bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodales Management nichtresektabler Lebermetastasen – neue Therapieoptionen mit Ausblick auf sekundäre Resektion
Authors: Braunwarth Eva , Stättner Stefan
Published: March 2021

Lebermetastasen treten bei 50 % der Patienten mit kolorektalem Karzinom auf. Bei resektablen Metastasen ist die chirurgische Resektion die Therapie der Wahl. Steht dies als Option nicht zur Verfügung, ist die primäre Behandlung eine systemische Chemotherapie. Die selektive interne Radiotherapie (SIRT) ist eine innovative Behandlungsform für primäre und sekundäre Lebertumoren. Es handelt sich um ein minimal-invasives Verfahren, bei dem kleine radioaktive Kügelchen, sog. Mikrosphären, über die Leberarterie in den Lebertumor bzw. die Lebermetastasen eingebracht werden. Die Mikrosphären führen zu einer Reduktion der Tumorlast durch hochenergetische Strahlung. Die Behandlung stellt eine vielversprechende Option für Patienten dar, deren Lebertumoren nicht mit einer Operation oder lokalen Verfahren wie der Radiofrequenzablation behandelbar sind und nicht mehr ausreichend auf eine Chemotherapie ansprechen. Die SIRT kann auch zur Leberaugmentation eingesetzt werden, um primär nichtresektable Patienten einer Resektion zugänglich zu machen. Die Behandlung ist umso erfolgreicher, je stärker die Blutversorgung des Primärtumors bzw. der Lebermetastasen aus der Leberarterie erfolgt. Anhand zahlreicher Studien wurde im Lauf der Jahre die Wirksamkeit dieser Therapie belegt. Sie stellt für selektionierte Patienten eine Erweiterung des therapeutischen Armamentariums dar, die in der First‑, Second- und Third-line-Behandlung eingesetzt werden kann.
Numerical simulation and experimental study of blade pitch effect on Darrieus straight-bladed wind turbine with high solidity
Authors: Babadi Soultanzadeh Milad , Moradi Alireza
Published: March 2021

Increasing the solidity in vertical axis wind turbines (VAWT) leads to the decreased coefficient of performance (COP) despite the improved start-up performance. To overcome this problem, the pitch regulation system is proposed in this paper for increasing the solidity. In most of the previous investigations, the effect of pitch angle was tested on low-solidity VAWT at uniform flow conditions and low turbulence intensity in wind tunnel test sections, which are different from the real conditions. In this investigation, the influence of pitch angle on the aerodynamic performance of a small Darrieus-type straight-bladed high-solidity VAWT equipped with a pitch regulation system is investigated numerically and experimentally under realistic condition. The proposed numerical procedure is validated through experimental test results. The COP is measured and calculated at different tip speed ratios and two pitch angles of 0 and 5°. The results reveal 25% enhancement in maximum COP with the increase of pitch angle up to 5°. Moreover, according to the numerical results, higher accuracy can be obtained at lower tip speed ratios for both pitch angles. Then, the numerical method is employed to calculate the power (performance) and torque coefficients as a function of Azimuth position as well as the flow field in rotor affected zone and lateral distance. It is found that increasing the pitch angle at a constant tip speed ratio is followed by accelerated vorticity generation, occurrence of maximum COP at lower tip speed ratio and smoother velocity profile in lateral distances of the rotor.
The Rise of Majority Rule in Early Modern Britain and Its Empire
Authors: Bulman William J.
Published: March 2021

This expansive history of the origins of majority rule in modern representative government charts the emergence of majority voting as a global standard for decision-making in popular assemblies. Majority votes had, of course, been held prior to 1642, but not since antiquity had they been held with any frequency by a popular assembly with responsibility for the fate of a nation. The crucial moment in the global triumph of majority rule was its embrace by the elected assemblies of early modern Britain and its empire. William J. Bulman analyzes its sudden appearance in the English House of Commons and its adoption by the elected assemblies of Britain's Atlantic colonies in the age of the English, Glorious, and American Revolutions. These events made it overwhelmingly likely that the United Kingdom, the United States, and their former dependencies would become and remain fundamentally majoritarian polities. Providing an insightful commentary on the state of democratic governance today, this study sheds light on the nature, promise, and perils of majority rule.
Institutional Theory
Authors: Jepperson Ronald L. , Meyer John W.
Published: March 2021

Over the past three decades, Meyer, Jepperson, and colleagues have contributed to the development of one of the leading approaches in social theory, by analyzing the cultural frameworks that have shaped modern organizations, states, and identities. Bringing together key articles and new reflections, this volume collects the essential theoretical ideas of 'sociological neoinstitutionalism.' It clarifies the core ideas and situates them within social theory writ large. Among other topics, the authors discuss the changing nature of the “actors” that have operated within contemporary social structure. The book concludes with the evolving frameworks that have structured social activity in the post–World War II period of 'embedded liberalism,' in the more recent neoliberal period, and in an emergent post-liberal period that appears to be a radical departure.
Stably stratified square cavity subjected to horizontal oscillations: responses to small amplitude forcing
Authors: Grayer II Hezekiah , Yalim Jason , Welfert Bruno D. , Lopez Juan M.
Published: March 2021

