bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular risk in axial spondyloarthritis—a systematic review
Authors: Hintenberger Rainer , Affenzeller Barbara , Vladychuk Valeriia , Pieringer Herwig
Published: July 2023

Cardiovascular manifestations are common in patients suffering axial spondyloarthritis and can result in substantial morbidity and disease burden. To give an overview of this important aspect of axial spondyloarthritis, we conducted a systematic literature search of all articles published between January 2000 and 25 May 2023 on cardiovascular manifestations. Using PubMed and SCOPUS, 123 out of 6792 articles were identified and included in this review. Non-radiographic axial spondyloarthritis seems to be underrepresented in studies; thus, more evidence for ankylosing spondylitis exists. All in all, we found some traditional risk factors that led to higher cardiovascular disease burden or major cardiovascular events. These specific risk factors seem to be more aggressive in patients with spondyloarthropathies and have a strong connection to high or long-standing disease activity. Since disease activity is a major driver of morbidity, diagnostic, therapeutic, and lifestyle interventions are crucial for better outcomes.

Key Points• Several studies on axial spondyloarthritis and associated cardiovascular diseases have been conducted in the last few years addressing risk stratification of these patients including artificial intelligence.• Recent data suggest distinct manifestations of cardiovascular disease entities among men and women which the treating physician needs to be aware of.• Rheumatologists need to screen axial spondyloarthritis patients for emerging cardiovascular disease and should aim at reducing traditional risk factors like hyperlipidemia, hypertension, and smoking as well as disease activity.
Simple odd $$\beta $$-cycle inequalities for binary polynomial optimization
Authors: Del Pia Alberto , Walter Matthias
Published: July 2023

We consider the multilinear polytope which arises naturally in binary polynomial optimization. Del Pia and Di Gregorio introduced the class of odd $$\beta $$
β
-cycle inequalities valid for this polytope, showed that these generally have Chvátal rank 2 with respect to the standard relaxation and that, together with flower inequalities, they yield a perfect formulation for cycle hypergraph instances. Moreover, they describe a separation algorithm in case the instance is a cycle hypergraph. We introduce a weaker version, called simple odd $$\beta $$
β
-cycle inequalities, for which we establish a strongly polynomial-time separation algorithm for arbitrary instances. These inequalities still have Chvátal rank 2 in general and still suffice to describe the multilinear polytope for cycle hypergraphs. Finally, we report about computational results of our prototype implementation. The simple odd $$\beta $$
β
-cycle inequalities sometimes help to close more of the integrality gap in the experiments; however, the preliminary implementation has substantial computational cost, suggesting room for improvement in the separation algorithm.
The globalization theorem for $$\textrm{CD}(K, N)$$ on locally finite spaces
Authors: Li Zhenhao
Published: July 2023

We establish the local-to-global property of the synthetic curvature-dimension condition for essentially non-branching locally finite metric-measure spaces, extending the work [Cavalletti and Milman in Invent Math 226(1):1–137, 2021].
Optimizing glucocorticoid therapy for Behçet's uveitis: efficacy, adverse effects, and advances in combination approaches
Authors: Li Biao , Li Haoran , Huang Qun , Zheng Yanlin
Published: July 2023

Behçet's uveitis (BU) is a debilitating manifestation of Behçet's disease, often requiring prompt and aggressive treatment to prevent vision loss. Glucocorticoids (GCS) serve as a first-line therapy for BU; however, their long-term, high-dose use can result in significant adverse effects. This review summarizes the efficacy, adverse effects, and advances in combination therapy involving GCS for the management of BU. We discuss the benefits and drawbacks of various GCS administration routes, including periocular and intravitreal injections, intravitreal sustained-release devices, and systemic therapy, highlighting the role of fluocinolone acetonide and dexamethasone as primary sustained-release formulations. Moreover, we underscore the importance of combining GCS with immunosuppressive drugs and biological agents to minimize adverse reactions and optimize therapeutic outcomes. The review concludes that, while GCS remain a crucial component of BU treatment, careful consideration of their administration and combination with other therapies is essential to achieve long-term remission and improved visual outcomes for patients with BU.
Financial literacy and advice perceptions among UK higher education students: an ethnicity tale?
Authors: Leone Vitor , Thompson Piers
Published: July 2023

Although considerable efforts have been made in many countries to raise the financial literacy of those from disadvantaged backgrounds, it is unclear whether these are having an effect. This is particularly the case for those of ethnic minority background, who may suffer from other disadvantages. This study examines the financial literacy of students from two universities in the East Midlands region of the UK. It considers the role played by ethnic background. It is found that significant differences in financial literacy remain between the White majority and particular ethnic groups. In part, this appears to reflect their perceptions of the types of decision they see financial literacy relating to. Some ethnic groups saw financial literacy as being of more relevance for larger, less frequent financial decisions, but saw less connection, and relevance, to the day to day choices they had to make. Ethnicity also potentially has an indirect effect, as informal sources of advice, and those that promote a financial market perspective, tend to be valued more highly. The implications are worrying given that the respondents are the more highly educated independent young members of the population. Current attempts to assist the development of financial literacy therefore appear to be failing those from some ethnic minority groups. This will leave them at a continuing disadvantage, unless interventions can highlight the day to day importance and value of financial literacy.
Scalable Gromov–Wasserstein Based Comparison of Biological Time Series
Authors: Kravtsova Natalia , McGee II Reginald L. , Dawes Adriana T.
Published: July 2023

