bluuebunny/crossref_metadata_2025 huggingface dataset:
The ‘hub and spoke model’ for the management of surgical patients during the COVID‐19 pandemic
Authors: Kasivisvanathan Ramanathan , Tilney Henry S. , Jhanji Shaman , O’Mahony Michelle , Gruber Pascale , Nicol David , Morgan Dominic , Kipps Emma , Rasheed Shahnawaz
Published: May 2021

During the on‐going COVID‐19 pandemic a number of key public health services have been severely impacted. These include elective surgical services due to the synergetic resources required to provide both perioperative surgical care whilst also treating acute COVID‐19 patients and also the poor outcomes associated with surgical patients who develop COVID‐19 in the perioperative period. This article discusses the important principles and concepts for providing important surgical services during the COVID‐19 pandemic based on the model of the RMCancerSurgHub which is providing surgical cancer services for a population of approximately 2 million people across London during the pandemic. The model focusses on creating local and regional hub centres which provide urgent treatment for surgical patients in an environment that is relatively protected from the burden of COVID‐19 illness. The model extensively utilises the extended multidisciplinary team to allow for a flexible approach with core services delivered in ‘clean’ sites which can adapt to viral surges. A key requirement is that of a clinical prioritisation process which allows for equity in access within and between specialties ensuring that patients are treated on the basis of greatest need, while at the same time protecting those whose conditions can safely wait from exposure to the virus. Importantly, this model has the ability to scale‐up activity and lead units and networks into the recovery phase. The model discussed is also broadly applicable to providing surgical services during any viral pandemic.
Mercury cycling during acid rain recovery at the forested Lesní potok catchment, Czech Republic
Authors: Navrátil Tomáš , Shanley James B. , Rohovec Jan , Dobešová Irena , Matoušková Šárka , Roll Michal , Nováková Tereza , Oulehle Filip
Published: May 2021

From 2011 to 2019, mercury (Hg) stores and fluxes were studied in the small forested catchment Lesní potok (LES) in the central Czech Republic using the watershed mass balance approach together with internal measurements. Mean input fluxes of Hg via open bulk deposition, beech throughfall and spruce throughfall during the periodwere 2.9, 3.9 and 7.6 μg m−2 year−1, respectively. These values were considerably lower than corresponding deposition Hg fluxes reported in the early years of the 21st century from catchments in Germany. Current bulk precipitation inputs at unimpacted Czech mountainous sites were lower than those in Germany. The largest Hg inputs to the catchment were via litterfall, averaging 22.6 and 17.8 μg m−2 year−1 for beech and spruce stands. The average Hg input, based on the sum of mean litterfall and throughfall deposition, was 23.0 μg m−2 year−1, compared to the estimated Hg output in runoff of 0.5 μg m−2 year−1, which is low compared to other reported values. Thus, only ~2% of Hg input is exported in stream runoff. Stream water Hg was only weakly related to dissolved organic carbon (DOC) but both concentrations were positively correlated with water temperature. The estimated total soil Hg pool averaged 47.5 mg m−2, only 4% of which was in the O‐horizon. Thus Hg in the O‐horizon pool represents 72 years of deposition at the current input flux and 3800 years of export at the current runoff flux. Age‐dating by 14C suggested that organic soil contains Hg from recent deposition, while mineral soil at 40–80 cm depth contained 4400‐year old carbon, suggesting the soil had accumulated atmospheric Hg inputs through millennia to reach the highest soil Hg pool of the soil profile. These findings suggest that industrial era intensification of the Hg cycle is superimposed on a slower‐paced Hg cycle during most of the Holocene.
A century of change: Reconstructing the biogeochemical history of Hubbard Brook
Authors: Likens Gene E. , Buso Donald C. , Bernhardt Emily S. , Rosi Emma
Published: May 2021

Ecosystems constantly adjust to altered biogeochemical inputs, changes in vegetation and climate, and previous physical disturbances. Such disturbances create overlapping ‘biogeochemical legacies’ affecting modern nutrient mass balances. To understand how ‘legacies’ affected watershed‐ecosystem (WEC) biogeochemistry during five decades of studies within the Hubbard Brook Experimental Forest (HBEF), we extended biogeochemical trends and hydrologic fluxes back to 1900 to provide an historical framework for our long‐term studies. This reconstruction showed acid rain peaking at HBEF in the late 1960s‐early 1970s near the beginning of the Hubbard Brook Ecosystem Study (HBES). The long‐term, parabolic arc in acid inputs to HBEF generated a corresponding arc in the ionic strength of stream water, with acid inputs generating increased losses of H+ and soil base cations between 1963 and 1969 and then decreased losses after 1970. Nitrate release after disturbance is coupled with previous N‐deposition and storage, biological uptake, and hydrology. Sulfur was stored in soils from decades of acid deposition but is now nearly depleted. Total exports of base cations from the soil exchange pool represent one of the largest disturbances to forest and associated aquatic ecosystems at the HBEF since the Pleistocene glaciation. Because precipitation inputs of base cations currently are extremely small, such losses can only be replaced through the slow process of mineral weathering. Thus, the chemistry of stream water is extremely dilute and likely to become even more dilute than pre‐Industrial Revolution estimates. The importance of calculating chemical fluxes is clearly demonstrated in reconstruction of acid rain impacts during the pre‐measurement period. The aggregate impact of acid rain on WEC exports is far larger than historical forest harvest effects, and even larger than the most severe deforestation experiment (Watershed 2) at HBEF. A century of acid rain had a calcium stripping impact equivalent to two W2 experiments involving complete deforestation and herbicide applications.
Ferroptosis: A potential therapeutic target for neurodegenerative diseases
Authors: Vitalakumar D. , Sharma Ankita , Flora Swaran J. S.
Published: May 2021