A stably stratified fluid-filled two-dimensional square cavity is subjected to harmonic horizontal oscillations with frequencies less than the buoyancy frequency. The static linearly stratified state, which is an equilibrium of the unforced system, is not an equilibrium for any non-zero forcing amplitude. As viscous effects are reduced, the horizontally forced flows computed from the Navier–Stokes–Boussinesq equations tend to have piecewise constant or piecewise linear vorticity within the pattern of characteristic lines originating from the corners of the cavity. These flows are well described in the inviscid limit by a perturbation analysis of the unforced equilibrium using the forcing amplitude as the small perturbation parameter. At first order, this perturbation analysis leads to a forced linear inviscid hyperbolic system subject to boundary conditions and spatio-temporal symmetries associated with the horizontal forcing. A Fredholm alternative determines the type of solutions of this system: either the response is uniquely determined by the forcing, or it is resonant and corresponds to an intrinsic mode of the cavity. Both types of responses are investigated in terms of a waveform function satisfying a set of functional equations and are related to the behaviour of the characteristics of the hyperbolic system. In particular, non-retracing (ergodic) characteristics may lead to fractal responses. Models of viscous dissipation are also formulated to adjust the linear inviscid model for viscous effects obtained in the viscous nonlinear simulations.
Trial of the State: Law and the Decline of Politics by Jonathan Sumption. London: Profile Books Ltd, 2019, 112 pp (£8.99 softback). ISBN 978-1-78-816373-6.
Authors: Higson-Bliss Laura
Published: March 2021

The UK is currently experiencing what can only be described as a political crisis. As faith in politics declines amongst citizens, there is an increasing trend to turn to the courts for answers – this is the thesis of Jonathan Sumption's Trial of the State: Law and the Decline of Politics. Based on the 2019 Reith Lectures, two recurring themes emerge throughout the book: the decline of politics; and the rise of law to compensate.
Eustatic and local tectonic impact on the Late Ordovician – early Silurian facies evolution on the SW margin of peri-Baltica (the southern Holy Cross Mountains, Poland)
Authors: Trela Wiesław
Published: March 2021

This paper provides insight into the Late Ordovician to earliest Silurian evolution of sedimentary environments in the southern Holy Cross Mountains (SE Poland), which at that time were a part of the SW periphery of Baltica. The facies layout in this area was influenced by the basement block faulting, which differentiated the basin bathymetry into submarine horst and grabens, controlling facies distribution. However, the local tectonism was insufficient to fully mask the global eustatic events. Therefore, it is possible to correlate some facies changes in the Upper Ordovician and lower Llandovery sedimentary record of the southern Holy Cross Mountains with eustatic and palaeoceanographic changes reported worldwide. The most noticeable influence of eustasy on the sedimentary record in the studied area occurs at the Ordovician/Silurian boundary. It is manifested by Hirnantian regressive coarse-grained clastic sediments overlain by a post-glacial anoxic/dysoxic interval represented by the Rhuddanian transgressive black cherts and shales. It is noteworthy that the pre- and post-Hirnantian sedimentary environments in the southern Holy Cross Mountains were affected by upwelling induced by the SE trade winds.
ON THE CHOW RING OF CERTAIN LEHN–LEHN–SORGER–VAN STRATEN EIGHTFOLDS
Authors: CAMERE CHIARA , CATTANEO ALBERTO , LATERVEER ROBERT
Published: March 2021

We consider a 10-dimensional family of Lehn–Lehn–Sorger–van Straten hyperkähler eightfolds, which have a non-symplectic automorphism of order 3. Using the theory of finite-dimensional motives, we show that the action of this automorphism on the Chow group of 0-cycles is as predicted by the Bloch–Beilinson conjectures. We prove a similar statement for the anti-symplectic involution on varieties in this family. This has interesting consequences for the intersection product of the Chow ring of these varieties.
Totally implantable active middle-ear implants: a large, single-surgeon cohort
Authors: McCarty Walsh E , Morrison D R , McFeely W J
Published: March 2021

Objectives

This study aimed to evaluate hearing outcomes and device safety in a large, single-surgeon experience with the totally implantable active middle-ear implants.

Methods

This was a retrospective case series review of 116 patients with moderate-to-severe sensorineural hearing loss undergoing implantation of active middle-ear implants.

Results

Mean baseline unaided pure tone average improved from 57.6 dB before surgery to 34.1 dB post-operatively, signifying a mean gain in pure tone average of 23.5 dB (p = 0.0002). Phonetically balanced maximum word recognition score improved slightly from 70.5 per cent to 75.8 per cent (p = 0.416), and word recognition score at a hearing level of 50 dB values increased substantially from 14.4 per cent to 70.4 per cent (p < 0.0001). Both revision and explant rates were low and dropped with increasing surgeon experience over time.

Conclusion

This study showed excellent post-operative hearing results with active middle-ear implants with regard to pure tone average and word recognition score at a hearing level of 50 db. Complication rates in this case series were significantly lower with increasing experience of the surgeon. Active middle-ear implants should be considered in appropriate patients with moderate-to-severe sensorineural hearing loss who have struggled with conventional amplification and are good surgical candidates.
Beyond the shrinking world: dementia, localisation and neighbourhood
Authors: Ward Richard , Rummery Kirstein , Odzakovic Elzana , Manji Kainde , Kullberg Agneta , Keady John , Clark Andrew , Campbell Sarah
Published: March 2021

