Objectives

Emerging evidence has shown a role for tumor antigen-specific regulation in cancer. Identifying individuals with pre-existing regulatory responses may be key to understand those who are more likely to respond to Programmed Death-1 (PD-1) or PD-1 Ligand 1 (PD-L1) checkpoint blockade. We hypothesized that a functional assay could identify the role of PD-1/PD-L1 interactions on tumor-specific immune cells in the peripheral blood in patients with advanced non-small-cell lung cancer (NSCLC).

Methods

We performed the trans vivo delayed-type hypersensitivity assay to identify the role of PD-1/PD-L1-mediated tumor-specific immune regulation in ten patients with advanced NSCLC.

Results

The majority of patients had PD-1-mediated anergic immune responses towards their tumor antigens. Eight out of nine of these patients did not respond to their own tumor antigens but responded in the presence of anti-PD-1 antibody (‘PD-1 anergy’ phenotype). A minority (3/9) also had ‘active’ PD-1-mediated immune suppressive regulatory responses. Our results suggest that PD-1-anergy is a common feature of NSCLC immune responses, whereas PD-1-mediated immune suppression is present only in a minority of patients. The latter was associated with poor clinical outcomes in our sample.

Conclusions

Overall, our results indicate that bystander suppression or the ‘anergy-only’ phenomenon may be novel biomarkers in NSCLC and suggest prediction value based on these phenotypes.
Nanopore sequencing as a scalable, cost-effective platform for analyzing polyclonal vector integration sites following clinical T cell therapy
Authors: Zhang Ping , Ganesamoorthy Devika , Nguyen Son Hoang , Au Raymond , Coin Lachlan J , Tey Siok-Keen
Published: June 2020

Background

Analysis of vector integration sites in gene-modified cells can provide critical information on clonality and potential biological impact on nearby genes. Current short-read next-generation sequencing methods require specialized instruments and large batch runs.

Methods

We used nanopore sequencing to analyze the vector integration sites of T cells transduced by the gammaretroviral vector, SFG.iCasp9.2A.ΔCD19. DNA from oligoclonal cell lines and polyclonal clinical samples were restriction enzyme digested with two 6-cutters,NcoIandBspHI; and the flanking genomic DNA amplified by inverse PCR or cassette ligation PCR. Following nested PCR and barcoding, the amplicons were sequenced on the Oxford Nanopore platform. Reads were filtered for quality, trimmed, and aligned. Custom tool was developed to cluster reads and merge overlapping clusters.

Results

Both inverse PCR and cassette ligation PCR could successfully amplify flanking genomic DNA, with cassette ligation PCR showing less bias. The 4.8 million raw reads were grouped into 12,186 clusters and 6410 clones. The 3′long terminal repeat (LTR)-genome junction could be resolved within a 5-nucleotide span for a majority of clusters and within one nucleotide span for clusters with ≥5 reads. The chromosomal distributions of the insertional sites and their predilection for regions proximate to transcription start sites were consistent with previous reports for gammaretroviral vector integrants as analyzed by short-read next-generation sequencing.

Conclusion

Our study shows that it is feasible to use nanopore sequencing to map polyclonal vector integration sites. The assay is scalable and requires minimum capital, which together enable cost-effective and timely analysis. Further refinement is required to reduce amplification bias and improve single nucleotide resolution.
Impact of thrombus surface on first pass reperfusion in contact aspiration and stent retriever thrombectomy
Authors: Kaiser Daniel , Laske Katharina , Winzer Robert , Hädrich Kevin , Wahl Hannes , Krukowski Pawel , Daubner Dirk , Pallesen Lars-Peder , Linn Jennifer , Puetz Volker , Gerber Johannes C
Published: June 2020

Background

To assess whether thrombus surface morphology has an impact on first pass reperfusion in contact aspiration (CA) and stent retriever (SR) thrombectomy.

Methods

From January 2016 to December 2018, consecutive stroke patients with an occlusion of the middle cerebral artery and thrombectomy (CA or SR) were examined in this retrospective study. We assessed patients’ characteristics, procedural data and clinical outcome. Thrombus surface on pretreatment digital subtraction angiography (DSA) was categorized into regular versus irregular phenotype by blinded three-reader-consensus. Primary outcome was successful reperfusion (modified treatment in cerebral ischemia (mTICI) 2b-3) after first pass. Data analysis was stratified according to thrombectomy technique and thrombus phenotype.

