bluuebunny/crossref_metadata_2025 huggingface dataset:
Cultural differences in geographic mobility readiness among business management students in Germany and Spain ahead of graduation
Authors: Baluku Martin Mabunda , Groh Janna , Dalbert Claudia , Otto Kathleen
Published: June 2021

Given the increased internationalization of organizations and economies of scale concentrated in urban centers, graduates are often expected to relocate for their first job. Based on Hofstede’s model and Theory of Planned Behavior (TPB), we examine the effects of cultural dimensions (individualism-collectivism and uncertainty tolerance) as well as subjective norms (parents’ and peers’ attitudes towards geographic mobility) on readiness for geographic job-related mobility in samples of German and Spanish business management students ahead of graduation from university. The study involved administering a survey questionnaire to 273 third- and fourth-year business management students of two large universities (one in Germany and another in Spain). Cross-cultural measurement invariance of the measures was confirmed, allowing for comparison of scores across the groups. We found that German students had generally a larger geographical mobility, whose readiness was predicted by parents’ and peers’ perceived attitude and uncertainty tolerance. Readiness for geographic mobility was also higher when social or material incentives are offered, yet geographic mobility readiness for career incentives and for social incentives was predicted by vertical individualism and horizontal collectivism, respectively. This study is one of the first to examine geographic mobility readiness among undergraduate management students in the two countries, who by nature of their training are expected to be mobile. The study also shows the differential effects of sub-dimensions of the Hofstede cultural dimensions.
Effects of Home Voice Assistants’ Autonomy on Instrusiveness and Usefulness: Direct, Indirect, and Moderating Effects of Interactivity
Authors: Lucia-Palacios Laura , Pérez-López Raúl
Published: June 2021

This research investigates whether interactivity of home voice assistants can reduce the consumer's perceptions of intrusiveness when using these products because of their autonomy. To do so, the authors applied structural equation modeling to 607 questionnaires. The results show that autonomy has a quadratic effect on intrusiveness and usefulness, being more intense for high levels of autonomy. Interactivity reduces intrusiveness both directly and indirectly through brand trust, and interactivity has a positive effect on usefulness. Furthermore, interactivity moderates the effect of autonomy on intrusiveness. These results lead to interesting managerial implications, such as the inclusion of interactive characteristics in smart products to enable consumers to control and communicate with them.
The Soviet Myth of World War II
Authors: Brunstedt Jonathan
Published: June 2021

How did a socialist society, ostensibly committed to Marxist ideals of internationalism and global class struggle, reconcile itself to notions of patriotism, homeland, Russian ethnocentrism, and the glorification of war? In this provocative new history, Jonathan Brunstedt pursues this question through the lens of the myth and remembrance of victory in World War II – arguably the central defining event of the Soviet epoch. The book shows that while the experience and legacy of the conflict did much to reinforce a sense of Russian exceptionalism and Russian-led ethnic hierarchy, the story of the war enabled an alternative, supra-ethnic source of belonging, which subsumed Russian and non-Russian loyalties alike to the Soviet whole. The tension and competition between Russocentric and 'internationalist' conceptions of victory, which burst into the open during the late 1980s, reflected a wider struggle over the nature of patriotic identity in a multiethnic society that continues to reverberate in the post-Soviet space. The book sheds new light on long-standing questions linked to the politics of remembrance and provides a crucial historical context for the patriotic revival of the war's memory in Russia today.
War Economies and International Law
Authors: Taylor Mark B.
Published: June 2021

Economic activity continues during war. But what rules apply when US troops occupy Syrian oil fields? Who is responsible when multinational companies use minerals extracted by child labourers in war zones? This book examines how international law regulates the war economies that are at the heart of strategic competition between great powers and help sustain the irregular warfare in today's war zones. Drawing on advances in our understanding of the social and economic dynamics in war zones, this book identifies predation, a combination of violence and economic opportunity, as the core pathology of war economies. The author presents a framework for understanding the regulation of war economies based on the history of international law and existing norms of international humanitarian law, international criminal law, international human rights law and the law of international peace and security. War Economies and International Law concludes that the pathologies of predation in war demand answers based on an international regulatory strategy.
The War on Witchcraft
Authors: Machielsen Jan
Published: June 2021

Historians of the early modern witch-hunt often begin histories of their field with the theories propounded by Margaret Murray and Montague Summers in the 1920s. They overlook the lasting impact of nineteenth-century scholarship, in particular the contributions by two American historians, Andrew Dickson White (1832–1918) and George Lincoln Burr (1857–1938). Study of their work and scholarly personae contributes to our understanding of the deeply embedded popular understanding of the witch-hunt as representing an irrational past in opposition to an enlightened present. Yet the men's relationship with each other, and with witchcraft sceptics – the heroes of their studies – also demonstrates how their writings were part of a larger war against 'unreason'. This Element thus lays bare the ways scholarly masculinity helped shape witchcraft historiography, a field of study often seen as dominated by feminist scholarship. Such meditation on past practice may foster reflection on contemporary models of history writing.
An application of three different field methods to monitor changes in Urumqi Glacier No. 1, Chinese Tien Shan, during 2012–18
Authors: Li Hongliang , Wang Puyu , Li Zhongqin , Jin Shuang , Xu Chunhai , Liu Shuangshuang , Zhang Zhengyong , Xu Liping
Published: June 2021