Ferroptosis is a newly identified regulated form of cell death, which is thought to play a major role in neurodegenerative diseases. In this review, we discuss recent studies elucidating the molecular mechanisms involved in the regulation and execution of ferroptotic cell death and also its role in the brain. Ferroptosis is regulated mainly via iron homeostasis, glutathione metabolism, and lipid peroxidation. Ferroptotic cell death and pro‐ferroptotic factors are correlated with the etiopathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD). Ferroptosis and etiological factors act synergistically in PD and AD pathogenesis. Furthermore, several preclinical and clinical studies targeting ferroptosis in PD and AD have also shown positive results. Evidence of ferroptosis in the brain thus gives new insights into understanding neurodegenerative diseases. Ferroptosis studies in the brain are still in their infancy, but the existing pieces of evidence suggest a strong correlation between ferroptotic cell death and neurodegenerative diseases. Thus, ferroptosis might be a promising target for treating neurodegenerative diseases.
Three ‐(pyridin‐2‐yl)‐2‐(pyridin‐2‐ylimino)thiazolidin‐4‐one as a novel inhibitor of cerebral MAO‐B activity with antioxidant properties and low toxicity potential
Authors: Carraro Junior Luiz Roberto , Alves Amália Gonçalves , Rech Taís da Silva Teixeira , Campos Júnior José Coan , Siqueira Geonir Machado , Cunico Wilson , Brüning César Augusto , Bortolatto Cristiani Folharini
Published: May 2021

Some brain diseases are associated with oxidative stress and altered monoamine oxidase (MAO) activity. The objective of this study was to evaluate the antioxidant and neuroprotective actions through MAO inhibition of 3‐(pyridin‐2‐yl)‐2‐(pyridine‐2‐ylimino) thiazolidin‐4‐one (PPIT, a synthetic molecule containing a thiazolidinone nucleus), as well as its effects on toxicity parameters in Swiss female mice. Five in vitro assays were carried out to verify the PPIT antioxidant capacity: protein carbonylation (PC), 2,2'‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS), 1,1‐diphenyl‐2‐picryl‐hydrazil (DPPH), ferric ion (Fe3+) reducing antioxidant power (FRAP), and superoxide dismutase (SOD)‐like activity. The results showed that PPIT reduced the level of PC in the homogenate of the brain. This compound did not demonstrate SOD mimetic activity, but it acted as a free radical scavenger (ABTS and DPPH) and exhibited reducing activity in the FRAP assay. In addition, the effects of PPIT on cerebral MAO activity (MAO‐A and B isoforms) were investigated in vitro. Our data revealed inhibition of the MAO‐B activity by PPIT with no effects on MAO‐A. Lastly, an acute oral toxicity test was conducted in mice. No changes in food intake, body weight, and biochemical markers of kidney and liver damage were detected in mice treated with a high dose of PPIT (300 mg/kg). In conclusion, the present study demonstrated that PPIT exhibits antioxidant activity and selectively inhibits the MAO‐B isoform without causing apparent toxicity. These findings suggest PPIT as a potential therapeutic candidate to be tested in preclinical models of brain diseases involving perturbations of MAO‐B activity and redox status.
Raman electronic effect for non‐destructive boron calibration in type IIb semiconducting diamond
Authors: Zhang Shengya , Zhang Zhuangfei , Yi Wencai , Chen Xin , Liu Xiaobing
Published: May 2021

Whereas p type semiconducting diamond is well‐developed with boron doping, it is still challenge to directly determine boron content within type IIb diamonds in material science. In this work, we show a systematic study on analysis of electronic Raman effect in boron‐doped diamond (BDD) containing boron ranging from several to ~104 ppm. Beside a sharp peak near 5.2 cm−1, a shoulder associated with the Raman electronic effect near 12.1 cm−1 presents in the BDD samples and the intensity is observed to increase significantly with the increasing boron content. Our results demonstrate that the electronic line can be employed as an effective indication for simple, non‐destructive, accurate and broadly applicable boron calibration in semiconducting BDD samples.
Micro‐Raman study of cesanite (Ca2Na3 (OH)(SO4)3) in chloride segregations from Udachnaya‐East kimberlites
Authors: Grishina Svetlana , Goryainov Sergey , Oreshonkov Aleksandr , Karmanov Nikolay
Published: May 2021

Cesanite (Ca2Na3(OH)(SO4)3), a rare mineral, has been found in a few places restricted to a geothermal field and caves. We report the new occurrence of cesanite in quite different geological site—within sulfate‐rich melt inclusions in chloride segregations from kimberlites of Udachnaya‐East pipe (Siberia). Two halite generations: сesanite free and сesanite‐bearing, were distinguished in concentrically zonal segregations according to the results of the mineral and sulfate melt inclusion study by micro‐Raman spectroscopy and SEM‐EDS. We have applied the Raman spectroscopy and first principles calculations to understand structural and vibrational properties of cesanite daughter mineral in polyphase sulfate inclusions. Polarized spectra provided additional information on the overlapped components of the spectral profile. The Raman spectra of cesanite in the range of OH stretching vibrations are reported for the first time. The study aims to clarify the source of the NaSCl‐enrichment in the Udachnaya‐East pipe, which is highly discussed.
Stress Disorders and the Risk of Nonfatal Suicide Attempts in the Danish Population
Authors: Street Amy E. , Jiang Tammy , Horváth‐Puhó Erzsébet , Rosellini Anthony J. , Lash Timothy L. , Sørensen Henrik T. , Gradus Jaimie L.
Published: May 2021

