bluuebunny/crossref_metadata_2025 huggingface dataset:
Strength of patient cohorts and biobanks for cardiomyopathy research
Authors: de Boer R. A. , Nijenkamp L. L. A. M. , Silljé H. H. W. , Eijgenraam T. R. , Parbhudayal R. , van Driel B. , Huurman R. , Michels M. , Pei J. , Harakalova M. , van Lint F. H. M. , Jansen M. , Baas A. F. , Asselbergs F. W. , van Tintelen J. P. , Brundel B. J. J. M. , Dorsch L. M. , Schuldt M. , Kuster D. W. D. , van der Velden J. ,   DOSIS consortium
Published: August 2020

In 2011 the Netherlands Heart Foundation allocated funding (CVON, Cardiovasculair Onderzoek Nederland) to stimulate collaboration between clinical and preclinical researchers on specific areas of research. One of those areas involves genetic heart diseases, which are frequently caused by pathogenic variants in genes that encode sarcomere proteins. In 2014, the DOSIS (Determinants of susceptibility in inherited cardiomyopathy: towards novel therapeutic approaches) consortium was initiated, focusing their research on secondary disease hits involved in the onset and progression of cardiomyopathies. Here we highlight several recent observations from our consortium and collaborators which may ultimately be relevant for clinical practice.
The history of transcatheter aortic valve implantation: The role and contribution of an early believer and adopter, the Netherlands
Authors: de Jaegere P. , de Ronde M. , den Heijer P. , Weger A. , Baan J.
Published: August 2020

This paper describes the history of transcatheter aortic valve implantation (TAVI) from its preclinical phase during which visionary pioneers developed its concept and prototype valves against strong head wind to first application in clinical practice (2002) and the clinical and scientific role of an early believer and adopter, the Netherlands (2005).
Clinical impact of PSMA PET in biochemically recurrent prostate cancer; a review of the literature
Authors: Wondergem Maurits , van der Zant Friso M. , Broos Wouter A. M. , Knol Remco J. J.
Published: August 2020

PSMA PET is increasingly used for localising biochemical recurrent prostate cancer (BCR) and is incorporated in European and national guidelines. Nevertheless, clinical implications of PSMA PET need to be clarified. In this report, the available literature on the clinical impact of PSMA PET in patients with BCR is reviewed. A comprehensive literature search was performed using the MEDLINE® database. All studies reporting data on PSMA PET directed patient management were considered relevant. In the review, 16 studies were included. Change of management was 45% for the pooled data (861/1899 patients), of which 50% changed from non-targeted to targeted approach. Change from targeted to non-targeted approaches was found in 17% of patients. High heterogeneity was found between presently available studies. It can be concluded that PSMA PET induces change of management in almost half of the patients with BCR. After PSMA PET more patients are selected for metastasis targeted therapies. Potential beneficial effects of metastasis directed therapies require further evaluation.
Psychological Stress: A Predisposing and Exacerbating Factor in Periodontitis
Authors: Spector Anna M. , Postolache Teodor T. , Akram Faisal , Scott Alison J. , Wadhawan Abhishek , Reynolds Mark A.
Published: August 2020

Purpose of Review

This review focuses on recent advances in our understanding of the interactions between psychological stress, the immune system, and periodontitis, including the dynamic role of host stress responses in altering immune function, altering the oral microbiome and biofilm formation, and promoting local and systemic disease progression.

Recent Findings

Within the context of periodontal health and disease, stress leads to an impairment of effective antimicrobial defense, shifts in oral microbiome profiles toward more pathogenic gene expression and taxa composition, increased translocation, and biofilm formation. The link between stress and periodontitis is multiform and includes hypothalamic–pituitary–adrenal (HPA) axis and catecholamine activation, production of immune mediators of inflammation and, clinically, syndromes of depression, bipolar disorder, anxiety disorders, and sleep-wake disorders.

Psychological stress appears to be an important modifiable risk factor for the development and progression of periodontitis and other periodontal diseases.
Effect of hydrothermal treatment on the carbon structure of Inner Mongolia lignite
Authors: Liu Peng , Zhang Dexiang
Published: August 2020

Understanding the structural properties of lignite during hydrothermal treatment would aid in predicting the subsequent behavior of coal during the pyrolysis, liquefaction, and gasification processes. Here, hydrothermal treatment of Inner Mongolia lignite (IM) was carried out in a lab autoclave. The distribution of carbon in the lignite was monitored via solid 13C nuclear magnetic resonance spectroscopy, and the functional groups of oxygen in lignite were determined by Fourier transform infrared spectroscopy. The curve-fitting method was used to calculate the content of the functional groups quantitatively. The results show that hydrothermal treatment is an effective method for upgrading the lignite. The side chains of the aromatic ring in lignite are altered, while the main macromolecular structure remains nearly the same. The hydrothermal treatment of IM could be divided into three temperature-dependent stages. The first stage (< 493 K) is the decomposition reaction of oxygen functional groups, where the O/C ratio decreases from 0.203 in raw IM to 0.185 for the IM treated at 493 K. In the second stage (493–533 K), hydrolysis of functional groups and hydrogen transfer between water and lignite occur. Here, the ratio of methylene to methyl increases from 0.871 in IM-493 to 1.241 for IM-533, and the content of quinone generates from the condensation of free phenol increased. The third stage (> 533 K) involves breakage of the covalent bond, and the content of CH4 and CO in the emission gas clearly increase.
Viability of Image Compression in Vibrothermography
Authors: Chi X. , Zhang Y. , Di Maio D. , Lieven N.A.J.
Published: August 2020