Results

Among 203 patients (76 years (IQR 65.5–81.9), 47.3% male, National Institutes of Health Stroke Scale Score 16 (IQR 12–20)), 155 patients were treated primarily with CA and 48 with SR. 40% (n=62/155) CA and 41.7% (n=20/48) SR-treated patients had a regular thrombus phenotype. In the CA group, successful reperfusion after first pass was more frequently obtained in patients with regular compared with irregular phenotype (69.4% (n=43/62) vs 34.4% (n=32/93); P<0.0001). In contrast, in the SR group, reperfusion after first pass was achieved in 35% (n=7/20; P=0.01) of patients with regular phenotypes. In the CA group, median number of passes (1 (1–2) vs 2 (1–4); P<0.00001) and time from reaching the thrombus to reperfusion (19±27 vs 38±36 min; P=0.0001) were lower among patients with a regular phenotype.

Conclusion

Direct CA is associated with higher rates of successful first pass reperfusion in patients with a regular thrombus phenotype in pretreatment DSA.
Underwater noise and Arctic marine mammals: review and policy recommendations
Authors: Halliday William D. , Pine Matthew K. , Insley Stephen J.
Published: June 2020

Underwater noise is an important issue globally. Underwater noise can cause auditory masking, behavioural disturbance, hearing damage, and even death for marine animals. While underwater noise levels have been increasing in nonpolar regions, noise levels are thought to be much lower in the Arctic where the presence of sea ice limits anthropogenic activities. However, climate change is causing sea ice to decrease, which is allowing for increased access for noisy anthropogenic activities. Underwater noise may have more severe impacts in the Arctic compared with nonpolar regions due to a combination of lower ambient sound levels and increased sensitivity of Arctic marine animals to underwater noise. Here, we review ambient sound levels in the Arctic, as well as the reactions of Arctic and sub-Arctic marine mammals to underwater noise. We then relate what is known about underwater noise in the Arctic to policies and management solutions for underwater noise and discuss whether Arctic-specific policies are necessary.
Optimization of powder metallurgy parameters of TiC- and B4C-reinforced aluminium composites by Taguchi method
Authors: Vairamuthu J. , Senthil Kumar A. , Stalin B. , Ravichandran M.
Published: June 2020

In this work, an aluminium-based metal matrix composite material was developed via powder metallurgy considering various input process parameters. Sintering time, sintering temperature, and compaction pressure were the three main factors used as input process parameters, which were varied at three levels. The research was planned with reference to the experimental design of an L9 orthogonal array using a 3 × 3 matrix. The density, Vickers hardness, and compression strength were tested and analyzed. The influence of individual input parameters were analyzed using the Taguchi-based S/N ratio and analysis of variance (ANOVA). The optimum parameter levels to achieve low density, high hardness, and high compressive strength were identified through main effect plots. Experimental results indicate that the sintering temperature and compaction pressure strongly influence properties such as density and hardness. Similarly, compression strength depends mainly on sintering time and sintering temperature. Through ANOVA analysis, the optimum levels were confirmed for the process parameters sintering time, compaction pressure, and sintering temperature to produce the most favorable metal matrix composite material.
Simulation of geodesic trajectory of charged BTZ black holes in massive gravity
Authors: Hendi S. H. , Tavakkoli A. M. , Panahiyan S. , Panah B. Eslam , Hackmann E.
Published: June 2020

In order to classify and understand structure of the spacetime, investigation of the geodesic motions of massive and massless particles is a key tool. So the geodesic equation is a central equation of gravitating systems and the subject of geodesics in the black hole dictionary attracted much attention. In this paper, we give a full description of geodesic motions in three-dimensional spacetime. We investigate the geodesics near charged BTZ black holes and then generalize our prescriptions to the case of massive gravity. We show that electric charge is a critical parameter for categorizing the geodesic motions of both lightlike and timelike particles. In addition, we classify the type of geodesics based on the particle properties and geometry of spacetime.
New Urbanization and Coordinated Regional Development
Authors: YANG Kaizhong
Published: June 2020

