bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancing Blood–Brain Barrier-on-a-Chip Models Through Numerical Simulations
Authors: Carvalho Violeta , Rodrigues Raquel O. , Shin Su Ryon , Lima Rui , Teixeira Senhorinha F. C. F.
Published: September 2024

Researchers have placed engineered or natural tissues within microfluidic chips originating the so-called organ-on-a-chip (OoC) devices. With this technology, organ models can be subjected to phenomena that replicate the complex in vivo biological environment. Furthermore, the OoC devices constitute a more valuable, cost-effective and ethical option when compared to assays performed in animal models for disease research and drug discovery. However, there are still many challenges in replicating some organs/diseases in vitro such as the Blood–Brain Barrier (BBB), given its complexity and structure. Despite the difficulties, many efforts have been made to develop improved in vitro BBB-on-a-chip models to investigate several neurological disorders. In the present review, a summary of the progress made in the development of BBB-on-a-chip is provided focusing on the importance of using numerical simulations for obtaining improved models and better planning the experimental assays. In addition, the future perspectives and current challenges are provided.
Botryosphaeriaceae species associated with branch dieback and decline of macadamia trees in South Africa
Authors: Maduke Angel N. , Slippers Bernard , van der Linde Elna , Wingfield Mike J. , Fourie Gerda
Published: September 2024

Botryosphaeriaceae species are important latent pathogens causing diseases on trees utilized in forestry and agriculture. In recent years, there has been an increase in the incidence and severity of branch dieback and decline on macadamia trees in South Africa, and species of Botryosphaeriaceae have been considered as a possible cause. Although botryosphaeria dieback has been well-studied in Australia, there is little information regarding these fungi on Macadamia in South Africa. The aims of this study were consequently to (i) identify species of Botryosphaeriaceae from Macadamia branches from main production regions in South Africa, (ii) compare the diversity of species between symptomatic and asymptomatic branches, as well as between different growing regions, (iii) and to consider their relative importance in causing dieback. Eight species and three putative hybrids of the Botryosphaeriaceae were identified based on a phylogenetic comparison of sequence data from the ITS rDNA, tub2, tef-1α and rpb2 loci. These included an unidentified Diplodia sp., and Lasiodiplodia sp., as well as L. gilanensis, L. theobromae, L. pseudotheobromae, Neofusicoccum kwambonambiense, N. luteum, N. parvum and three hybrid species. The unidentified species of Diplodia., Lasiodiplodia sp., L. gilanensis, and N. kwambonambiense are reported for the first time on Macadamia in South Africa. All species showed a potential to cause branch dieback symptoms, with species of Neofusicoccum identified as the most aggressive species. This study revealed a high level of diversity of Botryosphaeriaceae species and illustrates their potential as causal agents of dieback on Macadamia in South Africa.
Spiegelreferate in Regierungszentralen: Konsequenzen für die politikwissenschaftliche Lehre aus Forschungsstand und Regierungspraxis
Authors: Mai Manfred
Published: September 2024

Spiegelreferate in Regierungszentralen nehmen neben ihrer zugewiesenen Funktion – der Koordination der einzelnen Ressortaufgaben – weit mehr Aufgaben wahr. Faktisch sind sie an allen Vorgängen beteiligt, die in irgendeinem Zusammenhang mit einem Politikfeld stehen. Die Vorbereitung von Terminen, Reden und Voten für den Regierungschef nimmt einen größeren Umfang ein als die Koordinierung der Ressorts. In Forschung und Lehre dominiert dennoch die Vorstellung eines Hinwirkens auf eine einheitliche Linie der Regierung als Hauptaufgabe der Spiegelreferate. Im Berufsfeldkurs „Die öffentliche Verwaltung als Berufsfeld für Sozialwissenschaftler“ der Universität Düsseldorf werden unter anderem durch Rollenspiele und typische Aufgaben aus der Regierungsarbeit Einblicke in die Praxis der Ressortkoordination vermittelt. So soll nicht nur das in der Theorie verbreitete Bild der Ressortkoordination korrigiert, sondern auch eine realistische Vorbereitung auf eine spätere Tätigkeit in einer Regierungszentrale oder in einem Ressort vermittelt werden. Im vorliegenden Beitrag werden die formellen und informellen Tätigkeiten sowie die Konflikte der Ressortkoordination am Beispiel der Staatskanzlei Nordrhein-Westfalen dargestellt.
Management of Suspicions of Child Maltreatment at Child and Family Clinics: A Mixed-Methods Study
Authors: Midtsund Astrid Durdei , Valla Lisbeth , Lukasse Mirjam , Henriksen Lena
Published: September 2024

This study investigated Norwegian public health nurses working in child and family health clinics’ decision-making practices concerning child maltreatment. A one-phase convergent mixed-method design was utilized, with quantitative and qualitative data concurrently collected and separately analyzed from a questionnaire that included patient vignettes. These vignettes described three potential child maltreatment scenarios to assess public health nurses’ competence and clinical decision-making processes. A total of 554 public health nurses participated in the study conducted from October 24 to December 31, 2022. Findings reveal a high level of recognition of child maltreatment among public health nurses. However, despite their self-perceived confidence, the qualitative data underscore the complexity and uncertainty inherent in their assessment process. The most supported management approaches involved further exploration of the situation. Few public health nurses would file a report of concerns to Child Protective Services or report the police despite their level of concerns. The findings underscore the necessity for additional training and support to enhance public health nurses’ confidence and competence in reporting suspected child maltreatment cases, as well as the need for increased information exchange regarding the procedures and services provided by the child if Child Protective Service is involved.
Windshear analysis over six airports in Saudi Arabia
Authors: Zamreeg Arjan O. , Hasanean H. M.
Published: September 2024

