bluuebunny/crossref_metadata_2025 huggingface dataset:
Interference of tritrophic (grape × medfly × parasitoid) interactions by mineral and biomaterial films
Authors: Costa Daniela Ribeiro da , Leite Suzany Aguiar , Coelho Beatriz Sousa , Santos Mateus Pereira dos , Joachim-Bravo Iara Sordi , Montoya Pablo , Dias Vanessa Simões , Castellani Maria Aparecida
Published: November 2023

Fruit fly infestation is one of the main obstacles to the exportation of fresh agricultural produce. Films of mineral particles and biomaterials have the potential to protect fruits against tephritid fruit fly infestation. The present study evaluated the effects of particle films on the tritrophic interactions of grape (Vitis vinifera L.), the fruit fly Ceratitis capitata (Wiedemann) and the parasitoid Diachasmimorpha longicaudata (Ashmead) under semi-field conditions. Grapes were biometrically characterised (i.e. colour, firmness, mass, length and diameter), treated with mineral particles, biomaterials or distilled water (control), and then used in oviposition and parasitism bioassays. In the oviposition bioassay, the treated grapes were exposed to 50 C. capitata pairs in field cages, and after 48 h, the punctures and eggs on each fruit were counted. In the parasitism bioassay, treated grapes were artificially infested with third-instar C. capitata larvae (two per fruit), exposed (2 h) to 50 D. longicaudata pairs in field cages to determine parasitism index, larval and pupal viabilities and number of flies and parasitoids emerged. Treatment with the mineral film affected fruit colour and reduced C. capitata oviposition but failed to significantly affect the parasitism capacity of D. longicaudata. The ability of the parasitoid to locate and parasitise C. capitata larvae in kaolin-coated fruits suggests that kaolin films could be used in conjunction with biological agents to control fruit flies.
Isomorphisms of quadratic quasigroups
Authors: Drápal Aleš , Wanless Ian M.
Published: November 2023

Let $\mathbb F$ be a finite field of odd order and $a,b\in\mathbb F\setminus\{0,1\}$ be such that $\chi(a) = \chi(b)$ and $\chi(1-a)=\chi(1-b)$, where χ is the extended quadratic character on $\mathbb F$. Let $Q_{a,b}$ be the quasigroup over $\mathbb F$ defined by $(x,y)\mapsto x+a(y-x)$ if $\chi(y-x) \geqslant 0$, and $(x,y)
\mapsto x+b(y-x)$ if $\chi(y-x) = -1$. We show that $Q_{a,b} \cong Q_{c,d}$ if and only if $\{a,b\}
= \{\alpha(c),\alpha(d)\}$ for some $\alpha\in \operatorname{Aut}(\mathbb F)$. We also characterize $\operatorname{Aut}(Q_{a,b})$ and exhibit further properties, including establishing when $Q_{a,b}$ is a Steiner quasigroup or is commutative, entropic, left or right distributive, flexible or semisymmetric. In proving our results, we also characterize the minimal subquasigroups of $Q_{a,b}$.
Multivariate analysis of clinical and radiological risk factors for revision endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyps: can phenotype predict recurrence?
Authors: Eren Erdem , İşlek Akif , Bakiş Yaşar Batuhan , Altay Sedat
Published: November 2023

Objective

This study aimed to analyse clinical and radiological features (phenotypes) to predict revision risk after functional endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyps.

Method

Phenotype characteristics of the patients with chronic rhinosinusitis with nasal polyps who underwent functional endoscopic sinus surgery were analysed retrospectively.

Results

The rates of asthma, aspirin sensitivity, smoking and a positive prick test result were significantly higher in revision functional endoscopic sinus surgery cases (p < 0.001, 0.001, < 0.001 and < 0.001, respectively). Multivariate analysis demonstrated that only gender, pre-operative nasal steroid use, pre-operative systemic steroid use, intra-operative systemic steroid use and smoking were significant risk factors for revision functional endoscopic sinus surgery (p = 0.034, 0.001, 0.010, 0.007 and 0.001, respectively). In addition, only eosinophilia and aspirin sensitivity were significant risk factors for multiple revision functional endoscopic sinus surgery procedures (p = 0.043 and 0.005, odds ratio = 2.4 and 5.2).

Conclusion

Beyond the endotype of chronic rhinosinusitis with nasal polyps, defining clinical and radiological factors enables a valid prediction of patients at high risk of revision functional endoscopic sinus surgery.
Is auditory processing measured by the N100 an endophenotype for psychosis? A family study and a meta-analysis
Authors: Wang Baihan , Otten Leun J. , Schulze Katja , Afrah Hana , Varney Lauren , Cotic Marius , Saadullah Khani Noushin , Linden Jennifer F. , Kuchenbaecker Karoline , McQuillin Andrew , Hall Mei-Hua , Bramon Elvira
Published: November 2023

Background

The N100, an early auditory event-related potential, has been found to be altered in patients with psychosis. However, it is unclear if the N100 is a psychosis endophenotype that is also altered in the relatives of patients.

Methods

We conducted a family study using the auditory oddball paradigm to compare the N100 amplitude and latency across 243 patients with psychosis, 86 unaffected relatives, and 194 controls. We then conducted a systematic review and a random-effects meta-analysis pooling our results and 14 previously published family studies. We compared data from a total of 999 patients, 1192 relatives, and 1253 controls in order to investigate the evidence and degree of N100 differences.