This research focuses on the verification of the viability of image compression in infrared thermography in order to address the problem of data storage. Specifically, images from vibrothermographic tests were utilized due to their special characteristics compared to the results from alternative infrared thermography techniques, which are able to introduce additional uncertainties to the compression process. In this research, an adaptive algorithm based on the lifting discrete wavelet transform and set-partitioning embedded blocks was used for image compression. Five different methods, namely the compression ratio, mean squared error, peak signal-to-noise ratio, structural similarity index and coordinate modal assurance criterion, were applied to evaluate the performance of the compression process while identifying and locating the regions affected more significantly after image compression. Feature extraction through the independent component analysis was then applied to the images to separate the features such as the hot spots so that the influence from the image compression process on each important feature could be evaluated independently. In this article, the theoretical background of the applied data processing techniques is firstly presented. Through two sets of data acquired from vibrothermographic tests on an aerospace-grade composite plate containing delamination, the effects of the image compression process on the relevant hot spots are evaluated, and the effectiveness of the compression process is verified. It is demonstrated that the compression process was able to reduce the size of the images significantly without adversely affecting the quality of the important features indicating the presence of damage. The major characteristics of the key features have been successfully preserved after effective image compression.
3D simulation of gas-laden liquid flows in centrifugal pumps and the assessment of two-fluid CFD methods
Authors: Hundshagen Markus , Mansour Michael , Thévenin Dominique , Skoda Romuald
Published: August 2020

An assessment of a two-fluid model assuming a continuous liquid and a dispersed gas phase for 3D computational fluid dynamics (CFD) simulations of gas/liquid flow in a centrifugal research pump is performed. A monodisperse two-fluid model, in conjunction with a statistical eddy-viscosity turbulence model, is utilized. By a comprehensive measurement database, a thorough assessment of model inaccuracies is enabled. The results on a horizontal diffuser flow reveal that the turbulence model is one main limitation of simulation accuracy for gas/liquid flows. Regarding pump flows, distinctions of single-phase and two-phase flow in a closed and semi-open impeller are figured out. Even single-phase flow simulations reveal challenging requirements on a high spatial resolution, e.g., of the rounded blade trailing edge and the tip clearance gap flow. In two-phase pump operation, gas accumulations lead to coherent gas pockets that are predicted partly at wrong locations within the blade channel. At best, a qualitative prediction of gas accumulations and the head drop towards increasing inlet gas volume fractions (IGVF) can be obtained. One main limitation of two-fluid methods for pump flow is figured out in terms of the violation of the dilute, disperse phase assumption due to locally high disperse phase loading within coherent gas accumulations. In these circumstances, bubble population models do not appear beneficial compared to a monodisperse bubble distribution. Volume-of-Fluid (VOF) methods may be utilized to capture the phase interface at large accumulated gas cavities, requiring a high spatial resolution. Thus, a hybrid model, i.e., a dispersed phase two-fluid model including polydispersity for flow regions with a dilute gas phase, should be combined with an interphase capturing model, e.g., in terms of VOF. This hybrid model, together with scale-resolving turbulence models, seems to be indispensable for a quantitative two-phase pump performance prediction.
The Ripple Effect: The Political Consequences of Proximal Contact with Immigration Enforcement
Authors: Walker Hannah , Roman Marcel , Barreto Matt
Published: August 2020

A growing body of research suggests that proximal exposure to immigration enforcement can have important social and health-related consequences. However, there is little research identifying the impact of proximal contact with immigration policy on political attitudes and behaviors, and still less investigating the underlying mechanisms that might connect contact and political dispositions. Drawing on insights from criminal justice, we argue that proximal immigration contact influences political behavior via a sense of injustice with respect to the discriminatory application of immigration enforcement. The impact of a sense of injustice should primarily hold among Latinos, who are targeted on the basis of race, ethnicity, accent, and skin color. Nevertheless, it may also hold among Blacks, whose communities are targeted more generally, and Asians, to whom issues related to immigration are likewise important. In order to assess this theory, we leverage a survey with nationally representative samples of four different racial groups. We find that proximal contact motivates participation in protests, and does so indirectly via a sense of injustice for white and Asian respondents. Latino and Black respondents are primarily motivated by injustice irrespective of contact. In sum, the results suggest that immigration enforcement and non-immigration-related criminal justice policies may have similar political effects on those who are proximately affected.
Effect of dietary selenium on postprandial protein deposition in the muscle of juvenile rainbow trout (Oncorhynchus mykiss)
Authors: Wang Li , Wang Long , Zhang Dianfu , Li Sai , Yin Jiaojiao , Xu Zhen , Zhang Xuezhen
Published: August 2020

