bluuebunny/crossref_metadata_2025 huggingface dataset:
Setting empirically informed content knowledge policy benchmarks for physical science teaching
Authors: Lewis Elizabeth B. , Rivero Ana M. , Lucas Lyrica L. , Musson Aaron A. , Helding Brandon A.
Published: May 2021

In the United States, research on beginning science teachers provides little guidance regarding empirical minimum levels of discipline‐specific science coursework for sufficient subject matter knowledge to teach science. Accordingly, in this study we analyzed secondary physical science teachers' science coursework for subject matter knowledge (SMK) and resulting misconceptions of chemistry and physics concepts. Findings were compared with state‐level science teacher certification policies. Participants had either: (a) completed a master's level teacher preparation program with an undergraduate degree in science, (b) completed an undergraduate teacher preparation program with a minor degree or more in science, or (c) were undergraduate students enrolled in science courses required for chemistry and physics teacher certification. We analyzed participants' transcripts for discipline‐specific science coursework credit hours and GPAs and identified possible predictors of SMK predictors of the likelihood of passing chemistry and physics misconceptions tests. We categorized teachers' level of SMK and used multiple variable and logistic regressions (n = 212 participants; n = 109 chemistry and n = 103 physics). To identify teacher candidates' possible misconceptions, we analyzed chemistry (n = 97) and physics (n = 91) participants' item responses with the corresponding science credit hours and GPAs. With increasing numbers of credit hours teachers held fewer misconceptions. However, even with medium to high SMK levels, teachers still held misconceptions about chemical bonding, electromagnetism, and Newton's laws until they reached critical credit hour and GPA thresholds. Lastly, we provide recommendations for physical science teachers' programs of study and state‐level teaching certification policies, using empirical minimum quantity and quality of chemistry, physics, and mathematics coursework.
Redressing the Balance in the Native Speaker Debate: Assessment Standards, Standard Language, and Exposing Double Standards
Authors: Isaacs Talia , Rose Heath
Published: May 2021

In his philosophical novel, Thus spoke Zarathustra, Nietzsche (1883–85), famously wrote, ‘God is dead,’ signifying that God is no longer credible as an absolute moral compass. Over a century later, Paikeday (1985), proclaimed that The native speaker is dead! in his book title, implying that the native speaker as the arbiter of what is correct in a language is obsolete. This paper discusses this complex, contentious ideological issue from language assessment and sociolinguistic standpoints against the backdrop of global Englishes. After highlighting difficulties identifying standard language norms, we discuss the practical need of having some assessment standard against which to evaluate language performance. Proposals as to what that standard should be are then critiqued in view of ways that second language proficiency has been operationalized in assessment systems. Next, we argue against vilifying those who use the term ‘native speaker’ and consider terminological problems introduced by some reconceptualizing efforts. We argue that we have a long way to go as a field before reaching a truly post‐native speaker era, which would seem to be a reasonable aspiration for most, but not necessarily all contexts, and propose recommendations for addressing pressing research problems. This includes standardizing terminology to incorporate semantically transparent terms, exploring assessment alternatives that focus more on language use than standard language adherence, improving scoring systems to remove nativeness from the equation when inappropriate, and acknowledging a place for accuracy‐focused research within a broad tent of applied linguistics research traditions.
1D, 2D, and 3D Coordination Polymers based on 2,3‐Pyrazinedithiolate and d10 Metal Ions (Ag+, Zn2+)
Authors: Henfling Stefan , Saputra Ozi Adi , Krautscheid Harald
Published: May 2021

Dithiolene based coordination polymers, due to their coordinative bonds with covalent character, feature interesting electrical properties. We present the syntheses and crystal structures of three coordination polymers based on the ligand 2,3‐pyrazinedithiolate (pdt2−) and Ag+ and Zn2+ ions. 2D[Ag3(Hpdt)2](ClO4) (1) and Cs1D[Ag(pdt)] ⋅ CH3OH (2) feature short Ag⋅⋅⋅Ag distances, 3D[Zn(pdt)] (3) has a 3D network structure and is stable up to 480 °C. The optical band gaps of the three coordination polymers are within the visible range of the electromagnetic spectrum. The coordination polymer 1 has the smallest bandgap of 1.8 eV, 2 and 3, with the fully deprotonated ligand, exhibit wider bandgaps of 2.5 and 2.7 eV, respectively.
The primitive equations in the scaling-invariant space $$L^{\infty }(L^1)$$
Authors: Giga Yoshikazu , Gries Mathis , Hieber Matthias , Hussein Amru , Kashiwabara Takahito
Published: May 2021

Consider the primitive equations on$$\mathbb {R}^2\times (z_0,z_1)$$R2×(z0,z1)with initial dataaof the form$$a=a_1+a_2$$a=a1+a2, where$$a_1 \in \mathrm{BUC}_\sigma (\mathbb {R}^2;L^1(z_0,z_1))$$a1∈BUCσ(R2;L1(z0,z1))and$$a_2 \in L^\infty _\sigma (\mathbb {R}^2;L^1(z_0,z_1))$$a2∈Lσ∞(R2;L1(z0,z1)). These spaces are scaling-invariant and represent the anisotropic character of these equations. It is shown that for$$a_1$$a1arbitrary large and$$a_2$$a2sufficiently small, this set of equations admits a unique strong solution which extends to a global one and is thus strongly globally well posed for these data providedais periodic in the horizontal variables. The approach presented depends crucially on mapping properties of the hydrostatic Stokes semigroup in the$$L^\infty (L^1)$$L∞(L1)-setting. It can be seen as the counterpart of the classical iteration schemes for the Navier–Stokes equations, now for the primitive equations in the$$L^\infty (L^1)$$L∞(L1)-setting.
Thermischer Einfluss urbaner Untergrundstrukturen auf die Grundwassertemperaturen im Kanton Basel-Stadt
Authors: Becker Dominic , Epting Jannis
Published: May 2021

In Basel (CH) wurde mit Monitoringsystemen der thermische Einfluss unterschiedlicher Untergrundstrukturen, einschließlich fünf Tiefgaragen sowie einem Autobahntunnel, auf die urbanen Grundwasserressourcen untersucht. Die Daten wurden anschließend mit gemessenen Meteo- und Grundwassertemperaturdaten sowie Resultaten einer Wämetransportmodellierung zusammenhängend ausgewertet.

