bluuebunny/crossref_metadata_2025 huggingface dataset:
Burnout and engagement among PhD students in medicine: the BEeP study
Authors: Kusurkar Rashmi A. , Van der Bur Stéphanie M. E. , Isik Ulviye , Mak-van der Vossen Marianne , Wilschut Janneke , Wouters Anouk , Koster Andries S.
Published: December 2020

Introduction Using a self-determination theory framework, we investigated burnout and engagement among PhD students in medicine, and their association with motivation, work-life balance and satisfaction or frustration of their basic psychological needs.

Method This cross-sectional study was conducted among PhD students at a university medical centre (n = 990) using an electronic survey on background characteristics and validated burnout, engagement, motivation and basic psychological needs questionnaires. Cluster analysis was performed on the burnout subscale scores to find subgroups within the sample which had similar profiles on burnout. Structural equation modelling was conducted on a hypothesized model of frustration of basic psychological needs and burnout.

Results The response rate was 47% (n = 464). We found three clusters/subgroups which were composed of PhD students with similar burnout profiles within the cluster and different profiles between the clusters. Cluster 1 (n = 199, 47%) had low scores on burnout. Clusters 2 (n = 168, 40%) and 3 (n = 55, 13%) had moderate and high burnout scores, respectively, and were associated with low engagement scores. Cluster 3, with the highest burnout scores, was associated with the lowest motivational, engagement, needs satisfaction and work-life balance scores. We found a good fit for the “basic psychological needs frustration associated with burnout” model.

Discussion The most important variables for burnout among PhD students in medicine were lack of sleep and frustration of the basic psychological needs of autonomy, competence and relatedness. These add to the factors found in the literature.
Simplified surface heat source distribution for GMAW process simulation based on the EDACC principle
Authors: Mokrov O. , Simon M. S. , Sharma R. , Reisgen U.
Published: December 2020

A simplified surface heat source for gas metal arc welding (GMAW) process simulation based on the principle of evaporation determined arc cathode coupling (EDACC) is presented. It allows for a simple implementation in any GMAW weld pool simulation and is dependent on the width of the arc, as well as the weld pool surface temperature, but it can also be applied with the temperature and iron vapor density of the plasma instead of the width of the arc, if available. While it is considered separately from the droplets, it gives the heat flux as well as the current density distribution onto the weld pool surface, which are in general not axis-symmetric. The heat source distribution is normalized and multiplied to the value of any total heat and total current and it allows to calibrate for the maximum weld pool surface temperature. For the ionization and evaporation, only iron atoms are considered, and the shielding gas is assumed as argon. The result is given in graphical form as well as in the form of easy to implement functions for a reasonable range.
Urinary vitronectin identifies patients with high levels of fibrosis in kidney grafts
Authors: Carreras-Planella Laura , Cucchiari David , Cañas Laura , Juega Javier , Franquesa Marcella , Bonet Josep , Revuelta Ignacio , Diekmann Fritz , Taco Omar , Lauzurica Ricardo , Borràs Francesc Enric
Published: December 2020

Background

In kidney transplantation, fibrosis represents the final and irreversible consequence of the pathogenic mechanisms that lead to graft failure, and in the late stages it irremediably precedes the loss of renal function. The invasiveness of kidney biopsy prevents this condition from being frequently monitored, while clinical data are rather unspecific. The objective of this study was to find noninvasive biomarkers of kidney rejection.

Methods

We carried out proteomic analysis of the urinary Extracellular Vesicles (uEVs) from a cohort of kidney transplant recipients (n = 23) classified according to their biopsy-based diagnosis and clinical parameters as interstitial fibrosis and tubular atrophy (IFTA), acute cellular rejection (ACR), calcineurin inhibitors toxicity (CNIT) and normal kidney function (NKF).

Results

Shotgun mass spectrometry of uEV-proteins identified differential expression of several proteins among these different groups. Up to 23 of these proteins were re-evaluated using targeted proteomics in a new independent cohort of patients (n = 41) classified in the same diagnostic groups. Among other results, we found a differential expression of vitronectin (VTN) in patients displaying chronic interstitial and tubular lesions (ci and ct mean > 2 according to Banff criteria). These results were further confirmed by a pilot study using enzyme-linked immunosorbent assay (ELISA).

Conclusion

Urinary vitronectin levels are a potential stand-alone biomarker to monitor fibrotic changes in kidney transplant recipients in a non-invasive fashion.
Coal-bearing strata sequence stratigraphy of Paleogene Meihe Formation, Meihe Basin, NE China
Authors: Bai Yueyue , Lü Qingtian , Liu Zhaojun , Sun Pingchang , Liu Rong , Yao Shuqing
Published: December 2020