Se, an essential biological trace element, is required for fish growth. However, the underlying mechanisms remain unclear. Protein deposition in muscle is an important determinant for fish growth. This study was conducted on juvenile rainbow trout (Oncorhynchus mykiss) to explore the nutritional effects of Se on protein deposition in fish muscle by analysing the postprandial dynamics of both protein synthesis and protein degradation. Trout were fed a basal diet supplemented with or without 4 mg/kg Se (as Se yeast), which has been previously demonstrated as the optimal supplemental level for rainbow trout growth. After 6 weeks of feeding, dietary Se supplementation exerted no influence on fish feed intake, whereas it increased fish growth rate, feed efficiency, protein retention rate and muscle protein content. Results of postprandial dynamics (within 24 h after feeding) of protein synthesis and degradation in trout muscle showed that dietary Se supplementation led to a persistently hyperactivated target of rapamycin complex 1 pathway and the suppressive expression of numerous genes related to the ubiquitin–proteasome system and the autophagy–lysosome system after the feeding. However, the ubiquitinated proteins and microtubule-associated light chain 3B (LC3)-II:LC3-I ratio, biomarkers for ubiquitination and autophagy activities, respectively, exhibited no significant differences among the fish fed different experimental diets throughout the whole postprandial period. Overall, this study demonstrated a promoting effect of nutritional level of dietary Se on protein deposition in fish muscle by accelerating postprandial protein synthesis. These results provide important insights about the regulatory role of dietary Se in fish growth.
Dietary fibre and protein do not synergistically influence insulin, metabolic or inflammatory biomarkers in young obese Göttingen minipigs
Authors: Xu Yetong , Curtasu Mihai Victor , Bach Knudsen Knud Erik , Hedemann Mette Skou , Theil Peter Kappel , Lærke Helle Nygaard
Published: August 2020

The effects of dietary fibre (DF) and protein on insulin response, lipidaemia and inflammatory biomarkers were studied in a model experiment with juvenile obese Göttingen minipigs. After 20 weeks feeding on a high-fat fructose-rich low-DF diet, forty-three 30-week-old minipigs (31·3 (sem 4·0) kg body weight) were allocated to low- or high-DF and -protein diets for 8 weeks in a 2 × 2 factorial design. High DF contents decreased (P = 0·006) while high protein increased (P < 0·001) the daily gain. High protein contents increased fasting plasma concentrations of glucose (P = 0·008), NEFA (P = 0·015), ghrelin (P = 0·008) and non-fasting LDL:HDL ratios (P = 0·015). High DF increased ghrelin (P = 0·036) and C-peptide levels (P = 0·011) in the non-fasting state. High protein increased the gene expression of fructose-bisphosphatase 1 in liver tissue (P = 0·043), whereas DF decreased fatty acid synthase expression in adipose tissue (P = 0·035). Interactions between DF and protein level were observed in the expression of leptin receptor in adipose tissue (P = 0·031) and of PPARγ in muscle (P = 0·018) and adipose tissue (P = 0·004). In conclusion, high DF intake reduced weight gain and had potential benefit on β-cell secretory function, but without effect on the lipid profile in this young obese model. High dietary protein by supplementing with whey protein did not improve insulin sensitivity or lipidaemia, and combining high DF with high protein did not alleviate the risk of metabolic abnormalities.
Short- and long-term effects of rearing dairy calves with contact to their mother on their reactions towards humans
Authors: Waiblinger Susanne , Wagner Kathrin , Hillmann Edna , Barth Kerstin
Published: August 2020

In this Research Communication we address the hypotheses that reduced contact with humans during the first week of life would impair the relationship of dairy calves reared in dam-calf-contact systems to humans in comparison with artificially reared animals, but that this difference would vanish over time. Artificially reared calves (Artificial)that had been separated from their mother within 12 h after birth were bottle-fed with colostrum for 5 d and thereafter sucked milk from an automatic milk feeder. Animals reared with dam-calf contact (Dam-contact) were kept in the calving pen with their dam for 5 d, and then had permanent access to the cow barn and thus to their dam. Calves were weaned at an age of 12 weeks and kept in young stock groups mixed of both treatments until integration into the cow herd. We tested the animals’ relationship with humans by assessing the animals' responses towards an unfamiliar person in an avoidance distance (AD) test in the home environment at 4 weeks of age, at 15 months and at 33 months. In calves, we additionally measured AD in a novel arena after a stationary person test.Artificialanimals had lower AD, i.e. showed lower level of fear, thanDam-contactcalves. However, the AD inDam-contactcalves decreased with increasing number of days they experienced assistance for suckling. Further, there was no significant difference in later ages. In conclusion, gentle human contact in combination with feeding during the first 5 d of life improved calves' relationship to humans leading to differences between the two treatments as well as within theDam-contactcalves. Potential effects under different conditions regarding quantity and quality of human-animal interactions need further research.
Investigating data-driven biological subtypes of psychiatric disorders using specification-curve analysis
Authors: Beijers Lian , van Loo Hanna M. , Romeijn Jan-Willem , Lamers Femke , Schoevers Robert A. , Wardenaar Klaas J.
Published: August 2020

Background

Cluster analyses have become popular tools for data-driven classification in biological psychiatric research. However, these analyses are known to be sensitive to the chosen methods and/or modelling options, which may hamper generalizability and replicability of findings. To gain more insight into this problem, we used Specification-Curve Analysis (SCA) to investigate the influence of methodological variation on biomarker-based cluster-analysis results.

Methods

Proteomics data (31 biomarkers) were used from patients (n = 688) and healthy controls (n = 426) in the Netherlands Study of Depression and Anxiety. In SCAs, consistency of results was evaluated across 1200 k-means and hierarchical clustering analyses, each with a unique combination of the clustering algorithm, fit-index, and distance metric. Next, SCAs were run in simulated datasets with varying cluster numbers and noise/outlier levels to evaluate the effect of data properties on SCA outcomes.

