bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic lung inflammation and pulmonary fibrosis after multiple intranasal instillation of PM2.5 in mice
Authors: Xu Mengmeng , Wang Xiaohui , Xu Lu , Zhang Hai , Li Chenfei , Liu Qi , Chen Yuqing , Chung Kian Fan , Adcock Ian M. , Li Feng
Published: March 2021

Fine particulate matter (PM2.5) is an important component of air pollution and can induce lung inflammation and oxidative stress. We hypothesized that PM2.5 could play a role in the induction of pulmonary fibrosis. We examined whether multiple intranasal instillation of PM2.5 can induce pulmonary fibrosis in the mouse, and also investigated the underlying pro‐fibrotic signaling pathways. C57/BL6 mice were intranasally instilled with 50 μl of PM2.5 suspension (7.8 μg/g body weight) or PBS three times a week over 3 weeks, 6 weeks or 9 weeks. To observe the recovery of pulmonary fibrosis after the termination of PM2.5 exposure, 9 week‐PM2.5 instilled mice were also studied at 3 weeks after termination of instillation. There were significant decreases in total lung capacity (TLC) and compliance (Cchord) in the 9‐week PM2.5‐instilled mice, while there were increased histological fibrosis scores with enhanced type I collagen and hydroxyproline deposition, increased mitochondrial ROS levels and NOX activity, decreased total SOD and GSH levels, accompanied by decreased mitochondrial number and aberrant mitochondrial morphology (swelling, vacuolization, cristal disruption, reduced matrix density) in PM2.5‐instilled mice. Multiple PM2.5 instillation resulted in increased expression of TGFβ1, increases of N‐Cadherin and Vimentin and a decrease of E‐Cadherin. It also led to decreases in OPA1 and MFN2, and increases in Parkin, SQSTM1/p62, the ratio of light china (LC) 3B II to LC3B I, PI3k/Akt phosphorylation, and NLRP3 expression. Intranasal instillation of PM2.5 for 9 weeks induced lung inflammation and pulmonary fibrosis, which was linked with aberrant epithelial‐mesenchymal transition, oxidative stress, mitochondrial damage and mitophagy, as well as activation of TGFβ1‐PI3K/Akt, TGFβ1‐ NOX and TGFβ1‐NLRP3 pathways.
Troubling heroes: Reframing the environmental justice contributions of the Flint water crisis
Authors: Carrera Jennifer S. , Key Kent
Published: March 2021

While the story of the Flint water crisis has been shared widely, the popular narrative—described in multiple documentaries and as evidenced by accolades heaped upon a limited few number of actors involved with Flint—largely leaves out the broad experiences and actions of Flint residents in responding to the crisis, raising awareness, and advocating for change. Academic literature has contributed to reinforcing an abbreviated and disempowered version of the narrative where Flint residents needed rescue. In this article, we present an extended description of the Flint water crisis leading up to the water switch in April 2014, including descriptions of community mobilization efforts to call government actions into account and produce investigations that validated the concerns of the residents. We offer a review of prominent academic literature demonstrating patterns of erasure that suggest Flint residents were disempowered. In response, we offer three examples which demonstrate how Flint resident mobilizations have broad historical context, national reach, and individual actions that contradict the narrative that Flint residents lack agency and power. In our analysis, rather than viewing Flint residents as in need of rescue by science, we argue that the community mobilization in Flint is indicative of a highly successful implementation of popular epidemiology with profound effects on national conversations about lead in water, drinking water infrastructure management, and environmental justice.

This article is categorized under:

Human Water > Water Governance

Engineering Water
Rising Inequalities and a Changing Social Geography of Cities. An Introduction to the Global Segregation Book
Authors: van Ham Maarten , Tammaru Tiit , Ubarevičienė Rūta , Janssen Heleen
Published: March 2021

The book “Urban Socio-Economic Segregation and Income Inequality: a Global Perspective” investigates the link between income inequality and residential segregation between socio-economic groups in 24 large cities and their urban regions in Africa, Asia, Australia, Europe, North America, and South America. Author teams with in-depth local knowledge provide an extensive analysis of each case study city. Based on their findings, the main results of the book can be summarised as follows. Rising inequalities lead to rising levels of socio-economic segregation almost everywhere in the world. Levels of inequality and segregation are higher in cities in lower income countries, but the growth in inequality and segregation is faster in cities in high-income countries, which leads to a convergence of global trends. In many cities the workforce is professionalising, with an increasing share of the top socio-economic groups. In most cities the high-income workers are moving to the centre or to attractive coastal areas, and low-income workers are moving to the edges of the urban region. In some cities, mainly in lower income countries, high-income workers are also concentrating in out-of-centre enclaves or gated communities. The urban geography of inequality changes faster and is more pronounced than city-wide single-number segregation indices reveal. Taken together, these findings have resulted in the formulation of a Global Segregation Thesis.
Changes in Occupational Structure and Residential Segregation in Tokyo
Authors: Uesugi Masaya
Published: March 2021