‘Dementia-friendly communities’ herald a shift toward the neighbourhood as a locus for the care and support of people with dementia, sparking growing interest in the geographies of dementia care and raising questions over the shifting spatial and social experience of the condition. Existing research claims that many people with dementia experience a ‘shrinking world’ whereby the boundaries to their social and physical worlds gradually constrict over time, leading to a loss of control and independence. This paper reports a five-year, international study that investigated the neighbourhood experience of people with dementia and those who care for and support them. We interrogate the notion of a shrinking world and in so doing highlight an absence of attention paid to the agency and actions of people with dementia themselves. The paper draws together a socio-relational and embodied-material approach to question the adequacy of the shrinking world concept as an explanatory framework and to challenge reliance within policy and practice upon notions of place as fixed or stable. We argue instead for the importance of foregrounding ‘lived place’ and attending to social practices and the networks in which such practices evolve. Our findings have implications for policy and practice, emphasising the need to bolster the agency of people living with dementia as a route to fostering accessible and inclusive neighbourhoods.
“No Intrigue Is Spared”: Anglo-American Intelligence Networks in the Eighteenth-Century Dutch Republic
Authors: Tieleman Matthijs
Published: March 2021

This article surveys previously underexamined American and British intelligence networks that operated in the Netherlands during the eighteenth century and demonstrates the relevance of the eighteenth-century Dutch Republic to the larger history of the Netherlands, early modern Europe, and the revolutionary Atlantic. The Dutch Republic's favourable geographic location, its postal services, its sophisticated press, and its mercantile economy made it an ideal place to extract information and build intelligence networks, shaping power politics in the eighteenth-century British Atlantic. Additionally, this article illustrates how these Anglo-American intelligence networks affected the Dutch Republic and the revolutionary Atlantic. In the late 1770s, American revolutionaries successfully deployed their intelligence network to unleash a propaganda campaign that aimed to convince the Dutch public of their cause. By infiltrating the liberal and sophisticated Dutch printing press, the American revolutionaries not only succeeded in fostering political support among the Dutch public; they also created a transatlantic intellectual exchange with the Dutch opposition that laid the foundations of the Dutch Patriot movement of the 1780s and ultimately the dissolution of the Dutch Republic as a whole in 1795.
Child development as social action: Reflections on four underrated contributions of Edward Zigler to science and society
Authors: Reynolds Arthur J.
Published: March 2021

In a career spanning six decades, Edward Zigler redefined developmental psychology as the equal integration of scientific inquiry and evidence with social policy formulation and analysis to improve child well-being. The theme of his accumulated work was advancing child development as social action for children and families. Besides early childhood intervention and policy, for which he devoted most of his time, Dr. Zigler did pioneering work in education and school reform, social policy, prevention, child maltreatment, family support, developmental disabilities, and in service to government. In this article, I reflect on four of Dr. Zigler's major contributions to science and society that are underrated and, in many respects, under-appreciated in the larger context of the field. These are (a) historical analysis of Head Start, (b) conceptualization and analysis of motivation as a key component of early childhood program impacts, (c) development of preschool-to-third-grade programs and school reforms, and (d) critical analysis of theory, research, policy, and practice. Together, these and other contributions by Dr. Zigler provide a strong foundation to build a better society for all.
INDEPENDENCE PROOFS IN NON-CLASSICAL SET THEORIES
Authors: TARAFDER SOURAV , VENTURI GIORGIO
Published: March 2021

In this paper we extend to non-classical set theories the standard strategy of proving independence using Boolean-valued models. This extension is provided by means of a new technique that, combining algebras (by taking their product), is able to provide product-algebra-valued models of set theories. In this paper we also provide applications of this new technique by showing that: (1) we can import the classical independence results to non-classical set theory (as an example we prove the independence of
$\mathsf {CH}$
); and (2) we can provide new independence results. We end by discussing the role of non-classical algebra-valued models for the debate between universists and multiversists and by arguing that non-classical models should be included as legitimate members of the multiverse.
An Update to the Squire State Court of Last Resort Professionalization Index
Authors: Squire Peverill , Butcher Jordan
Published: March 2021

The current version of the Squire state court of last resort professionalization index is regularly used in studies of state courts. We have updated the index for 2019, producing a second and more recent index. Given the relative stability between this index and its predecessor, it is unlikely that many findings will change. During the 15 years that lapsed between the first index and the more recent one, little changed in most states, while reforms in a few places substantially shifted the relative standing of their court of last resort. It seems unlikely that the nation will experience any sweeping reform movements impacting state courts of last resort across the board. The more likely scenario is the sort of idiosyncratic changes impacting a few courts that were witnessed over the last decade and a half. Thus, looking to the future, it may be prudent to update the index every 5–10 years to capture any notable alterations.
Perinatal Outcome of Selective Intrauterine Growth Restriction in Monochorionic Twins: Evaluation of a Retrospective Cohort in a Developing Country
Authors: Aquino Carolina , Rodrigues Baião Ana Elisa , de Carvalho Paulo Roberto Nassar
Published: March 2021