Results

In our family study, patients showed reduced N100 amplitudes and prolonged N100 latencies compared to controls, but no significant differences were found between unaffected relatives and controls. The meta-analysis revealed a significant reduction of the N100 amplitude and delay of the N100 latency in both patients with psychosis (standardized mean difference [s.m.d.] = −0.48 for N100 amplitude and s.m.d. = 0.43 for N100 latency) and their relatives (s.m.d. = − 0.19 for N100 amplitude and s.m.d. = 0.33 for N100 latency). However, only the N100 latency changes in relatives remained significant when excluding studies with affected relatives.

Conclusions

N100 changes, especially prolonged N100 latencies, are present in both patients with psychosis and their relatives, making the N100 a promising endophenotype for psychosis. Such changes in the N100 may reflect changes in early auditory processing underlying the etiology of psychosis.
What a thousand children tell us about grammatical complexity and working memory: A cross-sectional analysis on the comprehension of clitics and passives in Italian
Authors: Moscati Vincenzo , Marini Andrea , Biondo Nicoletta
Published: November 2023

Data from 996 Italian-speaking children were collected and analyzed to assess whether a movement-based notion of grammatical complexity is adequate to capture the developmental trend of clitics and passives in Italian. A second goal of the study was to address the relationship between working memory and syntactic development, exploring the hypothesis that higher digit span values predict better comprehension of complex matrix sentences. The results confirm the validity of a ranking of grammatical structures based on constituent movement, with both clitics and passives developing in parallel and later than canonical SVO sentences. Working memory also shows an effect on sentence comprehension in general, but standard measures (digit span forward/backward) do not show a selective advantage in handling complex constructions such as clitics and passives.
Higher Education Partnerships with China: US and European Responses to a Changing Context
Authors: Dukalskis Alexander
Published: November 2023

Engaging with higher education institutions from the People’s Republic of China (China or the PRC) raises difficult tensions for universities in liberal democratic contexts. Universities in China are overseen by a political party that routinely silences dissent and does not respect principles of academic freedom in the social sciences and humanities. For decades in the post–Mao era, this tension remained relatively muted outside of the PRC, but it has gained newfound significance as China’s power and assertiveness have grown globally.
Teaching Chinese Politics in the “New Cold War”: A Survey of Faculty
Authors: Newland Sara A.
Published: November 2023

The past decade has been a difficult time to be a scholar of Chinese politics. After Xi Jinping came to power in 2012, opportunities for international collaboration began disappearing, and local interlocutors became increasingly nervous about speaking with foreign researchers. Since 2016, these problems have been compounded by the increasingly tense US–China relationship. Changing attitudes and policies in both countries have hindered those who conduct research on China, work with Chinese collaborators, and recruit Chinese students. The Fulbright Program in China and Hong Kong was closed; National Institutes of Health investigations into foreign influence in US science have caused US-based scientists’ research productivity to decline; and visa restrictions have hindered efforts to recruit Chinese graduate students (Jia et al. 2023). Legal changes in China, including the 2021 Personal Information Protection Law and the 2023 revised Counter-Espionage Law, could be used to target foreign scholars who conduct research in China (Lewis 2023; McCarthy and Gan 2023). The COVID-19 pandemic compounded these challenges in several ways: it caused a rise in anti-Chinese sentiment in the United States and created severe pedagogical challenges for those teaching Chinese politics and other courses containing “sensitive” material that could put students—some now physically located in China—at risk (Gueorguiev et al. 2020).
Response of soybean, cotton, and tobacco to volatility of 2,4-D and dicamba formulations in humidome
Authors: Polli Estefania G. , Gannon Travis W. , LeCompte Mathieu , Rogers Ronald R. , Beran Daniel D.
Published: November 2023

Dicamba and 2,4-D are postemergence herbicides widely used to control broadleaf weed species in crop and non-crop areas in the United States. Currently, multiple formulations of 2,4-D and dicamba are available on the market. Even though the active ingredient is the same, the chemical formulation may vary, which can influence the volatility potential of these herbicides. Therefore, the objective of this study was to evaluate the response of soybean, cotton, and tobacco plants exposed to vapors of 2,4-D and dicamba formulations alone or mixed in humidomes for 24 h. Humidome studies were conducted in an open pavilion at the Lake Wheeler Turfgrass Field Lab of the North Carolina State University in Raleigh, NC. Dicamba and mixture treatments injured and caused a reduction in the height of soybean. Injury varied from 55% to 70%, and average plant height was 8.8 cm shorter compared with untreated control plants. Treatments with 2,4-D caused the least injury to soybean (≤21%), and differences among formulations were identified (dimethylamine > choline > dimethylamine-monomethylamine). However, soybean height was not affected by 2,4-D treatments. No differences between treatments were observed when herbicides were applied to cotton. The greatest injury to tobacco (23.3%) was caused by dicamba dimethylamine. Overall, the effect of 2,4-D and dicamba vapor was species-specific and formulation-dependent. Additionally, environmental conditions in the humidomes may have played a major role on the outcome of this study.
Verantwortung für die Arbeit tragen
Authors: Kalisnik Felix
Published: November 2023

Was ist zu diesem Thema bereits bekannt?