Similar to other industrialized countries, Japan has experienced a growth in income inequality since the 1980s. Furthermore, in the past few decades, Tokyo has come to adopt a more liberalist position for not only welfare and housing policy of the state but also to urban policy. This chapter examines the changes in socio-spatial inequality in Tokyo from 2000 to 2015. During this period, segregation indices confirm some level of residential separation between the top and bottom occupational groups, and segregation is fairly stable over time. This suggests that certain factors counteract the increase of residential segregation. A comparison between the Tokyo Metropolitan Region and the core city reveals that the core city amplifies spatial inequality. In contrast to the limited change in the city-wide levels of segregation, the changes in the residential patterns show that people with high occupational status tend to concentrate around the main railway station in suburban areas in the region and inside the core city, especially adjacent to the central neighborhoods.
Socio-spatial Disparities in Brussels and its Hinterland
Authors: Costa Rafael , de Valk Helga A. G.
Published: March 2021

Brussels’ urban and suburban landscape has changed considerably since the 1980s. The consolidation of socioeconomic fractures inside the city, a reinforcement of long-lasting disparities between the city and its prosperous hinterland, as well as the increasing diversification of migration flows—both high- and low-skilled—contributed to these disparities. Recent evolutions of these patterns, however, have not been investigated yet and therefore remain unknown. Besides, the extent to which segregation is primarily related to economic inequalities and to migration flows—or a combination/interaction between the two—so far has not been studied. This chapter offers a detailed overview of the socio-spatial disparities in the Brussels Functional Urban Area. Our analyses relied on fine-grained spatial data, at the level of statistical sections and of individualised neighbourhoods built around 100 m x 100 m grids. We analysed socioeconomic segregation measures and patterns, as well as their evolution between 2001 and 2011. Socioeconomic groups were defined based on individuals’ position with respect to national income deciles. In line with previous research, our results show very marked patterns of socioeconomic segregation in and around Brussels operating both at a larger regional scale and at the local level.
Residential Segregation in a Highly Unequal Society: Istanbul in the 2000s
Authors: Işık Oğuz
Published: March 2021

Contrary to trends in many European countries, income inequality in Turkey, measured by the Gini coefficient, has declined between 1994 and 2014, with a small but consistent increase since then. Turkish income inequality is among the highest in OECD countries, with levels not lower than 0.4. This chapter will examine residential socio-economic segregation in Istanbul against the backdrop of this relatively stable and high-income inequality. The chapter shows signs that residential segregation is on the rise. Istanbul has undergone a radical change in the 2000s thanks to active intervention by the state in the real estate market by opening up large pieces of land in the outskirts and gentrifying inner-city areas once occupied by unauthorized settlements that once were home to the poor. Dynamics of urban development, fueled by rapid urban sprawl in peri-urban areas and ceaseless gentrification of inner-city areas, gave way to diverse patterns of segregation depending on the already existing divisions and physical geography of cities. Given the lack of neighbourhood level data on either occupations or income, this chapter analyses segregation through indices based on fertility and educational level, which we know from detailed household microdata are closely correlated with income. On the basis of 2000 and 2017 neighbourhood data, we show that in Istanbul, there is a clearly visible pattern where the poor are progressively pushed further to the city limits, while some parts of built-up areas once home to middle classes, were recaptured by the poor. The result in some parts of the city is a juxtaposition of seemingly conflicting patterns: parts of the inner city were reclaimed by the poor while some parts were gentrified led by the nascent urban elite. The urban periphery was partly occupied by the bourgeoning middle classes and was also home to the urban poor who were displaced by urban transformation projects.
Segregation in London: A City of Choices or Structures?
Authors: Manley David
Published: March 2021

This chapter provides a comprehensive overview of the socio-economic segregation in London. The cosmopolitan nature of the city means there is an interwoven complexity that prevents the separation of social, cultural and economic residential trajectories of the population. As a result, the chapter explores socio-economic segregation within the context of the changing nature of the (sub)urban contexts. In particular, the chapter documents not only the occupational segregation but also introduces the often-used dimension of ethnicity and pairs it with the less commonly explored age and tenure dimensions through which the social structure of the city is inscribed. This enables a broader understanding of the rapid changes that have been wrought on the micro-scale can be understood in the context of a city that has, in terms of the overall composition, changed little.
Changes in Spatial Inequality and Residential Segregation in Metropolitan Lima
Authors: Fernández-de-Córdova Graciela , Moschella Paola , Fernández-Maldonado Ana María
Published: March 2021

Since the 2000s, Lima city shows important changes in its socio-spatial structure, decreasing the long-established opposition between the centre and the periphery, developing a more complex arrangement. Sustained national economic growth has allowed better socio-economic conditions in different areas of the city. However, high inequality still remains in the ways of production of urban space, which affects residential segregation. To identify possible changes in the segregation patterns of Metropolitan Lima, this study focuses on the spatial patterns of occupational groups, examining their causes and relation with income inequality. The analysis is based on the 1993 and 2007 census data, measuring residential segregation by the Dissimilarity Index, comparing with the Diversity Index. The results confirm trends towards increased segregation between occupational groups. Top occupational groups are concentrated in central areas, expanding into adjacent districts. Bottom occupational groups are over-represented in distant neighbourhoods. In-between, a new, more mixed, transitional zone has emerged in upgraded formerly low-income neighbourhoods. Areas of lower occupational diversity coincide with extreme income values, forming spaces of greater segregation. In the metropolitan centre–periphery pattern, the centre has expanded, while the periphery has been shifted to outer peripheral rings.
Socio-economic and Ethnic Segregation in the Greater Paramaribo Region, Suriname
Authors: Fung-Loy Kimberley , Van Rompaey Anton
Published: March 2021