The windshear (WS) or wind gradient is a short-lived microscale or meso-gamma weather phenomenon and is potentially very dangerous for aviation everywhere. This research presents the calculation of WS frequency and intensity from radiosonde data at six airport stations namely Abha, Jeddah, Madinah, Tabuk, Riyadh, and Dammam airport in Saudi Arabia for the period 1991–2020. The frequency and intensity of WS indicate that the number of severe WS increased suddenly from 2015 below 30 m level at all stations except for Riyadh there is no sudden increase. At all other levels, the number of light WS increased from bottom to up to ~ 900 m and then gradually decreased at 1200 m irrespective of stations. Overall, the highest WS observed in the autumn season for all stations except it is in summer for Jeddah. The occurrence of WS is higher in the daytime as compared to the nighttime round the year for Dammam, Madinah, Riyad, and Tabuk while the pattern is opposite for Jeddah. In Abha, it depends on the season. The sudden increase of severe WS from 2015 can be linked to the increase of building areas surrounded the airport. However, further investigation is required to understand the large number of severe WS and its relation to climate change in the region along with teleconnection to the large-scale circulations.
The power of ESG factors in driving financial growth: insights from Palestine
Authors: Alslaibi Naji , Abdelkarim Naser
Published: September 2024

This study examines the effects of environmental, social, and governance disclosure (ESG) components on the financial performance (FP) of firms listed on the Palestine Stock Exchange (PEX) from 2016 to 2022, focusing on the moderating role of corporate governance. This study used primary data from 44 PEX-listed companies. A context analysis technique was used through company websites and disclosures, the entire population (308 observations) was used for this study, and the study used STATA utilizing the required statistical analysis for this research. The study finds that environmental, social, and governance disclosures significantly influence the Return on Equity and Return on Assets. Testing for the moderating role of Corporate Governance, especially board diversity and size, shows that board diversity moderates the association between social and governance disclosure and firm performance. Board size moderates the relationship between social disclosure and firm performance. By contrast, Board Size and Diversity do not moderate the relationship between environmental disclosure and firm performance. The study contributes to the literature as the first of its kind conducted in Palestine, examining the moderating effects of board size and diversity on the association between ESG disclosure and firm performance.
Prediction of Remaining Useful Life of Aero-engines Based on CNN-LSTM-Attention
Authors: Deng Sizhe , Zhou Jian
Published: September 2024

Accurately predicting the remaining useful life (RUL) of aircraft engines is crucial for maintaining financial stability and aviation safety. To further enhance the prediction accuracy of aircraft engine RUL, a deep learning-based RUL prediction method is proposed. This method possesses the potential to strengthen the recognition of data features, thereby improving the prediction accuracy of the model. First, the input features are normalized and the CMAPSS (Commercial Modular Aero-Propulsion System Simulation) dataset is utilized to calculate the RUL for aircraft engines. After extracting attributes from the input data using a convolutional neural network (CNN), the extracted data are input into a long short-term memory (LSTM) network model, with the addition of attention mechanisms to predict the RUL of aircraft engines. Finally, the proposed aircraft engine model is evaluated and compared through ablation studies and comparative model experiments. The results indicate that the CNN-LSTM-Attention model exhibits superior prediction performance for datasets FD001, FD002, FD003, and FD004, with RMSEs of 15.977, 14.452, 13.907, and 16.637, respectively. Compared with CNN, LSTM, and CNN-LSTM models, the CNN-LSTM model demonstrates better prediction performance across datasets. In comparison with other models, this model achieves the highest prediction accuracy on the CMAPSS dataset, showcasing strong reliability and accuracy.
Are you ready: disaster response in nursing education: a cross-sectional survey among Swedish universities and university colleges
Authors: Andersson Ulf , Lundberg Kristina , Andersson Henrik , Sterner Anders
Published: September 2024

Introduction

Registered nurses play a critical role in disaster response and patient care during crises. Recent global events underscore the importance of preparedness for disaster response. However, the readiness of registered nurses and their educational preparation vary. In Sweden, this prompted the National Board of Health and Welfare to introduce a new national curriculum for disaster response. This study aimed to assess how education for undergraduate and specialist registered nurses aligns with this curriculum.

Methods

A descriptive cross-sectional study was conducted among universities and university colleges in Sweden offering undergraduate and specialist nursing programs. Surveys were sent to all 25 higher education institutions providing nursing education in November 2023, comprising 29 questions related to the new curriculum.

Results

Findings revealed that half of the respondents had discussed the new curriculum, with 15 reporting some form of learning activities. Traditional lectures were the most commonly used format, and 11 respondents had designated teachers for the subject. Reasons for lacking disaster response education included prioritizing other acute care areas or a limited perspective at the academy.