Results

The real data SCA showed no robust patterns of biological clustering in either the MDD or a combined MDD/healthy dataset. The simulation results showed that the correct number of clusters could be identified quite consistently across the 1200 model specifications, but that correct cluster identification became harder when the number of clusters and noise levels increased.

Conclusion

SCA can provide useful insights into the presence of clusters in biomarker data. However, SCA is likely to show inconsistent results in real-world biomarker datasets that are complex and contain considerable levels of noise. Here, the number and nature of the observed clusters may depend strongly on the chosen model-specification, precluding conclusions about the existence of biological clusters among psychiatric patients.
Higher fire frequency impaired woody species regeneration in a south-eastern Amazonian forest
Authors: Cury Roberta Thays dos Santos , Balch Jennifer Kakareka , Brando Paulo Monteiro , Andrade Rafael Barreto , Scervino Renata Picolo , Torezan José Marcelo Domingues
Published: August 2020

Understorey wildfires harm tropical forests by affecting natural regeneration, but the trajectories of fire-disturbed forests after disturbance are poorly understood. To fill this gap, we conducted experimental burns in a transitional forest between the Amazon forests and the Brazilian Savanna (Cerrado) and investigated their effects on plant community diversity of regeneration. The experiment consisted of three 50-ha plots that between 2004 and 2010 were burned either annually (six times), every three years (thrice) or not at all (Control). To evaluate early post-fire recovery, we recorded grass occurrence and regenerating stems (≤1 cm in diameter at breast height). We noted that high fire-frequency plots had a reduction of species richness (62%) and abundance (84%) and were associated with floristic and structural changes, dominance of few species and increase of grass colonization when compared with low fire-frequency. We observed that resprouts were the main pathway for forest restoration in both burned regimes, particularly in low fire-frequency. However, the forest can recover from fires by means of resprouting, until a threshold in fire frequency is reached, when resprouts and seedlings declined for most of the species, with a few fire-tolerant species becoming dominant.
THE RETRIEVABILITY OF L2 ENGLISH MULTIWORD ITEMS IN A CONTEXT OF STRONGLY FORM-FOCUSED EXPOSURE
Authors: Lindstromberg Seth , Eyckmans June
Published: August 2020

Although retrieval of lexical forms is a prerequisite for language production, research of L2 vocabulary learning has focused much more on meanings and form-meaning mappings than on development of detailed, accessible mental representations of forms. This is particularly true with respect to multi-word items (MWIs). We report an experimental study involving a variety of intra-lexical, usage-based, and interlingual co-determinants of L2 vocabulary learnability pertaining to MWIs. Each learner (N = 60) encountered a randomly allocated set of 26 two-word MWIs (Nsets = 4) semi-randomly drawn from a larger pool of MWIs. Learners were asked to remember either the 13 MWIs showing the form variable assonance (e.g., change shape) or the 13 nonassonant control MWIs (e.g., sound good). Posttests of form recall revealed a large, durable effect of the focusing task in combination with forewarning of testing. Except when MWI concreteness (a semantic variable) was high, assonance had a positive effect on retrievability in recall tests given after delays of 15 minutes and one week. There was a consistent effect of the semi-semantic variable Mutual Information. Even in the context of a strong focus on forms, form variables are not the only variables that matter.
COVID-19 in India: transmission dynamics, epidemiological characteristics, testing, recovery and effect of weather
Authors: Chanda Arnab
Published: August 2020

The spread of COVID-19 is recent in India, which has within 4 months caused over 190 000 infections, as of 1 June 2020, despite four stringent lockdowns. With the current rate of the disease transmission in India, which is home to over 1.35 billion people, the infection spread is predicted to be worse than the USA in the upcoming months. To date, there is a major lack of understanding of the transmission dynamics and epidemiological characteristics of the disease in India, inhibiting effective measures to control the pandemic. We collected all the available data of the individual patients, cases and a range of parameters such as population distribution, testing and healthcare facilities, and weather, across all Indian states till May 2020. Numerical analysis was conducted to determine the effect of each parameter on the COVID-19 situation in India. A significant amount of local transmission in India initiated with travellers returning from abroad. Maharashtra, Tamil Nadu and Delhi are currently the top three infected states in India with doubling time of 14.5 days. The average recovery rate across Indian states is 42%, with a mortality rate below 3%. The rest 55% are currently active cases. In total, 88% of the patients experienced symptoms of high fever, 68% suffered from dry cough and 7.1% patients were asymptomatic. In total, 66.8% patients were males, 73% were in the age group of 20–59 years and over 83% recovered in 11–25 days. Approximately 3.4 million people were tested between 1 April and 25 May 2020, out of which 4% were detected COVID-19-positive. Given the current doubling time of infections, several states may face a major shortage of public beds and healthcare facilities soon. Weather has minimal effect on the infection spread in most Indian states. The study results will help policymakers to predict the trends of the disease spread in the upcoming months and devise better control measures.
Unbounded circumambient patterns in segmental phonology
Authors: McCollum Adam G. , Baković Eric , Mai Anna , Meinhardt Eric
Published: August 2020

