bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-22 promotes stem cell traits via activating Wnt/β-catenin signaling in cutaneous squamous cell carcinoma
Authors: Yuan Shukai , Zhang Peitao , Wen Liqi , Jia Shikai , Wu Yufan , Zhang Zhenlei , Guan Lizhao , Yu Zhengquan , Zhao Li
Published: August 2021

Emerging evidence suggests that the cancer stem cells (CSCs) are key culprits of cancer metastasis and drug resistance. Understanding mechanisms regulating the critical oncogenic pathways and CSCs function could reveal new diagnostic and therapeutic strategies. We now report that miR-22, a miRNA critical for hair follicle stem/progenitor cell differentiation, promotes tumor initiation, progression, and metastasis by maintaining Wnt/β-catenin signaling and CSCs function. Mechanistically, we find that miR-22 facilitates β-catenin stabilization through directly repressing citrullinase PAD2. Moreover, miR-22 also relieves DKK1-mediated repression of Wnt/β-catenin signaling by targeting a FosB-DKK1 transcriptional axis. miR-22 knockout mice showed attenuated Wnt/β-catenin activity and Lgr5+ CSCs penetrance, resulting in reduced occurrence, progression, and metastasis of chemically induced cutaneous squamous cell carcinoma (cSCC). Clinically, miR-22 is abundantly expressed in human cSCC. Its expression is even further elevated in the CSCs proportion, which negatively correlates with PAD2 and FosB expression. Inhibition of miR-22 markedly suppressed cSCC progression and increased chemotherapy sensitivity in vitro and in xenograft mice. Together, our results revealed a novel miR-22-WNT-CSCs regulatory mechanism in cSCC and highlight the important clinical application prospects of miR-22, a common target molecule for Wnt/β-catenin signaling and CSCs, for patient stratification and therapeutic intervention.
Transcriptional CDK inhibitors, CYC065 and THZ1 promote Bim-dependent apoptosis in primary and recurrent GBM through cell cycle arrest and Mcl-1 downregulation
Authors: Juric Viktorija , Hudson Lance , Fay Joanna , Richards Cathy E. , Jahns Hanne , Verreault Maïté , Bielle Franck , Idbaih Ahmed , Lamfers Martine L. M. , Hopkins Ann M. , Rehm Markus , Murphy Brona M.
Published: August 2021

Activation of cyclin-dependent kinases (CDKs) contributes to the uncontrolled proliferation of tumour cells. Genomic alterations that lead to the constitutive activation or overexpression of CDKs can support tumourigenesis including glioblastoma (GBM), the most common and aggressive primary brain tumour in adults. The incurability of GBM highlights the need to discover novel and more effective treatment options. Since CDKs 2, 7 and 9 were found to be overexpressed in GBM, we tested the therapeutic efficacy of two CDK inhibitors (CKIs) (CYC065 and THZ1) in a heterogeneous panel of GBM patient-derived cell lines (PDCLs) cultured as gliomaspheres, as preclinically relevant models. CYC065 and THZ1 treatments suppressed invasion and induced viability loss in the majority of gliomaspheres, irrespective of the mutational background of the GBM cases, but spared primary cortical neurons. Viability loss arose from G2/M cell cycle arrest following treatment and subsequent induction of apoptotic cell death. Treatment efficacies and treatment durations required to induce cell death were associated with proliferation velocities, and apoptosis induction correlated with complete abolishment of Mcl-1 expression, a cell cycle-regulated antiapoptotic Bcl-2 family member. GBM models generally appeared highly dependent on Mcl-1 expression for cell survival, as demonstrated by pharmacological Mcl-1 inhibition or depletion of Mcl-1 expression. Further analyses identified CKI-induced Mcl-1 loss as a prerequisite to establish conditions at which the BH3-only protein Bim can efficiently induce apoptosis, with cellular Bim amounts strongly correlating with treatment efficacy. CKIs reduced proliferation and promoted apoptosis also in chick embryo xenograft models of primary and recurrent GBM. Collectively, these studies highlight the potential of these novel CKIs to suppress growth and induce cell death of patient-derived GBM cultures in vitro and in vivo, warranting further clinical investigation.
Thromboembolism after COVID-19 vaccine in patients with preexisting thrombocytopenia
Authors: Mauriello Alessandro , Scimeca Manuel , Amelio Ivano , Massoud Renato , Novelli Antonio , Di Lorenzo Francesca , Finocchiaro Susanna , Cimino Carolina , Telesca Rossana , Chiocchi Marcello , Sun Qiang , Wang Ying , Shi Yufang , Novelli Giuseppe , Melino Gerry
Published: August 2021

While vaccination is the single most effective intervention to drastically reduce severe disease and death following SARS-CoV-2 infection, as shown in UK and Israel, some serious concerns have been raised for an unusual adverse drug reaction (ADR), including vaccine-induced immune thrombotic thrombocytopenia (VITT) with concurrent low platelets as well as capillary leak syndrome. In fact, the overall safety of the vaccine is highlighted by the low frequency of ADR considering that in UK, by the early June, 40 million first doses and 29 million second doses have been injected; nonetheless, 390 thrombotic events, including 71 fatal events have been reported. Interestingly, the cases reported low platelet counts with the presence of anti-platelet factor-4 (PF4) antibodies, indicating an abnormal clotting reaction. Here, out of three referred cases, we report a post-vaccine clinical case of fatal thrombosis with postmortem examination and whole exome sequencing (WES) analysis, whose pathogenesis appeared associated to a preexisting condition of thrombocytopenia due to myelodysplasia.
Population screening for glaucoma in UK: current recommendations and future directions
Authors: Hamid Sana , Desai Parul , Hysi Pirro , Burr Jennifer M. , Khawaja Anthony P.
Published: August 2021