The Meihe Basin is an important Paleogene coal-bearing basin located in the Dunhua-Mishan Fault Zone, northeastern China. Based on a comprehensive study of well logs, seismic profiles, cores and rock geochemical properties, the coal distribution, paleoenvironment evolution within a sequence stratigraphic framework and the accumulation model to explain how coal seams developed in small fault basin were discussed in detail. Three-third-order sequences were identified in the Paleogene Meihe Formation of Meihe Basin and the two coal-bearing sequences are the Lower Coal-bearing Member of Sequence I and the Upper Coal-bearing Member of Sequence III. All three types of system tracts are developed in both sequences, i.e., the lowstand systems tract (LST), the transgressive systems tract (TST), and the highstand systems tract (HST). In LST of Sequence I, fan delta plain marsh is the main coal accumulating environment where coal seams are thin, discontinuous and therefore uneconomic for mining, and it is the same with all coal seams developed in Sequence III. While in TST and HST of Sequence I, lake swamp is the main sedimentary environment where coal seams are thick, continuous, widely distributed, and thus economically attractive for mining. In the study area, the nice thick economical coal seams are usually developed in an ideal stable depositional environment where organic matter accommodation space grows at a balanced rate with peat, in other words, free of sediment input or channel migration. The key findings of this study could provide guidance for the exploration of coal seams in the Meihe Basin and other similar basins.
Fire as an Artifact—Advances in Paleolithic Combustion Structure Studies: Introduction to the Special Issue
Authors: Stahlschmidt Mareike C. , Mallol Carolina , Miller Christopher E.
Published: December 2020

Hearths present sedimentary features, artifacts, and direct evidence for maintained and controlled fire in the past. The use of hearths reflects regular access to fire and its diverse benefits. Among these benefits are cooked food, protection from the cold and from predators, and fire’s transformative power regarding raw materials. Hearths may have also served as focal points of activity at Paleolithic campsites and triggered changes in social structures. As sedimentary features, combustion structures function as behavioral as well as paleoenvironmental archives. The papers in this special issue focus on the former aspect, how combustion feature can serve as transmitters of behavior, and with what tools we can explore them. We here briefly present an overview on the range of topics explored in these papers, which include ethnoarchaeological research on fire use among recent hunter-gatherer groups, spatial analysis of burnt lithics, actualistic experiments regarding fire function and fire use in tool production.
Variations in the Number of Patients Presenting With Andrological Problems During the Coronavirus Disease 2019 Pandemic and the Possible Reasons for These Variations: A Multicenter Study
Authors: Duran Mesut Berkan , Yildirim Omer , Kizilkan Yalcin , Tosun Cagatay , Cirakoglu Abdullah , Gultekin Mehmet Hamza , Gul Umit , Altan Mesut , Sah Cem , Hasirci Eray , Ceyhan Erman , Ongun Sakir , Turunc Tahsin
Published: December 2020

Introduction

Coronavirus disease 2019 (COVID-19) pandemic caused unprecedented restrictions in outpatient services and surgical practices in urology as in other medical branches as well as in all areas of life.

Aim

To investigate whether there have been variations in the presentations of male patients with sexual and reproductive health problems to the outpatient urology clinics during the COVID-19 pandemic and to understand the underlying factors for these variations, if any.

Methods

Male patients aged ≥18 years who presented to the outpatient urology clinics in 12 centers across Turkey from February 1, 2020 to June 1, 2020 were retrospectively evaluated. The patients were divided into 2 groups: those who presented to the outpatient clinic from February 1, 2020 to March 11, 2020 comprised the “pre–COVID-19 pandemic period” group, whereas those who presented to the outpatient clinic from March 12, 2020 to June 1, 2020 comprised the “COVID-19 pandemic period” group and compared with each other.

Main Outcome Measures

The main outcome of this study was the number and diagnose of patients presented to urology outpatient clinics.

Results

Andrological problems were detected in 721 of 4,955 male patients included in the study. During the COVID-19 pandemic period, there was a significant increase in andrological diagnosis in these patients compared with the pre–COVID-19 pandemic period (n = 293 [17%] vs n = 428 [13.2%], P < .001, respectively). Similarly, there was a statistically significant increase in the number of patients diagnosed with male reproductive or sexual health problems during the COVID-19 pandemic period (n = 107 [6.2%] vs n = 149 [4.6%], P = .016 and n = 186 [10.8%] vs n = 279 [8.6%], P = .013, respectively). The number of patients diagnosed with erectile dysfunction during the pandemic was also significantly higher than the pre–COVID-19 pandemic period (n = 150 [8.7%] vs n = 214 [6.6%], P = .008).

Conclusion

Presentations to the outpatient urology clinics owing to andrological problems markedly increased during the pandemic period. Although these problems are of multifactorial origin, psychogenic factors are also considered to significantly trigger these problems.
Radiofrequency Thermocoagulation in Refractory Focal Epilepsy: The Montreal Neurological Institute Experience
Authors: Mirza Farhan A. , Hall Jeffery A.
Published: December 2020

Background:

Radiofrequency thermocoagulation (RF-TC) is a minimally invasive ablative option for refractory focal epilepsy.

Methods:

A retrospective chart review was conducted of all patients who underwent stereoelectroencephalography (SEEG)-guided RF-TC at our institution.