Berufseinsteiger_innen sind sich dem beruflichen Rollenwechsel hin zur Verantwortung bewusst. Dafür wird vor allem Zeit benötigt, damit das berufliche Selbstbewusstsein gestärkt wird.

Wie wird eine neue Perspektive eingebracht?

Insbesondere Gewalt, Aggression und Zwangsmaßnahmen stellen für Berufseinsteiger_innen eine Herausforderung im psychiatrischen Pflegesetting dar. Zwangsmaßnahmen werden kritisch betrachtet.

Was sind die Auswirkungen für die Praxis?

Berufseinsteiger_innen benötigen erfahrenes Personal, das Sicherheit und Wissen vermittelt.
Die Lücke schließen
Authors: Sonderegger Stefanie , Schlüer Anna-Barbara
Published: November 2023

Was ist zu diesem Thema bereits bekannt?

Jugendliche mit Anorexia nervosa (AN) haben ein hohes Risiko für einen chronischen Krankheitsverlauf mit wiederkehrenden Hospitalisationen.

Wie wird eine neue Perspektive eingebracht?

Die Advanced-Practice-Nurse (APN) begleitet Jugendliche und deren Eltern über die Hospitalisation hinaus. Sie ist als bekannte Vertrauensperson niederschwellig erreichbar und kann so kurzfristig in Krisen Hilfestellung bieten.

Was sind die Auswirkungen für die Praxis?

Die kontinuierliche Begleitung im Übergang von stationär ins häusliche Umfeld sollte gezielt sichergestellt werden.
Reviving the Aral Sea: A Hydro‐Eco‐Social Perspective
Authors: Wang Xiaolei , Zhang Junze , Wang Shuai , Ge Yongxiao , Duan Zihao , Sun Lin , Meadows Michael E. , Luo Yi , Fu Bojie , Chen Xi , Huang Yue , Ma Xiaoting , Abuduwaili Jilili
Published: November 2023

The rapid shrinkage and salinization of the Aral Sea over the last few decades has precipitated an environmental disaster, with widespread implications for people whose livelihoods depend on it. Although debated extensively, few viable strategies have yet been identified for reviving the Aral Sea. Here, we propose a hydro‐eco‐social framework to develop a viable, sustainable solution and explore its feasibility to resolve the Aral Sea problem. Based on eco‐environmental indicators, we contend that it is feasible to raise the Aral Sea by 40 m above the Baltic Sea level, while maintaining salinity levels tolerable for aquatic organisms, simultaneously reducing sandstorm risk by 58%. Basin‐wide water balance under climate change scenarios shows that this level can be supported through management interventions that reduce water usage by 22.0–23.2 km3/year and ensure sufficient recharge into the lake, without compromising socio‐economic opportunities. To implement this solution, we propose establishing a socio‐ecologically aligned water governance network for basin‐scale water management that has potential application for other, similarly declining, major lake systems.
The Geophysical Properties of FeHx Phases Under Inner Core Conditions
Authors: Yang Hua , Dou Peixue , Xiao Tingting , Li Yunguo , Muir Joshua M. R. , Zhang Feiwu
Published: November 2023

Hydrogen has been proposed as an important light element in planetary iron cores, while the crystal structure and thermoelasticity of FeHx (x = 1) (FeH hereafter) under inner core conditions remain largely unknown. Recent studies report that FeH adopts an face‐centered cubic (fcc) structure up to core conditions. In this study, using ab initio molecular dynamics, we calculate the free energy and elastic properties of FeH at high P‐T conditions. Our results indicate that the hexagonal close‐packed (hcp) structure of FeHx is favored by both the low hydrogen concentration and the elevated temperature of inner‐core conditions. We also clarify that lattice hydrogen hardens the wave velocities of iron while superionic hydrogen softens it. Both fcc‐ and hcp‐FeH can match inner‐core wave velocities and Poisson's ratio, which supports the hypothesis of hydrogen as a vital light element in the Earth's core.
Imaging the Plumbing System of the Asymmetric Vavilov Spreading Ridge (Tyrrhenian Sea Back‐Arc Basin) From Combined Bathymetry and Magnetic Data
Authors: Cocchi L. , Muccini F. , Palmiotto C. , Ventura G.
Published: November 2023

Back‐arc basins (BABs) are associated with plate margins where crustal shortening, seafloor spreading, and volcanism coexist. The Vavilov basin (Tyrrhenian Sea) is a Pliocene BAB associated with the Apennine‐Tyrrhenian Sea subduction system and characterized by mantle exhumation. The NNE‐SSW elongated Vavilov seamount represents the easternmost and younger spreading ridge of the Vavilov basin. Here we present results of a morphological and magnetic study of the Vavilov seamount. Our results show that the seamount represents the last stage of the eastward asymmetric opening of the BAB. Its plumbing system consists of a dike swarm emplaced during the reversed Matuyama epoch and a younger shallow reservoir feeding the central and eastern sectors during the normal Brunhes epoch. This evolution is associated with the progressive loading of the edifice due to lava flow emplacement. The asymmetry of the seamount mirrors the asymmetric opening of the Vavilov back‐arc basin.
Unique Collections of 14C‐Dated Vegetation Reveal Mid‐Holocene Fluctuations of the Quelccaya Ice Cap, Peru
Authors: Lamantia Kara , Thompson Lonnie , Davis Mary , Mosley‐Thompson Ellen , Stahl Henry
Published: November 2023