Income inequality has steadily increased in Suriname and it is considered to be at one of the highest levels in the Caribbean. This chapter analyses socio-economic and ethnic segregation between 2004 and 2012 in the Greater Paramaribo Region in Suriname. To investigate the link between income inequality and socio-economic segregation, occupation is used as a proxy for socio-economic status. The Dissimilarity Index is used to evaluate the level of segregation between different socio-economic and ethnic groups. The link between ethnicity and socio-economic status is also analysed. Results show that the highest level of socio-economic segregation exists between the higher socio-economic group (top occupational categories) and the lower socio-economic group (bottom occupational categories). It was also found that even though the Region is ethnically diverse, different ethnic groups tend to concentrate in different neighbourhoods. These segregated ethnicities are in turn linked to the higher and lower level socio-economic groups.
Dual Land Regime, Income Inequalities and Multifaceted Socio-Economic and Spatial Segregation in Hong Kong
Authors: Ng Mee Kam , Lau Yuk Tai , Chen Huiwei , He Sylvia
Published: March 2021

Hong Kong has a dual land regime in the urban and rural territories. The urban areas on both sides of Victoria Harbour (8.8% of land, excluding Country Parks on Hong Kong Island) and new towns (about 15.3% of land) house over 90% of the city’s population (about 7.5 million) with an extremely high population density of about 26,000 per km2. After deducting Country Parks and Special Areas (about 40% of land), the rest of the rural New Territories (traditional settlements leased by the British Government in 1898 for 99 years) constitutes about 35% of land, but houses 5.5% of all residents with a substantially lower population density of about 1,000 per km2. China’s Open Door Policy since 1978 has led to economic restructuring in Hong Kong, changing its occupational structure, intensifying income inequality, and leading to socio-economic and spatial segregation. Whilst the affluent classes continue to concentrate in traditionally central locations in urban areas, or in luxurious residential enclaves in rural New Territories, the less well-off tend to be marginalised and live in remote new towns or rural New Territories. The latter is also a result of a skewed power relationship between the government and the property sector in directing spatial development that breeds a hegemonic (dis)course and regime of urban-biased and property-dominant development, sustaining the government’s coffer through a high land price policy.
Income Inequality and Socioeconomic Segregation in Jakarta
Authors: Rukmana Deden , Ramadhani Dinar
Published: March 2021

Socioeconomic segregation has become a common phenomenon, both in the Global North and Global South, and highly relates to income inequality. The merging of these two notions affects the geography of residential areas which are based on the socio-occupational composition. This chapter focuses on the Jakarta Metropolitan Area (JMA). Not only is Jakarta the largest metropolitan area in Southeast Asia, it is also one of the most dynamic. Batavia, the colonial capital of the former Dutch East Indies in the first half of the twentieth century, was a small urban area of approximately 150,000 residents. In the second half of the century, Batavia became Jakarta, a megacity of 31 million people and the capital of independent Indonesia was beset with most of the same urban problems experienced in twenty-first-century Southeast Asia, including poverty, income inequality, and socioeconomic segregation. This study aims to identify the correlation among income inequality, socioeconomic segregation, and other institutional and contextual factors which caused residential segregation in JMA. The analysis consists of two stages. First, we examine income inequality measured by the Gini Index as well as the occupational structure based on the International Standard Classification of Occupations (ISCO). Second, we investigate residential segregation by using the Dissimilarity Index as a result of socioeconomic intermixing in residential areas. The data in this study comes from multiple sources including Indonesia’s Central Bureau of Statistics, Indonesia’s National Socio-economic Survey (Susenas), Indonesia’s Economic Census, Jakarta’s Regional Bureau of Statistics, and policies related to the housing system and investment in the JMA. This study also produces maps of socioeconomic segregation patterns from several sources including Jakarta’s Geospatial Information Centre, Jakarta’s Spatial Plan Information System, and the Indonesian Poverty Map by the SMERU Research Institute.
Intermediary Bodies of Governance
Authors: van der Burg Martijn
Published: March 2021

Following the phase of conquest, usually a temporary interim government was formed to supervise the incorporation of newly acquired territories. The timing of the incorporation, as well as the manner in which models from other parts of Europe were applied, influenced how Napoleonic governance worked out in practice. Importantly, the creation of so-called gouvernements généraux became a Napoleonic integration instrument. General-Governors Charles-François Lebrun in Amsterdam and Louis Nicolas Davout in Hamburg had similar tasks but made different choices. Their relationships with other actors, local and French, differed as well. In this chapter the two intermediary bodies are discussed, in relation to other Napoleonic institutions and their main protagonists. Often, Napoleonic officials who had already proven their worth elsewhere were employed in these areas. Thus, institutional examples and personal experiences from other parts of the Empire, such as Italy, influenced the integration of the North. Yet, being remote from the imperial core, many officials competed for power and hence for control of the integration process.
Prefects: ‘Tools of Conquest’
Authors: van der Burg Martijn
Published: March 2021