Results:

Fourteen patients underwent robot-guided electrode implantation and subsequent RF-TC. After RF-TC, one of the three patients with PVNH was seizure free, one had 18 months of seizure freedom (Engel 2b), and one required temporal neocortical/PVNH resection (Engel 1a). One of the four patients with focal cortical dysplasia (FCD) was seizure free (Engel 1a), two attained seizure freedom after resection (Engel 1a and 1b), while one continues to have significant seizures (Engel 4b). One patient with cavernoma and low central area epileptogenic zone (EZ) did not benefit from RF-TC and is planned for resection. Two of the MRI-negative patients achieved seizure freedom for 3 months and 1 year, respectively, subsequently requiring resection (Engel 1a). One remains seizure free at 4 weeks. Three had seizure recurrence immediately (Engel 4b). With RF-TC alone, two patients (14%) achieved Engel 1a, two were seizure free at 1 year, one had 3 months of seizure freedom, while the rest had recurrence immediately or within a few weeks. 7/14 patients underwent secondary interventions after RF-TC. Overall, seven patients achieved Engel 1a or 1b, one each 2b and 3a, and five Engel 4b.

Conclusion:

At our institution, RF-TC is a safe ablative procedure for refractory focal epilepsy. It can serve as a segue to secondary interventions and appears promising in PVNH cases. Its role in MRI-negative cases is less clear.
Laser-induced damage thresholds of ultrathin targets and their constraint on laser contrast in laser-driven ion acceleration experiments
Authors: Wang Dahui , Shou Yinren , Wang Pengjie , Liu Jianbo , Mei Zhusong , Cao Zhengxuan , Zhang Jianmin , Yang Pengling , Feng Guobin , Chen Shiyou , Zhao Yanying , Schreiber Joerg , Ma Wenjun
Published: December 2020

Single-shot laser-induced damage threshold (LIDT) measurements of multi-type free-standing ultrathin foils were performed in a vacuum environment for 800 nm laser pulses with durations τ ranging from 50 fs to 200 ps. The results show that the laser damage threshold fluences (DTFs) of the ultrathin foils are significantly lower than those of corresponding bulk materials. Wide band gap dielectric targets such as SiN and formvar have larger DTFs than semiconductive and conductive targets by 1–3 orders of magnitude depending on the pulse duration. The damage mechanisms for different types of targets are studied. Based on the measurement, the constrain of the LIDTs on the laser contrast is discussed.
The Civic Culture(s): Groups, Norms, and the Health of Democracy
Authors: Kingzette Jon , Neblo Michael A.
Published: December 2020

Democratic institutions need a healthy “civic culture” to function well. Many worry that civic cultures today are decaying in the United States and other established democracies. We note two problems with these assessments. First, there are several ways to measure civic culture, but scholars typically focus only on their preferred approach. Second, most scholars assume a single civic culture, despite racial, ethnic, class, and other differences. So talk of “the” civic culture erases non-dominant groups. Without a framework to integrate different approaches and account for group variation, we cannot assess decline, nor specify for whom. And without those, we are unable to intervene to make things better. We introduce a theory of civic culture as a system of norms that integrates the main approaches to measuring civic culture and does so in a way that leads to a principled framework for understanding racial, ethnic, and other group variation within countries.
GARIBALDI IN AUSTRALIA
Authors: PICKERING PAUL A.
Published: December 2020

One of the most famous public figures in later nineteenth-century Australia was Giuseppe Garibaldi. The man known as the ‘hero of two worlds’ – Europe and South America – was in fact also the hero of a third. The nature of Garibaldi's iconic status in the Australian colonies was complex, multi-faceted, and fractured and it occurred at a moment when the notion of celebrity was being transformed amid what was effectively a fundamental democratization of the public sphere in the Anglophone world. As such, it provides an important opportunity to ponder the implications of what has been called ‘intimacy at a distance’.
Fracturing Constitutional Rights: The Prosecution of Alleged Broadcast Infringers in Nigeria
Authors: Sodipo Bankole
Published: December 2020

Infringement of broadcasts is often treated as a crime. The Nigerian Constitution guarantees that no-one can be prosecuted for any act that is not prescribed in a written law. Section 20 of Nigeria's Copyright Act only criminalizes dealing with infringing copies. A “copy” is defined in terms of material form. An infringing broadcast therefore connotes a recorded broadcast or a copy of a broadcast. This article argues that, statutorily, not every act that gives rise to civil liability for broadcast copyright infringement constitutes a crime. The article reviews the first broadcast copyright prosecution Court of Appeal decision in Eno v Nigerian Copyright Commission. Eno was unlawfully prosecuted, convicted and imprisoned. The article seeks to stem the wave of prosecutions on the type of charges used in Eno. In the absence of law reform, the prosecutions based on the line of charges in Eno constitute a fracturing of constitutional rights.
Cochlear nerve anomalies in paediatric single-sided deafness – prevalence and implications for cochlear implantation strategies
Authors: Pollaers K , Thompson A , Kuthubutheen J
Published: December 2020

Objective

To determine the prevalence of cochlear nerve anomalies on magnetic resonance imaging in patients with unilateral or bilateral sensorineural hearing loss.

Methods

A retrospective case series was conducted at a tertiary referral centre. The inclusion criteria were paediatric patients with bilateral or unilateral sensorineural hearing loss, investigated with magnetic resonance imaging. The primary outcome measure was the rate of cochlear nerve hypoplasia or aplasia.

Results

Of the 72 patients with unilateral sensorineural hearing loss, 39 per cent (28 cases) had absent or hypoplastic cochlear nerves on the affected side. Fifteen per cent (11 cases) had other abnormal findings on magnetic resonance imaging. Eighty-four patients had bilateral sensorineural hearing loss, of which cochlear nerve hypoplasia or aplasia was identified only in 5 per cent (four cases). Other abnormal findings were identified in 14 per cent (12 cases).