A time series is an extremely abundant data type arising in many areas of scientific research, including the biological sciences. Any method that compares time series data relies on a pairwise distance between trajectories, and the choice of distance measure determines the accuracy and speed of the time series comparison. This paper introduces an optimal transport type distance for comparing time series trajectories that are allowed to lie in spaces of different dimensions and/or with differing numbers of points possibly unequally spaced along each trajectory. The construction is based on a modified Gromov–Wasserstein distance optimization program, reducing the problem to a Wasserstein distance on the real line. The resulting program has a closed-form solution and can be computed quickly due to the scalability of the one-dimensional Wasserstein distance. We discuss theoretical properties of this distance measure, and empirically demonstrate the performance of the proposed distance on several datasets with a range of characteristics commonly found in biologically relevant data. We also use our proposed distance to demonstrate that averaging oscillatory time series trajectories using the recently proposed Fused Gromov–Wasserstein barycenter retains more characteristics in the averaged trajectory when compared to traditional averaging, which demonstrates the applicability of Fused Gromov–Wasserstein barycenters for biological time series. Fast and user friendly software for computing the proposed distance and related applications is provided. The proposed distance allows fast and meaningful comparison of biological time series and can be efficiently used in a wide range of applications.
Protective role of plant growth-promoting fungi Aspergillus chevalieri OP593083 and Aspergillus egyptiacus OP593080 as biocontrol approach against Alternaria leaf spot disease of Vicia faba plant
Authors: Daigham Ghadir E. , Mahfouz Amira Y. , Abdelaziz Amer M. , Nofel Mohamed M. , Attia Mohamed S.
Published: July 2023

Crop loss brought on by phytopathogens is a significant issue that affects the entire world. Synthetic pesticides have been used for years to prevent economic losses caused by phytopathogens, raising severe worries about the environment and public health. Therefore, today, there is growing interest in using helpful microorganisms to control plant pathogens. In this way, Aspergillus chevalieri AGH-1 OP593083 and Aspergillus egyptiacus AGH-4 OP593080 isolated from wheat rhizosphere have been applied as plant growth-promoting fungi (PGPF) for combating early blight disease caused by Alternaria solani (A. solani) and inducing the defense system and growth promotional strategies in Vicia faba. Two milligrams per milliliter ethyl acetate crude extracts of A. chevalieri and A. egyptiacus demonstrated effective antifungal efficacy against A. solani with an inhibition zone of 18 and 16 mm respectively compared with 20 mm attained by fluconazole as a positive control. Moreover, the minimum inhibitory concentrations (MIC) were (0.25 and 0.5 mg/ml) for A. chevalieri and A. egyptiacus extracts respectively. Data showed that A. chevalieri was the best isolate producing indole acetic acid (IAA) and siderophores (+ + +) followed by A. egyptiacus (+ +). Also, the best isolates capable of phosphate solubilization in the soil was A. egyptiacus (+ + +), followed by A. chevalieri (+ +). It is interesting that the PGPF isolates used, whether single or mixed, showed a significant improvement in all growth and yield as well as photosynthetic pigments in Vicia faba. Moreover, A. chevalieri and A. egyptiacus played an important role in improving plant immunity by increasing phenol, proline, and antioxidant enzymes (POD and PPO) activities, as well as reducing oxidative stress by reducing MDA and H2O2. We can conclude that A. chevalieri and A. egyptiacus are considered eco-friendly safe strong inducers of Vicia faba plant immunity alternatives to chemical pesticides against A. solani early blight to preserve plant, soil, and human health.
Effects of SGM Education for Undergraduate Medical Students in a Canadian Context
Authors: Karsenti Nessika , Chambers Jason , Espinosa Aldo
Published: July 2023

Medical schools have been striving to equip students with the tools and skills needed to serve patients from the LGBTQ + community, also called the Sexual and Gender Minority (SGM) community. This study aims to assess student comfort with providing care, and faculty knowledge and preparedness in delivering SGM-centered education at our home institution. We conducted two mixed-methods surveys, one geared towards medical students across four years of study and one towards medicine faculty. Each survey collected first demographic information about participants, then used a validated tool to assess knowledge of the SGM community. The qualitative component of both surveys then consisted of a needs assessment to determine what students felt should be changed about their curriculum, and what faculty felt should change about their training to deliver this curriculum. We received 26 student responses from all 4 years of study and 35 faculty responses from a variety of medical specialties. Difference in knowledge assessment scores was not statistically significant across both cohorts. Most students felt overall comfortable providing care for sexual minority individuals, and faculty similarly felt comfortable teaching, but data showcases that perceived comfort is higher among the student cohort. We propose that students are acquiring knowledge and comfort with providing for SGM individuals from sources outside their curriculum, and that additional training of faculty is vital to ensure students not doing this independent learning do not fall through the cracks.
Decentralized fault-tolerant control of modular robot manipulators with actuator saturation: neural adaptive integral terminal sliding mode-based control approach
Authors: Lu Zengpeng , Li Yuanchun , Fan Xirui , Wang Qingyun , Li Yan
Published: July 2023