Since the 1990s, China has gradually put forward the theories featuring new urbanization and coordinated regional development, and put them into practice. In the Report on the Work of the Government 2019, Chinese Premier Li Keqiang proposed that “We will promote coordinated development across regions and improve the quality of new urbanization”, drawing the public’s attention to new urbanization and coordinated regional development again. This paper first sorts out China’s research on new urbanization and coordinated regional development, mainly concentrating on the connotations, dynamic mechanism, strategic paths and models, and policy tools. Then it summarizes the major research results, including (1) the strategic theory and policy for spatial integration; (2) the theory and policy of main functional zones; (3) the urbanization theory and policy with city clusters as the major form; (4) the agglomeration theory and policy in the context of integration. And finally it proposes the major directions for further research: (1) innovation-driven cities and coordinated regional development; (2) compact cities with green, low-carbon, smart and humane features; (3) difficulties in the innovation of new urbanization system and mechanism; (4) leading research on the agglomeration theory and policy in the context of inter-connectivity.
Neoproterozoic–paleozoic detrital sources in the Variscan foreland of northern Iberia: primary v. recycled sediments
Authors: Gutiérrez-Alonso G. , López-Carmona A. , Núñez-Guerrero E. , Martínez García A. , Fernández-Suárez J. , Pastor-Galán D. , Gutiérrez-Marco J. C. , Bernárdez E. , Colmenero J. R. , Hofmann M. , Linnemann U.
Published: June 2020

The Cantabrian Zone, in the Variscan belt of Western Europe, has one of the most continuous Ediacaran–Paleozoic stratigraphic successions in the world. This succession has been extensively studied, including several detrital zircon U–Pb geochronological studies on 30 samples spanning the aforementioned time slice. In this work, we present data from three new samples covering previously unsampled time-slices and perform multidimensional analysis on the 33 samples in order to quantify the similarity/dissimilarity among all of them with the aim of detecting potential changes in source areas through time and the role of recycling. The results indicate a continuous source of sediments from Ediacaran to late Devonian times punctuated by a sudden ephemeral change in the Early Cambrian that can be attributed to local causes during the inception of the Paleozoic passive margin.
Integrated geophysical and sedimentological datasets for assessment of offshore borrow areas: the CHIMERA project (western Portuguese Coast)
Authors: Mil-Homens Mário , Brito Pedro , Magalhães Vitor , Rosa Marcos , Neres Marta , Silva Marta , Salgueiro Emília , Drago Teresa , Rodrigues Ana Isabel , Guerra Miriam Tuaty , Gaudêncio Maria José , Almeida Eveline , Silva Mariana , Freitas Mafalda , Pinto Celso Aleixo , Bandarra Cidália , Terrinha Pedro
Published: June 2020

Coastal erosion impact on low-lying sandy shorelines represents a worldwide problem, which is particularly felt in various segments of the Portuguese coast where this geomorphological type represents 42% of its total length. Beach nourishment is a viable engineering alternative for shore protection and the assessment of offshore sources of beach-fill material is an essential aspect when implementing this mitigation strategy. The CHIMERA project carried out a multidisciplinary inspection on four segments of the west Portuguese coast to assess their potential as offshore borrow areas for beach nourishment. Altogether, these segments covered an area of
c
. 35 km
2
, at water depths between 20 and 42 m. They were surveyed using multibeam, sub-bottom profiler, ultra-high resolution multichannel seismics and a set of 126 surface samples and 72 vibrocores (with 3 m long each). To comply with the Portuguese legislation, sand types were assessed by granulometric and chemical analyses for evaluating the quality of sediments in terms of contamination. High-resolution magnetic surveys were conducted to find potential archaeological artefacts. The adopted methodology proved to be adequate to quantify and describe the spatial distribution of useful sediment volumes, supporting the ongoing Integrated Coastal Sediment Strategy for mainland Portugal.
A conversation with Tempestt Neal
Authors: Anjum Bushra
Published: June 2020

Ubiquity's senior editor Dr. Bushra Anjum chats with Dr. Tempestt Neal to discuss her work to improve access control on mobile devices, specifically developing continuous authentication methods.
“I Don’t Like to Make a Big Thing out of It”: A Qualitative Interview-Based Study Exploring Factors Affecting Whether Young People Tell or Do Not Tell Their Friends about Their IBD
Authors: Carter Bernie , Rouncefield-Swales Alison , Bray Lucy , Blake Lucy , Allen Stephen , Probert Chris , Crook Kay , Qualter Pamela
Published: June 2020