This chapter is concerned with the introduction of the prefectoral system in the North. The introduction of préfets was an expression of the desire to create a modern civil administration answerable to the central government. Attention is paid to its implementation, the selection and circulation of prefects, and their relationships with other actors. Napoleonic territorial governance meant a significant break with tradition, but its implementation was far from perfect. Although French legislation itself was not altered, in practice, many issues hindered the functioning of the prefectoral system in the incorporated departments, such as redrawing geographical borders and lack of understanding of Napoleonic governing practices. Creating support was difficult when no consideration was given to local circumstances and wishes—a challenge delegated to prefects. Stimulating personal mobility between different parts of the Empire was a possible means of accelerating integration. The case of the prefects in the Netherlands and Northwest Germany shows how the flow of imperial models, officials, and knowledge contributed to the interconnectedness of the different parts of the Napoleonic Empire, or conversely, how the lack thereof hindered integration.
The Minimum Tollbooth Problem in Atomic Network Congestion Games with Unsplittable Flows
Authors: Nickerl Julian
Published: March 2021

This work analyzes the minimum tollbooth problem in atomic network congestion games with unsplittable flows. The goal is to place tolls on edges, such that there exists a pure Nash equilibrium in the tolled game that is a social optimum in the untolled one. Additionally, we require the number of tolled edges to be the minimum. This problem has been extensively studied in non-atomic games, however, to the best of our knowledge, it has not been considered for atomic games before. By a reduction from the weighted CNF SAT problem, we show both the NP-hardness of the problem and the W[2]-hardness when parameterizing the problem with the number of tolled edges. On the positive side, we present a polynomial time algorithm for networks on series-parallel graphs that turns any given state of the untolled game into a pure Nash equilibrium of the tolled game with the minimum number of tolled edges.
Methotrexate-associated lymphoproliferative disorder of the thoracic spine in a patient with rheumatoid arthritis receiving methotrexate: a case report
Authors: Kamio Satoshi , Anazawa Ukei , Watanabe Itsuo , Sasaki Aya , Aoyama Ryoma
Published: March 2021

Methotrexate-associated lymphoproliferative disorder is recognized as a lymphoma that occurs following methotrexate administration. The lesion of the spine is extremely rare, and only one case of lesion in the lumbar spine has been reported so far. Here, we present a case of methotrexate-associated lymphoproliferative disorder of the thoracic spine in a 54-year-old woman with rheumatoid arthritis. The lesion formed an extra-skeletal tumor mass from lateral to the vertebral body to the paravertebral muscle extending posterior to the epidural space without bone destruction. Magnetic resonance imaging showed low signal intensities on both T1- and T2-weighted images and high signal intensity with short-tau inversion recovery. These radiological findings were similar to those for primary spinal lymphoma. The lesion rapidly paralyzed the patient, forcing her to be treated with posterior spinal decompression. The lesion could not be resected because it adhered to the dura. Following the histopathological diagnosis as methotrexate-associated lymphoproliferative disorder, methotrexate administration was terminated. The remaining mass lesion showed complete regression within 6 months. Methotrexate-associated lymphoproliferative disorder, which could be cured by the discontinuation of methotrexate, should be considered a differential diagnosis in spinal lesion cases showing lymphoma-like appearance with methotrexate treatment to avoid unnecessary treatments.
Predictive Values of Preoperative Markers for Resectable Pancreatic Body and Tail Cancer Determined by MDCT to Detect Occult Metastases
Authors: Cheng He , Luo Guopei , Jin Kaizhou , Xiao Zhiwen , Qian Yunzhen , Gong Yitao , Yu Xianjun , Liu Chen
Published: March 2021

Background

To evaluate the clinical value of preoperative markers in predicting occult metastases in resectable pancreatic body and tail cancer judged by a recent multidetector computed tomography (MDCT) scan of the abdomen.

Methods

The data from a retrospective collected database from 2010 to 2019 with 699 patients who had MDCT scan predicted resectable mass in pancreatic body and tail and were pathological confirmed as adenocarcinoma after surgery. Receiver operating characteristic (ROC) curve was plotted for serum CA19‐9, CA125, CEA and tumor size measured by MDCT. The optimal cut‐off point‐related sensitivity and specificity were calculated, respectively.

Results

Occult metastases were found in 73 (73/699, 10.4%) pancreatic body and tail cancer patients underwent exploration. The area under curve (AUC) for CA19‐9, CA125, CEA and tumor size were 0.624, 0.733, 0.561 and 0.697, respectively. The optimal cut‐off for CA19‐9, CA125 and tumor size is 226 U/ml, 22.1 U/ml and 3.3 cm, respectively. The sensitivity and specificity of CA19‐9 for predicting occult metastases were 67.1% and 60.4%, 72.6% and 64.7% for CA125, 80.8% and 51.4% for tumor size.