A novel neural adaptive integral terminal sliding mode control for decentralized fault-tolerant control strategy, including the integral terminal sliding mode surface, the nonlinear disturbance observer, the radial basis neural network and robust controller, is presented in this paper to achieve fault-tolerant control of modular robot manipulators. First, the integral terminal sliding mode is designed for the fault-tolerant controller. Then, to boost the performance of the controlled system, the radial basis neural network and disturbance observer are introduced to approximate the nonlinear terms and disturbances. The reconstructed approximate uncertainty term is applied as compensation. Next, the super-twisting technique is employed to compensate for estimation errors to ensure stability. In addition, for the actuator saturation problem, the radial basis function neural network-based compensation control is proposed. Finally, the stability of the closed-loop robotic system is demonstrated based on Lyapunov theory. Computer simulations verified the efficiency and advantages of the presented approach.
Curriculum reform in African higher education: solving society’s problems and meeting its needs
Authors: Agbaje Olaide
Published: July 2023

Higher education is often regarded as a crucial driver of development in Africa. Notably, the curricula in African higher education institutions are central to the discourse of development and the production of graduates who are sufficiently critical to challenge the historical, political, economic and social status quo in Africa. Curriculum experts in Africa have called for revisiting the purpose and the content of higher education curricula in Africa, and embracing an indigenous knowledge system that not only brings about development in nations themselves or the continent as a whole, but which also enhances human capacity. This paper argues that it is important for higher education institutions to embrace a curriculum that is synchronised to the particularities of African societies. One way to achieve this is by reforming the curriculum to reflect the realities and needs of the African continent, rather than providing a mere replica of the Western model. This paper also argues that curriculum reform is inevitable if the university is to fulfil this important role. This paper aims to answer the pertinent question; In what ways are Africa’s higher education curricula solving societal problems and meeting societal needs? This paper is guided by the theory of critical pedagogy developed by Paulo Freire and is developed through a review of the literature. The findings show that curriculum reform that promotes indigenous knowledge systems in Africa is imperative for meeting some of the needs of the African continent.
The effect of human serum albumin on ZIF-8 used in drug delivery: structural, linear and nonlinear optical properties
Authors: Al-Jouhani Saja , Al-Azwari Raghad , Al-Shemari Sara , Al-Anezi Rawan , Khasim Syed , Mohamed S. , Al-Ghamdi S. A. , Darwish A. A. , Hamdalla Taymour A.
Published: July 2023

Zeolitic Imidazolate Frameworks (ZIF-8) are extremely useful substances that have been utilized in a variety of commercial and medical applications due to their interesting properties. Understanding the properties of ZIF-8 doped human serum albumin with different concentrations can lead to the development of new applications in areas such as sensing, drug delivery, and catalysis. Here, we investigated the extent of interaction between ZIF-8 and HSA by examining the structural, linear, and nonlinear optical properties of ZIF-8@xHSA where x is 2.5, 5, 10 wt%. Scanning electron microscope and Transmission electron microscope images revealed that both ZIF-8 and ZIF-8@10 wt% HSA had regular cubic shapes, with average particle sizes of 38 nm and 49 nm, respectively. The X-ray diffraction shows a crystalline shape for ZIF-8 and ZIF-8@10 wt% HAS. The energy gap of our composite was calculated using the Wemple-Didomenico model, and it exhibited strong concentration-dependent behavior. The Z-scanner was used to investigate the nonlinear properties, which indicated that ZIF-8@10 wt%HSA had a high nonlinear response. As the understanding of this interaction deepens, it is expected that innovative applications in biomedical and pharmaceutical fields will emerge, highlighting the vital connection between HSA and ZIF-8.
Contract Law of Qatar
Authors: Bantekas Ilias , Al-Ahmed Ahmed
Published: July 2023

As Qatar's aspirations of becoming a key location for international dispute settlement and international trade grow, so too does the importance of understanding private law in Qatar and the Gulf states. In this innovative book, Ilias Bantekas and Ahmed Al-Ahmed provide an original, English-language treatise on the contract law of Qatar. Using an abundance of case law, the authors combine scholarly and practice-oriented expertise to develop a comprehensive treatment of Qatari contract law. The analysis is drawn from a wealth of judgements from the Qatari Court of Cassation and Court of Appeal, much of which was previously inaccessible to readers. Bringing sophisticated, detailed insights on Qatari law to an English-speaking legal audience, this is a vital text for academics, practitioners and students who wish to comprehend this increasingly influential global player. This title is available as Open Access on Cambridge Core.
Hosea, Joel, and Amos
Authors: Hamborg Graham R.
Published: July 2023

In this commentary, Graham Hamborg offers a timely and up to date assessment of the books of Hosea, Joel and Amos. Recognising that each had a compositional history leading to the final forms by which we know them, he brings a literary approach to the texts and connects them to other parts of the Hebrew Bible/Old Testament. Hamborg also draws attention to topics where there are a range of scholarly views. 'Closer Look' sections explore significant themes and terms in greater depth, and 'Bridging the Horizons' sections indicate how the texts are of continuing significance in today's world. Conveying the meaning and importance of Hosea, Joel, and Amos in non-technical language and in an accessible style, this volume will be a valuable commentary for biblical scholars, students, and non-specialists for years to come.
Confirmation by necropsy of a high prevalence of porcine cysticercosis in a rural district of Madagascar
Authors: Mananjara Diana Edithe Andria , Rakotoarinoro Mihajamanana , Rakotoarison Valisoa C. , Raliniaina Modestine , Razafindraibe Nivohanitra P. , Ravonirina Claudia , Randriamparany Tantely , Rasamoelina-Andriamanivo Harentsoaniaina , Rakotozandrindrainy Raphaël , Cardinale Eric , Lightowlers Marshall W. , Donadeu Meritxell , Mwape Kabemba E.
Published: July 2023

