bluuebunny/crossref_metadata_2025 huggingface dataset:
Plant-based meat substitute analysis using microextraction with deep eutectic solvent followed by LC-MS/MS to determine acrylamide, 5-hydroxymethylfurfural and furaneol
Authors: Osiecka Dominika , Vakh Christina , Makoś-Chełstowska Patrycja , Kubica Paweł
Published: December 2023

For the analysis of plant-based meat substitutes and the determination of Maillard reaction products such as acrylamide, 5-hydroxymethylfurfural and furaneol, a novel and effective procedure based on hydrophobic natural deep eutectic solvent and liquid chromatography coupled with tandem mass spectrometry was developed for the first time. The 49 compositions of the deep eutectic solvents were designed and screened to select the most suitable option. The terpenoids eugenol and thymol in a molar ratio of 2:1 were selected as precursors for solvent formation, allowing effective extraction of the target analytes. The developed procedure comprised two main steps: extraction — in which the analytes are isolated from the solid sample due to the salting-out effect and pre-concentrated in the deep eutectic solvent, and back-extraction — in which the analytes are re-extracted into the formic acid solution for subsequent mass spectrometric detection. As the density of the aqueous phases changed during the extraction and back-extraction steps, the phenomenon of inversion of the coalesced organic phase was observed, which simplified the withdrawing of the phases. The linear range was 1–50 ng/mL for acrylamide, 10–1000 ng/mL for 5-hydroxymethylfurfural and 200–1000 ng/mL for furaneol with coefficients of determination above 0.9952. The developed method was fully validated and found recoveries were in the range 83–120%, with CVs not exceeding 4.9%. The method was applied to real sample analysis of pea-based meat substitutes.

Graphical abstract
Real-world data on the management of pazopanib-induced liver toxicity in routine care of renal cell cancer and soft tissue sarcoma patients
Authors: Westerdijk K. , Krens S. D. , Steeghs N. , van der Graaf W. T. A. , Tjwa E. T. T. L. , Westdorp H. , Desar I. M. E. , van Erp N. P.
Published: December 2023

Purpose

Pazopanib is known to cause liver toxicity. A relationship between pazopanib exposure and alanine transaminase elevations has been described in clinical trials. This study investigated the relation between pazopanib exposure and liver toxicity in real-world patients and evaluated the management of pazopanib-induced liver toxicity in routine care.

Methods

A retrospective observational cohort study was performed in patients treated with pazopanib in whom pazopanib exposure was measured. The percentage of patients with and without liver toxicity during treatment with pazopanib was calculated as well as the average pazopanib exposure in both groups. Furthermore, the management of patients with liver toxicity was evaluated.

Results

Liver toxicity was observed in 25 out of the 133 patients included (19%). Pazopanib exposure was comparable in patients with or without liver toxicity (27.7 mg/L versus 28.1 mg/L). Seven patients permanently discontinued pazopanib after the occurrence of liver toxicity. Of the remaining 18 patients, continuation or restart of pazopanib after liver toxicity was successful in 16 patients and half of these patients were able to safely continue pazopanib at the same dose as prior to liver toxicity for the remaining duration of treatment.

Conclusion

Our study did not demonstrate a clear relationship between pazopanib exposure and the occurrence of pazopanib-induced liver toxicity. Half of the patients were able to safely continue or restart pazopanib treatment after liver toxicity and received the same dose as prior to drug withdrawal. Successful interventions to address pazopanib-induced toxicity in the clinic led to an algorithm for the management of pazopanib-induced liver toxicity.
Measurements of the local equivalence ratio and its impact on the thermochemical state in laminar partially premixed boundary layer flames
Authors: Greifenstein M. , Zentgraf F. , Johe P. , Boehm B. , Steinhausen M. , Hasse C. , Dreizler A.
Published: December 2023

Local fuel–air equivalence ratios, gas phase temperature and $$\hbox {CO}_2$$

CO
2

mole fractions were measured by a combination of laser-induced fluorescence of nitric oxide used as a tracer and dual-pump coherent anti-Stokes Raman spectroscopy in a vertically oriented partially premixed boundary layer flame under laminar flow conditions. By embedding a secondary effusive fuel inlet into the temperature-controlled wall of a sidewall-quenching configuration, different pyrolysis rates of a wall-embedded polymer are mimicked with reduced chemical complexity and well-controlled boundary conditions. The resulting boundary layer flames were investigated experimentally and numerically. The simulation results and measurements show a very good agreement on the complex interplay between local mixing and heat losses, even though inhomogeneities of the wall inlet complicate the comparison of data. Local equivalence ratios upstream of the reaction zone reach values of up to $$\varPhi = 2$$

Φ
=
2

. Under these conditions, a clear quenching location could not be identified based on the experimental data. A significant trend toward lower temperatures and $$\hbox {CO}_2$$

CO
2

mole fractions with increasing amount of secondary fuel was found in the thermochemical state close to the temperature-controlled wall, downstream of the effusive inlet.