Several studies have analyzed the ice margin behavior of the Quelccaya Ice Cap (QIC), Earth's largest tropical ice cap, through the Holocene. However, continuous integration of new information to produce a more cohesive history of the QIC is necessary. Here, the radiocarbon dates of 33 rooted plant specimens collected in situ along the western ice margin between 2002 and 2018 reveal the timing of its past extent as it advanced during the mid‐Holocene. The most recent evaluation of collected specimens indicates that the QIC margin advanced ∼350 m down the Challpacocha Valley between 7.1 and 4.5 ka BP. Past studies of documented ice extent on the western side of the QIC based on a variety of techniques are compiled to create a more comprehensive history of the QIC's behavior throughout the Holocene. Records of documented ice extent, as well as other proxy records, indicate a climate transition ∼5–7 ka BP that created the proper environmental conditions for the expansion of the QIC. Evidence from nearby valleys indicates that the QIC behaved similarly to the documented ice extent in the Challpacocha Valley in response to Holocene climatic fluctuations. The ability to collect the plant specimens and recent analysis of satellite imagery reveals rapid retreat rates of the western outlet glaciers from 1985 to 2020, leaving the western margin of the QIC at its smallest extent since the mid‐Holocene.
Deep learning-enhanced microscopy with extended depth-of-field
Authors: Zhang Yide
Published: November 2023

A computational imaging platform utilizing a physics-incorporated, deep-learned design of binary phase filter and a jointly optimized deconvolution neural network has been reported, achieving high-resolution, high-contrast imaging over extended depth ranges without the need for serial refocusing.
Multifunctional mesoporous silica nanoparticles for biomedical applications
Authors: Xu Bolong , Li Shanshan , Shi Rui , Liu Huiyu
Published: November 2023

Mesoporous silica nanoparticles (MSNs) are recognized as a prime example of nanotechnology applied in the biomedical field, due to their easily tunable structure and composition, diverse surface functionalization properties, and excellent biocompatibility. Over the past two decades, researchers have developed a wide variety of MSNs-based nanoplatforms through careful design and controlled preparation techniques, demonstrating their adaptability to various biomedical application scenarios. With the continuous breakthroughs of MSNs in the fields of biosensing, disease diagnosis and treatment, tissue engineering, etc., MSNs are gradually moving from basic research to clinical trials. In this review, we provide a detailed summary of MSNs in the biomedical field, beginning with a comprehensive overview of their development history. We then discuss the types of MSNs-based nanostructured architectures, as well as the classification of MSNs-based nanocomposites according to the elements existed in various inorganic functional components. Subsequently, we summarize the primary purposes of surface-functionalized modifications of MSNs. In the following, we discuss the biomedical applications of MSNs, and highlight the MSNs-based targeted therapeutic modalities currently developed. Given the importance of clinical translation, we also summarize the progress of MSNs in clinical trials. Finally, we take a perspective on the future direction and remaining challenges of MSNs in the biomedical field.
microRNA-184 in the landscape of human malignancies: a review to roles and clinical significance
Authors: Fattahi Mehdi , Rezaee Delsuz , Fakhari Fatemeh , Najafi Sajad , Aghaei-Zarch Seyed Mohsen , Beyranvand Parisa , Rashidi Mohammad Amin , Bagheri-Mohammadi Saeid , Zamani-Rarani Fahimeh , Bakhtiari Mohammad , Bakhtiari Abbas , Falahi Shahab , Kenarkoohi Azra , Majidpoor Jamal , Nguyen P. U.
Published: November 2023

MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) with a short length of 19–22 nucleotides. miRNAs are posttranscriptional regulators of gene expression involved in various biological processes like cell growth, apoptosis, and angiogenesis. miR-184 is a well-studied miRNA, for which most studies report its downregulation in cancer cells and tissues and experiments support its role as a tumor suppressor inhibiting malignant biological behaviors of cancer cells in vitro and in vivo. To exert its functions, miR-184 affects some signaling pathways involved in tumorigenesis like Wnt and β-catenin, and AKT/mTORC1 pathway, oncogenic factors (e.g., c-Myc) or apoptotic proteins, such as Bcl-2. Interestingly, clinical investigations have shown miR-184 with good performance as a prognostic/diagnostic biomarker for various cancers. Additionally, exogenous miR-184 in cell and xenograft animal studies suggest it as a therapeutic anticancer target. In this review, we outline the studies that evaluated the roles of miR-184 in tumorigenesis as well as its clinical significance.
Mode attraction, rejection and control in nonlinear multimode optics
Authors: Ji Kunhao , Davidson Ian , Sahu Jayanta , Richardson David J. , Wabnitz Stefan , Guasoni Massimiliano
Published: November 2023