Neurocysticercosis is recognized as an important health issue in the Malagasy population. To date, investigations into prevalence of infection with the causative agent, Taenia solium, in the parasite's natural animal intermediate hosts, have relied on serological methods which have been found to be non-specific. We determined the prevalence of porcine cysticercosis among pigs from a contiguous area of the Betafo and Mandoto administrative districts, Vakinankaratra Region, Madagascar. One hundred and four slaughter-weight pigs were examined by detailed necropsy examination including slicing of the heart, tongue, masseter muscles, diaphragm and carcase musculature. Thirty-seven animals (35.6%) were found infected with T. solium, representing one of the highest rates of infection ever reported, worldwide. These findings highlight the importance of T. solium in Madagascar and support the need for increased efforts to prevent the parasite's transmission to reduce its burden on the health of the Malagasy population.
Gender and Disability in US State Temporary Disability Systems 1942–1949
Authors: REMICK ELIZABETH J.
Published: July 2023

During the 1940s, four US states established a new form of social insurance, Temporary Disability Insurance (TDI), meant to provide wage replacement to breadwinners unable to work due to nonoccupational illness or injury. The first TDI state, Rhode Island, did not initially exclude coverage of pregnancy-related disabilities, threatening the health of the TDI trust fund. Administrators and lawmakers then sought to reduce or eliminate the pregnancy-related disability benefit on the grounds that pregnancy and related conditions were not “real” disabilities. Subsequently, Rhode Island administrators advised lawmakers in California, New Jersey, and New York to exclude pregnancy-related disabilities from coverage. The breadwinner gender ideology animating New Deal social welfare programs intersected with gendered ideas of disability, creating a form of social insurance that excluded or marginalized pregnancy-related disability and further circumscribed women’s social citizenship.
Incremental Lobby Reform: Elite Interests and Governance Policies
Authors: STRICKLAND JAMES
Published: July 2023

Common examples of governance policies include regulations of lobbying, campaign-finance restrictions, and term limitations. Although the public generally favors these good-government reforms, the laws often restrict the autonomy of political elites. The histories of lobby reform in New York, Georgia, and Michigan illustrate how governance policies might be adopted despite elite opposition. In the states, initial reform efforts came about due to agenda-setting events or policy entrepreneurs. Although legislators adopted lobby reforms, they preferred transparency to other lobby reforms given its limited effect on mutualistic relationships. Initial lobby laws required only disclosure and did not restrict legislator–lobbyist interactions much. Only with the advent of additional events and entrepreneurs were the initial laws strengthened to limit interactions. The histories of reform imply that narratives of policy innovation or diffusion may be complicated somewhat by elite interests and that governance policies, once adopted, may have a unique immunity from repeal.
Christian Democracy, Labor, and the Postwar Politics of Old-Age Pension Reform
Authors: OUDE NIJHUIS DENNIE
Published: July 2023

Christian-democratic parties not only constituted the most successful political force in much of Western Europe during most of the twentieth century; their attitudes toward solidaristic welfare reform have arguably also been more diverse than have those of most other major political groupings during this period. Whereas existing studies have mostly attributed this variation to electoral or strategic considerations, this article emphasizes the importance of interest group involvement. It analyzes and compares postwar old-age pension reform in three important Christian-democratic-ruled societies, Belgium, Germany, and the Netherlands, and shows how the very different attitudes of the main Christian-democratic parties toward solidaristic welfare reform in these countries related to the strength and unity of the Christian-democratic labor union movements there.
Simple mandates, monetary rules, and trend-inflation
Authors: Deák Szabolcs , Levine Paul , Pham Son T.
Published: July 2023

A mandate framework is proposed for delegating monetary policy to an instrument-independent, but goal-dependent central bank that emphasizes simplicity in both the objectives entering the welfare criterion and those in the instrument rule. It consists of: (i) a simple quadratic loss function penalizing deviations from target variables; (ii) a welfare-optimized, Taylor-type log-linear nominal interest-rate rule with targets that match those in the loss function; (iii) a zero-lower-bound (ZLB) constraint on the nominal interest rate imposing a low unconditional probability of ZLB episodes; and (iv) a long-run inflation target. In an estimated New Keynesian model with these features, we find that for a quarterly probability of 5%, an optimal annual inflation target is close to 2%, weights for real variables in the loss function are small compared with inflation except for the real wage growth mandate and the optimized rules mimic a price-level rule.
Hurricane Impacts on Land in the Central and Eastern Caribbean Since 1494 CE From Written Records
Authors: Chenoweth Michael , Howard Ian
Published: July 2023

