bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early impact of moderate preterm birth on the structure, function and gene expression of conduit arteries
Authors: Lombardo Paul , Nguyen Vivian B. , Flores Tracey J. , Sutherland Megan R. , Nitsos Ilias , Allison Beth J. , Parkington Helena , Tare Marianne , Harding Richard , De Matteo Robert , Schneider Michal , Polglase Graeme R. , Black M. Jane 
Published: May 2020

New Findings

What is the central question of this study?
What is the immediate impact of moderate preterm birth on the structure and function of major conduit arteries using a pre‐clinical sheep model?

What is the main finding and its importance?
Postnatal changes in conduit arteries, including a significant decrease in collagen within the thoracic aortic wall (predominately males), narrowed carotid arteries, reduced aortic systolic blood flow, and upregulation of the mRNA expression of cell adhesion and inflammatory markers at 2 days of age in preterm lambs compared to controls, may increase the risk of cardiovascular impairment in later life.

AbstractThe aim of this work was to compare the structure and function of the conduit arteries of moderately preterm and term‐born lambs and to determine whether vascular injury‐associated genes were upregulated. Time‐mated ewes were induced to deliver either preterm (132 ± 1 days of gestation; n = 11 females and n = 10 males) or at term (147 ± 1 days of gestation; n = 10 females and n = 5 males). Two days after birth, ultrasound imaging of the proximal ascending aorta, main, right and left pulmonary arteries, and right and left common carotid arteries was conducted in anaesthetized lambs. Lambs were then killed and segments of the thoracic aorta and left common carotid artery were either snap frozen for real‐time PCR analyses or immersion‐fixed for histological quantification of collagen, smooth muscle and elastin within the medial layer. Overall there were few differences in vascular structure between moderately preterm and term lambs. However, there was a significant decrease in the proportion of collagen within the thoracic aortic wall (predominantly in males), narrowing of the common carotid arteries and a reduction in peak aortic systolic blood flow in preterm lambs. In addition, there was increased mRNA expression of the cell adhesion marker P‐selectin in the thoracic aortic wall and the pro‐inflammatory marker IL‐1β in the left common carotid artery in preterm lambs, suggestive of postnatal vascular injury. Early postnatal differences in the function and structure of conduit arteries and evidence of vascular injury in moderately preterm offspring may place them at greater risk of cardiovascular impairment later in life.
Causal analyses to study autonomic regulation during acute head‐out water immersion, head‐down tilt and supine position
Authors: Corbier Christophe , Chouchou Florian , Roche Frédéric , Barthélémy Jean‐Claude , Pichot Vincent 
Published: May 2020

New Findings

What is the central question of this study?

Can Granger causality analysis of R–R intervals, systolic blood pressure and respiration provide evidence for the different physiological mechanisms induced during thermoneutral water immersion, 6 deg head‐down tilt and supine position tests that are not accessible using traditional heart rate variability and baroreflex methods?

What is the main finding and its importance?
The Granger analysis demonstrated a significant difference in the causal link from R–R intervals to respiration between water immersion and head‐down tilt. The underlying physiological mechanism explaining this difference could be the variation in peripheral resistances.

AbstractThermoneutral head‐out water immersion (WI) and 6 deg head‐down tilt (HDT) are used to simulate SCUBA diving, swimming and microgravity, because these models induce an increase in central blood volume. Standard methods to analyse autonomic regulation have demonstrated an increase in parasympathetic activity and baroreflex sensitivity during these experimental conditions. However, such methods are not adapted to quantify all closed‐loop interactions involved in respiratory and cardiovascular regulation. To overcome this limitation, we used Granger causality analysis between R–R intervals (RR), systolic blood pressure (SBP) and respiration (RE) in eight young, healthy subjects, recorded during 30 min periods in the supine position, WI and HDT. For all experimental conditions, we found a bidirectional causal relationship between RE and RR and between RR and SBP, with a dominant direction from RR to SBP, and a unidirectional causality from RE to SBP. These causal relationships remained unchanged for the three experimental tests. Interestingly, there was a lower causal relationship from RR to RE during WI compared with HDT. This causal link from RR to RE could be modulated by peripheral resistances. These results highlight differences in cardiovascular regulation during WI and HDT and confirm that Granger causality might reveal physiological mechanisms not accessible with standard methods.
Observation of Floquet solitons in a topological bandgap
Authors: Mukherjee Sebabrata , Rechtsman Mikael C. 
Published: May 2020