Conclusion

CA125 is superior to CA19‐9 and tumor size for predicting occulting metastases in MDCT scan suggested resectable pancreatic body and tail cancer. The high level of CA125 (≥ 22.1 U/ml) is regarded as high risk for occulting metastases, and laparoscopy should be applied for these patients.
The pharmacokinetics of pamiparib in the presence of a strong CYP3A inhibitor (itraconazole) and strong CYP3A inducer (rifampin) in patients with solid tumors: an open-label, parallel-group phase 1 study
Authors: Mu Song , Lin Chester , Skrzypczyk-Ostaszewicz Anna , Bulat Iurie , Maglakelidze Marina , Skarbova Viera , Andreu-Vieyra Claudia , Sahasranaman Srikumar
Published: March 2021

Purpose

Pamiparib is an investigational, selective, oral poly(ADP-ribose) polymerase 1/2 (PARP1/2) inhibitor that has demonstrated PARP–DNA complex trapping and CNS penetration in preclinical models, as well as preliminary anti-tumor activity in early-phase clinical studies. We investigated whether the single-dose pharmacokinetic (PK) profile of pamiparib is altered by coadministration of a strong CYP3A inducer (rifampin) or a strong CYP3A inhibitor (itraconazole) in patients with solid tumors.

Methods

In this open-label, phase 1 study, adults with advanced solid tumors received either oral pamiparib 60 mg (days 1 and 10) and once-daily oral rifampin 600 mg (days 3–11) or oral pamiparib 20 mg (days 1 and 7) and once-daily oral itraconazole 200 mg (days 3–8). Primary endpoints included pamiparib maximum observed concentration (Cmax), and area under the plasma concentration–time curve from zero to last quantifiable concentration (AUC0–tlast) and infinity (AUC0–inf). Secondary endpoints included safety and tolerability.

Results

Rifampin coadministration did not affect pamiparibCmax(geometric least-squares [GLS] mean ratio 0.94; 90% confidence interval 0.83–1.06), but reduced its AUC0–tlast(0.62 [0.54–0.70]) and AUC0–inf(0.57 [0.48–0.69]). Itraconazole coadministration did not affect pamiparibCmax(1.05 [0.95–1.15]), AUC0–tlast(0.99 [0.91–1.09]), or AUC0–inf(0.99 [0.90–1.09]). There were no serious treatment-related adverse events.

Conclusions

Pamiparib plasma exposure was reduced 38–43% with rifampin coadministration but was unaffected by itraconazole coadministration. Pamiparib dose modifications are not considered necessary when coadministered with CYP3A inhibitors. Clinical safety and efficacy data will be used with these results to recommend dose modifications when pamiparib is coadministered with CYP3A inducers.
Compressed sensing acceleration of cardiac cine imaging allows reliable and reproducible assessment of volumetric and functional parameters of the left and right atrium
Authors: Altmann Sebastian , Halfmann Moritz C. , Abidoye Ibukun , Yacoub Basel , Schmidt Michaela , Wenzel Philip , Forman Christoph , Schoepf U. Joseph , Xiong Fei , Dueber Christoph , Kreitner Karl-Friedrich , Varga-Szemes Akos , Emrich Tilman
Published: March 2021

Objectives

To compare volumetric and functional parameters of the atria derived from highly accelerated compressed sensing (CS)–based cine sequences in comparison to conventional (Conv) cine imaging.

Methods

CS and Conv cine sequences were acquired in 101 subjects (82 healthy volunteers (HV) and 19 patients with heart failure with reduced ejection fraction (HFrEF)) using a 3T MR scanner in this single-center study. Time-volume analysis of the left (LA) and right atria (RA) were performed in both sequences to evaluate atrial volumes and function (total, passive, and active emptying fraction). Inter-sequence and inter- and intra-reader agreement were analyzed using correlation, intraclass correlation (ICC), and Bland-Altman analysis.

Results

CS-based cine imaging led to a 69% reduction of acquisition time. There was significant difference in atrial parameters between CS and Conv cine, e.g., LA minimal volume (LAVmin) (Conv 24.0 ml (16.7–32.7), CS 25.7 ml (19.2–35.2),p < 0.0001) or passive emptying fraction (PEF) (Conv 53.9% (46.7–58.4), CS 49.0% (42.0–54.1),p < 0.0001). However, there was high correlation between the techniques, yielding good to excellent ICC (0.76–0.99) and small mean of differences in Bland-Altman analysis (e.g. LAVmin − 2.0 ml, PEF 3.3%). Measurements showed high inter- (ICC > 0.958) and intra-rater (ICC > 0.934) agreement for both techniques. CS-based parameters (PEF AUC = 0.965, LAVmin AUC = 0.864) showed equivalent diagnostic ability compared to Conv cine imaging (PEF AUC = 0.989, LAVmin AUC = 0.859) to differentiate between HV and HFrEF.

Conclusion

Atrial volumetric and functional evaluation using CS cine imaging is feasible with relevant reduction of acquisition time, therefore strengthening the role of CS in clinical CMR for atrial imaging.

Key Points

•Reliable assessment of atrial volumes and function based on compressed sensing cine imaging is feasible.

•Compressed sensing reduces scan time and has the potential to overcome obstacles of conventional cine imaging.