Written accounts of hurricanes and their impacts in the Caribbean region date back to 1494 CE We report a new compilation of hurricanes in the longest settled regions of the central and eastern Caribbean region (CECR) that is the most complete yet produced and present basic statistics. We assess likely undercounts of hurricanes due to incomplete documentary records in the earliest part of the record by using the most complete reporting from Puerto Rico relative to the remainder of the CECR. We compare our results with other documentary and proxy data from the region and demonstrate using wavelet analysis significant activity related to the El Niño‐Southern Oscillation (ENSO) at inter‐annual time scales and lower frequency activity from decadal to multi‐decadal scales. Our results offer evidence that, along with ENSO, fluctuations in sulfate aerosols are a possible contributor to the hurricane history. The frequency of hurricane landfalls and impacts in the CECR was lower in the 20th century than any time since 1494 CE.
Beyond Simple Trend Tests: Detecting Significant Changes in Design‐Flood Quantiles
Authors: Awasthi C. , Archfield S. A. , Reich B. J. , Sankarasubramanian A.
Published: July 2023

Changes in annual maximum flood (AMF), which are usually detected using simple trend tests (e.g., Mann‐Kendall test (MKT)), are expected to change design‐flood estimates. We propose an alternate framework to detect significant changes in design‐flood between two periods and evaluate it for synthetically generated AMF from the Log‐Pearson Type‐3 (LP3) distribution due to changes in moments associated with flood distribution. Synthetic experiments show MKT does not consider changes in all three moments of the LP3 distribution and incorrectly detects changes in design‐flood. We applied the framework on 31 river basins spread across the United States. Statistically significant changes in design‐flood quantiles were observed even without a significant trend in AMF and basins with statistically significant trend did not necessarily exhibit statistically significant changes in design‐flood. We recommend application of the framework for evaluating changes in design‐flood estimates considering changes in all the moments as opposed to simple trend tests.
Thank You to Our 2022 Peer Reviewers
Authors: Manighetti Isabelle , Abercrombie Rachel , Bernabé Yves , Bostock Michael , Dekkers Mark J. , Ide Satoshi , Schmitt Douglas R. , Han Shin‐Chan , Tregoning Paul
Published: July 2023

Editors of JGR‐Solid Earth express their appreciation to those who served as peer reviewers for the journal in 2022.
Experiences and recommendations from people with spinal cord injury following participation in a disability education session at an allopathic medical school: a qualitative study
Authors: Pekmezaris Renée , Patel Vidhi , Herman Paige , Stein Adam B. , Bloom Ona
Published: July 2023

Background

Students in half of US medical schools do not receive formal instruction in providing medical care for people with disabilities. To address this gap in training, our medical school developed several strategies, including a session for second year medical students to address communication skills, knowledge, and attitudes relevant to delivering healthcare for people with disabilities. Here, our objective was to explore perceptions of people with spinal cord injury (SCI) who participated in the session on its content and structure.

Methods

Qualitative research using a focus group of people with SCI who participated in an educational session for medical students in an LCME accredited allopathic US medical school. A purposive sample of adults with SCI (N = 8) participated in a focus group. Data were analyzed using a six-phase thematic analysis.

Results

Participants favorably viewed the educational session, felt their participation was valuable, and had suggestions for its improvement. Four major themes were identified: (1) session format, content; (2) addressing student discomfort and avoidance behaviors; (3) increasing student knowledge and preparation; and (4): important lessons from discussions of past and role-played doctor-patient interactions.

Conclusions

First-person input from people with SCI is critical to improve medical education and healthcare provision to the SCI community. To our knowledge, this is the first study to report feedback from stakeholders providing specific recommendations for teaching disabilities awareness to undergraduate medical students. We expect these recommendations to be relevant to the SCI and medical education communities in improving healthcare for people with SCI and other disabilities.
The TLR3 L412F polymorphism prevents TLR3-mediated tumor cell death induction in pediatric sarcomas
Authors: Bisaccia Joseph , Meyer Swann , Bertrand-Chapel Adrien , Hecquet Quentin , Barbet Virginie , Kaniewski Bastien , Léon Sophie , Gadot Nicolas , Rochet Isabelle , Fajnorova Iveta , Leblond Pierre , Cordier-Bussat Martine , Corradini Nadège , Vasiljevic Alexandre , Billaud Marc , Picard Cécile , Broutier Laura , Gallerne Cindy , Dutour Aurélie , Blay Jean-Yves , Castets Marie
Published: July 2023

Toll-like receptor 3 (TLR3) is a pattern recognition receptor mainly known for its role in innate immune response to infection. Indeed, binding of double-stranded RNA (dsRNA) to TLR3 triggers a pro-inflammatory cascade leading to cytokine release and immune cell activation. Its anti-tumoral potential has emerged progressively, associated with a direct impact on tumor cell death induction and with an indirect action on immune system reactivation. Accordingly, TLR3 agonists are currently being tested in clinical trials for several adult cancers. Meanwhile, TLR3 variants have been linked to auto-immune disorders, and as risk factors of viral infection and cancers. However, aside from neuroblastoma, TLR3 role in childhood cancers has not been evaluated. Here, by integrating public transcriptomic data of pediatric tumors, we unveil that high TLR3 expression is largely associated with a better prognosis in childhood sarcomas. Using osteosarcomas and rhabdomyosarcomas as models, we show that TLR3 efficiently drives tumor cell death in vitro and induces tumor regression in vivo. Interestingly, this anti-tumoral effect was lost in cells expressing the homozygous TLR3 L412F polymorphism, which is enriched in a rhabdomyosarcomas cohort. Thus, our results demonstrate the therapeutic potential associated with the targeting of TLR3 in pediatric sarcomas, but also the need to stratify patients eligible for this clinical approach with respect to the TLR3 variants expressed.
Kinome-wide CRISPR-Cas9 knockout screens revealed PLK1 as a therapeutic target for osteosarcoma
Authors: Wang Renxian , Wang Dingding , Bai Xueshan , Guo Jianxun , Xia Songxia , Cheng Yuning , Gu Yani , Wang Qian , Nie Jingjun , Chen Dafu , Liu Weifeng , Liang Junbo
Published: July 2023