Novel fundamental notions helping in the interpretation of the complex dynamics of nonlinear systems are essential to our understanding and ability to exploit them. In this work we predict and demonstrate experimentally a fundamental property of Kerr-nonlinear media, which we name mode rejection and takes place when two intense counter-propagating beams interact in a multimode waveguide. In stark contrast to mode attraction phenomena, mode rejection leads to the selective suppression of a spatial mode in the forward beam, which is controlled via the counter-propagating backward beam. Starting from this observation we generalise the ideas of attraction and rejection in nonlinear multimode systems of arbitrary dimension, which paves the way towards a more general idea of all-optical mode control. These ideas represent universal tools to explore novel dynamics and applications in a variety of optical and non-optical nonlinear systems. Coherent beam combination in polarisation-maintaining multicore fibres is demonstrated as example.
Functional diversity of sharks and rays is highly vulnerable and supported by unique species and locations worldwide
Authors: Pimiento Catalina , Albouy Camille , Silvestro Daniele , Mouton Théophile L. , Velez Laure , Mouillot David , Judah Aaron B. , Griffin John N. , Leprieur Fabien
Published: November 2023

Elasmobranchs (sharks, rays and skates) are among the most threatened marine vertebrates, yet their global functional diversity remains largely unknown. Here, we use a trait dataset of >1000 species to assess elasmobranch functional diversity and compare it against other previously studied biodiversity facets (taxonomic and phylogenetic), to identify species- and spatial- conservation priorities. We show that threatened species encompass the full extent of functional space and disproportionately include functionally distinct species. Applying the conservation metric FUSE (Functionally Unique, Specialised, and Endangered) reveals that most top-ranking species differ from the top Evolutionarily Distinct and Globally Endangered (EDGE) list. Spatial analyses further show that elasmobranch functional richness is concentrated along continental shelves and around oceanic islands, with 18 distinguishable hotspots. These hotspots only marginally overlap with those of other biodiversity facets, reflecting a distinct spatial fingerprint of functional diversity. Elasmobranch biodiversity facets converge with fishing pressure along the coast of China, which emerges as a critical frontier in conservation. Meanwhile, several components of elasmobranch functional diversity fall in high seas and/or outside the global network of marine protected areas. Overall, our results highlight acute vulnerability of the world’s elasmobranchs’ functional diversity and reveal global priorities for elasmobranch functional biodiversity previously overlooked.
Reputations for treatment of outgroup members can prevent the emergence of political segregation in cooperative networks
Authors: Simpson Brent , Montgomery Bradley , Melamed David
Published: November 2023

Reputation systems promote cooperation and tie formation in social networks. But how reputations affect cooperation and the evolution of networks is less clear when societies are characterized by fundamental, identity-based, social divisions like those centered on politics in the contemporary U.S. Using a large web-based experiment with participants (N = 1073) embedded in networks where each tie represents the opportunity to play a dyadic iterated prisoners’ dilemma, we investigate how cooperation and network segregation varies with whether and how reputation systems track behavior toward members of the opposing political party (outgroup members). As predicted, when participants know others’ political affiliation, early cooperation patterns show ingroup favoritism. As a result, networks become segregated based on politics. However, such ingroup favoritism and network-level political segregation is reduced in conditions in which participants know how others behave towards participants from both their own party and participants from the other party. These findings have implications for our understanding of reputation systems in polarized contexts.
Dynamical control enables the formation of demixed biomolecular condensates
Authors: Lin Andrew Z. , Ruff Kiersten M. , Dar Furqan , Jalihal Ameya , King Matthew R. , Lalmansingh Jared M. , Posey Ammon E. , Erkamp Nadia A. , Seim Ian , Gladfelter Amy S. , Pappu Rohit V.
Published: November 2023

Cellular matter can be organized into compositionally distinct biomolecular condensates. For example, inAshbya gossypii, the RNA-binding protein Whi3 forms distinct condensates with different RNA molecules. Using criteria derived from a physical framework for explaining how compositionally distinct condensates can form spontaneously via thermodynamic considerations, we find that condensates in vitro form mainly via heterotypic interactions in binary mixtures of Whi3 and RNA. However, within these condensates, RNA molecules become dynamically arrested. As a result, in ternary systems, simultaneous additions of Whi3 and pairs of distinct RNA molecules lead to well-mixed condensates, whereas delayed addition of an RNA component results in compositional distinctness. Therefore, compositional identities of condensates can be achieved via dynamical control, being driven, at least partially, by the dynamical arrest of RNA molecules. Finally, we show that synchronizing the production of different RNAs leads to more well-mixed, as opposed to compositionally distinct condensates in vivo.
Discovery of a novel cardiac-specific myosin modulator using artificial intelligence-based virtual screening
Authors: Parijat Priyanka , Attili Seetharamaiah , Hoare Zoe , Shattock Michael , Kenyon Victor , Kampourakis Thomas
Published: November 2023

Direct modulation of cardiac myosin function has emerged as a therapeutic target for both heart disease and heart failure. However, the development of myosin-based therapeutics has been hampered by the lack of targeted in vitro screening assays. In this study we use Artificial Intelligence-based virtual high throughput screening (vHTS) to identify novel small molecule effectors of human β-cardiac myosin. We test the top scoring compounds from vHTS in biochemical counter-screens and identify a novel chemical scaffold called ‘F10’ as a cardiac-specific low-micromolar myosin inhibitor. Biochemical and biophysical characterization in both isolated proteins and muscle fibers show that F10 stabilizes both the biochemical (i.e. super-relaxed state) and structural (i.e. interacting heads motif) OFF state of cardiac myosin, and reduces force and left ventricular pressure development in isolated myofilaments and Langendorff-perfused hearts, respectively. F10 is a tunable scaffold for the further development of a novel class of myosin modulators.
Epidemiology, mortality, and health service use of local-level multimorbidity patterns in South Spain
Authors: Alvarez-Galvez Javier , Ortega-Martin Esther , Ramos-Fiol Begoña , Suarez-Lledo Victor , Carretero-Bravo Jesus
Published: November 2023