We present an empirical challenge to Jardine's (2016) assertion that only tonal spreading patterns can be unbounded circumambient, meaning that the determination of a phonological value may depend on information that is an unbounded distance away on both sides. We focus on a demonstration that the ATR harmony pattern found in Tutrugbu is unbounded circumambient, and we also cite several other segmental spreading processes with the same general character. We discuss implications for the complexity of phonology and for the relationship between the explanation of typology and the evaluation of phonological theories.
Interventional recanalisation of long segment aortic atresia
Authors: Huntgeburth Michael , Ahmad Wael , Brunkwall Jan , Sreeram Narayanswami
Published: August 2020

We report the case of a long-segment aortic atresia as the cause for therapy resistant arterial hypertension in a young adult. Recanalization was achieved interventionally by wire-crossing and stent implantation with subsequent normalization of blood pressure.
Dietary total antioxidant capacity (TAC), general and central obesity	indices and serum lipids among adults: An updated systematic review and	meta-analysis
Authors: Farhangi Mahdieh Abbasalizad , Vajdi Mahdi , Fathollahi Pourya
Published: August 2020

Abstract. Background: In the present meta-analysis, we aimed to summarize the relationship between dietary total antioxidant capacity (TAC), general and central obesity indices and lipid profile in adult population. Methods: The electronic databases of Web of Sciences, PubMed, Scopus and Cochrane library were searched for relevant studies from inception to October 2019. The effect size was indicated as weighted mean difference (WMD) and 95% confidence intervals (CI) by using random effects model. The I2 index and Cochran’s Q-test were used for evaluating heterogeneity. Results: From 2,469 studies identified, thirty-four studies (nineteen cross-sectional studies, thirteen cohort studies, two case-control studies) were included in the meta-analysis. According to our results, higher categories of TAC were associated with significantly lower serum triglyceride concentartions (TG; WMD: −7.58; CI: −11.42, −3.75; P < 0.001) and waist circumference (WC; WMD: −1.17; 95% CI: −1.47, −0.87; P < 0.001); while no significant change in body mass index (BMI; WMD: −0.17; 95% CI: −0.35, 0.01; P = 0.12), high density lipoprotein cholesterol (HDL-C; WMD: 0.61; 95% CI: −0.16, 1.40; P = 0.12), low density lipoprotein cholesterol (LDL-C; WMD: 1.34; 95% CI: −0.61, 3.30; P = 0.17) and total cholesterol (TC; WMD: 1.19; 95% CI: −1.46, 3.855; P = 0.37) was reported. Conclusion: Higher dietary TAC was related to reduced prevalence of central obesity, reduced WC and TG concentrations in the current meta-analysis. Moreover, subgroup analysis showed that TAC measurement index, geographical area, dietary assessment tool, health status and gender were potential sources of heterogeneity.
Schnittstellenkoordination von systemübergreifenden Hilfen für Kinder und Jugendliche mit psychischen Beeinträchtigungen
Authors: Böge Isabel , DeKeijzer Deborah , Fegert Jörg M. , Schulze Ulrike
Published: August 2020

Zusammenfassung. Schnittstellen zwischen psychosozialen Hilfesystemen stellen Sollbruchstellen einer gelingenden systemübergreifenden Behandlung psychisch erkrankter Kinder/Jugendlicher dar. Daten zu Schnittstellenmanagement in Deutschland liegen bisher nicht vor. Ziel der Studie ASpeKT war es, zu vier Zeitpunkten (T1 Aufnahme, T2 Entlassung, T3 6 Mo und T4 12 Mo nach Entlassung) den Ist-Stand von installierten Hilfen bei psychisch erkrankten Kindern und Jugendlichen ( n=191) zu erheben, Patientenzufriedenheit zu evaluieren sowie dies an zwei, strukturell unterschiedlichen Standorten (Klinik A/Klinik B) zu vergleichen. Zu T2 erhielten 13 % der Patienten keine Hilfen. 43,6 % (A) bzw. 70,4 % (B) erhielten Psychotherapie (PT), 67,3 % (A) bzw. 80,3 % (B) Jugendhilfemaßnahmen (JH), 37,6 % (A) bzw. 16.9 % (B) schulische Unterstützung. Gute Schnittstellenkoordination ist prognostisch essentiell, um den meist noch komplexen Hilfebedarf psychisch erkrankter Kinder/Jugendlicher nach stationärer Behandlung abzubilden.
The Tidal Response in the Mesosphere/Lower Thermosphere to the Madden‐Julian Oscillation Observed by SABER
Authors: Kumari Komal , Oberheide Jens , Lu Xian
Published: August 2020

A statistical study of 18 years of diurnal temperature tides observed by the SABER instrument on board the TIMED satellite reveals a substantial response of the tides in the upper atmosphere (>60 km) to the Madden‐Julian Oscillation (MJO) in the tropical troposphere. Nonmigrating tidal amplitudes are modulated at the intraseasonal MJO periods up to ~25% relative to the seasonal mean, twice as much as for the migrating tides (~10%). We fully characterize the tidal response for active MJO days as a function of season and MJO location as prescribed by the MJO index. The MJO modulation of the tides was predicted by models but could not be unequivocally observed before. Our results further point to an important role of background winds that partly cause a different response for equatorial and nonequatorial tidal modes in different seasons, which has implications for the MJO imprint on the ionospheric dynamo region.
Vegetation Response to Elevated CO2 Slows Down the Eastward Movement of the 100th Meridian
Authors: Zhang Cicheng , Yang Yuting , Yang Dawen , Wang Zhengrong , Wu Xiuchen , Zhang Shulei , Zhang Wenjie
Published: August 2020