Selective intrauterine growth restriction (sIUGR) in monochorionic twin pregnancies is associated with greater morbidity and mortality for both fetuses when compared to singleton and dichorionic pregnancies. This retrospective cohort study aimed to assess the perinatal outcomes of monochorionic twin pregnancies affected by this disorder and conducted expectantly, by analyzing the results according to the end-diastolic flow in the umbilical artery Doppler of the smaller twin (type I: persistently forward/type II: persistently absent or reversed/type III: intermittently absent or reversed). Seventy-five monochorionic diamniotic twin pregnancies with sIUGR were included in this study. sIUGR was defined by estimated fetal weight below the 3rd centile for gestational age, or below the 10th centile, when associated with at least one of the following three criteria: abdominal circumference below the 10th percentile, umbilical artery pulsatility index of the smaller twin above the 95th percentile, or estimated fetal weight discordance of 25% or more. Perinatal outcomes were analyzed from the prenatal period to hospital discharge and included perinatal death, neurological injury, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and sepsis. The mortality rate was 1.33% in this cohort. The overall morbidity rate was lower in type I twin pregnancies. In conclusion, this study shows that sIUGR type I has lower morbidity than types II and III in expectant management.
Predicting the Interannual Variability of California's Total Annual Precipitation
Authors: Cheng Rui , Novak Lenka , Schneider Tapio
Published: March 2021

Understanding and predicting precipitation characteristics on seasonal and longer timescales can help California prepare for long‐term droughts and precipitation extremes. We find that interannual variations in total precipitation across California are primarily determined by precipitation frequency. As was shown previously for total precipitation, the precipitation frequency is linked to the North Pacific jet stream location. This indicates that California precipitation frequency is primarily controlled by where the jet guides precipitate weather systems rather than how moist or energetic the systems are. The jet's position, in turn, depends on the states of the El Niño‐Southern Oscillation (ENSO) and of the Pacific Decadal Oscillation (PDO). We use this to construct a regression model that predicts variations in California's annual total precipitation and precipitation frequency. Up to 20% of the wintertime precipitation variance in Southern California is predictable using decorrelated ENSO and PDO indices in the previous summer.
Temporal Patterns of Large Wildfires and Their Burn Severity in Rangelands of Western United States
Authors: Li Zheng , Angerer Jay P. , Wu X. Ben
Published: March 2021

Wildfires in forest ecosystems have been well studied, while wildfires in rangelands ecosystems have received less attention. This study evaluated temporal trends of large wildfires on rangelands in western United States from 1984 to 2017, using the Monitoring Trends in Burn Severity product (captured wildfires ≥405 ha in size in western United States) and Autoregressive Integrated Moving Average analysis. The results showed a significant increase (more than fivefold) in area of rangeland burned by large wildfires, but generally no significant trends in proportions of areas burned at different levels of severity. The trends for all rangelands, in total area burned and in areas burned at different levels of severity, were most similar to the trends for herbaceous‐dominated rangelands but largely different from the trends for shrub‐dominated rangelands. These findings can aid in the development of management strategies for anticipating and reducing wildfire risk and enhancing rangeland conservation and sustainability.
Drivers of Interannual Sea Ice Concentration Variability in the Atlantic Water Inflow Region North of Svalbard
Authors: Lundesgaard Øyvind , Sundfjord Arild , Renner Angelika H. H.
Published: March 2021

Sea ice concentration along the continental margin of the Arctic Ocean is influenced by a multitude of factors, including local freezing and melting due to atmospheric forcing, lateral advection of sea ice by winds and ocean currents, and melting from below by warm Atlantic Water (AW). Here, we characterize the evolution of sea ice concentration in an area on the continental shelf break north of Svalbard in the period between 2012 and 2019. During this period, a semi‐regular seasonal pattern in sea ice concentration was interrupted by three anomalous seasons; a high ice anomaly during autumn 2014 and low ice anomalies during spring 2016 and 2018. Neither type of anomaly can be explained by abnormal upper ocean heat content as measured by an ocean mooring located near the shelf break. Instead, we find that the predominant driver of interannual sea ice concentration variability during this period was variations in large‐scale ice drift. While heat flux from the ocean cannot explain the interannual variability, it plays a key role in maintaining periods of open water in the AW inflow region despite freezing air temperatures during most of the year. These results are consistent with the sea ice concentration flux divergence from satellite records, which suggests that the southern continental slope of the Eurasian Basin is an important melting area for sea ice advected in from the north.
Challenging and Improving the Simulation of Mid‐Level Mixed‐Phase Clouds Over the High‐Latitude Southern Ocean
Authors: Vignon É. , Alexander S. P. , DeMott P. J. , Sotiropoulou G. , Gerber F. , Hill T. C. J. , Marchand R. , Nenes A. , Berne A.
Published: March 2021

Climate models exhibit major radiative biases over the Southern Ocean owing to a poor representation of mixed‐phase clouds. This study uses the remote‐sensing dataset from the Measurements of Aerosols, Radiation and Clouds over the Southern Ocean (MARCUS) campaign to assess the ability of the Weather Research and Forecasting (WRF) model to reproduce frontal clouds off Antarctica. It focuses on the modeling of thin mid‐level supercooled liquid water layers which precipitate ice. The standard version of WRF produces almost fully glaciated clouds and cannot reproduce cloud top turbulence. Our work demonstrates the importance of adapting the ice nucleation parameterization to the pristine austral atmosphere to reproduce the supercooled liquid layers. Once simulated, droplets significantly impact the cloud radiative effect by increasing downwelling longwave fluxes and decreasing downwelling shortwave fluxes at the surface. The net radiative effect is a warming of snow and ice covered surfaces and a cooling of the ocean. Despite improvements in our simulations, the local turbulent circulation related to cloud‐top radiative cooling is not properly reproduced, advocating for the need to develop a parameterization for top‐down convection to capture the turbulence‐microphysics interplay at cloud top.
Compound Extremes Drive the Western Oregon Wildfires of September 2020
Authors: Abatzoglou John T. , Rupp David E. , O'Neill Larry W. , Sadegh Mojtaba
Published: March 2021