Multimorbidity –understood as the occurrence of chronic diseases together– represents a major challenge for healthcare systems due to its impact on disability, quality of life, increased use of services and mortality. However, despite the global need to address this health problem, evidence is still needed to advance our understanding of its clinical and social implications. Our study aims to characterise multimorbidity patterns in a dataset of 1,375,068 patients residing in southern Spain. Combining LCA techniques and geographic information, together with service use, mortality, and socioeconomic data, 25 chronicity profiles were identified and subsequently characterised by sex and age. The present study has led us to several findings that take a step forward in this field of knowledge. Specifically, we contribute to the identification of an extensive range of at-risk groups. Moreover, our study reveals that the complexity of multimorbidity patterns escalates at a faster rate and is associated with a poorer prognosis in local areas characterised by lower socioeconomic status. These results emphasize the persistence of social inequalities in multimorbidity, highlighting the need for targeted interventions to mitigate the impact on patients’ quality of life, healthcare utilisation, and mortality rates.
A self-stabilized and water-responsive deliverable coenzyme-based polymer binary elastomer adhesive patch for treating oral ulcer
Authors: Cui Chunyan , Mei Li , Wang Danyang , Jia Pengfei , Zhou Qihui , Liu Wenguang
Published: November 2023

Oral ulcer can be treated with diverse biomaterials loading drugs or cytokines. However, most patients do not benefit from these materials because of poor adhesion, short-time retention in oral cavity and low drug therapeutic efficacy. Here we report a self-stabilized and water-responsive deliverable coenzyme salt polymer poly(sodium α-lipoate) (PolyLA-Na)/coenzyme polymer poly(α-lipoic acid) (PolyLA) binary synergistic elastomer adhesive patch, where hydrogen bonding cross-links between PolyLA and PolyLA-Na prevents PolyLA depolymerization and slow down the dissociation of PolyLA-Na, thus allowing water-responsive sustainable delivery of bioactive LA-based small molecules and durable adhesion to oral mucosal wound due to the adhesive action of PolyLA. In the model of mice and mini-pig oral ulcer, the adhesive patch accelerates the healing of the ulcer by regulating the damaged tissue inflammatory environment, maintaining the stability of oral microbiota, and promoting faster re-epithelialization and angiogenesis. This binary synergistic patch provided a therapeutic strategy to treat oral ulcer.
Source, co-occurrence, and prognostic value of PTEN mutations or loss in colorectal cancer
Authors: Serebriiskii Ilya G. , Pavlov Valerii A. , Andrianov Grigorii V. , Litwin Samuel , Basickes Stanley , Newberg Justin Y. , Frampton Garrett M. , Meyer Joshua E. , Golemis Erica A.
Published: November 2023

Somatic PTEN mutations are common and have driver function in some cancer types. However, in colorectal cancers (CRCs), somatic PTEN-inactivating mutations occur at a low frequency (~8–9%), and whether these mutations are actively selected and promote tumor aggressiveness has been controversial. Analysis of genomic data from ~53,000 CRCs indicates that hotspot mutation patterns in PTEN partially reflect DNA-dependent selection pressures, but also suggests a strong selection pressure based on protein function. In microsatellite stable (MSS) tumors, PTEN alterations co-occur with mutations activating BRAF or PI3K, or with TP53 deletions, but not in CRC with microsatellite instability (MSI). Unexpectedly, PTEN deletions are associated with poor survival in MSS CRC, whereas PTEN mutations are associated with improved survival in MSI CRC. These and other data suggest use of PTEN as a prognostic marker is valid in CRC, but such use must consider driver mutation landscape, tumor subtype, and category of PTEN alteration.
An intelligent framework for forecasting and investigating corrosion in marine conditions using time sensor data
Authors: Ben Seghier Mohamed El Amine , Knudsen Ole Øystein , Skilbred Anders Werner Bredvei , Höche Daniel
Published: November 2023

Corrosion of marine steel structures can be regarded as a time-dependent process that might result in critical strength loss and, eventually, failures. The availability of reliable forecasting models for corrosion would be useful, enabling intelligent maintenance program management, and increasing marine structure safety, while lowering in-service expenses. In this study, an intelligent framework based on a data-driven model is developed that employs a group method of data handling (GMDH) type neural network to forecast free atmospheric corrosion as time-series problem. Therefore, data from sensor data with a 30-min interval over a 110 day period that includes free atmospheric corrosion as well as environmental factors are used. In addition, the Shapley additive explanations (SHAP) technique is used to investigate the impact of the surrounding environmental factors on free atmospheric corrosion. For the performance evaluation of the proposed intelligent framework, selected comparative metrics are used. Findings demonstrate the high accuracy and efficiency of the time series data-driven framework for tackling free atmospheric corrosion progression in marine environments.
Effects of three orthodontic retainers on periodontal pathogens and periodontal parameters
Authors: Li Bowen , Lu Cailian , Yao Xinhui , Wu Xiaojun , Wu Guilin , Zeng Xiantao
Published: November 2023