Topological insulators go nonlinear
Whereas solid-state insulators tend to be fixed by material properties, photonic topological insulators can be designed at will to mimic a variety of scenarios and complex interactions. Mukherjee and Rechtsman go beyond the linear optical regime that has been studied to date and show that photonic topological insulators can also exhibit nonlinear optical features (see the Perspective by Ablowitz and Cole). Their array of laser-written waveguides can support solitons, which are also found to exhibit topological features, performing cyclotron-like orbits associated with the topology of the lattice. The nonlinear properties provide a rich playground for further exploration, with the possibility of mimicking other interacting bosonic systems.

Science
, this issue p.
856
; see also p.
821
Prevalence of hyperuricaemia in an Eastern Chinese population: a cross-sectional study
Authors: Han Bing , Wang Ningjian , Chen Yi , Li Qin , Zhu Chunfang , Chen Yingchao , Lu Yingli 
Published: May 2020

ObjectivesIn the past decade, China has been characterised by large-scale urbanisation as well as rapid economic growth. The aim of this study was to further investigate the prevalence of hyperuricaemia (HUA) in an Eastern Chinese population.DesignCross-sectional study.SettingSurvey of Prevalence in East China of Metabolic Diseases and Risk Factors China study.ParticipantsIn this study, 12 770 residents from 22 sites in Eastern China were recruited. Finally, 9225 subjects were included.Main outcome measuresThe serum levels of uric acid (UA), fasting plasma glucose (FPG), glycated haemoglobin and other metabolic parameters were tested. Waist circumference, weight, height and blood pressure were also measured. Questionnaires regarding smoking, drinking, education were collected from the subjects. HUA was defined as serum UA >420 µmol/L for men and >360 µmol/L for women.ResultsThe prevalence of HUA in this Eastern Chinese population was 11.3% (9.9, 12.7) overall, 20.7% (17.7, 23.7) in men and 5.6% (4.3, 6.7) in women. The prevalence of HUA in urban subjects was higher than that in rural subjects (12.9 vs 10.8%, p<0.01). The prevalence of HUA was negatively and positively associated with age in men and women, respectively. Residents with high body mass index levels had a higher prevalence of HUA. In the logistic regression analysis, male sex, urban residency, total cholesterol, triglyceride, overweight, obesity, systolic blood pressure and low economic status were independently correlated with HUA.ConclusionsThe estimated prevalence of HUA in this Eastern Chinese population was 11.3% (9.9, 12.7) overall and 20.7% (17.7, 23.7) and 5.6% (4.3, 6.7) in men and women, respectively. HUA has gradually become an important public health issue in China.Trial registration numberChiCTR-ECS-14005052.
Estimation of injury costs: financial damage of English Premier League teams’ underachievement due to injuries
Authors: Eliakim Eyal , Morgulev Elia , Lidor Ronnie , Meckel Yoav 
Published: May 2020

BackgroundIn individual sports, the effect that injuries have on an athlete’s performance, success and financial profit is implicit. In contrast, the effect of a single player’s injury or one player’s absence in team sports is much more difficult to quantify, both from the performance perspective and the financial perspective.ObjectivesIn this study, we attempted to estimate the effect of injuries on the performance of football teams from the English Premier League (EPL), and the financial implications derived from this effect.MethodsOur analysis is based on data regarding game results, injuries and estimations of the players’ financial value for the 2012–2013 through the 2016–2017 seasons.ResultsWe found a statistically significant relationship (r=−0.46, 95% CI −0.6 to −0.28, p=0.001) between the number of days out due to injuries suffered by team members during a season and the place difference between their actual and expected finish in the EPL table (according to overall player value). Moreover, we can interpolate that approximately 136 days out due to injury causes a team the loss of one league point, and that approximately 271 days out due to injury costs a team one place in the table. This interpolation formula is used as a heuristic model, and given the relationship specified above accounts for a significant portion of the variance in league placement (21%), the remaining variance is related to other factors. Calculating the costs of wage bills and prize money, we estimate that an EPL team loses an average of £45 million sterling due to injury-related decrement in performance per season.ConclusionProfessional football clubs have a strong economic incentive to invest in injury prevention and rehabilitation programmes.
Effects of the Simulation Using Team Deliberate Practice (Sim-TDP) model on
the performance of undergraduate nursing students
Authors: Platt Alan , McMeekin Peter , Prescott-Clements Linda 
Published: May 2020