In den Tiefgaragen wurden auch über die Wintermonate deutlich erhöhte durchschnittliche Temperaturen zwischen 18,8 und 21,1 °C erfasst. Über den weitaus größten Zeitraum emittieren die Tiefgaragen somit Wärme in den Untergrund. Die Messdaten im Autobahntunnel hingegen deuten darauf hin, dass in den Sommermonaten zwar auch Wärme in den Untergrund emittiert, im Winterhalbjahr aber Wärme aus dem Untergrund absorbiert wird.

Zudem zeigen die Temperaturverläufe in den Tiefgaragen eine klare Abhängigkeit von der Nutzungsart: bei höherem Aufkommen täglicher Ein- und Ausfahrten konnten größere tägliche Temperaturanstiege nachgewiesen werden, mit Unterschieden von bis zu 2 °C in den Tagesmittelwerten. Besonders deutlich wird dies im Zeitraum des „Lockdowns“ während der COVID-19-Pandemie zwischen März und Mai 2020.
Recrystallization and size distribution of dislocated segments in cellulose microfibrils—a molecular dynamics perspective
Authors: Khodayari Ali , Hirn Ulrich , Spirk Stefan , Van Vuure Aart W. , Seveno David
Published: May 2021

The arrangement of cellulose molecules in natural environment on the nanoscale is still not fully resolved, with longitudinal disorder in cellulose microfibrils (CMF) being one relevant question. Particularly the length of the dislocated cellulose segments in CMFs is still under debate. Using molecular dynamics simulations, we are first investigating the phenomenon of pseudo-recrystallization of dislocated cellulose regions after cleavage of CMFs. Based on our simulations we propose that 3–4 glucose residues bordering to each side of a cellulose nanocrystal are actually reorganizing to a quasi-crystalline state, which are corroborating recent analytical investigations reporting an increase in crystallinity after acid vapor hydrolysis of CMFs. Combining our molecular dynamics simulation results with these analytical data we can estimate the length of the dislocated cellulose segments in CMFs. We propose that, for the investigated sources of biomass (cotton and ramie), the dislocation lengths are between 3.1–5.8 nm equaling to 6–11 glucose residues in the cellulose crystallites.

Graphic abstract
Seeking Justice and Redress for Victim-Survivors of Image-Based Sexual Abuse
Authors: Rackley Erika , McGlynn Clare , Johnson Kelly , Henry Nicola , Gavey Nicola , Flynn Asher , Powell Anastasia
Published: May 2021

Despite apparent political concern and action—often fuelled by high-profile cases and campaigns—legislative and institutional responses to image-based sexual abuse in the UK have been ad hoc, piecemeal and inconsistent. In practice, victim-survivors are being consistently failed: by the law, by the police and criminal justice system, by traditional and social media, website operators, and by their employers, universities and schools. Drawing on data from the first multi-jurisdictional study of the nature and harms of, and legal/policy responses to, image-based sexual abuse, this article argues for a new joined-up approach that supports victim-survivors of image-based sexual abuse to ‘reclaim control’. It argues for a comprehensive, multi-layered, multi-institutional and multi-agency response, led by a government- and industry-funded online or e-safety organisation, which not only recognises the diversity of victim-survivor experiences and the intersection of image-based sexual abuse with other forms of sexual and gender-based violence and discrimination, but which also enables victim-survivors to reclaim control within and beyond the criminal justice system.
Volatile Anesthetic Sevoflurane Precursor 1,1,1,3,3,3-Hexafluoro-2-Propanol (HFIP) Exerts an Anti-Prion Activity in Prion-Infected Culture Cells
Authors: Shimizu Takuto , Nogami Emiko , Ito Yuka , Morikawa Kazuo , Nagane Masaki , Yamashita Tadashi , Ogawa Tsuyoshi , Kametani Fuyuki , Yagi Hisashi , Hachiya Naomi
Published: May 2021

Prion disease is a neurodegenerative disorder with progressive neurologic symptoms and accelerated cognitive decline. The causative protein of prion disease is the prion protein (PrP), and structural transition of PrP from the normal helix rich form (PrPC) to the abnormal β-sheet rich form (PrPSc) occurs in prion disease. While so far numerous therapeutic agents for prion diseases have been developed, none of them are still useful. A fluorinated alcohol, hexafluoro isopropanol (HFIP), is a precursor to the inhalational anesthetic sevoflurane and its metabolites. HFIP is also known as a robust α-helix inducer and is widely used as a solvent for highly aggregated peptides. Here we show that the α-helix-inducing activity of HFIP caused the conformational transformation of the fibrous structure of PrP into amorphous aggregates in vitro. HFIP added to the ScN2a cell medium, which continuously expresses PrPSc, reduced PrPSc protease resistance after 24-h incubation. It was also clarified that ScN2a cells are more susceptible to HFIP than any of the cells being compared. Based on these findings, HFIP is expected to develop as a therapeutic agent for prion disease.
Uncertainties of Sub-Scaled Supply and Demand in Agent-Based Mobility Simulations with Queuing Traffic Model
Authors: Saprykin Aleksandr , Chokani Ndaona , Abhari Reza S.
Published: May 2021