Inflammatory Bowel Disease (IBD) describes a group of conditions that includes Crohn’s disease and ulcerative colitis. Unlike some chronic conditions, to a greater or lesser extent, IBD is hidden from or invisible to others which enables concealment of the condition, especially when stigma is associated with the condition. Concealment or nondisclosure allows a means of identity management. Disclosure of a chronic condition is not a single event, and it is dependent on many factors. There is little literature that specifically addresses stigma and/or disclosure in relation to children and young people with IBD. An in-depth qualitative study was undertaken, framed by Interpretive Description and using interviews, friendship maps, and photographs within a participatory framework. Public and patient involvement and engagement (PPIE) was undertaken throughout (inception to dissemination) the study. Young people aged 14-25 years with IBD who had participated in the survey phase of the larger study self-selected to participate in interviews that focused broadly on friendship and feelings of social connectedness. Data were analysed using an iterative, interpretive approach. Preliminary themes were developed and these were explored further, and then tentative theoretical connections about friendship were developed. One superordinate theme focused on disclosure. Thirty-one young people (16 males, 15 females, mean age 18.7 years; 24 Crohn’s, 7 colitis) participated in the interviews (of these, five created friendship maps and six utilised photographs). Three discrete, but interlinked, themes were generated, revealing young people’s experiences of disclosure: to tell or not to tell; controlling the flow: the who, when, what, and how of telling; and reactions and responses to telling: anticipated and actual. Decisions about telling friends about having IBD are challenging for many young people. Having control over disclosure is not always possible, and the potential consequences can feel risky. However, most young people had positive experiences of disclosure and gained support from friends and romantic partners. Most young people downplayed the seriousness of their IBD, revealing some facets of their condition, aiming to sustain their self-identity. Only one young person had been given professional support to disclose. Provision of support and opportunities to discuss whether, when, who, and how to tell friends and what the risks and benefits may be is something that could be woven into an ongoing and wider person-centred dialogue between young people and health professionals within routine clinic visits.
Rail Corrugation Characteristics of Cologne Egg Fastener Section in Small Radius Curve
Authors: Wang Zhiqiang , Lei Zhenyu , Zhao Yang , Xu Yao
Published: June 2020

By analyzing the measured data of rail corrugation in a small radius curve track with Cologne fasteners, the typical passing frequencies of corrugation were obtained. Then, according to actual line conditions, the vehicle-track coupled model and rail material friction and wear model were established and simulated, and rail corrugation characteristics of the curved section were studied. The results show that the variation amplitude of creep force on the inside of a guiding wheelset is large, and it coincides with that of the saturated creep force partially and the coincident part appears periodically. The variation amplitude of creep force on the outside of the guiding wheelset is small, and it is approximately equal to that of the saturated creep force. In addition, the variation range of the wear depth curve on inner rail is mainly changing from 0 μm to 0.0014 μm, showing periodic wavy wear, and when the creep force is equal to the saturated creep force, the wear depth reaches the peak. The variation range of the wear depth curve on outer rail is mainly changing from 0.0005 μm to 0.0008 μm, showing uniform wear. Combined with the predicted profile of rail wear, it can be seen that the inner rail mainly suffers from corrugation on the top of rail and the outer rail mainly suffers from uniform wear on the side, which results in serious corrugation on inner rail and slight corrugation on outer rail. The frequency characteristics analysis of wear shows that the inner rail wear has characteristic frequencies similar to the passing frequencies. Modal analysis results show that the vibration of inner rail at the characteristic frequencies is greater than that of outer rail, which lead to the corrugation of the corresponding frequencies more easily. The wear growth rates at the characteristic frequencies are relatively large, which indicates that the wear at the corresponding frequencies will continue to develop and eventually form corrugation.
Multiple Attribute Group Decision-Making Based on Power Heronian Aggregation Operators under Interval-Valued Dual Hesitant Fuzzy Environment
Authors: Jiang Shenqing , He Wei , Qin Fangfang , Cheng Qingqing
Published: June 2020

In this paper, we focus on new methods to deal with multiple attribute group decision-making (MAGDM) problems and a new comparison law of interval-valued dual hesitant fuzzy elements (IVDHFEs). More explicitly, the interval-valued dual hesitant fuzzy 2nd-order central polymerization degree (IVDHFCP2) function is introduced, for the case that score values of different IVDHFEs are identical. This function can further compare different IVDHFEs. Then, we develop a series of interval-valued dual hesitant fuzzy power Heronian aggregation operators, i.e., the interval-valued dual hesitant fuzzy power Heronian mean (IVDHFPHM) operator, the interval-valued dual hesitant fuzzy power geometric Heronian mean (IVDHFPGHM) operator, and their weighted forms. Some desirable properties and their special cases are discussed. These proposed operators can simultaneously reflect the interrelationship of aggregated arguments and reduce the influence of unreasonable evaluation values. Finally, two approaches for interval-valued dual hesitant fuzzy MAGDM with known or unknown weight information are presented. An illustrative example and comparative studies are given to verify the advantages of our methods. A sensitivity analysis of the decision results is analyzed with different parameters.