Background
The use of simulation has grown in prominence, but variation in the
quality of provision has been reported, leading to calls for further research
into the most effective instructional designs. Simulation Using Team Deliberate
Practice (Sim-TDP) was developed in response. It combines the principles of
simulation with deliberate practice, therefore, providing participants with
opportunities to work towards well-defined goals, rehearse skills and reflect
on performance whilst receiving expert feedback. This study aimed to compare
the effects of Sim-TDP, versus the use of traditional simulation, on the
performance of second year adult nursing students.

Methods
Using a longitudinal quasi-experimental design, the effects of the two
approaches were compared over a 1-year period. Sixteen groups, each containing
an average of six participants, were randomised into an intervention arm (n=8)
or comparison arm (n=8). Data collection took place at 3 monthly intervals, at
which point the performance and time to complete the scenario objectives/tasks,
as a team, were recorded and analysed using a validated performance
tool.

Results
The independent t-tests, comparing the performance of the groups, did not
demonstrate any notable differences during the three phases. However, in phase
1, the independent t-tests suggested an improvement in the Sim-TDP
participants’ time spent on task
(t(14) = 5.12, p<0.001),
with a mean difference of 7.22 min. The mixed analysis of covariance inferred
that the use of the Sim-TDP led to an improvement, over time, in the
participants’ performance (F(1, 5) = 12.91, p=0.016), and
thus, an association between Sim-TDP and the enhanced performance of
participants.

Conclusion
The results suggest that Sim-TDP, potentially, optimised participant
performance, while maximising the use of Simulation-based education (SBE)
resources, such as simulation facilities and equipment. The model could be of
practical benefit to nurse educators wishing to integrate SBE into their
programmes.
Bi-allelicTTC5variants cause delayed developmental milestones and intellectual disability
Authors: Rasheed Arisha , Gumus Evren , Zaki Maha , Johnson Katherine , Manzoor Humera , LaForce Geneva , Ross Danica , McEvoy-Venneri Jennifer , Stanley Valentina , Lee Sangmoon , Virani Abbir , Ben-Omran Tawfeg , Gleeson Joseph G , Naz Sadaf , Schaffer Ashleigh 
Published: May 2020

BackgroundIntellectual disability syndromes (IDSs) with or without developmental delays affect up to 3% of the world population. We sought to clinically and genetically characterise a novel IDS segregating in five unrelated consanguineous families.MethodsClinical analyses were performed for eight patients with intellectual disability (ID). Whole-exome sequencing for selected participants followed by Sanger sequencing for all available family members was completed. Identity-by-descent (IBD) mapping was carried out for patients in two Egyptian families harbouring an identical variant. RNA was extracted from blood cells of Turkish participants, followed by cDNA synthesis and real-time PCR forTTC5.ResultsPhenotype comparisons of patients revealed shared clinical features of moderate-to-severe ID, corpus callosum agenesis, mild ventriculomegaly, simplified gyral pattern, cerebral atrophy, delayed motor and verbal milestones and hypotonia, presenting with an IDS. Four novel homozygous variants inTTC5: c.629A>G;p.(Tyr210Cys), c.692C>T;p.(Ala231Val), c.787C>T;p.(Arg263Ter) and c.1883C>T;p.(Arg395Ter) were identified in the eight patients from participating families. IBD mapping revealed that c.787C>T;p.(Arg263Ter) is a founder variant in Egypt. Missense variants c.629A>G;p.(Tyr210Cys) and c.692C>T;p.(Ala231Val) disrupt highly conserved residues of TTC5 within the fifth and sixth tetratricopeptide repeat motifs which are required for p300 interaction, while the nonsense variants are predicted to decreaseTTC5expression. Functional analysis of variant c.1883C>T;p.(Arg395Ter) showed reducedTTC5transcript levels in accordance with nonsense-mediated decay.ConclusionCombining our clinical and molecular data with a recent case report, we identify the core and variable clinical features associated withTTC5loss-of-function variants and reveal the requirement for TTC5 in human brain development and health.
Middle meningeal artery embolization reduces the post-operative recurrence rate of at-risk chronic subdural hematoma
Authors: Shotar Eimad , Meyblum Louis , Premat Kevin , Lenck Stéphanie , Degos Vincent , Grand Teodor , Cortese Jonathan , Pouvelle Arnaud , Pouliquen Geoffroy , Mouyal Samuel , Boch Anne-Laure , Carpentier Alexandre , Sourour Nader-Antoine , Mathon Bertrand , Clarençon Frédéric 
Published: May 2020

