bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecularly Imprinted and Cladded Nanotags Enable Specific SERS Bioimaging of Tyrosine Phosphorylation
Authors: Guo Zhanchen , Zhao Jialing , He Hui , Liu Zhen
Published: October 2022

Tyrosine phosphorylation is an important post‐translational modification of proteins, and its accurate analysis is of vital importance. However, due to limited abundance of tyrosine phosphorylation as well as severe interference of serine/threonine phosphorylation and other phosphate‐containing species, approaches that can directly analyse tyrosine phosphorylation on the cell membrane still remain limited. Herein, we report the rational development of molecularly imprinted and cladded Raman nanotags and their successful application in surface enhanced Raman spectroscopy (SERS) imaging of tyrosine phosphorylation on cancerous cells and tissues. The prepared molecularly imprinted and cladded SERS nanotags could specifically recognize phosphotyrosine and thereby allowed for distinguishing phosphotyrosine from other phosphate‐containing species on cancerous cells and tissues by SERS imaging. Therefore, the molecularly imprinted and cladded nanotags‐based SERS imaging can be a promising tool for tyrosine phosphorylation analysis and tyrosine phosphorylation‐related studies, showing great potential for biomedical applications.
A dark side of hope: Understanding why investors cling onto losing stocks
Authors: Luo Siria Xiyueyao , van Horen Femke , Millet Kobe , Zeelenberg Marcel
Published: October 2022

Investors are often inclined to keep losing stocks too long, despite this being irrational. This phenomenon is part of the disposition effect (“people ride losers too long, and sell winners too soon”). The current research examines the role of hope as a potential explanation of why people ride losers too long. Three correlational studies (1A, 1B, and 2) find that people's trait hope is positively associated with their inclination to keep losing stocks, regardless of their risk‐seeking tendency (Study 2). Further, three experimental studies (3, 4, and 5) reveal that people are inclined to hold on to losing (vs. not‐losing) stocks because of their hope to break even and not because of their hope to gain. Studies 4 and 5 provide process evidence confirming the role of hope and indicate potential interventions to decrease people's tendency to keep losing stocks by reducing the hope. The findings contribute to the limited empirical literature that has investigated how emotions influence the disposition effect by providing empirical evidence for the role of hope. Moreover, the findings add to the literature of hope by revealing its role in financial decision‐making and show a “dark side” of this positive emotion.
Oxidized phospholipids and lipoprotein‐associated phospholipase A2 (Lp‐PLA2) in atherosclerotic cardiovascular disease: An update
Authors: Pantazi Despoina , Tellis Constantinos , Tselepis Alexandros D.
Published: October 2022

Inflammation and oxidative stress conditions lead to a variety of oxidative modifications of lipoprotein phospholipids implicated in the occurrence and development of atherosclerotic lesions. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) is established as an independent risk biomarker of atherosclerosis‐related cardiovascular disease (ASCVD) and mediates vascular inflammation through the regulation of lipid metabolism in the blood and in atherosclerotic lesions. Lp‐PLA2 is associated with low‐ and high‐density lipoproteins and Lipoprotein (a) in human plasma and specifically hydrolyzes oxidized phospholipids involved in oxidative stress modification. Several oxidized phospholipids (OxPLs) subspecies can be detoxified through enzymatic degradation by Lp‐PLA2 activation, forming lysophospholipids and oxidized non‐esterified fatty acids (OxNEFAs). Lysophospholipids promote the expression of adhesion molecules, stimulate cytokines production (TNF‐α, IL‐6), and attract macrophages to the arterial intima. The present review article discusses new data on the functional roles of OxPLs and Lp‐PLA2 associated with lipoproteins.
Vascular stiffening in aging females with a hypertension‐induced HIF2A gain‐of‐function mutation
Authors: Volkova Eugenia , Procell Linda , Kong Lingyang , Santhanam Lakshmi , Gerecht Sharon
Published: October 2022

Pulmonary arterial hypertension (PAH) is more prevalent in females than males; the causes of this sex difference have not been adequately explored. Gain‐of‐function (GOF) mutations in hypoxia‐inducible factor 2α (HIF2A) lead to PAH and thrombotic consequences in patients and mice. Additionally, multiple emerging studies suggest that elevated systemic arterial stiffening (SAS) occurs in PAH; this could have critical prognostic value. Here, we utilized a HIF2A GOF mouse model to determine how SAS can be used as a prognosticator in sex‐divergent PAH. We analyzed survival, vascular mechanics, and vascular phenotypes in young adult (8–16 weeks) and middle age (9–12 months) Hif2a GOF mice. We find that Hif2a heterozygous (HT) female mice, but not Hif2a HT male mice, exhibit poor survival, SAS upon aging, and decreased ability to withstand repeated physiological strain. Hif2a HT female mice also display thickening of the adventitial intima and increased collagen I and collagen III in all layers of the thoracic aorta. Our findings demonstrate differing PAH progression in female and male Hif2a GOF mice. Specifically, alterations in extracellular matrix (ECM) content led to vascular stiffening in aged females, resulting in poor survival. Moreover, we show that SAS emerges early in mice with PAH by coupling studies of vascular mechanics and analyzing vascular structure and composition. Importantly, we present a model for assessing sex differences in hereditary PAH progression and sex‐specific prognosis, proposing that aortic stiffening can be used to prognosticate future poor outcomes in PAH.
Azaphilones from the Endophyte Diaporthe sp. and Their Toxicity
Authors: Huang Fangfang , Lin Xiao , Lu Quanyi
Published: October 2022