Discussion

In conclusion, this study suggests that nursing education may not sufficiently prepare registered nurses for disaster response and armed conflicts. Education tends to focus more on acute care rather than taking a broader perspective. As a result, registered nurses may lack the competence and readiness required to effectively respond to disasters.
The potential of immunomodulators in shaping the future of healthcare
Authors: Sharma Yash , Arora Muskan , Bala Kumud
Published: September 2024

Immunomodulators play a crucial role in modern medical practice, offering both stimulatory and suppressive effects to regulate and control the immune response. These substances, which include immunostimulants and immunosuppressants, modulate the immune system by delivering cytokines and stimulating immune cells. Immunosuppressants are vital in liver and kidney transplantation, where they reduce the immune system’s activation to prevent organ rejection. They are also essential in managing autoimmune disorders by providing controlled suppression of immune activities to avoid self-damage. Conversely, immunostimulants enhance the body’s innate immunity, preventing infections, and boosting resistance against various viral and bacterial diseases. These agents strengthen the body’s natural defenses, making them indispensable in infection control and immunoprophylaxis. The mechanisms of immunomodulators are intricate, involving interactions with key molecules such as cytokines and signaling pathways to shape immune responses, mitigate inflammation, and regulate immune cell functions. Mesenchymal stem cells (MSCs) have emerged as a promising component due to their ability to suppress immune reactions, regulate inflammatory responses, induce immune tolerance, and aid in tissue regeneration. MSCs’ unique properties underscore their potential in treating immune-related disorders, supporting organ transplantation, and promoting tissue repair. Clinically, immunomodulators are central to managing autoimmune diseases, enhancing cancer immunotherapy, combating infectious diseases, and preventing organ rejection in transplant recipients. Innovative therapies like checkpoint inhibitors, CAR T-cell therapy, and cancer vaccines have revolutionized oncology by leveraging the immune system's capabilities. This review explores the critical roles and mechanisms of immunomodulators, highlighting their impact on contemporary healthcare and their potential for future therapeutic developments.

Graphical Abstract
Escaping Poverty Traps and Unlocking Prosperity in the Face of Climate Risk
Authors: Jensen Nathaniel D. , Fava Francesco P. , Mude Andrew G. , Barrett Christopher B. , Wandera-Gache Brenda , Vrieling Anton , Taye Masresha , Takahashi Kazushi , Lung Felix , Ikegami Munenobu , Ericksen Polly , Chelanga Philemon , Chantarat Sommarat , Carter Michael , Bashir Hassan , Banerjee Rupsha
Published: September 2024

This Element outlines the origins and evolution of an international award-winning development intervention, index-based livestock insurance (IBLI), which scaled from a small pilot project in Kenya to a design that underpins drought risk management products and policies across Africa. General insights are provided on i) the economics of poverty, risk management, and drylands development; ii) the evolving use of modern remote sensing and data science tools in development; iii) the science of scaling; and iv) the value and challenges of integrating research with operational implementation to tackle development and humanitarian challenges in some of the world's poorest regions. This title is also available as Open Access on Cambridge Core.
Homeostats: The hidden rulers of ion homeostasis in plants
Authors: Dreyer Ingo , Hernández-Rojas Naomí , Bolua-Hernández Yasnaya , Tapia-Castillo Valentina de los Angeles , Astola-Mariscal Sadith Z. , Díaz-Pico Erbio , Mérida-Quesada Franko , Vergara-Valladares Fernando , Arrey-Salas Oscar , Rubio-Meléndez María E. , Riedelsberger Janin , Michard Erwan
Published: September 2024

Ion homeostasis is a crucial process in plants that is closely linked to the efficiency of nutrient uptake, stress tolerance and overall plant growth and development. Nevertheless, our understanding of the fundamental processes of ion homeostasis is still incomplete and highly fragmented. Especially at the mechanistic level, we are still in the process of dissecting physiological systems to analyse the different parts in isolation. However, modelling approaches have shown that it is not individual transporters but rather transporter networks (homeostats) that control membrane transport and associated homeostatic processes in plant cells. To facilitate access to such theoretical approaches, the modelling of the potassium homeostat is explained here in detail to serve as a blueprint for other homeostats. The unbiased approach provided strong arguments for the abundant existence of electroneutral H+/K+ antiporters in plants.
Synthetic Aperture Radar for Geosciences
Authors: Meng Lingsheng , Yan Chi , Lv Suna , Sun Haiyang , Xue Sihan , Li Quankun , Zhou Lingfeng , Edwing Deanna , Edwing Kelsea , Geng Xupu , Wang Yiren , Yan Xiao‐Hai
Published: September 2024

Synthetic Aperture Radar (SAR) has emerged as a pivotal technology in geosciences, offering unparalleled insights into Earth's surface. Indeed, its ability to provide high‐resolution, all‐weather, and day‐night imaging has revolutionized our understanding of various geophysical processes. Recent advancements in SAR technology, that is, developing new satellite missions, enhancing signal processing techniques, and integrating machine learning algorithms, have significantly broadened the scope and depth of geosciences. Therefore, it is essential to summarize SAR's comprehensive applications for geosciences, especially emphasizing recent advancements in SAR technologies and applications. Moreover, current SAR‐related review papers have primarily focused on SAR technology or SAR imaging and data processing techniques. Hence, a review that integrates SAR technology with geophysical features is needed to highlight the significance of SAR in addressing challenges in geosciences, as well as to explore SAR's potential in solving complex geoscience problems. Spurred by these requirements, this review comprehensively and in‐depth reviews SAR applications for geosciences, broadly including various aspects in air‐sea dynamics, oceanography, geography, disaster and hazard monitoring, climate change, and geosciences data fusion. For each applied field, the scientific advancements produced because of SAR are demonstrated by combining the SAR techniques with characteristics of geophysical phenomena and processes. Further outlooks are also explored, such as integrating SAR data with other geophysical data and conducting interdisciplinary research to offer comprehensive insights into geosciences. With the support of deep learning, this synergy will enhance the capability to model, simulate, and forecast geophysical phenomena with greater accuracy and reliability.
Separation of Electron Flux in Pitch Angle Distribution During the Drift Echo Event and Shabansky Orbits Effect
Authors: Luo Zhekai , Xie Lun , Fu Suiyan , Pu Zuyin , Zhou Xuzhi , Zhao X. X.
Published: September 2024