The 100th meridian is a conceptual arid‐humid divide that effectively bisects the continent of the United States into the humid east and arid west. Here, we examine the historical and future shifts of the 100th meridian from atmospheric, hydrologic, and agroecological perspectives. We find that the effective arid‐humid divide regarding vegetation greenness and runoff has been moving toward west with a mean shift of 0.73° (1982–2015) and 2.08° (1961–2010), respectively, suggesting decreased agroecological and hydrologic aridity in the region. For future periods, the agroecological divide shows a persistent westward movement, whereas eastward shifts of the 100th meridian are detected from the atmospheric and hydrologic perspectives. Nevertheless, the eastward movements of the atmospheric and hydrologic divide substantially slow down when the vegetation response to elevated atmospheric CO2 is accounted for. This finding demonstrates that CO2 fertilization on vegetation could largely alleviate the warming‐induced drying tendency around the 100th meridian region.
Storm‐Time Modeling of the African Regional Ionospheric Total Electron Content Using Artificial Neural Networks
Authors: Okoh Daniel , Habarulema John Bosco , Rabiu Babatunde , Seemala Gopi , Wisdom Joshua Benjamin , Olwendo Joseph , Obrou Olivier , Matamba Tshimangadzo Merline
Published: August 2020

This paper presents the development of a storm‐time total electron content (TEC) model over the African sector for the first time. The storm criterion used was |Dst| ≥ 50 nT and Kp ≥ 4. We have utilized Global Positioning System (GPS) observations from 2000 to 2018 from about 252 receivers over the African continent and surroundings within spatial coverage of 40°S–40°N latitude and 25°W–60°E longitude. To increase data coverage in areas devoid of ground‐based instrumentation including oceans, we used the available radio occultation Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) TEC from 2008 to 2018. The model is based on artificial neural networks which are used to learn the relationship between TEC and the corresponding physical/geophysical input parameters representing factors which influence ionospheric variability. An important result from this effort was the inclusion of the time history of the geomagnetic activity indicators
which improved TEC modeling by about 5% and 12% in middle and low latitudes, respectively. Overall, the model performs comparatively well with, and sometimes better than, the earlier single station modeling efforts even during quiet conditions. Given that this is a storm‐time model, this result is encouraging since it is challenging to model ionospheric parameters during geomagnetically disturbed conditions. Statistically, the average root‐mean‐square error (RMSE) between modeled and GPS TEC is 5.5 TECU (percentage error = 30.3%) and 5.0 TECU (percentage error = 30.4%) for the Southern and Northern Hemisphere midlatitudes respectively compared to 7.5 TECU (percentage error = 22.0%) in low latitudes.
The oxytocin receptor signalling system and breast cancer: a critical review
Authors: Liu Huiping , Gruber Christian W. , Alewood Paul F. , Möller Andreas , Muttenthaler Markus
Published: August 2020

Breast cancer is making up one-quarter of all new female cancer cases diagnosed worldwide. Breast cancer surgeries, radiation therapies, cytotoxic chemotherapies and targeted therapies have made significant progress and play a dominant role in breast cancer patient management. However, many challenges remain, including resistance to systemic therapies, tumour recurrence and metastasis. The cyclic neuropeptide oxytocin (OT) elicits a plethora of biological responses via the oxytocin receptor (OTR) in both the central and peripheral nervous system, including social bonding, stress, maternal behaviour, sexual activity, uterus contraction, milk ejection and cancer. As a typical member of the G protein-coupled receptor family, OTR represents also an intriguing target for cancer therapy. There is emerging evidence that OTR plays a role in breast cancer development and progression, and several breast cancer cell lines express OTR. However, despite supporting evidence that OT lowers breast cancer risks, its mechanistic role in breast cancer development and the related signalling pathways are not fully understood. Here, we review the current knowledge of the OT/OTR signalling system in healthy breast tissue as well as in breast cancer, and discuss OTR as a potential therapeutic target for breast cancer management.
CD146, from a melanoma cell adhesion molecule to a signaling receptor
Authors: Wang Zhaoqing , Xu Qingji , Zhang Nengwei , Du Xuemei , Xu Guangzhong , Yan Xiyun
Published: August 2020

CD146 was originally identified as a melanoma cell adhesion molecule (MCAM) and highly expressed in many tumors and endothelial cells. However, the evidence that CD146 acts as an adhesion molecule to mediate a homophilic adhesion through the direct interactions between CD146 and itself is still lacking. Recent evidence revealed that CD146 is not merely an adhesion molecule, but also a cellular surface receptor of miscellaneous ligands, including some growth factors and extracellular matrixes. Through the bidirectional interactions with its ligands, CD146 is actively involved in numerous physiological and pathological processes of cells. Overexpression of CD146 can be observed in most of malignancies and is implicated in nearly every step of the development and progression of cancers, especially vascular and lymphatic metastasis. Thus, immunotherapy against CD146 would provide a promising strategy to inhibit metastasis, which accounts for the majority of cancer-associated deaths. Therefore, to deepen the understanding of CD146, we review the reports describing the newly identified ligands of CD146 and discuss the implications of these findings in establishing novel strategies for cancer therapy.
Cytogenetic abnormalities in multiple myeloma: association with disease characteristics and treatment response
Authors: Abdallah Nadine , Rajkumar S. Vincent , Greipp Patricia , Kapoor Prashant , Gertz Morie A. , Dispenzieri Angela , Baughn Linda B. , Lacy Martha Q. , Hayman Suzanne R. , Buadi Francis K. , Dingli David , Go Ronald S. , Hwa Yi L. , Fonder Amie , Hobbs Miriam , Lin Yi , Leung Nelson , Kourelis Taxiarchis , Warsame Rahma , Siddiqui Mustaqeem , Lust John , Kyle Robert A. , Bergsagel Leif , Ketterling Rhett , Kumar Shaji K.
Published: August 2020