Agent-based models for dynamic traffic assignment simulate the behaviour of individual, or group of, agents, and then the simulation outcomes are observed on the scale of the system. As large-scale simulations require substantial computational power and have long run times, most often a sample of the full population and downscaled road capacities are used as simulation inputs, and then the simulation outcomes are scaled up. Using a massively parallelized mobility model on a large-scale test case of the whole of Switzerland, which includes 3.5 million private vehicles and 1.7 million users of public transit, we have systematically quantified, from 6 105 simulations of a weekday, the impacts of scaled input data on simulation outputs. We show, from simulations with population samples ranging from 1% to 100% of the full population and corresponding scaling of the traffic network, that the simulated traffic dynamics are driven primarily by the flow capacity, rather than the spatial properties, of the traffic network. Using a new measure of traffic similarity, that is based on the chi-squared test statistic, it is shown that the dynamics of the vehicular traffic and the occupancy of the public transit are adversely impacted when population samples less than 30% of the full population are used. Moreover, we present evidence that the adverse impact of population sampling is determined mostly by the patterns of the agents’ behaviour rather than by the traffic model.
Management of a district heating network using model predictive control with and without thermal storage
Authors: Quaggiotto Davide , Vivian Jacopo , Zarrella Angelo
Published: May 2021

District heating and cooling networks are a key infrastructure to decarbonise the heating and cooling sector. Besides the design of new networks according to the principles of the 4th and 5th generation, operational aspects may significantly contribute to improve the efficiency of existing networks from both economic and environmental standpoints. This article is the second step of a work that aims to exploit the flexibility of existing networks and improve their economic and environmental performance, using the district heating network of Verona as a case study. In particular, the first part of the research demonstrated through numerical simulations that the thermal inertia of the water contained in the pipes can be used to shift the heat production of the generators over time by acting on the flow rate circulating in the network. This article shifts the focus from the heat distribution side to the heat supply. A model predictive control strategy was formulated as a MILP optimization problem to schedule the heat supply of the cogeneration plants, heat pump and gas boilers as a function of heat load, waste heat production and electricity price forecasts. Computer simulations of considered district heating network were carried out executing the optimization with a rolling-horizon scheme over two typical weeks. Results show that the proposed look-ahead control achieves a reduction in the operational costs of about 12.5% and 5.8%, respectively in a middle season and a winter representative week. Increasing the flexibility of the system with a centralized heat storage tank connected to the CHP and HP units, these percentage rise to respectively 20% and 6.3%. In the warmest periods, when the total installed power of the CHP and HP plants is sufficient to supply the entire heat demand during the peak, and the modulation of these plants has a higher impact, the cost reduction related to the additional thermal energy storage is more relevant.
Arithmetic, enumerative induction and size bias
Authors: Paseau A. C.
Published: May 2021

Number theory abounds with conjectures asserting that every natural number has some arithmetic property. An example is Goldbach’s Conjecture, which states that every even number greater than 2 is the sum of two primes. Enumerative inductive evidence for such conjectures usually consists of small cases. In the absence of supporting reasons, mathematicians mistrust such evidence for arithmetical generalisations, more so than most other forms of non-deductive evidence. Some philosophers have also expressed scepticism about the value of enumerative inductive evidence in arithmetic. But why? Perhaps the best argument is that known instances of an arithmetical conjecture are almost always small: they appear at the start of the natural number sequence. Evidence of this kind consequently suffers from size bias. My essay shows that this sort of scepticism comes in many different flavours, raises some challenges for them all, and explores their respective responses.
Recent Trends on the Dehydrogenation Catalysis of Liquid Organic Hydrogen Carrier (LOHC): A Review
Authors: Sekine Yasushi , Higo Takuma
Published: May 2021

Considering the expansion of the use of renewable energy in the future, the technology to store and transport hydrogen will be important. Hydrogen is gaseous at an ambient condition, diffuses easily, and its energy density is low. So liquid organic hydrogen carriers (LOHCs) have been proposed as a way to store hydrogen in high density. LOHC can store, transport, and use hydrogen at high density by hydrogenation and dehydrogenation cycles. In this review, we will focus on typical LOHCs, methylcyclohexane (MCH), 18H-dibenzyltoluene (DBT), and 12H-N-ethylcarbazole (NECZ), and summarize recent developments in dehydrogenation catalytic processes, which are key in this cycle.
CT radiomic models to distinguish COVID-19 pneumonia from other interstitial pneumonias
Authors: Cardobi Nicolò , Benetti Giulio , Cardano Giuseppe , Arena Cinzia , Micheletto Claudio , Cavedon Carlo , Montemezzi Stefania
Published: May 2021

Purpose

To classify COVID-19, COVID-19-like and non-COVID-19 interstitial pneumonia using lung CT radiomic features.

Material and Methods

CT data of 115 patients with respiratory symptoms suspected for COVID-19 disease were retrospectively analyzed. Based on the results of nasopharyngeal swab, patients were divided into two main groups, COVID-19 positive (C +) and COVID-19 negative (C−), respectively. C− patients, however, presented with interstitial lung involvement. A subgroup of C−, COVID-19-like (CL), were considered as highly suggestive of COVID pneumonia at CT. Radiomic features were extracted from the whole lungs. A dual machine learning (ML) model approach was used. The first one excluded CL patients from the training set, eventually included on the test set. The second model included the CL patients also in the training set.