Effective population screening for glaucoma would enable earlier diagnosis and prevention of irreversible vision loss. The UK National Screening Committee (NSC) recently published a review that examined the viability, effectiveness and appropriateness of a population-based screening programme for primary open-angle glaucoma (POAG). In our article, we summarise the results of the review and discuss some future directions that may enable effective population screening for glaucoma in the future. Two key questions were addressed by the UK NSC review; is there a valid, accurate screening test for POAG, and does evidence exist that screening reduces morbidity from POAG compared with standard care. Six new studies were identified since the previous 2015 review. The review concluded that screening for glaucoma in adults is not recommended because there is no clear evidence for a sufficiently accurate screening test or for better outcomes with screening compared to current care. The next UK NSC review is due to be conducted in 2023. One challenge for POAG screening is that the relatively low disease prevalence results in too many false-positive referrals, even with an accurate test. In the future, targeted screening of a population subset with a higher prevalence of glaucoma may be effective. Recent developments in POAG polygenic risk prediction and deep learning image analysis offer potential avenues to identifying glaucoma-enriched sub-populations. Until such time, opportunistic case finding through General Ophthalmic Services remains the primary route for identification of glaucoma in the UK and greater public awareness of the service would be of benefit.
Coherent coupling between vortex bound states and magnetic impurities in 2D layered superconductors
Authors: Park Sunghun , Barrena Víctor , Mañas-Valero Samuel , Baldoví José J. , Fente Antón , Herrera Edwin , Mompeán Federico , García-Hernández Mar , Rubio Ángel , Coronado Eugenio , Guillamón Isabel , Yeyati Alfredo Levy , Suderow Hermann
Published: August 2021

Bound states in superconductors are expected to exhibit a spatially resolved electron-hole asymmetry which is the hallmark of their quantum nature. This asymmetry manifests as oscillations at the Fermi wavelength, which is usually tiny and thus washed out by thermal broadening or by scattering at defects. Here we demonstrate theoretically and confirm experimentally that, when coupled to magnetic impurities, bound states in a vortex core exhibit an emergent axial electron-hole asymmetry on a much longer scale, set by the coherence length. We study vortices in 2H-NbSe2 and in 2H-NbSe1.8S0.2 with magnetic impurities, characterizing these with detailed Hubbard-corrected density functional calculations. We find that the induced electron-hole imbalance depends on the band character of the superconducting material. Our results show that coupling between quantum bound states in superconductors is remarkably robust and has a strong influence in tunneling measurements.
Guided accumulation of active particles by topological design of a second-order skin effect
Authors: Palacios Lucas S. , Tchoumakov Serguei , Guix Maria , Pagonabarraga Ignacio , Sánchez Samuel , G. Grushin Adolfo
Published: August 2021

Collective guidance of out-of-equilibrium systems without using external fields is a challenge of paramount importance in active matter, ranging from bacterial colonies to swarms of self-propelled particles. Designing strategies to guide active matter and exploiting enhanced diffusion associated to its motion will provide insights for application from sensing, drug delivery to water remediation. However, achieving directed motion without breaking detailed balance, for example by asymmetric topographical patterning, is challenging. Here we engineer a two-dimensional periodic topographical design with detailed balance in its unit cell where we observe spontaneous particle edge guidance and corner accumulation of self-propelled particles. This emergent behaviour is guaranteed by a second-order non-Hermitian skin effect, a topologically robust non-equilibrium phenomenon, that we use to dynamically break detailed balance. Our stochastic circuit model predicts, without fitting parameters, how guidance and accumulation can be controlled and enhanced by design: a device guides particles more efficiently if the topological invariant characterizing it is non-zero. Our work establishes a fruitful bridge between active and topological matter, and our design principles offer a blueprint to design devices that display spontaneous, robust and predictable guided motion and accumulation, guaranteed by out-of-equilibrium topology.
Mechanical metric for skeletal biomechanics derived from spectral analysis of stiffness matrix
Authors: Henyš Petr , Kuchař Michal , Hájek Petr , Hammer Niels
Published: August 2021

A new metric for the quantitative and qualitative evaluation of bone stiffness is introduced. It is based on the spectral decomposition of stiffness matrix computed with finite element method. The here proposed metric is defined as an amplitude rescaled eigenvalues of stiffness matrix. The metric contains unique information on the principal stiffness of bone and reflects both bone shape and material properties. The metric was compared with anthropometrical measures and was tested for sex sensitivity on pelvis bone. Further, the smallest stiffness of pelvis was computed under a certain loading condition and analyzed with respect to sex and direction. The metric complements anthropometrical measures and provides a unique information about the smallest bone stiffness independent from the loading configuration and can be easily computed by state-of-the-art subject specified finite element algorithms.
Exploring tailor-made Brønsted acid sites in mesopores of tin oxide catalyst for β-alkoxy alcohol and amino alcohol syntheses
Authors: Manjunathan Pandian , Prasanna Varsha , Shanbhag Ganapati V.
Published: August 2021

The generation of Brønsted (Sn–OH) and Lewis (coordinatively unsaturated metal centers) acidic sites on the solid surface is a prime demand for catalytic applications. Mesoporous materials are widely employed as catalysts and supports owing to their different nature of acidic sites. Nevertheless, the procedure adopted to generate acid functionalities in these materials involves tedious steps. Herein, we report the tunable acidic sites containing Brønsted sites with relatively varied acid strength in tin oxide by employing soft template followed by simple thermal treatment at various temperatures. The readily accessible active sites, specifically Brønsted acidic sites distributed throughout the tin oxide framework as well as mesoporosity endow them to perform with exceptionally high efficiency for epoxide ring opening reactions with excellent reusability. These features promoted them to surpass stannosilicate catalysts for the epoxide ring opening reactions with alcohol as a nucleophile and the study was extended to aminolysis of epoxide with the amine. The existence of relatively greater acid strength and numbers in T-SnO2-350 catalyst boosts to produce a high amount of desired products over other tin oxide catalysts. The active sites responsible in mesoporous tin oxide for epoxide alcoholysis were studied by poisoning the Brønsted acidic sites in the catalyst using 2,6-lutidine as a probe molecule.
Changing characteristics of S. aureus bacteremia caused by PVL-negative, MRSA strain over 11 years
Authors: Yang Eunmi , Kim Eunsil , Chung Hyemin , Lee Yun Woo , Bae Seongman , Jung Jiwon , Kim Min Jae , Chong Yong Pil , Kim Sung-Han , Choi Sang-Ho , Lee Sang-Oh , Kim Yang Soo
Published: August 2021

Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important cause of infection. We conducted a longitudinal study to evaluate changes in clinical and microbiological characteristics as well as outcomes of sequence type (ST) 72 MRSA bacteremia. We reviewed adult patients enrolled in a prospective cohort with ST72 MRSA bacteremia from August 2008 to December 2018 at Asan Medical Center, Seoul, South Korea. Changes in clinical characteristics, outcomes, and microbiological characteristics of patients over time were evaluated. Generalized linear and linear regression models were used to evaluate changes. Of the 1,760 isolates, 915 (62%) were MRSA bacteremia and 292 (31.9%) were ST72 MRSA. During the study period, the relative risk (RR) of MRSA bacteremia decreased annually by 3.7%; however, among MRSA bacteremia, RR of ST72 MRSA increased annually by 8.5%. Vancomycin minimum inhibitory concentration (MIC) decreased over the study period. Metastatic infection, persistent bacteremia, and recurrence of bacteremia within 12 weeks decreased significantly. There were no significant changes in 30-d and 12-week mortality. Antibiotic susceptibility of ST72 MRSA was evaluated, and the resistance rate to erythromycin decreased significantly. ST72 MRSA incidence increased annually; its vancomycin MIC and erythromycin resistance rate decreased over the 11 years.
Effect of sowing proportion on above- and below-ground competition in maize–soybean intercrops
Authors: Ren Yuanyuan , Zhang Li , Yan Minfei , Zhang Yanjun , Chen Yinglong , Palta Jairo A. , Zhang Suiqi
Published: August 2021

The relative contribution of above- and below-ground competition to crop yield under intercropping systems is critical to understanding the mechanisms of improved yield. Changes in the content of above- and below-ground biomass, leaf photosynthetic rate (Pn), leaf area index (LAI), chlorophyll meter reading (SPAD), diffuse non interceptance (DIFN), soil water storage (SWS), crop nitrogen (N), and phosphorus (P) uptake were examined in a 2-year trial of different maize–soybean intercropping systems on the Loess Plateau, China. Compared with the sole cropping system, shoot biomass of maize was increased by 54% in M2S2 and 62% in M2S4 strip intercropping treatment. The crop N and P uptake of maize increased significantly, by 54% and 50% in M2S2 and by 63% and 52% in M2S4 compared with their respective sole crop. LAI values of maize in intercropping systems were 14% and 15% for M2S2 and M2S4 less than that in the sole crop. The DIFN of intercropped maize was increased by 41% and 48% for M2S2 and M2S4 compared to monocrop. There were no significant differences in Pn and SWS in both crops between the two cropping systems. The contribution rate of DIFN in M2S2 and crop P uptake in M2S4 on the biological yield in intercropping system was the highest among all factors. We conclude that the sowing proportion affects above- and below-ground competition in maize–soybean intercropping systems.
Towards estimation of CO2 adsorption on highly porous MOF-based adsorbents using gaussian process regression approach
Authors: Gheytanzadeh Majedeh , Baghban Alireza , Habibzadeh Sajjad , Esmaeili Amin , Abida Otman , Mohaddespour Ahmad , Munir Muhammad Tajammal
Published: August 2021

In recent years, new developments in controlling greenhouse gas emissions have been implemented to address the global climate conservation concern. Indeed, the earth's average temperature is being increased mainly due to burning fossil fuels, explicitly releasing high amounts of CO2 into the atmosphere. Therefore, effective capture techniques are needed to reduce the concentration of CO2. In this regard, metal organic frameworks (MOFs) have been known as the promising materials for CO2 adsorption. Hence, study on the impact of the adsorption conditions along with the MOFs structural properties on their ability in the CO2 adsorption will open new doors for their further application in CO2 separation technologies as well. However, the high cost of the corresponding experimental study together with the instrument's error, render the use of computational methods quite beneficial. Therefore, the present study proposes a Gaussian process regression model with four kernel functions to estimate the CO2 adsorption in terms of pressure, temperature, pore volume, and surface area of MOFs. In doing so, 506 CO2 uptake values in the literature have been collected and assessed. The proposed GPR models performed very well in which the exponential kernel function, was shown as the best predictive tool with R2 value of 1. Also, the sensitivity analysis was employed to investigate the effectiveness of input variables on the CO2 adsorption, through which it was determined that pressure is the most determining parameter. As the main result, the accurate estimate of CO2 adsorption by different MOFs is obtained by briefly employing the artificial intelligence concept tools.
Numerical investigation of nanoparticles slip mechanisms impact on the natural convection heat transfer characteristics of nanofluids in an enclosure
Authors: Amidu Muritala Alade , Addad Yacine , Riahi Mohamed Kamel , Abu-Nada Eiyad
Published: August 2021