Several very large high‐impact fires burned nearly 4,000 km2 of mesic forests in western Oregon during September 7–9, 2020. While infrequent, very large high‐severity fires have occurred historically in western Oregon, the extreme nature of this event warrants analyses of climate and meteorological drivers. A strong blocking pattern led to an intrusion of dry air and strong downslope east winds in the Oregon Cascades following a warm‐dry 60‐day period that promoted widespread fuel flammability. Viewed independently, both the downslope east winds and fuel dryness were extreme, but not unprecedented. However, the concurrence of these drivers resulted in compound extremes and impacts unmatched in the observational record. We additionally find that most large wildfires in western Oregon since 1900 have similarly coincided with warm‐dry summers during at least moderate east wind events. These results reinforce the importance of incorporating a multivariate lens for compound extremes in assessing wildfire hazard risk.
Inner Magnetospheric Magnetic Dips and Energetic Protons Trapped Therein: Multi‐Spacecraft Observations and Simulations
Authors: Yin Ze‐Fan , Zhou Xu‐Zhi , Zong Qiu‐Gang , Liu Zhi‐Yang , Yue Chao , Xiong Ying , Xie Lun , Wang Yong‐Fu , Fu Sui‐Yan
Published: March 2021

Localized magnetic field depressions in the inner magnetosphere, known as magnetic dips, are produced by the diamagnetic motion of energetic ions injected via substorm activities. The magnetic dips, if deep enough, can produce a local minimum in the radial profile of the field strength to trap the injected protons. Therefore, the trapped protons would drift at the same speed as the dip propagation, which leads to the simultaneous enhancements of proton fluxes in multiple energy channels at the leading edge of the dip structure. On the trailing side, the reduction of proton fluxes shows dispersive features, which can be attributed to the energy‐dependent drift motion of the injected protons in the absence of the local field minimum. This scenario is examined based on comparisons between multi‐spacecraft observations and test‐particle simulations, and their good agreement validates the scenario to shed new light on the dynamics of the inner magnetosphere‐magnetotail coupled system.
Early oxygen levels contribute to brain injury in extremely preterm infants
Authors: Rantakari Krista , Rinta-Koski Olli-Pekka , Metsäranta Marjo , Hollmén Jaakko , Särkkä Simo , Rahkonen Petri , Lano Aulikki , Lauronen Leena , Nevalainen Päivi , Leskinen Markus J. , Andersson Sture
Published: March 2021

Background

Extremely low gestational age newborns (ELGANs) are at risk of neurodevelopmental impairments that may originate in early NICU care. We hypothesized that early oxygen saturations (SpO2), arterial pO2 levels, and supplemental oxygen (FiO2) would associate with later neuroanatomic changes.

Methods

SpO2, arterial blood gases, and FiO2 from 73 ELGANs (GA 26.4 ± 1.2; BW 867 ± 179 g) during the first 3 postnatal days were correlated with later white matter injury (WM, MRI, n = 69), secondary cortical somatosensory processing in magnetoencephalography (MEG-SII, n = 39), Hempel neurological examination (n = 66), and developmental quotients of Griffiths Mental Developmental Scales (GMDS, n = 58).

Results

The ELGANs with later WM abnormalities exhibited lower SpO2 and pO2 levels, and higher FiO2 need during the first 3 days than those with normal WM. They also had higher pCO2 values. The infants with abnormal MEG-SII showed opposite findings, i.e., displayed higher SpO2 and pO2 levels and lower FiO2 need, than those with better outcomes. Severe WM changes and abnormal MEG-SII were correlated with adverse neurodevelopment.

Conclusions

Low oxygen levels and high FiO2 need during the NICU care associate with WM abnormalities, whereas higher oxygen levels correlate with abnormal MEG-SII. The results may indicate certain brain structures being more vulnerable to hypoxia and others to hyperoxia, thus emphasizing the role of strict saturation targets.

Impact

This study indicates that both abnormally low and high oxygen levels during early NICU care are harmful for later neurodevelopmental outcomes in preterm neonates.

Specific brain structures seem to be vulnerable to low and others to high oxygen levels.

The findings may have clinical implications as oxygen is one of the most common therapies given in NICUs.

The results emphasize the role of strict saturation targets during the early postnatal period in preterm infants.
Zoology of domain walls in quasi-2D correlated charge density wave of 1T-TaS2
Authors: Park Jae Whan , Lee Jinwon , Yeom Han Woong
Published: March 2021

Domain walls in correlated charge density wave compounds such as 1T-TaS2 can have distinct localized states which govern physical properties and functionalities of emerging quantum phases. However, detailed atomic and electronic structures of domain walls have largely been elusive. We identify using scanning tunneling microscope and density functional theory calculations the atomic and electronic structures for a plethora of discommensuration domain walls in 1T-TaS2 quenched metastably with nanoscale domain wall networks. The domain walls exhibit various in-gap states within the Mott gap but metallic states appear in only particular types of domain walls. A systematic understanding of the domain-wall electronic property requests not only the electron counting but also including various intertwined interactions such as structural relaxation, electron correlation, and charge transfer. This work guides the domain wall engineering of the functionality in correlated van der Waals materials.
LLL12B, a small molecule STAT3 inhibitor, induces growth arrest, apoptosis, and enhances cisplatin-mediated cytotoxicity in medulloblastoma cells
Authors: Chen Xiang , Pan Li , Wei Jia , Zhang Ruijie , Yang Xiaozhi , Song Jinhua , Bai Ren-Yuan , Fu Shengling , Pierson Christopher R. , Finlay Jonathan L. , Li Chenglong , Lin Jiayuh
Published: March 2021

Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor and an oncogene product, which plays a pivotal role in tumor progression. Therefore, targeting persistent STAT3 signaling directly is an attractive anticancer strategy. The aim of this study is to test the efficacy of a novel STAT3 small molecule inhibitor, LLL12B, in suppressing medulloblastoma cells in vitro and tumor growth in vivo. LLL12B selectively inhibited the induction of STAT3 phosphorylation by interleukin-6 but not induction of STAT1 phosphorylation by INF-γ. LLL12B also induced apoptosis in human medulloblastoma cells. In addition, LLL12B exhibited good oral bioavailability in vivo and potent suppressive activity in tumor growth of medulloblastoma cells in vivo. Besides, combining LLL12B with cisplatin showed greater inhibition of cell viability and tumorsphere formation as well as induction of apoptosis comparing to single agent treatment in medulloblastoma cells. Furthermore, LLL12B and cisplatin combination exhibited greater suppression of medulloblastoma tumor growth than monotherapy in vivo. The present study supported that LLL12B is a novel therapeutic agent for medulloblastoma and the combination of LLL12B with a chemotherapeutic agent cisplatin may be an effective approach for medulloblastoma therapy.
No difference of survival between cruciate retaining and substitution designs in high flexion total knee arthroplasty
Authors: Kim Gun-Woo , Jin Quan He , Lim Jun-Hyuk , Song Eun-Kyoo , Seon Jong-Keun
Published: March 2021

The aim of this study was to compare the long-term implant survival and outcomes in patients with high-flexion cruciate-retaining (CR) or high-flexion posterior cruciate-substituting (PS) knee implants. A total of 253 knees (CR group: 159 vs. PS group: 94) were available for examination over a mean follow-up of 10 years. Clinical outcomes were assessed including the Hospital for Special Surgery score, Knee Society score and Western Ontario and McMaster Universities Osteoarthritis Index score at the final follow-up. Radiologic measurements were also assessed including the hip-knee-ankle angle and radiolucent lines according to the KSS system at the final follow-up. The survival rate was analyzed using the Kaplan–Meier method. At the final follow-up, the mean total HSS scores were similar between the two groups (p = 0.970). The mean hip-knee-ankle angle at the final follow-up was similar between groups (p = 0.601). The 10- and 15-year survival rates were 95.4% and 93.3% in the CR group and 92.7% and 90.9% in the PS group, respectively, with no significant difference. Similar clinical and radiographic outcomes could be achieved with both the high-flexion CR and high-flexion PS total knee designs without a difference in survival rate after a 10-year follow-up.
Sucrose interferes with endogenous cytokinin homeostasis and expression of organogenesis-related genes during de novo shoot organogenesis in kohlrabi
Authors: Ćosić Tatjana , Motyka Václav , Savić Jelena , Raspor Martin , Marković Marija , Dobrev Petre I. , Ninković Slavica
Published: March 2021

Cross-talk between phytohormones and sugars is intensely involved in plant metabolism, growth and regeneration. We documented alterations in cytokinin (CK) homeostasis in four developmental stages during de novo shoot organogenesis (DNSO) of kohlrabi (Brassica oleraceavar.gongylodescv. Vienna Purple) seedlings induced by exogenous CKs,trans-zeatin (transZ) and thidiazuron (TDZ), added together with elevated sucrose concentration (6% and 9%). Significant impact of CK and sucrose treatment and their interaction was recorded in all investigated stages, including plantlet development before calli formation (T1 and T2), calli formation (T3) and shoot regeneration (T4). Results showed remarkable increase in total CK levels fortransZ treatment, particularly with 9% sucrose. This trend was observed for all physiological and structural groups of CKs. Application of TDZ contributed to little or no increase in CK levels regardless of sucrose concentration. Analysis of expression profiles of organogenesis-related genes involved in auxin transport, CK response, shoot apical meristem formation and cell division revealed that higher sugar concentration significantly downregulated the analysed genes, particularly in T3. This continued on TDZ, buttransZ induced an opposite effect with 9% sucrose in T4, increasing gene activity. Our results demonstrated that phytohormone metabolism might be triggered by sucrose signalling in kohlrabi DNSO.
Serum C-reactive protein metabolite (CRPM) is associated with incidence of contralateral knee osteoarthritis
Authors: Bay-Jensen Anne-Christine , Bihlet Asger , Byrjalsen Inger , Andersen Jeppe Ragnar , Riis Bente Juhl , Christiansen Claus , Michaelis Martin , Guehring Hans , Ladel Christoph , Karsdal Morten A.
Published: March 2021