Accurate documentation of the associations between stress disorders and suicide attempts provides important information about a high‐risk population and target group for preventative interventions. In this case‐cohort study, cases were all individuals born or residing in Denmark who made a nonfatal suicide attempt during 1995–2015 (n = 22,974). The comparison subcohort included a 5% random sample of the Danish population on January 1, 1995 (n = 265,183). Stress disorder diagnoses and suicide attempts were identified using ICD‐10 codes from national medical registries. The presence of any stress disorder substantially increased the rate of suicide attempts versus the comparison subcohort, rate per 100,000 person‐years (PYs) = 604 vs. 13. We observed associations between each type of stress disorder and suicide attempts, hazard ratios (HRs) = 10.1–37.6, even after adjustment for potential confounders, adjusted HRs = 1.8–8.3, with the strongest associations for adjustment disorder relative to other diagnoses. After adjusting for demographic and health variables, the rate of suicide attempts among individuals with any stress disorder diagnosis was nearly 13 times the suicide attempt rate in the comparison cohort. A bias analysis demonstrated that associations remained robust despite potential differential misclassification of suicide attempts. Study strengths included the use of individual‐level data linked across administrative and medical registries in the setting of universal health care and the use of longitudinal analyses capturing data over 20 years. The study demonstrated associations between the full range of stress disorders and suicide attempts, extending research specific to posttraumatic stress disorder.
Optical Vernier Effect: Recent Advances and Developments
Authors: Gomes André D. , Bartelt Hartmut , Frazão Orlando
Published: May 2021

The optical analog of the Vernier effect applied to fiber interferometers is a recent tool to enhance the sensitivity and resolution of optical fiber sensors. This effect relies on the overlap between the signals of two interferometers with slightly detuned interference frequencies. The Vernier envelope modulation generated at the output spectrum presents magnified sensing capabilities (i.e., magnified wavelength shift) compared to that of the individual sensing interferometers that constitute the system, leading to a new generation of highly sensitive fiber sensing devices. This review analyses the recent advances and developments of the optical Vernier effect from a fiber sensing point‐of‐view. Initially, the fundamentals of the effect are introduced, followed by an extensive review on the state‐of‐the‐art, presenting all the different configurations and types of fiber sensing interferometers used to introduce the optical Vernier effect. This paper also includes an overview of the complex case of enhanced Vernier effect and the introduction of harmonics to the effect.
Long‐Term Retarded Release for the Proteasome Inhibitor Bortezomib through Temperature‐Sensitive Dendritic Glycopolymers as Drug Delivery System from Calcium Phosphate Bone Cement
Authors: Lai Thu Hang , Keperscha Bettina , Qiu Xianping , Voit Brigitte , Appelhans Dietmar
Published: May 2021

For the local treatment of bone defects, highly adaptable macromolecular architectures are still required as drug delivery system (DDS) in solid bone substitute materials. Novel DDS fabricated by host–guest interactions between β‐cyclodextrin‐modified dendritic glycopolymers and adamantane‐modified temperature‐sensitive polymers for the proteasome inhibitor bortezomib (BZM) is presented. These DDS induce a short‐ and long‐term (up to two weeks) retarded release of BZM from calcium phosphate bone cement (CPC) in comparison to a burst release of the drug alone. Different release parameters of BZM/DDS/CPC are evaluated in phosphate buffer at 37 °C to further improve the long‐term retarded release of BZM. This is achieved by increasing the amount of drug (50–100 µg) and/or DDS (100–400 µg) versus CPC (1 g), by adapting the complexes better to the porous bone cement environment, and by applying molar ratios of excess BZM toward DDS with 1:10, 1:25, and 1:100. The temperature‐sensitive polymer shells of BZM/DDS complexes in CPC, which allow drug loading at room temperature but are collapsed at body temperature, support the retarding long‐term release of BZM from DDS/CPC. Thus, the concept of temperature‐sensitive DDS for BZM/DDS complexes in CPC works and matches key points for a local therapy of osteolytic bone lesions.
Workplace incivility and work engagement: The mediating role of job insecurity and the moderating role of self‐perceived employability
Authors: Guo Ju , Qiu Yanjun , Gan Yongtao
Published: May 2021

Drawing upon the job demand–resource model and the theory of existence, relatedness, and growth needs, we established and checked a model that connects workplace incivility to employee work engagement (i.e., vigor, dedication, and absorption) through job insecurity. Furthermore, we propose and test self‐perceived employability as the boundary condition of this connection. The conclusions of two substudies with time‐delay design provided evidence to support theoretical models. Specifically, the conclusions of both studies show that workplace incivility has negative impacts on work engagement (i.e., vigor, dedication, and absorption) through job insecurity. The results of Study 2 show that self‐perceived employability not only weakens the negative influences of job insecurity on work engagement (i.e., vigor, dedication, and absorption) but also moderates the mediating roles of job insecurity in the relationships between workplace incivility and work engagement (i.e., vigor, dedication, and absorption). The theoretical and practical implications and limitations are discussed based on the conclusions of the two substudies.
Synthesis and properties of low‐cost, photochromic transparent hydrogel based on ethaline‐assisted binary tungsten oxide‐molybdenum oxide nanocomposite for optical memory applications
Authors: Oderinde Olayinka , Ejeromedoghene Onome , Fu Guodong
Published: May 2021