BackgroundEmbolization of the middle meningeal artery (MMA) has emerged as a potential treatment of chronic subdural hematomas (CSDHs).ObjectiveTo evaluate the impact on recurrence rate of postsurgical embolization of CSDH in patients with a higher than average risk of recurrence.MethodsA monocentric retrospective study was performed on retrospectively collected data. From March 2018 to December 2019, embolization of the MMA was proposed as an adjunct postoperative treatment after burr-hole surgery in patients operated for a recurrent CSDH or a CSDH with an independent recurrence risk factor, including antiplatelet therapy, full anticoagulation therapy, coagulation disorder, hepatopathy, or chronic alcoholism. Patients who had undergone postoperative embolization were compared with a historic group of patients operated between March 2016 and March 2018, selected based on the same inclusion criteria.ResultsDuring the study period, 89 patients (with 74 unilateral and 15 bilateral CSDHs) were included and underwent an embolization procedure, leading to 91 out of a total of 104 MMA being embolized (88%). These were compared with 174 patients (138 unilateral and 36 bilateral CSDH) in the historic control group. One major procedure-related adverse event was registered. Four of the 89 patients (4%) required surgery for a CSDH recurrence in the embolization group, significantly less than the 24 of 174 patients (14%) in the control group (OR=0.28, 95% CI 0.07 to 0.86, p=0.02).ConclusionsPostsurgical embolization of the MMA may reduce the recurrence rate of CSDHs with a risk factor of recurrence.
A Pan-cancer Clinical Study of Personalized Neoantigen Vaccine Monotherapy in Treating Patients with Various Types of Advanced Solid Tumors
Authors: Fang Yong , Mo Fan , Shou Jiawei , Wang Huimin , Luo Kai , Zhang Shanshan , Han Ning , Li Hongsen , Ye Shengli , Zhou Zhan , Chen Rongchang , Chen Lin , Liu Liang , Wang Huina , Pan Hongming , Chen Shuqing 
Published: May 2020

Abstract

Purpose:
Because of their high tumor specificity and immunogenicity, neoantigens have been considered as ultimate targets for cancer immunotherapy. Neoantigen-based vaccines have demonstrated promising efficacy for several cancer types. To further investigate the antitumor potentials for other types of solid tumors, we designed a peptide-based neoantigen vaccine, iNeo-Vac-P01, and conducted a single-arm, open-labeled, investigator-initiated clinical trial (NCT03662815).

Patients and Methods:
Personalized neoantigen vaccines were designed and manufactured according to our bioinformatics analysis results from the whole-exome sequencing of tumor and peripheral blood cell DNAs. Patients were scheduled to be vaccinated subcutaneously with adjuvant on days 1, 4, 8, 15, and 22 (prime phase), and days 78 and 162 (boost phase). Additional immunizations were administrated every 2–3 months as per patient's potential benefit. The safety and efficacy were assessed through adverse events (AE), progression-free survival (PFS), overall survival (OS), and other parameters.

Results:
Of the 22 patients enrolled with advanced malignancies, 20 had no or mild AEs, while 2 had grade 3 or 4 acute allergic reactions only after their sixth boost vaccination. The disease control rate was 71.4%. The median PFS was 4.6 months, whereas the median OS was not reached (12-month OS = 55.1%). Around 80% of individual peptides or peptide pools elicited measurable specific immune response. In addition, our findings revealed several potential biomarkers for the prediction of better response.