The objective of this study was to compare and evaluate the changes in periodontal pathogens and periodontal status within 6 months of wearing three orthodontic retainers, namely, vacuum-formed retainer (VFR), Hawley retainer (HR), and lingual fixed retainer (LR). In total, 48 patients who underwent orthodontic treatment with ordinary metal brackets were divided into VFR, HR, and LR groups (n = 16 per group). Saliva samples were collected at the time of debonding (T0) and after 1 month (T1), 3 months (T2), and 6 months (T3). Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) were quantitatively analyzed using real-time PCR. Gingival index (GI), plaque index (PLI), and probing depth (PD) were measured at the four time points to evaluate changes in periodontal state. SPSS20.0 software was used to analyze the data, and P < 0.05 was considered statistically significant. The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2300073704), the registration was retrospective. Compared to baseline (T0) values, Pg, Aa, GI, PLI, and PD were significantly decreased in all three groups 1 month after wearing the retainer (p < 0.05). Significant differences were observed in Aa at T3 among the three groups, whereby the HR group exhibited significantly better results compared to the VFR and LR groups (p < 0.05). Differences were found among the three groups’ Porphyromonas gingivalis at T3, and the HR group was significantly better than the VFR and LR groups (P < 0.05). From T1 to T2, GI, PLI, and PD of the three groups tended to be stable, however differences were observed at T3, with the PLI and PD of the HR group being the lowest among the three groups (p < 0.05). Regardless of the type of retainer used, the periodontal condition of patients was significantly improved after removal of the metal brackets. After 6 months of retainer use, the Hawley retainer was superior to vacuum-formed retainer and lingual fixed retainer with regard to Pg, Aa, and periodontal clinical parameters.
Effects of disliked music on psychophysiology
Authors: Merrill Julia , Ackermann Taren-Ida , Czepiel Anna
Published: November 2023

While previous research has shown the positive effects of music listening in response to one’s favorite music, the negative effects of one’s most disliked music have not gained much attention. In the current study, participants listened to three self-selected disliked musical pieces which evoked highly unpleasant feelings. As a contrast, three musical pieces were individually selected for each participant based on neutral liking ratings they provided to other participants’ disliked music. During music listening, real-time ratings of subjective (dis)pleasure and simultaneous recordings of peripheral measures were obtained. Results showed that compared to neutral music, listening to disliked music evoked physiological reactions reflecting higher arousal (heart rate, skin conductance response, body temperature), disgust (levator labii muscle), anger (corrugator supercilii muscle), distress and grimacing (zygomaticus major muscle). The differences between conditions were most prominent during “very unpleasant” real-time ratings, showing peak responses for the disliked music. Hence, disliked music has a strenuous effect, as shown in strong physiological arousal responses and facial expression, reflecting the listener’s attitude toward the music.
Effect of intra-articular injection of a hyaluronic acid-alendronate conjugate on post-traumatic osteoarthritis induced by destabilization of the medial meniscus in rats
Authors: Scanu Anna , Luisetto Roberto , Pavan Mauro , Guarise Cristian , Beninatto Riccardo , Giraudo Chiara , Galuppini Francesca , Lazzarin Vanni , Guzzardo Vincenza , Pennelli Gianmaria , Galesso Devis , Masiero Stefano
Published: November 2023

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by pain and cartilage damage. Intra-articular (i.a) viscosupplementation with hyaluronic acid (HA) is frequently used for the management of OA. Preclinical studies have reported that bisphosphonates (BPs) may have a therapeutic potential to slow down or reverse the progression of OA. Among these, alendronate (ALN) has demonstrated chondroprotective effects in both in vitro and vivo experiments. This study evaluated the effects of a novel alendronate-hyaluronic acid (ALN-HA) conjugate on an OA in vivo model induced by medial meniscus destabilization (DMM). DMM surgery was performed on the knees of Sprague Dawley rats that received, after four weeks, one intra-articular (i.a.) injection of: (1) ALN-HA; (2) HA; (3) sodium chloride (NaCl). Sham-operated rats were used as control. Allodynia was assessed by Von Frey test. Joint degeneration was evaluated eight weeks after treatment by micro-computed tomography (micro-CT), histology, and immunohistochemistry. Collagen cross-linked C-telopeptides (CTX-I and CTX-II) serum levels were determined by ELISA. Paw withdrawal threshold increased in ALN-HA group when compared to rats treated with NaCl or HA. Micro-CT did not show differences between ALN-HA, HA and NaCl groups. ALN-HA injection produced significant improvements in articular cartilage degeneration showing an OARSI score lower than those of HA and NaCl, and reduced matrix metalloproteinase (MMP)-13, MMP-3, interleukin-6, vascular endothelial growth factor and Caspase-3 expression. CTX-I was reduced after ALN-HA treatment when compared to NaCl. Our results indicate that i.a. use of ALN after conjugation with HA limits OA development and progression in the rat DMM model, and may lead to the development of novel therapeutic strategies in OA management.
Detecting radio- and chemoresistant cells in 3D cancer co-cultures using chromatin biomarkers
Authors: Pekeč Tina , Venkatachalapathy Saradha , Shim Anne R. , Paysan Daniel , Grzmil Michal , Schibli Roger , Béhé Martin , Shivashankar G. V.
Published: November 2023