Results

The first model classified C + and C− pneumonias with AUC of 0.83. CL median response (0.80) was more similar to C + (0.92) compared to C− (0.17). Radiomic footprints of CL were similar to the C + ones (possibly false negative swab test). The second model, however, merging C + with CL patients in the training set, showed a slight decrease in classification performance (AUC = 0.81).

Conclusion

Whole lung ML models based on radiomics can classify C + and C− interstitial pneumonia. This may help in the correct management of patients with clinical and radiological stigmata of COVID-19, however presenting with a negative swab test. CL pneumonia was similar to C + pneumonia, albeit with slightly different radiomic footprints.
A systematic review of pathophysiology and management of familial hyperaldosteronism type 1 in pregnancy
Authors: Sanga Viola , Seccia Teresa Maria , Rossi Gian Paolo
Published: May 2021

Purpose

Familial hyperaldosteronism type 1 (FH-1) is a rare autosomal dominant form of primary aldosteronism, which features a marked phenotypic heterogeneity, ranging from mild to severe forms of arterial hypertension that can be complicated by stroke and cardiovascular events at a young age. As affected patients usually reach the fertile age, transmission of the disease to offspring is common. Notwithstanding this, reports of FH-1 in pregnancy are limited and there is a lack of treatment guidelines.

Methods and results

We searched the PubMed and EuropePMC databases with a PICO strategy to retrieve available information on management of FH-1 patients during pregnancy. We could identify seven relevant articles, which are herein reviewed.

Conclusion

Based on available information on pathophysiology and treatment of FH-1 in pregnancy, recommendations for the rational management of FH-1 in pregnancy are provided.
Identification of novel plant architecture mutants in barley
Authors: Mohammadi Aghdam Sina , Abdollahi Mandoulakani Babak , Rossini Laura , Janiak Agnieszka , Shaaf Salar
Published: May 2021

In grasses, biomass and grain production are affected by plant architecture traits such as tiller number, leaf size and orientation. Thus, knowledge regarding their genetic basis is a prerequisite for developing new improved varieties. Mutant screens represent a powerful approach to identify genetic factors underpinning these traits: the HorTILLUS population, obtained by mutagenesis of spring two-row cultivar Sebastian, is a valuable resource for this purpose in barley. In this study, 20 mutant families from the HorTILLUS population were selected and evaluated for tiller number, leaf angle and a range of other plant architecture and agronomic traits using an unreplicated field design with Sebastian as a check cultivar. Principal Component Analysis revealed strong relationships among number of tillers, upper canopy leaf angle, biomass and yield-related traits. Comparison to the Sebastian background revealed that most mutants significantly differed from the wild-type for multiple traits, including two mutants with more erect leaves and four mutants with increased tiller number in at least one phenological stage. Heatmap clustering identified two main groups: the first containing the two erect mutants and the second containing Sebastian and the high-tillering mutants. Among the high-tillering mutants, two showed significantly higher biomass and grain yield per plant compared to Sebastian. The selected mutants represent promising materials for the identification of genetic factors controlling tillering and leaf angle in barley.
Point Processes and Jump Diffusions
Authors: Björk Tomas
Published: May 2021

The theory of marked point processes on the real line is of great and increasing importance in areas such as insurance mathematics, queuing theory and financial economics. However, the theory is often viewed as technically and conceptually difficult and has proved to be a block for PhD students looking to enter the area. This book gives an intuitive picture of the central concepts as well as the deeper results, while presenting the mathematical theory in a rigorous fashion and discussing applications in filtering theory and financial economics. Consequently, readers will get a deep understanding of the theory and how to use it. A number of exercises of differing levels of difficulty are included, providing opportunities to put new ideas into practice. Graduate students in mathematics, finance and economics will gain a good working knowledge of point-process theory, allowing them to progress to independent research.
Fatty acids: facts vs. fiction
Authors: Waehler Reinhard
Published: May 2021

Abstract: During the last 100 years official dietary guidelines have recommended an increased consumption of fats derived from seeds while decreasing the consumption of traditional fats, especially saturated fats. These recommendations are being challenged by recent studies. Furthermore, the increased use of refining processes in fat production had deleterious health effects. Today, the number of high-quality studies on fatty acids is large enough to make useful recommendations on clinical application and everyday practice. Saturated fats have many beneficial functions and palmitic acid appears to be problematic only when it is synthesized due to excess fructose consumption. Trans fatty acids were shown to be harmful when they are manmade but beneficial when of natural origin. Conjugated linoleic acid has many benefits but the isomer mix that is available in supplement form differs from its natural origin and may better be avoided. The ω3 fatty acid linolenic acid has rather limited use as an anti-inflammatory agent – a fact that is frequently overlooked. On the other hand, the targeted use of long chain ω3 fatty acids based on blood analysis has great potential to supplement or even be an alternative to various pharmacological therapies. At the same time ω6 fatty acids like linoleic acid and arachidonic acid have important physiological functions and should not be avoided but their consumption needs to be balanced with long chain ω3 fatty acids. The quality and quantity of these fats together with appropriate antioxidative protection are critical for their positive health effects.
Parameterization of Submesoscale Symmetric Instability in Dense Flows Along Topography
Authors: Yankovsky Elizabeth , Legg Sonya , Hallberg Robert
Published: May 2021