Tungsten oxide‐based composites are important smart materials for wider usage in efficient energy windows, rewritable inks and other colored displays. However, the problem of agglomeration has made it challenging to be employed in transparent, photo‐reversible materials especially in functional hydrogels. We herein report the preparation of high transparent hydrogel using water‐soluble tungsten oxide‐molybdenum oxide nanocomposites. The hydrogel was characterized with FTIR, TGA, XPS, SEM, and UV–Vis–NIR, while the mechanical properties were also analyzed. The FTIR confirmed that the metal oxides combined with the polymer units via strong metal‐oxygen bond. For the TGA, the as‐prepared hydrogel was still able to maintain a weight loss of 18.12% at 500°C compared to 10.45% for pristine hydrogel. Also, the EDX mapping revealed microscopic metal oxides particles sizes, without any cluster phenomenon appearance. Additionally, the as‐prepared hydrogel revealed good mechanical properties as it could sustain a high deformation ratio (λ) of 86.3% at a stress of 60.3 MPa due to hydrogen bond crosslinking and ionic bond linkages. Moreover, the hydrogel exhibited high percentage transmittance (T%) of ~83%, as well as remarkable photochromic response, with absorption peaks at ~490, ~630 and ~730 nm appearing as the exposure time of the UV light increases. Furthermore, change in color was observed in 5 s, deepening to deep blue‐black at 300 s exposure to UV, while complete reverse fading was achieved in ~6 h in ambient air without external stimulus, hence making it a good potential for applications in various optical memory, sensors and rewritable devices.
Hypersensitivity pneumonitis: Lessons from a randomized controlled trial in children
Authors: Griese Matthias , Stehling Florian , Schwerk Nicolaus , Rosewich Martin , Jerkic Pera‐Silvija , Rock Hans , Ruckes Christian , Kronfeld Kai , Sebah Daniela , Wetzke Martin , Seidl Elias
Published: May 2021

Introduction

Hypersensitivity pneumonitis (HP) in children is a severe interstitial lung disease and potentially, a chronic condition, if not treated appropriately. No evidence‐based guidelines are available; in particular, the role of systemic glucocorticoid therapy is unclear.

Methods

The aim of this randomized, double‐blind, placebo‐controlled, parallel‐group, multi‐center, phase II trial in pediatric HP was to assess the outcome of HP in children after 6 months of treatment and to compare 3 months of treatment with oral prednisolone or placebo.

Results

After 1.5 years and the inclusion of only four children, we terminated the study prematurely. Two of the children randomized to prednisolone did not achieve the predefined response of FVC to normal. One child treated with placebo recovered to normal, similar to another child treated with prednisolone. All children treated with steroids developed drug‐related side effects.

Discussion

This uncompleted study illustrates the urgent medical need for evidence‐based treatment protocols for this condition. We discuss the hurdles which were specific for completion of this trial in a rare condition. Among other options, we suggest the inclusion of children into an all‐age study of HP, as in adults the same questions are unanswered.
Polyphenol‐solubility alters amyloid fibril formation of α‐synuclein
Authors: So Masatomo , Kimura Yuto , Yamaguchi Keiichi , Sugiki Toshihiko , Fujiwara Toshimichi , Aguirre Cesar , Ikenaka Kensuke , Mochizuki Hideki , Kawata Yasushi , Goto Yuji
Published: May 2021

Amyloid fibril formation is associated with various amyloidoses, including neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Amyloid fibrils form above the solubility of amyloidogenic proteins or peptides upon breaking supersaturation, followed by a nucleation and elongation mechanism, which is similar to the crystallization of solutes. Many additives, including salts, detergents, and natural compounds, promote or inhibit amyloid formation. However, the underlying mechanisms of the opposing effects are unclear. We examined the effects of two polyphenols, that is, epigallocatechin gallate (EGCG) and kaempferol‐7─O─glycoside (KG), with high and low solubilities, respectively, on the amyloid formation of α‐synuclein (αSN). EGCG and KG inhibited and promoted amyloid formation of αSN, respectively, when monitored by thioflavin T (ThT) fluorescence or transmission electron microscopy (TEM). Nuclear magnetic resonance (NMR) analysis revealed that, although interactions of αSN with soluble EGCG increased the solubility of αSN, thus inhibiting amyloid formation, interactions of αSN with insoluble KG reduced the solubility of αSN, thereby promoting amyloid formation. Our study suggests that opposing effects of polyphenols on amyloid formation of proteins and peptides can be interpreted based on the solubility of polyphenols.
A Holistic Review of the State‐of‐the‐Art Microfluidics for Exosome Separation: An Overview of the Current Status, Existing Obstacles, and Future Outlook
Authors: Ding Lihua , Yang Xiaonan , Gao Zibo , Effah Clement Yaw , Zhang Xiaoju , Wu Yongjun , Qu Lingbo
Published: May 2021