This study deploys RTK-GNSS in 2012, TLS in 2015 and UAV in 2018 to monitor the changes of Urumqi Glacier No. 1 (UG1), eastern Tien Shan, and analyzes the feasibility of three technologies in monitoring the mountain glaciers. DEM differencing shows that UG1 has experienced a pronounced thinning and mass loss for the period of 2012–18. The glacier surface elevation change of −0.83 ± 0.57 m w.e. a−1 has been recorded for 2012–15, whereas the changes of glacier tongue surface elevation in 2015–18 and 2012–18 were −2.03 ± 0.95 and −1.34 ± 0.88 m w.e. a−1, respectively. The glacier area shrunk by 0.07 ± 0.07 × 10−3 km2 and the terminus retreat rate was 6.28 ± 0.83 m a−1 during 2012–18. The good agreement between the glaciological and geodetic specific mass-balances is promising, showing the combination of the three technologies is suitable to monitor glacier mass change. We recommend application of the three technologies to assess each other in different locations of the glacier, e.g. RTK-GNSS base stations, ground control points, glacier tongue and terminus, in order to avoid the inherent limitations of each technology and to provide reliable data for the future studies of mountain glacier changes in western China.
Evaluation of AquaCrop model of cucumber under greenhouse cultivation
Authors: Khafajeh H. , Banakar A. , Minaei S. , Delavar M.
Published: June 2021

Water consumption in agriculture is impossible without considering relations between water, soil and plant. In this regard, there are various models and developed software in order to evaluate relation between soil, water and crop growth stages. These models can be used for irrigation planning if properly optimized and applied. AquaCrop is one of the known crop models, which was developed by the Food and Agriculture Organization of the United Nations. In order to optimize this model for crop production and irrigation management, an experiment was developed in a hydroponic cucumber greenhouse. Various parameters including water consumption volume, crop yield and leaf area index were measured during a season. A fuzzy control system was utilized for controlling temperature, relative humidity, planting bed moisture, light intensity and carbon dioxide values. The main purpose of designing a control system in the greenhouse is to achieve the desired values of temperature and relative humidity. In this model, evapotranspiration, irrigation requirements and crop yield were simulated. The results show that the AquaCrop model can estimate evapotranspiration with the least error in the greenhouse environment, which is controlled by a fuzzy controller. Also the system has estimated the crop yield and biomass of the product with a good degree of precision and it may support crop production in a greenhouse, including crop management and environmental control.
The use of magnetic resonance imaging in the investigation of patients with unilateral non-pulsatile tinnitus without asymmetrical hearing loss
Authors: Saxby C , Koumpa F , Mohamed S , Singh A
Published: June 2021

Background

Tinnitus is a common condition presenting to the ENT out-patient clinic. Vestibular schwannomas are benign cerebellopontine angle tumours that usually present with unilateral sensorineural hearing loss. Magnetic resonance imaging of the internal auditory meatus is the definitive investigation in their detection. The current recommendation is for unilateral tinnitus patients to undergo magnetic resonance imaging of the internal auditory meatus to exclude vestibular schwannoma.

Objective

To evaluate magnetic resonance imaging in the investigation of patients with unilateral non-pulsatile tinnitus without asymmetrical hearing loss.

Method

A retrospective case series was conducted of all patients who underwent magnetic resonance imaging of the internal auditory meatus to investigate unilateral non-pulsatile tinnitus without asymmetrical hearing loss, from 1 January 2014 to 1 January 2019.

Results

Of 2066 scans, 566 (27 per cent) were performed to investigate patients (335 female, 231 male) with unilateral non-pulsatile tinnitus without asymmetrical hearing loss. Three vestibular schwannomas were detected on imaging, and 134 incidental findings were discovered.

Conclusion

The detection rate of vestibular schwannoma in this group was just 0.3 per cent. This paper questions the utility of magnetic resonance imaging evaluation in these patients.
When Informality Matters: Participatory Security Reform and Mechanisms of Social Embeddedness in Nezahualcóyotl, Mexico
Authors: Montambeault Françoise , Dias Félix Annabelle
Published: June 2021

What are the conditions underlying successful implementation of participatory security mechanisms? Drawing on the case of Ciudad Nezahualcóyotl and from the notion of social embeddedness, we argue that participatory security reforms that aim to include citizens in defining security priorities allow for better adoption of reforms in practice. Local level reforms are not implemented in a social vacuum but rather in pre-existing social networks that are key to their adoption in practice by citizens. However, not all social networks are equal, nor do they operate in the same manner. In ‘Neza’, it is through existing clientelistic networks and socially embedded local brokers that the redes vecinales were implemented and adopted by citizens, leading to varied reform adoption patterns at the very local level.
SARS-CoV-2 outbreak in a synagogue community: longevity and strength of anti-SARS-CoV-2 IgG responses
Authors: Gozlan Yael , Reingold Stephen , Koren Ravit , Halpern Osnat , Regev-Yochay Gili , Cohen Carmit , Biber Asaf , Picard Orit , Mendelson Ella , Lustig Yaniv , Mor Orna
Published: June 2021