We develop a parameterization for representing the effects of submesoscale symmetric instability (SI) in the ocean interior. SI may contribute to water mass modification and mesoscale energy dissipation in flow systems throughout the World Ocean. Dense gravity currents forced by surface buoyancy loss over shallow shelves are a particularly compelling test case, as they are characterized by density fronts and shears susceptible to a wide range of submesoscale instabilities. We present idealized experiments of Arctic shelf overflows employing the GFDL‐MOM6 in z* and isopycnal coordinates. At the highest resolutions, the dense flow undergoes geostrophic adjustment and forms bottom‐ and surface‐intensified jets. The density front along the topography combined with geostrophic shear initiates SI, leading to onset of secondary shear instability, dissipation of geostrophic energy, and turbulent mixing. We explore the impact of vertical coordinate, resolution, and parameterization of shear‐driven mixing on the representation of water mass transformation. We find that in isopycnal and low‐resolution z* simulations, limited vertical resolution leads to inadequate representation of diapycnal mixing. This motivates our development of a parameterization for SI‐driven turbulence. The parameterization is based on identifying unstable regions through a balanced Richardson number criterion and slumping isopycnals toward a balanced state. The potential energy extracted from the large‐scale flow is assumed to correspond to the kinetic energy of SI which is dissipated through shear mixing. Parameterizing submesoscale instabilities by combining isopycnal slumping with diapycnal mixing becomes crucial as ocean models move toward resolving mesoscale eddies and fronts but not the submesoscale phenomena they host.
Low-intensity ultrasound restores long-term potentiation and memory in senescent mice through pleiotropic mechanisms including NMDAR signaling
Authors: Blackmore Daniel G. , Turpin Fabrice , Palliyaguru Tishila , Evans Harrison T. , Chicoteau Antony , Lee Wendy , Pelekanos Matthew , Nguyen Nghia , Song Jae , Sullivan Robert K. P. , Sah Pankaj , Bartlett Perry F. , Götz Jürgen
Published: May 2021

Advanced physiological aging is associated with impaired cognitive performance and the inability to induce long-term potentiation (LTP), an electrophysiological correlate of memory. Here, we demonstrate in the physiologically aged, senescent mouse brain that scanning ultrasound combined with microbubbles (SUS+MB), by transiently opening the blood–brain barrier, fully restores LTP induction in the dentate gyrus of the hippocampus. Intriguingly, SUS treatment without microbubbles (SUSonly), i.e., without the uptake of blood-borne factors, proved even more effective, not only restoring LTP, but also ameliorating the spatial learning deficits of the aged mice. This functional improvement is accompanied by an altered milieu of the aged hippocampus, including a lower density of perineuronal nets, increased neurogenesis, and synaptic signaling, which collectively results in improved spatial learning. We therefore conclude that therapeutic ultrasound is a non-invasive, pleiotropic modality that may enhance cognition in elderly humans.
Whole-exome sequencing in eccrine porocarcinoma indicates promising therapeutic strategies
Authors: Denisova Evgeniya , Westphal Dana , Surowy Harald M. , Meier Friedegund , Hutter Barbara , Reifenberger Julia , Rütten Arno , Schulz Alexander , Sergon Mildred , Ziemer Mirjana , Brors Benedikt , Betz Regina C. , Redler Silke
Published: May 2021

Malignant sweat gland tumours are rare, with the most common form being Eccrine porocarcinoma (EP). To investigate the mutational landscape of EP, we performed whole-exome sequencing (WES) on 14 formalin-fixed paraffin-embedded samples of matched primary EP and healthy surrounding tissue. Mutational profiling revealed a high overall median mutation rate. This was attributed to signatures of mutational processes related to ultraviolet (UV) exposure, APOBEC enzyme dysregulation, and defective homologous double-strand break repair. All of these processes cause genomic instability and are implicated in carcinogenesis. Recurrent driving somatic alterations were detected in the EP candidate drivers TP53, FAT2, CACNA1S, and KMT2D. The analyses also identified copy number alterations and recurrent gains and losses in several chromosomal regions including that containing BRCA2, as well as deleterious alterations in multiple HRR components. In accordance with this reduced or even a complete loss of BRCA2 protein expression was detected in 50% of the investigated EP tumours. Our results implicate crucial oncogenic driver pathways and suggest that defective homologous double-strand break repair and the p53 pathway are involved in EP aetiology. Targeting of the p53 axis and PARP inhibition, and/or immunotherapy may represent promising treatment strategies.
Retinoic acid signaling is critical during the totipotency window in early mammalian development
Authors: Iturbide Ane , Ruiz Tejada Segura Mayra L. , Noll Camille , Schorpp Kenji , Rothenaigner Ina , Ruiz-Morales Elias R. , Lubatti Gabriele , Agami Ahmed , Hadian Kamyar , Scialdone Antonio , Torres-Padilla Maria-Elena
Published: May 2021

Totipotent cells hold enormous potential for regenerative medicine. Thus, the development of cellular models recapitulating totipotent-like features is of paramount importance. Cells resembling the totipotent cells of early embryos arise spontaneously in mouse embryonic stem (ES) cell cultures. Such ‘2-cell-like-cells’ (2CLCs) recapitulate 2-cell-stage features and display expanded cell potential. Here, we used 2CLCs to perform a small-molecule screen to identify new pathways regulating the 2-cell-stage program. We identified retinoids as robust inducers of 2CLCs and the retinoic acid (RA)-signaling pathway as a key component of the regulatory circuitry of totipotent cells in embryos. Using single-cell RNA-seq, we reveal the transcriptional dynamics of 2CLC reprogramming and show that ES cells undergo distinct cellular trajectories in response to RA. Importantly, endogenous RA activity in early embryos is essential for zygotic genome activation and developmental progression. Overall, our data shed light on the gene regulatory networks controlling cellular plasticity and the totipotency program.
Passive sampling and benchmarking to rank HOC levels in the aquatic environment
Authors: Allan Ian John , Vrana Branislav , de Weert Jasperien , Kringstad Alfhild , Ruus Anders , Christensen Guttorm , Terentjev Petr , Green Norman Whitaker
Published: May 2021