Graphical abstract
Next-generation sequencing and comprehensive data reassessment in 263 adult patients with neuromuscular disorders: insights into the gray zone of molecular diagnoses
Authors: Krenn Martin , Wagner Matias , Zulehner Gudrun , Weng Rosa , Jäger Fiona , Keritam Omar , Sener Merve , Brücke Christof , Milenkovic Ivan , Langer Agnes , Buchinger Dominic , Habersam Richard , Mayerhanser Katharina , Brugger Melanie , Brunet Theresa , Jacob Maureen , Graf Elisabeth , Berutti Riccardo , Cetin Hakan , Hoefele Julia , Winkelmann Juliane , Zimprich Fritz , Rath Jakob
Published: December 2023

Background

Neuromuscular disorders (NMDs) are heterogeneous conditions with a considerable fraction attributed to monogenic defects. Despite the advancements in genomic medicine, many patients remain without a diagnosis. Here, we investigate whether a comprehensive reassessment strategy improves the diagnostic outcomes.

Methods

We analyzed 263 patients with NMD phenotypes that underwent diagnostic exome or genome sequencing at our tertiary referral center between 2015 and 2023. We applied a comprehensive reassessment encompassing variant reclassification, re-phenotyping and NGS data reanalysis. Multivariable logistic regression was performed to identify predictive factors associated with a molecular diagnosis.

Results

Initially, a molecular diagnosis was identified in 53 cases (20%), while an additional 23 (9%) had findings of uncertain significance. Following comprehensive reassessment, the diagnostic yield increased to 23%, revealing 44 distinct monogenic etiologies. Reasons for newly obtained molecular diagnoses were variant reclassifications in 7 and NGS data reanalysis in 3 cases including one recently described disease-gene association (DNAJB4). Male sex reduced the odds of receiving a molecular diagnosis (OR 0.42; 95%CI 0.21–0.82), while a positive family history (OR 5.46; 95%CI 2.60–11.76) and a myopathy phenotype (OR 2.72; 95%CI 1.11–7.14) increased the likelihood. 7% were resolved through targeted genetic testing or classified as acquired etiologies.

Conclusion

Our findings reinforce the use of NGS in NMDs of suspected monogenic origin. We show that a comprehensive reassessment enhances diagnostic accuracy. However, one needs to be aware that genetic diagnoses are often made with uncertainty and can even be downgraded based on new evidence.
Feature-based multimodal registration framework for vertebral pose estimation
Authors: kiran Usha , Bhat Shyamasunder N. , Anitha H. , Naik Roshan Ramakrishna
Published: December 2023

Purpose

The reliable estimation of the vertebral body posture helps to aid a safe and effective spine surgery. The proposed work aims to present an MR to X-ray image registration to assess the 3D pose of the vertebral body during spine surgery. The 3D assessment of vertebral pose assists in analyzing the position and orientation of the vertebral body to provide information during various clinical diagnosis conditions such as curvature estimation and pedicle screw insertion surgery.

Methods

The proposed feature-based registration framework extracted vertebral end plates to avoid the mismatch between the intensities of MR and X-ray images. Using the projection matrix, the segmented MRI is forward projected and then registered to the X-ray image using binary image matching similarity and the CMA-ES optimizer.

Results

The proposed method estimated the vertebral pose by registering the simulated X-ray onto pre-operative MRI. To evaluate the efficacy of the proposed approach, a certain number of experiments are carried out on the simulated dataset.

Conclusion

The proposed method is a fast and accurate registration method that can provide 3D information about the vertebral body. This 3D information is useful to improve accuracy during various clinical diagnoses.
Mutation in the TRKB Cholesterol Recognition Site that blocks Antidepressant Binding does not Influence the Basal or BDNF-Stimulated Activation of TRKB
Authors: Biojone Caroline , Cannarozzo Cecilia , Seiffert Nina , Diniz Cassiano R. A. F. , Brunello Cecilia A. , Castrén Eero , Casarotto Plinio
Published: December 2023

Brain-derived neurotrophic factor (BDNF) acting upon its receptor Neurotrophic tyrosine kinase receptor 2 (NTRK2, TRKB) plays a central role in the development and maintenance of synaptic function and activity- or drug-induced plasticity. TRKB possesses an inverted cholesterol recognition and alignment consensus sequence (CARC), suggesting this receptor can act as a cholesterol sensor. We have recently shown that antidepressant drugs directly bind to the CARC domain of TRKB dimers, and that this binding as well as biochemical and behavioral responses to antidepressants are lost with a mutation in the TRKB CARC motif (Tyr433Phe). However, it is not clear if this mutation can also compromise the receptor function and lead to behavioral alterations. Here, we observed that Tyr433Phe mutation does not alter BDNF binding to TRKB, or BDNF-induced dimerization of TRKB. In this line, primary cultures from embryos of heterozygous Tyr433Phe mutant mice (hTRKB.Tyr433Phe) are responsive to BDNF-induced activation of TRKB, and samples from adult mice do not show any difference on TRKB activation compared to wild-type littermates (TRKB.wt). The behavioral phenotype of hTRKB.Tyr433Phe mice is indistinguishable from the wild-type mice in cued fear conditioning, contextual discrimination task, or the elevated plus maze, whereas mice heterozygous to BDNF null allele show a phenotype in context discrimination task. Taken together, our results indicate that Tyr433Phe mutation in the TRKB CARC motif does not show signs of loss-of-function of BDNF responses, while antidepressant binding to TRKB and responses to antidepressants are lost in Tyr433Phe mutants, making them an interesting mouse model for antidepressant research.
Another HSS iteration method
Authors: Smotzer Thomas , Buoni John
Published: December 2023