Osteosarcoma is the most common malignant bone tumor, tending to be aggressive and recurrent. The therapeutic development for treating osteosarcoma has been largely hampered by the lack of effective and specific targets. Using kinome-wide CRISPR-Cas9 knockout screens, we systematically revealed a cohort of kinases essential for the survival and growth of human osteosarcoma cells, in which Polo-like kinase 1 (PLK1) appeared as a specific prominent hit. PLK1 knockout substantially inhibited proliferation of osteosarcoma cells in vitro and the tumor growth of osteosarcoma xenograft in vivo. Volasertib, a potent experimental PLK1 inhibitor, can effectively inhibit the growth of the osteosarcoma cell lines in vitro. It can also disrupt the development of tumors in the patient-derived xenograft (PDX) models in vivo. Furthermore, we confirmed that the mode of action (MoA) of volasertib is primarily mediated by the cell-cycle arrest and apoptosis triggered by DNA damage. As PLK1 inhibitors are entering phase III clinical trials, our findings provide important insights into the efficacy and MoA of the relevant therapeutic approach for combating osteosarcoma.
Structural insights into RNA bridging between HIV-1 Vif and antiviral factor APOBEC3G
Authors: Kouno Takahide , Shibata Satoshi , Shigematsu Megumi , Hyun Jaekyung , Kim Tae Gyun , Matsuo Hiroshi , Wolf Matthias
Published: July 2023

Great effort has been devoted to discovering the basis of A3G-Vif interaction, the key event of HIV’s counteraction mechanism to evade antiviral innate immune response. Here we show reconstitution of the A3G-Vif complex and subsequent A3G ubiquitination in vitro and report the cryo-EM structure of the A3G-Vif complex at 2.8 Å resolution using solubility-enhanced variants of A3G and Vif. We present an atomic model of the A3G-Vif interface, which assembles via known amino acid determinants. This assembly is not achieved by protein-protein interaction alone, but also involves RNA. The cryo-EM structure and in vitro ubiquitination assays identify an adenine/guanine base preference for the interaction and a unique Vif-ribose contact. This establishes the biological significance of an RNA ligand. Further assessment of interactions between A3G, Vif, and RNA ligands show that the A3G-Vif assembly and subsequent ubiquitination can be controlled by amino acid mutations at the interface or by polynucleotide modification, suggesting that a specific chemical moiety would be a promising pharmacophore to inhibit the A3G-Vif interaction.
Atypical splicing variants in PKD1 explain most undiagnosed typical familial ADPKD
Authors: Hort Yvonne , Sullivan Patricia , Wedd Laura , Fowles Lindsay , Stevanovski Igor , Deveson Ira , Simons Cas , Mallett Andrew , Patel Chirag , Furlong Timothy , Cowley Mark J. , Shine John , Mallawaarachchi Amali
Published: July 2023

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of kidney failure and is primarily associated with PKD1 or PKD2. Approximately 10% of patients remain undiagnosed after standard genetic testing. We aimed to utilise short and long-read genome sequencing and RNA studies to investigate undiagnosed families. Patients with typical ADPKD phenotype and undiagnosed after genetic diagnostics were recruited. Probands underwent short-read genome sequencing, PKD1 and PKD2 coding and non-coding analyses and then genome-wide analysis. Targeted RNA studies investigated variants suspected to impact splicing. Those undiagnosed then underwent Oxford Nanopore Technologies long-read genome sequencing. From over 172 probands, 9 met inclusion criteria and consented. A genetic diagnosis was made in 8 of 9 (89%) families undiagnosed on prior genetic testing. Six had variants impacting splicing, five in non-coding regions of PKD1. Short-read genome sequencing identified novel branchpoint, AG-exclusion zone and missense variants generating cryptic splice sites and a deletion causing critical intron shortening. Long-read sequencing confirmed the diagnosis in one family. Most undiagnosed families with typical ADPKD have splice-impacting variants in PKD1. We describe a pragmatic method for diagnostic laboratories to assess PKD1 and PKD2 non-coding regions and validate suspected splicing variants through targeted RNA studies.
Quantum reservoir computing implementation on coherently coupled quantum oscillators
Authors: Dudas Julien , Carles Baptiste , Plouet Erwan , Mizrahi Frank Alice , Grollier Julie , Marković Danijela
Published: July 2023