This study intends to give qualitative results toward the understanding of different slip mechanisms impact on the natural heat transfer performance of nanofluids. The slip mechanisms considered in this study are Brownian diffusion, thermophoretic diffusion, and sedimentation. This study compares three different Eulerian nanofluid models; Single-phase, two-phase, and a third model that consists of incorporating the three slip mechanisms in a two-phase drift-flux. These slip mechanisms are found to have different impacts depending on the nanoparticle concentration, where this effect ranges from negligible to dominant. It has been reported experimentally in the literature that, with high nanoparticle volume fraction the heat transfer deteriorates. Admittingly, classical nanofluid models are known to underpredict this impairment. To address this discrepancy, this study focuses on the effect of thermophoretic diffusion and sedimentation outcome as these two mechanisms turn out to be influencing players in the resulting heat transfer rate using the two-phase model. In particular, the necessity to account for the sedimentation contribution toward qualitative modeling of the heat transfer is highlighted. To this end, correlations relating the thermophoretic and sedimentation coefficients to the nanofluid concentration and Rayleigh number are proposed in this study. Numerical experiments are presented to show the effectiveness of the proposed two-phase model in approaching the experimental data, for the full range of Rayleigh number in the laminar flow regime and for nanoparticles concentration of (0% to 3%), with great satisfaction.
Author Correction: Dynamic consolidated bioprocessing for innovative lab-scale production of bacterial alkaline phosphatase from Bacillus paralicheniformis strain APSO
Authors: Abdelgalil Soad A. , Soliman Nadia A. , Abo-Zaid Gaber A. , Abdel-Fattah Yasser R.
Published: August 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Green development of China’s Pan-Pearl River Delta mega-urban agglomeration
Authors: Liu Tao , Li Yue
Published: August 2021

Mega-urban agglomerations in developing countries have been main parts of economic development. But at the same time, they have become the most prominent and sensitive areas of resource and environment problems. It is important to clarify the mechanism and driving factors of green growth in mega-urban agglomerations. Based on the panel data of 28 major cities in China's Pan-Pearl River Delta urban agglomeration from 2006 to 2015, this paper evaluates the level of green development of urban agglomeration by green total factor productivity index (GTFP) based on Global Malmquist DEA model, and decomposes GTFP into technological progress, pure technical efficiency change, scale efficiency change and technological scale change. On this basis, this paper constructs a panel econometric model to analyze the influencing factors of GTFP and its decomposition factors. The results show that GTFP of Pan-Pearl River Delta urban agglomeration is growing, and the scale effect caused by technological progress is the main driving factor. Green development in the Pearl River Delta urban agglomeration takes into account efficiency and regional fairness, which causes differences in GTFP growth patterns of sub-urban agglomerations within mega-urban agglomerations. The technological progress and technical efficiency improvement are becoming the main driving force of GTFP growth in relatively backward areas. Furthermore, according to the influencing factors of GTFP and its decomposition factors, mega-urban agglomeration should eliminate internal administrative barriers to build an integrated market. It should also increase the proportion of technology industries in core cities, and give full play to the role of technology spillover effect on surrounding cities. In addition, improving the efficiency of resource and energy utilization is also helpful to promote the transformation of urban agglomeration development from factor-driven to efficiency-driven and innovation-driven. Our research results have implications for the coordinated development of economy and environment in developing countries.
An activatable near-infrared fluorescent probe facilitated high-contrast lipophagic imaging in live cells
Authors: Chen Wen , Luo Na , Zhang Yuan , Tang Li-Juan , Wang Fenglin , Jiang Jian-Hui
Published: August 2021

The schematic illustration of Q-lipo for activatable imaging of lipophagy.
Electrochemical heterodifunctionalization of α-CF3alkenes to access α-trifluoromethyl-β-sulfonyl tertiary alcohols
Authors: Ye Zhi-Peng , Gao Jie , Duan Xin-Yu , Guan Jian-Ping , Liu Fang , Chen Kai , Xiao Jun-An , Xiang Hao-Yue , Yang Hua
Published: August 2021

An unprecedented electrochemical heterodifunctionalization of α-CF3alkenes with benzenesulfonyl hydrazides was accomplished in this work, wherein a β-sulfonyl and a α-hydroxyl group were simultaneously incorporated across the olefinic double bond in a single operation.
Electrically tunable band gap in strained h-BN/silicene van der Waals heterostructures
Authors: de Vargas Douglas D. , Köhler Mateus H. , Baierle Rogério J.
Published: August 2021

The charge redistribution and orbital hybridization due to external electric fields and compressive strain are very promising for silicene-based nanoelectronics.
Experimental and computational characterization of phase transitions in CsB3H8
Authors: Zavorotynska Olena , Sørby Magnus H. , Vitillo Jenny G. , Deledda Stefano , Frommen Christoph , Hauback Bjørn C.
Published: August 2021

CsB3H8 undergoes two phase transitions to an orthorhombic and then a cubic phase prior to decomposition.
Exploring the thermodynamic, kinetic and inhibitory mechanisms of 5-iTU targeting mitotic kinase haspin by integrated molecular dynamics
Authors: Wang Qianqian , Zhang Qinggao , Leung Elaine Lai Han , Chen Yingqing , Yao Xiaojun
Published: August 2021

Thermodynamic and kinetic mechanisms of 5-iTU inhibiting human kinase haspin were studied by biased and unbiased molecular dynamics.
High-voltage liquid electrolytes for Li batteries: progress and perspectives
Authors: Fan Xiulin , Wang Chunsheng
Published: August 2021

Recent advances, fundamental mechanisms and design strategies of high-voltage liquid electrolytes are comprehensively summarized in this review.
Self-standing SnS nanosheet array: a bifunctional binder-free thin film catalyst for electrochemical hydrogen generation and wastewater treatment
Authors: Patil Supriya A. , Bui Hoa Thi , Hussain Sajjad , Rabani Iqra , Seo Yongho , Jung Jongwan , Shrestha Nabeen K. , Kim Hyungsang , Im Hyunsik
Published: August 2021

A binder-free array of self-standing SnS nanosheets is demonstrated as a bifunctional catalytic platform for simultaneous decontamination of urea waste in water and green H2generation.
High precision MC-ICP-MS measurements of11B/10B ratios from ng amounts of boron in carbonate samples using microsublimation and direct injection (μ-dDIHEN)
Authors: Buisson Matthieu , Louvat Pascale , Thaler Caroline , Rollion-Bard Claire
Published: August 2021