Conclusion

Paediatric patients with unilateral sensorineural hearing loss are more likely to have cochlear nerve anomalies than those patients with bilateral sensorineural hearing loss. This has important implications regarding cochlear implantation for patients with single-sided deafness.
On the Relation Between Collective Responsibility and Collective Duties
Authors: de Haan Niels
Published: December 2020

There is good reason to think that moral responsibility as accountability is tied to the violation of moral demands. This lends intuitive support to Type-Symmetry in the collective realm: A type of responsibility entails the violation or unfulfillment of the same type ofall-things-consideredduty. For example, collective responsibility necessarily entails the violation of a collective duty. But Type-Symmetry is false. In this paper I argue that a non-agential group can be collectively responsible without thereby violating a collective duty. To show this I distinguish between four types of responsibility and duty in collective contexts: corporate, distributed, collective, shared. I set out two cases: one involves a non-reductive collective action that constitutes irreducible wrongdoing, the other involves a non-divisible consequence. I show that the violation of individual or shared duties both can lead to irreducible wrongdoing for which only the group is responsible. Finally, I explain why this conclusion does not upset any work on individual responsibility.
A review and analysis of the components of potentially effective perinatal mental health interventions for infant development and mother-infant relationship outcomes
Authors: Newton Katherine , Taylor Buck Elizabeth , Weich Scott , Uttley Lesley
Published: December 2020

Children of mothers with serious mental health difficulties are at increased risk of developing mental health difficulties themselves in their own lifetime. Specialist interventions delivered in perinatal mental health services offer an opportunity to support the infant's development and long-term mental health. This review aimed to systematically evaluate the shared elements of successful perinatal mental health interventions that underpin improved outcomes for infants whose mothers experience perinatal mental health difficulties. Nine electronic databases were searched comprehensively for relevant controlled studies of perinatal mental health interventions, and a narrative synthesis undertaken to assess whether statistically significant benefits were noted. Sixteen studies, trialing 19 interventions, were analyzed using a narrative approach and grouped according to reported effectiveness. Eight interventions demonstrated significant improvements in infant outcomes and/or mother–infant relationship outcomes and were used to inform the analysis of the included interventions’ components. While the interventions identified were diverse, there were common components which potentially underpin successful interventions for infants whose mothers are experiencing mental health difficulties, including: facilitation of positive Mother×Infant interactions; helping mothers to understand their infant's perspective or inner world; and the use of video feedback.
Woe to the vanquished? State, ‘foreign’ banking and financial development in Southern Italy in the nineteenth century
Authors: Chiaruttini Maria Stella
Published: December 2020

After Southern Italy became part of a new, national state in 1860, its financial sector was radically transformed under Piedmontese influence. This article challenges the conventional wisdom that the aggressive penetration of a Northern credit institution, the future Bank of Italy, into the South following unification harmed the local banking system and highlights instead its transformative role in modernising and deepening regional credit markets. On the basis of new statistics, banking and political records, this contribution shows that the introduction of ‘foreign’ banking from Northern Italy under the auspices of a national, constitutional government resulted in a financial revolution and a democratisation of credit supply to the advantage of the whole South. Public banking under the Bourbons had privileged the needs of an absolute government over those of the private economy and of the capital city over those of the rest of the country, retarding financial development. Credit undersupply and regional fragmentation could only be overcome through the integration of the South within a larger Italian market, in which, however, the lion's share went to a predominantly Northern institution.
Historical Mistranslations: Identity, Slavery, and Genre in Eighteenth-Century India
Authors: KHOJA NEELAM
Published: December 2020

Colonial and postcolonial historians writing in English relied upon an emancipated slave's eighteenth-century Persian text,Tahmās Nāma, to construct the history of the Punjab in the same period. In this process, they have mistranslated the text and the genre. Rather than readingTahmās Nāmaas factual history or as a moral text of refinement, this article argues that if we return to the original account, in Persian, we see that the text is primarily auto/biographical. While this auto/biography does provide some insight into eighteenth-century political history of the Punjab and Mughal Hindustan, it—more importantly—sheds light on the ethnic, religious, social, economic and gendered lives of the author, Miskin, and the people whom he includes in his narrative. These intersecting and overlapping identities have been erased, flattened or misrepresented in translations of the text. Based on a re-reading of the auto/biography in its original language, this article considers how identity and slavery—conceptual categories of the present that are elided in the mistranslations—function in the text, and how those categories were understood, negotiated and leveraged during the eighteenth century.
Explaining system-level change in welfare governance: the role of policy indeterminacy and concatenations of social mechanisms
Authors: Ongaro Edoardo , Longo Francesco
Published: December 2020

This paper argues that a certain level of indeterminacy in policy design may be a factor facilitating rather than hindering system-level change in welfare governance arrangements, provided it is combined with the triggering of specific concatenations of social mechanisms shaping the dynamics of the change process. The argument is illustrated by an analysis of a case of systemic change in chronic disease management occurred in the Italian region of Lombardy over 2016–2017, when a radically novel governance of chronic disease for the 10 million population was put in place (a health care system that was later tested to its limits by the COVID-19 pandemic outburst which reached dramatic intensity in this region). This represented a major change in a key area of social and health policy. We claim that such change processes may be studied by means of the conceptual tools of social mechanisms. The analysis of social mechanisms represents a lively research agenda for explaining change in public governance and public policy.
Reconsidering the Conditions for Conducting Confirmatory Factor Analysis
Authors: Ondé Daniel , Alvarado Jesús M.
Published: December 2020