Conclusions:
iNeo-Vac-P01 as monotherapy is feasible and safe for patients with advanced solid tumors. It could elicit T-cell–mediated immune response targeting tumor neoantigens, and might have promising antitumor efficacy.
See related commentary by Filderman and Storkus, p. 4429
Prognostic Significance of Immune Cell Populations Identified by Machine Learning in Colorectal Cancer Using Routine Hematoxylin and Eosin–Stained Sections
Authors: Väyrynen Juha P. , Lau Mai Chan , Haruki Koichiro , Väyrynen Sara A. , Dias Costa Andressa , Borowsky Jennifer , Zhao Melissa , Fujiyoshi Kenji , Arima Kota , Twombly Tyler S. , Kishikawa Junko , Gu Simeng , Aminmozaffari Saina , Shi Shanshan , Baba Yoshifumi , Akimoto Naohiko , Ugai Tomotaka , Da Silva Annacarolina , Song Mingyang , Wu Kana , Chan Andrew T. , Nishihara Reiko , Fuchs Charles S. , Meyerhardt Jeffrey A. , Giannakis Marios , Ogino Shuji , Nowak Jonathan A. 
Published: May 2020

Abstract

Purpose:
Although high T-cell density is a well-established favorable prognostic factor in colorectal cancer, the prognostic significance of tumor-associated plasma cells, neutrophils, and eosinophils is less well-defined.

Experimental Design:
We computationally processed digital images of hematoxylin and eosin (H&E)–stained sections to identify lymphocytes, plasma cells, neutrophils, and eosinophils in tumor intraepithelial and stromal areas of 934 colorectal cancers in two prospective cohort studies. Multivariable Cox proportional hazards regression was used to compute mortality HR according to cell density quartiles. The spatial patterns of immune cell infiltration were studied using the GTumor:Immune cell function, which estimates the likelihood of any tumor cell in a sample having at least one neighboring immune cell of the specified type within a certain radius. Validation studies were performed on an independent cohort of 570 colorectal cancers.

Results:
Immune cell densities measured by the automated classifier demonstrated high correlation with densities both from manual counts and those obtained from an independently trained automated classifier (Spearman's ρ 0.71–0.96). High densities of stromal lymphocytes and eosinophils were associated with better cancer-specific survival [Ptrend &lt; 0.001; multivariable HR (4th vs 1st quartile of eosinophils), 0.49; 95% confidence interval, 0.34–0.71]. High GTumor:Lymphocyte area under the curve (AUC0,20μm; Ptrend = 0.002) and high GTumor:Eosinophil AUC0,20μm (Ptrend &lt; 0.001) also showed associations with better cancer-specific survival. High stromal eosinophil density was also associated with better cancer-specific survival in the validation cohort (Ptrend &lt; 0.001).

Conclusions:
These findings highlight the potential for machine learning assessment of H&E-stained sections to provide robust, quantitative tumor-immune biomarkers for precision medicine.
Prostate Epithelial RON Signaling Promotes M2 Macrophage Activation to Drive Prostate Tumor Growth and Progression
Authors: Sullivan Camille , Brown Nicholas E. , Vasiliauskas Juozas , Pathrose Peterson , Starnes Sandra L. , Waltz Susan E. 
Published: May 2020

AbstractEffective treatment of advanced prostate cancer persists as a significant clinical need as only 30% of patients with distant disease survive to 5 years after diagnosis. Targeting signaling and tumor cell–immune cell interactions in the tumor microenvironment has led to the development of powerful immunotherapeutic agents, however, the prostate tumor milieu remains impermeable to these strategies highlighting the need for novel therapeutic targets. In this study, we provide compelling evidence to support the role of the RON receptor tyrosine kinase as a major regulator of macrophages in the prostate tumor microenvironment. We show that loss of RON selectively in prostate epithelial cells leads to significantly reduced prostate tumor growth and metastasis and is associated with increased intratumor infiltration of macrophages. We further demonstrate that prostate epithelial RON loss induces transcriptional reprogramming of macrophages to support expression of classical M1 markers and suppress expression of alternative M2 markers. Interestingly, our results show epithelial RON activation drives upregulation of RON expression in macrophages as a positive feed-forward mechanism to support prostate tumor growth. Using 3D coculture assays, we provide additional evidence that epithelial RON expression coordinates interactions between prostate tumor cells and macrophages to promote macrophage-mediated tumor cell growth. Taken together, our results suggest that RON receptor signaling in prostate tumor cells directs the functions of macrophages in the prostate tumor microenvironment to promote prostate cancer.Implications:Epithelial RON is a novel immunotherapeutic target that is responsible for directing the macrophage antitumor immune response to support prostate tumor growth and progression.