Quantum reservoir computing is a promising approach for quantum neural networks, capable of solving hard learning tasks on both classical and quantum input data. However, current approaches with qubits suffer from limited connectivity. We propose an implementation for quantum reservoir that obtains a large number of densely connected neurons by using parametrically coupled quantum oscillators instead of physically coupled qubits. We analyze a specific hardware implementation based on superconducting circuits: with just two coupled quantum oscillators, we create a quantum reservoir comprising up to 81 neurons. We obtain state-of-the-art accuracy of 99% on benchmark tasks that otherwise require at least 24 classical oscillators to be solved. Our results give the coupling and dissipation requirements in the system and show how they affect the performance of the quantum reservoir. Beyond quantum reservoir computing, the use of parametrically coupled bosonic modes holds promise for realizing large quantum neural network architectures, with billions of neurons implemented with only 10 coupled quantum oscillators.
Morphomigrational description as a new approach connecting cell's migration with its morphology
Authors: Kołodziej Tomasz , Mielnicka Aleksandra , Dziob Daniel , Chojnacka Anna Katarzyna , Rawski Mateusz , Mazurkiewicz Jan , Rajfur Zenon
Published: July 2023

The examination of morphology and migration of cells plays substantial role in understanding the cellular behaviour, being described by plethora of quantitative parameters and models. These descriptions, however, treat cell migration and morphology as independent properties of temporal cell state, while not taking into account their strong interdependence in adherent cells. Here we present the new and simple mathematical parameter called signed morphomigrational angle (sMM angle) that links cell geometry with translocation of cell centroid, considering them as one morphomigrational behaviour. The sMM angle combined with pre-existing quantitative parameters enabled us to build a new tool called morphomigrational description, used to assign the numerical values to several cellular behaviours. Thus, the cellular activities that until now were characterized using verbal description or by complex mathematical models, are described here by a set of numbers. Our tool can be further used in automatic analysis of cell populations as well as in studies focused on cellular response to environmental directional signals.
Vocalizations of wild West Indian manatee vary across subspecies and geographic location
Authors: Reyes-Arias Jessica D. , Brady Beth , Ramos Eric A. , Henaut Yann , Castelblanco-Martínez Delma Nataly , Maust-Mohl Maria , Searle Linda , Pérez-Lachaud Gabriela , Guzmán Héctor M. , Poveda Héctor , Merchan Fernando , Contreras Kenji , Sanchez-Galan Javier E. , Collom Kristi A. , Magnasco Marcelo O.
Published: July 2023

Geographic variation in the vocal behavior of manatees has been reported but is largely unexplored. Vocalizations of wild West Indian manatees (Trichechus manatus) were recorded with hydrophones in Florida from Florida manatees (Trichechus manatus latirostris), and in Belize and Panama from Antillean manatees (Trichechus manatus manatus) to determine if calls varied between subspecies and geographic regions. Calls were visually classified into five categories: squeaks, high squeaks, squeals, squeak-squeals, and chirps. From these five categories, only three call types (squeaks, high squeaks and squeals) were observed in all three populations. Six parameters from the temporal and frequency domains were measured from the fundamental frequency of 2878 manatee vocalizations. A repeated measures PERMANOVA found significant differences for squeaks and high squeaks between each geographic location and for squeals between Belize and Florida. Almost all measured frequency and temporal parameters of manatee vocalizations differed between and within subspecies. Variables that may have influenced the variation observed may be related to sex, body size, habitat and/or other factors. Our findings provide critical information of manatee calls for wildlife monitoring and highlight the need for further study of the vocal behavior of manatees throughout their range.
Ceramide releases exosomes with a specific miRNA signature for cell differentiation
Authors: Fiorani Federico , Domenis Rossana , Dalla Emiliano , Cataldi Samuela , Conte Carmela , Mandarano Martina , Sidoni Angelo , Cifù Adriana , Beccari Tommaso , Mirarchi Alessandra , Arcuri Cataldo , Curcio Francesco , Albi Elisabetta
Published: July 2023

Exosomes are well established effectors of cell–cell communication. Their role on maturation of embryonic cells located in hippocampus, seat of memory, is unknown. Here we show that ceramide facilitates release of exosomes from HN9.10e cells extending information for cell differentiation to neighboring cells. We found only 38 miRNAs differentially expressed in exosomes derived from ceramide-treated cells in comparison with control cells (including 10 up-regulated and 28 down-regulated). Some overexpressed miRNAs (mmu-let-7f-1-3p, mmu-let-7a-1-3p, mmu-let-7b-3p, mmu-let-7b-5p, mmu-miR-330-3p) regulate genes encoding for protein involved in biological, homeostatic, biosynthetic and small molecule metabolic processes, embryo development and cell differentiation, all phenomena relevant for HN9.10e cell differentiation. Notably, the overexpressed mmu-let-7b-5p miRNA appears to be important for our study based on its ability to regulate thirty-five gene targets involved in many processes including sphingolipid metabolism, sphingolipid-related stimulation of cellular functions and neuronal development. Furthermore, we showed that by incubating embryonic cells with exosomes released under ceramide treatment, some cells acquired an astrocytic phenotype and others a neuronal phenotype. We anticipate our study to be a start point for innovative therapeutic strategies to regulate the release of exosomes useful to stimulate delayed brain development in the newborn and to improve the cognitive decline in neurodegenerative disorders.
Heat exposure following encoding can interfere with subsequent recognition memory
Authors: Cudeiro Jesús , Soto David , Gutiérrez Emilio
Published: July 2023