Chemotherapy and targeted therapies are increasingly used as conventional means to control tumor growth and prolong survival. Patient treated with anti‐neoplastic agents experience severe side effects, especially those cytotoxic chemotherapies. Exploring chemo agents with less side effects is the hot spot of anticancer research. In this study, three azaphilone derivatives (chaetoviridin A (1), chaetoviridin E (2) and chaetomugilin D (3)) were isolated from the endophyte of the plant Anoectochilus roxburghii (Wall.) Lindl, their structures were elucidated by NMR. The toxicity of these compounds was evaluated by zebrafish model. The results show that these compounds had no toxicity against zebrafish. These compounds may act as safe anticancer drug leads according to this result. These three azaphilone derivatives were first time reported isolated from Diaporthe species which mainly used to isolate from Chaetomium species.
Sesquiterpenes fromRhododendron nivaleand Their Anti‐Inflammatory Activity
Authors: Zeng Xi , Liu Wei , Yuan Tao
Published: October 2022

Two new germacrane sesquiterpenes, named nivalenoids A and B (1and2), along with four known sesquiterpenes (3–6), were isolated from theRhododendron nivale. The structures of compounds1and2were elucidated by integrating spectroscopic analyses, including NMR, UV, IR, as well as HR‐MS data. Anti‐inflammatory activity by inhibiting lipopolysaccharide (LPS)‐induced NO production in RAW 264.7 cells revealed that compared with the positive control dexamethasone (IC50=2.50 μM), compounds1and2showed mild anti‐inflammatory activity, with IC50value of 27.55 μM and 53.26 μM, respectively.
Cu/Cu3P@CNT Flexible Film Electrode for Highly Efficient Electrocatalytic Hydrogen Evolution in Alkaline Solution
Authors: Wu Wanying , Zhang Maohui , Xia Xinyao , Yang Zhiyun , Li Di , Zhang Quansheng , Xie Jingying
Published: October 2022

Global warming and the global energy crisis are worsening owing to the increasing consumption of fossil fuels; thus, there is a need to explore renewable and clean energy sources. The energy conversion efficiency of water electrolysis – an important and feasible means to obtain green hydrogen energy – can be improved by developing catalytic electrode materials with high activity and low overpotential. Herein, low‐temperature phosphating of copper deposited on flexible carbon nanotube (CNT) films was conducted to fabricate high‐performance Cu/Cu3P@CNT electrocatalysts for the hydrogen evolution reaction (HER). The optimal conditions for the preparation of catalytic electrodes were determined by adjusting the electrodeposition time. Owing to the porous CNT framework and the heterostructure of the Cu3P/Cu nanoparticles, the Cu/Cu3P@CNT exhibited long‐term stability and highly efficient catalytic HER in an alkaline electrolyte with an overpotential of only 77 mV at 10 mA cm−2. This study provided a facile strategy for designing inexpensive and efficient electrocatalytic HER systems using highly active transition metal phosphides heterostructures and CNT materials.
Design and Synthesis of Fsp3‐Enriched Spirocyclic‐Based Biological Screening Compound Arrays via DOS Strategies and Their NNMT Inhibition Profiling
Authors: Iusupov Ildar R. , Lukyanenko Evgeny R. , Altieri Andrea , Kurkin Alexander V.
Published: October 2022

Medicinal chemists are keen to explore tridimensional compounds, especially when it comes to small molecules. It has already been stressed that the majority of known drugs tend to be flat, whereas natural products tend to be more tridimensional and represent a good source of active compounds. 3D metrics have been implemented and computational descriptors are available to evaluate and prioritize compounds based on their 3D geometry. This is usually done by comparing the saturated carbon atoms in a molecule with the total number of its non‐hydrogen atoms (the Fsp3 value). While this aspect is clear, still there are not enough synthetic tools that support the realization of novel chemotypes that conform to these criteria. Herein we describe a diversity oriented synthesis (DOS) synthetic cascade technology that starts from two simple reagents, and generates highly enriched Fsp3 novel and diverse spiro‐scaffolds with pragmatic synthetic handles (points of diversity). The spiro nature of these scaffolds not only ensures high Fsp3 values but renders the compounds more rigid and therefore more effective in forming precise stereo‐interactions with their potential biological targets. These compounds were also profiled for their drug‐like properties and as potential modulators of the NNMT enzyme.
Effects of Structural Variations on Antibacterial Properties for Conjugated Diynes Generated through Glaser Hay Couplings
Authors: Hale Emma A. , Ryan Hannah M. , McOsker Alexandra M. , Funk Cody M. , Green Lauren C. , Mazur Lauren E. , Uthappa Diya M. , Flood Brian M. , Young Douglas D. , Hinkle Robert J.
Published: October 2022

Antibiotic resistance is a growing problem facing global societies today. Many new antibiotics are derivatized versions of already existing antibiotics, which allows for antibiotic resistance to arise. To combat this issue, new antibiotics with different core structures need to be elucidated. Asymmetrical polyacetylenes have been isolated from natural products and they have previously been demonstrated to exhibit antimicrobial and antibacterial activity; however, their synthetic preparation has not made them easily amenable to rapid derivatization for SAR studies. Using a combination of solution and solid‐supported chemistries, an array of diynes inspired by a known natural product were prepared and assessed for antibacterial activity. Ultimately, several compounds were identified with improved activity in bacterial viability assays. Moreover, some compounds were discovered that displayed a degree of specificity forE. colioverP. fluorescensand vice versa. These new compounds show promise, and further investigation is needed to pinpoint the specific structural components that elicit biological activity.
Magnetic Field‐Assisted Construction and Enhancement of Electrocatalysts
Authors: Jiang Xueliang , Chen Yana , Zhang Xianzheng , You Feng , Yao Junlong , Yang Huan , Xia Bao Yu
Published: October 2022