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic is still ongoing along with the global vaccination efforts against it. Here, we aimed to understand the longevity and strength of anti-SARS-CoV-2 IgG responses in a small community (n = 283) six months following local SARS-COV-2 outbreak in March 2020. Three serological assays were compared and neutralisation capability was also determined. Overall 16.6% (47/283) of the participants were seropositive and 89.4% (42/47) of the IgG positives had neutralising antibodies. Most of the symptomatic individuals confirmed as polymerase chain reaction (PCR) positive during the outbreak were seropositive (30/32, 93.8%) and 33.3% of the individuals who quarantined with a PCR confirmed patient had antibodies. Serological assays comparison revealed that Architect (Abbott) targeting the N protein LIASON® (DiaSorin) targeting the S protein and enzyme-linked immunosorbent assay (ELISA) targeting receptor binding domain detected 9.5% (27/283), 17.3% (49/283) and 17% (48/283), respectively, as IgG positives. The latter two assays highly agreed (kappa = 0.89) between each other. In addition, 95%, (19/20, by ELISA) and 90.9% (20/22, with LIASON) and only 71.4% (15/21, by Architect) of individuals that were seropositive in May 2020 were found positive also in September. The unexpected low rate of overall immunity indicates the absence of un-noticed, asymptomatic infections. Lack of overall high correlation between the assays is attributed mainly to target-mediated antibody responses and suggests that using a single serological assay may be misleading.
Seeing What Is Said: Teaching Niccolò Machiavelli’s The Prince Through Its Images
Authors: Haddad Khristina H. , Mesa Higuera Claudia
Published: June 2021

This multidisciplinary pedagogy offers eight allegorical images in support of a visually contextual reading of The Prince. Responding to the pedagogical problem of students treating the text as an ahistorical manual for action addressed to them, our approach resituates The Prince in its visual cultural context. This allows us to specify Machiavelli’s innovations as a theorist in terms of the importance of plurality and particularity in regard to political action. An online supplemental appendix provides access to databases and additional resources. Exploring Machiavelli’s politicized moral concepts of prudence, parsimony, liberality, fortune, and impetuosity using these images, we show his masterful invocation and redeployment of the cultural codes of his time. In presenting a visual history of concepts, we hope to move students beyond common contemporary ideological biases and literal readings and to alert them to the complex stories and relationships evident in the visual history of civic humanism.
Feeding practices and factors associated with the provision of iron-rich foods to children aged 6–23 months in Matam area, Senegal
Authors: Akpaki Kossi , Galibois Isabelle , Blaney Sonia
Published: June 2021

Objective:

The objectives of this study were to document feeding practices amongst rural Senegalese children aged 6 to 23 months and to investigate psychosocial and environmental factors associated with the provision of iron-rich foods (IRF).

Design:

This was a cross-sectional study conducted from January to July 2018.

Setting:

The study took place in the region of Matam, northern Senegal.

Participants:

Ninety-eight mothers of children aged 6–23 months.

Results:

Results show that 27·6 % of children were fed according to the minimum acceptable diet, and 55·1 % and 53·1 % had the minimum diet diversity and minimum meal frequency, respectively. About 65·3 % of mothers provided IRF to young children the day before the survey, mostly fish. Mother’s intention to provide IRF to their children was not associated with the provision of these foods neither was the perceived behavioural control. Child’s age (OR = 1·14, 95 % CI (1·03, 1·26), P = 0·012) and household food insecurity score (OR = 0·80, 95 % CI (0·68, 0·96), P = 0·014) were the predictors of the provision of IRF to children aged 6–23 months.

Conclusions:

Household food insecurity status and age of the child rather than mothers’ psychosocial factors were significant predictors of IRF consumption amongst children aged 6–23 months in the study area. More attention should be given to food environment and child-related factors in order to improve children feeding practices and, in particular, their consumption of IRF in the study setting. For instance, home visits and the 5-month-old vaccine consultation in health centres might be opportunities to reinforce the importance of providing IRF as part of complementary foods from the age of 6 months. Implementation of measures for the improvement of socio-economic conditions and food security of households would also be valuable.
Ultra-processed food consumption and its correlates among Italian children, adolescents and adults from the Italian Nutrition & Health Survey (INHES) cohort study
Authors: Ruggiero Emilia , Esposito Simona , Costanzo Simona , Di Castelnuovo Augusto , Cerletti Chiara , Donati Maria Benedetta , de Gaetano Giovanni , Iacoviello Licia , Bonaccio Marialaura
Published: June 2021

Objective:

To assess ultra-processed food (UPF) consumption and its socio-demographic, psychosocial and behavioural correlates in a general population of Italian children, adolescents and adults.

Design:

Cross-sectional telephone-based survey

Setting:

Italy, 2010–2013.

Participants:

In total, 9078 participants (5–97 years) from the Italian Nutrition & Health Survey. Dietary intakes were collected by a 1-d 24-h dietary recall. UPF was defined by the NOVA classification and expressed as percentage of total energies.