The heterogeneous nature of osteoarthritis (OA) and the need to subtype patients is widely accepted in the field. The biomarker CRPM, a metabolite of C-reactive protein (CRP), is released to the circulation during inflammation. Blood CRPM levels have shown to be associated with disease activity and response to treatment in rheumatoid arthritis (RA). We investigated the level of blood CRPM in OA compared to RA using data from two phase III knee OA and two RA studies (N = 1591). Moreover, the association between CRPM levels and radiographic progression was investigated. The mean CRPM levels were significantly lower in OA (8.5 [95% CI 8.3–8.8] ng/mL, n = 781) compared to the RA patients (12.8 [9.5–16.0] ng/mL, n = 60); however, a significant subset of OA patients (31%) had CRPM levels (≥ 9 ng/mL) comparable to RA. Furthermore, OA patients (n = 152) with CRPM levels ≥ 9 ng/mL were more likely to develop contra-lateral knee OA assessed by X-ray over a two-year follow-up period with an odds ratio of 2.2 [1.0–4.7]. These data suggest that CRPM is a blood-based biochemical marker for early identification OA patients with an inflammatory phenotype.
Close linkage between blood total ketone body levels and B-type natriuretic peptide levels in patients with cardiovascular disorders
Authors: Kashiwagi Yusuke , Nagoshi Tomohisa , Inoue Yasunori , Tanaka Yoshiro , Takahashi Hirotake , Oi Yuhei , Kimura Haruka , Minai Kousuke , Yoshimura Michihiro
Published: March 2021

In patients with cardiovascular disorders, blood total ketone body (TKB) levels increase with worsening heart failure and are consumed as an alternative fuel to fatty acid and glucose. We investigated factors contributing to the increase in the blood TKB levels in patients with cardiovascular disorders. The study population consisted of 1030 consecutive patients who underwent cardiac catheterization. Covariance structure analyses were performed to clarify the direct contribution of hemodynamic parameters, including the left ventricular end-diastolic pressure (LVEDP), left ventricular end-systolic volume index (LVESVI), left ventricular end-diastolic volume index (LVEDVI), and B-type natriuretic peptide (BNP) levels, to TKB by excluding other confounding factors. These analyses showed that the TKB levels were significantly associated with the BNP level (P = 0.003) but not the LVEDP, LVESVI, or LVEDVI levels. This was clearly demonstrated on a two-dimensional contour line by Bayesian structure equation modeling. The TKB level was positively correlated with the BNP level, but not LVEDP, LVESVI or LVEDVI. These findings suggested that elevated blood TKB levels were more strongly stimulated by the increase in BNP than by hemodynamic deterioration. BNP might induce the elevation of TKB levels for use as an important alternative fuel in the failing heart.
A learning curve in using organ retractor for single-incision laparoscopic right colectomy
Authors: Shiraishi Toshio , Tominaga Tetsuro , Nonaka Takashi , Hamada Kiyoaki , Araki Masato , Sumida Yorihisa , Takeshita Hiroaki , Fukuoka Hidetoshi , To Kazuo , Tanaka Kenji , Sawai Terumitsu , Nagayasu Takeshi
Published: March 2021

Single-incision laparoscopic surgery (SILS) has the potential to improve perioperative outcomes, including less postoperative pain, shorter operation time, less blood loss, and shorter hospital stay. However, SILS is technically difficult and needs a longer learning curve. Between April 2016 and September 2019, a total of 198 patients with clinical stage I/II right colon cancer underwent curative resection. In the case of the SILS approach, an organ retractor was usually used to overcome SILS-specific restrictions. The patients were divided into two groups by surgical approach: the SILS with organ retractor group (SILS-O, n = 33) and the conventional laparoscopic surgery group (LAC, n = 165). Clinical T status was significantly higher in the LAC group (p = 0.016). Operation time was shorter and blood loss was lower in the SILS-O group compared to the LAC group (117 vs. 197 min, p = 0.027; 10 vs. 25 mL, p = 0.024, respectively). In the SILS-O group, surgical outcomes including operation time, blood loss, number of retrieved lymph nodes, and postoperative complications were not significantly different between those performed by experts and by non-experts. Longer operation time (p = 0.041) was significantly associated with complications on univariate and multivariate analyses (odds ratio 2.514, 95%CI 1.047–6.035, p = 0.039). SILS-O was safe and feasible for right colon cancer. There is a potential to shorten the learning curve of SILS using an organ retractor.
A single day fasting may increase emergency room visits due to renal colic
Authors: Zilberman Dorit E. , Drori Tomer , Shvero Asaf , Mor Yoram , Winkler Harry Z. , Kleinmann Nir
Published: March 2021

We aimed to explore whether a single-day of fasting (SDF) increase emergency room (ER) visits due to renal colic (RC). We elected to concentrate on Yom-Kippur (i.e.: SDF), the holiest day in Judaism. Food and liquid consumption is prohibited during this day for 25 h, and an estimated 50–70% fasting rate is observed. SDF always takes place between mid-September and mid-October during which the temperature in the Middle-East ranges between 19 and 30 °C. ER visits for RC between 01/2012 and 11/2019 were reviewed, and the Gregorian days on which SDF occurred were retrieved. The number of ER visits for RC was compared between SDF and the surrounding days/months as well as to another single-day "standard" holiday (SDSH) that precedes SDF in 10 days and is not associated with fasting. Of 11,717 ER visits for RC, 8775 (74.9%) were males. Male:Female ratio was 3:1. The mean daily number of ER visits for RC during the 3 days following SDF was 6.66 ± 2.49, significantly higher compared with the mean annual daily visits (4.1 ± 2.27, p < 0.001), the mean daily visits during the week prior to SDF (5.27 ± 2.656, p = 0.032), and the mean daily visits during September (5.06 ± 2.659, p = 0.005), and October (4.78 ± 2.23, p < 0.001). The mean number of ER daily visits for RC during the 3 days following SDSH, 5.79 ± 2.84, did not differ compared with the mean daily visits during September and October (p = 0.207; p = 0.13, respectively). It was lower compared to SDF, however statistically insignificant (p = 0.285). A single-day fasting may increase ER visits for RC. The mechanism underlying this phenomenon is unknown.
Targeting natural splicing plasticity of APOBEC3B restricts its expression and mutagenic activity
Authors: Rouf Banday A. , Onabajo Olusegun O. , Lin Seraph Han-Yin , Obajemu Adeola , Vargas Joselin M. , Delviks-Frankenberry Krista A. , Lamy Philippe , Bayanjargal Ariunaa , Zettelmeyer Clara , Florez-Vargas Oscar , Pathak Vinay K. , Dyrskjøt Lars , Prokunina-Olsson Ludmila
Published: March 2021