•No significant differences for subjective image quality, inter- and intra-rater agreement, and ability to differentiate healthy volunteers and heart failure patients were detected between conventional and compressed sensing cine imaging.
Impact of pulse pressure on clinical outcome in extracorporeal cardiopulmonary resuscitation (eCPR) patients
Authors: Rilinger Jonathan , Riefler Antonia M. , Bemtgen Xavier , Jäckel Markus , Zotzmann Viviane , Biever Paul M. , Duerschmied Daniel , Benk Christoph , Trummer Georg , Kaier Klaus , Bode Christoph , Staudacher Dawid L. , Wengenmayer Tobias
Published: March 2021

Background

Hemodynamic response to successful extracorporeal cardiopulmonary resuscitation (eCPR) is not uniform. Pulse pressure (PP) as a correlate for myocardial damage or recovery from it, might be a valuable tool to estimate the outcome of these patients.

Methods

We report retrospective data of a single-centre registry of eCPR patients, treated at the Interdisciplinary Medical Intensive Care Unit at the Medical Centre, University of Freiburg, Germany, between 01/2017 and 01/2020. The association between PP of the first 10 days after eCPR and hospital survival was investigated. Moreover, patients were divided into three groups according to their PP [low (0–9 mmHg), mid (10–29 mmHg) and high (≥ 30 mmHg)] at each time point.

Results

One hundred forty-three patients (age 63 years, 74.1% male, 40% OHCA, average low flow time 49 min) were analysed. Overall hospital survival rate was 28%. A low PP both early after eCPR (after 1, 3, 6 and 12 h) and after day 1 to day 8 was associated with reduced hospital survival. At each time point (1 h to day 5) the classification of patients into a low, mid and high PP group was able to categorize the patients for a low (5–20%), moderate (20–40%) and high (50–70%) survival rate. A multivariable analysis showed that the mean PP of the first 24 h was an independent predictor for survival (p = 0.008).

Conclusion

In this analysis, PP occurred to be a valuable parameter to estimate survival and maybe support clinical decision making in the further course of patients after eCPR.

Graphic abstract
Evaluating growth and intrinsic water-use efficiency in hardwood and conifer mixed plantations
Authors: Gentilesca Tiziana , Battipaglia Giovanna , Borghetti Marco , Colangelo Michele , Altieri Simona , Ferrara Agostino M. S. , Lapolla Antonio , Rita Angelo , Ripullone Francesco
Published: March 2021

Key message

Juglans, Fraxinus, Quercus and Pinus species seem to better maximize the carbon–water ratio providing useful indications on species selection for forestry plantations in areas with increasing drought risk.

Maximizing carbon sequestration for a given water budget is extremely important in the contest of climate change in the Mediterranean region, which is characterized by increasing temperatures and rising water stress. This issue is fundamental for plantation stands, where limited water availability during the growing season reduces CO2 assimilation and, consequently, tree growth. In this study, the main objective was to investigate the performances in terms of carbon–water balance of conifer (Pinus halepensis and Cupressus sempervirens) and hardwood (Quercus robur, Juglans regia, Fraxinus excelsior and Populus spp.) mixed plantations. To this aim, we used carbon isotope signatures to evaluate the intrinsic water-use efficiency (iWUE) and the species-specific relationship between basal area increments (BAI) and iWUE. At the species level, the highest iWUE values corresponded to the lowest carbon accumulation in terms of BAI, for water-saving species such as Cupressus. Conversely, Populus had the lowest iWUE and the highest BAI accumulation. Juglans, Fraxinus, and Pinus showed the most balanced ratio between BAI and iWUE. Overall, no clear correlation of iWUE and BAI was evident within all species, except for Populus and Cupressus. Considering projected aridification and increased temperatures that will negatively impact the growth, our data suggest that Pinus, for conifers, and Quercus, Juglans, Fraxinus for hardwood species should be preferred when choosing species for forestry plantation, as they performed better in terms of BAI and iWUE ratio.
The impact of authors’ medical specialty on publication patterns and published results of adjuvant radiotherapy for WHO grade 2 meningiomas—a systematic review
Authors: Strand Per Sveino , Solheim Ole
Published: March 2021

Background

The role of adjuvant radiotherapy after gross total resection (GTR) of WHO grade 2 meningioma remains unclear, and conflicting results have been published. We hypothesized that authors’ medical specialties could be associated with reported findings on the role of adjuvant radiotherapy after GTR of WHO grade 2 meningiomas.

Method

A systematic review was conducted in Embase and Medline databases, in addition to screening of all relevant bibliographies. Articles including patients aged 18 years or older, with histologically confirmed WHO grade 2 meningioma, were included. We extracted data on medical subspecialties using the author list. We registered study design, median follow-up, number of included patients, WHO classification in use, and years of study inclusion.

Results

Thirty-seven relevant studies were identified, where 34 (92%) were retrospective cohort studies, two studies (5%) were systematic reviews, and one study (3%) was a meta-analysis. If the last author was a radiation-oncologist, the study was more likely to favor adjuvant radiotherapy, and if a neurosurgeon was last author, the study was more likely to not advocate adjuvant radiotherapy (p=0.009). There was no significant association between study result and whether the study was published in a neurosurgical or oncological journal (p=0.802). There was no significant difference in follow-up time, years of inclusion, or number of included patients between studies favoring or not favoring adjuvant radiotherapy.