Driven by the energy crisis and environmental pollution, developing sustainable clean energy is an effective strategy to realize carbon neutrality. Electrocatalytic reactions are crucial to sustainable energy conversion and storage technologies, and advanced electrocatalysts are required to improve the sluggish electrocatalytic reactions. The magnetic field, as a thermodynamic parameter independent of temperature and pressure, is vital in the construction of electrocatalysts and enhancement of electrocatalysis. In this Review, the recent progress of magnetic field‐assisted construction of electrocatalysts and enhancement of electrocatalysis is comprehensively summarized. Originating from the structure‐activity‐performance relationship of electrocatalysts, the fundamentals of the magnetic field‐induced construction of electrocatalysts, including the magnetocaloric effect, nucleation and growth, and phase regulation, have been illustrated. In addition, the magnetic effect on the electrocatalytic reaction, namely, the magnetothermal, magnetohydrodynamic and micro magnetohydrodynamic, Maxwell stress, Kelvin force, and spin selection effects, are discussed. Finally, the perspective and challenges for magnetic field‐assisted construction of electrocatalysts and enhancement of electrocatalysis are proposed.
Neutral and adaptive loci reveal fine‐scale population structure in Eleginops maclovinus from north Patagonia
Authors: Canales‐Aguirre Cristian B. , Larson Wesley A. , McKinney Garrett J. , Claure C. Eliza , Rocha J. Dellis , Ceballos Santiago G. , Cádiz María I. , Yáñez José M. , Gomez‐Uchida Daniel
Published: October 2022

Patagonia is an understudied area, especially when it comes to population genomic studies with relevance to fishery management. However, the dynamic and heterogeneous landscape in this area can harbor an important but cryptic genetic population structure. Once such information is revealed, it can be integrated into the management of infrequently investigated species. Eleginops maclovinus is a protandrous hermaphrodite species with economic importance for local communities that are currently managed as a single genetic unit. In this study, we sampled five locations distributed across a salinity cline from Northern Patagonia to investigate the genetic population structure of E. maclovinus. We used restriction site‐associated DNA (RAD) sequencing and outlier tests to obtain neutral and adaptive loci, using FST and GEA approaches. We identified a spatial pattern of structuration with gene flow and spatial selection by environmental association. Neutral and adaptive loci showed two and three genetic groups, respectively. The effective population sizes estimated ranged from 572 (Chepu) to 14,454 (Chaitén) and were influenced more by locality than by salinity cline. We found loci putatively associated with salinity suggesting that salinity may act as a selective driver in E. maclovinus populations. These results suggest a complex interaction between genetic drift, gene flow, and natural selection in this area. Our findings also suggest several evolutionary significant units in this area, and the information should be integrated into the management of this species. We discussed the significance of these results for fishery management and suggest future directions to improve our understanding of how E. maclovinus has adapted to the dynamic waters of Northern Patagonia.
Repeated habitat mapping data reveal gains and losses of plant species
Authors: Lüttgert Lina , Heisterkamp Samuel , Jansen Florian , Klenke Reinhard , Kreft Kerstin‐Angelika , Seidler Gunnar , Bruelheide Helge
Published: October 2022

Detecting species trends across different habitat types and larger regions is required to generate a general and reliable foundation for conservation planning. While direct monitoring data covering a large spatial and temporal extent are mostly lacking, data collected for other purposes than monitoring can be considered to detect trends. Here we analyzed both habitat type and plant species trends over several decades (1979–2017), using repeated habitat survey data from the habitat mapping program of the city and federal state of Hamburg. Next to transitions between habitat types, we looked for differences between winner and loser species, considering also their habitat type preference, red list, and non‐native status. Furthermore, we assessed the consistency between trends of habitat types and species that are characteristic of those habitat types. We found declines in habitat area of semi‐natural (semi‐)dry grasslands and semi‐ruderal vegetation and increases in habitat area of species‐poor grasslands, pioneer forests, and human settlements. More species showed positive than negative trends over time, with winners including many forest and scrub as well as non‐native species, while losers were represented mostly by endangered and ruderal species. Most habitat types included a mixture of both winner and loser species. Habitat type trends were mostly not reflected in trends of species that were characteristic of a particular habitat, such as semi‐natural (semi‐)dry grasslands. This can be explained, on the one hand, by species extinction debts, and on the other hand, by a low habitat specificity of some species that find refuges also in secondary habitats. Our study not only shows the difficulties but also offers methods on how to use repeated habitat mapping data to detect trends for habitat types and plant species. In contrast to monitoring programs focusing on individual endangered habitats, results from repeated habitat surveys allow the identification of those secondary habitats of a species that might contribute the most to preserving populations of their primary habitat.
Pear polyphenol oxidase enhances theaflavins in green tea soup through the enzymatic oxidation reaction
Authors: Li Yan , Bai Ruoxue , Wang Jintao , Li Yonglin , Hu Yongdan , Ren Dabing , Dong WenJiang , Yi Lunzhao
Published: October 2022