Correlational studies suggest that high temperatures may impair online cognitive performance and learning processes. Here, we tested the hypothesis that heat exposure blocks offline memory consolidation. We report two studies, including a pre-registered replication. First, during a study phase, participants were familiarized with neutral and negatively valenced images. One day later, half of the participants were exposed to high temperatures in a sauna session at 50 °C. Recognition memory was tested 24 h later. We found that participants exposed to high temperature showed an impairment in recognition memory performance, relative to a control group of participants that were not exposed to heat or that had a sauna at 28 °C. This occurred for both emotional and neutral items. These results indicate that heat exposure impairs memory consolidation, thereby opening the possibility of using heat exposure as an agent for the treatment of clinical mental disorders.
Starvation decreases immunity and immune regulatory factor NF-κB in the starlet sea anemone Nematostella vectensis
Authors: Carrión Pablo J. Aguirre , Desai Niharika , Brennan Joseph J. , Fifer James E. , Siggers Trevor , Davies Sarah W. , Gilmore Thomas D.
Published: July 2023

Lack of proper nutrition has important consequences for the physiology of all organisms, and nutritional status can affect immunity, based on many studies in terrestrial animals. Here we show a positive correlation between nutrition and immunity in the sea anemone Nematostella vectensis. Gene expression profiling of adult anemones shows downregulation of genes involved in nutrient metabolism, cellular respiration, and immunity in starved animals. Starved adult anemones also have reduced protein levels and activity of immunity transcription factor NF-κB. Starved juvenile anemones have increased sensitivity to bacterial infection and also have lower NF-κB protein levels, as compared to fed controls. Weighted Gene Correlation Network Analysis (WGCNA) is used to identify significantly correlated gene networks that were downregulated with starvation. These experiments demonstrate a correlation between nutrition and immunity in an early diverged marine metazoan, and the results have implications for the survival of marine organisms as they encounter changing environments.
Shortcuts to adiabaticity in superconducting circuits for fast multi-partite state generation
Authors: Cárdenas-López Francisco Andrés , Retamal Juan Carlos , Chen Xi
Published: July 2023

Shortcuts to adiabaticity provide a flexible method to accelerate and improve a quantum control task beyond adiabatic criteria. However, their application to the fast generation of multi-partite quantum gates is still not optimized. Here we propose the reverse-engineering approach to design the longitudinal coupling between a set of qubits coupled to several field modes, for achieving a fast generation of multi-partite quantum gates in photonic or qubit-based architecture. We show that the enhancing generation time is at the nanosecond scale that does not scale with the number of system components. In addition, our protocol does not suffer noticeable detrimental effects due to the dissipative dynamics. Finally, the possible implementation is discussed with the state-of-the-art circuit quantum electrodynamics architecture.
Evaluating cpn60 for high-resolution profiling of the mammalian skin microbiome and detection of phylosymbiosis
Authors: Umbach Alexander K , Fernando Champika , Hill Janet E , Neufeld Josh D
Published: July 2023

Despite being the most widely used phylogenetic marker for amplicon-based profiling of microbial communities, limited phylogenetic resolution of the 16S rRNA gene limits its use for studies of host-microbe co-evolution. In contrast, the cpn60 gene is a universal phylogenetic marker with greater sequence variation capable of species-level resolution. This research compared mammalian skin microbial profiles generated from cpn60 and 16S rRNA gene sequencing approaches, testing for patterns of phylosymbiosis that suggest co-evolutionary host-microbe associations. An ~560 bp fragment of the cpn60 gene was amplified with universal primers and subjected to high-throughput sequencing. Taxonomic classification of cpn60 sequences was completed using a naïve-Bayesian QIIME2 classifier created for this project, trained with an NCBI-supplemented curated cpn60 database (cpnDB_nr). The cpn60 dataset was then compared to published 16S rRNA gene amplicon data. Beta diversity comparisons of microbial community profiles generated with cpn60 and 16S rRNA gene amplicons were not significantly different, based on Procrustes analysis of Bray-Curtis and UniFrac distances. Despite similar relationships among skin microbial profiles, improved phylogenetic resolution provided by the cpn60 gene sequencing permitted observations of phylosymbiosis between microbial community profiles and their mammalian hosts that were not previously observed with 16S rRNA gene profiles. Subsequent investigation of Staphylococcaceae taxa using the cpn60 gene showed increased phylogenetic resolution compared the 16S rRNA gene profiles, revealing potential co-evolutionary host-microbe associations. Overall, our results demonstrate that 16S rRNA and cpn60 marker genes generate comparable microbial community composition patterns while cpn60 better facilitates analyses, such as phylosymbiosis, that require increased phylogenetic resolution.
pH-driven optical changes of platinum(ii) complexes having carboxy-appended salophen ligands
Authors: Fujii Shun , Yagi Hajime , Kawaguchi Tomohiro , Ishikawa Mitsuru , Izumiyama Naoki , Nakaya Manabu
Published: July 2023

The present carboxy-appended platinum(ii) complexes exhibit UV-vis and luminescence spectra changes by the protonation/deprotonation trrigered by the addition of acid and base.