There is a series of conventions governing how Confirmatory Factor Analysis gets applied, from minimum sample size to the number of items representing each factor, to estimation of factor loadings so they may be interpreted. In their implementation, these rules sometimes lead to unjustified decisions, because they sideline important questions about a model’s practical significance and validity. Conducting a Monte Carlo simulation study, the present research shows the compensatory effects of sample size, number of items, and strength of factor loadings on the stability of parameter estimation when Confirmatory Factor Analysis is conducted. The results point to various scenarios in which bad decisions are easy to make and not detectable through goodness of fit evaluation. In light of the findings, these authors alert researchers to the possible consequences of arbitrary rule following while validating factor models. Before applying the rules, we recommend that the applied researcher conduct their own simulation studies, to determine what conditions would guarantee a stable solution for the particular factor model in question.
Impact of Extreme Hot Climate on COVID‐19 Outbreak in India
Authors: Sasikumar Keerthi , Nath Debashis , Nath Reshmita , Chen Wen
Published: December 2020

Coronavirus Disease 2019 (COVID‐19) pandemic poses extreme threat to public health and economy, particularly to the nations with higher population density. The disease first reported in Wuhan, China; later, it spreads elsewhere, and currently, India emerged as COVID‐19 hotspot. In India, we selected 20 densely populated cities having infection counts higher than 500 (by 15 May) as COVID‐19 epicenters. Daily COVID‐19 count has strong covariability with local temperature, which accounts approximately 65–85% of the explained variance; i.e., its spread depends strongly on local temperature rise prior to community transmission phase. The COVID‐19 cases are clustered at temperature and humidity ranging within 27–32°C and 25–45%, respectively. We introduce a combined temperature and humidity profile, which favors rapid COVID‐19 growth at the initial phase. The results are highly significant for predicting future COVID‐19 outbreaks and modeling cities based on environmental conditions. On the other hand, CO2 emission is alarmingly high in South Asia (India) and entails high risk of climate change and extreme hot summer. Zoonotic viruses are sensitive to warming induced climate change; COVID‐19 epicenters are collocated on CO2 emission hotspots. The COVID‐19 count distribution peaks at 31.0°C, which is 1.0°C higher than current (2020) and historical (1961–1990) mean, value. Approximately, 72% of the COVID‐19 cases are clustered at severe to record‐breaking hot extremes of historical temperature distribution spectrum. Therefore, extreme climate change has important role in the spread of COVID‐19 pandemic. Hence, a strenuous mitigation measure to abate greenhouse gas (GHG) emission is essential to avoid such pandemics in future.
Vertical Eddy Diffusivity Parameterization Based on a Large‐Eddy Simulation and Its Impact on Prediction of Hurricane Landfall
Authors: Li Xin , Pu Zhaoxia
Published: December 2020

The vertical eddy diffusivity (VED) in the planetary boundary layer (PBL) affects tropical cyclones' structure and evolution. Uncertainties of VED in the PBL parametrization scheme of a mesoscale model could be caused by the model's inability to represent large eddies (LEs). Using a large‐eddy simulation (LES) of Hurricane Harvey (2017) as a benchmark, the YSU PBL scheme is improved by adding effects of LEs derived from the LES. It is found that LEs' maximum intensity is linearly significantly related to the square of mean horizontal divergence below 400 m of height at the same air column with a slope coefficient of 1.97. The revised YSU scheme relates the VED of momentum (Km) to the square root of LEs' intensity with a slope coefficient of 0.08 in PBL and 0.20 in a free atmosphere. Compared to the original scheme, the modified YSU scheme leads to improved forecasts of landfalling hurricanes.
The Seasonal and Regional Transition to an Ice‐Free Arctic
Authors: Årthun Marius , Onarheim Ingrid H. , Dörr Jakob , Eldevik Tor
Published: December 2020

The Arctic sea ice cover is currently retreating and will continue its retreat in a warming world. However, the loss of sea ice is neither regionally nor seasonally uniform. Here, we present the first regional and seasonal assessment of future Arctic sea ice loss in CMIP6 models under low (SSP126) and high (SSP585) emission scenarios, thus spanning the range of future change. We find that Arctic sea ice loss—at present predominantly limited to the summer season—will under SSP585 take place in all regions and all months. The summer sea ice is lost in all the shelf seas regardless of emission scenario, whereas ice‐free conditions in winter before the end of this century only occur in the Barents Sea. The seasonal transition to ice‐free conditions is found to spread through the Atlantic and Pacific regions, with change starting in the Barents Sea and Chukchi Sea, respectively.
Discrete Rising Tone Elements of Whistler‐Mode Waves in the Vicinity of the Moon: ARTEMIS Observations
Authors: Sawaguchi W. , Harada Y. , Kurita S.
Published: December 2020