Polyphenol oxidase (PPO) is a necessary medium for converting catechins into theaflavins in tea. This study aimed to provide an efficient and cost‐effective method for the purpose of developing a tea beverage rich in four main theaflavins (TFs) by optimizing the key factors affecting the enzymatic oxidation reaction to produce TFs. Autumn green tea (AT) soup was mixed with pear PPO crude enzyme solution and then reacted for different time at varying reaction temperatures, pH, ratios of tea soup to crude enzyme solution, and ratios of tea to water. The content of TFs in tea beverage was monitored by UPLC‐Q‐Orbitrap‐MS/MS to select the optimal process parameters to produce the maximum TFs. The TFs content after the reaction increased 968.49 times compared with that before the reaction. The results showed that the use of the enzymatic oxidation reaction of pear PPO crude enzyme solution to improve the TFs in AT soup was efficient. This method helped regulate the strong bitter and astringent taste sensation in AT, and it is unnecessary to purify the PPO enzyme source. This method is expected to be a breakthrough to use AT to produce high TFs tea beverages in a cost‐effective way with high value.
Exercise‐induced changes in pulmonary artery wedge pressure in adults post‐Fontan versus heart failure with preserved ejection fraction and non‐cardiac dyspnoea
Authors: Miranda William R. , Borlaug Barry A. , Jain C. Charles , Anderson Jason H. , Hagler Donald J. , Connolly Heidi M. , Egbe Alexander C.
Published: October 2022

Aims

Despite their universal predisposition, diagnosing diastolic dysfunction in patients post‐Fontan palliation is challenging. Our aim was to compare exercise haemodynamics between adults post‐Fontan and patients with heart failure with preserved ejection fraction (HFpEF) and non‐cardiac dyspnoea (NCD).

Methods and results

Twenty‐four adults (age ≥18 years) post‐Fontan palliation with resting and exercise pulmonary artery wedge pressure (PAWP) measured during supine biking were identified. Forty‐eight patients with HFpEF and 48 with NCD diagnosed at catheterization were selected for comparison. Mean age for Fontan patients was 30.3 ± 7.5 years; median ventricular ejection fraction was 52.5% (45–55.8), being <50% in 37.5%. Resting PAWP among Fontan patients was 10.2 ± 3.5 mmHg (>12 mmHg in 25%); PAWP was lower in Fontan patients than in HFpEF but higher than NCD. During exercise, PAWP was lower in the Fontan group than HFpEF (22.5 mmHg [19.3–28] vs. 28.2 ± 6.3; p = 0.0006) but higher than NCD (11.2 ± 4.2, p ≤ 0.0001). However, there were no differences in ΔPAWP/ΔQs between Fontan and HFpEF patients (4.0 [2.1–7.3] vs. 2.7 [1.6–4.4]; p = 0.10) with the ratio being higher post‐Fontan than in NCD (0.6 [0.2–1.2]; p < 0.0001). ΔPAWP/ΔQs remained similar between HFpEF and Fontan patients even when those with ejection fraction <50% were excluded (2.7 [1.6–4.4] vs. 2.7 [1.0–5.8]; p = 0.97).

Conclusion

There were no differences in ΔPAWP/ΔQs ratios between post‐Fontan and HFpEF patients, supporting markedly abnormal single ventricle compliance despite lower resting and exercise PAWP. Therefore, exercise invasive haemodynamics may represent a novel tool for the diagnosis of diastolic dysfunction in Fontan patients.
Effects of empagliflozin on cardiovascular and renal outcomes in heart failure with reduced ejection fraction according to age: a secondary analysis of EMPEROR‐Reduced
Authors: Filippatos Gerasimos , Anker Stefan D. , Butler Javed , Farmakis Dimitrios , Ferreira João Pedro , Gollop Nicholas D. , Brueckmann Martina , Iwata Tomoko , Pocock Stuart , Zannad Faiez , Packer Milton ,   the EMPEROR‐Reduced Trial Committees and Investigators
Published: October 2022

Aims

Empagliflozin improves cardiovascular and renal outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF), but its efficacy and safety across patient's age is not well established.

Methods and results

We assessed the effects of empagliflozin (10 mg daily) versus placebo, on top of standard HF therapy, in symptomatic HFrEF patients with a left ventricular ejection fraction ≤40% and increased natriuretic peptides stratified by age (<65, 65–74, ≥75 years). The primary endpoint was a composite of cardiovascular death or HF hospitalization. Key secondary endpoints included first and recurrent HF hospitalizations and slope of change in estimated glomerular filtration rate (eGFR); the latter was supported by an analysis of a renal composite endpoint (chronic dialysis or renal transplantation or profound and sustained reduction in eGFR). Of 3730 patients, 38% were <65 years, 35% were 65–74 years and 27% were ≥75 years. Compared with placebo, empagliflozin reduced the primary endpoint consistently across the three age groups (hazard ratio 0.71 [95% confidence interval 0.57–0.89] for <65 years, 0.72 [0.57–0.93] for 65–74 years, 0.86 [0.67–1.10] for ≥75 years, interaction p‐trend test = 0.24). The effects of empagliflozin were also consistent across age groups for key secondary endpoints of first and recurrent HF hospitalization (p‐trend = 0.30), the rate of decline in eGFR (p‐trend = 0.78) and the renal composite (p‐trend = 0.94). Adverse events (AEs), serious AEs and AEs leading to drug discontinuation increased with age in both treatment arms, but empagliflozin did not increase their incidence over placebo within each age group.