The identification and prioritisation of water bodies presenting elevated levels of anthropogenic chemicals is a key aspect of environmental monitoring programmes. Albeit this is challenging owing to geographical scales, choice of indicator aquatic species used for chemical monitoring, and inherent need for an understanding of contaminant fate and distribution in the environment. Here, we propose an innovative methodology for identifying and ranking water bodies according to their levels of hydrophobic organic contaminants (HOCs) in water. This is based on a unique passive sampling dataset acquired over a 10-year period with silicone rubber exposures in surface water bodies across Europe. We show with these data that, far from point sources of contamination, levels of hexachlorobenzene (HCB) and pentachlorobenzene (PeCB) in water approach equilibrium with atmospheric concentrations near the air/water surface. This results in a relatively constant ratio of their concentrations in the water phase. This, in turn, allows us to (i) identify sites of contamination with either of the two chemicals when the HCB/PeCB ratio deviates from theory and (ii) define benchmark levels of other HOCs in surface water against those of HCB and/or PeCB. For two polychlorinated biphenyls (congener 28 and 52) used as model chemicals, differences in contamination levels between the more contaminated and pristine sites are wider than differences in HCB and PeCB concentrations endorsing the benchmarking procedure.
Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes
Authors: Baratchian Mehdi , McManus Jeffrey M. , Berk Mike P. , Nakamura Fumihiko , Mukhopadhyay Sanjay , Xu Weiling , Erzurum Serpil , Drazba Judy , Peterson John , Klein Eric A. , Gaston Benjamin , Sharifi Nima
Published: May 2021

The sex discordance in COVID-19 outcomes has been widely recognized, with males generally faring worse than females and a potential link to sex steroids. A plausible mechanism is androgen-induced expression of TMPRSS2 and/or ACE2 in pulmonary tissues that may increase susceptibility or severity in males. This hypothesis is the subject of several clinical trials of anti-androgen therapies around the world. Here, we investigated the sex-associated TMPRSS2 and ACE2 expression in human and mouse lungs and interrogated the possibility of pharmacologic modification of their expression with anti-androgens. We found no evidence for increased TMPRSS2 expression in the lungs of males compared to females in humans or mice. Furthermore, in male mice, treatment with the androgen receptor antagonist enzalutamide did not decrease pulmonary TMPRSS2. On the other hand, ACE2 and AR expression was sexually dimorphic and higher in males than females. ACE2 was moderately suppressible with enzalutamide administration. Our work suggests that sex differences in COVID-19 outcomes attributable to viral entry are independent of TMPRSS2. Modest changes in ACE2 could account for some of the sex discordance.
Identification of mucin degraders of the human gut microbiota
Authors: Raimondi Stefano , Musmeci Eliana , Candeliere Francesco , Amaretti Alberto , Rossi Maddalena
Published: May 2021

Mucins are large glycoproteins consisting of approximately 80% of hetero-oligosaccharides. Gut mucin degraders of healthy subjects were investigated, through a culture dependent and independent approach. The faeces of five healthy adults were subjected to three steps of anaerobic enrichment in a medium with sole mucins as carbon and nitrogen sources. The bacterial community was compared before and after the enrichment by 16S rRNA gene profiling. Bacteria capable of fermenting sugars, such as Anaerotruncus, Holdemania, and Enterococcaceae likely took advantage of the carbohydrate chains. Escherichia coli and Enterobacteriaceae, Peptococcales, the Coriobacteriale Eggerthella, and a variety of Clostridia such as Oscillospiraceae, Anaerotruncus, and Lachnoclostridium, significantly increased and likely participated to the degradation of the protein backbone of mucin. The affinity of E. coli and Enterobacteriaceae for mucin may facilitate the access to the gut mucosa, promoting gut barrier damage and triggering systemic inflammatory responses. Only three species of strict anaerobes able to grow on mucin were isolated from the enrichments of five different microbiota: Clostridium disporicum, Clostridium tertium, and Paraclostridium benzoelyticum. The limited number of species isolated confirms that in the gut the degradation of these glycoproteins results from cooperation and cross-feeding among several species exhibiting different metabolic capabilities.
A plant endophyte Staphylococcus hominis strain MBL_AB63 produces a novel lantibiotic, homicorcin and a position one variant
Authors: Aftab Uddin M. , Akter Shammi , Ferdous Mahbuba , Haidar Badrul , Amin Al , Shofiul Islam Molla A. H. M. , Khan Haseena , Islam Mohammad Riazul
Published: May 2021