The Shabansky orbit effect can exert a significant influence on the dynamics of particle motion. However, the north‐south asymmetry of the Shabansky orbits has received relatively little attention in previous research. This study investigates this asymmetry to elucidate the recently observed phenomenon of flux separation in the pitch angle distribution during drift echo events. The asymmetry in Shabansky orbits between the northern and southern hemispheres leads to two distinct drift periods for particles with specific equatorial pitch angles, resulting in the flux separation. To quantify this phenomenon, we develop a mathematical model for the magnetic field, enabling the generation of asymmetrical Shabansky orbits. The calculated drift periods for particles with different equatorial pitch angles corresponds with the characteristics of flux separation, providing evidence to support our hypothesis that the north‐south asymmetry of Shabansky orbits is responsible for flux separation.
Dynamic Simulation of Rock‐Avalanche Fragmentation
Authors: Pudasaini Shiva P. , Mergili Martin , Lin Qiwen , Wang Yufeng
Published: September 2024

Fragmentation is a common phenomenon in complex rock‐avalanches. The fragmentation intensity and process determines exceptional spreading of such mass movements. However, studies focusing on the simulation of fragmentation are still limited and no operational dynamic simulation model of fragmentation has been proposed yet. By enhancing the mechanically controlled landslide deformation model (Pudasaini & Mergili, 2024, https://doi.org/10.1029/2023jf007466), we propose a novel, unified dynamic simulation method for rock‐avalanche fragmentation. The model includes three important aspects: mechanically controlled rock mass deformation, momentum loss while the rock mass fiercely impacts the ground, and the energy transfer during fragmentation resulting in the generation of dispersive lateral pressure. We reveal that the dynamic fragmentation, resulting from the overcoming of the tensile strength by the impact on the ground, leads to enhanced spreading, thinning, run‐out and hypermobility of rock‐avalanches. Thereby, the elastic strain energy release caused by fragmentation becomes an important process. Energy conversion between the front and rear parts caused by the fragmentation results in the enhanced forward movement of the front and hindered motion of the rear of the rock‐avalanche. The new model describes this by amplifying the lateral pressure gradient in the opposite direction: enhanced for the frontal particles and reduced for the rear particles after the fragmentation. The main principle is the switching between the compressional stress and the tensile stress, and therefore from the controlled deformation to substantial spreading of the frontal part in the flow direction while backward stretching of the rear part of the rock mass. Laboratory experiments and field events support our simulation results.
Classifying Plant Communities in the North American Coastal Plain With PRISMA Spaceborne Hyperspectral Imagery and the Spectral Mixture Residual
Authors: Rogers Jennifer A. , Robertson Kevin M. , Hawbaker Todd J. , Sousa Daniel J.
Published: September 2024

The effort to map terrestrial biodiversity, in recent years limited mostly to the use of broadband multispectral remote sensing at decameter scales, can be greatly enhanced by harnessing hyperspectral imagery. Interpretation of hyperspectral imagery may be aided by the Mixture Residual (MR) spectral preprocessing transformation. MR integrates the benefits of spectral mixture analysis with the absorption peak‐enhancing characteristics of continuum removal. MR characterizes each pixel as a linear combination of generic end‐members estimating the spectral continuum, from which the residual of each wavelength is computed and treated as a source of additional information. Using Hyperspectral Precursor of the Application Mission (PRISMA) imagery, we tested the ability of MR‐transformed reflectance as compared to untransformed surface reflectance (SR) to map plant associations and land cover using ground truthing and random forest classifications across four landscapes within the North American Coastal Plain. We used a forward stepwise selection algorithm to choose bands for each classification and subsequently compared these between SR and MR. Our MR classifications distinguished land cover with 5% greater balanced accuracy on average than the SR‐based classifications across all four landscapes. The MR‐based classification that integrated data from all landscapes into a unified model encompassing all 21 land cover types achieved a 76% average balanced accuracy over three iterations. Generally, MR utilized the near‐infrared region to a greater degree than SR while deemphasizing the green peak. Based on our results, MR improves the accuracy of mapping terrestrial biodiversity, likely extending to other current and planned satellite hyperspectral missions.
Varying optimal power for height-standardisation of childhood weight, fat mass and fat-free mass across the obesity epidemic
Authors: Hudda Mohammed T. , Aarestrup Julie , Owen Christopher G. , Baker Jennifer L. , Whincup Peter H.
Published: September 2024

Introduction

Childhood adiposity markers can be standardised for height in the form of indices (marker/heightp) to make meaningful comparisons of adiposity patterns within and between individuals of differing heights. The optimal value of p has been shown to differ by birth year, sex, age, and ethnicity. We investigated whether height powers for childhood weight and fat mass (FM) differed by birth year, sex, or age over the period before and during the child obesity epidemic in Copenhagen.