Conclusion

The efficacy and safety of empagliflozin in improving cardiovascular and renal outcomes in HFrEF was consistent across the spectrum of age, including older patients (aged ≥75).
Experimental and Theoretical Evaluation of Four NLO‐Active Divalent Transition‐Metal Complexes Supported by an Enantiomerically Pure Tetradentate Schiff Base Ligand
Authors: Celedón Salvador , Hamon Paul , Artigas Vania , Fuentealba Mauricio , Kahlal Samia , Ledoux‐Rak Isabelle , Carrillo David , Saillard Jean‐Yves , Manzur Carolina , Hamon Jean‐René
Published: October 2022

This paper reports on a series of five chiral Schiff base push‐pull compounds derived from enantiomerically pure (1R,2R)‐(−)‐1,2‐diaminocyclohexane. The NiII, CuII, ZnII and PdII complexes supported by a ferrocene‐containing unsymmetrically‐substituted N2O2 quadridentate Schiff base ligand were prepared via template reactions and isolated in 74–87 % yields. A combination of EA, IR, UV/vis and 1H/13C{1H} NMR spectroscopy, HRMS spectrometry, cyclic voltammetry and single‐crystal X‐ray analysis (for the proligand 2 and its NiII derivative 3), together with computational methods (DFT and TD‐DFT) was used to fully characterize and study the properties of all products. Both 2 and 3 crystallize in the orthorhombic non‐centrosymmetric space group P212121, with two (R,R)‐(−)‐chiral carbon atoms in their structure. Second‐order nonlinear polarizabilities β have been measured by using Harmonic Light Scattering at 1.91 μm, with the Pd(II) species showing the higher NLO response of 460×10−30 esu.
Asymmetric Pd(II)‐Catalyzed C−O, C−N, C−C Bond Formation Using Alkenes as Substrates: Insight into Recent Enantioselective Developments
Authors: Giofrè Sabrina , Molteni Letizia , Beccalli Egle M.
Published: October 2022

This Review summarizes the advances in the catalytic enantioselective mono‐ and difunctionalization of alkenes, highlighting the fundamental role of ligands. Several types of asymmetric reactions have been developed involving different bonds formation, C−O, C−N and C−C, highlighting the urgency to go ahead in the search for new ligands and synthetic methodologies in order to improve the control over the reaction selectivity and activity and thus, to increase the applications in the synthesis of heterocyclic scaffolds and biologically active compounds. The Review is organized into paragraphs, which discuss the type of bond formed during the nucleopalladation, C−O, C−N, C−C bonds, and the type of reaction involved.
Electrochemical Rearrangement of Indoles to Spirooxindoles in Continuous Flow
Authors: Liu Dingjin , Xu Hai‐Chao
Published: October 2022

The oxidative rearrangement of indoles induced by various chemical oxidants is a frequently employed method for the construction of spirooxindole structures. Herein, we report an electrochemical method for the oxidative rearrangement of indoles to spirooxindoles in continuous flow. The electrochemical reactions require no chemical oxidants and can be scaled up easily without need for re‐optimization of reaction conditions by passing more starting material through parallel reactors.
Decision‐making traps behind low regional absorption of Cohesion Policy funds
Authors: Cunico Giovanni , Aivazidou Eirini , Mollona Edoardo
Published: October 2022

Within European Cohesion Policy, some regions manifest chronic problems with absorbing structural funds, probably due to inadequate administrative capacity. Despite the continuous assistance to improve capacity and the accumulation of learning and experience, poor performances still persist in some territories, rendering the initial explanation partial. By collecting (reports' analysis and field research), consolidating (grounded theory), and mapping (system dynamics) two Italian regions with contrasting absorption performance, this study investigates how regional authorities may be trapped in systemic decision‐making structures that prioritize short‐term outcomes perpetuating low absorption rates. Within a multilevel‐governance context, we suggest that these decision‐making traps stem from the discrepancy between European and local policy‐makers' mental models; although European policies aim to promote timely absorption, sometimes they fail to acknowledge local authorities' actual agenda and may unintentionally prompt regions to overemphasize short term funds' expenditure instead of improving administrative capacity in the long term.
Berechnung der Versagenswahrscheinlichkeit von Böschungen unter Berücksichtigung der Bodenvariabilität
Authors: Buschendorf Phil , Schorr Joshua , Pena Olarte Andres Alfonso
Published: October 2022

The soil is a heterogeneous three‐phase system with varying mechanical properties. It is usually abstracted to a subsurface model with homogeneous layers. The basic data for this model are individual probings/boreholes. Assumptions are made to describe the structure of the unsampled areas and the general scatter of the soil properties within the layers is not taken into account. This results in an approximation of the real conditions, which leads to uncertainties. In order to compensate this, the soil variability can be covered by a number of different parameter combinations. In the field of geotechnical engineering, this approach is called the Random Finite Element Method (RFEM).