Results:

Average energy intake from UPF (95 % CI) was 17·3 % (17·1 %, 17·6 %) among adults and 25·9 % (24·8 %, 27·0 %) in children/adolescents. Top sources of UPF were processed meats (32·5 %) and bread substitutes (16·7 %). Among adults, age (β= −3·10; 95 % CI (−4·40, −1·80) for >65 yearsv. 20–40 years;βs are dimensionless) and residing in Southern Italy (β= −0·73; 95 % CI (−1·32, −0·14)v. Northern) inversely associated with UPF. Screen view during meals was directly linked to UPF, as well as poor self-rated health (β= 5·32; 95 % CI (2·66, 7·99)), adverse life events (β= 2·33; 95 % CI (1·48, 3·18)) and low sleep quality (β= 2·34; 95 % CI (1·45, 3·23)). Boys consumed two-point percent more UPF of the total energy than girls (β= 2·01; 95 % CI (0·20, 3·82)). For all ages, a Mediterranean diet was inversely associated with UPF (β= −4·86; 95 % CI (−5·53, −4·20) for goodv. poor adherence in adults and (β= −5·08; 95 % CI (−8·38, −1·77) for kids).

Conclusions:

UPF contributes a modest proportion of energy to the diets of Italian adults while being one-quarter of the total energies in children/adolescents. UPF was associated with several psychosocial factors and eating behaviours. Increased adherence to Mediterranean diet would possibly result in lower UPF consumption.
The Evolution of Plume Fronts in the Rhine Region of Freshwater Influence
Authors: Rijnsburger Sabine , Flores Raúl P. , Pietrzak Julie D. , Horner‐Devine Alexander R. , Souza Alejandro J. , Zijl Firmijn
Published: June 2021

The Rhine region of freshwater influence (ROFI) is strongly stratified, rotational, relatively shallow and has large tides, resulting in a dynamic field of fronts that are formed by multiple processes. We use a 3D numerical model to obtain a conceptual picture of the frontal structure and the processes responsible for generating this multiple front structure in the Rhine ROFI. The horizontal salinity gradient and numerical tracers are used to identify three different types of fronts: outer, inner, tidal plume and relic tidal plume fronts. Tidal plume front (TPF) trajectories together with the tracers demonstrate that TPFs exist for longer than one tidal cycle. A Lagrangian frontogenesis analysis shows that the fronts are strengthened mainly as a result of increased convergence, which is observed to occur at times when tidal straining is large. Additionally the alongshore tidal excursion and the dominance of the tidal currents over the intrinsic frontal propagation speed, trap TPFs within 20 km from the river mouth. Trapping and re‐strengthening maintain several fronts at a time in the mid‐field region, resulting in a multi‐frontal system. The observation of a complex river plume system is expected to be important for cross‐shore exchange, transport and coastal ecology.
The Architecture of the Southern Puna Magmatic System: Integrating Seismic and Petrologic Observations With Geochemical Modeling
Authors: Delph Jonathan R. , Shimizu Kei , Ratschbacher Barbara C.
Published: June 2021

Improvements in geochemical, petrologic, and geophysical methods and data have led to a paradigm‐shift in understanding magmatic system architecture away from isolated magmatic chambers toward transcrustal “mushy” magmatic systems. Geochemical and petrologic studies indicate that magma storage and differentiation occurs over a range of depths throughout the crust, while geophysical techniques delineate in situ spatial distributions of melt at similar scales. However, seismic properties are nonunique with respect to composition and melt percentage, and must be integrated with geochemical observations to better understand the architecture and chemical evolution of magmatic systems. The southern Puna Plateau represents a locality where extensive geochemical and seismic data can be combined to investigate the role of depth‐dependent processes in generating compositionally diverse volcanism. By combining geochemical modeling with seismic images of shear‐wave velocity and attenuation, we find that magma storage and differentiation occurs predominantly at two depth ranges: (a) near the base of the crust (>40 km), where shear‐wave velocities are anomalously slow compared to what is expected (<4.0 km/s) and geochemical signatures indicate fractional crystallization and crustal assimilation in the garnet stability field, and (b) in the mid‐crust (∼20 km) beneath the Cerro Galan Caldera, where shear‐wave velocities necessitate the presence of melt (∼2.7 km/s) and europium (Eu) anomalies indicate low‐pressure differentiation. These geochemical and seismic results provide evidence for multi‐level melt evolution and are consistent with petrological features of exposed arcs, whose transcrustal architecture is characterized by discrete and compositionally evolved intrusive bodies in the mid‐crust and a compositionally heterogeneous lower crust.
Relating Far‐Field Coseismic Ionospheric Disturbances to Geological Structures
Authors: Liu Haitao , Zhang Keke , Imtiaz Nadia , Song Qian , Zhang Ying
Published: June 2021