Exosomes, a class of small extracellular vesicles (30–150 nm), are secreted by almost all types of cells into virtually all body fluids. These small vesicles are attracting increasing research attention owing to their potential for disease diagnosis and therapy. However, their inherent heterogeneity and the complexity of bio‐fluids pose significant challenges for their isolation. Even the “gold standard,” differential centrifugation, suffers from poor yields and is time‐consuming. In this context, recent developments in microfluidic technologies have provided an ideal system for exosome extraction and these devices exhibit some fascinating properties such as high speeds, good portability, and low sample volumes. In this review, the focus is on the state‐of‐the‐art microfluidic technologies for exosome isolation and highlight potential directions for future research and development by analyzing the challenges faced by the current strategies.
Perovskite Quantum Dot Solar Cells: An Overview of the Current Advances and Future Perspectives
Authors: Dias Jeferson A. , Santagneli Silvia H. , Ribeiro Sidney J. L. , Messaddeq Younès
Published: May 2021

Perovskite quantum dots (PQDs) have revolutionized the field of perovskite solar cells in recent years. Using PQDs improves the operational stability of these devices, which is one of their main drawbacks for applications. This factor has motivated an intense search for new advances, from a fundamental aspect to improved performance in devices. Therefore, the developments obtained for PQD solar cells are discussed, presenting the challenges already overcome and the upcoming tendencies for research. Thus, the fundamental aspects of halide perovskite structures are first introduced. The advantages of their preparation as quantum dots are presented as well. The advances for post‐treatments (purification, passivation, and ligand exchange) are then discussed. Next, an in‐depth discussion of the PQD solar cell architectures is made, highlighting both the obsolete configurations and upcoming tendencies. A more specific view of the PQD compositions is then made, including lead‐free compositions and strategies for ionic substitution. Links of the photovoltaic performance are constructed with the devices’ architecture, post‐treatments, and perovskite composition, providing a wide‐ranging overview of these parameters for the devices’ efficiencies. Finally, the authors’ point of view about the future of PQD solar cell technology is presented, showing the main drawbacks, advantages, and opportunities for research.
4‐in‐1 Multipurpose Excipient from Musa acuminata Fruit by Alkaline‐Steeping/Retrogradation (ASR) in Acetaminophen Tablet Formulation
Authors: Autamashih Musa , Ebrahim Naushaad , Egieyeh Samuel , Aucamp Marique , Rosa Paulo Cesar Pires , Poka Madan S. , Ngilirabanga Jean Baptiste , Samsodien Halima
Published: May 2021

The conventional approach in the tablet formulation of acetaminophen (ACM) suggests the use of five or more different excipients in a wet granulation tableting process. The use of many excipients in tablet formulation may negatively create excipient–excipient interactions, excipient–drug interactions, exaggerated product side effects, and high drug load. Cutting‐edge technology would be the use of one excipient with a quadrupled functional purpose (4‐in‐1) by direct compression tableting. In this study, a novel two‐phase process called “alkaline‐steeping/retrogradation” (ASR) is employed to obtain the desired starch polymer excipient of quadrupled functional purpose. In phase I, the biopolymer is extracted from the unripe fruits of Musa acuminata by a modified alkaline solution steeping method, while in phase II, 50% w/w of the extracted polymer is retrograded. The retrograded product is re‐mixed with the non‐retrograded 50% w/w that is left from phase I. This gives a novel 50–50% w/w blend named Musa acuminata advanced starch polymer (MAP). To authenticate the efficiency of the ASR, the physicomechanical, analytical, and drug release properties of different concentrations of MAP/ACM solid systems are characterized to ascertain the compatibility. The ASR method produces a unique semi‐hygroscopic biopolymer excipient of quadruple‐function in ACM high‐dose tablet formulation by direct compression.
Machine learning for hydrologic sciences: An introductory overview
Authors: Xu Tianfang , Liang Feng
Published: May 2021

The hydrologic community has experienced a surge in interest in machine learning in recent years. This interest is primarily driven by rapidly growing hydrologic data repositories, as well as success of machine learning in various academic and commercial applications, now possible due to increasing accessibility to enabling hardware and software. This overview is intended for readers new to the field of machine learning. It provides a non‐technical introduction, placed within a historical context, to commonly used machine learning algorithms and deep learning architectures. Applications in hydrologic sciences are summarized next, with a focus on recent studies. They include the detection of patterns and events such as land use change, approximation of hydrologic variables and processes such as rainfall‐runoff modeling, and mining relationships among variables for identifying controlling factors. The use of machine learning is also discussed in the context of integrated with process‐based modeling for parameterization, surrogate modeling, and bias correction. Finally, the article highlights challenges of extrapolating robustness, physical interpretability, and small sample size in hydrologic applications.