In this paper, we study a variation of the HSS iteration method which was first formulated by Bai et al. in 2003. This variation is similar to that of Kellogg’s variation of the Peaceman-Radford method.
Hormetic action of cyanide: plant gasotransmitter and poison
Authors: Krasuska Urszula , Ciacka Katarzyna , Staszek Pawel , Tyminski Marcin , Wal Agnieszka , Gniazdowska Agnieszka
Published: December 2023

Hydrogen cyanide (HCN) occurs in living organisms and in the environment. This is a widely known poison but is also considered as a gasotransmitter. For most higher plants, microorganisms and animals HCN is toxic, especially at elevated concentrations. However, plants’ sensitivity to this compound is lower than animals’ due to the activity of an alternative oxidase in the mitochondrial respiration chain. All higher plants synthesize HCN as a co-product during the final step of ethylene biosynthesis, whilst some plant species release it from cyanogenic compounds, accumulated for diverse physiological purposes. This molecule is used as a toxic bomb against herbivores, as a source of nitrogen in N-deficient plants, or as a regulator of seed dormancy state. The toxicity of HCN is mainly due to the inhibition of the activity of several metalloenzymes: iron-containing enzymes, molybdoenzymes and enzymes that contain zinc or copper. HCN impacts cellular metabolism by modulation of the reactive oxygen species and reactive nitrogen species levels, and via modifications of proteins (S-cyanylation, oxidation). The aim of this work is to describe the dual (toxic and signalling) mode of cyanide action in plants at a cellular level.
The Preparation of Nanosized Pd/ZSM-23 Bifunctional Catalysts for n-Hexadecane Hydroisomerization by Employing PHMB as the Growth Modifier
Authors: Sun Jiazheng , Xiong Shuxiang , Wu Qiong , Wang Wei , Wu Wei
Published: December 2023

The development of highly effective metal–zeolite bifunctional catalysts for the hydroisomerization of n-alkanes is a paramount strategy to produce second-generation biofuels with high quality. In this study, polyhexamethylene biguanide hydrochloride (PHMB) is precisely added to the initial gel to synthesize nanosized ZSM-23 zeolites (Z23-xPH). Due to orientation adsorption and steric hindrance effects of PHMB, each sample of Z23-xPH demonstrates enhanced mesoporosity in comparison with the conventional Z23-C zeolite. Furthermore, the Brønsted acid density of the Z23-xPH samples is also significantly reduced due to a reduction in the distribution of framework Al at T2–T5 sites. The corresponding Pd/23-C and Pd/Z23-xPH bifunctional catalysts with 0.5 wt% Pd loading for n-hexadecane hydroisomerization are prepared by incorporating ZSM-23 zeolites as acid supports. According to the catalytic test results, the suitable addition of PHMB can effectively promote the iso-hexadecane yield. The Pd/Z23-2PH catalyst with an nPHMB/nSi molar ratio of 0.002 demonstrates the highest maximum iso-hexadecane yield of 74.1% at an n-hexadecane conversion of 88.3%. Therefore, the employment of PHMB has provided a simple route for the development of highly effective Pd/ZSM-23 catalysts for n-alkane hydroisomerization.
Regulations Governing Medicines for Maternal and Neonatal Health: A Landscape Assessment
Authors: Alexe Amalia , Garg Anju , Kovacs Birgit , Abramova Nadezda , Apara Olatayo , Eisele Osa , Fernandes Maria Fernanda Scantamburlo , Balramsingh-Harry Leesha , Wurst Keele , Lewis David
Published: December 2023

Limited evidence related to the safety or efficacy of medicines in pregnancy and during breastfeeding is available to inform patients and healthcare professionals. Understanding the current regulatory landscape in the clinical trial and postmarketing settings is critical to facilitate the development of applicable processes and tools for studying medicine use during pregnancy and breastfeeding and comply with health authority expectations. This review summarizes key findings from a landscape assessment of regulations, guidelines, and guidance on the use of medicines in pregnancy and breastfeeding issued by health authorities in various territories (including the Americas, Europe, Africa, and Asia Pacific) and outlines relevant initiatives undertaken by health authorities, academic institutions, industry consortia, and public–private organizations. While global pharmacovigilance legislation regarding medication use during pregnancy and breastfeeding exists and continues to evolve, the landscape assessment revealed that there is a lack of global legislative harmonization in both the clinical trial and postmarketing surveillance settings and regulatory gaps still exist in many countries/regions. Despite ongoing efforts from health authorities and public and private organizations, intensive efforts for legislation harmonization and stakeholder collaboration are required to improve the current environment of medication safety in pregnancy and breastfeeding.
Assessing deep learning: a work program for the humanities in the age of artificial intelligence
Authors: Segessenmann Jan , Stadelmann Thilo , Davison Andrew , Dürr Oliver
Published: December 2023

Following the success of deep learning (DL) in research, we are now witnessing the fast and widespread adoption of artificial intelligence (AI) in daily life, influencing the way we act, think, and organize our lives. However, much still remains a mystery when it comes to how these systems achieve such high performance and why they reach the outputs they do. This presents us with an unusual combination: of technical mastery on the one hand, and a striking degree of mystery on the other. This conjunction is not only fascinating, but it also poses considerable risks, which urgently require our attention. Awareness of the need to analyze ethical implications, such as fairness, equality, and sustainability, is growing. However, other dimensions of inquiry receive less attention, including the subtle but pervasive ways in which our dealings with AI shape our way of living and thinking, transforming our culture and human self-understanding. If we want to deploy AI positively in the long term, a broader and more holistic assessment of the technology is vital, involving not only scientific and technical perspectives, but also those from the humanities. To this end, we present outlines of a work program for the humanities that aim to contribute to assessing and guiding the potential, opportunities, and risks of further developing and deploying DL systems. This paper contains a thematic introduction (Sect. 1), an introduction to the workings of DL for non-technical readers (Sect. 2), and a main part, containing the outlines of a work program for the humanities (Sect. 3). Readers familiar with DL might want to ignore 2 and instead directly read 3 after 1.
The current impacts and future prospects of graphene derivatives in polymer-based supercapacitors
Authors: Mombeshora Edwin T. , Muchuweni Edigar
Published: December 2023