In terms of a master thesis, the technical implementation of such method has been investigated. It was used for the stability analysis of a theoretical slope and the results were compared with the Limit Equilibrium Method (LEM) and the Strength Reduction Finite Element Method (SRFEM). The last one was also used to identify the relevant failure criteria for the finite element. By using different meshes of the same slope, their effect on the safety factor was observed.
Practical recommendations for machine learning in underground rock engineering – On algorithm development, data balancing, and input variable selection
Authors: Morgenroth Josephine , Unterlaß Paul J. , Sapronova Alla , Khan Usman T. , Perras Matthew A. , Erharter Georg H. , Marcher Thomas
Published: October 2022

Research has demonstrated that machine learning algorithms (MLAs) are a powerful addition to the rock engineering toolbox, and yet they remain a largely untapped resource in engineering practice. The reluctance to adopt MLAs as part of standard practice is often attributed to the ‘opaque’ nature of the algorithms, the complexity in developing them, and the difficulty in determining how the algorithms use the datasets. This article presents tools and processes for developing MLAs, input selection, and data balancing for practical underground rock engineering. MLAs for classification and regression – two main machine learning applications – are presented in terms of developing MLA to extract information from the dataset to obtain the desired output. Engineering verification metrics are selected based on their suitability for specific output. Methods for input selection and data balancing are discussed with a focus on selecting appropriate input data for the problem without introducing bias or excess complexity. Each tool and process for algorithm development, data preparation, and input selection is illustrated with a case study. This article demonstrates that geotechnical practitioners can extract additional value by applying MLAs to rock engineering problems. Once an understanding of the functions of MLAs is reached, the building blocks and open‐source code are available to be adapted to suit the rock mass behaviour of interest.
Prevalence and predictors of Motoric Cognitive Risk syndrome in a community‐dwelling older Scottish population: A longitudinal observational study
Authors: Mullin Donncha S. , Stirland Lucy E. , Welstead Miles , Russ Tom C. , Luciano Michelle , Muniz‐Terrera Graciela
Published: October 2022

Objectives

Motoric Cognitive Risk (MCR) is a gait‐based predementia syndrome that is easy to measure and prognostic of dementia and falls. We aimed to examine the prevalence and risk factors for MCR, and assess its overlap with Mild Cognitive Impairment, Prefrailty, and Frailty, in a cohort of older Scottish adults without dementia.

Methods

In this longitudinal prospective study, we classified 690 participants (mean [SD] age 76.3 [0.8] years; wave 3) of the Lothian Birth Cohort 1936 (LBC1936) into non‐MCR or MCR groups. We examined their baseline (age 69.5 [0.8] years; wave 1) risk factors for MCR at waves 3, 4, and 5 (6, 9, and 12 years later respectively).

Results

MCR prevalence rate ranged from 5.3% to 5.7% across the three waves. The presence of MCR was associated with older baseline age (6 and 9 years later), lower occupational socioeconomic status (6 years later), and worse scores in a range of tests of executive function (6, 9 and 12 years later). Approximately 46% of the MCR group also had Mild Cognitive Impairment, and almost everyone in the MCR group had either Prefrailty or Frailty.

Conclusions

The prevalence of MCR in this Scottish cohort is lower than the pooled global average, possibly reflecting the general good health of the LBC cohort. However, it is higher than the prevalence in two neighbouring countries' cohorts, which may reflect the younger average ages of those cohorts. Future LBC1936 research should assess the risk factors associated with MCR to validate previous findings and analyse novel predictive factors, particularly socioeconomic status.
Role of sentinel lymph node biopsy for oral squamous cell carcinoma: Current evidence and future challenges
Authors: Jang Sophie S. , Davis Morgan E. , Vera David R. , Lai Stephen Y. , Guo Theresa W.
Published: October 2022

Sentinel lymph node biopsy (SLNB) has been used across oncological specialties for prognostication, staging, and identification of occult nodal metastasis. Recent studies demonstrated the potential clinical utility of SLNB in oral cavity squamous cell carcinoma (OCSCC). Elective neck dissection is the current standard of care in early management of OCSCC with depth of invasion greater than 2–4 mm; however, majority of patients ultimately do not have nodal disease on final pathology. SLNB is an alternative procedure widely adopted in early cancer management in many oncological subspecialities. Several considerations such as depth of invasion, nodal mapping, histopathology methods, operator variability, postoperative complications, and advancement in preoperative and intraoperative imaging technology can guide the appropriate application to SLNB in OCSCC. The aim of this review is to discuss the current evidence for SLNB in the treatment of early stage OCSCC, imaging technologies that support SLNB procedures, and studies that are currently underway.
Safety, pharmacokinetics, and antiviral activity of the capsid inhibitor AB‐506 from Phase 1 studies in healthy subjects and those with hepatitis B
Authors: Yuen Man‐Fung , Berliba Elina , Sukeepaisarnjaroen Wattana , Ahn Sang Hoon , Tanwandee Tawesak , Lim Young‐Suk , Kim Yoon Jun , Poovorawan Kittiyod , Tangkijvanich Pisit , Schwabe Christian , Eley Timothy , Brown Joanne , Lee Amy C. H. , Thi Emily P. , Paratala Bhavna , Mani Nagraj , Sofia Michael J. , Picchio Gaston , Sims Karen D. , Gane Edward J.
Published: October 2022