Clear near‐epicentral coseismic ionospheric disturbances (CIDs) are observed following the Gorkha and May 2015 Nepal earthquakes and only the Gorkha earthquake excited observable far‐field CIDs up to 3,000 km from the epicenter. The near‐epicentral CIDs exhibit concentric fields to the south and north of the epicenter. A north‐south asymmetry of the CIDs is clearly observed in the near‐epicentral area of both earthquakes. The velocity and period of the main part of the near‐epicentral CIDs are ∼1,000 m/s and ∼6 min, respectively. The wavefronts of the far‐field CIDs related to the Gorkha earthquake are mostly straight lines that completely differ from the near‐epicentral CIDs. The horizontal trace of the far‐field CIDs reaches velocities of ∼2.5 km/s based on their distance from the epicenter and the CID arrival time. After identifying the propagation direction of the far‐field CIDs on a series of two‐dimensional (2D) total electron content (TEC) maps, we obtain the real horizontal velocity of far‐field CIDs, which is ∼1.0 km/s, and the period is ∼3 min, which corresponds to that of acoustic waves in the ionosphere. We find a discontinuity of the far‐field CIDs around the Sichuan Basin, which suggests that deep sedimentation can reduce seismic energy coupling into the atmosphere and then the ionosphere. In addition, by introducing a simple acoustic source into the SAMI2 simulation, we show that the large electron density of the background ionosphere and steep inclination of the geomagnetic field are favorable conditions for the generation of detectable CIDs.
Seismic Imaging of the Mw 7.1 Ridgecrest Earthquake Rupture Zone From Data Recorded by Dense Linear Arrays
Authors: Qiu Hongrui , Ben‐Zion Yehuda , Catchings Rufus , Goldman Mark R. , Allam Amir A. , Steidl Jamison
Published: June 2021

We analyze seismograms recorded by four arrays (B1–B4) with 100 m station spacing and apertures of 4–8 km that cross the surface rupture of the 2019 Mw 7.1 Ridgecrest earthquake. The arrays extend from B1 in the northwest to B4 in the southeast of the surface rupture. Delay times between P wave arrivals associated with ∼1,200 local earthquakes and four teleseismic events are used to estimate local velocity variations beneath the arrays. Both teleseismic and local P waves travel faster on the northeast than the southwest side of the fault beneath arrays B1 and B4, but the velocity contrast is less reliably resolved at arrays B2 and B3. We identify several 1–2 km wide low‐velocity zones with much slower inner cores that amplify S waveforms, inferred as damage zones, beneath each array. The damage zones at arrays B2 and B4 also generate fault‐zone head and trapped waves. An automated detector, based on peak ground velocities and durations of high‐amplitude waves, identifies candidate fault‐zone trapped waves (FZTWs) in a localized zone for ∼600 earthquakes at array B4. Synthetic waveform modeling of averaged FZTWs, generated by ∼30 events with high‐quality signals, indicates that the trapping structure at array B4 has a width of ∼300 m, depth of 3–5 km, S wave velocity reduction of ∼20% with respect to the surrounding rock, Q‐value of ∼30, and S wave velocity contrast of ∼4% across the fault (faster on the northeast side). The results show complex fault‐zone internal structures (velocity contrasts and low‐velocity zones) that vary along fault strike.
A Numerical Study of Gravity Waves Propagation Characteristics in the Mesospheric Doppler Duct
Authors: Dong Wenjun , Hickey Michael P. , Zhang Shaodong
Published: June 2021

Dong et al. (2018,https://doi.org/10.1029/2018JD029190, hereafter D18) employed a compressible model to examine the long‐distance horizontal propagation of gravity waves (GWs) in a stratospheric thermal duct in a two‐dimensional domain. Here, we extend this previous work to explore the ducting of GWs in the mesospheric Doppler duct. While most of the characteristics of the thermal duct described in D18 are found to be operative in the Doppler duct, there are some important differences. The propagation velocity of the fundamental (0th) wave mode is always largest in the Doppler duct and smallest in the thermal duct. We find that regardless of the type of duct (Doppler or thermal duct) the energy dissipation rates of wave modes in the duct region are inversely proportional to their horizontal group velocities. Our results suggest that observations of ducted GWs, particularly those made from multiple observation sites, should reveal characteristics that are germane to the particular duct type. For example, we find that the frequency of the dominant wave mode in the Doppler duct increases with increasing distance from the wave source. This behavior is exactly the opposite of what was obtained for the thermal duct by D18.
Measurable residual disease in chronic lymphocytic leukemia: expert review and consensus recommendations
Authors: Wierda William G. , Rawstron Andrew , Cymbalista Florence , Badoux Xavier , Rossi Davide , Brown Jennifer R. , Egle Alexander , Abello Virginia , Cervera Ceballos Eduardo , Herishanu Yair , Mulligan Stephen P. , Niemann Carsten U. , Diong Colin P. , Soysal Teoman , Suzuki Ritsuro , Tran Hoa T. T. , Wu Shang-Ju , Owen Carolyn , Stilgenbauer Stephan , Ghia Paolo , Hillmen Peter
Published: June 2021

Assessment of measurable residual disease (often referred to as “minimal residual disease”) has emerged as a highly sensitive indicator of disease burden during and at the end of treatment and has been correlated with time-to-event outcomes in chronic lymphocytic leukemia. Undetectable-measurable residual disease status at the end of treatment demonstrated independent prognostic significance in chronic lymphocytic leukemia, correlating with favorable progression-free and overall survival with chemoimmunotherapy. Given its utility in evaluating depth of response, determining measurable residual disease status is now a focus of outcomes in chronic lymphocytic leukemia clinical trials. Increased adoption of measurable residual disease assessment calls for standards for nomenclature and outcomes data reporting. In addition, many basic questions have not been systematically addressed. Here, we present the work of an international, multidisciplinary, 174-member panel convened to identify critical questions on key issues pertaining to measurable residual disease in chronic lymphocytic leukemia, review evaluable data, develop unified answers in conjunction with local expert input, and provide recommendations for future studies. Recommendations are presented regarding methodology for measurable residual disease determination, assay requirements and in which tissue to assess measurable residual disease, timing and frequency of assessment, use of measurable residual disease in clinical practice versus clinical trials, and the future usefulness of measurable residual disease assessment. Nomenclature is also proposed. Adoption of these recommendations will work toward standardizing data acquisition and interpretation in future studies with new treatments with the ultimate objective of improving outcomes and curing chronic lymphocytic leukemia.
Cellular and metabolic mechanisms of nutrient actions in immune function
Authors: Newsholme Philip
Published: June 2021