For sustainability motives, the world must accelerate current work towards meeting the rising energy demands whilst reducing the current huge dependency on fossil energy resources. Fossil fuels contaminate the environment, cause health-related complications to humankind and are finite. Renewables are promising in countering these adversities. However, renewable energy resources have sporadic characteristics, thus, need effective energy storage systems for clean energy transition. One such energy storage system with the potential to grow towards large-scale commercialisation is the supercapacitor (SC). Current research foci in SCs include improved capacitance, lifespan, stability, energy and power densities through the development of effective and highly stable electrode materials. One typical and promising electrode material is the conducting polymer (CP). However, CPs still face some drawbacks; such as ion depletions, mechanical issues, operational stability and short-term stability; to develop further. Hence, compositing CPs with carbonaceous materials, namely graphene derivatives, is among the current suitable strategies to counter these setbacks. Henceforth, the current work reviews the impact of graphene derivatives as additives to CP-based SCs regarding tuneable band gap, nontoxicity, lightweight, remarkable flexibility, low costs emanating from abundant sources, facile synthesis methods and easy scalability. The review also provides recommendations for future directions to enhance the sustainability of both CPs and SCs. The discussed literature outlines that graphene derivative additives to polymers has phenomenal potential to achieve long-term stability and highly performing SCs through synergism.

Graphical Abstract
Journaling your challenges: mechanisms of resilience journals to support German first-semester business students during their transition to university
Authors: Lohner Max S. , Aprea Carmela
Published: December 2023

Transition to university can be challenging, but writing interventions can be a helpful way of supporting first-semester students. Why these interventions are effective is still not fully understood, however. To explore the underlying mechanisms, two versions of a resilience journal were used in this study. They were designed to either broaden attention toward all challenges or to prime students’ attention to successfully mastered challenges. It was hypothesized that priming toward mastery is more effective but that both versions would increase students’ resilience and satisfaction. Hypotheses were tested in a pre-post design with 62 first-semester students randomly filling out one of the two versions for 6 weeks. The outcomes were compared to students without an intervention, and journal entries were analyzed for challenges and coping strategies. A content analysis of the journal entries revealed that most challenges were directly related to university. Problem-focused coping strategies were most often used to address challenges. Both intervention groups showed a decrease in life satisfaction during the first 6 weeks of university, but the intervention designed to broaden attention was more effective in mitigating this decrease. The same intervention was also more advantageous in promoting students’ resilience. The results highlight the vulnerability of students during their transition to university and the potential of writing interventions that include reflection on all challenges.
Politics of the North Korean Diaspora
Authors: Greitens Sheena Chestnut
Published: December 2023

Politics of the North Korean Diaspora examines how authoritarian security concerns shape global diaspora politics. Empirically, it traces the recent emergence of a North Korean diaspora – a globally-dispersed population of North Korean émigrés – and argues that the non-democratic nature of the DPRK homeland regime fundamentally shapes diasporic politics. Pyongyang perceives the diaspora as a threat to regime security, and attempts to dissuade emigration, de-legitimate diasporic voices, and deter or disrupt diasporic political activity, including through extraterritorial violence and transnational repression. This, in turn, shapes the North Korean diaspora's perceptions of citizenship and patterns of diasporic political engagement: North Korean émigrés have internalized many host country norms, particularly the civil and participatory dimensions of democratic citizenship, and émigrés have played important roles in both host-country and global politics. This Element provides new empirical evidence on the North Korean diaspora; demonstrates that regime type is an important, understudied factor shaping transnational and diasporic politics; and contributes to our understanding of comparative authoritarianism's global impact.
Translation in Analytic Philosophy
Authors: Ervas Francesca
Published: December 2023

This Element aims to introduce the different definitions of translation provided in the history of analytic philosophy. Starting from the definitions of translation as paraphrase, calculus, and language games, the Element explores the main philosophical-analytic notions used to explain translation from Frege and Wittgenstein onwards. Particular attention is paid to the concept of translation equivalence in the work of Quine, Davidson, and Sellars, and to the problem of translating implicit vs. explicit meaning into another language as discussed by Grice, Kripke, and the contemporary trends in analytic philosophy of language.
Musics Lost and Found
Authors: Church Michael
Published: December 2023

This book is a piece of serious musicology by a man who has worked as a song collector himself, but his erudition is lightly worn.
Contesting the English Polity, 1660-1688
Authors: Goldie Mark
Published: December 2023

What did people in Restoration England think the correct relationship between church and state should be? And how did this thinking evolve?
Ireland and Empire in the Late Nineteenth Century
Authors: O'Leary Fergal
Published: December 2023

This book examines the place of imperialism in the cultural, political and economic life of late nineteenth-century Irish society.
The Life and Music of Gérard Grisey
Authors: Brown Jeffrey Arlo
Published: December 2023