Setting/methods

Population-based cross-sectional study of 391,801 schoolchildren aged 7 years, 10 years and 13 years, born between 1930 and 1996, from the Copenhagen School Health Records Register. Sex- and age-specific estimates of the height powers for weight and FM were obtained using log–log regression, stratified by a decade of birth.

Results

For weight, amongst children born 1930–39, optimal height powers at 7 years were 2.20 (95% CI: 2.19–2.22) for boys and 2.28 (95% CI: 2.26–2.30) for girls. These increased with birth year to 2.82 (95% CI: 2.76–2.87) and 2.92 (95% CI: 2.87–2.97) for boys and girls born in 1990–96, respectively. For FM, amongst those born 1930–39, powers at 7 years were 2.46 (95% CI: 2.42–2.51) and 2.58 (95% CI: 2.53–2.63) for boys and girls, respectively, and increased with birth year reaching 3.89 (95% CI: 3.75–4.02) and 3.93 (95% CI: 3.80–4.06) for boys and girls born 1990–96, respectively. Powers within birth cohort groups for weight and FM were higher at 10 years than at 7 years, though similar increases across groups were observed at both ages. At 13 years, height powers for weight and FM initially increased with the birth year before declining from the 1970s/80s.

Conclusion

Due to increases in the standard deviation of weight and FM during the obesity epidemic, optimal height powers needed to standardise childhood weight and FM varied by birth year, sex, and age. Adiposity indices using a uniform height power mean different things for different birth cohort groups, sexes, and ages thus should be interpreted with caution. Alternative methods to account for height in epidemiological analyses are needed.
Rewarding properties of L-Dopa in experimental parkinsonism are mediated by sensitized dopamine D1 receptors in the dorsal striatum
Authors: Plewnia Carina , Masini Débora , Fisone Gilberto
Published: September 2024

Treatment of Parkinson’s disease (PD) is based on the use of dopaminergic drugs, such as L-Dopa and dopamine receptor agonists. These substances counteract motor symptoms, but their administration is accompanied by motor and non-motor complications. Among these latter conditions a neurobehavioral disorder similar to drug abuse, known as dopamine dysregulation syndrome (DDS), is attracting increasing interest because of its profound negative impact on the patients’ quality of life. Here we replicate DDS in a PD mouse model based on a bilateral injection of 6-hydroxydopamine (6-OHDA) into the dorsal striatum. Administration of L-Dopa induced locomotor sensitization and conditioned place preference in 6-OHDA lesion, but not in control mice, indicative of the acquisition of addictive-like properties following nigrostriatal dopamine depletion. These behavioral effects were accompanied by abnormal dopamine D1 receptor (D1R) signaling in the medium spiny neurons of the dorsal striatum, leading to hyperactivation of multiple signaling cascades and increased expression of ΔFosB, a stable transcription factor involved in addictive behavior. Systemic administration of the D1R antagonist, SCH23390, abolished these effects and the development of place preference, thereby counteracting the psychostimulant-like effect of L-Dopa. The rewarding properties of L-Dopa were also prevented by chemogenetic inactivation of D1R-expressing neurons in the dorsal striatum. Our results indicate the association between abnormal D1R-mediated transmission and DDS in PD and identify potential approaches for the treatment of this disorder.
Late-onset major depressive disorder: exploring the therapeutic potential of enhancing cerebral brain-derived neurotrophic factor expression through targeted microRNA delivery
Authors: Lai Giovanni , Malavolta Marco , Marcozzi Serena , Bigossi Giorgia , Giuliani Maria Elisa , Casoli Tiziana , Balietti Marta
Published: September 2024

Major depressive disorder (MDD) is a severe psychiatric condition that significantly impacts the overall quality of life. Although MDD can occur across all age groups, it is notably prevalent among older individuals, with the aggravating circumstance that the clinical condition is frequently overlooked and undertreated. Furthermore, older adults often encounter resistance to standard treatments, experience adverse events, and face challenges associated with polypharmacy. Given that late-life MDD is associated with heightened rates of disability and mortality, as well as imposing a significant economic and logistical burden on healthcare systems, it becomes imperative to explore novel therapeutic approaches. These could serve as either supplements to standard guidelines or alternatives for non-responsive patients, potentially enhancing the management of geriatric MDD patients. This review aims to delve into the potential of microRNAs targeting Brain-Derived Neurotrophic Factor (BDNF). In MDD, a significant decrease in both central and peripheral BDNF has been well-documented, raising implications for therapy response. Notably, BDNF appears to be a key player in the intricate interplay between microRNA-induced neuroplasticity deficits and neuroinflammation, both processes deeply implicated in the onset and progression of the disease. Special emphasis is placed on delivery methods, with a comprehensive comparison of the strengths and weaknesses of each proposed approach. Our hypothesis proposes that employing multiple microRNAs concurrently, with the ability to directly influence BDNF and activate closely associated pathways, may represent the most promising strategy. Regarding vehicles, although the perfect nanoparticle remains elusive, considering the trade-offs, liposomes emerge as the most suitable option.
Information search under uncertainty across transdiagnostic psychopathology and healthy ageing
Authors: Mohr Greta , Ince Robin A. A. , Benwell Christopher S. Y.
Published: September 2024