Various nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of diverse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.
Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity
Authors: Tomé Daniel
Published: June 2021

Defences to pathogens such as SarCoV2 in mammals involves interactions between immune functions and metabolic pathways to eradicate infection while preventing hyperinflammation. Amino acid metabolic pathways represent with other antimicrobial agent potential targets for therapeutic strategies. iNOS-mediated production of NO from Arg is involved in the innate inflammatory response to pathogens and NO overproduction can induce hyperinflammation. The two Arg- and Trp-catabolising enzymes Arg1 and IDO1 reduce the hyperinflammation by an immunosuppressive effect via either Arg starvation (for Arg1) or via the immunoregulatory activity of the Trp-derived metabolites Kyn (for IDO1). In response to amino acid abundance mTOR activates the host protein translation and Coronaviruses use this machinery for their own protein synthesis and replication. In contrast GCN2, the sensor of amino acid starvation, activates pathways that restrict inflammation and viral replication. Gln depletion alters the immune response that become more suppressive, by favouring a regulatory T phenotype rather than a Th1 phenotype. Proliferating activated immune cells are highly dependent on Ser, activation and differentiation of T cells need enough Ser and dietary Ser restriction can inhibit their proliferation. Cys is strictly required for T-cell proliferation because they cannot convert Met to Cys. Restricting Met inhibits both viral RNA cap methylation and replication, and the proliferation of infected cells with an increased requirement for Met. Phe catabolism produces antimicrobial metabolites resulting in the inhibition of microbial growth and an immunosuppressive activity towards T lymphocytes.
Visuopathy of prematurity: is retinopathy just the tip of the iceberg?
Authors: Ingvaldsen Sigrid Hegna , Morken Tora Sund , Austeng Dordi , Dammann Olaf
Published: June 2021

Research on retinopathy of prematurity (ROP) focuses mainly on the abnormal vascularization patterns that are directly visible for ophthalmologists. However, recent findings indicate that children born prematurely also exhibit changes in the retinal cellular architecture and along the dorsal visual stream, such as structural changes between and within cortical areas. Moreover, perinatal sustained systemic inflammation (SSI) is associated with an increased risk for ROP and the visual deficits that follow. In this paper, we propose that ROP might just be the tip of an iceberg we call visuopathy of prematurity (VOP). The VOP paradigm comprises abnormal vascularization of the retina, alterations in retinal cellular architecture, choroidal degeneration, and abnormalities in the visual pathway, including cortical areas. Furthermore, VOP itself might influence the developmental trajectories of cerebral structures and functions deemed responsible for visual processing, thereby explaining visual deficits among children born preterm.
Coral mucus rapidly induces chemokinesis and genome-wide transcriptional shifts toward early pathogenesis in a bacterial coral pathogen
Authors: Gao Cherry , Garren Melissa , Penn Kevin , Fernandez Vicente I , Seymour Justin R , Thompson Janelle R , Raina Jean-Baptiste , Stocker Roman
Published: June 2021

Elevated seawater temperatures have contributed to the rise of coral disease mediated by bacterial pathogens, such as the globally distributed Vibrio coralliilyticus, which utilizes coral mucus as a chemical cue to locate stressed corals. However, the physiological events in the pathogens that follow their entry into the coral host environment remain unknown. Here, we present simultaneous measurements of the behavioral and transcriptional responses of V. coralliilyticus BAA-450 incubated in coral mucus. Video microscopy revealed a strong and rapid chemokinetic behavioral response by the pathogen, characterized by a two-fold increase in average swimming speed within 6 min of coral mucus exposure. RNA sequencing showed that this bacterial behavior was accompanied by an equally rapid differential expression of 53% of the genes in the V. coralliilyticus genome. Specifically, transcript abundance 10 min after mucus exposure showed upregulation of genes involved in quorum sensing, biofilm formation, and nutrient metabolism, and downregulation of flagella synthesis and chemotaxis genes. After 60 min, we observed upregulation of genes associated with virulence, including zinc metalloproteases responsible for causing coral tissue damage and algal symbiont photoinactivation, and secretion systems that may export toxins. Together, our results suggest that V. coralliilyticus employs a suite of behavioral and transcriptional responses to rapidly shift into a distinct infection mode within minutes of exposure to the coral microenvironment.
LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer
Authors: Xu Jian , Wang Jie , He Zhiwei , Chen Peng , Jiang Xueyi , Chen Yankun , Liu Xinyuan , Jiang Jianxin
Published: June 2021