Here we report a jute endophyte Staphylococcus hominis strain MBL_AB63 isolated from jute seeds which showed promising antimicrobial activity against Staphylococcus aureus SG511 when screening for antimicrobial substances. The whole genome sequence of this strain, annotated using BAGEL4 and antiSMASH 5.0 to predict the gene clusters for antimicrobial substances identified a novel antimicrobial peptide cluster that belongs to the class I lantibiotic group. The predicted lantibiotic (homicorcin) was found to be 82% similar to a reported peptide epicidin 280 having a difference of seven amino acids at several positions of the core peptide. Two distinct peaks obtained at close retention times from a RP-HPLC purified fraction have comparable antimicrobial activities and LC–MS revealed the molecular mass of these peaks to be 3046.5 and 3043.2 Da. The presence of an oxidoreductase (homO) similar to that of epicidin 280- associated eciO or epilancin 15X- associated elxO in the homicorcin gene cluster is predicted to be responsible for the reduction of the first dehydrated residue dehydroalanine (Dha) to 2-hydroxypropionate that causes an increase of 3 Da mass of homicorcin 1. Trypsin digestion of the core peptide and its variant followed by ESI–MS analysis suggests the presence of three ring structures, one in the N-terminal and other two interlocking rings at the C-terminal region that remain undigested. Homicorcin exerts bactericidal activity against susceptible cells by disrupting the integrity of the cytoplasmic membrane through pore formation as observed under FE-SEM.
Synthesis, structure, and photoluminesence of the chloridoaluminates [BMIm][Sn(AlCl4)3], [BMPyr][Sn(AlCl4)3], and [BMIm][Pb(AlCl4)3]
Authors: Wolf Silke , Liebertseder Mareike , Feldmann Claus
Published: May 2021

The chloridoaluminates [BMIm][Sn(AlCl4)3], [BMPyr][Sn(AlCl4)3], and [BMIm][Pb(AlCl4)3] exhibit infinite 1∞[M(AlCl4)3]n– chains (M: Sn, Pb) with the tin compounds showing efficient emission and quantum yields up to 76%.
Diacyl peroxides: practical reagents as aryl and alkyl radical sources
Authors: Liu Han , Yu Jin-Tao , Pan Changduo
Published: May 2021

This feature article describes the recent achievements in utilizing diacyl peroxides as arylating and alkylating reagents in organic synthesis via the formation of aryl and alkyl radicals.
Beneficial effects of Lactobacillus-fermented black barley on high fat diet-induced fatty liver in rats
Authors: Guan Qi , Ding Xin-Wen , Zhong Ling-Yue , Zhu Chuang , Nie Pan , Song Li-Hua
Published: May 2021

A long-term high-fat diet can cause metabolic disorders, which might induce visceral obesity and hepatic steatosis, and increase hepatic oxidative stress. While Lactobacillus fermented black barley could regulate the disorders.
A coumarin-based reversible fluorescent probe for Cu2+ and S2− and its applicability in vivo and for organism imaging
Authors: Lu Wen , Shi Jiuzhou , Chen Jichao , Sun Lu , Shao Lingcen , Ren Hongyu , Huang Mengmeng , Wang Yanqin , Yang Shilong , Li Xu
Published: May 2021

A highly selective fluorescent probe was designed to detect Cu2+ and S2− in HeLa cells, zebrafish, and soybean root tissue.
A potential barrier in the diffusion of nanoparticles in ordered polymer networks
Authors: Lu Yu , Hu Guo-Hui
Published: May 2021

Diffusion of nanoparticles in a polymer matrix is of significant importance in diverse research fields. Based on DPD simulation, we found potential barrier induced by deformation of polymer network is crucial in studying nanoparticle diffusion.
LncRNA AWPPH as a prognostic predictor in human cancers in Chinese population: evidence from meta-analysis
Authors: Li Yongfeng , Rui Xinmiao , Chen Daobao , Xuan Haojun , Yang Hongjian , Meng Xuli
Published: May 2021

Background: Long non-coding RNA associated with poor prognosis of hepatocellular carcinoma (AWPPH) is dysregulated in a variety of human cancers. However, the prognostic value of AWPPH in various cancers remains unclear.

Methods: Comprehensive literature search was performed in PubMed, Web of Science, CNKI and Wangfang databases, and eligible studies were obtained according to the inclusion and exclusion criteria. The pooled hazard ratios (HRs) and odds ratios (ORs) were applied to assess the clinical value of AWPPH expression for overall survival (OS) and clinicopathological features.

Results: A total of 19 articles including 1699 cancer patients were included in the study. The pooled results demonstrated that evaluated AWPPH expression was positively related to a poorer overall survival of patients with cancers (HR = 1.79, 95%CI: 1.44–2.14, P<0.001). Subgroup analysis revealed that tumor type and sample size affect the predictive value of AWPPH on OS, whereas cut-off value and HR estimation method have no impact on it. In addition, the pooled data also showed that AWPPH was positively linked to advanced TNM stage (OR = 2.50, 95%CI: 1.94–3.22, P<0.001), bigger tumor size (OR = 2.64, 95%CI: 1.47–4.73, P=0.001), macro-vascular invasion (OR = 2.08, 95%CI: 1.04–4.16, P=0.04) and lymph node metastasis (OR = 2.68, 95%CI: 1.82–3.96, P<0.001). Moreover, the results of the trim and fill analysis confirmed the reliability of our finding.