Conclusions

In this systematic review of the literature, we found that if a radiation-oncologist was the last author of the study, the study was more likely to favor adjuvant radiotherapy after gross total resection of WHO grade 2 meningioma. Clinicians and researchers should be aware of a possible genealogy bias in the neuro-oncological literature.
Gingival phenotype assessment methods and classifications revisited: a preclinical study
Authors: Fischer Kai R. , Büchel Jasmin , Testori Tiziano , Rasperini Giulio , Attin Thomas , Schmidlin Patrick
Published: March 2021

Objective

To compare gingival phenotype assessment methods based on soft tissue transparency on different backgrounds and assessor experience levels.

Methods

For this purpose, 24 gingival specimens were retrieved from pig jaws with tissue thicknesses from 0.2 to 1.25 mm. Three methods were assessed: periodontal probe PCP12 (thin/thick), double-ended periodontal probe DBS12 (thin/moderate/thick) and colour-based phenotype probe CBP (thin/moderate/thick/very thick). Each sample was photographed with each probe underneath and categorized whether the probe was visible or not using different coloured backgrounds. To measure experience level influence, dentists, dental undergraduate students and laypersons (n= 10/group) performed the evaluation.

Results

PCP12 probe showed a threshold between 0.4 and 0.5 mm. To distinct between thin and moderate thick gingiva, a comparable range for DBS12 was found while moderate thickness was between 0.5 and 0.8 mm and for thick above 0.8 mm. CBP also showed a comparable threshold of 0.5 mm for thin versus moderate as compared with the other methods; above 0.8 mm, predominantly a very thick tissue was measured. In general, the background colour had a minor impact on PCP12 and DBS12, and investigator experience showed no clear influence on GP assessment.

Conclusion

Based on probe transparency and within the limitation of a preclinical study, we suggest GP differentiation into three entities: thin (< 0.5 mm; high risk), moderate (0.5–0.8 mm; medium risk) and thick (> 0.8 mm; low risk).

Clinical relevance

All three GP assessment methods are easy to perform and seem to have a high predictive value with a three entities classification for DBS12 and CBP.
Adaptation and validation of the Carolinas Comfort Scale: a questionnaire-based cross-sectional study
Authors: Parseliunas A. , Paskauskas S. , Simatoniene V. , Vaitekunas J. , Venskutonis D.
Published: March 2021

Purpose

Quality of life (QoL) is an important outcome following surgery. The Carolinas Comfort scale (CCS) is a specific questionnaire used to evaluate QoL in patients who underwent abdominal hernia repair with mesh. The aim of this study was to create a Lithuanian version of the CCS.

Methods

A questionnaire-based cross-sectional study was conducted. A Lithuanian version of the CCS was created by translating the original questionnaire in accordance with the guidelines. The Lithuanian questionnaire was provided to hernia patients at 1 week and at 1 month postoperatively. The main validation characteristics of the Lithuanian CCS were assessed and compared to the original version.

Results

The complete response rate of patients was close to 90%. Internal consistency was excellent, with a Cronbach’s α of 0.953. Correlation coefficients ranged from 0.361 to 0.703 in the test–retest analysis. In the construct validity analysis, the strongest correlations were observed in the domains of physical functioning and bodily pain (− 0.655 and − 0.584, respectively) and the weakest correlations in role-emotional and mental health (− 0.268 and − 0.230, respectively). The mean scores of all CCS domains and the total score for satisfied patients were significantly lower (p < 0.001) than those of dissatisfied patients. The principal component analysis identified 3 components, with the first accounting for 56% of the variance.

Conclusions

The Lithuanian version of CCS maintains the original validity and is a reliable and valid tool for assessing specific QoL factors after the repair of inguinal hernia with mesh. We recommend using this CCS version in personal, local, and international contexts.
Evidence for pathogenicity of variant ATM Val1729Leu in a family with ataxia telangiectasia
Authors: Shalash Ali S. , Rösler Thomas W. , Salama Mohamed , Pendziwiat Manuela , Müller Stefanie H. , Hopfner Franziska , Höglinger Günter U. , Kuhlenbäumer Gregor
Published: March 2021

Ataxia telangiectasia is a rare autosomal recessive multisystem disorder caused by mutations in the gene of ATM serine/threonine kinase. It is characterized by neurodegeneration, leading to severe ataxia, immunodeficiency, increased cancer susceptibility, and telangiectasia. Here, we discovered a co-segregation of two ATM gene variants with ataxia telangiectasia in an Egyptian family. While one of these variants (NM_000051.4(ATM_i001):p.(Val128*)) has previously been reported as pathogenic, the other one (NM_000051.4(ATM_i001):p.(Val1729Leu)) is regarded as a variant of uncertain significance. Our findings in this family provide additional evidence for causality of the second variant and argue that its status should be changed to pathogenic.
Pharmacokinetics and pharmacodynamics of ampreloxetine, a novel, selective norepinephrine reuptake inhibitor, in symptomatic neurogenic orthostatic hypotension
Authors: Lo Arthur , Norcliffe-Kaufmann Lucy , Vickery Ross , Bourdet David , Kanodia Jitendra
Published: March 2021

Purpose

Ampreloxetine is a novel, selective, long-acting norepinephrine reuptake (NET) inhibitor being investigated as a once-daily oral treatment for symptomatic neurogenic orthostatic hypotension (nOH) in patients with autonomic synucleinopathies. The purpose of this study was to characterize the pharmacokinetic and pharmacodynamic profiles of ampreloxetine in this target population.