The first biography of the composer Gérard Grisey shows how the artist's sensuality and rigor came together to form the musical genre known as spectralism.
Neuropsychologische Demenzdiagnostik: Umfrage zum klinischen Standardvorgehen im Rahmen des Deutschen Netzwerks Gedächtnisambulanzen e. V.
Authors: Schild Ann-Katrin , Meiberth Dix , Frommann Ingo , Wagner Michael , Belz Michael , Bartels Claudia , e. V. Deutsches Netzwerk Gedächtnisambulanzen
Published: December 2023

Zusammenfassung: Gedächtnisambulanzen sind spezialisierte und multidisziplinäre Einrichtungen zur (Früh-)Erkennung demenzieller Erkrankungen, welche zwar unterschiedliche institutionelle Rahmenbedingungen und inhaltliche Schwerpunkte aufweisen, die aber auch viele Gemeinsamkeiten haben in Bezug auf diagnostische Abläufe und therapeutisches Handeln. Für die neuropsychologische Diagnostik als Kernelement der Demenzdiagnostik liegen zahlreiche etablierte Testverfahren vor, einheitliche Standards für die Auswahl und Anwendung geeigneter Verfahren wurden jedoch in Deutschland bisher nicht formuliert. Eine Onlineumfrage unter 28 Zentren des Deutschen Netzwerks Gedächtnisambulanzen e. V. (DNG) stellt den aktuellen Stand der klinischen Praxis in der neuropsychologischen Demenzdiagnostik in diesen Gedächtnisambulanzen dar und zeigt mittels Empfehlungen Ansätze zu einer möglichen Harmonisierung im Vorgehen auf.
Correcting for Undercounting of Lightning Flashes by Space‐Based Optical Sensors
Authors: McFarland P. J. , Brune W. H.
Published: December 2023

Accurate measurements of global lightning are essential for understanding present and future atmospheric electricity, composition, and climate. The latest space‐based lightning detector, the Geostationary Lightning Mapper (GLM), was the first to be placed in geostationary orbit, with a continuous view of most of the American continents. Prior to the GLM, the Lightning Imaging Sensor (LIS) on the Tropical Rainfall Measuring Mission (TRMM) satellite collected lightning measurements from which numerous lightning climatologies have been developed, including those used in global models. However, this study finds that both the GLM and a second, similar LIS placed on the International Space Station (ISS) in 2017 detect lightning at similar rates and are undercounting lightning compared to ground‐based Lightning Mapping Arrays (LMAs). The GLM undercounts lightning by an average factor of 7.0, reaching a maximum over 120 as a function of satellite zenith angle, radar reflectivity at a height where the temperature is −10°C, flash height, and thunderstorm polarity. The LIS is estimated to undercount lightning by an average factor of 5.6, reaching a maximum of 75.0 as a function of radar reflectivity at the −10°C level, flash height, and thunderstorm polarity. Preliminary predictive equations for the GLM and LIS lightning undercount factor, or scaling factor (SF), use ice‐water content, equilibrium level, flash height, and satellite zenith angle, all of which can be derived in models. These equations are developed to encourage updating lightning parameterizations within global models and will likely increase modeled lightning's effects on atmospheric electrical circuits, composition, chemistry, and climate change.
Stratosphere‐Troposphere Exchanges of Air Mass and Ozone Concentrations From ERA5 and MERRA2: Annual‐Mean Climatology, Seasonal Cycle, and Interannual Variability
Authors: Wang Mingcheng , Fu Qiang , Hall Anna , Sweeney Aodhan
Published: December 2023

Stratosphere‐Troposphere exchange (STE) of air mass and ozone in ERA5 and Modern Era Retrospective analysis for Research and Application, version 2 (MERRA2) reanalyses from 1980 to 2022 are investigated on their seasonal cycle, annual‐mean climatology, and monthly anomalies smoothed using a 1‐year Lanczos low‐pass filter. We employ a lowermost stratosphere mass budget approach with dynamic isentropic surfaces fitted to tropical tropopause as the upper boundary of lowermost stratosphere. The annual‐mean ozone STEs over the NH extratropics, SH extratropics, tropics, extratropics, and globe in ERA5 are −342, −239, 201, −581, and −380 Tg year−1, respectively, versus −305, −224, 168, −529, −361 Tg year−1 from MERRA2. The annual‐mean global ozone STE difference between ERA5 and MERRA2 is dominated by the diabatic heating difference, partly compensated by the ozone concentration difference. There are about 40% (−40%) differences between ERA5 and MERRA2 in global ozone STEs in boreal summer (autumn), mainly due to the difference in seasonal breathing of the lowermost stratosphere ozone mass between reanalyses. The correlation coefficient between ERA5 and MERRA2 global ozone mass STE monthly anomalies is 0.57 and thus ERA5 and MERRA2 can only explain each other's variance by 33%. Multiple linear regression analysis shows that El Niño–Southern Oscillation, quasi‐biennial oscillation, and Brewer‐Dobson circulation explain the variance in the ERA5 (MERRA2) global ozone STE monthly anomalies by 17.3 (5.0), 5.4 (7.2), and 1.0 (3.1)%, respectively. The volcanic aerosol impacts on ozone STEs from ERA5 and MERRA2 have opposite signs and thus are inconclusive. Cautions are therefore needed when using ERA5 and MERRA2 to investigate the STE seasonal cycle and interannual variability.
Arctic Sea Ice Loss, Long‐Term Trends in Extratropical Wave Forcing, and the Observed Strengthening of the QBO‐MJO Connection
Authors: Hood Lon L. , Hoopes Charles A.
Published: December 2023