We report on discrete rising‐tone elements of whistler‐mode waves observed by Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moon's Interaction with the Sun (ARTEMIS) in the vicinity of the Moon. The two‐probe ARTEMIS observations suggest that a free energy source for the wave generation is provided by electron anisotropy resulting from lunar surface absorption and magnetic reflection. High time resolution dynamic spectra reveal that the waves consist of multiple rising tone elements, exhibiting striking similarities to the well‐known whistler‐mode chorus in planetary magnetospheres. The observed frequency sweep rates are generally consistent with those predicted by the nonlinear growth theory of chorus emissions by Omura et al. (2008, https://doi.org/10.1029/2007JA012622). These results imply that whistler‐mode waves can grow nonlinearly into chorus‐like emissions even around airless bodies without magnetospheres and that a well‐defined dipole field is not a prerequisite for the chorus generation.
Initiation of an Elevated Mesoscale Convective System With the Influence of Complex Terrain During Meiyu Season
Authors: Zhang Fan , Zhang Qinghong , Sun Juanzhen
Published: December 2020

A mesoscale convective system (MCS) was initiated on the lee side of the Wuling Mountain in central‐east China in the late afternoon (1700 LT) on June 27, 2016, and led to an early morning precipitation peak. We investigated the convective initiation (CI) mechanism of this MCS using radars and automatic weather station observations, WRF model simulation, and analysis from the radar data assimilation system Variational Doppler Radar Analysis System. It was found that the convection initiation was elevated as indicated by an elevated convergence zone and updraft located above 1,625 m from the ground. A zero convective inhibition layer was located at 850 hPa, over a stable boundary layer (BL) resulting from the daytime rainfall in the plain region, and provided a favorable condition for the elevated CI. Our study suggested that the transition of mountain‐plain thermal wind near sunset was the trigger for the convective initiation. An early afternoon mountain‐plain thermal circulation was disrupted when the east‐facing lee side slope was in the shadow of sunshine after 4 p.m. As a result, a local‐scale northwest downslope wind accelerated and led to a downstream convergence above the stable BL, where the elevated convection was initiated near 1,625 m above ground level. By combining the model simulation, the analysis from data assimilation, and the observations, this study is the first to provide a detailed analysis of CI mechanism of elevated convection in a complex topography region during the Meiyu season in China.
Process‐Based Climate Model Development Harnessing Machine Learning: I. A Calibration Tool for Parameterization Improvement
Authors: Couvreux Fleur , Hourdin Frédéric , Williamson Daniel , Roehrig Romain , Volodina Victoria , Villefranque Najda , Rio Catherine , Audouin Olivier , Salter James , Bazile Eric , Brient Florent , Favot Florence , Honnert Rachel , Lefebvre Marie‐Pierre , Madeleine Jean‐Baptiste , Rodier Quentin , Xu Wenzhe
Published: December 2020

The development of parameterizations is a major task in the development of weather and climate models. Model improvement has been slow in the past decades, due to the difficulty of encompassing key physical processes into parameterizations, but also of calibrating or “tuning” the many free parameters involved in their formulation. Machine learning techniques have been recently used for speeding up the development process. While some studies propose to replace parameterizations by data‐driven neural networks, we rather advocate that keeping physical parameterizations is key for the reliability of climate projections. In this paper we propose to harness machine learning to improve physical parameterizations. In particular, we use Gaussian process‐based methods from uncertainty quantification to calibrate the model free parameters at a process level. To achieve this, we focus on the comparison of single‐column simulations and reference large‐eddy simulations over multiple boundary‐layer cases. Our method returns all values of the free parameters consistent with the references and any structural uncertainties, allowing a reduced domain of acceptable values to be considered when tuning the three‐dimensional (3D) global model. This tool allows to disentangle deficiencies due to poor parameter calibration from intrinsic limits rooted in the parameterization formulations. This paper describes the tool and the philosophy of tuning in single‐column mode. Part 2 shows how the results from our process‐based tuning can help in the 3D global model tuning.
Chloroquine reverses chemoresistance via upregulation of p21WAF1/CIP1 and autophagy inhibition in ovarian cancer
Authors: Hwang Jae Ryoung , Kim Woo Young , Cho Young-Jae , Ryu Ji-Yoon , Choi Jung-Joo , Jeong Soo Young , Kim Myeong-Sun , Kim Ji Hye , Paik E. Sun , Lee Yoo-Young , Han Hee-Dong , Lee Jeong-Won
Published: December 2020