This article is categorized under:

Science of Water
Introduction
Authors: Löbner Sebastian , Gamerschlag Thomas , Kalenscher Tobias , Schrenk Markus , Zeevat Henk
Published: May 2021

In order to help to explain cognition, cognitive structures are assumed to be present in the mind/brain. While the empirical investigation of such structures is the task of cognitive psychology, the other cognitive science disciplines like linguistics, philosophy and artificial intelligence have an important role in suggesting hypotheses. Researchers in these disciplines increasingly test such hypotheses by empirical means themselves. In philosophy, the traditional way of referring to such structures is viaconcepts, i.e. those mental entities by which we conceive reality and with the help of which we reason and plan. Linguists traditionally refer to the cognitive structures asmeanings—at least those linguists with a mentalistic concept of meaning do who do not think of meaning as extra-mental entities.
Modification and Default Inheritance
Authors: Strößner Corina , Schuster Annika , Schurz Gerhard
Published: May 2021

Modification usually decreases the judged likelihood of typicality statements. People judge “Old coyotes howl” as less likely than just “Coyotes howl”. This paper addresses this so-called modification effect. In order to analyse the effect, we propose an extended modification model based on the selective modification model by Smith et al. (1988) and Barsalou’s (1992) frames. In this model we introduce cross-attributional constraintsModification effect, relevant modification that explain how a change in one dimension leads to an alteration of another attribute, especially if the modifierModification is not typical. Finally, we discuss data from Connolly et al. (2007) and present new experimental evidence from an explorative study.
Escitalopram Restores Reversal Learning Impairments in Rats with Lesions of Orbital Frontal Cortex
Authors: Tait David S. , Bowman Ellen E. , Miller Silke , Dovlatyan Mary , Sanchez Connie , Brown Verity J.
Published: May 2021

The term ‘cognitive structures’ is used to describe the fact that mental models underlie thinking, reasoning and representing. Cognitive structures generally improve the efficiency of information processing by providing a situational framework within which there are parameters governing the nature and timing of information and appropriate responses can be anticipated. Unanticipated events that violate the parameters of the cognitive structure require the cognitive model to be updated, but this comes at an efficiency cost. In reversal learning a response that had been reinforced is no longer reinforced, while an alternative is now reinforced, having previously not been (A+/B− becomes A−/B+). Unanticipated changes of contingencies require that cognitive structures are updated. In this study, we examined the effect of lesions of the orbital frontal cortex (OFC) and the effects of the selective serotonin reuptake inhibitor (SSRI), escitalopram, on discrimination and reversal learning. Escitalopram was without effect in intact rats. Rats with OFC lesions had selective impairment of reversal learning, which was ameliorated by escitalopram. We conclude that reversal learning in OFC-lesioned rats is an easily administered and sensitive test that can detect effects of serotonergic modulation on cognitive structures that are involved in behavioural flexibility.
We Can Do This: The Institute for Healthcare Improvement Adverse Drug Events Collaborative
Authors: Leape Lucian L.
Published: May 2021

Rewind to 1995, before Annenberg and the NPSF. “Patient safety” was not on many agendas, but methods to change systems to improve quality of care were beginning to be developed. Policy-makers and the healthcare establishment were slow to respond to the new information on the extent of medical error and our calls for a new approach, but one person instantly recognized the challenge: Don Berwick of the Institute for Healthcare Improvement (IHI).
Introduction: “Fully Nonlinear”
Authors: Gowanlock Jordan
Published: May 2021

The introduction to Animating Unpredictable Effects establishes a specific category of digital animation that is based on making unpredictable simulations. The book situates this form of animation in the context of key discussions about the relationship between animation and automation, and about the agency digital animators have when working with increasingly opaque software tools. The introduction further situates this type of animation in the history of cinema, which has long been preoccupied with natural motion and topics of contingency.
Topologically twisted index of T[SU(N)] at large N
Authors: Coccia Lorenzo
Published: May 2021

Abstract

We compute, in the large N limit, the topologically twisted index of the 3d T[SU(N)] theory, namely the partition function on $$ {\Sigma}_{\mathfrak{g}}\times {S}^1 $$

Σ
g

×

S
1

, with a topological twist on the Riemann surface $$ {\Sigma}_{\mathfrak{g}} $$

Σ
g

. To provide an expression for this quantity, we take advantage of some recent results obtained for five dimensional quiver gauge theories. In case of a universal twist, we correctly reproduce the entropy of the universal black hole that can be embedded in the holographically dual solution.
Efficient TALEN-mediated gene knockin at the bovine Y chromosome and generation of a sex-reversal bovine
Authors: Wang Ming , Sun ZhaoLin , Ding Fangrong , Wang Haiping , Li Ling , Li Xue , Zheng Xianjin , Li Ning , Dai Yunping , Wu Changxin
Published: May 2021

Functional elucidation of bovine Y-chromosome genes requires available genome editing technologies. Meanwhile, it has yet to be proven whether the bovine Sry gene is the main or single factor involved in the development of the male phenotype in bovine. Here, we efficiently knocked out four Y-linked genes (Sry, ZFY, DDX3Y, and EIF2S3Y) in bovine fetal fibroblasts (BFFs) with transcription activator-like effector nucleases (TALENs) individually. Furthermore, we used TALEN-mediated gene knockin at the Sry gene and generated a sex-reversal bovine by somatic cell nuclear transfer (SCNT). The resulting bovine had only one ovary and was sterile. We demonstrate, for the first time, that the Sry gene is an important sex-determining gene in bovine. Our method lays a solid foundation for detecting the biology of the bovine Y chromosome, as it may provide an alternative biological model system for the study of mammalian sex determination, and new methods for the practical application in agricultural, especially for sex predetermination.
Was machen Urologen in der Praxis?
Authors: Goebell Peter J. , El-Khadra Sulafah , Horstmann Marcus , Kollenbach Peter , Lüdecke Gerson , Quack Thomas , Rug Michael , Stephan-Odenthal Michael , Bode-Greuel Kerstin , Zink Saskia , Lieberkühn Patrick , Schulze Matthias
Published: May 2021