The heterogenous treatment response of tumor cells limits the effectiveness of cancer therapy. While this heterogeneity has been linked to cell-to-cell variability within the complex tumor microenvironment, a quantitative biomarker that identifies and characterizes treatment-resistant cell populations is still missing. Herein, we use chromatin organization as a cost-efficient readout of the cells’ states to identify subpopulations that exhibit distinct responses to radiotherapy. To this end, we developed a 3D co-culture model of cancer spheroids and patient-derived fibroblasts treated with radiotherapy. Using the model we identified treatment-resistant cells that bypassed DNA damage checkpoints and exhibited an aggressive growth phenotype. Importantly, these cells featured more condensed chromatin which primed them for treatment evasion, as inhibiting chromatin condensation and DNA damage repair mechanisms improved the efficacy of not only radio- but also chemotherapy. Collectively, our work shows the potential of using chromatin organization to cost-effectively study the heterogeneous treatment susceptibility of cells and guide therapeutic design.
Selection, characterization and in vivo evaluation of novel CD44v6-targeting antibodies for targeted molecular radiotherapy
Authors: Mortensen A. C. L. , Berglund H. , Segerström L. , Walle M. , Hofström C. , Persson H. , Nygren P.-Å. , Nilvebrant J. , Frejd F. Y. , Nestor M.
Published: November 2023

Molecular radiotherapy combines the advantages of systemic administration of highly specific antibodies or peptides and the localized potency of ionizing radiation. A potential target for molecular radiotherapy is the cell surface antigen CD44v6, which is overexpressed in numerous cancers, with limited expression in normal tissues. The aim of the present study was to generate and characterize a panel of human anti-CD44v6 antibodies and identify a suitable candidate for future use in molecular radiotherapy of CD44v6-expressing cancers. Binders were first isolated from large synthetic phage display libraries containing human scFv and Fab antibody fragments. The antibodies were extensively analyzed through in vitro investigations of binding kinetics, affinity, off-target binding, and cell binding. Lead candidates were further subjected to in vivo biodistribution studies in mice bearing anaplastic thyroid cancer xenografts that express high levels of CD44v6. Additionally, antigen-dependent tumor uptake of the lead candidate was verified in additional xenograft models with varying levels of target expression. Interestingly, although only small differences were observed among the top antibody candidates in vitro, significant differences in tumor uptake and retention were uncovered in in vivo experiments. A high-affinity anti-CD44v6 lead drug candidate was identified, mAb UU-40, which exhibited favorable target binding properties and in vivo distribution. In conclusion, a panel of human anti-CD44v6 antibodies was successfully generated and characterized in this study. Through comprehensive evaluation, mAb UU-40 was identified as a promising lead candidate for future molecular radiotherapy of CD44v6-expressing cancers due to its high affinity, excellent target binding properties, and desirable in vivo distribution characteristics.
Analysis of the response subsidence and grouting treatment in the goaf of multi-layer inclined coal seam
Authors: Gao Xuhe , Tian Weiping , Pang Qinggang , Li Jiachun , Qi Hongliang , Xu Bin , Zhang Zhipei
Published: November 2023

Based on existing researches, field drillings and numerical simulations are carried out in this paper to analyze the problems of subsidence control in the goaf of multi-layer inclined coal seam. Midas/GTS NX is used to build a three-dimensional calculation model of the goaf. A new method of using borehole data to check simulation parameters is proposed. The whole process of goaf excavation, construction of roadbed (pile foundation) and grouting treatment is analyzed. Analysis theory of different subgrade construction schemes and grouting treatment process on goaf is established. Response characteristics of displacement and equivalent stress and strain of goaf in multilayer inclined coal seam are obtained. A new method for analyzing the characteristics of the stress and deformation of the rock strata before and after grouting in the goaf under the conditions of different foundation schemes on the surface is provided in this research.
Research on nonlinear dynamic characteristics of high-speed gear in two-speed transmission system
Authors: Tan Wuzhong , Wu Jiangming , Liu Zhihui , Wu Xueshen , Zhang Jiahao
Published: November 2023

The working performance and service life of the two-speed transmission system directly affects the performance and service life of helicopters and other equipment. One of the main tasks of the two-speed transmission system research is to improve its dynamic characteristics. For the two-speed transmission system in high-speed gear, a purely torsional nonlinear dynamic differential equation set considering the number of planetary gears, backlash, and clutch dynamic load is established by using the lumped parameter method, and the equations are dimensionless. Then the dimensionless differential equation set is solved by using the variable step-size fourth-order Runge–Kutta method, and the phase diagram and Poincare diagram of high-speed gear are obtained. By changing the dynamic friction coefficient of the friction clutch and the backlash of the gear pair, the influence of parameter change on the nonlinear dynamic characteristics of the system is analyzed. The results show that, with the increase of excitation frequency, the system has experienced single cycle, quasi-cycle, chaos, and double cycle, then changed from double cycle to chaotic motion, and then changed from chaotic motion to double cycle and single cycle motion in turn, and found the path to chaos. In the low-frequency band, reducing the friction coefficient of the friction clutch can reduce vibration amplitude; In the middle-frequency band, reducing the friction coefficient will make the system tend to unstable vibration. In the high-frequency band, it is a single-cycle movement, which is not affected by friction coefficient.