A modulation has been identified of the tropical Madden‐Julian oscillation (MJO) by the stratospheric quasi‐biennial oscillation (QBO) such that the MJO in boreal winter is ∼40% stronger and persists ∼10 days longer during the easterly QBO phase (QBOE) than during the westerly phase. A proposed mechanism is reductions of tropical lower stratospheric static stability during QBOE caused by (a) the QBO induced meridional circulation; and (b) QBO influences on extratropical wave forcing of the stratospheric residual meridional circulation during early winter. Here, long‐term variability of the QBO‐MJO connection and associated variability of near‐tropopause tropical static stability and extratropical wave forcing are investigated using European Center reanalysis data for the 1959–2021 period. During the most reliable (post‐satellite) part of the record beginning in 1979, a strengthening of the QBO‐MJO modulation has occurred during a time when tropical static stability in the lowermost stratosphere and uppermost troposphere has been decreasing and extratropical wave forcing in early winter has been increasing. A high inverse correlation (R = −0.87) is obtained during this period between early winter wave forcing anomalies and wintertime tropical lower stratospheric static stability. Regression relationships are used to show that positive trends in early winter wave forcing during this period have likely contributed to decreases in tropical static stability, favoring a stronger QBO‐MJO connection. As shown in previous work, increased sea level pressure anomalies over northern Eurasia produced by Arctic sea ice loss may have been a significant source of the observed positive trends in early winter wave forcing.
Novel waves structures for the nonclassical Sobolev-type equation in unipolar semiconductor with its stability analysis
Authors: Shahzad Tahir , Ahmed Muhammad Ozair , Baber Muhammad Zafarullah , Ahmed Nauman , Akgül Ali , Din Sayed M. El
Published: December 2023

In this study, the Sobolev-type equation is considered analytically to investigate the solitary wave solutions. The Sobolev-type equations are found in a broad range of fields, such as ecology, fluid dynamics, soil mechanics, and thermodynamics. There are two novel techniques used to explore the solitary wave structures namely as; generalized Riccati equation mapping and modified auxiliary equation (MAE) methods. The different types of abundant families of solutions in the form of dark soliton, bright soliton, solitary wave solutions, mixed singular soliton, mixed dark-bright soliton, periodic wave, and mixed periodic solutions. The linearized stability of the model has been investigated. Solitons behave differently in different circumstances, and their behaviour can be better understood by building unique physical problems with particular boundary conditions (BCs) and starting conditions (ICs) based on accurate soliton solutions. So, the choice of unique physical problems from various solutions is also carried out. The 3D, line graphs and corresponding contours are drawn with the help of the Mathematica software that explains the physical behavior of the state variable. This information can help the researchers in their understanding of the physical conditions.
Complex adaptive learning cortical neural network systems for solving time-fractional difference equations with bursting and mixed-mode oscillation behaviours
Authors: Chu Yu-Ming , Rashid Saima , Alzahrani Taher , Alhulayyil Hisham , Alsagri Hatoon , Rehman Shafiq ur
Published: December 2023

Complex networks have been programmed to mimic the input and output functions in multiple biophysical algorithms of cortical neurons at spiking resolution. Prior research has demonstrated that the ineffectual features of membranes can be taken into account by discrete fractional commensurate, non-commensurate and variable-order patterns, which may generate multiple kinds of memory-dependent behaviour. Firing structures involving regular resonator chattering, fast, chaotic spiking and chaotic bursts play important roles in cortical nerve cell insights and execution. Yet, it is unclear how extensively the behaviour of discrete fractional-order excited mechanisms can modify firing cell attributes. It is illustrated that the discrete fractional behaviour of the Izhikevich neuron framework can generate an assortment of resonances for cortical activity via the aforesaid scheme. We analyze the bifurcation using fragmenting periodic solutions to demonstrate the evolution of periods in the framework’s behaviour. We investigate various bursting trends both conceptually and computationally with the fractional difference equation. Additionally, the consequences of an excitable and inhibited Izhikevich neuron network (INN) utilizing a regulated factor set exhibit distinctive dynamic actions depending on fractional exponents regulating over extended exchanges. Ultimately, dynamic controllers for stabilizing and synchronizing the suggested framework are shown. This special spiking activity and other properties of the fractional-order model are caused by the memory trace that emerges from the fractional-order dynamics and integrates all the past activities of the neuron. Our results suggest that the complex dynamics of spiking and bursting can be the result of the long-term dependence and interaction of intracellular and extracellular ionic currents.
Sea level rise and the drivers of daily water levels in the Sacramento-San Joaquin Delta
Authors: Baranes H. , Dykstra S. L. , Jay D. A. , Talke S. A.
Published: December 2023