Overcoming drug-resistance is a big challenge to improve the survival of patients with epithelial ovarian cancer (EOC). In this study, we investigated the effect of chloroquine (CQ) and its combination with cisplatin (CDDP) in drug-resistant EOC cells. We used the three EOC cell lines CDDP-resistant A2780-CP20, RMG-1 cells, and CDDP-sensitive A2780 cells. The CQ-CDDP combination significantly decreased cell proliferation and increased apoptosis in all cell lines. The combination induced expression of γH2AX, a DNA damage marker protein, and induced G2/M cell cycle arrest. Although the CQ-CDDP combination decreased protein expression of ATM and ATR, phosphorylation of ATM was increased and expression of p21WAF1/CIP1 was also increased in CQ-CDDP-treated cells. Knockdown of p21WAF1/CIP1 by shRNA reduced the expression of γH2AX and phosphorylated ATM and inhibited caspase-3 activity but induced ATM protein expression. Knockdown of p21WAF1/CIP1 partly inhibited CQ-CDDP-induced G2/M arrest, demonstrating that knockdown of p21WAF1/CIP1 overcame the cytotoxic effect of the CQ-CDDP combination. Ectopic expression of p21WAF1/CIP1 in CDDP-treated ATG5-shRNA/A2780-CP20 cells increased expression of γH2AX and caspase-3 activity, demonstrating increased DNA damage and cell death. The inhibition of autophagy by ATG5-shRNA demonstrated similar results upon CDDP treatment, except p21WAF1/CIP1 expression. In an in vivo efficacy study, the CQ-CDDP combination significantly decreased tumor weight and increased expression of γH2AX and p21WAF1/CIP1 in A2780-CP20 orthotopic xenografts and a drug-resistant patient-derived xenograft model of EOC compared with controls. These results demonstrated that CQ increases cytotoxicity in combination with CDDP by inducing lethal DNA damage by induction of p21WAF1/CIP1 expression and autophagy inhibition in CDDP-resistant EOC.
Author Correction: Synthesizing ginsenoside Rh2 in Saccharomyces cerevisiae cell factory at high-efficiency
Authors: Wang Pingping , Wei Wei , Ye Wei , Li Xiaodong , Zhao Wenfang , Yang Chengshuai , Li Chaojing , Yan Xing , Zhou Zhihua
Published: December 2020

A Correction to this paper has been published: https://doi.org/10.1038/s41421-020-00234-1.
Benefits of clinical criteria and high-throughput sequencing for diagnosing children with syndromic craniosynostosis
Authors: Tønne Elin , Due-Tønnessen Bernt Johan , Mero Inger-Lise , Wiig Ulrikke Straume , Kulseth Mari Ann , Vigeland Magnus Dehli , Sheng Ying , von der Lippe Charlotte , Tveten Kristian , Meling Torstein Ragnar , Helseth Eirik , Heimdal Ketil Riddervold
Published: December 2020

An accurate diagnosis of syndromic craniosynostosis (CS) is important for personalized treatment, surveillance, and genetic counselling. We describe detailed clinical criteria for syndromic CS and the distribution of genetic diagnoses within the cohort. The prospective registry of the Norwegian National Unit for Craniofacial Surgery was used to retrieve individuals with syndromic CS born between 1 January 2002 and 30 June 2019. All individuals were assessed by a clinical geneticist and classified using defined clinical criteria. A stepwise approach consisting of single-gene analysis, comparative genomic hybridization (aCGH), and exome-based high-throughput sequencing, first filtering for 72 genes associated with syndromic CS, followed by an extended trio-based panel of 1570 genes were offered to all syndromic CS cases. A total of 381 individuals were registered with CS, of whom 104 (27%) were clinically classified as syndromic CS. Using the single-gene analysis, aCGH, and custom-designed panel, a genetic diagnosis was confirmed in 73% of the individuals (n = 94). The diagnostic yield increased to 84% after adding the results from the extended trio-based panel. Common causes of syndromic CS were found in 53 individuals (56%), whereas 26 (28%) had other genetic syndromes, including 17 individuals with syndromes not commonly associated with CS. Only 15 individuals (16%) had negative genetic analyses. Using the defined combination of clinical criteria, we detected among the highest numbers of syndromic CS cases reported, confirmed by a high genetic diagnostic yield of 84%. The observed genetic heterogeneity encourages a broad genetic approach in diagnosing syndromic CS.
Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions
Authors: OʼShea Timothy M. , Wollenberg Alexander L. , Kim Jae H. , Ao Yan , Deming Timothy J. , Sofroniew Michael V.
Published: December 2020

Biomaterials hold promise for therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo, or about how such responses influence biomaterial function. Here, we probed these factors in mice using a platform of injectable hydrogels readily modified to present interfaces with different physiochemical properties to host cells. We found that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. We show that the nature and intensity of CNS FBRs are determined by definable properties that significantly influence hydrogel functions, including resorption and molecular delivery when injected into healthy brain or stroke injuries. Cationic interfaces elicit stromal cell infiltration, peripherally derived inflammation, neural damage and amyloid production. Nonionic and anionic formulations show minimal levels of these responses, which contributes to superior bioactive molecular delivery. Our results identify specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications.
A ventrolateral medulla-midline thalamic circuit for hypoglycemic feeding
Authors: Sofia Beas B. , Gu Xinglong , Leng Yan , Koita Omar , Rodriguez-Gonzalez Shakira , Kindel Morgan , Matikainen-Ankney Bridget A. , Larsen Rylan S. , Kravitz Alexxai V. , Hoon Mark A. , Penzo Mario A.
Published: December 2020