Conclusions: Up-regulation of AWPPH was associated with advanced TNM stage, bigger tumor size, worse lymph node metastasis, macro-vascular invasion and shorter overall survival, suggesting that AWPPH may serve as a biomarker for prognosis and clinicopathological characteristics in human cancers among the Chinese population.
Bar quenching: Evidence from star-formation-rate indicators
Authors: George K. , Subramanian S.
Published: May 2021

The central regions of star-forming barred spiral galaxies can be devoid of star formation because of the redistribution of gas along the length of the bar. However, there can be gas outside the length of the bar that can host star formation. We study a sample of barred disc galaxies in the local Universe with an aim to discriminate between centrally quenched and globally quenched galaxies based on their positions on star-formation-rate–stellar mass (SFR−M⋆) plots and to find a connection between the SFR of quenched galaxies and the length of their bar. We classified barred galaxies as centrally quenched and globally quenched based on their position on SFR−M⋆ plots, with SFRs derived from Hα flux and spectral energy distribution fits on combined ultraviolet and optical flux. We selected galaxies as passive based on the distance from the main sequence relation. From a total 2514 barred galaxies studied here, we present 651 with suppressed star formation in their central region but hosting star formation outside. We also find a possible correlation between bar length and SFR for the galaxies that are fully quenched because of the stellar bar.
Implementation and results of a gastrointestinal cancer screening program in an Amazon rainforest village: A descriptive study
Authors: Averbach Pedro , Ferrari Angelo Paulo , Toscano Cristiana M , Borges José Luiz , Averbach Marcelo
Published: May 2021

Background and study aims Gastrointestinal cancer is an important cause of death worldwide. Remote populations are especially vulnerable to these conditions due to reduced access to screening and adequate treatment. In this context, the Belterra project was designed as a pilot taskforce to deliver gastrointestinal screening to an underserved Amazonian population and to spread knowledge and practice to local health workers. This study aimed to describe the implementation and present the results of the Belterra Project.

Patients and methods The project took place between October 2014 and December 2017 in Belterra, Pará, Brazil. Public-private partnerships were obtained and were essential for funding. The project required complex logistic solutions to provide gastrointestinal screening to every inhabitant between 50 and 70 years of age, including medical equipment and personal transportation to a remote area. Subjects were asked about their medical history, and received a physical examination, endoscopic examinations, and stool tests.

Results Over the course of 19 expeditions, we screened 2,022 inhabitants of Belterra, aged 50 to 70 years. Five colorectal and six gastric adenocarcinomas were diagnosed, as were several lower-stage lesions. Overall, 26 % of the participants undergoing colonoscopy showed some type of colonic lesion.

Conclusions Notwithstanding the geographical, cultural, and financial barriers, this study suggests that the implementation of a gastrointestinal cancer screening program for remote Brazilian populations is feasible, reaching high adherence. Although logistics is very demanding, such campaigns may be a good strategy to provide mass gastrointestinal cancer screening for underserved populations.
Evaluation of post-ERCP pancreatitis after biliary stenting with self-expandable metal stents vs. plastic stents in benign and malignant obstructions
Authors: Martinez Nichol S. , Inamdar Sumant , Firoozan Sheila N. , Izard Stephanie , Lee Calvin , Benias Petros C. , Trindade Arvind J. , Sejpal Divyesh V.
Published: May 2021

Background and study aims There are conflicting data regarding the risk of post-ERCP pancreatitis (PEP) with self-expandable metallic stents (SEMS) compared to polyethylene stents (PS) in malignant biliary obstructions and limited data related to benign obstructions.

Patients and methods A retrospective cohort study was performed of 1136 patients who underwent ERCP for biliary obstruction and received SEMS or PS at a tertiary-care medical center between January 2011 and October 2016. We evaluated the association between stent type (SEMS vs PS) and PEP in malignant and benign biliary obstructions.

Results Among the 1136 patients included in our study, 399 had SEMS placed and 737 had PS placed. Patients with PS were more likely to have pancreatic duct cannulation, pancreatic duct stent placement, double guidewire technique, sphincterotomy and sphincteroplasty as compared to the SEMS group. On multivariate analysis, PEP rates were higher in the SEMS group (8.0 %) versus the PS group (4.8 %) (OR 2.27 [CI, 1.22, 4.24]) for all obstructions. For malignant obstructions, PEP rates were 7.8 % and 6.6 % for SEMS and plastic stents, respectively (OR 1.54 [CI, 0.72, 3.30]). For benign obstructions the PEP rate was higher in the SEMS group (8.8 %) compared to the PS group (4.2 %) (OR 3.67 [CI, 1.50, 8.97]). No significant differences between PEP severity were identified based on stent type when stratified based on benign and malignant.

Conclusions PEP rates were higher when SEMS were used for benign obstruction as compared to PS. For malignant obstruction, no difference was identified in PEP rates with use of SEMS vs PS.
Management of intra-abdominal hypertension during ECMO: Total water-assisted colonoscopy as a step-up minimally invasive treatment, and a literature review
Authors: Martucci Gennaro , Amata Michele , di Francesco Fabrizio , Traina Mario , Arcadipane Antonio , Lorusso Roberto , Granata Antonino
Published: May 2021

Background and study aims During extracorporeal membrane oxygenation (ECMO), intra-abdominal hypertension (IAH) can impair ECMO venous drainage, reducing its ability to provide an adequate oxygenated blood flow. When medical therapy is ineffective in managing IAH, guidelines recommend a decompressive laparotomy (DL), though the procedure is associated with several complications and poor outcomes.

Patients and methods This was a case series of IAH in patients affected with acute respiratory distress syndrome (ARDS) on veno-venous (V-V) ECMO, in whom we performed total water-assisted colonoscopy (t-WAC) to treat IAH.

Results In three patients who underwent t-WAC, we report a real-time intra-procedural reduction of IAH, normalization of ECMO blood flow, and a reduction of vasopressors and lactates. t-WAC was performed in the context of evident abdominal compartment syndrome with multiorgan failure, and in one case was performed because of IAH and ECMO impairment. One patient was discharged alive, while the other two died of multiorgan failure, although the cause of death was apparently not secondary to IAH.

Conclusions During ECMO, in select cases,T-WAC may represent a first-line non-invasive approach.