Water levels in deltas and estuaries vary on multiple timescales due to coastal, hydrologic, meteorologic, geologic, and anthropogenic factors. These diverse factors increase the uncertainty of, and may bias, relative sea level rise (RSLR) estimates. Here, we evaluate RSLR in San Francisco Bay and the Sacramento-San Joaquin Delta, USA by applying a physics-based, nonlinear regression to 50 tide gauges that determines the spatially varying controls on daily mean water level for water years 2004–2022. Results show that elevated river flow and pumping (99th percentile) raise water level up to 6 m and lower it up to 0.35 m, respectively, and coastal water level variations are attenuated by 30-60% within the Delta. Strong westerly winds raise water level up to 0.17 m, and tidal-fluvial interaction during spring tides and low discharge raises water level up to 0.15 m. Removal of these interfering factors greatly improves RSLR estimates, narrowing 95% confidence intervals by 89–99% and removing bias due to recent drought. Results show that RSLR is spatially heterogeneous, with rates ranging from − 2.8 to 12.9 mm y-1(95% uncertainties < 1 mm y-1). RSLR also exceeds coastal SLR of 3.3 mm y-1in San Francisco at 85% of stations. Thus, RSLR in the Delta is strongly influenced by local vertical land motion and will likely produce significantly different, location-dependent future flood risk trajectories.
Architecture of a dual biocompatible platform to immobilize genistin: fabrication with physio-chemical and in vitro evaluation
Authors: Esmaeilneia S. , Amiri Dehkharghani R. , Zamanlui Benisi S.
Published: December 2023

The design of biocompatible cell culture substrates and electrospun nanofibers can improve cell proliferation and behavior in laboratory conditions for tissue engineering applications in medicine. In this research, genistin was obtained by extracting from soybean meal powder, and then by adding polycaprolactone (PCL), genistin nanocapsules were prepared. For the first time, we used a lipophilic nanophase (encapsulated genistin) coated in a hydrophilic nanophase (gelatin /polyvinyl alcohol) as a dual nanosystem by the electrospinning method. In the approach, the nanofibers mimic the natural extracellular matrix, interact favorably with cells being cultured from one side, and raise the local concentration of a bioactive compound at the cell surface. The encapsulated drug which was inserted in fibers with a loading percentage of 92.01% showed appropriate and significant controlled release using high-performance liquid chromatography (HPLC). To prove the experiments, analysis using an ultraviolet–visible spectrometer (UV–Vis), 1H NMR spectrometer, Fourier transforms infrared spectrometer (FTIR), mechanical test, scanning electron microscope (SEM) and microscope transmission electron microscopy (TEM) was performed. The sample synthesized with 40% drug using the MTT method exhibited remarkable biological effects, viability, and non-toxicity. Additionally, significant proliferation and adhesion on the mouse fibroblast cell line L929 were observed within a 72-h timeframe.
Comparison of models for stroke-free survival prediction in patients with CADASIL
Authors: Chhoa Henri , Chabriat Hugues , Chevret Sylvie , Biard Lucie
Published: December 2023

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which is caused by mutations of the NOTCH3 gene, has a large heterogeneous progression, presenting with declines of various clinical scores and occurrences of various clinical event. To help assess disease progression, this work focused on predicting the composite endpoint of stroke-free survival time by comparing the performance of Cox proportional hazards regression to that of machine learning models using one of four feature selection approaches applied to demographic, clinical and magnetic resonance imaging observational data collected from a study cohort of 482 patients. The quality of the modeling process and the predictive performance were evaluated in a nested cross-validation procedure using the time-dependent Brier Score and AUC at 5 years from baseline, the former measuring the overall performance including calibration and the latter highlighting the discrimination ability, with both metrics taking into account the presence of right-censoring. The best model for each metric was the componentwise gradient boosting model with a mean Brier score of 0.165 and the random survival forest model with a mean AUC of 0.773, both combined with the LASSO feature selection method.
Intermittent alternating magnetic fields diminish metal-associated biofilm in vivo
Authors: Shaikh Sumbul , Lapin Norman A. , Prasad Bibin , Sturge Carolyn R. , Pybus Christine , Pifer Reed , Wang Qi , Evers Bret M. , Chopra Rajiv , Greenberg David E.
Published: December 2023

Prosthetic joint infection (PJI) is a complication of arthroplasty that results in significant morbidity. The presence of biofilm makes treatment difficult, and removal of the prosthesis is frequently required. We have developed a non-invasive approach for biofilm eradication from metal implants using intermittent alternating magnetic fields (iAMF) to generate targeted heating at the implant surface. The goal of this study was to determine whether iAMF demonstrated efficacy in an in vivo implant biofilm infection model. iAMF combined with antibiotics led to enhanced reduction of biofilm on metallic implants in vivo compared to antibiotics or untreated control. iAMF-antibiotic combinations resulted in a > 1 − log further reduction in biofilm burden compared to antibiotics or iAMF alone. This combination effect was seen in both S. aureus and P. aeruginosa and seen with multiple antibiotics used to treat infections with these pathogens. In addition, efficacy was temperature dependent with increasing temperatures resulting in a greater reduction of biofilm. Tissue damage was limited (< 1 mm from implant-tissue interface). This non-invasive approach to eradicating biofilm could serve as a new paradigm in treating PJI.
Overexpression of microRNA-205-5p promotes cholangiocarcinoma growth by reducing expression of homeodomain-interacting protein kinase 3
Authors: Mon Aye Myat , Intuyod Kitti , Klungsaeng Sirinapha , Jusakul Apinya , Pongking Thatsanapong , Lert-itthiporn Worachart , Luvira Vor , Pairojkul Chawalit , Plengsuriyakarn Tullayakorn , Na-Bangchang Kesara , Pinlaor Somchai , Pinlaor Porntip
Published: December 2023