AB‐506 is a potent, pan‐genotypic small molecule capsid inhibitor that inhibits hepatitis B virus (HBV) pregenomic RNA encapsidation. We assessed the safety, pharmacokinetics, and antiviral activity of AB‐506 in two randomized, double‐blinded Phase 1 studies in healthy subjects (HS) and subjects with chronic HBV infection (CHB). Single ascending and multiple doses of AB‐506 or placebo (30–1000 mg or 400 mg daily for 10 days) were assessed in HS. AB‐506 or placebo was assessed at either 160 mg or 400 mg daily for 28 days in subjects with CHB. A second follow‐up study examined AB‐506 or placebo at 400 mg daily for 28 days in 14 Caucasian and 14 East‐Asian HS. Twenty‐eight days of AB‐506 at 160 mg and 400 mg produced mean HBV‐DNA declines from baseline of 2.1 log10 IU/ml and 2.8 log10 IU/ml, respectively. Four subjects with CHB (all Asian) had Grade 4 alanine aminotransferase (ALT) elevations (2 at each dose) as HBV DNA was declining; three events led to treatment discontinuation. In the second follow‐up study, 2 Asian HS had serious transaminitis events leading to treatment and study termination. No subjects had bilirubin elevations or signs of hepatic decompensation. Conclusion: AB‐506 demonstrated mean HBV‐DNA declines of >2 log10; however, transient but severe ALT flares were observed in 4 Asian subjects with CHB. In the follow‐up study in HS, 2 additional Asian HS had Grade 4 flares, suggesting that AB‐506 hepatotoxicity contributed to the ALT elevations. The AB‐506 development program was terminated because of these findings.
Zinc fingers and homeoboxes 2 is required for diethylnitrosamine‐induced liver tumor formation in C57BL/6 mice
Authors: Jiang Jieyun , Turpin Courtney , Qiu Guofang (Shirley) , Xu Mei , Lee Eun , Hinds Terry D. , Peterson Martha L. , Spear Brett T.
Published: October 2022

Liver cancer, comprised primarily of hepatocellular carcinoma (HCC), is the third leading cause of cancer deaths worldwide and increasing in Western countries. We previously identified the transcription factor zinc fingers and homeoboxes 2 (Zhx2) as a regulator of hepatic gene expression, and many Zhx2 target genes are dysregulated in HCC. Here, we investigate HCC in Zhx2‐deficient mice using the diethylnitrosamine (DEN)–induced liver tumor model. Our study using whole‐body Zhx2 knockout (Zhx2

KO
) mice revealed the complete absence of liver tumors 9 and 10 months after DEN exposure. Analysis soon after DEN treatment showed no differences in expression of the DEN bioactivating enzyme cytochrome P450 2E1 (CYP2E1) and DNA polymerase delta 2, or in the numbers of phosphorylated histone variant H2AX foci between Zhx2

KO
and wild‐type (Zhx2

wt
) mice. The absence of Zhx2, therefore, did not alter DEN bioactivation or DNA damage. Zhx2

KO
livers showed fewer positive foci for Ki67 staining and reduced interleukin‐6 and AKT serine/threonine kinase 2 expression compared with Zhx2

wt
livers, suggesting that Zhx2 loss reduces liver cell proliferation and may account for reduced tumor formation. Tumors were reduced but not absent in DEN‐treated liver‐specific Zhx2 knockout mice, suggesting that Zhx2 acts in both hepatocytes and nonparenchymal cells to inhibit tumor formation. Analysis of data from the Cancer Genome Atlas and Clinical Proteomic Tumor Consortium indicated that ZHX2 messenger RNA and protein levels were significantly higher in patients with HCC and associated with clinical pathological parameters. Conclusion: In contrast to previous studies in human hepatoma cell lines and other HCC mouse models showing that Zhx2 acts as a tumor suppressor, our data indicate that Zhx2 acts as an oncogene in the DEN‐induced HCC model and is consistent with the higher ZHX2 expression in patients with HCC.
Autologous hematopoietic cell transplantation versus whole‐brain radiotherapy consolidation in primary central nervous system lymphoma: A systematic review and meta‐analysis
Authors: Epperla Narendranath , Reljic Tea , Chowdhury Sayan Mullick , Ferreri Andrés J. M. , Kumar Ambuj , Hamadani Mehdi
Published: October 2022

The management of newly diagnosed primary central nervous system lymphoma (PCNSL) includes administration of high‐dose methotrexate based regimens followed by consolidation therapy to minimize the risk of relapse. However, the best consolidation strategy (autologous hematopoietic cell transplant [auto‐HCT] vs. whole‐brain radiotherapy [WBRT]) is controversial. Hence, we performed a systematic review and meta‐analysis of all randomized controlled trials that compared auto‐HCT versus WBRT consolidation for patients with PCNSL after first‐line treatment.The primary outcome was overall survival (OS), while the secondary outcomes included progression‐free survival (PFS), response rates (overall response rate [ORR] and complete remission [CR]), relapse rate, treatment‐related mortality (TRM), and neuropsychological adverse events. We performed a pooled analysis of the single‐arm studies that incorporated auto‐HCT or WBRT consolidation and evaluated neurocognitive outcomes. Only two studies met the inclusion criteria (n = 240). There was no significant difference in OS (HR = 1.50; 95% CI = 0.95–2.36), PFS (HR = 0.99; 95% CI = 0.44–2.22), ORR (RR = 1.48; 95% CI = 0.90–2.44), CR rate (RR = 1.21; 95% CI = 0.90–1.63), relapse rate (RR = 0.46; 95% CI = 0.05–4.28), and TRM (RR = 5.67; 95% CI = 1.01–31.91). The neuropsychological tests to assess neurocognitive domains were different and inconsistently reported in the two studies and therefore we were unable to perform a meta‐analysis but provide a descriptive assessment. Both the studies showed a significant decline in the attention/executive function (based on the trail making test A and trail making test B) in those receiving WBRT compared to auto‐HCT. We found 9 single‐arm phase II studies that reported data on outcomes associated with either auto‐HCT (5 studies) or WBRT (4 studies) consolidation. Of these, two studies (n = 43) reported data on neurocognitive decline following auto‐HCT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 6% (95% CI, 0%–17%) for those receiving auto‐HCT and there was no heterogeneity between studies (I2 = 0%). Three studies (n = 122) reported data on neurocognitive decline following WBRT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 43% (95% CI, 11%–78%) for those receiving WBRT and there was high heterogeneity between studies (I2 = 94%). There was significant heterogeneity between subgroups (p = 0.035). The outcomes were not significantly different in patients with PCNSL receiving auto‐HCT or WBRT consolidation therapies, however, there is a higher degree of neurocognitive decline associated with WBRT compared to auto‐HCT consolidation. The decision to choose a consolidation strategy needs to be individualized based on age, frailty, and co‐morbidities.
Foreign ownership, bank efficiency and stability: Whether the institutional quality of countries is important?
Authors: Kallel Hela , Triki Mohamed
Published: October 2022