When making decisions in everyday life, we often rely on an internally generated sense of confidence to help us revise and direct future behaviours. For instance, confidence directly informs whether further information should be sought prior to commitment to a final decision. Many studies have shown that aging and both clinical and sub-clinical symptoms of psychopathology are associated with systematic alterations in confidence. However, it remains unknown whether these confidence distortions influence information-seeking behaviour. We investigated this question in a large general population sample (N = 908). Participants completed a battery of psychiatric symptom questionnaires and performed a perceptual decision-making task with confidence ratings in which they were offered the option to seek helpful information (at a cost) before committing to a final decision. Replicating previous findings, an ‘anxious-depression’ (AD) symptom dimension was associated with systematically low confidence, despite no detriment in objective task accuracy. Conversely, a ‘compulsive behaviour and intrusive thoughts’ (CIT) dimension was associated with impaired task accuracy but paradoxical over-confidence. However, neither symptom dimension was significantly associated with an increased or decreased tendency to seek information. Hence, participants scoring highly for AD or CIT did not use the option to information seek any more than average to either increase their confidence (AD) or improve the accuracy of their decisions (CIT). In contrast, older age was associated with impaired accuracy and decreased confidence initially, but increased information seeking behaviour mediated increases in both accuracy and confidence for final decisions. Hence, older adults used the information seeking option to overcome initial deficits in objective performance and to increase their confidence accordingly. The results show an appropriate use of information seeking to overcome perceptual deficits and low confidence in healthy aging which was not present in transdiagnostic psychopathology.
The disruption of NEAT1-miR-125b-5p-SLC1A5 cascade defines the oncogenicity and differential immune profile in head and neck squamous cell carcinoma
Authors: Liu Ying-Chieh , Liu So-Yu , Lin Yu-Cheng , Liu Chung-Ji , Chang Kuo-Wei , Lin Shu-Chun
Published: September 2024

Metabolic reprogramming sustains malignant head and neck squamous cell carcinoma (HNSCC) to overcome stressful microenvironments, and increased glutamine uptake is a common metabolic hallmark in cancers. Since metabolic reprogramming has been recognized as a new therapeutic target for tumor cells, understanding the regulatory axis of glutamine uptake in HNSCC and its potential downstream effects in its pathogenesis of HNSCC would be incredibly beneficial. Bioinformatic analysis of the Cancer Genome Atlas (TCGA)-HNSCC dataset and RNAseq analysis performed on HNSCC indicated that SLC1A5 was the most dysregulated transporter among the seven homologous glutamate or neutral amino acid transporters in the SLC1A family. To further clarify the role of SLC1A5 in HNSCC, we knocked down SLC1A5 expression. This knockdown decelerated cell growth, induced G0/G1 arrest, diminished tumorigenicity, and increased cleavage caspase3, LC3B, and intracellular Fe2+. Inhibitors against apoptosis, autophagy, or ferroptosis rescued the cell viability repressed by SLC1A5 knockdown. SLC1A5 knockdown also suppressed glutamine uptake, enhanced oxidative stress, and increased sensitivity to cisplatin. CRISPR/dCas9-mediated SLC1A5 induction conferred cisplatin resistance and reduced apoptosis, autophagy, and ferroptosis. Reporter assays and western blot data demonstrated that miR-125b-5p targets and attenuates SLC1A5, while the si-NEAT1 increases miR-125b-5p expression. Analysis of the TCGA-HNSCC databases showed concordant upregulation of NEAT1 and downregulation of miR-125b-5p, along with SLC1A5 upregulation in tumors. Analysis of transcriptomic data revealed that tumors harboring higher SLC1A5 expression had significantly lower immune scores in CD8+, monocytes, and dendritic cells, and higher scores in M0 and M1 macrophages. Disruptions in immune modulation, metabolism, and oxidative stress components were associated with SLC1A5 aberrations in HNSCC. This study concludes that the NEAT1/miR-125b-5p/SLC1A5 cascade modulates diverse activities in oncogenicity, treatment efficacy, and immune cell profiles in head and neck/oral carcinoma.
Costs and cost-effectiveness of the Kerala pilot screening programme for diabetic retinopathy in the public health system
Authors: Wittenberg Raphael , Anderson Robert , Redding Stuart , Gopal Bipin , Sadanandan Rajeev , Sahasranamam Vasudeva Iyer , George Simon , Premnazir Lakshmi , Netuveli Gopalakrishnan , Srinath Jyotsna , Ramakrishnan Radha , Conroy Dolores , Sivaprasad Sobha
Published: September 2024

Background/objectives

The Government of Kerala initiated a pilot screening programme for diabetic retinopathy in 16 Family Health Centres in Thiruvananthapuram district in 2019 in collaboration with the ORNATE India project. The evaluation of this pilot included a study of its costs and cost-effectiveness to inform decisions about extending the programme throughout Kerala.

Subjects/methods

The participants comprise all 5307 people who were screened for diabetic retinopathy under the pilot programme for whom data could be collected.

Results

The costs of the pilot programme are estimated at INR 11.3 million (including INR 1.9 million costs to individuals) and the benefits at 514 QALYs, slightly over one QALY per person treated. The cost per QALY was INR 22,000, which is well below India’s Gross National Income per person.