Cytogenetic abnormalities are found in most multiple myeloma (MM) patients. Although their prognostic value has been well studied, there are limited data on the association of primary cytogenetic abnormalities with disease characteristics and treatment response. This study was designed to evaluate these associations. This is a retrospective study including 2027 Mayo Clinic patients diagnosed with MM between February 2004 and February 2018 who had cytogenetic testing by FISH at diagnosis. Translocations t(4;14), t(14;16), t(6;14), and t(14;20) were associated with anemia, beta2microglobulin >5.5 µg/ml and ≥50% bone marrow plasma cells; t(4;14) was associated with higher serum monoclonal protein and plasma cell proliferation. Overall response rate to proteasome inhibitor (PI)-based treatment was higher for IgH translocations compared to trisomies (83% vs. 71%, P = 0.002), but was higher for trisomies with immunomodulatory drug (IMiD)-based treatment (87% vs. 75%, P < 0.001). Time to next treatment was longer with trisomies than IgH translocation with IMiD-based (32.1 vs. 18.4 months, P < 0.001) and PI + IMiD-based (44.0 vs. 27.4 months, P = 0.003) treatments. Outcomes were superior with PI + IMiD combinations in all groups. Our results show that t(4;14), t(14;16), t(6;14), and t(14;20) are associated with high-risk disease characteristics, and IgH translocations and trisomies may be associated with better responses to PIs and IMiDs, respectively.
Plasma-based early screening and monitoring of EGFR mutations in NSCLC patients by a 3-color digital PCR assay
Authors: Song Xiang , Gong Jian , Zhang Xiaoling , Feng Xiaoyan , Huang Hui , Gao Min , Chu Li
Published: August 2020

Background

Noninvasive plasma-based detection of EGFR mutations using digital PCR promises a fast, sensitive and reliable approach to predicting the efficiency of EGFR-TKI. However, the low throughput and high cost of digital PCR restricts its clinical application.

Methods

We designed a digital PCR assay, which can simultaneously detect 39 mutations of exons 18–21 of the EGFR gene. To assess overall performance, retrospective FFPE tissues from 30 NSCLC patients and plasma from 33 NSCLC patients were collected and analysed.

Results

The LoD of the EGFR mutations was as low as 0.308 copies/μL, and the linear correlation between the detected and expected values at different concentrations (0.01–10%) was low as well. Compared to ARMS-PCR in FFPE, the accuracy values of the dEGFR39 assay in plasma from 33 patients was 87.88% (29/33, 95% CI 72.67–95.18%). While monitoring the 33 patients, the EGFR mutation load as assessed by dEGFR39 was associated with the objective response to treatment. Thirteen samples from eight patients were identified by dEGFR39 to harbour the T790M mutation over time; of these patients, only nine (69%) were detected using SuperARMS.

Conclusion

Our results indicate that dEGFR39 assay is reliable, sensitive and cost-efficient. This method is beneficial for profiling EGFR mutations for precision therapy and prognosis after TKI treatment, especially in patients with insufficient tissue biopsy samples.
Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer
Authors: Yang Moran , Zhang Guodong , Wang Yiying , He Mengdi , Xu Qing , Lu Jiaqi , Liu Haiou , Xu Congjian
Published: August 2020

Background

Tumour associated neutrophils (TANs) play a controversial role in regulating immune surveillance and immune evasion in various malignancies. Here, we investigated the relevance of TANs with the prognosis and immune microenvironment of epithelial ovarian cancer (EOC).

Methods

We characterised TANs using flow cytometric analysis and immunofluorescence analysis. The prognostic merit of TANs in EOC was evaluated using cox regression analysis. Furthermore, we explored the therapeutic merit of targeting Notch signalling in EOC and determined its involvement in the immune microenvironment.

Results

High level of TANs is associated with a dismal prognosis and immune tolerance in EOC. TANs impaired cytotoxic effects of CD8+ T cells partly through Jagged2 (JAG2). Notch pathway blocked using γ-secretase inhibitor LY3039478 and anti-JAG2 antibody led to retarded tumour growth and augmented cytotoxic effects of CD8+ T cells. IL-8 contributes to the recruitment of TANs and the induction of JAG2 expression in TANs. Blockade of CXCR2 signalling reduces tumour growth rate, accompanied by a decreasing amount of TANs and increasing activity of CD8+ T cells. JAG2+TANs is an independent predictor of clinical outcomes.