Boron extraction from the samples by microsublimation, use of a miniaturized direct injection system (μ-dDIHEN) and of 1013Ω amplifiers on the MC-ICP-MS allow preciseδ11B measurements of very small and B-poor samples, such as marine carbonates.
Surface and morphological studies of LiNbO3: p-type semiconductivity on stoichiometric surfaces
Authors: Lacerda Luis Henrique da Silveira , San-Miguel Miguel Angel , de Lazaro Sergio Ricardo
Published: August 2021

The surface and morphological properties of LiNbO3 surfaces were calculated, and particular semiconductor types for crystal morphologies were found.
Cheminformatic analysis of natural product-based drugs and chemical probes
Authors: Stone Samantha , Newman David J. , Colletti Steven L. , Tan Derek S.
Published: August 2021

Cheminformatic analyses illustrate that drugs from natural product-based and synthetic origins have distinctive structural and physicochemical features. These drugs also cluster by biosynthetic origin and, to some extent, by therapeutic class.
Analysis of the electron emission characteristics and working mechanism of a planar bottom gate vacuum field emission triode with a nanoscale channel
Authors: Wang Xiao , Xue Tao , Shen Zhihua , Long Minggang , Wu Shengli
Published: August 2021

A separate planar lateral VFET device with a nanoscale channel was fabricated, which exhibited good emission characteristics in vacuum and can be operated in air. Field-assisted thermal emission explains the emission mechanism at low voltage.
Dust in brown dwarfs and extra-solar planets
Authors: Köhn C. , Helling Ch. , Bødker Enghoff M. , Haynes K. , Sindel J. P. , Krog D. , Gobrecht D.
Published: August 2021

Context. Modelling the formation of cloud condensation nuclei (CCNs) is key for predicting cloud properties in planet and brown dwarf atmospheres. The large diversity of exoplanets (rocky planets, mini-Neptunes, giant gas planets) requires a fundamental approach to cloud formation modelling in order to allow a full analysis of observational data contributing to exoplanet characterisation.

Aims. We aim to understand the onset of cloud formation and study the formation of TiO2-CCNs. The formation of (TiO2)N clusters as precursors to extrasolar cloud formation is modelled by two different methods in order to understand their potential, identify underlying shortcomings, and to validate our methods. We propose potential spectral tracers for TiO2-CCN formation.

Methods. We applied three-dimensional Monte Carlo (3D MC) simulations to model the collision-induced growth of TiO2-molecules to (TiO2)N-clusters in the free molecular flow regime of an atmospheric gas. We derived individual, time-dependent (TiO2)N cluster number densities. For T = 1000 K, the results are compared to a kinetic approach that utilises thermodynamic data for individual (TiO2)N clusters.

Results. The (TiO2)N cluster size distribution is temperature dependent and evolves in time until a steady state is reached. For T = 1000 K, the 3D MC and the kinetic approach agree well regarding the cluster number densities for N = 1 … 10, the vivid onset of cluster formation, and the long transition into a steady state. Collision-induced growth and evaporation simulated using a 3D MC approach enables a faster onset of cluster growth through nucleation bursts. Different size distributions develop for monomer-cluster and for cluster-cluster growth, with the largest clusters appearing for cluster-cluster growth.

Conclusions. The (TiO2)N cluster growth efficiency has a sweet-spot temperature at ≈1000 K at which CCN formation is triggered. The combination of local thermodynamic conditions and chemical processes therefore determines CCN formation efficiency. The onset of cloud formation may be observable through the (TiO2)4, (TiO2)5, and (TiO2)6 vibrational lines, which may be detectable with the Mid-Infrared Instrument on the James Webb Space Telescope or the Extremely Large Telescope’s mid-IR imager, but more complete line-list data are desirable.
Akute Nierenschädigung – Update 2021
Authors: Schmidt-Ott Kai M.
Published: August 2021

Was ist neu?

Automatisierte Detektion von akuter Nierenschädigung (AKI) und AKI-Alert-Systeme Computersysteme zur automatisierten Erkennung von akuter Nierenschädigung (AKI-Alerts) halten Einzug in Kliniken. Diese alarmieren Ärzte automatisiert, wenn AKI anhand von Kreatininverläufen erkannt wird. Neue Studienergebnisse zeigen, dass der klinische Einsatz solcher Alarmsysteme sorgfältig geplant und mit konkreten Schulungen und Handlungsempfehlungen gekoppelt werden sollte.

Nierenersatzverfahren bei akuter Nierenschädigung Der Einsatz von Nierenersatzverfahren bei kritisch kranken Patienten mit AKI erfolgt derzeit nicht nach völlig einheitlichen Kriterien. Neue Daten liegen nun zum optimalen Zeitpunkt für den Therapiebeginn und zur Antikoagulation vor.

COVID-19 und akute Nierenschädigung Das gehäufte Auftreten von AKI bei Coronavirus disease-2019 (COVID-19) stellt Nephrologen und Intensivmediziner vor große Herausforderungen. Eine Vielzahl kürzlich erschienener Arbeiten untersucht die zugrunde liegende Epidemiologie und Pathophysiologie dieses neuen Krankheitsbilds. Das derzeitige klinische Vorgehen wird durch eine Kombination aus Beobachtungsstudien an COVID-19-Patienten und prospektiven Daten aus dem Non-COVID-19-Bereich instruiert.
Volumentherapie und Nierenschädigung – was gibt es Neues?
Authors: Willam Carsten , Schley Gunnar
Published: August 2021

Was ist neu?

Welche Menge an Volumenersatzstoff geben? Im Schock erfolgt die Flüssigkeitstherapie mit Kristalloiden nach zielgerichteten Kriterien und unter Kontrolle des Laktats. Zur Wiederherstellung des Reäquilibriums ist oft eine Negativbilanz durch Flüssigkeitsrestriktion, Schleifendiuretika und maschinelle Ultrafiltration erforderlich. Bei einer maschinellen Ultrafiltration sollten 1,75 ml/kg/h nicht überschritten werden.