Conclusions

Kerala’s 2019 pilot screening programme for diabetic retinopathy was highly cost-effective.
Detection and spread of high pathogenicity avian influenza virus H5N1 in the Antarctic Region
Authors: Banyard Ashley C. , Bennison Ashley , Byrne Alexander M. P. , Reid Scott M. , Lynton-Jenkins Joshua G. , Mollett Benjamin , De Silva Dilhani , Peers-Dent Jacob , Finlayson Kim , Hall Rosamund , Blockley Freya , Blyth Marcia , Falchieri Marco , Fowler Zoe , Fitzcharles Elaine M. , Brown Ian H. , James Joe
Published: September 2024

Until recent events, the Antarctic was the only major geographical region in which high pathogenicity avian influenza virus (HPAIV) had never previously been detected. Here we report on the detection of clade 2.3.4.4b H5N1 HPAIV in the Antarctic and sub-Antarctic regions of South Georgia and the Falkland Islands, respectively. We initially detected H5N1 HPAIV in samples collected from brown skuas at Bird Island, South Georgia on 8th October 2023. Since this detection, mortalities were observed in several avian and mammalian species at multiple sites across South Georgia. Subsequent testing confirmed H5N1 HPAIV across several sampling locations in multiple avian species and two seal species. Simultaneously, we also confirmed H5N1 HPAIV in southern fulmar and black-browed albatross in the Falkland Islands. Genetic assessment of the virus indicates spread from South America, likely through movement of migratory birds. Critically, genetic assessment of sequences from mammalian species demonstrates no increased risk to human populations above that observed in other instances of mammalian infections globally. Here we describe the detection, species impact and genetic composition of the virus and propose both introductory routes and potential long-term impact on avian and mammalian species across the Antarctic region. We also speculate on the threat to specific populations following recent reports in the area.
Two KaiABC systems control circadian oscillations in one cyanobacterium
Authors: Köbler Christin , Schmelling Nicolas M. , Wiegard Anika , Pawlowski Alice , Pattanayak Gopal K. , Spät Philipp , Scheurer Nina M. , Sebastian Kim N. , Stirba Florian P. , Berwanger Lutz C. , Kolkhof Petra , Maček Boris , Rust Michael J. , Axmann Ilka M. , Wilde Annegret
Published: September 2024

The circadian clock of cyanobacteria, which predicts daily environmental changes, typically includes a standard oscillator consisting of proteins KaiA, KaiB, and KaiC. However, several cyanobacteria have diverse Kai protein homologs of unclear function. In particular, Synechocystis sp. PCC 6803 harbours, in addition to a canonical kaiABC gene cluster (named kaiAB1C1), two further kaiB and kaiC homologs (kaiB2, kaiB3, kaiC2, kaiC3). Here, we identify a chimeric KaiA homolog, named KaiA3, encoded by a gene located upstream of kaiB3. At the N-terminus, KaiA3 is similar to response-regulator receiver domains, whereas its C-terminal domain resembles that of KaiA. Homology analysis shows that a KaiA3-KaiB3-KaiC3 system exists in several cyanobacteria and other bacteria. Using the Synechocystis sp. PCC 6803 homologs, we observe circadian oscillations in KaiC3 phosphorylation in vitro in the presence of KaiA3 and KaiB3. Mutations of kaiA3 affect KaiC3 phosphorylation, leading to growth defects under both mixotrophic and chemoheterotrophic conditions. KaiC1 and KaiC3 exhibit phase-locked free-running phosphorylation rhythms. Deletion of either system (∆kaiAB1C1 or ∆kaiA3B3C3) alters the period of the cellular backscattering rhythm. Furthermore, both oscillators are required to maintain high-amplitude, self-sustained backscatter oscillations with a period of approximately 24 h, indicating their interconnected nature.
Multi-protein assemblies orchestrate co-translational enzymatic processing on the human ribosome
Authors: Klein Marius , Wild Klemens , Sinning Irmgard
Published: September 2024

Nascent chains undergo co-translational enzymatic processing as soon as their N-terminus becomes accessible at the ribosomal polypeptide tunnel exit (PTE). In eukaryotes, N-terminal methionine excision (NME) by Methionine Aminopeptidases (MAP1 and MAP2), and N-terminal acetylation (NTA) by N-Acetyl-Transferase A (NatA), is the most common combination of subsequent modifications carried out on the 80S ribosome. How these enzymatic processes are coordinated in the context of a rapidly translating ribosome has remained elusive. Here, we report two cryo-EM structures of multi-enzyme complexes assembled on vacant human 80S ribosomes, indicating two routes for NME-NTA. Both assemblies form on the 80S independent of nascent chain substrates. Irrespective of the route, NatA occupies a non-intrusive ‘distal’ binding site on the ribosome which does not interfere with MAP1 or MAP2 binding nor with most other ribosome-associated factors (RAFs). NatA can partake in a coordinated, dynamic assembly with MAP1 through the hydra-like chaperoning function of the abundant Nascent Polypeptide-Associated Complex (NAC). In contrast to MAP1, MAP2 completely covers the PTE and is thus incompatible with NAC and MAP1 recruitment. Together, our data provide the structural framework for the coordinated orchestration of NME and NTA in protein biogenesis.
Carrier-phonon decoupling in perovskite thermoelectrics via entropy engineering
Authors: Zheng Yunpeng , Zhang Qinghua , Shi Caijuan , Zhou Zhifang , Lu Yang , Han Jian , Chen Hetian , Ma Yunpeng , Zhang Yujun , Lin Changpeng , Xu Wei , Ma Weigang , Li Qian , Yang Yueyang , Wei Bin , Yang Bingbing , Zou Mingchu , Zhang Wenyu , Liu Chang , Dou Lvye , Yang Dongliang , Lan Jin-Le , Yi Di , Zhang Xing , Gu Lin , Nan Ce-Wen , Lin Yuan-Hua
Published: September 2024