Marked deficits in glucose availability, or glucoprivation, elicit organism-wide counter-regulatory responses whose purpose is to restore glucose homeostasis. However, while catecholamine neurons of the ventrolateral medulla (VLMCA) are thought to orchestrate these responses, the circuit and cellular mechanisms underlying specific counter-regulatory responses are largely unknown. Here, we combined anatomical, imaging, optogenetic and behavioral approaches to interrogate the circuit mechanisms by which VLMCA neurons orchestrate glucoprivation-induced food seeking behavior. Using these approaches, we found that VLMCA neurons form functional connections with nucleus accumbens (NAc)-projecting neurons of the posterior portion of the paraventricular nucleus of the thalamus (pPVT). Importantly, optogenetic manipulations revealed that while activation of VLMCA projections to the pPVT was sufficient to elicit robust feeding behavior in well fed mice, inhibition of VLMCA–pPVT communication significantly impaired glucoprivation-induced feeding while leaving other major counterregulatory responses intact. Collectively our findings identify the VLMCA–pPVT–NAc pathway as a previously-neglected node selectively controlling glucoprivation-induced food seeking. Moreover, by identifying the ventrolateral medulla as a direct source of metabolic information to the midline thalamus, our results support a growing body of literature on the role of the PVT in homeostatic regulation.
Pandemic Vibrio cholerae shuts down site-specific recombination to retain an interbacterial defence mechanism
Authors: Santoriello Francis J. , Michel Lina , Unterweger Daniel , Pukatzki Stefan
Published: December 2020

Vibrio cholerae is an aquatic microbe that can be divided into three subtypes: harmless environmental strains, localised pathogenic strains, and pandemic strains causing global cholera outbreaks. Each type has a contact-dependent type VI secretion system (T6SS) that kills neighbouring competitors by translocating unique toxic effector proteins. Pandemic isolates possess identical effectors, indicating that T6SS effectors may affect pandemicity. Here, we show that one of the T6SS gene clusters (Aux3) exists in two states: a mobile, prophage-like element in a small subset of environmental strains, and a truncated Aux3 unique to and conserved in pandemic isolates. Environmental Aux3 can be readily excised from and integrated into the genome via site-specific recombination, whereas pandemic Aux3 recombination is reduced. Our data suggest that environmental Aux3 acquisition conferred increased competitive fitness to pre-pandemic V. cholerae, leading to grounding of the element in the chromosome and propagation throughout the pandemic clade.
A substrateless, flexible, and water-resistant organic light-emitting diode
Authors: Keum Changmin , Murawski Caroline , Archer Emily , Kwon Seonil , Mischok Andreas , Gather Malte C.
Published: December 2020

Despite widespread interest, ultrathin and highly flexible light-emitting devices that can be seamlessly integrated and used for flexible displays, wearables, and as bioimplants remain elusive. Organic light-emitting diodes (OLEDs) with µm-scale thickness and exceptional flexibility have been demonstrated but show insufficient stability in air and moist environments due to a lack of suitable encapsulation barriers. Here, we demonstrate an efficient and stable OLED with a total thickness of ≈ 12 µm that can be fully immersed in water or cell nutrient media for weeks without suffering substantial degradation. The active layers of the device are embedded between conformal barriers formed by alternating layers of parylene-C and metal oxides that are deposited through a low temperature chemical vapour process. These barriers also confer stability of the OLED to repeated bending and to extensive postprocessing, e.g. via reactive gas plasmas, organic solvents, and photolithography. This unprecedented robustness opens up a wide range of novel possibilities for ultrathin OLEDs.
High-throughput preparation of radioprotective polymers via Hantzsch’s reaction for in vivo X-ray damage determination
Authors: Liu Guoqiang , Zeng Yuan , Lv Tong , Mao Tengfei , Wei Yen , Jia Shunji , Gou Yanzi , Tao Lei
Published: December 2020

Radioprotectors for acute injuries caused by large doses of ionizing radiation are vital to national security, public health and future development of humankind. Here, we develop a strategy to explore safe and efficient radioprotectors by combining Hantzsch’s reaction, high-throughput methods and polymer chemistry. A water-soluble polymer with low-cytotoxicity and an excellent anti-radiation capability has been achieved. In in vivo experiments, this polymer is even better than amifostine, which is the only approved radioprotector for clinical applications, in effectively protecting zebrafish embryos from fatally large doses of ionizing radiation (80 Gy X-ray). A mechanistic study also reveals that the radioprotective ability of this polymer originates from its ability to efficiently prevent DNA damage due to high doses of radiation. This is an initial attempt to explore polymer radioprotectors via a multi-component reaction. It allows exploiting functional polymers and provides the underlying insights to guide the design of radioprotective polymers.
Split-pulse X-ray photon correlation spectroscopy with seeded X-rays from X-ray laser to study atomic-level dynamics
Authors: Shinohara Yuya , Osaka Taito , Inoue Ichiro , Iwashita Takuya , Dmowski Wojciech , Ryu Chae Woo , Sarathchandran Yadu , Egami Takeshi
Published: December 2020

With their brilliance and temporal structure, X-ray free-electron laser can unveil atomic-scale details of ultrafast phenomena. Recent progress in split-and-delay optics (SDO), which produces two X-ray pulses with time-delays, offers bright prospects for observing dynamics at the atomic-scale. However, their insufficient pulse energy has limited its application either to phenomena with longer correlation length or to measurement with a fixed delay-time. Here we show that the combination of the SDO and self-seeding of X-rays increases the pulse energy and makes it possible to observe the atomic-scale dynamics in a timescale of picoseconds. We show that the speckle contrast in scattering from water depends on the delay-time as expected. Our results demonstrate the capability of measurement using the SDO with seeded X-rays for resolving the dynamics in temporal and spatial scales that are not accessible by other techniques, opening opportunities for studying the atomic-level dynamics.