Welche Volumenersatzstoffe geben? Balancierte Kristalloide sind Mittel der Wahl zur Flüssigkeitstherapie. Neue Volumenersatzstoffe mit einer höheren Anionenlücke haben einen alkalisierenden Effekt und können möglicherweise die Flüssigkeitstherapie optimieren.

Welche Volumenersatzstoffe führen zu AKI? Kochsalz führt aufgrund einer hyperchlorämischen Azidose in moderaten Mengen zu einer funktionellen Einschränkung der renalen Filtration. In höheren Mengen ist NaCl mit einem schlechten Outcome vergesellschaftet. HES und vermutlich auch Gelatine haben zytotoxische Effekte und können zu einer akuten Nierenschädigung führen.
Quantifizierung der Entwicklungen des Mangels an
Fachärzten/innen für Öffentliches
Gesundheitswesen im Öffentlichen Gesundheitsdienst und seine
Auswirkungen
Authors: Tinnemann Peter , Bruns-Philipps Elke , Schumacher Jakob
Published: August 2021

Für die Gesundheit der Bevölkerung in Deutschland spielen die
Einrichtungen des Öffentlichen Gesundheitsdienstes auf der Ebene der
Kommunen, der Länder und des Bundes eine zentrale Rolle. Zur
Bewältigung der vielfältigen praktischen Aufgaben des
Gesundheitsschutzes, der Krankheitsvermeidung und Gesundheitsförderung
nach rechtlichen Vorgaben arbeiten Mitarbeitende mit unterschiedlichen
Kompetenzen zusammen und tragen zur sozialen Kohärenz bei. Die
bundesweite Personalausstattung wird nicht empirisch erhoben. Unterschiedliche
Akteure kolportieren seit Jahren eine abnehmende Zahl an
Fachärzten/innen und damit verbundene
Qualitätseinschränkungen. Ziel dieser Untersuchung ist, den
Rückgang an Fachärzten/innen für das
Öffentliche Gesundheitswesen zu quantifizieren und regionale Trends
darzustellen. Regelmäßig erhobene und frei verfügbare
Daten zu den in dem Zeitraum von 1998 bis 2018 in Deutschland registrierten
Ärzte/innen wurden deskriptiv analysiert, in Bezug auf
Entwicklungen der Zahl an Fachärzte/innen in Deutschland, in den
Landesärztekammer Regionen, nach Facharztgebieten und Alter.
Während die Anzahl der Fachärzte/innen in Deutschland
insgesamt kontinuierlich steigt (52%), bleibt die Zahl derer, die in
Behörden, Körperschaften u. a. tätig sind mit
2% relativ konstant. Dagegen hat die Zahl der in Behörden und
Körperschaften tätigen Fachärzte/innen
für Öffentliches Gesundheitswesen in den letzten 20 Jahren um
fast 30% abgenommen. Ähnliche Entwicklungen zeigen sich in allen
Regionen, mit zum Teil noch größeren regionalen Abnahmen. Bayern
ist die einzige Region mit einer gegensätzlichen Entwicklung.
Für Fachärzte/innen für Öffentliches
Gesundheitswesen gibt es nahezu kaum Nachwuchs und Überalterung in
diesem Facharztgebiet nimmt zu. Vor dem Hintergrund der Entwicklungen
fachärztlicher Qualifikationen im Öffentlichen Gesundheitsdienst
muss eine ausreichend fachärztliche Bearbeitung hoheitlicher und anderer
für die Bevölkerungsmedizin relevanter Aufgaben in Frage
gestellt werden. Diese Entwicklungen bedrohen die Bevölkerungsgesundheit
im Allgemeinen, die öffentliche Sorge um vulnerable
Bevölkerungsgruppen im Speziellen und letztendlich den funktionierenden
demokratischen Sozialstaat.
How the COVID-19 Pandemic has Changed the Game of Soccer
Authors: Link Daniel , Anzer Gabriel
Published: August 2021

This study explores the influence of corona-specific training and playing conditions - especially empty stadiums - on match performance, contact behavior, and home advantage in the Bundesliga (BL) and Bundesliga 2 (BL2). We analyzed the 2017/18, 2018/19, and 2019/20 seasons and compared matches in rounds 26–34 before shutdown with “ghost” matches after restart. Results show increased running activity for high intensity distance: (+ 6.1%) and total distance covered (+ 4.3%). In BL2 in particular there were also changes in tactical aspects of the game (time in last third: –6.3%, pressure on pass receiver: –8.6%, success of attacking duels: –7.9%, share of long passes completed: + 15.6%, outplayed opponents per pass: –14.7%). Contact time to other players (< 2 m distance) was 15:35 mins per match. After restart, contact was reduced, especially when the ball was not in the last third (–11.2%). Away wins increased by +44.2% in BL and the home-away difference in yellow cards changed in favor of the away team (+31.2%) in BL2. We conclude that empty stadiums have reduced home advantage and decreased referee bias when awarding yellow cards. Player behavior might have been affected by tactical demands and/or conscious or unconscious self-protection.
Rezidivierende Pankreatitiden bei einer 43-jährigen Patientin mit High-Output Stoma
Authors: Jessen Bosse , Möhlig Matthias , Siegmund Britta , Treese Christoph
Published: August 2021

Die Hyperkalzämie ist nur selten ein Auslöser der akuten Pankreatitis. Um die Ursache einer Hyperkalzämie zu eruieren, ist eine sorgfältige Differenzialdiagnostik nötig. In diesem Fallbeispiel beruhte die Hyperkalzämie auf einer Immobilisation bei Vorliegen eines High-Output-Stomas. Diese besondere Ätiologie der Pankreatitis ist bisher nicht beschrieben.
Zurück in die Pflege: Zwischen „Sollen“,
„Wollen“ und „Können“ –
Berufsidentitäten von Pflegefachkräften in Krisensituationen am
Beispiel der Sars-CoV-2-Pandemie
Authors: Tezcan-Güntekin Hürrem , Schmidt Julia Margarethe , Özer-Erdogdu Ilknur
Published: August 2021

Ziel Es werden Anforderungen, Motivationen und Herausforderungen bei der
pandemiebedingten Rückkehr von ausgebildeten Pflegefachkräften
in den Pflegeberuf analysiert, um Erkenntnisse zu Berufsidentitäten von
Pflegefachkräften in Krisensituationen abzuleiten und
Handlungsansätze für eine gelingende Rückkehr –
vorübergehend oder dauerhaft – in den Pflegeberuf zu
formulieren.