Conclusion

JAG2+TANs are closely linked to IL-8-driven immune evasion microenvironment and may serve as a promising therapeutic target for the reinvigoration of anti-tumour immunity.
Endogenous activity modulates stimulus and circuit-specific neural tuning and predicts perceptual behavior
Authors: Li Yuanning , Ward Michael J. , Richardson R. Mark , G’Sell Max , Ghuman Avniel Singh
Published: August 2020

Perception reflects not only sensory inputs, but also the endogenous state when these inputs enter the brain. Prior studies show that endogenous neural states influence stimulus processing through non-specific, global mechanisms, such as spontaneous fluctuations of arousal. It is unclear if endogenous activity influences circuit and stimulus-specific processing and behavior as well. Here we use intracranial recordings from 30 pre-surgical epilepsy patients to show that patterns of endogenous activity are related to the strength of trial-by-trial neural tuning in different visual category-selective neural circuits. The same aspects of the endogenous activity that relate to tuning in a particular neural circuit also correlate to behavioral reaction times only for stimuli from the category that circuit is selective for. These results suggest that endogenous activity can modulate neural tuning and influence behavior in a circuit- and stimulus-specific manner, reflecting a potential mechanism by which endogenous neural states facilitate and bias perception.
Mechanisms of drug interactions between translation-inhibiting antibiotics
Authors: Kavčič Bor , Tkačik Gašper , Bollenbach Tobias
Published: August 2020

Antibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by “translation bottlenecks”: points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further show that growth laws, combined with drug uptake and binding kinetics, enable the direct prediction of a large fraction of observed interactions, yet fail to predict suppression. However, varying two translation bottlenecks simultaneously supports that dense traffic of ribosomes and competition for translation factors account for the previously unexplained suppression. These results highlight the importance of “continuous epistasis” in bacterial physiology.
In vitro Cas9-assisted editing of modular polyketide synthase genes to produce desired natural product derivatives
Authors: Kudo Kei , Hashimoto Takuya , Hashimoto Junko , Kozone Ikuko , Kagaya Noritaka , Ueoka Reiko , Nishimura Takehiro , Komatsu Mamoru , Suenaga Hikaru , Ikeda Haruo , Shin-ya Kazuo
Published: August 2020

One major bottleneck in natural product drug development is derivatization, which is pivotal for fine tuning lead compounds. A promising solution is modifying the biosynthetic machineries of middle molecules such as macrolides. Although intense studies have established various methodologies for protein engineering of type I modular polyketide synthase(s) (PKSs), the accurate targeting of desired regions in the PKS gene is still challenging due to the high sequence similarity between its modules. Here, we report an innovative technique that adapts in vitro Cas9 reaction and Gibson assembly to edit a target region of the type I modular PKS gene. Proof-of-concept experiments using rapamycin PKS as a template show that heterologous expression of edited biosynthetic gene clusters produced almost all the desired derivatives. Our results are consistent with the promiscuity of modular PKS and thus, our technique will provide a platform to generate rationally designed natural product derivatives for future drug development.
Pupil-linked arousal signals track the temporal organization of events in memory
Authors: Clewett David , Gasser Camille , Davachi Lila
Published: August 2020

Everyday life unfolds continuously, yet we tend to remember past experiences as discrete event sequences or episodes. Although this phenomenon has been well documented, the neuromechanisms that support the transformation of continuous experience into distinct and memorable episodes remain unknown. Here, we show that changes in context, or event boundaries, elicit a burst of autonomic arousal, as indexed by pupil dilation. Event boundaries also lead to the segmentation of adjacent episodes in later memory, evidenced by changes in memory for the temporal duration, order, and perceptual details of recent event sequences. These subjective and objective changes in temporal memory are also related to distinct temporal features of pupil dilations to boundaries as well as to the temporal stability of more prolonged pupil-linked arousal states. Collectively, our findings suggest that pupil measures reflect both stability and change in ongoing mental context representations, which in turn shape the temporal structure of memory.
Adsorption and activation of molecular oxygen over atomic copper(I/II) site on ceria
Authors: Kang Liqun , Wang Bolun , Bing Qiming , Zalibera Michal , Büchel Robert , Xu Ruoyu , Wang Qiming , Liu Yiyun , Gianolio Diego , Tang Chiu C. , Gibson Emma K. , Danaie Mohsen , Allen Christopher , Wu Ke , Marlow Sushila , Sun Ling-dong , He Qian , Guan Shaoliang , Savitsky Anton , Velasco-Vélez Juan J. , Callison June , Kay Christopher W. M. , Pratsinis Sotiris E. , Lubitz Wolfgang , Liu Jing-yao , Wang Feng Ryan
Published: August 2020

Supported atomic metal sites have discrete molecular orbitals. Precise control over the energies of these sites is key to achieving novel reaction pathways with superior selectivity. Here, we achieve selective oxygen (O2) activation by utilising a framework of cerium (Ce) cations to reduce the energy of 3d orbitals of isolated copper (Cu) sites. Operando X-ray absorption spectroscopy, electron paramagnetic resonance and density-functional theory simulations are used to demonstrate that a [Cu(I)O2]3− site selectively adsorbs molecular O2, forming a rarely reported electrophilic η2-O2 species at 298 K. Assisted by neighbouring Ce(III) cations, η2-O2 is finally reduced to two O2−, that create two Cu–O–Ce oxo-bridges at 453 K. The isolated Cu(I)/(II) sites are ten times more active in CO oxidation than CuO clusters, showing a turnover frequency of 0.028 ± 0.003 s−1 at 373 K and 0.01 bar PCO. The unique electronic structure of [Cu(I)O2]3− site suggests its potential in selective oxidation.