Auch (berufs)politisch hat das Thema Versorgung und Versorgungsforschung an Relevanz gewonnen und stellt für die Gesundheitspolitik und die an der Versorgung Beteiligten eine wichtige Basis dar. Der Zugang zu relevanten Daten und die Möglichkeiten zur Analyse sind daher umkämpfter denn je, liefern sie doch die besten Argumente und Fakten in jedem Diskurs um letztlich begrenzte Ressourcen des gesamten Gesundheitssektors. Allen randomisierten klinischen Studien und prospektiven Datensammlungen ist gemein, dass sie einen festen vordefinierten Rahmen der zu erfassenden verschiedenen Datenpunkte zugrunde gelegt haben, um störende Einflussfaktoren möglichst zu kontrollieren. Auch Analysen aus retrospektiven Datensammlungen benutzen eine vordefinierte Auswertematrix und filtern die vorhandenen Daten auf diese festgelegten Datenpunkte. Ein ungefilterter Blick auf alle Daten wäre aber der Idealzustand. Näherungsweise sollten in diesem Projekt so viele Daten wir möglich „ungefiltert“ erfasst werden und in einem Datenpool gesammelt werden, die dann durch sich ständig verbessernde Analysealgorithmen aufgearbeitet werden können. Über die automatisierte Extraktion von Daten aus dem Arzt‑/Praxisinformationssystem (AIS) in UROscience wird ein Datenpool entstehen, der für viele Fragestellungen zur Versorgungsrealität genutzt werden kann. Die hier vorgestellte erste Analyse zeigt, dass auf Basis der bereits vorhandenen Daten eine vielseitig einsetzbare Stichprobe für die Darstellung des Versorgungsalltags aus der urologischen Praxis zur Verfügung steht.
Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity – initial experience and comparison to [18F]FDG PET/CT and MRI
Authors: Linz Christian , Brands Roman C. , Kertels Olivia , Dierks Alexander , Brumberg Joachim , Gerhard-Hartmann Elena , Hartmann Stefan , Schirbel Andreas , Serfling Sebastian , Zhi Yingjun , Buck Andreas K. , Kübler Alexander , Hohm Julian , Lapa Constantin , Kircher Malte
Published: May 2021

Purpose

While [18F]-fluorodeoxyglucose ([18F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT.

Methods

Ten consecutive, treatment-naïve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [18F]FDG and [68Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUVmax) and peak (SUVpeak) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference.

Results

[18F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([18F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3% vs. 87.5%; P = 0.32) and specificity (93.3% vs. 81.3%; P = 0.16) to [18F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples.

Conclusion

FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.
Comparison of MRI, PET, and 18F-choline PET/MRI in patients with oligometastatic recurrent prostate cancer
Authors: Evangelista Laura , Cassarino Gianluca , Lauro Alberto , Morlacco Alessandro , Sepulcri Matteo , Nguyen Alex Ahn Li , Ietto Francesco , Cecchin Diego , Lacognata Carmelo , Zucchetta Pietro
Published: May 2021

Objectives

The aims of the study were (i) to examine the PCa detection rate of 18F-choline (FCH) PET/MRI and (ii) to assess the impact of PET/MRI findings in patients with PCa who develop OMD using PSA response as a biomarker.

Methods

We retrospectively analyzed a cohort of 103 patients undergoing FCH PET/MRI for biochemical recurrence of PCa. The inclusion criteria were (1) previous radical prostatectomy (RP) with or without adjuvant radiotherapy (RT); (2) PSA levels available at the time of PET; (3) OMD, defined as a maximum of 5 lesions on PET/MRI; and (4) follow-up data available for at least 6 months after PET. All images were reviewed by two nuclear medicine physicians and interpreted with the support of two radiologists.

Results

Seventy patients were eligible for the study: 52 patients had a positive FCH PET/MRI and 18 had a negative scan. The overall PCa detection rates for MRI, PET, and PET/MRI were 65.7%, 37.1%, and 74.3%, respectively. Thirty-five patients were treated with radiotherapy (RT), 16 received hormonal therapy (HT), 3 had a combined therapy (RT + HT), and 16 (23%) underwent PSA surveillance. At follow-up, PSA levels decreased in 51 patients (73%), most of whom had been treated with RT or RT + HT. Therapeutic management was guided by PET/MRI in 74% of patients, which performed better than MRI alone (68% of patients).

Conclusion

FCH PET/MRI has a higher detection rate than MRI or PET alone for PCa patients with OMD and PSA levels > 0.5 ng/mL, prompting a better choice of treatment.
Oncologic impact of delaying radical prostatectomy in men with intermediate- and high-risk prostate cancer: a systematic review
Authors: Laukhtina Ekaterina , Sari Motlagh Reza , Mori Keiichiro , Quhal Fahad , Schuettfort Victor M. , Mostafaei Hadi , Katayama Satoshi , Grossmann Nico C. , Ploussard Guillaume , Karakiewicz Pierre I. , Briganti Alberto , Abufaraj Mohammad , Enikeev Dmitry , Pradere Benjamin , Shariat Shahrokh F.
Published: May 2021

Purpose

To summarize the available evidence on the survival and pathologic outcomes after deferred radical prostatectomy (RP) in men with intermediate- and high-risk prostate cancer (PCa).