Methodik Auf der Grundlage des Diskrepanz-Modells nach Heinzer et al. [11]
und einer strukturierenden qualitativen Inhaltsanalyse [13] wurden 15
Expert*inneninterviews mit Pflegefachkräften
durchgeführt und analysiert.

Ergebnisse Die Ergebnisse zeigen auf, dass sich Pflegefachkräfte,
die beabsichtigen zeitweise in den Pflegeberuf zurückzukehren oder
bereits wieder in der Pflege arbeiten, in Zwiespälten befinden, die sich
in Kontinuen zwischen Pflichtgefühl, kollegialer Hilfsbereitschaft,
Fürsorge und Selbstfürsorge bewegen.

Schlussfolgerungen Um Pflegefachkräften den Wiedereinstieg in den
Pflegeberuf zu erleichtern, bedarf es einer transparenten Kommunikation von
Zugängen und einer Verringerung von Barrieren, einem
wertschätzenden Umgang und Möglichkeiten der Mitgestaltung von
Arbeitsbedingungen.
The Effects of Physical Exercise on Tumor Vasculature: Systematic Review and Meta-analysis
Authors: Esteves Mário , Monteiro Mariana P. , Duarte Jose Alberto
Published: August 2021

A wealth of evidence supports an association between physical exercise, decreased tumor growth rate, and reduced risk of cancer mortality. In this context, the tumor vascular microenvironment may play a key role in modulating tumor biologic behavior. The present systematic review and meta-analysis aimed to summarize the evidence regarding the effects of physical exercise on tumor vasculature in pre-clinical studies. We performed a computerized research on the PubMed, Scopus, and EBSCO databases to identify pre-clinical studies that evaluated the effect of physical exercise on tumor vascular outcomes. Mean differences were calculated through a random effects model. The present systematic review included 13 studies involving 373 animals. From these, 11 studies evaluated chronic intratumoral vascular adaptations and 2 studies assessed the acute intratumoral vascular adaptations to physical exercise. The chronic intratumoral vascular adaptations resulted in higher tumor microvessel density in 4 studies, increased tumor perfusion in 2 studies, and reduced intratumoral hypoxia in 3 studies. Quantitatively, regular physical exercise induced an increased tumor vascularization of 2.13 [1.07, 3.20] (p<0.0001). The acute intratumoral vascular adaptations included increased vascular conductance and reduced vascular resistance, which improved tumor perfusion and attenuated intratumoral hypoxia. In pre-clinical studies, physical exercise seems to improve tumor vascularization.
Advances in [1,2]-Sigmatropic Rearrangements of Onium Ylides via Carbene Transfer Reactions
Authors: Koenigs Rene M. , Empel Claire , Jana Sripati
Published: August 2021

This review article summarizes progress made on [1,2]-sigmatropic rearrangements using carbenes in the ylide formation step. While other rearrangements, such as the [2,3]-sigmatropic, Doyle–Kirmse, or Sommelet–Hauser rearrangements, have been studied in detail over the past decades, investigations on [1,2]-sigmatropic rearrangements are still limited. Based on the application of diazoalkanes as carbene precursors, research on diazoalkanes in ylide formation reactions started flourishing in the 1990s. This Short Review covers milestones from the advent of [1,2]-sigmatropic rearrangements using carbenes to generate ammonium, oxonium and other ylide species, and should serve as an overview to further promote research in this area.

1 Introduction

2 Ammonium Ylides

3 Oxonium Ylides

4 Sulfonium and Selenium Ylides

5 Halonium Ylides

6 Conclusion and Outlook
Recent Advances in Light-Driven Carbon–Carbon Bond Formation via Carbon Dioxide Activation
Authors: Jung Jieun , Saito Susumu
Published: August 2021

Carbon dioxide (CO2) is an attractive renewable one-carbon (C1) feedstock in terms of its earth abundance, low cost, and non-toxicity. Developing new catalytic systems to realize the practical insertion of CO2 into organic molecules has been of great importance for ecological economics. In recent years, outstanding improvements have been carried out in the field of light-driven catalytic carboxylation via the activation of CO2 as the key reagent. In this short review, the recent developments of light-promoted carboxylation utilizing CO2 to synthesize value-added chemicals using a dual visible-light photoredox/transition-metal catalyst or a photoredox catalyst are highlighted.

1 Introduction

2 Visible-Light-Driven Carboxylation Using Transition-Metal Photocatalysts

2.1 Transition-Metal-Catalyzed Carboxylation of Alkenes

2.2 Transition-Metal-Catalyzed Carboxylation of C(sp2)–X (X = Cl, Br, OTf) Bonds

2.3 Transition-Metal-Catalyzed Carboxylation of Alkynes

2.4 Transition-Metal-Catalyzed Carboxylation of Carbons Attached to Nitrogen

3 Light-Driven Carboxylation via Organo-Photocatalysis

3.1 Photocatalytic Carboxylation of Alkenes

3.2 Photocatalytic Carboxylation of C(sp3)–H Bonds

4 Conclusion
Synthesis of α-exo-Methylene-γ-butyrolactones: Recent Developments and Applications in Natural Product Synthesis
Authors: Liu Weilong , Winssinger Nicolas
Published: August 2021

The α-exo-methylene-γ-butyrolactone moiety is present in a vast array of structurally diverse natural products and is often central to their biological activity. In this short review, we summarize new approaches to α-exo-methylene-γ-butyrolactones developed over the past decade as well as their applications in total synthesis.