This article is aimed to investigate the extent to which the home and host countries' institutional quality helps explain the efficiency and stability differences between the domestic and foreign banks operating in Tunisia and Morocco over the 2005–2017. For this purpose, a simultaneous equations approach was considered to investigate the dynamics between efficiency and stability. Our framework follows the premise that stability is endogenously related to efficiency only for Moroccan banks' sample when models' estimation has been administered considering each country separately. The findings reveal also the persistence of a positive effect of foreign ownership on bank efficiency, highlighting that banking efficiency need be effectively sustained with a reasonable level of institutional development. Moreover, the institutional differences characterizing the home and host countries has a negative impact on the foreign banks' stability. Accordingly, policy makers in the Great Maghreb area could well aspire to enhance foreign ownership in their banking sector, on the ground that it helps remarkably in improving corporate governance and boosting efficiency, given mainly the acquired technical advantages often associated with their developed home countries. The generalized moments method estimator outlines the persistence of a noticeable banking inefficiency and stability, with a significant effect of the stability variable on banks' inefficiency and performance, suggesting that banking‐efficiency boosting policies might well ultimately guide and veer management choices towards less risky investments.
ATL1 inhibits the proliferation and invasion of trophoblast cells via inhibition of the mTOR signaling pathway
Authors: Zhang Guanli , Feng Yan , Wang Min , Liu Xin
Published: October 2022

Pre‐eclampsia (PE) is a major cause of hypertension in maternal and fetal. Atlastin‐1 (ATL1), one regulator of endoplasmic reticulum (ER) morphology, participates in tubular ER formation and protein synthesis. The objective of this study is to investigate the role and molecular mechanism of ATL1 in PE. GEO databases showed that ATL1 was upregulated in PE patients. Our data also found that ATL1 was highly expressed in PE placental tissues. The cell viability, proliferation, migration, and invasion of HTR‐8/SVneo cells increased/decreased after the downregulation/upregulation of ATL1. The mTOR pathway is the downstream pathway of ATL1. The levels of p‐p70S6K and p‐mTOR were increased/decreased after the downregulation/upregulation of ATL1. Moreover, rapamycin, an inhibitor of mTOR pathway, reversed the promotive effect of siATL1 on proliferation, migration, and invasion in HTR‐8/SVneo cells. In conclusion, ATL1 inhibits the proliferation and invasion of trophoblast cells via the inhibition of the mTOR signaling pathway in HTR‐8/SVneo cells.
Fenton oxidation of biochar improves retention of cattle slurry nitrogen
Authors: Cao Xinyue , Reichel Rüdiger , Brüggemann Nicolas
Published: October 2022

Nitrogen (N) losses during fertilization with livestock slurry, mainly in the form of ammonia (NH3), can cause environmental problems and reduce fertilizer efficiency. Leonardite, which is characterized by oxygen‐rich functional groups and low pH, has been found to decrease losses of slurry N. However, leonardite, as a byproduct of open‐cast lignite mining, is not a renewable resource. The objective of this study was to modify biochar by chemical surface oxidation in order to find a sustainable but similarly effective substitute for leonardite. Biochar was produced from spruce sawdust in a pyrolysis oven at a maximum temperature of 610 °C. Then the biochar was oxidized using the Fenton reaction, with a ratio of Fe2+/H2O2 of 1:1,000, as a source of highly reactive HO· radicals to introduce oxygen‐rich functional groups to the biochar surface. The ammonium (NH4+) adsorption capacity of biochar, oxidized biochar, and leonardite was tested in ammonium sulfate [(NH4)2SO4] solution, pH‐adjusted (NH4)2SO4 solution, and cattle slurry. The results showed that biochar had the highest total NH4+ adsorption of 1.4 mg N g−1 in (NH4)2SO4 solution, whereas oxidized biochar had the highest reversible NH4+ adsorption of 0.8 mg N g−1. In the pH‐adjusted ammonium solution, all materials reduced NH3 emissions by ≥90%, and oxidized biochar reduced NH3 emissions by 99.99%. In contrast, leonardite reduced NH3 emissions the most in cattle slurry, and oxidation of biochar increased the reduction in NH3 emissions from 22 to 67% compared with non‐oxidized biochar. In conclusion, biochar oxidized by means of the Fenton reaction greatly decreased NH3 emissions by increased adsorption of NH4+ in cattle slurry compared with non‐oxidized biochar, indicating the great potential of oxidized biochar for reducing N losses during slurry application.