Methods

The PubMed database and Web of Science were searched in November 2020 according to the PRISMA statement. Studies were deemed eligible if they reported the survival and pathologic outcomes of patients treated with deferred RP for intermediate- and high-risk PCa compared to the control group including those patients treated with RP without delay.

Results

Overall, nineteen studies met our eligibility criteria. We found a significant heterogeneity across the studies in terms of definitions for delay and outcomes, as well as in patients’ baseline clinicopathologic features. According to the currently available literature, deferred RP does not seem to affect oncological survival outcomes, such as prostate cancer-specific mortality and metastasis-free survival, in patients with intermediate- or high-risk PCa. However, the impact of deferred RP on biochemical recurrence rates remains controversial. There is no clear association of deferring RP with any of the features of aggressive disease such as pathologic upgrading, upstaging, positive surgical margins, extracapsular extension, seminal vesicle invasion, and lymph node invasion. Deferred RP was not associated with the need for secondary treatments.

Conclusions

Owing to the different definitions of a delayed RP, it is hard to make a consensus regarding the safe delay time. However, the current data suggest that deferring RP in patients with intermediate- and high-risk PCa for at least around 3 months is generally safe, as it does not lead to adverse pathologic outcomes, biochemical recurrence, the need for secondary therapy, or worse oncological survival outcomes.
Drug toxicity in the proximal tubule: new models, methods and mechanisms
Authors: Hall Andrew M. , Trepiccione Francesco , Unwin Robert J.
Published: May 2021

The proximal tubule (PT) reabsorbs most of the glomerular filtrate and plays an important role in the uptake, metabolism and excretion of xenobiotics. Some therapeutic drugs are harmful to the PT, and resulting nephrotoxicity is thought to be responsible for approximately 1 in 6 of cases of children hospitalized with acute kidney injury (AKI). Clinically, PT dysfunction leads to urinary wasting of important solutes normally reabsorbed by this nephron segment, leading to systemic complications such as bone demineralization and a clinical scenario known as the renal Fanconi syndrome (RFS). While PT defects can be diagnosed using a combination of blood and urine markers, including urinary excretion of low molecular weight proteins (LMWP), standardized definitions of what constitutes clinically significant toxicity are lacking, and identifying which patients will go on to develop progressive loss of kidney function remains a major challenge. In addition, much of our understanding of cellular mechanisms of drug toxicity is still limited, partly due to the constraints of available cell and animal models. However, advances in new and more sophisticated in vitro models of the PT, along with the application of high-content analytical methods that can provide readouts more relevant to the clinical manifestations of nephrotoxicity, are beginning to extend our knowledge. Such technical progress should help in discovering new biomarkers that can better detect nephrotoxicity earlier and predict its long-term consequences, and herald a new era of more personalized medicine.
Hemoadsorption with CytoSorb® and the early course of linezolid plasma concentration during septic shock
Authors: Köhler Thomas , Schwier Elke , Kirchner Carmen , Winde Günther , Henzler Dietrich , Eickmeyer Claas
Published: May 2021

Hemoadsorption with CytoSorb® becomes increasingly established in treatment of various, predominantly inflammation-associated diseases. In septic shock, results suggest improvements in hemodynamics and organ function. However, little is known about the in vivo adsorption properties for various antibiotics. We present the case of a 61-year-old female patient with known Ulrich Turner syndrome who treated supportively with CytoSorb® and with linezolid due to a Staphylococcus epidermidis bloodstream infection as part of her intensive care treatment for septic shock. After establishment of a new adsorber, 600 mg of linezolid administered over 1 h. Linezolid levels measured before adsorber inlet (cpre) and after adsorber outlet (cpost) at 0, 15, 60, 120 and 480 min after starting infusion. Out of the ten samples, only the cpre samples 60 min (3.25 mg/l) and 120 min (4.7 mg/l) showed sufficiently high linezolid levels (therapeutic range 3–9 mg/l). After 480 min, cpre decreased to 2.8 mg/l, cpost increased to 1.85 mg/l, and thus clearance decreased to 67.86 ml/min (from 200 ml/min at 60 min), with greatly reduced adsorption capacity of CytoSorb® after 8 h. A loading dose (additional 600 mg) would have been urgently needed. Linezolid therapy under hemadsorption with CytoSorb® requires a clear indication and close monitoring of levels to avoid underdosing.
Popular branchings and their dual certificates
Authors: Kavitha Telikepalli , Király Tamás , Matuschke Jannik , Schlotter Ildikó , Schmidt-Kraepelin Ulrike
Published: May 2021

LetGbe a digraph where every node has preferences over its incoming edges. The preferences of a node extend naturally to preferences overbranchings, i.e., directed forests; a branchingBispopularifBdoes not lose a head-to-head election (where nodes cast votes) against any branching. Such popular branchings have a natural application in liquid democracy. The popular branching problem is to decide ifGadmits a popular branching or not. We give a characterization of popular branchings in terms ofdual certificatesand use this characterization to design an efficient combinatorial algorithm for the popular branching problem. When preferences are weak rankings, we use our characterization to formulate thepopular branching polytopein the original space and also show that our algorithm can be modified to compute a branching withleast unpopularity margin. When preferences are strict rankings, we show that “approximately popular” branchings always exist.