The microRNA miR-205-5p has diverse effects in different malignancies, including cholangiocarcinoma (CCA), but its effects on CCA progression is unclear. Here we investigated the role and function of miR-205-5p in CCA. Three CCA cell lines and human serum samples were found to have much higher expression levels of miR-205-5p than seen in typical cholangiocyte cell lines and healthy controls. Inhibition of miR-205-5p suppressed CCA cell motility, invasion and proliferation of KKU-213B whereby overexpression of miR-205-5p promoted cell proliferation and motility of KKU-100 cells. Bioinformatics tools (miRDB, TargetScan, miRWalk, and GEPIA) all predicted various miR-205-5p targets. Experiments using miR-205-5p inhibitor and mimic indicated that homeodomain-interacting protein kinase 3 (HIPK3) was a potential direct target of miR-205-5p. Overexpression of HIPK3 using HIPK3 plasmid cloning DNA suppressed migration and proliferation of KKU-100 cells. Notably, HIPK3 expression was lower in human CCA tissues than in normal adjacent tissues. High HIPK3 expression was significantly associated with longer survival time of CCA patients. Multivariate regression analysis indicated tissue HIPK3 levels as an independent prognostic factor for CCA patients. These findings indicate that overexpression of miR-205-5p promotes CCA cells proliferation and migration partly via HIPK3-dependent way. Therefore, targeting miR-205-5p may be a potential treatment approach for CCA.
Bridging functional and anatomical neural connectivity through cluster synchronization
Authors: Baruzzi Valentina , Lodi Matteo , Sorrentino Francesco , Storace Marco
Published: December 2023

The dynamics of the brain results from the complex interplay of several neural populations and is affected by both the individual dynamics of these areas and their connection structure. Hence, a fundamental challenge is to derive models of the brain that reproduce both structural and functional features measured experimentally. Our work combines neuroimaging data, such as dMRI, which provides information on the structure of the anatomical connectomes, and fMRI, which detects patterns of approximate synchronous activity between brain areas. We employ cluster synchronization as a tool to integrate the imaging data of a subject into a coherent model, which reconciles structural and dynamic information. By using data-driven and model-based approaches, we refine the structural connectivity matrix in agreement with experimentally observed clusters of brain areas that display coherent activity. The proposed approach leverages the assumption of homogeneous brain areas; we show the robustness of this approach when heterogeneity between the brain areas is introduced in the form of noise, parameter mismatches, and connection delays. As a proof of concept, we apply this approach to MRI data of a healthy adult at resting state.
Integrated network pharmacology and metabolomics reveal the mechanisms of Jasminum elongatum in anti-ulcerative colitis
Authors: Qiu Jinyan , Xiao Guanlin , Yang Minjuan , Huang Xuejun , Cai Dake , Xie Canhui , Chen Zhao , Bi Xiaoli , Xu Aili
Published: December 2023

Jasminum elongatum (JE), an ethnic Chinese medicine, is widely used in the Lingnan region of China, because of its analgesic and antidiarrheal action, as well as its anti-inflammatory effects in gastrointestinal diseases. However, whether JE could against ulcerative colitis (UC) remains unclear. This research aims to reveal JE in treating UC and clarify the underlying mechanism. We used the 2.5% dextran sulfate sodium (DSS)-induced UC mice (C57BL/6J) to evaluate the therapeutic effects of JE. Metabolomics of serum and network pharmacology were combined to draw target-metabolite pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using immunohistochemistry. The pharmacodynamic results, including disease activity index (DAI), histological evaluation, and inflammatory cytokines in colon tissues, demonstrated that JE significantly relieved the physiological and pathological symptoms of UC. Network pharmacology analysis indicated 25 core targets, such as TNF, IL-6, PTGS2 and RELA, and four key pathways, including the NF-κB signaling pathway and arachidonic acid metabolism pathway, which were the key connections between JE and UC. Metabolomics analysis identified 45 endogenous differential metabolites and 9 metabolic pathways by enrichment, with the arachidonic acid metabolism pathway being the main metabolism pathway, consistent with the prediction of network pharmacology. IκB, p65 and COX-2 were identified as key targets and this study demonstrated for the first time that JE reverses 2.5% DSS-induced UC in mice via the IκB/p65/COX-2/arachidonic acid pathway. This study reveals the complex mechanisms underlying the therapeutic effects of JE on UC and provides a new approach to identifying the underlying mechanisms of the pharmacological action of Chinese natural medicines such as JE.
Investigation of drag reduction by slurry-like drag-reducing agent in microtube flow using response surface methodology (RSM)
Authors: Cheng Zhensong , Zhang Xin , Song Xinwang , Wang Xudong , Zhang Guoxin , Lu Yuan , Li Lei , Liu Feifan , Dai Xiaodong
Published: December 2023

In this study, we investigated the drag reduction property of a premixed slurry drag reducer in a millimeter-scale pipe. The aim of this study is to establish the correlation between Darcy friction factor and drag reducer concentration (C) and volume flow (Q). First, the experimental plan was designed by using the response surface method (RSM), and then the experimental data were processed to establish the quadratic correlation between the response variable and the description variable. After that, ANOVA analysis of variance was used to verify the accuracy of the experimental data and the correlation. Finally, the prediction model is extended to a larger concentration and volume flow range, and it is found that the accuracy between the predicted value of friction coefficient and the experimental value is ± 30%, thus verifying that the correlation is suitable for the small-scale fully turbulent region. Compared with traditional experimental design and correlation methods, the implementation of Response Surface Methodology (RSM) in this study not only reduces the experimental time but also yields a more robust correlation for predicting the friction coefficient.