Methods

Patients with nOH were enrolled in a multicenter, phase II clinical trial of ampreloxetine (NCT02705755). They received escalating doses over 5 days in the clinical research unit, followed by 20 weeks of open-label treatment and then a 4-week withdrawal. As neurochemical biomarkers of NET inhibition, we assayed plasma concentrations of norepinephrine (NE) and its main intraneuronal metabolite 3,4-dihydroxyphenylglycol (DHPG) pre- and post-ampreloxetine.

Results

Thirty-four patients with nOH were enrolled. Plasma ampreloxetine concentrations increased with repeated escalating doses, with peak concentrations observed 6–9 h post-drug administration. The median ampreloxetine dose in the 20-week treatment phase was 10 mg once daily. Plasma ampreloxetine concentrations reached steady state by 2 weeks, with stable plasma levels over 24 h. No influence of age or renal function on ampreloxetine plasma concentrations was observed. On treatment, compared to baseline, plasma NE significantly increased by 71% (p < 0.005), plasma DHPG significantly declined by 22% (p < 0.05), and the NE:DHPG ratio significantly increased (p < 0.001).

Conclusions

Persistent elevation of plasma NE levels accompanied by reduced DHPG levels after ampreloxetine suggests reduced neuronal reuptake and metabolism of NE in postganglionic efferent sympathetic neurons. The findings are consistent with long-lasting NET inhibition, which may increase vasoconstrictor tone, supporting once-daily ampreloxetine dosing in patients with nOH.
Successful ageing in the oldest old: objectively and subjectively measured evidence from a population-based survey in Germany
Authors: Plugge Marina
Published: March 2021

Despite rapid increase of people aged 80 and over, concepts of successful ageing (SA) are primarily examined for people below that age. Therefore, successful ageing was examined in a population-based representative sample of N = 1863 people aged 80 to 102 (NRW80+) with 11% living in institutionalized settings. In this survey on quality of life and well-being, multiple linear and logistic regression models were used to calculate the distribution of successful agers. According to Rowe and Kahn’s objective definition, 9% of the sample aged successfully, but one-third (33%) still met four to five SA criteria. This is in line with the theoretical a priori criterion of 10% in a normal distribution of a sample, while 80% age normally and 10% pathologically. However, averages of life satisfaction, affective well-being, positive ageing experience and valuation of life were high. The majority of the oldest old (65%) are successful agers in their own subjective perception, which is not in line with objective measurements. Moreover, 11% of objectively measured successful agers do not meet subjective criteria. These empirical findings reveal a remarkable discrepancy between objective and subjective criteria of SA. Future research on concepts that define successful ageing for the oldest old should consider more holistic markers of success, e.g., outcomes of productive social engagement.
SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis
Authors: Ruter Dana L. , Liu Ziqing , Ngo Kimlynn M. , X Shaka , Marvin Allison , Buglak Danielle B. , Kidder Elise J. , Bautch Victoria L.
Published: March 2021

Fluid shear stress provided by blood flow instigates a transition from active blood vessel network expansion during development, to vascular homeostasis and quiescence that is important for mature blood vessel function. Here we show that SMAD6 is required for endothelial cell flow-mediated responses leading to maintenance of vascular homeostasis. Concomitant manipulation of the mechanosensor Notch1 pathway and SMAD6 expression levels revealed that SMAD6 functions downstream of ligand-induced Notch signaling and transcription regulation. Mechanistically, full-length SMAD6 protein was needed to rescue Notch loss-induced flow misalignment. Endothelial cells depleted for SMAD6 had defective barrier function accompanied by upregulation of proliferation-associated genes and down regulation of junction-associated genes. The vascular protocadherin PCDH12 was upregulated by SMAD6 and required for proper flow-mediated endothelial cell alignment, placing it downstream of SMAD6. Thus, SMAD6 is a required transducer of flow-mediated signaling inputs downstream of Notch1 and upstream of PCDH12, as vessels transition from an angiogenic phenotype to maintenance of a homeostatic phenotype.
Computational Models in Electroencephalography
Authors: Glomb Katharina , Cabral Joana , Cattani Anna , Mazzoni Alberto , Raj Ashish , Franceschiello Benedetta
Published: March 2021

Computational models lie at the intersection of basic neuroscience and healthcare applications because they allow researchers to test hypotheses in silico and predict the outcome of experiments and interactions that are very hard to test in reality. Yet, what is meant by “computational model” is understood in many different ways by researchers in different fields of neuroscience and psychology, hindering communication and collaboration. In this review, we point out the state of the art of computational modeling in Electroencephalography (EEG) and outline how these models can be used to integrate findings from electrophysiology, network-level models, and behavior. On the one hand, computational models serve to investigate the mechanisms that generate brain activity, for example measured with EEG, such as the transient emergence of oscillations at different frequency bands and/or with different spatial topographies. On the other hand, computational models serve to design experiments and test hypotheses in silico. The final purpose of computational models of EEG is to obtain a comprehensive understanding of the mechanisms that underlie the EEG signal. This is crucial for an accurate interpretation of EEG measurements that may ultimately serve in the development of novel clinical applications.