1 Introduction

2 Approaches to α-exo-Methylene-γ-butyrolactones

2.1 Enantioselective Synthesis via Lactonization Approaches

2.2 Enantioselective Halolactonizations

2.3 Enantioselective Barbier-Type Allylation

2.4 C–H Insertion/Olefination Sequences

2.5 Alkene Cyclization

2.6 Strain-Driven Dyotropic Rearrangement

3 β-(Hydroxymethylalkyl)-α-exo-methylene-γ-butyrolactones

4 Applications in Total Synthesis

4.1 Sesquiterpene Lactones

4.2 Lignans

4.3 Other Monocyclic Natural Products

4.4 Choice of Methodology in Recent Total Syntheses

5 Summary and Outlook
Transition-Metal-Catalyzed Nucleophilic Dearomatization of Electron-Deficient Heteroarenes
Authors: Hu Fangdong , Xia Ying , Jia Jie
Published: August 2021

In recent decades, transition-metal-catalyzed nucleophilic dearomatization of electron-deficient heteroarenes, such as pyridines, quinolines, isoquinolines and nitroindoles, has become a powerful method for accessing unsaturated heterocycles. This short review summarizes nucleophilic dearomatizations of electron-deficient hetero­arenes with carbon- and heteroatom-based nucleophiles via transition-metal catalysis. A significant number of functionalized heterocycles are obtained via this transformation. Importantly, many of these reactions are carried out in an enantioselective manner by means of asymmetric catalysis, providing a unique method for the construction of enantio­enriched heterocycles.

1 Introduction

2 Transition-Metal-Catalyzed Nucleophilic Dearomatization of Hetero­arenes via Alkynylation

3 Transition-Metal-Catalyzed Nucleophilic Dearomatization of Heteroarenes­ via Arylation

4 Transition-Metal-Catalyzed Nucleophilic Dearomatization of Heteroarenes­ with Other Nucleophiles

5 Transition-Metal-Catalyzed Nucleophilic Dearomatization with Nucleophiles Formed In Situ

6 Conclusion and Outlook
Development of Synthetic Strategies to Access Optically Pure ­Feringa’s Motors
Authors: Qin Yu-Nan , Zhang Chen , Li Quan , Du Guang-Yan
Published: August 2021

Light-driven unidirectional molecular motors have gained significant attention since the pioneering work by Prof. Ben Feringa in 1999, and they hold great promise as next-generation smart materials. The intrinsic feature of point chirality and the helicity of these molecular motors requires efficient strategies to access their optically pure forms, especially when chirality-sensitive materials are fabricated. In this short review, we summarize synthetic strategies to access optically pure first- and second-generation molecular motors. Three general strategies are discussed: direct asymmetric synthesis, chiral auxiliary methods and chiral separation aided by a resolving agent. We hope that this review will ignite the enthusiasm of synthetic chemists to address very fundamental but unavoidable synthetic questions on chiral-alkene-based molecular motors concerning their large-scale appli­cations.

1 Introduction

2 Synthesis of First-Generation Molecular Motors

2.1 Direct Asymmetric Synthesis of Molecular Motors

2.2 Resolving-Agent-Aided Chiral Resolution of Molecular Motors

3 Synthesis of Second-Generation Molecular Motors

3.1 Direct Asymmetric Synthesis of Molecular Motors

3.2 Chiral Auxiliary Strategy

3.3 Domino Strategy

4 onclusions
The Effect of Electronic Health Record Burden on Pediatricians' Work–Life Balance and Career Satisfaction
Authors: Frintner Mary Pat , Kaelber David C. , Kirkendall Eric S. , Lourie Eli M. , Somberg Chloe A. , Lehmann Christoph U.
Published: August 2021

Objectives To examine pediatricians' perspectives on administrative tasks including electronic health record (EHR) documentation burden and their effect on work–life balance and life and career satisfaction.

Methods We analyzed 2018 survey data from the American Academy of Pediatrics (AAP) Pediatrician Life and Career Experience Study (PLACES), a longitudinal cohort study of early and midcareer pediatricians. Cohorts graduated from residency between 2002 and 2004 or 2009 and 2011. Participants were randomly selected from an AAP database (included all pediatricians who completed U.S. pediatric residency programs). Four in 10 pediatricians (1,796 out of 4,677) were enrolled in PLACES in 2012 and considered participants in 2018. Data were weighted to adjust for differences between study participants and the overall population of pediatricians. Chi-square and multivariable logistic regression examined the association of EHR burden on work–life balance (three measures) and satisfaction with work, career, and life (three measures). Responses to an open-ended question on experiences with administrative tasks were reviewed.

Results A total of 66% of pediatrician participants completed the 2018 surveys (1,192 of 1,796; analytic sample = 1,069). Three-fourths reported EHR documentation as a major or moderate burden. Half reported such burden for billing and insurance and 42.7% for quality and performance measurement. Most pediatricians reported satisfaction with their jobs (86.7%), careers (84.5%), and lives (66.2%). Many reported work–life balance challenges (52.5% reported stress balancing work and personal responsibilities). In multivariable analysis, higher reported EHR burden was associated with lower scores on career and life satisfaction measures and on all three measures of work–life balance. Open-ended responses (n = 467) revealed several themes. Two predominant themes especially supported the quantitative findings—poor EHR functionality and lack of support for administrative burdens.

Conclusion Most early to midcareer pediatricians experience administrative burdens with EHRs. These experiences are associated with worse work–life balance including more stress in balancing responsibilities and less career and life satisfaction.