LncRNAs play essential regulatory roles in pancreatic cancer (PC) tumorigenesis and progression. We aimed to investigate the role of lncRNA CERS6-AS1 in PC. CERS6-AS1 expression was determined in PC tissues and cell lines by PCR analysis. The roles of CERS6-AS1 on proliferation, migration, invasion, and epithelial to mesenchymal transition (EMT) were confirmed via CCK-8 assay, EDU assay, transwell assay, wound healing assay, and western blot assay. Besides, the interaction between CERS6-AS1 and their target genes was verified by luciferase report assays and RIP assays. Animal assays and clinical data analysis were performed to validate the functions in vivo. We found that lncRNA CERS6-AS1 was highly expressed in PC tissues and cells. Additionally, high expression of CERS6-AS1 was obviously associated with poor prognosis. Functional assays demonstrated that CERS6-AS1 downregulation significantly inhibited PC cell growth and migration. Moreover, CERS6-AS1 exerted as a molecular sponge for miR-217-5p (miR-217), and miR-217 was confirmed as a potential target of CERS6-AS1. Subsequently, miR-217 suppressed PC cell proliferation and metastasis by directly targeting YWHAG, which interacted with RAF1 and promoted its phosphorylation, leading to RAF1-mediated ERK signaling activation and translocation of phosphorylated ERK from the cytoplasm to the nucleus. Mechanically, CERS6-AS1 silencing significantly inhibited PC cell proliferation and metastasis via a miR-217/YWHAG/RAF1 signaling axis. CERS6-AS1 exerts as a carcinogen in PC to promote malignant features and behaves as a competitive endogenous RNA for miR-217. We identified CERS6-AS1 as a potential biomarker or therapeutic target to improve PC diagnosis and treatment outcomes.
Marizomib sensitizes primary glioma cells to apoptosis induced by a latest-generation TRAIL receptor agonist
Authors: Boccellato Chiara , Kolbe Emily , Peters Nathalie , Juric Viktorija , Fullstone Gavin , Verreault Maïté , Idbaih Ahmed , Lamfers Martine L. M. , Murphy Brona M. , Rehm Markus
Published: June 2021

Due to the absence of curative treatments for glioblastoma (GBM), we assessed the efficacy of single and combination treatments with a translationally relevant 2nd generation TRAIL-receptor agonist (IZI1551) and the blood–brain barrier (BBB) permeant proteasome inhibitor marizomib in a panel of patient-derived glioblastoma cell lines. These cells were cultured using protocols that maintain the characteristics of primary tumor cells. IZI1551+marizomib combination treatments synergistically induced apoptotic cell death in the majority of cases, both in 2D, as well as in 3D spheroid cultures. In contrast, single-drug treatments largely failed to induce noticeable amounts of cell death. Kinetic analyses suggested that time-shifted drug exposure might further increase responsiveness, with marizomib pre-treatments indeed strongly enhancing cell death. Cell death responses upon the addition of IZI1551 could also be observed in GBM cells that were kept in a medium collected from the basolateral side of a human hCMEC/D3 BBB model that had been exposed to marizomib. Interestingly, the subset of GBM cell lines resistant to IZI1551+marizomib treatments expressed lower surface amounts of TRAIL death receptors, substantially lower amounts of procaspase-8, and increased amounts of cFLIP, suggesting that apoptosis initiation was likely too weak to initiate downstream apoptosis execution. Indeed, experiments in which the mitochondrial apoptosis threshold was lowered by antagonizing Mcl-1 re-established sensitivity to IZI1551+marizomib in otherwise resistant cells. Overall, our study demonstrates a high efficacy of combination treatments with a latest-generation TRAIL receptor agonist and the BBB permeant proteasome inhibitor marizomib in relevant GBM cell models, as well as strategies to further enhance responsiveness and to sensitize subgroups of otherwise resistant GBM cases.
A new high protein-to-energy enteral formula with a whey protein hydrolysate to achieve protein targets in critically ill patients: a prospective observational tolerability study
Authors: Tedeschi-Jockers Franziska , Reinhold Simona , Hollinger Alexa , Tuchscherer Daniel , Kiss Caroline , Gantner Lukas , Ledergerber Katrin , Zimmermann Sibylle , Scheuzger Jonas , Huber Jan , Siegemund Martin
Published: June 2021

Objectives

Current guidelines and expert recommendations stress the need to implement enteral feeds with a higher protein-to-energy ratio to meet protein requirements as recommended while avoiding gastrointestinal side effects and energy overfeeding in ICU patients.

Materials and methods

Prospective tolerability study in 18 critically ill patients with a high protein formula (high protein-to-energy (HP:E) formula = Fresubin® Intensive; HPG) compared to a contemporary matched conventional therapy group (CTG). The primary outcome was GI intolerance defined as ≥300 ml daily gastric residual volume (GRV), vomiting, or diarrhea on days 1 and 2. Secondary outcomes were the percentage of patients reaching their protein target on day 4 and overall protein intake.

Results

Groups were comparable regarding demographic characteristics, disease severity, organ failures, mechanical ventilation, and NUTRIC score at baseline. Eighteen patients completed the 4-day feeding period. The number of events of GRV of ≥300 ml/day was equal in both groups (33.3%). The incidence of diarrhea and vomiting was low in the HPG (two patients concerned). EN did not need to be discontinued due to intolerance in any group. Seventy-two percent of patients reached protein targets ≥1.3 g/kgBW/d within 4 days after initiation of enteral feeding, which was superior to the CTG (33%). Post-hoc testing showed group differences of protein intake between HPG and CTG were significant at t = 72 h and t = 96 h. Energy targets were met in both groups.