Thermoelectrics converting heat and electricity directly attract broad attentions. To enhance the thermoelectric figure of merit, zT, one of the key points is to decouple the carrier-phonon transport. Here, we propose an entropy engineering strategy to realize the carrier-phonon decoupling in the typical SrTiO3-based perovskite thermoelectrics. By high-entropy design, the lattice thermal conductivity could be reduced nearly to the amorphous limit, 1.25 W m−1 K−1. Simultaneously, entropy engineering can tune the Ti displacement, improving the weighted mobility to 65 cm2 V−1 s−1. Such carrier-phonon decoupling behaviors enable the greatly enhanced μW/κL of ~5.2 × 103 cm3 K J−1 V−1. The measured maximum zT of 0.24 at 488 K and the estimated zT of ~0.8 at 1173 K in (Sr0.2Ba0.2Ca0.2Pb0.2La0.2)TiO3 film are among the best of n-type thermoelectric oxides. These results reveal that the entropy engineering may be a promising strategy to decouple the carrier-phonon transport and achieve higher zT in thermoelectrics.
Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions
Authors: Mohren Lars , Erdlenbruch Friedrich , Leitão Elsa , Kilpert Fabian , Hönes G. Sebastian , Kaya Sabine , Schröder Christopher , Thieme Andreas , Sturm Marc , Park Joohyun , Schlüter Agatha , Ruiz Montserrat , Morales de la Prida Moisés , Casasnovas Carlos , Becker Kerstin , Roggenbuck Ulla , Pechlivanis Sonali , Kaiser Frank J. , Synofzik Matthis , Wirth Thomas , Anheim Mathieu , Haack Tobias B. , Lockhart Paul J. , Jöckel Karl-Heinz , Pujol Aurora , Klebe Stephan , Timmann Dagmar , Depienne Christel
Published: September 2024

Repeat expansions in FGF14 cause autosomal dominant late-onset cerebellar ataxia (SCA27B) with estimated pathogenic thresholds of 250 (incomplete penetrance) and 300 AAG repeats (full penetrance), but the sequence of pathogenic and non-pathogenic expansions remains unexplored. Here, we demonstrate that STRling and ExpansionHunter accurately detect FGF14 expansions from short-read genome data using outlier approaches. By combining long-range PCR and nanopore sequencing in 169 patients with cerebellar ataxia and 802 controls, we compare FGF14 expansion alleles, including interruptions and flanking regions. Uninterrupted AAG expansions are significantly enriched in patients with ataxia from a lower threshold (180–200 repeats) than previously reported based on expansion size alone. Conversely, AAGGAG hexameric expansions are equally frequent in patients and controls. Distinct 5’ flanking regions, interruptions and pre-repeat sequences correlate with repeat size. Furthermore, pure AAG (pathogenic) and AAGGAG (non-pathogenic) repeats form different secondary structures. Regardless of expansion size, SCA27B is a recognizable clinical entity characterized by frequent episodic ataxia and downbeat nystagmus, similar to the presentation observed in a family with a previously unreported nonsense variant (SCA27A). Overall, this study suggests that SCA27B is a major overlooked cause of adult-onset ataxia, accounting for 23–31% of unsolved patients. We strongly recommend re-evaluating pathogenic thresholds and integrating expansion sequencing into the molecular diagnostic process.
Phenazines are involved in the antagonism of a novel subspecies of Pseudomonas chlororaphis strain S1Bt23 against Pythium ultimum
Authors: Chi Sylvia I. , Akuma Mercy , Xu Renlin , Plante Véronique , Hadinezhad Mehri , Tambong James T.
Published: September 2024

Long-term use of chemical fungicides to control plant diseases caused by fungi and oomycetes has led to pathogen resistance and negative impacts on public health and environment. There is a global search for eco-friendly methods and antagonistic bacteria are emerging as alternatives. We isolated a potent antagonistic bacterial strain (S1Bt23) from woodland soil in Québec, Canada. Taxonomic characterization by 16S rRNA, multi-locus sequence analysis, pairwise whole-genome comparisons, phylogenomics and phenotypic data identified strain S1Bt23 as a novel subspecies within Pseudomonas chlororaphis. In dual culture studies, strain S1Bt23 exhibited potent mycelial growth inhibition (60.2–66.7%) against Pythium ultimum. Furthermore, strain S1Bt23 was able to significantly bioprotect potato tuber slices from the development of necrosis inducible by P. ultimum. Annotations of the whole genome sequence of S1Bt23 revealed the presence of an arsenal of secondary metabolites including the complete phenazine biosynthetic cluster (phzABCDEFG). Thin-layer (TLC) and high-performance liquid (HPLC) chromatographic analyses of S1Bt23 extracts confirmed the production of phenazines, potent antifungal compounds. CRISPR/Cas9-mediated deletion of phzB (S1Bt23ΔphzB) or phzF (S1Bt23ΔphzF) gene abrogated phenazine production based on TLC and HPLC analyses. Also, S1Bt23ΔphzB and S1Bt23ΔphzF mutants lost antagonistic activity and bioprotection ability of potato tubers against P. ultimum. This demonstrated that phenazines are involved in the antagonistic activity of S1Bt23 against P. ultimum. Finally, based on genotypic and phenotypic data, we taxonomically conclude that S1Bt23 represents a novel subspecies for which the name Pseudomonas chlororaphis subsp. phenazini is proposed.