APOBEC3A (A3A) and APOBEC3B (A3B) enzymes drive APOBEC-mediated mutagenesis. Identification of factors affecting the activity of these enzymes could help modulate mutagenesis and associated clinical outcomes. Here, we show that canonical and alternatively splicedA3AandA3Bisoforms produce corresponding mutagenic and non-mutagenic enzymes. Increased expression of the mutagenicA3Bisoform predicted shorter progression-free survival in bladder cancer. We demonstrate that the production of mutagenic vs. non-mutagenic A3B protein isoforms was considerably affected by inclusion/skipping of exon 5 inA3B. Furthermore, exon 5 skipping, resulting in lower levels of mutagenic A3B enzyme, could be increased in vitro. Specifically, we showed the effects of treatment with an SF3B1 inhibitor affecting spliceosome interaction with a branch point site in intron 4, or with splice-switching oligonucleotides targeting exon 5 ofA3B. Our results underscore the clinical role of A3B and implicate alternative splicing ofA3Bas a mechanism that could be targeted to restrict APOBEC-mediated mutagenesis.
Transcriptomic analyses of the termite, Cryptotermes secundus, reveal a gene network underlying a long lifespan and high fecundity
Authors: Lin Silu , Werle Jana , Korb Judith
Published: March 2021

Organisms are typically characterized by a trade-off between fecundity and longevity. Notable exceptions are social insects. In insect colonies, the reproducing caste (queens) outlive their non-reproducing nestmate workers by orders of magnitude and realize fecundities and lifespans unparalleled among insects. How this is achieved is not understood. Here, we identified a single module of co-expressed genes that characterized queens in the termite speciesCryptotermes secundus. It encompassed genes from all essential pathways known to be involved in life-history regulation in solitary model organisms. By manipulating its endocrine component, we tested the recent hypothesis that re-wiring along the nutrient-sensing/endocrine/fecundity axis can account for the reversal of the fecundity/longevity trade-off in social insect queens. Our data from termites do not support this hypothesis. However, they revealed striking links to social communication that offer new avenues to understand the re-modelling of the fecundity/longevity trade-off in social insects.
A four-gene signature predicts survival and anti-CTLA4 immunotherapeutic responses based on immune classification of melanoma
Authors: Mei Ying , Chen Mei-Ju May , Liang Han , Ma Li
Published: March 2021

Cutaneous melanoma is the most malignant skin cancer. Biomarkers for stratifying patients at initial diagnosis and informing clinical decisions are highly sought after. Here we classified melanoma patients into three immune subtypes by single-sample gene-set enrichment analysis. We further identified a four-gene tumor immune-relevant (TIR) signature that was significantly associated with the overall survival of melanoma patients in The Cancer Genome Atlas cohort and in an independent validation cohort. Moreover, when applied to melanoma patients treated with the CTLA4 antibody, ipilimumab, the TIR signature could predict the response to ipilimumab and the survival. Notably, the predictive power of the TIR signature was higher than that of other biomarkers. The genes in this signature, SEL1L3, HAPLN3, BST2, and IFITM1, may be functionally involved in melanoma progression and immune response. These findings suggest that this four-gene signature has potential use in prognosis, risk assessment, and prediction of anti-CTLA4 response in melanoma patients.
High-resolution cryo-EM structure of photosystem II reveals damage from high-dose electron beams
Authors: Kato Koji , Miyazaki Naoyuki , Hamaguchi Tasuku , Nakajima Yoshiki , Akita Fusamichi , Yonekura Koji , Shen Jian-Ren
Published: March 2021

Photosystem II (PSII) plays a key role in water-splitting and oxygen evolution. X-ray crystallography has revealed its atomic structure and some intermediate structures. However, these structures are in the crystalline state and its final state structure has not been solved. Here we analyzed the structure of PSII in solution at 1.95 Å resolution by single-particle cryo-electron microscopy (cryo-EM). The structure obtained is similar to the crystal structure, but a PsbY subunit was visible in the cryo-EM structure, indicating that it represents its physiological state more closely. Electron beam damage was observed at a high-dose in the regions that were easily affected by redox states, and reducing the beam dosage by reducing frames from 50 to 2 yielded a similar resolution but reduced the damage remarkably. This study will serve as a good indicator for determining damage-free cryo-EM structures of not only PSII but also all biological samples, especially redox-active metalloproteins.
Author Correction: An extended Weight Kernel Density Estimation model forecasts COVID-19 onset risk and identifies spatiotemporal variations of lockdown effects in China
Authors: Shi Wenzhong , Tong Chengzhuo , Zhang Anshu , Wang Bin , Shi Zhicheng , Yao Yepeng , Jia Peng
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s42003-021-01924-6