Conclusion

The HP:E formula containing 33% whey protein hydrolysate is well tolerated in this tolerability study. Due to the HP:E ratio protein targets can be reached faster. Larger randomized trials are needed to confirm preliminary results.

Trial registration

ClinicalTrials.gov Identifier: NCT02678325. Registered 2 May 2016.
Accurate localization microscopy by intrinsic aberration calibration
Authors: Copeland Craig R. , McGray Craig D. , Ilic B. Robert , Geist Jon , Stavis Samuel M.
Published: June 2021

A standard paradigm of localization microscopy involves extension from two to three dimensions by engineering information into emitter images, and approximation of errors resulting from the field dependence of optical aberrations. We invert this standard paradigm, introducing the concept of fully exploiting the latent information of intrinsic aberrations by comprehensive calibration of an ordinary microscope, enabling accurate localization of single emitters in three dimensions throughout an ultrawide and deep field. To complete the extraction of spatial information from microscale bodies ranging from imaging substrates to microsystem technologies, we introduce a synergistic concept of the rigid transformation of the positions of multiple emitters in three dimensions, improving precision, testing accuracy, and yielding measurements in six degrees of freedom. Our study illuminates the challenge of aberration effects in localization microscopy, redefines the challenge as an opportunity for accurate, precise, and complete localization, and elucidates the performance and reliability of a complex microelectromechanical system.
Allosteric modulation of ghrelin receptor signaling by lipids
Authors: Damian Marjorie , Louet Maxime , Gomes Antoniel Augusto Severo , M’Kadmi Céline , Denoyelle Séverine , Cantel Sonia , Mary Sophie , Bisch Paulo M. , Fehrentz Jean-Alain , Catoire Laurent J. , Floquet Nicolas , Banères Jean-Louis
Published: June 2021

The membrane is an integral component of the G protein-coupled receptor signaling machinery. Here we demonstrate that lipids regulate the signaling efficacy and selectivity of the ghrelin receptor GHSR through specific interactions and bulk effects. We find that PIP2 shifts the conformational equilibrium of GHSR away from its inactive state, favoring basal and agonist-induced G protein activation. This occurs because of a preferential binding of PIP2 to specific intracellular sites in the receptor active state. Another lipid, GM3, also binds GHSR and favors G protein activation, but mostly in a ghrelin-dependent manner. Finally, we find that not only selective interactions but also the thickness of the bilayer reshapes the conformational repertoire of GHSR, with direct consequences on G protein selectivity. Taken together, this data illuminates the multifaceted role of the membrane components as allosteric modulators of how ghrelin signal could be propagated.
Order-by-disorder from bond-dependent exchange and intensity signature of nodal quasiparticles in a honeycomb cobaltate
Authors: Elliot M. , McClarty P. A. , Prabhakaran D. , Johnson R. D. , Walker H. C. , Manuel P. , Coldea R.
Published: June 2021

Recent theoretical proposals have argued that cobaltates with edge-sharing octahedral coordination can have significant bond-dependent exchange couplings thus offering a platform in 3d ions for such physics beyond the much-explored realisations in 4d and 5d materials. Here we present high-resolution inelastic neutron scattering data within the magnetically ordered phase of the stacked honeycomb magnet CoTiO3 revealing the presence of a finite energy gap and demonstrate that this implies the presence of bond-dependent anisotropic couplings. We also show through an extensive theoretical analysis that the gap further implies the existence of a quantum order-by-disorder mechanism that, in this material, crucially involves virtual crystal field fluctuations. Our data also provide an experimental observation of a universal winding of the scattering intensity in angular scans around linear band-touching points for both magnons and dispersive spin-orbit excitons, which is directly related to the non-trivial topology of the quasiparticle wavefunction in momentum space near nodal points.
PGRL2 triggers degradation of PGR5 in the absence of PGRL1
Authors: Rühle Thilo , Dann Marcel , Reiter Bennet , Schünemann Danja , Naranjo Belen , Penzler Jan-Ferdinand , Kleine Tatjana , Leister Dario
Published: June 2021

In plants, inactivation of either of the thylakoid proteins PGR5 and PGRL1 impairs cyclic electron flow (CEF) around photosystem I. Because PGR5 is unstable in the absence of the redox-active PGRL1, but not vice versa, PGRL1 is thought to be essential for CEF. However, we show here that inactivation of PGRL2, a distant homolog of PGRL1, relieves the need for PGRL1 itself. Conversely, high levels of PGRL2 destabilize PGR5 even when PGRL1 is present. In the absence of both PGRL1 and PGRL2, PGR5 alters thylakoid electron flow and impairs plant growth. Consequently, PGR5 can operate in CEF on its own, and is the target of the CEF inhibitor antimycin A, but its activity must be modulated by PGRL1. We conclude that PGRL1 channels PGR5 activity, and that PGRL2 triggers the degradation of PGR5 when the latter cannot productively interact with PGRL1.